Difficult Decisions in Colorectal PDF

Difficult Decisions in Surgery:
An Evidence-Based Approach
Neil Hyman
Konstantin Umanskiy Editors
Difficult
Decisions in
Colorectal
Surgery
Difficult Decisions in Surgery:
An Evidence-Based Approach
Series Editor
Mark K. Ferguson
For further volumes:

http://www.springer.com/series/13361
Neil Hyman • Konstantin Umanskiy
Editors
Difficult Decisions in
Colorectal Surgery
Editors
Neil Hyman Konstantin Umanskiy
Medical Center Medical Center
University of Chicago University of Chicago
Chicago, IL Chicago, IL
USA USA
ISSN 2198-7750 ISSN 2198-7769 (electronic)

Difficult Decisions in Surgery: An Evidence-Based Approach
ISBN 978-3-319-40222-2 ISBN 978-3-319-40223-9 (eBook)
DOI 10.1007/978-3-319-40223-9
Library of Congress Control Number: 2016959469
© Springer International Publishing Switzerland 2017

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I dedicate this book to my sons EJ and Seth,
who have been a never-ending source of
pride and joy from the moment they were
born, and always the reason for everything.
Neil Hyman
I dedicate this book to my parents Yakov and

Eugenia.
Konstantin Umanskiy
Preface
Colon and rectal surgery may very well be on the cusp of a golden age. Our spe-
cialty is thriving and our ACGME-approved training programs are extremely popu-
lar among the best and brightest general surgery residents. Breathtaking advances in
minimally invasive surgery have occurred over the past quarter century including
laparoscopic bowel resection, robotic surgery, endoscopic techniques such as endo-
scopic mucosal/submucosal resection, and transanal approaches such as transanal
endoscopic microsurgery and transanal minimally invasive surgery. Innovation in
these areas has made surgery safer for many of our patients, enabled sphincter pres-
ervation, and reduced the period of disability that many experience after treatment.
However, in addition to the obvious benefits of these disruptive technologies, many
long-standing questions persist and new ones have been raised.
1. What is the most appropriate use of this new and often more expensive technol-
ogy? Does the evidence really support the notion that everything new is really
better?
2. Considering the primacy of patient safety, how do we decide who should be
credentialed to do what?
3. Should any surgeon be able to use any technique they wish, irrespective of cost,
efficacy, and demonstrated competence?
4. Should these new technologies be evaluated first by a select group of high vol-
ume/experienced surgeons in a controlled and measured environment before
more widespread adoption?
5. Do we really have adequate hypotheses and frameworks of understanding for the
common diseases we treat?
6. Without them, can we really devise rational treatment approaches for these
maladies?
7. As such, are almost all our treatments largely empiric and lacking in the basic
scientific underpinnings that would move us beyond therapeutic “hail Mary’s”?
With this state of affairs, the practice of colon and rectal surgery has largely been
driven by expert opinion and the practice of thought leaders – it is often the best we
have. In this book, we have put together a select and highly respected group of
vii
viii Preface
leaders in our field and asked them both to critically review the evidence in a con-
troversial area which they have typically contributed to and investigated during their
career. We also asked them to supplement this with their clinical insights and per-
sonal experience. This is not a comprehensive textbook of colon and rectal surgery
which attempts to review the basic anatomy and physiology of the vast spectrum of
problems one may encounter in the small intestine, colon, rectum, and anus. Many
excellent textbooks like this already exist. Rather, we have selected a broad array of
difficult and often controversial problems that the surgeon who deals with colorectal
disease often encounters. We asked our experts to imagine that they received a
phone call from a busy surgeon in the surgeon’s lounge who wanted to know how a
particular challenging patient management issue should be handled. The goal was
not to list every treatment that has ever been described or utilized.
1 . What are my best options?
2. What is the best evidence for/against these options in the literature?
3. How do I decide?
4. What do you think and what do you do?
The reader will be able to see what the highest quality evidence available exists
to guide our management decisions. However, it will be evident that there is always
going to be considerable room for alternative opinions and approaches. A different
acknowledged expert with considerable clinical experience and knowledge of the
applicable evidence may see things differently and approach the same problem
using a very different algorithm. Indeed, as much as we like to talk about evidence-
based approaches, the “evidence” for much of what we do is often lacking and
meager. We hope that the reader will find real help and a sense of perspective from
this book. We particularly hope that we inspire our trainees and junior colleagues to
uncover new paradigms of care, contribute high quality evidence to the literature,
and advance the scientific underpinnings of our management decisions. Our patients
deserve no less!
Chicago, IL, USA Neil Hyman

Acknowledgments
We gratefully acknowledge the talents, expertise, and assistance of Ms. Abby

Larson – without her, there would be no book. We also thank Dr. Mark Ferguson for
his guidance and leadership and Kumar Athiappan of Springer for his diligence and
responsiveness. We also thank our mentors, colleagues, fellows, residents, students,
and patients who provide us the inspiration to learn and improve every day.
ix
Contents
1 Introduction�� 1
Konstantin Umanskiy
2 Evaluating Evidence�� 7
W. Donald Buie
Part I IBD
3 IBD: Management of Symptomatic Anal Fistulas

in Patients with Crohn’s Disease�� 19
Lisa S. Poritz
4 IBD: Management of a Painful Anal Fissure
and Skin Tags in Patients with Crohn’s Disease �� 29
Nicole M. Saur and Joshua I.S. Bleier
5 IBD: Elective Surgical Management in Patients
with Ulcerative Colitis-How Many Stages? �� 35
Roger D. Hurst
6 Which Ulcerative Colitis Patients Should Not
Have Ileal Pouch-Anal Anastomosis�� 45
Scott A. Strong
7 Management of Pouch-Vaginal Fistulas�� 53
Ido Mizrahi and Steven D. Wexner
8 Crohn’s Colitis and Ileal Pouch Anal Anastomosis�� 65
C. Peirce and Feza H. Remzi
9 Steroid Management in Patients Undergoing
Surgery for IBD�� 73
Karen Zaghiyan and Phillip Fleshner
xi
xii Contents
10 IBD: Management of Dysplasia in Patients with

Ulcerative Colitis�� 83
Tara M. Connelly and Walter A. Koltun
11 Post-operative Prophylaxis in Patients with Crohn’s Disease�� 97
Jonathan Erlich and David T. Rubin
Part II Colon Cancer
12 Follow-Up in Patient’s After Curative Resection

for Colon Cancer Surveillance for Colon Cancer �� 115
Clifford L. Simmang
13 Management of Patients with Acute Large Bowel
Obstruction from Colon Cancer�� 121
Marc A. Singer and Bruce A. Orkin
14 Utility of Primary Tumor Resection in Asymptomatic,
Unresectable Metastatic Colon and Rectal Cancer�� 139
Michael Pezold, Geoffrey K. Ku, and Larissa K. Temple
15 Management of Large Sessile Cecal Polyps�� 153
Brett Howe and Richard L. Whelan
16 Stage II Colon Cancer: Towards an Individualized Approach�� 163
Blase N. Polite
Part III Rectal Cancer
17 Rectal Cancer: Management of T1 Rectal Cancer �� 175

Woon Kyung Jeong and Jose G. Guillem
18 Management of T2 Rectal Cancer �� 183
Peter A. Cataldo
19 Clinical Complete Response after Neoadjuvant
Chemoradiotherapy in Rectal Cancer:
Operative or Non-Operative Management?�� 191
Miranda Kusters and Julio Garcia-Aguilar
20 Management of the Patient with Rectal Cancer Presenting
with Synchronous Liver Metastasis�� 205
Shafik M. Sidani and Maher A. Abbas
21 Who Needs a Loop Ileostomy After Low Anterior Resection
for Rectal Cancer? �� 233
Walker Julliard and Gregory Kennedy
Contents xiii
22 Selection Factors for Reoperative Surgery

for Local Recurrent Rectal Cancer�� 241
Scott R. Kelley and David W. Larson
Part IV Anal Dysplasia/Cancer
23 Anal Dysplasia/Cancer: Management

of Patients with AIN 3�� 255
Amy L. Lightner and Mark L. Welton
24 Management of the Abnormal Pap Smear
in HIV Positive Patients�� 267
Brad Champagne
Part V Benign Colon Disease
25 Indications for Surgery in Patients with Severe

Clostridium Difficile Colitis�� 275
Vikram Reddy and Walter Longo
26 Do We Need to Operate on Patients After Successful
Percutaneous Drainage of a Diverticular Abscess?�� 283
Wolfgang B. Gaertner and Robert D. Madoff
27 The Role of Laparoscopic Peritoneal Lavage in the Operative
Management of Hinchey III Diverticulitis�� 291
Lisa Marie Cannon
28 Surgery for Acute Complicated Diverticulitis:
Hartmann vs. Primary Anastomosis�� 307
Nitin Mishra and David A. Etzioni
29 Who Needs Elective Surgery for Recurrent Diverticulitis? �� 319
Janice Rafferty
30 Deciding on an IRA vs. IPAA for FAP �� 337
James Church
31 Rectal Prolapse: What Is the Best Approach for Repair? �� 347
Saleh Eftaiha and Anders Mellgren
Part VI Benign Anal Disease
32 Optimal Management of the Transsphincteric Anal Fistula �� 361

Richard T. Birkett and Jason F. Hall
33 Benign Anal Disease: Management of the Recurrent
Anovaginal/Rectovaginal Fistula�� 371
Elise H. Lawson and Patricia L. Roberts
xiv Contents
34 Benign Anal Disease: When to Operate on the Patient with

an Anal Fissure�� 383
David J. Berler and Randolph M. Steinhagen
35 Anal Fissure: Recurrence After Lateral
Internal Sphincterotomy �� 395
Christy Cauley and Liliana Bordeianou
36 Benign Anal Disease: Third Degree Hemorrhoids – Who Really
Needs Surgery?�� 403
Aneel Damle and Justin Maykel
37 Which Patients with Fecal Incontinence Require
Physiologic Workup? �� 413
Tracy Hull
38 Benign Anal Disease: Who Are the Right Candidates
for Sacral Nerve Stimulation?�� 423
Teresa C. Rice and Ian M. Paquette
39 When Is an Anal Sphincter Repair Indicated? �� 439
Jan Rakinic and V. Prasad Poola
Part VII Quality Improvement
40 Checklists in Surgery�� 451

Eric A. Sparks and Harry T. Papaconstantinou
41 Quality Improvement: Where Are We with Bowel Preps
for Patients Undergoing Colon Resection?�� 467
Anthony J. Senagore
42 Quality Improvement: Are Fast Track Pathways
for Laparoscopic Surgery Needed?�� 475
Avery S. Walker, Michael Keating,
and Scott R. Steele
43 Quality Improvement: Enhanced Recovery Pathways
for Open Surgery �� 485
W. Conan Mustain and Conor P. Delaney
44 Quality Improvement: Preventing Readmission
After Ileostomy Formation�� 503
Najjia N. Mahmoud and Emily Carter Paulson
Contents xv
Part VIII Technique
45 Trans-anal Endoscopic Surgery vs. Conventional

Transanal Surgery�� 511
Theodore J. Saclarides
46 Laparoscopic Versus Robotic Versus Open Surgery
for Rectal Cancer �� 519
Campbell S. Roxburgh and Martin R. Weiser
47 Reservoir Construction After Low Anterior Resection:
Who and What? �� 535
David A. Liska and Matthew F. Kalady
48 Conventional vs Single Port Approaches to Laparoscopic
Colectomy �� 545
H. Hande Aydinli and Meg Costedio
49 Anastomotic Leak Management Following Low
Anterior Resections�� 557
Nathan R. Smallwood and James W. Fleshman
50 Management of the Unhealed Perineal Wound
After Proctectomy�� 567
Jesse Moore and Sean Wrenn
Index�� 581
Contributors
Maher A. Abbas Digestive Disease Institute, Cleveland Clinic Abu Dhabi,

Abu Dhabi, United Arab Emirates
David J. Berler, MD Department of Surgery, Icahn School of Medicine at Mount
Sinai, New York, USA
Richard T. Birkett, MD Lahey Hospital and Medical Center,
Burlington, MA, USA
Joshua I.S. Bleier, MD, FACS, FASCRS Division of Colon and Rectal Surgery,
Department of Surgery, University of Pennsylvania Perelman School of Medicine,
Philadelphia, PA, USA
Liliana Bordeianou, MD, MPH Colorectal Surgery Program, Department
of Surgery, Massachusetts General Hospital (MGH), Boston, MA, USA
MGH Center for Pelvic Floor Disorders, Boston, MA, USA
W. Donald Buie, MD, MSc, FRCSC Department of Surgery, University
of Calgary, Calgary, AB, Canada
Lisa Marie Cannon, MD Section of Colon and Rectal Surgery, Department
of General Surgery, University of Chicago Medicine, Chicago, IL, USA
Peter A. Cataldo Colon and Rectal Surgery, University of Vermont College
of Medicine, Burlington, VT, USA
C.E. Cauley Colorectal Surgery Program, Department of Surgery,
Massachusetts General Hospital (MGH), Boston, MA, USA
Brad Champagne Lerner College of Medicine, Cleveland Clinic, Cleveland,
OH, USA
Cleveland Clinic, Fairview Hospital, Cleveland, OH, USA
xvii
xviii Contributors
James Church, MBChB, FRACS Department of Colorectal Surgery, Sandford

R. Weiss Center for Hereditary Colorectal Cancer, Cleveland Clinic Foundation,
Cleveland, OH, USA
Tara M. Connelly, MB, BCh, PhD Department of Surgery, Waterford University
Hospital, Waterford, Ireland
Meg Costedio Department of Colorectal Surgery, Digestive Disease Institute,
Cleveland Clinic, Cleveland, OH, USA
Aneel Damle, MD, MBA Division of Colon and Rectal Surgery, University
of Massachusetts Medical Center, Worcester, MA, USA
Conor P. Delaney, MD, MCh Digestive Disease Institute, Cleveland Clinic,
Cleveland, OH, USA
Saleh Eftaiha, MD Division of Colon & Rectal Surgery, University of Illinois
Chicago, Chicago, CL, USA
Jonathan Erlich University of Chicago Medicine, Section of Hospital Medicine,
Chicago, IL, USA
David A. Etzioni, MD, MSHS Mayo Clinic College of Medicine, Rochester,
MN, USA
James W. Fleshman Department of Surgery, Baylor University Medical Center,
Dallas, TX, USA
Texas A&M Healthsciences, Dallas, TX, USA
Phillip Fleshner, MD Section of Colon and Rectal Surgery, Cedars-Sinai
Medical Center, Los Angeles, CA, USA
Wolfgang B. Gaertner Division of Colon & Rectal Surgery, Department of
Surgery, University of Minnesota, Minneapolis, MN, USA
Julio Garcia-Aguilar, MD Colorectal Service, Department of Surgery, Memorial
Sloan Kettering Cancer Center, New York, NY, USA
Jose G. Guillem Colorectal Service, Department of Surgery,
Memorial Sloan-Kettering Cancer Center, New York, NY, USA
Jason F. Hall, MD, MPH, FACS Lahey Hospital and Medical Center,
Burlington, MA, USA
Brett Howe, MD Mount Sinai School of Medicine, Mount Sinai West Hospital,
New York, NY, USA
Tracy Hull Department of Colon and Rectal Surgery, Digestive Disease Institute,
The Cleveland Clinic Foundation, Cleveland, OH, USA
Roger D. Hurst, MD Department of Surgery, University of Chicago Pritzker
School of Medicine, Chicago, IL, USA
Contributors xix
Woon Kyung Jeong Colorectal Service, Department of Surgery, Memorial

Sloan-Kettering Cancer Center, New York, NY, USA
Walker Julliard Department of Surgery, University of Wisconsin School
of Medicine and Public Health, Madison, WI, USA
Matthew F. Kalady, MD Department of Colorectal Surgery, Cleveland Clinic,
Cleveland, OH, USA
Michael Keating, BA Case Western Reserve University School of Medicine,
Cleveland, OH, USA
Scott R. Kelley, MD, FACS, FASCRS Division of Colon and Rectal Surgery,
Mayo Clinic, Rochester, MN, USA
Gregory Kennedy Division of Gastrointestinal Surgery, Department of Surgery,
University of Alabama at Birmingham, Birmingham, AL, USA
Walter A. Koltun, MD, FRCS, FASCRS Division of Colon and Rectal Surgery,
Inflammatory Bowel Disease, The Pennsylvania State University, College
of Medicine, Hershey, PA, USA
Geoffrey K. Ku, MD Gastrointestinal Oncology Service, Department of
Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
Miranda Kusters Department of Surgery, Catharina Hospital,
Eindhoven, The Netherlands
David W. Larson, MD, MBA, FACS, FASCRS Division of Colon and Rectal
Surgery, Mayo Clinic, Rochester, MN, USA
Elise H. Lawson, MD, MSHS Colon and Rectal Surgery, Farmington, CT, USA
Amy L. Lightner Mayo Clinic, Division of Colon and Rectal Surgery, Rochester,
MN, USA
David A. Liska, MD Department of Colorectal Surgery, Cleveland Clinic,
Cleveland, OH, USA
Walter Longo, MD, MBA Department of Surgery, Yale University School of
Medicine, New Haven, CT, USA
Robert D. Madoff Division of Colon & Rectal Surgery, Department of Surgery,
University of Minnesota, Minneapolis, MN, USA
Najjia Mahmoud Department of Surgery, University of Pennsylvania,
Justin Maykel, MD Division of Colon and Rectal Surgery, University
of Massachusetts Medical Center, Worcester, MA, USA
Anders Mellgren, MD, PhD Division of Colon & Rectal Surgery, University
of Illinois Chicago, Chicago, CL, USA
xx Contributors
Nitin Mishra, MD Mayo Clinic College of Medicine, Rochester, MN, USA

Ido Mizrahi, MD Department of Colorectal Surgery, Cleveland Clinic Florida,
Weston, FL, USA
Jesse Moore, MD, FACS, FASCRS University of Vermont Medical Center,
University of Vermont College of Medicine, Burlington, VI, USA
W. Conan Mustain, MD Division of Colon and Rectal Surgery, University
of Arkansas for Medical Sciences,, Little Rock, AR, USA
Bruce A. Orkin, MD, FACS, FASCRS Section of Colon and Rectal Surgery,
Rush University School of Medicine, Chicago, IL, USA
Harry T. Papaconstantinou, MD Department of Surgery, Baylor Scott & White
Healthcare, Texas A&M University College of Medicine, Baylor Scott & White
Memorial Hospital, Temple, TX, USA
Ian M. Paquette, MD Division of Colon and Rectal Surgery, University
of Cincinnati College of Medicine, Cincinnati, OH, USA
Emily Carter Paulson Department of Surgery, University of Pennsylvania,
C. Peirce Department of Colorectal Surgery, Cleveland Clinic, Cleveland, OH, USA
Michael Pezold, MD, MS Department of Surgery, New York Presbyterian
Hospital-Weill Cornell Medical, New York, NY, USA
Blase N. Polite, MD, MPP Section of Hematology/Oncology, University
of Chicago Biological Science Division, Chicago, IL, USA
V. Prasad Poola, MD Southern Illinois University School of Medicine,
Springfield, IL, USA
Lisa S. Poritz The Milton S. Hershey Medical Center, Pennsylvania State
University College of Medicine, Hershey, PA, USA
Janice Rafferty, MD, FACS, FASCRS Division of Colon & Rectal Surgery,
UC Health, Cincinnati, OH, USA
Jan Rakinic, MD, FACS, FASCRS Southern Illinois University School of
Medicine, Springfield, IL, USA
Vikram Reddy, MD, PhD Department of Surgery, Yale University School
of Medicine, New Haven, CT, USA
Feza H. Remzi Department of Colorectal Surgery, Digestive Disease Institute,
Cleveland Clinic, Cleveland, OH, USA
Teresa C. Rice, MD University of Cincinnati Medical Center,
Cincinnati, OH, USA
Contributors xxi
Patricia L. Roberts, MD Division of Surgery, Lahey Hospital and Medical

Center, Burlington, MA, USA
Campbell S. Roxburgh Memorial Sloan Kettering Cancer Center, New York,
NY, USA
David T. Rubin University of Chicago Inflammatory Bowel Disease Center,
Chicago, IL, USA
Theodore J. Saclarides, MD Loyola University School of Medicine, Maywood,
IL, USA
Nicole M. Saur, MD Division of Colon and Rectal Surgery, Department of
Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia,
PA, USA
Anthony J. Senagore, MD, MBA Department of Surgery, UTMB- Galveston,
Galveston, TX, USA
Shafik M. Sidani Department of Surgery, Virginia Hospital Center, Arlington,
VA, USA
Clifford L. Simmang Chief Medical Officer and Vice President of Medical
Affairs, Baylor Scott and White Medical Center at Grapevine, Grapevine,
TX, USA
Marc A. Singer, MD, FACS, FASCRS Section of Colon and Rectal Surgery,
Rush University School of Medicine, Chicago, IL, USA
Nathan R. Smallwood Division of Colon and Rectal Surgery, Baylor University
Medical Center, Dallas, TX, USA
Eric A. Sparks, MD Department of Surgery, Baylor Scott & White Healthcare,
Scott & White Memorial Hospital, Temple, TX, USA
Scott R. Steele, MD Department of Colon and Rectal Surgery, Case Western
University, Cleveland, OH, USA
Randolph M. Steinhagen, MD Division of Colon and Rectal Surgery,
Department of Surgery, Icahn School of Medicine at Mount Sinai, New York,
NY, USA
Scott A. Strong, MD, FACS, FASCRS Chief, Gastrointestinal and Oncologic
Surgery, Surgical Director, Digestive Health Center, Northwestern Medicine James
R. Professor of Surgery, Northwestern University Feinberg School of Medicine,
Chicago, IL, USA
Larissa K. Temple Colorectal Service, Department of Surgery, Memorial Sloan
Kettering Cancer Center, New York, NY, USA
Konstantin Umanskiy Medical Center, University of Chicago, Chicago,
IL, USA
xxii Contributors
Avery S. Walker, MD Department of Surgery, Brian Allgood Army Community

Hospital, Yongsan, South Korea
Martin R. Weiser, MD Colorectal Service, Department of Surgery, Memorial
Sloan Kettering Cancer Center, New York, NY, USA
Mark L. Welton Department of Surgery, Stanford University School of Medicine,
Stanford, CA, USA
Steven D. Wexner, MD, PhD (Hon) Department of Colorectal Surgery,
Cleveland Clinic Florida, Weston, FL, USA
Richard L. Whelan, MD Mount Sinai School of Medicine, Mount Sinai West
Hospital, New York, NY, USA
Sean Wrenn, MD University of Vermont Medical Center, University of Vermont
College of Medicine, Burlington, VI, USA
Karen Zaghiyan, MD Colon and Rectal Surgery, Cedars-Sinai Medical Center,
Los Angeles, CA, USA
Chapter 1
Introduction
Konstantin Umanskiy
Where is the wisdom we have lost in knowledge? Where is the

knowledge we have lost in information?
T.S. Eliot 1934
Tell Me a Story. The Importance of an Anecdote
At the center of medical decision-making is always the patient; their story, their feel-
ings, their family support and their unique perception of the problem. At this intersec-
tion of medical art and science stands the surgeon who must combine the unique
aspects of the ancient art of healing with modern medical science to provide the treat-
ment most likely to create a good outcome. Instinctively we as surgeons tend to rely on
impressions from our clinical practice, experiences during surgical training, or maybe
what we have just heard at the morbidity and mortality conference this week. This
anecdotal decision making, while typically thought of as rudimentary and not “evi-
dence-based”, is in fact one of the most basic forms of evidence based medicine(EBM).
This method of medical practice has been known since antiquity where early EBM was
based on ancient historical or anecdotal accounts. Teaching during this time was mainly
authoritative and passed on with stories. By the seventeenth century, a renaissance era
of medical practice had ushered the earliest form of modern EBM. During this period,
written journals were kept and textbooks began to become more prominent.
Information Literacy. Learning the New Language
Fast forward to 1970–1990s, the era often called the transitional era of EBM. This
time period was characterized by the rise of biomedical informatics, driven by the
explosion of published information related to health care. At the same time came
K. Umanskiy
Medical Center, University of Chicago, Chicago, IL, USA
e-mail: [email protected]
© Springer International Publishing Switzerland 2017 1

N. Hyman, K. Umanskiy (eds.), Difficult Decisions in Colorectal Surgery,
Difficult Decisions in Surgery: An Evidence-Based Approach,
DOI 10.1007/978-3-319-40223-9_1
2 K. Umanskiy
the advent of the clinical trials and of clinical research, in general. An electronic
version of Index Medicus which would ultimately become MEDLINE was expand-
ing rapidly. An early version of what would become a World Wide Web was in
advanced phases of development. The stage was set for an entirely new relation-
ship between the world of medical practice, health care and the biomedical
literature.
In 1991 the term ‘evidence-based medicine’ was declared to be both ‘a new
approach to teaching the practice of medicine’ and ‘a new paradigm of medical
practice’. In 1992, the Journal of the American Medical Association proposed a
radical change in the hierarchy of knowledge in which clinical evidence, particu-
larly that stemming from randomized trials and meta-analyses, was placed above
the pathophysiological understanding of disease process and ‘clinical experi-
ence.’[1] This concept, while controversial, took the medical community by storm,
fueled by reports such as the one published by Antman et al. [2] that demonstrated
that thousands of patients with myocardial infarction had died unnecessarily as a
result of failure to adequately summarize the trial evidence on the efficacy of throm-
bolytic therapy.
With the advent of public access to the Internet via the World Wide Web in 1995,
the door had swung open to the proliferation of electronic biomedical resources. But
with the rapid explosion of medical information, came the necessity of equipping
the practitioners and teachers of medicine with resources to acquire ‘information
literacy’[3], a concept defined as an identification of the information needed and the
process of performing a search, evaluating the quality of the evidence and, finally,
integrating it with independent pre-existing information. This process that can be
described as ‘ask’, ‘acquire’, ‘appraise’ and ‘apply’ became the instructional model
for EBM [4].
Since the mid-1990’s medical journals have featured a number of well-designed
analyses and clinical practice guidelines put together by well-respected groups of
experts. The number of publications with the keyword ‘evidence-based medicine’
has risen dramatically from 1984 to 2015 (Fig. 1.1). While the emphasis on evidence-
based practice has been robust and quite persistent over the past two decades, the
evidence provided often conflicts with other evidence, may be overtly misleading or
even just plain wrong. One such conspicuous example was the recent excitement
about avoidance of mechanical bowel prep in colon surgery [5], only to later realize
that mechanical bowel prep with oral antibiotics as originally proposed by Nichols
and Condon decades ago is demonstrably superior [6].
Without a doubt evidence-based medicine provides surgeons with a rational
basis to support guidelines for treatment modalities and contributes to standardiza-
tion of care, which in many instances results in improved quality of care and better
patient outcomes. But with the guidelines may come an unwelcomed restrictiveness;
many surgeons are reluctant to alter their practice and may have very legitimate
concerns whether the generalized evidence really provides the best solution for the
individual patient. The interpretation of data as presented in medical literature may
require the reader to become ‘information literate’ to appraise the quality of the
evidence and its true applicability to the individual surgeon’s practice.
1 Introduction 3
14,000
12,000
10,000
Number of publications
8000
6000
4000
2000
0
20 2
03
04
05
06
07
20 8
09
10
20 1
12
20 3
14
15
84
85
19 6
19 7
88
19 9
19 0
91
19 2
19 3
94
95
19 6
97
19 8
99
20 0
01
0
1
8
8
8
9
9
9
0
19
19
19
19
20
20
20
20
20
20
20
20
20
20
20
19
19
19
19
Year of publication
Fig. 1.1 PubMed entries with keywords ‘evidence based medicine’
Introduction of new technology into colon and rectal surgical practice is result-
ing in a rapidly expanding technical armamentarium. Some surgeons self-described
as “early adaptors” are quick to jump on the bandwagon to embrace new and often
unproven technology, driven by a general desire to advance the field and push the
envelope. An unbiased and thoughtful review of data and careful reflection on the
ethical considerations based on the surgical dictum of “do no harm” should be liber-
ally exercised.
Bringing It Together
Initially, EBM focused primarily on determining the best evidence and applying
that evidence to the clinical situation at hand. This early approach lacked emphasis
on traditional aspects of clinical decision-making such as physiologic rationale and
individual clinical experience. Fortunately, with evolution of EBM came the realiza-
tion that research-based evidence alone may not be an adequate guide to action.
Instead, clinicians must combine their experience, the applicable scientific evidence
and the patient’s wishes and values before making a treatment recommendation.
Figure 1.2 depicts a model for evidence-based decisions, which emphasizes “clini-
cal expertise” as an overarching component in EBM decision-making. Clinical
4 K. Umanskiy
Fig. 1.2 Current model of

evidence-based clinical
decision making (Adapted Clinical state and
from: Haynes et al. [9]) circumstances
Clinical Expertise
Patient preferences Research evidence

and actions
expertise encompasses the patient’s clinical state and surrounding circumstances,

combining it with relevant research evidence, and the patient’s preferences. Getting
the diagnosis and prognosis right and knowing how to provide treatment demand
more skill now than ever before because the options are many and patient expecta-
tions are high. Surgeons in the current clinical environment must be abreast of not
only the scientific evidence; they must also acquire and hone skills needed to both
interpret the evidence and apply it appropriately in clinical settings. Finally, and
very importantly, the patients’ goals, values and wishes remain the cornerstone to
the best and informed decisions [7].
Why This Book?
How do we know that a parachute works? Well, one can say we don’t know.
Apparently there has never been a randomized, double blind, prospective, placebo-
controlled trial assessing the efficacy of the parachute [8].
Sometimes common sense is all that is needed, and medicine in this regard is no
exception. This book was conceived as an opportunity to hear the voice of a no-
nonsense, wise mentor, who can build on the available evidence, put it in p erspective
and provide practical advice to tough clinical problems. While not all encompass-
ing, this book has been designed to help surgeons with their decision-making on a
very practical level based on the best available evidence. We asked many of the most
‘information literate’ experts in the field of colon and rectal surgery to comb through
the evidence, evaluate and summarize it for our readers and provide their opinion
and recommendation based on the years of experience caring for patients with com-
1 Introduction 5
plex colon and rectal disorders. We are sincerely grateful to a wonderful group of
colleagues and friends, recognized experts in the field of colon and rectal surgery,
for their contributions to this book.
References
1. Evidence-Based Medicine Working Group. A new approach to teaching the practice of medi-
cine. JAMA. 1992;268(17):2420–5.
2. Antman EM, Lau J, Kupelnick B, Mosteller F, Chalmers TC. A comparison of results of meta-
analyses of randomized control trials and recommendations of clinical experts. Treatments for
myocardial infarction. JAMA. 1992;268(2):240–8.
3. Presidential Committee on Information Literacy. Final report. Chicago: Association of College
& Research Libraries; 1989.
4. Straus SE, Green ML, Bell DS, Badgett R, Davis D, Gerrity M, Ortiz E, Shaneyfelt TM,
Whelan C, Mangrulkar R. Evaluating the teaching of evidence based medicine: conceptual
framework. Society of General Internal Medicine Evidence-Based Medicine Task Force. BMJ.
2004;329(7473):1029–32.
5. Zmora O, Mahajna A, Bar-Zakai B, Hershko D, Shabtai M, Krausz MM, Ayalon A. Is mechani-
cal bowel preparation mandatory for left-sided colonic anastomosis? Results of a prospective
randomized trial. Tech Coloproctol. 2006;10(2):131–5.
6. Kiran RP, Murray AC, Chiuzan C, Estrada D, Forde K. Combined preoperative mechanical
bowel preparation with oral antibiotics significantly reduces surgical site infection, anasto-
motic leak, and ileus after colorectal surgery. Ann Surg. 2015;262(3):416–25.
7. Deber RB, Kraetschmer N, Irvine J. What role do patients wish to play in treatment decision
making? Arch Intern Med. 1996;156:1414–20.
8. Smith GC, Pell JP. Parachute use to prevent death and major trauma related to gravitational
challenge: systematic review of randomized controlled trials. BMJ. 2003;327(7429):1459–61.
9. Haynes RB, Devereaux PJ, Guyatt GH. Clinical expertise in the era of evidence-based medi-
cine and patient choice. ACP J Club. 2002;136(2):A11–4.
Chapter 2
Evaluating Evidence
W. Donald Buie
Introduction
Evidence can be defined in the broadest sense as “… any empirical observation,

whether systematically collected or not” [1]. Clinical evidence can include every-
thing from the unsystematic observations of the individual clinician, physiologic
experiments in animal models or the systematic observation of clinical events. Due
to this wide variety of sources, it is of varying quality and applicability. How confi-
dent are we in the stated results? How accurate are the estimates of effect? Can the
results be generalized to my patient? Evidence based decisions require not only the
identification of all relevant evidence for a specified outcome but a systematic eval-
uation of the evidence such that best available evidence is used to support good
clinical decisions.
Throughout this book, the quality of evidence and in turn the strength of the
recommendations that follow is based primarily on GRADE (Grading of
Recommendations Assessment, Development and Evaluation) [2]. GRADE is a
transparent, structured, reproducible system for reviewing and evaluating medical
evidence for any specified outcome. In its basic form, it can be used by a clinician
to help identify the best treatment course for a specific clinical situation, and in its
complete form by guideline developers to assess the literature on a broad topic to
produce clinical practice guidelines (CPGs) on important patient specific outcomes
[2]. This chapter will briefly outline the steps that are required to apply GRADE
when evaluating evidence for specific clinical decisions. It will summarize the pro-
cess of evaluating evidence by exploring stratification by study design, assessing
random error and bias, identifying methodological limitations and assessing
W.D. Buie, MD, MSc, FRCSC

Department of Surgery, University of Calgary, Calgary, AB, Canada

DOI 10.1007/978-3-319-40223-9_2
8 W.D. Buie
confidence in the measured effect. For a complete review of the GRADE system
clinicians are encouraged to read a series of articles from the British Medical Journal
[3–5] or a more recent series from the Journal of Clinical Epidemiology designed
for guideline developers [2, 6–13]. The ideas and concepts in this chapter are sum-
marized primarily from the latter series and the reader is encouraged to seek out
these references for a more in depth discussion.
Initial Evaluation
Evaluation of evidence begins with a well-constructed clinical question including a

specified population, a specific intervention, a comparator and specific outcomes, a
process often abbreviated as PICO [14] (Fig. 2.1). A poorly designed question nega-
tively affects the appropriateness of the collected evidence and in turn the evalua-
tion of that evidence. With the ever increasing volume of evidence present in the
medical literature and the constant turnover of best evidence, it is difficult for the
clinician with limited time and resources to keep up to date. This has fuelled an
explosion in structured reviews and CPGs that aim to summarize the literature in a
structured and transparent fashion. Not all subjects are covered with a CPG and thus
the clinician must be able to formulate an appropriate search and evaluate the litera-
ture independently.
Once a literature review is complete, each individual study must be vetted for its
relevance to the topic. Does it address the outcomes of interest? Does it apply to the
particular practice setting? Does it apply to the particular patient population? Not all
studies will address all outcomes. However, the evidence for all important patient
outcomes in a specific clinical situation must be evaluated. For example, in Stage IV
rectal cancer when considering a palliative resection versus long-term chemotherapy,
evidence for each management strategy must be evaluated for both quality and quan-
tity of life. In addition the risk of a poor outcome as viewed by the patient due to either
surgical or medical complications must be considered. For many questions a struc-
tured review or CPG exists that covers most of the outcomes of interest but a primary
literature search may be required to supplement evidence for specific outcomes.
Stratifying Evidence
Once the evidence is collected, it is initially stratified by study methodology. Well

designed structured reviews and meta-analysis based on well-designed RCTs are
the highest order of evidence, followed by well designed RCTs themselves, lower
quality RCT studies with methodological limitations and finally observational stud-
ies (cohort and case control). Within the GRADE system, expert opinion is not
viewed as evidence in and of itself. In other words, while an expert is required to
interpret evidence, expert opinion may or may not be based on best evidence.
2 Evaluating Evidence 9
Health Care Question (PICO)

Systematic review
Studies S1 S2 S3 S4 S5
Outcomes OC1 OC2 OC3 OC4

Important Critical
outcomes outcomes
Generate an estimate of effect for each outcome
Rate the quality of evidence for each outcome, across studies

RCTs start with a high rating, observational studies with a low rating
Rating is modified downward: Rating is modified upward:
- Study limitations - Large magnitude of effect
- Imprecision - Dose response
- Inconsistency of results - Confounders likely minimize
- Indirectness of evidence the effect
- Publication bias likely
Final rating of quality for each outcome: high, moderate, low, or very low
Rate overall quality of evidence

(lowest quality among critical outcomes)
Decide on the direction (for/against) and grade strength (strong/weak*)

of the recommendation considering:
Quality of the evidence
Balance of desirable/undesirable outcomes
Values and sp.
Decide if any revision of direction or strength is necessary considering: Resource use
Fig. 2.1 The GRADE process for developing recommendations (Adapted from Guyatt et al. [2])
Random Error and Systematic Error (Bias)
All studies are subject to error, which may to a greater or lesser extent affect the
results of a study and our confidence in the stated results. Error can be classified into
two major categories: random error and systematic error or bias. Random error is the
variation in outcomes due to chance alone. Studies are performed on sample popula-
tions from the population at large, thus the results of each study are estimates of the
actual effect of an experimental intervention on the overall population. If a study is
performed on 20 different sample populations replicating strict methodology each
time, the final results of each trial will be closely approximated but will vary due to
chance, much like a coin toss performed multiple times will not always add up to
10 W.D. Buie
exactly 50 % heads and 50 % tails. Random error is by definition variable and can
occur in either direction, (you can toss 7 heads or 6 tails in a row), resulting in a posi-
tive or negative effect on the estimate of an outcome of interest. It can be minimized
through the use of large sample sizes either in individual studies or by combining
similar smaller studies in a meta-analysis. A well designed prospective study should
have a sample size calculation for a specific outcome as part of its methodology.
Systematic error or bias results in a systematic or fixed effect on a study. This
type of error is not affected by sample size as it is related to study methodology.
Virtually no study is devoid of all bias. However, when evaluating a study one must
try to determine whether the effect from systematic error or bias is large enough to
significantly alter the observed effect of an experimental intervention.
Methodological Limitations (Bias)
There are four levels of evidence in the GRADE system; high quality, moderate
quality, low quality and very low quality (Table 2.1) [7]. Evidence from RCTs starts
out as high quality evidence but may be down graded to moderate or even low qual-
ity if bias or methodological issues are identified. Similarly, although evidence from
observational trials is generally classified as low or very low quality, it may be
upgraded under certain circumstances (Fig. 2.1).
Bias in randomized trials can occur in three parts of a study; differences observed
at the start of a study, differences that arise as a study progresses and differences at
the completion of a study [16] (Table 2.2). Blinding should be present at all levels
of a trial starting with allocation and randomization, and including the patient, the
care giver, the assessors and the data analysts. When absent, the results usually favor
an overestimation of effect. Differences in treatment or exposure to confounding
treatments in the experimental arm, incomplete follow up or loss to follow up and
failure to adhere to the intention to treat principle in superiority trials are also asso-
ciated with over estimation of effect. Loss to follow up takes on greater importance
when the number of events in either the experimental or control group is small rela-
tive to the percentage lost to follow up or if the loss to follow up is imbalanced
between the two groups.
Studies that investigate treatment with observational design are inherently sub-
ject to bias. While the investigator does not have any control over these biases, the
clinician should look for statistical adjustments or the use of hard endpoints by the
investigator. The clinician must evaluate whether the observed biases could poten-
tially account for an observed treatment effect [16].
Although study design is important, GRADE applies to each specific outcome
within a study. Bias may affect specific outcomes within the same study to a greater
or lesser degree increasing or reducing our confidence in each observed outcome.
For example lack of blinding of assessors may not affect the assessment of a post-
operative outcome such as death but may be responsible for bias in the assessment
of a wound infection.
Table 2.1 GRADE: levels of evidence and definitions

Category Definition Examples
High We are very confident that the true effect Randomized trials without serious
lies close to that of the estimate of the limitations
effect Well performed observational
studies with very large effects
Moderate We are moderately confident in the effect Randomized trials with serious
estimate: the true effect is likely to be limitations
close to the estimate of the effect, but there Well-performed observational
is a possibility that it is substantially studies yielding large effects
different
Low Our confidence in the effect estimated is Randomized trials with very
limited: the true effect may be substantially serious limitations
different from the estimate of the effect Observational studies without
special strengths or important
limitations
Very low We have very little confidence in the effect Randomized trials with very
estimate: the true effect is likely to be serious limitations and inconsistent
substantially different from the estimated of results
effect Observational studies with serious
limitations
Unsystematic clinical observations
(case series or case reports)
Adapted from Balshem et al. [7]
Table 2.2 Study limitations in randomized trials

1. Lack of allocation concealment
Those enrolling patients are aware of the group to which the next enrolled patient will be
allocated (e.g., “pseudo” randomized trials with allocation by day of the week, birth date,
chart number etc.)
2. Lack of blinding
Patient, care givers, those recording outcomes, those adjudicating outcomes or data analysts
are aware of which arm patients are allocated
3. Incomplete accounting of patients and outcome events
Loss to follow-up and failure to adhere to the intention-to-treat principle in superiority
trials; or in noninferiority trials, loss to follow-up and failure to conduct both analysis
considering only those who adhered to treatment, and all patients for whom outcome data
are available
4. Selective outcome reporting bias
Incomplete or absent reporting of some outcomes and not others on the basis of results
5. Other limitations
Stopping early for benefit
Use of unvalidated outcome measures (e.g. patient reported outcomes)
Carryover effects in crossover trial
Recruitment bias in cluster randomized trials
Adapted from Balshem et al. [7]
12 W.D. Buie
Confidence in Effect
Downgrading Evidence
A study may be well designed with minimal bias yet we may lack confidence in the
degree to which the experimental effect is demonstrated. In other words, is the treat-
ment really as good as the results suggest? In GRADE there are four additional
qualities that must be evaluated for each specific outcome which when present will
downgrade the evidence from a RCT either one or two categories depending on how
serious the shortcomings are (Fig. 2.2)
Imprecision
Imprecision refers to the accuracy of the point estimation of effect. It is most easily
identified by examining the 95 % confidence interval (CI) around the difference in
effect; the larger the interval the less precise the estimate [10]. Examine the absolute
and not the relative difference as the latter will inflate any observed effect. Use a
theoretic test: if the true value was equal to the upper or lower 95 % CI and if this
result would change the course of action, then consider the results imprecise and
downgrade the evidence [10]. Be suspicious when the effect is large, yet both the
sample size and the number of events are small even if the CIs are narrow; in other
words, relatively few patients with relatively few incidents should call a large mag-
nitude of effect into question.
Inconsistency
When the results of several well conducted RCT vary widely with respect to a spe-
cific outcome the evidence is inconsistent [11]. An attempt should be made to
A summary of GRADE’s approach to rating quality of evidence

Initial quality of a body of
Study design evidence Lower if Higher if Quality of a body of evidence
Randomized High Risk of Bias Large effect High (four plus: )
trials –1 Serious +1 Large
–2 Very serious +2 Very large
Inconsistency Dose response Moderate (three plus: )
–1 Serious +1 Evidence
Observational Low –2 Very serious of a gradient
studies Indirectness All plausible residual Low (two plus: )
–1 Serious confounding
–2 Very serious +1 Would reduce a
Imprecision demonstrated effect Very low (one plus: )
–1 Serious +1 Would suggest a spurious
–2 Very serious effect if no effect was
Publication bias observed
–1 Likely
–2 Very likely
Fig. 2.2 A summary of GRADE’s approach to rating quality of evidence (Adapted from Balshem
et al. [7])
explain the variability between studies based on differences in populations, inter-

ventions, outcome measurement or other methodologic issues. Subgroup and sensi-
tivity analysis may be necessary to illuminate these differences which may or may
not downgrade the evidence based on the perceived effect on the outcome of
interest.
Indirectness
There are two types of indirectness recognized within the GRADE system [12].
The first is when there is evidence comparing intervention A with intervention B
and intervention B with C but no direct evidence from a comparison of A with
C. In this case an inference can be made but the level of evidence for that outcome
is marked down one level. This type of indirectness is more common in pharmaco-
logic trials. Evidence may also be classified as indirect if there are differences
between the best available evidence with respect to the populations under study,
specific interventions, co-interventions or outcome measurements and the PICO
(population, intervention, comparator and outcome) of the initial clinical
question.
Publication Bias
Negative studies are less likely to be published resulting in publication bias [9].
These studies also suffer from lag time bias being published at a later date. Negative
studies are often relegated to lower impact journals or as a thesis or abstract in an
obscure publication such as proceedings of a meeting and in languages other than
English. Omission of negative studies may lead to an overestimation of treatment
effect.
Another form of publication bias is selective outcome reporting [9]. This should
be suspected if some of the expected outcomes for a specific clinical problem are
suspiciously absent. Selective outcome reporting may also occur when composite
or derived outcomes are reported as significant and primary outcomes are either not
significant or not discussed. It also causes an overestimation of the effects of an
intervention.
Upgrading Evidence
Occasionally outcomes from descriptive or observational studies which are nor-

mally classified as low level evidence may be upgraded one level. GRADE has
specified three situations whereby observational evidence may be upgraded usually
from very low to low level evidence (Fig. 2.2).
14 W.D. Buie
Large Magnitude of Effect
Occasionally an observational study demonstrates a very large treatment effect [13].

GRADE defines a large effect as a relative risk (RR) of >2.0 and <5.0 based on
consistent evidence from at least two studies with no significant confounders. A
very large magnitude of effect is defined as a relative risk of >5.0 and <0.2. The
effect should be based on direct evidence with no other perceived forms of bias. An
example of this would be the original case series published on mesorectal excision
where the reduction in local recurrence was far greater than either accepted levels
in the literature following standard surgery at the time or the improvements obtained
by adjuvant therapy [15].
Plausible Confounders
In this situation, a confounder effect would be expected to act in opposition to the

observed effect [13]. For example, all plausible confounders would reduce the dem-
onstrated effect or increase it if no effect was observed. Thus the presence of the
confounder increases the likelihood that the observed effect is real and therefore the
evidence may be upgraded.
Dose Response Gradient
When increased exposure to an intervention is associated with a larger treatment

effect or greater harm, this may be considered a dose response gradient [13]. In this
situation, the evidence may be upgraded as we have more confidence in the observed
effect. This is not likely to occur in surgical studies as the treatment effect is usually
an all or none phenomena.
Overall Quality Rating
Once the evidence for each outcome has been identified, stratified and evaluated for
the presence of bias, an estimation of the confidence in the observed effect is deter-
mined based on the qualities in the previous section. This information is best sum-
marized in an evidence profile table (EP) [2]. Next, a quality rating of the best
available evidence is assigned for each separate outcome to one of the four catego-
ries (Table 2.1). This becomes the overall estimate of the confidence in the expressed
treatment effect for a specific outcome [16]. Prior to a recommendation, an overall
quality rating for all the evidence for all outcomes is determined. When there are
different levels of quality for each outcome, the GRADE system by convention
bases the overall quality rating on the lowest quality of available evidence for the
specified outcomes (Fig. 2.2).
The overall quality rating is the basis for the strength of any recommendations
that follows (Fig. 2.1). Strength of recommendation is defined as “the extent to
which we can be … confident that desirable consequences of an intervention out-
weigh undesirable consequences” [16]. GRADE classifies recommendations into
two categories based on how strongly the evidence supports the recommendation. A
strong recommendation indicates that a specific course of action would be appropri-
ate for most patients in most situations. A weak recommendation on the other hand
indicates that although the recommended course of action would be appropriate for
most patients in this situation, for many patients it would not [17]. Occasionally
evidence for a specific outcome is so inadequate that no evidence based recommen-
dation can be made.
Conclusion
Clinical decisions must be based on best evidence. High quality structured reviews
or CPGs with transparent evaluation of quality of the evidence using a system such
as GRADE are invaluable. While the clinician may not have the time or training to
perform a structured review, they must be able to evaluate studies for quality when
information on a desired outcome is not part of a CPG.
While evidence is essential for good clinical decision-making, it cannot be
applied in isolation. A clinician must consider the risks versus benefits and the bur-
dens and costs of each management strategy. In addition, the goals, values and
expectations of the patient as well as the experience of the clinician in similar situ-
ations must be considered. It is the responsibility of the clinician to assess and
interpret the evidence as it applies to each individual patient’s situation and guide
the patient in the quest for optimal, safe, patient centered care.
References
1. Guyatt G, Drummond R, Meade MO, Cook DJ, Glossary. In: Users’ Guides to the Medical
Literature: a manual for evidence based clinical practice. 3rd ed. New York: McGraw-Hill
Professional; 2015. p. 655.
2. Guyatt G, Oxman AD, Akl EA, et al. GRADE guidelines: 1. Introduction – GRADE evidence
profiles and summary of findings tables. J Clin Epidemiol. 2011;64:383–94.
3. Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating quality of
evidence and strength of recommendations. BMJ. 2008;336:924–6.
4. Guyatt GH, Oxman AD, Kunz R, et al. What is “quality of evidence” and why is it important
to clinicians? BMJ. 2008;336:995–8.
16 W.D. Buie
5. Guyatt GH, Oxman AD, Kunz R, et al. Going from evidence to recommendations. BMJ.
2008;336:1049–51.
6. Guyatt GH, Oxman AD, Kunz R, Atkins D, Brozek J, et al. GRADE guidelines: 2. Framing
the question and deciding on important outcomes. J Clin Epidemiol. 2011;64:395–400.
7. Balshem H, Helfand M, Schunemann HJ, et al. GRADE guidelines: 3. Rating the quality of
evidence. J Clin Epidemiol. 2011;64:401–6.
8. Guyatt G, Oxman AD, Kunz R, et al. GRADE guidelines: 4. Rating the quality of evidence
study limitations (risk of bias). J Clin Epidemiol. 2011;64:407–15.
9. Guyatt GH, Oxman AD, Montori V, et al. GRADE guidelines: 5. Rating the quality of
evidence-publication bias. J Clin Epidemiol. 2011;64:1277–82.
10. Guyatt GH, Oxman AD, Kunz R, Broxzek J, et al. GRADE guidelines: 6. Rating the quality of
evidence – imprecision. J Clin Epidemiol. 2011;64:1283–93.
11. Guyatt GH, Oxman AD, Kunz R, et al. GRADE guidelines: 7. Rating the quality of evidence-
inconsistancy. J Clin Epidemiol. 2011;64:1294–302.
12. Guyatt GH, Oxman AD, Kunz R, et al. GRADE guidelines: 8. Rating the quality of evidence-
indirectness. J Clin Epidemiol. 2011;64:1303–10.
13. Guyatt GH, Oxman AD, Sultan S, et al. GRADE guidelines: 9. Rating up the quality of evi-
dence. J Clin Epidemiol. 2011;64:1211–6.
14. Guyatt G, Meade MO, Agoritsas T, et al. What is the question. In: Guyatt G, Drummond R,
Meade MO, Cook DJ, editors. Users’ guides to the medical literature: a manual for evidence
based clinical practice. 3rd ed. New York: McGraw-Hill Professional; 2015. p. 22.
15. MacFarlane JK, Heald RJ. Mesorectal excision for rectal cancer. Lancet. 1993;341:457–60.
16. Brozek JL, Aki EA, Alonson-Coello P, et al. Grading quality of evidence and strength of rec-
ommendations in clinical practice guidelines: part 1 of 3 an overview of the GRADE approach
and grading quality of evidence about interventions. Allergy. 2009;64:669–77.
17. Andrews JC, Schunemann HJ, Oxman AD, et al. GRADE Guidelines: 15. Going from evi-
dence to recommendations-determinant of a recommendations direction and strength. J Clin
Epidemiol. 2013;66:726–35.
Part I
IBD
Chapter 3
IBD: Management of Symptomatic Anal
Fistulas in Patients with Crohn’s Disease
Lisa S. Poritz
Introduction
Approximately 30 % of patients with Crohn’s disease (CD) will have or develop
perianal fistulas (PF) during the course of their disease. Not only do symptomatic
PF cause pain and drainage, they may also lead to sepsis, incontinence, restriction
of activities, and decreased quality of life. Ultimately, some patients may end up
with permanent fecal diversion either due to progression of disease or in some cases
owing to complications from aggressive treatment.
The optimal treatment of these fistulas is controversial. The purpose of this chap-
ter is to compare the results of medical and surgical treatment for symptomatic PF
in CD patients. While there are numerous studies looking at the results of either
medical or surgical treatment, little high quality comparative data exists and evi-
dence based comparisons are challenging at best.
Not all fistulas in patients with CD are the same and both fistula characteristics
and patient factors are integral in determining the best therapy. It is important to
know whether there is active mucosal disease in the rectum, whether or not the
patient is concurrently receiving medical therapy for luminal disease, the history of
medication use and any adverse reactions, previous surgical treatment, and level of
continence.
For the purposes of this chapter we will divide patients into three categories and
assume that patients are not on medications for luminal CD. The literature and rec-
ommendations will be discussed as they pertain to the following patient scenarios:
L.S. Poritz
The Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine,
Hershey, PA, USA

DOI 10.1007/978-3-319-40223-9_3
20 L.S. Poritz
Scenario 1: The patient with a simple fistula and no macroscopic rectal disease
Scenario 2: The patient with either a simple or a complex fistula and macroscopic
rectal disease
Scenario 3: The patient with a complex fistula and no macroscopic rectal disease
Search Strategy
A systematic review of the literature using PubMed was performed for the period:
1995–2015. Search terms included: CD, PF, fistula plug, ligation of internal fistula
tract (LIFT) procedure, and mucosal advancement flap. Articles were limited to
peer reviewed reports in English. Additional studies were identified from the refer-
ences of the initial articles retrieved as appropriate.
The studies discussed will be primarily randomized controlled trials and large
observational studies. In the case where neither exists for a given treatment modal-
ity, the best available data will be discussed. The quality of evidence and recom-
mendations were made according to modified GRADE system (Tables 3.1 and 3.2).
Results
Patients who present with fistulizing perianal CD typically require examination

under anesthesia (EUA), assessment of the rectal mucosa for disease activity, drain-
age of any abscesses and placement of setons as the initial step. The primary pur-
pose of seton placement is control of anorectal sepsis; setons allow for continued
drainage from the fistula tract and usually prevent abscess formation. Antibiotics
are often prescribed simultaneously (primarily ciprofloxacin or metronidazole) until
the perianal sepsis has resolved. Further therapy depends on the disease activity of
the rectal mucosa and complexity of the fistula.
cenario 1: The Patient with a Simple Fistula and No

S
Macroscopic Rectal Disease
Patients with a simple superficial fistulas and no macroscopic rectal disease can
often be treated by surgery alone without the need for medical therapy beyond ini-
tial antibiotics. If the fistula does not traverse any sphincter muscle, these patients
Table 3.1 PICO table

Patient population Intervention Comparator Outcomes studied
Crohn’s patients with symptomatic anal Surgery Medical Therapy Remission rate
fistulas Cure rate
Adverse event
Table 3.2 Quality of evidence
Quality of
Study Patients Treatment Comparator Response rate Remission rate Type of study evidence
van Koperen 61 Fistulotomy/Seton/or None NA 44–82 % Retrospective Low
et al. [2] advancement flap
Pearson et al. 9 RCT AZA or 6MP Placebo 54 %: AZA or NA Meta-analysis Moderate
[6] 6MP
21 %: placebo
Present et al. 94 Infliximab Placebo IFX: 62 % IFX: 46 % RCT Moderate
[7] Placebo: 26 % Placebo: 13 %
Sands et al. 195 Infliximab Placebo IFX: 46 % NA RCT Moderate
(ACCENT II) Placebo: 23 %
[8]
Dewint et al. 76 ADA and Cipro ADA and Cipro: 71 % Cipro: 65 % RCT Moderate
(ADAFI) [13] placebo Placebo: 47 % Placebo: 33 %
Grimaud et al. 77 Fibrin glue Observation NA 38 %: fibrin glue RCT Moderate
[15] 16 %: observation
Makowiec 32 Endorectal advancement flap None NA 50 % (initial primary Prospective Low
et al. [18] healing 89 %)
Hyman [19] 14 Endorectal advancement flap None NA 50 % (initial rate 71 %) Prospective Low
Gingold et al. 15 LIFT None NA 60 % at 2 months Prospective Low
[20]
Molendijk 232 Surgical therapy Medical Therapy Surgery: 97 % Surgery: 91.7 % Retrospective Low
et al. [23] Medicine: Medicine: 64.3 %
72.2 % Both: 86.6 %
Both: 93.2 %
Gaertner et al. 226 IFX and surgery Surgery NA 60 %: surgery Retrospective Low
3 IBD: Management of Symptomatic Anal Fistulas in Patients with Crohn’s Disease
[24] 59 %: surgery and IFX

RCT randomized controlled trial, AZA Azathioprine, 6MP 6-mercaptopurine, IFX Infliximab, LIFT Ligation internal fistula tract, ADA Adalimumab
21
22 L.S. Poritz
are good candidates for fistulotomy. For patients in whom the fistula traverses the
sphincter muscle, fistulotomy may still be appropriate if the amount of muscle is
small and the continence is not already compromised. Healing rates of up to 100 %
have been reported [1–3]. The risk associated with primary fistulotomy is poor
wound healing, recurrence and incontinence [2]. For patients in whom fistulotomy
is not appropriate, a seton can be considered the primary treatment and left for long
term drainage [4]. In some patients. the setons can be removed after the perianal
sepsis resolves and the fistula tracts will close [1]. Indeed, a healing rate of up to
25 % has been found in the placebo groups in the medical trials discussed below. If
the fistula recurs, the patients should be then be treated as if they have a complex
fistula (scenario 3).
cenario 2: The Patient with Either a Simple or a Complex

S
Fistula and Macroscopic Rectal Disease
The presence of active disease in the rectum will significantly compromise the suc-
cess rate of surgical intervention. After drainage of sepsis and placement of a
seton(s), these patients should be evaluated for medical therapy to try and eradicate
the inflammation in the rectum. In some cases, medical therapy may also cure the
fistula. Placement of a draining seton prior to inititation of medical treatment has
been shown to improve the results with anti-TNF therapy [5]. Below is a brief sum-
mary of the major classes of drugs used to treat perianal CD.
Antibiotics are useful to help control perianal sepsis and may also decrease pain,
but there are no randomized clinical trials (RCT) that show that antibiotics alone can
result in fistula closure. Uncontrolled studies show a benefit with the use of metro-
nidazole or ciprofloxacin that is quickly lost on withdrawal of the drug.
As with antibiotics, there are no RCTs that support the use of azathioprine or its
derivatives as single therapy for the treatment of PF in patients with CD. Pearson
et al. performed a meta-analysis of RCTs using these drugs and in the subset of
patients with perianal disease, found a 54 % response with the drugs versus 21 %
with placebo [6]. However, these drugs are slow in onset and are rarely used as first
line mono drug therapy for fistulizing perianal disease.
The first randomized placebo controlled trial using anti-TNF therapy in fistuliz-
ing CD was performed by Present et al. in 1999. They studied 94 patients and com-
pared a 3 dose induction regimen with either 5 or 10 mg/kg of infliximab to placebo.
They found a significantly higher number of patients treated with infliximab had a
response and or achieved remission [7]. In this study there was no maintenance
therapy and the duration of fistula closure was about 3 months. Subsequently, a
maintenance study (ACCENT II) was performed taking patients who responded to
induction with infliximab and randomizing them to maintenance every 8 weeks with
infliximab or placebo. The infliximab maintenance group had a longer time until
loss of response as compared to the placebo group [8].
3 IBD: Management of Symptomatic Anal Fistulas in Patients with Crohn’s Disease 23
Initial RCTs with adalimumab included a subgroup analysis for patients with
fistulizing disease. In CLASSIC-1 and GAIN there was no benefit to adalimumab
over placebo [9, 10]. However, in CHARM there was a significant benefit to the use
of adalimumab [11].
Results in studies combining antibiotics and anti-TNF agents have been mixed.
West et al. combined infliximab with either ciprofloxacin or placebo, and observed
a nonsignificant trend toward a better response with concomitant antibiotics [12].
Dewint et al. performed a RCT adding either placebo or ciprofloxacin to adalim-
umab and found a significant increase in response and remission with combined
therapy. However, the added benefit of the antibiotic was lost when it was discontin-
ued [13].
The anti-TNF drugs have convincingly been shown to reduce fistula drainage
and induce remission, but not without high cost and risks including infections, infu-
sion reactions and malignancy. Even when fistula tracts are healed with biologic
therapy, numerous studies have demonstrated residual tracts by ultrasound suggest-
ing that the track may not be truly healed [14].
If the patient has a good response to medical therapy, drainage from the fistula
will decrease and the setons will become more snug in the fistula tract. At that point
they should be removed so as not to prevent complete healing. If the fistulas persist
but the rectal mucosal disease resolves with medical treatment, then further surgical
therapy may be considered. Simple fistulas can now be treated with fistulotomy as
discussed above. For complex fistulas the most commonly utilized options include
fibrin glue, fistula plug, endorectal advancement flap, and LIFT.
Fibrin glue has been used with inconsistent results in both patients with and
without CD. Grimaud et al. performed a RCT comparing fibrin glue to observation
and found a significantly higher response rate at 8 weeks (38 % vs. 16 %) [15].
A systematic review of the anal fistula plug was performed by O’Riordan et al.
Of the 530 patients within the studies reviewed, 42 had CD. The rate of healing in
this population was 54.8 % [16]. However, the authors felt that the population was
too small and heterogeneous to be adequately evaluated.
Most studies looking at endorectal advancement flap for PF do not specify the
disease etiology and segregating out the results for patients with CD can be difficult.
A systematic review of all endorectal advancement flaps (CD and non CD) in 2010
identified only 91 CD patients treated by flap repair [17]. The weighted success rate
was 64 % (range 33.3–92.9). Some of the best results were obtained by Makowiec
et al. who had an initial 89 % success rate with a 33 % recurrence rate, however, half
of the patients had a diverting stoma, and Hyman who had an initial 71 % healing
rate with a 50 % long term healing rate [18, 19].
Gingold et al. performed a prospective evaluation of the LIFT procedure in 15
patients with CD related PF. They had a 60 % rate of healing of both the external
opening and the surgical site at 2 months [20]. Newer surgical therapies such as
injection of stem cells into the fistula tract may hold promise, but there is not enough
data to warrant conclusions at this time.
For patients with severe complicated PF disease often coupled with inconti-
nence, temporary fecal diversion is often a necessary adjunct to medical and sur-
24 L.S. Poritz
gical therapy. However, most patients who undergo temporary diversion ultimately
end up with permanent diversion. In a meta-analysis of 16 studies reporting tem-
porary fecal diversion in patients with refractory perianal CD, Singh et al. found
that only 16.6 % of patients were able to have their intestinal continuity restored
long term. [21] Ultimately, some patients with PF and CD end up with a perma-
nent stoma, with or without proctectomy. Mueller et al. reported their long term
follow-up on 102 consecutive patients with complicated perianal CD. They had a
31 % permanent diversion rate; on multivariate analysis, the significant risk
factors were complex PF, fecal incontinence, temporary diversion and rectal
resection [22].
cenario 3: The Patient with a Complex Fistula and No

S
Macroscopic Rectal Disease
This group of patients is often the most difficult to evaluate because there are so
many options. In the absence of rectal mucosal disease, medical therapy does not
have to be instituted before surgical intervention and the choice between primary
medical and surgical options is most pertinent. Unlike patients with a simple fistula,
these patients should not be treated with fistulotomy as there is a significant risk of
incontinence; however, the other surgical options discussed above are all usually
applicable.
Medical therapy is a viable first option with success rates as discussed previ-
ously. However, treatment with anti-TNF agents require maintenance therapy for
persistent remission. With longer exposure to these agents, the risk of untoward
effects such as infusion reactions, opportunistic infections and cancer increase.
Choosing between medical therapy and surgical therapy in these patients can
be difficult. In an attempt to compare medical and surgical therapy for PF in CD,
Molendijk retrospectively evaluated 232 patients who had presented to their unit
over a 20 year period [23]. They found that those patients who received medical
therapy had a 72.2 % response rate and a 64.3 % rate of remission. Patients who
had surgical therapy alone had a 97 % response rate with 91.7 % achieving remis-
sion. Patients who had combined therapy had a 93.2 % response and 86.6 %
remission rate respectively Follow-up showed that in patients who achieved
remission, the recurrence rate in the medical group was 15.6 %, surgery only
21.9 %, and combined group was 64.8 %. This is a retrospective study so the
patients were not randomly assigned to the treatment groups and selection bias
undoubtedly existed. Regardless, the efficacy of surgery in properly selected
patients is clearly evident; however, a high recurrence rate is observed with all
therapies.
Looking specifically at anti-TNF therapy, Gaertner et al. retrospectively exam-
ined 226 patients with CD and PF to evaluate the impact of infliximab on surgical
results [24]. They reported a 60 % healing rate in surgical patients who received
infliximab versus 59 % in patients who had surgery alone. While this was also a
retrospective study with potential selection bias, the success rate of surgery alone
was equal to surgery plus anti-TNF therapy and similar to the success rate of medi-
cal therapy reported in other studies. Overall, anti-TNF therapy had a 46–65 %
response/remission rate whereas surgery was associated with a 38–82 % remission
rate. Based on this data it would be appropriate to treat patients with PF who do not
have mucosal rectal disease with surgical intervention initially and then consider
medical therapy if surgery fails to cure the fistula.
Recommendations Based on the Data
Scenario 1: The patient with a simple fistula and no macroscopic rectal disease: No
specific recommendation can be made based on the low quality of the data
Scenario 2: The patient with either a simple or a complex fistula and macroscopic
rectal disease: Examination under anesthesia, abscess drainage, seton placement
followed by biologic therapy. If the fistula persists but the mucosal disease resolves,
further surgical therapy should be considered (Strong recommendation).
Scenario 3: The patient with a complex fistula and no macroscopic rectal disease:
Surgical therapy (weak/conditional recommendation)
Medical therapy (weak/conditional recommendation)
A Personal View of the Data
I recommend patients undergo initial EUA with abscess drainage and assessment of
rectal disease. The situation is then typically triaged into one of the categories
discussed above. Patients without rectal disease are initially treated surgically with-
out biologic therapy as this accomplishes 3 things: it avoids the adverse events
associated with biologic therapy, it avoids committing the patient to long term medi-
cal therapy, and it “saves” biologic therapy for a later time when the patient may
need it.
1. Simple fistulas without rectal disease:
At the time of EUA, I consider fistulotomy if the patient is fully continent and the
fistula does not involve a large amount of muscle or soft tissue. If these require-
ments are not met, I treat the patients as if they have complex fistulas without
rectal disease.
2. Complex fistulas without rectal disease:
At the time of EUA, these patients undergo seton placement and a course of
antibiotics (usually Cipro or Flagyl) until the sepsis has resolved. After 1 month,
if the sepsis is resolved, definitive surgical therapy is performed.
26 L.S. Poritz
(a) Patients with imperfect continence or anal stenosis prohibiting advancement

flap: These patients are often offered fibrin glue or fistula plug as the first line
option. Although these modalities have lower cure rates, they also have little
risk of incontinence and do not require the exposure necessary to perform an
advancement flap. For patients who fail this therapy, I recommend a trial of
biologic therapy (see #3)
(b) For patients with preserved continence and no rectal stricture, I offer (but do
not recommend) fibrin glue or a fistula plug. Rather, I recommend advance-
ment flap for these patients. If the fistula recurs after surgery, I recommend a
trial of biologic therapy (see #3). If the patient cannot have biologic therapy
(no response in the past, antibodies, severe adverse reaction) I would attempt
a repeat advancement flap after several months if the fistula persists.
3. Simple and complex fistulas with rectal disease:
At the time of EUA, these patients also undergo seton placement and a course of
antibiotics (usually Cipro or Flagyl) until the sepsis has resolved. Simultaneously,
the patients are referred for biologic therapy. Once the patient is on biologic therapy,
I reassess the perianal disease and if the fistula tracts are healing, which can often
be determined by how easily the setons move in the tracts, I remove the setons. This
can be during induction therapy or after maintenance therapy has started.
(a) If the fistula closes, medical therapy is continued at direction of the

gastroenterologist.
(b) If the fistula remains symptomatic despite medical therapy, I repeat the EUA,
reassess for any undrained abscesses, unidentified new fistula tracts and
reassess the rectal disease activity.
(i) If rectal disease persists, I would ask the gastroenterologist to reassess
the patient and consider adding an agent, switching agents, or increasing
dosage.
(ii) If rectal disease has resolved, I then treat the patient as a complex fistula
without rectal disease (Sect. 2) but maintain them on medical therapy
throughout surgical treatment.
Additional comments:
1. Long term setons: When there are no good options for closing the fistulas, leav-
ing setons in long term can control sepsis and substantially improve the quality
of life for these patients.
2. Diversion:
(a) Some patients present with multiple fistulas and abscesses. Fecal diversion may
need to be one of the first steps in treatment to control the sepsis, pain, drainage,
and often accompanying incontinence while medical therapy is being initiated.
(b) Despite our best medical and surgical therapy, some patients will require
proctectomy.
References
1. Sandborn WJ, Fazio VW, Feagan BG, Hanauer SB. AGA technical review on perianal Crohn’s
disease. Gastroenterology. 2003;125:1508–30.
2. vanKoperen PJ, Safiruddin F, Bemelman WA, Slores JFM. Outcome of surgical treatment for
fistula in ano in Crohn’s disease. Br J Surg. 2009;96:675–9.
3. Sangwan YP, Schoetz DJ, Murray JJ, Roberts PL, Coller JA. Perianal Crohn’s disease results
of local surgical treatment. Dis Colon Rectum. 1996;39:529–35.
4. Thorton M, Solomon MJ. Long-term indwelling seton for complex anal fistulas in Crohn’s
disease. Dis Colon Rectum. 2005;48:459–63.
5. Regueiro M, Mardini H. Treatment of perianal fistulizing Crohn’s disease with Infliximab
alone or as an adjunct to exam under anesthesia with seton placement. Inflamm Bowel Dis.
2003;9:98–103.
6. Pearson DC, Gary RM, Gordon HF, Sutherland LR. Azathioprine and 6-Mecaptopurine in
Crohn’s disease. Ann Intern Med. 1995;122:132–42.
7. Present DH, Rutgeerts P, Targan S, et al. Infliximab for the treatment of fistulas in patients with
Crohn’s disease. N Engl J Med. 1999;340:1398–405.
8. Sands BE, Anderson FH, Bernstein CN, et al. Infliximab maintenance therapy for fistulizing
Crohn’s disease. N Engl J Med. 2004;350:876–85.
9. Hanauer SB, Sandborn WJ, Rutgeets P. Human anti-tumor necrosis factor monoclonal anti-
body (adalimumab) in Crohn’s disease: the CLASSIC-1 trial. Gastroenterology.
2006;130:323–32.
10. Sandborn WJ, Rutgeets P, Enns R, et al. Adalimumab induction therapy for Crohn disease
previously treated with infliximab: a randomized trial. Ann Intern Med. 2007;146:829–38.
11. Colombel JF, Sandborn WJ, Rutgeerts P. Adalimumab for maintenance of clinical response
and remission in patients with Crohn’s disease: the CHARM trial. Gastroenterology.
2007;132:52–65.
12. West R, Van Der Woude CJ, Hansen BE, et al. Clinical and endosonographic effect of cipro-
floxacin on the treatment of perianal fistulae in Crohn’s disease with infliximab: a double-blind
placebo-controlled study. Aliment Pharmacol Ther. 2004;20:1329–36.
13. Dewint P, Hansen BE, Verhey E, et al. Adalimumab combined with ciprofloxacin is superior
to adalimumab monotherapy in perianal fistula closure in Crohn’s disease: a randomized,
double-blind, placebo controlled trial (ADAFI). Gut. 2014;63:292–9.
14. vanBodegraven AA, Sloots CE, Felt-Bersma RJ, Meuwissen SG. Endosonographic evidence
of persistence of Crohn’s disease-associated fistulas after infliximab treatment, irrespective of
clinical response. Dis Colon Rectum. 2002;45:39–45.
15. Grimaud JC, Munoz-Bongrand N, Siproudhis L, et al. Fibrin glue is effective healing perianal
fistulas in patients with Crohn’s disease. Gastroenterology. 2010;138:2275–81.
16. O’Riordan JM, Datta I, Johnston C, Baxter NN. A systematic review of the anal fistula plug for
patients with Crohn’s and non-Crohn’s related Fistula-in-ano. Dis Colon Rectum.
2012;55:351–8.
17. Soltani A, Kaiser A. Endorectal advancement flap for cryptoglandular or Crohn’s fistula-in-
ano. Dis Colon Rectum. 2010;53:486–95.
18. Makowiec F, Jehle EC, Becker HD, Starlinger M. Clinical course after transanal advancement
flap repair of perianal fistula inpatients with Crohn’s disease. Br J Surg. 1995;82:603–6.
19. Hyman N. Endoanal advancement flap repair for complex anorectal fistulas. Am J Surg.
1999;178:337–40.
20. Gingold DS, Murrell ZA, Fleshner PR. A prospective evaluation of the ligation of the inter-
sphincteric tract procedure for complex anal fistula in patients with Crohn’s Disease. Ann
Surg. 2014;260:1057–61.
21. Singh S, Ding NS, Mathis KL, et al. Systematic review with meta-analysis: fecal diversion for
management of perianal Crohn’s disease. Aliment Pharmacol Ther. 2015;42:783–92.
28 L.S. Poritz
22. Mueller MH, Geis M, Glatzle J, et al. Risk of fecal diversion in complicated perianal Crohn’s
disease. J Gastrointest Surg. 2007;11:529–37.
23. Molendijk I, Nuij VJAA, van der Meulen-de Jong AE, van der Woude CJ. Disappointing
durable remission rates in complex Crohn’s disease fistula. Inflamm Bowel Dis.
2014;20:2022–8.
24. Gaertner WB, Decanini A, Mellgren A, et al. Does Infliximab infusion impact results of opera-
tive treatment for Crohn’s perianal fistulas. Dis Colon Rectum. 2007;50:1754–60.
Chapter 4
IBD: Management of a Painful Anal Fissure
and Skin Tags in Patients with Crohn’s Disease
Nicole M. Saur and Joshua I.S. Bleier
Introduction
Perianal manifestations of CD disease are usually chronic in nature, and often char-
acterized by waxing and waning symptoms. The goals of treatment are typically
achieved through multimodal management, which minimizes ablative surgical
intervention and preserves the sphincter complex [1, 2]. While there is a spectrum
of severity in the observed impact of perianal CD, even the minor issues of skin tags
and fissuring can present the clinician with difficult decisions in management. In
this chapter, we have attempted to provide some clarity to the decision process.
Question What is the best way to manage a painful fissure and skin tags in the set-
ting of a patient with known Crohn’s disease?
Fissures are identified in 19 % of patients with CD and although they were his-
torically thought to be painless, 40–85 % of anal fissures in CD patients are associ-
ated with pain [1]. Additionally, persistent, unhealed fissures can lead to perianal
abscess/fistulae in up to 20 % of patients with CD; this presents quality of life issues
for the patient and a treatment dilemma for the surgeon [2]. Classically, the pathog-
nomonic, ‘elephant ear’ or ‘cock’s comb’ skin tags associated with CD are usually
painless. However, skin tags that don’t have the classic appearance are more likely
to be associated with a chronic fissure, which is commonly characterized by pain.
The long standing teaching has been to avoid removing these skin tags for fear of
much more significant complications such as anal stenosis, sepsis or fecal inconti-
N.M. Saur, MD • J.I.S. Bleier, MD, FACS, FASCRS (*)

Division of Colon and Rectal Surgery, Department of Surgery, University of Pennsylvania
Perelman School of Medicine, 800 Walnut St. 20th Floor, Philadelphia, PA 19107, USA

DOI 10.1007/978-3-319-40223-9_4
30 N.M. Saur and J.I.S. Bleier
nence [3–5]. The primary thrust of this chapter will focus solely on the management
of the painful anal fissure, rather than the incidental tag.
When chronic anal fissures in patients without CD fail to respond to conservative
measures, limited lateral internal sphincterotomy (LIS) is performed with a high
degree of success and limited morbidity. In the setting of active anorectal CD, how-
ever, even a minor anorectal procedure may carry an enhanced risk of morbidity,
including wound complications, anorectal sepsis, fistulous disease and incontinence
[1, 6]. Thus, a significant degree of caution must be applied when managing the
refractory symptomatic fissure in the setting of CD.
Search Strategy
A MEDLINE search was conducted for the past 25 years (1990–2015) secondary to
the paucity of the literature. Search terms included ‘anal, fissure, Crohn’s, and peri-
anal, inflammatory bowel disease, skin tag’. Table 4.1 summarizes the population,
intervention, comparator, and key outcomes (PICO) for the patient population.
Data Review/Recommendations
A review of the literature is summarized in Table 4.2 and the quality evaluated using
the GRADE system. The studies in the literature are all retrospective small studies
with little power and no standardization of outcomes. Only a single study compared
botulinum toxin (Botox) to LIS after failure of medical management. D’Ugo et al
compared Botox with or without fissurectomy to LIS. However, in patients with
confirmed CD, Botox was performed instead of LIS and therefore there is no com-
parison between Botox and LIS in known CD patients [2]. Lozynskyy et al reported
a 75 % healing rate with medical management in CD patients and reported they had
not performed surgical treatment of a fissure associated with CD in the last 5 years
of their study [7]. Fleshner et al reported a 50 % healing rate with medical fissure
management. They then compared fissure healing rates when patients underwent
anorectal procedures versus bowel resection for proximal disease. They showed an
Table 4.1 PICO table for painful fissure associated with Crohn’s disease
Patient
population Intervention Comparator Key outcomes
Patients with Lateral internal Conservative medical Morbidity, pain resolution/
Crohn’s sphincterotomy (LIS) management healing, need for additional
disease and (including Botox intervention
painful anal injection in internal
fissure anal sphincter)
Table 4.2 Literature reported outcomes and quality of evidence
Morbidity
Healing (%) Healing (%) (%) Quality of
Outcome medical surgical surgical evidence
Study Patients (n) Interventions (n) classification management management treatment (GRADE)
D’Ugo (2013) 41, CD (22 with Medical management (27), Healing rate, 65.8 78.5 % 57.1 Very low
[2] definitive surgical treatment (Botox/ complication rate (recurrences) quality
diagnosis) fissurectomy vs LIS; 14)
Lozynskyy 60 CD Medical management (45), Healing rate 75 NR NR Very low
(2009) [7] surgical treatment quality
(Maslyak’s method; 15)
4 Management of Fissure and Skin Tags in Crohn’s Disease
Fleshner 56 CD (49 Medical management (35), Healing rate 50 67 NR Low quality

(1995) [8] symptomatic) surgical treatment (LIS,
fissurectomy, bowel
resection; 15 (8 anorectal))
31
88 % healing rate with anorectal procedures (LIS, fissurectomy) versus 43 % with
proximal bowel resection for active ileal or colonic CD [8].
Several additional retrospective studies have been performed but very little out-
come data exists. For example, Wolkomir et al evaluated 25 CD patients undergoing
27 procedures for anal fissure. However, they did not directly report on the healing
or complication rates in their study. They did describe a mean follow up of greater
than 7 years and noted that 22 patients had a healed wound by 2 months; however,
11 patients subsequently developed anorectal pathology of whom three developed
recurrent fissure [9]. Similarly, Sangwan et al studied 21 patients with anal fissure
of whom six underwent LIS and one underwent fissurectomy. However, again, no
outcome data was reported in this study [10].
Although it is stated in many review articles that LIS should be reserved for
patients without active anorectal CD [1, 6, 11], active CD simply has not been
assessed as a study variable in any recent literature. This may be because it is
assumed to be unsafe to proceed with LIS in the setting of active CD. However, this
assumption may not be valid, especially in the era of biologic treatment for CD, and
should be validated in future studies.
In summary, there is a paucity of literature evaluating medical versus surgical
management of painful Crohn’s fissures. Additionally, the literature to date consists
of low to very low quality retrospective studies with incomplete outcome data. To
further clarify the treatment algorithm in the presence of CD, new, well-designed
studies are needed, especially those comparing Botox to LIS in patients who have
failed conservative medical management.
Personal View of the Data
Our approach to painful anal fissures in CD revolves around treating the underlying
CD first in the setting of active anorectal CD. Multidisciplinary management is
standard and medical management (eg biologics) is the first line treatment for peri-
anal disease associated with CD. Conservative management to treat anal fissures is
employed including optimization of bowel habits and a trial of topical nitroglycerin
paste or calcium channel blocker cream. In the presence of a CD fissure failing
medical management, Botox (20–50 units) can be injected on either side of the fis-
sure into the internal sphincter muscle or in the intersphincteric groove for tempo-
rary paralysis. If Botox injection does not result in healing of the fissure, continued
medical management should be undertaken with fecal diversion only as a last resort
to palliate symptoms. LIS is not performed in the presence of active anorectal CD.
In patients without active anorectal disease, the algorithm is essentially the same
as for patients without a diagnosis of CD. Medical management is attempted as a
first line and followed by Botox injection or LIS in the event of an unhealed fissure
(Fig. 4.1). Even in the apparent absence of active anorectal CD, the presence of an
atypical fissure, or a fissure located anywhere other than the anterior- or posterior-
midline, should raise suspicion for CD involvement.
4 Management of Fissure and Skin Tags in Crohn’s Disease 33
Crohn’s Disease
With Painful
Fissure
No Active
Active Anorectal
Anorectal
Crohn’s Disease
Crohn’s Disease
AND
Multidisciplinary Nitroglycerin/ Nitroglycerin/

Management of Calcium Channel Calcium Channel
Crohn’s Disease Blocker Cream Blocker Cream
NOT HEALED NOT HEALED

OR
Botox Injection
in Internal Botox Injection
Sphincter in Internal LIS
Sphincter
NOT HEALED
Continued
Crohn’s - ACTIVE DISEASE
Management
NOT HEALED + ACTIVE DISEASE
Consider Fecal
Diversion
Fig. 4.1 Algorithm for management of fissure associated with Crohn’s disease
In patients with Crohn’s disease and asymptomatic anal fissure, medical man-
agement should be initiated. Surgical intervention is reserved only for patients with
a persistent or recurrent fissure without evidence of active anorectal Crohn’s Disease
(evidence quality very low, weak recommendation).
References
1. Lewis RT, Maron DJ. Anorectal Crohn’s disease. Surg Clin North Am. 2010;90(1):83–97.
2. D’Ugo S, Franceschilli L, Cadeddu F, et al. Medical and surgical treatment of haemorrhoids and
anal fissure in Crohn’s disease: a critical appraisal. BMC Gastroenterol. 2013;13(1):13–47.
3. Korelitz BI. Anal skin tags: an overlooked indicator of Crohn’s disease. J Clin Gastroenterol.
2010;44(2):151–2.
4. Bonheur JL, Braunstein J, Korelitz BI, Panagopoulos G. Anal skin tags in inflammatory bowel
disease: new observations and a clinical review. Inflamm Bowel Dis. 2008;14(9):1236–9.
5. Molnár T, Nagy F, Wittmann T. Anal skin tag: do not injure the elephants. J Clin Gastroenterol.
2010;44(10):722.
6. Lu KU, Hunt SR. Surgical management of Crohn’s disease. Surg Clin North Am.
2013;93(1):167–85.
7. Lozynskyy YS. Treatment algorithms in the case of perianal complications of Crohn’s disease.
Dig Dis. 2009;27(4):565–70.
8. Fleshner PR, Schoetz DJ, Roberts PL, Murray JJ, Coller JA, Veidenheimer MC. Anal fissure
in Crohn’s disease: a plea for aggressive management. Dis Colon Rectum. 1995;38(11):
1137–43.
9. Wolkomir AF, Luchtefeld MA. Surgery for symptomatic hemorrhoids and anal fissures in
Crohn’s disease. Dis Colon Rectum. 1993;36(6):545–7.
10. Sangwan YP, Schoetz DJ, Murray JJ, Roberts PL, Coller JA. Perianal Crohn’s disease. Results
of local surgical treatment. Dis Colon Rectum. 1996;39(5):529–35.
11. Singh B, George BD, McC Mortensen NJ. Surgical therapy of perianal Crohn’s disease. Dig
Liver Dis. 2007;39(10):988–92.
Chapter 5
IBD: Elective Surgical Management
in Patients with Ulcerative Colitis-How Many
Stages?
Roger D. Hurst
Introduction
For the last three decades, restorative proctocolectomy with J-pouch ileoanal anas-
tomosis has been the primary treatment for ulcerative colitis patients who require
surgery. While most patients requiring surgery for ulcerative colitis are young and
are at baseline in good health, many are at least temporarily debilitated from either
severity of disease, infection, malnutrition, obesity, or from side effects of immuno-
suppressant medications. These factors can greatly increase the risk for poor surgi-
cal outcomes both in the short and long term. Even when conditions are optimized,
the ileoanal anastomosis is known to be a high risk anastomosis with frequent leaks
and pelvic sepsis. Leak rates for the procedure are reported to be between 5 and
14 % [1]. This high risk for anastomotic dehiscence was recognized early in the
development of the procedure and strategies have been implemented in the hopes of
diminishing the risks and consequences of poor anastomotic healing. For these rea-
sons performing the operation in multiple stages was the initial standard approach.
However, the absolute need for staging has been questioned and many have advo-
cated for a strategy of omitting the approach of multiple stages in selected cases and
some have advocated for omitting staging in almost all cases [2–4]. This chapter
will review the current available evidence to support the need for staging of the
operations for the treatment of ulcerative colitis.
The ileoanal pouch procedure can be performed in either a single stage, two-step,
or three-step approach [5, 6]. The decision points for the staging center around two
separate issues (Tables 5.1 and 5.2).
R.D. Hurst, MD
Department of Surgery, University of Chicago Pritzker School of Medicine,
5841 S. Maryland Ave, Chicago, IL 60637, USA

DOI 10.1007/978-3-319-40223-9_5
36 R.D. Hurst
Table 5.1 Omission of diverting stoma

Pt population Intervention Comparator Outcomes studied
Ulcerative colitis Omission of Diversion of Anastomotic leaks, pelvic
patient Undergoing diverting Stoma fecal stream sepsis, long-term function, cost,
ileo-anal procedure length of hospital stay
Table 5.2 Total colectomy as initial operation

Ulcerative colitis Total abdominal Ileo-anal Anastomotic leaks, pelvic
patient Colectomy as anastomosis as sepsis, long-term function,
Undergoing initial initial operation initial operation cost, length of hospital stay
surgery
1. When constructing the ileal pouch-anal reservoir and performing the ileoanal
anastomosis, should the fecal stream be diverted from the pouch and the anasto-
mosis with a loop ileostomy to allow for healing?
2. In patients who are temporarily debilitated, should a total abdominal colectomy
with end ileostomy and de-functionalized Hartmann’s pouch be performed to
allow for physiologic recovery prior to undertaking the more risky reservoir con-
struction and ileoanal anastomosis?
This chapter will review each of these controversies.
Search Strategy
A medline Ovid database search was performed on publications from 1985 through
October 2015 comparing ileal pouch-anal anastomosis with or without diverting
loop ileostomy. MeSH search headings utilized: restorative proctocolectomy, ileo-
anal, ileo-anal anastomosis, ileal pouch, ileal reservoir, ileostomy, loop ileostomy
and infliximab. References found from these articles were also searched and
reviewed. Additionally “Find Citing Articles” function was utilized to further
enhance the extent of the search.
Results
Diverting Loop Ileostomy
Multiple reports have been published regarding the value of diverting loop ileos-
tomy when performing pouch construction and creating the ileoanal anastomosis.
No definitive conclusive study exists as each of these studies is flawed by either a
lack of adequate numbers, poor study design, or significant bias. Many studies are
retrospective reports comparing only highly selected cases. Case control studies do
5 IBD: Elective Surgical Management in Patients with Ulcerative Colitis 37
exist, but again in most instances these studies involve highly selected patients or
insufficient numbers. Further complicating matters, the results of these studies have
been conflicting. Some studies suggest an increased risk for anastomotic leaks and
pelvic sepsis when the diverting stoma is omitted [7–12] while other studies suggest
that the presence of the stoma does not affect the rate of anastomotic complications
[13–29]. The studies supporting and opposing the use of a temporary diverting
stoma are listed in Tables 5.3 and 5.4.
Table 5.3 Studies supporting the use of diverting stomas

Patients
Patients without Quality of
Author Date Study type with stoma stoma evidence
Cohen et al. [7] 1992 Retrospective, selected 87 71 Low
Tjandra et al. [8] 1993 Matched controls 50 50 Moderate
Williamson et al. [9] 1997 Selected 50 50 Low
Kienle et al. [10] 2003 Prospective cohort, 27 32 Low
Selected
Weston-Petrus [11] 2008 Meta-analysis Moderate
Mennigen et al. [12] 2011 Selected, retrospective 89 33 Low
Table 5.4 Studies supporting omission of diverting stoma

Patients Patients
with without Quality of
Author Date Study type stoma stoma evidence
Everett et al. [13] 1990 Selected 35 29 Low
Matikainen et al. [14] 1990 Consecutive 21 25 Low
Galandiuk et al. [15] 1991 Retrospective matched 37 37 Low
controls, selected
Grobler et al. [16] 1992 Randomized control 23 22 Low
study, selected
Sagar et al. [17] 1992 Consecutive, selected 28 30 Very Low
Gorfine et al. [18] 1995 Retrospective, selected 69 74 Low
Gullberg et al. [19] 1995 Consecutive 7 13 Low
Hainsworth et al. [20] 1998 Selected 30 72 Low
Antos et al. 1999 Selected 20 23 Low
Dolgin et al. [22] 1999 Consecutive, prospective 14 16 Low
nonrandomized
Mowschenson et al. [23] 2000 Retrospective, selectided 28 102 Low
Heuschen et al. [24] 2001 Matched controls, 144 57 Moderate
selected
Lepisto et al. [25] 2002 Retrospective 154 332 Moderate
Ikeuchi et al. [26] 2005 Retrospective, selected 92 150 Low
Remzi et al. [27] 2006 Retrospective, selected 1725 277 Low
Joyce [28] 2010 Retrospective 715 120 Low
Gray et al. [29] 2012 Selected 28 22 Low
38 R.D. Hurst
A common design strategy employed in many of these reports is to allow the

operative surgeon to make a judgment regarding the need for the loop ileostomy
(those with “selected” study designs as designated in Tables 5.3 and 5.4). The sur-
geon therefore decides who is at high risk and then places these patients in the
diverted group and patients judged to be a low risk are placed in the un-diverted
group. While this strategy may well be a reasonable approach in the management
for patients undergoing surgery for ulcerative colitis, when applied to a clinical
study, this method of patient selection creates bias such that interpretation of the
results can be difficult. So when such studies show no difference between the two
groups, it would be difficult to conclude that there is no benefit to the loop
ileostomy.
The absence of a difference between the two groups may result from the loop
ileostomy effectively taking high risk patients and decreasing their risk to that of the
lower risk group. It should also be noted that there are several studies with results
that would indicate that even in patients selected in this manner, those without a
loop ileostomy have an inferior outcome [7, 9, 12].
So one can really only claim that patients judged to be at low risk for anastomotic
complications will do as well as a high risk cohort when the loop ileostomy is
omitted.
There is only one randomized controlled trial looking at the value of diverting
loop ileostomy in restorative proctocolectomy [16]. But this study was markedly
underpowered with only 23 patients in the loop ileostomy group and 22 patients in
the un-diverted group. In each group there is only one incidence of anastomotic
leak; even with this study the patients that were randomized had been preselected by
the operating surgeon as having had a low risk for anastomotic leak.
Perhaps the best the available study to suggest that loop ileostomy may not be
necessary is a matched-pair controlled study conducted by Heuschen et al. [24] In
this study 57 patients in the study group (no diversion) were compared to 114
matched controls. Heuschen et al. found no significant differences in early compli-
cations including pouch related septic complications. Conversely, Tjandra, et al.,
also reported a study with matched controls with 50 patients in each group and
found a 14 % risk for anastomotic leak and pelvic sepsis in patients who had not
been diverted compared to 4 % in the controls [8].
In 2008, Weston-Petrides published a meta-analysis for the data available from
1978 through 2005 from all comparative studies looking at restorative
proctocolectomy with or without covering ileostomy [11]. This analysis indicated
that restorative proctocolectomy without a diverting loop ileostomy resulted in sim-
ilar long-term functional results but was associated with an increased risk for anas-
tomotic leak and pelvic sepsis. The conclusion of the authors was that the loop
ileostomy should only be omitted in carefully selected patients.
The goal of avoiding an anastomotic leak is worthwhile as poor anastomotic
healing has major consequences both in the short and long term. Pelvic sepsis after
ileal pouch-anal anastomosis has significant effects on long-term outcomes. For
instance, patients who experience pelvic sepsis are five times more likely to require
excision of their pouches when compared to those patients who avoided anastomotic
leakage and pelvic sepsis [1, 30, 31]. Those patients who have pelvic sepsis but are
able to retain their pouches are more likely to have anal incontinence [1].
While many of the studies looking at the value of fecal diversion focus on the
risk for anastomotic leak, there are other considerations that come into play when
deciding which operative strategy is best for the patient. Studies looking at the total
length of stay and total costs have favored the approach of performing the ileoanal
anastomosis without a loop ileostomy. While performing the operation in a single
step tends to lead to a longer initial hospitalization, when the length of hospital stay
for the reversal of the loop ileostomy is taken into account, the total hospitalization
is shorter with the one step approach [9, 12, 14, 16–18, 20, 21, 26, 28]. Additionally
total costs have been shown to be lower in those patients undergoing the procedure
without a diverting loop ileostomy [28].
When considering a staged approach the morbidity associated with the loop ile-
ostomy itself must also be considered [32]. Some have suggested that the overall
morbidity associated with loop ileostomy is substantial [33], but others have noted
that severe complications are not frequent [34]. Additionally a large study published
in 2005 involving 1504 patients from the Cleveland Clinic demonstrated that clo-
sure of the ileostomy can be accomplished with an overall complication rate of
11.4 % and a risk of intra-abdominal sepsis of only 1 % [35].
Initial Colectomy Prior to IPAA
The value of an initial total abdominal colectomy prior to ileal pouch-anal anasto-
mosis in patients with intra-abdominal sepsis or severe co-morbid disease has not
been subject to comparative studies, as the risks to these sick patients would be dif-
ficult to justify. However, reports of patients who have undergone either a two or
three step approach have identified certain parameters under which a three stage
approach would be prefered [36–38]. Traditionally these have included urgent sur-
gery, sepsis, fulminate disease, anemia, hypoalbuminemia, steroids, and uncertain
diagnosis [3, 5, 38, 39].
A more recent and significant controversy surrounds the risks for perioperative
complications for patients who are being treated with anti-TNF agents. In 2005 the
anti-TNF antibody, infliximab, was approved for use in patients with ulcerative c olitis
[40]. Shortly after the widespread use of infliximab for the treatment of ulcerative
colitis, the Mayo Clinic and the Cleveland clinic both reported a substantial increase
in postoperative related infectious complications in ulcerative colitis patients treated
with infliximab [41, 42]. This finding is not entirely consistent across all reports and
is somewhat surprising, given that infliximab had been used for many years in the
treatment of Crohn’s disease and no significant increase in perioperative complica-
tions had been seen in these patients [43–49]. This may be explained by the fact that
the ileal pouch-anal anastomosis is normally a high risk anastomosis even under ideal
conditions. It may well be that infliximab generates a relatively small effect on heal-
ing in general, but that this effect is magnified in this very delicate anastomosis.
40 R.D. Hurst
In response to the findings suggesting that anti-TNF therapy increases risk for
anastomotic leaks, many surgeons have changed their approach to the surgical man-
agement by utilizing a three-step approach in patients treated with anti-TNF agents
[50, 51]. In a study from the Cleveland clinic Gu et al. looked at patients undergoing
surgery for ulcerative colitis without an initial total abdominal colectomy [50]. They
found that those patients on anti-TNF therapy had a significantly greater risk for
pelvic sepsis (32 % versus 16 %; p = 0.012) when the procedure is not staged with an
initial total abdominal colectomy. However, they reported no difference in outcomes
between the patients who had been treated with anti-TNF therapy as compared to
those who had never been treated with anti-TNF agents when patients initially
undergo a staged colectomy. These findings not only indicate that the use of anti-
TNF therapy increases the risk for septic complications, they also indicate that uti-
lizing an initial total abdominal colectomy can mitigate the negative effects of the
anti-TNF agents.
1. A diverting loop ileostomy may be omitted in highly selected patients undergo-

ing ileal pouch-anal anastomosis. (Weak Recommendation based upon low-
quality of evidence)
From the current available data it is difficult to give strong recommendations as
to appropriateness of omitting a diverting loop ileostomy with restorative procto-
colectomy. Even investigators intimately involved in the subject have had difficul-
ties with this. For instance in 1992 Sagar, et al. initially reported a comparison of
one stage versus two-stage ileoanal procedures and found no significant difference
in the risk for anastomotic leaks or other complications and concluded that omission
of the loop ileostomy may be a reasonable option in selected patients [17]. The same
group later reported in 1997 that with further experience, they found that patients
undergoing a one stage restorative proctocolectomy had significantly higher risk for
severe septic complications and cautioned against the routine use of a one stage
proctocolectomy [9]. Similarly, Tjandra et al. initially reported 1994 a matched
control study and found that in equally favorable cases restorative proctocolectomy
without diversion was not as safe as with diversion [8]. The same institution later
reported a retrospective study indicating no difference in septic complications [27].
The senior author on both of these studies subsequently co-authored a meta-analysis
indicating that restorative proctocolectomy without a diverting ileostomy was asso-
ciated with an increased risk for anastomotic leak [11].
Even with these difficulties, there is general consensus among experts that the
diverting loop ileostomy can be omitted in highly selected patients. And this has
been the recommendation from expert panels from both Europe and North America
[52, 53]. Patient selected for omission of loop ileostomy are best not to have any of
the risk factors listed in Table 5.5. Despite the recommendations from these expert
Table 5.5 Factors that may 1. Severe or fulminate colitis

increase risk for poor
2. Sepsis
anastomotic healing
3. Malnutrition
4. Hypoalbuminemia
5. Obesity
6. Technical difficulties
7. Steroid use
8. Use of immunosuppressants
9. Technical concerns
10. Tension on anastomosis
11. Fecal contamination
12. Anemia
13. Anti-TNF therapy
panels that omission of the loop ileostomy is reasonable in selected patients, many
practicing surgeons appear to adopt a very conservative approach to this issue. A
recent survey of colorectal surgeons in North America indicated that 73 % would
perform a diverting loop ileostomy even in low risk patients [54].
2. Ulcerative colitis patients with sepsis, severe comorbid factors, or who have been
treated with anti-TNF therapy should undergo an initial total abdominal colec-
tomy prior to ileal pouch-anal anastomosis. (Weak recommendation based upon
low-quality of evidence)
There is little controversy that the sickest of patients should undergo a three stage
approach. At the same time, there is insufficient evidence to accurately delineate the
circumstances in which the three stage approach is the best option. Early evidence
suggests that the use of anti-TNF therapy poses a risk for increase in anastomotic
leaks and pelvic sepsis and that these risks can be diminished by utilizing a three-
stage approach [50]. Further study, however, is required to confirm the advantage of
this approach.
Unfortunately the data on the value of staging the surgeries for the ileoanal proce-
dure are conflicting. Thus, it is truly a difficult decision as to whether to omit the
diverting loop ileostomy. Likewise it is also a difficult decision as to when to per-
form an initial total abdominal colectomy prior to the ileoanal procedure. Ultimately
it is up to the discretion of the experienced surgeon working in concert with the
patient’s wishes to determine the best approach for each individual case.
In the past as many as one third of this author’s patients underwent an ileoanal
procedure in a single step. With the advent of anti-TNF therapy, this however has
changed and now most patients in my practice undergo surgery with a staged
42 R.D. Hurst
approach. The reports of poor anastomotic healing with anti-TNF therapy are con-
cerning. This combined with my personal, albeit anecdotal, experience with anasto-
motic problems in patients receiving anti-TNF therapy has made staging in my
practice much more common. Additionally, the decision to stage the operations has
become somewhat more attractive with the advent of laparoscopic surgery. The
decrease morbidity and enhanced recovery after laparoscopic total abdominal col-
ectomy makes the decision for staging easier to accept as it is much better tolerated
than an open procedure [55].
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Chapter 6
Which Ulcerative Colitis Patients Should Not
Have Ileal Pouch-Anal Anastomosis
Scott A. Strong
Approximately 10–15 % of patients diagnosed with ulcerative colitis will ultimately

require operative management of their disease [1, 2], and proctocolectomy with ileal
pouch-anal anastomosis (IPAA) has evolved into the most commonly performed
procedure [3, 4]. However, not all patients are best managed by a proctocolectomy
and ileal pouch-anal anastomosis, and some are better served by undergoing another
operation such as proctocolectomy with end ileostomy. The most appropriate choice
of operation is largely predicated upon multiple patient-dependent variables that
may impact long-term outcome best measured as health-related quality of life.
PICO table
Patients Intervention Comparator Outcome
Patients with Proctocolectomy with ileal Proctocolectomy with Health-related
ulcerative colitis pouch-anal anastomosis end ileostomy quality of life
requiring (HRQOL)
operation
Search Strategy
A comprehensive literature search of Cochrane Database of Collected Research,

EMBASE, MEDLINE, and PubMed was performed to identify all of the English-
language publications related to ulcerative colitis, colectomy, and ileal pouch-anal
S.A. Strong, MD, FACS, FASCRS

Chief, Gastrointestinal and Oncologic Surgery, Surgical Director, Digestive Health Center,
Northwestern Medicine James R. Professor of Surgery,
Northwestern University Feinberg School of Medicine, Chicago, IL, USA

DOI 10.1007/978-3-319-40223-9_6
46 S.A. Strong
anastomosis and quality of life (QOL) outcomes from 1985 to 2015. Key search
terms included the following: “colectomy,” “colitis,” “ileal pouch-anal anastomo-
sis,” “inflammatory bowel disease,” “proctocolectomy,” and “ulcerative colitis.”
Studies were excluded if they did not directly contrast proctocolectomy with ileal
pouch-anal anastomosis to proctocolectomy with ileostomy, failed to measure any
component of health-related quality of life, included patients with Crohn’s disease
or familial adenomatous polyposis, included only patients with ulcerative colitis
plus specific conditions (e.g., primary sclerosing cholangitis), or included pediatric
patients. Only the most recent study was included if similar studies from the same
institution were encountered. The references of the included studies were reviewed
to identify additional studies that were incorporated as appropriate.
Results
Over the past three decades, only a few studies have reported health-related quality of
life outcomes in patients with ulcerative colitis undergoing proctocolectomy and ileal
pouch-anal anastomosis or ileostomy. Some of the initial studies were plagued by
poor methodology using quality of life metrics that had not been validated. However,
reports published in past 15 years have tended to use validated global, generic, or
disease-specific instruments to measure health-related quality of life [5–12].
Studies that employed global instruments to contrast health-related quality of life
between patients who underwent proctocolectomy and ileal pouch-anal anastomosis
or ileostomy reported conflicting results. Emblem and associates [5] used a non-
validated questionnaire that showed patients managed by an ileostomy were mark-
edly more likely to experience social restrictions. While McLeod et al. [6] found no
differences in several global measures, Kuruvilla and colleagues [11] reported the
Cleveland Global QOL was significantly better for patients with an ileal pouch-anal
anastomosis, particularly related to current energy level and current quality of health.
Of the studies using a generic measure, no difference in scores was found
between the two patient groups regardless whether the non-validated “lifestyle sat-
isfaction score,” [7] validated EuroQol Group’s EQ-5D-3 L questionnaire [11], or
validated Short Form (SF)-36 Health Survey [9, 10] was used. However, O’Bichere
and associates [8] used a questionnaire developed in-house to specifically measure
seven selected items, and they found patients with an ileostomy were significantly
less bothered by altered bowel emptying and diet.
A disease-specific instrument, the Inflammatory Bowel Disease Questionnaire
(IBDQ), was employed in three studies [9, 10, 12] and an abbreviated version, the
short (S) IBDQ, was used in another report [11]. No differences in scores were
found between the two groups in any of the studies [9–12], but van der Kalk et al.
[12] did report ileal pouch-anal anastomosis patients had higher quality-adjusted
life years compared to ileostomy patients.
6 Which Ulcerative Colitis Patients Should Not Have Ileal Pouch-Anal Anastomosis 47
Health-related quality of life is obviously a different outcome measure than mor-

bidity. But, it is interesting that the morbidity rate of ileostomy patients was higher
in three of the four studies that reported this outcome parameter [5, 6, 10, 12].
Study Patients (N) QOL measure Results Quality of

IPAA vs IPAA vs evidence
Ileostomy Ileostomy
Emblem [5] 19 vs 35 Social restriction 0 % vs 67 % Low
(P < 0.05)
McLeod [6] 37 vs 28 Direct questioning of Comparable Moderate
objections Comparable
Sickness-Impact Comparable
Profile Time
trade-off
Liddell [7] 25 vs 10 Lifestyle satisfaction Comparable Low
O’Birchere [8] 30 vs 30 SF-36 Comparable Moderate
Altered bowel 8 vs 5 (P = 0.01)
emptying Comparable
Body image Comparable
Clothes 5.5 vs 2
Diet (P = 0.02)
Noise Comparable
Odor Comparable
Sexual relationship Comparable
Nordin [9] 56 vs 42 IBDQ Comparable Moderate
SF-36 Comparable
Camilleri- 19 vs 19 IBDQ Comparable High
Brennan [10] SF-36 Comparable
Kuruvilla [11] 35 vs 24 EQ-5D-3 L Comparable Moderate
Cleveland QOL 0.9 vs 0.8
FIQL (P = 0.03)
SIBDQ Comparable
Comparable
van der Valk 81 vs 48 IBDQ Comparable High
[12] Quality-adjusted life 0.9 vs 0.84
years (P < 0.01)
Recommendations
Patients requiring an operation for ulcerative colitis can undergo proctocolectomy

and ileostomy rather than proctocolectomy and ileal pouch-anal anastomosis with-
out compromising their health-related quality of life. (Evidence: moderate;
Recommendation: strong)
48 S.A. Strong
Patients needing surgery for ulcerative colitis are typically offered a proctocolec-
tomy and ileal pouch-anal anastomosis in one, two, or three stages with the two-
stage approach most often employed in elective scenarios. However, this restorative
procedure is occasionally contraindicated because of disease-related complications,
unachievable for technical reasons, or ill-advised due to excessive risk for operative
morbidity or impaired quality of life. In these selected settings, proctocolectomy
and ileostomy may be offered, and the patient can be reassured that her/his health-
related quality of life will be comparable to that associated with a sphincter-sparing
procedure.
Personal View
Patients with colorectal adenocarcinoma complicating their ulcerative colitis need

to undergo a sound oncologic operation. If the tumor encroaches upon the sphincter
mechanism, excision of the levators and anal canal is usually required, and a
sphincter-sparing procedure such as an ileal pouch-anal anastomosis is contraindi-
cated. Colorectal cancers that have metastasized to distant sites are commonly man-
aged with chemotherapy unless bleeding or obstruction mandates resection or
diversion. Regardless, a restorative proctocolectomy and ileal pouch-anal anasto-
mosis would be generally contraindicated because it would potentially delay the
more important systemic therapy.
Management of adenocarcinomas of the mid or lower rectum penetrating the
muscularis propria or involving one or more mesorectal lymph nodes without dis-
tant metastases usually entails a combination of chemotherapy, radiotherapy, and
resection. If the tumor is situated above the anorectal ring, a sphincter-sparing oper-
ation can be performed. However, patients receiving pre-operative external beam
radiotherapy are at increased risk for ileal pouch failure secondary to pouch dys-
function [13] despite no significant increase in operative morbidity [14]. Pouch fail-
ure also occurs more frequently in patients receiving post-operative radiotherapy
[15]. Accordingly, an ileal pouch-anal anastomosis should be likely avoided in
many patients with ulcerative colitis and rectal cancer when management requires
external beam radiotherapy.
Successful restoration of bowel continuity after proctocolectomy warrants con-
struction of a tension-free ileal pouch-anal anastomosis. Patients with visceral obe-
sity may have a shortened mesentery that physically precludes reach of the ileal
pouch to the anal canal. In those where reach can be achieved, the risk for pouch-
related complications (e.g., anastomotic separation, anastomotic/pouch stricture,
pouch fistula) is generally increased [16–18].
Proctocolectomy and diverted ileal pouch-anal anastomosis is an operation asso-
ciated with a relative high risk for operative morbidity. Specifically, stricture, pelvic
sepsis, and fistula occur in 10.7 %, 7.5 %, and 4.5 % of patients, respectively [19],
and hemorrhage complicates 3.6 % of the operations [20]. Patients with cardiac dis-
ease, pulmonary disorder, or renal impairment can expect an even greater likelihood
of experiencing a post-operative complication. These co-morbidities in isolation or

combination can introduce prohibitive risk that serves as a relative contraindication
to proctocolectomy and ileal pouch-anal anastomosis.
Patients with primary sclerosis cholangitis complicating their ulcerative colitis
represent a special group of patients because some are at greater risk for compro-
mised outcomes following proctocolectomy with ileal pouch-anal anastomosis.
An ileal pouch operation in a cirrhotic with primary sclerosis cholangitis is associ-
ated with a high incidence of early post-operative complications such as bleeding
(44 %), worsening liver function (31 %), and pelvic abscess (19 %) [21]. Pelvic
sepsis is a particular concern in this population because of its link with patient
death [21].
Regardless of the degree of liver dysfunction, patients with primary sclerosis
cholangitis and ulcerative colitis are at significantly greater risk for acute pouchitis
and tend to have worse ileal pouch function compared to those without primary
sclerosis cholangitis [22]. Moreover, patients with large duct primary sclerosis chol-
angitis experience even worse pouch function and a significantly compromised
quality of life [22].
Liver transplantation prior to proctocolectomy and ileal pouch-anal anastomosis
can ameliorate some problems, and these patients can expect an acceptable risk for
operative morbidity and reasonable pouch function [23].
Another cohort of patients who may experience impaired ileal pouch function
and diminished quality of life are those with low (<40 mmHg) pre- and post-
operative anal sphincter resting pressures. These reduced pressures are associated
with an increased incidence of pad usage, seepage, and incontinence as well as
reduced quality of life and satisfaction with surgery that do not improve over time
[24]. Similarly, patients with pre-operative fecal incontinence unrelated to urgency
are not good candidates for an ileal pouch-anal anastomosis because of the same
reasons. However, a patient with pre-operative continence despite an anterior
sphincter defect does not usually experience a similar outcome [25].
Selected patients with absent proctitis, adequate rectal compliance, and reason-
able sphincter strength are potential candidates for colectomy and ileoproctostomy
[26]. In these cases, the benefits of less operative morbidity, preserved female
fecundity, and reasonable function must be weighed against the risk of neoplasia
and recurrent disease. The likelihood of the patient requiring a proctectomy is
16–26 % at 10 years and 31–54 % at 20 years [4].
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Gastroenterology, Practice Parameters Committee. Am J Gastroenterol. 2010;105:501–23.
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Van Assche G. Second European evidence-based consensus on the diagnosis and management
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3. Ross H, Steele SR, Varma M, Dykes S, Cima R, Buie WD, Rafferty J, Standards Practice Task
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Angriman I, Serclova Z, de Buck van Overstraeten A, Gionchetti P, Stassen L, Warusavitarne
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5. Emblem R, Larsen S, Torvet SH, Bergan A. Operative treatment of ulcerative colitis: conven-
tional proctectomy with Brooke ileostomy versus mucosal proctectomy with ileoanal anasto-
mosis. Scand J Gastroenterol. 1988;23:493–500.
6. McLeod RS, Churchill DN, Lock AM, Vanderburgh S, Cohen Z. Quality of life of patients
with ulcerative colitis preoperatively and postoperatively. Gastroenterology. 1991;101:
1307–13.
7. Liddell A, Pollett WG, MacKenzie DS. Comparison of postoperative satisfaction between
ulcerative colitis patients who chose to undergo either a pouch or an ileostomy operation. Int
J Rehabil Heal. 1995;1:89–96.
8. O’Bichere A, Wilkinson K, Rumbles S, Norton C, Green C, Phillips RK. Functional outcome
after restorative panproctocolectomy for ulcerative colitis decreases an otherwise enhanced
quality of life. Br J Surg. 2000;87:802–7.
9. Nordin K, Påhlman L, Larsson K, Sundberg-Hjelm M, Lööf L. Health-related quality of life
and psychological distress in a population-based sample of Swedish patients with inflamma-
tory bowel disease. Scand J Gastroenterol. 2002;37:450–7.
10. Camilleri-Brennan J, Munro A, Steele RJ. Does an ileoanal pouch offer a better quality of life
than a permanent ileostomy for patients with ulcerative colitis? J Gastrointest Surg. 2003;7:
814–9.
11. Kuruvilla K, Osler T, Hyman NH. A comparison of the quality of life of ulcerative colitis
patients after IPAA vs ileostomy. Dis Colon Rectum. 2012;55:1131–7.
12. van der Valk ME, Mangen MJ, Severs M, van der Have M, Dijkstra G, van Bodegraven AA,
Fidder HH, de Jong DJ, Pierik M, van der Woude CJ, Romberg-Camps MJ, Clemens CH,
Jansen JM, van de Meeberg PC, Mahmmod N, van der Meulen-de Jong AE, Ponsioen CY,
Bolwerk C, Vermeijden JR, Siersema PD, Leenders M, Oldenburg B, COIN study group,
Dutch Initiative on Crohn and Colitis. Comparison of costs and quality of life in ulcerative
colitis patients with an ileal pouch-anal anastomosis, ileostomy and anti-TNF therapy. J Crohns
Colitis. 2015;9:1016–23.
13. Wu XR, Kiran RP, Remzi FH, Katz S, Mukewar S, Shen B. Preoperative pelvic radiation
increases the risk for ileal pouch failure in patients with colitis-associated colorectal cancer.
J Crohns Colitis. 2013;7:e419–26.
14. Wertzberger BE, Sherman SK, Byrn JC. Differences in short-term outcomes among patients
undergoing IPAA with or without preoperative radiation: a National Surgical Quality
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15. Radice E, Nelson H, Devine RM, Dozois RR, Nivatvongs S, Pemberton JH, Wolff BG, Fozard
BJ, Ilstrup D. Ileal pouch-anal anastomosis in patients with colorectal cancer: long-term func-
tional and oncologic outcomes. Dis Colon Rectum. 1998;41:11–7.
16. Kiran RP, Remzi FH, Fazio VW, Lavery IC, Church JM, Strong SA, Hull TL. Complications
and functional results after ileoanal pouch formation in obese patients. J Gastrointest Surg.
2008;12:668–74.
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18. Klos CL, Safar B, Jamal N, Hunt SR, Wise PE, Birnbaum EH, Fleshman JW, Mutch MG,
Dharmarajan S. Obesity increases risk for pouch-related complications following restorative
proctocolectomy with ileal pouch-anal anastomosis (IPAA). J Gastrointest Surg. 2014;18:

573–9.
19. de Zeeuw S, Ahmed Ali U, Donders RA, Hueting WE, Keus F, van Laarhoven CJ. Update of
complications and functional outcome of the ileo-pouch anal anastomosis: overview of evi-
dence and meta-analysis of 96 observational studies. Int J Colorectal Dis. 2012;27:843–53.
20. Fazio VW, Kiran RP, Remzi FH, Coffey JC, Heneghan HM, Kirat HT, Manilich E, Shen B,
Martin ST. Ileal pouch anal anastomosis: analysis of outcome and quality of life in 3707
patients. Ann Surg. 2013;257:679–85.
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Rectum. 2012;55:79–84.
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Chapman R. Outcomes after ileal pouch anal anastomosis in patients with primary sclerosing
cholangitis. J Crohns Colitis. 2014;8:662–70.
23. Cho CS, Dayton MT, Thompson JS, Koltun WA, Heise CP, Harms BA. Proctocolectomy-ileal
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24. Halverson AL, Hull TL, Remzi F, Hammel JP, Schroeder T, Fazio VW. Perioperative resting
pressure predicts long-term postoperative function after ileal pouch-anal anastomosis.
J Gastrointest Surg. 2002;6:316–20.
25. Gearhart SL, Hull TL, Schroeder T, Church J, Floruta C. Sphincter defects are not associated
with long-term incontinence following ileal pouch-anal anastomosis. Dis Colon Rectum.
2005;48:1410–5.
26. Scoglio D, Ahmed Ali U, Fichera A. Surgical treatment of ulcerative colitis: ileorectal vs ileal
pouch-anal anastomosis. World J Gastroenterol. 2014;20:13211–8.
Chapter 7
Management of Pouch-Vaginal Fistulas
Ido Mizrahi and Steven D. Wexner
Introduction
Since the initial description of restorative proctocolectomy in 1978 by Parks and

Nicholls [1], the stapled ileal-pouch anal anastomosis (IPAA) has evolved into the
mainstay surgical treatment for most patients who require surgery for ulcerative
colitis (UC) and many others with familial adenomatous polyposis (FAP) [2–5].
Pouch vaginal fistula (PVF) is a specific complication after IPAA, first reported by
Wong et al. in 1985 [6]. Though not a common problem, with reported incidence
rates ranging from 2.9 to 16.7 % [7–19], PVF is a source of considerable morbidity
for the patient and a technical challenge for the surgeon. PVF typically presents in
the first year after surgery; however, a late presentation might occur even after 10
years from surgery. The optimal management of PVF is not yet determined due to
the relative paucity of published data. Most authors agree that the management
depends on four basic etiologic/clinical factors: surgery related, sepsis related, dis-
ease related, and the location of the fistula.
Surgical technique in any operation is important for successful clinical results,
especially in complex procedures such as IPAA. In fact, increased experience has
been shown to decrease complications after IPAA [20, 21]. Tissue ischemia at the
anastomosis must strictly be avoided and therefore a tension-free anastomosis with
good blood supply should be obtained. It is crucial not to damage the rectovaginal
septum or “button hole” the vagina when dissecting the rectum, and to avoid incor-
poration of the posterior vaginal wall when firing the stapler. If identified at the time
of surgery, the anastomosis can be disconnected, the vagina repaired, and a hand-
sewn anastomosis re-constructed.
I. Mizrahi, MD • S.D. Wexner, MD, PhD (Hon) (*)

Department of Colorectal Surgery, Cleveland Clinic Florida, Weston, FL, USA

DOI 10.1007/978-3-319-40223-9_7
54 I. Mizrahi and S.D. Wexner
Despite this specific mechanism of injury associated with the double stapled
technique, large scale studies have shown no difference in the incidence of PVF
after stapled and hand-sewn anastomosis [18, 22–25]. Further, it is important to
note that a stapled anastomosis is likely to be more cephalad. Therefore pouch
advancement to the dentate line is more likely to be a good remedial option when
PVF complicates a stapled anastomosis. Conversely, following an index hand-
sewn anastomosis, pouch advancement may not be a viable option. As for pouch
type, Wexner et al. found no difference in the incidence of PVF for different pouch
types [15].
Pelvic sepsis remains a major determinant in the development of PVF, as high-
lighted by the high rate of this complication in patients with PVF. Groom et al. [14]
found that 65 % of patients with PVF had pelvic sepsis compared with 16 % without
PVF. Wexner et al. [15] reported pelvic sepsis in 35 % of their PVF patients. Lee
et al. [23] found a significantly greater incidence of pelvic sepsis in patients with a
PVF than in those without (26.3 % vs. 6.3 %; p = 0.003). Pelvic sepsis can either be
ascending – originating from a disrupted anastomosis, or descending – resulting
from an intraoperative contamination or a pelvic hematoma [15, 23]. These mecha-
nisms further emphasize the importance of meticulous technique with attention to
hemostasis, contamination, and a tension-free anastomosis with adequate blood
supply. Furthermore, pelvic sepsis might be caused by cryptoglandular perianal dis-
ease, which is more common in patients with colitis and may lead to an anovaginal
fistula [8]. Typically, PVF of cryptoglandular origin is associated with an internal
opening of the fistula below the IPAA. A series from St Mark’s Hospital reported 2
out of 17 PVFs arising below the IPAA and most likely independent of the original
pouch procedure [14].
Careful review of appropriate histopathologic materials by an expert gastrointes-
tinal pathologist may be crucial to future management options. This step is espe-
cially true for the small percentage of patients, approximately 2–3 %, who undergo
IPAA for UC only to find the long-term diagnosis is Crohn’s disease (CD). Lee et al.
[23] found a high correlation between PVF and CD, with 12 of the 23 women
(52 %) with a preoperative diagnosis of UC eventually diagnosed with CD. Other
studies have shown similar results. The average time to development of a PVF is
typically longer in patients with CD. Importantly, these patients suffer from a sig-
nificantly higher rate of pouch failure and ultimately excision. Patients who undergo
IPAA for indeterminate colitis also have a high rate of pouch complications includ-
ing PVF and pouch failure [26]. However, patients whose indication for surgery is
familial adenomatous polypos present with a significantly low rate of PVF when
compared to IBD patients [27, 28], implying inflammation plays a role in the patho-
genesis of PVF.
Patients with PVF may be asymptomatic or present with minor symptoms. They
may also present with severe symptoms such as vaginal discharge of fecal material
or gas, recurrent vaginitis, and vulvar irritation. Some cases of asymptomatic PVF
are found on routine pouchography prior to ileotomy closure. Once PVF is
7 Management of Pouch-Vaginal Fistulas 55
suspected, further investigation is needed to confirm the diagnosis and establish its
nature. As noted above, the surgeon should request the pathology slides for expert
pathology review. If not clinically evident, a perineogram and a water soluble con-
trast pouchogram may help to diagnose the presence and the level of the fistula tract.
Imaging with computed tomography (CT) scanning, ideally with contrast enema,
may also help to identify fistulous tracts, although magnetic resonance imaging
(MRI) (T1 weighted with fat suppression and IV gadolinium) is preferable. In
expert hands, endoanal ultrasound is also helpful in detecting sphincter deformity,
especially in women with a history of vaginal delivery. However, the reliability of
endoanal ultrasound is poor for fistula detection because the fistulous tracts in PVF
are short and wide.
Although clinical examination in the office will often confirm the diagnosis,
careful examination under anesthesia (EUA) may be preferable. EUA allows
access to the fistula and excludes associated sepsis while overcoming the potential
limitations of patient discomfort. It also allows identification of the level of the
internal opening, its relation to the anastomosis (usually the staple line), the direc-
tion of the tract, and the location of the external orifice in relation to the vaginal
wall, vaginal fourchette, labia, or perineum. While most tracts are short and
straight, they can be complex and branched, and a low PVF can mask the presence
of a higher fistula from the pouch-body to the mid-body of the vagina. If neces-
sary, introduction of dye, such as methylene blue, into the pouch with white swabs
in the vagina to identify staining is useful. Alternatively, for low fistulae, hydro-
gen peroxide gently instilled into the anus may demonstrate bubbles as they
emerge from the vaginal opening. Lastly, patients should typically undergo anal
manometry to assess the sphincter pressures, and a pudendal nerve terminal motor
latency study to assess for neural impairment, especially in women after
childbirth.
Search Strategy (See Table 7.1)
A literature search was carried out to identify articles on PVF. The search was done
on the electronic databases PubMed, Embase, and Medline, from 1980 to December
2015. The main search terms used were ‘pouch-vaginal fistula’, ‘ileoanal pouch-
vaginal fistula’ or ‘anal pouch-vaginal fistula’.
Table 7.1 Search Strategy

P (patients) I (intervention) C (comparator) O (outcomes)
Patients who underwent restorative See Table 1 Not applicable Fistula healing
proctocolectomy with ileal pouch anal Pouch retention
anastomosis and developed pouch-
vaginal fistula
Results
Many procedures have been proposed for the treatment of PVF, most of them
adopted from rectovaginal fistula repairs [29, 30]. The procedures can basically be
divided into those performed via a perineal approach or via an abdominal approach.
Of note, there are no randomized controlled trials and only one systematic review
on the management of PVF. All studies provide level IV evidence. Significant het-
erogeneity, a small number of patients, and differing reporting practices preclude
meta-analysis of the data. Pooled results for the different types of PVF repair are
presented in Table 7.2.
Perineal Approach
Seton Drain A draining seton is mainly used for establishing drainage of an associ-
ated abscess and for defining the fistula tract. Keighley et al. [12] reported a success
rate of 25 % in patients with the use of a seton as definitive treatment. However,
Wexner et al. (0/2) [15], Mallick et al. (0/3) [10] and Shah et al. (0/5) [18] all
reported 100 % failure rates. Tsujinaka et al. [31] showed complete healing in one
patient with an asymptomatic fistula. Arguments against its use are that the seton
may damage any residual anal sphincter, which is already thinned out in many
women, and that it may encourage further leakage. To date, there is no evidence to
Table 7.2 Pooled results for the different types of PVF repair
Type of repair Success rate
Perineal approach
Seton [10, 12, 15, 18, 31] 5/15 (33 %)
Fistulectomy [12, 14, 15] 3/22 (14 %)
Biological 0/11 (0 %)
Collagen plug [33] 2/6 (33 %)
Fibrin glue [31, 42]
Transanal ileal advancement flap [9, 10, 14, 15, 18, 23, 31, 34] 81/173 (47 %)
Transvaginal [10, 12–15, 18, 35, 36] 48/79 (60 %)
Gracilis muscle interposition [15, 31, 37–39] 6/10 (60 %)
Trans-anal pouch advancement [19, 41] 2/4 (50 %)
Abdominoperineal approach
(a) Abdominoperineal approach [10, 15, 16, 18, 19, 31, 42–44] Overall success rates
50–75 %
Pouch advancement 8/16 (50 %)
Redo pouch 20/39 (51 %)
(b) Pouch excision 60/401 (15 %) 100 %
(a) Some studies not indicating different success rates for pouch advancement vs. redo pouch
(b) Number represents the percentage of patients eventually requiring pouch excision
support seton use except for initial control of sepsis before definitive repair.
However, there are no studies to show whether use of a seton before definitive repair
of PVF improves outcomes. One exception might be a fistula below the IPAA
involving little or no sphincter muscle, where a draining seton followed by fistulot-
omy may be successful.
Fistulectomy Coring out of the fistula tract with repair of the internal opening at the
pouch level has been described with disappointing results [12, 14, 15]. There is cur-
rently no evidence to support its use in the management of PVF.
Biological Therapy
The use of a collagen button plug to treat PVF was first reported by Gonsalves et al.,
with healing observed in 4/7 (57 %) of ileal pouch-vaginal fistulas at 16 weeks [32].
The technique involves securing the button portion of the collagen plug on the
pouch side of the fistula with four dissolvable sutures. The button of the plug
detaches within 4 weeks with the collagen matrix left in situ. Disappointingly, these
results were not maintained long-term with 0/11 PVF successfully healed at 2 years
[33]. Early success probably related to the persistence of the collagen plug within
the tract, but failure of local tissue in-growth coupled with the relatively short length
of PVF led to long-term failure. Given these results, the use of biological tissue
plugs cannot be recommended for the management of PVF. Tsujinaka et al. [31]
reported the instillation of fibrin glue in the fistula tract with complete healing in 1
patient with a minimally symptomatic fistula and failure in 2/3 symptomatic patients
who eventually required pouch advancement and a redo pouch.
Transanal Ileal Advancement Flap
An ileal pouch advancement is essentially a variation of the mucosal advancement

flap used for a high perianal fistula. A flap of mucosa and submucosa is mobilized
from the ileal pouch, the internal opening is excised, and the flap is advanced and
sutured beyond the internal fistula opening. Mallick et al. [10] reported healing rates
of 42 % (20/48) when advancement flap was performed as a primary procedure and
66 % (4/6) when performed secondarily after a different procedure. Similar results
have been reported by others. Tsujinaka et al. [31] showed healing rates of 60 %
(6/10), while Shah et al. [18] and Ozuner et al. [34] reported success rates of 44 %
(17/39) and 45 % (15/24), respectively. Lee et al. [23] had a slightly higher success
rate of 50 % (10/20), with the rate increasing to 83 % (10/12) when excluding
patients with CD. Wexner et al. [15] reported successful fistula healing in 8/16
patients with this approach in a survey of North American colorectal units, whereas
Groom et al. [14] reported only one success in 10 attempts. Advantages of the ileal
pouch advancement flap include the relative simplicity of the procedure and that the
flap has more distal mobility [9]. The disadvantages of this approach include the
suboptimal exposure, the risk of damage to the sphincters in patients with border-
line incontinence, and the fact that the flap lies on the high pressure side of the
PVF. Circumferential advancement of the pouch is both technically easier and
ensures more mobilization than does anterior or anterolateral flap advancement.
Transvaginal Repair
Sagar et al. [35] reported the results of transvaginal repair for PVF in 11 patients,
each of whom had previously undergone an attempt to close the fistula with a col-
lagen button plug. Nine (81 %) were successful at a median follow-up of 14 (6–56)
months and the remaining two patients described symptomatic improvement.
Burke et al. [36] published the St. Mark’s Hospital experience with transvaginal
repair for PVF in 14 patients. They reported total success in 11/14 patients (78 %),
although 8 required multiple attempts to achieve long-term success. The largest
series of transvaginal repair of PVF reported by Mallick et al. [10] from the
Cleveland Clinic described a 55 % healing rate (15/27) when repair was performed
as a primary procedure and 40 % (2/5) when performed secondarily after a differ-
ent procedure. O’Kelly et al. [13] reported successful repair in 5/7 patients (71 %)
with this approach, and once again some patients in this series required more than
one attempt before complete healing was achieved. Others have reported success
rates of 0 % (0/1) [18, 31], 27 % (3/11) [15], and 100 % (1/1) [12, 14]. The repair
can also be augmented by placement of a collagen patch between the pouch and the
vagina.
Advantages of the transvaginal approach include better exposure than the trans-
anal approach, decreased risk of damage to the anal sphincters, and decreased ten-
sion. The procedure can be repeated if necessary and yields satisfactory results with
relatively less morbidity. Possible complications include dyspareunia, although
none of the patients reported dyspareunia in the series from St. Mark’s [36], and
hematoma because of the vascularity of the vagina. However, this risk can be mini-
mized with meticulous technique, drainage, and use of a vaginal pack [13, 18]
Gracilis Muscle Interposition Flap
There are five small published series reporting on the utility of the gracilis muscle
interposition flap specifically for the treatment of PVF. Gorenstein et al. [37]
reported successful repair in two women with PVF. Previous attempts at local
repair had failed in both patients and a simultaneous diverting loop ileostomy was
constructed. Anterior sphincteroplasty was performed in one patient for associ-
ated incontinence. Wexner et al. [15] reported results of a multicenter study
including treatment of PVF in 26 patients, 4 of whom underwent gracilis interpo-
sition flap with a 50 % success rate. In a later publication, Wexner et al. [38] pub-
lished results of gracilis flap in 53 patients, two of whom for the indication of
PVF. One patient had complete healing and the patient who did not heal was
eventually diagnosed with CD and opted to have a permanent ileostomy. Zmora

et al. [39] published their experience with the gracilis interposition flap in 9
patients. Only one patient had a PVF and the fistula ultimately completely healed.
Another report by Tsujinaka et al. [31] described one patient with a failed gracilis
interposition. In general, interposition flaps are particularly useful after previous
failed repairs as well as when abdominal procedures are contraindicated. The
expected perioperative morbidity is 33–50 % and includes perineal wound infec-
tion, urethral stricture, fever, urinary retention, and perineal bleeding [38, 40].
Perhaps because of the technical challenge, the procedure seems to have been
underused. This procedure should be preceded by fecal diversion. At present, the
low reported numbers and the relative complexity of the procedure prevent it from
being strongly recommended as a first-line treatment. Another form of flap used
for treating rectovaginal fistulas is the martius flap; however results with treating
PVF have not been published.
Transanal Pouch Advancement
The technique of transanal disconnection of the ileal pouch from the IPAA, advance-
ment of the pouch, and re-suture at the dentate line can be employed in patients with
PVF, especially in slimmer patients with demonstrable mobility of the pouch above
the level of the anastomosis. As noted above, advantage of this procedure is that it
allows healthy, full thickness tissue to be delivered to the perineum. This operation
should be offered after stoma creation. Both Fazio et al. [41] and Heriot et al. [19]
showed that this procedure was successful in 1/2 of their patients.
Abdominoperineal Approach
“High” PVF that arises from the mid-body of the ileal pouch requires a transab-
dominal approach. This approach may also be selected after failed local repairs and
in patients with ongoing pelvic sepsis due to abscess cavities with granulation tis-
sue that cannot be completely removed using a local approach. The pouch needs to
be carefully mobilized down to the level of the pelvic floor with attention given to
the anterior wall of the pouch and the posterior wall of the vagina. There are basi-
cally three surgical options: pouch advancement, pouch redo with a new handsewn
IPAA, and pouch excision. The reported overall success rates for treating a PVF via
the abdominoperineal approach are approximately 50–75 %[10, 15, 16, 18, 19, 31,
42–44]. Despite these relatively high success rates, it should be noted that
transabdominal revision of the pouch is technically demanding, carries a significant
risk of loss of the pouch [10, 16, 18], and an unsuccessful attempt may result in
significant loss of small bowel with the risk of short gut syndrome. The patient
needs to be fully counseled about these risks and preferably referred to a center of
excellence in this field.
Diversion
A diverting ileostomy is commonly used in patients with PVF, mainly to control

patient symptoms and pelvic sepsis and to divert fecal material from the repair.
Some authors have reported healing with the ileostomy only [15, 31]; however,
most authors combine construction of the diverting ileostomy either before or at the
time of repair [10, 18, 23]. Lee et al. [23] found higher success rates (60 % vs. 45 %)
when a diverting ileostomy was performed before a transanal pouch advancement.
However, there is little evidence that a diverting ileostomy improves the chance of
PVF healing. A permanent diversion, with or without pouch excision, is opted when
all other attempts have failed.
Recommendations
As noted above, all studies provide low quality data, providing weak
recommendations.
1 . Patients presenting with pelvic sepsis should undergo EUA and seton drainage.
2. A diverting ileostomy should be considered for all patients before or at the time
of repair.
3. Local repair should be attempted first for low PVF.
4. An abdominoperineal approach should be reserved for “high” PVF and failed
attempts at local repair.
A suggested algorithm based on results and recommendations is presented in
Fig. 7.1.
The management of pouch complications such as PVF presents a major challenge

to the surgeon. Therefore, these patients should ideally be referred to large volume
experienced centers for a more optimal outcome. The surgeon should diligently
study the patients’ prior relevant history including pathology and operative reports,
as well as physiologic and imaging tests in order to tailor the correct procedure for
each patient. Patient counseling includes explaining that successful treatment often
requires several operations over a long time period in order to achieve healing.
Patients with CD should also be aware of the higher rate of pouch failure they may
encounter. Local repair via the perineal approach should be considered when deal-
ing with a low PVF, and that the transanal ileal advancement flap, gracilis interposi-
tion, and pouch advancement are all viable options with equivalent success rates.
The abdominoperineal approach should be left for high fistulas and those failing
previous local attempts. Although not supported by high quality data, a laparoscopic
PVF
Seton drain
Control sepsis and symptoms
Diversion
Review pathology
Evaluation
EUA
Imaging (perineogram, pouchogram, MRI, CT, endo-anal US)
Physiology (anal manometry, PNTML)
Non-Crohn’s disease Crohn’s disease
Fistula below IPAA Low PVF High PVF

(cryptoglandular origin)
Medical treatment
Local repair: Local repair: Abdominoperineal approach: Success

seton, fistulotomy, transanal advancement flap, laparotomy vs. laparoscopy Failure
advancement flap transvaginal repair,
gracilis interposition,
transanal pouch advancement Consider local repair
Pouch
Redo pouch Pouch excision
advancement
Fig. 7.1 Suggested treatment algorithm
diverting loop ileostomy before or at the time of repair offers the patient symptom
relief, better sepsis control, and perhaps an increased chance of healing. It seems
that no single procedure is appropriate for all cases of PVF; therefore the surgeon
should be familiar with the existing armamentarium of treatment options and be
continually updated on their success rates.
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Lippincott, Williams, and Wilkins.
Chapter 8
Crohn’s Colitis and Ileal Pouch Anal
Anastomosis
C. Peirce and Feza H. Remzi
Introduction
Traditionally, the ileal pouch anal anastomosis (IPAA) operation has not been
offered to patients with Crohn’s disease (CD). Patients with Crohn’s colitis are often
excluded from undergoing IPAA related to a number of key concerns: the risk of
developing recurrent disease in the pouch necessitating pouch excision with possi-
ble ensuing short bowel syndrome, coupled with the risks of significant pouch dys-
function and the need for long-term medical therapy. However, surgical dogma is
being challenged in more recent times with authors now reporting encouraging out-
comes following IPAA in patients with either a preoperative or postoperative diag-
nosis of Crohn’s colitis.
Patients with Crohn’s colitis for whom an end ileostomy is not an acceptable
option at that time have three potential reconstructive options to restore bowel con-
tinuity: ileorectal anastomosis, ileal pouch rectal anastomosis (IPRA) or ileal pouch
anal anastomosis (IPAA), also known as restorative proctocolectomy. The first two
restorative operations require either complete rectal sparing or sparing of the distal
rectum whereas the latter is the only option to restore intestinal continuity in patients
requiring proctectomy as a result of Crohn’s proctitis. This chapter focuses specifi-
cally on these patients i.e., patients with documented CD of the colon and rectum
requiring either a proctocolectomy or completion proctectomy after initial subtotal
colectomy for disease management.
C. Peirce
Department of Colorectal Surgery, Cleveland Clinic, Cleveland, OH, USA
F.H. Remzi (*)
Department of Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic,
9500 Euclid Avenue – A30, Cleveland, OH, USA

DOI 10.1007/978-3-319-40223-9_8
66 C. Peirce and F.H. Remzi
Methods
A search of all English language PubMed articles from 1990 to 2015 was performed
using the following terms: Crohn’s disease, Crohn’s colitis, ileal pouch anal anasto-
mosis, restorative proctectomy, restorative proctocolectomy, completion proctec-
tomy, proctocolectomy and ileostomy. These terms were in keeping with the PICO
table below on which this chapter is based. All relevant articles were reviewed and
appropriate references interrogated.
Patient Outcomes
Population Intervention Comparator studied
Crohn’s Ileal pouch anal Proctocolectomy/completion Pouch morbidity;
colitis anastomosis proctectomy with end ileostomy pouch excision;
(IPAA) quality of life
Results
There is a clear division in the literature regarding the outcomes of IPAA in CD in

terms of the time of diagnosis of the primary disease. Studies divide the timing of
the CD diagnosis as preoperative (resulting in an ‘intentional’ IPAA formation),
perioperative (IPAA formation with ‘incidental’ or ‘accidental’ CD diagnosis on
analysis of the surgical specimen) or at a later date following IPAA creation (so
called ‘delayed’ diagnosis). A comparison of the data for these three distinct groups
has been reported in prior studies. However, the ensuing recommendations and
debate are based solely on those studies pertaining to patients with a documented
diagnosis or high clinical suspicion of CD prior to undergoing IPAA, the aforemen-
tioned ‘intentional’ IPAA cohort.
The first published paper of ‘intentional’ IPAA formation in CD (patients in
whom there was a high clinical suspicion based on the findings described below)
was from Hyman and colleagues from the Cleveland Clinic in 1991 [1]. They
reported on 25 patients with a postoperative pathologic diagnosis of CD out of 362
consecutive patients undergoing IPAA for a preoperative diagnosis of ulcerative
colitis (UC). Of these 25 patients, 9 had preoperative features suggestive of CD: 5
with perianal disease (fistula, fissure or stricture), 2 with abnormal distribution of
colonic disease, 1 with a cecal stricture and possible terminal ileal disease and 1
with a rectovaginal fistula. Although none of these 9 patients had a definitive preop-
erative diagnosis of CD, the above pathology would frequently be cited as a reason
not to perform IPAA in cases with indeterminate pathology. At a mean follow-up of
34.8 months, only 1 of the 9 patients had a functioning pouch. Of the remainder, 1
died, 1 remained diverted and 6 had their pouch excised at a mean of 17.6 months
postoperatively. The authors concluded that patients who manifest clinically as CD
and have confirmatory pathology do very poorly following IPAA with short disease-
free intervals and a high pouch failure rate.
8 Crohn’s Colitis and Ileal Pouch Anal Anastomosis 67
Following this, Panis and colleagues published their initial results [2]. From
1985 onwards, they considered IPAA in selected CD patients in whom a proctec-
tomy was required for either proctitis or rectal stenosis. Strict inclusion criteria were
employed to ensure the disease was confined solely to the colorectum: all patients
underwent an examination under anesthesia prior to IPAA to exclude anoperineal
disease and also had a small bowel contrast study to exclude concurrent enteric
disease. Eighteen patients were recruited over an initial 7-year period. These 18
patients were combined with a further 13 patients with a pre-IPAA diagnosis of
indeterminate colitis (IC) which was subsequently shown to be CD in the postopera-
tive specimen. This group then totaled 31 patients and reported outcomes were for
the group as a whole (i.e., n = 31) and were not subdivided into the specific diagnos-
tic timeframes of pre-operative (n = 18) or post-operative (n = 13) CD diagnosis. The
results were encouraging: 6 patients had a CD-related complication with 2 of these
ultimately requiring pouch excision and the remaining 4 patients reporting accept-
able pouch function. Overall, 90 % of the cohort had a functional pouch at 5-year
follow up. When compared with a corresponding ulcerative colitis (UC) cohort
(n = 71) over the same time period, there was no demonstrable difference in terms of
stool frequency, continence, gas/stool discrimination, leak or need for protective
pads and sexual activity.
The same group subsequently reported on their experience with 41 patients, 26
of whom had a preoperative CD diagnosis [3]. Once again, the results in terms of
CD-related complications are reported for the whole group and not reported in sub-
group analysis for the intentional IPAA patients and incidentally diagnosed CD
patients following IPAA. Twenty patients were followed for 10 years or more with
a CD-related complication rate of 35 % and an impressive pouch excision rate of
only 10 %.
The Cleveland Clinic adopted the intentional IPAA in CD patients in the late
1990’s and subsequently reported its initial experience [4]. The analysis included 20
patients who underwent an intentional IPAA out of the study cohort of 204 patients
(additional 97 patients with incidental diagnosis and 87 patients with delayed diag-
nosis). These 20 patients had a median time of 6.6 years from CD diagnosis to IPAA
with a median follow up of 5 years and were more likely to be female. The 10- year
pouch retention rate in the 20 patient strong intentional group was 85 % and thus
closely mirrored the long-term follow up reported by Regimbeau and colleagues of
90 % pouch retention at 10 years as described above. For those patients with retained
IPAA, 72 % reported near-perfect or perfect continence, 68 % reported rare or no
fecal urgency and the median number of daily bowel movements was 7 (range 2 –
20). Interestingly, these patients also reported their quality of life and quality of
health as 9/10 and 9/10 respectively and happiness with the IPAA procedure as
10/10.
The Mount Sinai Medical Center, New York, reported their experience with 13
patients who received an IPAA, 4 of whom were definitively diagnosed preopera-
tively with CD [5]. None of these patients had perianal disease and all had disease
solely limited to the colon. Two of these 4 patients (50 %) subsequently developed
perianal disease, 2 (50 %) developed postoperative complications and 1 patient
(25 %) required a pouch excision. Of note, the outcomes for all 13 CD patients were
compared with a matched cohort of patients undergoing IPAA for chronic UC; the
CD patients had fewer bowel movements per 24 h, a lower incidence of inconti-
nence and a lower incidence of pouchitis.
The most recent series on the intentional use of IPAA in CD patients reported on
17 patients [6]. Seven of 17 patients (41 %) developed recurrent CD following IPAA
and this compared with a corresponding postoperative incidence of 11 % in a UC
cohort undergoing IPAA during the same time period. The pouch excision rate over
an average follow up of 60 months in the 17 preoperatively diagnosed CD patients
was an impressive 6 %. This study is also notable in that 9 of the 17 patients had a
preoperative diagnosis of CD outside of the colorectum: 5 patients had previously
undergone small bowel resections with no evidence of active small bowel disease
and 4 patients had perianal disease (3 perianal fistulae, 1 anal stenosis), where the
fistulae were managed by insertion of draining setons with subsequent evaluation
demonstrating no evidence of active perianal sepsis.
The most current study on this topic is a United States multi-institutional study
examining the cost-effectiveness of two surgical options in patients with Crohn’s
colitis [7]. They compared what is referred to as ‘colectomy with permanent ileos-
tomy’ with IPAA. It should be noted that some of the evidence for the former group
involves patients described in a prior study who underwent either total abdominal
colectomy with end ileostomy or panproctocolectomy with end ileostomy [8] and
the reader cannot determine whether it was only the panproctocolectomy patients
who were included in the cost analysis by Taleban and colleagues. Additionally,
Taleban and colleagues assumed that patients undergoing J-pouch formation would
have ‘complete mucosectomy’, yet this is clearly not the operative approach
employed by all. Nonetheless, colectomy with permanent end ileostomy was shown
to be more cost-effective unless the associated surgical cost exceeded $20,167 at
which point IPAA was the more effective option. They also reported that IPAA was
the more effective strategy with an incremental cost-effectiveness ratio of $70,715
per QALY gained.
Postoperative Pouch Quality of

Author Year Number of patients morbidity excision evidence
Hyman 1991 9 8/9 (89 %) 6/9 (67 %) Low
Panis 1996 31 (18 intentional; 13 11/31 early (35 %) 2/31 (6 %) Low
incidental) 6/31 CD related
(19 %)
Regimbeau 2001 41 (26 intentional; 15 10/41 early (24 %) 3/41 (7 %) Low
incidental) 11/41 CD related
(27 %)
Melton 2008 20 Not reported 2/20 Low
(10 %)
Grucela 2011 4 2/4 (50 %) 1/4 (25 %) Low
Le 2013 17 4/17 early (24 %) 1/17 (6 %) Low
7/17 CD related
(41 %)
Since the introduction of IPAA as part of our surgical armamentarium, there have
only been 67 patients reported with a preoperative diagnosis of CD and thus an
intentional IPAA. This number can be increased to 76 when the 9 patients with a
high preoperative suspicion of CD reported in the initial study from the Cleveland
Clinic are included. Based on this, the evidence for intentional IPAA in Crohn’s
colitis is low and the recommendation for IPAA formation in patients with Crohn’s
colitis is weak.
The top priority is providing a personalized and tailored plan of care for each
patient. We believe that some of the most critical and complex parts of working
with a patient with Crohn’s disease occur outside of the operating room. Not only
is it imperative that detailed medical and surgical histories are obtained, but it is
also essential to develop a relationship with the patient at the first encounter and
to gain an understanding of the patient’s goals in terms of the potential for surgery
and possible outcomes. The patient and their family/caregivers should be
approached on a personal level, understanding their own goals and work for open,
honest dialogue whilst forming a specific individual surgical strategy. Having
done this, together the patient and colorectal surgeon embark on a lifelong rela-
tionship. In our experience, this specific group of patients are very well informed
on the potential surgical options and present to us with the intention of undergoing
IPAA.
The formation of an IPAA for Crohn’s colitis is considered provided there are no
gross manifestations of small bowel disease (unless it is backwash ileitis) or peri-
anal CD; a single, limited perianal fistula can be acceptable but a rectovaginal fistula
is not. CT enterography is the preoperative imaging modality of choice to examine
the small bowel and a thorough bedside perianal examination is performed and if
there are questionable findings, patients proceed to a formal examination under
anesthesia. Risk factors, especially a personal history of smoking and a family his-
tory of CD, are always sought as these patients are at increased risk for subsequent
development of CD of the ileal pouch. Patients referred from other institutions may
undergo repeat colonoscopy with biopsies and all previous outside pathology slides
are reviewed again by a dedicated inflammatory bowel disease histopathology team.
All patients have their nutritional status optimized preoperatively. Preoperative
counseling regarding the potential for complications is extensive, with particular
emphasis on the risk for significant small bowel loss if there is a requirement for
pouch excision and that a re-do pouch may not be an option. Similarly, patients are
advised that even if preoperative imaging is reassuring, there is always the potential
that small bowel CD may be discovered perioperatively.
The technical approach to IPAA relies on careful and meticulous handling of the
bowel and dissection in natural, anatomic tissue planes. When presented with a new
patient with isolated Crohn’s colitis, a 3-stage procedure is recommended and
patients should ideally be steroid and biologic free prior to the second stage (i.e.,
pouch formation). We do not recommend a one-stage procedure and will perform a
2-stage procedure in select cases. Regardless of the operative approach (open or
laparoscopic), the small bowel must be examined in its entirety from the ligament
of Treitz to the ileocecal valve and if there is a suspicious area, this should be inter-
rogated and may require an enterotomy to ensure there is no luminal evidence of
disease. We strongly favor the total mesorectal excision technique when performing
proctectomy. Residual distal tissue may lead to pouch emptying issues, which may
significantly affect pouch function and quality of life. The J-configuration is the
pouch subtype of choice and the double-stapled pouch-anal anastomosis technique
is favored. In highly motivated patients who wish to avoid a permanent ostomy in
whom there is limited perianal disease as previously referred to, a mucosectomy
and hand-sewn anastomosis can be utilized when necessary. We have previously
reported on the learning curve for IPAA formation which is estimated to be 23 cases
when performing the stapling technique [9]. All new IPAAs are defunctioned after
their creation for a minimum of 3 months and interrogated with a radiological con-
trast enema prior to ileostomy closure.
In the unfortunate case when a Crohn’s patient with an IPAA develops anoperi-
neal sepsis or anastomotic issues, the algorithm is to begin by checking one’s own
‘footsteps’: it is critical to distinguish symptoms due to sequelae of Crohn’s disease
from a technical complication (which are more likely to develop within 3 months of
surgery). These have very different solutions and management approaches to say
the least.
IPAA surgery in patients with Crohn’s disease is technically and emotionally
challenging, but is also rewarding in that it offers a life-changing avenue for the
patient and surgeon alike.
Patients with Crohn’s colitis and no evidence of small bowel or perianal

disease are candidates for IPAA following thorough preoperative counseling
and discussion regarding potential postoperative outcomes (evidence low;
weak recommendation).
References
1. Hyman NH, Fazio VW, Tuckson WB, Lavery IC. Consequences of ileal pouch-anal anastomo-
sis for Crohn’s colitis. Dis Colon Rectum. 1991;34:653–7.
2. Panis Y, Poupard B, Nemeth J, Lavergne A, Hautefeuille VP. Ileal pouch/anal anastomosis for
Crohn’s disease. Lancet. 1996;347:854–7.
3. Regimbeau MD, Panis Y, Pocard M, Bouhnik Y, Lavergne-Slove A, Rufat P, Matuchansky C,
Valleur P. Long-term results of ileal pouch-anal anastomosis for colorectal Crohn’s disease. Dis
Colon Rectum. 2001;44:769–78.
4. Melton GB, Fazio VW, Kiran RP, He J, Lavery IC, Shen B, Achkar J-P, Church JM, Remzi
FH. Long-term outcomes with ileal pouch-anal anastomosis and Crohn’s disease. Ann Surg.
2008;248:608–16.
5. Grucela AL, Bauer JJ, Gorfine SR, Chessin DB. Outcome and long-term function of restorative
proctocolectomy for Crohn’s disease: comparison to patients with ulcerative colitis. Colorectal
Dis. 2011;13:426–30.
6. Le Q, Melmed G, Dubinsky M, McGovern D, Vasiliauskas EA, Murrell Z, Ippoliti A, Shih D,
Kaur M, Targan S, Fleshner P. Surgical outcome of ileal pouch-anal anastomosis when used
intentionally for well-defined Crohn’s disease. Inflamm Bowel Dis. 2013;19:30–6.
7. Taleban S, Van Oijen MG, Vasiliauskas EA, Fleshner PR, Shen B, Ippoliti AF, Targan SR,
Melmed GY. Colectomy with permanent end ileostomy is more cost-effective than ileal pouch-
anal anastomosis for Crohn’s colitis. Dig Dis Sci. 2016;61(2):550–9.
8. Fichera A, McCormack R, Rubin MA, Hurst RD, Michelassi F. Long-term outcome of surgi-
cally treated Crohn’s colitis: a prospective study. Dis Colon Rectum. 2005;48:963–9.
9. Tekkis PP, Fazio VW, Lavery IC, Remzi FH, Senagore AJ, Wu JS, Strong SA, Poloneicki JD,
Hull TL, Church JM. Evaluation of the learning curve in ileal pouch-anal anastomosis surgery.
Ann Surg. 2005;241:262–8.
Chapter 9
Steroid Management in Patients Undergoing
Surgery for IBD
Karen Zaghiyan and Phillip Fleshner
Introduction
Often faced with the challenge of operating on steroid-treated patients with inflam-
matory bowel disease (IBD), colorectal surgeons must be well versed in the periop-
erative steroid management of this patient cohort. Historically, standard practice has
entailed stress-dose or high-dose perioperative steroids in these patients undergoing
surgery to prevent perioperative adrenal insufficiency (AI), cardiovascular collapse
and death. Stress-dose steroids typically consist of hydrocortisone 100 mg intrave-
nous (IV) given preoperatively and continued every 8 h postoperatively with a taper
down to the preoperative dose over 2–3 days [1]. However, this practice is anecdotal
and largely based on case reports from the 1950 s [2, 3] demonstrating cardiovascu-
lar collapse and death in 2 patients whose steroids were abruptly discontinued
before surgery.
Furthermore, perioperative high-dose steroids are not without consequence and
have been associated with impaired wound healing, hyperglycemia, hypertension,
fluid and electrolyte imbalance, immunosuppression and psychological effects [4]. It
has been suggested that the typical recommendation for supplementation with 200–
300 mg of hydrocortisone per day is supraphysiologic and a much smaller (maximum
of 150 mg/day) dose is necessary to overcome surgical stress [5]. While suppression
of the hypothalamic-pituitary-adrenal (HPA) axis is known to occur with chronic
corticosteroid supplementation [4], the amount and duration of steroid exposure nec-
essary to suppress an appropriate response to surgical stress is unknown, nor is the
K. Zaghiyan, MD • P. Fleshner, MD (*)

Section of Colon and Rectal Surgery, Cedars-Sinai Medical Center,
8737 Beverly Blvd. Suite 101, Los Angeles, CA, USA
e-mail: [email protected]; [email protected]

DOI 10.1007/978-3-319-40223-9_9
74 K. Zaghiyan and P. Fleshner
Table 9.1 PICO questions

Steroid-treated Low-dose High-dose or Perioperative
patients with or perioperative stress-dose hemodynamic instability,
without IBD steroids perioperative adrenal insufficiency,
undergoing colorectal steroids morbidity, mortality,
or non-colorectal infectious complications
surgery
Patients with or No corticosteroids High-dose or Perioperative
without IBD, stress-dose hemodynamic instability,
previously treated perioperative adrenal insufficiency,
with steroids within 1 steroids morbidity, mortality,
year undergoing infectious complications
colorectal or
non-colorectal
surgery
duration of time necessary to overcome this HPA axis dysfunction [6]; some reports
suggest this may take up to a year [7]. Thus, stress-dose steroids have even been
advocated for patients previously treated with corticosteroids within the past year.
Over the past 6 decades, several studies in IBD and non-IBD patients have
challenged the treatment algorithms for the use of perioperative stress-dose ste-
roids. Yet, there remains great variability in perioperative steroid dosing for IBD
patients undergoing colorectal surgery [8]. In this chapter, the literature pertaining
to perioperative steroid dosing is reviewed and followed by our recommendations
for steroid management in patients with IBD undergoing colorectal surgery.
Search Strategy
Relevant PICO (Population, Intervention, Comparator, Outcome) questions were

generated (Table 9.1). A Medline and PubMed search was conducted for publica-
tions in the English language between January 1952 and November 2015 using the
following search terms: (‘inflammatory bowel disease’ or ‘IBD’ or ‘ulcerative coli-
tis’ or ‘Crohn’s’ or ‘organ transplant’ or ‘transplant’ or ‘rheumatoid arthritis’ or
‘steroid-treated’) and (‘corticosteroid’ or ‘steroid’) and (‘colorectal’ or ‘colorectal
surgery’ or ‘surgery’ or ‘surgical’ or ‘operation’ or ‘operative’ or ‘perioperative’)
and (‘stress-dose’ or ‘high-dose’ or ‘low-dose’ or ‘dosing’ or ‘coverage’ or ‘previous
steroid’) and (‘adrenal insufficiency’ or ‘hemodynamic’ or ‘outcome’ or ‘complica-
tion’ or ‘morbidity’ or ‘mortality’). We also searched the reference section of each
relevant article to identify additional articles pertaining to this topic. Retrospective
and prospective, observational and randomized studies were included. Given the
paucity of studies investigating IBD patients undergoing colorectal surgery, the
search was expanded to include organ transplant recipients and other non-IBD ste-
roid treated patients undergoing non-colorectal surgery.
9 Steroid Management in Patients Undergoing Surgery for IBD 75
Results
Over the years, several studies have been performed to assess the clinical utility and
optimal dose of perioperative corticosteroids in steroid-treated patients undergoing
surgery (Table 9.2). Initial studies challenging the concept of stress-dose steroids
were performed in an era where there were serious concerns about operative wound
healing. In these studies, patients underwent surgery without any perioperative ste-
roids, and clinical parameters and HPA function were evaluated. In 1962, Solem
and Lund reported 30 patients whose steroids had been stopped more than 4 weeks
before surgery undergoing various surgical procedures (IBD undergoing major
colorectal surgery, n = 4) without perioperative steroid cover and showed no impend-
ing hemodynamic collapse with this management [9]. Two studies investigated
patients on steroids at the time of surgery who were operated on without periopera-
tive steroids, measured HPA axis testing and clinical parameters. Hypotension
attributed to AI occurred in 4 out of 125 patients combined [10, 11].
In a follow up study, Kehlet and Binder showed that preoperative ACTH stimula-
tion testing correlated with perioperative HPA function in 48 steroid treated patients
undergoing surgery (colorectal, n = 7) without perioperative steroids, but no patients
had perioperative hemodynamic instability or required stress-dose steroids [12]. In
1981, Knudsen performed a retrospective study evaluating 250 steroid-treated IBD
patients undergoing major colorectal surgery [13]. In 50 patients, perioperative ste-
roid cover was provided whereas the remaining 200 patients underwent surgery
without perioperative steroids. The study included 3 groups of patients: (1) patients
on steroids at the time of surgery (n = 48); (2) patients whose steroids were stopped
1 week to 2 months before surgery (n = 76); and (3) patients off steroids greater than
2 months before surgery (n = 126). Intraoperative hypotension occurred in 29
patients (11.6 %) but was less common in the cohort off steroids more than 2 months
before surgery (5.6 %). In 9 patients, intraoperative rescue hydrocortisone was
given, although none of these patients had proven biochemical evidence of adreno-
cortical insufficiency. Of 8 patients developing postoperative hypotension, 2 patients
on steroids at the time of surgery who underwent surgery without steroid cover were
thought to have AI (1 biochemically proven). These early studies suggested the
need for perioperative steroids in patients on steroids at the time of surgery. However
the optimal perioperative steroid dose necessary to prevent AI and the utility of
stress-dose steroids remained unclear at that time.
Subsequent studies evaluated various perioperative steroid dosing regimens con-
sisting of low-dose steroids or maintaining patients on their preoperative steroid
dose without a stress-dose. In 1981, the utility of a single preoperative stress-dose
(hydrocortisone 100 mg) versus no stress-dose followed by reinstitution of the
patient’s preoperative steroid dose after surgery was prospectively studied in 61
steroid-treated patients with rheumatoid arthritis undergoing 107 major or minor
orthopedic operations [14]. The authors found no significant difference in the need
for perioperative rescue steroids in patients treated with stress-dose steroids (24 %)
or not (17 %). In a small study of 14 steroid-treated patients (IBD, n = 7) compared
76
Table 9.2 Studies evaluating perioperative steroid dosing

Study Quality of
First author (year) Patients studied Intervention design N Outcome evidence
Solem (1962) [9] Patients previously treated with No periop R 30 No unexplained death Very low
steroids/various surgeries (n = 4 steroids attributed to AI
IBD/CRS).
Jasani (1968) [10] RA/anterior synovectomy No periop PO 21 steroid 1 patient with abnormal Very low
steroids treated vs. 20 preop ACTH had
controls hypotension responsive to
steroids.
Kehlet (1973) Steroid-treated patients No periop PO 104 3 patients with Low
[11] undergoing various major/minor steroids hypotension and low
operations cortisol thought to be AI
Knudsen (1981) IBD/CRS 200 with no R 250 11 cases of hypotension Very low
[13] periop steroids, treated with steroids/
50 received possible AI
steroids
Lloyd (1981) [14] RA/Orthopedic surgery Stress-dose vs. PO 61 No difference in periop Very low
usual daily dose. steroid supplementation
between the 2 groups
Symreng (1981) Various patients (n = 7 IBD, If impaired PO 14 steroid- No hemodynamic Very low
[15] n = 16, CRS) ACTH stim treated instability
test > HC 25 mg patients and 8
IV preop then steroid-naïve
100 mg IV/24 h. controls
If normal ACTH
stim test: no
periop steroids.
Return to usual
daily dose
postop.
K. Zaghiyan and P. Fleshner
Study Quality of
Bromberg (1991) Renal transplant patients admitted Usual daily dose PO 40 No unexplained Very low
[16] w/significant physiologic stress hemodynamic instability
Bromberg (1995) Renal transplant patients/various Usual daily dose PO 52 No clinical or laboratory Very low
[17] surgeries evidence of
adrenocortical
insufficiency
Friedman (1995) Renal-transplant or RA/major Usual daily dose PO 28 All patients with Very low
[18] orthopedic surgery endogenous adrenal
function. No unexplained
hemodynamic instability.
Glowniak (1997) Various (colorectal n = 2) with Stress-dose vs. RCT 18 No episodes of AI. One in Very low
[20] positive ACTH stim test placebo. Return each group with
to usual daily hypotension.
dose postop.
Thomason (1999) Organ transplant/gingival surgery Stress-dose vs. RCT 20 No hemodynamic Very low
[21] placebo. Return instability
to usual daily
dose postop.
9 Steroid Management in Patients Undergoing Surgery for IBD
Mathis (2004) Organ transplant/lymphocele Stress-dose vs. R 58 No hypotension, Very low

[19] drainage no steroid. arthralgia, ileus, mental
Return to usual status changes. Blood
daily dose glucose higher with
postop. stress-dose
Zaghiyan (2011) IBD/CRS previously on steroids No periop R 49 No difference in Low
[24] within 1 year steroids hemodynamic instability
Zaghiyan (2012) IBD/CRS HDS vs. LDS RO 32 No unexplained Very low
[22] hemodynamic instability
(continued)
77
78
Table 9.2 (continued)
Study Quality of
Zaghiyan (2012) IBD/CRS HDS vs. LDS R 97 No difference in Moderate
[23] hemodynamic instability
Aytac (2013) [25] IBD/CRS Stress-dose vs. R 235 More tachycardia with Moderate
usual daily dose stress-dose otherwise no
difference in
hemodynamic instability
Zaghiyan (2014) IBD/CRS HDS vs. LDS RCT 92 Non-inferiority of LDS High
[26] vs. HDS with respect to
postural hypotension; no
difference in
hemodynamic instability.
More infections with
HDS.
IBD inflammatory bowel disease, CRS colorectal surgery, RA rheumatoid arthritis, ACTH adrenocorticotropic hormone, HDS high-dose steroids, LDS low-dose
steroids, R retrospective, PO prospective observational, RO retrospective observational, RCT randomized controlled trial
We recommend that steroid-treated patients undergoing major colorectal surgery be managed with low-dose perioperative steroids in the perioperative period
(evidence quality high; strong recommendation)
K. Zaghiyan and P. Fleshner
with 8 steroid-naïve controls undergoing various operations (major colorectal sur-

gery, n = 16), Symreng and colleagues showed that steroid-treated patients with
abnormal preoperative ACTH-stimulation testing (n = 6) can be managed with low-
dose steroids (hydrocortisone 25 mg IV at the induction of anesthesia followed by
100 mg IV over the next 24 h) followed by reinstitution of the preoperative dose,
whereas patients with a normal ACTH stimulation testing can be managed without
steroids on the day of the operation [15]. This steroid regimen resulted in periopera-
tive plasma cortisol levels similar to steroid-naïve patients and no patients had signs
of hemodynamic collapse.
In the 1990s, Bromberg and colleagues performed 2 prospective cohort studies
evaluating renal transplant recipients admitted with significant physiologic stress
(n = 40) or for various operations (n = 52) who were managed with only their usual
steroid dose [16, 17]. Whereas almost all patients had normal urinary cortisol levels
and no signs of unexplained clinical hemodynamic insufficiency, ACTH-stimulation
testing appeared to overestimate adrenal dysfunction in a majority of patients. In
1995, Friedman and colleagues prospectively evaluated 28 renal-transplant or rheu-
matoid arthritis patients on an average prednisone dose of 10 mg/day undergoing
major orthopedic surgery [18]. All patients had endogenous adrenal function and no
episodes of AI occurred. In 2004, another retrospective study of 58 pancreas and
kidney transplant recipients undergoing lymphocele drainage showed no difference
in hypotension, arthralgia, mental status changes, ileus or wound healing in patients
treated with stress-dose steroids or not, but patients treated with stress-dose steroids
had more hyperglycemia [19].
Two underpowered randomized-controlled studies were performed in the 1990s.
The first was a randomized, double-blind study of 18 steroid-treated patients with
positive ACTH stimulation test undergoing various surgical procedures (2 colorec-
tal) managed with either stress-dose steroids or placebo plus the patient’s baseline
steroid dose [20]. Two episodes of hypotension occurred, one in each group, both
related to bleeding or hypovolemia. The authors concluded that patients with sec-
ondary AI do not experience hypotension or tachycardia when given only their pre-
operative steroid dose for surgical procedures. The second study was a randomized,
double-blind, crossover study of 20 organ transplant recipients on prednisone (5 –
10 mg) undergoing gingival surgery, randomized to hydrocortisone 100 mg IV or
placebo preoperatively during their first surgery and the opposite for the second
surgery [21]. Despite several cases of abnormal ACTH stimulation testing, no
patients developed perioperative hypotension or tachycardia.
With these studies, the concept of maintaining steroid-treated patients on their
preoperative steroid dose in the perioperative period emerged. Despite this, colorec-
tal surgeons managing IBD patients on high doses of preoperative steroids undergo-
ing major colorectal surgery remained reluctant to apply this practice [1, 8].
Recently, our group performed several studies comparing low-dose steroids (LDS)
versus high-dose steroids (HDS) in steroid-treated IBD patients undergoing major
colorectal surgery. Our LDS protocol entailed one-third IV hydrocortisone equiva-
lent to the daily preoperative steroid dose (IVED) given at the time of surgical inci-
sion, then one-third IVED every 8 h postoperatively, followed by a taper. For
patients off steroids at the time of surgery, no perioperative steroids were given.
HDS entailed hydrocortisone 100 mg IV given preoperatively, then every 8 h after
surgery followed by a taper to oral prednisone over 3 days. On hospital discharge,
steroids were either discontinued or tapered.
In 2012, we performed a pilot study evaluating 32 steroid-treated IBD patients
(10 patients on steroids up until surgery and 22 patients treated with steroids in the
past year) managed with LDS [22]. Hypotension occurred in 16 % of patients, but
all cases resolved with no intervention, fluid bolus, or blood transfusion and no
patients were treated with vasopressors or high-dose corticosteroids for AI. We then
compared LDS (n = 54) versus HDS (n = 43) in IBD patients on steroids (n = 48) or
previously treated with steroids (n = 49) undergoing major colorectal surgery [23,
24]. For patients previously treated with steroids, median duration since last steroid
dose was 4 months (range: 0.1 – 12 months) and median maximum steroid dose in
the past year was equivalent to prednisone 25 mg/day (range: 5 – 60 mg/day). Aside
from a higher incidence of tachycardia in patients previously treated with steroids
managed with HDS [24], we found no significant difference in hemodynamic insta-
bility between the 2 patient groups and no patients required rescue high-dose ste-
roids for AI.
Another study performed by Aytac and colleagues in 2013, retrospectively ana-
lyzed 48 IBD patients on steroids and 187 patients off steroids at the time of proc-
tocolectomy [25]. Eighty-nine patients were treated with stress-dose steroids and
146 without. There was more sinus tachycardia in patients managed with stress-
dose steroids. While there were no episodes of adrenal crisis, one patient in the
stress-dose group was readmitted with hypotension, fatigue and bloating and diag-
nosed with AI. In 2014, our group performed a prospective, randomized non-
inferiority study evaluating 92 steroid-treated IBD patients undergoing major
colorectal surgery randomized to HDS or LDS [26]. LDS were found to be non-
inferior to HDS with respect to our primary outcome, absence of postural hypoten-
sion on postoperative day 1, which occurred in 95 % of patients randomized to HDS
versus 96 % of patients assigned to LDS, p = 0.007. This study included 41 patients
previously treated with steroids (median duration since last steroid dose of 4 months;
interquartile range: 2 – 6 months), of which 25 were randomized to LDS (no peri-
operative steroids given). There was no difference in hemodynamic instability
between the 2 patient groups and no patients were treated with rescue HDS for
AI. There was, however, an insignificant trend toward more infectious complica-
tions in HDS (16 %) versus LDS-treated patients (4 %); p = 0.11.
Recommendations Based on Data
Based on various retrospective and observational studies and few randomized pro-
spective studies, stress-dose steroids appear to be unnecessary in IBD patients
undergoing major colorectal surgery. Several studies in both IBD and non-IBD
patients have suggested that patients can be maintained on their usual preoperative
steroid dose in the perioperative period. For patients previously treated with steroids
within the past year, perioperative steroids can be avoided altogether [9, 13, 24, 26].
While preoperative ACTH stimulation and perioperative plasma cortisol levels may
be evaluated, these tests tends to overestimate adrenal insufficiency and a majority
of patients do not experience hemodynamic instability even when perioperative ste-
roids are held altogether [11, 12, 15–17, 20]. Thus a low-dose perioperative steroid
protocol consisting of the intravenous equivalent to the patient’s preoperative dose
appears to not only be sufficient, but may avoid infectious complications associated
with high-dose steroids. Based on the available data, we recommend that steroid-
treated IBD patients undergoing major colorectal surgery be managed with low-
dose perioperative steroids in the perioperative period (evidence quality high; strong
recommendation).
Personal View of Data
In our view, high-dose perioperative steroids are unnecessary and may increase
perioperative risk. In our practice we maintain patients on their preoperative steroid
dose in the perioperative period. Our perioperative protocol entails one-third IVED
given at the time of surgical incision, then one-third IVED every 8 h postopera-
tively, followed by a taper. For patients off steroids at the time of surgery, no peri-
operative steroids are given. Patients are monitored closely in the perioperative
period and any unexplained hemodynamic instability is followed by ACTH stimula-
tion test. If patients are unresponsive to conservative measures and ACTH stimula-
tion testing is positive, then high-dose steroids are given. In our experience, however,
no patients have required additional high-dose steroids for AI with this protocol.
References
1. Hammond K, Margolin DA, Beck DE, Timmcke AE, Hicks TC, Whitlow CB. Variations in
perioperative steroid management among surgical subspecialists. Am Surg. 2010;76:1363–7.
2. Fraser CG, Preuss FS, Bigford WD. Adrenal atrophy and irreversible shock associated with
cortisone therapy. J Am Med Assoc. 1952;149:1542–3.
3. Lewis L, Robinson RF, Yee J, Hacker LA, Eisen G. Fatal adrenal cortical insufficiency precipitated
by surgery during prolonged continuous cortisone treatment. Ann Intern Med. 1953;39:116–26.
4. Stewart PM. The adrenal cortex. In: Kronenberg HM, Melmed S, Polonsky KS, Larsen PR,
editors. Williams textbook of endocrinology. 11th ed. Philadelphia, PA: WB Saunders Co;
2008. p. 445–505.
5. Salem M, Tainsh Jr RE, Bromberg J, Loriaux DL, Chernow B. Perioperative glucocorticoid
coverage. A reassessment 42 years after emergence of a problem. Ann Surg. 1994;219:416–25.
6. Coursin DB, Wood KE. Corticosteroid supplementation for adrenal insufficiency. JAMA.
2002;287:236–40.
7. Lamberts S, Bruining H, de Jong F. Corticosteroid therapy in severe illness. N Engl J Med.
1997;337:1285–92.
8. Lamore RF, Hechenbleikner EM, Ha C, et al. Perioperative glucocorticoid prescribing habits

in patients with inflammatory bowel disease: a call for standardization. JAMA Surg.
2014;149:459–66.
9. Solem JH, Lund I. Prophylaxis with corticosteroids in surgical patients receiving cortisone or
other steroid therapy. Acta Anaesthesiol Scand. 1962;6:99–105.
10. Jasani MK, Freeman PA, Boyle JA, Reid AM, Diver MJ, Buchanan WW. Studies of the rise in
plasma 11-hydroxycorticosteroids (11-OHCS) in corticosteroid-treated patients with rheuma-
toid arthritis during surgery: correlations with the functional integrity of the hypothalamo-
pituitary-adrenal axis. Q J Med. 1968;37:407–21.
11. Kehlet H, Binder C. Adrenocortical function and clinical course during and after surgery in
unsupplemented glucocorticoid-treated patients. Br J Anaesth. 1973;45:1043–8.
12. Kehlet H, Binder C. Value of an ACTH test in assessing hypothalamic-pituitary-adrenocortical
function in glucocorticoid-treated patients. Br Med J. 1973;2:147–9.
13. Knudsen L, Christiansen LA, Lorentzen JE. Hypotension during and after operation in

glucocorticoid-treated patients. Br J Anaesth. 1981;53:295–301.
14. Lloyd EL. A rational regimen for perioperative steroid supplements and a clinical assessment
of the requirement. Ann R Coll Surg Engl. 1981;63:54–7.
15. Symreng T, Karlberg BE, Kagedal B, Schildt B. Physiological cortisol substitution of long-
term steroid-treated patients undergoing major surgery. Br J Anaesth. 1981;53:949–54.
16. Bromberg JS, Alfrey EJ, Barker CF, et al. Adrenal suppression and steroid supplementation in
renal transplant recipients. Transplantation. 1991;51:385–90.
17. Bromberg JS, Baliga P, Cofer JB, Rajagopalan PR, Friedman RJ. Stress steroids are not
required for patients receiving a renal allograft and undergoing operation. J Am Coll Surg.
1995;180:532–6.
18. Friedman RJ, Schiff CF, Bromberg JS. Use of supplemental steroids in patients having ortho-
paedic operations. J Bone Joint Surg Am. 1995;77:1801–6.
19. Mathis AS, Shah NK, Mulgaonkar S. Stress dose steroids in renal transplant patients undergo-
ing lymphocele surgery. Transplant Proc. 2004;36:3042–5.
20. Glowniak JV, Loriaux DL. A double-blind study of perioperative steroid requirements in sec-
ondary adrenal insufficiency. Surgery. 1997;121:123–9.
21. Thomason JM, Girdler NM, Kendall-Taylor P, Wastell H, Weddel A, Seymour RA. An investi-
gation into the need for supplementary steroids in organ transplant patients undergoing gingi-
val surgery. A double-blind, split-mouth, cross-over study. J Clin Periodontol.
1999;26:577–82.
22. Zaghiyan K, Melmed G, Murrell Z, Fleshner P. Safety and feasibility of using low-dose peri-
operative intravenous steroids in inflammatory bowel disease patients undergoing major
colorectal surgery: a pilot study. Surgery. 2012;152:158–63.
23. Zaghiyan KN, Murrell Z, Melmed GY, Fleshner PR. High-dose perioperative corticosteroids
in steroid-treated patients undergoing major colorectal surgery: necessary or overkill? Am
J Surg. 2012;204:481–6.
24. Zaghiyan K, Melmed G, Murrell Z, Fleshner P. Are high-dose perioperative steroids necessary
in patients undergoing colorectal surgery treated with steroid therapy within the past 12
months? Am Surg. 2011;77:1295–9.
25. Aytac E, Londono JM, Erem HH, Vogel JD, Costedio MM. Impact of stress dose steroids on
the outcomes of restorative proctocolectomy in patients with ulcerative colitis. Dis Colon
Rectum. 2013;56:1253–8.
26. Zaghiyan K, Melmed GY, Berel D, Ovsepyan G, Murrell Z, Fleshner P. A prospective, ran-
domized, noninferiority trial of steroid dosing after major colorectal surgery. Ann Surg.
2014;259:32–7.
Chapter 10
IBD: Management of Dysplasia in Patients
with Ulcerative Colitis
Tara M. Connelly and Walter A. Koltun
Introduction
The risk of colorectal cancer (CRC) in the ulcerative colitis (UC) population is real
and is the cause of death for up to 15 % of inflammatory bowel disease (IBD)
patients [1, 2]. Controversy surrounds the use of prophylactic colectomy when dys-
plasia is detected. The relatively high risk of progression to CRC must be weighed
against the risks associated with total proctocolectomy (TPC) ± ileal pouch anal
anastomosis (IPAA), which, in contrast, are relatively low, particularly when per-
formed in an elective setting and by an experienced surgeon. In addition to substan-
tially reducing the CRC risk, TPC results in the elimination of future UC flares and
the necessity for medical treatment whilst eliminating the need for frequent CRC
surveillance. As more powerful techniques for lesion detection become widespread,
the detection of dysplasia will likely increase, increasing the relevance of the ques-
tion ‘What is the most appropriate management of patients with ulcerative colitis
and dysplasia?’
T.M. Connelly, MB, BCh, PhD

Department of Surgery, Waterford University Hospital, Waterford, Ireland
W.A. Koltun, MD, FRCS, FASCRS (*)
Division of Colon and Rectal Surgery, Inflammatory Bowel Disease, The Pennsylvania State
University, College of Medicine, 500 University Drive, Hershey, PA 17033-0850, USA

DOI 10.1007/978-3-319-40223-9_10
84 T.M. Connelly and W.A. Koltun
Search Strategy
The PubMed database was searched using the following terms ‘dysplasia, carci-
noma, neoplasia, DALM, ALM, dysplasia associated mass or lesion, adenoma like
lesion or mass and ulcerative colitis or inflammatory bowel disease or IBD.’ The
search was limited to full length English language manuscripts published between
Jan 1, 1980 and Oct 1, 2015. All references in each manuscript identified from the
PubMed search were then individually reviewed and examined for relevance and
potential inclusion.
Results
Patients, interventions, comparator and outcomes are highlighted in Table 10.1. The

most salient studies reviewed are shown in Table 10.2.
Incidences of Dysplasia and Colorectal Cancer (CRC)
Studies on UC dysplasia typically provide incidence rates obtained from the use of
conventional endoscopy. Any grade of dysplasia is found in up to 2 % of UC patients
at 5 years and 33 % at 15 years [4, 18]. Ten and 15 year rates of high grade dysplasia
(HGD) of 7 % and 12 % respectively have been reported. Similar to CRC, incidence
is highest in patients with pancolitis [15].
Median time from UC diagnosis to CRC diagnosis varies from 4 to 23 years [4,
19]. Compared to the general population, the relative risk of CRC in UC patients is
as high as 16-fold [20]. Meta-analysis inclusive of 116 studies has demonstrated an
overall prevalence of CRC in UC patients of 3.7 %, increasing to 5.4 % in the pres-
ence of pancolitis [21]. IBD-CRC patients are approximately 7 years younger than
sporadic CRC and share the same cancer specific mortality rates on a stage for stage
basis [22]. The mean age at CRC diagnosis ranges from 43 to 60 years and the mean
interval between diagnosis of UC and CRC is approximately 16 years [17, 23, 24],
which is consistent with the majority of UC diagnoses being made in individuals in
their 20s to early 30s [21].
Table 10.1 PICO
UC patients with dysplasia Surgery Expectant management Cancer risk
Table 10.2 Studies examined
Typical risk of cancer for Quality
immediate surgery when of
Study Ulcerative colitis patients dysplasia is detected Relative risk of cancer for surveillance evidence
Choi et al. (2015) [3] Patients with extensivea UC 33 and 14 % of colectomy 13 and 8.6 % developed HGD or CRC respectively High-
and LGD (median follow specimens demonstrated CRC found in 5 of 11 specimens of patients who mod
up = 48 months) CRC and HGD developed HGD and underwent colectomy
21 = immediate colectomy respectively Only 30 % of patients who developed CRC had a prior
151 = surveillance HGD lesion
Jess et al. (2006) [4] 29 of 692 IBD registry NA 0 of 5 with fLGD who underwent surveillance Mod-low
patients with neoplasiaa (CD progressed to HGD or CRC (median of 17.8 years)
patients included) 2 of 18 with ALMs developed LGD or DALM (median
9.3 years)
PSC and dysplasia proximal to the splenic flexure were
associated with risk for progression
Zisman et al. (2012) [5] 42 with pancolitis ≥8 years’ NA A higher grade in the colectomy specimen was found High-
with LGD (mean follow in 27 % who underwent resection mod
up = 3.9 years) 6 and 2 progressed to HGD and CRC respectively
17 % had persistent LGD, 64 % had indefinite dysplasia
or no dysplasia at the end of the study
Ullman et al. (2003) [6] 46 with fLGD (median Colectomy specimens 19 had LGD and 2 had HGD at the study’s end High-
follow up = 15 months) showed: LGD n = 7, 14 of the 46 progressed to advanced neoplasia (median mod
11 = immediate colectomy no dysplasia n = 1, time to progression = 25 months)
10 IBD: Management of Dysplasia in Patients with Ulcerative Colitis
21 = surveillance HGD n = 1 and CRC n = 2 57 % of colectomy specimens showed more advanced
neoplasia than biopsy specimens
6 DALM patients were managed with polypectomy
followed by surveillance. No CRC developed
(continued)
85
86

Blackstone et al. (1981) 27 with fLGD in random 6 colectomy specimens Of the 2 DALMs that underwent surveillance, 1 Low
[7] biopsies had CRC (including all developed CRC
12 with DALMS polypoid lesions). None Of 20 fLGD undergoing surveillance, 6 underwent
9 = immediate colectomy had a preoperative CRC colectomy. 1 CRC was found. The degree of dysplasia
22 = surveillance diagnosis was less severe or absent on follow up in 12
Woolrich et al. (1992) 22 with neoplasia (mean NA The first repeat set of biopsies showed dysplasia in six Mod
[8] disease duration = 13.5 years) and a CRC in one patient
Of the 13 patients with negative first repeat biopsies,
who did not undergo colectomy to avoid surveillance:
23 % had CRC in the colectomy specimen (including 1
resection for UC symptoms)
Befrits et al. (2002) [9] 60 with flGD and UC > years NA LGD was only present at index colonoscopy in 16. 73 % Mod
(mean follow up = 10 years) had LGD in subsequent colonoscopies. None progressed
to HGD in fLGD, except in 2 cases with DALM
Five of the 11 with DALMs underwent colectomy. Six
underwent endoscopic removal of lesions. None
developed HGD or CRC (mean follow-up of 6 years).
Ullman et al. (2002) 18 with fLGD (median NA 50 % developed advanced neoplasia (only 1 CRC) Mod-
[10] follow up = 32 months) Of the patients who underwent colectomy: Low
2 for DALMs (1 = DALM in colectomy specimen,
1 = no dysplasia)
1 for HGD and 3 for LGD (all had the same results in
the colectomy specimen)
5 for refractory disease (1 = DALM, 1 = LGD in the
colectomy specimen)
The cumulative incidences of progression = 13 % at 1
year, 26 % at 2 years, and 33 % at 5 years
T.M. Connelly and W.A. Koltun
All three DALMs that were found on subsequent

colonoscopies eventually developed HGD
Lim et al. (2003) [11] 29 with extensive UC >8 NA After 10 years, 10 % of LGD patients underwent Low
years and LGD and 97 UC colectomy for CRC vs 4 % without LGD
without dysplasia No difference in colectomy or death rates between the
two groups was seen
Agreement of LGD diagnosis between pathologists
was poor
Rutter et al. (2006) [12] 46 with LGD, 19 with HGD, CRC was found in 20 and Of the 36 LGD surveillance patients: 16 = no further Mod
28 DALMs and 32 ALMs 45 % LGD and HGD dysplasia, 8 = further LGD, 9 = HGD, 3 = CRC
with extensive disease for colectomies respectively Of the 8 HGD surveillance patients: 1 = developed
>8 years (mean follow 30 % of LGD DALM and CRC, 6 = developed HGD, 1 = subsequent LGD
up = 8.5 years) 33 % HGD DALM 21 % with LGD DALMs developed CRC, 28 % with
patients had CRC in their HGD DALMs developed CRC, none who had
resection specimen endoscopic resection developed CRC, 6.3 % of 32
ALM patients developed CRC
13 of the 30 CRCs did not have a preoperative
diagnosis of CRC
Pekow et al. (2010) 28 with LGD (Mean follow NA 1 fLGD progressed to HGD and 1 polypoid LGD Mod
[13] up = 50 months) progressed to CRC
For fLGD, polypoid LGD and PSC the incident rate of
advanced neoplasia was 4.3, 1.5 and 10.5 cases per 100
person-years at risk
Goldstone et al. (2011) 121 with extensive NA 7.9 % with raised and 25 % with flat dysplasia Mod
[14] UC > 7 years and LGD progressed to advanced neoplasia
10 IBD: Management of Dysplasia in Patients with Ulcerative Colitis
(median follow The interval for progression was significantly shorter

up = 37 months) among patients with distal vs. proximal LGD
(continued)
87
88

Stolwijk et al. (2013) 293 with UC >8 years NA Dysplasia of any grade was detected in 24.6 % (LGD Mod
[15] n = 55)
33 % who had subsequent colonoscopies progressed to
HGD and/or CRC. LGD preceded HGD/CRC in 44 %
5.1 % were diagnosed with CRC with a minimal
interval from symptom onset to CRC of 10.2 years
The cumulative incidence of any dysplasia, HGD and
CRC after 10 years was 23.5 %, 6.6 and 4.0 %. After 15
years it was 33.3, 12.1, and 6.8 %
In the colectomy specimens, 82 % confirmed the
biopsy result, 13 % showed a higher degree of
dysplasia
Provenzale et al. (1995) A computer generated Prophylactic colectomy Yearly colonoscopic surveillance for LGD increased Poor
[16] population of 10,000 30 year increased life expectancy life expectancy by up to 1.2 years vs no surveillance. If
old UC patients with by 2–10 months vs colectomy for LGD is not undertaken, surveillance
pancolitis >10 years surveillance and by every 3 years for the first 20 years, every 2 years for
1.1–1.4 years vs. with no the next 8 years, and yearly thereafter and colectomy
surveillance. for HGD or CRC provides the greatest life expectancy.
Wanders et al. (2014) Meta-analysis of 10 studies, NA The pooled CRC and HGD rates were 6.7 and 9 per High
[17] 376 patients with polypoid thousand years of patient follow-up
dysplasia (combined 1704 Increased study duration did not correlate with an
years’ follow-up) increase in advanced neoplasia rates
UC ulcerative colitis, LGD low grade dysplasia, CRC colorectal cancer, HGD high grade dysplasia, CD Crohn’s disease, fLGD flat low grade dysplasia, DALM
dysplasia associated mass or lesion, ALM adenoma-like mass or lesion
a
Extensive UC = UC proximal to the splenic flexure
T.M. Connelly and W.A. Koltun
10 IBD: Management of Dysplasia in Patients with Ulcerative Colitis 89
isease Defined Risk Factors: Disease Duration, Age of Onset,

D
Disease Extent, PSC
CRC incidence dramatically increases 8–10 years after the onset of UC symptoms.
Cumulative probabilities of developing CRC are up to 4 % by 10 years and 8 % by
20 years [15, 21, 25]. Rates after 30 years are less uniformly reported and vary from
2.6 to 34 % [20, 25, 26]. Primary sclerosing cholangitis (PSC) has consistently been
shown to increase the risk of CRC through a yet undetermined pathophysiological
mechanism. Studies on a potential correlation between young age at UC diagnosis
and/or childhood onset and CRC are conflicting with the majority showing no cor-
relation [25]. Dysplasia is typically but not universally found in areas of current or
burnt out colitis [27, 28], leading to an increased risk in more extensive disease
distribution [20, 25]. An earlier CRC onset has also been suggested in pan vs left
sided colitis [29].
atient Defined Risk Factors: Family History of CRC,

P
Medication Usage, Smoking, Patient Awareness
Family history is a known risk factor for both sporadic carcinoma and IBD associ-
ated CRC. CRC risk is at least doubled in UC patients with relatives with CRC and
is ninefold greater if the relative is under the age of 50 at CRC diagnosis [23, 30].
Conversely, a family history of IBD does not increase UC-CRC risk [20]. Studies on
medication usage in UC and CRC are limited to the older anti-inflammatory drugs,
with data on the newer biologics and anti-integrins lacking. Several previous studies
including a meta-analysis of 9 studies and 1932 patients, have suggested a protec-
tive effect with regular 5-aminosalicylic acid (5-ASA) use [21, 23, 24, 31]. Although
a paradoxical effect of smoking and decreased UC incidence and disease severity is
well known, the effect of smoking on UC-CRC risk is understudied. Eaden’s small
case control study demonstrated no association [23].
CRC risk may be underappreciated by UC patients themselves and probably
negatively impacts care. The majority of 199 survey respondents with UC for an
average of 8 years recognized that CRC risk was increased, however approximately
75 % stated that they were “unlikely” or “very unlikely” to develop CRC within the
next 10 years [32].
Classification of UC Dysplasia
Dysplasia in UC has typically been regarded as flat in most cases. When it is raised
and found within areas of inflammation, it has been termed a dysplasia associated
lesion or mass (DALM) and classically has been viewed as colonoscopically
unresectable. These definitions and concepts are now in question with the develop-
ment of newer more advanced techniques of endoscopic polyp removal. A polypoid
lesion found in an area free of inflammation is termed an adenoma-like mass or
lesion (ALM) and is akin to an adenomatous polyp in a non-UC patient.
Grading of dysplasia ranges from mild or low grade (LGD) to more severe or
high grade dysplasia (HGD). LGD is histologically similar to inflammation with tall
columnar epithelial cells with mild nuclear stratification. HGD is similar to carci-
noma in situ [7]. Salient features of HGD include prominent heterochromatin and
more irregular nuclear stratification within the epithelial layer. These subtle differ-
ences lead to poor interobserver agreement between grading pathologists especially
for LGD. When LGD slides are reviewed by a second set of pathologists, agreement
with the original LGD diagnosis ranges from 7 to 43 % and varies depending on the
number of pathologists reviewing [4, 11, 33, 34]. Dixon et al demonstrated a simi-
larly poor consensus of agreement on HGD, as low as 33 % [35]. Correlation was
not improved when specialist gastrointestinal pathologists grated the specimens,
compared to general histopathologists [36].
1. A second pathologist’s opinion for LGD is often necessary (Strong recom-

mendation based on moderate-high quality evidence).
Inadequate tissue sampling during colonoscopy may lead to missed lesions.

Mathematical modelling to determine the number of random biopsies required to
detect dysplasia with 90 % confidence calculated that 45 biopsies would be required.
When the number of biopsies decreases to 10, 26 % confidence was predicted [37,
38]. New enhanced methods of lesion detection including chromoendoscopy which
began in the early 2000s, have dramatically increased the sensitivity of surveillance
colonoscopy particularly for difficult to detect, flat dysplastic lesions [39–42].
Dysplasia Management
Neoplastic Progression
Unlike sporadic CRC which follows a usual sequence of normal mucosa → ade-
noma → carcinoma, UC associated CRC does not necessarily follow the expected
progression of LGD → HGD → CRC. This makes surgical recommendations prob-
lematic, especially in the individual patient. As demonstrated in several studies in
Table 10.2, carcinoma is often detected in colectomy specimens in which only LGD
or even no dysplasia was detected in prior colonoscopies. In Stolwijk’s study of over
290 UC patients undergoing surveillance, LGD preceded HGD or CRC in only
44 % of cases [15]. None of the 5 of 46 flat LGD (fLGD) patients that progressed to
CRC had an interval finding of HGD in Ullman’s study [43]. In Rutter’s
surveillance program of 600 patients with extensive colitis, CRC was found in 20 %
of specimens that were resected for only LGD [12]. Choi and Zisman report similar
rates of unexpected CRC in resections performed for LGD [3, 5].
A focus of UC dysplasia, especially HGD has been suggested to be a marker for
synchronous lesions, including CRC [44–46]. An early study of 590 UC TPC speci-
mens demonstrated that patients with a focus of HGD or LGD were 36 times more
likely to have a concomitant CRC found as compared to UC specimens without
dysplasia. Up to a 25 % synchronous tumor rate and 55 % synchronous dysplasia
rate has been demonstrated in other TPC studies [19, 47].
Flat LGD
In patients with LGD and extensive UC for over 8 years, progression to CRC has
been reported to be 13 % at 1 year to 33 % at 5 years [3, 5, 6, 10, 12, 15, 18] with a
mean time to progression of 1.8–2.3 years [5, 6, 10]. Woolrich determined LGD to
be an indicator of future carcinoma in 18 % of 121 patients [8]. A meta-analysis of
20 studies with 508 LGD patients provided a calculated positive predictive value
(PPV) of 22 % for flat LGD (fLGD) as a predictor of CRC [48]. Zisman determined
nonpolyoid dysplasia, size >1 cm, previous history of indefinite dysplasia and the
presence of a stricture as risk factors for LGD progression. He stratified patients
showing that CRC risk at 5 years ranged from 1.8 % in patients with no risk factors
to over 60 % with three risk factors [3]. Befrits’ study, the only study which has
shown no progression of LGD to subsequent HGD or CRC was small with only 16
patients with LGD [9]. Multiple retrospective studies and Thomas’ meta-analysis
did not demonstrate differences in characteristics between patients with and without
LGD prior to HGD and/or CRC [6, 15, 48] again showing the difficulty in making
care recommendations in the specific patient.
2. Flat LGD warrants colectomy in the otherwise healthy patient due to the
increased risk of unrecognized synchronous high risk lesions and the likeli-
hood of developing subsequent HGD or CRC (Strong recommendation based
on moderate-high quality evidence).
High Grade Dysplasia
Recent studies on long term HGD surveillance are lacking as patients typically
undergo resection due an inordinately high risk of synchronous CRC, as high as
45 % in earlier studies [49, 50]. In a systematic review, 32 % (of 47 patients) with
HGD on colonoscopy had CRC discovered on resection pathology [50]. Some
smaller studies report lower rates, [27] but sampling errors, the need for repetitive
colonoscopy, and the fear of synchronous CRC or progression over time has led to
TPC being the immediate recommendation in the otherwise healthy UC patient with
HGD. HGD identified on random biopsies represents an especially concerning cir-
cumstance, since overt signs of polyp formation that would focus the attention of
the examiner is lacking. Similarly, multiple areas of dysplasia, especially when flat,
can only be addressed by colectomy.
3. HGD, multifocality and flat dysplasia are all high risk features for the
development of CRC in the UC patient and warrants total proctocolectomy in
the surgically fit patient (Strong recommendation based on moderate-high
quality evidence).
DALMS
The PPV for DALMs as predictors of CRC is 41 % as calculated by meta-analysis

[48]. 43 % of 47 DALM patients in the small systematic review described above
were found to ultimately have CRC [50]. Blackstone et al described a series of 12
resected DALMs. CRC was found in 7, including all 5 single polypoid masses.
None had invasive carcinoma on preoperative biopsy [7]. Selective resection of
DALMs in the form of polypectomy was proposed by one meta-analysis of 10 stud-
ies and 376 UC patients, but with a mean follow up of only 2.8 colonoscopies after
resection. Many of these studies had very low patient numbers and mean follow up
and number of colonscopies varied greatly across the study cohorts included [17].
Kisiel reported higher rates in 77 of 95 DALM patients who underwent polypec-
tomy with cumulative incidences of cancer of 2 % at 1 year and 13 % at 5 years cited
[51]. The value of more advanced colon sparing techniques such as endoscopic
mucosal resection, has not been fully evaluated in this high risk group of patients.
Thus close colonoscopic surveillance is required after colonoscopic excision.
4. DALMS should be viewed as very high risk lesions in the UC patient justi-
fying TPC in most fit individuals. If able to be completely removed colono-
scopically, aggressive subsequent surveillance is necessary (Strong
recommendation based on moderate-high quality evidence).
ALMS
By definition, ALMs are within areas of the colon without inflammation. Thus they
may be treated similarly to sporadic adenomas due to a low risk of CRC. Hurlstone
followed ALMs and DALMs in over 180 patients over a median follow-up of
4.1 years as compared with over 1600 non-UC Controls who had undergone endo-
scopic mucosal resection (EMR) or polypectomy for lesions. Recurrence rates were
low in both groups [52]. Torres et al studied ALMs and DALMs in 59 CD and UC
patients and found that CRC only developed in DALMs. However, the group was
highly selected leading to the recommendation of endoscopic resection with close,
6 monthly surveillance with colonoscopy [30].
5. ALMs can be viewed as typical polyps, amenable to polypectomy (Weak

recommendation based on low quality evidence).
Due to the lack of consistent progression of inflammation to LGD to HGD to CRC,

recommendations for surgical management of UC dysplasia leans towards treating
the worst case scenario. This is especially the case since UC patients with dysplasia
are frequently middle aged with a life expectancy that should not be foreshortened
by preventable malignancy. Couple this with the above described poor concordance
between pathologists and one is frequently led to the recommendation of early
resection when any form of dysplasia is found on colonoscopy, but especially when
HGD or flat dysplasia is found on random sampling. The high incidence of unex-
pected synchronous CRC when TPC is done for dysplasia further justifies an aggres-
sive surgical approach.
Recently, chromoendoscopy has suggested itself to be a more sensitive and accu-
rate method of following the equivocal patient; however this has not been thor-
oughly studied. Similarly the use of EMR for DALMs is also understudied, but
really is only considered in highly specialized centers by very committed caregiv-
ers, and then only with intense colonoscopic follow up (every 6 months). This sur-
veillance itself becomes an added burden, with attendant complications, costs and
potential difficulty with patient compliance.
Thus, in the surgically fit patient we advocate TPC in all patients with any grade
of pathologically confirmed dysplasia [45]. In the patient with LGD, this may some-
times require a second colonoscopy (frequently chromoendoscopy) for confirma-
tory biopsies, possibly after a period of intense medical management to minimize
inflammation. However, any single confirmed focus of HGD should send the other-
wise healthy and consenting patient directly to surgery. Besides eliminating the risk
of CRC, patients are effectively “cured” of their colitis by TPC, with elimination of
most medications and their attendant side effects and costs, improvement in bowel
habit (especially with the IPAA) and elimination of burdensome surveillance colo-
noscopies [53]. The more difficult dilemma is the surgical high risk or elderly
patient or patient refusing surgery, who has a less compelling indication for surgery,
a single focus of LGD for example. After thorough counselling, such a patient can
be considered for close surveillance using chromoendoscopy and/or EMR if a lesion
is visualized. If the dysplasia is colonic (not rectal), and localized as can be best
determined, a subtotal colectomy and ileorectal anastomosis, or even segmental col-
ectomy will decrease the risk of synchronous or metachronous lesions, and will be
surgically less morbid. The patient will still need close colonoscopic surveillance,
however. Similarly, a segmental resection (or even TAC/IRA) for DALM is possible
in the higher risk patient. It avoids a stoma, but any procedure less that TPC needs
preoperative confirmation of a dysplasia free rectum which then requires continued
surveillance after this more limited surgery.
Editor’s Note The concepts and controversies surrounding the identification and management of
dysplasia in IBD are evolving rapidly. It appears that most areas of dysplasia are actually grossly
visible with high definition scopes and enhancement techniques (e.g., chromoendoscopy). If
lesions can be clearly defined, they can be more readily removed endoscopically and followed
carefully with serial endoscopy.
The authors have outlined an aggressive approach, especially to the management of low grade
dysplasia; many IBD specialists may espouse a more nuanced view with careful endoscopic sur-
veillance offered as an alternative for many of these patients.
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Chapter 11
Post-operative Prophylaxis in Patients
with Crohn’s Disease
Jonathan Erlich and David T. Rubin
Introduction
Crohn’s disease (CD) is a chronic relapsing inflammatory condition, characterized

by abscesses, fistulization and stricturing that can affect any part of the gastrointes-
tinal tract, but most commonly affects the terminal ileum and proximal colon. Up to
80 % of CD patients will require at least one abdominal surgery in their lifetime [1].
Unfortunately, surgery is not curative and recurrence is the norm, rather than the
exception. Endoscopic recurrence occurs in upwards of 70–90 % of patients within
1 year of surgery [2, 3]. Clinical recurrence is seen in approximately one third of
patients within 3 years of surgery [4]. Additionally, up to 50 % of patients will
require a repeat surgery within 5 years, while up to 70 % will require a repeat opera-
tion within 20 years of their original procedure [4–7]. While prevention of post-
operative recurrence is a significant challenge in clinical practice, it is essential for
not only the maintenance of the patient’s health status and quality of life, but also
for the prevention of disease relapse and future surgeries [8]. Having a multidisci-
plinary approach involving collaboration between surgeons and gastroenterologists
is critical for optimizing post-operative care; however patients often delay their
follow-up with their gastroenterologist, leaving the surgeon as the sole manager of
the patient’s post-operative treatment. Communicating a well-organized and clear
J. Erlich
University of Chicago Medicine, Section of Hospital Medicine,
5841 S. Maryland Ave, MC 5000, Room 304, Chicago, IL 60637, USA
D.T. Rubin (*)
University of Chicago Inflammatory Bowel Disease Center,
5841 S Maryland Ave, MC4076, Chicago, IL 60302, USA

DOI 10.1007/978-3-319-40223-9_11
98 J. Erlich and D.T. Rubin
plan shortly after resection is especially important because patients who are at high
risk of recurrence may be less likely to accept treatment as they enjoy their
surgically-induced “remission [9].”
In this chapter, we describe the clinically relevant risk factors for post-operative
recurrence as well as the medical options available for prevention. Finally, we pro-
vide a practical guide on how to approach the post-operative Crohn’s patient based
on an individualized, evidence-based plan.
We conducted a Pubmed search from 2005 to 2016 using a combination of the
search terms “Crohn’s disease”, “postoperative”, “prophylaxis”, “recurrence”,
“relapse”, “prevention”, “risk factors”, “anastomosis type”, and “treatment”.
Selected embedded references that were published prior to 2005 and considered
seminal papers by the authors were also included.
PICO table
Patients Intervention Comparator Outcome
Patients with Crohn’s Medical Endoscopic Disease recurrence, need
disease following prophylaxis surveillance for reoperative surgery
surgical resection
Recurrence in Post-operative Crohn’s
The recurrence rates of CD after surgery are very high, especially in those not
receiving medical prophylaxis. Endoscopic findings that indicate recurrence of dis-
ease include aphthous erosions, deep linear ulcers, mucosal inflammation, fistulae
and strictures [10]. Typically, the prevailing phenotype of a patient’s disease are
thought to be consistent before and after resection, meaning that patients who ini-
tially had penetrating disease as an indication for their surgery will often experience
penetrating disease when they recur [11].
The most common site of recurrence is at the surgical anastomosis, especially the
proximal side [2]. Luminal contents, specifically intestinal flora, appear to play an
important role in the pathogenesis of recurrence. While a sustained remission is
common among patients with a diverting ileostomy even without medical therapy,
those patients who undergo re-anastomosis often have disease recurrence shortly
following the procedure [12–14].
Risk Factors for Relapse
Identifying possible risk factors for recurrence in Crohn’s patients is essential for
optimizing care for the postoperative patient. Risk stratifying patients based on
these factors allows tailoring of therapy to help avoid both over- and under-treatment
of patients.
11 Post-operative Prophylaxis in Patients with Crohn’s Disease 99
Patient Factors
Smoking cigarettes has been the most consistently identified patient-related risk
factor for disease recurrence. Compared to non-smokers, smokers have increased
rates of endoscopic recurrence and clinical relapse, shorter time to clinical relapse
and increased risk of requiring additional surgical intervention [15–19]. There also
appears to be a dose effect, with heavier smokers having an increased risk of recur-
rence compared to milder smokers [20, 21]. Additionally, studies have shown that
patients who quit smoking have significantly reduced surgical re-intervention rates,
which are comparable to that of non-smokers [18, 22, 23].
There is interest in whether certain genetic variants or profiles of the gut micro-
biome are potential risk factors for post-operative recurrence, as both are known to
be important in the pathogenesis of IBD. Whereas mutations in NOD2 have been
identified as a marker for the need for resection in CD cohorts, it has not been shown
to have a consistent association with post-operative relapse. However, a recent study
identified an association between CAD8 homozygosity and an increased risk of
surgical recurrence [24, 25]. Another recent study suggested that microbiota pro-
files at the time of surgery may have some prognostic value in identifying those
patients at risk for developing earlier disease recurrence [26]. Both of these areas of
inquiry require further research to help clarify their roles in the pathogenesis of
disease recurrence.
Gender, age, age at diagnosis, and prior family history are not consistent risk
factors in the literature [27–30].
Crohn’s Disease Behavior
Perforating-type disease, perianal disease and previous surgery for CD have been
shown to be associated with increased risk of disease recurrence [11, 31–33].
An association between the presence of granulomas in the resected specimen and
recurrence has also been consistently demonstrated [13, 28, 30, 34]. The
evidence for duration of disease prior to surgery as a risk factor for recurrence is
inconsistent [35, 36].
Surgical Factors
Certain perioperative events, such as sepsis, blood transfusions and post-operative

complications have not been associated with CD recurrence. While clearing mar-
gins of macroscopic disease is imperative, there appears to be no relationship
between microscopic CD found at the resection margin and disease recurrence [37].
As laparoscopic surgery has become more popular, there has been interest in
whether the technique reduces post-operative disease recurrence. Whereas
laparoscopic technique can offer advantages in the surgical management of CD,

including reduced duration of hospital stay, reduced cost and lower morbidity, stud-
ies have shown no significant difference in endoscopic or surgical recurrence rates
when compared to open procedures [38, 39].
Type of anastomosis has been considered an important potential risk factor for
CD recurrence. Due to the subsequent wide lumen created with side-to-side anasto-
mosis, which in theory would prevent early stenosis, subsequent fecal stasis and
secondary ischemia, it has been postulated that this technique offers some outcome
benefits. Unfortunately, observational studies have not supported this [40]. In a mul-
ticenter randomized controlled trial by Mcleod et al., anastomotic type did not affect
the recurrence rate of CD after ileocolonic resection [41]. Despite this, other studies
have suggested that side-to-side anastomosis may reduce post-operative complica-
tions and surgical recurrence [42–44]. Of note, the Kono-S anastomosis, which is a
novel antimesenteric functional end-to-end handsewn anastomosis, is a technique
with improved endoscopic and surgical recurrence rates; however, long-term out-
comes and comparative studies need to be performed in order to confirm its superi-
ority [45].
Myenteric plexitis found during surgery has been consistently shown to be asso-
ciated with higher rates of endoscopic and surgical recurrence [46–48]. Visceral fat
area has also been associated with post-operative recurrence and is believed to have
clinical implications with respect to optimizing prophylaxis [49]. Additionally, the
European Crohn’s and Colitis Organization determined that disease of more than
100 cm should be considered a risk factor for increased incidence of post-operative
recurrence [50].
Assessment of Recurrence
Endoscopically identified disease recurrence occurs early and therefore is the

preferred measure of relapse in post-operative patients. This is because it pre-
cedes clinical symptoms, which do not correlate well with endoscopic findings
[51, 52].
The most commonly used endoscopic scoring system to evaluate disease recur-
rence after resection in CD is the Rutgeerts’ score [2]. This is a reliable scoring
system that assesses the presence and severity of recurrence in the distal neotermi-
nal [53] (Fig. 11.1). The Rutgeerts’ scoring system has become widely used because
it has been shown to correlate with subsequent clinical relapse: while less than 5 %
of those with scores of i0 and i1 will develop clinical recurrence within 3 years, 14,
40 and 90 % of patients with i2, i3 and i4 scores will develop clinical relapse, respec-
tively [2, 13, 54]. When using this system, it is important to recognize that ulcers are
not necessarily due to disease recurrence, and that it is common to have suture-
related trauma or marginal ulceration/ischemia at the anastomosis site. Such ulcers
should not be included when grading within the scoring system.
Rutgeerts 0 Rutgeerts 1 Rutgeerts 2
Normal ileal mucosa <5 aphthous ulcers >5 aphthous ulcers, normal
intervening mucosa
Ulceration without
Severe ulceration
normal
with nodules,
intervening
cobblestoning, or stricture
mucosa
Rutgeerts 3 Rutgeerts 4
Fig. 11.1 The Neo-TI: the Rutgeert’s Score
In terms of timing of evaluation for post-operative recurrence in asymptomatic

patients, many guidelines suggest performing a colonoscopy within a year after
surgery. More recent evidence has shown that a substantial proportion of endo-
scopic recurrence occurs within 6 months, many of which were severe with
Rutgeerts’ score ≥ i3. These findings highlight the importance of earlier evaluation
for post-operative recurrence [55].
Non-invasive Methods of Assessing Post-operative Recurrence
While endoscopy is the gold standard for monitoring post-operative recurrence,

there is a lot of interest in findings surrogate markers that would avoid the risks,
expense and inconvenience inherent in an invasive procedure. Clinical scoring
systems, such as the Crohn’s Disease Activity Index (CDAI) and the Harvey-
Bradshaw index poorly correlate with endoscopic findings [56–58]. Additionally,
commonly used biochemical markers of inflammation, such as ESR and CRP, also
have not been shown correlate with endoscopic recurrence in post-operative
patients [58, 59].
The evidence behind fecal calprotectin (FC) has been very promising for ful-
filling the role of a non-invasive method for assessing post-operative recurrence.
FC levels correlate well with endoscopic recurrence as measured by the Rutgeerts’
score, and patients who have received treatment for their recurrence with subse-
quent endoscopic improvement have also seen improvement in their FC [58,
60–62]. In a study by Yamamoto and Kotze, a cutoff value of 170 μg/g for FC
Table 11.1 Effectiveness of Evaluation method Efficacy Quality of evidence

various methods to assess
Endoscopy +++ High
post-operative endoscopic
recurrence FC +++ High
SICUS ++ Moderate
WCE ++ Low
ESR/CRP − High
Clinical disease − High
scores
had a sensitivity of 0.83 and a specificity of 0.93 to predict clinical recurrence

[62]. In another study, Wright et al. found FC to correlate with endoscopic recur-
rence and endoscopic severity scores. The authors determined that a cutoff for
FC of 100 μg/g had a sensitivity of 0.89 and a negative predictive value of 91 %
for disease recurrence. The study concluded that utilizing FC to monitor post-
operative patients may allow for 47 % of patients to avoid colonoscopy [58].
Based on these findings, FC may play a valuable role in the post-operative man-
agement algorithm, possibly allowing for endoscopy to be reserved for only
those patients with abnormal values.
Other non-invasive methods of monitoring postoperative patients have shown
promise. In a study by Calabrese et al, small intestinal contrast ultrasonography
(SICUS) was shown to have a sensitivity of 92.5 %, specificity 20 % and accuracy
of 87.5 % when compared to endoscopy [52]. Additionally, bowel wall thickness
was found to correspond with endoscopic severity, although SICUS findings have
not been shown to correlate with clinical recurrence [52, 63, 64, [65]. While it’s use
may be limited by its low specificity, SICUS may have a role in assessing the neo-
terminal ileum in patients with stenotic lesions not allowing passage of the endo-
scope [66].
Wireless capsule endoscopy (WCE) also has good sensitivity and specificity in
assessing post-operative recurrence. In prospective studies, WCE identified lesions
in upwards of 76 % of study subjects that could not be visualized by endoscopy
(ibid) [67, 68]. While initial findings are encouraging, further research on WCE role
in the post-operative patient needs to be performed (Table 11.1).
Symptoms After Surgery Are Not Necessarily due to Recurrence
It is important to know that common post-operative symptoms, such as diarrhea and

pain, may not necessarily be due to CD recurrence. Therefore, prior to initiating treat-
ment for suspected disease recurrence, objective markers of disease should be pursued.
Ideally this can be done with endoscopy, although FC may be an acceptable alternative.
As clinical symptoms poorly correlate with endoscopic activity, treatment should be
based on endoscopic findings or appropriate surrogate markers and not solely on clinical
symptoms, in order to prevent both over- and under-treating the patient.
Medical Prophylaxis Options
Following surgical resection, CD patients are often cleared of all of their disease,
thus marking an ideal time to prevent further disease from occurring. As discussed
above, most patients will unfortunately experience recurrence if not on medical
therapy. Many studies have focused on the efficacy of medical therapies in prevent-
ing progressive disease, disability and further surgical interventions in the post-
operative setting.
Minimal Benefit: Probiotics/5-ASA/Corticosteroids
Given the role that the gut flora plays in the recurrence of disease and evidence of
the effectiveness of antibiotics in preventing disease, there has been growing inter-
est in the use of probiotics to alter the microbiota and prevent recurrence. However,
multiple studies have failed to show any benefit in the use of probiotics in the post-
operative setting [69, 70]. 5-ASA medications are appealing for post-operative
treatment, due to their favorable safety profile, ease of administration and low cost,
however the results have been inconsistent and their effect on clinical and endo-
scopic recurrence is minimal at best [71–73]. Furthermore, neither systemic nor
local corticosteroids have been shown in the literature to be effective at reducing
post-operative recurrence [74, 75].
Moderate Benefit: Antibiotics/Immunomodulators
Due to evidence suggestive of the role of bacteria in disease recurrence, many stud-
ies have evaluated the effectiveness of antibiotics in preventing relapse. Whereas
ciprofloxacin has not been shown to prevent relapse, nitroimidazole antibiotics
(metronidazole and ordinazole) decrease the risk of clinical and endoscopic recur-
rence [76–78]. Rutgeerts’ et al. demonstrated that only 3 months of treatment with
metronidazole led to a decrease in recurrence that extended to 12-months follow-
ing surgery compared to those taking placebo [79]. Studies have shown a further
reduction in recurrence rates when metronidazole is used in combination with aza-
thioprine compared to either medication used alone [80]. Additionally, antibiotics
have been shown to be cost-effective for preventing post-operative recurrence,
even in low-risk patient, although widespread use may be limited by high rates of
intolerance [81].
Immunomodulators (IMM) appear to have a modest effect on preventing post-
operative recurrence. Thiopurines (azathioprine and 6-MP) have been found to be
more efficacious than placebo at reducing clinical relapse and severe endoscopic
recurrence at 1 year [77, 82]. They have also been shown to reduce the risk of endo-
scopic recurrence compared to mesalamine [77]. Long term data has suggested that
thiopurine treatment for over 36 months decreased the need for additional surgical
intervention when compared to use of less than 36 months or no treatment at all
[83]. In a comparative cost-effectiveness analysis, Azathioprine and 6MP had the
most favorable incremental cost effectiveness ratio [84]. Because of the strong evi-
dence of its effectiveness, the AGA has recommended that thiopurines should be
used in those with “high risk” for recurrence or in whom postoperative recurrence
would be deleterious [85].
High Benefit: Biological Therapy
Biologics have been growing in popularity over the past 10 years and have been found
to be the most effective at reducing post-operative recurrence risk. An early small
study by Regueiro et al. demonstrated that endoscopic recurrence was reduced from
84.6 % in the placebo arm to 9.1 % in the infliximab treated group at 1 year [86]. In the
larger PREVENT study, Regueiro et al. again showed that infliximab decreases endo-
scopic recurrence compared to placebo, however the reduction of clinical recurrence,
which was the primary endpoint, did not reach statistical significance. Of note, adverse
event rates, including infections, were similar between the groups [87].
Adalimumab has also been studied and is considered to be equally efficacious
at reducing recurrence [88]. Savarino et al. reported that the adalimumab was
highly effective at prevention of endoscopic and clinical recurrence at 2 years.
Endoscopic recurrence of CD was seen in only 6.3 % of patients receiving adali-
mumab c ompared to 64.7 % and 83.3 % of patients who received azathioprine and
mesalamine monotherapy, respectively [8]. In the recent Postoperative Crohn’s
Endoscopic Recurrence (POCER) study, 79 % of high-risk patients who received
adalimumab remained in endoscopic remission compared to 55 % of patient
receiving a thiopurine [89].
While the focus of this chapter is on post-operative prophylaxis, it is important
to know that for patients who experience endoscopic recurrence, biologics have
been shown to be superior at reducing endoscopic scores and clinical relapse com-
pared to immunomodulators or 5-ASA [61, 86, 90].
There is currently no data in the post-operative setting or certolizumab pegol,
natalizumab or vedolizumab.
Table 11.2 The effectiveness Therapy Effectiveness Level of evidence

for preventing endoscopic
Probiotics − High
recurrence with associated
level of evidence of potential Corticosteroids − Moderate
therapies for post-operative Mesalamine + Moderate
prophylaxis Nitroimidazole antibiotics ++ High
Ciprofloxacin − Moderate
Immunomodulators ++ Moderate
Anti-TNF +++ High
Authors’ Approach to Post-operative Crohn’s Patients
While the costs of over-treatment cannot be ignored, under-treatment may place the
patient at risk for disease recurrence, as most post-operative patients without pro-
phylaxis will experience recurrence within a year. Despite evidence of its far supe-
rior effectiveness in preventing relapse, initiating biological therapies as prophylaxis
even for high risk patients may be prohibitively expensive and exposes more patients
unnecessarily to potential side-effects [81, 84]. Responsible choice of therapeutic
approach therefore must be individualized for each patient. Studies have demon-
strated the benefit of early evaluation of recurrence within 6 months of surgery. The
recent prospective, randomized POCER study demonstrated that tailoring prophy-
laxis to risk category coupled with early disease assessment and subsequent treat-
ment “step-up” if recurrence occurred significantly reduced disease relapse and led
to increased macroscopic normality compared to those who did not receive the early
evaluation [89].
Given the strength of the evidence, we have adopted an approach that all patients
who can tolerate metronidazole receive 3 months of treatment at a dose of 350 mg
TID following surgery. Low-risk patients are those with long-standing disease
(>10 years), who are undergoing their first surgical intervention for a short (<10 cm)
fibrostenotic lesion. It is believed that disease recurrence progresses more slowly in
these patients and therefore chronic prophylactic therapy is not required at the out-
set. For high-risk patients, those who smoke, have penetrating or perianal disease,
history of multiple prior resections and those with evidence of granulomas or myen-
teric plexitis in the resected sections, initial combination therapy with an anti-TNF
and an IMM should be considered. All smokers should be counseled on its contribu-
tion to disease recurrence and be offered assistance with quitting or access to a
smoking cessation program. For moderate risk patients, those who do not fit into the
other categories mentioned, we recommend treating with IMM monotherapy in the
post-operative period.
While early monitoring of disease recurrence has been shown to be beneficial,
there is no standard approach on how to do so. In our practice, we measure fecal
calprotectin in patients 3 months post-surgery, as levels of FC are known to stay
elevated for the first 2 months. Given its high NPV, for patients with FC values
<100 mg/kg, we continue them on their current therapy and either repeat FC or
perform colonoscopy at 6 months. While some evidence suggests that patients with
FC > 100 should have a colonoscopy at 6 months, we risk stratify these patients
depending on their level of calprotectin. In the study by Sorrentino et al., patients
who had no post-operative recurrence had FC levels <200 mg/kg. Therefore, for
patients with FC between 100 and 200, we continue their current medical therapy
and perform a colonoscopy at 6 months [8]. For patients with FC levels >200 mg/kg,
we optimize or escalate their medical therapy at that time and then perform a
colonoscopy at 6 months.
At colonoscopy, patients with i0 or i1 Rutgeerts’ score are continued on their
current medical therapy, while for patients with i2 or higher, therapy is initiated,
optimized or escalated. This may be accomplished by starting IMM or anti-TNF

therapy and optimizing their dosing using therapeutic drug monitoring. A careful
assessment of the history, examination and need for therapeutic drug monitoring
should be considered when deciding which option to implement.
Once a patient has had their medical therapy optimized and their disease status is
stable, it is necessary to assess them every 6–12 months with a measure of disease
recurrence, either with FC or colonoscopy. If objective evidence of recurrence
occurs, we recommend further optimization of therapy using the algorithm dis-
cussed above.
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Part II
Colon Cancer
Chapter 12
Follow-Up in Patient’s After Curative
Resection for Colon Cancer Surveillance
for Colon Cancer
Clifford L. Simmang
PICO table
Pt Population Intervention Comparators Outcomes studied
Pts after curative resection Intensive follow Clinical Early detection of recurrence,
of colorectal cancer up followup salvage rates, cost
Introduction
According to the American Cancer Society, 134,490 new cases of colon and rectal
cancer will be diagnosed in 2016. The effect is nearly equal between men and
women, with 70,820 diagnosed in men, and 63,670 diagnosed in women [1]. Colon
and rectal cancer is the fourth most common cancer, however it is the second most
common cause of cancer deaths [1]. At least, one third (25–49 % reported) of
patients treated with stage II or stage III colon cancer will experience a recurrence,
and this has remained fairly steady over the past 20 years [1–3].
The purpose of surveillance following potentially curative surgery for colorectal
cancer, is the early identification of recurrent cancer in those patients who might
potentially be cured by secondary surgical intervention. Secondly, surveillance also
enables screening for metachronous primary cancers and polyps. The diagnosis of
an asymptomatic recurrence is more likely to result in attempts at curative reopera-
tion [4]. Even with an intensive investigative program, up to 50 % of asymptomatic
recurrences may not be detected [4]. Several studies have also demonstrated that
asymptomatic recurrences of colorectal cancer are more amenable to a surgical
resection with negative margins (R0) [5].
C.L. Simmang, MD, MS

Chief Medical Officer and Vice President of Medical Affairs,
Baylor Scott and White Medical Center at Grapevine, Grapevine, TX, USA
DOI 10.1007/978-3-319-40223-9_12
116 C.L. Simmang
Table 12.1 Surveillance recommendations-curative colon and rectal cancer

Intervention Frequency
1–2 years 3–5 years >5 years
H&P 3–6 months 6 months Annual
CEA 3–6 months 6 months None
Colonoscopy 1 yeara 3 yearsb 5 yearsc
Flexible Sigmoidoscopy rectal cancer 6–12 months Annual Noned
CT scan Annual Annual Annual
a
3–6 months if not cleared at surgery
b
Continue at 3 years if adenoma is identified
c
If cleared at 3 years
d
Follow colonoscopy
Although there is extensive literature of evaluating the benefit of surveillance

strategies for colorectal cancer, there remains ongoing debate. The cost of intensive
follow-up is unclear but remains central to the discussion [5].
Search Strategy
An electronic search of the PubMed database was performed from 1996 to 2016. This
search terms included “cancer follow-up”, “colon surgery” and “postoperative sur-
veillance for colon cancer” with 444 matches. The National Comprehensive Cancer
Network (NCCN) [6], along with society guidelines from the American Society of
Colorectal Surgeons (ASCRS), American Cancer Society of Clinical Oncology
(ASCO) were reviewed. In addition the search included the Cochrane database,
Google search and the Ontario evidence based series 26–2 on follow-up care surveil-
lance protocol and secondary measures for survivors of colorectal cancer.
Results
Guidelines
The vast majority of studies exploring the benefits of surveillance have been con-
ducted on patients with resected stage II or stage III disease. Intensive postoperative
surveillance programs have been justified in the hope that early detection of asymp-
tomatic recurrences will increase the proportion of patients potentially eligible for
curative therapy [7]. Although individual randomized trials have not demonstrate a
survival benefit, meta-analyses suggest a modest but significant survival benefit
from intensive surveillance after resection of colorectal cancer [8–13]. It does seem
clear patients with a recurrence detected by more intense surveillance are more
12 Follow-Up in Patient’s After Curative Resection for Colon Cancer Surveillance 117
likely to undergo curative resection, whereas the actual reported survival advantage
is more variable.
For a starting template, we began with the National Comprehensive Cancer
Network guidelines version 2.2015(6) which reccommend;
1. History and physical every 3–6 months for 2 years and then every 6 months for
a total of 5 years
2. CEA every 3–6 months for 2 years, then every 6 months for a total of 5 years
3. CT scan of the chest, abdominal and pelvis annually up to 5 years, especially for
patient’s at high risk for recurrence. High risk patients would include those with
lymphatic, venous or perineural invasion, with poorly differentiated tumors, or
patients presenting with obstruction or perforation.
4. Colonoscopy at 1 year when the colon was cleared prior to or at the time of sur-
gery – repeat in 3 years and then every 5 years.
5. If colonoscopy not performed at the time of surgery, then colonoscopy in 3–6
months.
6. PET CT scan is not routinely recommended
Most guidelines are based on the above recommendations. We will now review
each of the recommendations.
History and physical examination – low quality evidence – strong
recommendation
Recommendation – Office visit with history and physical every 3–6 months for
2 years and every 6 months for a total of 5 years
While the benefit of office visits has not been well established, up to one-half of
symptomatic patients may not report their symptom(s) until it is time for the visit
with her physician [14, 15]. In addition, this provides an opportunity to discuss the
results of surveillance testing. The evidence is limited to suggest that the physician
visits provide psychological support and reassurance for patients three, but is a good
time to reinforce healthy behaviors such as physical activity.
CEA testing –moderate quality evidence – strong recommendation
Recommendation – CEA every 3–6 months for 2 years and then every 6 months
for a total of 5 years- should correlate with the office visit
The use of CEA has been extensively studied. The rationale for postoperative
CEA monitoring is to detect an asymptomatic recurrence. Its greatest use has been
in patients that have an elevated CEA before surgery which returns to normal after
surgery. The strongest argument in favor of CEA testing is that resection of limited
metastases, particularly involving the liver, leads to long-term relapse free survival
in as many as 40 % of patients that undergo an attempted resection [7].
An asymptomatic elevation of the CEA increases the likelihood of a complete
resection and will be associated with better long-term outcomes. Of note, approxi-
mately 30 % of all colorectal cancer recurrences are not associated with a CEA
elevation. A false-negative CEA result is more commonly observed in poorly
118 C.L. Simmang
differentiated tumors. Even in patients with a normal preoperative CEA, there may
be an elevated CEA in over 40 % of recurrences.
When an elevated CEA is detected, it should be confirmed by retesting. False
positive elevations are seen in up to 50 % of patients at some time during their sur-
veillance and follow-up. Also the CEA level is elevated in cigarette smokers.
However a progressively rising CEA confirmed on retesting is indicative of meta-
static or recurrent disease. These patients need to undergo further evaluation and
testing.
Colonoscopy – High quality evidence – strong recommendation
Recommendation –
Colonoscopy at 1 year when the colon was cleared prior to or at the time of
surgery – repeat in 3 years and then every 5 years thereafter.
If colonoscopy not performed prior to or at the time of surgery, for instance
due to an obstructing lesion, perform a clearing colonoscopy at 3–6 months
after surgery.
Flexible sigmoidoscopy or proctoscopy may be performed every 6 months for
the first 2 years and annually for up to 5 years, following resection for rectal
cancer. When poor prognostic factors are present suggesting a higher risk of
local recurrence, proctosigmoidoscopy may be considered every 6 months
for 3–5 years.
Synchronous colon cancers occur in 2–5 % of patients with colorectal cancer
[16]. Further, all patients with a history of colorectal cancer are at increased risk for
developing adenomatous polyps. The National Polyp Study demonstrated a 76–90 %
reduction incidence of colorectal cancer when surveillance colonoscopy was used
in the setting of adenomatous polyps.
Periodic colonoscopy then enables detection of metachronous cancers at a more
favorable stage and even better, the prevention of metachronous cancers by identify-
ing and removing adenomatous polyps. In an analysis of 9029 patients performed
by the American Cancer Society-Multi Society Taskforce for Colorectal Cancer,
137 (1.5 %) developed metachronous cancers detected by colonoscopy. This inci-
dence compares favorably with screening colonoscopy.
The guidelines on the frequency for endoscopic surveillance following rectal
cancer was traditionally based on a high pelvic recurrence rate. The use of more
uniform surgical techniques including total mesorectal excision and the use of neo-
adjuvant therapy have resulted in local recurrence rates of less than 10 %. The
American Society of Clinical Oncology, the American Cancer Society and the US
Multisociety Taskforce all have issued different recommendations. The American
Society for Clinical Oncology, for example, no longer recommends proctosigmoid-
oscopy every 6 months in patients treated with adjuvant radiation for rectal cancer,
but does recommend proctosigmoidoscopy every 6 months for 2–5 years for patients
with rectal cancer not treated with radiation.
12 Follow-Up in Patient’s After Curative Resection for Colon Cancer Surveillance 119
CT scan – medium quality evidence – strong recommendation

Recommendation – CT scan of the chest, abdomen and pelvis yearly for 5 years
The current recommendation for CT scan of the chest, abdomen and pelvis has
evolved over the past several years. Much of the data has come from surveillance
studies where patients underwent more intense versus less intensive follow-up. In
one meta-analysis 9, the survival benefit was most significant in patients that had
had undergone both CT imaging and CEA measurement.
The most common sites for systemic recurrence for colorectal cancer are the
liver and the lungs. 80 % of recurrences will develop in the first 2–3 years. No study
has directly compared the evidence regarding the benefit of CT scans every 6 months
versus annually. Very high risk patients, such as those with prior liver metastases,
N2 disease, or an indeterminate lesion on prior imaging may be imaged every 6
months [3].
There is less evidence for chest surveillance than for abdominal (liver) imaging.
However in one European trial, there were seven asymptomatic patients with nor-
mal CEA levels [17] who had their pulmonary recurrences diagnosed only by CT
scan, and therefore would have gone undetected without surveillance chest CT. The
CT detected group had a significantly longer median survival from time of recur-
rence compared with their symptomatic counterparts (26.4 versus 12.6 months), but
not significantly longer than the CEA detected group (19.2 months). The largest
proportion of resectable recurrences were found using chest CT, even though a
larger proportion of recurrences was found with abdominal imaging.
MRI and PET Scans
These imaging modalities are not routinely recommended. MRI may be considered
in a patient that has a contraindication to intravenous contrast. Both MRI and PET
scanning may be indicated for an equivocal abnormality found on a CT scan
(Table 12.1).
Overall Utility
Many have questioned the cost-effectiveness of surveillance programs. A Cochrane

systematic review revealed no effect on overall survival, no difference in disease
specific survival as well and no difference in detection of recurrence [18]. The cost
has been reported anywhere from $1–$4 million for life saved. On the other hand,
the data described above clearly suggests that those patients who have a recurrence
detected prior to symptoms have a higher resectability rate for cure with an associ-
ated higher 5 year survival rate
120 C.L. Simmang
Personal Review of the Data
We believe that surveillance gives patients the best opportunity to detect a recur-
rence while it is still curable. In our practice, we generally follow the guidelines as
outlined above. A careful, individualized evaluation of the patient’s risks for recur-
rence as well as their comorbidities/ability to tolerate additional treatment will
impact the recommendation for surveillance.
References
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8. Pita-Fernandez S, Alhayek-Ai M, Gonzalez-Martin C, et al. Intensive follow-up strategies to
improve outcomes and non-metastatic colorectal cancer patient’s after curative surgery: sys-
tematic review of that analysis. Ann Oncol. 2015;26:644.
9. Renehan AG, Egger M, Saunders MP, O’Dwyer ST. Impact on survival of intensive follow-up
after curative resection for colorectal cancer, systematic review and medical analysis random-
ized trials. BMJ. 2002;324:813.
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colorectal cancer: a practice guidelines. Bio Med Central. 2003;3:26. bmccancer.biomedcen-
tral.com/articles/10.1186/1471-2407-3-26
11. Jeffrey M, Hickey BE, Hider PN. Follow-up strategies for patients treated for a non-metastatic
colorectal cancer Cochrane Database Sys Rev. 2007;(1):CD002200.
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review. Dis Colon Rectum. 2011;54:1036.
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ary prevention measures for survivors of colorectal cancer: American Cancer Society of clini-
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Chapter 13
Management of Patients with Acute Large
Bowel Obstruction from Colon Cancer
Marc A. Singer and Bruce A. Orkin
Introduction
Although colorectal cancer remains the third most common malignancy worldwide
[1], it is highly treatable in its early stages. Unfortunately, 10–29 % of patients with
colorectal cancer will present with a large bowel obstruction [2–5]. This poses a
challenging clinical dilemma for patients and physicians alike.
Bowel obstruction is highly morbid condition. Intervention to relieve the obstruc-
tion is appropriate for the large majority of patients. Patients with newly diagnosed
colorectal cancer will benefit from relief of the obstruction, allowing time to ade-
quately evaluate comorbidities and complete tumor staging. Modern systemic che-
motherapy may afford patients with metastatic disease up to 2 years survival [6].
Therefore palliative procedures to relieve obstruction are an important component
of the management of obstructed colorectal cancer patients, even in the setting of
stage IV disease.
Surgery has traditionally been the primary treatment of malignant large bowel
obstruction. More recently, endoscopic stenting has become a viable alternative and
has grown in popularity. Endoscopic insertion of a self-expanding metallic stent
(SEMS) to relieve the obstruction was first described as a palliative procedure, but
was quickly adopted as a bridge to surgery. An endoscopic palliative procedure is an
attractive option if it relieves the obstruction, with a low morbidity and requirement
for stoma. Similarly, stents as a bridge to surgery allow for conversion of an emer-
gency operation to a safer, elective, one-stage operation (Table 13.1).
M.A. Singer, MD, FACS, FASCRS (*) • B.A. Orkin, MD, FACS, FASCRS
Section of Colon and Rectal Surgery, Rush University School of Medicine,
Professional Office Building, Suite 1138, 1725 West Harrison Street, Chicago, IL, USA

DOI 10.1007/978-3-319-40223-9_13
122 M.A. Singer and B.A. Orkin

Patients with Surgery Self expanding Technical success, morbidity,
obstructing metallic stents bridging to surgery, oncologic
colorectal cancer outcomes, survival
Methods: Search Strategy
This review is based on the results of a search of the English language literature pub-
lished in databases including PubMed, Ovid, Google Scholar, and the Cochrane
Library. Publications were included from inception through December 2015. Search
terms included “stent,” “stenting,” “colon,” “rectum,” “colorectal cancer,” “obstruc-
tion,” “prospective,” “palliation,” “randomized,” and “review.” Relevant completed and
ongoing trials cited on www.clinicaltrials.gov were also reviewed. Emphasis was
placed on publications since 2010, so as to provide the most relevant practices and up
to date information. Systematic reviews, randomized trials, and prospective compara-
tive trials were reviewed in detail, and summarized in the Results Table. Level of evi-
dence and strength of recommendation according to the GRADE system were assigned
to each [7]. Case series and technical reports were reviewed and referenced as needed.
Results
Emergency surgery has long been the standard treatment for obstructing colorectal
cancers, despite the high risk of mortality and complication rates approaching 50 %
[4, 8–16]. Long-term survival for patients undergoing emergency operations for
malignant obstruction is inferior to those undergoing elective operations [17, 18]
This is likely due to a combination of both patient specific factors related to the
emergency nature of the operation, as well as more advanced stage tumors tending
to present with obstruction [12, 19–21].
Even in the setting of advanced pathology, medically suitable patients may ben-
efit from resection of the primary tumor. In addition to relieving the obstruction,
palliative resection appears to convey a survival benefit in patients with metastatic
disease [21–24]. The absolute survival advantage is modest, but may be important
to a patient with a limited life expectancy.
After resection, a decision must be made between primary anastomosis and creation
of an intestinal stoma. A large number of patients treated with a “temporary” stoma
will never undergo stoma closure. Further, primary reconstruction avoids the hidden
costs of a stoma to the patient, such as appliances, new clothing, and loss of work [25].
Surgeons must honestly counsel patients and families that in the setting of can-
cer, especially metastatic, that there is a 20–50 % likelihood of the stoma being
permanent [26–29]. For this reason, surgeons should construct every stoma with the
same attention to detail as if it were a permanent stoma. Emergent colostomies are
well known to carry a high rate of stoma specific complications [30].
13 Management of Patients with Acute Large Bowel Obstruction from Colon Cancer 123
Self-Expanding Metal Stents (SEMS)
Endoscopically deployed self-expanding metal stents can be used to restore intesti-

nal continuity in patients with obstructing colon tumors. First introduced as a pallia-
tive treatment for unresectable malignancies in the early 1990s, [31] the practice
rapidly evolved into a bridge towards one stage curative resections. The purported
benefits include transformation from an emergent to an elective operation with
reduced morbidity, mortality, length of stay, cost, rate of stoma formation, and
increased minimally invasive techniques and survival [32–34].
Multiple case reports and institutional series have demonstrated the safety and effi-
cacy of self-expanding metal stents to treat obstructing colorectal tumors. The large
majority of treated tumors are left sided or rectal tumors. These tend to obstruct more
often than right sided tumors, which are more commonly treated with right colectomy.
Rectal tumors can be stented, however stents placed into the distal rectum are at risk of
causing pain, tenesmus, or prolapsing through the anus. Most endoscopists can achieve
a very high degree of technical success, on the order of 90–95 % [35, 36]. Success is
dependent upon tumor size and location, but also the skill and experience of the endos-
copist. Some authors have suggested a learning curve of 20–30 procedures [37–39].
Common procedural complications include perforation, migration, and late occlusion
due to tumor in growth or stool impaction. A recent review of over 4000 procedures
documented a perforation rate of 7.4 % [35]. Covered stents are more resistant to tumor
in growth and late obstruction, while uncovered stents carry a lower rate of migration.
Stenting has grown in popularity as it provides a less invasive treatment for obstruc-
tion. Biagi et al. [40] demonstrated that the time to initiation of adjuvant chemother-
apy effects survival, and stents have at least the theoretical benefit of enabling a far
more expeditious initiation of treatment. Two general strategies have developed from
the early experience: stenting as definitive palliation, and stenting as a bridge to sur-
gery [41]. The minimally invasive nature of stenting makes it an attractive option for
either goal, but this must be balanced by the effectiveness, morbidity, mortality, cost,
rate of stomas, etc. A large number of publications have addressed these issues. The
largest numbers of these are single center experiences and retrospective reviews.
There are few high quality prospective or comparative trials. For this reason, system-
atic reviews and meta-analyses are useful approaches to evaluation of the relative
value of stenting versus surgery.
Stenting as Palliation
The data supporting the safety and effectiveness of stenting to relieve obstruction is
plentiful, however this is mostly low quality data in the form of small case series and
retrospective reviews. Few authors have directly compared palliative stenting to sur-
gical resection. There are no randomized controlled trials to support colectomy for
right sided cancers, but this remains the widely accepted standard of care. Stenting
of right sided lesions is technically feasible, [42–45] and may be considered for pal-
liation. This review will primarily consider data regarding stenting of left sided
lesions. There have been several recently published systematic reviews specifically
examining stenting compared to surgery in the palliative setting.
In 2011, Lee et al. [46] reported the long term outcomes of palliative stenting in
patients with incurable obstructing cancers by conducting a retrospective review of 71
patients treated with stents and 73 patients treated with palliative surgery during 2000–
2008. Stenting was as successful as surgery in relieving the obstruction (96 vs 100 %;
p = 0.12). Fewer early complications occurred in patients treated with stents (16 vs
33 %; p = 0.015), which included a 5.6 % perforation rate with stenting. Primary patency
of the stents was shorter than surgery, but patency after a second endoscopic interven-
tion was comparable to surgery (patency 229 vs 268 days; p = 0.239). There were more
late complications in the stenting group, but there were similar rates of major complica-
tions (p = .07). The number of patients requiring stomas was reduced in the stent group
(18 vs 51 %; p < 0.001). The time to chemotherapy was significantly reduced in the
stented patients (16 vs 31 days; p < 0.001). Overall survival was similar between groups.
The authors concluded that stenting is an effective therapy for initial palliation, reduces
time to chemotherapy and stoma requirements, with comparable longer term efficacy.
Young et al. [47] recently published an Australian randomized controlled trial of
stenting vs surgical decompression in patients specifically diagnosed with malig-
nant, incurable colon obstruction. The primary outcome measure was change in
quality of life. 52 patients (26 each arm) were enrolled. Stenting was technically
successful in 73 % of patients, with a 79 % rate of clinical success, and zero perfora-
tions. The quality of life scores (QLQ-CR29) were reduced in both groups, however
there was less reduction in quality of life scores in the stent group from baseline to
12 months (p = 0.01). Mortality and median survival were similar (5.2 vs 5.5 months).
The rate of stomas in the stent group was drastically reduced (27 vs 92 %). The
stented patients also enjoyed a shorter length of stay and return of bowel function.
The rate of patients proceeding to chemotherapy was the same in both groups
(42 %). The morbidity was similar between groups (38 vs 54 %).
Due to the relative lack of high quality prospective or comparative data, multiple
authors have written systematic reviews and performed meta-analyses combining
multiple small cohort studies. In 2012, Zhang et al. [48] performed a meta-analysis
including eight trials evaluating stenting vs surgery for palliative treatment of incur-
able disease. Outcomes of 601 patients (232 stent, 369 surgery) were detailed. There
were fewer stomas created in the patients undergoing stenting compared to surgery
(34 vs 51 %; p = 0.04). Mortality (6 vs 5 %; p = 0.47) and permanent stoma rate (17
vs 26 %; p = 0.52) were similar between groups. Complications were lower in the
stent group (21 vs 50 %; p = 0.001). There were no significant differences in recur-
rence or survival (57 vs 56 %; p = 0.39).
Zhao et al. [49] published a meta-analysis in 2013 which reviewed 13 trials, includ-
ing 3 randomized controlled trials (RCTs) comparing palliative stenting to surgery.
These trials included 837 patients with 404 stented and 433 undergoing surgery. The
30-day mortality favored stenting (4.2 vs 10.5 %; p = 0.01). Early complications also
favored stenting (14 vs 34 %; p = 0.03-stent perforation rate was 10.1 %). However,
late complications were lower with surgery (32 vs 13 %; p < 0.0001). Clinical relief of
obstruction was similar (93 vs 99.8 %; =0.0009). The post procedure length of stay
(LOS) favored stenting (9.6 vs 18.8 days; p < 0.00001). The requirement for stoma
significantly was reduced by stenting (13 vs 54 %; p < 0.00001). The time to postop-
erative chemotherapy also was improved by stenting compared to surgery (15.5 vs
33.4 days). Survival time was similar (7.6 vs 7.9 months; p > 0.05). The authors con-
cluded that stenting provided similar survival in the palliative setting, with reduced
30-day mortality, LOS, need for stomas, and time to chemotherapy.
In 2014, Liang et al. [50] published a similar systematic review and meta-
analysis, but included 9 studies (3 RCT) including 410 total patients (195 stented,
215 surgery). The technical success of stenting was 94 %, with clinical success at
94 %. The stent related perforation rate was 3.7 %. The mortality (7.1 vs 11.6 %;
p = 0.22) and short term complications were similar (26 vs 35 %; p = 0.22). Stenting
again demonstrated a higher long rate of complications (OR 2.34; p = 0.03).
Takahashi et al. [51] recently reviewed the available data from controlled trials
of stenting vs surgery as palliation for unresectable cancers. This review included
10 studies, with 793 patients (stenting 375, surgery 418). Similar outcomes to the
previous reviews were noted for mortality (2.1 vs 8.6 %; p < 0.01) and stoma cre-
ation (11 vs 41 %; p < 0.01). Stenting did improve early complications (12.3 vs
29.7 %; p < 0.01), and longer term survival. Stenting complications included perfo-
rations (7.4 %), migration (8.4 %), and obstruction (13 %). Stenting caused a higher
rate of total late complications (24 vs 14 %; p = 0.03).
Stenting as a Bridge to Surgery
Early reports [52] of stenting as a bridge to surgery offered patients an opportunity

for a safe one stage operation, with a significantly lower rate of colostomy formation.
Multiple European centers began to adopt and refine this treatment strategy. In 2011,
Jimenez-Perez et al. [53] detailed the experience of 182 patients prospectively
enrolled into two large European multinational registries. Procedural success was
achieved in a remarkable 98 % of patients. Clinical success with resolution of
obstructive symptoms was realized in 94 % of patients. Perforation occurred in 1.7 %
of patients, and overall stent complications were observed in 7.8 % Elective surgery
was performed in 90 % of patients at a median of 14 days later. A stoma was required
at the time of surgery in only 6 % of surgical patients. This experience detailed the
successful application of the bridge to surgery strategy, with a high degree of techni-
cal success, and a low rate of stoma formation. It did not however describe oncologic
results or long term outcomes of these patients.
Meisner et al., [54] also in 2011, similarly documented the short term safety and
efficacy of stenting as a bridge to surgery. They examined 447 patients enrolled
prospectively in 2 registries at 39 hospitals. In this cohort, the technical success of
stenting was 95 %, with clinical success (relief of obstruction) in 91 %. Perforations
occurred in 3.9 %. Successful procedures led to elective surgery in 90 % of patients
at a mean of 16 days after stenting. Stomas were created in only 6 % of these
patients. Thirty day mortality was 9 %, primarily due to perforation and cancer-
related death. This growing experience continued to suggest that stenting as a bridge
to surgery was reasonably safe in patients with obstructing colon tumors.
The first prospective randomized controlled trial comparing stenting as a bridge to

surgery vs immediate surgery was published in 2011 by Pirlet et al. [55]. The primary
outcome measure was the need for a stoma for any reason. This trial was performed at
nine centers. Only 30 patients were enrolled in each group. Surprisingly, 43 % of the
stented patients required a stoma compared to 57 % of the immediate surgery patients
(p = 0.30). Both groups had similar morbidity, mortality, and length of stay. A bridging
stent did not reduce the need for stoma, however the technical success of stenting in
this trial was only 47 % (perforation rate was 6.7 %), considerably lower than most
other prospective groups. In fact, of the patients that underwent a technically and clini-
cally successful stenting, none required a stoma at the time of surgery. Therefore, this
trial can be interpreted to suggest that if endoscopic stenting is successful, then the
need for stoma is eliminated. But the rate of perforation was much higher and the rate
of successful stenting was much lower than in other contemporary studies, suggesting
a lower level of experience and expertise or possibly patient selection bias.
Despite early concern for perforations, the Dutch continued to examine stenting
as a bridge to surgery. A cooperative trial at 25 hospitals randomizing 98 patients to
stenting (47) or surgery (51) was reported in 2011 [56]. Enrollment in this trial was
suspended due to increased morbidity in the stenting group at interim analysis.
Stoma rates at latest follow up were similar (69 vs 60 %), although the initial stoma
rate was lower in the stent group (51 vs 75 %). The initial trend of increased morbid-
ity in stoma patients was not confirmed in 98 patients with long-term follow up.
In 2013, Kavanagh et al. [57] published described the short and medium term
results of a retrospective review of patients who underwent either stenting as a bridge
to surgery or immediate surgery between 2005 and 2011. The final analysis included
22 patients in the bridging group and 26 in the emergent surgery group. Initial stoma
rates were similar (48 vs 42 %; p = 0.23). The permanent stoma rates were also similar.
There were no early mortalities and early morbidity was similar (59 vs 65 %). Stenting
was successful in 91 % of attempts with a 5 % perforation rate. The rate of patients
starting chemotherapy within 8 weeks was similar in each group (22 vs 15 %; p = 0.13).
The cancer specific survival and overall survival were also similar between groups.
The authors concluded that stenting is an effective bridge to surgery, resulting in a
similar stoma rate, primary anastomosis rate, morbidity, and mortality.
In 2013, Ghazal et al. [58] published a prospective randomized trial comparing
stenting as a bridge to surgery compared to immediate total abdominal colectomy with
ileorectal anastomosis. Sixty patients were randomized. The rate of technical success
for the stent group was 97 %, and was followed by elective resection 7–10 days later.
Morbidity was reduced in the stent group (13 vs 50 %; p = 0.012). Anastomotic leak
was 3.3 % in the subtotal colectomy group. There were no mortalities. The subtotal
colectomy patients experienced more frequent bowel movements postoperatively.
Cancer recurrence was similar between groups (17 vs 13 %; p = 0.228). In this study,
the authors concluded that stenting as a bridge to segmental resection was safer, with
fewer bowel movements postoperatively.
Gianotti et al. [28] published their results from 134 prospectively evaluated patients
with malignant obstruction. They were treated with either stenting as a bridge to sur-
gery (n = 49), stents as palliation (n = 34), or with immediate surgery (n = 51). Here the
technical success of stenting was again quite high at 95 % with a clinical success in
98 % of patients. Perforation rate was a remarkably low 1 %. Complications were sig-
nificantly reduced in stented patients compared to surgical patients (33 vs 61 %;
p = 0.005), as was length of stay (10 vs 15 days; p = 0.001). Mortality was 2 % in both
groups. The rate of stoma formation was significantly reduced in the stented patients (6
vs 22 %; p = 0.01). Interestingly, the stented patients had improved overall survival.
Although prospective, randomized comparative data on stenting remains sparse,
additional studies with larger cohorts have recently been published. In 2015, Saito
et al from Japan described a prospective cohort of 518 patients stented from 2012 to
2013 [59]. Stenting as a bridge to surgery was performed in 312 of these patients.
The technical and clinical success rates were 98 and 92 %. Perforation identified dur-
ing stenting was 1.6 %, and an additional 1.3 % perforations were identified at the
time of surgery, yielding an overall perforation rate of 3.8 %. Surgery was electively
performed in 297 (95 %) patients, with a median time to surgery of 16 days. The
primary anastomosis rate was 92 %, and the overall stoma rate was 10 %. Mortality
was 0.7 %, and postoperative morbidity was 16 % (including a 4 % anastomotic leak
rate). This is the largest multicenter prospective cohort of patients managed with
stenting as a bridge to elective surgery. The vast majority of patients were success-
fully stented and subsequently underwent a one stage operation with low morbidity.
Because there are relatively few prospective trials evaluating stenting as a bridge
to surgery, multiple authors have performed systematic reviews in the last 5 years in
an effort to draw meaningful conclusions from pooled data. In 2011, Sagar et al.
[60] provided a Cochrane review with a meta-analysis including 5 RCT trials with
207 patients. The primary objective was to evaluate the clinical success rate of
stents compared to emergency surgery. Surgery offered a higher rate of relief of
obstruction, but stenting offered a shorter length of stay. There were similar rates of
complications. However, the included trials had several different definitions of
return of GI function and resolution of obstruction.
In 2012, Tan et al. [61] performed a meta-analysis of 4 RCT which included a
total of 234 patients. Summarized technical and clinical success rates for stenting
were 71 and 69 %, with a perforation rate of 6.9 %. Stenting as a bridge to surgery
resulted in a significantly higher rate of primary anastomoses (RR 1.58, 95 %CI
1.22–2.04; p < 0.001), and lower overall stoma rate (RR 0.71; p = 0.004). There were
no differences in the rates of permanent stomas, mortality, anastomotic leak, or sur-
gical site infection. It should be noted that 3 of the included trials were terminated
early due to complications (2 in their stenting group, and 1 in their surgery group).
Cirocchi [62] published a meta-analysis in 2013 of 3 RCTs specifically comparing
stenting as a bridge to surgery vs immediate surgery for left colon and rectal cancers.
The clinical success rates were 53 % for stenting vs 99 % for surgery. Mortality was
similar between groups (8 vs 9 %). Overall complications were similar (48 vs 51 %),
but the stented patients had a somewhat lower rate of stoma formation (45 vs 62 %).
In 2014, Huang [63] performed a systematic review of 7 RCTs which included
382 patients (stenting 195, surgery 187). The technical success of stenting was
77 %. There were no differences in mortality (11 vs 12 %), but the stented patients
experienced fewer complications (33 vs 54 %; p = 0.03). Also, there was a higher
rate of primary anastomoses (67 vs 55 %; p < 0.01) and lower permanent stoma rates
with stenting as a bridge to surgery (9 vs 27 %; p < 0.01).
Most recently, in 2015 Matsuda described the effect of stenting on long term onco-
logic outcomes in a systematic review, [64] which included 11 studies. These were a
combination of prospective, retrospective, and RCTs with a total of 1136 patients (432
stents as bridge to surgery, and 704 emergency surgeries). Overall survival, disease free
survival, and recurrence rates were similar between groups. Five year overall survival
was available in eight reports, with generally similar results between groups (57 vs 67 %,
P = 0.66), however the data was heterogeneous. Five year disease free survival reported
in 5 trials was also not significantly different between groups (48 vs 59 %; p = 0.43).
Eight trials reported recurrence rates, with no significant differences. The authors con-
cluded that stenting as a bridge to surgery was oncologically comparable to emergency
surgery with respect to overall survival, disease free survival, and recurrence.
This issue of oncologic safety has been specifically addressed by several authors
who focused on defining the oncologic risks of stenting as bridge to surgery com-
pared to immediate resection. It is possible that a delay in surgery, procedure related
perforation, or occult perforation may lead to increased tumor recurrence. A 2015
Danish study [65] sought to clarify if self-expanding metal stents used specifically
as a bridge to surgery were safe and useful by examining a population-based data-
base with procedures performed from 2005 to 2010. Patients that survived 30 days
postoperatively were analyzed (581 stent, 3333 resection). Five-year survival was
improved in the stented patients (49 vs 40 %; adjusted mortality ratio 0.98, 95 %CI
0.90–1.07), however the 5-year recurrence was greater (39 vs 30 %; adjusted
incidence rate ratio 1.12, 95 % CI 0.99–1.28). The authors concluded that stenting
and emergent resection have similar 5-year survival, but stenting may cause
increased recurrence. Other authors have suggested that there may be an increased
rate of tumor spillage from stent perforations, and that there may be a higher rate of
metastatic disease or shorter survival if a perforation occurs [66–68].
Conclusions
Review of this literature seems to indicate that although it may be possible that stent
perforation can increase recurrence or metastatic disease, it is much clearer that
stenting as a bridge to surgery significantly reduces perioperative complications. A
reduction in complications, in turn, has been correlated with improved survival in a
recent analysis of more than 12,000 patients [69]. Therefore, patients with a high
risk of perioperative complications may be best suited for stenting as a bridge [70,
71]. To be efficacious and maintain a reasonable level of safety, institutional rates of
successful stent placement should be 90 % or better, and the rates of stent-related
perforation should be 5–7 % or lower.
It is unlikely that a large scale RCT comparing stenting as a bridge to surgery
will be conducted due the requirement of a very large sample size, difficulty with
technical standardizations, and need for long-term cancer follow up. It would also
be very difficult to standardize the surgical arm of such a trial – segmental resection
vs Hartmann’s procedure vs total colectomy, stoma, etc. Therefore, meta-analyses,
as imperfect as they are, may be the best source of data and recommendations.
The American Society of Colon and Rectal Surgeons (ASCRS) 2013 Practice
Parameters for the Management of Rectal Cancer [72] addresses the issue of stent-
ing. The authors reiterate that stenting should not be considered in the setting of
perforation, massive bleeding, or lack of technical expertise. Technical success may
be achievable, but is at risk for failure due to migration, pain, and incontinence
when placed in the rectum. The authors do conclude that a stent may function as a
bridge to surgery, and facilitate a primary anastomosis, or as a component of pallia-
tive treatment in the setting of metastatic disease. Surgeons were cautioned about
the limited duration of patency of stents in light of the improving survival of patients
on modern palliative chemotherapy. The recommendation was graded as a strong
recommendation in favor of stenting based on low quality evidence.
Currently, trials of stenting versus surgery are being conducted at Nanfang Hospital
in southern China, and at the Chinese University of Hong Kong (www.clinicaltrials.
gov). In addition, other trials in progress are comparing devices such as covered ver-
sus uncovered stents.
The Approach to the Patient with Obstructing Colon Cancer
When a patient with an obstructing colorectal cancer presents, the first decision that
must addressed is the goals of care. Some patients may prefer to seek hospice care
with comfort measures only, especially in the setting of metastatic disease. If the
patient elects to pursue treatment, then the next decision is how to acutely manage
the obstruction. The primary options are stenting or surgery. Most right-sided colon
lesions are treated with right colectomy. These patients should undergo a brief
period of resuscitation and optimization, followed by right colectomy with either
primary anastomosis, ileostomy and mucous fistula, or anastomosis with proximal
loop ileostomy, depending on the condition of the patient and the colon.
For left-sided colon lesions, endoscopic stenting is an attractive option. If the
endoscopist has experience with stenting and there are no compelling reasons to
proceed immediately to the operating room, such as perforation, then stenting
should be considered. If successful, a thorough metastatic workup and medical
optimization can proceed. If the patient has incurable disease, the stent may serve
as definitive palliation. Patency can be expected for many months and may be
repeated if needed. Occasionally, resection may be performed subsequently if the
metastatic disease is stabilized and the primary tumor is symptomatic. If the patient
appears to have potentially curable disease, stenting is also a good initial approach.
Stenting as a bridge to surgery does appear to reduce the need for a stoma and
reduces the rate of postoperative complications. Although not all stents are techni-
cally successful and there is a 5–7 % rate of perforation, stenting has the distinct
advantage of conversion of an emergency operation into an elective operation with
the ability to stage and stabilize the patient. Patients and their families should
clearly understand that stenting is not universally successful, that there are compli-
cations, and that, if unsuccessful, immediate surgery would be necessary, as would
have been offered otherwise.
130
Published data of stenting compared to surgery (2010–2015)

Technical Quality of
success of evidence
Publication Design Patients stenting Stenting results Surgery results (GRADE)
Palliative stenting – prospective trials
Young (2015) [47] RCT 26 Stent 73 % Mortality 8 % Mortality 15 % High
26 Surgery Morbidity 28 % Morbidity 54 %
Perforation 0 Perforation 0
LOS 7 days LOS 11 days
Stoma 27 % Stoma 92 %
Postop chemotx 42 % Postop chemotx 42 %
Survival 5.2 months Survival 5.5 months
Palliative stenting – systemic reviews
Takahashi Meta-analysis 10 trials 95 % Mortality 2 % Mortality 9 % High
(2015) [51] 375 stent Morbidity 12 % Morbidity 30 %
418 surgery Perforation 7 % Stoma 41 %
Stoma 11 % Late 14 %
Late complications 24 % complications
Survival improved
Liang (2014) [50] Meta-analysis 9 trials 94 % Mortality 7 % Mortality 12 % High
195 stent Morbidity 26 % Morbidity 35 %
215 surgery Perforation 3.7 %
Zhao (2013) [49] Meta-analysis 13 trials 93 % Mortality 4 % Mortality 11 % High
433 Surgery Perforation 10 % Perforation –
M.A. Singer and B.A. Orkin
Time to Chemotx 16d Time to Chemotx 33 d

Survival 7.6 months Survival 7.9 months
Stenting as a bridge to surgery – prospective trials
Saito (2015) [59] Prospective 312 stent 98 % Mortality 0.7 % Moderate
cohort Morbidity 16 %
Perforation 3.8 %
Initial stoma 8 %
Final stoma 10 %
Bridged to surgery 95 %
Erichsen Prospective 581 stent 5-year survival 49 % 5-year survival 40 % Moderate
(2015) [65] cohort 3333 surgery Recurrence 39 % Recurrence 30 %
Ghazal RCT 30 stent bridge 97 % Mortality 0 Mortality 0 Moderate
(2013) [58] to segmental Morbidity 1 % Morbidity 50 %
colectomy LOS 13 days LOS 8 days
30 subtotal
Recurrence 17 % Recurrence 13 %
colectomy with
ileorectal More frequent bowel
movements
Gianotti Prospective 49 stent as 95 % Mortality 2 % Mortality 2 % Moderate
(2013) [27] cohort bridge; 34 stent Morbidity 33 % Morbidity 61 %
as palliation Perforation 1 % LOS 15 days
51 surgery
LOS 10 days Stoma 22 %
Stoma 6 % 5 year survival 55 %
5 year survival 80 %
Gorissen (2013) Prospective 62 stent 90 % Morbidity 8 % Morbidly 21 % Moderate
[73] cohort 43 surgery Mortality 3 % Mortality 9 %
5-year survival 71 % 5-year survival 56 %
13 Management of Patients with Acute Large Bowel Obstruction from Colon Cancer
Chemo 42 % Chemo 26 %
(continued)
131
132

success of evidence
Alcantara RCT 15 stent 100 % Morbidity 13 % Mortality 8 % Moderate
(2011) [74] 13 surgery Mortality 0 Morbidity 54 %
Perforation 0 Anastomotic leak 31 %
Stoma 7 % Stoma 0
5-year survival 57 % 5-year survival 69 %
Pirlet (2011) [55] RCT 30 stent 47 % Mortality 9 % Mortality 4 % High
30 surgery Morbidity 49 % Morbidity 53 %
Perforation 7 % Stoma 57 %
Stoma 43 % (0 %
in patients
successfully
bridged
with stent)
Van Hooft RCT 47 stent 70 % Mortality 11 % Mortality 10 % Moderate
(2011) [56] 51 surgery Morbidity 53 % Morbidity 45 %
Perforation 13 % Initial stoma 75 %
Initial stoma 51 % Final stoma 60 %
Final stoma 69 %
Bridge to surgery 94 %
Ho (2012) [75] RCT 20 stent 75 % Morbidity 35 Morbidity 58 Moderate
19 surgery Mortality 0 Mortality 16
Perforation 0 Stoma 32 %
Stoma 10 % LOS 13
LOS 14
Stenting as a bridge to surgery – systematic reviews
Matsuda Meta-analysis 11 trials 5 year survival 57 % 5 year survival 67 % Moderate
(2015) [64] 432 stent Recurrence 31 % Recurrence 27 %
704 surgery
Huang Meta-analysis 195 stent 77 % Mortality 11 %s Mortality 12 % High
Permanent stoma 9 % Permanent stoma 27 %
Cennamo Meta-analysis 178 stent 74 % Mortality 8.4 % Mortality 8 % High
Perforations 8 % Stoma 48 %
Stoma 25 %
Tung (2013) [77] RCT 24 stent 83 % Mortality 0 Morality 0 Moderate
24 surgery Morbidity 8 % Morbidity 33 %
Stoma 0 Stoma 25 %
5 years survival 48 % 5 years survival 27 %
Chemotx 75 % Chemotx 54 %
Cirocchi Meta-analysis 3 trials Mortality 8.2 % Mortality 9 % Moderate
(2013) [62] 97 stent Complications 48 % Complications 51 %
100 surgery Stoma 45 % Stoma 62 %
Clinical success 53 % Clinical success 99 %
Zhang (2012) [48] Meta-analysis 8 trials 87 % Mortalitys 6 % Mortality 5 % Moderate
369 surgery Primary anastomosis 78 % Primary 43 %
anastomosis
13 Management of Patients with Acute Large Bowel Obstruction from Colon Cancer
Permanent stoma 17 % Permanent stoma 26 %

5 year survival 57 % 5 year survival 56 %
133
(continued)
134

success of evidence
Tan (2012) [61] Meta-analysis 4 trials 71 % Mortality 7 % Mortality 6 % Moderate
116 Stent Perforation 6.9 % Primary 44 %
118 Surgery anastomosis
Primary anastomosis 66 % Stoma 64 %
Stoma 44 % Permanent stoma 44 %
Permanent stoma 32 %
Sagar (2011) [60] Cochrane/ 5 RCT 86 % Mortality 2.3 % Mortality 2.3 % High
Meta-analysis 102 stent Morbidity 39 % Morbidity 46 %
105 surgery Perforation 5.9 % LOS 17 days
LOS 11.5 days Relief of 99 %
Relief of obstruction 78 % obstruction
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Chapter 14
Utility of Primary Tumor Resection
in Asymptomatic, Unresectable Metastatic
Colon and Rectal Cancer
Michael Pezold, Geoffrey K. Ku, and Larissa K. Temple
Introduction
One in five patients diagnosed with colorectal cancer (CRC) present with synchro-
nous metastatic disease, and of these, only 13 % survive to 5 years [1]. Curative
resection of the primary tumor and metastases can improve 5-year overall survival
(OS) to 30–50 % [2]. Unfortunately, about three-quarters of patients with metastatic
CRC present with unresectable disease to the liver [3]. In this setting, the principal
treatment is chemotherapy, with an overall median survival in randomized-
controlled trials of >20 months [4, 5]; in fact, a recent phase III study suggested that
patients who were able to receive all currently available systemic treatment options
had a median OS of nearly 30 months [6].
While receiving chemotherapy, about 10–20 % of patients may develop symp-
toms from the primary colonic tumor (e.g. obstruction, perforation, and severe
bleeding) that necessitate acute intervention [7–11]. Upfront resection of the pri-
mary colon cancer prior to the development of symptoms could potentially prevent
morbidity, and improve outcomes. Early retrospective data has suggested a survival
benefit with primary colon resection, combined with chemotherapy, in the presence
M. Pezold, MD, MS
Department of Surgery, New York Presbyterian-Weill Cornell Medicine,
New York, NY, USA
G.K. Ku, MD
Gastrointestinal Oncology Service, Department of Medicine, Memorial Sloan Kettering
Cancer Center, New York, NY, USA
L.K. Temple, MD, MS (*)
Colorectal Service, Department of Surgery, Memorial Sloan Kettering Cancer Center,
New York, NY, USA

DOI 10.1007/978-3-319-40223-9_14
140 M. Pezold et al.
Table 14.1 Clinical question

P Patient population Unresectable, metastatic colon cancer with an asymptomatic
primary tumor
I Intervention Primary tumor resection (colectomy) followed by 1st line
chemotherapy,
C Comparator 1st line chemotherapy with primary tumor resection only if/when
patient becomes symptomatic
O Outcomes Overall survival, Hazard Ratio
of unresectable metastases [8, 12]. However, up to half of the patients in these

analyses did not receive chemotherapy after surgery, and these patients had no sur-
vival benefit when compared to those receiving chemotherapy alone [12].
As a surgeon, it is difficult to draw conclusions from the literature, which is
limited to retrospective data, with considerable susceptibility to selection bias.
Further complicating the decision to pursue upfront surgery is the fact that there
have been significant survival gains over the last decade as a result of multi-drug
regimens and targeted therapies [13–20]. Depending on one’s perspective, the
improved survival associated with modern-era systemic therapy may either obvi-
ate the need for resection by providing significant reduction in tumor size and
control of local symptoms, or may result in a greater number of patients develop-
ing symptoms from the primary tumor because they live longer, thereby requir-
ing surgery. No good data exists regarding the likelihood of curative resection
after chemotherapy in patients who present with initially unresectable disease;
thus, the clinical choices in this setting are primarily colon resection followed by
chemotherapy, or chemotherapy alone. In this chapter, we examine emerging
data regarding primary tumor resection with chemotherapy in patients with unre-
sectable metastatic disease and an asymptomatic primary, versus patients receiv-
ing upfront multidrug chemotherapy (Table 14.1).
Search Strategy
A detailed search of the Embase-Medline databases was conducted for current med-
ical literature published from 2010 to 2015. The following search terms were
employed to identify relevant articles: (“colon” OR “colorectal”) AND (“cancer”
OR “carcinoma” OR “adenocarcinoma”) AND (“metastatic” OR “Stage IV” OR
“Stage 4”) AND “asymptomatic” AND (“surgery” OR “colectomy” OR “resec-
tion”). Duplicate articles were excluded. We included 14 articles, published from
2010 to 2015, that were identified in a Cochrane review and meta-analysis on this
specific topic, and were not identified in our initial literature search [21, 22]. The
title and abstracts of English-language articles were assessed for relevance. We
excluded articles for the following reasons: not relevant, no comparator group (trend
14 Utility of Primary Tumor Resection in Asymptomatic 141
Medline/Embase Literature Search 2010-2015

Search terms:
(“colon” OR “colorectal”) AND
(“cancer” OR “carcinoma” OR “adenocarcinoma”) AND
(“metastatic” OR “Stage IV” OR “Stage 4”) AND
“asymptomatic” AND
(“surgery” OR “colectomy” OR “resection”)
Records identified through Embase Additional records identified

& Medline database searching through SLR/Meta-Analysis
(n = 306) (n = 14)
Duplicate records removed

(n = 130)
Articles excluded by title

& abstract:
n = 160
Records screened
Irrelevant (127)
(n = 190)
No comparator (12)
Opinion/Review (19)
SLR/Meta-analysis (2)
Full-text articles assessed Full-text articles excluded:

for eligibility n = 15
(n = 30) Duplicate data/diff
journal (1)
Ongoing trial (2)
Abstract/Poster (12)
Studies included in
qualitative synthesis
(n = 15)
Fig. 14.1 PRISMA diagram, systematic literature search results
analysis), review/opinion articles without primary data, and systematic literature

reviews/meta-analyses. A total of 30 articles met the inclusion criteria for full
review. Full-text articles were excluded if they were limited to an abstract/poster,
contained data duplicated in a different journal, or reported on ongoing trials with-
out reporting any preliminary data. Fifteen manuscripts remained for analysis, five
of which were identified from the Cochrane Review and meta-analysis. The litera-
ture review process, following PRISMA guidelines, is detailed in Fig. 14.1. Selected
articles were abstracted for several variables including study design, time interval,
patient population, chemotherapy, survival, and quality (Table 14.2).
Table 14.2 Literature search results
142
Median Acute
overall surgery
Patient Chemotherapy Patients (n) survival (mo) Survival (NR) Quality of
First author Year Study design Interval population regimen(s) R NR R NR HR % evidence
Seo 2010 Retrospective 2001–2008 umCRC FL ± Ox/Iri ± 196 83 22 14 – 8.4 Low
cohort + APT Bev/Cetux
Chan 2010 Retrospective 2000–2002 mCRC Not reported 286 125 14 6 – – Very low
cohort
Venderbosch 2011 Retrospective 2003–2004 mCRC CAPOXIRI 258 141 16.7 11.4 0.63 – Very low
review of RCT
(CAIRO I)
2011 Retrospective 2005–2006 mCRC CAPOX/Bev 159 289 20.7 13.4 0.65 – Very low
review of RCT ± Cetux
(CAIRO II)
Karoui 2011 Retrospective 1998–2007 umCC ± APT FL ± Ox/Iri 85 123 30.7 21.9 – 19 Low-Mod
cohort, ± Bev/Cetux
propensity
scored
Verberne 2011 Retrospective 2002–2006 mRC ± APT Not reported 26 21 26 17 0.5 – Very low
cohort
Cetin 2013 Retrospective 2006–2010 umCRC + APT CAPOX/IFL/ 53 46 23 17 – 4.4 Low
cohort FOLFIRI ± Bev
Boselli 2013 Retrospecitve 2010–2011 umCRC + APT FOLOX ± Bev 17 31 4 5 – – Very low
cohort
Ferrand 2013 Retrospective 1997–2001 mCRC (mCC) FL 156 56 16.3 9.5 – 7 Low
review of RCT (15.2) (11.1)
(FFCD 9601)
M. Pezold et al.
Yun 2014 Retrospective 2000–2008 umCRC + APT ± FL ± Ox/ 113 113 17.2 14.4 – 4.5 Moderate
cohort, umCRC + APT Iri ± Bev/ (286) (198)
propensity Cetux
matched
Watanabe 2014 Retrospective 2002–2009 umCRC + APT FL ± Ox/ 46 112 19.9 19.0 – 21 Low
cohort Iri ± Bev/
Cetux
Yoon 2014 Retrospective 2000–2007 umCRC ± APT FL/Cape ± Ox/ 51 51 16.5 12 0.68 - Low-Mod
cohort, Iri ± Bev/ (195) (66)
propensity Cetux
matched
Matsumoto 2014 Retrospective 2005–2011 umCRC + APT Fl ± Ox/ 41 47 23.9 23.6 0.72 25.5 Low
cohort Iri ± Bev/
Cetux
Tsang 2014 Retrospective 1996–2007 mCRC Not reported 8599 3117 21 10 – – Very low
cohort (SEER)
Tarantino 2015 Retrospective 1998–2008 mCRC Not reported 22858 17575 – – 0.40 – Very low
cohort,
14 Utility of Primary Tumor Resection in Asymptomatic
propensity
scored (SEER)
Ahmed 2015 Retrospective 1992–2005 mCRC + APT Not reported 521 313 18.0 8.1 0.52 – Very low
cohort
APT asymptomatic primary tumor, Bev bevacizumab, Cape capecitabine, CAPOX capecitabine/oxaliplatin, CAPOXIRI capecitabine/oxaliplatin/irinotecan,
Cetux cetuximab, FL fluropymidine/leucovorin, FOLFOX leucovorin/infusional 5-FU/oxaliplatin, FOLFIRI leucovorin/infusional 5-FU/irinotecan, Iri irinote-
can, mCC metastatic colon cancer, mCRC metastatic colorectal cancer, mRC metastatic rectal cancer, Ox oxaliplatin, umCC unresectable metastatic colon
cancer, umCRC unresectable metastatic colorectal cancer.
143
Results
Our literature search identified 15 recently published retrospective studies, in which

patients received primarily multi-drug chemotherapy. No prospective observational
or randomized controlled trials (RCTs) have been published to date, and secondary
analyses of these trials are limited.
Four RCTs were initiated to address this question, although two have already
closed due to poor accrual [23, 24]. The Dutch Colorectal Cancer Group (CAIRO4)
and the German SYNCHRONOUS trial group have opened multicenter, random-
ized, superiority trials comparing primary tumor resection + fluoropyrimidine-based
regimens with targeted therapy, vs. fluoropyrimidine-based regimens with targeted
therapy alone [25, 26]. The results of these trials are not anticipated for several
years, but will obviously have a significant impact on surgical decision-making.
Until that time, the data from our literature search represents the body of knowledge
available on which surgeons may base decisions. Many studies report upfront resec-
tion vs. no resection, but do not address the more important question of upfront
surgery and chemotherapy vs. chemotherapy alone. Among both groups, there were
limited or no data regarding chemotherapy received, and need for acute surgery
while on chemotherapy. Recognizing these limitations, a review of the current lit-
erature does provide some guidance to the practicing surgeon who is attempting to
decide whether or not to resect the primary colon tumor before initiating chemo-
therapy in patients with unresectable metastatic disease.
Overall Survival
Twelve of the 15 studies identified in our search demonstrated better OS with pri-
mary tumor resection vs. no resection in patients with metastatic colon cancer, with
a median survival benefit of 7 months. At face value, these results suggest superior
OS with primary tumor resection prior to the development of symptoms in patients
with unresectable metastatic CRC. Yet on closer analysis, there are serious limita-
tions to these findings, and they should therefore be interpreted with ample
skepticism.
To reduce the impact of selection bias and potential confounders, four studies
used propensity score modeling, with variable results. Two groups from Korea
used propensity scores to match patients who underwent initial primary tumor
resection + chemotherapy vs. chemotherapy alone. The smaller of these studies
found a statistically significant OS benefit with primary tumor resection (16.5 vs.
12 months, p = 0.048) [21], whereas the other, much larger study found no statisti-
cal difference in OS between these groups (17.2 vs. 14.4 months, p = 0.27) [27, 28].
In the remaining two studies, the data were not sufficiently defined or granular, and
the results are less compelling [29, 30]. A French publication reported that OS was
superior with primary tumor resection + chemotherapy vs. chemotherapy (30.7 vs.
21.9 months, p = 0.031) even after propensity analysis; however, a significant pro-
portion of patients in both groups had obstructive primary tumors at initial presen-
tation (38.8 % vs 26.5 %), and it remains unclear if the survival advantage was from
primary resection vs. stent placement or chemotherapy [29]. Similarly, a large
U.S. SEER Database analysis demonstrated a dramatic survival advantage with
primary tumor resection vs. no resection (HR = 0.40, p < 0.001) even after propen-
sity matching (for such factors as age, grade, baseline carcinoembryonic antigen
level), but potential confounders such as chemotherapy, performance status,
comorbidity, and metastatic disease extent/resectability were not reported [30]. In
the end, after controlling for confounding and sufficiently defining the target popu-
lation, the data did not suggest a significant survival advantage with upfront sur-
gery in asymptomatic patients.
Chemotherapy and Survival
A central criticism of earlier retrospective studies comparing primary tumor resec-

tion vs. initial chemotherapy has been the reliance on 5-fluorouracil (5-FU)/leu-
covorin monotherapy, which was the only chemotherapy agent available prior to the
early 2000s. To restrict our literature search to modern chemotherapeutic regimens,
we limited our investigation to studies published from 2010 to the present. Despite
these efforts, seven of the selected articles included patients receiving 5-FU/leu-
covorin or the oral 5-FU pro-drug capecitabine alone [27–29, 31–34], and five stud-
ies failed to report whether chemotherapy was even administered [30, 35–38].
Furthermore, considerable heterogeneity in chemotherapy regimens existed in all
but three of the studies. In these three studies, patients received only irinotecan- or
oxaliplatin-based chemotherapy, with or without the monoclonal antibodies bevaci-
zumab (anti-vascular endothelial growth factor) and cetuximab (anti-epidermal
growth factor receptor) [39–41]. One of these studies retrospectively analyzed two
RCTs and demonstrated a 5-month survival benefit with primary tumor resection
and subsequent palliative chemotherapy; however, this study was limited by the fact
that patients in the chemotherapy-only group had a statistically greater metastatic
disease burden [39]. In the two remaining studies, primary resection followed by
chemotherapy vs. chemotherapy alone did not significantly improve OS [40, 41].
The delay in initiating chemotherapy has frequently been considered a draw-
back to primary tumor resection. In the three studies reporting time-to-chemother-
apy in asymptomatic patients who underwent upfront surgery, the data demonstrate
a median 4–5 week delay in chemotherapy initiation, compared to patients who
had upfront chemotherapy [31, 33, 41]. In addition to this delay, the data suggest
that a significant proportion (15–50 %) of asymptomatic patients who undergo
upfront surgery do not proceed to chemotherapy most likely due to debilitation
from surgery [28, 33, 34, 37, 41] and only one of these studies showed an improved
OS with upfront surgery [37]. Two publications included patients for either strat-
egy only if they had received some chemotherapy; one of the two studies reported
that primary tumor resection was associated with a significantly better OS (30.7 vs.
21.9 months, p = 0.03 [29]; 23 vs. 17 months, p = 0.32 respectively) [40]. These
data suggest that OS is potentially optimized in patients who have upfront surgery
when they are able to receive postoperative chemotherapy. Identification of those
patients who will be able to proceed from surgery to chemotherapy in an expedi-
tious manner remains challenging.
Metastatic Disease Burden and Survival
Careful patient selection for upfront surgery is critical, as the disease burden of
metastatic CRC has a dramatic influence on candidacy for curative resection and
OS. Of the studies that reported a survival benefit with primary tumor resection [27,
29–32, 35–40], more than half did not report the extent or resectability of metastatic
disease [30, 32, 35–39]. For example, two studies attempting to identify an optimal
strategy through examination of SEER data reported that patients with stage IV
CRC lived significantly longer after primary resection [30, 35]. However, neither
study described the extent and resectability of metastatic disease, receipt of chemo-
therapy, or symptoms related to the primary tumor.
In a retrospective analysis of two Dutch RCTs (CAIRO I and II), OS was bet-
ter with resection compared to no resection (16.7 vs. 11.4 months, p = 0.004; 20.7
vs. 13.4 months, p < 0.0001), although there was evidence to suggest that patients
who did not have surgery were more likely to have an abnormal LDH, more
extrahepatic disease, and oligo-metastases, all independent predictors of poor
survival [39].
Amongst the eight manuscripts that provided sufficient documentation of the
burden of unresectable metastatic disease, the majority of studies found that pri-
mary tumor resection did not provide a significant survival advantage over chemo-
therapy [27–29, 31, 33, 34, 40, 41]. Only two demonstrated a significant difference
in median OS with upfront primary resection vs. initial chemotherapy (30.7 vs.
21.9 months, p = 0.03) [29], (21 vs. 10 months, p < 0.001) [27]. In a study by Chan
et al., patients receiving chemotherapy first were significantly more likely to be of
older age, to have adjacent organ invasion, extensive liver metastases, poorer per-
formance status, and a rectal primary tumor, all of which are poor prognostic fea-
tures. In the studies showing no survival benefit, three were of relatively small
sample size (n < 100), and two limited primary resection to patients with non-tra-
versable tumors only [33, 34, 40, 41]. However, in the overwhelming majority of
studies with documented unresectable metastatic disease, OS was not significantly
different between groups.
Further Considerations
While there is no compelling evidence that supports upfront surgery vs. chemo-
therapy with respect to survival benefit, surgeons face additional issues when decid-
ing between primary surgery and chemotherapy. These deserve further discussion.
Acute Surgery During Chemotherapy
Removal of the primary tumor in an elective setting prior to the development of obstruc-
tion, perforation or severe bleeding should theoretically result in lower morbidity and
mortality. Within our selected studies, 4–25 % of patients receiving chemotherapy first
developed symptoms requiring acute surgery [22, 24–28]; and except for differences in
the study sizes, no discernible trend could be found between low- and high-incidence
studies with respect to patient population, chemotherapy received, or time interval. In
three of the four largest studies (n > 200 patients), less than 10 % of patients required
acute surgery while on chemotherapy; the most frequent indication was obstruction,
and rarely tumor perforation or bleeding [28, 31, 32]. If the theoretical primary benefit
of upfront resection is to avoid acute surgery at a later time, somewhere between five
and ten patients would receive an unnecessary intervention in order to prevent acute
surgery in one patient. Thus, the prevention of acute surgery with elective resection is
less common than is purported. Additionally, one cannot ignore the potential delay in
chemotherapy initiation, and the potential deterioration in performance status associ-
ated with serious surgical complications. From a prevention standpoint, primary tumor
resection does not provide a significant benefit for most patients.
Postoperative Complications: Elective Versus Acute Surgery
Colorectal resection, even in the elective setting, is plagued by a variety of complica-

tions, and can delay the initiation of chemotherapy. Understandably, acute surgery
comes with an even greater risk for complications that may significantly delay or pre-
vent the re-institution of palliative chemotherapy. No study in our search reported on the
delay or completion of chemotherapy associated with complications. Three studies
reported complications after surgery [31, 33, 34], one of which provided data only on
complications after elective resection, thus preventing inter-group comparisons [31].
The results from the remaining two publications failed to show a difference with regards
to the incidence of complications, after either elective or acute surgery [33, 34]. The
smaller of the two studies found similar rates of severe complications (Clavien-Dindo
Grade 3 and 4) [34]; paradoxically, the larger study found that elective surgery was
associated with more complications [33]. Although primary tumor resection should
intuitively be associated with the lower morbidity of elective surgery, no study has actu-
ally demonstrated any such difference in morbidity between elective vs. acute surgery.
Systemic Inflammation and Primary Resection
Emerging evidence suggests that the benefits of primary tumor resection may involve
more than the prevention of primary tumor symptoms. Tumor-associated systemic
inflammation is associated with significant reductions in survival in patients with
solid-tumor cancers [42]. Increased neutrophil-to-lymphocyte ratio (NLR) is a well-

established biomarker of systemic inflammation, and can be calculated with a simple
complete blood count. However, none of the manuscripts identified in this search
included NLR in their analyses. Two retrospective studies of patients with metastatic
CRC who underwent primary tumor resection in the setting of asymptomatic disease,
demonstrated a persistent survival benefit with a low NLR or reversal of NLR from
high to low [43, 44]. Both studies stratified outcomes by NLR level; reversal of NLR
with tumor resection was associated with an 11-month survival benefit compared to a
persistently high NLR. These two studies were limited by the fact that they were ret-
rospective analyses, lacked comparator groups, and did not clarify the extent of meta-
static burden (other than reporting the presence of oligo-metastases). Nevertheless,
these observations are intriguing and should be validated prospectively.
Recommendations
No definitive evidence supports upfront primary tumor resection in patients with

unresectable, metastatic CRC and an asymptomatic primary who plan to receive
multi-drug chemotherapy. Existing evidence for or against primary tumor resection
is severely limited by data that is mostly retrospective and observational. There is
considerable potential for selection bias when healthier patients with predicted bet-
ter survival pursue surgery. No recent studies support primary tumor resection for
the prevention of future symptoms, as none have clearly shown a diminished mor-
bidity with upfront surgery. A meta-analysis and Cochrane Review have demon-
strated no survival benefit with primary tumor resection in asymptomatic patients.
Given the paucity of data, the National Cancer Center Network (NCCN)
Guidelines for colon cancer do not endorse resection of a primary tumor in the set-
ting of unresectable synchronous liver and/or lung metastasis, unless the patient is
at imminent risk for obstruction or severe bleeding [45]. Furthermore, the guide-
lines recommend synchronous or staged resection in the setting of resectable dis-
ease. Although the emerging retrospective evidence linking improved survival to
lower systemic inflammation after primary resection in CRC is intriguing, many
more basic science and clinical investigations are warranted. Randomized con-
trolled trials are needed in order to clarify the benefits of primary tumor resection in
asymptomatic individuals; biomarker and correlative analyses are essential to the
attempt to identify a subpopulation that might benefit from initial surgery.
My current practice embraces chemotherapy first in asymptomatic patients with

unresectable, metastatic colon cancer, except in the cohort with lung-only metasta-
ses, as these patients tend to have more indolent metastatic disease. Less than 7 % of
patients at our institution ever require surgery for their primary tumor while receiv-
ing initial chemotherapy [11]. In this setting, multi-drug chemotherapy has proven
effective and safe in the long-term treatment of metastatic disease. Moreover, in a
subset of patients, current multimodality therapies have substantially improved our
ability to obtain a curative resection at a later date. Given the survival benefits of a
staged or synchronous resection, treatment should focus on improving the probabil-
ity of resection. Clinical judgment, however, should ultimately direct decision-
making, with the goal of optimizing survival and quality of life. In determining a
treatment plan, I very carefully evaluate the patient for symptoms, reviewing colo-
noscopy reports and CT scans. In patients who present with anemia, I generally find
that the symptoms can be managed medically, and this improves within 2–4 cycles
of chemotherapy. In patients with mild obstructive symptoms, I tend to recommend
upfront chemotherapy with careful observation, and find it quite common to see
resolution of symptoms within 2 cycles of treatment. This approach is supported by
data on our patients with locally advanced rectal cancer, in whom we routinely
administer oxaliplatin-based induction chemotherapy and observe high radio-
graphic, clinical and pathologic complete response rates [46]. For patients with sig-
nificant symptoms and/or evidence of proximal dilation on CT scan, I recommend
resection, bearing in mind the increased risk of complications and potential delay in
chemotherapy. Although the data do not support primary tumor resection in patients
with unresectable disease, there is considerable equipoise between strategies, and
there is need for a randomized trial in the future.
Recommendations
• Patients with unresectable, metastatic colon cancer and an asymptomatic or
minimally symptomatic primary tumor should not undergo resection of the
primary tumor (Evidence quality low, weak conditional recommendation)
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Chapter 15
Management of Large Sessile Cecal Polyps
Brett Howe and Richard L. Whelan
Overview/Introduction
The subject matter of this chapter are large sessile adenomas of the cecum. The
audience is presumed to be general or colorectal surgeons who regularly perform
colonoscopy. This chapter is intended for a Western audience. It is important to note
that the literature referenced in this chapter pertains to large bowel adenomas and is
not necessarily specific to cecal lesions.
It is important to realize from the outset that there is presently a huge gulf
between the Far East and the Western Hemisphere regarding the treatment of large
sessile polyps. The high incidence of gastric cancer in Japan led to aggressive
screening programs that were applied nationwide in an effort to detect premalignant
lesions and cancers at an early stage. The technique of Endoscopic Mucosal
Resection (EMR), now a piecemeal resection method, was initially used to obtain
large gastric biopsies. Endoscopic Submucosal Dissection (ESD), which allows en
bloc excision of mucosal lesions with normal tissue margins after submucosal injec-
tions to ‘lift’ the lesion off of the muscularis propria, was next developed for the
management of early gastric cancer [1]. After learning and mastering these methods
in the thick walled stomach a subset of Japanese endoscopists ventured into the
large bowel more than a decade ago. Presently, large sessile polyps in all parts of the
colon are routinely removed via ESD methods in Japan and other countries in the
Far East with completion rates ranging from 80 to 91.5 %, a bleeding rate between
0 and 1.5 %, and perforation rates of 1.4–10.4 % [2–8].
B. Howe, MD • R.L. Whelan, MD (*)

Mount Sinai School of Medicine, Mount Sinai West Hospital,
New York, NY, USA

DOI 10.1007/978-3-319-40223-9_15
154 B. Howe and R.L. Whelan
It should be noted that there are experts who believe that EMR (and not ESD) is
the preferred method for removal of large sessile polyps outside the operating room
setting [9–11]. Certainly, EMR is, by far, the more commonly used polypectomy
method world wide. A clear disadvantage of EMR is that piecemeal resection makes
it impossible to confirm complete resection via pathologic analysis.
It is also important to understand that there is also a large gap between the Far
East and West as regards the ability to accurately distinguish between adenomas,
advanced dysplastic lesions, and superficial cancers based on a lesion’s surface
appearance in the absence of tissue biopsies. Currently used methods include
chromoendoscopy (use of surface dyes to reveal polyp surface anatomy and pit
patterns), narrow band imaging, and magnification (via endoscope up to 150 X).
A separate endoscopic examination may be performed wherein some or all of
the above methods are applied to a large polyp and many photos obtained; in
many centers this data is reviewed by experts at a polyp staging conference [akin
to a tumor board] at which time a consensus diagnosis is made. The ability of
these methods to distinguish between adenomas with varying degrees of dyspla-
sia, SM-1 cancer, and SM-2 cancer has been verified in numerous large case
series [12–16]. The end result is that in Japan far fewer colectomies are done for
large benign sessile colorectal adenomas and noninvasive highly dysplastic
lesions.
At present, a relatively small subset of Western gastroenterologists, are learning
and employing these techniques in a limited number of centers. In an effort to avoid
colectomy and its attendant morbidity and mortality, several combined surgical and
endoscopic polyp removal methods have also been developed and utilized [17–19].
Nonetheless, the vast majority of large sessile lesions in the U.S. are still treated via
segmental colectomy, most often a standard oncologic resection. An assumption of
this chapter is that, where safe and feasible, avoidance of colectomy is desirable.
It should also be noted that the endoscopic and combined endoscopic/laparo-
scopic skill sets and experience of surgeons varies greatly in the U.S. and that we
are on the threshold of substantial changes in this arena. This reality makes general
recommendations applicable to all settings impossible. Each surgeon must look
within their medical/surgical community and, perhaps, refer patients to interven-
tionalists familiar with advanced polypectomy methods or combined laparoscopic/
endoscopic methods. Alternately, having made the commitment to learn one or
more of these newer methods, appropriate training and skills acquisition must take
place prior to embarking on the employment of these techniques. The learning pro-
cess is facilitated by identifying an interested and experienced surgical colleague
who is willing to participate in these cases. The consent process must be honest and
fully explain the potential benefits and complications of the new methods. When
performed by surgeons, in the authors’ opinion, these procedures are best carried
out in the operating room. Also, it is advised that a broad consent be obtained that
gives permission for either endoscopic or laparoscopic surgical removal of the
polyp, via wedge resection or standard colectomy. In the authors institution, these
cases are covered by an Institutional Review Board (IRB) approved protocol and an
IRB consent is obtained prior to surgery [19].
15 Management of Large Sessile Cecal Polyps 155
Treatment Options
Polyp treatment options include: (1) EMR (standard piecemeal snare polypectomy
with/without saline lift), (2) ESD polypectomy, (3) laparoscopic-facilitated colono-
scopic piecemeal polypectomy, (4) “wedge” partial circumference cecectomy, (5)
standard segmental bowel resection. As mentioned, although ESD experts perform
the procedure in the endoscopy suite, presently, in the U.S., the small number of
surgical endoscopists performing ESD or EMR for the large and most challenging
polyps do so in the operating room usually under general anesthesia. In this way,
after the ESD is completed, a laparoscopy can be performed to inspect the bowel for
perforations or weaknesses which, if found, can be closed with seromuscular
sutures. Alternately, if the ESD/EMR attempt fails, then the polyp can be removed
surgically (wedge or segmental resection). Of note, it is mandatory that CO2 gas be
used for endoscopic insufflation of the large bowel when ESD or EMR is performed
in conjunction with laparoscopy in order to avoid bowel distension and loss of the
operative field.
A brief discussion of these methods follows:
EMR and Laparoscopic Inspection
It is strongly advised that a submucosal lift be established prior to snare polypec-

tomy EMR. The lift makes full thickness perforation less likely by increasing the
distance between the muscularis propria and the lesion. Also, failure of a part of
the lesion to lift alerts the endoscopist to the possibility that a cancer may be pres-
ent and invading into the deep muscular layer (vs. scarring from a prior removal
attempt). It is important that a concerted effort be made to fully remove the polyp
during the first attempt since subsequent efforts will be more difficult and associ-
ated with a higher perforation risk due to scarring between the mucosa and muscu-
laris propria. As regards bleeding, rates between 3.1 and 11.3 % have been reported
in EMR series [20–22]. After successful completion of the EMR, a laparoscopy
may be performed to evaluate the bowel wall integrity and repair or to reinforce the
bowel wall if needed. In failed cases a laparoscopic bowel resection can be carried
out.
ESD and Laparoscopic Inspection
The following tools are necessary for ESD: lifting solution, sclerotherapy catheter,
needle knife (variety available), dissection cap (fits on scope tip and facilitates
submucosal dissection), polypectomy snare (specialty snares available), and,
importantly, a high frequency electrosurgical current generator (HFEC, that
provides pulsed, adjustable currents). A More detailed description of the method

can be found elsewhere. Briefly, the patient is positioned so that the lesion is “up”.
After injection of the lifting solution (usually with methylene blue added) the
resection margin is superficially marked with the knife (HFEC soft coagulation
setting) after which the mucosa is fully scored for about 25–35 % of the circumfer-
ence. Next the cut mucosal edge is undermined with the knife creating a submuco-
sal pocket into which the scope tip (with dissection cap affixed) is inserted; the
submucosal dissection is then continued beneath the lesion. As needed, the cir-
cumference of the specimen is completely scored. Gravity assists by retracting the
partly detached polyp. A snare may be used to complete the resection. Clips may
be used to close to the mucosal defect. As for EMR, laparoscopic inspection and
repair of the bowel wall (vs wedge or ileocolectomy if major injury is found) may
be performed after ESD completion.
Laparoscopic-Facilitated Colonoscopic Polypectomy Method
Milsom, Franklin, and Lee have championed this method carried out in the operat-
ing room wherein a piecemeal colonoscopic EMR is carried out after submucosal
lift with the help of simultaneous extrinsic manipulation of the polyp and colon
segment via laparoscopic instruments. After polypectomy the bowel wall is
inspected (after submersion under water) via laparoscope and endoscope. Full
thickness injuries and smaller perforations are repaired laparscopically with sero-
muscular sutures. The specimens are removed transanally. If necessary, a laparo-
scopic segmental colectomy can be performed. This method requires an experienced
laparoscopist in addition to an expert endoscopist. The laparoscopic bowel manipu-
lation is challenging and more dangerous than usual because the colon (and possi-
bly the small bowel) is fully insufflated which notably decreases the operative
working space [17–19].
aparoscopic “Wedge” Partial Circumference Full Thickness

L
Resection
This method is an option for well placed cecal lesions. A laparoscopic linear GIA
type stapler is used to resect a portion of the cecum containing the polyp (identified
via tattooing and simultaneous colonoscopy). It is critical that the ileocecal (IC)
valve be protected and that the polyp be fully removed. The authors recommend that
the stapler be applied only after the colonoscope has been inserted into the terminal
ileum (protects the valve and TI). After closing the stapler, the colonoscope is with-
drawn into the right colon and the stapler’s position assessed. After resection, the
cecal specimen must be removed from the abdomen and then opened and inspected.
If the margin is in question, frozen sections should be obtained. If a clean margin is

not obtained then either more cecum need be removed or an ileocectomy performed.
Practically, it is very difficult to wedge resect polyps that lie between the appendi-
ceal orifice and the IC valve because either the IC valve may need to be partially
resected or the polypectomy is incomplete [17, 19].
Standard Segmental Bowel Resection
Performed laparoscopically, when necessary. The main question here is whether to

do a limited ileocectomy (as for Crohn’s disease) vs a standard oncologic right
hemicolectomy. It is the author’s preference to do a right hemicolectomy because of
the risk that an invasive cancer will be found on final pathology.
Treatment Algorithm
It is also not possible to provide a simple algorithm for the treatment of sessile cecal
polyps because specific characteristics of the polyp (size, degree of dysplasia, fail-
ure to lift, etc.) and the specific location of the polyp (involvement of ileocecal valve
or appendiceal orifice) may dictate treatment. Table 15.1 provides the treatment
option(s) for each of these situations.
Table 15.1 Treatment algorithm for large sessile cecal polyps
Cecal Polyp (Large Sessile)
Prohibitively large polyp High grade

Involvement of Involvement of the Nonlifting All other
OR high suspicion for dysplasia with
Ileocecal valve base of the polyp polyps
malignancy based on majority of lesion
appendix
colonoscopy in OR still in place
EMR See
Ileocolectomy Table 2
Wedge Right Colectomy
(versus Right Resection
Right Colectomy
Colectomy)
Ileocolectomy Wedge
(versus Right Resection
Colectomy)
Ileocolectomy
(versus Right
Colectomy)
Polyp Characteristics
Very large size is a relative contraindication for endoscopic removal (the skill set of
the endoscopist is also a factor); polyps that involve the great majority of the cecum
are best dealt with via bowel resection.
Regarding large sessile polyps for which prior biopsies show high grade dyspla-
sia and where the majority of the polyp remains in place; the two largest series sug-
gest that there is a 30–41% chance of there being invasive cancer on final pathology
[23, 24]. Given the present inability of the vast majority of Western endoscopists to
make the distinction between a highly dysplastic polyp and a cancer based on the
surface appearance or other means, the authors recommend a standard oncologic
right colectomy for patients with large sessile adenomas with high grade
dysplasia.
Polyps that do not fully “lift” with submucosal injection also pose a problem.
Failure to lift may signify either the presence of cancer invading into the muscularis
propria or a scar that is the residua of prior polypectomy attempts. The treatment
options in this situation are: EMR via snare, wedge partial circumference full thick-
ness resection, or ileocolectomy (vs right hemicolectomy).
Location
ESD and complete EMR are not options for lesions involving the ileocecal valve or
appendix base since the inner polyp edge and margin may not be visible or acces-
sible. The appropriate treatment for the former is an ileocolic bowel resection (vs
right colectomy) whereas for the latter a wedge resection may be possible vs. an
ileocolectomy.
lgorithm (for Polyps That Do Not Fall into the Above

A
Categories) (Table 15.2)
As stated, an assumption has been made that surgical endoscopists would perform
these advanced colonoscopic procedures in the operating room in conjunction with
laparoscopy. Since there are multiple advanced colonoscopic methods that can be
used and because the preference and experience of each surgeon will largely deter-
mine the method chosen, the algorithm includes all 3 methods.
The ESD and EMR methods are listed side by side in the table since the algo-
rithm for each is the same. After successful polypectomy, laparoscopy is done to
interrogate the bowel for perforations and to repair the bowel wall with seromuscu-
lar sutures, if necessary. If the polypectomy is not successful, a wedge resection
would be carried out, if feasible. Laparoscopic-assisted colectomy is reserved for
Table 15.2 Treatment algorithm for large cecal polyps amenable to combined endoscopic/laparo-
scopic treatment
All Other Sessile Cecal Polyps
Laparoscopic-facilitated
ESD EMR
colonoscopic piecemeal
(en bloc resection) (Piecemeal snare excision)
polypectomy
Success Failure Success Failure
Laparoscopic Inspection of
inspection of bowel Laparoscopic bowel wall & Laparoscopic Ileocolectomy
Laparoscopic
wall & repair/ Ileocolectomy repair/ wedge (versus right
Wedge
reinforcement if (versus right reinforcement if Resection colectomy)
Resection
necessary colectomy) necessary
failed polypectomy patients for whom wedge resection is not an option or if the
bowel has been injured beyond repair during endoscopic polyp removal.
Proponents of the laparoscopic-facilitated colonoscopic method (Milsom,
Franklin) would follow the right most track on Table 15.2; in these cases, the lapa-
roscopy would be done simultaneously so that the polyp can be presented to endos-
copist during the polypectomy. After successful colonoscopic polypectomy the
bowel wall is inspected and laparoscopically repaired if need be. A laparoscopic
wedge resection or ileocolectomy is reserved for patients in whom the colonoscopic
removal attempt fails.
Conclusion
It is appropriate to utilize advanced colonoscopic methods to remove large benign pol-

yps in order to avoid colectomy and its attendant morbidity. Numerous methods are
available, however, in the authors opinion, ESD is the current gold standard. Since ESD
has not yet been widely embraced by gastroenterologists in the U.S., the combined
colonoscopic and laparoscopic methods discussed in this chapter have been devised
and employed by surgeons in the West. Use of these methods holds the promise of
organ preservation in patients in whom the current alternative is a segmental colec-
tomy. Having said this, it is likely that in a decade or so these lesions will be excised
endoscopically in the endoscopy suite without the need for concomitant laparoscopy.
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Chapter 16
Stage II Colon Cancer: Towards
an Individualized Approach
Blase N. Polite
Introduction
Like many oncologists, the sight of a stage II colon cancer patient on my schedule
draws a sigh. I know the discussion will be long and the concepts confusing even to the
statistically literate; and at the end of the day, I will have to leave it up to the patient to
make the decision because neither guidelines nor data in the vast majority of the cases
clearly point to the correct answer of whether they should or should not receive che-
motherapy. The problem is that stage II colon cancer is a wastebasket of likely differ-
ent cancers biologically with SEER 5-year survival rates ranging from 66 % in stage
IIA cancers to 37 % for stage IIC disease [1]. In this chapter, I will present the current
state of science for stage II colon cancer with the hopes of allowing the practitioner to
better risk stratify patients and thereby select those who are most likely to benefit or
not benefit from adjuvant chemotherapy. I will conclude with my recommendations
for specific cases with the strength of that recommendation based on the science.
Search Strategy
PICO table
Pt population Intervention Comparators Outcomes studied

Pts with stage 2 colon Chemo Observation Disease free survival, overall
cancer survival
B.N. Polite, MD, MPP

Section of Hematology/Oncology, University of Chicago Biological Science Division,
Chicago, IL, USA

DOI 10.1007/978-3-319-40223-9_16
164 B.N. Polite
I searched the PubMed data base using the following MeSH terms: Colonic
Neoplasms/drug therapy, Colonic neoplasms/pathology, Colonic neoplasms/surgery,
chemotherapy/adjuvant, gene expression, DNA mismatch repair, fluorouracil, oxali-
platin, irinotecan, meta-analysis, randomized controlled trials. References of relevant
articles were searched for missed studies. I also reviewed major abstracts relevant to
these topics presented at the ASCO annual meeting and ASCO GI s ymposium from
2012 to 2015. Finally, I cross checked my references with those in the UpToDate
article entitled “Adjuvant chemotherapy for resected stage II colon cancer.” [2]
Results
Non-risk Stratified Patients
Table 16.1 lists the most relevant studies which have attempted to answer the utility
of chemotherapy in stage II colon cancer. While not a perfect study, only the
QUASAR trial [3] comes close to being a truly randomized trial of stage II colon
cancer patients with reasonable power to answer the question of a chemotherapy
benefit. All the other studies are either underpowered or are pooled subset analyses
of randomized trials. Most of these are very well done scientifically, including a
meta-analysis done by the Cochrane group [4], but suffer from biases inherent in
pooled analysis. To this mix we also add registry data which are the weakest of all
the study types in the table because of uncontrolled threats to internal validity. In the
QUASAR trial, 5-FU chemotherapy resulted in a statistically significant improve-
ment in overall survival and disease free survival. The absolute magnitude of the
survival benefit was 3.6 % (95 % CI: 1–6 %) meaning you would have to treat 28
patients with chemotherapy to save one life. No other study confirms this survival
advantage statistically, but most suggest a magnitude of benefit which is not incon-
sistent with the QUASAR results either for overall survival (OS) or at least for dis-
ease free survival (DFS) [4–11]. The exception to this are 2 registry studies from the
United States and British Columbia which fail to show any advantage to chemo-
therapy and may even suggest it is detrimental [12, 13]. The two trials utilizing
more modern oxaliplatin-based chemotherapy do not appear to show a significant
improvement over 5-FU alone for stage II colon cancer patients, although they are
underpowered to answer this question with any certainty [6, 11].
Risk-Stratification-Clinical and Pathologic Factors
It is important to clarify terminology surrounding risk stratification, namely the

distinction between a prognostic versus a predictive factor. Prognostic factors relate
to the expected outcome of patients with those factors. Predictive factors are ones
which determine how well a patient will respond to a particular therapy or
Table 16.1 Role of chemotherapy for stage II colon cancer
Stage II
Study Trial type cancer Pts Therapies RFS (95 % CI) OS (95 % CI) Strength
QUASAR [3] RCT 2,146 5-FU vs surgery alone 0.78 (0.66–0.93) 0.82 (95 % CI: High
0.7–0.95)
NACCP [10] RCT (subset) 468 5-Fu vs surgery alone 71 % vs. 65 % (OR 5 year: 78 % vs Moderate
crosses 1) 70 % (OR crosses 1)
INT-0035 [9] RCT 318 5-Fu vs surgery alone 7 years: 79 % vs 7 year: 72 % vs Moderate
71 % (p = 0.1) 72 % (p = 0.83)
Nordic [8] Pooled RCT 812 5-FU vs surgery alone NR 79 % vs 79 % Moderate
(p = 0.81)
IMPACT-B2 [5] Pooled RCT 1016 5-Fu vs surgery alone 5 year: 76 % vs 5 year: 82 % vs. Moderate
73% (p = 0.061) 80 % (p = 0.057)
Gill et al. [7] Pooled RCT 1440 5-FU versus surgery 5 year: 76 % vs. 5 year: 81 % vs Moderate
(IMPACT-B2 + 2 alone 72 % (p = 0.049) 80 % (p = 0.1127)
additional trials)
MOSAIC [6] RCT (subset) 899 FOLFOX vs 5-FU 5 year: 83.7 % vs 6 year OS: 86.9 vs Moderate
79.9 % (p = 0.258) 86.8 (0.986)
NSABP C-07 [11] RCT (subset) 699 FLOX vs 5-FU 5 year: 82.1 % vs. 89.7 vs 89.6 Moderate
80.1 %
16 Stage II Colon Cancer: Towards an Individualized Approach
Cochrane [4] Meta-analysis 7097 Chemo vs. surgery HR 0.83 HR 0.96 Moderate
alone (0.77–0.92) (0.91–1.02)
SEER-Medicare [13] Registry 6,234a Chemo vs surgery NR 5 year: 70 % vs. Moderate
alone 69.5 %
BCCA data base [12] Registry 1,697a Chemo vs surgery 5 year: 87.1 % vs. 5 year: 82.9 vs 83.3 Moderate
alone 92 % (p = 0.18) (p = 0.561)
NR not reported
a
Stage II with no poor prognostic feature (obstruction/perf, T4, poor/undiff histology, >12 LN, emergent surgery)
165
166 B.N. Polite
intervention. A common fallacy to which we are all susceptible is that patients with
the worst prognosis are the ones most likely to benefit from aggressive treatment. It
is sometimes the case but often it is not. In stage II colon cancer, the most com-
monly recognized prognostic factors are as follows: T4 disease, inadequate lymph
node sampling (<12 lymph nodes), poorly differentiated histology (in MSI-L/S
patients), perforation, obstruction, lymphovascular invasion, perineural invasion,
and positive resection margins [14]. It is very important that the reader pay special
attention to the high grade tumor histology and the importance of interpreting this
in the context of the mismatch repair (MMR) or microsatellite instability (MSI)
status of the tumor. As we will go into detail below, tumors with MMR deficiency
or MSI-H phenotype are often high grade yet have an excellent prognosis.
Whether these adverse risk factors are predictive of benefit to chemotherapy is
less clear. The strongest data to suggest a benefit of chemotherapy in high risk
groups comes from the British Columbia Cancer Agency (BCCA) registry which
found a significant survival advantage for patients with T4 tumors who received
5-FU chemotherapy (HR 0.5 95 % CI: 0.33–0.77) [12]. In contrast neither a US
Intergroup meta-analysis nor a SEER registry study could discern any differential
chemotherapy advantage for high versus low risk groups [7, 13]. In the MOSAIC
study utilizing oxaliplatin-based therapy, there was a suggestion of a disease free
survival advantage in the high risk stage II group with 5 year DFS of 82.3 % versus
74.6 % (HR 0.72; 95 % CI: 0.5–1.02) for FOLFOX versus infusional 5-FU alone [6].
Risk-Stratification-Molecular Factors
The strongest data for both a prognostic and predictive factor exists for a deficiency
in the mismatch repair pathway. It is beyond the scope of this chapter to explain the
nuances of MMR deficiency and testing for it; but in brief, patients with defective
MMR tumors either have a germline loss of one of the MMR proteins (MLH1,
MSH2, MSH6, PMS2) or epigenetic silencing of the MLH1 promoter [15]. The for-
mer is associated with Lynch syndrome and the later often in the setting of a CpG
Island methylator phenotype (CIMP). Defective MMR tumors can either be tested for
using a PCR panel of 5 reference microsatellite sites; if at least 2 show instability then
the tumor is characterized as MSI-H. More often in the clinical setting, immunohis-
tochemistry testing (IHC) is used to stain for the presence or absence of one of the
MMR proteins. By convention in the literature, we call a tumor as defective MMR
(dMMR) if they are either MSI-H or have an absence of an MMR protein by IHC.
Table 16.2 lists the major studies which have explored the prognostic and
predictive value of MMR testing in stage II colon cancer. The majority of these
studies clearly show that those with dMMR stage II tumors have a superior progno-
sis compared to those with pMMR with hazards of recurrence or death often 50 %
lower [16–20]. In the study by Sargent, et al. [19] patients with dMMR tumors who
received chemotherapy had a hazard of death which was nearly three times those
who were on observation (HR 2.95; 95 % CI: 1.02–8.54). The reason why this may
be the case is speculative, but we know patients with dMMR often have an intense
Table 16.2 Role of dMMR as prognostic and predictive marker for stage II colon cancer
dMMR colon DFS (vs DFS w/chemo vs w/o OS w/chemo vs w/o
Study patients Therapies pMMR) chemo OS (vs pMMR) chemo
Sargent et al. [19] 102 (stage II) 5-FU vs surgery 0.51 (95 % CI: HR 2.3 (95 % CI: 0.47 2.95 (95 % CI:1.02–8.54)
alone 0.29–0.89)a 0.84–6.24) (0.26-0.83)a
Jover et al. [27] 76 (38 stage 5-Fu vs surgery 6 year: 71 % vs 6 year: 57.7 % vs 67.6 % 76 % vs 71 % 69.2 % vs 73.5 % (p = 0.8)b
II) alone 63 % (p = 0.3) (p = 0.6)b (p = 0.5)
Kim et al.(NSABP 98 (II and III) 5-Fu vs surgery HR 0.77 (95 % Interaction p = 0.68b HR 0.82 (95 % Interaction p = 0.62b
c01-c04) [28] alone CI: 0.4–1.48)a CI: 0.44–1.51)
Klingbiel et al. 86 (stage II) FOLFIRI vs 5FU HR 0.26 (95 % HR 1.27 (0.65–2.49) HR 0.16 HR 1.47 (0.65–3.36)
(PETACC-3) [18] CI: 0.1–0.65) (0.04–0.64)
Hutchings et al. 167 (stage II) 5-Fu vs surgery RR 0.44 (95 % 2 year: 2.2 % vs 5.1 % NR NR
(QUASAR) [17] alone CI: 0.29–0.67) Interaction p = 0.55
Gavin et al (NSABP 207 (93 stage FOLFOX HR 0.48 (95 % Interaction 0.97 HR 0.64 (95 % Interaction p = 0.848
C07-C08) [16] II) CI: 0.3–0.7) CI: 0.46–0.89)
dMMR defective DNA mismatch repair, pMMR proficient mismatch repair, NR not reported
a
Includes only patients not treated with chemotherapy
b
Includes stage II and III
16 Stage II Colon Cancer: Towards an Individualized Approach
167
168 B.N. Polite
immune response to their tumors and are in fact the only colon cancer cohort to date
where immune checkpoint inhibitors appear to be effective in the metastatic setting
[21]. It is suggested that chemotherapy may blunt this immune response. This
hypothesis is further corroborated by recent data suggesting that if there is a
chemotherapy benefit for these patients, it is only for those with germline tumors
which tend not to express the hyper-mutated phenotype [22]. These findings of a
detrimental impact have not been corroborated by the other studies listed in
Table 16.2. However, no study has found a clearly beneficial impact of chemother-
apy for this cohort, who have an otherwise excellent prognosis. It is important to
note that all of these studies are severely limited by power to test for the interaction
between dMMR status and chemotherapy effect.
Several studies have also looked at other molecular mutations in the BRAF and
KRAS genes including interactions of these factors with dMMR status as well as
those with CpG Island methylator phenotype [16, 17, 23, 24]. No clear consensus
has emerged with one study suggesting a BRAF mutation is prognostic for poorer
overall survival in all stage II patients [16] and another in only those with pMMR
status [23]. An additional study suggested a poorer survival for KRAS mutant
tumors but not BRAF [17]. In none of the studies were KRAS, BRAF, or CIMP
predictive of benefit from chemotherapy and as such have not found their way into
our treatment algorithms.
Risk-Stratification-Gene Expression Profiling
Genomic Health (Redwood City, CA), developed an 12 gene recurrence panel and
tested an 11 gene treatment benefit panel marketed as the Oncotype DX Colon
Cancer Assay [20]. The recurrence score was able to segregate patients with stage II
colon cancer into low, intermediate and high risk groups with those in the lowest
risk group (44 % of patients) having a 13 % 3 year risk of recurrence and those in the
highest risk group (26 % of patients) having a 21 % risk of recurrence. The recur-
rence score remained prognostic even after controlling for other pathologic and
clinical characteristics. A further validation study using CALGB 9581 patients and
a more contemporaneous cohort of patients treated with oxaliplatin in the NSABP
C-07 study found similar results [25, 26]. Unfortunately, in none of these studies
was the recurrence score or the treatment score able to predict the patients most
likely to benefit from chemotherapy. That is, the gene panel is prognostic but not
predictive, meaning the proportional benefit from chemotherapy was similar regard-
less of recurrence score. Can such a test be useful? The answer is, yes if small dif-
ferences in absolute benefit are important to your patient. For example, assuming a
20 % proportional benefit to chemotherapy (consistent with the QUASAR data) a
patient with a low risk score would expect about a 2.6 % absolute benefit from che-
motherapy whereas one in the high risk group a 4.2 % absolute benefit. I have found
very few patients who find these types of differences helpful in their decision mak-
ing but it is a discussion that I have especially in my T3N0 pMMR patients.
16 Stage II Colon Cancer: Towards an Individualized Approach 169
1. All stage II patients should be tested for dMMR either by IHC or PCR and those
with dMMR should not receive chemotherapy (evidence quality high, strong
recommendation)
2. Patients with T4 tumors, high grade (pMMR), <12 LN sampled, or with perfora-
tion should receive 5-FU-based chemotherapy (evidence quality moderate, mod-
erate recommendation)
3. Patients with T4b tumors should receive oxaliplatin based chemotherapy (evi-
dence quality weak, moderate recommendation)
4. Patients with T3N0 pMMR tumors should be offered Oncotype DX testing to aid
in decision making (evidence quality moderate, weak recommendation).
Stage II colon cancer confronts us with the battle of the head versus the heart. Only
for dMMR patients are the two well aligned where I believe the data compel us not
to offer these patients chemotherapy. For pMMR T3N0 patients with no high risk
features (High grade and <12 lymph nodes positive being the main ones I pay atten-
tion to in this setting) I remain at true equipoise. I am comfortable with whatever
decision my patients make and see my role as trying to ensure they understand the
risks and benefits so that they can make a truly informed decision. It is in the stage
IIB and IIC patients I struggle most. My heart (or my gut) wants to treat all IIB
patients with fluoropyrimidine- based chemotherapy and all IIC with FOLFOX. I
rationalize that the IIC patients have a worse 5 year survival than IIIB patients and
therefore should be treated as aggressively, but I am at a loss to point a single piece
of strong evidence to support this. Nevertheless, that is my practice.
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much? J Clin Off J Am Soc Clin Oncol. 2004;22(10):1797–806. doi:10.1200/JCO.2004.09.059.
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chemotherapy in colorectal cancer: a joint analysis of randomised trials by the Nordic
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doi:10.1080/02841860500355900.
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study of fluorouracil plus levamisole as adjuvant therapy for stage II/Dukes’ B2 colon cancer.
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Part III
Rectal Cancer
Chapter 17
Rectal Cancer: Management of T1 Rectal
Cancer
Woon Kyung Jeong and Jose G. Guillem
Introduction
The widespread implementation of screening colonoscopy has led to a parallel

increase in the detection of early staged rectal cancer including T1N0M0 lesions.
Rectal cancers at this stage have invaded into the submucosal layer of the rectal wall
without metastasis to lymph nodes and other organs and have been traditionally
managed with a transabdominal radical resection (RR). However, since a RR is
associated with significant postoperative morbidity, local excisional approaches
(LE) such as transanal excision (TAE), transanal endoscopic microsurgery (TEM),
and transanal minimally invasive surgery (TAMIS), have been adopted. Whether
the oncological results of a less morbid LE approach is comparable to a more mor-
bid RR approach for T1N0M0 rectal cancer is the essential question of this
chapter.
When confronted with a patient with a presumed T1N0M0 rectal cancer based
on preoperative physical exam and imaging studies, both LE and RR options have
to be considered and the pros and cons of each approach and their associated long-
term and short-term oncological outcomes and functional consequences and impli-
cations for the specific patient at hand carefully discussed.
W.K. Jeong • J.G. Guillem (*)

Colorectal Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center,
New York, NY, USA

DOI 10.1007/978-3-319-40223-9_17
176 W.K. Jeong and J.G. Guillem
Search Strategy

Patients with T1 rectal Local excision Radical resection Oncologic outcomes,
cancer quality of life
A literature search in Pubmed, Embase, and Scopus databases was performed. The
terms used for the search included: “T1 rectal cancer”; “early staged rectal cancer”;
“local excision”; “radical resection”; “recurrence”; “sexual function”; “anorectal
function” and “quality of life”. Only articles written in English and published
between 2010 and 2015 and reporting original data or meta-analysis on T1 rectal
cancer were selected. Important and evidence-based studies published before 2010
were also included.
Results
We found two meta-analyses which met our search criteria and included most of the
significant data on the topic (Table 17.1) [1, 2]. Of these two studies, one was larger
(2896 patients from 13 studies [1] versus 860 patients from seven studies [2]) and
reported detailed preoperative diagnostic workup and oncologic data including lym-
phovascular invasion and surgical margin status as well as the use of neoadjuvant
and/or adjuvant therapy [1]. However, these two meta-analyses included studies that
were retrospective and non-randomized [3–15], and some of the retrospective stud-
ies included small numbers of patients. The one prospective randomized study on
this topic which was included in both meta-analyses only enrolled 50 patients [16].
Oncologic Outcomes
Local Recurrence
In our review of these two meta-analyses, rates of local recurrence were higher in
patients undergoing a LE when compared to patients undergoing a RR (4–33 %
versus 0–6 %, respectively) [1, 2].
Distant Metastasis
Of these two meta-analyses, only one compared distant metastasis rates between LE
and RR and showed no significant differences (0–8 % versus 0–4 %, respectively)
[2]. However, it is important to point out that this study included only patients
undergoing TEM and did not include TAE or TAMIS.
Table 17.1 Comparison of meta-analysis studies on T1 rectal cancer
Study Patients Local Distant Quality of
Study Year design (LE/RR) recurrence metastasis DFS OS Morbidity Mortality evidence
Kidane 2015 Meta- 2896 LE > RR n/a 5-years DFS, 5-years OS, LE < RR LE < RR moderate
et al. [1] analysis (1315/1581) (relative risk, LE < RR LE < RR (relative (relative
(TAE, 2.36; 95 % (relative risk, (relative risk, risk, 0.20; risk,
TEM, CI, 1.54; 95 % CI, 1.46; 95 % CI, 95 % CI, 0.31;
TAMIS 1.64–3.39) 1.15–2.05) 1.19–1.77) 0.10–0.41) 95 % CI,
vs. RR) 0.14–
17 Rectal Cancer: Management of T1 Rectal Cancer
0.71)
Lu et al. 2015 Meta- 860 LE > RR(OR, no difference no no n/a n/a moderate
[2] (TEM analysis (303/557) 4.62; 95 % (OR, 0.74; difference(OR, difference(OR,
vs. RR) CI, 95 % CI, 1.12; 95 % CI, 0.87; 95 % CI,
2.03–10.53) 0.32–1.72) 0.31–4.12) 0.55–1.38)
LE local excision, RR radical resection, DFS disease-free survival, OS, overall survival, TAE, transanal excision, TEM, transanal endoscopic microsurgery,
TAMIS, transanal minimally invasive surgery, CI, confidence interval, OR, overall risk, SEER, surveillance, epidemiology, and end results, HR hazard risk
177
Overall Outcome
In one meta-analysis, disease-free survival rate was higher in patients undergoing a

RR [1]. However, in the other meta-analysis, no significant difference was noted in
disease-free survival between the two surgical treatment options [2]. This may be
due to the fact that in the latter met-analysis, only 2 studies reporting disease-free
survival were included.
With regard to overall survival, one meta-analysis showed better results for RR
over LE [1]. The other meta-analysis did not, even though it did demonstrate a sig-
nificantly higher local recurrence rate in patients undergoing a LE (odds ratio, 4.62;
95 % confidence interval, 2.03–10.53) [2]. The authors do not provide an explana-
tion for this. However, it is possible that salvage radical surgery and adjuvant che-
motherapy and/or radiation therapy may have eradicated some of the locally
recurrent rectal cancer and impacted survival in a positive manner. However, other
studies suggest that failure following a local excision may not be salvageable in a
significant number of cases [17].
Quality of Life
Of the two meta-analyses, only one reported on morbidity and noted a higher mor-
bidity rate for RR over LE [1]. LE was associated with a much lower need for per-
manent stoma [1]. However, a number of the studies included were from over 20
years ago when sphincter sparing TME was not as established as it is today.
There is a paucity of literature comparing sexual or anorectal functions following
RR and LE and none are prospective randomized studies. Therefore, the two meta-
analyses [1, 2] did not discuss this topic. One study not included in the two meta-
analysis, however, did compare the quality of life after TEM and TME in sex- and
age-matched patients and reported no significant differences in quality of life between
TEM and TME; but more frequent defecation disorders were observed after TME
[18]. A trend toward better sexual function after TEM was also reported. However, a
greater portion of patients in the TME group were T3 and received preoperative radio-
therapy (18 % versus 0 %) which probably had a negative impact on sexual function.
Other Studies
There are several recently published papers comparing local excision to radical
resection that were not included in our analyses for specific reasons. One study
included T1 and T2 rectal cancers and did not provide a subset analysis on T1 cancers
[19] and the other included endoscopic polypectomy in the LE group [20]. One sin-
gle institution study comparing LE to RR was not included in either of the meta-
analyses [21]. It was a small sample (n = 124), retrospective study which demonstrated
17 Rectal Cancer: Management of T1 Rectal Cancer 179
a local recurrence rate of 11 % in the LE group versus 1.6 % in the RR group, but no
difference in the disease-free and overall survival between the two groups. Our insti-
tutional experience at Memorial Sloan-Kettering Cancer Center (MSKCC) on a
larger cohort (n = 282) with a similar length of follow-up demonstrated an inferior
disease-specific survival for patients with a T1 rectal cancer undergoing a LE relative
to those undergoing a RR (87 % versus 96 %) [12].
In summary, the best available data suggest that a RR offers an oncologic advan-
tage over a LE approach for early staged (T1N0M0) rectal cancer. This is probably
related to the increased likelihood of a local recurrence noted after a LE approach,
which is not always salvageable.
Evidence Based Recommendations
A review of the published oncological results demonstrates that a RR provides the

best oncologic outcome for a T1 rectal cancer. LE is an option for patients with T1
rectal cancer without high risk features who either are not suitable for a RR or are
willing to accept the oncological risks in the interest of avoiding the functional
consequences of a RR. There should not be enlarged mesorectal lymph nodes suspi-
cious for metastasis on preoperative images nor evidence of poor differentiation
(PD), lymphovascular invasion (LVI), perineural invasion (PNI), or submucosal
(Sm) invasion >1 mm on pathological analysis. If one of these high risk features in
noted, a RR is recommended [22, 23]. If such a patient were to insist on having a LE
rather than the recommended RR, they have to understand that local recurrence
rates after LE of a T1 rectal cancer range between 12 and 29 % with long-term fol-
low-up, despite applying careful selection criteria for LE [5, 10, 15, 24, 25]. If a
local recurrence develops and a salvage surgery is pursued, it would likely be exten-
sive as one study reported the need for multivisceral pelvic resection in 33 % and
total pelvic exenteration in 5 % of patients undergoing a RR after a recurrence fol-
lowing a LE of T1 rectal cancer [17].
1. Patients with a T1N0M0 rectal cancer that are otherwise fit should be offered a
radical resection incorporating mesorectal excision.
2. Patients with a T1N0M0 rectal cancer not able to undergo a radical resection
may be offered a local excision understanding the increased risk for failure with
possible limited salvage options.
Grade of data: moderate quality
A Personal View/Approach
If a patient is found to have a biopsy proven rectal adenocarcinoma that clinically

looks and feels like it is not deeply invasive (mobile, non tethered, exophytic rather
than ulcerated) and possibly amenable to a LE, a careful review of the pathology as
well as local [endorectal ultrasonography (ERUS) or rectal magnetic resonance
imaging (MRI)] and distant [computed tomography (CT) of chest, abdomen and
pelvis] staging has to occur in order to further determine if indeed a LE approach is
appropriate. The presence of any adverse pathological features (PD, LVI, PNI, or
Sm invasion >1 mm) would be associated with an increased likelihood of mesorec-
tal lymph node involvement and in an otherwise healthy individual with good ano-
rectal sphincter function (good baseline tonicity, squeeze, no paradoxical motion of
puborectalis sling, etc.), a RR would be offered. In an elderly individual with signifi-
cant co-morbidities and/or poor anorectal function, a LE approach would be a safer
initial approach (lower morbidity, mortality, and probable better function) than a RR
but would be associated with a possible increased risk of local and distant failure. A
more challenging scenario is the otherwise healthy individual with a very distal
(1 cm above upper part of anorectal sphincter) invasive (T1N0M0 on imaging) rec-
tal adenocarcinoma with good pathological features who is interested in a restor-
ative curative resection. In this situation, the patient has to be informed that if LE is
pursued initially and pathology identifies a T2 lesion and he/she were to pursue a
subsequent salvage RR, this may or may not be feasible since the prior suture line
fibrosis of LE would compromise creation of coloanal anastomosis and function.
Numerous other clinical scenarios exist based upon the local and distant staging
of the rectal cancer, the presence or absence of poor pathological features, the distal-
most location of the lesion relative to the upper most portion of the anorectal sphinc-
ters, the function of the anorectal sphincters, the presence or absence of
co-morbidities, etc. Optimal matching of the treatment plan to the individual patient
requires that all the above variables be taken into consideration and that the patient
and family be informed and engaged in a discussion where short and long term
wishes, risks, gains and losses are clearly discussed and agreed upon.
References
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gery and radical resection for T1 carcinoma of the rectum. Surg Endosc. 1998;12(9):1145–8.
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stage I rectal carcinoma in comparison with radical resection methods. Chirurg. 1999;
70(12):1469–74.
5. Mellgren A, Sirivongs P, Rothenberger DA, et al. Is local excision adequate therapy for early
rectal cancer? Dis Colon Rectum. 2000;43(8):1064–71; discussion 1071–4.
6. Lee W, Lee D, Choi S, et al. Transanal endoscopic microsurgery and radical surgery for T1 and
T2 rectal cancer. Surg Endosc. 2003;17(8):1283–7.
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7. Langer C, Liersch T, Süss M, et al. Surgical cure for early rectal carcinoma and large adenoma:
transanal endoscopic microsurgery (using ultrasound or electrosurgery) compared to conven-
tional local and radical resection. Int J Colorectal Dis. 2003;18(3):222–9.
8. Nascimbeni R, Nivatvongs S, Larson DR, et al. Long-term survival after local excision for T1
carcinoma of the rectum. Dis Colon Rectum. 2004;47(11):1773–9.
9. Endreseth BH, Myrvold HE, Romundstad P, et al. Transanal excision vs. major surgery for T1
rectal cancer. Dis Colon Rectum. 2005;48(7):1380–8.
10. You YN, Baxter NN, Stewart A, et al. Is the increasing rate of local excision for stage I rectal
cancer in the United States justified?: a nationwide cohort study from the National Cancer
Database. Ann Surg. 2007;245(5):726–33.
11. Tarantino I, Hetzer FH, Warschkow R, et al. Local excision and endoscopic posterior mesorec-
tal resection versus low anterior resection in T1 rectal cancer. Br J Surg. 2008;95(3):375–80.
12. Nash GM, Weiser MR, Guillem JG, et al. Long-term survival after transanal excision of T1
13. Palma P, Horisberger K, Joos A, et al. Local excision of early rectal cancer: is transanal endo-
scopic microsurgery an alternative to radical surgery? Rev Esp Enferm Dig. 2009;101(3):
172–8.
14. Ptok H, Marusch F, Meyer F, et al. Oncological outcome of local vs radical resection of low-
risk pT1 rectal cancer. Arch Surg. 2007;142(7):649–55; discussion 656.
15. De Graaf EJ, Doornebosch PG, Tollenaar RA, et al. Transanal endoscopic microsurgery versus
total mesorectal excision of T1 rectal adenocarcinomas with curative intention. Eur J Surg
Oncol. 2009;35(12):1280–5.
16. Winde G, Nottberg H, Keller R, et al. Surgical cure for early rectal carcinomas (T1). Transanal
endoscopic microsurgery vs. anterior resection. Dis Colon Rectum. 1996;39(9):969–76.
17. You YN, Roses RE, Chang GJ, et al. Multimodality salvage of recurrent disease after local
excision for rectal cancer. Dis Colon Rectum. 2012;55(12):1213–9.
18. Doornebosch PG, Tollenaar RA, Gosselink MP, et al. Quality of life after transanal endoscopic
microsurgery and total mesorectal excision in early rectal cancer. Colorectal Dis. 2007;
9(6):553–8.
19. Sajid MS, Farag S, Leung P, et al. Systematic review and meta-analysis of published trials
comparing the effectiveness of transanal endoscopic microsurgery and radical resection in the
management of early rectal cancer. Colorectal Dis. 2014;16(1):2–14.
20. Bhangu A, Brown G, Nicholls RJ, et al. Survival outcome of local excision versus radical
resection of colon or rectal carcinoma a surveillance, epidemiology, and end results (SEER)
population-based study. Ann Surg. 2013;258(4):563–9.
21. Peng J, Chen W, Sheng W, et al. Oncological outcome of T1 rectal cancer undergoing standard
resection and local excision. Colorectal Dis. 2011;13(2):e14–9.
22. Beaton C, Twine CP, Williams GL, et al. Systematic review and meta-analysis of histopatho-
logical factors influencing the risk of lymph node metastasis in early colorectal cancer.
Colorectal Dis. 2013;15(7):788–97.
23. Huh JW, Kim HR, Kim YJ. Lymphovascular or perineural invasion may predict lymph node
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14(7):1074–80.
24. Paty PB, Nash GM, Baron P, et al. Long-term results of local excision for rectal cancer. Ann
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Chapter 18
Management of T2 Rectal Cancer
Peter A. Cataldo
Introduction
What’s “best” for the cancer, may not always be “best” for the patient. This is par-
ticularly true for T2 rectal cancer; more specifically for patients with rectal cancer.
More radical treatments may in certain circumstances, result in higher disease free
survival, but not in improvements in overall survival, and certainly not a better func-
tional result or enhanced quality of life. In selecting treatment options one must
understand multiple important factors regarding the tumor and the patient in whom
it resides.
Regarding patient factors: (1) Some patients wish to do “everything possible” to
minimize any risk of tumor recurrence, while others want to avoid a colostomy “at
all costs”. (2) Some patients’ anorectal function is poor enough that a radical resec-
tion with permanent colostomy will result in the best chance for cure and provide
the best functional outcome. (3) In others, even a well performed low anterior resec-
tion for a mid or proximal tumor will result in an unacceptable deterioration in anal
function, and significantly impact quality of life. (4) Finally, in some individuals
with significant comorbidities curing the cancer may be an unnecessary goal as life
span is already severely limited.
Regarding the tumor: (1) Location is everything; proximal T2 rectal tumors are
very different from distal T2 tumors. (2) Accurate tumor staging is often difficult
prior to surgical resection. Differentiating T1 from T2 lesions may be impossible for
MRI and difficult for endorectal ultrasound [1, 2]. Even radiologists experienced in
MRI evaluation of rectal cancer find it difficult to differentiate between advanced T2
lesions and early T3 cancers. (3) Diagnostic imaging, both MRI and endorectal
ultrasound, may be little better than “flipping a coin” when predicting metastatic
P.A. Cataldo
Colon and Rectal Surgery, University of Vermont College of Medicine,
Burlington, VT, USA

DOI 10.1007/978-3-319-40223-9_18
184 P.A. Cataldo
lymphadenopathy in association with early rectal cancers. Large lymph nodes may
look worrisome but are often benign, while up to 50 % of metastatic lymph nodes
are less than 5 mm and missed on both MRI and ultrasound [3, 4].
As one critically evaluates the literature, particularly when comparing radical to
local surgical treatment, there is subtle, unintentional selection bias that is ubiqui-
tous, incredibly important, and rarely mentioned. Authors compare patients under-
going local excision for T2 (lymph node status estimated by inaccurate imaging;
with a 50 % false negative rate) N0, with individuals undergoing radical TME for
pathologically staged T2 N0 (with microscopic evaluation of regional nodes), com-
monly in a retrospective analysis. In these studies, authors often implicate occult
lymph node metastases as responsible for the local recurrence following local exci-
sion. If this is truly the case (which is likely), then many patients in the local exci-
sion group are truly T2 N+. Therefore, as we compare local with radical resection,
it’s important to realize a percentage of patients in any “local excision group” have
Stage III rectal cancer while essentially none of the patients in the radical resection
group are Stage III. As described above, it is often inaccurate staging that leads to
increased recurrence in the local excision group rather than inadequate treatment.
Why is the choice between local and radical resection so important, and so often
discussed in rectal cancer while it’s rarely mentioned and of little clinical impor-
tance in colon cancer? The consequences of radical resection in the vast majority of
colon cancers is minimal, such that there is no real functional benefit to local exci-
sion. In addition, laparotomy or laparoscopy is required for both local and radical
resection. Regarding rectal cancer, radical resection requires a transabdominal
approach while local excision is accomplished via an endoluminal approach with no
cutaneous incision and minimal complications, often as an outpatient procedure.
Importantly, the functional consequences of a successful radical resection include
significant diminution of anorectal, urinary and sexual function, and a significant
percentage of these individuals will require a permanent or temporary stoma [5–9].
In treating rectal cancer of any stage, three modalities are commonly considered;
surgery, radiation, and chemotherapy. Some individuals may require all three, each
associated with its own unique consequences. As more modalities are used, compli-
cations and long term consequences increase. Chemotherapy is a “systemic” treat-
ment designed to decrease systemic recurrence, and is generally associated with
systemic consequences. Both surgery and radiation are local therapies, and are pre-
dominately associated with local consequences. The combination of radiation and
surgery particularly compounds complications and functional consequences.
Patient population Intervention Comparators Outcomes

Patient with T2N0 Local excision with Radical resection Oncologic
rectal cancer chemoradiation Chemoradiation alone outcomes
Functional
outcomes
18 Management of T2 Rectal Cancer 185
Search Strategy
A literature search was conducted including the following databases: MEDLINE

(using PubMed) and the Cochrane Library. Publications not written in English were
excluded. Titles and abstracts of retrieved studies were reviewed for relevance and
eligibility. Results from the most recent meta-analyses were also included in this
review. Full texts of all eligible studies were retrieved and evaluated.
Surgical Decision Making
Extensive literature review revealed very few trials that actually compared local and
radical resection for T2 rectal tumors. In fact, there is only one prospective trial that
compared local excision (transanal endoscopic microsurgery) with radial resection
following neoadjuvant chemoradiation for T2N0 rectal cancer [10]. There are no tri-
als that compare local excision to “watch and wait” following chemoradiation for T2
lesions. There are several “database” reviews that compare both local and radical
resection, but suffer from the traditional shortcomings associated with database
queries [11, 12]. Therefore, decision making for patients with T2N0 rectal cancer
remains difficult and cannot generally be based on level I data. It must come from
review of trials that separately evaluate local excision, radical resection, and obser-
vation therapy.
The tables that are compiled below are a result of contemporary literature review
in the management of early rectal cancer. Unfortunately, direct comparisons between
treatment modalities are rare. The best an informed surgeon can hope for is to
review this data and apply it individually to each patient, looking at functional data,
oncologic results, stoma and complication rates.
Table 18.1 depicts local recurrence, cancer specific survival, morbidity, and
length of follow-up for available techniques. Table 18.2 looks at permanent stoma
rates following local excision, radical resection and chemoradiation alone.
Table 18.3 looks at response rates, local recurrence and overall survival following
“watch and wait” therapy.
Recommendations
There is little debate in the literature regarding treatment of proximal T2N0 rectal
cancer. All individuals who are medically fit should undergo radical resection, most
commonly anterior resection with total (or tumor specific) mesorectal excision, and
anastomosis. Current trials suggest this will result in high survival rates, a low inci-
dence of local recurrence, and minimal functional consequences. Neoadjuvant or
adjuvant treatment is not necessary.
186 P.A. Cataldo
Table 18.1 Oncologic intervention and results [10–12, 14, 18–24]

Local Cancer
recurrence survival F/U Morbidity
Trial Stage Intervention N (%) (%) (months) (%)
LeZoche T2N0 Pre-op 35 5.7 94 84 13.8
et al. chemoXRT & 35 2.8 94 16.7
TEM
Pre-op
chemoXRT &
TME
Guerrieri T2N0 Pre-op 139 10 92 225 9.2
et al. chemXRT and
TEM
Chen et al. T2N0 TEM 30 7.1 100 18 21
(selective 30 0 100 18 20
XRT)
LAR
(selective
chemo)
You et al. T2–3N0 Pre-op chemo 60 10 85.9 36 7.5
XRT & TEM
ACOSOG T2N0 Pre-op 79 4 88.2 56 16
Z6041 chemoXRT &
local excision
You et al. T2N0 LE 164 22.1 67.6 60 5.8
Radical 866 15.1 76.5 14.6
resection
SEER T2N0 LE (selective 332 81 60
Database radiation) 2,362 90.5
Radical
resection
Swedish Stage Pre-op XRT 454 9 72 156 26
Rectal I, II, & Surgery 454 26 62 19
Cancer III Surgery alone
Trial
German Stage Pre-op 404 7.1 68.1 134 36
Rectal II and chemXRT & 395 10.1 67.8 34
Cancer III Surgery
Trial Surgery &
post-op
chemoXRT
Dutch Stage XRT & 924 5.6 64.2 60
Rectal I, II, Surgery 937 10.9 63.5
Cancer III Surgery alone
For distal T2N0 tumors, local recurrence increases, as do stoma rates, functional
consequences and morbidity and mortality. Literature review suggests cancer spe-
cific survival, and overall survival are broadly similar for radical resection, local
excision with neoadjuvant or adjuvant chemoradiation, or chemoradiation followed
by “watch and wait”. Older studies have suggested local recurrence rates are higher
Table 18.2 Stoma rates following various treatment interventions [10, 14, 18–24]
Trial Intervention N Permanent stoma
LeZoche, et al. Pre-op chemoXRT &TEM 0
Pre-op chemoXRT & TME 26
Guerrieri et al. Pre-op chemoXRT & TEM 139 0
Chen et al. TEM 30 0
LAR 30 0
Yu et al. TEM 60 0
ACOSOG Z6041 Pre-op chemoXRT & LE 79 9
Swedish Rectal Cancer trial Preop XRT & Surgery 454 55
Surgery alone 454 59
German Rectal Cancer Trial Pre-op chemoXRT & Surgery 404 34
Surgery & post-op chemoXRT 395 30
Dutch Rectal Cancer Trial Pre-op XRT & surgery 924 33
Surgery alone 937 29
Table 18.3 Outcomes following non-operative management of rectal cancer [15, 25–27]
Clinical Local
Tumor complete recurrence Follow-up Disease free
Trial N stage response (%) (%) (months) survival (%)
Appelt et al 40 Stage I, 73 15.5 24 75
II, III
Smith et al. 32 22 19 17 88
MSKCC
Maas et al. 21 Stage I, 11 4.8 25 93
Netherlands II, III
for local excision when compared to radical resection; however, the majority of
these studies evaluated traditional transanal techniques [12]. More recent data,
although small case series, have identified equivalent local recurrence rates when
comparing TEM to radical resection [13, 14]. More large scale, multicenter trials
will be necessary to confirm comparable local recurrence rates. There is clear evi-
dence that local excision alone is inadequate treatment for T2 rectal cancer, resulting
in unacceptable local recurrence rates and subsequent decreases in cancer specific
survival [12]. There is currently sufficient data to suggest that traditional transanal
excision is technically inferior to advanced techniques for local excision (most data
evaluates TEM, but more date is becoming available for TEO, TAMIS, and SILS
approaches) [13]. There is no debate that permanent stoma rates, functional (defeca-
tory, urinary, and sexual) consequences, and morbidity and mortality are signifi-
cantly higher following radical resection.
Regarding “watch and wait” observational therapy following chemoradiation,
oncologic outcomes are similar to radical resection for the select group of patients
with a complete clinical response [15, 16]. These are observational trials,
predominately from one center. There are no prospective randomized data available.
There are no trials comparing observational therapy with local excision.
188 P.A. Cataldo
Based on this literature review, treatment must be individualized. The main ben-
efits associated with radical resection are accurate pathologic staging, the avoidance
of chemotherapy and radiation, and possibly lower rates of local recurrence. These
benefits come at the cost of higher complication rates, greater functional conse-
quences, and higher permanent stoma rates.
The benefits of local excision are obvious; avoidance of laparotomy or laparos-
copy, outpatient surgery, minimal morbidity and mortality, fewer functional conse-
quences, and avoidance of a permanent stoma. However, local excision requires
neoadjuvant chemoradiation and may be associated with higher rates of local recur-
rence. In addition, accurate pathologic staging cannot be achieved.
Author’s Approach
It can’t be emphasized enough that treatment for T2N0 rectal cancer must be indi-
vidualized. A detailed history identifying a patient’s desires, fears, physical, and
social limitations is essential for developing a treatment plan. As previously stated,
I separate proximal and distal T2N0 rectal cancer into two distinct treatment groups.
All medically fit patients with proximal lesions undergo radical resection without
neoadjuvant therapy.
For distal lesions, decision making is more complex. Enrollment in open clinical
trials is offered if appropriate. After discussion, if patients are most concerned about
tumor recurrence and need to have definitive evidence regarding mesorectal lymph
node spread, they undergo radical resection (either LAR or APR depending upon
tumor location). Perineal dissection for all APRs is performed prone with a cylin-
dral excision [17]. For patients more concerned about anorectal function, a multi-
modality approach is used. Pathology is reviewed, patients with poor differentiation
or lymphovascular invasion identified on biopsy (this is uncommon) are counseled
that radical resection is preferred.
For others, treatment begins with neoadjuvant chemoradiation (after discussions
in a rectal cancer multidisciplinary tumor conference). Five fluorouracil based che-
motherapy, without oxaliplatin, combined with 5040 rads over 5 weeks is most
common. Patients are then evaluated 4 weeks following completion of chemoradia-
tion with physical examination and flexible sigmoidoscopy. Photographs of the
tumor site are taken and stored electronically. If there is significant tumor response,
patients undergo 2–4 more cycles of chemotherapy and then subsequent repeat
endoscopic evaluation of the tumor. If there is little or no treatment response, radical
resection is recommended. If no tumor is identified or if the tumor continues to
decrease in size, patients complete 4 months of chemotherapy. After completion of
the entire neoadjuvant regimen, patients have another endoscopic rectal evaluation,
and CT chest, abdomen and pelvis. Provided there is no metastatic disease, patients
will either undergo TEM or careful observation. TEM was used for all patients in
the past but recovery is very slow with significant delays in wound healing if local
excision is performed following radiation [18]. Now only patients with actual or a
question of a small residual rectal tumor undergo TEM. Patients with a cCR are
individualized to observation vs TEM depending upon patient and physician prefer-

ence. This is an area of cancer management that is changing rapidly and will likely
change significantly in the next decade.
For individuals who have little or no response to neoadjuvant therapy, local exci-
sion is not an option. These patients are at very high risk for local recurrence follow-
ing TEM and radical resection is recommended. Only patients that are medically
unfit or refuse radical resection are considered for TEM, and are at risk to fail this
treatment plan.
Conclusions
T2N0 rectal cancer comprises a heterogeneous group of patients with varied worries,
goals, and expectations. In addition, risk of recurrence, both local or systemic, may
be influenced by factors beyond TNM Stage, such as lymphovascular invasion,
degree of differentiation, and response to neoadjuvant therapy. Importantly, multi-
ple treatment options exist, each with different risks of recurrence and with different
effects on post treatment quality of life. Current surgical literature is inadequate to
provide an absolute “standard” treatment regimen at the present time Therefore,
treatment must be tailored to match the patient’s personal needs (desire to avoid a
colostomy, concerns regarding anorectal, urinary, and sexual function, and need to
know accurate lymph node status) in addition to curing the cancer. This can only be
successfully accomplished by taking the time to thoroughly learn the patient’s goals
and to assess subtle tumor factors in order to assure the treatment is not worse than
the disease.
References
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3. Brown G, Richards CJ, Bourne MW, et al. Morphologic predictors of lymph node status in
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9. Ball M, Nelson CJ, Shuk E, Starr TD, et al. Men’s experience with sexual dysfunction post-
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11. You YN, Baxter NN, Stewart A, Nelson H. Is the increasing rate of local excision for Stage I
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12. Hazard LJ, Sklow B, Pappas L, Boucher KM, et al. Local excision vs. radical resection in T1-2
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13. Moore JS, Cataldo PA, Osler T, Hyman NH. Transanal endoscopic microsurgery is more effec-
tive than traditional transanal excision for resection of rectal masses. Dis Colon Rectum.
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14. Guerrieri M, Ortenzi M, Cappelletti Trombettoni MM, Kubolli I, et al. Local excision of early
rectal cancer by transanal endoscopic microsurgery (TEM): The 23-year experience of a single
centre. J Cancer Ther. 2015;6(11):1000–7.
15. Habr-Gama A, Gama-Rodrigues J, São Julião P, Proscurshim I, et al. Local recurrence after
complete clinical response and watch and wait in rectal cancer after neoadjuvant chemoradia-
tion: impact of salvage therapy on local disease control. Int J Radiat Oncol Biol Phys.
2014;88(4):822–8.
16. Habr-Gama A, Perez RO, Nadalin W, Sabbago J, et al. Operative versus nonoperative treat-
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conventional versus cylindrical abdominoperineal resection for locally advanced lower rectal
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Z6041): results of an open-label, single-arm multi-institutional, phase 2 trial. Lancet.
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rectal carcinoma: a prospective randomized trial. Cancer. 1990;66:49–55.
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Chapter 19
Clinical Complete Response after
Neoadjuvant Chemoradiotherapy in Rectal
Cancer: Operative or Non-Operative
Management?
Miranda Kusters and Julio Garcia-Aguilar
PICO table
Patient population Intervention Comparator Outcomes
Patients with complete Non-operative Surgery Cancer recurrence,
response after neoadjuvant management (TME) morbidity, disease-free
treatment of rectal cancer survival, overall survival
Introduction
Surgical excision of the rectum and its mesorectal envelope has been the mainstay
of rectal cancer treatment for over a century [1]. Despite advances in surgical tech-
nique and perioperative care, total mesorectal excision (TME) remains an operation
associated with some mortality, significant morbidity, and sequelae that perma-
nently impair quality of life [2].
Some patients with locally advanced rectal cancer (LARC) have a pathologic
complete response (pCR) to neoadjuvant chemoradiotherapy (nCRT). Patients with
pCR have lower local recurrence (LR) and improved survival rates compared to
non-pCR patients, raising the question of whether they truly need surgery [3]. As
most of the mortality, morbidity, and long-term sequelae from multimodality ther-
apy are related to excision of the rectum, avoiding TME selectively in patients who
obtain a sustained response to nCRT will improve the quality of life, with the added
benefit of avoiding overtreatment.
M. Kusters
Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands
J. Garcia-Aguilar, MD (*)
New York, NY, USA

DOI 10.1007/978-3-319-40223-9_19
192 M. Kusters and J. Garcia-Aguilar
While the evidence suggesting that some rectal cancers can be treated with radia-
tion alone is almost a century old, it is Angelita Habr-Gama from Sao Paulo who
should be credited with suggesting that rectal cancer patients with clinically com-
plete responses (cCR) to neoadjuvant chemoradiation could achieve long-term local
tumor control without surgery [4].
These ideas were initially received with disbelief, but reports from other institu-
tions have confirmed that surgery can be avoided in select rectal cancer patients
treated with nCRT. However, the evidence supporting this treatment approach is
based on small institutional series of heterogenous groups of patients who were
staged using different imaging modalities, treated according to diverse radiation and
chemotherapy regimens, evaluated at different times after completion of the neoad-
juvant therapy, selected for observation using different criteria, and followed for
relatively short periods of time. In spite of these limitations, clinicians are starting
to accept a paradigm shift for this select group of rectal cancer patients, often pushed
by patients motivated to avoid the consequences of a low colorectal anastomosis or
a permanent colostomy. The treatment plan after neoadjuvant therapy that consists
of close active surveillance, rather than surgery, is called watch-and-wait or non-
operative management (NOM).
Uncertainties about Tumor Response to Neoadjuvant Therapy
While the above-mentioned studies all suggest that most patients with cCR after
neoadjuvant chemotherapy can achieve prolonged local tumor control without sur-
gery, a number of questions must be answered before NOM can be considered a
standard option for patients with LARC.
The proportion of patients responding completely to neaodjuvant chemoradia-
tion seems small and the optimal time to assess clinical response unknown. Tumor
response depends on radiation dose, but doses beyond 54 Gy are rarely used in
LARC patients. Adding other drugs effective in colon cancer as radiosensitizers
beyond fluorpyrimidines has been found to be ineffective or prohibitively toxic [5–
8]. Tumor response to chemoradiation is closely associated with time, and in
patients undergoing TME after nCRT, the proportion of tumors with pCR increases
with the time interval between chemoradiation and surgery [9]. As prolonging the
interval to surgery and postoperative systemic chemotherapy may be unsafe in
patients at risk of LR, attempts have been made to deliver systemic chemotherapy
immediately before or after chemoradiation [10]. Delivering systemic chemother-
apy before rather than after surgery has been shown to increase tumor response
without delaying the treatment of potential micrometastatic disease. In these
patients, the assessment of the clinical response, with the potential recommendation
of NOM or surgery, is performed at the completion of both chemoradiation and
systemic chemotherapy [10, 11]. This approach has resulted in pCR rates as high as
38 % in patients with clinical stage II and III disease and has the added advantage of
increasing compliance with adjuvant systemic chemotherapy as well as shortening
ileostomy time for patients after low anterior resection [10].
19 Clinical Complete Response after Neoadjuvant Chemoradiotherapy 193
The lack of a reliable and uniform method of distinguishing post-treatment scar

from residual tumor in the bowel wall or regional lymph nodes is the main obstacle
to NOM in patients treated with neoadjuvant therapy. Most authors agree that digital
rectal examination, endoscopy, and imaging studies should be used (Table 19.1). A
flat white scar with or without telangiectasia and a normal digital exam are good
predictors of pCR, while the presence of superficial ulceration or a palpable modu-
larity on digital rectal exam considered an indicator of incomplete response [12, 13].
While clinical assessment tends to underestimate tumor response, there is always a
possibility that tumors are concealed in or behind an apparently normal scar in the
rectal wall [14]. Endorectal ultrasound, computed tomography (CT), and positron
emission tomography with [18F]fludeoxyglucose provide a rough estimate of tumor
regression but are not sensitive enough to identify pCR [15]. Conventional MRI mor-
phological sequences (e.g. T2- and T1-weighted images) cannot differentiate resid-
ual tumor from surrounding fibrosis, but diffusion-weighted (DW) MRI sequences
may improve the diagnostic performance of morphological MRI sequences in dif-
ferentiating pCR from residual tumor [16]. The criteria used to grade response
undoubtedly influence the observed clinical outcomes: a strict definition reduces the
proportion eligible but increases the chance of NOM success, while looser criteria
increase the number of eligible patients but also risk of local tumor regrowth and
distant metastasis. Currently, there are no validated criteria defining clinical and
radiological tumor response, but a new set of criteria categorizing response in a 3-tier
system is currently being tested in a prospective clinical trial [17].
Table 19.1 Criteria of complete response, near-complete response, and incomplete response [13]
Complete response Near-complete response Incomplete response
Endoscopy Flat, white scar Irregular mucosa Visible tumor
Telangiectasia Small mucosal nodules
No ulcer or minor mucosal
No nodularity abnormality
Superficial ulceration
Mild persisting erythema
of the scar
Digital rectal Normal Smooth induration or Palpable tumor nodules
exam minor mucosal
abnormalities
MRI-T2W Only dark T2 signal, no Mostly dark T2 signal, More intermediate than
intermediate T2 signal some remaining dark T2 signal, no T2
AND intermediate signal scar
No visible lymph nodes AND/OR AND/OR
Partial regression of No regression of lymph
lymph nodes nodes
MRI-DW No visible tumor on Significant regression of Insignificant regression
B800-B1000 signal signal on B800-B1000 of signal on
AND/OR AND/OR B800-B1000
Lack of or low signal on Minimal or low residual AND/OR
ADCa map signal on ADC map Obvious low signal on
Uniform, linear signal in ADC map
wall above tumor is ok
ADC, apparent diffusion coefficient
a
A number of patients with apparent cCR develop tumor regrowth during follow-
u p. As most regrowth occurs in the bowel wall, repeated endoscopic exams are
essential. Any suspicious changes in the scar should be biopsied. MRI should also
be performed regularly to detect nodal disease. Changes in the size, contour, hetero-
geneity, or restriction of diffusion should raise the possibility of relapse. Repeated
exams and continuous monitoring are often necessary to confirm recurrence.
Ultimately, finding reliable predictors of response to neoadjuvant therapy would
help identify patients most likely to benefit from NOM and reduce toxicity for those
who will likely have poor response. Tumor size and stage seem to predict response,
with smaller, early-stage tumors being more likely to yield pCR. The search for
molecular predictors of tumor response has not yielded any breakthrough findings
so far. We have previously shown that rectal tumors with a KRAS mutation are less
likely to respond to nCRT [18]. However, these findings await validation by studies
of large independent cohorts.
reatment Options for Patients with a cCR after Neoadjuvant

T
Therapy: Observation or Surgery?
Unfortunately, there is no level 1 evidence regarding the oncological and functional

outcomes of NOM versus standard TME after a cCR. Ideally, a randomized study
should be performed, with a non- inferiority design for the non-operative arm.
However, there are 2 reasons why this kind of study is difficult to perform. First, a
non-inferiority study requires investigators to demonstrate that survival will not be
compromised in NOM. Such a study requires a large sample size that will be difficult
to achieve. Second, it is unlikely that patients who are told that NOM is an alternative
option potentially offering similar oncological results would opt for randomization
with a chance of undergoing surgery anyway.
Meta-analyses are also not available. Thus, the only types of studies we can ana-
lyze are retrospective series or prospectively followed patient series. Our search
terms on PubMed were “complete response,” “rectal cancer,” “non-operative man-
agement,” “watch and wait,” and “wait and see.” We will discuss the oncological
and functional results in the next chapters.
Evidence Supporting NOM
In this overview, we included studies in which patients with a cCR as established by

digital rectal examination, endoscopy, and MRI were compared to a cohort of
patients who had a resection and demonstrated pCR on pathologic examination.
There is also one study in which patients were managed by NOM after cCR diagno-
sis established by MRI alone. In our opinion this is not the standard of care, so we
did not include this study [19]. Table 19.2 shows the oncological outcomes of the 5
comparative studies in order of publication.
Table 19.2 Studies in which oncological outcomes for NOM in patients with cCR were compared to those for OM in patients with pCR
No of No of Difference Difference Disease-free

cCRs pCRs Difference in distance in adj. Overall survival survival Evidence
Reference (NOM) (OM) in T-stagea of tumora chemoa NOM OM p-value NOM OM p-value level
Habr-Gama 71 22 Equal Equal Equal 5-year 5-year 0.01 5-year 5-year 0.09 3b
et al. [20] 100 % 88 % 92 % 83 %
Maas et al. 21 20 nm nm nm 2-year 2-year 0.23 2-year 2-year 0.77 3b
[4] 100 % 93 % 89 % 91 %
Smith et al. 32 57 NOM OM OM 2-year 2-year 0.56 2-year 2-year 0.27 3b
[21] 96 % 100 % 88 % 98 %
Araujo 42 69 NOM OM Equal 5-year 5-year 0.32 5-year 5-year 0.04 4
et al. [22] 72 % 90 % 61 % 83 %
Li et al. 30 92b Equal Equal nm 5-year 5-year 0.26 5-year 5-year 0.51 4
[23] 100 % 96 % 90 % 94 %
nm not mentioned
a
In favor of NOM (non-operative management) or OM (operative management), meaning less advanced T-stage, higher location of the tumor or more adjuvant
19 Clinical Complete Response after Neoadjuvant Chemoradiotherapy
chemotherapy (adj. chemo)

b
cCR patients who underwent surgery
195
The first comparison between 71 NOM patients with a cCR and 22 OM patients
with a pCR was reported by Habr-Gama [20]. Patients were well-informed about
the risks and benefits of NOM. In a retrospective series of 194 patients with near-
complete response, NOM was considered too risky and surgery was performed; 22
(8.3 %) of these patients ended up having a pCR. Regarding clinical parameters and
postoperative treatment, there was no significant difference between the NOM and
OM patients, although it seemed that there were slightly more T3/T4 tumors in the
OM group. The NOM group’s disease-free survival (DFS) was similar to that of the
OM group; 1-year survival (OS) was significantly better. The authors do not explain
this; the question remains whether the deaths were related to the surgery, although
no perioperative deaths were reported.
In a small but very carefully selected series of prospectively followed patients by
Maas et al., 21 well-informed NOM patients were compared to 20 retrospectively
selected OM patients with pCR. Of the 20 OM patients, 5 had cCRs and were treated
before the wait-and-see policy was introduced, and 15 had a near-complete clinical
response [4]. Although the study’s data tables show no differences between the
patient groups, no statistics were presented. There was no difference in OS and DFS
between the groups.
The third study, by Smith et al., describes 32 NOM patients and 57 OM patients
with a pCR [3]. NOM was described to the patients as a non-standard treatment
which might compromise oncological outcomes, but the majority opted for this man-
agement because of high medical comorbidity or because they did not want to
undergo surgery. The OM patients had slightly more proximal tumors and received
adjuvant treatment more often but had more advanced tumors compared to the
OM-patients. Even so, DFS and OS were not significantly different.
Araujo et al. conducted a retrospective analysis of 42 patients treated with NOM
and compared them to 69 patients who had a pCR after resection [22]. NOM was
not the standard of care in this institution, so most patients in this group were
patients who refused surgery or wanted to postpone it as long as possible. DFS was
significantly worse in the NOM group, but the authors also mentioned that this
might be due to the fact that there were more distal cancers in this group. DFS was
not significantly different if only patients with low rectal cancers were included.
The most striking element of this paper is the inclusion of 20 patients in the NOM
group (54 %) with residual tumor or ulceration. Although statistically this did not
influence DFS, this weakens the study considerably, as in our opinion patients
should be referred for surgery in the case of residual disease.
Li et al. published the only series in which patients with cCR who underwent
NOM were compared to patients with cCR who underwent surgical management
[23]. There seemed to be no difference clinically between the two groups. However,
the reasons for treatment selection were not explained by the authors. It is unclear
whether there is a time bias due to NOM’s introduction at a certain time point or
whether there was informed consent for this strategy. For these reasons, we consider
it a weak study.
A group from the United Kingdom has recently reported a multi-institutional
experience with a NOM approach versus surgical resection in rectal cancer patients
treated with chemoradiation [24]. In contrast to the previously discussed series, this
study compared the outcomes of 129 patients with cCR and 228 rectal cancer
patients who had surgical resection after neoadjuvant chemoradiation independent
of the pathological stage. The neoadjuvant therapy regimens in the two groups were
similar. After a median follow-up of 33 months from start of chemoradiation, 44
(34 %) patients with cCR had local regrowths, corresponding to an actuarial 3-year
local regrowth rate of 38 %. Similar to previous findings, most local regrowths were
in the bowel wall, and most underwent successful salvage treatment. The authors
developed one-to-one paired cohorts (109 patients in each group) using propensity-
score matching for the key confounders. The 3-year non-regrowth DFS rate (time
until death, local recurrence, or distant metastasis, not including local regrowths)
was 88 % for the NOM group and 78 % for the surgical group (log rank P = 0.22).
The colostomy-free survival rates were 74 % and 47 %, respectively. The authors
concluded that NOM is oncologically safe in a multi-institutional setting, support-
ing the standard adoption of NOM. However, the results of this study should be
interpreted with caution, as tumors in NOM patients had earlier pretreatment tumor
stage, were less likely to have nodal involvement, rarely had unfavorable histologi-
cal features, and were more likely to have normal carcinoembryonic antigen levels.
In addition, comparing patients with and without cCR, independent of the patho-
logical stage, introduces significant bias, as tumor response is associated with
improved outcome compared to non-responders.
On the basis of the first 3 studies, although they are based on only level 3b evi-
dence, we can carefully conclude that NOM results in similar oncological outcomes
associated with recurrence-free survival and overall survival compared to OM. A
prerequisite for NOM is a cCR, not a near-complete response. Since about 70 % of
patients with cCR would have a pCR after resection, you might expect less favor-
able oncological outcomes compared to the patients who had a resection and 100 %
pCR. Instead, the similar outcomes suggest even more strongly that NOM is onco-
logically safe.
ocal Regrowth and Salvage Therapy vs. Stoma Rates

L
and Operative Mortality
Table 19.3 summarizes local-regrowth, stoma, and mortality rates in the 5 retro-
spective studies. Overall, the mean time to local regrowth in NOM patients with
cCR was 31 months. Local regrowth appeared in an average of 8 % of all patients,
although this also includes the Araujo study, which included near-complete
responders. Ninety-four percent of all local regrowths could be salvaged, and 4 %
of all cCR patients ended up with a permanent stoma. By contrast, 35 % of patients
receiving OM had a permanent colostomy. The mean mortality rate after OM was
2 %. Local recurrence after this management was still present in 2 % of the cases,
despite the pCR after primary surgery.
As mentioned earlier, the timing and definition of cCR can greatly influence the
proportion of patients considered as having a cCR as well as associated local recur-
rence rates. One should bear in mind that the above-mentioned 8 % local regrowth
198
Table 19.3 Comparison of the rates of local failure, stoma, and operative mortality after NOM in patients with cCR and after OM in patients with pCR
NOM patients undergoing salvage
Mean No. of therapy OM No. of
interval to No. of LR salvage-able No/temporary Permanent stoma No. of LR peri-operative
LR in NOM cases in LR cases in stoma (% of all (% of all NOM No/temporary Permanent cases in mortality
Reference (months) NOM (%) NOM (%)a NOM patients) patients) stoma (%) stoma (%) OM (%) cases (%)
Habr-Gama 60 2 (3) 2 (100) 1 local excision 0 (0) 13 (59) 9 (41) 0 (0) 0 (0)
et al. [20] 1 brachytherapy
Maas et al. 22 1 (5) 1 (100) 1 local excision 0 (0) 11 (55) 9 (45) 0 (0) 1 (5)
[4]
Smith et al. 11 6 (19) 6 (100) 3 (9) 3 (9) nm nm 0 (0) nm
[21]
Araujo et al. 48 5 (12) 4 (80) 1 (2) 3 (7) 56 (81) 13 (19) 4 (6) 3 (4)
[22]
Li et al. [23] 22 2 (7) 2 (100) 1 local excision nm 52 (57) 40 (43) 2 (2) 0 (0)
1 nm
Meana 31 16 (8) 15 (94) 6 (4) 71 (35) 6 (2) 4 (2)
a
Mean excludes studies in which there were ‘nm’ (not mentioned) data
M. Kusters and J. Garcia-Aguilar
rate is for a strongly sub-selected patient cohort. For example, in Maas et al. this
cohort represented 21 patients, which was 11 % of the patients treated with chemo-
radiotherapy. Also, in the later Habr-Gama series, local regrowth numbers varied
depending on the group of patients considered. When 68 % of the patients treated
with chemoradiotherapy were managed with NOM, long-term sustained response
could be achieved in 57 % [25]. These numbers are consistent with the first pub-
lished prospective trial (NCT00952926) by Appelt et al. [26] This study showed
58 % local tumor control after 2 years in patients with primary low T2/T3 rectal
cancers treated with chemoradiotherapy resulting in a cCR. The patients in this
study had their assessment at 6 weeks after treatment completion, which is early
(resulting in a 78 % cCR rate), also explaining the high local regrowth rate. All local
recurrences (9 of 9) after NOM underwent resection with clear resection margins.
Functional Outcomes and Toxicity Associated with NOM
It is generally believed that functional outcomes are better in patients who have
undergone NOM than in patients who have undergone a resection, owing to the risk
for nerve damage and low-anterior resection syndrome. The only study comparing
functional outcomes after NOM versus resection with a pCR is by Maas et al.,
which confirmed that functional outcomes are better after NOM [4]. Bowel function
in patients in the OM group was significantly more affected by food intake, and
these patients used pads and colonic irrigation more frequently, had less control
over flatus, and reported more changes in their post-diagnosis/treatment bowel hab-
its. Also, patients who had NOM had a lower mean Wexner incontinence score (0.8
versus 3.5) and a lower mean defecation frequency (1.8/day versus 2.8/day) than
patients who had a resection. Appelt et al. also described good functional outcomes;
there was no self-reported fecal incontinence in 72 % of patients after 1 year and in
69 % at 2 years after NOM. The median Wexner incontinence score was 0 at all
time-points [26].
Regarding NOM toxicity, only one study measured it accurately: the prospective
study of Appelt et al. [26]. However, in this study brachytherapy was given as a
boost to 60 Gy chemoradiotherapy. Rectal bleeding was the most common symp-
tom, reported by 78 % of the patients after 1 year, although this was mild in most
patients; 6 % had grade 3 rectal bleeding, which needed transfusion or intervention,
at 2 years. The authors hypothesized that this unexpected high toxicity rate might be
due to the combination of chemoradiotherapy with a brachytherapy boost, which
could be replaced by a boost of external beam radiotherapy. This study describes the
short-term toxicity of NOM, but follow-up was too short to determine long-term
radiation effects. There are reports of long-term toxicity of the rectum after irradia-
tion of the reproductive organs in patients receiving treatment with old radiation
techniques. Still, it is very difficult to weigh long-term toxicity against the morbid-
ity prevented by avoiding an operation.
Non-Operative Management in the Elderly
Most surgery studies focus on young and healthy patients. There is strong evidence
however, that in elderly patients and patients with comorbidities, surgery is associ-
ated with not only increased in-hospital mortality and 30-day mortality but also
above-baseline death rates up to 1 year postoperatively [27–29].
A very thorough analytic decision model study from Smith et al. took into account
the 90-day mortality rate and used a probabilistic Markov simulation to model out-
comes in patients with a cCR after nCRT for rectal cancer treated with either empiric
surgery or a NOM strategy [30]. Several NOM studies and the outcomes in the UK
National Health Registries empiric surgery database were used in the model. The
primary endpoint was overall survival; secondary outcomes were DFS and quality-
adjusted life years. The model was run for 3 categories: 60-year old cohort with mild
comorbidities, 80-year-old fit patient cohort with mild comorbidities (Charlson
score < 3), and 80-year-old cohort with significant comorbidities (Charlson score
≥3). The results of the study showed that, because of the increased operative risk
associated with elderly and comorbidity patients, conservative management options
result in superior survival at 1 year after treatment. Further, equivalent DFS and
quality of life can be achieved compared with surgery in patients with a cCR. Even
though the potential improvement in survival after 1 year is marginal in younger
patients treated with NOM, surgery did not improve DFS and quality of life.
Future Prospective Studies
There are currently several open prospective studies and registries concerned with
the question of NOM vs. OM. Many can be found on www.clinicaltrials.gov.
The only one comparing NOM versus resection in cCR is being conducted at the
Cancer Institute Hospital in Sao Paulo (NCT02052921), but that trial is suffering
from low accrual, which was to be expected due to previously discussed reasons. A
prospective study sponsored by Royal Marsden (NCT01047969) seeks to prove the
safety of NOM. It has 2 primary outcome measures at 2 years after the end of nCRT:
estimation of the percentage of patients for whom surgery can be omitted and the
percentage of patients with local failure, defined as positive margin status of the
resected tumor or surgically unsalvageable disease.
Further, Memorial Sloan Kettering Cancer Center in New York is currently coor-
dinating a prospective randomized trial that incorporates NOM (NCT02008656)
[17]. The primary purpose is to evaluate 3-year DFS in patients with locally
advanced rectal cancer randomized between induction chemotherapy with nCRT
versus nCRT with consolidation chemotherapy. Patients with a cCR according to
clearly defined criteria will undergo NOM. Also, quality of life and functional out-
comes will be evaluated and validated. Further, molecular markers will be studied
in all patients to see whether there are profiles that can predict a complete response.
Another initiative is the International Watch and Wait Database (www.iwwd.

org), a prospective registry in which all patients with a near complete or clinically
complete response can be entered in a secure Internet database. Dozens of centers
cooperate in this project, and the actual entered patient-number is regularly updated
on the website. There are frequent teleconferences between the participating centers
to exchange ideas and to coordinate and optimize data analyses. The purpose is to
evaluate long-term outcomes of NOM in large numbers of patients, although the
differences between the centers will make this statistically challenging.
Expert Opinion
• In patients with cCR, there is more and more evidence that NOM does not com-
promise DFS.
• Patients with cCR should be referred to specialized surgeons who have consider-
able experience with cCR in LARC. Experience is essential.
• There is not enough evidence to guide decision-making in patients with near-
complete clinical responses.
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results of an open-label, single-arm, multi-institutional, phase 2 trial. Lancet Oncol.
16(15):1537–46.
11. Cercek A, Goodman KA, Hajj C, Weisberger E, Segal NH, Reidy-Lagunes DL, Stadler ZK,
Wu AJ, Weiser MR, Paty PB, Guillem JG, Nash GM, Temple LK, Garcia-Aguilar J, Saltz
LB. Neoadjuvant chemotherapy first, followed by chemoradiation and then surgery, in the
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Chapter 20
Management of the Patient with Rectal
Cancer Presenting with Synchronous Liver
Metastasis
Shafik M. Sidani and Maher A. Abbas
Introduction
An estimated 39,610 new cases of rectal cancer (RC) are expected in the United
States in 2015 [1]. Synchronous colorectal liver metastasis (SCRLM) occurs in
20 % of patients with locally advanced RC [2, 3]. Median overall survival (OS) for
patients with SCRLM is 20–24 months without resection as opposed to 5-year OS
of up to 50 % with R0 resection of metastatic disease [4]. Oncologic outcomes con-
tinue to improve with the development of new effective chemotherapy regimens
and increased hepatectomy rates [5, 6]. Patients with SCRLM constitute a hetero-
geneous group with varying preoperative fitness, tumor biology, tumor resectabil-
ity, and symptomatology related to the primary tumor. Potential cure is dependent
on the ability to resect all disease, and requires a multidisciplinary approach.
Locally advanced RC requires chemoradiation (CRT) with surgery, whereas
SCRLM is initially addressed with chemotherapy. Surgery for symptomatic relief
is reserved for select cases. The optimal sequence of multimodality treatment to
address the primary tumor and associated metastatic disease is under active
investigation.
S.M. Sidani (*) • M.A. Abbas

Digestive Disease Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates

DOI 10.1007/978-3-319-40223-9_20
206 S.M. Sidani and M.A. Abbas
Search Strategy
An electronic search was conducted using the PubMed database for reports pub-
lished in the English language between January 1990 and October 2015 using the
key words rectal cancer in various combinations with liver metastasis(es), hepatic
metastasis(es), staged resection, simultaneous resection, synchronous resection,
combined resection, liver-first, chemotherapy, and radiation. Referenced studies
from identified reports were reviewed if relevant. The “related articles” function
was used to further expand the search. Only studies published between 2000 and
2015 clearly identifying at least 20 patients with RC and synchronous liver metas-
tases were included in the tables summarizing the studies. If more than one study
was reported from the same institution, the most recent study focusing on RC was
included.

Patients with RC Staged rectum-first Liver-first approach Perioperative morbidity
and SCRLM approach Simultaneous resections Disease free survival
approach (DFS)
OS
Results
valuation of the Patient with Rectal Cancer and Synchronous

E
Hepatic Metastasis
The initial evaluation of patients with rectal cancer and SCRLM includes determi-
nation of symptomatology, colonoscopy, staging, determination of resectability
from an oncologic standpoint, and evaluation of the future liver remnant based on
imaging before and after multimodality treatment, as well as assessment of fitness
for surgery. In addition to imaging of the primary tumor with magnetic resonance
imaging (MRI) and endorectal ultrasound [7], computed tomography (CT) is useful
to evaluate distant disease. Contrast-enhanced MRI can detect or further character-
ize small hepatic lesions and is superior to CT in the setting of post-chemotherapy
hepatic steatosis [8]. Fluorodeoxyglucose-positron emission tomography (FDG-
PET) can detect extrahepatic disease that would preclude curative resection and
change management in up to 24 % of cases [9, 10]. Two randomized prospective
trials reported conflicting results regarding the utility of FDG-PET [11, 12]. Ruers
et al. demonstrated that non-curative surgery was avoided in one of six patients as a
result of PET findings [11] whereas Moulton et al. failed to confirm these results
[12]. Additional studies have supported the use of FDG-PET in patients with rectal
cancer and SCRLM [13–20]. Sensitivity of PET after chemotherapy is reduced due
to decreased metabolic activity of residual tumor [21–24].
20 Management of the Patient with Rectal Cancer Presenting with Synchronous 207
Liver biopsy can be helpful in select cases with equivocal imaging findings but
should not be performed routinely due to the risk of tract seeding [25–28].
Treatment Options
Following a diagnosis of rectal cancer with SCRLM, the treatment plan is formu-
lated with the goal of prolonging survival and maximizing the prospects of a cura-
tive resection. Many studies combine both colon and rectal cancer and are
compromised by selection bias; no prospective randomized data comparing treat-
ment approaches exists to guide management decisions. Rectal cancer presents
additional challenges compared to colon cancer with concerns for local recurrence,
potential need for adjuvant or neoadjuvant radiation therapy, and complexity of pel-
vic surgery. The heterogeneity of scientific data pertaining to chemotherapy and
radiation regimens, and the introduction of various drugs during the last two decades
add to the challenges of data interpretation [29, 30].
Table 20.1 summarizes studies directly comparing the perioperative results of
surgical approaches for colorectal cancer with SCRLM. Table 20.2 shows compara-
tive oncologic outcomes of those studies. Table 20.3 presents outcomes of case
series of the different surgical approaches.
Multimodality Treatment Although chemotherapy is generally included in the
treatment plan of patients with SCRLM, there is no consensus on timing, benefit,
and risk. The EORTC 40983 randomized trial demonstrated improvement in pro-
gression free survival but not overall survival when six cycles of neoadjuvant and
six cycles of adjuvant FOLFOX were administered perioperatively, compared to
surgery alone. Resection rates were equivalent in both groups showing that the win-
dow of resectability is not lost with neoadjuvant chemotherapy. Notably, the chemo-
therapy group had fewer nontherapeutic laparotomy rates (5 % versus 11 %) [76,
77]. Similarly, two meta-analyses comparing surgery with or without chemotherapy
demonstrated the benefit of chemotherapy in disease free but not overall survival
[78, 79].
Neoadjuvant chemotherapy allows early treatment of micrometastatic disease,
and provides upfront information regarding tumor biology and response to adjuvant
chemotherapy. Outcomes after hepatectomy are superior in patients with a positive
tumor response to neoadjuvant chemotherapy as opposed to nonresponders [6, 80,
81]. This selects out patients with progression of disease on chemotherapy prior to
surgery, who have significantly lower disease free and overall survival [82].
Neoadjuvant chemotherapy may also improve resectability in borderline resectable
or initially unresectable SCRLM [83–85]. Disadvantages of upfront chemotherapy
include the risk of progression of initially resectable disease [86], the dilemma of
disappearing liver metastases, as well as liver injury prior to hepatectomy. There is
conflicting evidence regarding the safety of neoadjuvant chemotherapy prior to liver
surgery [87–92], and the response to treatment should typically be assessed every
Table 20.1 Studies comparing morbidity and mortality of surgical approaches for CRC with SCRLM
208
RC cases
N (RC Approach, N analyzed
with Follow-up (RC with Mortality separately Quality of
Author (year) SCRLM) (months) SCRLM) Morbidity (%) P value (%) P value (Y/N) Evidence
Weber (2003) [31] 97 (34) 30 SR, 35 (10) 23 0.326 0 NS N low
RF, 62 (24) 32 0
Chua (2004) [32] 96 (45) NR SR, 64 (32) 53 0.25 0 NS N low
RF, 32 (13) 41 0
Capusotti (2007) [33] 79 (27) NR SR, 31 (10) 33 0.037 1 0.392 N low
RF, 48 (17) 56 0
Reddy (2007) [34] 610 (162) NR SR, 135 (54) 36 0.86 3 NR N low
RF, 475 39 1
(108)
Thelen (2007) [35] 219 (78) 70 SR, 40 (6), 18 0.166 10 0.012 N low
RF, 179 (72) 25 1.1
Turrini (2007) [36] 119 (44) 66 SR, 57 (24) 21 0.07 3.5 0.09 N low
RF, 62 (20) 31 5
Yan (2007) [37] 103 (42) 24 SR, 73 (27) 32 NR 0 NS N low
RF, 30 (15) 43 0
Assumpcaoa (2008) [38] 141 (57) 31 SR, 21 (21) 20 (for liver – 2.1 – Y (all RC) low
RF, 36 (36) resection)
Martin (2009) [39] 230 (53) NR SR, 70 (30) 56 0.24 2 NS N low
RF, 160 (23) 55 2
Moug (2009) [40] 64 (24) NR SR, 32 (12) 34 0.69 0 NS N low
RF, 32 (12) 59 0
Slupski (2009) [41] 89 (24) NR SR, 28 (10) 14 0.9 0 NR N low
RF, 61 (14) 13 1
S.M. Sidani and M.A. Abbas
RC cases
Brouquet (2010) [42] 156 (81) 25 SR, 43 (18) 47 NS 5 NS N low
RF, 72 (35) 51 3
LF, 27 (19) 37 0
Cellini (2010) [43] 74 (74) 23 SR, 30 (30) NR – 0 NS Y (all RC) low
RF, 13 (13) NR 0
De Haas (2010) [44] 228 (41) 41 SR, 55 (12) 11 0.015 0 0.557 N low
RF, 173 (29) 25 0.6
Luo (2010) [45] 405 (206) NR SR, 129 (69) 47 >0.05 1.5 1.000 N low
RF, 276 54 2
(137)
van der Pool (2010) [46] 57 (57) 34 SR, 8 (8) 25Rb, 25 L 0.59R 0 NS Y (all RC) low
40 RF, 29 (29) 31R, 17 L 0.39 L 0
28 LF, 20 (20) 20R, 30 L 0
Vigano (2011) [47] 36 (36) 39 SR, 32 (32) 31 NR 5 NR Y (all low/ very low
RF, 4 (4) 25 0 mid RC)
Abbott (2012) [48] 144 (87) 36 SR, 60 (34) 38 NR 3.3 0.38 N low
RF, 84 (53) 41 1.2
Dexiang (2012) [49] 1061 (357) 19 SR, NR 25 NS 2 NS N low
RF, NR 21 2.4
20 Management of the Patient with Rectal Cancer Presenting with Synchronous
(continued)
209
210
RC cases
Mayo (2013) [50] 1004 (276) 34 SR, 329 (91) 27 >0.05 2.7 >0.05 N low
RF, 647 25 3.2
(170)
LF, 28 (15) 39 0
Slesser (2013) [51] 112 (49) NR SR, 36 (19) 25 0.161 6 0.241 N low
RF, 76 (30) 45 1.3
van Dijk (2013) [52] 50 (50) 32 SR, 26 (26) 31 – 0 – Y (all RC) low
RF, 12 (12)
LF, 7 (7)
Fukami (2015) [53] 63 (28) NR SR, 41 (16) 22 0.758 0 NS N low
RF, 22 (12) 27 0
Sabbagh (2015) [54] 52 (52) 42 SR, 15 (15) 58Rb, 15 L 0.06R 0 NS Y (all low/ low
RF, 27 (27) 30R, 10 L 0.9 L 0 mid RC)
LF, 10 (10) 60R, 20 L 20
She (2015) [55] 116 (32) 23 SR, 28 (13) 25 0.28 7.1 0.29 N low
28 RF, 88 (19) 16 1.1
Silberhumer (2015) [56] 198 (198) NR SR, 145 41 0.30 0 NS Y (all RC) low
(145)
RF, 53 (53) 47 0
CRC colorectal cancer, RC rectal cancer, SCRLM synchronous colorectal liver metastasis, NR not reported, NS not significant, DFS disease free survival, OS
overall survival, SR simultaneous resection approach, RF rectum-first approach, LF liver-first approach
a
Study included both synchronous and metachronous metastatic disease and no separate analysis of synchronous disease was performed. This study was not
focused on surgical outcomes
b
Morbidity related to rectal resections (R) and liver resections (L) reported separately
Table 20.2 Studies comparing DFS and OS of surgical approaches for CRC with SCRLM
RC cases
Approach, N analyzed
N (RC with Follow-up (RC with DFS (% 5-year OS (% 5-year separately Quality of
Author (year) SCRLM) (months) SCRLM) or months) P value or months) P value (Y/N) Evidence
Weber (2003) 97 (34) 30 SR, 35 (10) NR – 21 % 0.967 N Low
[31] RF, 62 (24) NR 22 %
Chua (2004) [32] 96 (45) NR SR, 64 (32) 9 % 0.53 29 % 0.52 N Low
RF, 32 (13) 14 % 43 %
Minagawa (2006) 160 (76) 49 SR, 142 (72) NR – 37 months 0.95 N Low
[57] RF, 18 (4) NR 31 month
Thelen (2007) 219 (78) 70 SR, 40 (6), NR – 53 % 0.983 N Low
[35] RF, 179 (72) NR 39 %
Turrini (2007) 119 (44) 66 SR, 57 (24) 19 months 0.04 32 % 0.06 N Low
[36] RF, 62 (20) 14 months 25 %
Yan (2007) [37] 103 (42) 24 SR, 73 (27) 14 % NS 36 % 0.9 N Low
RF, 30 (15) 14 % 37 %
Assumpcao 141 (57) 31 SR, 21 (21) 33 % – 34 % – Y (all RC) Low
(2008) [38] RF, 36 (36)
Yoshidome 137 (59) NR SR, 116 (49) 52 %a 0.003 NR – Y Low
(2008) [58] RF, 21 (10) 87 %
Moug (2009) [40] 64 (24) NR SR, 32 (12) 10 month 0.487 21 % 0.838 N Low
RF, 32 (12) 14 months 24 %
Slupski (2009) 89 (24) NR SR, 28 (10) NR – 45 % 0.006 N Low
[41] RF, 61 (14) NR 38 %

(continued)
211
212
RC cases
Brouquet (2010) 156 (81) 25 SR, 43 (18) 11 month NS 55 % 0.389 N Low
[42] RF, 72 (35) 11 month 48 %
LF, 27 (19) 11 month 39 %
Cellini (2010) 74 (74) 23 SR, 30 (30) NR – 54 months 0.1 Y (all RC) Low
[43] RF, 13 (13) NR 50 month
De Haas (2010) 228 (41) 41 SR, 55 (12) 8 %b 0.005 74 %b 0.871 N Low
[44] RF, 173 (29) 26 % 70 %
van der Pool 57 (57) 34 SR, 8 (8) 15 months – 73 % NR Y (all RC) Low
(2010) [46] 40 RF, 29 (29) 28 %
28 LF, 20 (20) 67 %
Vigano (2011) 36 (36) 39 SR, 32 (32) 40 % – 59 % – Y (all low/ Very low
[47] RF, 4 (4) mid RC)
Abbott (2012) 144 (87) 36 SR, 60 (34) 18 months 0.95 66 months 0.62 N Low
[48] RF, 84 (53) 18 months 66 months
Andres (2012) 787 (202) NR RF, 729 26 % 0.992 46 % 0.965 N Low
[59] (169)
LF, 58 (33) 30 % 48 %
Dexiang (2012) 1061 (357) 19 SR, NR NR – 44 % NS N Low
[49] RF, NR NR 49 %
Mayo (2013) [50] 1004 (276) 34 SR, 329 (91) NR – 42 % 0.526 N Low
RF, 647 NR 44 %
(170)
LF, 28 (15) NR
RC cases
Slesser (2013) 112 (49) NR SR, 36 (19) 33 %b 0.837 75 %b 0.379 N Low
[51] RF, 76 (30) 32 % 64 %
van Dijk (2013) 50 (50) 32 SR, 26 (26) 36%c – 80 % c – Y (all RC) Low
[52] RF, 12 (12)
LF, 7 (7)
Fukami (2015) 63 (28) NR SR, 41 (16) NR – 66 %b 0.054 N Low
[53] RF, 22 (12) NR 67 %
Sabbagh (2015) 52 (52) 42 SR, 15 (15) 32 months 0.1 48 months 0.4 Y (all low/ Low
[54] RF, 27 (27) 31 month 60 month mid RC)
LF, 10 (10) 8 months 38 months
She (2015) [55] 116 (32) 23 SR, 28 (13) 28 %b 0.089 0 0.003 N Low
28 RF, 88 (19) 11 % 33 %
overall survival, SR simultaneous resection approach, RF rectum-first approach, LF liver-first approach
a
Tweleve-month hepatic disease free survival reported
b
Three-year survival rates reported
c
Two-year survival rates reported
213
Table 20.3 Case series reporting outcomes of surgical approaches for CRC with SCRLM
214
RC cases
analyzed
Follow-up Morbidity Mortality DFS (% 5-year OS (% 5-year separately Quality of
Author (year) Approach N (RC) (months) (%) (%) or months) or months) (Y/N) Evidence
de Santibanes SR 71 (41) 29 21 0 9 % 38 % N Very low
(2002) [60]
Tsai (2007) SR 97 (21) 29 8 0 10 % 34 % N Very low
[61]
Huh (2010) SR 91 (50) 28 37 1.1 NR 27 % N Very low
[62]
van der Pool BF 105 (33) 26 17 2 25 % 34 % N Very low
(2010) [63]
Boostrom SR 45 (45) 60 57 0 28 % 32 % Y (all RC) Very low
(2011) [64]
An (2012) [65] SR 108 48 NR NR 18 months 62 months Y (all RC) Very low
(108)
Nakajima SR 86 (38) 73 64 0 NR 45 % N Very low
(2012) [66]
Roxburgh SR 46 (24) 37 33 0 NR NR Y Very low
(2012) [67]
Ayez (2013) LF 42 (42) 31 24 L, 31Ra NR 40 % 67 % Y (all RC) Very low
[68]
De Rosa LF 37 (25) NR 40 L, 25Ra 0 L, 4.2Ra NR 30 %b N Very low
(2013) [69]
Hatwell (2013) SR 51 (20) NR 55 0 NR NR Y Very low
[70]
Yoshioka SR 127 (49) 45 61 0 17 % 65 % N Very low
(2013) [71]
RC cases
analyzed
Follow-up Morbidity Mortality DFS (% 5-year OS (% 5-year separately Quality of
Author (year) Approach N (RC) (months) (%) (%) or months) or months) (Y/N) Evidence
Gall (2014) BF 53 (53) 30 32c NR 19 % 39 % Y (all RC) Very low
[72]
Lin (2014) SR 154 (47) 36 29.9 NR 35 % 46 % N Very low
[73]
Buchs (2015) LF 34 (34) 36 27 0 NR 53 % Y (all RC) Very low
[74]
Ferretti (2015) SR 142 (58) 29 31 2.1 63 % 72 % N Very low
[75]
overall survival, SR simultaneous resection approach, BF bowel-first approach, LF liver-first approach
a
Morbidity and mortality related to rectal resections (R) and liver resections (L) reported separately
b
Three-year survival rates reported
c
Morbidity only related to liver resection reported
215
2 months [93]. Some studies have demonstrated no survival advantage to using

preoperative vs postoperative chemotherapy [94, 95]. Nevertheless, patients with
rectal cancer and SCRLM are more likely to have a locally advanced primary tumor
[38, 96], and strong consideration should be given to neoadjuvant therapy.
Targeted chemotherapy with agents such as Cetuximab, Panitumumab, and
Bevacizumab has demonstrated improvements in response and resection rates [97–
108]. Hepatic arterial infusion chemotherapy may improve resectability or reduce
recurrence in experienced centers [109–113].
Combined modality treatment including FU-based chemotherapy plus pelvic
radiation is well established for nonmetastatic locally advanced rectal cancer as it
has been shown to reduce local recurrence. However, the precise role, necessity and
timing of radiation has not been established in the setting of locally advanced rectal
cancer in the setting of SCRLM. Of 185 patients who underwent complete resection
of rectal cancer and SCRLM by Butte et al., only 4 % developed isolated pelvic
recurrence. The majority of recurrences were distant and concomitant radiation
therapy was not associated with a reduction in pelvic recurrences [114]. Others have
reported similar results [65, 115]. Lee et al. showed that radiation reduced local
recurrence only in patients with T4 tumors [116].
FU-based chemotherapy alone, as commonly used as a sensitizer during the
administration of pelvic radiation, is probably suboptimal treatment for the syn-
chronous liver disease [117], and more intensive chemotherapy is likely required
[29, 118, 119]. Indeed, there is early evidence to suggest that chemotherapy alone
without radiation may result in adequate local control. Schrag et al. showed that of
30 patients who completed 6 cycles of FOLFOX with bevicizumab without RT, all
had tumor regression and underwent total mesorectal excision with a 25 % complete
pathologic response and a 0 % 4-year LR rate [120]. This concept shows promise for
patients with rectal cancer and SCRLM.
Classic Staged Resection: Rectum- First Approach The classic staged bowel-
first approach addresses the primary tumor prior to liver resection. As such, local
symptoms which may interrupt subsequent treatment can be avoided. Additionally,
aggressive disease may reveal itself between the staged resections to avoid unneces-
sary hepatectomy. Gall and colleagues reported on 53 patients with rectal cancer
and SCRLM who underwent the rectum-first approach. Chemotherapy followed by
combined modality chemoradiation were administered based on locoregional stag-
ing of the primary tumor. Proctectomy was performed, followed by hepatectomy
6 weeks later with additional chemotherapy. No patients had progression of liver
disease prior to second stage surgery, and all proceeded without a delay caused by
complications from the proctectomy. Two patients had unresectable disease at the
time of hepatectomy. Five-year DFS and OS were 19 % and 39 % respectively [72].
Yoshidome et al. noticed that 43 % of patients who underwent the staged bowel-
first approach for colorectal cancer and SCRLM developed new liver lesions prior
to hepatectomy, which changed the initial surgical plan. None developed extrahepatic
disease and all were ultimately resectable. The majority of new lesions occurred
elsewhere in the liver, suggesting the presence of occult micrometastasis undetect-
able at initial evaluation. Further, hepatic disease free survival was improved when
delayed hepatectomy was performed as opposed to simultaneous resection [58].
Disease progression to unresectability between stages is usually related to the iden-
tification of new liver or extrahepatic metastases rather than growth of the preexist-
ing liver lesions. This may spare 36 % of patients a nontherapeutic hepatectomy
without affecting survival [121].
Staged Resection: Liver-First Approach In the liver-first approach to rectal can-
cer with SCRLM, 2–6 cycles of neoadjuvant chemotherapy are typically adminis-
tered prior to liver resection. Chemoradiation followed by proctectomy is then
performed [74, 122]. An advantage of the liver first approach is that it avoids the
period of at least 3 months required to treat the primary tumor with neoadjuvant
chemoradiation and proctectomy prior to addressing the SCRLM, which is the
prognostic determinant [122, 123]. Postoperative complications after proctectomy
delay timely treatment in up to 50 % of cases [124]. In fact, less than 30 % of patients
undergoing bowel-first surgery proceed to the initially planned hepatectomy due to
disease progression, whereas up to 80 % undergo liver resection with the liver first
approach [59, 125]. Further, resection of the primary tumor as an initial step may
result in a loss of inhibition, and progression of metastatic disease [126–130].
A liver first approach with preliminary chemotherapy allows for some respond-
ers with initially unresectable SCRLM to be resected. For those whose liver disease
remains unresectable for cure, a nontherapeutic proctectomy may be avoided [131].
Complications related to the primary tumor are uncommon during chemotherapy
[132–139], and symptoms of bleeding, pain, and mild obstruction at presentation
usually resolve after 1–2 cycles of chemotherapy [140].
Mentha et al. first described the liver first approach [122]. They subsequently
reported their experience of 33 patients with rectal cancer demonstrating a 5-year
overall survival of 61 %, with 15 % developing a pelvic recurrence. Complications
related to the primary tumor requiring emergency intervention occurred in two
patients (6 %), both of which had R1 rectal resections and ultimately developed
recurrences [74].
In the largest reported experience of 42 patients with locally advanced rectal
cancer and SCRLM, 74 % of patients completed the entire protocol including resec-
tion of the rectal primary. The remaining patients developed metastatic disease prior
to addressing the primary tumor, of which 91 % were spared needless rectal surgery.
Notably, five patients received a diverting stoma at some point during the protocol
to prevent obstruction. Five-year disease free and overall survival were 40 % and
67 % respectively [68]. de Jong et al. reported the option of “watchful waiting” of
the primary tumor with this approach should there be a complete clinical response
[141].
Simultaneous Resections With advances in perioperative care, anesthesia, surgi-
cal technique, and outcomes after liver surgery [4–6, 142, 143], this approach allows
resection of both the primary tumor and SCRLM in one operation, but is not recom-
mended during emergent surgery for complications secondary to the rectal tumor
[144]. There are reports of laparoscopic simultaneous resections performed safely

[70, 75, 145–152]. Advantages of this approach include shorter cumulative hospital
stay, as well as patient convenience of a single operation with less interruption of
chemotherapy. The majority of reports describing this approach combines colon and
rectal resections, and have significant selection bias towards less extensive SCRLM
and liver resections [153].
Boostrom et al. reported the Mayo Clinic experience with 45 patients who under-
went synchronous resection for rectal cancer with SCRLM. There were no mortali-
ties and 16 % suffered severe complications, which did not differ amongst patients
undergoing abdominoperineal resection or major liver resection (three or more seg-
ments). Five-year disease free and overall survival were 28 % and 32 % respectively
[64]. Vigano et al. described combined resection for 34 patients with locally
advanced mid or low rectal cancer and SCRLM after neoadjuvant chemotherapy,
chemoradiation, or both. There was one mortality and a 36 % morbidity rate. Five-
year disease free and overall survival were 40 % and 59 % respectively. Five patients
had major liver resections [47].
Ferretti et al. studied 142 patients from 14 centers internationally who underwent
laparoscopic synchronous resections of SCRLM, 41 % of whom had rectal prima-
ries; only 12 % involved major liver resection. Overall morbidity was 31 % with a
5.6 % anastomotic leak rate, and a mortality rate of 2.1 %. The independent predic-
tors of morbidity were ASA score more than or equal to three and operative time.
Rectal primary and major liver resections were not predictors [75].
Utilizing the synchronous approach, there have been successful reports of two-
stage hepatectomy for bilobar or advanced SCRLM. This approach allows for proc-
tectomy with the less extensive first stage hepatectomy, followed by major second
stage hepatectomy with diverting stoma reversal. Bilobar advanced SCRLM can be
addressed while minimizing the number of operations and optimizing timing of
chemotherapy delivery [154, 155].
There are reports of increased mortality when extensive liver resections are com-
bined with colorectal resections [34, 156]. Factors shown to increase morbidity of
this approach include the presence of a diverting stoma, a rectal primary, duration of
surgery, blood loss, and transfusion need [66, 157], indicating that more extensive
surgery may be associated with increased morbidity. Others have demonstrated pre-
operative patient fitness to be the significant predictor as represented by age, ASA
grade, and POSSUM score [67]. Outcomes from some reports suggest that this
approach may not be appropriate for elderly patients [35, 158], those with locally
advanced rectal cancer [144], or those requiring major resections [34, 35]. These
data suggest that patient selection is critical to the safety of this approach.
Comparison of Surgical Approaches There are no prospective randomized trials
comparing surgical approaches, and most studies combine colon and rectal cancer
without analyzing results pertaining to rectal cancer specifically. Comparison of
approaches is difficult given the selection bias of staging more extensive SCRLM
resections, and difficulty determining cumulative resection rates and morbidity
from staged procedures [159, 160].
There are only two small retrospective studies comparing all three approaches
for rectal cancer with SCRLM [46, 54]. Sabbagh et al. showed similar complete
resection rates, overall complications, mortality, DFS, and OS between all three
groups [54]. van der Pool et al. also showed similar morbidity and mortality
between the groups. The simultaneous approach was associated with shorter hospi-
tal stay, but was applied to patients with early stage primaries and limited liver
disease [46].
Silberhumer et al. compared 43 patients who underwent staged rectal first resec-
tion with 145 who underwent synchronous resections. The staged group included a
larger number of major liver resections for larger liver lesions, and patients under-
going abdominoperineal resection. Morbidity and mortality rates were similar, even
in a subgroup analysis of those undergoing major hepatectomy. Hospital stay was
significantly shorter in the simultaneous group [56].
Mayo et al. performed the largest multi-institutional retrospective comparison of
all 3 approaches including 1004 patients with colorectal cancer and SCRLM, of
which 276 had rectal cancer. The liver first group was more likely to have a rectal
primary, bilobar disease, and more hepatic lesions treated during liver surgery.
Patients in the simultaneous group were less likely to undergo major hepatectomy.
Morbidity and mortality rates were similar between groups, even in those undergo-
ing major hepatectomy, although there was a nonsignificant trend towards increased
mortality in patients undergoing extended hepatectomy in the simultaneous group.
Five-year overall survival was similar among all three groups. Notably, a rectal pri-
mary was independently associated with worse survival [50]. Brouquet et al.
reviewed the MD Anderson experience of 156 patients with colorectal cancer and
SCRLM, 52 % of whom had rectal cancer. Morbidity, mortality, R0 resection rates,
DFS, and OS were similar between all 3 approaches. Interestingly, 5 % of patients
undergoing the liver first approach developed symptoms related to the primary
tumor requiring colostomy, both of whom had nontraversable tumors on initial colo-
noscopy [42]. Similarly, a meta-analysis comparing all three approaches for CRC
showed no difference in morbidity, mortality, or survival despite the tendency of
patients with a larger burden of SCRLM to undergo a liver first approach. This sug-
gests that the liver first approach may be appropriate for this group of patients [161].
Evaluation of the Rectal Cancer Patient with Synchronous

Hepatic Metastasis
In addition to standard imaging for staging, contrast-enhanced MRI of the abdomen

increases detection and further characterizes SCRLM, particularly after neoadju-
vant chemotherapy (evidence moderate; weak recommendation). FDG-PET can
detect extrahepatic disease prior to surgery; however sensitivity after chemotherapy
is reduced (evidence moderate; weak recommendation).
Treatment Options: Multimodality Treatment
Patients with rectal cancer and SCRLM should receive perioperative chemotherapy
(evidence high; strong recommendation), however there is no consensus on timing.
Neoadjuvant chemotherapy can be recommended, particularly for patients with ini-
tially borderline resectable or unresectable SCRLM. Reassessment at 2–4 months
from onset of therapy is recommended to minimize liver damage prior to hepatec-
tomy (evidence low; weak recommendation). Radiation therapy may have a benefit
in preventing morbid local complications in patients at high risk for pelvic recur-
rence (evidence low; weak recommendation). Priority should be given towards
addressing more common and prognostically more significant distant disease.
Isolated local recurrence is uncommon.
Treatment Options: Surgical Approach
All three approaches (rectum first, liver first and synchronous resection) are equiva-
lent regarding safety and oncologic outcome. Patient selection and local expertise
are important considerations (evidence low; weak recommendation). Fit patients
undergoing surgery with low anticipated blood loss and operative time can safely
undergo synchronous resection (evidence low; weak recommendation). Initially
diverted, asymptomatic, or mildly symptomatic patients with a locally advanced
primary tumor and/or advanced bilobar SCRLM are suitable for the liver first
approach (evidence low; weak recommendation). Resectional surgery can be
avoided in cases of disease progression. Non-diverted patients with significant
symptoms secondary to the primary tumor who may not tolerate the simultaneous
approach are well-suited for the rectum first approach (evidence low; weak
recommendation.)
The summarized evidence regarding management of rectal cancer metastatic to the

liver is heterogeneous. An individualized approach based on patient characteristics,
disease factors, and degree of symptomatology is proposed in Fig. 20.1. In the
absence of severe symptoms related to the primary tumor, the authors’ approach is
to initiate systemic chemotherapy in patients who are potentially resectable. Patients
with diffuse bilobar metastatic disease or additional extrahepatic lesions can be pal-
liated based on extent of disease, functional status, and degree of symptoms.
Potentially resectable patients should be reassessed following systemic chemother-
apy to select out nonresponders who can be palliated non-surgically. Patients who
are resectable following chemotherapy can undergo synchronous resection if medi-
cally fit, R0 rectal resection is possible, and anticipated morbidity from liver
Stage4
Rectal Cancer
Extensive
Potentially
Metastasis
Resectable
Unresectable
Chemotherapy
Palliative care
+
Intervalre assessment
• Chemotherapy
2-4months
• Radiation
• Symptoms control
Resectable Unresectable
Assessment
• Functional Status
• Extent of liverresection
• Primary tumor extent
Patient fit for Patient unfit for

synchronous liver synchronou sliver
+ rectalre section + rectalre section
Curativere section
Liver resection
of primary possible
Yes No
Synchronou sliver Curative resection

+ Liver resection
rectal resection
Yes No
Chemoradiation Rectalre section Chemoradiation
Rectal resection Rectal resection
Fig. 20.1 Suggested algorithm for approach of patients with RC and SCRLM
resection based on extent of disease is minimal. Otherwise, a staged liver first

approach is advisable, as systemic disease determines disease free and overall sur-
vival. Furthermore, complications of rectal resection may further delay treatment if
the rectal tumor is resected first.
Following liver resection, proctectomy is performed if curative resection is pos-
sible. If radial and/or distal margins are threatened with a higher risk of pelvic recur-
rence, then chemoradiation precedes rectal resection. Not reflected in the provided
algorithm is one additional variation. In healthy patients with extensive SCRLM
requiring two-stage hepatectomy, the first stage (minor left-sided resection) is per-
formed with rectal surgery. The second major hepatectomy can be performed with
ileostomy reversal in diverted cases. Finally, these recommendations do not apply to
patients who present with acute obstruction or profuse rectal bleeding. The former
subgroup can be addressed by fecal diversion or in select cases endoluminal stent-
ing, while the latter can benefit from resection of the primary tumor, endoluminal
fulguration, or external beam radiation therapy.
Summary of Recommendations
1. In addition to standard imaging for staging, contrast-enhanced MRI of the abdo-

men increases detection and further characterizes SCRLM, particularly after
NCT (evidence moderate; weak recommendation).
2. FDG-PET can detect extrahepatic disease prior to surgery, however sensitivity
after chemotherapy is reduced (evidence moderate; weak recommendation).
3. Patients with rectal and SCRLM should receive perioperative chemotherapy (evi-
dence high; strong recommendation), however there is no consensus on timing.
4. Neoadjuvant chemotherapy can be recommended, particularly for patients with
initially borderline resectable or unresectable SCRLM. Reassessment at
2–4 month intervals is recommended to minimize liver damage prior to hepatec-
tomy (evidence low; weak recommendation).
5. Radiation therapy may have a benefit in preventing morbid local recurrence in
patients at high risk for local recurrence (evidence low; weak recommendation).
6. All three surgical approaches are equivalent regarding safety and oncologic out-
come. Patient selection and local expertise are important considerations (evi-
dence low; weak recommendation).
7. Fit patients undergoing surgery with low anticipated blood loss and operative time
can safely undergo synchronous resection (evidence low; weak recommendation).
8. Initially diverted, asymptomatic, or mildly symptomatic patients with a locally
advanced primary tumor and/or advanced bilobar SCRLM are suitable for the
liver first approach (evidence low; weak recommendation).
9. Non-diverted patients with significant symptoms secondary to the primary tumor
who may not tolerate the simultaneous approach are well-suited for the rectum
first approach (evidence low; weak recommendation).
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Chapter 21
Who Needs a Loop Ileostomy After Low
Anterior Resection for Rectal Cancer?
Walker Julliard and Gregory Kennedy

Pts after LAR Proximal diversion No diversion Leak rate, consequences
Introduction
The standard of care for rectal cancers has evolved over recent years to be restor-
ative anterior proctectomy. The most feared complication after low anterior resec-
tion (LAR) is anastomotic leak. Overall risk of anastomotic leak varies between 3
and 21 % [1]. Anastomotic leak has a reported mortality of 2.1–22 % and requires
intervention with methods ranging from interventional radiologic drainage to reop-
eration [2]. Furthermore, colonic conduit function after anastomotic leak is signifi-
cantly worse than in patients without leakage [2]. Other complications from
anastomotic leak include increased rate of local recurrence and decreased disease-
free and overall survival [3, 4]. This increase in cancer recurrence may be due to a
W. Julliard (*)
Department of Surgery, University of Wisconsin School of Medicine and Public Health,
600 Highland Drive, Madison, WI, USA
G. Kennedy
Division of Gastrointestinal Surgery, Department of Surgery, University of Alabama at
Birmingham, KB 430, 1720 2nd Ave S, Birmingham, AL 35294-0016, USA

DOI 10.1007/978-3-319-40223-9_21
234 W. Julliard and G. Kennedy
delay or abandonment of the necessary adjuvant chemoradiotherapy [4]. Because of

the serious morbidity associated with anastomotic leak, measures to minimize leak
rates and the morbidity from such leaks has been implemented, the most ubiquitous
of these being temporary fecal diversion. However, in recent years, the dogma of
mandatory fecal diversion after LAR has been called into question.
Methods
A detailed search of the Embase-Medline databases was conducted for medical lit-
erature. The following search terms were employed to identify relevant articles:
(“rectal” OR “colon” OR “colorectal”) AND (“resection” OR “low anterior resec-
tion” OR “proctectomy”) AND (“ileostomy” OR “ostomy” OR “colostomy” OR
“diversion” OR “fecal diversion”). The title and abstracts of English-language arti-
cles were assessed for relevance
Why Not Divert?
When deciding if a patient should undergo fecal diversion, it is essential to fully

understand the consequences of the procedure. Despite the widespread use of fecal
diversion, it is not without complications. These complications include both short-
and long-term problems and range from minor, requiring only local care, to major
complications requiring reoperation and prolonged hospitalization [5, 6]. The most
common complication after stoma construction is peristomal skin irritation [7]. While
not necessarily defined by most members of the surgical community as a “major”
complication, this can have major implications for a patient’s quality of life [8].
A recent retrospective review using ACS NSQIP data identified multiple complica-
tions that were increased in patients undergoing low anterior resection with fecal
diversion [6]. Patients who underwent diversion were found to have a higher rate of
progressive renal insufficiency (2.1 % vs. 0.8 %) without an increased risk of acute
renal failure (1.3 % vs. 0.7 %). Using a risk adjusted model, this increased rate of renal
insufficiency was 2.37 times more likely to occur in patients undergoing fecal diver-
sion. Furthermore, patients with fecal diversion had a significantly higher rate of deep
surgical site infections (7.5 % vs 5.3 %) and a higher rate of 30-day readmission
(20.3 % vs 11 %). Although not specifically discussed in this study, the findings of
renal insufficiency and readmission are not surprising following stoma creation, as
one of the most commonly encountered problems with diverting ileostomy is dehydra-
tion from high ostomy output. This complication has a reported incidence of 1–16 %,
is most common 4–8 days postoperatively as bowel edema is resolving, and leads to
electrolyte abnormalities, hypovolemia, and readmission [9]. Further out from the
index operation, parastomal hernia occurs at a rate of 15–40 % [10]. Once identified,
most hernias will require operative repair, which traditionally has overall poor results.
21 Who Needs a Loop Ileostomy After Low Anterior Resection for Rectal Cancer? 235
Finally, by definition, all temporary diverting ostomies require reversal; while

this is technically not a difficult procedure, it is not without risk. In a study from
Pokorny et al. in 2006, 243 patients who underwent loop ileostomy closure were
retrospectively reviewed for complications [5]. An overall complication rate of
19 % was identified; 3 % had anastomotic leak, 6 % developed significant
postoperative ileus, 1 % had bleeding complications, and 9 % had wound infections.
In total, 4 % of patients undergoing ileostomy closure required reoperation for their
complication.
Does Fecal Diversion Decrease Anastomotic Leak Rate?
The key question when considering fecal diversion following low anterior resection
of the rectum is whether diversion changes the rate of anastomotic leak. There have
been numerous retrospective studies over the years that have reported mixed results.
While the number of large retrospective studies is quite high, all of these studies are
inherently biased, as surgeons concerned about a particular anastomosis will favor
temporary diversion. Given the fact that there are numerous studies on both sides of
the issue of fecal diversion, it is difficult to draw sound conclusions from this retro-
spective data. Therefore, although limited in number and patients enrolled, random-
ized controlled trials comparing fecal diversion to anastomosis without diversion
provide more reliable data with significantly less bias.
Graffner et al. were the first to design such a trial in 1983 and randomized 50
patients to fecal diversion versus no diversion [11]. 25 patients were in each group
and there was a low overall leakage rate (4 % in the stoma group versus 12 % in the
no stoma group). The next study was performed in 1997 by Pakkastie et al. In this
study of 134 patients, there was a clinically detected 16 % leak rate in the stoma group
versus a 32 % leak rate in the no stoma group. Importantly, there was also a lower
re-operation rate in the stoma group, as only one of three leaks required re-operation
compared to all six leaks requiring return to the OR in the no stoma group [12].
The next major study to address this issue was published in 2007 by Matthiessen
et al. [13]. Importantly, this was a large multicenter trial, which enrolled a total of
234 patients for randomization, 116 in the stoma group and 118 in the no stoma
group. Postoperatively, patients were monitored clinically for signs of anastomotic
leak. There was a significantly higher leak rate in patients without a stoma (28.2 %)
compared to those with a stoma (10.3 %; p < 0.001). Furthermore, there was a sig-
nificantly higher rate of reoperation in the no stoma group with overall 25.4 % of
patients requiring any reoperation versus 8.6 % in the stoma group. The largest of
such studies, published in 2008 by Chude et al., included 256 patients, 120 without
diversion and 136 with diversion [14]. Postoperatively, 12 of the 120 patients with-
out diversion developed anastomotic leak (10 %) versus only 3 patients in the
diverted group (2.2 %). Furthermore, two of the non-diverted patients required
return to the OR for their anastomotic leak whilst none of the diverted patients
required reoperation.
Another small study was performed by Ulrich et al. and reported in 2009 [15].
This study was much smaller than the other two published around the same time,
with only 34 patients randomized. Again, there was a significantly higher rate of
clinically detected anastomotic leaks in the no stoma group (37.5 %) compared to
the stoma group (5.5 %, p = 0.02). All patients who developed a leak in the no stoma
group required reoperation while none of the stoma patients with a leak returned to
the OR. The differences in the study were in fact so dramatic that the study was
halted after 34 patients were accrued due to clear superiority in the diverted group.
All of the above randomized trials were analyzed in a meta-analysis performed
by the Cochrane Database and reported in 2010 [16]. When the results from these
individual studies were combined, there was found to be a dramatic reduction in
anastomotic leakage using fecal diversion (RR 0.33; 95 % CI [0.21, 0.53]).
Furthermore, diverted patients had a decreased rate of urgent reoperation (RR 0.23;
95 % CI [0.12, 0.42]). Despite these differences, there was no significant decrease in
terms of overall mortality (RR 0.58; 95 % CI [0.14, 2.33]). The conclusion of the
review was that fecal diversion is an effective method in reducing the rates of anas-
tomotic leak in patients undergoing low anterior resection and therefore the proce-
dure can be offered routinely. This review did note significant limitations in all of
the above studies and found that the methodology was overall poor; it was also
observed that there was a lack of reporting of long-term mortality and quality of life.
Since the Cochrane Review was completed, at least one further study has been
performed in a prospective, randomized fashion [17]. Thoker et al. reported in 2014
on 78 patients undergoing LAR randomized to stoma versus no stoma. In their
study, they demonstrated a lower leak rate in the diverted group at 6 % compared to
a rate of 11 % in the non-diverted group. Of note, they also followed patients for
stoma related complications and found a higher rate of electrolyte imbalance in the
postoperative period, as well as significant stomal complication rate of 25.4 %.
Finally, they demonstrated that stoma closure was associated with an overall com-
plication rate of 67.7 %.
Taken together, these data demonstrate that fecal diversion offers a clear benefit
in LAR in lowering anastomotic leak rate and need for reoperation. While early
retrospective studies arrived at varying conclusions, prospective randomized trials
have all demonstrated a clear benefit to fecal diversion. Therefore, at this point, it is
clear that at a population level, fecal diversion should be the default operation in
combination with LAR. However, what these studies fail to address is which patients
are at decreased risk of anastomotic leak and therefore could avoid defunctioning
stoma placement.
Who Is at Highest Risk for Developing a Leak?
There are multiple risk factors for development of anastomotic leak, some which are
associated with wound healing in general, and some which are specific to rectal
cancer. Patient factors that increase the risk of developing an anastomotic leak are
risk factors that are associated with poor wound healing in general. Patients that
have malnutrition, preoperative weight loss, preoperative steroids, and obesity are at
higher risk for developing an anastomotic leak [18]. In a retrospective analysis from
2010 which reviewed 1495 consecutive patients who underwent LAR, an overall
leak rate of 11 % was observed [19]. In reviewing specific patient factors associated
with anastomotic leak, distance from anal verge was found to have the strongest
association with leak rate (OR = 2.0 for anastomosis 10 cm from anal verge, OR = 3.6
for anastomosis 7 cm from anal verge, and OR = 5.4 for anastomosis 5 cm from anal
verge). This finding that anastomoses close to the anal verge were at high risk for
anastomotic leak was also observed by Rullier et al. [20]. Their study examined
outcomes in 272 consecutive patients undergoing LAR and found by multivariate
analysis that anastomoses within 5 cm of the anal verge were six times more likely
to develop an anastomotic leak. Further operative factors related to anastomotic leak
include male gender (OR = 2.36), and intraoperative blood loss (OR = 1.05).
Finally, intraoperative assessment of the anastomosis may play an important role
in reducing the leak rate and in deciding on the need for proximal diversion.
Common methods of evaluating a colorectal anastomosis include air leak testing,
saline leak, methylene blue leak tests and endoscopic assessment. Two randomized
trials have evaluated the validity of performing an intraoperative leak test and have
found that the risk of leak in those tested was significantly lower than the untested
controls (5.8 % versus 16 %, p < 0.05) [21, 22]. Therefore, intraoperative leak testing
should be performed and patients found to have concerning findings on exam should
undergo repair, revision, or anastomotic resection.
One area of continued controversy is the role of neoadjuvant radiotherapy in
promoting anastomotic leak. The largest study which compared preoperative radio-
therapy to selective postoperative chemoradiotherapy was published in 2009 by
Sebag-Montefiore et al. [23]. In this multicenter randomized trial, 1350 patients
with rectal cancer were randomized to neoadjuvant radiotherapy versus adjuvant
chemoradiotherapy. While the purpose of the study was to identify best timing of
treatment in relation to overall and disease-free survival, one of the data points col-
lected was the rate of anastomotic leak. After low anterior resection with fecal
diversion, 9 % of patients treated with neoadjuvant therapy developed an anasto-
motic leak compared to 7 % in the adjuvant group, which was not statistically sig-
nificant. However, the application of these findings is limited by the fact that both
groups underwent fecal diversion and only clinically significant leaks were reported;
therefore leaks which may have been clinically significant if not diverted were not
detected.
In a retrospective study published in 2012 by Nisar et al., 1862 patients who
underwent resection between 1980 and 2010 were stratified into two groups based
on preoperative radiotherapy and assessed for anastomotic leak [24]. An overall
leak rate of 6.3 % was identified with no difference between the two groups (8 %
neoadjuvant group versus 5.7 % in the no radiotherapy group, p = 0.06). On multi-
variate analysis, neoadjuvant therapy was not found to be associated with increased
leak rate (OR = 1.44; CI 0.85, 2.46; p = 0.18). However, there were significant pre-
operative differences between the groups, including a rate of defunctioning ostomy
of 87 % in the neoadjuvant group versus 44 % in the no radiotherapy group. These
differences make interpretation of the data difficult.
To further evaluate this issue, a recent meta-analysis was performed by Qin et al.
and included seven randomized controlled trials comparing preoperative radiotherapy
to no preoperative therapy [25]. Pooling these studies, a total of 1660 patients
formed the preoperative radiotherapy group while 1715 patients formed the control
group. In this analysis, rates of anastomotic leak were not increased in the preopera-
tive radiotherapy group (OR = 1.02; CI 0.80, 1.30; p = 0.88). This study, however, is
once again limited by the use of clinically detected anastomotic leaks in the indi-
vidual trials making up the analysis, which may underreport anastomotic leaks that
would be clinically significant if no defunctioning stoma were in place. Because of
the lack of studies which truly examine the rate of all leaks, not only clinically sig-
nificant leaks in the presence of a defunctioning stoma, making strong recommenda-
tions in patients who received preoperative radiotherapy remains difficult.
What Type of Diverting Ostomy Should We Use?
When considering fecal diversion, there are two common options; loop ileostomy or
loop colostomy. Four randomized trials have compared these two options to each
other, with two studies favoring the use of loop colostomy [26, 27] and two favoring
loop ileostomy [28, 29]. In 2007, a Cochrane review was conducted which found
five randomized studies involving 334 patients: 168 in the loop Ileostomy group and
166 in the loop colostomy group [30]. There was a very large difference in rates of
stomal prolapse, with a rate of only 2 % in the ileostomy group versus 19 % in the
colostomy group (p < 0.01), however, there were no other differences noted. Given
the large difference in rates of prolapse, current recommendations are to create a
loop ileostomy when possible.
While it is clear that proximal diversion is not without risks, the consequences of an
anastomotic leak are such that the benefits often outweigh the risks. Therefore,
proximal fecal diversion following anterior resection for rectal cancer should be
considered standard practice in all but a select few patients. This group of patients
should include those at the lowest risk for developing an anastomotic leak such as
non-smoking women with high rectal lesions who have not had preoperative radia-
tion therapy. After creation, all colorectal anastomoses should be tested for the pres-
ence of an anastomotic leak. A positive test may necessitate a revision of the
anastomosis followed by proximal diversion.
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leakage after anterior resection of the rectum. Colorectal Dis. 2004;6(6):462–9.
doi:10.1111/j.1463-1318.2004.00657.x.
3. Arbman G, Nilsson E. Local recurrence following total mesorectal excision for rectal cancer.
Br J Surg. 1996;83:375–9.
4. Jung SH, Yu CS, Choi PW, et al. Risk factors and oncologic impact of anastomotic leakage
after rectal cancer surgery. Dis Colon Rectum. 2008;51(6):902–8. doi:10.1007/
s10350-008-9272-x.
5. Pokorny H, Herkner H, Jakesz R, Herbst F. Predictors for complications after loop stoma clo-
sure in patients with rectal cancer. World J Surg. 2006;30(8):1488–93. doi:10.1007/
s00268-005-0734-1.
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American College of Surgeons National Surgical Quality Improvement Program. Am Surg.
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7. Colwell J, Goldberg M, Carmel J. The state of standard diversion. J Wound Ostomy Continence
Nurs. 2001;28(1):6–17. doi:10.1002/0471743941.
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factors and complications and their management. Colorectal Dis. 2003;5(1):49–52.
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9. Baker ML, Williams RN, Nightingale JMD. Causes and management of a high-output stoma.
Colorectal Dis. 2011;13(2):191–7. doi:10.1111/j.1463-1318.2009.02107.x.
10. Robertson I, Leung E, Hughes D, et al. Prospective analysis of stoma-related complications.
Colorectal Dis. 2005;7(3):279–85. doi:10.1111/j.1463-1318.2005.00785.x.
11. Graffner H, Fredlund P, Olsson SA, Oscarson J, Petersson BG. Protective colostomy in low
anterior resection of the rectum using the EEA stapling instrument. A randomized study. Dis
Colon Rectum. 1983;26(2):87–90.
12. Pakkastie TE, Ovaska JT, Pekkala ES, Luukkonen PE, Järvinen HJ. A randomised study of
colostomies in low colorectal anastomoses. Eur J Surg. 1997;163(2):929–33.
13. Matthiessen P, Hallböök O, Rutegård J, et al. Defunctioning stoma reduces symptomatic anas-
tomotic leakage after low anterior resection of the rectum for cancer. Ann Surg.
2007;246(2):207–14. doi:10.1097/SLA.0b013e3180603024.
14. Chude GG, Rayate NV, Patris V, et al. Defunctioning loop ileostomy with low anterior resec-
tion for distal rectal cancer: should we make an ileostomy as a routine procedure? A prospec-
tive randomized study. Hepatogastroenterology. 2008;55(86–87):1562–7.
15. Ulrich AB, Seiler C, Rahbari N, Weitz J, Büchler MW. Diverting stoma after low anterior
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16. Montedori A, Cirocchi R, Farinella E, Sciannameo F, Abraha I. Covering ileo-or colostomy in
anterior resection for rectal carcinoma. Cochrane database Syst Rev. 2010;(5):CD006878.
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leakage after resection for rectal cancer. Br J Surg. 1998;85:355–8.
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postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG
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doi:10.1007/s11605-012-1936-0.
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transverse colostomy for faecal diversion following total mesorectal excision. Br J Surg.
2002;89(6):704–8. doi:10.1046/j.1365-2168.2002.02082.x.
28. Khoury GA, Lewis MC, Meleagros L, Lewis AA. Colostomy or ileostomy after colorectal
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Chapter 22
Selection Factors for Reoperative Surgery
for Local Recurrent Rectal Cancer
Scott R. Kelley and David W. Larson
Introduction
In the modern era of total mesorectal excision combined with neoadjuvant or adju-
vant therapy, local recurrence following curative resection for rectal cancer has
decreased from approximately 30 to around 10 % or less [1–4]. Recurrence treated
with chemoradiation alone affords a median survival of 12–15 months compared to
the alternative of no therapy (3–8 months) [2, 3]. However, up to 40–50 % of
patients with local recurrence are candidates for re-resection. With multimodal ther-
apy, 5-year overall survival can be as high as 55 % after a microscopically negative
resection (R0) [2, 4–9]. With preoperative chemoradiation, radical/extended radical
R0 resection, and intraoperative radiotherapy when appropriate, patients are offered
the best chance for cure.
A multitude of variables need to be taken into consideration prior to pursuing
surgery including the patient’s physical condition, the presence of metastatic dis-
ease, local extent of the recurrence, and purpose of surgery (palliative or curative).
Reoperative surgery for locally recurrent rectal cancer is technically challenging
with morbidity rates ranging from 20 to 80 % and mortality up to 8 % [5, 6, 8]. In
light of the potential for major complications, a multidisciplinary approach is
imperative for surgical evaluation, planning, and execution [10, 11]. These high-
risk surgeries should be performed in dedicated referral centers capable of manag-
ing these complex patients [13–15].
Herein we review the literature and discuss selection factors for reoperative sur-
gery in the setting of locally recurrent rectal cancer.
S.R. Kelley, MD, FACS, FASCRS • D.W. Larson, MD, MBA, FACS, FASCRS (*)
Division of Colon and Rectal Surgery, Mayo Clinic, 200 First Street SW,
Rochester, MN 55905, USA

DOI 10.1007/978-3-319-40223-9_22
242 S.R. Kelley and D.W. Larson
Search Strategy
Utilizing PubMed and Google Scholar a systematic review of the English literature
was conducted using the terms recurrent rectal cancer, locally recurrent rectal can-
cer, unresectable, multimodal therapy, sacrectomy, and intraoperative radiotherapy.
We limited our search timeline to the last 10 (2015–2005) years. Original studies
evaluating outcomes of patients treated for local recurrence of rectal cancer were
included and manuscript reference lists were searched for additional articles. Studies
from the same institution/author were excluded if previously reported. A total of
102 studies were chosen for review.
Patients Intervention Comparator Outcomes

Locally recurrent rectal cancer Reoperation Non-operative Cure
Palliation Survival
Morbidity
Mortality
Quality of life
Results
Suspicion of recurrence should prompt evaluation with imaging to assess anatomy,

extent of localized and/or disseminated disease, and to determine resectability.
Differentiating between tumor and inflammatory changes can be difficult and a
complement of imaging modalities is often necessary [16]. Computed tomography
(CT) of the chest, abdomen, and pelvis should be obtained to assess for extrapelvic
metastasis and the extent of local involvement. Since CT is less discerning for pre-
dicting local tumor infiltration and adjacent organ involvement, magnetic resonance
imaging (MRI) of the pelvis should typically be performed to evaluate for invasion
of surrounding structures [17, 18]. High resolution MRI has been shown to have a
negative predictive value of 93–100 % for identification of local invasion, however
is also limited in its ability to distinguish recurrence from diffuse fibrosis [19–21].
Despite lower accuracy for anterior recurrence close to the bladder and mucinous
tumors, PET – CT has a sensitivity and specificity of nearly 100 and 96 %, respec-
tively, for diagnosing local recurrence [22–28].
For any patient with a suspicion for recurrence, histologic proof should be vigor-
ously sought prior to proceeding with surgery, though at times can be difficult to defini-
tively obtain. If unable to confirm histologically, other factors should be taken into
consideration such as an increase in the dimensions of the area of interest over time,
invasion of surrounding structures, a rising carcinoembryonic antigen (CEA), the devel-
opment of symptoms (e.g. pain from neural or osseous involvement, urinary, fecal, or
neurologic complications, bleeding), and overall multidisciplinary assessment [29].
Different classification systems to assess tumor resectability and provide prog-
nostic information are based on the anatomic location of pelvic recurrence, degree
22 Selection Factors for Reoperative Surgery for Local Recurrent Rectal Cancer 243
and site(s) of fixation, and symptoms. None can unfailingly predict resectability
prior to surgery since new findings may be discovered intraoperatively. The system
utilized at the Mayo Clinic classifies recurrence based on pain (S0 – asymptomatic,
S1 – symptomatic without pain, S2 – symptomatic with pain) and fixation to sur-
rounding structures (F0 – not fixed, F1 – fixed to 1 site, F2 – fixed to 2 sites, F3 –
fixed to ≥3 sites). Fixation is defined anatomically as anterior, posterior, and lateral
[30, 31]. Wanebo developed a system identifying five stages of invasion. (TR1)
limited muscularis propria invasion, (TR2) full thickness muscularis propria
involvement, (TR3) anastomotic recurrence into perirectal soft tissue, (TR4) adja-
cent organ invasion/not fixed, and (TR5) invasion of sidewalls or bony ligaments
[32]. A system proposed by the Leeds group classifies recurrence as central (con-
fined to pelvic organs without osseous involvement), sidewall (involving lateral
sidewall), sacral (abutting or invading sacrum), or composite (sacral and sidewall
involvement) [33]. Yamada and colleagues devised a system evaluating the pattern
of pelvic fixation as localized (adjacent organs or tissue), sacral (lower sacrum – S3/
S4/S5, coccyx, periosteum), and lateral (sciatic nerve, greater sciatic foramen, lat-
eral sidewall, upper sacrum – S1/S2) [34]. Memorial Sloan Kettering utilizes a sys-
tem based on involvement of surrounding structures and anatomic location; axial
(anastomotic recurrence, perineal and perirectal invasion), anterior (urogenital
involvement), posterior (presacral fascia or sacral invasion), and lateral (sidewall
and bony pelvis involvement) [35]. The Royal Marsden Hospital system evaluates
the extent of tumor invasion in seven different pelvic compartments based on MRI;
(C) central, (P) posterior, (I) inferior, (L) lateral, (PR) peritoneal reflection, (AA-
PR) anterior above and (AB-PR) anterior below the peritoneal reflection [36].
Hruby and colleagues evaluated sites of pelvic recurrence in 269 patients with
rectal cancer untreated with radiotherapy and found nearly 90 % in the posterior or
central pelvis, with 20 % at the level of the anastomosis [32]. The Mayo system
found worse outcomes in those presenting with pain and increased points of fixation
[30, 31]. Yamada found a 5 year survival rate of 38 % for localized disease, 10 % for
sacral involvement, and 0 % for lateral invasion [34]. The Memorial Sloan Kettering
group documented the likelihood of a R0 resection for axial only recurrence as
90 %, versus 36 % for lateral involvement [24]. Based on findings from the Royal
Marsden Hospital, survival is decreased when MRI reveals involvement of more
than two compartments, or when the lateral or posterior planes are involved [36].
Surgery, chemotherapy, and radiation alone result in high rates of local and dis-
tant failure; but when combined in a multimodal fashion have been shown to
improve local control, survival, rates of salvage surgery, and resection with R0 mar-
gins [7, 31, 38–44]. Radiotherapy naïve patients should receive a full course
(5040 cGy/50.4 Gy) of external beam radiotherapy (EBRT) administered concur-
rently with sensitizing 5-floururacil (5-FU) based chemotherapy The addition of
other cytotoxic (oxaliplatin, irinotecan) and biologic (cetuximab, bevacizumab)
agents along with 5-FU has not shown benefit to date [45]. For those previously
irradiated, a hyperfractionated course of 2000–3000 cGy EBRT along with 5-FU
can be completed prior to surgery. Although safe and effective, there is a lack of
high quality data to support this approach [39, 42, 46, 47]. Intensity modulated
radiotherapy reduces the dose of radiation to surrounding structures, though sup-

porting evidence is limited regarding a benefit over conventional radiotherapy [48].
To maximize tumor response, surgery is planned for 6–8 weeks following comple-
tion of radiation [49].
As part of a multimodal treatment approach, intraoperative radiotherapy (IORT)
has been shown to increase survival by 15 % or more and improve local control in
selected patients [50, 51]. Intraoperative radiotherapy overcomes the dose restriction
of EBRT by limiting exposure to surrounding unaffected structures. The total dose
administered is dependent on preceding amounts of preoperative radiotherapy deliv-
ered. The Mayo Clinic has a dedicated operating room with a linear accelerator to
provide electron beam radiotherapy, and a dose of 1000 cGy is given for minimal
residual disease (margin microscopically involved or clear by <5 mm), 1500 cGy for
unresectable gross disease less than 2 cm, and 2000 cGy for more than 2 cm [52].
Other means of administering locally directed radiation include high dose intraop-
erative brachytherapy (HDR-IORT), perioperative brachytherapy, and photon radio-
surgery [53, 54]. Multiple institutions have shown improved disease free and overall
survival, as well as local control, following R0 and microscopically positive (R1)
resections when IORT is incorporated into a multimodal treatment regimen, regard-
less of the IORT approach chosen [50, 51, 55–62]. Others have not been able to
document a benefit [42, 63–65]. The largest series evaluating 304 patients with
locally recurrent rectal cancer was reported by the Mayo Clinic in 2003. Of those,
138 underwent a R0 resection, 27 a R1, and 139 had gross (R2) residual disease. The
5 year survival rates were greatest for R0 versus the R1 and R2 resections (37 versus
16 %, p < 0.001). Survival after extended procedures (sacrectomy, pelvic exentera-
tion, cystectomy with ileal conduit) was comparable to more limited resections (28
versus 21 %, p = 0.11) [31]. Overall, results from specialized centers support an onco-
logic advantage for IORT in select patients. However, there is a significant amount of
heterogeneity between centers, making broad consensus statements challenging.
A R0 resection provides the highest rate of local control as well as cancer spe-
cific and overall survival. The presence of microscopically or grossly positive (R2)
margins decreases survival [66]. Resection is based on defining invasion into adja-
cent structures, as well as the presence of metastatic disease. Factors typically asso-
ciated with the inability to pursue a curative (R0) resection include poor performance
status, encasement of external iliac vessels, presence of venous or lymphatic
obstruction, distant metastasis, fixation to two or more sites (F2 or F3 involvement),
predicted R1/R2 resection, sacral invasion above S2, extension though the greater
sciatic notch, circumferential or multiple sites of pelvic sidewall involvement, bilat-
eral ureteral obstruction outside the bladder trigone, and S1/S2 nerve root involve-
ment [35, 67–70].
Upwards of 50 % of patients with local recurrence will have a metastatic lesion
noted during initial evaluation. If resectable, surgical intervention can be pursued in
a synchronous or staged approach, and in highly selected patients outcomes are
favorable [71, 72]. En bloc resection of involved ureteral or iliac vessels is possible
and is associated with an increased R0 resection rate [6, 35, 69, 73–75]. Extended
resections to achieve negative margins, including a high sacrectomy, improve local
control and survival [6, 8, 68, 73, 76–84], though can result in significant life alter-
ing morbidity. Complications are higher for fixed tumors, and reduced tumor free
resection margins and survival has been demonstrated in those with symptomatic
pain and fixation to more than one area [30, 31]. Other factors noted to decrease R0
resections are male sex, increased age, previous abdominoperineal resection, higher
stage of primary tumor, and elevated CEA level [35]. If the morbidity of an extended
resection to obtain a R0 margin outweighs the potential benefit, an R1 resection
with IORT should be pursued.
Following radiation, surgery, and IORT, complications occur in upwards of 65 %
of patients owing to the heavily irradiated field [31, 46]. The most common compli-
cations include pelvic abscesses (6.6 %), bowel obstruction (5.3 %), enteric fistulas
(4.3 %), and wound complications (4.6 %). Those with extended resections and
more than two sites of fixed recurrence, experience the highest rates of postoperative
complications [31]. Nelson and colleagues from the Mayo Clinic reported reduced
wound complications and length of hospital stay when flap repairs were utilized in
comparison to primary closure. Other studies have corroborated the benefit of peri-
neal defect closure/reconstruction with techniques including omentoplasty com-
bined with biologic implants, vertical rectus or myocutaneous oblique abdominis
muscle flaps, gluteal rotation flaps, gracilis flaps, and free flaps [85–91].
If cure is not possible (R2 resection would be required), then palliation of symp-
toms may be sought with a combination of modalities (chemoradiotherapy, urinary
and colonic stents, nephrostomy tubes, endoscopic laser ablation, targeted surgery),
all of which have been shown to improve quality of life, though rarely halt disease
progression [92–96]. External beam radiation, therapy (EBRT) including reirradia-
tion when necessary, has been noted to control pain in 50–90 % of patients [97, 98].
The addition of chemotherapy to EBRT also improves symptoms, but not 5 year
survival [41, 99, 100]. Improvement in symptoms and quality of life has been
shown to be superior following surgery compared to non-surgical approaches, even
for selective cases with distant metastasis, although less so for extended resections
[25, 101, 102].
The available evidence regarding the management of locally recurrent rectal cancer
consists primarily of single institution case control and retrospective studies. Few
multicenter studies exist and there are no randomized trials.
High resolution MRI is the preferred imaging modality to evaluate for pelvic
recurrence. Computed tomography of the chest, abdomen, and pelvis should be
obtained to assess for extrapelvic metastasis. Questionable findings can be further
investigated with PET – CT (evidence moderate, strong recommendation).
A classification system to assess for tumor resectablilty and prognostic informa-
tion should be incorporated into the preoperative workup and evaluation (evidence
moderate, strong recommendation).
Neoadjuvant chemoradiotherapy should be administered to radiotherapy naïve

patients (evidence moderate; strong recommendation) and re-irradiation prior to
surgery can be administered in those previously irradiated (evidence low, weak
recommendation).
Re-staging should be performed 4–6 weeks prior to surgery (evidence low, strong
recommendation) and surgery should be planned 6–8 weeks after completing neo-
adjuvant therapy (evidence moderate, strong recommendation). IORT, when indi-
cated, should be part of the multimodal treatment regimen (evidence moderate,
strong recommendation). To decrease issues with postoperative pelvic wound com-
plications, flap reconstruction should be pursued for large defects (evidence moder-
ate, strong recommendation).
The best chance for survival is a R0 resection, which may require an extended
radical resection (evidence moderate, strong recommendation). If morbidity out-
weighs the benefit of an extended resection to achieve a R0 margin, an R1 resection
with IORT should be pursued, which has better outcomes than R1 without IORT
(evidence moderate, strong recommendation). Surgery does not offer adequate sur-
vival or local tumor control following a R2 resection and should be avoided (evi-
dence moderate, strong recommendation).
If curative resection is not possible, palliation of symptoms should be sought
with a combination of modalities to improve quality of life (evidence moderate,
strong recommendation).
Based on our experience at the Mayo Clinic, as well as the literature, we perform a
high resolution CT of the chest, abdomen, and pelvis to evaluate for metastases. A
high resolution musculoskeletal pelvic MRI that includes axial, sagittal, and coro-
nal/oblique views is the imaging modality of choice when evaluating for local
recurrence. Questionable findings are further investigated with PET – CT. A classi-
fication system to assess for tumor resectablilty and provide prognostic information
should be incorporated into the preoperative workup and evaluation. Tumor loca-
tion and local extent of involvement are two of the most important factors in deter-
mining resectability. For those cases with a high probability of an R0 resection, the
collaboration of an experienced multidisciplinary team (colorectal surgery, urology,
gynecology, plastic reconstructive, vascular, neurosurgery, orthopedics, radiation
oncology) should be pursued.
Although the literature is controversial regarding the benefit of reirradiating pre-
viously irradiated patients, we have found it to be beneficial in our patient population.
A short course boost is often followed by surgery within a week. Unless contraindi-
cated, all radiotherapy naïve patients should receive neoadjuvant chemoradiation.
Multimodal therapy with IORT improves local control and survival and offers the
best possibility of cure, though is does not compensate for inadequate or incomplete
resections (R2). IORT reaches its peak effect if delivered within 8 weeks following
EBRT. Imaging should be repeated 4 weeks after completion of CRT and if no pro-

gression or metastasis is found, surgery should be pursued within the next 4 weeks.
It has become widely accepted that the surgical management of locally recurrent
rectal cancer offers the potential for cure and improved quality of life in patients
who are candidates for re-resection. A planned R2 resection should be avoided since
outcomes are no different than non-operative measures. These high-risk surgeries
should be performed in dedicated referral centers capable of managing such com-
plex patients.
Abstracted Recommendations
High resolution MRI is the preferred imaging modality to evaluate for pelvic
recurrence. Computed tomography of the chest, abdomen, and pelvis should
be obtained to assess for extrapelvic metastasis. Questionable findings can
be further investigated with FGD\PET – CT (evidence moderate, strong
recommendation).
Histologic confirmation of recurrence should be ascertained whenever possible
(evidence moderate; strong recommendation).
Neoadjuvant chemoradiotherapy should be administered in radiotherapy naïve
patients (evidence moderate; strong recommendation).
Re-irradiation prior to surgery can be administered in those previously irradiated
(evidence low, weak recommendation).
Re-staging should be performed 4–6 weeks prior to surgery (evidence low, strong
recommendation).
Surgery should be planned for 6–8 weeks after completing neoadjuvant therapy
(evidence moderate, strong recommendation).
IORT, when indicated, should be part of the multimodal treatment regimen (evi-
dence moderate, strong recommendation).
To decrease postoperative pelvic wound complications closure/reconstruction should
be pursued for large defects (evidence moderate, strong recommendation).
The best chance for cure is a R0 resection, which may require an extended radical
(involvement of surrounding organs/structures) resection (evidence moderate,
strong recommendation).
If morbidity outweighs the benefit of an extended resection to achieve a R0 margin
a R1 resection with IORT should be pursued, which has better outcomes than R1
without IORT (evidence moderate, strong recommendation).
Surgery does not offer adequate survival or local tumor control following a R2
resection and should be avoided (evidence moderate, strong recommendation).
If the potential for cure is not possible palliation of symptoms should be sought with
a combination of modalities to improve quality of life (evidence moderate, strong
recommendation).
Patients with local recurrence of rectal cancer, or suspicion of, should be referred to
dedicated centers for care (evidence low, strong recommendation).
References
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Part IV
Anal Dysplasia/Cancer
Chapter 23
Anal Dysplasia/Cancer: Management
of Patients with AIN 3
Amy L. Lightner and Mark L. Welton
Pt population Intervention Comparator Outcome studied

Pts with AIN 3 HRA Clinical followup Cancer prevention, cost
Introduction
Anal squamous cell carcinoma (ASCC) is an uncommon malignancy caused by

infection with oncogenic strains of Human papilloma virus (HPV). The precursor
lesion, anal intraepithelial neoplasia III(AIN III) or high-grade squamous intraepi-
thelial lesion (HSIL), has a similar causal association with HPV [1–3]. Although
HPV infections are extremely common, peaking in the third decade of life, they are
usually transient with evidence of infection absent by the end of that decade. This
tends not to be true in high-risk groups – those who practice anoreceptive inter-
course and those immunocompromised from drugs or disease. The frequency of
progression of HSIL to anal squamous cell cancer is uncertain, but has an estimated
risk in the range of 8.5–13 % [2–4].
Despite the known association of HSIL and anal squamous cell carcinoma, many
patients go undiagnosed, or potentially worse yet, diagnosed and not treated. Many
factors contribute to the lack of treatment. Historically, poor adoption of preventa-
tive techniques resulted from a lack of standardized definitions and treatment pat-
terns, leaving treating physicians confused regarding evidence-based practice. In
addition, a lack of clear screening guidelines for low risk patients (eg heterosexual
females who do not practice receptive anal intercourse) resulted in affected patients
A.L. Lightner
Mayo Clinic, Division of Colon and Rectal Surgery,
200 1st St SW, Rochester, MN 55901, USA
M.L. Welton (*)
Department of Surgery, Stanford University School of Medicine, 300 Pasteur Drive, Stanford,
CA, USA

DOI 10.1007/978-3-319-40223-9_23
256 A.L. Lightner and M.L. Welton
being missed owing to the misconception that this was a disease limited to men who
have sex with other men (MSM) and/or men and women who are HIV positive.
There has been relatively limited adoption of high-resolution anoscopy (HRA)
likely owing to unfamiliarity with the equipment and poor physician reimburse-
ment. Further, there continues to be a lively ongoing debate regarding the necessity
and cost effectiveness of this treatment modality when compared to simple observa-
tion and clinical followup. The argument is that the relatively small subset of patients
who do progress from HSIL to anal carcinoma can be identified early and treated
successfully, without exposing the entire cohort to serial HRA. However, the 5-year
survival for Stage I and Stage IV anal cell cancer remains at 80 % and 30 % respec-
tively [5]. Thus, withholding treatment until a patient has developed anal squamous
cell cancer, even in the setting of stage I disease,, may result in avoidable mortality
from the disease not to mention the morbidity of chemoradiation therapy.
For the trained clinician, whether it is an advanced practice provider or physi-
cian, the screening tools (anal cytology and HRA) are relatively simple and cost
effective [6]. However, no RCTs have shown that such screening programs are effi-
cacious at reducing anal cancer incidence and mortality. Many believe that this is
because the procurement techniques for anal cytology and the performance of HRA
are highly variable and non-standardized. Fortunately, trials are currently underway
in order to evaluate the efficacy of cancer prevention with screening and treatment.
Further, national guidelines published by the National Comprehensive Cancer
Network (NCCN) and American College of Colon and Rectal Surgeons (ASCRS)
are now able to make recommendations based on higher quality of evidence [7, 8].
Search Strategy
An electronic search of the PubMed database was performed to obtain key literature in
the field of anal cancer published between January 1 2000 and July 1 2015, using the
following search terms: (anal cancer) OR (anal squamous cell carcinoma) OR (high-
grade squamous intraepithelial lesion). The PubMed database was chosen because it
remains the most widely used resource for medical literature and indexes only peer
reviewed biomedical literature, and is used by the NCCN when formulating updated
guidelines. The search results were narrowed by selecting studies in humans published
in English with full-length text. Results were then confined to the following article
types: clinical trial, Phase II; Clinical trial, Phase III; Clinical Trial, Phase IV; practice
guidelines, randomized controlled trial, meta analysis, systematic reviews, and valida-
tion studies. The PubMed search resulted in 17,299 citations and their potential rele-
vance was examined. When ‘and treatment’ was added to the search terms, 15,227 items
were resulted. These were sorted by relevance to improve detection of relevant studies.
The National Comprehensive Cancer Network (NCCN) and American College
of Colon and Rectal Surgeons (ASCRS) were then searched for additional relevant
studies for inclusion. This did not result in any further inclusion that was not found
in the PubMed search.
23 Anal Dysplasia/Cancer: Management of Patients with AIN 3 257
Results
Prevention
Prior to discussing treatment of AIN, brief mention will be made of prevention. A

quadrivalent HPV vaccine is currently available, and has been proven effective in
preventing high-grade cervical intraepithelial neoplasia related to HPV strains 6,
11, 16 or 18 in women, and genital lesions associated with the same HPV strains in
men [9–11]. Thus, a study was prompted to look at the efficacy of the vaccine for
prevention of HSIL and ASCC in MSM [12]. Although none of the 602 healthy men
aged 16 to 26 developed ASCC within the 3-year follow-up period, there were 5
cases of grade HSIL in the vaccine arm and 24 cases in the placebo arm. This
amounted to an observed efficacy of 77.5 % for prevention of HSIL, suggesting the
quadrivalent HPV vaccine may reduce the risk of ASCC in this patient population.
Recently, the quadrivalent HPV vaccine has been tested in HIV positive children,
a group at high risk for HPV, and subsequent associated cervical and anal cancer. A
randomized clinical trial found the vaccine to be safe and immunogenic in 126 HIV
positive aged 7–12 years. Initially, antibody titers were lower for HPV 6 and 18
compared with historic age-matched immunocompetent controls [13], but this dif-
ference was lost after the fourth dose of vaccine [14]. The success of vaccines could
lead to a significant decrease or near elimination of ASCC if used early and univer-
sally. Thus, their clinical importance cannot be underscored enough.
Patients with condyloma acuminatum or low-grade squamous intraepithelial
lesion (LSIL) have very low potential for malignancy [15]. It is not clear that LSIL
actually directly progresses to HSIL or ASCC. Rather, LSIL may be a marker in
certain at risk groups for the presence of virus. Those patients that are symptomatic
may wish to have the lesions excised or destroyed and this can be done with cautery,
IRC or chemical agents. Follow up of these patients depends heavily on age, risk
factors, underlying disease states and behavior patterns.
Treatment
The goal of treating HSIL is the prevention of ASCC while maintaining anal func-
tion, including continence of stool and gas. Several therapies are available for the
treatment of HSIL including surgical excision, electrocautery, topical imiquimod,
trichloracetic acid and topical fluorouracil (5-FU). Limited studies, largely in the
form of case series, have addressed the relative efficacy of the potential treatment
options.
In 2000, a survey of 663 members of the ASCRS found that 87 % of respondents
chose surgical excision with clear margins as the optimal treatment for HSIL [16].
However, a number of subsequent studies have suggested that surgery may not be
the best treatment approach. Brown reported 34 patients with HSIL treated
surgically in the UK. Within 41 months, 14 of 34 patients had macroscopic recur-

rences and 25 % of patients had anal function deficits postoperatively [17].
Scholefield reported on 35 patients who underwent limited excision for HSIL and
were followed for 63 months. Three of 35 (9 %) had progression to ASCC [2].
Watson reported their experience with 72 patients treated surgically, of whom nine
developed incontinence; four of these required a colostomy. Despite their aggres-
sive surgical approach, 8 patients (11 %) progressed to invasive ASCC [3]. These
studies have suggested surgical excision is not an ideal treatment due to incomplete
excisions, frequent recurrences, and complications including stenosis and inconti-
nence. They argued further that because chemoradiation for small invasive anal car-
cinoma is effective, a less radical approach may be warranted, because early surgical
intervention with the associated complications may compromise later definitive
treatment.
Other investigators suggest that rather than using an excisional approach, the use
of HRA allows targeted destruction of suspicious lesions with the lowest reported
rates of progression to cancer and preservation of anorectal function. HRA is used
to identify dysplastic epithelium under the magnification of a standard colposcope
or operating microscope. The technical application of HRA itself is discussed in
more detail in the section regarding our treatment approach; but, briefly, HRA can
be used with either targeted infrared coagulation (IRC) or electrocautery (EC). Both
procedures are outpatient with only enemas given in preparation. IRC can be used
with facility for lesions above the dentate line although local anesthesia is often
necessary because the heat generated by the instrument causes pain. It coagulates
lesions using 1.6 s pulses until the entire surface and an approximately 3 mm sur-
rounding border are coagulated. The coagulated tissue is then scraped off with a
small cotton Q-tip or forceps. This is repeated until the submucosal vessels are
identified and coagulated. HRA directed EC, unlike IRC, uses bipolar cautery creat-
ing a smoke plume that requires a smoke evacuator to prevent transmission of
HPV. Across the four listed studies (Table 23.1) regarding HRA targeted IRC for
HSIL, there was no reported anal function compromise, 10–38 % had recurrence of
HSIL, and none had progression to ASCC [18–21]. Similarly, in the two listed stud-
ies regarding HRA targeted EC, there was no reported anal function compromise,
17–31 % had recurrence of HSIL, and 0.4 % had progression to anal squamous cell
carcinoma [22, 23]. Of note, recurrence of HSIL was higher in HIV patients and
patients with higher burden of disease.
The use of topical medical treatments has recently become more widespread.
Topical fluorouracil (5-FU) and imiquimod have the advantages of treating AIN
by the patient themselves without compromising anorectal function. However,
topical treatments have the disadvantage of extended treatment courses and sig-
nificant side effects including perianal pain and irritation that may result in
non-compliance. Treatment with 5-FU is not standardized. The amount and fre-
quency are variable. Despite several treatment interruptions due to side effects
and variable protocols administered, there has been very little progression to
ASCC. Only one patient among the three studies listed in Table 23.1 had pro-
gression to ASCC [24].
Table 23.1 Treatment practices for HSIL

Anal Grade of
function evidence
compromised HSIL at last Developed (GRADE
Study ID Patients (%) f/u (%) ASCC (%) system)
Surgery
Excision
Watson 10/62 13 Not reported 11 Moderate
et al. [3] immunocompromised
Scholefield 6/35 0 Not reported 9 Moderate
Devaraj 40 HIV + MSM 3 Not reported 8 Moderate
and
Cosman
[4]
Brown 34 M and F 15 Not reported 0 Moderate
et al. [17]
Marchesa 16 M, 31 F 0 38 % 6 Moderate
et al. [36]
HRA-targeted IRC
Goldstone 52 HIV-MSM/44 0 HIV + 18 %; 0 High
et al. [19] HIV + MSM HIV-10 %
Weis et al. 99 M/25 F all HIV+ 0 Treated 0 Moderate
[21] 13 %;
untreated
93 %
Stier et al. 16 M/2 F all HIV+ 0 38 % 0 Moderate
[37]
Cranston 68 HIV + MSM 0 36 % 0 Moderate
et al. [18]
HRA-targeted EC
Marks and 132 HIV + MSM; 100 0 HIV + 31 % 0.4 High
Goldstone HIV-MSM HIV-17 %
[22]
HRA-targeted EC f/u IRC or TCA
Pineda 194/246 0.8 22 % 1.2 High
Topical medical therapy
5-FU
Snyder 11 HIV + MSM 0 72 % 0 Moderate
et al. [29]
Richel 46 HIV + MSM 0 30 % 0 Moderate
et al. [28]
Graham 1/9 HIV+ 0 13 % 13 (n = 1) Low
et al. [24]
(continued)
Anal Grade of
function evidence
compromised HSIL at last Developed (GRADE
Study ID Patients (%) f/u (%) ASCC (%) system)
Imiquimod
Wieland 28 HIV + MSM 0 9 % 0 Moderate
et al. [30]
Kreuter 10 HIV + MSM 0 Not reported 0 Low
et al. [27]
Fox et al. 64 HIV + MSM 0 39 % 3 High
[25]
Van der 44 HIV + MSM Not reported 34 % Not Low
Snoek reported
et al. [38]
TCA
Singh et al. 54 MSM; 35 HIV+ 0 39 % 0 Moderate
[39]
Cranston 72 HIV+ MSM Not reported 20 % Not Moderate
et al. [18] reported
RCT
Richel O 246 HIV + MSM 0 At 72 1.2 % High
et al. [26] weeks: 71 % (n = 3)
imiquimod;
58 % 5-FU;
68 % EC
Similarly the use of topical imiquimod 5 % cream applied three times weekly has
been associated with very little progression to ASCC, with only one series reporting
2 patients with progression (3 %) [25]. Importantly, with topical medical treatments,
significant education of patients is required. Namely, patients should be told that
symptoms of itching, burning, and pain are evidence that imiquimod is working and
is not a sign that treatment should be discontinued. Additionally, imiquimod can
actually cause transient flu like symptoms the day following treatment. If patients
do not develop signs of erythema or erosions, the imiquimod frequency can be
increased throughout the treatment course. Unfortunately, the adherence rate of
topical imiquimod is low due to these side effects, and therefore make this treatment
strategy less effective.
Recently, RCTs are beginning to compare the aforementioned treatment
approaches. A recent RCT looking at 246 HIV-positive MSM found that electrocau-
tery had significantly increased rates of complete resolution compared to both
topical imiquimod and topical fluorouracil, and concluded that EC was the superior
treatment option [26]. Recurrence rates of HSIL were high in all treatment groups
underscoring the need for frequent surveillance and follow up. At week 24, 48 and
72, 22 %, 46 %, and 67 % of patients had recurrence respectively. Specifically, recur-
rence at 72 weeks was found in 71 % (n = 10/14) of patients treated with imiquimod,
58 % (n = 7/12) of patients treated with 5-FU, and 68 % (n = 13/19) of patients treated
with EC. Treatment side-effects, most commonly pain, bleeding and itching were
significantly more common in the imiquimod and 5-FU group at 43 % and 27 %
respectively, as compared to 18 % in the electrocautery group.
Expectant Management
It has been suggested by many that expectant management may be an appropriate,

cost effective approach for HSIL rather than treatment, as there are no associated
treatment costs or side effects. A trial addressing this approach was conducted at a
university and VA practice. Forty 40 HIV infected patients were followed for a
mean of 32 months [4]. Patients had a clinical exam every 6 months, and biopsies of
new macroscopic or symptomatic disease. Of the 40 patients, 23 had HSIL. Three
of the 28 patients developed ASCC at 10, 16 and 84 months, all of whom had a
cancer less than 2.5 cm in diameter. This trial suggested that very few patients prog-
ress to cancer, and, if so, were diagnosed at an early stage. To better understand this
question, a large ongoing randomized phase III trial comparing topical or ablative
treatment with active monitoring in HIV-positive patients with HSIL is currently
ongoing. The primary measure is time to anal cancer. The study is estimated to be
completed in 2022 (clinicaltrials.gov NCT02135419) and may provide additional
answers regarding active monitoring versus treatment in a high-risk group with
HSIL. No trials are currently underway for low risk patient cohort with HSIL, likely
because there are so few patients, and even fewer who progress to ASCC.
Several limitations exist when interpreting the aforementioned data. Studies of

HSIL screening and treatment practices are largely comprised of only immunosup-
pressed patients. And the single RCT to date includes only high risk HIV+ MSM,
limiting the applicability of the results to other patient cohorts. Treatments reported
for HSIL are not standardized, and reports of treatment outcome are mainly in the
form of case series and open-label studies, with only the one aforementioned RCT.
Despite these limitations, there is strong evidence that HSIL, left untreated, can
and does progress to ASCC [1]. Once diagnosed, these patients then require chemo-
therapy with radiation, and possible surgical intervention, all with associated mor-
bidity. Several studies, albeit small in patient number, have demonstrated nearly
zero progression to malignancy with both electrocautery and topical medical ther-
apy [22, 27–30]. A RCT has suggested electrocautery is the superior ablative modal-
ity [26]. This suggests patients with HSIL should be actively treated with EC in
order to prevent progression to ASCC.
Given that women have largely been left out of the discussion but develop anal
cancer at a higher rate than men, consensus guidelines developed by an international
panel of experts are available to guide the approach to a given patient based on their
specific risk factors [31].
There is no controversy that colonic polyps should be removed to prevent progres-

sion to colon and rectal cancer. However, there seems to be controversy regarding
the definition, prognosis, method of diagnosis, surveillance, and treatment for AIN/
HSIL. Part of the challenge lies in the fact that the disease prevalence is low, making
RCTs difficult to perform based on a primary outcome measure of progression to
cancer. Additionally, potential prevention practices with HRA have low reimburse-
ment rates and serve as a barrier to implementation..
However, therapy with HRA targeted EC may be performed as an office based
procedure without the need for anorectal preparation or narcotics upon dismissal if
the lesions are above the dentate line or limited in extent. Alternatively, for exten-
sive disease below the dentate line involving anal mucosa and or perianal skin, the
patients may be treated on an outpatient basis and discharged with instructions for
sitz baths, topical analgesics (5 % Lidocaine Cream – Recticare (Ferndale labs) pre-
ferred), and either Ultram, Tylenol with codeine, NSAIDS or Tylenol. HRA tar-
geted destruction is technically straightforward and can be performed by colorectal
surgeons, family practitioners, gynecologists and advanced practice providers, to
name a few. The obstacles to performing HRA targeted destruction of lesions may
be cost, reimbursement, clinical practice and the training required to visualize
lesions via either a microscope, the colposcope or even surgical loupes. Training is
readily available through the ASCCP (www.asccp.org) and may be efficiently built
into one’s office based practice.
As is well recognized by our readers, many patients referred for colorectal evalu-
ation with a diverse array of symptoms and findings often come with a chief com-
plaint of “hemorrhoids.” We perform a history to document risk factors for anal
dysplasia including HPV infection (anal-genital warts), history of receptive anal
intercourse or sexually transmitted disease, a history of cervical vulvar or vaginal
cancer, immunosuppression after solid organ transplant or HIV infection, hemato-
logic malignancies, certain autoimmune disorders including Crohn’s disease [32]
and smoking. Physical exam includes perianal inspection, digital rectal exam, and
anoscopy as indicated.
We prefer the operating room for the initial examination and treatment of patients
with HSIL, and for needed re-treatment of extensive disease or disease complicated
by synchronous anal pathology (eg overlying hermorrhoidal tissue or complicating
fistulous disease). HRA in the operating room is preferred for our initial evaluation
and treatment because we feel we get the best exposure with the sphincters com-
pletely relaxed with an anal block which allows for flattening of the hemorrhoidal
complexes and clear visualization of the tissues that might otherwise hide at the
base of a large complex when visualized with a plastic anoscope in the office.
In the operating room, the patient is positioned prone jack knife with the but-
tocks taped apart. Anesthesia with MAC local with 0.25 % Marcaine in the subcu-
taneous tissues and 0.5 % Marcaine with 1:200,000 epinephrine in the sphincters
for the anal block are administered. A thorough examination looking for hyperpig-
mentation, erythema, elevation, or scaling is performed. The distal rectal mucosa,
anal mucosa, and perianal skin is then treated with 3 % acetic acid by placing one
acetic acid soaked Ray-Tec in the anal canal and distal rectum, and one over the
anus/perianal skin. We use an operating microscope for magnification. We look for
a distinct vascular pattern within the acetowhitened rectal and anal mucosa or peri-
anal skin that is characteristic of HSIL. Any concerning lesions are biopsied and
then treated with needle tip cautery [23]. A deep burn is avoided by quickly moving
superficially across the surface of the tissue, sparing the surrounding normal
mucosa. Our experience is that we can limit the depth of injury to less than that
observed with excision, which may contribute significantly to our low observed
rate of complications [33]. This is safe and effective in both HIV (+) and HIV (−)
men and women [34].
We inform patients with condyloma acuminatum (low-grade intraepithelial neo-
plasia LSIL, AIN-1) that they have a very low potential for malignancy [15]. We
therefore offer treatment to symptomatic patients or those who simply want to have
the lesions removed (the vast majority). In high risk groups, LSIL can be a marker
for the presence of HSIL, especially in immunosuppressed populations; annual sur-
veillance including digital anal rectal examination, anal cytology, and HRA for
early detection of HSIL may be beneficial. Recently some have suggested that the
rate of anal cancer is extremely low before age 30 so that close surveillance might
begin after age 30 even in the high risk patients. How to follow “low-risk” patients
with LSIL remains unclear. This is where routine typing of HPV may be beneficial
in stratifying follow up. For patients who have been treated for HSIL, we perform a
1 and 6 month follow up examination with anoscopy.
If the patient is not involved in high risk behavior, we recommend annual surveil-
lance, again with digital anal examination and anal cytology. If involved in high risk
behavior, HRA is added to this algorithm on an annual basis. If immunosuppressed,
or if the patient has “high risk disease”, this interval may be shortened to 3–6 months
on a case by case basis. If a recurrence is found, we treat them in the office with
trichloracetic acid, IRC or hyfrecation unless the disease is complex as noted above.
We, and others, have experienced excellent control of HSIL and minimal progres-
sion to cancer using this approach [19, 23, 33, 35]. We cannot comment on topical
treatments as we have no personal experience with their use. However, we are
referred patients who have been on them with recurrence. There may be benefit in
combination with electrocautery to prevent recurrence, but this has yet to be
studied.
Ultimately, the goals of treating patients with HSIL is preventing morbidity asso-
ciated with the treatment of anal cancer without causing disturbances of anal func-
tion. We have low cost, outpatient tools to do this and evidence from RCT supporting
its use. We do not feel annual surveillance, in isolation, provides adequate care of
our patients.
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Chapter 24
Management of the Abnormal Pap Smear
in HIV Positive Patients
Brad Champagne
Introduction
Condylomaacuminata, anal intraepithelial neoplasia and anal cancer are diseases

that commonly afflict men who have sex with men (MSM). The disease process may
often be complicated by a coexisting infection with the Human Immunodeficiency
Virus (HIV). Other than patients with HIV and MSM populations, transplant recipi-
ents on immunosuppression or other immunosuppressed states, and women with a
history of genital cancers are at increased risk [1, 2] High risk populations have been
encouraged to undergo screening with anal pap smear with increasing frequency and
intensity over recent years. However, the appropriate follow-up, diagnostic work-up
and treatment modality for patients with a positive smear remains nebulous.
Although anal squamous cell carcinoma (ASCC) represents only approximately
2 % of all GI cancers, its incidence has steadily risen over the past decade [1, 3, 4].
This increase is particularly remarkable in specific populations, such as individuals
infected with HIV, and even more so among men who have sex with men (MSM),
which makes this patient group a primary focus for screening [5]. It has long been
recognized that, much like cervical cancer, there is a strong, causal relationship
between anal cancer and human papilloma virus (HPV) infection [6, 7]. Anal
intraepithelial neoplasia (AIN), HPV-related dysplastic changes in the cells at the
anal transition zone, is the presumed precursor lesion for ASCC [1, 8]. Anal intraep-
ithelial neoplasia is classified into three grades, corresponding to low-grade (AIN I),
moderate grade (AIN II), and high-grade dysplasia (AIN III). The terms low-grade
(LGAIN) and high grade (HGAIN) have been used to refer to AIN I/II and AIN III,
B. Champagne
Lerner College of Medicine, Cleveland Clinic, Cleveland, OH, USA
Cleveland Clinic, Fairview Hospital, Cleveland, OH, USA

DOI 10.1007/978-3-319-40223-9_24
268 B. Champagne
respectively [1]. The epithelium in both the cervix and anus may contain atypical
squamous cells of undetermined significance, low grade squamous intraepithelial
lesions, and high grade squamous intraepithelial lesions. It is fairly well established
that high grade squamous intraepithelial lesions represent the precursor to cervical
SCC [9]. Given the similarities between cervical and anal intraepithelial lesions and
the association with anogenital HPV, this precursor pathway is similarly applied to
concepts of progression to anal SCC [10]. Therefore, recognizing its effectiveness
in relation to cervical cancer, anal Pap smear cytology has been adapted as one of
the first steps in screening for AIN [2, 11]. There is little debate that the destruction
of AIN is paramount in the prevention of progression to ASCC [1–3].
However, once AIN has been identified, there is considerable debate on the opti-
mal protocol for management and surveillance of these lesions, specifically in high
risk populations [12]. This controversy is largely centered on recommendations of
routine high-resolution Anoscopy (HRA) in all patients with suspected AIN versus
clinical follow-up with expectant management (EM). High resolution anoscopy
(HRA) is similar to colposcopy, wherein the anal canal and transition zone are
inspected under a high resolution microscope with the addition of acetic acid and/or
Lugol’s iodine solution to identify areas of dysplasia, which are then biopsied [13–
17]. Expectant management includes regular office-based examination, operative
fulguration of larger lesions, and treatment of dysplasia with imiquimod [18]. With
this debate in mind, we set out to analyze the literature in an effort to answer the ques-
tion regarding optimal follow up of HIV patients with an abnormal anal Pap smear.
Methods
Our search strategy involved a Pubmed search with the following keywords: High
Resolution Anoscopy (HRA), Anal Intraepithelial Neoplasia (AIN), Papanicolaou
(pap) smear, cost, and screening. We limited our search from the year 1995 to pres-
ent. The evidence is analyzed, described, and placed in tabular form.
Patient population (P) Intervention (I) Comparator (C) Outcome studied (O)
HIV pts with abnormal High resolution Clinical Cancer prevention,
pap smear anoscopy (HRA) follow-up cost
Results
Screening HIV-infected MSM with annual anal cytology has been shown to be cost-
effective, with an incremental cost-effectiveness ratio compared to no screening of
$16,600 per quality –adjusted life year (QALY) saved, which is similar to other
accepted screening test such as colorectal cancer screening [10].
24 Management of the Abnormal Pap Smear in HIV Positive Patients 269
Currently, there are no randomized controlled trials comparing the efficacy of

HRA versus clinical follow-up with regards to ASCC prevention. We are thus left
with observational studies and retrospective reviews. A meta-analysis of published
studies suggests that the pooled prevalence of histological high grade AIN in MSM
with HIV was 29.1 % [7], with incidences of 8.5 % and 15.4 % per year respectively
in two estimates [19, 20]. The pooled anal cancer incidence was 45.9 per 100,000
men [7]. This number is corroborated by a pilot study which found that high grade
AIN (AIN II and III) was found on histological analysis after HRA in approxi-
mately 32 % of asymptomatic MSM living with HIV. In this population of 368
asymptomatic MSM, 1.4 % developed invasive anal cancer at a median follow up of
4.2 years after HRA. All patients had high grade AIN at initial HRA screening.
Additionally, during this study, the cumulative risk of anal cancer following HSIL
diagnosis was 0.6 % at 5 years [14]. It is clear from this and other studies that AIN
II-III represents a significant risk factor for development of ASCC.
However, does the incidence of ASCC support the widespread usage of HRA,
and does the cost outweigh the benefit? A recent large retrospective review addresses
the utility of routinely performing HRA. Crawshaw et al performed a single institu-
tion retrospective analysis of 424 patients from 2007 to 2013 comparing HRA to
clinical follow-up. Surgeons in the group differed in their views on this controversy
and their use of HRA, creating a natural experiment of sorts. 220 patients underwent
HRA after abnormal pap smear, and 204 patients underwent clinical follow-up. The
authors found no significant difference in progression to ASCC among the two
groups [12]. It is important to note, however, that the surgeons in the clinical follow-
up group performed mapping biopsies, ablated all visible lesions, and readily used
imiquimod. Therefore, the only real difference between the groups was the use of
HRA. HRA was not associated with prevention of ASCC when compared to the non
HRA arm.
A recent Markov model analysis suggests that surveillance strategies after treat-
ment for HGAIN that included HRA at 6 and 12 month intervals, with or without
anal cytology testing, were more effective than using HRA only for confirmatory
testing of abnormal anal cytology testing. However, a combined strategy of HRA
and anal cytology extended life expectancy and quality-adjusted life expectancy
(QALE) while remaining below the commonly-cited threshold of 100,000/QALY
gained [21]. Similarly, Lam et al built a decision analytic model, and found that of
18 screening strategies, the direct use of HRA was the most cost-effective approach
for the detection of high grade AIN [22]. However, neither of these analyses com-
pare HRA to that of clinical follow-up.
Proponents of clinical management without HRA cite the increased morbidity as
well as the additional cost incurred with repeated procedures often seen with HRA,
as well as the low rate of disease progression to ASCC in compliant patients [1].
However, whilst HRA has been shown to be more effective in the detection of AIN
than standard anoscopy with biopsies, this has failed to translate into lower rates of
disease progression to ASCC [14, 16, 17]. The purpose of cancer screening is to
reduce cancer-related mortality; there is a paucity of high quality evidence to make
clear recommendations regarding the true benefit of HRA.
270 B. Champagne
MSM with HIV are consistently more affected by HPV and HPV related abnormali-
ties than are HIV-negative MSM. Furthermore, longitudinal data suggests a very
high annual incidence of high grade AIN in HIV-positive men. Therefore, we
strongly recommend based on high and moderate quality evidence that HIV positive
MSM undergo screening with anal pap. In regards to treatment, the absence of data
from randomized and longitudinal trials showing that treatment of high-grade AIN
reduces the incidence of anal cancer and the morbidity associated with treatment
needs to be considered. Therefore, the recommendation that approaches to cervical
cancer prevention and treatment can be extrapolated to anal cancer are weak and
based on very low quality evidence.
High-resolution anoscopy is costly, time consuming and technically demanding
when compared to colposcopy for cervical cancer or to clinical follow-up with map-
ping biopsies in patients with a positive pap. The recommendation that HRA is
superior to clinical follow-up or expectant management is weak with very low qual-
ity evidence. In addition, the low progression rates of high grade AIN to anal cancer
also question the real value of repeated surgical treatments in this patient popula-
tion. Therefore, the recommendation that aggressive and repeated treatments are
warranted in patients with AIN to prevent anal cancer is weak and based on very
low quality evidence. Lastly, the argument that the cost of HRA is nominal when
compared to the cost savings achieved with cancer progression is not substantiated
by high quality data. Therefore, the recommendation that HRA is cost-effective
when applied to HIV positive MSM is weak with low quality data.
There is little debate that the destruction of AIN is paramount in the prevention of
progression to ASCC. Thus, identification of, and surveillance for the presence of
AIN is a key step in any screening protocol. While HRA has been shown to be more
effective in the detection of AIN than standard anoscopy with biopsies, there has not
been definitive proof that its utilization results in lower progression to ASCC than
more traditional expectant management. Recent studies at our institution, as out-
lined above, showed that there was no progression to ASCC in patients regardless
of their treatment protocol (HRA vs EM), if they were compliant with therapy.
The majority of our patients now follow the expectant management (EM)
algorithm.
All patients are initially evaluated in the office with DRE and anoscopy. If they
had a positive anal pap smear or visible condyloma they are brought to the operating
room for evaluation. During surgery, all visible abnormal areas are both biopsied
and ablated. Furthermore, representative biopsies are performed from every quad-
rant in the anal canal and the anal margin in areas with no identifiable lesions.
24 Management of the Abnormal Pap Smear in HIV Positive Patients 271
Postoperatively, patients with anal intraepithelial neoplasia are treated with imiqui-
mod and followed. Recurrent lesions amendable to office-based therapy with acetic
acid and or podophyllin are not brought back to the operating room for ablation
unless the disease persists for 3 months after treatment.
. Overall, in our recently published data, we found that patients with anal intraep-
ithelial neoplasia rarely progress to squamous cell cancer after ablation when fol-
lowed with expectant management or high-resolution anoscopy. Our results support
the concept that physicians treating these diseases should utilize the technique that
they are most comfortable with. The cost, morbidity and value of high-resolution
anoscopy should be further critically evaluated before it is regarded as the gold
standard in anal cancer screening.
Specific Recommendations
1. HIV positive men who have sex with men (MSM) should undergo routine
screening with anal pap (Grade: High. Recommendation: Strong)
2. Approaches to cervical cancer prevention and treatment can be extrapo-
lated to anal cancer. (Grade: Low. Recommendation Weak)
3. HRA is superior to clinical follow-up or expectant management for AIN.
(Grade: Low. Recommendation: Weak)
4. Aggressive and repeated treatments with HRA are warranted in patients
with AIN to prevent anal cancer. (Grade: Low. Recommendation: Weak.)
5. HRA is a cost-effective strategy to prevent anal cancer in HIV positive
MSM. (Grade: Low. Recommendation: Weak).
Questions Utility/sens/spec of abnormal pap smears, cost of HRA, sens/spec of

HRA, increased incidence with HIV positivity, cost of pap smears
References
1. Steele SR, Varma MG, Melton GB, et al. Practice parameters for anal squamous neoplasms.
Dis Colon Rectum. 2012;55(7):735–49.
2. Smyczek P, Singh AE, Romanowski B. Anal intraepithelial neoplasia: review and recommen-
dations for screening and management. Int J STD AIDS. 2013;24(11):843–51.
3. Goldstone SE, Johnstone AA, Moshier EL. Long-term outcome of ablation of anal high-grade
squamous intraepithelial lesions: recurrence and incidence of cancer. Dis Colon Rectum.
2014;57(3):316–23.
4. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63(1):
11–30.
5. Sendagorta E, Herranz P, Guadalajara H, et al. Prevalence of abnormal anal cytology and high-
grade squamous intraepithelial lesions among a cohort of HIV-infected men who have sex with
men. Dis Colon Rectum. 2014;57(4):475–81.
6. Frisch M, Glimelius B, van den Brule AJ, et al. Sexually transmitted infection as a cause of
anal cancer. N Engl J Med. 1997;337(19):1350–8.
272 B. Champagne
7. Machalek DA, Poynten M, Jin F, et al. Anal human papillomavirus infection and associated
neoplastic lesions in men who have sex with men: a systematic review and meta-analysis.
Lancet Oncol. 2012;13(5):487–500.
8. Berry JM, Jay N, Cranston RD, et al. Progression of anal high-grade squamous intraepithelial
lesions to invasive anal cancer among HIV-infected men who have sex with men. Int J Cancer.
2014;134(5):1147–55.
9. Palefsky JM, Holly EA. Molecular virology and epidemiology of human papillomavirus and
cervical cancer. Cancer Epidemiol Biomarkers Prev. 1995;4(4):415–28.
10. Goldie SJ, Kuntz KM, Weinstein MC, Freedberg KA, Welton ML, Palefsky JM. The clinical
effectiveness and cost-effectiveness of screening for anal squamous intraepithelial lesions in
homosexual and bisexual HIV-positive men. JAMA. 1999;281(19):1822–9.
11. Darragh TM, Winkler B. Anal cancer and cervical cancer screening: key differences. Cancer
Cytopathol. 2011;119(1):5–19.
12. Crawshaw BP, Russ AJ, Stein SL, et al. High-resolution anoscopy or expectant management
for anal intraepithelial neoplasia for the prevention of anal cancer: is there really a difference?
13. Goldstone SE. High-resolution anoscopy is a crucial component of anal dysplasia screening.
14. Dalla Pria A, Alfa-Wali M, Fox P, et al. High-resolution anoscopy screening of HIV-positive
MSM: longitudinal results from a pilot study. AIDS. 2014;28(6):861–7.
15. Richel O, Hallensleben ND, Kreuter A, van Noesel CJ, Prins JM, de Vries HJ. High-resolution
anoscopy: clinical features of anal intraepithelial neoplasia in HIV-positive men. Dis Colon
Rectum. 2013;56(11):1237–42.
16. Silvera R, Gaisa MM, Goldstone SE. Random biopsy during high-resolution anoscopy

increases diagnosis of anal high-grade squamous intraepithelial lesions. J Acquir Immune
Defic Syndr. 2014;65(1):65–71.
17. Gimenez F, Costa-e-Silva IT, Daumas A, Araújo J, Medeiros SG, Ferreira L. The value of
high-resolution anoscopy in the diagnosis of anal cancer precursor lesions in HIV-positive
patients. Arq Gastroenterol. 2011;48(2):136–45.
18. Devaraj B, Cosman BC. Expectant management of anal squamous dysplasia in patients with
HIV. Dis Colon Rectum. 2006;49(1):36–40.
19. de Pokomandy A, Rouleau D, Ghattas G, et al. HAART and progression to high-grade anal
intraepithelial neoplasia in men who have sex with men and are infected with HIV. Clin Infect
Dis. 2011;52(9):1174–81.
20. Palefsky JM, Holly EA, Ralston ML, Jay N, Berry JM, Darragh TM. High incidence of anal
high-grade squamous intra-epithelial lesions among HIV-positive and HIV-negative homo-
sexual and bisexual men. AIDS. 1998;12(5):495–503.
21. Assoumou SA, Mayer KH, Panther L, Linas BP, Kim J. Cost-effectiveness of surveillance
strategies after treatment for high-grade anal dysplasia in high-risk patients. Sex Transm Dis.
2013;40(4):298–303.
22. Lam JM, Hoch JS, Tinmouth J, Sano M, Raboud J, Salit IE. Cost-effectiveness of screening for
anal precancers in HIV-positive men. AIDS. 2011;25(5):635–42.
Part V
Benign Colon Disease
Chapter 25
Indications for Surgery in Patients with Severe
Clostridium Difficile Colitis
Vikram Reddy and Walter Longo
Introduction
Clostridium difficile colitis (CDC) is the leading cause of nosocomial diarrhea in

the United States, with a broad spectrum of symptoms ranging from mild diarrhea
to fulminant colitis which can lead to multisystem organ failure and death. For the
majority of cases, surgical therapy is unnecessary as CDC responds to antibiotic
therapy. Medically refractory colitis carries a high morbidity and mortality, and
often necessitates surgical intervention which may also be associated with poor
outcomes. The timing of surgery in the setting of CDC is critical; surgical interven-
tion early in the course of disease may lead to an unnecessary colectomy with ileos-
tomy when medical therapy may have been sufficient, but delaying surgical therapy
in fulminant colitis commonly leads to a fatal outcome.
Recommendations for intervention requires is based on the severity of disease.
Mild disease is characterized by diarrhea without any systemic symptoms.
Endoscopic findings in mild disease show non-specific diffuse or patchy erythema-
tous colitis, and pseudomembranes are usually not found. Imaging shows no evi-
dence of colitis. Moderate disease is associated with more severe diarrhea, and mild
systemic signs such as fever, leukocytosis, nausea and general malaise. Pseudo-
membranes, though not specific for CDC, are likely to be noted on endoscopy.
Severe disease is progressively worsening CDC with hypoalbuminema (<3 g/dL) in
the setting of worsening leukocytosis (>15,000 cells/mm3) or abdominal tenderness.
Fulminant colitis is a rare but life-threatening progression of severe CDC character-
ized by segmental or total colonic distention with signs of systemic toxicity (fever,
V. Reddy, MD, PhD • W. Longo, MD, MBA (*)

Department of Surgery, Yale University School of Medicine, New Haven, CT 06510, USA

DOI 10.1007/978-3-319-40223-9_25
276 V. Reddy and W. Longo
leukocytosis, distention, tenderness, hemodynamic instability, and organ dysfunc-

tion) and clinical deterioration with peritonitis and sepsis. Unfortunately, a clear
algorithmic approach to surgical management is difficult as the ability to categorize
the severity of the disease is challenging. Most of the studies addressing indications
for surgery are limited by small sample sizes, retrospective analysis, and inconsis-
tent criteria in distinguishing severe from fulminant colitis.
Non-surgical options include treatment with antibiotics, fecal microbiota trans-
plant (FMT) and intravenous immunoglobulin (IVIG) transfers. Antibiotic therapy
includes single agent therapy with oral metronidazole or vancomycin for mild to
moderate disease, and dual coverage with metronidazole and vancomycin for severe
disease. Nitazoxanide and fidaxomicin have also been used, but their utility in
severe CDC needs to be more fully addressed. FMT is the transfer of stool from a
heathy donor to a patient with CDC to remedy the decreased colonic diversity that
is thought to drive CDC [1]. Instillation can be done by colonoscopy, upper endos-
copy, per nasogastric tube, or by retention enemas. Lower GI tract instillations are
associated with better outcomes.
Surgical options for the management of fulminant colitis include segmental col-
ectomy, total or subtotal abdominal colectomy (TAC) with a stoma, or a diverting
stoma with lavage of the distal bowel [2]. Of these, TAC with end ileostomy is the
gold standard [3] which eliminates the diseased colon while avoiding the added
morbidity of a pelvic dissection. Diverting stoma and lavage of the distal bowel
markedly decreases the magnitude of the surgical procedure and diminishes the
likelihood of a permanent ileostomy.
Search Strategy
The MEDLINE database was searched using the following MeSH headings:
“Clostridium difficile”, “surgery”, and “outcome.” The time interval of the retreived
articles was limited to 2005–2015. Non-english language publications were excluded.
Information obtained was graded according to published GRADE guidelines. In gen-
eral, the strength of the evidence is moderate to low, as it has been difficult to initiate
large randomized controlled trials to evaluate the role of surgery in severe Clostridium
difficile colitis. Meta-analyses, case reports, and reviews not containing original data
were also excluded (Table 25.1).

C
P (patient population) I (intervention) (comparator) O (key outcomes)
Patients with severe Surgery No surgery Morbidity, mortality,
Clostridium difficile colitis quality of life
25 Indications for Surgery in Patients with Severe Clostridium Difficile Colitis 277
Results
The overall quality of the evidence is very low. Of the articles which met the search
criteria, there were no randomized controlled trials, and only one was a prospective
study (Table 25.2). Note that the data in the table shows some studies which included all
patients with CDC while others show patients who underwent an intervention for CDC.
The mortality for surgical intervention was 19–67 % in the included studies
(Table 25.2). Koss et al. showed that 80 % of those undergoing a segmental colec-
tomy died, while mortality was significantly lower in those undergoing total abdom-
inal colectomy; 6 of the 9 patients who underwent a TAC eventually had
re-establishment of continuity [4]. Kenneally et al. studied CDC patients in the
intensive care setting (ICU) [5]. The overall 30-day mortality was 36.7 % and the
surgical mortality was 33.3 %. This study is limited by the selection of the popula-
tion: patients in the ICU setting who were more likely to have other co-morbidities
and likely at a greater risk of hospital mortality. Lamontagne et al. studied CDC in
the ICU setting and noted that patients undergoing surgery had fewer co-morbidities,
higher leukocytosis and increased probability of sepsis, but lower mortality [6]. Ali
et al. studied factors associated with survival after colectomy and noted higher mor-
tality with delaying surgical intervention, worsening leukocytosis, multisystem
organ failure and the preoperative use of pressors [7].
Byrn et al. showed increased mortality with mental status changes, vasopressor
requirement and delayed surgical therapy [8]. Hall et al. reported a lower mortality
after colectomy in the absence of preoperative vasopressor requirement and ventila-
tor support [9]. Hermensen et al. reported that in patients considered candidates for
surgery, mortality was 46 %, while all patients who declined surgery died [10].
Pepin et al. showed that mortality after surgery increased with age, preoperative
lactic acidosis, leukocytosis and hypoalbuminemia [12]. Sailhamer et al. studied
patients with fulminant CDC and noted a decreased mortality with surgical inter-
vention [13]. Age greater that 70 years, severe leukocytosis, leukopenia or ban-
demia, and cardiopulmonary failure were associated increased mortality (57 %
when all three were noted, but 0 % in the absence of all three factors). Care on the
surgical service was associated with higher operative intervention and better sur-
vival. Seder et al. also noted increasing age, acute respiratory failure and acute renal
failure to be associated with increased mortality [14]. Dudukgian et al. noted that
among the patients with CDC who died, 12.2 % underwent surgery while 87.8 % did
not. Non-survivors who were medically managed had a longer pre-CDC hospital
stay and more co-morbidities. Halabi et al. reviewed the Nationwide Inpatient
Sample and noted an inpatient mortality of 30.7 % in patients undergoing colectomy
[20]. Delaying surgery was associated with worse outcomes.
In assessing overall mortality, there are few studies comparing surgical to medical
therapy for severe disease [22]. Two studies show a decrease in mortality with surgical
intervention in the setting of severe CDC [6, 13]. Lamontage et al. identified patients
in the ICU with CDC and noted a significant decrease in mortality with surgical inter-
Table 25.2 Summary of studies
278
Surgery (N) Mortality (%)

Year Study Design (quality) Study size (N) Total TAC Other Overall Surgical Medical
2006 Koss et al. [4] Retrospective (very low) 3472 14 9 5 – 36 –
2007 Kenneally et al. [5] Retrospective (very low) 278 6 – – 37 33 37
2007 Lamontagne et al. [6] Retrospective (very low) 165 38 35 – 53 34 58
2008 Ali et al. [7] Retrospective (very low) 36 36 28 8 – 47 –
2008 Byrn et al. [8] Retrospective (very low) 5718 73 63 10 – 34 –
2008 Hall and Berger [9] Retrospective (very low) 3237 36 34 2 – 36 –
2008 Hermsen et al. [10] Retrospective (very low) 7588 13 13 – – 46 –
2009 Chan et al. [11] Retrospective (very low) 15 15 12 3 – 67 –
2009 Pepin et al. [12] Retrospective (low) 130 130 124 6 – 37 –
2009 Sailhamer et al. [13] Retrospective (low) 4796 75 69 6 35 24 45
2009 Seder et al. [14] Retrospective (very low) 6841 69 68 1 – 42 –
2010 Al-Abed et al. [15] Retrospective (very low) 528 20 17 3 – 40 –
2010 Dudukgian et al. [16] Retrospective (very low) 398 14 11 3 – 36 –
2010 Gash et al. [17] Retrospective (very low) 1398 17 16 1 – 53 –
2010 Perera et al. [18] Retrospective (very low) 35 35 32 3 – 46 –
2011 Markelov et al. [19] Retrospective (very low) 13 13 12 1 – 46 –
2011 Neal et al. [2] Prospective (low) 42 42 – 42 – 19 –
2013 Halabi et al. [20] Retrospective (low) 2,773,521 19,374 3900 – – 31 –
2015 van der Wilden et al. [21] Retrospective (very low) 100 100 100 – – 25 –
V. Reddy and W. Longo
vention [6]. Sailhamer et al. reviewed all patients with severe CDC at their institution,
and noted a trend towards decreased mortality with surgery [13]. Care on the surgical
service was associated with a significantly lower mortality rate (12.8 % vs 39.3 %).
When comparing TAC with a segmental resection, several studies show the infe-
riority of segmental resection, need for additional intervention and ultimately, the
increased mortality [4, 8, 9, 12, 14–16, 18, 19]. Interestingly, segmental colectomy
as the first intervention was associated with a slightly lower mortality as noted on two
meta-analyses [3, 23]. However, when corrected for re-intervention and an eventual
completion colectomy in patients undergoing a segmental resection, the relative risk
of a TAC trended lower [23]. Of the patients who undergo a segmental colectomy,
15.9 % need an eventual re-operation to decrease the disease burden [3].
A less aggressive alternative to a subtotal colectomy was studied prospectively,
and involved the creation of a loop ileostomy, washout of the colon with warm poly-
ethylene glycol 3550, and postoperative antegrade colonic vancomycin flushes [2].
When compared to historical controls, a lower mortality (19 vs 50 %) was noted and
preservation of the colon was achieved in 93 % of subjects. However, selection and
management bias cannot be ruled out as this was a small study cohort with no ran-
domization and retrospective comparison to historical controls.
Several studies show that delaying surgical intervention is associated with worse
outcomes. Respiratory failure [4, 8, 9, 13, 14, 20], renal failure [4, 9, 14, 20], and
vasopressor requirement due to hemodynamic instability [4, 7–10, 12–14, 18–20]
were associated with increased mortality. Ali et al. showed that survivors had surgery
at a mean of 3.2 days vs. 5.4 days [7]. Sailhamer et al. similarly showed that the mean
time to surgery was lower for survivors at 1.9 days vs. 3.9 days [13]. Halabi et al.
reviewed a large administrative database and noted that surgical intervention more
than 3 days after admission for CDC was associated with poorer prognosis [20].
Antibiotic treatment of patients after TAC for CDC was addressed by van der
Wilden et al. who noted that intravenous metronidazole or enteral vancomycin for
no more than 7 days was sufficient [21]. Mortality did not improve with antibiotic
usage more than 7 days. Studies on the long-term follow-up of patients after colec-
tomy for CDC are limited. Though Koss et al. [4] showed a 67 % re-establishment
of continuity in survivors after colectomy, Miller et al. noted that the 5-year survival
rate after colectomy was 38 % and intestinal continuity was re-established in only
20 % of the patients [24].
Mortality rates attributable to CDC remain high and even with surgery are as high
as 19–67 %. The judgement for surgical intervention is empirical, and no clear evi-
dence exists due to the lack of prospective, randomized controlled studies.
Compounding the decision to intervene surgically is the lack of data on the timing
of the intervention. Overall, the quality of the data is low, but most patients and all
clinicians would place a high value on the reduction in mortality; despite the adverse
280 V. Reddy and W. Longo
effects of surgery (for example on quality of life), surgical intervention in compli-

cated severe CDC warrants a strong recommendation.
Patients with complicated severe CDC benefit from early surgical intervention,
as delaying definitive surgery will increase the morbidity and mortality. Intervention
should be considered prior to the onset of cardiopulmonary collapse (need for ven-
tilator assistance or the use vasopressors) and renal failure. Transfer to or admission
to the surgical service may be prudent for closer monitoring and quicker interven-
tion. Intervention within 3 days of medically refractory severe disease may be war-
ranted to improve outcomes.
Of all the surgical options, TAC with ileostomy has the best outcome. Long-term
prognosis of the patients who undergo colectomy for CDC is limited. A retrospec-
tive study of 61 patients from a single institution estimated a mean survival of
18.1 months [25]. The cause of death could not be distinguished between CDC,
colectomy for CDC, or comorbid diseases.
A diverting loop ileostomy with colonic lavage is a more palatable approach and
may enable both the medical and surgical teams to intervene more quickly as there
is less fear of a permanent ileostomy and a major abdominal operation. However,
the evidence supporting this approach is limited, and extreme caution is warranted
when proceeding with diversion and lavage alone.
Our approach to a patient with severe CDC has always been to assess the risk vs.
benefit of the surgery, be aggressive about the approach, and if uncertain, proceed
with surgical resection. Patients with severe CDC are transferred to our service in
the ICU. Close hemodynamic monitoring, serial abdominal exams, laboratory eval-
uations and computed tomography (CT) imaging are obtained. Immunosuppressed
patients or those in whom a reliable abdominal exam cannot be obtained are more
likely to undergo TAC with ileostomy. Early signs of hemodynamic compromise
such as fluid responsive hypotension, decreasing urine output, labored breathing or
subtle mental status changes warrant surgery. Worsening leukocytosis, hypoalbu-
minemia, or lactic acidosis also decrease the threshold for surgery. Patients with
severe comorbidities who may not survive a TAC with ileostomy are considered
candidates for a diverting loop ileostomy and colonic lavage. Survivors after TAC
will more than likely need disposition to long-term care facilities, and prolonged
recuperation prior to consideration of ileosigmoid or ileorectal anastomoses.
References
1. Chang JY, et al. Decreased diversity of the fecal Microbiome in recurrent Clostridium difficile-
associated diarrhea. J Infect Dis. 2008;197:435–8.
2. Neal MD, Alverdy JC, Hall DE, Simmons RL, Zuckerbraun BS. Diverting loop ileostomy
and colonic lavage: an alternative to total abdominal colectomy for the treatment of severe,
complicated Clostridium difficile associated disease. Ann Surg. 2011;254:423–7; discussion

427–9.
3. Bhangu A, et al. Systematic review and meta-analysis of outcomes following emergency sur-
gery for Clostridium difficile colitis. Br J Surg. 2012;99:1501–13.
4. Koss K, et al. The outcome of surgery in fulminant Clostridium difficile colitis. Colorectal Dis.
2006;8:149–54.
5. Kenneally C, et al. Analysis of 30-day mortality for clostridium difficile-associated disease in
the ICU setting. Chest. 2007;132:418–24.
6. Lamontagne F, et al. Impact of emergency colectomy on survival of patients with fulminant
Clostridium difficile colitis during an epidemic caused by a hypervirulent strain. Ann Surg.
2007;245:267–72.
7. Ali SO, Welch JP, Dring RJ. Early surgical intervention for fulminant pseudomembranous
colitis. Am Surg. 2008;74:20–6.
8. Byrn JC, et al. Predictors of mortality after colectomy for fulminant Clostridium difficile coli-
tis. Arch Surg. 2008;143:150–4; discussion 155.
9. Hall JF, Berger D. Outcome of colectomy for Clostridium difficile colitis: a plea for early
surgical management. Am J Surg. 2008;196:384–8.
10. Hermsen JL, Dobrescu C, Kudsk KA. Clostridium difficile infection: a surgical disease in
evolution. J Gastrointest Surg. 2008;12:1512–7.
11. Chan S, et al. Outcomes following colectomy for Clostridium difficile colitis. Int J Surg.
2009;7:78–81.
12. Pépin J, Valiquette L, Gagnon S, Routhier S, Brazeau I. Outcomes of Clostridium difficile-
associated disease treated with metronidazole or vancomycin before and after the emergence
of NAP1/027. Am J Gastroenterol. 2007;102:2781–8.
13. Sailhamer EA, et al. Fulminant Clostridium difficile colitis: patterns of care and predictors of
mortality. Arch Surg. 2009;144:433–9; discussion 439–40.
14. Seder CW, et al. Early colectomy may be associated with improved survival in fulminant
Clostridium difficile colitis: an 8-year experience. Am J Surg. 2009;197:302–7.
15. Al-Abed YA, Gray EA, Rothnie ND. Outcomes of emergency colectomy for fulminant
Clostridium difficile colitis. Surgeon. 2010;8:330–3.
16. Dudukgian H, Sie E, Gonzalez-Ruiz C, Etzioni DA, Kaiser AMC. Difficile colitis – predictors
of fatal outcome. J Gastrointest Surg. 2010;14:315–22.
17. Gash K, Brown E, Pullyblank A. Emergency subtotal colectomy for fulminant Clostridium
difficile colitis – is a surgical solution considered for all patients? Ann R Coll Surg Engl.
2010;92:56–60.
18. Perera AD, et al. Colectomy for fulminant Clostridium difficile colitis: predictors of mortality.
Am Surg. 2010;76:418–21.
19. Markelov A, Livert D, Kohli H. Predictors of fatal outcome after colectomy for fulminant
Clostridium difficile Colitis: a 10-year experience. [email protected]. Am Surg.
2011;77:977–80.
20. Halabi WJ, et al. Clostridium difficile colitis in the United States: a decade of trends, outcomes,
risk factors for colectomy, and mortality after colectomy. J Am Coll Surg. 2013;217:802–12.
21. van der Wilden GM, et al. Antibiotic regimen after a total abdominal colectomy with ileostomy
for fulminant clostridium difficile colitis: a multi-institutional study. Surg Infect (Larchmt).
2015;16:455–60.
22. Stewart DB, Hollenbeak CS, Wilson MZ. Is colectomy for fulminant Clostridium difficile
colitis life saving? A systematic review. Colorectal Dis. 2013;15:798–804.
23. Ferrada P, et al. Timing and type of surgical treatment of Clostridium difficile-associated dis-
ease: a practice management guideline from the Eastern Association for the Surgery of
Trauma. J Trauma Acute Care Surg. 2014;76:1484–93.
24. Miller AT, et al. Long-term follow-up of patients with fulminant Clostridium difficile colitis.
25. Dallas KB, Condren A, Divino CM. Life after colectomy for fulminant Clostridium difficile
colitis: a 7-year follow up study. Am J Surg. 2014;207:533–9.
Chapter 26
Do We Need to Operate on Patients After
Successful Percutaneous Drainage
of a Diverticular Abscess?
Wolfgang B. Gaertner and Robert D. Madoff
Introduction
Sigmoid diverticular disease is a significant health problem, resulting in annual esti-

mated costs of over 2.6 billion dollars and 312,000 hospital admissions in the USA
[1, 2]. Most cases of diverticular abscess are managed non-operatively with intrave-
nous antibiotics, and the addition of percutaneous drainage (PD) in selective cases
[3–5].
The natural history of diverticular disease after PD of a diverticular abscess is not
well defined. Clinical practice guidelines from the American Society of Colon and
Rectal surgeons have evolved over the past 10 years from recommending elective
colectomy after one episode of diverticular abscess treated non-operatively to an
individualized approach for elective colectomy based on the severity of the disease
and not on the number of recurrent episodes or attacks [6, 7].
Search Strategy
A comprehensive literature search of PubMed, MEDLINE, EMBASE, and the

Cochrane Database of Collected Reviews was performed to identify all English
language publications related to non-operative management and outcomes of diver-
ticular abscesses from 1986 to 2015. Key search terms included the following:
“management,” “colon,” “sigmoid,” “diverticulitis,” “abscess,” “percutaneous
drainage,” “surgery,” “colectomy,” and “resection”. Studies that focused on the
W.B. Gaertner • R.D. Madoff (*)

Division of Colon & Rectal Surgery, Department of Surgery, University of Minnesota,
420 Delaware St SE, MMC 450, Minneapolis, MN 55455, USA

DOI 10.1007/978-3-319-40223-9_26
284 W.B. Gaertner and R.D. Madoff

Patients status post percutaneous Colectomy Expectant Recurrent
drainage of diverticular abscess management diverticulitis
management of Hinchey 3/4 diverticulitis, surgical management of diverticular dis-

ease, antibiotic treatment alone for diverticular abscess, laparoscopic peritoneal
lavage, case reports, letters, review articles, non-sigmoid diverticulitis, and dupli-
cate articles were excluded. The reference lists from the included articles were
manually reviewed, and additional studies were included when appropriate.
Patients undergoing elective colectomy after successful PD were compared with
those followed by observation. The primary outcome reviewed for each study was
the rate of recurrent diverticulitis after PD (Table 26.1). Secondary outcomes and
parameters recorded included failure of PD, elective colectomy after successful PD,
and postoperative morbidity after elective colectomy.
Results
The initial literature search retrieved 362 studies. After applying the exclusion cri-
teria, 21 studies were included in the final review. There are no randomized clinical
trials comparing outcomes of different management strategies for diverticular
abscess. The majority of studies are retrospective series from single institutions
reporting on different treatment strategies for diverticular abscess with short follow-
up intervals (Table 26.2). The outcomes from these studies are heavily influenced by
institutional policy and surgeon preference, and biased towards performing colec-
tomy even after successful PD. Furthermore, patients who did not undergo colec-
tomy after PD commonly followed a non-operative pathway because they were unfit
for surgery, refused colectomy or lost to follow-up.
Failure of PD requiring urgent fecal diversion with or without colectomy was
reported in 20 studies and was required in 9.4 (0–33) percent of cases with various
definitions of failure (Table 26.3). Operative indications for failed PD largely
depended on clinical parameters of infection and peritonitis, as well as surgeon
preference. Elective colectomy after successful PD was performed in 64.3 (33–100)
percent of cases with no clear operative criteria. Gaertner et al [23] reported the
largest experience with interval colectomy (137 of 191 patients [72 %]) after suc-
cessful PD but did not specify operative indications or the morbidity of interval
colectomy after successful PD. The overall postoperative morbidity rate of elective
colectomy after successful PD was 7 (0–28.6) percent in 7 of 21 studies. Severity of
postoperative morbidity after interval colectomy and its association with operative
approach (laparoscopic vs. open) was not described in detail in the reviewed
studies.
Table 26.2 Descriptive data of the analyzed studies
Patients managed Average size Immunosuppressed patients
Level of with percutaneous of drained managed with percutaneous Average
Author (year) Study type evidence drainage (%) abscess (cm) drainage alone (%) follow-up (m)
Saini et al. (1986) [8] PSI 4 8 (73) NS NS NS
Mueller et al. (1987) [9] PSI 4 21 (100) NS NS 10
Neff et al. (1987) [10] PSI 4 16 (100) NS NS 12–29
Stabile et al. (1990) [11] PNR 4 19 (100) 8.7 NS 17.4
Hachigian et al. (1992) [12] PSI 4 4 (31) NS NS NS
Ambrosetti et al. (1992) [13] PSI 3b 1 (4.5) NS NS 24
Bahadursingh et al. (2003) [14] R 4 6 (24) NS NS NS
Macias et al. (2004) [15] R 4 10 (36) 5.8 NS NS
Ambrosetti et al. (2005) [16] PSI 3b 19 (26) 6.7 NS 43a
Kaiser et al. (2005) [17] R 4 16 (16) 7.1 NS 46.5
Siewert et al. (2006) [18] R 4 4 (13) 5.9 NS 13.1a
Durmishi et al. (2006) [19] R 4 34 (100) 6.0 NS NS
Brandt et al. (2006) [5] CC 3b 34 (52) 6.0 NS NS
Singh et al. (2008) [20] R 4 16 (100) 8.5 3 (19) 34.8
Dharmarajan (2011) [21] R 4 38 (39) >4.0 NS 19.7
Van de Wall (2013) [22] R 4 54 (8.1) >5.0 NS 27.5a
Gaertner et al. (2013) [23] R 4 191 (100) 4.7 7 (21.8) 88.8
Felder et al. (2013) [24] R 4 40 (100) 5.6 ± 2.0 5 (13) 46.8a
Subhas et al. (2014) [25] R 4 42 (35.8) 6.3 NS NS
Elagili et al. (2015) [26] R 4 133 (100) 5.0 1/18 (5.5) 90a
26 Do We Need to Operate on Patients After Successful Percutaneous Drainage
Knapp et al. (2015)b [27] R 4 29 (100) NS NS NS

R retrospective series, CC case control study, PSI prospective single institution series, PNR prospective nonrandomized series, NA not applicable, NS not specified
a
Median
b
Meeting abstract
285
Table 26.3 Outcomes after percutaneous drainage of diverticular abscess
286
Postoperative morbidity for Overall symptomatic

Colectomy or fecal diversion Elective colectomy after elective colectomy after recurrence after
for failed percutaneous successful percutaneous successful percutaneous percutaneous drainage
Author (year) drainage (%) drainage (%) drainage (%) alone (%)
Saini et al. (1986) [8] 0 (0) 7 (87.5) 0 (0) NA
Mueller et al. (1987) [9] 0 (0) 17 (80.9) NS 2/3 (66.6)
Neff et al. (1987) [10] 1 (6.2) 11 (68.7) 0 (0) 1/4 (25)
Stabile et al. (1990) [11] 3 (15.7) 14 (73.6) 0 (0) 3/3 (100)
Hachigian et al. (1992) [12] 0 (0) 4 (100) NS NA
Ambrosetti et al. (1992) [13] 0 (0) 1 (100) NS NA
Bahadursingh et al. (2003) [14] 0 (0) NS NS NS
Macias et al. (2004) [15] 0 (0) NS NS 3/10 (30)
Ambrosetti et al. (2005) [16] NS NS NS NS
Kaiser et al. (2005) [17] 1 (6.2) 3 (18.7) NS 5/16 (41.7)
Siewert et al. (2006) [18] 0 (0) 4 (100) NS 1/4 (25)
Durmishi et al. (2006) [19] 10 (29.4) 12 (52.1) 0 (0) 2/11 (18.1)
Brandt et al. (2006) [5] 10 (29.4) 12 (52.1) 0 (0) 2/11 (18.1)
Singh et al. (2008) [20] 0 (0) 8 (50) NS 2/8 (25)
Dharmarajan (2011) [21] NS NS 16 (21) NS
Van de Wall (2013) [22] 0 (0) 22 (40.7) NS 18/54 (33.4)
Gaertner et al. (2013) [23] 22 (11.5) 137 (71.7) NS 10/32 (31.2)
Felder et al. (2013) [24] 13 (33) 20 (50) NS 0/7 (0)
Subhas et al. (2014) [25] 13 (30.9) 14 (33.3) NS NS
Elagili et al. (2015) [26] 22 (16.5) NS NS 7/15 (46.6)
Knapp et al. (2015)** [27] 0 (0) 14 (49.7) 4 (28.6) NS
NA not applicable, NS not specified
W.B. Gaertner and R.D. Madoff
26 Do We Need to Operate on Patients After Successful Percutaneous Drainage 287
The definition of recurrent diverticulitis after successful PD varied amongst stud-

ies and included clinical recurrence of abdominal and infectious symptoms as well as
computed tomography-proven diverticulitis or abscess. Persistent colo-cutaneous
fistula as a result of PD was not specifically described as persistent or recurrent dis-
ease in any of the studies. Overall, recurrent diverticulitis after successful PD was
reported in 13 of 21 studies and occurred in 35.4 % (0–100 %) of cases. Average fol-
low-up of patients after PD was 41.0 (13.1–90) months. Van de Wall and colleagues
[22] demonstrated that colectomy for recurrent diverticulitis after successful PD was
most commonly performed in the first year after initial abscess presentation.
The presence of severe medical comorbidities and immunosuppression was
inconsistently reported in patients who underwent PD alone. Four studies reported
the number of immunosuppressed patients with an average rate of 14.8 %. Factors
associated with recurrent diverticulitis and the need for colectomy included abscess
size >5 cm [23], pelvic abscess [16], and >2 PD procedures [25]. Felder et al [24]
identified immunosuppression and renal insufficiency as independent risk factors
for failure of PD and need for emergent colectomy. No significant associations
between failure of PD or recurrent diverticulitis and previous episodes of diverticu-
litis and patient age were identified [17, 23, 26].
Percutaneous drainage allows for the resolution of intra-abdominal sepsis for most
cases of diverticular abscess, and has been associated with an increased rate of
single-stage colectomy with primary colorectal anastomosis, as well as decreased
perioperative morbidity and mortality when compared to urgent Hartmann’s proce-
dure [17, 28]. The majority of cases of successful PD for diverticular abscess
reported in the literature underwent interval colectomy regardless of symptoms,
with no clear operative criteria. Patients treated with PD alone are typically man-
aged this way because of prohibitive operative risk, severe co-morbidities, or refusal
of colectomy. Based on the current literature, patients with diverticular abscess who
undergo successful PD alone have a 35 % rate of recurrent diverticulitis, while those
who undergo interval colectomy have a 7 % postoperative morbidity rate and negli-
gible recurrent diverticulitis.
• Elective colectomy should typically be considered in patients with appropriate
operative risk, after an acute episode of diverticular abscess has resolved with
PD. Grade of Recommendation: weak recommendation based on low-quality
evidence, 2C.
• Percutaneous drainage of colonic diverticular abscess without subsequent colec-
tomy appears to be a safe, low-risk, and reasonable management option in selec-
tive patients with prohibitive operative risk or in healthy patients who prefer to
avoid surgery. Grade of Recommendation: weak recommendation based on low-
quality evidence, 2C.
The need for colectomy after successful PD of a diverticular abscess has not been
well studied. The majority of studies describing the use of PD of diverticular abscess
did so to demonstrate its feasibility and safety with imaging guidance, as well as a
temporizing measure to decrease the perioperative morbidity of interval colectomy.
Many agree with the decision to not operate on patients with prohibitive operative
risk after successful PD, but what about the otherwise healthy individual? The cur-
rent literature would favor interval colectomy with low (7 %) morbidity as com-
pared to the risk of recurrent diverticulitis (35 %). Although limited, the current
literature would also support that recurrent diverticulitis after successful PD does
not typically require an emergency operation nor is it associated with an increased
risk of stoma with operative treatment. Recurrent or persistent disease after PD
alone typically presents with abdominal symptoms, CT-evidence of diverticulitis
without abscess or perforation, or a persistent colo-cutaneous fistula. Could patients
be followed closely for recurrent symptoms and managed accordingly without the
pre-emptive decision of performing interval colectomy? We believe that, ultimately,
the decision of whether to undergo colectomy after successful PD also depends
upon other factors including the number of episodes before abscess occurrence,
disease-free intervals, ready access to health care, and patient preference.
Our current practice is to recommend interval elective colectomy after successful
PD of a diverticular abscess in those patients with persistent abdominal symptoms
or complications such as fistula, those with a pattern of recurrent symptomatic
diverticulitis, and immunosuppressed patients who do not have prohibitive opera-
tive risk.
1. Elective colectomy should typically be considered in patients with appro-

priate operative risk, after an acute episode of diverticular abscess has
resolved with PD. Grade of Recommendation: weak recommendation
based on low-quality evidence, 2C.
2. Percutaneous drainage of colonic diverticular abscess without subsequent
colectomy appears to be a safe, low-risk, and reasonable management
option in selective patients with prohibitive operative risk or in healthy
patients who prefer to avoid surgery. Grade of Recommendation: weak
recommendation based on low-quality evidence, 2C.
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5. Brandt D, Gervaz P, Durmishi Y, Platon A, Morel P, Poletti PA. Percutaneous Ct scan-guided
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6. Rafferty J, Shellito P, Hyman NH, Buie WD. Standards Committee of American Society of
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7. Feingold D, Steele SR, Lee S, Kaiser A, Boushey R, Buie WD, Rafferty JF. Practice parame-
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11. Stabile BE, Puccio E, van Sonnenberg E, Neff CC. Preoperative percutaneous drainage of
diverticular abscesses. Am J Surg. 1990;159:99–104.
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Colon Rectum. 2005;48:787–91.
17. Kaiser AM, Jiang JK, Lake JP, et al. The management of complicated diverticulitis and the role
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Chapter 27
The Role of Laparoscopic Peritoneal Lavage
in the Operative Management of Hinchey III
Diverticulitis
Lisa Marie Cannon
Introduction
The 2014 American Society of Colon and Rectal Surgeons practice parameters for
the treatment of sigmoid diverticulitis recommend urgent sigmoid colectomy for
patients presenting with diffuse peritonitis or for those in whose initial nonoperative
management fails [1]. While open Hartmann’s procedure has been long considered
the ‘gold standard’ in these situations, primary anastomosis with proximal diversion
is increasingly supported in recent literature [2, 3]. Laparoscopic sigmoidectomy in
the emergency setting is safe, with decreased morbidity compared to open sigmoid-
ectomy [4].
In the only recent randomized clinical trial (RCT)comparing primary anastomo-
sis with diversion to Hartmann’s procedure in the emergency setting, Oberkofler [3]
reported similar outcomes with the initial colectomy, but superior overall results in
the primary anastomosis group owing to the higher rate of stoma closure and rela-
tive safety/efficiency of ileostomy closure as opposed to Hartmann takedown. The
trial has been criticized for the influence of surgeon discretion on the choice of
technique, as well as calculation of the sample size [5, 6]. A similar RCT [7] was
prematurely terminated due to slow accrual.
Stoma avoidance altogether in the emergency setting is also described in limited
and somewhat dated series; intraoperative colonic lavage is often employed in these
studies to prepare the colon for primary anastomosis, with acceptable morbidity and
anastomotic leak rates [8, 9]. Two recent retrospective analysis also concluded that
primary anastomosis without diversion is an appropriate option in the urgent s etting,
L.M. Cannon, MD
Section of Colon and Rectal Surgery, Department of General Surgery, University of Chicago
Medicine, 5841 S. Maryland Avenue, MC 5094, Chicago, IL 60637, USA

DOI 10.1007/978-3-319-40223-9_27
292 L.M. Cannon
including patients with Hinchey III (purulent) and Hinchey IV (feculent) peritonitis;
careful patient selection is advised [10, 11].
The broad body of literature does not stratify outcomes based on intraoperative
Hinchey classification, though authors recognize that patients with Hinchey IV dis-
ease are likely to have increased perioperative morbidity and mortality as compared
to those with Hinchey III disease. Pending further meta-analysis or randomized
trials, choice of operation in the emergency setting is still predicated on surgeon
experience and preference.
Attempts at nonoperative management in patients presenting with complicated
diverticulitis including extra-digestive air and free fluid is supported by single-
institution series. In one series including 136 patients, ~88 % of patients with extra-
digestive air >2 cm, non-loculated fluid, or abscess >4 cm were able to be successfully
treated without surgery [12]. Another study reported similar results, with an 86 %
success rate in 132 patients with nonoperative management in the absence of diffuse
peritonitis or free pelvic fluid [13]. One study including 39 patients, ¾ of whom
presented with signs of peritonitis, described a 92 % success rate with nonoperative
management [14].
Elective sigmoidectomy after episodes of acute uncomplicated diverticulitis is an
individualized, case by case decision based on patient specific factors. In contrast,
patients with complicated diverticulitis who are successfully managed nonopera-
tively are still generally offered elective resection owing to high recurrence rates [1].
The technique of laparoscopic peritoneal lavage, first described and largely pop-
ularized in European centers [15], challenges both the notion that sigmoidectomy is
necessary in patients requiring emergency operative intervention, and that elective
resection is really required in patients that do successfully navigate an initial nonre-
sectional approach. This chapter aims to examine the evidence for or against lapa-
roscopic peritoneal lavage.
Search Strategy
Using the PICO format, laparoscopic peritoneal lavage (hereafter also referred to as
simply ‘lavage’) was compared to any technique of sigmoidectomy—laparoscopic
or open Hartmann’s procedure or primary anastomosis with or without diversion—
in patients presenting with Hinchey III diverticulitis requiring operative intervention
due to generalized peritonitis or failure of medical management (Table 27.1). The
outcomes evaluated were morbidity and mortality, non-resolution requiring reinter-
vention and sigmoidectomy, rate of disease recurrence requiring sigmoidectomy,

Hinchey III Sigmoidectomy (Hartmann’s or Laparoscopic Resolution
diverticulitis primary resection and anastomosis peritoneal lavage recurrence
with or without diversion) (washout)
27 Role of Lavage in Hinchey III Diverticulitis 293
and the number of patients who are symptom free with no episodes of recurrence
(definitive lavage), or those who were successfully able to undergo elective sigmoid-
ectomy prior to a recurrent episode (lavage as a bridge to elective resection).
A systematic literature search was performed of MEDLINE and PubMed to iden-
tify English language publications related to utilization of laparoscopic peritoneal
lavage in perforated diverticulitis, published from January 1990 through December
2015. Combinations of key words were constructed and applied to these databases.
The search strategy used in MEDLINE included both MeSH subject headings when
possible and/or keyword mapping alias operator commands for the terms ‘diverticu-
litis’ or ‘diverticulum’, AND ‘laparoscopy’ or ‘laparoscopic’, AND ‘peritoneal
lavage’, ‘lavage’, or ‘therapeutic irrigation’. Similar combinations were then applied
to PubMed. The biographies of all the original articles were then explored for any
additional germane publications. Studies that did not include more than one laparo-
scopic peritoneal lavage or therapeutic irrigation patient were excluded. Case
reports, letters, systematic reviews, and duplicate articles were also excluded.
Results
Twenty-two English language studies were identified. Several studies represented

extended series including previously reported patients [15–22]. One database analy-
sis out of Ireland [23] may include the patients reported by Myers et al. [24].
Results of Low and Very-Low Quality Studies
Using the GRADE system approach to developing practice guidelines, 19 of 22

studies were rated either low or very low quality; reasons for this included small
sample size, lack of institutional comparator, allocation concealment, surgeon bias,
failure to adhere to the intention-to-treat principle, and lack of reporting on salient
outcome metrics such as non-resolution or recurrence requiring resection. Most of
the excluded studies had more than one of these limitations. These studies are sum-
marized in Table 27.2.
There are a total of 946 patients represented by low or very low quality studies
undergoing laparoscopic peritoneal lavage and at least 758 are presumed unique
patients across a 22-year period (1991–2013). Of studies clearly reporting intraop-
erative Hinchey classification, 76 % of patients (311 of 416) had Hinchey III diver-
ticulitis, defined as free purulent contamination of the peritoneal cavity. Some
studies allowed patients who had failed an initial trial of medical management with
or without percutaneous drainage of accessible abscess cavities; others only
included patients determined to be urgent surgical candidates on presentation. Four
studies included an intraoperative decision point to proceed with lavage, recogniz-
ing the inherent surgeon bias in this approach.
Table 27.2 Low and very low quality evidence on laparoscopic peritoneal lavage
294
Non- Elective
resolution resection
Unique requiring Recurrence without Symptom
Study lavage Morbidity Death resection requiring recurrence free, no
Study period patients H3 Lavage population (%) (%) (%) resection (%) (%) resection (%)
O’Sullivan ‘91–‘94 8 8 CD and GP 2 (25) 0 0 0 0 6 (75)
et al. [16] intra-op; (H3 only)
Faranda et al. ‘94-‘98 18 16 CD and GP on 3 (17) 0 0 NR 15 (83) NR
[24] presentation ~4 m
Mutter et al. ’96–‘03 10 10 CD, (−) PCD, 0 0 1 (10) 0 6 (60) NR
[29] intra-op with (−) ~2–3 m
GP, (−) visible
perforation, (−) H4
Taylor et al. ’02–‘05 14 10 CD with 0 (major) 0 3 (21) 0 8 (57) 2 (14)
[20] perforation 2–15 m ~6w later 2–15 m
Bretagnol ’00–‘04 24 18 CD and GP or 2 (8) 0 0 0 24 (100 %) 0
et al. [18] FoMM or septic ~4 m; 2–6 m ~4 m;
shock 2–6 m
Franklin et al. ’91–‘06 40 32 CD and GP 8 (20) 0 0 0 24a (60) 16 (40)
[22] 96 m; 96 m;
1–168 m 1–168 m
Myers et al. ’00–‘07 92 67 CD and GP; (+) (4) 3 (3.2) 1 (2) 0 0 88 (96)
[26] free air, (−) H4 36 m; 36 m; 36 m;
12–84 m 12–84 m 12–84 m
Favuzza et al. NR 7 NR CD and peritonitis; NR 0 1 (14) 1 (14) 5 (71) 0
[30] Imaging (+) fluid 3 m
(−) discrete
abscess
L.M. Cannon
Karoui et al. ’94–‘06 35 35 CD and GP on 9 (26) 0 1 (3) 0 25 (71) 8 (23)
[23] presentation (H3 4 m; 2–7 21 m; 7–48 m
only)
White et al. ’99–‘08 35 11 CD and GP, or (+) 19 (54) 0 8 (23) 8 (23) 8 (23) 11 (31)
[19] free air or 2QP (+) 6 m; 2–12 m 2–3 m later 20 m; 6–60 m
>3 cm collection
with FoMM
Liang et al. ’91–‘10 47 36 CD and GP with 2 (4) 0 3 (6.4) 0 18a (38) 26 (55)
[21] (+) free air and (+)
contrast
extravasation
Rogers et al. ’95–‘08 427 NR NR 60 (14) 17 (4) NR NR NR NR
[25]
Edieken et al. ’09–‘12 10 8 CD with FoMM or NR 0 3 (30) 3 (30) 0 NR
[31] (+) free air; (+)
27 Role of Lavage in Hinchey III Diverticulitis
HDS
Swank et al. ’08–‘10 38 33 CD with 17 (45) 4 (11) 5 (13) 3 (8) 0 30 (79)
[32] perforation; (+) 6–12 m 3 m
free air or H3
Gentile et al. ’09–‘12 14 3 CD with 3 (21) 1 (7) NR NR NR NR
[33] perforation (H2-3
only)
Rade et al. ’00–‘13 71 47 CD with GP; (−) 20 (28) 4 (6) 11 (15) NR 55 (77) NR
[17] shock (−) 3 m; 1–9 m
distention (−)
previous surg (−)
H4
(continued)
295
296
Non- Elective
resolution resection
Unique requiring Recurrence without Symptom
Study lavage Morbidity Death resection requiring recurrence free, no
Study period patients H3 Lavage population (%) (%) (%) resection (%) (%) resection (%)
Rossi et al. ’06–‘13 46 46 CD with GP; 11 (24) 0 5 (11) NR NR NR
[34] intra-op H3 only,
(+) HDS
Horesh et al. ’07–‘12 10 7 CD and peritonitis 3 (30 %) 0 1 (10 %) 2 (20 %) NR 6 (60 %)
[35] with (+) free air, or ~9 m
FoMM
Sorrentino ’01–‘13 63 54 CD and intra-op; 9 (14) 1 (2) 6 (10) 4 (7) 0 53 (84)
et al. [36] (−) fecal peritonitis ~5y ~5y
>1 quadrant
Shaded studies are those whose patients are represented within more current studies in the table
CD complicated diverticulitis, FoMM failure of medical management, GP generalized or 4-quadrant peritonitis, H Hinchey, HDS Hemodynamic stability, NR
Not recorded, PCD percutaneous drainage, 2QP 2-quadrant peritonitis
a
Value inferred from text
L.M. Cannon
Lavage technique varied, including decision to disrupt inflammatory adhesions,

use of pelvic drains, decision to patch, suture, or apply fibrin glue to visible perfora-
tions, volume of warm saline used, addition of agents to the irrigant (betadine or
heparin) and duration of postoperative antibiotics. It is not known whether any one
lavage technique positively or negatively influenced outcome.
Of unique studies reporting appropriate outcomes, the morbidity of lavage was
~19 %, with ~3 % mortality. Approximately 10 % of patients experienced non-
resolution after lavage requiring return to the operating room and sigmoidectomy
(~2/3 of studies reporting on this outcome); ~ 6 % of patients experienced a recur-
rence requiring sigmoid resection over a time frame ranging from 2 months to 14
years, ~28 % of patients underwent elective resection within 2–9 months after peri-
toneal lavage, and ~68 % of patients are symptom-free without any further interven-
tion over an unknown time interval (~1/2 of studies reporting on the aforementioned
three outcomes). The decision to proceed with elective resection was an institu-
tional tenet defining lavage as a strategy to bridge patients through an emergency
presentation so that they could undergo surgery in the elective setting. Other studies
highlighted lavage as a potentially definitive procedure.
If we are to define success of peritoneal lavage as those patients who are either
symptom-free with no recurrences or further intervention, or were able to undergo
elective resection prior to any recurrent episode, then lavage was known to be suc-
cessful in ~46 % of the total unique patient population represented by these studies,
with approximately half of studies not reporting on these outcomes.
Several authors suggested criteria to identify those who are likely to fail lavage,
including patients with elevated American Society of Anesthesia (ASA) classifica-
tion, immune suppression, or advanced age [17], those with Hinchey IV diverticuli-
tis (most series) or a visible perforation, and those with distention or obstruction
limiting technical feasibility of lavage.
Results of Randomized-Controlled Trials
Of the 22 studies identified, 3 are recent randomized controlled multicenter trials,

all rated high quality based on the GRADE system [37, 38, 39]. The results of these
studies are summarized in Table 27.3. To allow for better comparison between tri-
als, the author of this chapter utilized supplementary data from these trials to report
on similar outcomes; that is 30–90 day morbidity beyond IIIb, and mortality, exclud-
ing Hinchey IV patients.
The DILALA Trial [37] included patients at 9 Swedish and Danish institutions
from February 2010 to February 2014. All patients had extra-digestive fluid or gas
on radiologic evaluation, were intraoperatively determined to have Hinchey III gen-
eralized purulent peritonitis, and were randomized to either lavage or open
Hartmann’s procedure. The primary end-point of the published study was short-term
morbidity and mortality [37]; the primary endpoint of the trial will be the number of
re-operations at 12-month follow-up with additional secondary endpoints [25].
Table 27.3 Randomized controlled trials on laparoscopic peritoneal lavage
298
Elective
Non- resection
resolution Recurrence w/o Symptom
Patients requiring requiring recurrence free, no
excluded after Morbidity Death resection resection Stoma resection
Study N H3 randomization (%) (%) (%) (%) reversal (%) Conclusion
DILALA 83 CD and (+) free fluid/air and intra-op H3 Lavage is feasible and
Angente et al. [37] safe in short-term
Laparoscopic 43 43 4 8 (21) 3 (8) NR 0 0 NR analysis of patients.
lavage 2 neoplasm ≥IIIb; 30d 90d 3 m 3 m Long-term outcomes
2 other awaiting publication
Open Hartmann’s 40 40 4 6 (17) 4 (11) NR
1 neoplasm ≥IIIb; 30d 90d
3 other
LOLA/LADIES 90 CD and GP with (+) free fluid/air and intra-op H3; (−) HDS, (−) high dose steroids DSMB terminated
Vennix et al. [38] LOLA arm early due
Laparoscopic 47 47 1 protocol 20 (44) 2 (4) 9 (20) 6 (13) 1b (2) 24 (52) to high short-term
Lavage violation ≥IIIb; 90d 30d ~12 m ~12 m ~12 m morbidity in the
Sigmoidectomya 43 43 1 intra-op 12 (29) 1 (2) 24/35 (71) lavage group
neoplasm ≥IIIb; 90d 30d <12 m
L.M. Cannon
SCANDIV 199 CD and GP; (−) obstruction, (−) pregnancy; intra-op (−) H4c, (−) wrong diagnosis Lavage led to worse
Schultz et al. [39] outcomes; Findings
Lavage 101 69 27c 19 (26) 6 (8) NR NR NR NR do not support lavage
12 with no CD ≥IIIbc; 90d 90dc in the treatment of
15 with H4 diverticulitis
Sigmoidectomya 98 61 28c 10 (14) 5 (7) NR
27 Role of Lavage in Hinchey III Diverticulitis
13 with no CD ≥IIIbc; 90d 90dc

13 with H4
2 other
CD complicated diverticulitis, NR Not recorded, H Hinchey, HDS Hemodynamic stability, GP generalized peritonitis, DSMB Data & safety monitoring board
a
Laparoscopic or open Hartmann’s procedure, or primary resection and anastomosis +/− diversion at surgeon’s discretion
b
Four additional resections for cancer
c
H4 included in primary outcome analysis in SCANDIV; shown are only H1-3 values to allow for better comparison between RCTs
299
300 L.M. Cannon
The LOLA group of the LADIES trial [38] involved 42 hospitals in Belgium,
Italy, and the Netherlands from July 2010 to February 2013. The LOLA group was
designed to compare lavage to sigmoidectomy—Hartmann’s or primary anastomo-
sis with or without diversion—in Hinchey III diverticulitis. A separate subgroup
analysis compared Hartmann’s procedure vs. resection and primary anastomosis in
both Hinchey III and IV diverticulitis and is not relevant to the aim of this chapter.
Patients with generalized peritonitis and radiologic evidence of diffuse extra-
digestive fluid or gas were randomized during diagnostic laparoscopy; those with
Hinchey III purulent peritonitis were then eligible for the LOLA group. Patients on
high-dose steroids, dementia, advanced age, or hemodynamic instability were
excluded. The primary end-point of the LOLA group was a composite including
major morbidity and mortality within 12 months.
The SCANDIV Trial [39] included patients at 21 participating centers in Sweden
and Norway from February 2010 to June 2014. Patients with diverticulitis and perito-
nitis were randomized to receive lavage or sigmoidectomy— Hartmann’s or primary
anastomosis with or without diversion— and then underwent diagnostic laparoscopy.
Those with a non-diverticular pathology identified intraoperatively were then excluded
from all but the primary analysis. Those with Hinchey IV feculent peritonitis were
randomized but were included only in a modified intention-to-treat analysis, as they
all underwent sigmoidectomy. Those with Hinchey I-III disease, and those with
Hinchey IV disease, were analyzed separately in regard to secondary outcome mea-
sures. The primary outcome was severe postoperative complications within 90 days.
The short-term analysis of the DILALA trial concluded that lavage for Hinchey
III diverticulitis, as compared to open Hartmann’s procedure, is feasible and safe in
the short term with no difference in30-day ≥ IIIb morbidity (21 % vs. 17 %, respec-
tively) or 90-day mortality (7.7 % vs. 11.4 %, respectively), and resulted in shorter
operating time and length of stay. This trial is awaiting final review and publication
of its 12-month outcomes.
The other trials, LOLA/LADIES and SCANDIV, did not support use of lavage.
The LOLA group of the LADIES trial was terminated early by the Data Safety &
Monitoring Board (DSMB) due to increased event rate defined as in-hospital major
morbidity or mortality in the laparoscopic lavage group, with 37 events in the lavage
group and 10 events in the sigmoidectomy group (p = 0.0005), owing mainly to an
increased rate of surgical re-intervention. The study was not sufficiently powered to
make a statement on inferiority of lavage, but suggested that it is not superior.
Twenty percentage of lavage patients required sigmoidectomy due to non-resolution
of their inflammatory process. 52 % of lavage patients were symptom free with no
recurrence at 12-month follow up. Four cancers were missed in the lavage group
and later required resection.
The SCANDIV trial was carried to completion. While 90-day ≥ IIIb morbidity
and mortality was no different, patients undergoing lavage had a significantly higher
reoperation rate within 90 days (20.3 % vs. 5.7 % in the sigmoidectomy group,
p 0.01) in patients with Hinchey I-III diverticulitis. Hospital stay was not signifi-
cantly different. As with LOLA/LADIES, four cancers were missed in the lavage
group and later required resection.
There are some outcome measures for which lavage is clearly superior. The signifi-
cantly shorter operating time offered by lavage is widely supported by both low-
and high quality literature. While this makes lavage a tempting strategy for the
surgeon to deploy in the emergency setting, the clinical benefit of a 1-h lavage vs. a
2- or 3- h sigmoidectomy is questionable. Length of stay in the lavage group was not
significantly different in the SCANDIV or LOLA/LADIES Trials; it was signifi-
cantly shorter in the DILALA Trial (6 vs. 9 days; p 0.037) [37, 38, 39].
In order to make a recommendation on the role of laparoscopic peritoneal lavage
in the management of Hinchey III diverticulitis, one must define what is an accept-
able and unacceptable outcome. For whom is this intervention applicable, how
should it be applied, and what are the outcomes of alternative techniques? Is laparo-
scopic peritoneal lavage a rescue procedure meant to bridge a patient to elective
resection with the goal of stoma avoidance, or is lavage better defined as a definitive
intervention?
The author defined unacceptable outcomes in utilization of the lavage technique
as significantly increased morbidity and mortality, non-resolution requiring resec-
tion, and missed neoplasm.
In patients presenting with Hinchey III diverticulitis and peritonitis, there is no
subset for which laparoscopic peritoneal lavage is clearly the preferred method, as
compared to sigmoidectomy. (Recommendation: Conditional; Quality of
Evidence: High)
In patients presenting with Hinchey III diverticulitis and generalized peritonitis
or who are failing nonoperative management, there is no subset of patients for
which laparoscopic peritoneal lavage is clearly the preferred method compared to
sigmoidectomy. This is a conditional recommendation based on high quality evi-
dence with limited long-term data and lack of reporting on some of the outcomes of
interest. Two randomized trials demonstrated a significant rate of surgical reinter-
vention in the lavage group, many of which were take-backs for sigmoidectomy.
Thirty to ninety day major (≥IIIb) morbidity in the three RCTs ranged from
21–44 % in the lavage group and 17–29 % in the sigmoidectomy group. Thirty to
ninety day mortality ranged from 4–8 % in the lavage group and 2–11 % in the sig-
moidectomy group. The overall reported major morbidity and mortality in the
sigmoidectomy group in these three RCTs is lower than historically reported for the
emergency setting, which may not be entirely explained by increased use of laparo-
scopic resection or improved perioperative care. The rate of recurrent diverticulitis
after laparoscopic peritoneal lavage, when reported, is markedly lower than is
expected after an episode of complicated diverticulitis and suggests further research
is needed.
Patients with high ASA class, advanced age, immune suppression, distention or
obstruction, or feculent peritonitis (Hinchey IV) should not be offered laparoscopic
peritoneal lavage. An intraoperative assessment prior to any decision to proceed with
lavage is reasonable. (Recommendation: Conditional; Quality of Evidence: Low)
302 L.M. Cannon
There is no defined group for which laparoscopic peritoneal lavage is clearly

favored, but there are several patient subsets in whom lavage should not be consid-
ered. The majority of low and very-low quality studies do not recommend this
approach in Hinchey IV feculent peritonitis [16–20, 23, 26, 31, 33, 35–37].
Obstruction and bowel distention, as with any laparoscopic technique, limits visibil-
ity and precludes lavage [19, 31]. Rade et al. were the only authors to analyze factors
predicting failure of the approach; patients with ASA class >2, advanced age
>80 years, and immunocompromised patients were significantly more likely to
require re-intervention due to failure of lavage [17]. The recommendation to exclude
patients with Hinchey IV peritonitis, obstruction, advanced age, immune suppres-
sion, and high ASA class is conditional based on low quality evidence. Recognizing
that not all patients with Hinchey III purulent peritonitis are alike, fully embracing
surgeon discretion with diagnostic laparoscopy and intraoperative assessment prior
to the decision to proceed with lavage is reasonable if use of the technique is desired,
pending further data which may better guide patient selection and risk stratification.
If laparoscopic peritoneal lavage is to be used as a definitive or bridging strat-
egy, recent complete colonoscopy should be documented in order to avoid missed
neoplasm. (Recommendation: Strong; Quality of Evidence: Low)
While most studies excluded patients in whom cancer was apparent during initial
operation, this cannot always be known intraoperatively. In the case of neoplasm
masquerading as perforated diverticulitis, the strategy of sigmoidectomy clearly
results in a more immediate diagnosis and therapy. Resection according to onco-
logic principles should be considered if recent colonoscopy is not documented.
Three observational studies [19, 26, 33] and two randomized controlled trials [38,
39] reported on a total of 12 cancers that were not noted during laparoscopic perito-
neal lavage. How many patients need to benefit from successful lavage for a missed
neoplasm to be acceptable? It is unclear whether the delay in diagnosis caused by
utilization of lavage influenced recurrence or survival these patients. If laparoscopic
peritoneal lavage is to be used as a definitive strategy or as a bridge to elective resec-
tion, complete colonoscopy should be performed in order to avoid missed neoplasm.
This is a strong recommendation based on low quality evidence, with risk of harm
clearly outweighing reported benefit.
In the author’s opinion, the current evidence forecasts a future of low applicability
of the technique of laparoscopic peritoneal lavage. There is no clear patient popula-
tion standing to benefit, and this approach is not used in practice at our institution.
Stoma formation is an undesirable consequence of emergency surgery for diver-
ticulitis. Though the morbidity is lower than end colostomy takedown, diverting
loop ileostomy reversal does carry risk [3]. The technique of primary anastomosis
without diversion for diverticulitis in the emergency setting is described but limited
to observational series [9–12]. Stoma avoidance was not factored in to the proposed
recommendations. This is because the small number of patients present in the lavage
literature who underwent sigmoidectomy without stoma formation limits this
author’s ability to make an evidence-based recommendation. That said, the LOLA/
LADIES Trial [38] and the SCANDIV Trial [39] both reported on quality of life in
patients up to 6 months postoperatively, with no significant differences in the lavage
and sigmoidectomy groups; 16–24 % vs. 69–83 % had a stoma, respectively. This
suggests patients are capable of adapting reasonably well to temporary stoma for-
mation in the setting of emergent surgery for diverticulitis.
Future randomized controlled trials as well as longer follow up of the current
laparoscopic peritoneal lavage cohort are likely to influence the author’s conclusion.
After successful nonoperative management of acute complicated diverticulitis,
recurrence rates range from 28 to >40 %, and elective resection is recommended [1,
26, 27]. Particularly for surgeons’ whose attitude is in support of restorative resec-
tion and primary anastomosis without stoma formation—including in the setting of
Hinchey III diverticulitis— laparoscopic lavage does not avoid a secondary major
surgical intervention and attendant morbidity, making it an unappealing option. If
the validity of laparoscopic primary resection and anastomosis as one-stage man-
agement of Hinchey III diverticulitis is demonstrated in larger prospective studies,
this is likely to further weaken the case for lavage. We would no longer need to fac-
tor in the known morbidity of a temporary stoma and takedown in those undergoing
emergent resection.
The high recurrence rates reported after nonoperative management has also led
to reasonable speculation that in these instances of short-term “recurrence”, the
original episode has actually not resolved— so-called ‘smoldering’ diverticulitis. In
contrast, after appropriate resection with colorectal anastomosis, recurrence is <3 %
[28]. Follow up of the current lavage cohort indicates astonishingly lower recur-
rence rates then are historically expected for complicated diverticulitis; does this
suggest that lavage may alter the natural history of Hinchey III diverticulitis in a
way not previously described? If this is substantiated, the increased rate of interven-
tion with lavage due to non-resolution may be acceptable if it means the greater
cohort is able to avoid emergent stoma formation, need for elective resection, and
future recurrence. One can easily envision a shift toward the strategy of laparo-
scopic peritoneal lavage in lower acuity patients, with greater applicability to
Hinchey II patients, if long-term symptom-free resolution and these compellingly
low recurrence rates are observed in prospective studies. As mentioned earlier, any
nonresectional management approach should be limited to patients with recent
complete colonoscopy, in order to avoid missed neoplasm.
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Chapter 28
Surgery for Acute Complicated Diverticulitis:
Hartmann vs. Primary Anastomosis
Nitin Mishra and David A. Etzioni
Introduction
Acute diverticulitis is a significant and growing problem within the United States,
accounting for over 160,000 hospitalizations per year and 875,000 days of inpatient
care [1]. Rates of admission for acute diverticulitis are increasing, especially in the
younger population [1, 2]. While the vast majority of cases can be managed without
surgery, approximately 14 % require surgical intervention [1].
Historically, the most commonly performed operation performed for sigmoid
diverticulitis is a Hartmann’s procedure, in which the diseased segment of bowel is
resected and an end colostomy formed [3]. As a surgical option, the Hartmann’s
procedure eliminates the risk of anastomotic complications at the time of initial
surgery. By delaying anastomosis until there is complete resolution of pelvic inflam-
mation, the risk of anastomotic leak is theoretically minimized. The risk of subse-
quent operation for restoration of bowel continuity is not without its own morbidity,
however, with reported anastomotic leak rates of up to 30 %, and a reported mortal-
ity of up to 14.3 % [3–9]. As a result of the burden associated with colostomy rever-
sal, a significant number of patients will never have the colostomy reversed, resulting
in a permanent stoma [10, 11].
The natural alternative to a Hartmann’s procedure is resection with primary anas-
tomosis. The goal of this approach is to reduce the morbidity and mortality associ-
ated with the reversal of Hartmann’s procedure, while maintaining an acceptable
level of risk associated with anastomosis at the time of an urgent operation [6, 12].
With the intent of minimizing this risk, surgeons may choose to employ a defunc-
tioning ostomy. Defunctioning ostomies (either loop ileostomy or loop colostomy)
N. Mishra, MD • D.A. Etzioni, MD, MSHS (*)

Division of Colon and Rectum Surgery, Mayo Clinic Hospital, Phoenix, AZ, USA

DOI 10.1007/978-3-319-40223-9_28
308 N. Mishra and D.A. Etzioni
may serve to reduce rates of anastomotic leak while lowering the burden of the
subsequent reoperation and restoration of gastrointestinal continuity.
The choice of which of these operations is controversial, and depends upon
patient and surgeon factors. Current guidelines published by the American Society
of Colon and Rectal Surgeons recommend immediate resection in the setting of
purulent or fecal peritonitis (Hinchey III and IV), but do not offer any distinct guid-
ance regarding the decision between Hartmann’s procedure or primary anastomosis
[13]. In this chapter, studies published over the last 20 years are evaluated to decide
which operation (Hartmann’s vs. primary anastomosis) should be preferred in treat-
ing acute diverticulitis. Options such as laparoscopic lavage have been intentionally
excluded as the purpose of the chapter is to compare Hartmann’s procedure to a
primary anastomosis.
Methods/Search Strategy
To identify articles for inclusion in this review, we searched the MEDLINE data-
base. The primary goal was to identify studies reporting outcomes of patients with
acute diverticulitis who underwent surgical treatment with either Hartmann’s proce-
dure or primary anastomosis. Case reports, case series with 20 or fewer patients,
case series with less than 10 patients in either of the intervention groups, and studies
where no novel patient outcomes were reported (e.g. review articles) were excluded.
Systematic reviews and meta-analyses were included, but considered separately.
We started our search by querying for diverticulitis, Hartmann and anastomosis
as keywords, in the following orientation: (“diverticulitis” AND [“Hartmann” OR
“anastomosis”]). The following limits were placed on the search: articles written in
English, involving humans and published from January 1, 1995 to 2016. This initial
search strategy yielded 295 articles. Abstracts of all articles were reviewed, as well
as full text when a study potentially met the inclusion criteria. References from
articles retrieved through this query were also examined for inclusion. A total of 24
articles were eligible for the final review.
Pt population Intervention Comparator Outcome studies

Pts with complicated Primary anastomosis (with Hartmann’s Morbidity,
diverticulitis or without diversion) procedure mortality
Results
The articles included in this review were individually analyzed for quality of evidence
as per the GRADE criteria [14]. The results of the search are listed in Table 28.1.
A total of 24 articles (2 RCTs, 2 meta-analyses, 3 large database studies, 2 sys-
tematic reviews, 2 prospective cohort studies and 13 retrospective cohort studies)
were reviewed. Analysis of the results based on study types and outcomes are sum-
marized below:
Table 28.1 Summary of all studies included in this review
Patients Patients Patients Evidence
Author Year Study design/data source (HP) (PA) (PAD) Author’s conclusion quality
Oberkofler [15] 2012 RCT 30 – 32 No difference in primary outcomes Low
between HP and PAa
Binda [16] 2012 RCT 34 56 – No difference in primary outcomes NA
between HP and PAa
Jafferji [17] 2014 Retrospective Cohort Study 74 20 32 PA is underutilized Very low
Hergoz [18] 2011 Retrospective Cohort Study 19 21 – PA superior to HP with lower morbidity Very low
and mortality
Miccini [19] 2011 Retrospective Cohort Study 85 28 – No difference in morbidity between PA Very low
and HP
Trenti [20] 2011 Retrospective Cohort Study 60 22 5 PA is safe with no difference in morbidity Very low
or mortality between PA and HP
Thornell [21] 2011 Retrospective Cohort Study 82 24 – Randomized trial needed to accurately Very low
answer this question
Mueller [22] 2011 Retrospective Cohort Study 26 36 11 Decision to make anastomosis should be Very low
made on patients general condition, not
local factors
Zingg [23] 2010 Retrospective Cohort Study 65 35 11 PA is not superior to HP. Diversion should Very low
be considered if PA is performed
Vermeulen [24] 2007 Retrospective Cohort Study 139 45 16 PA is not inferior to HP in carefully Very low
selected patients
Stumpf [25] 2007 Retrospective Cohort Study 30 36 – PA is safe in selected patients Very low
Zorcolo [26] 2003 Retrospective Cohort Study 86 29 – PA is safe and comparable to HP Very low
Blair [27] 2002 Retrospective Cohort Study 64 28 5 PA is safe Very low
Gooszen [28] 2001 Retrospective Cohort Study 28 – 32 Both PA and HP equivalent Very low
28 Surgery for Acute Complicated Diverticulitis: Hartmann vs. Primary Anastomosis
Wedell [29] 1997 Retrospective Cohort Study 15 10 4 PA superior to HP Very low
(continued)
309
310
Patients Patients Patients Evidence

Author Year Study design/data source (HP) (PA) (PAD) Author’s conclusion quality
Regenet [30] 2003 Prospective Cohort Study 33 27 – PA has less morbidity than HP Very low
Schilling [31] 2001 Prospective Cohort Study 42 13 – PA has lower cost than HP Very low
Tadlock [32] 2013 Retrospective Cohort Study 991 285 38 PA and PAD are safe compared to HP Low
NSQIP
Masoomi [33] 2012 Retrospective Cohort Study 56,875 39,023 3361 PA with diversion is superior to HP Low
NIS
Gawlick [34] 2012 Retrospective Cohort Study 1678 340 – No difference in morbidity and mortality Low
NSQIP between PA and HP
Cirocchi [35] 2013 Systematic review plus 246 174 – No conclusion could be drawn as evidence Low
meta-analysis quality low
Constantinides [36] 2006 Meta-analysis 416 547 – Overall reduced mortality in PA group Low
compared to HP
Abbas [37] 2006 Systematic review 526 358 – PA compares favorably to HP Very low
Salem [38] 2004 Systematic review 1051 431 93 PA is a safe alternative to HP Very low
HP Hartmann’s procedure, NIS Nationwide Inpatient Sample, NSQIP National Surgical Quality Improvement Program, PA primary anastomosis, PAD primary
anastomosis with diversion, RCT randomized controlled trial
a
Trial prematurely terminated due to poor patient accrual
N. Mishra and D.A. Etzioni
28 Surgery for Acute Complicated Diverticulitis: Hartmann vs. Primary Anastomosis 311
Randomized Control Trials (RCTs)
Two RCTs have been completed comparing outcomes between Hartmann’s proce-
dure and primary anastomosis in patients undergoing surgery for acute diverticulitis
[15, 16]. These studies, however, fare poorly on the Cochrane Collaboration’s tool
for assessing risk of bias [39]. Additionally, both studies were terminated prema-
turely due to lack of accrual of patients.
Oberkofler et al. conducted a multicenter RCT in Switzerland to compare
Hartmann’s and primary anastomosis with loop ileostomy in patients with left-sided
diverticulitis [15]. Their analytic approach considered the initial operation together
with the subsequent ostomy reversal. Their power analysis included a very liberal
estimate of expected differences in complication rates (40 % for primary anastomo-
sis, 80 % for Hartmann’s), and estimated that 68 patients should be enrolled. During
the 3 years that the study was conducted, the researchers were only able to recruit a
total of 62 patients (30 in Hartmann’s and 32 in primary anastomosis + ileostomy
group). In addition, 52 potential study patients were not assessed for eligibility
because of the surgeons’ choice not to enroll patients resulting in the potential for
significant selection bias [15]. Their analysis revealed differences in several end-
points in favor of primary anastomosis with loop ileostomy. Only 15 of 26 (58 %)
end colostomies (after Hartmann’s procedure) were eventually reversed, whereas the
stoma reversal rate after ileostomy was significantly higher at 90 % (26/29, P < 0.012).
Diverting ileostomies were reversed much earlier than the end colostomies after
Hartmann’s procedure (median 3 months vs. 6 months, respectively). The rate of
severe complications (20 % vs. 0 %, P = 0.046), as well as the total number of com-
plications per patient (median 1 vs. median 0, P < 0.001), was significantly higher
after reversal of Hartmann’s procedure (colostomy) compared to ileostomy reversal.
Anastomotic dehiscence, sepsis, and bleeding occurred only after reversal of the end
colostomy. Furthermore, the duration of the operation (183 min vs. 73 min, P < 0.001)
as well as the hospital stay (9 days vs. 6 days, P = 0.016) was significantly longer
after reversal of Hartmann’s procedure. Of note, all the advantages of primary anas-
tomosis with diverting ileostomy relate to the reversal operation.
Binda et al. from Norway conducted a multicenter RCT, but terminated it prema-
turely as they could recruit only 15 % of the target sample size (300 patients in each
group) in 9 years [16]. No conclusions could be drawn from this study.
Meta-analyses
Two meta-analyses have been performed that examined evidence regarding out-
comes in patients undergoing Hartmann’s procedure vs. primary anastomosis. The
first of these, conducted by Constantinides et al. in 2006 included a total of 15 stud-
ies; 10 of these studies were published between 1984 and 1995 and 5 after 1995 –
these 5 studies are a part of our review [36]. Results from this meta-analysis show
lower mortality with primary anastomosis than with Hartmann’s operation, (4.9 %
vs. 15.1 %). Another meta-analysis of 14 studies was performed by Cirocchi et al.

in 2013, and also found lower mortality rates with primary anastomosis than
Hartmann’s procedure (9.8 % vs. 22.0 %) in the treatment of acute diverticulitis. The
authors, however, found that the heterogeneity of the included studies was very high
and recommended that their findings be interpreted with caution [35].
Despite the intuitive appeal of relying on meta-analyses as a quantitative synthe-
sis of existing evidence, there is good reason to discount the findings from these two
studies. First, the technique of meta-analysis does not apply well to small, non-
randomized studies with heterogenous populations/interventions. This limitation
was articulated nicely in the study performed by Cirocchi [35]. Second, these stud-
ies are ambiguous as to whether they are estimating the clinical burden of the initial
operation or the initial operation plus any subsequent operations (to restore intesti-
nal continuity).
Database Studies
Three studies have been conducted using secondary databases in order to compare
outcomes of primary anastomosis vs. Hartmann’s procedure for acute diverticulitis
[32–34].
In 2012, Gawlick et al. published a study using patient data from the NSQIP
database in 2005–2009 to analyze 2018 patients undergoing surgery for acute diver-
ticulitis [34]. This study used wound classification (contaminated and dirty) as a
surrogate marker for severity in patients who underwent emergent surgery with a
diagnosis code of diverticulosis or diverticulitis. The study found no significant dif-
ference in the risk of infectious complications, return to the operating room, pro-
longed ventilator use, death, or hospital length of stay between Hartmann’s
procedure and primary anastomosis with diversion. In examining the subgroup of
patients where the operation was classified as dirty/infected, however, the adjusted
mortality rate was twice as high when primary anastomosis with diversion was per-
formed compared to the Hartmann’s procedure.
Also in 2012, Masoomi et al. published a study using discharge data from the
NIS between 2002 and 2007 to analyze 99,259 patients undergoing primary anasto-
mosis with diversion vs. Hartmann’s procedure for acute diverticulitis [33]. This
study found a lower complication rate in the primary anastomosis (plus diversion)
group compared with the Hartmann’s group (primary anastomosis: 39.06 % vs.
Hartmann’s: 40.84 %; p = 0.04). Mortality was lower in the primary anastomosis
group (3.99 % vs. 4.82 %, p = 0.03). However, patients in the Hartmann’s group had
a shorter mean length of stay (12.5 vs. 14.4 days, p < 0.001) and lower mean hospital
costs (USD 65,037 vs. USD 73,440, p < 0.01) compared with the primary anastomo-
sis group. This study, while based on a very large cohort of patients, may suffer
from issues regarding the granularity and accuracy of administrative coding. The
International Classification of Disease (ICD) coding scheme is not a perfect system
in terms of describing the type of operation performed, and there is the potential that
many of the patients in this study were mischaracterized in terms of the type of
surgical care they received.
In 2013, Tadlock et al. published a study using patient data from the NSQIP
database in 2005–2008 to analyze 1313 patients undergoing surgery for acute diver-
ticulitis [32]. Three operative approaches were analyzed: Hartmann’s procedure,
primary anastomosis without diversion, and primary anastomosis with diversion. In
this study, the 30-day mortality was 7.3 %, 4.6 %, and 1.6 %, respectively (P = 0.163),
while surgical site infections occurred in 19.7 %, 17.9 %, and 13.2 % of patients
(p = 0.59). In addition, the three groups did not have significant differences in surgi-
cal infectious complications, acute kidney injury, cardiovascular incidents, or
venous thromboembolism after surgery. The authors of this study concluded that
primary anastomosis in the acute setting is a safe alternative to a Hartmann’s proce-
dure, with no significant difference in mortality or postoperative surgical site
infections.
As with meta-analyses, the results from large database studies should be inter-
preted with caution. Statistical differences in outcomes may not always be clinically
significant due to the large sample sizes. This is illustrated by the small difference
in complication rate between the primary anastomosis group (39.06 %) compared
with the Hartmann’s procedure group (40.84 %) in the NIS study above which was
statistically significant (p = 0.04). More importantly, the translation of clinical phe-
nomena into accurate representation in codes (ICD or otherwise) may lead to inac-
curacy, bias, and confounding.
Retrospective/Prospective Cohort Studies
We reviewed 13 retrospective cohort studies and 2 prospective observational studies

examining patient outcomes with Hartmann’s vs. primary anastomosis [17–31, 40].
The quality and sample size vary widely, and taken together do not provide signifi-
cant guidance regarding the central topic of this chapter.
Focus on Mortality
All studies, except two [19, 21] reported procedure-specific mortality. The mortality
data from the studies included in this review are compiled in Table 28.2.
Most studies did not find a statistically significant difference in mortality between
Hartmann’s procedure and primary anastomosis. The three studies which showed a
statistically significant difference in mortality were by Masoomi et al., Trenti et al.
and Mueller et al. [20, 22, 33]. Masoomi’s study analyzed a discharge database
(NIS) and is not the best method for clinical assessment of cause specific mortality
[33]. The study by Trenti et al. is a retrospective chart review with small patient
numbers and an unusually high mortality rate (45 % mortality overall). Authors of
Table 28.2 Mortality data of studies included in this review
314
Author Year HP (n/N) (%) PA (n/N) (%) P HP (n/N) (%) PAD (n/N) (%) P
Jafferji [17] 2014 1/74 (1.4 %) 0/20 (0 %) NS 1/74 (1.4 %) 0/32 (0 %) NS
Tadlock [32] 2013 72/991 (7.3 %) 13/285 (4.6 %) 0.465 72/991 (7.3 %) 1/38 (2.6 %) 0.479
Cirocchi [35] 2013 54/246 (22 %) 17/174 (9.8 %) 0.02 – – NA
Oberkofler [15] 2012 4/30 (13.3 %) – NA 4/30 (13.3 %) 3/32 (9.4 %) NS
Binda [16] 2012 1/34 (2.9 %) 6/56 (10.7 %) 0.24 – – NA
Toro [41] 2012 139/800 (17.4 %) 38/1010 (3.8 %) NA 139/800 (17.4 %) 11/153 (7.2 %) NA
Masoomi [33] 2012 2741/56,875 (4.8 %) NR NA 2741/56,875 (4.8 %) 134/3361 (4 %) 0.03
Gawlick [34] 2012 89/1674 (5.2 %) 25/340 (7.4 %) NS – – NA
Hergoz [18] 2011 6/19 (31.6 %) 1/21 (4.8 %) 0.15 – – NA
Miccini *[19] 2011 –/85 –/28 NA – – NA
Trenti [20] 2011 27/60 (45 %) 2/22 (9.1 %) 0.001 27/60 (45 %) NR NA
Mueller [22] 2011 7/26 (26.9 %) 2/36 (5.6 %) 0.008 7/26 (26.9 %) 0/11 (0 %) NR
Zingg [23] 2010 19/65 (29.2 %) 8/35 (22.9 %) 0.156 19/65 (29.2 %) 0/11 (0 %) NR
Vermeulen [24] 2007 47/139 (33.8 %) 6/45 (13.3 %) <0.01 47/139 (33.8 %) 1/16 (6.3 %) <0.01
Stumpf [25] 2007 5/30 (16.7 %) 0/36 (0 %) 0.025 – – NA
Constantinides [36] 2006 63/416 (15.1 %) 27/547 (4.9 %) 0.13 – – NA
Abbas [37] 2006 102/526 (19.4 %) 32/358 (8.9 %) NA – – NA
Salem [38] 2004 198/1051 (18.8 %) 56/569 (9.8 %) NA 198/1051 (18.8 %) 9/93 (9.7 %) NA
Regenet [30] 2003 4/33 (12.1 %) 3/27 (11.1 %) 0.9 – – NA
Zorcolo [26] 2003 19/86 (22.1 %) 3/29 (10.3 %) 0.3 – – NA
Blair [27] 2002 13/64 (20.31 %) 3/33 (9.1 %) 0.2 13/64 (20.31 %) NR NA
Gooszen [28] 2001 6/32 (18.8 %) – NS 6/32 (18.8 %) 5/28 (17.9 %) NS
Schilling [31] 2001 4/42 (9.5 %) 1/13 (7.7 %) 0.9 – – NA
Wedell [29] 1997 4/15 (26.7 %) 0/10 (0 %) NR 4/15 (26.7 %) 1/4 (25 %) NR
HP Hartmann’s procedure, NS not significant, NR not reported, NA not applicable, PA primary anastomosis, PAD primary anastomosis with diversion
*
N. Mishra and D.A. Etzioni
Procedure specific mortality not reported

this study attributed the high mortality to the fact that surgical quality was heteroge-
neous in their institution, with a disproportionate number of deaths being in the
patients operated upon by general surgeons. This study is limited by selection bias
and lack of generalizability. In addition, the groups were not matched and con-
founding factors were not accounted for. Thus, the results of this study are not reli-
able [20]. Mueller et al. found a statistically significant lower mortality with primary
anastomosis compared with Hartmann’s procedure. However, this was a retrospec-
tive chart review with a very small sample size. The number of deaths in the
Hartmann’s procedure group was 7/26 (27 %) and in the primary anastomosis group
was 2/36 (6 %). However, it must be recalled that larger database studies show surgi-
cal mortality rates (both types of procedures combined) less than 5 % [1].
Focus on Anastomotic Leak
In the studies reviewed here, ten reported clinical anastomotic leak rate after pri-
mary anastomosis, with rates ranging from 3 to 28 % [18–20, 22–27, 30]. In one of
the larger retrospective studies, the clinical anastomotic leak rate was 13/46 (28 %)
in the primary anastomosis group [23]. During the same time period, the authors
reported a 3 % anastomotic leak rate for their elective colon resections. This study
highlights the increased risk for anastomotic leak in patients undergoing an urgent/
emergent operation for acute diverticulitis compared with elective anastomoses.
The procedures most reasonably performed in an urgent/emergent setting for acute

diverticulitis are Hartmann’s procedure, primary anastomosis without diversion,
and primary anastomosis with diversion. Recent randomized trials have found
increased rates of severe complications in patients undergoing laparoscopic lavage,
and this avant garde approach is no longer widely considered appropriate [42, 43].
In analyzing the existing body of experiences for properly selected patients, each of
these three procedures are equivalent in terms of morbidity and mortality from the
index procedure. Some lessons can be taken however, to guide decision-making.
Morbidity from anastomotic leak in patients with primary anastomosis is substan-
tial, and higher than for elective resections. The likelihood of restoration of intesti-
nal continuity is higher in patients who undergo primary anastomosis with loop
ileostomy compared to those who undergo a Hartmann’s resection. Finally, the mor-
bidity and mortality from a Hartmann’s reversal procedure is substantially higher
than that of ileostomy reversal.
Thus, primary anastomosis with diverting loop ileostomy is recommended in
stable patients undergoing surgery for acute diverticulitis. (Evidence quality:
Low, Weak recommendation)
Personal View of Data
Each patient has a unique set of risk factors, and general/colorectal surgeons are
well-acquainted with these. For the sake of discussion, these factors include sepsis/
hemodynamic instability, age, functional status, immunosuppression, extent/dura-
tion of inflammation, and degree of involvement of regional tissues with the acute
inflammatory process. For a patient who manifests with the most severe profile of
disease (e.g. septic, feculent peritonitis), it would be foolhardy to challenge conven-
tional surgical wisdom by constructing an anastomosis. The reverse may be true as
well. A patient with refractory diverticulitis and localized disease may be best
served with an anastomosis (with or without diversion), thereby minimizing the
burden of subsequent reoperation.
The choice of surgery for acute diverticulitis, therefore, clearly depends on an
individual surgeon’s estimation of a patient’s degree of risk, and a mechanism for
translating this estimation into the selection of one of three competing options. In the
authors’ practice, primary anastomosis with diverting loop ileostomy (with or with-
out colonic lavage) is preferred in patients who are stable and are not at an unduly
high risk for anastomotic failure. The authors rarely perform primary anastomosis
without diversion in patients undergoing urgent/emergent surgery for acute divertic-
ulitis. For patients who are clinically unstable, the priority is to minimize the risk of
mortality, and in these situations an anastomosis is an avoidable source of risk.
It is tempting to look to ongoing randomized studies, such as the Dutch LADIES
trial [44] to give better guidance regarding the preferability of one approach over
another. It is unlikely, however, that any trial will quantify the risk factors described
above adequately, or allow for a translation of this quantification into standardized
surgical decision-making. Given this, surgeons treating patients for acute diverticu-
litis will need to continue to exercise their best judgment, encompassing a broad
spectrum of potential risks and challenges that face each patient.
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41. Toro A, Mannino M, Reale G, Cappello G, Di Carlo I. Primary anastomosis vs Hartmann
procedure in acute complicated diverticulitis. Evolution over the last twenty years. Chirurgia
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43. Vennix S, Musters GD, Mulder IM, et al. Laparoscopic peritoneal lavage or sigmoidectomy for
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44. Swank HA, Vermeulen J, Lange JF, et al. The ladies trial: laparoscopic peritoneal lavage or
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2010;10:29.
Chapter 29
Who Needs Elective Surgery for Recurrent
Diverticulitis?
Janice Rafferty
Introduction
Diverticulitis a common condition encountered by the practicing surgeon. Currently,

one of the more contentious topics in the management of diverticulitis is which
patients with chronic or recurrent disease should be selected for elective sigmoid
colectomy. Historic dogma dictated prophylactic colectomy after two episodes for
uncomplicated diverticulitis, and after one episode in patients under 40, to reduce
the risk of future emergency surgery with colostomy [1–5]. The use of CT scan to
gauge severity of disease, construction of larger clinical databases, and the advent of
less invasive techniques (percutaneous drainage, intraperitoneal lavage), has
changed the way surgeons think and manage diverticulitis [6]. As a result, current
guidelines recommend a more selective approach to sigmoid colectomy after an
uncomplicated episode, and in the setting of chronic recurrent diverticulitis [7–9].
Despite these recommendations the frequency of elective colectomy appears to
be increasing [10]. A prospective study by Simianu et al. [11], concluded that 31 %
of patients failed to meet surgical indications of either complicated diverticulitis or
three or more episodes prior to undergoing elective sigmoidectomy for diverticulitis
[11]. To date, there are no published randomized controlled trials comparing out-
comes for elective sigmoid colectomy to expectant management after an episode of
diverticulitis. This chapter will attempt to provide the clinician with up to date
graded evidence based recommendations regarding treatment.
J. Rafferty, MD, FACS, FASCRS

Division of Colon & Rectal Surgery, UC Health,
2123 Auburn Avenue, Suite #524, Cincinnati, OH 45219, USA

DOI 10.1007/978-3-319-40223-9_29
320 J. Rafferty
Search Strategy

Patients with recurrent Resection Expectant Risk of recurrence,
diverticulitis management morbidity, quality of life
We performed a systematic literature search with the aim of answering the following
PICO (Patients, Intervention, Comparator, Outcome) question: “Who needs elective
colon surgery for recurrent diverticulitis?” A targeted search of English language
literature in MEDLINE, PubMed, EMBASE, and the Cochrane Database of
Collected Reviews was performed. Key-word combinations using the Medical
Subject Headings (MeSH) terms included “diverticulitis,” “diverticular,” “abscess,”
“fistula,” “perforation,” “complicated,” “uncomplicated,” “colectomy,” “antibiotics,”
“resection,” and “expectant management.” Directed searches of the embedded refer-
ences from the primary articles were also performed in selected circumstances.
Review papers were also searched for cross-references. We decided to include exclu-
sively those papers written in English language with a date of publication within the
last 15 years in order to produce updated recommendations. The grade of both litera-
ture reviewed and final recommendation was performed by using the Grades of
Recommendation, Assessment, Development, and Evaluation (GRADE) system
[12, 13]. The search was carried out in November 2015.
Results
Uncomplicated Diverticulitis
Historically the recommendation was to proceed with elective resection after the
second episode of uncomplicated diverticulitis, due to the presumed morbidity and
mortality of subsequent attacks [1]. However close scrutiny of the evidence fails to
support this practice; therefore the decision to proceed with surgery should take into
account other factors. When recommending elective colectomy vs. expectant man-
agement for uncomplicated diverticulitis, the following should be considered: risk
of recurrence, risk of developing complicated diverticulitis, patient comorbidities,
possibility of emergency surgery, and quality of life.
Recurrence rates for uncomplicated diverticulitis treated nonoperatively vary
from 8 to 48 % and are gathered from studies with varying lengths of follow up
(Tables 29.1 and 29.2). The two largest series include ~181,000 [14] and ~179,000
[15] patients, and report recurrence rates of 8.7 and 16.3 %, respectively. Patients
with uncomplicated disease were less likely to recur than their complicated counter-
parts [14, 16]. Of patients who recur, most recur within 12 months of the index
admission [16, 17]. Patients who dorecur have a greater chance of yet another epi-
sode as well. Overall recurrence rates in patients with uncomplicated diverticulitis
Table 29.1 Diverticulitis outcomes
Study N Treatment Results Median F/U QOE
Ho et al. [14] 237,869 with 181,115/237,869 (76.1 %) 8.7 % recurrence rate Variable – NR Moderate
Retrospective multicenter diverticulitis treated non-surgically 23.2 % re-recurrence
(unspecified)
Hall et al. [20] 672 (index case of Non-surgical management Overall recurrence 36 % 5 years Low
Retrospective diverticulitis) Complicated recurrence 3.9 %
Ambrosetti et al. [42] 542 patients with 405/542 (74.7 %) treated 87/405 (21.2 %) had “bad 62 months Low
Prospective diverticulitis non-surgically outcome” (recurrence, abscess,
(unspecified) stenosis, fistula)
Risk factors for bad outcome:
Age <50
Severity of disease as seen on
CT
Trenti et al. [16] 560 with Non-surgical management Recurrence observed in 14.8 %, 67 months Low
Prospective diverticulitis Severe recurrence in 3.4 %
(unspecified) Risk factors for recurrence:
Chronic steroids
Presence of abscess
Rose et al. [15] 210,268 with 179,569 (85 %) treated 16.3 % recurrence rate Variable – up Moderate
29 Who Needs Elective Surgery for Recurrent Diverticulitis?
Retrospective multicenter diverticulitis non-surgically 29.3 % rerecurrence to 15 years

(unspecified) Risk factors for recurrence:
Complicated index episode
Abscess
Age <50
Anay and Elum [21] 25,058 with acute Non-surgical 19 % had recurrence Variable – NR Moderate
Retrospective multicenter diverticulitis management = 20,136/25,058 5.5 % required emergency
(unspecified) operation at recurrence
Risk factor for recurrences:
Age <50 more likely to have
recurrence (27 % vs 17 %)
321
(continued)
322

Broderick-Villa et al. [18] 3156 with acute Non-surgical Elective colectomy = 185/2551 8.9 years Low
Retrospective multicenter diverticulitis management = 2551/3156 Non-operative
(unspecified) (80.6 %) management = 2336/2551
13.3 % had recurrence
Risk factors for recurrence:
Younger patients
Presence of comorbidities
increased recurrence
Klarenbeek et al. [40] 291 patients 111 non op treatment Recurrence rate of 48 % in non Low
Retrospective 108 urgent/emergent surgery op group
72 elective surgery Risk of recurrence:
Complicated disease
Immunosuppression
Chronic renal failure
Collagen vascular disease
Holmer et al. [43] 153 with acute 113 surgical resection 32 % of non surgically treated 32 months Low
Prospective cohort diverticulitis 40 treated non-surgically patients recurred
(unspecified) 4 % of surgically treated patients
recurred
Risk factors for needing surgery:
Perforated disease
Recurrent episodes
Li et al. [22] 14,124 with acute Non-operative management 9 % readmission for recurrence 3.9 years Moderate
Retrospective multicenter diverticulitis 1.9 % emergency surgery
(unspecified) Risk factors for readmission/
recurrence:
Patients with initial complicated
disease
Age <50 likely to be readmitted
J. Rafferty
Chapman et al. [25] 150 with prior Non-operative and operative Perforation occurred more NR Low
Retrospective episodes of management frequently in Group A
diverticulitis Fecal Diversion occurred more
Group A – Pts frequently in Group A
with 1–2 previous When needing surgery: no
episodes difference in operative
Group B – Pts morbidity/mortality
with >2 previous
episodes
Eglinton et al. [17] 502 with Non surgical management: Uncomplicated 101 months Low
Retrospective diverticulitis Uncomplicated = 320/337 recurrence = 23.4 %
Uncomplicated = 337 Complicated = 62/165 Complicated recurrence = 24 %
Complicated = 165 Complicated diverticulitis more
likely to undergo surgical
resection
Lamb and Kaiser [38] 1051 patients – from Urgent/emergent surgery (30 %) Recurrence in patients waiting Variable Moderate
Systematic review/ 22 studies – Elective surgery (36 %) for elective resection = 39 %
metanalysis diverticulitis with Non-operative management Recurrence in Non operative
abscess formation (35 %) group = 18 %
28 % had no surgery and no
recurrence
Ambrosetti et al. [44] 73 patients with Surgical and non-surgical 22/45 (49 %) mesocolic 43 months Moderate
Prospective diverticular abscesses management abscesses & 8/28 (29 %) pelvic
abscesses, successfully managed
conservatively
Kaiser et al. [45] 511 patients with Urgent, elective surgery Of 99 patients with abscess: NR Low
Retrospective diverticulitis Non-surgical management 22 % required urgent operation
15 % underwent elective
operation
41.2 % recurred after non
operatively treatment
323
(continued)
324

Chapman et al. [19] 375 patients with Urgent, elective surgery 46 % had had previous episodes NR Low
Retrospective complicated Non surgical management of diverticulitis
diverticulitis 53 % was index episode of
diverticulitis
6.5 % overall mortality rate
Risk of morbidity and mortality:
Older age
Steroids/Immunodeficiency
Diabetes
Perforation on presentation
Nelson et al. [39] 256 with complicated 99/256 (38.7 %) treated 46/99 had recurrence 14 years Low
Retrospective diverticulitis non-surgically 20/46 recurrences required
sigmoid resection
Gaertner et al. [41] 218 patients treated 32/218 (15 %) treated Recurrence rate was 42 % 7.4 years Low
Retrospective with perc drain for non-surgically Risk Factors associated with
complicated recurrence:
diverticulitis Abscess >5 cm
Bridoux et al. [28] 114 patients with 81/114 (71.1 %) treated 7.4 % recurrence (median time 32 months Low
Retrospective Complicated non-surgically of 12 months)
diverticulitis
J. Rafferty
Table 29.2 Quality of life
Andeweg et al. [29] 1858 patients – from 21 Elective surgical vs Higher QOL scores in laparoscopic surgical NR Moderate
Systematic review/ studies – uncomplicated non surgical group
metanalysis diverticulitis treatment of Lower GI symptoms in surgical group
recurrent Less chronic abdominal pain in surgical group
diverticulitis
van de Wall et al. [30] 105 patients with Elective surgical Elective resection: 1 year Low
Retrospective cohort diverticulitis resection Improved QOL
(unspecified) Reduced chronic abdominal pain
Decreased discomfort from defecation
Forgione et al. [32] 46 patients with Elective surgical 36/46 patients significantly had increased GIQLI 1 year Low
Prospective cohort diverticulitis resection scores
(unspecified) (laparoscopic) Patients with lowest GIQLI scores increased
benefited the most from surgery
Levack et al. [35] 249 patients with Laparoscopic and 24.8 % reported relevant fecal incontinence NR Low
Retrospective diverticulitis open 19.6 % reported fecal urgency
(unspecified) sigmoidectomy 20.8 % reported incomplete emptying
Symptoms: risk factors
Fecal incontenence: pre-op abscess, female
Urgency: divertiting ostomy, female

Incomplete emptying : post-op sepsis, female
Pasternak et al. [31] 130 patients with Elective surgical 83 % of patients with GIQOL >100 after surgery 40 months Low
Retrospective diverticulitis resection vs before (43 %)
(unspecified) (laparoscopic) Mean QOL score of 114 after surgery vs before
(95)
(continued)
325
326

Scarpa et al. [33] 71 patients with 25/71 underwent Cleveland global QOL: 47 months Low
Retrospective uncomplicated resection No difference in total score
diverticulitis 46/71 non-surgical No difference in symptom frequency
management Current quality of health was lower in surgical
group
Egger et al. [36] 124 patients 68 patients – 25 % suffered persistent symptoms: constipation, 33 months Low
Retrospective elective colectomy abdominal distention, abdominal cramps,
diarrhea
Complicated vs uncomplicated were unrelated
to symptomatology
Technique (open vs laparoscopic) were
unrelated to symptomatology
J. Rafferty
29 Who Needs Elective Surgery for Recurrent Diverticulitis? 327
are approximately 4.7 % after the index episode, according to one study [17]. Two
multicenter retrospective trials demonstrated re-recurrence risk of 23.2 and 29 % in
patients who had had at least one previous recurrence [14, 18].
Most patients presenting with complicated diverticulitis do so at their index admis-
sion for diverticulitis; 89 % of patients who die of the disease have no prior history of
diverticulitis [19]. These data suggest that in most cases, the first episode is the worst
episode. That is not to say that patients with uncomplicated diverticulitis can’t recur
with a complicated form of the disease, and unequivocally will not require emergency
surgery or a colostomy. However, rates of recurrent disease that is complicated range
from 3 to 5 % in the literature [16, 17, 20]. Infact, most patients with a complicated or
severe recurrence have had a previous episode of complicated/severe diverticulitis
[16]. In addition, the risk of recurrent diverticulitis is positively associated with fam-
ily history, length of colon involvement >5 cm [20], and presence of comorbidities
[18]. Additionally risk of recurrence is associated with age <50 [14, 18, 21–23].
The risk of requiring an emergent colostomy after an initial episode of diverticu-
litis is strikingly low. A retrospective, multicenter study by Li et al. [22], described
14,124 patients treated nonoperatively, and found only 1.9 % of these patients sub-
sequently had emergency surgery for perforation, with a median follow up of
3.9 years [22]. These findings are similar to another population-based study, which
reviewed 25,058 patients where 20,136 patients were initially treated nonopera-
tively. While 19 % had a recurrence, only 5.5 % required a subsequent emergency
colectomy [21]. The hazard ratio for emergency colectomy/colostomy was 2.2×
higher in patients for each subsequent admission. According to this study, 18 patients
would need to undergo elective colectomy to prevent one emergency surgery for
recurrent diverticulitis [21].
After recovery from an initial episode of diverticulitis, the estimated risk of need-
ing emergency Hartmann resection with stoma formation is 1 in 2000 patient-years
of follow-up [24]. A study by Chapman et al. [25], grouped patients with diverticu-
lar recurrence in two categories: those with 1–2 previous episodes, and those with
>2 previous episodes. Perforation and need for diversion occurred more in the group
with only 1–2 previous episodes, and there were no differences in morbidity and
mortality between groups. This suggests that patients with more than two episodes
of diverticulitis are not at increased risk for poor outcomes [25]. To support this, a
Markov model, developed by Salem et al. determined that performing colectomy
after the fourth episode of diverticulitis rather than the second episode resulted in
0.5 % fewer deaths, 0.7 % fewer colostomies, and a reduction in cost per patient
[26]. As practice patterns have shifted away from elective surgical management of
diverticulitis, there has been an increase in the number of abscesses, but no increase
in diverticular perforations requiring emergency surgery [27]. Because of this data,
except in certain circumstances (see below), the current American Society of Colon
and Rectal Surgeons (ASCRS) guideline states that patients with uncomplicated
diverticulitis should not be counseled to undergo prophylactic elective colectomy as
a means to prevent future emergency surgery and stoma creation [7].
Persistence of symptoms and quality of life is another factor to consider when
recommending elective surgical resection for uncomplicated diverticulitis. In one
328 J. Rafferty
study of patients with uncomplicated diverticulitis treated nonoperatively, 68/81

(84 %), remained asymptomatic, while 13/81 (16 %) had recurrent abdominal pain
at a mean follow up of 32 months [28].
Few studies are able to convincingly support elective resection for uncompli-
cated chronic diverticulitis. A single meta-analysis of 21 studies demonstrated
higher QOL scores, fewer GI symptoms, and less chronic abdominal pain in those
who had surgery for chronic and recurrent diverticulitis, compared to those who
were managed nonoperatively [29]. Unfortunately none of the studies included in
the meta-analysis were head-to-head comparisons of surgical vs. non-surgical
management. A retrospective examination of 105 patients undergoing elective sur-
gery for diverticulitis found that quality of life, abdominal pain, and discomfort
with defecation were improved at 1 year after surgery [30]. This trend was seen in
another retrospective review of 130 patients in which quality of life score was sig-
nificantly improved after surgery [31]. A single prospective evaluation of 46
patients found improvement in QOL scores 3 months after surgery, which was
maintained at 1 year. This study also demonstrated that improvement was most
notable in patients with the lowest preoperative QOL score [32]. While these find-
ings are worth noting, these studies only compare one subset of patients before and
after surgery. In a study comparing colon resection (25/71) vs. non-surgical ther-
apy (46/71) for uncomplicated diverticulitis, Scarpa M et al. [33], found no differ-
ence in total quality of life score or symptom frequency at median follow up of
47 months [33].
The surgeon must counsel the patient that sigmoid colectomy can negatively
impact QOL as well. When compared with sigmoid colectomy for colon cancer,
elective sigmoid colectomy for diverticular disease has relatively poor outcomes,
and is associated with increased ostomy creation, postoperative infection, prolonged
hospital stay, and increased cost [34]. A study by Levack et al. [35] found that in
patients who underwent sigmoid colectomy, 24.8 % reported clinically relevant
fecal incontinence, 19.6 % experienced fecal urgency, and 20.8 % reported incom-
plete emptying [35]. Whether patients presented with complicated or uncompli-
cated disease did not seem to matter regarding persistent symptoms after elective
sigmoid colectomy [36].
A Markov model simulating patients with two episodes of non-surgically man-
aged diverticulitis found that after the third episode of diverticulitis, surgical or
conservative or medical treatments provide similar quality of life adjusted years, but
rates of abdominal symptoms are lower with the medical treatment strategy [37]. In
the setting of uncomplicated diverticulitis, functional assessment and quality of life
should be considered in deciding who would or would not benefit in elective resec-
tion surgery.
In agreement with the current ASCRS guidelines [7], the decision to recommend
elective colectomy after recovery from uncomplicated acute diverticulitis should be
approached on case-by-case basis [7]. The risk of recurrence, the persistence of
symptoms, the patient’s overall medical condition, lifestyle factors, and the quality
of life should be considered against potential risks and benefits of surgery.
Complicated Diverticulitis
The decision to recommend elective surgery after resolution of an episode of com-

plicated diverticulitis is a little more straightforward. Complicated diverticulitis
includes free perforation, abscess, fistula, obstruction, or stricture. A large propor-
tion of patients with complicated diverticulitis will ultimately undergo sigmoid
resection [38] after successful medical management, where the goal is to convert an
urgent or emergent operation with a high likelihood of stoma creation, into an elec-
tive procedure without an ostomy if possible.
Risk of recurrence is higher in patients with complicated diverticulitis, and has
been reported as high as 46–48 % [39, 40]. If recurrence does occur, it is much more
likely to be a complicated recurrence [38], and as many as 43 % who do recur will
go on to require sigmoid resection [39]. A meta-analysis evaluating elective resec-
tion vs. non-operative management in the setting of diverticulitis with abscess,
assessed 1051 patients across 22 studies. While 30 % of patients required urgent
surgery, 35 % of patients went on to have elective surgery. Only 28 % of patients had
no surgery and no recurrence [38]. In a series of 218 patients requiring percutaneous
drainage for diverticular abscess, colectomy free survival was 0.17 at 7.4 years [41],
meaning patients had a 17 % chance of having no colectomy (either emergent or
elective) if they survived to 7.4 years after an episode of diverticulitis associated
with abscess.
Many studies have evaluated risk factors for recurrence [22]. Risk factors include
extra-luminal contrast on initial cross sectional imaging [42], abscess [38, 41, 42],
extra-luminal perforation [42, 43], stenosis, and fistula [40]. One prospective study
evaluated 73 patients with either mesocolicor pelvic abscesses with a mean follow
up of 43 months, and found that 71 % of patients with pelvic abscess ultimately
required surgery, but only 51 % of patients with mesocolic abscesses required sur-
gery. The remaining patients were managed conservatively with success [44]. In
fact presence of a pelvic abscess due to perforated diverticulitis is associated with
recurrence rates up to 41 % [45].
Evaluation of subsequent morbidity and mortality due to complicated disease
suggests that prior episodes of complicated disease were associated with
increased risk for subsequent emergency surgery during recurrence [22]. In
another large population based study, mortality for emergent resection during a
second episode of diverticulitis was 4.6 % compared to an elective operative mor-
tality of 0.3 %. Individual predictors of mortality with recurrence in this study
were complicated initial presentation, age >50, and smoking [15]. These was
echoed in another study where complicated diverticulitis and abscess were asso-
ciated with recurrence, need for emergency surgery and increased mortality dur-
ing recurrence [14].
Because of these findings including a higher risk of recurrence, and increased
risk of morbidity and mortality after complicated diverticulitis, current recommen-
dations are that elective colectomy should be strongly considered after recovery
from an acute episode of complicated diverticulitis [7].
330 J. Rafferty
Special Populations
Historically, diverticulitis among younger patients has been associated with worse
clinical outcomes, however careful review of the accumulated data does not entirely
support this association. Age under 50 years does appear be associated with
increased risk of recurrence [14, 18, 21–23]. However, despite a slightly higher risk
of recurrence in patients <50 vs. >50 (27 % vs. 17 %) [21], younger age does not
appear to predict worse outcomes [39, 46]. Specifically, risk of diverticular perfora-
tion and need for subsequent emergency colectomy in the young appears to be com-
parable to the risk in older age groups [23, 47]. Current recommendations are that
younger patients should not routinely be counseled to undergo elective resection
based on age alone [7].
While diverticulitis incidence may be similar in the immunosuppressed and the
general population [48], the disease behavior is different in these groups. One sys-
tematic review [49] identified 11,966 post-transplant patients (kidney, liver, heart),
across 17 different series, and evaluated the incidence of diverticulitis. It was esti-
mated that 1.7 % of these patient experienced diverticulitis, and that approximately
40.1 % of these patients presented with complicated diverticulitis. This suggests that
transplant patients are more prone to severe disease, rather than mild/moderate/
uncomplicated diverticulitis [49]. Scotti et al. [50] looked at 717 kidney transplant
patients, and found that while only 17 patients (2.3 %) developed diverticulitis, 9/17
(52.9 %) presented with perforated diverticulitis [50]. More severe presentation in
this patient population is thought to be due, in part, to immunosuppressive medica-
tions masking early signs and symptoms of disease, and thus patients present later
in the course of the disease.
Nonoperative management is more likely to fail in patients on chronic steroids or
transplant medications, and a mortality rate as high as 56 % has been reported [51].
Not only are immunosuppressed patients more prone to a severe initial presentation,
diverticular perforation in immunosuppressed patients is associated with higher
morbidity and mortality (20–30 %) [52–56]. Other studies support the finding that
immunosuppression leads to more severe bouts of diverticulitis and recurrence [16].
In a retrospective study, Chapman et al. [19], was able to show that steroid use,
diabetes, and immunosuppression were associated with increased morbidity and
mortality in patients presenting with complicated diverticulitis [19]. Another study
demonstrated a five-fold risk of perforation during recurrent episodes for patients
who were immunosuppressed, had chronic renal failure, or had collagen-vascular
disease [40].
A recent study compared diverticulitis outcomes in immunocompetent vs. immu-
nocompromised patients and found that immunocompromised patients presenting
with a severe first episode of diverticulitis had significantly higher rates of recur-
rence and more severe episodes than their immunocompetent counterparts.
Perioperative mortality in this study following emergency sigmoidectomy was
33.3 % in the immunocompromised group, vs. 15.9 % in the immunocompetent
group [56]. This finding is consistent with another study [53] which demonstrated
that the morbidity and mortality for emergent/urgent surgery was increased in trans-
plant patients compared to case-matched immunocompetent counterparts. In this
same study, transplant patients undergoing elective surgery for diverticulitis had no
difference in morbidity and mortality compared to case matched immunocompetent
patients, although they did have a longer hospital stay [53].
Because of the high mortality of nonoperative management, high risk of com-
plicated recurrence, and high mortality of emergent colectomy in immunocom-
promised and transplant patients, surgeons should consider “early” operative
intervention in a semi-urgent/semi-elective manner during the first hospitaliza-
tion for acute diverticulitis in these patients. Interestingly, this recommendation
does not necessarily apply to patients receiving certain chemotherapies, who
while more likely to recur with severe disease, also are much more likely to have
post-operative complication (100 % vs. 9.1 %) and mortality compared to non-
chemotherapy patients. These patients should be approached on a case-by-case
basis [57].
While patients with end stage renal disease (ESRD) do have a much higher rate
of recurrence of diverticulitis [40] than “healthy” counterparts, whether to pursue
elective colectomy in this population remains controversial. A recent study by
Mora-Atkin and colleagues [58], demonstrates that urgent/emergent surgery for
patients with ESRD is associated with increased mortality, myocardial infarction,
wound infection, length of stay and cost, compared with non-ESRD undergoing
urgent/emergent colectomy. Surprisingly, these trends are similar to patients in this
group undergoing elective colectomy as well [58]. Decreased risk of recurrence
must be balanced against risk of surgery in patients with ESRD when recommend-
ing elective sigmoid colon resection.
1. Need for elective sigmoid colectomy following an episode of acute uncompli-

cated diverticulitis should be determined on a case-by-case basis, taking into
account risk of recurrence, patient comorbidities, and patient lifestyle factors.
(Moderate quality evidence; strong recommendation; 1B)
2. After recovery from an episode of acute complicated diverticulitis, elective col-
ectomy should be considered, especially in settings of diverticulitis associated
with pelvic abscess. (Moderate quality evidence; strong recommendation; 1B)
3. Recommending elective colon resection to patients under the age of 50 with
uncomplicated diverticulitis should be individualized (low quality of evidence,
moderate recommendation; 2C)
4. Immunosuppressed individuals should typically undergo elective colon resec-
tion either during or following an episode of acute uncomplicated diverticulitis,
due to risk of more severe disease and higher morbidity and mortality (moderate
quality evidence; strong recommendations; 1B)
332 J. Rafferty
More and more patients are being referred to the surgeon for elective resection of
diverticular disease, most likely due to the impression that laparoscopic surgery is
easy and risk-free. While there may be less blood loss, shorter hospital stay, and
lower rate of incisional hernia, the technique should not beget the procedure. The
disease process has not changed, yet our understanding has evolved significantly. In
the past we told patients that after two episodes it was safest to have surgery. Now
we know their quality of life and complication rate is essentially no better after
surgery in the setting of uncomplicated recurrent diverticulitis. I spend more time
today talking patients out of surgery for uncomplicated disease than ever.
On the other hand, the evidence is compelling for resection after complication,
including sizeable pelvic abscess, in select patients. If the patient is an acceptable
risk for general anesthesia, I generally recommend it. That being said, I do try to
minimize their risk for postoperative complication by insisting on smoking cessa-
tion and weight loss. I believe laparoscopic inspection for feasibility of minimally
invasive resection should be done in the appropriate abdomen, if surgery is indi-
cated. In other words, planning a laparoscopic resection for complicated diverticu-
litis is reasonable; if the induration or scarring is intense, a hand can be placed or the
procedure can be converted to open, as long as this decision is made early in the
course of the procedure.
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Chapter 30
Deciding on an IRA vs. IPAA for FAP
James Church
Setting the Stage
Familial adenomatous polyposis (FAP) is a dominantly inherited form of cancer

predisposition due to a germline mutation in the colorectal cancer gateway gene,
APC. The syndrome usually presents as colorectal adenomatous polyposis of vary-
ing severity, which, if untreated, will lead to colorectal cancer at a young age. While
other organs are also affected by the cancer predisposition, by far the most serious
threat to life and lifestyle comes from the large bowel. This is therefore the initial
focus of treatment.
Patients with FAP are usually diagnosed on screening because dominant inheri-
tance combined with 100 % penetrance makes the family history compelling.
Genetic testing identifies affected family members, who begin colonoscopic sur-
veillance at puberty. If genetic testing is not done or is uninformative, colonoscopic
surveillance is the same, but is applied to every at risk relative. Patients diagnosed
by screening are usually asymptomatic and the polyps are small. There is plenty of
time to answer the next two important questions: what surgery and when?
About 25 % of patients with FAP do not have a family history, do not suspect the
syndrome they have and the risks they carry, and ultimately present with symptoms
due to relatively advanced disease [1]. These patients have a high risk of having a
colorectal cancer at diagnosis, and in general have more severe disease that those
diagnosed by screening. The same two questions apply however: what surgery, and
when?
J. Church, MBChB, FRACS

Department of Colorectal Surgery, Sandford R. Weiss Center for Hereditary Colorectal
Cancer, Cleveland Clinic Foundation, Cleveland, OH, USA

DOI 10.1007/978-3-319-40223-9_30
338 J. Church
Aims of Surgery in Patients with FAP
Some studies addressing the issue of colorectal surgery in FAP seem to have lost
sight of the true aims of the procedure [2, 3]. The focus tends to be exclusively on
treating and preventing cancer (in particular, preventing death from cancer) while
the secondary aim of lifestyle preservation is often disregarded. This leads to the
preference of ileal pouch-anal anastomosis over ileorectal anastomosis for all or
most patients with FAP, regardless of polyposis severity. However, when operating
on young asymptomatic patients at a critical time in their social, sexual, academic,
educational and psychological development, it is critical that prophylactic surgery
does not cause harm. In fact, the two main surgical options are considerably differ-
ent in their impact on lifestyle.
The Surgical Options
To absolutely prevent colorectal cancer, all of the colon and rectum must be
removed. This leads to an end ileostomy, which is unacceptable to most patients,
especially if they are young and asymptomatic. Before 1980, total colectomy and
ileorectal anastomosis (IRA) was performed as a reasonable compromise, reducing
the risk of cancer considerably but maintaining normal defecation. However, in
patients with profuse polyposis, the risk of rectal cancer after IRA was high, as the
surgery was too conservative [4]. The game changed in 1979 when the ileal pouch-
anal anastomosis (IPAA) entered practice. It achieved near-complete removal of the
colon and rectum while per anal defecation was preserved. Since then the IPAA has
become an important option for the treatment of patients with FAP, and yet there is
still debate over the indications for IRA and IPAA in patients with FAP. This chapter
is devoted to a discussion of this choice and to providing guidance about making it.
How Are the Outcomes of Surgery to Be Judged?
Surgery is judged on the extent to which it achieves its aims. Prevention of cancer
after surgery in patients with FAP is judged on the rate of metachronous cancer.
However one of the advantages of an IRA is that the rectum can be removed at a
second operation before cancer arises or before cancer has spread. In this circum-
stance, proctectomy can almost always be accomplished, and an IPAA can be con-
structed most of the time [5–7]. On the other hand patients with an IPAA are not free
of cancer risk, either in the pouch- anal anastomosis, or the body of the pouch itself
[8]. Anal transition zone (ATZ) cancer is more likely in patients with a stapled IPAA
than a handsewn IPAA, arising from residual glandular epithelium [9, 10]. However
30 Deciding on an IRA vs. IPAA for FAP 339
both types of anastomosis carry some type of risk [8, 9]. The literature is split in terms
of the relative complication rates and function of stapled IPAA vs mucosectomy and
hand-sewn IPAA [11–14]. However stapled IPAA is certainly easier to survey.
Quality of life, the second outcome to be considered, is difficult to measure or
judge. There is often little correlation between bowel function and quality of life, as
this measurement is always subjective and relative [15]. Under the best of circum-
stances, both IRA and IPAA can be followed by a nearly normal lifestyle. Under the
worst of outcomes, life is miserable [16]. The quality of functional outcomes after
IRA and IPAA depend largely on surgical skills and patient factors such as BMI,
gender and compliance with follow-up. Adding to the complexity of evaluating
these operations is the source of much of the information, specialty units, where
there is broad experience and high skill. The relevance of these reports to the less
experienced surgeon in usual practice can be debated.
Quality of Surgery
The “elephant in the room” when discussing surgery for patients with FAP is the
quality of surgery, as this has a huge effect on quality of life. The stakes are high in
this disease because many patients are young and are at critical developmental
stages physically, emotionally, socially and academically. In addition, the majority
are asymptomatic. To take a young, asymptomatic patient and leave them inconti-
nent, impotent, or dealing with a permanent ileostomy may be considered a tragedy,
especially when the operation that was so complicated was either unnecessary or
too radical for the disease [16].
Both operations for FAP are technically challenging. An ileorectal anastomosis
involves a difficult anastomosis between two ends of very different diameters. It is
probably the most prone of intra-abdominal anastomoses to leak. An IPAA is also
technically demanding, as there are multiple aspects of techniques that have to go
well. There can be no tension on the small bowel mesentery. The bowel has to
descend into the pelvis straight, without as much as a 90° twist to the side. The
anastomosis should be at the level of the pelvic floor or below and the pelvic nerves
and other organs must be protected. We have seen many poor outcomes due to sub-
optimal technique and have reported on some of them, including a 360 twist in the
small bowel around its mesentery, an ultra-long efferent limb of small bowel from
an S pouch to the anus, an IPAA 7 or 8 cm from the dentate line, incorporation of
the vagina in an anastomotic staple line, and construction of a tiny pouch that holds
very little stool [16]. Functional problems include passing up to 20 stools per day,
severe fecal incontinence, disabling anal pain, and impotence. Surgeons should be
very familiar with the technique of whichever operation they choose, or refer the
patient to a high volume center. Bad outcomes have effects beyond the patient when
relatives fail to be screened or to follow through on surgery out of fear of having a
similar outcome.
340 J. Church
What Do the Data Say?
A Medline and Pubmed search using the terms FAP, Familial adenomatous polypo-
sis, surgery, ileal pouch anal anastomosis, ileo-anal anastomosis was conducted and
then extended by searching by the names of those this author knew had written
about the topic, going from 2015 back to 1946.
There are no randomized, prospective studies upon which to base surgical deci-
sions in patients with FAP. Most are retrospective reviews of experience from large
clinics, comparing cohorts of patients [17–22]. There is also one decision analysis
[23] and one reasonable meta-analysis [24]. The decision analysis is flawed due to
the weight given to the incidence of rectal cancer after IRA, many of which date
back to the “pre pouch” era. Many studies of IPAA function include patients with
ulcerative colitis and FAP, and should be excluded from consideration, as the dis-
eases are so different. In addition there are few recent studies, most dating back at
least 10 years. During this time surgery has changed considerably with minimally
invasive techniques now almost routine [25].
Perhaps the most sensible datas on oncologic outcome of an IRA come from the
Cleveland Clinic. They were the first to explain the high rates of rectal cancer after
IRA as being due to the lack of surgical options prior to 1980, when IPAA entered
practice [4]. When the only options are IRA or a permanent ileostomy, it is not sur-
prising that most patients choose IRA, even those with severe polyposis. These are
the patients who would go on to develop rectal cancer or advanced rectal polyposis.
After 1980, patients with profuse polyposis had an IPAA and the incidence of rectal
cancer after IRA dropped significantly.
The Cleveland group also set the criteria for either operation, based on rectal and
colonic polyp counts at the preoperative colonoscopy [26]. Patients with <20 rectal
polyps could safely have an IRA while those with >20 rectal polyps would be better
served by an IPAA. These standards have stood the test of time and have resulted in
an almost 50:50 ratio of IRA to IPAA in that institution [25].
While some institutions perform IPAA on every patient with FAP [2], most
use criteria to select for IRA. Polyp count is the most powerful factor but others
enter into the decision-making. Genotype has been suggested as a criterion for
triaging patients according to the location of their mutation [27, 28]. However
operating by genotype adds nothing to the use of polyp counts, as the correlation
between profuse polyposis and genotype is close to absolute, and that between
genotype and attenuated polyposis is also predictable. In young female patients
an IRA may be selected to avoid the possibility of reduced fecundity after an
IPAA. This sort of “staged” pouch (IRA first, knowing that proctectomy is likely
to be needed later after childbirth) also avoids a stoma in the young, provides
better bowel function during the key stages of a patient’s life, and may well
reduce the risk of desmoid disease [29]. It is a strategy that has become increas-
ingly popular, especially as there is often a spontaneous decrease in rectal pol-
yps for several years after IRA [30], and rectal polyposis can often be controlled
by aggressive endoscopy. Of course a rectum that is carpeted with adenomas,

usually in a symptomatic patient, has to be removed and some patients must
have an IPAA.
Studies measuring functional outcomes and quality of life after IRA and IPAA
generally report similar themes: that bowel function is better after IRA than IPAA
with less lifestyle restrictions and is stable over time [31–35]. IPAA function is very
variable over a range of stool frequencies and continence scores. However, quality
of life seems high. In many reports there is an important difference between a sta-
pled IPAA and a handsewn IPAA with a mucosectomy. A stapled IPAA generally
has better function with fewer complications than a handsewn IPAA, and is defi-
nitely easier to survey. It has twice the incidence of anastomotic and ATZ neoplasia
however [9, 36]. This ATZ neoplasia can be difficult to deal with if the residual
ATZ/rectal stump is over 2 cm long. A handsewn IPAA does not guarantee a
neoplasia-free zone, and is trickier to survey during unsedated pouchoscopy. Some
studies report good functional results with low complication rates after handsewn
IPAA [2, 11–14]. If the technical ability of the surgeon can produce such results
then a handsewn IPAA is a good choice. Some surgeons have better outcomes after
a stapled IPAA, and this option offers the chance of an undiverted pouch. We would
recommend that residual ATZ be less than 2 cm in length for easier management of
neoplasia [36].
The role of surgical choice in stimulating desmoid disease is controversial. Data
from the Cleveland Clinic suggest that IPAA doubles the risk of desmoid disease,
and that laparoscopic IPAA is particularly desmoidogenic [29]. Others disagree and
confirmatory data has not been reported to date [37, 38]. However there have been
no other similar studies. It is plausible that the stretching of the small bowel mesen-
tery that is part of an IPAA is the key factor in producing desmoid disease in the
small bowel mesentery. When this is done in young women with a family history of
desmoid disease, the perfect storm for desmoid formation occurs. Such patients
should have an IRA.
Recommendation
Patients with <20 rectal and <1000 colonic adenomas are candidates for IRA. Patients
with >20 rectal and >1000 colonic adenomas, or a curable rectal cancer on presenta-
tion, are better served with an IPAA. The IPAA can be stapled as long as the ATZ is
free of adenomas and the length of the residual ATZ is minimized (<2 cm). Patients
at high risk of desmoid disease should have an IRA.
Regardless of the procedure chosen, every patient should be surveyed endoscopi-
cally at least once a year.
Table 30.1 shows the advantages and disadvantages of IRA and IPAA, and the
indications and contraindications for these procedures. Table 30.2 show the indica-
tions and contraindications for each operation.
Table 30.1 Indications and contraindications, advantages and disadvantages of ileorectal anastomosis and ileal pouch-anal anastomosis, in patients with
342
familial adenomatous polyposis

Ileal pouch-anal anastomosis (IPAA), mucosectomy and Ileal pouch-anal anastomosis (IPAA),
Ileorectal anastomosis (IRA) handsewn anastomosis stapled anastomosis
Indications <20 rectal adenomas >20 rectal adenomas >20 rectal adenomas
Young patient Older patient Older patient
High desmoid risk Low desmoid risk Low desmoid risk
Woman Adenomas in ATZ ATZ clear of adenomas
Contraindication Rectal cancer Fecal incontinence Fecal incontinence
Uncontrollable rectal polyposis Obese Obese
High desmoid risk High desmoid risk
ATZ adenomas
Advantages No ileostomy Minimal risk of rectal cancer Minimal risk of rectal cancer
Low complications Per anal defecation Per anal defecation
Good bowel function No urgency No urgency
Low risk of desmoid disease Low risk of ATZ neoplasia Minimal seepage/incontinence
Disadvantages Risk of rectal cancer Temporary stoma High risk of ATZ neoplasia
Higher complication rate, both early and late
Abnormal bowel function with seepage and
incontinence
High risk of desmoid disease
Risk of ATZ polyps and cancer
J. Church
Table 30.2 The outcomes of ileorectal anastomosis and ileal pouch-anal anastomosis: a literature review
Study Variable IRA IPAA P
Campos et al. (2009) Complications 19.0 % 48.1 % 0.03
N = 88 Cancer 16.6 % 3.8 %
1977–2006
Gunter et al. (2003)
N = 151
1970–2000
Soravia et al. (1999) Anastomotic leak 3 % 12 % 0.21
n = 131 Bowel obstruction 15 % 24 % 0.58
1980–1997 Function Less nighttime stooling, better continence,
less skin irritation
Bjork et al. (2001) Complications 26 % 40 % <0.05
n = 131 Function Less night time stooling, better continence,
30 Deciding on an IRA vs. IPAA for FAP
1984–1996 less skin irritation

Vasen et al. (2001) Cancer Risk of death from cancer 12.5 % by age 65 Increase in life expectancy by
1.8 years
Koskenvuo et al. Secondary proctectomy 39/140
(2014) Anus preservation rate during 49 %
secondary proctectomy 24 % at 30 years
Cancer rate
Niewenhuis et al. Secondary proctectomy by genotype 10 %
(2009) Attenuated 39 %
Intermediate 61 %
Severe
Ko et al. Bowel movements per day 5.2 7.5 <0.05
Leakage 0 43 % 0.01
Pads usage 0 17 % <0.01
Perianal skin problems 7 % 33 % <0.01
Food avoidance 43 % 80 % <0.01
Inability to distinguish gas 7 % 37 % <0.01
343
Wuthrich Soiling 25 %

>6 bowel movements/24 h 67 %
344 J. Church
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Chapter 31
Rectal Prolapse: What Is the Best Approach
for Repair?
Saleh Eftaiha and Anders Mellgren
Introduction
Rectal prolapse can be repaired through an abdominal or perineal approach.

Choosing between these approaches has traditionally focused on patient age and
comorbidities; younger, healthier patients undergo an abdominal procedure while
elderly patients often receive a perineal procedure [1, 2]. In North America, abdom-
inal repair is frequently carried out with laparoscopic posterior rectopexy, with or
without resection, while perineal repair is performed with an Altemeier procedure.
Meanwhile, in Europe, and laparoscopic ventral rectopexy takes precedence as the
preferred abdominal repair and the Delorme procedure is utilized more frequently [2].
However, solely using a framework of abdominal vs. perineal approach infers an
oversimplification of the principles and choices for the surgical correction of rectal
prolapse. As we consider the available approaches, we inevitably encounter differ-
ent operations associated with each approach: suture posterior rectopexy, with or
without resection, vs. ventral rectopexy and the Altemeier procedure vs. the Delorme
procedure. There is a paucity of high quality evidence regarding the optimal surgery
for the treatment of rectal prolapse [3]. In our examination of the literature, we have
included findings of two Cochrane reviews (2000 and 2008), two additional system-
atic reviews, two nonrandomized control trials (NRCT), seven randomized control
trials (RCT), and a number of retrospective reviews.
The PROSPER trial, a multicenter RCT primarily based in the United Kingdom,
represents the largest and most ambitious exploration in the choice of procedure for
rectal prolapse. It included a power analysis and revealed a method of randomiza-
tion. This trial, however, did not explicitly state whether the assessors were blinded
S. Eftaiha, MD • A. Mellgren, MD, PhD (*)

Division of Colon & Rectal Surgery, University of Illinois Chicago, Chicago, IL, USA

DOI 10.1007/978-3-319-40223-9_31
348 S. Eftaiha and A. Mellgren
and the trial was underpowered. The majority of the other reported RCT’s were
performed in a single center, often did not carry out a power analysis, usually
included less than 50 patients, and frequently did not state method of randomiza-
tion. One of them was limited to 6 months of follow-up [27]. With these method-
ological weaknesses in mind, the present assessment aimed to evaluate different
types of rectal prolapse repair and review different types of outcomes including
recurrence rates, function, quality of life and morbidity.
Search Strategy
The following broad PICO terms were used: patients with rectal prolapse, abdomi-
nal approach, and perineal approach, outcomes including recurrence of prolapse,
functionality, quality of life, morbidity and mortality (Table 31.1).
Pubmed/Medline, Cochrane databases were searched for relevant articles includ-
ing meta-analysis and systematic reviews. The following keywords and phrases
were used in various combinations: ‘rectal prolapse’, ‘procidentia’, ‘Altemeier’,
‘Delorme’, ‘open’, ‘laparoscopic’, ‘rectopexy’, ‘resection’, and ‘abdominal
approach procidentia/prolapse’, ‘perineal approach procidentia/prolapse.’ All arti-
cles identified within the initial search were screened for relevance and content, and
their references were searched for additional relevant articles. Articles not written in
English, retrospective series under 40 patients, and case reports were excluded.
Results
Abdominal Verses Perineal Approach

Recurrence Rates
Abdominal procedures usually considered to have a lower recurrence rate than peri-
neal procedures, but this is not demonstrated in RCTs. There are two RCTs assess-
ing the abdominal vs. perineal approach. The PROSPER trial [1] randomized 23
Table 31.1 PICO table utilized

Patient
population Intervention Comparator Outcomes
Patients’ with Abdominal approach to Perineal approach to Recurrence of prolapse
rectal prolapse correction of prolapse correction of prolapse Functional outcomes
Quality of life
Morbidity
Mortality
31 Rectal Prolapse: What Is the Best Approach for Repair? 349
patients to abdominal procedures (suture posterior rectopexy and posterior recto-

pexy with resection) and 26 patients to perineal procedures (Altemeier and
Delorme). The group allocation was controlled for age, ASA status and preoperative
bowel function, with a median length of follow up of 36 months. Although under-
powered, there was no statistical significance between abdominal (26 %) and peri-
neal (20 %) operations regarding the incidence of recurrence (p = 0.8). In addition,
PROSPER performed a non-randomized comparison between abdominal and peri-
neal procedures, with reported recurrence rates of 13/68 (19 %) vs. 56/202 (28 %)
respectively (p = 0.2). This is a higher abdominal recurrence rate (19-26 %) than
previously quoted in the literature (~10 %). In another RCT, Deen et al. [4] allocated
ten patients to each arm and median follow-up was 17 months. They reported no
recurrence in the abdominal group and one recurrence in the perineal procedure
group (NS). A third RCT from Germany comparing posterior rectopexy with resec-
tion and Delorme is ongoing and results are pending [5].
The University of Minnesota group reported their experience in one of the largest
retrospective reviews in the literature [6]. They compared abdominal procedures
(posterior rectopexy with and without resection) and perineal procedures (Altemeier
or Delorme). Patients in the perineal group were significantly older and sicker
(p = 0.001) and had shorter recurrence free survival than the abdominal group
(p = 0.0001). The authors reported significantly lower recurrence rates after abdomi-
nal vs. perineal procedures (5 % vs. 16 %), despite longer follow up in the abdomi-
nal group (98 vs. 47 months respectively; p = 0.002; Table 31.2). Recurrences were
usually seen within 3 years, regardless of the type of procedure.
Lee et al. [7] reported similar results in a retrospective review of 104 patients,
noting more recurrences after perineal (15 %) than abdominal (6.3 %) procedures
(p = 0.14). Yakut et al. [8] retrospectively looked at 94 patients and reported no
recurrences after abdominal procedures (0/67) and four recurrences in 27 patients
undergoing Delorme procedures (p < 0.01; Table 31.2). A smaller 10 year retrospec-
tive review from Ochsner Clinic [9] reported a higher incidence of recurrences after
perineal procedures (16 %) compared to abdominal approach (8 %). However, this
was not significant, possibly because of the small sample size.
Table 31.2 Abdominal vs. perineal proctectomy recurrence rates

Patients Abdominal Follow up
Study (year) Type Quality (N) (N) Perineal (N) (months) P value
PROSPER (2013) RCT Moderate 49 5/19 (26 %) 5/25 (20 %) 36 0.8
PROSPER (2013) Non-RCT Moderate 270 13/68 (19 %) 56/202 (28 %) 36 0.2
Deen (1994) RCT Low 20 0/10 1/10 (10 %) 17 NS
Kim (1999) RR Moderate 359 9/176 (5 %) 29/183 (16 %) 98, 47 (P) 0.002
Yakut (1998) RR Low 94 0/67 4/27 (15 %) 36 <0.01
Hammond (2007) RR Low 75 1/13 (8 %) 10/62 (16 %) 39 0.7
Lee (2014) RR Low 104 4/64 (6.3 %) 6/40 (15 %) 60 0.14
RCT randomized control trial, RR retrospective review, NS not significant, P perineal
Function and Quality of Life
The PROSPER trial [1] reported significant improvements from baseline for incon-
tinence (Vaizey score), bowel function and quality of life (EQ-5D) after abdominal
and perineal procedures, without significant differences between the groups.
However, it is noteworthy that patients with a recurrence of their prolapse had sig-
nificantly worse quality of life (p = 0.0009). In the abdominal arm, patients reported
significantly increased ‘straining’, possibly related with constipation.
Deen et al. [4] reported that the perineal group had greater residual fecal incon-
tinence (OR 13.50) and significantly lower maximal resting and squeeze pressures
on manometry (p = 0.003; Table 31.3).
Mirroring PROSPER’s findings, Madoff and coworkers [6] large retrospective
series noted improvement in continence, constipation, and overall satisfaction fol-
lowing both abdominal and perineal procedures, without significant differences
between the two groups. However, Lee et al. [7] reported higher rates of persistent
constipation following abdominal procedures (20.3 %) than after perineal proce-
dures (15 %; p = 0.49), while perineal procedure patients struggled more often with
persistent fecal incontinence (p = 0.054).
Yakut et al. [8] noted that both the abdominal (posterior rectopexy with and with-
out resection) and perineal (Delorme) were effective treatments for rectal prolapse.
They reported, however, a significant risk for sexual dysfunction in males (retro-
grade ejaculation and/or impotence) after posterior rectopexy, likely secondary to
the pelvic dissection [8, 10].
Sexual dysfunction and persistent constipation may be more frequently encoun-
tered after abdominal procedures, while persistent incontinence may be more fre-
quently encountered after perineal procedures.
Table 31.3 Abdominal vs. perineal functional outcome and morbidity comparison
Study Type Quality Patients Incontinence Constipation QOLa Morbidity
Prosper (2013) RCT Moderate 49 Abd = Per – Abd = Per –
(P = 0.5) (P = 0.5)
Deen (1994) RCT Low 20 Abd < Perb – – Abd > Per
(P = NS)
Kim (1999) RR Low 359 Abd < Per Abd > Per Abd = Perc Abd > Per
(P = NS) (P = NS) (P = NS) (P = NS)
Lee (2014) RR Low 104 Abd < Per Abd > Per – Abd > Per
(P = 0.054) (P = 0.49) (P = 0.40)
Young (2015) RR Moderate 3,254 Abd > Per
(P = 0.03)
Abd abdominal procedure, Per perineal procedure, RCT randomized control trial, RR retrospective
review, QOL quality of life
a
EQ-5D
b
OR13.5; 95 % CI (1.2–152.2)
c
Patient satisfaction, not validated QOL score
Morbidity and Mortality
There has been no significant difference in mortality in RCT or large retrospective

reviews comparing abdominal and perineal procedures [1, 6, 7, 11, 12]. Morbidity
is more frequent after abdominal procedures with longer length of stay, especially
after open procedures. Morbidity reported in the PROSPER trial included four
anastomotic leaks after Altemeier procedures, three of which were reported by one
center. Deen et al. [4] reported prolonged ileus (n = 2), wound infection (n = 1), and
anastomotic stricture (n = 1) following posterior rectopexy with resection [11].
Madoff and coworkers [6] reported bowel obstruction (n = 21) and anastomotic
complications, such as leak, bleeding, and stricture (n = 7). Lee et al. [7] reported
more frequent morbidity in the abdominal group, although not statistically signifi-
cant, when compared to perineal resections (p = 0.40). Young et al. [12] evaluated
30 day NSQIP morbidity data after abdominal vs. perineal procedures in 3,254
patients of abdominal and found an increased morbidity after open posterior recto-
pexy with resection when compared to perineal procedures (OR: 1.89, p = 0.03;
Table 31.3). Length of postoperative stay has been consistently shown to be sig-
nificantly shorter after perineal procedure than after abdominal procedures [6, 7, 9,
11, 12].
Altemeier Verses Delorme’s Procedure
Recurrence Rates
Recurrence rates after Altemeier and Delorme procedures range vastly in the litera-
ture. In retrospective reviews with at least 40 patients, the recurrence rates range
between 3–18 % after Altemeier procedures and 6–26 % after Delorme procedures
[6, 13–17]. Follow-up in different series varied, up to 60 months, and recurrence
rates tended to be higher with longer follow-up.
The only RCT to compare recurrence rates between the two perineal approaches
is the PROSPER trial [1]. With 36 month follow up data and controlling for age and
ASA status, there were fewer recurrences after Altemeier procedures (24/102; 24 %)
than after Delorme procedures (31/99; 31 %; p = 0.4; Table 31.4).
Elagali et al. [18] recently compared recurrence rates between these two proce-
dures and reported a significantly higher recurrence rate after Delorme procedures
(16 % vs. 9 %; p = 0.07) with 13 months of follow-up in a retrospective study.
Agachan et al. [19] reported no significant difference in recurrence rates between
Delorme procedures and Altemeier procedures without levatorplasty. Patients with
a concurrent levatorplasty at time of Altemeier procedure had a lower recurrence
rate (p < 0.05). Concurrent levatorplasty has been shown to improve continence as
well. Chun et al. [20] supported this finding in a retrospective review, noting signifi-
cantly reduced recurrence rates (p = 0.05) and improved continence (p = 0.002) with
Table 31.4 Altemeier vs. Delorme recurrence rate comparison

Quality of Pts Altemeier Delorme Follow-up
Study Type evidence (N) (N) (N) (months) P value
PROSPER (2013) RCT Moderate 201 24/102 (24 %) 31/99 (31 %) 36 P = 0.4
Elagili (2015) RR Low 75 2/22 (9 %) 9/53 (16 %) 13 P = 0.07
Agachan (1997) RR Low 61 5/53 (9 %) 3/8 (38 %) 27 P = NS
RCT randomized control trial, RR retrospective review, NS not significant
the addition of levatorplasty with perineal proctectomy, when compared to perineal

proctectomy only. Of historic interest, Dr. Altemeier originally described a
concurrent levator plication with the proctectomy [13], but this has not always been
used after the procedure was ‘re-introduced’ in the 1980s and 1990s by Gopal,
Eftaiha et al. and Prasad et al. [21–23]. With respect to hand sewn vs. stapled anas-
tomosis when performing the Altemeier technique, Boccasanta et al. [24], random-
ized 20 patients in each arm and found no significant difference in recurrence
between the two techniques.
Quality of life after rectal prolapse surgery is important and is more frequently
reported in the recent literature. The PROSPER trial [1] randomized Altemeier
(n = 102) and Delorme (n = 99) cohorts. They found an overall improvement in qual-
ity of life (EQ-5D), overall bowel function and continence (Vaizey score) after 36
months of follow-up, without any statistical significance between both groups
(Table 31.5). The only significance noted is an increased number of outpatient visits
in the Delorme group (unknown reason) (p < 0.01) [1]. Elagali et al. [18] retrospec-
tively looked at QOL after both procedures without noticeable differences between
the groups, or from baseline. Agachan et al. [25] reported resolution of postopera-
tive constipation.
Anastomotic complications are more frequently encountered after Altemeier than

after Delorme procedures (Table 31.5). As previously mentioned, anastomotic leaks
constituted the most severe morbidity with the Altemeier procedure in the PROSPER
trial [1]. Agachan et al. [25] reported significantly higher complications in the
Altemeier group when compared to Delorme, secondary to anastomotic leaks after
perineal proctectomy (p < 0.05). In a recent retrospective series, Elagali et al. [18]
found significantly higher complication rates after Altemeier procedures when com-
pared to Delorme procedures (p = 0.04). They reported an 18 % leak rate after
Altemeier, but no mortality was recorded.
Posterior Rectopexy Without or With Resection
Recurrence Rates
Three RCTs have compared recurrence rates after posterior rectopexy with or with-
out resesction [1, 26, 27]. In the PROSPER trial [1], posterior rectopexy with resec-
tion had fewer recurrences than posterior rectopexy without resection at 36 month
follow up. However, this difference was not statistically significant (p = 0.2;
Table 31.6). Mckee et al. [26] randomized nine patients each to posterior rectopexy
with or without resection and they reported no recurrences in either group at 20
month follow-up. Luukkonen et al. [27] randomized 15 patients in each arm, compar-
ing posterior rectopexy with resection vs. posterior rectopexy with mesh and found
no recurrences in either group. Follow-up was limited to six months. Sayfan et al.
[28] reported no recurrences in 29 patients in a non-randomized trial. Raftopoulos
et al. [29] evaluated recurrence rates after abdominal procedures for prolapse in a 643
patient multicenter, systematic review. They concluded that surgical technique (pos-
terior mobilization only, posterior rectopexy with and without resection), means of
access (laparoscopy vs. open), and method of posterior rectopexy had no impact on
Table 31.5 Altemeier and Delorme procedure functional outcome and morbidity
Study Type Quality Incontinence Constipation QOL Morbidity
PROSPER RCT Moderate Alt = Del – Alt = Dela –
(2013) (P = 0.8) (P = 0.6)
Elagili RR Low Alt > Del Alt > Del Alt = Delb Alt > Del
(2015) (P = 0.72) (P = 0.42) (P = 0.59) (P = 0.04)
Agachan RR Low Alt < Del Alt = Del – Alt > Delc
(1997) (P = NS) (P = NS) (P < 0.05)
Alt Altemeier procedure, Del Delorme procedure, RCT randomized control trial, RR retrospective
review, NS not significant
a
EQ-5D quality of life survey
b
Cleveland Global Quality of Life survey
c
Difference seen with leak & stricture rates, highest with perineal rectosigmoidectomy without
levatorplasty
Table 31.6 Recurrence rates after posterior rectopexy without and with resection
Suture Resection Follow up
Type Patients Quality (N) (N) (months) P-value
PROSPER RCT 39 Moderate 9/35 4/32 36 0.2
(2013) (26 %) (13 %)
Luukkonen RCT 30 Low 0/15 0/15 6 NS
(1992)
McKee (1992) RCT 18 Low 0/9 0/9 20 NS
Sayfan (1990) NRCT 29 Low 0/16 0/13 ? NS
Suture suture rectopexy without resection, Resection resection rectopexy, RCT randomized control
trial, NRCT non randomized control trial, NS not significant
recurrence of prolapse. Laparoscopy did not infer an increase in recurrent prolapse.

The study highlighted that the recurrence increases with time and the 1, 5, and 10
year recurrence rates were 1 %, 7 % and 29 % respectively.
The PROSPER trial [1] found that continence, bowel function and quality of life
improved regardless of whether resection was performed with posterior rectopexy.
Patients undergoing sutured posterior rectopexy reported more frequent usage of
laxatives (Table 31.7). Other reports have demonstrated less postoperative constipa-
tion when posterior rectopexy is combined with resection [26, 27]. Sayfan et al. [28]
reported similar findings in a non-randomized trial, describing increased rates of
constipation rates following mesh posterior rectopexy than after posterior rectopexy
with resection (p < 0.05). The majority of patients in both groups experienced an
improvement in continence and there was no statistically significant difference
between the groups in regards to continence [26, 27].
Mortality was observed in two patients across all three RCTs, including one
patient in the resection group and the other in the posterior rectopexy without
resection group [1, 27]. The morbidity seen in posterior rectopexy with resection
included two anastomotic strictures [27]. There was no statistical significant dif-
ference in morbidity or mortality whether posterior rectopexy was performed with
or without resection [1, 26–28]. However retrospectively, Lee et al. [7] observed
an increase in anastomotic morbidity in the group of patients undergoing resection
(p = 0.009) [7].
Table 31.7 Functional outcome and morbidity after posterior rectopexy with or without resection
Study Type Quality Incontinence Constipation QOL Morbidity
PROSPER RCT Moderate RR = R R > RRa RR = R –
(2013) (P = 0.7) (P = 0.05) (P = 0.1)
Luukkonen RCT Low RR > R R > RR – RR = R
(1992) (P = NS) (P = 0.04) (P = NS)
McKee (1992) RCT Low RR > R R > RRb – –
(P = NS) (P = 0.06)
Sayfan (1990) Non Low RR > R R > RR – RR = R
RCT (P = NS) (P = NS) (P = NS)
Lee (2014) RR Low – – RR > R
(P = 0.009)
RR resection rectopexy, R rectopexy (mesh/suture), RCT randomized control trial, NS not significant
a
Higher use of laxatives reported in the rectopexy group
b
Data combined from Luukkonen and McKee p = 0.003; OR0.07 95 % CI 0.01–0.4
Laparoscopic Verses Open Rectopexy
Laparoscopic posterior rectopexy has been evaluated in two RCTs [30, 31]. A total of
61 patients were randomized to laparoscopic mesh posterior rectopexy (n = 28) and
open mesh posterior rectopexy (n = 32). There were no significant differences detected
in recurrence rates, with two recurrences in the open group, one of which was muco-
sal recurrence [30, 31]; the combined mean follow up was 26 months. Laparoscopic
mesh posterior rectopexy was associated with longer operative time, but shorter
length of stay (p < 0.05) when compared to open cohorts [30, 31]. Continence was
improved, without any significant difference between the groups. Open posterior rec-
topexy significantly increased cardio-respiratory postoperative morbidity compared
to laparoscopic cohorts (p < 0.01) [31]. There was a trend towards new onset constipa-
tion in the open group compared to the laparoscopic group, however this was not
significant [30]. Cost was lower with the laparoscopic vs. open procedure (p < 0.01)
across two different healthcare systems (USA and Australia) [30–32].
Ventral Rectopexy
Laparoscopic ventral rectopexy with mesh is a relatively new abdominal approach

for the correction of rectal prolapse [33]. Data regarding this procedure is mostly
limited to non-randomized retrospective case series and systematic reviews. The
observed recurrence rate ranges between 5-15 % at a median follow-up of 3-61
months [34].
Functional outcomes indicate significant improvements in continence and con-
stipation in the majority of patients. Significant quality of life improvement was
documented in a 31 patient prospective review [35] at 1 year follow-up (p < 0.01).
The mesh erosion rate was reported at 2 % over a 14 year span in a systemic
multicenter review of 2,200 laparoscopic ventral rectopexy; there was no significant
differences if using biologic or synthetic mesh [36]. Mortality at 30 days was
reported at 0.1 %. As there is a propensity for laparoscopic ventral rectopexy in
Europe and laparoscopic posterior rectopexy with resection in North America,
results from a non-randomized, multi-institutional international trial comparing the
two approaches is ongoing (LaProS study) [2].
Recommendations
• Correction of rectal prolapse through an abdominal approach connfers less recur-

rence (although higher than previously reported) compared to a perineal
approach. However, consideration should be given to perineal procedures in frail
patients as morbidity is lower with acceptable function and quality of life.
(Evidence quality moderate; conditional recommendation).
• Abdominal approaches can be performed with laparoscopy with similar out-

comes. (Evidence quality moderate; strong recommendation).
• Posterior rectopexy with resection and ventral rectopexy have acceptable recur-
rence rates and improve both quality of life and bowel function. Sutured poste-
rior rectopexy without resection may carry an increased risk for postoperative
functional problems, but avoids the risk of anastomotic dehiscence or mesh com-
plications. (Evidence quality moderate; strong recommendation).
• If the perineal approach is chosen, both the Altemeier and Delorme procedures
are acceptable in terms of recurrence, functional outcome and quality of life.
Although there is a trend towards less recurrence and higher quality of life fol-
lowing Altemeier procedures, there is an increased risk for postoperative mor-
bidity when compared to the Delorme procedure. (Evidence quality low;
conditional recommendation).
• Concurrent levatorplasty with Altemeier procedure should be performed.
(Evidence quality moderate; strong recommendation).
Personal View
• Women with rectal prolapse have a significant incidences of concomitant geni-

tal prolapse and we therefore recommend that the majority of patients undergo
a pelvic evaluation by a urogynecologist before proceeding with surgical repair.
• Abdominal approach is preferred for a majority of patients, because of a lower
risk for recurrence. Perineal approaches are usually reserved for elderly patients
or patients with significant comorbidities.
• The Altemeier procedure is chosen for a majority of patients operated with a
perineal technique. The Delorme procedure is reserved for patients with a small
prolapse.
• The risk for sexual dysfunction should be discussed with young males with rectal
prolapse. This risk is lower with perineal procedures, but will need to be weighed
against the higher risk for recurrence.
• Posterior rectopexy can be performed with laparoscopic, robotic or open tech-
nique. We prefer open technique using a pfannenstiel incision or robotic tech-
nique. These two techniques provides a good mobilization combined with a
stable suspension.
• Posterior rectopexy with resection is reserved for patients with significant preop-
erative constipation, because of the risk for anastomotic problems. Ventral recto-
pexy is an intriguing alternative for these patients (please see below).
• Ventral rectopexy is an intriguing alternative for rectal prolapse repair, because
of improved functional outcome in recent studies. This surgery can be performed
with open, laparoscopic or robotic technique. We prefer using the robot, which
offers excellent visualization combined with excellent ability for suturing.
Patients need to be counseled about the risks with pelvic mesh. We prefer using
biologic mesh, which may have a better risk profile, but could increase the risk
for recurrence.
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Colon Rectum. 2009;52(4):698–703.
18. Elagili F, et al. Comparing perineal repairs for rectal prolapse: Delorme vs Altemeier. Tech
Coloproctol. 2015;19(9):521–5.
19. Agachan F, et al. Results of perineal procedures for the treatment of rectal prolapse. Am Surg.
1997;63(1):9–12.
20. Chun SW, et al. Perineal rectosigmoidectomy for rectal prolapse: role of levatorplasty. Tech
Coloproctol. 2004;8(1):3–8; discussion 8–9.
21. Gopal KA, et al. Rectal procidentia in elderly and debilitated patients. Experience with the
Altemeier procedure. Dis Colon Rectum. 1984;27(6):376–81.
22. Ramanujam PS, Venkatesh KS. Perineal excision of rectal prolapse with posterior levator ani
repair in elderly high-risk patients. Dis Colon Rectum. 1988;31(9):704–6.
23. Prasad ML, et al. Perineal proctectomy, posterior rectopexy, and postanal levator repair for the
treatment of rectal prolapse. Dis Colon Rectum. 1986;29(9):547–52.
24. Boccasanta P, et al. Impact of new technologies on the clinical and functional outcome of
Altemeier’s procedure: a randomized, controlled trial. Dis Colon Rectum. 2006;49(5):
652–60.
25. Agachan F, et al. Comparison of three perineal procedures for the treatment of rectal prolapse.
South Med J. 1997;90(9):925–32.
26. McKee RF, et al. A prospective randomized study of abdominal rectopexy with and without
sigmoidectomy in rectal prolapse. Surg Gynecol Obstet. 1992;174(2):145–8.
27. Luukkonen P, Mikkonen U, Jarvinen H. Abdominal rectopexy with sigmoidectomy vs. recto-
pexy alone for rectal prolapse: a prospective, randomized study. Int J Colorectal Dis.
1992;7(4):219–22.
28. Sayfan J, et al. Sutured posterior abdominal rectopexy with sigmoidectomy compared with
Marlex rectopexy for rectal prolapse. Br J Surg. 1990;77(2):143–5.
29. Raftopoulos Y, et al. Recurrence rates after abdominal surgery for complete rectal prolapse: a
multicenter pooled analysis of 643 individual patient data. Dis Colon Rectum.
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30. Boccasanta P, et al. Comparison of laparoscopic rectopexy with open technique in the treat-
ment of complete rectal prolapse: clinical and functional results. Surg Laparosc Endosc.
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31. Solomon MJ, et al. Randomized clinical trial of laparoscopic vs. open abdominal rectopexy for
rectal prolapse. Br J Surg. 2002;89(1):35–9.
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33. D’Hoore A, Cadoni R, Penninckx F. Long-term outcome of laparoscopic ventral rectopexy for
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34. Samaranayake CB, et al. Systematic review on ventral rectopexy for rectal prolapse and intus-
susception. Colorectal Dis. 2010;12(6):504–12.
35. Maggiori L, et al. Laparoscopic ventral rectopexy: a prospective long-term evaluation of func-
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pexy. Dis Colon Rectum. 2015;58(8):799–807.
Part VI
Benign Anal Disease
Chapter 32
Optimal Management of the Transsphincteric
Anal Fistula
Richard T. Birkett and Jason F. Hall
Introduction
Management of transsphincteric fistulas can pose a difficult challenge for surgeons.

The goal is to cure the fistula while retaining functional capacity of the sphincter
complex. The Parks system is the classic classification system, which divides fistu-
las into five types: intersphincteric, transsphincteric (high and low), suprasphinc-
teric, and extrasphincteric (Fig. 32.1), based on the course of the track in relation to
the anal sphincter complex [2]. Goals of management include eradicating sepsis,
promoting healing of the fistula tract, maintaining continence through preservation
of the sphincter complex, and preventing future recurrence. Simple submucosal,
intersphincteric, and low transsphincteric fistulas can be managed effectively with
conventional fistulotomy and represents the gold standard comparator owing to low
incontinence and recurrence rates [3]. However, transsphincteric fistulas cross
through the internal and external sphincter, predisposing patients to higher rates of
incontinence following fistulotomy. Therefore, a number of alternative approaches
have been developed to tackle these complex fistulas although no consensus algo-
rithm for management exists.
In this chapter, the data regarding sphincter-saving approaches to complex trans-
sphincteric fistulas is reviewed. We discuss the following techniques in our
review:fistulotomy, seton placement, fibrin glue, plug, endorectaladvancement flap
(ERAF) and ligation of the intersphincteric fistula tract procedure (LIFT). Our rec-
ommendations are based on data presented in Table 32.1, comparing fistulotomy,
R.T. Birkett, MD
Lahey Hospital and Medical Center, Burlington, MA, USA
J.F. Hall, MD, MPH, FACS (*)
Department of Surgery, Boston Medical Center, Boston, MA, USA

DOI 10.1007/978-3-319-40223-9_32
362 R.T. Birkett and J.F. Hall
Fig. 32.1 Parks
classification (A)
superficial fistula (B)
intersphincteric fistula (C)
transsphincteric fistula (D)
suprasphinteric fistula (E)
extrasphincteric fistula
(From Simpson et al. [1])
plug, ERAF and LIFT. In addition, we comment on the experience at our institution
and our personal approach to this problem (Table 32.2).
Search Strategy
We performed a literature search in the MEDLINE database (using PUBMED)

under the search titles “transsphincteric fistula” or “fistula-in-ano”. We initially
focused on prospective trials randomized studies. Further mining was performed
using the reference lists of published systematic reviews. Given the lack of random-
ized trials involving all treatment interventions, especially the LIFT procedure, we
did include multicenter prospective observation studies and multicenter center ret-
rospective review studies. Although discussed in text, we excluded meta-analyses,
single-surgeon reviews, single-surgeon observational studies and those published in
foreign languages.
Results
Fistulotomy
Fistulotomies are performed by unroofing the track between the internal and exter-
nal openings (Fig. 32.2). Reported recurrence rates are low. A zero recurrence rate
was reported by a single surgeon case series of 38 patients over 5 years [17]. A more
recent multicenter retrospective review of 537 patients undergoing fistulotomy for
low perianal fistula reports a primary healing rate of 83.6 %, 81.7 % for transsphinc-
teric, and a secondary healing rate of 90.3 % after treatment for recurrence [4].
Table 32.1 Summary of evidence
Function
Author (year) Population Procedure N Median follow-up Success change post-op Between groups
Gottgens [4] (2015) Low transsphincteric Fistulotomy 164 38.9 months (6–74.8) 134 (81.7 %)
Abramowitz [5] Low transsphincteric Fistulotomy 93 12 months =
(2015) High transsphincteric Seton + staged 59 −
fistulotomy
Schwander [6] Transsphincteric after seton Plug 66 12 months 37 (62 %) =
(2009)
Stamos [7] (2015) Complex transsphincteric Plug 55 12 months 49 % +
Perez [8] (2006)* High transsphincteric & Fistulotomy 28 38 months (24–52) 26 (92.8 %) = =
suprasphincteric ERAF 27 25 (92.5 %) =
Ortiz [9] (2009)* High transsphincteric Plug 15 12 months 3 (20 %)
ERAF 16 14 (87.5 %)
Van Koperen [10] High transsphincteric Plug 31 11 months (5–27) 9 (29 %) = =
(2011)* ERAF 29 14 (48 %) =
Hall [11] (2014) Low tanssphincteric LIFT 17 3 months 14 (82 %) +
32 Optimal Management of the Transsphincteric Anal Fistula
High transsphincteric 19 15 (79 %) +

Sileri [12] (2014) Complex fistulas LIFT 26 20 months (16–24) 19 (73 %) =
Han [13] (2015)* Transsphincteric LIFT 118 6 months 99 (83.9 %) = =
LIFT-Plug 117 110 (95 %) =
Madbouly [14] High transsphincteric ERAF 35 12 months 23 (65.7 %) = =
(2014)* LIFT 35 26 (74.3 %) =
Mushaya [15] Transsphincteric or complex ERAF 14 19.2 months 13 (92.9 %) = =
(2012)* LIFT 25 (1.7–32.2) 23 (92 %) =
*Randomized study; + improvement incontinence score; − worsening incontinence score; = no statistic difference in incontinence score
363
Table 32.2 Comparison of available approaches for management of transphincteric fistulas

Patients with transsphincteric Fistulotomy Sphincter saving Cure, continence
fistulas approach
Fig. 32.2 Fistulotomy
(Fischer et al. [16])
Incontinence rates following fistulotomy depends on both the amount of muscle

divided at the time of operation as well as any preexisting sphincter damage.
Although Gottgens et al. reported a major incontinence rate of 28 %, the risk of
incontinence in simple fistulas is very low. Abramowitz et al. described only a
1-point increase in Wexner score postoperatively after 1 year in patients undergoing
fistulotomy for low fistula with a reported score ≤5 in 69 %. However, the median
Wexner score worsened by 3 points for patients with high transsphincteric fistulas,
which was statistically significant [5].
32 Optimal Management of the Transsphincteric Anal Fistula 365
Setons
Setons are the oldest recorded surgical approach to fistula management, first
described by the Indian Surgeon Shushruta 1200 BC. A seton serves to drain sepsis,
enables preservation of the sphincter mechanism and can prepare the patient for a
two-stage procedure. A draining seton prevents the internal and external orifices of
the fistulas from closing, allowing infection to dissipate. Cutting setons enable slow
division of a fistula tract by pressure necrosis of the intervening tissue. Because the
division is slow, it is postulated that this leads to greater fibrosis without a signifi-
cant gap in the sphincter complex.
Short-term healing rates with draining setons have been reported to be between
44 and 83 % [18]. These durability of these results must be questioned as draining
setons do little to alter the underlying anatomy and physiology of a fistula tract.
While they may reduce symptoms, it is doubtful that they lead to eradication of the
fistula tract in any circumstance. A recent retrospective analysis of 121 patients with
transsphincteric fistulas reported a 98 % healing rate with cutting setons.
Preoperatively, 23 (19 %) of the patients reported incontinence to feces or gas. At
follow-up, only 14 (11.6 %) reported seepage of stool or loss of flatus control, 0 and
none experienced major continence issues. Of the initial 23 patients that reported
continence disturbances preoperatively, symptoms had resolved in 17 patients after
surgery (73.9 %). New onset incontinence did occur in eight patients, but all denied
change in lifestyle or the need to wear a pad [19].
Although cutting setons have been reported to be effective, their use has been
limited due to concerns about subsequent fecal incontinence. A large review of
multiple studies on cutting setons including over 500 patients reported an average
incontinence rate of 32 % across all types of fistulas and 20.5 % when used for trans-
sphincteric fistulas. However, the definitions and grading of incontinence were
missing in over a third of the studies [20]. A UK position statement described simi-
lar results with incontinence rates ranging up to 62 % including major incontinence
in 10 % reported in seven studies reviewed [21]. Additionally, one must account for
the need of interval tightening and associated discomfort caused by cutting setons.
Advancement Flaps
ERAF is an alternative option to avoid division of the sphincter complex. A semi-

circular flap or U-shaped flap of mucosa, submucosa and a few muscle fibers is
raised from the level of the dentate line over a distance of 4–5 cm proximally. The
flap is then lifted to expose the fistula tract, which is cored out and the associated
muscle defect is sutured closed. The flap is then advanced down to the dentate line
and anchored with absorbable sutures.
A recent meta-analysis of 35 studies reported an 80.7 % success rate and 13.2 %
incontinence rates for cryptoglandular fistulas, although the quality of the reports
were low [22]. A study on long-term outcomes of advancement flaps in high trans-
sphincteric, suprasphincteric and extrasphincteric fistulas reports a meager success
rate of 37 % with a mean follow-up of 72 months [23]. Although this study accumu-
lated a reasonable sample size, it is a single-center observational study and the fis-
tula etiology was Crohn’s disease in more than a quarter of the patients. Perez et al.,
conducted a randomized, prospective trial randomizing 55 patients with high
transsphincteric fistulas and suprasphincteric fistulas to ERAF or fistulotomy with
sphincter reconstruction and found no difference in recurrence or incontinence
rates. The success rates in both groups remarkably exceeded 92 % and there was no
change in continence scores between groups [8]. Additional studies comparing
ERAF to LIFT will be discussed later in the chapter. The best reported outcomes
have been associated with a full-thickness flap in conjunction with fistulectomy,
without fibrin glue or preliminary draining seton [24].
Biologic Products
Fibrin glue is another sphincter-sparing option for complex fistulas, however, suc-
cess rates generally appear to be poor. The glue is a combination of fibrinogen,
thrombin and factor XIII which cross-links with collagen in the tissue, sealing the
tract and stimulates the growth of fibroblasts and pluripotent endothelial cells pro-
moting collagen deposition and wound healing.
One study looking at long-term results of fibrin glue over an average of 22 months
after seton drainage, reported an initial closure rate of 60 % which increased to 69 %
with retreatment [25]. In contrast, Buchanan et al. found successful healing in only 3
of 22 patients (14 %) with complex fistulas with fibrin glue after tract curettage [26].
An alternative to fibrin glue is a synthetic anal fistula plug. The plug rolled into
a conical configuration, then secured into the primary opening of the fistula tract to
promote healing. Schwander et al. followed 66 patients in a multicenter study over
12 months with transsphincteric fistulas treated with seton placement followed by
anal fistula plug 8 weeks later and reported a 62 % success rate [6]. A more recent
multicenter study of cryptoglandular transsphincteric anal fistulas included 55
patients from 11 centers and reported a 12-month healing rate of 49 %; all had sig-
nificantly improved Wexner scores by 6 months. There were 8 total and 5 partial
plug extrusions [7].
Ortiz et al. compared ERAF with anal fistula plugs. The study was cut short sec-
ondary to high recurrence rates in the plug arm whereas only 2 of 116 patients
treated with ERAF had recurrence [9]. These results were confirmed in another
double-blinded multicenter trial which found a recurrence rate of 71 % using fistula
plug vs 52 % with ERAF, although this was not a significant difference given the
number of patients completing the study. Interestingly, there were no differences in
post-operative pain or incontinence scores [10]. The plug procedure has been aban-
doned by many owing to poor results.
LIFT Procedure
The LIFT procedure was first described by Rojanasakul et al. in 2007 [27]. The
procedure involves dissection in the intersphincteric plane to define and encircle the
fistula tract. The fistula is then ligated without division of the sphincter complex.
The mean success rate at 10 months was 76.5 %, with a 5.5 % post-operative com-
plication rate in one review [28]. Another recent review analyzed 26 studies which
included one randomized controlled trial and 25 cohort/case series. Seven technical
variations of the ligation of the intersphincteric fistula tract procedure were identi-
fied and classified according to the surgical technique. Primary healing rates ranged
from 47 to 95 %. In 12 of these studies, the classic LIFT procedure was used, and
healing rates ranged between 61 and 94.4 %. Several technical modifications have
been described, including LIFT combined with excision of the intersphincteric
tract, coring out of the fistula tract, intraoperative seton, advancement flap, plug and
adjunctive use of a bioprosthetic graft; a similar range of success was observed [29].
Early results from a multicenter study in China suggest a higher primary healing
rate with placement of a bioprosthetic plug in the tract extending to the external open-
ing. Han et al. randomized over 100 patients to either a LIFT or LIFT-plug arm. Initial
results include an 83.9 % success rate after LIFT and 95 % combined with the plug.
No difference was found in continence scores; longer follow-up is necessary [13].
A prospective multicenter study of high volume New England centers reported
results of operative options for surgical management of anal fistulas. These authors
were particularly interested in short term outcomes of the LIFT procedure. They
found that of the 43 LIFT procedures, 88 % of were performed for transsphincteric
fistulas. Hospital site was the only variable associated with healing. Hospitals that
performed more LIFT procedures had higher healing rates. At 3 months, 79 % of
high transsphincteric fistulas had healed versus 82 % for low fistulas, with no statis-
tical difference. Patients that had a seton placed preoperatively before LIFT proce-
dure did not appear to have higher healing when compared to patients treated with
LIFT alone. Mean continence scores improved in all groups [11]. Sileri et al. found
similar results with respect to the success rate after LIFT. This multicenter prospec-
tive study reported an 73 % healing rate in 26 patients followed over 20 months,
with no change in function.
Two randomized studies compared LIFT to ERAF in managing complex trans-
sphincteric fistulas. Mabdouly et al. found a cure rate of 74.3 % with LIFT versus
65.7 % after ERAF at 1 year. No change in Wexner score was reported, however,
mean healing time was shorter (22.6 days) after LIFT than ERAF (32 days) and
patients reported less immediate postoperative pain in the LIFT group [14]. An
earlier, smaller study found a comparable success rates of over 92 % in both groups,
and similar secondary outcomes to other studies. They found that the LIFT group
had faster healing times, less postoperative pain and higher patient satisfaction
scores in comparison to patients undergoing ERAF.15
Conclusion and Personal View
Low transsphincteric fistulas can usually be managed readily with fistulotomy.

These patients usually go on to prompt healing with low rates of long term fecal
incontinence. More complex fistulas are often very challenging as one must balance
the desire for healing with the risk of fecal incontinence. Management should be
individualized and tailored to the patient’s current bowel habits and sphincter
function.
The initial approach for all patients should be control of sepsis and precise evalu-
ation of the anatomy. Examination in the clinic setting or under anesthesia are both
effective tools for defining the anatomy of the fistula tract. Occasionally, imaging
might be required to delineate the anatomy of a fistula. We often find that placement
of a seton helps to clearly delineate the anatomy of the fistula tract as well as reduce
local sepsis. Once these objectives have been accomplished, then a rational choice
can be made regarding the most appropriate definitive strategy for addressing the
fistula.
For high transphincteric fistulas where the fistula traverses more than a third of
the external sphincter, we favor a sphincter-saving approach over fistulotomy. Also,
patients with low transsphincteric fistulas and higher baseline fecal incontinence
scores are typically better served with a sphincter-sparing procedure.
Level 1 data comparing advancement flap to the LIFT procedure are limited.
Both randomized trials comparing ERAF to LIFT reported largely equivalent results
and involve only short follow-up. Smaller case-series examining each technique are
limited by selection bias.
Our approach is to offer ERAF or LIFT to patients with high transsphincteric
fistulas or in those with poor sphincter function. Some important technical details
merit consideration when making a decision about which technique to use. We have
found that identification of the fistula in the intersphincteric groove can be difficult
in patients with posterior fistulas. This makes ligation of the fistula track difficult
and often leads to technical failure of a LIFT procedure. Thus, we offer most patients
with posterior fistulas ERAF. Most other patients can be offered LIFT as we have
demonstrated that it can be performed safely with good short term healing rates. In
the evaluation and treatment of patients with complex fistulas, there is no substitute
for the patient’s understanding of the anatomic complexity and technical consider-
ations that are associated with each approach.
References
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1976;63:1–12.
3. Whiteford M, Kilkenny J, Hyman N, et al. Practice parameters for the treatment of perianal
abscess and fistula-in-ano (revised). Dis Colon Rectum. 2005;48:1337–42.
4. Gottgens KWA, Janssen PTJ, Heemskerk J, van Dielen FMH, Konsten JLM, Lettinga T,
Hoofwijk AGM, Belgers HJ, Stassen LPS, Breukink SO. Long-term outcome of low perianal
fistulas treated by fistulotomy: a multicenter study. Int J Colorectal Dis. 2015;20:213–9.
5. Abramowitz L, Soudan D, Souffran M, Bouchard D, Castinel A, Suduca JM, Staumont G,
Devulder F, Pigot F, Ganansia R, Varastet M. The outcome of fistulotomy for anal fistula at one
year: a prospective multicentre French study. Colorectal Dis. 2015;18:279–85.
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ment of complex anal fistulas with the anal fistula plug: a prospective, multicenter study. Dis
Colon Rectum. 2009;52(9):1578–83.
7. Stamos MJ, Snyder M, Robb BW, Ky A, Singer M, Stewart DB, Sonoda T, Abcarian
H. Prospective multicenter study of a synthetic bioabsorbable anal fistula plug to treat crypto-
glandular transsphincteric anal fistulas. Dis Colon Rectum. 2015;58(3):344–51.
8. Perez F, Arroyo A, Serrano P, et al. Randomized clinical and manometric study of advance-
ment flap versus fistulotomy with sphincter reconstruction in the management of complex
fistula-in-ano. Am J Surg. 2006;192:34–40.
9. Ortiz H, Marzo J, Ciga MA, et al. Randomized clinical trial of anal fistula plug versus endorec-
tal advancement flap for the treatment of high cryptoglandular fistula in ano. Br J Surg.
2009;96:608–12.
10. Van Koperen PJ, Bemelman WA, Gerhards MF, Janssen LW, van Tets WF, van Dalsen AD,
Slors JF. The anal fistula plug treatment compared with the mucosal advancement flap for
cryptoglandular high transsphincteric perianal fistula: a double-blinded multicenter random-
ized trial. Dis Colon Rectum. 2011;54(4):387–93.
11. Hall JF, Bordeianou L, Hyman N, Read T, Bartus C, Schoetz D, Marcello PW. Outcomes after
operations for anal fistula: results of a prospective, multicenter, regional study. Dis Colon
Rectum. 2014;57(11):1304–8.
12. Sileri P, Giarratano G, Franceschilli L, Limura E, Perrone F, Stazi A, Toscana C, Gaspari
AL. Ligation of the intersphincteric fistula tract (LIFT): a minimally invasive procedure for
complex anal fistula two-year results of a prospective multicentric study. Surg Innov.
2014;21(5):476–80.
13. Han JG, Jun WZ, Zheng Y, Chen CW, Wang XQ, Che XM, Song WL, Cui JJ. Ligation of
intersphincteric fistula tract vs ligation of intersphincteric fistula tract plus a bioprosthetic anal
fistula plug procedure in patients with transsphincteric anal fistula: early results of a multi-
center prospective randomized trial. Ann Surg. 2015:24. [Epub ahead of print].
14. Madbouly KM, El Shazly W, Abbas KS, Hussein AM. Ligation of intersphincteric fistula tract
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spective randomized trial. Dis Colon Rectum. 2014;57(10):1202–8.
15. Mushaya C, Bartlett L, Schulze B, Ho YH. Ligation of intersphincteric fistula tract compared
with advancement flap for complex anorectal fistulas requiring initial seton drainage. Am
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16. Fischer JE, Jones DB, Pomposelli FB, Upchurch GR, Klimberg VS, Schwaitzberg SD, Bland
KI. Fischer’s mastery of surgery. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2012.
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las. Dis Colon Rectum. 2007;50:1535–9.
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2015;21(1):12–20.
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or charm? Colorectal Dis. 2015;18(5):488–95. doi:10.1111/codi.13120.
20. Ritchie RD, Sackier JM, Hodde JP. Incontinence rates after cutting seton treatment for anal
fistula. Colorectal Dis. 2009;11:564–71.
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statement. Colorectal Dis. 2007;9 Suppl 4:18–50.
22. Soltani A, Kaiser AM. Endorectal advancement flap for cryptoglandular or Crohn’s fistula-in-
ano. Dis Colon Rectum. 2010;53(4):486–95.
23. Van der Hagen SJ, Baeten CG, Soeters PB, van Gemert WG. Longterm outcome following
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2003;46(4):498–502.
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Chapter 33
Benign Anal Disease: Management
of the Recurrent Anovaginal/Rectovaginal
Fistula
Elise H. Lawson and Patricia L. Roberts
Introduction
Rectovaginal fistula represents a challenging and often frustrating clinical entity for
patients and surgeons alike. Despite a plethora of available approaches for repair,
rates of non-healing and recurrence remain high. As a result, patients often require
multiple attempts at repair before a satisfactory outcome is achieved. The surgical
literature is replete with observational studies consisting of single-institution case
series; however, there is a lack of level 1 evidence to support definitive recommen-
dations. In this chapter, we summarize the available literature regarding procedures
used to treat recurrent rectovaginal fistulas, then, supplement this with recommen-
dations and observations from clinical practice. Specifically, we focused on endorec-
tal/mucosal advancement flaps, tissue transposition techniques, and biologic mesh
repair.
Search Strategy
We performed a MEDLINE literature search limited to years 2005–2015 using the

search terms “anovaginal fistula” OR “rectovaginal fistula.” Abstracts were reviewed
for the 166 titles produced by this search strategy. To be included, articles had to be
E.H. Lawson, MD, MSHS

Lahey Hospital and Medical Center, Burlington, MA, USA
P.L. Roberts, MD (*)
Department of Colon and Rectal Surgery, Lahey Hospital and Medical Center,
41 Mall Rd, Burlington, MA 01805, USA

DOI 10.1007/978-3-319-40223-9_33
372 E.H. Lawson and P.L. Roberts
an original research study addressing the repair of rectovaginal fistula in an adult.

We included studies on initial rectovaginal fistula repair because of the paucity of
studies specifically focused on recurrent fistula. References were mined to identify
additional articles for inclusion. Articles focused on plugs, sealants, diversion alone
or simple repair with episioproctotomy/fistulotomy or levatorplasty were excluded
due to lack of efficacy of these methods for recurrent rectovaginal fistula.
Additionally, we excluded retrospective single-institution experience case review
studies describing a heterogeneous mix of approaches to repair. The exception to
this was 3 studies focused on Crohn’s-related fistula. Ultimately, our search strategy
produced 22 studies for inclusion (Table 33.1).
PICO table for rectovaginal fistula
Patient
population Intervention Comparator Outcomes studied
Recurrent Tissue transposition Endorectal/mucosal Rate of non-healing and/or
rectovaginal techniques (Martius, advancement flaps, recurrence, postoperative
fistula gracilis muscle) mesh repair adverse events
Results
A common approach for initial or recurrent rectovaginal fistula is the endorectal or

mucosal advancement flap repair. This method involves extending a U-shaped flap
of rectal mucosa, and often submucosa, over the internal opening of the fistula. A
study by de Pareades [1] described this technique combined with muscular plication
in 23 patients (10 initial fistula, 13 recurrent) and reported a success rate of 65 %.
The authors further reported that symptoms were not worsened in the 8 patients
with a failed repair. Notably, patients with active Crohn’s proctitis, malignant or
radiation-induced fistula, stricture of the anorectum or an external sphincter defect
were excluded from the study.
Similarly, Hull [2] reported a 62 % success rate for full thickness rectal advance-
ment flaps performed on 37 women with rectovaginal fistula resulting from obstetri-
cal trauma or cryptoglandular origin. About half the patients also had a protective
stoma. This study also described the authors’ experience with episioproctotomy,
which is their preferred approach for repair when there is a significant anterior
sphincter muscle defect identified by anal endosonography. Though not explicitly
stated, the report implies that patients undergoing advancement flap did not have a
significant sphincter defect identified preoperatively. Finally, a study by Ellis [3]
described the authors’ experience with advancement flap repair (mucosal or anoder-
mal) in women with an initial or recurrent fistula but without active Crohn’s disease
or acute injury. The rate of healing was 62 % for the 29 patients who underwent
mucosal advancement flap and 73 % for the 27 patients who underwent anodermal
flap. Sphincteroplasty and/or levatorplasty was performed if an associated muscle
injury was identified preoperatively.
Table 33.2 Summary of evidence for rectovaginal fistula repair
Population (time Number of Diverting Quality of
Author (Year) period) Method of repair patients stoma? Results Follow-up evidence
De Parades Rectovaginal Endorectal advancement 23 (10 initial, No 15 (65 %) healed Mean 14 Low
(2011) [1] fistula flap with muscular 13 recurrent) months (2–67)
(2003–2008) plication
Hull (2011) Rectovaginal fistula Rectal advancement flap 37 19 (54 %) 23 (62 %) healed Median 39 Low
[2] from obstetrical or with stoma months
33 Rectovaginal Fistula
cryptoglandular (13–70)
origin (1997–2009)
Ellis (2008) Rectovaginal Mucosal advancement 29 MAF, 15 No Healed: Mean 11 Low
[3] fistula flap (MAF), anodermal AAF, 27 MAF – 18 (62 %) months (3–26)
(2000–2006) advancement flap (AAF), bioprosthetic AAF – 11 (73 %)
bioprosthetic mesh Bio mesh – 22 (81 %)
interposition mesh repair interposition, Plug – 6 (86 %)
with or without plug 7 mesh plus
plug
Gottgens, Recurrent Transperineal or 12 (10 8 with 8 (67 %) healed Median 22 Low
(2014) [4] rectovaginal or transvaginal repair with transperineal stoma, 4 1 (8 %) healed after months (2–45)
pouch-vaginal collagen matrix biomesh repair, 2 without subsequent rectus
fistula transvaginal) abdominal transposition
(2009–2012) 3 (25 %) unhealed or
recurrent
Schwander Fistula in lower 2/3 Surgisis mesh 21 (18 recurrent, 8 (38 %) with 15 (71 %) healed Mean 12 Low
(2009) [5] of rectovaginal 3 initial) stoma 4 (19 %) healed after months (3–18)
septum subsequent repair
(2007–2008) 2 (10 %) unhealed or
recurrent fistula.
4 (19 %) minor
postoperative
complications
373
(continued)
374

Schouten Low rectovaginal Rectal sleeve 8 2 with stoma 5 (63 %) healed. Median 12 Low
(2009) [6] fistula from advancement months (3–17)
obstetrical,
iatrogenic or
cryptoglandular
origin (2006–2009)
Lamazza Rectovaginal fistula Endoscopic placement of 15 (11 initial, 4 Yes, for 12 (80 %) healed Mean 22 Low
(2015) [7] after XRT and self-expandable metal recurrent) recurrent 1 (7 %) didn’t tolerate months (4–39)
anterior resection stent fistula stent
for rectal cancer
(not available)
Pitel (2011) [8] Low rectovaginal Martius advancement flap 20 (5 initial, 14 14 with 13 (65 %) healed Median 29 Low
fistula (2000–2010) with prior rectal stoma, 6 3 (15 %) minor wound months (2–210)
advancement without complications.
flap, 1 prior
Martius flap)
Songne (2006) Rectovaginal fistula Martius advancement flap 14 (10 initial, 4 Yes 13 (93 %) healed Mean 40 Low
[9] (1994–2004) recurrent) 1 (7 %) healed with months (8–120)
subsequent repair
McNevin Rectovaginal fistula Martius advancement flap 16 6 with, 10 15 (94 %) healed Mean 75 weeks Low
(2007) [10] (2002–2006) without 1 (6 %) recurrent (24–190)
Cui (2009) [11] Rectovaginal fistula Martius advancement flap 9 (3 initial, 6 Yes, for 100 % healed Median 14 Low
(2003–2007) recurrent) recurrent months (6–48)
fistulas
Troja (2013) Recurrent Graciloplasty 10 (5 Yes 6 (60 %) healed Median 50 Low
[12] rectovaginal, rectovaginal, 4 1 (10 %) perineal wound months (20–63)
pouch-vaginal or pouch-vaginal, 1 defect
anovaginal fistula anovaginal) 1 (10 %) hematoma
after primary closure
E.H. Lawson and P.L. Roberts
(2004–2010)
Nassar (2011) Iatrogenic Graciloplasty 11 Yes 11 (100 %) healed Mean 35 Low
[13] rectovaginal fistula 4 (36 %) minor months (12–67)
(2002–2009) postoperative
complications
Lefevre (2009) Recurrent Graciloplasty 8 Yes 6 (75 %) healed Median 28 Low
[14] rectovaginal fistula 1 (13 %) healed after months (4–55)
33 Rectovaginal Fistula
(2003–2006) subsequent repair

1 (13 %) recurrence
Ulrich (2009) Recurrent Graciloplasty 9 Yes 7 (78 %) healed Mean 28 month Low
[15] rectovaginal fistula (3–52)
(2003–2008)
Zmora (2006) Rectovaginal and Graciloplasty 6 4 with, 2 5 (83 %) healed Median 26 Low
[16] pouchvaginal without 1 (17 %) recurrence months (9–74)
fistula w/history of 1 (17 %) perineal wound
prior repair or infection
pelvic irradiation
(1999–2005)
Wexner (2008) Rectovaginal and Graciloplasty 17 (4 initial, 13 Yes 7 (41 %) healed Not reported Low
[17] pouchvaginal recurrent) 2 (12 %) healed after
fistula (1995–2007) repeat repair
8 (47 %) unhealed
8 (47 %) minor wound
complications
Schloericke Low or mid- Transabdominal/ 9 Yes (except 8 (89 %) healed Median 22 Low
(2011) [18] rectovaginal fistula transperineal omental flap 1) 1 (11 %) healed after months
(2000–2010) subsequent repair
2 (22 %) with minor
complications
(continued)
375
376
van der Hagen Rectovaginal fistula Laparoscopic excision and 40 2 (5 %) 38 (95 %) healed Median 28 Low
(2011) [19] between middle omentoplasty underwent 1 (3 %) necrotic omentum months (10–35)
third of rectum and stoma requiring reoperation
posterior vaginal because 1 (3 %) abscess requiring
fornix (2006–2009) omentoplasty drainage
not feasible
El-Gazzaz Crohn’s-related Multiple 65 39 with 30 (46 %) healed Median 45 Low
(2009) [20] rectovaginal fistula stoma (60 %) months (13–79)
(1997–2007)
Ruffolo (2008) Crohn’s-related Multiple 52 Some with 29 (56 %) healed Median 109 Low
[21] rectovaginal fistula stoma 13 (25 %) healed after months
(1993–2006) (number not subsequent repair(s) (24–180)
given)
Löffler (2009) Crohn’s-related Multiple 45 No 24 (53 %) healed with Median 48 Low
[22] rectovaginal fistula initial or subsequent months
(1991–2001) repair
E.H. Lawson and P.L. Roberts
33 Rectovaginal Fistula 377
In the same report, Ellis also described their experience with rectovaginal fistula
repair using bioprosthetic mesh with or without a plug in women with an initial or
recurrent rectovaginal fistula [3]. Patients with an acute injury were again excluded;
however, 7 patients (21 %) with Crohn’s disease were included. The mesh was
placed as an interposition graft after transecting the fistula tract and closing the
rectal and vaginal openings. Sphincteroplasty and/or levatorplasty were again per-
formed as needed. For the 27 patients who underwent mesh repair and the 7 patients
who underwent mesh plus plug repair, rates of healing were 81 % and 86 %,
respectively.
Use of collagen matrix biomesh as an interposition graft was also described
by Göttgens [4] for 12 patients with recurrent rectovaginal fistula from a variety
of etiologies, including Crohn’s disease. Among this group, 67 % were success-
fully healed with the mesh approach. Two-thirds of the study group had protec-
tive stomas, including all 4 of the patients who underwent a failed repair. In a
prospective study by Schwandner [5], 21 patients with initial or recurrent recto-
vaginal fistula underwent fistulectomy followed by endorectal advancement flap
and transvaginal placement of bioprosthetic mesh. Just over one-third of the
patients also had a protective stoma. This combined approach resulted in a heal-
ing rate of 71 %.
Rectal sleeve advancement is a more invasive treatment option for rectovaginal
fistula that involves circumferential mucosectomy, transanal transection of the rec-
tum and rectoanal anastomosis. Schouten [6] described use of this technique to treat
8 women with recurrent rectovaginal fistula and reported a successful healing rate
of 63 %. One patient (13 %) developed fecal incontinence postoperatively.
Endoscopic placement of a metallic stent has recently been described as a novel
treatment for iatrogenic initial or recurrent rectovaginal fistula [7]. In a series of 15
patients who developed a fistula after undergoing radiation and anterior resection
for rectal cancer, Lamazza reported successful healing in 80 % of the women. One
patient (7 %) did not tolerate the stent and had to have it removed after 3 days.
Notably, 100 % of the 11 patients with an initial rectovaginal fistula were success-
fully healed by this technique.
A number of techniques for tissue transposition have been described for repair
of recurrent rectovaginal fistula. These procedures bring healthy tissue into the rec-
tovaginal septum, essentially creating a well-vascularized barrier between the rec-
tum and vagina. The Martius advancement flap is one such technique, in which the
bulbocavernosus muscle and surrounding fibroadipose tissue is harvested from the
labia majora and tunneled into the rectovaginal septum, preserving the vascular
pedicle. In a series of 20 patients with initial or recurrent rectovaginal fistula from
a variety of etiologies who underwent repair with a Martius advancement flap, Pitel
[8] reported a successful healing rate of 65 %. The majority of patients had a pro-
tective stoma at the time of surgery and 3 patients (15 %) had minor wound compli-
cations. In a similarly heterogeneous group of 14 patients, Songne [9] reported a
successful healing rate of 93 %. The one patient with recurrence was successfully
healed with a repeat Martius advancement flap procedure from the contralateral
side. Of note, all patients in this study had a protective stoma. McNevin [10] and
Cui [11] have reported similarly high successful healing rates of 94 % in 16 patients
and 100 % in 9 patients, respectively, with initial or recurrent rectovaginal fistula.
In McNevin’s study, just over a third of the patients had a protective stoma, while
in Cui’s study, a protective stoma was only used for patients with a recurrent
fistula.
Gracilis muscle transposition, or graciloplasty, is another tissue transposition
technique in which the gracilis muscle is mobilized from the medial thigh and trans-
posed into a defect created by a perineal incision after excising the fistula. In a series
reported by Troja [12], 10 patients with recurrent rectovaginal, pouch-vaginal or
anovaginal fistula underwent graciloplasty, with a success rate of 60 %. All patients
had a protective stoma. Nassar [13] reported a 100 % rate of healing for 11 patients
with an iatrogenic postoperative rectovaginal fistula who underwent graciloplasty
with protective stoma. For a group of 8 patients with recurrent rectovaginal fistula
due to Crohn’s disease, obstetrical injury or iatrogenic injury, Lefevre [14] reported
a 75 % successful healing rate after graciloplasty with protective stoma. Using this
same approach, Ulrich [15] reported a successful healing rate of 78 % in a similar
population of 9 patients with recurrent rectovaginal fistula. Zmora [16] reported a
successful healing rate of 83 % for 6 patients with history of a previous failed repair
or pelvic irradiation who underwent graciloplasty. Notably, the one patient with
recurrence in this study did not have a protective stoma. Finally, among 17 patients
with a recurrent rectovaginal or pouch-vaginal fistula, Wexner [17] reported 41 %
successful healing after graciloplasty. Successful healing was achieved in 75 % of a
subgroup of 8 patients without Crohn’s disease.
Mobilization of the greater omentum for use as an interposition flap in the rec-
tovaginal space has also been described. Schloericke [18] reported using a transab-
dominal/transperineal approach for low or mid rectovaginal fistulas, in which the
omental flap is first harvested transabdominally then fixed in the rectovaginal space
transperineally after dissection of the fistula. The reported successful healing rate
was 89 % for the 9 patients who underwent this procedure, and the one patient with
a recurrence was successfully healed with repeat repair. Nearly all patients had a
protective stoma. For 40 patients with a fistula between the middle third of the
rectum and the posterior vaginal fornix, van der Hagen [19] described attempting a
laparoscopic fistulectomy followed by omental interposition into the rectovaginal
septum. Two patients (5 %) ultimately underwent diversion instead as
intraoperatively the omentum was found to be unsuitable for omentoplasty. One
patient developed necrosis of the omental flap requiring reoperation, and another
patient developed an abscess requiring drainage. Overall, the successful healing
rate was 95 %.
Crohn’s-related rectovaginal fistulas are particularly challenging to treat. Our
literature search produced three reports specifically focused on this patient popula-
tion. El-Gazzaz [20] described the Cleveland Clinic experience with 65 women
with Crohn’s disease and a rectovaginal fistula over a 10 year period. A variety of
treatment approaches were undertaken and the overall rate of successful healing
was 46 %. Mucosal advancement flap was the most commonly performed proce-
dure (47 patients) and was associated with a rate of healing of 43 %. On multivariate
analysis, smoking and steroids were associated with recurrence while use of immu-
nomodulators was associated with successful healing. Ruffolo [21] reported a suc-
cessful healing rate of 56 % among 52 women with Crohn’s related rectovaginal
fistula who underwent a range of repairs. Successful healing was achieved in an
additional 25 % of the patient population after subsequent repair(s). As in the previ-
ous study, mucosal advancement flap was the most commonly performed proce-
dure. Finally, in a series of 45 women with Crohn’s related rectovaginal fistula,
Löffler [22] reported a successful healing rate of 53 % after one or more attempts at
repair.
• Patients with a recurrent rectovaginal fistula should be assessed for the presence
of a sphincter defect and, if identified, the defect should be addressed at the time
of definitive repair (evidence low; weak recommendation).
• Endorectal advancement flap is a safe procedure for recurrent rectovaginal fistula
but may not have high efficacy (evidence low; weak recommendation).
• For patients with multiple failed rectovaginal fistula repairs, consider fecal diver-
sion with a protective stoma at the time of further attempts at repair (evidence
low; weak recommendation).
• Repair of recurrent rectovaginal fistula with biologic mesh is a safe procedure
(evidence low; weak recommendation).
• Repair of recurrent rectovaginal fistula with tissue transposition such as Martius
flap or graciloplasty is safe and may have greater efficacy than other less invasive
repair techniques (evidence low; weak recommendation).
• Patients with Crohn's-related rectovaginal fistula should not undergo definitive
repair in the face of active proctitis (evidence low; weak recommendation).
Rectovaginal fistulas are difficult to treat with no clear consensus on the best method
of repair and no level 1 evidence to guide the surgeon. As the best reported out-
comes result in recurrent fistula and/or breakdown of the repair in 1 in 4 women
overall, and up to 1 in 2 women with Crohn’s who undergo repair, the preoperative
discussion with the patient should be extensive and include a detailed discussion of
the potential results. Furthermore, if a rectovaginal fistula recurs after repair, it is
our clinical experience that it is often initially larger than the original fistula and
usually more symptomatic. This results in great distress to the patient who often
wishes to have a repeat repair as soon as possible; in our opinion, it is generally best
to wait at least 3 months to allow the tissues to become less inflamed and to optimize
the chance of a successful repair.
Our approach to recurrent rectovaginal fistulas is first to assess why the repair
failed. Were there technical aspects of the repair that resulted in fistula recurrence?
Was the appropriate procedure selected? Is there a sphincter defect that was not
recognized? For advancement flaps, necrosis of the distal extent or entire flap or
hematoma of the flap may cause failure in addition to inadvertent button-holing of
the flap during dissection. Our preference is to incorporate part of the internal
sphincter in the flap, which results in a thicker flap, in an attempt to get better heal-
ing and coverage of the internal opening of the fistula. On occasion, the flap may not
have been adequately mobilized and tension on the distal portion of the flap may
result in dehiscence and failure of the repair. In women with a rectovaginal fistula
from obstetric injury, a sphincter defect (which is more the rule than the exception)
that is not addressed at the time of repair is an additional cause of flap failure.
There is increasingly a push to use setons prior to a definitive anal fistula repair,
such as the LIFT procedure. We have not found setons useful for the majority of
patients with rectovaginal fistulas as the tract is quite short and any associated
abscess generally well drained through the short tract. The exception is women with
Crohn’s disease, who in addition to a rectovaginal fistula may have additional fistu-
las (resulting in a so-called watering can perineum) and require setons for long term
drainage.
There is no clear consensus on the best repair for recurrent rectovaginal fistula
and we approach each patient on a case-by-case basis. We use a fairly simple
approach of “if it didn’t work the first time, try something different the next time.”
Thus, if an advancement flap was not successful the first time, we would generally
not repeat the procedure and would instead proceed to another option such as
episioproctotomy.
We generally recommend proximal fecal diversion for the majority of patients
with rectovaginal fistula and Crohn’s disease and use it selectively for women who
have failed prior repairs. If a prior repair was associated with a wound infection,
there is a potential advantage to proximal diversion with a subsequent repair to
ameliorate the consequences of the wound infection and optimally improve the
chances of a successful outcome. Anecdotally, morbidly obese patients seem to
have a much higher incidence of wound infection, and while stoma creation has its
own challenges in this group, we generally recommend proximal fecal diversion in
this cohort of patients.
For recurrent fistulas, it is important to bring well-vascularized tissue into the
rectovaginal septum. If patients have had multiple repairs, this area is generally
quite scarred and tissue transposition is needed. Gracilis flaps are most commonly
performed, but have significant morbidity and a lengthy recovery period. The
pudendal thigh flap, or Singapore flap, is another potential option for tissue transpo-
sition and we have increasingly used this technique for patients with recurrent fistu-
las. There are few reports of this technique in the literature [23]. Tissue transposition
techniques and other repairs may be associated with dyspareunia and perceptions of
changes in body image. These outcomes are not routinely reported but are increas-
ingly important patient reported outcomes to consider in assessing the optimal
repair for this challenging condition.
References
1. de Parades V, Dahmani Z, Blanchard P, Zeitoun JD, Sultan S, Atienza P. Endorectal advance-

ment flap with muscular plication: a modified technique for rectovaginal fistula repair.
Colorectal Dis. 2011;13(8):921–5.
2. Hull TL, El-Gazzaz G, Gurland B, Church J, Zutshi M. Surgeons should not hesitate to per-
form episioproctotomy for rectovaginal fistula secondary to cryptoglandular or obstetrical ori-
gin. Dis Colon Rectum. 2011;54(1):54–9.
3. Ellis CN. Outcomes after repair of rectovaginal fistulas using bioprosthetics. Dis Colon
Rectum. 2008;51(7):1084–8.
4. Gottgens KW, Heemskerk J, van Gemert W, et al. Rectovaginal fistula: a new technique and
preliminary results using collagen matrix biomesh. Tech Coloproctol. 2014;18(9):817–23.
5. Schwandner O, Fuerst A, Kunstreich K, Scherer R. Innovative technique for the closure of
rectovaginal fistula using Surgisis mesh. Tech Coloproctol. 2009;13(2):135–40.
6. Schouten WR, Oom DM. Rectal sleeve advancement for the treatment of persistent rectovagi-
nal fistulas. Tech Coloproctol. 2009;13(4):289–94.
7. Lamazza A, Fiori E, Sterpetti AV, Schillaci A, De Cesare A, Lezoche E. Endoscopic placement
of self-expandable metallic stents for rectovaginal fistula after colorectal resection: a compari-
son with proximal diverting ileostomy alone. Surg Endosc. 2016;30(2):797–801.
8. Pitel S, Lefevre JH, Parc Y, Chafai N, Shields C, Tiret E. Martius advancement flap for low
rectovaginal fistula: short- and long-term results. Colorectal Dis. 2011;13(6):e112–5.
9. Songne K, Scotte M, Lubrano J, et al. Treatment of anovaginal or rectovaginal fistulas with
modified Martius graft. Colorectal Dis. 2007;9(7):653–6.
10. McNevin MS, Lee PY, Bax TW. Martius flap: an adjunct for repair of complex, low rectovagi-
nal fistula. Am J Surg. 2007;193(5):597–9. discussion 599.
11. Cui L, Chen D, Chen W, Jiang H. Interposition of vital bulbocavernosus graft in the treatment
of both simple and recurrent rectovaginal fistulas. Int J Colorectal Dis. 2009;24(11):1255–9.
12. Troja A, Kase P, El-Sourani N, Raab HR, Antolovic D. Treatment of recurrent rectovaginal/
pouch-vaginal fistulas by gracilis muscle transposition - a single center experience. J Visc
Surg. 2013;150(6):379–82.
13. Nassar OA. Primary repair of rectovaginal fistulas complicating pelvic surgery by gracilis
myocutaneous flap. Gynecol Oncol. 2011;121(3):610–4.
14. Lefevre JH, Bretagnol F, Maggiori L, Alves A, Ferron M, Panis Y. Operative results and qual-
ity of life after gracilis muscle transposition for recurrent rectovaginal fistula. Dis Colon
Rectum. 2009;52(7):1290–5.
15. Ulrich D, Roos J, Jakse G, Pallua N. Gracilis muscle interposition for the treatment of recto-
urethral and rectovaginal fistulas: a retrospective analysis of 35 cases. J Plast Reconstr Aesthet
Surg. 2009;62(3):352–6.
16. Zmora O, Tulchinsky H, Gur E, Goldman G, Klausner JM, Rabau M. Gracilis muscle transpo-
sition for fistulas between the rectum and urethra or vagina. Dis Colon Rectum.
2006;49(9):1316–21.
17. Wexner SD, Ruiz DE, Genua J, Nogueras JJ, Weiss EG, Zmora O. Gracilis muscle interposi-
tion for the treatment of rectourethral, rectovaginal, and pouch-vaginal fistulas: results in 53
patients. Ann Surg. 2008;248(1):39–43.
18. Schloericke E, Hoffmann M, Zimmermann M, et al. Transperineal omentum flap for the ana-
tomic reconstruction of the rectovaginal space in the therapy of rectovaginal fistulas. Colorectal
Dis. 2012;14(5):604–10.
19. van der Hagen SJ, Soeters PB, Baeten CG, van Gemert WG. Laparoscopic fistula excision and
omentoplasty for high rectovaginal fistulas: a prospective study of 40 patients. Int J Colorectal
Dis. 2011;26(11):1463–7.
20. El-Gazzaz G, Hull T, Mignanelli E, Hammel J, Gurland B, Zutshi M. Analysis of function and
predictors of failure in women undergoing repair of Crohn's related rectovaginal fistula.
J Gastrointest Surg. 2010;14(5):824–9.
21. Ruffolo C, Penninckx F, Van Assche G, et al. Outcome of surgery for rectovaginal fistula due
to Crohn's disease. Br J Surg. 2009;96(10):1190–5.
22. Loffler T, Welsch T, Muhl S, Hinz U, Schmidt J, Kienle P. Long-term success rate after surgi-
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2009;24(5):521–6.
23. Sathappan S, Rica MA. Pudendal thigh flap for repair of rectovaginal fistula. Med J Malaysia.
2006;61(3):355–7.
Chapter 34
Benign Anal Disease: When to Operate
on the Patient with an Anal Fissure
David J. Berler and Randolph M. Steinhagen
Introduction and Problem
Anal fissures have been reported to affect an estimated 235,000 individuals per year,
though the true incidence is likely higher. The majority of anal fissures are associ-
ated with high internal anal sphincter tone. The etiology is thought to be related to
local trauma caused by hard stool and/or related to chronic ischemia associated with
increased sphincter pressures. While most acute fissures heal spontaneously with
stool bulking, local care, and topical treatments, the management of chronic fis-
sures, specifically the decision on when lateral internal sphincterotomy (LIS) is
appropriate, represents a clinical challenge.
While non-surgical therapies, such as botulinum toxin and calcium channel
blockers are safe and more effective than placebo in healing fissures, lateral internal
sphincterotomy has been shown to be far superior in promoting healing and is asso-
ciated with the lowest rates of recurrence. However, the decision to recommend
sphincterotomy should not be made lightly, as there is always concern that the pro-
cedure will be associated with some degree of incontinence. Given the choice
between a painful fissure and a permanent deficit in continence, many patients may
prefer coping with the pain of the fissure. The true incidence and extent of conti-
nence disturbances following surgical sphincterotomy is often disputed; this leads
to the difficulty in deciding when to recommend it.
D.J. Berler, MD
Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
R.M. Steinhagen, MD (*)
Division of Colon and Rectal Surgery, Department of Surgery, Icahn School of Medicine at
Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA

DOI 10.1007/978-3-319-40223-9_34
384 D.J. Berler and R.M. Steinhagen
Search Methods
All data and studies were collected via searching the MEDLINE and Pubmed search
engines for numerous terms including ‘anal fissure,’ ‘continence,’ ‘sphincterotomy,’
‘constipation,’ ‘advancement flap,’ and ‘recurrence.’ Preferential inclusion and
higher level of quality were given to studies that were prospective, randomized,
published between 2004 and 2015 in journals based within the US and Europe, as
well as in English. Twenty-three such studies, including two Cochrane reviews,
were identified and were included as a basis for the set of recommendations listed
at the end of this chapter. A standard PICO table outlining the clinical question
explored is illustrated below.

Patients with Surgical Medical Cure, recurrence,
chronic anal management management postoperative incontinence
fissure
Results
Lifestyle modifications consisting of sitz baths, implementing a high fiber diet,

increasing fluid intake, and the use of stool-bulking agents, have been shown to be
safe and effective in promoting spontaneous healing in 90 % of patients with an
acute anal fissure. For the remaining 10 % who progress to chronic fissure, treat-
ments include those that are primarily medical (topical calcium channel blockers,
nitroglycerin ointment, botulinum toxin injection) or surgical, typically lateral
internal sphincterotomy.
A 2012 Cochrane review of 75 randomized clinical trials included over 5,000
patients with chronic fissures who were either treated with surgery or conventional
medical therapies [1]. Nitroglycerine ointment was found to be marginally though
significantly superior to placebo in achieving healing (48.9 % vs. 35.5 %, p < 0.0009).
However, late recurrence developed in 50 % of these patients. Similar efficacy has
been observed with topical calcium channel blockers and botulinum toxin injection.
Such nonsurgical interventions lead to resolution of symptoms in up to 60 % of
affected patients, making them worthwhile to attempt in patients with fissures of
less than 12 months duration. The evidence supports the concept that they should
typically be tried prior to surgery, given that they are safe and may be effective.
Most surgeons do not advocate surgery as first-line therapy, primarily because of
concerns related to incontinence.
However, it is well recognized that no medical therapies have enduring cure rates
that are at all comparable to those associated with LIS (80–95 %, depending on the
case series). Indeed, numerous studies have demonstrated the superiority of surgery
in both the healing of and prevention of recurrence of chronic fissures [2–5]. The
previously described Cochrane review of 75 RCTs found an odds-ratio of 0.11
34 Benign Anal Disease: When to Surgery for the Patient with an Anal Fissure 385
(95 % CI 0.06–0.23) when comparing non-healing, defined as persistence or recur-

rence, at a median of 2 months in patients who underwent medical therapies com-
pared to those who underwent any form of surgery for anal fissure [1].
A prospective randomized trial of 142 patients with anal fissure compared heal-
ing rates and defecatory pain following treatment with either LIS or anal dilation
plus topical nifedipine [6]. 68.9 % of patients in the nifedipine group and 88.2 % of
patients in the LIS group were healed by 8 weeks (p = 0.0077). Those who under-
went LIS had significantly less pain with defecation at 3 and 7 days. A parallel,
randomized controlled trial of 99 patients with chronic fissure found no significant
difference in healing rates in patients with fissures of less than 12 months duration
who underwent botulinum toxin injection with supplemental calcium channel
blocker therapy compared to those who underwent LIS. However, in patients who
had chronic fissures for more than 12 months, the healing rate was significantly
higher in the LIS group (86 % vs 23 %, p < 0.001) [7].
Of all the medical therapies that are currently available, botulinum toxin injec-
tion has increasingly been used as first-line therapy for recalcitrant anal fissures, and
nitroglycerine ointment may act in synergy with botulinum toxin [8]. Still, there is
currently no consensus on the ideal dosage, precise location of injection (external vs
internal sphincter), and number of injections of botulinum toxin needed to achieve
optimal results. Higher doses do seem to correspond with higher healing rates and
are just as safe as lower doses, though the recurrence rate remains higher than that
following LIS (up to 42 %), making LIS a superior procedure for cure. Incontinence
scores are higher in patients treated with LIS [8], however, incontinence to stool and
flatus is also a potential complication of botulinum toxin injection, which occurs in
up to 18 % of cases.
With the goal being to promote permanent cure while minimizing the likelihood
of a disturbance in continence, some have advocated combined fissurectomy with
botulinum toxin injection as a viable alternative to LIS. In a prospective nonran-
domized study of 105 patients who underwent this procedure, 95 % of patients had
resolution or improvement of symptoms at 12-weeks; 93 % had no complications;
however 7 % developed postoperative incontinence to stool and/or flatus which
proved to be transient (all patients had restored continence at 12 weeks) [9]. The
authors argue that even though LIS remains the procedure with the highest cure and
lowest recurrence rates, botulinum toxin injection with fissurectomy has similar
efficacy and may be preferable given that it does not permanently alter the anal
musculature, as LIS does. The latter consideration is important since muscular tone
diminishes with aging (further increasing the probability of late incontinence) and
LIS may distort planes for future anorectal surgeries that may become necessary.
While other studies have demonstrated similar findings [10, 11], it remains difficult
to make a broad recommendation on fissurectomy with botulinum toxin injection as
an alternative to LIS due to a paucity of adequately-powered, prospective studies.
Similarly, pneumatic dilation as a means to reduce the hypertonicity of the internal
sphincter has also been explored as a nonsurgical means to healing. While the initial
data seems promising with 94 % of patients reporting healing between 3 and 5
weeks, the few trials that have been reported are underpowered [12, 13].
The tradeoff for the high efficacy of LIS is an increased risk for incontinence.
After all, diminishing anal canal resting pressure is the primary mechanism by
which surgery heals chronic anal fissures. Long-term manometric studies have
established that preoperative resting anal pressure is high in patients with fissures
and significantly declines following LIS. The sphincter tone and resting pressure
gradually increase over a 12-month period, but they nevertheless remain elevated
relative to normal controls without fissures. This makes incontinence in such
patients possible, though still unlikely [14]. Retrospective studies have postulated
that the likelihood of incontinence following LIS is unpredictable, though a history
of vaginal delivery may increase this risk [15]. A recent systematic review of 22
studies including over 4500 patients who underwent LIS for chronic fissure showed
an overall postoperative continence disturbance rate in 14 %, with a mean follow-up
time of 24–124 months (flatus incontinence 9 %, soilage/seepage 6 %, and acciden-
tal defecation in 0.91 %) [16].
Still, most agree that the majority of incontinence following LIS is a transient
phenomenon, and that the risk of this is far outweighed by the risk of failed, pro-
longed medical management with continuing distress of patients related to an
unhealed symptomatic fissure. A retrospective cohort study of 38 patients who
underwent LIS between 1998 and 2004 found that long-term symptomatic inconti-
nence was reported by only two patients (5.6 %) [17]. The authors’ final recommen-
dation is that patients with risk factors for the development of incontinence
(preoperative incontinence, multiparous women) should arguably be treated with
non-surgical therapies prior to LIS. Finally, there is speculation that incontinence
may actually be a feature of the underlying condition itself, and is not solely a com-
plication of surgical management [18].
The degree of sphincter division may proportionately dictate the likelihood of
the development of postoperative incontinence. Numerous prospective studies have
found that partial sphincterotomy, limited to division just beyond the fissure apex,
correlates with a lower risk of postoperative incontinence than does complete
sphincterotomy to the level of the dentate line [14–18]. In general, internal sphinc-
terotomy to the level of the dentate line is associated with higher rates of healing as
well as more rapid healing of chronic fissures, although it is associated with a higher
risk for incontinence than is partial sphincterotomy [19]. A 2011 Cochrane review
of 27 studies, including 2,056 patients, concluded that open and closed partial lat-
eral sphincterotomy were equally efficacious and not different in terms of the risk
of developing postoperative incontinence. The conclusion is that more data are
needed to determine the effectiveness of alternate procedures such as posterior
internal sphincterotomy, anterior levatorplasty, and bilateral internal sphincterot-
omy [20].
There has been recent interest in alternate surgical treatments for chronic fissures
that do not carry as substantial a risk for even transient incontinence, as does
LIS. Fissurectomy with advancement flap, particularly in patients without internal
sphincter hypertonia, has been advocated as a promising option for such patients.
One study of 26 patients with fissures refractory to medical therapy showed that
fissurectomy with advancement flap led to complete healing by 30 days, and that the
intensity of pain with defecation was substantially diminished. At 1 year, only three
patients reported ongoing incontinence [21]. The obvious problem, of course, is that
the etiology behind the large majority of chronic fissures is high internal sphincter
tone. Fissurectomy with advancement flap does not address this, and therefore, most
patients would conceivably neither benefit nor heal from such treatment.
Other prospective studies have suggested that what has been called “modified
LIS” (partial sphincterotomy to the level of the fissure apex with dermal advance-
ment flap) results in better healing and less postoperative discomfort than does iso-
lated, conventional LIS to the dentate line. One such study of 32 patients found that
modified sphincterotomy with a VY flap from perianal skin was associated with less
postoperative defecatory pain and faster objective healing than was conventional
LIS (p < 0.01) [22]. Similar findings have been reported by others [23, 24]. For obvi-
ous reasons, modified LIS carries less risk for postoperative incontinence than does
conventional LIS. It may be useful and more appropriate in patients with preopera-
tive incontinence or known risk factors for developing incontinence postoperatively
(prior vaginal delivery, older age). There have been some low-powered studies sug-
gesting that fissurectomy with advancement flap may be effective as a first line pro-
cedure in patients with chronic fissures, irrespective of anal sphincter tone [25, 26].
Recommendations
1. Medical therapy is safe and should be attempted prior to surgical intervention

for chronic anal fissure. Evidence high; strong recommendation.
2. No medical therapies possess the efficacy for healing chronic anal fissures as
does surgery, and surgery should be considered in patients with fissures that fail
to heal in response to medical therapy. Evidence high; strong
recommendation.
3. Botulinum toxin injection in the setting of chronic fissures is superior to placebo
and to other medical therapies with respect to healing and recurrence. A stan-
dard for optimal delivery has not been established. Results are usually inferior
to LIS. Evidence moderate; weak recommendation.
4. Although the risk of incontinence exists with LIS, this risk is largely overstated
and should not discourage its use for definitive management in patients with
chronic fissure that have failed nonsurgical therapies. Evidence high; strong
recommendation.
5. Patients with chronic anal fissures, anal hypertonia, and no preoperative risk
factors for incontinence should undergo LIS. Evidence high; strong
recommendation.
6. In patients with chronic anal fissure and diminished anal tone, fissurectomy with
anal advancement flap or modified LIS with advancement flap should be consid-
ered as an alternative to LIS. Evidence moderate; weak recommendation.
7. Pneumatic dilation may lower sphincter tone and induce healing of chronic anal
fissures without causing incontinence. Evidence low; weak recommendation.
A Personal View of the Problem and the Data
The vast majority of patients who have a symptomatic anal fissure seek advice and
treatment for what they or their referring providers refer to as ‘hemorrhoids.’ Taking
a complete history and performing a thorough physical exam is the key to making
the correct diagnosis. It is important to educate patients about the nature of their
condition and how it differs from hemorrhoids. Since the majority of fissures will
heal with non-operative management, patients should be advised that surgery is not
mandatory and that nonsurgical treatments are generally the preferred first line ther-
apy. The importance of a high fiber diet and drinking sufficient quantities of liquids
cannot be overemphasized.
For most, the addition of a fiber supplement such as psyllium and/or a stool soft-
ener such as docusate will be beneficial. Often, a topical medication such as nitro-
glycerine or diltiazem is prescribed from the outset. Since most patients are
concerned that cutting any portion of the sphincter will leave them incontinent, they
should be reassured that the reason they have a fissure is that their sphincter is
excessively tight. They are informed that, while cutting a portion of the sphincter
will reduce the pressure, the surgery will leave them with a sphincter pressure that
is still often higher than normal. The data shows that the incidence of clinically
meaningful incontinence after partial LIS is extremely low, and that is also my own
experience. Still, while we know that the surgery is very effective and the risks are
small, we never push a patient to have surgery; We tell them that it is available and
it will always be their decision as to if and when it should be utilized.
Nonsurgical therapies which reduce internal anal sphincter tone, can be predic-
tive of the likelihood of success with sphincterotomy. It is critical to choose patients
appropriately. If the sphincter tone is lax, then other etiologies for the fissure must
be considered and sphincterotomy is likely to have a poor outcome. The few patients
with chronic fissures and low resting tone or preexisting incontinence who fail non-
operative therapy, are best managed with fissurectomy and advancement flap. There
is another group of patients who initially respond well to nonoperative manage-
ment, but then the fissure recurs as do the symptoms. These patients should typi-
cally repeat the therapies that were effective, but if the recurrences are too frequent
and the asymptomatic intervals too short, sphincterotomy will be an effective long-
term solution.
Although the risk of any degree of incontinence in appropriately selected patients
is very low, this should never be minimized and the patient should never feel that
this is not a significant concern. Patients want to be treated by a surgeon who is not
in a rush to operate, and by one who is as concerned about their ability to control
their bowels as they are themselves.
Anal fissure: literature search results
Medical Follow-up Recurrence Incontinence
Patients LIS management time Cure rate rate rate
First author Year Study design Interval (n) n (%) n (%) (months) (M, S) % (M, S) % (M, S) %
Libertiny 2002 Prospective, 1998 70 35 (50) 35 (50) 24 (54.3, (5.26, NA
RCT GTN 100)* 2.86)
Mentes 2003 Prospective, NA 111 50 (45) 61 (55) 2, 6, 12 (86.9, 98) (24.6, 6) (0, 16)*
RCT BTI
Arroyo 2005 Prospective, 1998– 80 40 (50) 40 (50) 36 (45, (0,0) (0, 5)
RCT 2000 BTI 92.5)*
Iswariah 2005 Prospective, 2000– 38 21 (55.3) 17 (44.7) 6, 26-week (86, 91)* (53, 9.5)* See study
RCT 2002 BTI
Derosa 2013 Prospective, 2008– 142 68 (47.9) 74 (52.1) 2, 4, (68.9, (23, 11.7) (0, 3)
RCT 2010 TCCB 8-week 88.2)*
Gamdokar 2015 Prospective, 2010– 99 50 (50.5) 49 (49.5) 2, 6, 12 (65, 94)* (10.2, 0)* (0,2)
RCT 2012 TCCB + BTI [Overall]
Barnes 2015 Prospective 2008– 102 0 102 (100) 12 66.7 0 0
cohort 2012 Fiss + BTI
Lindsey 2004 Prospective 2001– 31 0 31 (100) 16-week 93 NA 7
cohort 2003 Fiss. + BTI
Scholz 2007 Retrospective 2001– 40 0 40 (100) 12 95 10.6 0
2004 Fiss. + BTI
Renzi 2005 Prospective 1999– 33 0 33 (100) 26 (mean) 94 3 6
cohort 2002 PBD
Yucel 2009 Prospective, 2004– 40 20 (50) 20 (50) 2 (90, 85) (10, 5) (0,0)
34 Benign Anal Disease: When to Surgery for the Patient with an Anal Fissure
RCT 2005 PBD

(continued)
389
Anal fissure: literature search results (continued)
390

Kement 2011 Retrospective 2003– 253 253 (100) 0 23 (mean) NA NA 11.7
review 2006
Garg 2013 Metaanalysis 1969– 4512 4512 (100) 0 24–124 68–100 NA 15
2012 (mean)
Davies 2014 Retrospective 1998– 38 38 (100) 0 5-years 92 8 5.6
2004 (mean)
Mentes 2005 Prospective, NA 80 To apex: 40 0 1, 2, 12 Apex: Apex: 13.2 Postop AIS,
RCT (50) 97.5 Dentate: 0 apex: 0.42
To dentate Dentate: Postop AIS,
line: 40 (50) 100 dentate: 0.58*
[both mean]
Patti 2010 Prospective 2002– 26 26 (100) 0 1, 6, 12 100 0 11.5
cohort 2007 Fiss. + AF
Theodoropoulos 2015 Prospective, 2005– 62 LIS: 32 0 57.9 (LIS), LIS: 100 LIS: 6.2 LIS: 28.1
nonrandomized 2012 (51.6) 20.6 LIS + AF: LIS + AF: LIS + AF: 6.6*
LIS + AF: (LIS + AF) 100 0*
30 (48.4)
Magdy 2012 Prospective, 2009– 150 LIS: 50 0 3, 6, 12 LIS: 84 LIS: 4 LIS: 14
RCT 2010 (33.3) AF: 48 AF: 22 AF: 0
AF: 50 LIS + AF: LIS + AF: LIS + AF: 2*
(33.3) 94* 2*
LIS + AF:
50 (33.3)
D.J. Berler and R.M. Steinhagen
Patel 2011 Retrospective NA 100 LIS: 50 (50) 0 20–22 LIS: 88 NA LIS: 0
Fiss + AF: Fiss + AF: Fiss + AF: 0
50, (50) 96
Patti 2012 Prospective 2002– 48 Fiss + AF: 0 24 100 8 12.5
cohort 2008 48 (100)
Giordano 2009 Prospective 2000– 51 SCAFA: 51 0 2, 4, 6+ 98 5.9 0
2007 (100)
Nelson 2012 Metaanalysis 1966– 979 (15 Overall cure rate with surgery: 89 % (adjusted for drop-outs: 95 %)
2010 studies) Overall risk of incontinence: 9–10 %
Statistically significant differences in healing, recurrence, and incontinence rates are bolded and adjoined to an asterisk (*)
In the event of multiple follow-up times, all results listed denote data corresponding to the longest follow-up point
Parameters not reported in an above-listed study are marked ‘NA’
Key: M medical management, S surgical management, GTN topical glyceryl trinitrate, TCCB topical calcium channel blocker, BTI botulinum toxin injection,
PBD pneumatic balloon dilation, Fiss. fissurectomy, AF anorectal advancement flap, SCAFA simple cutaneous advancement flap anoplasty, RCT randomized
controlled trial, AIS anal incontinence score
34 Benign Anal Disease: When to Surgery for the Patient with an Anal Fissure
391
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Database Syst Rev. 2012;(2):CD003431.
2. Libertiny G, Knight JS, Farouk R. Randomised trial of topical 0.2% glyceryl trinitrate and
lateral internal sphincterotomy for the treatment of patients with chronic anal fissure: long-
term follow-up. Eur J Surg. 2002;168:418–21.
3. Mentes BB, Irkorucu O, Akin M, Leventoglu S, Tatlicioglu E. Comparison of botulinum toxin
injection and lateral internal sphincterotomy for the treatment of chronic anal fissure. Dis
Colon Rectum. 2003;46:232–7.
4. Arroyo A, Perez F, Serrano P, Candela F, Lacueva J, Calpena R. Surgical versus chemical
(botulinum toxin) sphincterotomy for chronic anal fissure: long-term results of a prospective
randomized clinical and manometric study. Am J Surg. 2005;189:429–34.
5. Iswariah H, Stephens J, Rieger N, Rodda D, Hewett P. Randomized prospective controlled trial
of lateral internal sphincterotomy versus injection of botulinum toxin for the treatment of
idiopathic fissure in ano. ANZ J Surg. 2005;75:553–5.
6. Derosa M, Cestaro G, Vitiello C, Massa S, Gentile M. Conservative versus surgical treatment
for chronic anal idiopathic fissure: a prospective randomized trial. Updates Surg.
2013;65(3):197–200.
7. Gandomkar H, Zeinoddini A, Heidari R, Amoli HA. Partial lateral internal sphincterotomy
versus combined botulinum toxin A injection and topical diltiazem in the treatment of chronic
anal fissure: a randomized clinical trial. Dis Colon Rectum. 2015;58(2):228–34.
8. Denardi P, Ortolano E, Radaelli G, Staudacher C. Comparison of glycerine trinitrate and botu-
linum toxin-a for the treatment of chronic anal fissure: long-term results. Dis Colon Rectum.
2006;49(4):427–32.
9. Barnes TG, Zafrani Z, Abdelrazeq AS. Fissurectomy combined with high-dose botulinum
toxin is a safe and effective treatment for chronic anal fissure and a promising alternative to
surgical sphincterotomy. Dis Colon Rectum. 2015;58(10):967–73.
10. Lindsey I, Cunningham C, Jones OM, Francis C, Mortensen NJ. Fissurectomy-botulinum
toxin: a novel sphincter-sparing procedure for medically resistant chronic anal fissure. Dis
Colon Rectum. 2004;47(11):1947–52.
11. Scholz T, Hetzer FH, Dindo D, Demartines N, Clavien PA, Hahnloser D. Long-term follow-up
after combined fissurectomy and Botulinum toxin injection for chronic anal fissures. Int
J Colorectal Dis. 2007;22(9):1077–81.
12. Renzi A, Brusciano L, Pescatori M, et al. Pneumatic balloon dilatation for chronic anal fissure:
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2005;48(1):121–6.
13. Yucel T, Gonullu D, Oncu M, Koksoy FN, Ozkan SG, Aycan O. Comparison of controlled-
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14. Ram E, Alper D, Stein GY, Bramnik Z, Dreznik Z. Internal anal sphincter function following
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J Surg. 2009;33(5):1058–63.
Chapter 35
Anal Fissure: Recurrence After Lateral
Internal Sphincterotomy
Christy Cauley and Liliana Bordeianou
Introduction
Anal fissure is a common cause of perianal pain. When patients fail medical treat-
ments, surgical management through a lateral internal sphincterotomy (LIS) pro-
vides relief with cure rates as high as 96–100 % [1–5]. However, some patients
present with recurrent anal fissures after surgical treatment. This represents a diffi-
cult problem for the patient and their colorectal surgeon. While cure of the painful
anal fissure is the ultimate goal, repeat interventions come with the potential
increased risk of incontinence.
In recommending a treatment solution to patients with recurrent anal fissure, the
surgeon must evaluate the patient carefully and weigh the decrement to quality of
life from continued pain with chronic fissure versus the risk of incontinence. The
first step in determining the proper treatment for these patients is to ensure that there
is not an alternative underlying cause for the fissure. This can be done by perform-
ing a focused history and physical exam. Due to the significant pain associated with
anal fissure, exam under anesthesia is often appropriate. Secondary etiologies of
anal fissure, such as inflammatory bowel disease, syphilis, tuberculosis, leukemia,
and human immunodeficiency virus, and alternative diagnoses, such as cancer, can
thus be ruled out in refractory cases. Furthermore, examination under anesthesia
C. Cauley
Colorectal Surgery Program, Department of Surgery, Massachusetts General Hospital
(MGH), 15 Parkman Street, ACC 460, Boston, MA 02114, USA
L. Bordeianou, MD, MPH (*)
Colorectal Surgery Program, Department of Surgery, Massachusetts General Hospital
(MGH), 15 Parkman Street, ACC 460, Boston, MA 02114, USA
MGH Center for Pelvic Floor Disorders, Boston, MA, USA

DOI 10.1007/978-3-319-40223-9_35
396 C. Cauley and L. Bordeianou
can allow for inspection of the extent of the fissure and completeness of previous
LIS. This may provide important insight into why previous interventions were
unsuccessful. In addition, biopsy of the fissure may be performed if cancer is
suspected.
In addition to an exam under anesthesia, we also advocate for adjunct testing
with anal manometry and anal ultrasound. The anal ultrasound can help quantify the
extent of the previous LIS. Inadequate sphincterotomy is thought to be a common
cause of recurrent fissure. Anal manometry, which is done in an awake patient who
can hopefully tolerate the insertion of the probe into their anus, can help determine
if the fissure is associated with low or high resting sphincter tone. Resting anal pres-
sure of the internal anal sphincter can be useful in identifying the cause of anal fis-
sure. Primary anal fissure is due to compression of end arteries associated with
elevated resting pressure, while sphincter hypotonia is usually due to secondary
problems, such as anal trauma, previous anal surgery, anal stricture with secondary
anal canal tearing with defecation, or infection. The findings of these adjunct stud-
ies have important implications on treatment decisions, though not all patients can
tolerate these additional exams. In these instances the surgeon must still use their
clinical judgement in deciding on the presence or absence of sphincter hypertonia.
Treatment Options
As described above, the treatment of recurrent fissures should be based on the pres-
ence or absence of hypertonia. Patients with high resting sphincter tone can still
benefit from interventions aiming to improve blood flow. Repeat sphincterotomy,
which involves the permanent destruction of of additional muscle fibers within the
internal sphincter, or botulinum toxin injection which causes temporary flaccid
paralysis of these muscle fibers, can achieve this goal by decreasing the resting pres-
sure generated by the sphincter muscle. In contrast, patients with internal sphincter
hypotonia will not benefit from decreasing sphincter muscle tone further. Instead,
these patients are more likely to benefit from attempts at replacing their diseased
anoderm with healthy tissue.
In this chapter we will discuss the current evidence supporting these treatment
options and their outcomes for patients with recurrent anal fissure after failure of
prior lateral internal sphincterotomy.
Search Strategy
A literature search was performed querying the Cochrane Library and Pubmed to
identify guidelines and studies on treatments of recurrent anal fissure. The search
terms “anal fissure” and “surgery” were used in the Cochrane Library to identify
relevant articles. Search terms “recurrent” or “redo” and “anal fissure” as part of the
35 Anal Fissure: Recurrence After Lateral Internal Sphincterotomy 397
article title were performed in Pubmed. Two case series describing treatment of
patients with recurrent anal fissure were identified on Pubmed. No articles discuss-
ing treatment of recurrent anal fissure were identified at the Cochrane Library. The
two case series identified on Pubmed included (1) a case series describing the use of
botulinum toxin after LIS and its outcomes with no comparison group and (2) a case
series study of redo LIS with no comparison group. In addition the reference lists of
these two articles were reviewed to identify further studies addressing treatment of
patients with failure of LIS, and no references were identified. There were no limits
placed on the search for type of article, language, or dates. Due to the lack of pub-
lished research on this patient population the majority of this chapter will discuss
expert opinion on this topic due to very low quality evidence.
Results
The first study of patients with recurrent anal fissure following LIS was published
in 2008 by Brisinda and colleagues [6]. It describes the injection of lyophilized type
A botulinum toxin (either 30 units of Botox® or 90 units of Dysport®) into the
internal anal sphincter at two sites, on either side of the anterior or posterior midline
depending on the fissure location. Patients with posterior fissures received anterior
injections and patients with anterior fissures received posterior injections. Eighty
patients received the described treatment and those who had persistent symptoms at
the 2-month follow-up evaluation (21 patients) received re-treatment with a higher
dose of botulinum toxin (either 50 units of Botox® or 150 units of Dysport®). The
authors found that 68 % of patients had complete healing at 1 month after the pro-
cedure with 10 % reporting mild incontinence of flatus, which improved at 2 months.
In 5 year follow-up there were no reported recurrences. This study has several limi-
tations. The study did not provide any comparison group and no preoperative conti-
nence assessment was performed. In addition, the conclusion that there was a lack
of recurrence with an average 5 year follow-up was determined by no patients
returning to the clinic to report symptoms. There was no documented effort to con-
tact patients to see if they presented to another hospital system and there were no
comments on patients lost to follow-up for the study.
The second case series discussing patients with recurrent fissure after surgery
addresses the use of repeat LIS. This study, published in 2015, describes the out-
comes of a 57 patient cohort who received repeat LIS by a single surgeon [7].
Incontinence was assessed pre- and postoperatively using the modified Cleveland
Clinic Incontinence Score. In addition, overall satisfaction and pre- and postopera-
tive quality of life scores were obtained on a 10 point scale. One patient (2 %)
reported fissure recurrence after repeat LIS and 19 % of patients reported a compli-
cation, including minor bleeding, urinary retention, urinary infection, and fecal
impaction. Regarding incontinence, 53 % of patients had preoperative incontinence
and these patients reported improved or unchanged incontinence postoperatively.
Of patients with no preoperative continence issues, 2 of 27 (7.4 %) reported the
development of minor incontinence postoperatively, one for gas and the other for
gas and seepage. This study also reported an improvement in overall quality of life
score from 5.7 preoperatively to 9.3 out of 10 (p < 0.001) postoperatively. Limitations
of this study included the lack of a comparison group and its report of outcomes
from a single surgeon. In addition, no specific information about the validity of the
satisfaction or quality of life questionnaire was provided in the study methods.
Recommendations Based on Current Data
The current data available is of very low quality; therefore, no firm, evidence based
recommendation can be made regarding treatment of recurrent anal fissure after
surgical intervention. Specifically, recommendation for or against the use of botuli-
num toxin or repeat LIS cannot be confidently made due to the very low quality of
the available evidence. Decision aids may be useful in helping patients decide what
treatment will be most beneficial for them, delineating the risk of future recurrence
and risk of incontinence after repeat interventions. Colorectal surgeons treating this
condition should practice shared decision making with their patients since no clear
evidence exists regarding outcomes of interventions in these patients.
The data available are from single institution case series that lack comparison
groups. In addition, both of these studies had a small sample size and one of the
studies reported outcomes from a single surgeon. Due to the limitations of these
studies, it is difficult to draw evidence based conclusions from the available data.
Therefore, our recommendations here are based on expert opinion integrating per-
sonal experience, the data presented in this query, and published data discussing
outcomes after primary anal fissure treatment.
In patients who present with hypertonia despite prior LIS, we advocate consider-
ation of repeat LIS on the contralateral side. Repeat LIS was shown in the case
series cited above to have a 98 % cure rate with a low rate of new onset incontinence
(7.4 %). In addition, the authors were able to show a significantly improved overall
quality of life for these patients. While this study reports that its findings are from a
prospectively maintained database, it suffers from the lack of a comparison treat-
ment group and discloses outcomes from only one surgeon at a single site. However,
the authors’ findings are consistent with previous literature published on the out-
comes of patients with primary chronic anal fissure treated with LIS. Specifically,
there were similar rates of complications at 19 % compared to 7–42 % [8–10] and
new incontinence of 7 % compared to 10–14 % [11, 12].
We do not typically use botulinum toxin as a treatment for recurrent anal fissure.
While the case series cited above states that 68 % of patients were able to heal their
recurrent fissures with the use of botulinum toxin, a recent systematic review
revealed that this therapy is only slightly better at healing fissures than placebo for
first time fissures [13]. Because there is no comparison to placebo or alternative
treatment in this case series, it is hard to know if these findings were significant.
Further studies using a comparison group are needed to show the true effect of botu-
linum toxin in these recurrent anal fissure patients.
For patients presenting with hypotonia or severe incontinence already, neither
repeat LIS nor Botox injections are appropriate. For these patients, we advocate
consideration of anal advancement flaps. We have no data to support this advice
aside from the previous studies comparing outcomes of anal advancement flap with
LIS as the standard treatment of de novo anal fissures. These studies found equiva-
lent outcomes between the two groups [14, 15]. The postoperative complication rate
in the flap group was 10 % compared to 18 % in the LIS group and the fissure cure
rate was 96 % in the flap group compared to 88 % in the LIS group in a retrospective
study in 2011 [14]. Due to small sample size in the treatment groups (n = 50 in each
treatment arm), these differences did not reach statistical significance. The other
study, published in 1995, revealed similar results with an incontinence rate of zero
in both groups and equivalent failure rates of 0 % in the LIS group and 3 of 20
(15 %) in the anal advancement flap group. Clearly, further studies of anal advance-
ment flaps, LIS and redo LIS with manometric baseline data should be performed to
establish the efficacy of this treatment versus others.
Conclusion
When considering different treatment options for recurrent anal fissure it is impor-
tant to recognize that inadequate primary LIS may be the cause of the recurrence.
Over the years, several variations of LIS including open, closed, tailored, and the
standard approaches to sphincter division have been developed in an attempt to
decrease the risk of incontinence. By performing a less complete sphincter division,
surgeons are likely placing patients at an increased risk of treatment failure. The
case series cited above demonstrate that repeat standard LIS can provide the patient
with a low recurrence rate as well as low risk of incontinence, though one must only
consider this option in the setting of clearly documented hypertonia.
In patients presenting with unhealed fissures and hypotonia, anal advancement
flaps may be a better option. We do not recommend botulinum toxin injection for
any anal fissure patient due to the temporary nature of the therapy, and its unknown
benefit in chronic fissures. The lack of published research on patients with recur-
rent anal fissure brings to light the need to perform future cohort studies compar-
ing treatments with particular attention paid to preoperative stratification for
sphincter tonicity. This would better enable colorectal surgeons to provide more
realistic information to patients regarding key outcomes including rates of cure,
rates of new incontinence, and patient satisfaction or quality of life (Tables 35.1
and 35.2).
Table 35.1 PICO outline for clinical problem

Patients with recurrent fissure Repeat LIS 1. Advancement flap Cure, continence,
after Lateral Internal 2. Botox patient satisfaction
Sphincterotomy
Table 35.2 Results of literature search

New Other
Year Study # of Treatments Failure incontinence outcomes
Authors published type patients compared rate rate measured
Brisinda 2008 Case 80 Botulinum 22 % at Baseline NA
et al. Series Toxin Inject vs. 1 incontinence
No comparison month not measured;
provided 10 %
incontinence at
1 month; none
long term
Liang 2015 Case 57 Lateral Internal 2 % 7.4 % Patient
et al. Series sphincterotomy Satisfaction:
vs. No Significantly
comparison improved after
provided intervention
Summary for Box

No recommendation can be made regarding treatment of recurrent anal fissure after
lateral internal sphincterotomy. (evidence quality: very low).
References
1. Abcarian H et al. The role of internal sphincter in chronic anal fissures. Dis Colon Rectum.
1982;25(6):525–8.
2. Garcia-Aguilar J et al. Open vs. closed sphincterotomy for chronic anal fissure: long-term
results. Dis Colon Rectum. 1996;39(4):440–3.
3. Hsu TC, MacKeigan JM. Surgical treatment of chronic anal fissure. A retrospective study of
1753 cases. Dis Colon Rectum. 1984;27(7):475–8.
4. Khubchandani IT, Reed JF. Sequelae of internal sphincterotomy for chronic fissure in ano. Br
J Surg. 1989;76(5):431–4.
5. Lund JN, Scholefield JH. Aetiology and treatment of anal fissure. Br J Surg.
1996;83(10):1335–44.
6. Brisinda G et al. Botulinum toxin for recurrent anal fissure following lateral internal sphincter-
otomy. Br J Surg. 2008;95(6):774–8.
7. Liang J, Church JM. Lateral internal sphincterotomy for surgically recurrent chronic anal fis-
sure. Am J Surg. 2015;210(4):715–9.
8. Kiyak G et al. Results of lateral internal sphincterotomy with open technique for chronic anal
fissure: evaluation of complications, symptom relief, and incontinence with long-term follow-
up. Dig Dis Sci. 2009;54(10):2220–4.
9. Mentes BB et al. Results of lateral internal sphincterotomy for chronic anal fissure with par-
ticular reference to quality of life. Dis Colon Rectum. 2006;49(7):1045–51.
10. Ortiz H et al. Quality of life assessment in patients with chronic anal fissure after lateral inter-
nal sphincterotomy. Br J Surg. 2005;92(7):881–5.
11. Garg P, Garg M, Menon GR. Long-term continence disturbance after lateral internal sphincter-
otomy for chronic anal fissure: a systematic review and meta-analysis. Colorectal Dis.
2013;15(3):12108.
12. Elsebae MM. A study of fecal incontinence in patients with chronic anal fissure: prospective,
randomized, controlled trial of the extent of internal anal sphincter division during lateral
sphincterotomy. World J Surg. 2007;31(10):2052–7.
13. Nelson R. A systematic review of medical therapy for anal fissure. Dis Colon Rectum.
2004;47(4):422–31.
14. Patel SD, Oxenham T, Praveen BV. Medium-term results of anal advancement flap compared
with lateral sphincterotomy for the treatment of anal fissure. Int J Colorectal Dis.
2011;26(9):1211–4.
15. Leong AF, Seow-Choen F. Lateral sphincterotomy compared with anal advancement flap for
chronic anal fissure. Dis Colon Rectum. 1995;38(1):69–71.
Chapter 36
Benign Anal Disease: Third Degree
Hemorrhoids – Who Really Needs Surgery?
Aneel Damle and Justin Maykel
Introduction
Surgeons posess a wide variety of therapeutic options to treat hemorrhoids. Grade I/

II hemorrhoids can usually be readily managed with dietary modification and/or
office based treatments whereas grade IV hemorrhoids commonly require surgery.
However, there are no clear-cut guidelines for the optimal treatment of grade III
hemorrhoids. Further complicating matters, the hemorrhoid grading system devel-
oped by Goligher in 1954 (grades I-IV) does not account for key factors that may
drive decision making, such as size or whether the hemorrhoids are isolated or cir-
cumferential [1].
The surgeon must decide when office-based techniques are most appropriate as
opposed to surgical intervention [2]. In broad terms, excisional hemorrhoidectomy
(EH), has an excellent success rate, but is associated with a significant amount of
postprocedural pain and related disability, not to mention cost [3]. Newer opera-
tive techniques such as the procedure for prolapse and hemorrhoids (PPH) or
Doppler-guided hemorrhoidal artery ligation (DGHAL) may be associated with
less postoperative pain but carry higher recurrence rates. Office based techniques
such as rubber band ligation (RBL), sclerotherapy or infrared coagulation offer a
relative safe and simple approach for many patients, although long-term durability
A. Damle, MD, MBA

Division of Colon and Rectal Surgery, University of Massachusetts Medical Center, 55 Lake
Avenue North, Worcester, MA 01655, USA
J. Maykel, MD (*)
Division of Colon and Rectal Surgery, University of Massachusetts Medical Center,
67 Belmont Street, Worcester, MA 01605, USA

DOI 10.1007/978-3-319-40223-9_36
404 A. Damle and J. Maykel
remains a concern. RBL is relatively contra-indicated in patients using clopido-

grel, warfarin, or heparin due to the significant incidence of post-procedure bleed-
ing [4]. However, of the available office-based procedures, RBL is typically the
most e ffective option and has been used as the comparison group to surgical hem-
orrhoidectomy [5].
Complications may result from any technique and can range from minor to life-
threatening. They include bleeding, urinary retention, wound infection, inconti-
nence, anal-stricture, ectropion, and local sepsis [3]. To appropriately answer the
question of who should have surgery for grade III hemorrhoids, we must evaluate
the ability of a treatment to control symptoms, the re-treatment rate, postoperative
pain, complication rates, disability, and patient satisfaction (Table 36.1).
Search Strategy/Methods
A literature search of MEDLINE, PubMed, the Cochrane Database of Collected

Reviews, and Google Scholar was performed using English language articles from
January 2000 to present. Search terms included hemorrhoids, internal and external
hemorrhoids, hemorrhoid disease, rubber band ligation, hemorrhoidectomy, hemor-
roidopexy, and Doppler-guided hemorrhoidectomy. Selected references from arti-
cles identified in the primary literature search were used when relevant. Literature
was evaluated using the GRADE evidence quality classification system [6]. Post-
hoc data analysis was conducted using Fisher's exact test.
Results
High quality evidence comparing office techniques to surgical hemorrhoidectomy

for grade III hemorrhoids is lacking. The majority of the available evidence
focuses on EH versus RBL. A recent Cochrane Review comparing these two
groups was able to include only three of 1186 abstracts reviewed as most studies
failed to meet inclusion criteria or contained methodological problems [7]. Of
these studies, only two evaluated grade III hemorrhoids. There is a similar lack of
high quality data comparing other operative techniques such as PPH or DGHAL
to RBL. The following discussion includes the results of available studies
(Table 36.2).
Table 36.1 Identification of patient population, intervention, comparison, and outcomes

Patients with 3rd degree Hemorrhoidectomy Rubber Band Symptom control and
hemorrhoids Ligation morbidity
36 Benign Anal Disease: Third Degree Hemorrhoids – Who Really Needs Surgery? 405
Table 36.2 Results of studies comparing surgery to office management of grade III hemorrhoids
No. of
patients Quality of
Study Group (Gr 3/total) Results evidence
Murie EH vs 56/88 RR 0.12 for prolapse for grade III (95 % Low
et al. [14] RBL CI, 0.02–0.87, p = 0.04)
RR 0.55 for bleeding for all patients (95 %
CI, 0.2–1.3, p = 0.2)
RR 1.54 for pain > 48 h for all patients
(95 % CI, 1.2–1.9, p < 0.01)
WMD + 29 days off work for all patients
(95 % CI, 21.2–36.8, p < 0.01)
Lewis EH vs 56a RR 0.40 for short-term symptom Low
et al. [15] RBL recurrence (95 % CI, 0.2–0.7, p < 0.01)
RR 0.18 for long-term symptom recurrence
(95 % CI, 0.1–0.4, p < 0.01)
RR 3.75 for pain requiring systemic
analgesia (95 % CI, 2.1–6.8, p < 0.01)
Gagloo EH vs 38/100 RR 0.25 for prolapsed for grade III (95 % Low
et al. [17] RBL CI, 0.1–0.8, p = 0.02)
RR 5.0 for requiring post-operative
analgesia for all patients (95 % CI, 2.8–8.7,
p < 0.01)
Peng et al. PPH vs 55/65 RR 0.21 for bleeding symptoms 2 weeks Moderate
[19] RBL post-op (95 % CI, 0.1–0.4, p < 0.01)
Gr grade, RR relative risk, WMD weighted mean difference
a
A total of 112 patients were in the study, but patients who had anal dilation or cryotherapy were
excluded from ad-hoc analysis
Control of Symptoms
Excisional hemorrhoidectomy is often referred to as the "gold standard" for the

treatment of hemorrhoids when it comes to control of symptoms [8]. A large retro-
spective case series of 693 patients who underwent EH (Ferguson closed technique)
for grade III and IV hemorrhoids reported a recurrence rate of 1 % and 3 % at 1 and
2 years [9]. When compared to other surgical techniques such as PPH, a meta-
analysis demonstrated that patients undergoing EH were significantly less likely to
complain of ongoing hemorrhoidal symptoms than those who underwent PPH (6
trials, 388 patients, OR 0.52, 95 % CI, 0.3–0.91; p = 0.02) [10]. DGHAL has also
been shown to have a high recurrence rate with 31 % of patients having symptoms
within the subsequent 5 years [11]. Conversely, a recent clinical trial comparing EH
to DGHAL with mucopexy demonstrated no difference in symptoms including pain
and bleeding at 2 years post-procedure [12].
RBL has also been shown to control symptoms for many individuals, but to a
lesser extent. A retrospective study of 701 patients showed an overall success rate
(alleviation of symptoms) of 70 % [13]. When only patients with grade III hemor-
rhoids were included, the success rate decreased to 59 %. Three studies were identi-
fied that compared outcomes of EH directly to RBL. Murie et al. evaluated 100
patients with either grade II or III hemorrhoids and randomized them to EH or RBL
[14]. Of the 56 patients with grade III hemorrhoids, 97 % of patients undergoing EH
had no symptoms of prolapse at 1 year compared to 70 % in the RBL group
(p = 0.04). When adding in the patients with grade II hemorrhoids, 86 % of EH
patients had no bleeding at 1 year compared to 74 % in the RBL group (p = 0.28).
Lewis et al. compared EH with anal dilatation, RBL and cryotherapy [15]. Of the
26 patients undergoing EH, 100 % had fewer symptoms and 65 % had no symptoms
at 1 year, as opposed to 67 % and 13 % for RBL. In the long-term (6 months–5
years) 100 % of EH patients had fewer symptoms and 86 % had no symptoms. Only
40 % of RBL patients had fewer symptoms and 23 % were symptom free. No
patients in the EH group required further treatment compared to 80 % in the RBL
group.
A systematic review of the two aforementioned trials demonstrated greater effi-
cacy for EH over RBL for the treatment of grade III hemorrhoids (2 trials, 116
patients, RR 1.23, 95 % CI 1.0–1.5, p = 0.01). However, this difference was not seen
with grade II hemorrhoids (1 trial, 32 patients, RR 1.07, 95 % CI 0.9–1.2, p = 0.32)
[16].
A 2011 study randomized 100 patients with grade II/III hemorrhoids to EH or
RBL [17]. Of the grade III patients (38 patients), 12.5 % of the EH group experi-
enced recurrent prolapse symptoms after 6 months compared to 50 % in the RBL
group. Although no statistical analysis was included in the study, post-hoc analysis
reveals this is a statistically significant finding (p = 0.03). Consistent with the sys-
tematic review is the finding that RBL leads to better results with grade II hemor-
rhoids compared to grade III (77 % vs. 50 % without prolapse at 6 months,
respectively).
In a comparison of PPH with RBL, there was a significant decrease in the per-
centage of patients experiencing the symptoms of bleeding from hemorrhoids at
2-weeks post-procedure in the PPH group (27 % vs. 68 %, p < 0.005). This differ-
ence was not seen for prolapse, pruritis, or wound discharge [18]. By 2 months,
there was no difference in symptoms experienced in either group.
We did not identify any published results comparing DGHAL to RBL. However,
there is currently a multi-center randomized controlled trial that has been completed
comparing these two interventions for grade II and III hemorrhoids, with results
pending [19].
Post-Treatment Pain and Complications
A systematic review of trials comparing EH to RBL for grade II/III hemorrhoids

(including Murie and Lewis, et al.) demonstrated significantly more patients that
underwent EH experienced post-operative pain (3 trials, 212 patients, RR 1.94,
95 % CI 1.62–2.33, p < 0.001) [16]. There was no statistically significant difference
in other postoperative complications such as urinary retention, hemorrhage, or anal

stenosis. A meta-analysis of the same three trials revealed similar results [5]. Gagloo
et al. found 100 % of patients undergoing EH required postoperative analgesia com-
pared to 20 % of patients after RBL [17]. Severe pain from RBL may result from
placement of the band below the dentate line, which precludes the banding of exter-
nal hemorrhoids [3].
While EH has been repeatedly shown to be associated with more postoperative
pain than RBL, a recent Cochrane Review has demonstrated a significant decrease
in pain when hemorrhoidectomy is performed with a LigaSure device [20]. Pain
scores on the first post-operative day showed a WMD of −2.07 (10 studies, 835
patients, CI −2.77−1.38). There was no relevant difference in other postoperative
complications. A study comparing DGHAL with mucopexy to EH demonstrated no
significant difference in post-operative pain scores up to 2 weeks [12].
In a comparison of PPH with RBL, PPH was associated with a higher maximal
pain score at discharge (5 vs 2, p < 0.001) and at 2 weeks (5 vs 0, p < 0.001). However,
by 2 months, no patient in either group complained of pain. There was no difference
in other complications such as urinary retention, bleeding, anal stenosis, or change
in continence. However, his study was not sufficiently powered for these endpoints
[18].
Lifestyle (Return to Work and Patient Satisfaction)
Murie et al. reported that 100 % of working patients undergoing EH lost time from
work with a mean of 32 days compared to 44 % of the RBL group with an average
time away from work of 3 days (SD 7 days-p < 0.01) [14]. However, the newer tech-
niques of hemorrhoid surgery have considerably improved return to work times. A
Cochrane review comparing LigaSure hemorrhoidectomy to standard EH demon-
strated a return to work 4.88 days earlier (4 studies, 451 patients, CI 2.18–7.59).
When comparing DGHAL to EH, DGHAL patients returned to work after 10 days
compared to 22 days in the EH group (p = 0.09) [12].
A systematic review demonstrated similar overall patient satisfaction in both EH
and RBL patients (RR 1.02, 2 studies, 148 patients, 95 % CI, 0.94–1.10) [16].
Gagloo, et al. reported 70 % of patients considered EH an “excellent” modality
compared to 64 % for RBL [17]. There was no difference noted between PPH and
RBL in terms of patient satisfaction at discharge, 2 weeks, 2 or 6 months [18].
Cost
None of the identified studies comparing EH to RBL evaluated cost. However, in the
current healthcare climate, cost of therapy must be a consideration. Factors that may
impact cost include operative time, equipment, and need for further treatment. In
addition, the time of convalescence financially impacts patients, and the economy as
a whole.
There is considerable variation of operative time based on surgical technique.
Multiple studies have demonstrated EH to have longer operative times than other
techniques such as PPH [21]. However, when accounting for equipment costs, EH
was demonstrated to be less expensive than PPH ($252 vs. $504) [22]. The addition
of disposable LigaSure diathermy forceps adds an additional $225 per operation to
EH [23].
RBL does not require operating room time and the cost of equipment is minimal.
However, a long-term study of over 700 patients demonstrated that 30 % of patients
require re-treatment with a median 2 bandings per patient and a range of 1–17 bands
placed [13]. Also, as previous studies have demonstrated increased pain with mul-
tiple bandings in a single session, patients often need to be brought back for several
sessions [13, 24, 25]. However, as stated above, RBL does allow a considerably
earlier return to work, reducing lost wages.
Recommendations
There are insufficient randomized controlled trials to make a strong recommenda-

tion based on high-quality evidence. However, there are trends in the literature suf-
ficient for recommendations.
Recommendation 1
Most patients with uncomplicated grade III internal hemorrhoids may be
effectively treated with office procedures as first line treatment after appropri-
ate medical therapy. Strong recommendation based on moderate quality
evidence.
Due to the relatively low complication rate, decreased pain, faster return to work
and reasonable efficacy, office techniques such as rubber band ligation may be an
appropriate first option for many patients. While not as efficacious as surgical hem-
orrhoidectomy, many patients may succeed without a trip to the operating room.
This technique does burn any bridges and therapy may always be escalated to surgi-
cal management.
Recommendation 2
Patients with large multi-column grade III hemorrhoids or a mixed internal/
external component should undergo surgical hemorrhoidectomy. Strong rec-
ommendation based on moderate quality evidence.
Large hemorrhoids may not be treated as effectively with office-based proce-

dures. This may be due to the small size of the ligation barrel limiting the size of the
hemorrhoid banded [26]. In these cases, surgical hemorrhoidectomy is the better
choice to remove all affected tissue. In addition, as multi-column disease may
require multiple banding episodes, these patients may be good candidates for sur-
gery. Finally, as rubber band ligation should not be applied below the dentate line,
patients who seek treatment for mixed component hemorrhoids should preferably
undergo surgery.
Recommendation 3
Patients who are unable to tolerate or have failed office-based techniques
should undergo surgical hemorrhoidectomy. Strong recommendation based
on moderate quality evidence.
While office based procedures such as rubber band ligation may have the advan-
tages of decreased invasiveness, many patients require repeat therapy. In addition,
while the risk of late bleeding after RBL is similar in patients who take no anti-
thrombotic therapy and those who hold antithrombotic therapy, not all patients are
able to do so [27]. Patient preference may play a large role in how many times this
is done. In patients who continue to be symptomatic from their hemorrhoids or no
longer wish to have repeat procedures, surgical therapy is appropriate.
Expert Opinion
When we see patients with symptomatic grade III hemorrhoids, they are typically
complaining of tissue prolapse, bleeding, and mucous drainage. Occasionally they
will complain of pain from hemorrhoidal engorgement with straining. By the time
the rectal mucosal prolapse requires manual reduction, we do not think that non
operative treatment alone, such as fiber supplementation, will likely provide suc-
cessful and durable relief of symptoms.
Patients with discrete, localized internal grade III hemorrhoids will be offered
in-office rubber band ligation, using a suction banding device. The rubber band is
positioned directly above the dentate line and the suction is held long enough to fill
the chamber fully with excess hemorrhoid tissue/rectal mucosa. Although caution
has been expressed re banding more than one column at a single session due to an
increased risk of complications and/or pain, we routinely band the two most promi-
nent columns at the initial session. This approach expedites the successful treatment
of the hemorrhoids while minimizing return office visits and additional procedures.
We warn all patients they should expect 48 h of rectal “pressure” but do not prescribe
pain medications beyond Tylenol. We caution them regarding the risks of bleeding,
pain, and infection, although serious complications are rare. We see patients back in
1 month for repeat banding if necessary, recognizing that the majority of patients
will not return when the initial RBL has successfully resolved their symptoms. When
patients are anticoagulated on medications beyond aspirin, we hold the anticoagula-
tion prior to RBL due to the risk of hematoma and bleeding.
When patients present with symptomatic, circumferential internal grade III hem-
orrhoids or when they do not tolerate in office anoscopy and/or RBL, we typically
offer them PPH hemorrhoidectomy. When the purse string stitch is properly placed
one cm above the hemorrhoids themselves, we have found this to be a very success-
ful and durable option for symtomatic grade III hemorrhoids. This provides a
single-procedure solution for extensive disease, as opposed to serial RBL sessions.
Patient pain experience varies based on location of the staple line as well as vari-
ability of anal canal innervation. An alternative remains Doppler-guided hemor-
rhoid artery ligation; the addition of a mucopexy significantly improves outcomes
and long term success.
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23. Jayne DG, Botterill I, Ambrose NS, et al. Randomized clinical trial of LigasureTM versus con-
ventional diathermy for day-case haemorrhoidectomy. Br J Surg. 2002;89:428–32.
24. Kombrorozos VA, Skrekas GJ, Pissiotis CD. Rubber band ligation of symptomatic internal
hemorhoids: results of 500 cases. Dig Surg. 2000;17:71–6.
25. Lee HH, Spencer RJ, Beart RW. Multiple hemorrhoidal bandings in a single session. Dis
Colon Rectum. 1994;37:37–41.
26. Cintron J, Abcarian H. Benign anorectal: hemorrhoids. In: Wolff BG, Fleshman JW, Beck DE,
et al., editors. The ASCRS textbook of colon and rectal surgery. New York: Springer; 2007.
p. 156–77.
27. Nelson RS, Ewing BM, Ternent C, et al. Risk of late bleeding following hemorrhoidal banding
in patients on antithrombotic prophylaxis. Am J Surg. 2008;196(6):994–9.
Chapter 37
Which Patients with Fecal Incontinence
Require Physiologic Workup?
Tracy Hull
Introduction
Anal physiology testing is part of the initial diagnostic workup used in patients
presenting with fecal incontinence (FI) but the value in defining the disease severity,
predicting and assessing treatment outcomes has been debated [1]. This chapter will
present the available evidence in the literature to define the role of anal physiology
testing for FI.
Search Strategy
PubMed was queried using different combinations of search terms. The search
terms were: faecal/fecal incontinence, anal incontinence, assessment, testing, evalu-
ation, fecal incontinence/diagnosis, outcome and process assessment (Health Care),
diagnostic techniques and procedures, diagnosis, physical examination, diagnostic
techniques, digestive system workup, diagnostic evaluation, predictive value of test,
physiological test, physiologic workup, manometry, anal manometry, anorectal
manometry, balloon expulsion, pudendal nerve terminal motor latency, costs and
cost analysis, cost, and quality of life. The filters used were: English; adult: 19+
years; dates: January 1994-present; and humans. References of relevant articles
were also reviewed.
T. Hull
Department of Colon and Rectal Surgery, Digestive Disease Institute, The Cleveland Clinic
Foundation, Cleveland, OH, USA

DOI 10.1007/978-3-319-40223-9_37
414 T. Hull
P (Patients) I (Intervention) C (Comparator) O (Outcomes)

Patients with fecal Physiologic Clinical Decision Diagnosing the
incontinence. workup. Making. underlying cause.
Predicting treatment
outcome.
Results
We feel that obtaining a detailed history and physical exam is usually the most
important determinant that influences the decision making [2, 3]. Therefore when
considering a diagnostic test, the key question is whether this test will affect the
overall management plan.
Some studies reported that physiologic testing could guide the physician in treat-
ing patients with FI. Vaizey and Kamm prospectively studied 100 patients to evalu-
ate the impact of anorectal investigations (this included anal ultrasound) on the
management decisions. They found that the information provided by anorectal
physiologic assessment had an impact on management in patients with benign ano-
rectal disorders. However, carefully evaluating their study, even though anorectal
assessment had an important diagnostic and prognostic role in managing patients
with benign anorectal disorders, endoanal ultrasound was actually the driving test
that changed their plans in FI patients (n = 51); anorectal physiology helped guide
decision making for patients with constipation [4]. Therefore, anorectal physiology
testing did not really seem to influence FI decisions.
Wexner and Jorge conducted a prospective study on 308 patients presenting with
various complaints (constipation, fecal incontinence and chronic intractable rectal
pain) to assess the usefulness of colorectal physiological studies to identify all rel-
evant causes that could be treated [5]. Out of 308 patients, 80 presented with FI. The
etiology of FI was revealed by history and physical examination alone in 9 patients
(11 %) and by physiological testing (anal manometry, cinedefaecography, anal elec-
tromyography and pudendal nerve terminal motor latency PNTML) in 44 (55 %).
The etiology remained undiagnosed in 27 patients (34 %) even after testing. The
causes of FI were loss of muscle fibers (26 %), neuropathy (13 %), combined muscle
loss and neuropathy (19 %), and rectoanal intussusception (9 %). They concluded
that physical examination might detect anorectal scarring, attenuation of the recto-
vaginal septum/anal sphincters, and poor contraction of the sphincter; however
clinical evaluation cannot confirm the presence of iatrogenic injury. Physical exami-
nation also was not capable of detecting pudendal neuropathy. In their view, find-
ings of colorectal physiological testing permit assignment of patients to treatment
regimens. It is important to note that this study also included more investigations
than just anal physiology and they reported using all this data when making their
conclusion. Therefore the role of anal physiology could not be determined.
37 Which Patients with Fecal Incontinence Require Physiologic Workup? 415
On the other hand, more recent studies reported no benefit to physiologic testing
for FI. Lam et al. [3] prospectively assessed 600 patients referred for anorectal test-
ing and compared those with and without FI (48 % with fecal incontinence and 87 %
female) in order to formulate a statistical model to determine which factors would
predict FI, particularly after a stoma closure. In regards to anorectal physiology test-
ing, women with FI had lower anal pressures, shorter sphincter length, and smaller
rectal capacity. Men with FI had lower anal pressures. Incontinent and continent
patients had a broad overlap in anorectal physiology testing. They did find that all
patients with a rectal capacity <60 cc had FI and of those with maximum basal and
squeeze pressures ≤20 mmHg, only 4 % were continent. They used six items to cre-
ate a statistical model for FI (female, age, stool consistency, maximum rest and
squeeze pressures, rectal capacity, and anal sphincter defects). They then used this
model on 5 women to accurately predict the risk of FI following stoma closure.
While this study did demonstrate some utility for anal physiology testing, this was
used in combination with other tests and consideration of patient characteristics.
Similar findings were also reported by Raza and Bielefeldt [6]. They reviewed
298 patients who had anorectal manometry mainly for FI (51 %) and constipation
(42 %). Patients with fecal incontinence had significantly lower pressures compared
to individuals with constipation, but the data overlapped significantly. The sensitiv-
ity of resting and squeeze pressures were 50 and 59 %, respectively while the speci-
ficity for low squeeze pressures was only 69 %. They concluded that manometry
should not be used routinely because it has poor discriminatory power.
Zutshi et al. conducted a retrospective study on 53 women who had a sphincter
repair. They reported that anal manometry did not correlate with severity of incon-
tinence nor did it assess or predict response to treatment [1]. Bordeianou et al.
looked at the relationship between anorectal manometry, fecal incontinence severity
(FISI scores), and findings at endoanal ultrasound in 351 women [7]. They found
FISI scores were equally severe in patients with or without a sphincter defect; a
weak correlation was observed between resting anal pressure and the severity of
defects on anal ultrasound; and no correlation existed between maximum squeeze
pressure and FISI scores. In the subset of patients with a sphincter defect (n = 148),
a weak and negative correlation was reported between the mean resting pressures
and maximum resting pressures, the size of the internal and external sphincter
defects, as well as the size of the perineal body.
In a Cochrane review evaluating the effects of sacral nerve stimulation (SNS) for
FI and constipation, anorectal manometry did not appear to predict which patients
would benefit from SNS and the authors concluded that testing with anorectal
manometry did not appear to provide clinically useful information [8].
Anal manometry has many limitations. One drawback is that it is very difficult to
compare results between institutions because manometric findings are not standard-
ized; the normal range of values varies at each institution [9]. There are no normal
values stratified by sex and age [10] and different companies manufacture different
types of machines that also adds to the variability.
Intact pudendal nerves may contribute to the success of FI treatment such as SNS
or sphincter repair. However PNTML reflects the activity of the fastest fibers, which
416 T. Hull
makes it a poor indicator of damage to the entire range of nerves that supply the
sphincter complex. Additionally it is operator dependent. This has led many inves-
tigators to no longer recommended PNTML when evaluating FI [11–13]. In a sys-
tematic review by Glasgow and Lowry, 900 patients from 16 studies (2 case control,
1 prospective and 13 retrospective studies) were included as they looked at the out-
comes of anal sphincter repair for FI [14]. In five studies, pudendal neuropathy,
resting and squeeze anal pressures, anal canal length, and rectal compliance did not
predict long-term outcomes following sphincteroplasty [15–19]. However, there
was one retrospective study that reported pudendal neuropathy predicted the out-
come after sphincter repair for FI [20].
The majority of published studies examining the role of physiologic workup in FI

are retrospective (low quality of evidence). FI is multifactorial in etiology and since
there is no gold standard test of the overall continence mechanism [10], this makes
as assessment of utility more challenging. The available clinical assessment tools
also have a subjective component which adds to the challenge of using them for
management decisions. Based on this review, we provide a weak recommendation
against the use of anal physiology testing routinely. Anorectal physiologic testing
does not generally harm the patient; however, most of the available data shows no
impact for choosing treatment or predicting outcomes. There may be some benefit
when combined with a total anorectal assessment and testing. Results of anal physi-
ology testing overall do not correlate with the severity of symptoms nor does it
assess response to treatment.
Summary of Recommendation Options
Strength of Implications for Implications for

recommendation patients Implications for clinicians policy makers
Weak against anal It does not cause In some circumstances, it Should be
physiology testing. harm but may not may aid treatment considered but
improve outcome. recommendation. used selectively.
37 Which Patients with Fecal Incontinence Require Physiologic Workup? 417
At our institution we start all work-up for patients with FI utilizing a detailed history
and physical exam. We believe this is the most important factor in discerning con-
tributing factors and making management decision in FI. We do obtain anal physiol-
ogy testing; however as we have gained more data and experience, we do not feel it
overall guides our therapy for FI. One exception would be FI related to rectal dys-
function. When looking at first perception of a balloon inflated in the rectum, urge
to defecate, and maximum tolerated volume, a rectum that is hypersensitive may
push stool past a sphincter that has acceptable tone on physical exam. This finding
would prompt us to communicate with the physical therapist so appropriate therapy
can be used to try to desensitize the rectum. Also suppositories that decrease spas-
ticity may be considered. Conversely, for patients detected to have a hyposensitive
rectum with a maximum tolerated volume of >300 cc (the limit of what the balloon
can hold), FI can be a result of overflow which may be difficult to detect by history
and physical exam only. For patients with a hyposensitive rectum, communication
with the physical therapist is essential so they work on appropriate retraining. Also
enema therapy may be more efficacious in this group.
We do not feel overall that resting pressures and squeeze pressures are helpful.
We also agree that PNTML does not correlate with what we find on physical exam.
For instance when doing a digital and asking a patient to contract against the exam-
ining finger there may be no movement at all in the levator or sphincter complex, but
the PNTML may be normal. Nearly all patients should initially be offered conserva-
tive management which consists of dietary adjustments, antidiarrheal medications,
enema therapy, skin care, and physical therapy retraining. If conservative measures
fail, then patients are considered for further workup and treatment. We used to feel
that anal ultrasound was our preferred test, but with the popularity of SNS for treat-
ment, we do not rely on this test as much as in the past (Tables 37.1 and 37.2).
References
1. Zutshi M, Salcedo L, Hammel J, Hull T. Anal physiology testing in fecal incontinence: is it of

any value? Int J Colorectal Dis. 2010;25(2):277–82.
2. Hull TL. Fecal incontinence. In: Complexities in colorectal surgery. Springer; New York 2014.
p. 203–18.
3. Lam T, Kuik D, Felt‐Bersma R. Anorectal function evaluation and predictive factors for faecal
incontinence in 600 patients. Colorectal Dis. 2012;14(2):214–23.
4. Vaizey CJ, Kamm MA. Prospective assessment of the clinical value of anorectal investiga-
tions. Digestion. 2000;61(3):207–14.
5. Wexner SD, Jorge JM. Colorectal physiological tests: use or abuse of technology? Eur J Surg.
1994;160(3):167–74.
6. Raza N, Bielefeldt K. Discriminative value of anorectal manometry in clinical practice. Dig
Dis Sci. 2009;54(11):2503–11.
7. Bordeianou L, Lee KY, Rockwood T, et al. Anal resting pressures at manometry correlate with
the fecal incontinence severity index and with presence of sphincter defects on ultrasound. Dis
Colon Rectum. 2008;51(7):1010–4.
Table 37.1 Anal physiology in diagnosis of FI
418
Quality of
Author Year Patients Study type Results evidence Comment
Dobben et al. 2007 FI (n = 312) Prospective Anal inspection and Low Anal inspection and DRE in
[21] digital rectal some centers done by
examination DRE residents, gynecologists, or
can give accurate gastroenterologist. The
information about clinicians were unblinded to
anal sphincters but patients’ history.
do not detect EAS
defects <90°.
Raza and 2009 FI vs. chronic Retrospective Manometric findings Low
Bielefeldt [6] constipation and have low sensitivity
others (n = 298) and specificity and
do not discriminate
well between
continent and
incontinent patients.
Pehl et al. [22] 2012 Healthy controls Retrospective Single data from the Low
(n = 144) vs. FI entire spectrum of
patients (n = 599) manometry
information is
moderate for the
pressure data and
poor for the sensory
data.
The entire data set
has excellent
sensitivity (91.4 %)
and moderate
specificity (62.5 %).
T. Hull
Quality of
Author Year Patients Study type Results evidence Comment
Lam et al. [3] 2012 FI vs. continent Prospective There was a large Moderate
patients (n = 600) overlap between
incontinent and
continent patients.
Lam et al. [23] 2012 FI (n = 218) Prospective Anal manometry did Moderate
not detect anorectal
sphincter defects.
Anorectal
manometry and
ultrasound do not
correlate well with
FI scores.
37 Which Patients with Fecal Incontinence Require Physiologic Workup?
419
Table 37.2 Anal physiology in predicting FI treatment outcomes
420
Quality of
Study Year Type of treatment Type of study Results evidence Comment
Buie et al. [24] 2001 Anterior sphincteroplasty Retrospective Anorectal manometry Low 33 % of the patients
(n = 191) and PNTML are not did not have
predictive of manometry and 53 %
postoperative function. did not have PNTML
Gearhart et al. 2005 Sphincter repair (n = 20) Prospective The physiologic Moderate
[25] parameters are not
predictive of functional
outcome.
Zutshi et al. [1] 2010 Sphincter repair (n = 53) Retrospective No correlation of pre- Low
and postoperative
manometric parameters
with incontinence scores.
Glasgow and 2012 Anal sphincter repair Systematic review No consistent predictive Moderate
Lowry [14] (n = 900) factors for outcomes
were identified.
Bols et al. [26] 2012 Physiotherapy (n = 80) Secondary analysis of Results of physical Moderate
a randomized trial examination, diagnostic
tests, and physiotherapy
assessment were not
predictive of outcomes.
Feretis and 2013 Biofeedback (n = 137) Retrospective Anorectal investigations Low
Chapman [27] are of doubtful role in
patient selection for
biofeedback therapy.
T. Hull
Quality of
Study Year Type of treatment Type of study Results evidence Comment
Roy et al. [28] 2014 SNS (n = 60) Prospective No pre-treatment or Moderate
post-treatment
assessment parameters
that predict the outcome
of SNS.
Quezada et al. 2015 SNS (n = 60) Retrospective Anal physiology testing, Low
[29] PNTML and
ultrasonography were not
predictive of clinical
outcomes of SNS.
37 Which Patients with Fecal Incontinence Require Physiologic Workup?
421
422 T. Hull
8. Thaha MA, Abukar AA, Thin NN, Ramsanahie A, Knowles CH. Sacral nerve stimulation for
faecal incontinence and constipation in adults. Status and date: New search for studies and
content updated (no change to conclusions), published in. 2015(8).
9. Chaliha C, Sultan A, Emmanuel A. Normal ranges for anorectal manometry and sensation in
women of reproductive age. Colorectal Dis. 2007;9(9):839–44.
10. Fruehauf H, Fox MR. Anal manometry in the investigation of fecal incontinence: totum pro
parte, not pars pro toto. Digestion. 2012;86(2):75–7.
11. Azpiroz F, Enck P, Whitehead WE. Anorectal functional testing: review of collective experi-
ence. Am J Gastroenterol. 2002;97(2):232–40.
12. Dudding TC, Vaizey CJ. Current concepts in evaluation and testing of posterior pelvic floor
disorders. Semin Colon Rectal Surg. 2010;21(1):6–21.
13. Barnett JL, Hasler WL, Camilleri M. American gastroenterological association medical posi-
tion statement on anorectal testing techniques. american gastroenterological association.
Gastroenterology. 1999;116(3):732–60.
14. Glasgow SC, Lowry AC. Long-term outcomes of anal sphincter repair for fecal incontinence:
a systematic review. Dis Colon Rectum. 2012;55(4):482–90.
15. Malouf AJ, Norton CS, Engel AF, Nicholls RJ, Kamm MA. Long-term results of overlapping
anterior anal-sphincter repair for obstetric trauma. Lancet. 2000;355(9200):260–5.
16. Grey BR, Sheldon RR, Telford KJ, Kiff ES. Anterior anal sphincter repair can be of long term
benefit: a 12-year case cohort from a single surgeon. BMC Surg. 2007;7:1.
17. Maslekar S, Gardiner AB, Duthie GS. Anterior anal sphincter repair for fecal incontinence:
good longterm results are possible. J Am Coll Surg. 2007;204(1):40–6.
18. Zorcolo L, Covotta L, Bartolo DC. Outcome of anterior sphincter repair for obstetric injury:
comparison of early and late results. Dis Colon Rectum. 2005;48(3):524–31.
19. Halverson AL, Hull TL. Long-term outcome of overlapping anal sphincter repair. Dis Colon
Rectum. 2002;45(3):345–8.
20. Londono-Schimmer E, Garcia-Duperly R, Nicholls R, Ritchie J, Hawley P, Thomson

J. Overlapping anal sphincter repair for faecal incontinence due to sphincter trauma: five year
follow-up functional results. Int J Colorectal Dis. 1994;9(2):110–3.
21. Dobben AC, Terra MP, Deutekom M, et al. Anal inspection and digital rectal examination
compared to anorectal physiology tests and endoanal ultrasonography in evaluating fecal
incontinence. Int J Colorectal Dis. 2007;22(7):783–90.
22. Pehl C, Seidl H, Scalercio N, et al. Accuracy of anorectal manometry in patients with fecal
incontinence. Digestion. 2012;86(2):78–85.
23. Lam T, Mulder C, Felt-Bersma R. Critical reappraisal of anorectal function tests in patients
with faecal incontinence who have failed conservative treatment. Int J Colorectal Dis.
2012;27(7):931–7.
24. Buie WD, Lowry AC, Rothenberger DA, Madoff RD. Clinical rather than laboratory assess-
ment predicts continence after anterior sphincteroplasty. Dis Colon Rectum.
2001;44(9):1255–60.
25. Gearhart S, Hull T, Floruta C, Schroeder T, Hammel J. Anal manometric parameters: predic-
tors of outcome following anal sphincter repair? J Gastrointest Surg. 2005;9(1):115–20.
26. Bols E, Hendriks E, de Bie R, Baeten C, Berghmans B. Predictors of a favorable outcome of
physiotherapy in fecal incontinence: secondary analysis of a randomized trial. Neurourol
Urodyn. 2012;31(7):1156–60.
27. Feretis M, Chapman M. The role of anorectal investigations in predicting the outcome of bio-
feedback in the treatment of faecal incontinence. Scand J Gastroenterol.
2013;48(11):1265–71.
28. Roy AL, Gourcerol G, Menard JF, Michot F, Leroi AM, Bridoux V. Predictive factors for suc-
cessful sacral nerve stimulation in the treatment of fecal incontinence: lessons from a compre-
hensive treatment assessment. Dis Colon Rectum. 2014;57(6):772–80.
29. Quezada Y, Whiteside JL, Rice T, Karram M, Rafferty JF, Paquette IM. Does preoperative anal
physiology testing or ultrasonography predict clinical outcome with sacral neuromodulation
for fecal incontinence? Int Urogynecol J. 2015;26(11):1613–7.
Chapter 38
Benign Anal Disease: Who Are the Right
Candidates for Sacral Nerve Stimulation?
Teresa C. Rice and Ian M. Paquette
Introduction
Fecal incontinence (FI) is defined as the involuntary passage of stool or flatus over
at least 1 month’s duration [1, 2]. It is a physically and socially debilitating condi-
tion that affects between 1 and 15 % of adult patients [3–5]. The disease can dra-
matically limit an individual’s activity, negatively impacting quality of life and
resulting in significant morbidity. The etiology of FI is often multifactorial and con-
sequently management of the disease is complex. Initial therapy typically begins
with conservative measures including dietary or medical management [6–8] and
biofeedback [9, 10]. However, when patients do not respond to these initial mea-
sures, consideration is given to surgical management including sacral nerve stimu-
lation (SNS), sphincteroplasty [11], sphincter replacement strategies [12, 13], or
stoma creation [14, 15]. Sacral nerve stimulation was initially developed for man-
agement of urinary incontinence but was first used for the successful treatment of FI
by Matzel et al. in 1995 [16]. Due to its reported long-term efficacy and low morbid-
ity, SNS continues to develop as an emerging and promising technique for the man-
agement of severe FI. Here, we aim to identify which patients with FI would benefit
from SNS. Further, we describe the utility of SNS for management of FI in the
subset of patients with a complete external sphincter defect.
T.C. Rice, MD
Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA
I.M. Paquette, MD (*)
Division of Colon and Rectal Surgery, University of Cincinnati College of Medicine,
Cincinnati, OH 45219, USA

DOI 10.1007/978-3-319-40223-9_38
424 T.C. Rice and I.M. Paquette
Table 38.1 PICO Table

P (Patients) I (Intervention) C (Comparator) O (Outcomes)
Patients Sacral nerve All other Success of therapy, decrease in FI
with FI stimulation interventions episodes, change in CCIS,
morbidity
Search Strategy
A systematic review of MEDLINE, PubMed, and the Cochrane Database of

Collected Reviews was performed from 1995 through December 2015. Search
terms included “fecal incontinence” and “sacral nerve stimulation” or “sacral neu-
romodulation” or “percutaneous nerve evaluation”. All English language manu-
scripts and studies in adult patients were reviewed. Case reports were excluded from
review. The primary outcome examined was success of therapy based on greater
than 50 % improvement in FI severity following permanent implantation with
SNS. Other outcomes examined included changes in the Cleveland Clinic Florida
Incontinence Score (CCIS) [17] (0–20, 0 – perfect continence; 20 – severe inconti-
nence) and decrease in episodes of fecal incontinence (Table 38.1). Each study was
graded on its quality of evidence based on the GRADE approach [18].
Results
In the SNS studies reviewed, 55–100 % percent of patients had a successful periph-
eral nerve evaluation (PNE) test as defined by >50 % improvement in FI severity
during the testing phase. A successful PNE test is highly predictive of a successful
permanent implant. Preoperative anal physiology testing and ultrasonography do
not appear to be predictive of SNS success for the management of fecal inconti-
nence [19]. Factors associated with failure of PNE testing phase include increased
age [20, 21], defects in the external anal sphincter [20, 22], and repeated PNE
attempts [20, 22]. However, if a PNE test was successful, the aforementioned fac-
tors were not associated with reduced success of a permanent implant [22].
Of the SNS studies reviewed, the majority were prospective case studies with
only two randomized trials [23, 24]. Most studies were of moderate to low quality
evidence by the GRADE approach [18] and were limited by the lack of a direct
comparator. In a randomized double blind crossover trial, there was a significant
improvement in frequency of episodes, symptom severity, and quality of life during
the device ON versus device OFF phase, indicating that improvement was due to the
device and not due to placebo [23]. When SNS was compared to optimal medical
management in a randomized controlled trial, those treated with SNS had a statisti-
cally significant improvement in weekly fecal incontinence episodes (from 9.5 to
3.1) and an improvement in quality of life [24]. Further, 47.2 % of patients achieved
perfect continence with SNS. In contrast, the optimal medical management group
had no improvement in fecal incontinence, nor quality of life scores. Meurette et al.
38 Benign Anal Disease: Who Are the Right Candidates for Sacral Nerve Stimulation? 425
compared SNS to artificial bowel sphincter (ABS) and noted that the SNS had
higher postoperative CCIS scores (9.4 vs. 4.7), but less constipation and a similar
improvement in quality of life [25]. Additionally, there was no significant morbidity
in the SNS group while 53 % of patients in the ABS group required further surgical
revision due to mechanical failure or ulceration/erosion of the anal canal. Aside
from these studies, there are no other direct comparative studies of SNS versus
alternative therapies.
The success rates for SNS based upon an improvement of at least 50 % in FI
severity following permanent implantation are shown in Table 38.2, in a per proto-
col analysis (success of patients who received a full-system implantation). Overall,
54–100 % of patients undergoing permanent implantation experienced a statistically
significant greater than 50 % improvement of FI in all follow up stages. Perfect
continence was achieved in 4–73 % of patients. Table 38.2 demonstrates an improve-
ment in CCIS score across all follow up lengths. SNS therapy for FI was shown to
be effective in studies with follow-up as long as 9 years [51, 78], though patients
need ongoing follow up; many patients will need a battery change or lead revision
over time [82].
Traditionally, patients with FI secondary to sphincter injury were managed with
sphincteroplasty and good short-term results were achieved [11]. However, addi-
tional studies demonstrated a decline in long-term efficacy [92–94]. As a result, the
utility of sphincteroplasty has been questioned as SNS has emerged as a novel, mini-
mally invasive therapy. Recent studies have demonstrated that SNS can be effective
even in patients with sphincter injury as seen in Table 38.3. These results were
achieved in patients with defects up to 180°. Additionally, SNS was proposed as a
treatment option for patients following failed sphincteroplasty. In a study that com-
pared SNS, artificial bowel sphincter (ABS), and repeat sphincteroplasty, no differ-
ence was found between CCIS scores or quality of life at follow up [105]. No head
to head comparison of SNS versus sphincteroplasty has been conducted to date.
Few studies have been performed to evaluate efficacy of SNS in the setting of
rectal prolapse [106, 107]. One small study demonstrated that SNS was less effi-
cacious in patients with high-grade rectal prolapse [106]. However, a more recent
prospective study has demonstrated that when SNS is performed following lapa-
roscopic ventral rectopexy, 55.7 % of patients were able to achieve greater than
50 % improvement in FI at 1 year follow up [107]. While initial prospective case
series have had encouraging results in the setting of FI following LAR for rectal
cancer [108, 109], or in severe perianal Crohn’s disease [96], large prospective
studies are necessary to validate the success of SNS in these select patient
populations.
In summary, SNS is a relatively safe procedure with no reported mortality and low
complication rates. The most commonly reported adverse events include pain at the
implantation site and infection [60, 70]. An advantage of SNS treatment is the
Table 38.2 Outcomes following permanent implantation with sacral nerve stimulator
426
Temp PNE/ % Patient improvement CCIS FI episodes

Study Perm 100 %
Study type Grade implant F/U (months) >50 % continent Baseline F/U Baseline F/U
Kenefick [26] PS Low 15/15 24 – 73.3 11 0
Ripetti [27] PS Low 21/4 15 100 12.2 12 2
Ratto [28] PS Low 10/10 –
Matzel [29] PS Low 37/34 23.9 88 39.4 16.4 2
Jarrett [30] PS Low 59/46 12 100 41.3 14 6 7.5 1
Rasmussen [31] PS Low 43/37 6 86 16 6
Uludag [32] PS Low 75/50 12 7.5 0.67
Altomare [33] PS Low 14/14 24 7 1
Jarrett [34] PS Low 13/12 12 – 41.7 9.33 2.39
Jarrett [35] PS Low 16/16 24 100 25 12 1.5
Leroi [23] RCT High 34/28 6 – 26.3 16 8.5 7 1
Hetzer [36] PS Low 20/13 1 100 14 4
Uludag [37] PS Low 14/14 1 100 8.7 0.67
Michelsen [38] PS Low 29/29 6 100 16 4
Faucheron [39] PS Low 40/29 6 – 17 6
Kenefick [40] PS Low 19/19 24 100 73.7 12 0
Holzer [41] PS Low 36/29 35 – 7 2
Gourcerol [21] PS Low 61/33 12 69 21 14.4 5 1
Hetzer [42] PS Low 44/37 13 91.9 14 5 8 2
Melenhorst [43] PS Mod 134/100 25.5 81 31.3 4.8
Navarro [44] PS Low 26/24 12 100 15 4.87
Tjandra [24] RCT High 60/53 12 71 47.2 16 1 10 3
Jarrett [45] PS Low 8/8 26.5 75 5.5 1.5
T.C. Rice and I.M. Paquette
Study Perm 100 %
O’Riordan [46] PS Low 14/10 – 100 16 5
Munoz-Duyos PS Low 47/29 34.7 86.2 48.3 7.1 <1
[47]
Dudding [48] PS Low 70/51 24 85.4 39.6 6 0.5
Roman [49] PS Low 18/18 3 77.8 14.9 4.9
Stelzner [50] PS Low 20/13 10 9.9 4.5
Meurette [25] PS Mod A: 15 43 A: 5.6
B:27/15 15 B:
SNS
Matzel [51] PS Low 12/12 118 77.8 44.4 17 10
Altomare [52] PS Low 94/60 74 74 18 15 5 4 1
Govaert [53] PS Mod 208/145 31 80
Vallet [54] PS Low 45/32 33 71.9 4.3 16.1 10
Oom [55] PS Low 46/37 32 81.1 5.4 9 0
Koch [56] PS Low 35/19 24 89.5 21 11 2
Otto [57] PS Low 14/14 6 16.3 9.6
Wexner [58] PS Mod 133/120 28 39a 30a 9.4 2.9
Michelsen [59] PS Mod 177/142 24 54 16 10
Wexner [60] PS Mod 133/120 28 83 41 9 2
Maeda [61] PS Mod 191/191 – 16 14.5
Faucheron [62] PS Mod 123/87 48.5 13 8.2
Lombardi [63] RS Low 16/11 38 100 27.3 19.91 6.82 5 1
38 Benign Anal Disease: Who Are the Right Candidates for Sacral Nerve Stimulation?
Uludag [64] PS Low 12/12 6 13.09 4.91 4.55 1.32

(continued)
427
428

Study Perm 100 %
Uludag [65] PS Low 50/50 85 84 8 0
Soria-Aledo [66] PS Low 23/23 – 3.1 0.5
Gallas [67] PS Mod 200/200 12 67.3 12 7
Hollingshead PS Low 113/86 21.5 83 15 9 9 1
[68]
Lim [69] PS Low 80/53 54 11.5 8
Mellgren [70] PS Mod 133/120 3 86 40 39.9a 29a 9.4 1.7
Maeda [71] PS Mod 245/176 13
Boyle [72] PS Low 50/37 17 81.8 39.4 15 8 14 2
Wong [73] RS Low 91/61 31 14.3 7.6
Devroede [74] PS Mod 133/120 39 85.9 33.3 39.9a 28a 9.4 1.9
Faucheron [75] PS Low 57/49 62.8 14.1 6.9
George [76] PS Low 30/23 44 100 56 19a 10a 10 0
Dueland- PS Mod 129/129 46 75 36 19 2.5
Jakobsen [77]
George [78] PS Low 25/23 114 20 8 22 0
Santoro [79] PS Low 28/28 6 68 16 3 14.7 0.4
Benson-Cooper PS Low 29/27 10.7 7.25 1
[80]
Damon [81] PS Mod 119/102 48 75.5
Hull [82] PS Mod 133/120 60 88.9 36.1 38a 28a
McNevin [83] PS Low 33/29 – 19 3
Moya [84] PS Low 50/50 55.5 15 4
Study Perm 100 %
Maeda [85] PS Mod 141/101 60 59.4 16 6 22.5 2
Ruiz Carmona PS Low 49/33 37 16.04 5.6
[86]
Roy [87] PS Low 89/60 36 55
Quezada [19] RS Low 60/55 12 15 4
Gorissen [88] PS Low 82/61 13 98.4 31a 27a
Altomare [89] PS Mod 407/272 84 85.1 16 7 7 0.25
Dueland- PS Mod 164/164 22 15 9 12 1
Jakobsen [90]
Johnson [91] PS Mod 152/145 12 94.4 18 14 3
PS prospective, RS retrospective, RCT randomized control trial, ABS artificial bowel sphincter, A Treated with artificial bowel sphincter, B treated with SNS,
mod moderate
a
Fecal incontinence score index used to assess fecal severity
429
Table 38.3 Outcomes following permanent implantation of sacral nerve stimulator in patients with anal sphincter defect
430
% Patient
improvement CCIS FI episodes
Study Temp PNE/ F/U 100 %
Study type Grade Perm implant (months) >50 % continent Baseline F/U Baseline F/U Defect
Conaghan [95] PS Low 5/3 3 100 67 6 0.7 EAS 90–120°
Dudding [22] PS Low 81/58 29 56.9 15 9.9 1 Not reported
Vitton [96] PS Low 5/3 14 100 15 6 7 2 IAS, EAS
<180°
Chan [97] PS Low A: 21 12 15.7 1 A:13.8 A: 5 A: EAS <120°
B: 32 B: 6.7 B:2 B: Intact
Melenhorst R Mod A: 20/16 29.2 69 26.6 12.5 Post repair
[98] B: 20/14 22.6 79 24.9 4.1 A: EAS <120°
Jarrett [45] PS Low 8/8 26.5 75 5.5 1.5 B: EAS
30–150°
Boyle [99] PS Low 15/13 77 12 9 15 3 IAS, EAS
<180°
Govaert [20] RS Low 245/173 34.7 77 Mean EAS 65°
Ratto [100] PS Mod 14a 60 85.7 16.4 7.7 IAS, EAS
<180°
10/10 33 100 18.3 9.7 IAS, EAS
<180°
Brouwer [101] PS Low 55/55 37 100 15 6 EAS, not
reported
Dudding [102] PS Low 9/8 4 77.8 33.3 6.1 1.7 IAS > 30°
Pascual [103] PS Low 50/48 17.02 93.8 18 4 Not reported
(continued)
% Patient
improvement CCIS FI episodes
Study Temp PNE/ F/U 100 %
Study type Grade Perm implant (months) >50 % continent Baseline F/U Baseline F/U Defect
Iachetta [104] PS Low A: 9/6 6 12 1 A: Disrupted
B: 11/8 6 14.1 3.5 B: Intact
Quezada [19] RS Low 60/55 12 15 4 Mean EAS
113°
Hong [105] R Mod 33 RS 31 17.5 11.5
11 ABS 31 45 18.7 8.6
15 SNS 31 67 17.6 9.1
PS prospective, R retrospective, RS, ABS artificial bowel sphincter, EAS external anal sphincter, IAS internal anal sphincter, mod moderate
a
Patients receiving sphincteroplasty as comparator group
431
ability to trial the therapy before permanent implantation, with a successful test
being highly predictive of successful permanent implantation. Further, the ability to
modify stimulation parameters following implantation allows physicians to reduce
adverse effects. SNS is an effective treatment in patients who are non-responsive to
medical or conservative management of fecal incontinence. Patients with severe FI
may undergo SNS as first line surgical management, though comparative studies to
other modalities are lacking. The use of SNS to treat FI in subgroups of patients
such as post-LAR for rectal cancer, or in patients with rectal prolapse, is inconclu-
sive and require additional studies in order to validate initial reports.
Recommendations
1. SNS may be considered a first line surgical option in patients with severe fecal
incontinence with or without a sphincter defect. (evidence quality moderate;
strong recommendation, 1B).
Once a patient has failed conservative measures for FI, it is up to the surgeon to
devise a treatment plan with potential to improve quality of life. Based upon the data
presented above, the ASCRS clinical practice guideline recommendation [110], and
vast personal experience, I would consider SNS to be a first line therapy for patients
with severe FI who have failed conservative measures. Importantly, studies have
failed to show any single factor, which is predictive of response to SNS other than
the patient’s response to a temporary test stimulation [19]. Aside from its very high
success rate, the other main advantage of this procedure is the opportunity for the
patient to use the therapy during a trial period. This period allows the patient and the
surgeon to be sure that they are choosing a regimen that will provide them a success-
ful outcome. For patients with severe FI, refractory to conservative measures and no
sphincter defect, I proceed with a test stimulation for SNS. I choose to use the
ambulatory based percutaneous nerve evaluation (PNE), which places a temporary
lead under local anesthesia, and can be accomplished in the office setting. Patients
with a successful PNE test would then proceed with a full-system implantation,
while the 10–15 % of patients with an inconclusive PNE would proceed with a sur-
gically placed test lead in the operating room, followed by a 2-week test
stimulation.
Currently, the main alternative treatment is sphincteroplasty. For a patient with a
sphincter defect, the decision is whether to correct the defect, or proceed with
SNS. SNS outcomes are highly successful even with a sphincter defect. In a younger
patient with an obstetric sphincter disruption in the prior year, I think that a sphinc-
ter repair is a reasonable first line treatment, reserving SNS for the longer-term
sphincter repair failures. The other indication for sphincter repair would be for a
near cloacal defect, which may be causing issues such as dyspareunia or body image
issues in addition to the FI. In older patients, or patients without a clear reason to
repair the sphincter, my preference is to proceed directly to a trial of SNS due to its
lower morbidity profile and excellent long-term results. However, direct compari-
sons of SNS to other modalities are currently lacking in the literature.
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Chapter 39
When Is an Anal Sphincter Repair Indicated?
Jan Rakinic and V. Prasad Poola
This chapter will discuss anal sphincter repair in adult fecal incontinence.
Populations not discussed include children, patients with anorectal malformations,
and patients who have undergone rectal resection or pelvic radiation.
Introduction
Any adult patient with a disturbance in fecal continence must have a directed his-
tory taken and appropriate physical examination conducted. Initial therapy usually
consists of dietary manipulation, bulking agents, and occasionally antidiarrheal
medications. The details of these important parts of the therapeutic strategy are well
described elsewhere. Etiology of fecal incontinence and presence of a demonstrable
sphincter defect are key points is to identify, as these will impact therapeutic deci-
sions as well as expected outcomes. Endoanal sonography is most commonly used
to identify anal sphincter defects.
If best conservative management is not sufficient for control of moderate to
severe fecal incontinence symptoms, further interventions may be discussed.
Noninvasive therapies include biofeedback or pelvic floor retraining. While these
therapies are very low risk, expected improvement is modest, variable, and seems
to deteriorate over the short to medium term [1–4]. Standardized pelvic floor func-
tion testing has a limited role in predicting success of biofeedback or pelvic floor
retraining [5]. In addition, literature suggests that these therapies are less effective
in patients with sphincter defects [6].
J. Rakinic, MD, FACS, FASCRS (*) • V.P. Poola, MD

Southern Illinois Department of Surgery, Division of General Surgery, Section of Colorectal
Surgery, Southern Illinois University School of Medicine, Springfield, IL, USA

DOI 10.1007/978-3-319-40223-9_39
440 J. Rakinic and V.P. Poola
Patients with moderate to severe fecal incontinence and a demonstrated sphincter

defect who have not had sufficient response to noninvasive management methods
may be candidates for other, more invasive forms of treatment. The use of bulking
agents injected into the submucosa overlying the sphincter, or targeted radiofre-
quency energy applications to the same area, appear to be low-risk interventions.
However, benefits and short-term outcomes are modest [7, 8]. Additionally, sur-
geons have concerns that these modalities alter the tissue planes in the anal canal
and so may be reluctant to employ them in patients who are or may become candi-
dates for anal sphincter repair.
Surgical Approaches to Fecal Incontinence
Surgical sphincter repair and sacral nerve stimulation are the most frequently per-
formed surgical procedures for adult fecal incontinence. In contemplating interven-
tion for fecal incontinence, treatment must be individualized for each patient.
Functional and quality of life (QOL) related outcomes as well as potential compli-
cations of treatment must be considered. This chapter will present an outline for
surgeon clinicians to use in determining whether a patient may be best served by an
anal sphincter repair, with discussion of patient population (those with a sphincter
defect), intervention (anal sphincter repair), comparator (sacral nerve stimulation),
and outcomes (improvement in fecal continence).
Patient population Intervention Comparator Outcomes evaluated

Pts with sphincter defect Sphincter repair SNS QOL, decreased incontinence
and FI episodes
Anal Sphincter Repair
For the patient with moderate to severe fecal incontinence and a demonstrated
sphincter defect in whom best conservative management has not produced suffi-
cient improvement, anal sphincter repair may be considered. A number of authors
have reported good to excellent short term results in 60–80 % of patients as evalu-
ated by follow-up questionnaires and QOL measures over 35 years of accumulated
data (See Table 39.1) [9–18]. However, the reports are generally small series with
retrospective data collection, and few have any comparison groups. It is important
to note that most surgeons exclude gaps over 120° from repair.
Important information regarding the longer term durability of anal sphincter
repair has been accumulated in the past 13 years [17–23]. The proportion of patients
reporting good to excellent outcomes in the long term, approximately 10 years after
sphincteroplasty, varies from 14 to 62 % (See Table 39.2.). This is significantly less
than that reported in the short term, suggesting that function after anal sphincter
39 When Is an Anal Sphincter Repair Indicated? 441
Table 39.1 Short term (up to 5 years) outcomes of sphincteroplasty

Author/year N % Excellent/good % Fair % Poor
Fleshman (1991) 55 72 22 6
Wexner (1991) 16 76 19 5
Engel (1994) 55 79 – 21
Oliveira (1996) 55 71 9 20
Felt-Bersma (1996) 18 72 – 28
Nikiteas (1996) 42 60 17 24
Sitzler (1996) 31 74 – 26
Ternent (1997) 16 44 31 25
Zorcolo (2005) 93 65 9 27
Barisic (2006) 65 74 17 9
Table 39.2 Long term (10 year) outcomes of sphincteroplasty

Author/year N % Excellent/good % Fair % Poor
Halverson (2002) 49 14 32 54
Bravo Gutierrez (2004) 130 22 19 57
Zorcolo (2005) 62 45 10 45
Barisic (2006) 65 48 13 39
Maslekar (2007) 64 62 24 15
Mevik (2009) 25 36 – –
Oom (2009) 120 38 23 40
repair tends to deteriorate over time. However, available literature is limited, and as
with the data on short term outcomes, these reports are mostly small series with
retrospective data collection and few have any comparison groups. In addition,
patient populations and methods of assessing outcomes are heterogeneous, which
makes it difficult to draw clear conclusions.
Predicting Outcome After Anal Sphincter Repair
With the realization that long term outcome after anal sphincter repair appears to
deteriorate over time, a number of authors have attempted to define what variables
might predict outcome. Of nine studies that evaluated the effect of age at surgery on
outcome [17, 20–22, 24–27], four [20, 22, 24, 27] reported poorer outcome in
patients over age 50. One [24] of three studies that looked at parity [17, 24, 28]
found that patients with a history of two or more vaginal births had a poorer out-
come after sphincteroplasty. Obstetric injury etiology was associated with better
outcome compared to other causes of incontinence in one study that commented on
this [22]; however, the number of patients with differing etiologies was small. An
observational study of estrogen therapy in postmenopausal women with fecal
incontinence found symptomatic improvement in 90 % after 6 months of hormone

replacement therapy, with increases in resting and squeeze pressures and an increase
in maximum tolerated rectal volume [29]. The patients with an identifiable sphinc-
ter defect had no difference in outcome. However, the potential application of this
to the population of patients who are candidates for sphincteroplasty is not clear. All
authors felt that older patients should still be considered for anal sphincter repair,
though the risk of a possible inferior outcome should be discussed.
Several studies assessed outcome related to initial physiologic and anatomic
variables, including resting and squeeze pressures, anal canal length, rectal compli-
ance, pudendal neuropathy, and presence of internal anal sphincter defect [17, 19–
21, 25, 28]. None found resting or squeeze pressures, anal canal length, rectal
compliance, or presence of internal anal sphincter defect predictive of outcome.
Only one [30] of the five studies that evaluated pudendal neuropathy [17, 21, 25, 28,
30] reported that this was predictive of a poorer outcome. However, all authors felt
that anal sphincter repair should be offered to patients with pudendal neuropathy,
with a discussion of possible poorer outcome.
There is little solid information regarding predictive value of technical aspects of
anal sphincter repair. Most surgeons perform overlapping repair. One study [22]
evaluated outcome after overlapping repair vs end-to-end repair of the sphincter. No
predictive effect was identified. Maslekar et al. [21] felt their good results (86 %
good outcome at 7 years) were related to their technique of dissecting each sphinc-
ter separately, though they did not include any comparison group. Three studies
compared outcomes using fecal diversion with repair performed without diversion
[28, 30, 31]. No predictive effect regarding outcome was seen; fecal diversion is not
routinely used in anal sphincter repair in the United States.
Relationship of Short and Long Term Outcomes
There does appear to be a predictive relationship between short and long term out-
comes. Vaizey et al. [31] found that patients who had good outcomes in short term
tended to have more durable outcomes, compared to those who did poorly initially.
Malouf et al. [28] reported that the Parks score at 15 months after anal sphincter
repair was predictive of long term success. Bravo Gutierrez et al. [20] found that a
poor outcome at 3 years after surgery was a strong predictor of poor long term
outcome.
Repeat Sphincteroplasty Outcomes
Identification of a recurrent or persistent anal sphincter defect after sphincteroplasty

is important, as these patients may be offered a repeat anal sphincter repair. Giordano
et al. [32] reported on 36 patients who underwent a repeat sphincter repair after
demonstration of a persistent sphincter defect. The repeat repair group reported

good (50 %) and adequate (11 %) function at a median of 20 months, compared with
the patients undergoing first-time repair (58 % good, 17 % adequate). Vaizey et al.
[31] reported on 23 patients with a repeat anal sphincter repair. Twenty-one were
evaluable at 20 months after repeat repair. One was fully continent, 12 reported
50 % or more symptom improvement over preoperative function, and four were
unchanged. Hong et al. [33] reported retrospectively on 59 patients with failed
sphincteroplasty. In this cohort, 33 underwent repeat sphincteroplasty, 11 had artifi-
cial bowel sphincter (ABS) implant, and 15 underwent sacral nerve stimulation
(SNS). Observed improvements in continence were similar; however, the rate of
complications and reoperations was significantly lower in the repeat sphinctero-
plasty group, leading the authors to suggest that repeat sphincteroplasty should be
considered the first choice in the management of failed anal sphincter repair.
However, function after repeat sphincteroplasty may deteriorate over time more
markedly than after a first repair [34].
Reporting and Comparing Outcomes
Comparing outcomes of anal sphincter repair is made more difficult by the hetero-
geneity of the measures utilized in reporting. Many methods of assessment are com-
mon, and while those most widely used contain elements of incontinence frequency
and severity, not all include patient-defined quality of life measures. However, the
quality of life determination may be the most important consideration for the patient
who must weigh the effect on daily life activities against the possible risks of treat-
ment. Evaluation of function in 62 patients a mean of 70 months after anal sphincter
repair showed that while 70 % had objective clinical improvement, only 55 % con-
sidered their bowel control improved and only 45 % were satisfied with the outcome
[17]. The authors note that urgency was the most important symptom related to
patient satisfaction after anal sphincter repair: 24 of 26 patients in whom urgency
had improved reported that they were happy with the outcome.
Sacral Nerve Stimulation
Sacral nerve stimulation (SNS) has been suggested as the first line of treatment in
adult fecal incontinence regardless of etiology, in part related to the reported dete-
rioration of function after sphincteroplasty. However, the data on SNS for adult
fecal incontinence is still maturing, and concerns exist regarding the rates of com-
plications and reoperation. In a study of 61 patients who underwent temporary
electrode stimulation for refractory fecal incontinence, only 35 (57 %) attained the
50 % or greater improvement in incontinent episodes needed to proceed to perma-
nent implant [35]. Of the 33 patients in this study who eventually underwent
permanent implant, 31 % failed to reach the 50 % reduction threshold defined as
success. Younger age was related to success with temporary stimulation. A neuro-
logic disorder as etiology for incontinence was related to success with permanent
implant.
SNS was compared to optimal medical therapy in a randomized study including
60 patients with severe fecal incontinence in each arm [36]. Ninety percent (54
patients) in the SNS group reached the threshold of 50 % improvement of inconti-
nent episodes; 53 were implanted with 47 % reporting perfect continence. There
were no septic complications at a mean follow up of 12 months. There was no sig-
nificant improvement reported in the medical therapy group.
A short version Cochrane review of SNS for fecal incontinence published in
2008 included two small crossover studies [37]. The authors concluded that while
results were very limited, it suggested that SNS could improve fecal continence in
selected patients. However, it was also noted that temporary percutaneous stimula-
tion did not always successfully identify those for whom a permanent implant
would be beneficial, exposing some group of patients to having an ineffective inva-
sive procedure and foreign body implant.
Several longer term reports on SNS results from a multi-institutional study group
illuminate the risk of adverse events and significant complications requiring reop-
eration. The most common device or therapy related adverse events were implant
site pain (28 %), paresthesia (15 %), change in stimulation sensation (12 %), and
infection (10 %) [38]. Of particular note, infection carries a 50 % risk of permanent
system explantation [39]. Additionally, 36 % of patients followed for at least 5 years
required a device revision, replacement, or explant [40].
The most recent Cochrane review of SNS for fecal incontinence included four
crossover trials and two parallel group trials. The authors concluded that the limited
evidence from the included trials suggested SNS could improve continence in a
proportion of patients with fecal incontinence. However, authors also noted the fre-
quency of reported adverse events ranged from 15 to 21 % [41].
Discussion
Direct comparison of data regarding anal sphincter repair and SNS is difficult. Most
of the studies of sphincteroplasty are small, single institution, often retrospective,
and the populations included and measures used to quantify outcome are heteroge-
neous. This is underscored by the conclusions of the most recent Cochrane review
of surgery for fecal incontinence in adults, which comments on the lack of high
quality randomized controlled trials for fecal incontinence surgery [42]. While short
to medium term outcomes for anal sphincter repair are good, function deteriorates
over time. However, long term outcomes still seem at least as good as the definition
of SNS “success”, and patient quality of life and reported satisfaction remain high.
Many of the published studies of SNS in fecal incontinence are small crossover
or parallel trials, with a lack of comparison to anal sphincter repair. The included
populations are heterogeneous, and the outcome measures often differ from those
used in the evaluation of anal sphincter repair outcomes. The frequency with which
patients achieve the 50 % reduction threshold to proceed to permanent electrode
implant varies, with predictive factors not clearly identified, and success with tem-
porary implant does not guarantee success with permanent implant. Finally, the risk
of complications leading to reoperation appears to be 15–20 %.
Conclusions
A. In patients with a demonstrated sphincter defect, if best conservative manage-

ment is not sufficient for control of moderate to severe fecal incontinence symp-
toms, sphincteroplasty should be strongly considered. Discussion of possible
worse short and long term outcomes should be undertaken with patients over
age 50 (or 60), and possibly also for those with pudendal neuropathy. Grade of
strength of recommendation is STRONG.
B. Outcomes of sphincteroplasty are at least as good as SNS outcomes with fewer
complications requiring reoperation. Grade of strength of recommendation is
STRONG.
C. Those who fail sphincteroplasty can be considered for repeat sphincteroplasty
with the expectation of reasonable results. Grade of recommendation is
CONDITIONAL.
D. Sphincteroplasty is unlikely to produce improvement for flatus incontinence.
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Group. Long-term efficacy and safety of sacral nerve stimulation for fecal incontinence. Dis
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Shobeiri AS, Margolin D, England M, Kaufman H, Snape WJ, Mutlu E, Chua H, Pettit P,
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40. Hull T, Giese C, Wexner SD, Mellgren A, Devroede G, Madoff RD, Stromberg K, Coller JA,
SNS Study Group. Long-term durability of sacral nerve stimulation therapy for chronic fecal
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Part VII
Quality Improvement
Chapter 40
Checklists in Surgery
Eric A. Sparks and Harry T. Papaconstantinou
Introduction
Nearly two decades have passed since the publication of To Err is Human [1], and
there has been considerable subsequent interest in research and interventions to
describe and prevent health care associated injuries and improve patient outcomes.
The WHO launched its “Safe Surgery Saves Lives” campaign in 2008 as a means to
prevent unnecessary mortality and improve outcomes for surgical patients [2]. This
program resulted in the WHO Surgical Safety Checklist (SSC) [3], which has been
widely considered successful in reducing the rates of perioperative complications
and mortality. Use of the WHO and similar checklists has now become widespread.
However, not all investigations have confirmed their utility and checklists have cer-
tainly met some resistance wherever implemented. The purpose of this chapter is to
(1) summarize the current body of literature describing the use of surgical checklists
and (2) offer expert opinion as to what role checklists may serve for the practicing
colorectal surgeon.
E.A. Sparks, MD
Department of Surgery, Baylor Scott & White Healthcare, Scott & White Memorial Hospital,
Temple, TX, USA
H.T. Papaconstantinou, MD (*)
Department of Surgery, Baylor Scott & White Healthcare, Texas A&M University College of
Medicine, Baylor Scott & White Memorial Hospital,
2401 South 31st Street, Temple, TX 76508, USA

DOI 10.1007/978-3-319-40223-9_40
452 E.A. Sparks and H.T. Papaconstantinou
Methods and Search Strategy
Prior to literature search, a PICO table and four specific questions were formulated
as shown below. The literature review was performed under guidelines suggested by
the GRADE approach. A systematic literature search was undertaken using
MEDLINE via PUBMED and the Cochrane Library. Publications in English dated
from January 2000 to May 2015 were included. MeSH search terms and their com-
bination included “checklist”, “safety”, “randomized control trial”, “mortality”,
“morbidity”, “surgery”, and “colorectal.” Specific database functions such were
used to maximize the search. Reference lists of retrieved articles were further
screened for additional publications. All identified studies involving evaluation of
implementation of, attitudes towards, or outcomes following use of surgical safety
checklists were reviewed in depth. The PICO table defined below was used to guide
literature search and interpretation of findings.
Question 1: Do surgical checklists reduce perioperative morbidity & mortality?
Question 2: Do surgical checklists have other costs or benefits?
Question 3: Are there costs or barriers to use of surgical checklists?
Question 4: Do surgical checklists offer specific benefits to colorectal surgery?

All adult patients Use of checklists for Historical management Mortality
undergoing colon quality improvement systems without Morbidity
resection checklists Errors (wrong site,
procedure, etc)
Cost
Efficiency
Attitudes and barriers
Results
Question 1: Do surgical checklists reduce perioperative morbidity & mortality?

The WHO surgical safety checklist was implemented in 2008. In 2009, Haynes’
et al. published a landmark study which began a growing mountain of evidence to
support the use of these checklists [2]. This study prospectively collected data on
approximately 4000 patients from a diverse group of eight hospitals worldwide
before and after implementation of the SSC. The authors demonstrated reductions
in death (1.5–0.8 %, p = 0.003) and inpatient complications (11.0–7.0 %, p < 0.001)
with checklist use. Many of the studies that followed have been prospective or ret-
rospective observational studies to evaluate the results of SCC implementation in
more specific clinical settings (Table 40.1).
While no prospective randomized control studies have been (or likely will be)
done, Gillespie et al. performed a robust meta-analysis including seven prospective
Table 40.1 Question 1: Do surgical checklists reduce perioperative mortality & mortality?
n/type of Quality of
Author/year Study design procedure Outcome measures Conclusions evidence
Gillespie et al. (2014) [4] Meta-analysis 37,339/general Major complications, Use of a SSC reduces all complications, High
mortality, minor wound infections, blood loss. No
complications significant reductions in mortality,
pneumonia, or unplanned reoperation.
Kwok et al. (2013) [5] Prospective cohort 2145/general Process adherence, SSC implementation resulted in a Moderate
40 Checklists in Surgery
major 30 days decrease in overall, infectious, and

complications, noninfectious complications in a
intraoperative resource-limited setting
hypoxemia
Bliss et al. (2012) [6] Prospective cohort 319/general Checklist completion, Implementation of SSC results in Moderate
30 days morbidity, reduction in adverse events from
adverse events expected (NSQIP data) rates.
Weiser et al. (2010) [7] Prospective cohort 1750/general 30 day morbidities and SSC implementation reduces overall Moderate
mortality complication rate and mortality
Haynes et al. (2009) [2] Prospective cohort 7688/general 30 day morbidities and SSC implementation significantly Moderate
mortality reduced inpatient morbidity and
mortality in a group of 8 international
hospitals
Haugen et al. (2015) [8] Prospective cohort 2212/general 30 day morbidities and SSC implementation significantly Moderate
mortality reduced inpatient morbidity and
mortality using a model to adjust for
possible confounders
(continued)
453
454
Tillman et al. (2013) [9] Prospective cohort 824/general Compliance with SCIP Implementation of SSC improves Moderate
Measures compliance with SSI reduction
strategies and may reduce SSI rates in
colorectal procedures
Askarian et al. (2011) [10] Prospective cohort 294/general Any complication SSC implementation decreases Moderate
perioperative complications in a small
Iranian hospital
Sewell et al. (2011) [3] Prospective cohort 965/ Any complication, SSC was not associated with a Moderate
orthopedics mortality significant reduction in early
complications and mortality in patients
undergoing orthopaedic surgery
Yuan et al. (2012) [11] Prospective cohort 481/general Any complication, SSC implementation is associated with Moderate
mortality variable improvements in surgical
process compliance and surgical
outcomes
McCarroll et al. (2015) [12] Retrospective 89/ 30 day readmission Decreased readmissions (13.5 % vs Very low
cohort laparoscopic/ Length of stay 4.1 %), no difference in LOS or OR
robotic Operative time time
Garcia-Paris et al. (2015) [13] Retrospective 134/podiatric LOS, SSI, antibiotic Use of a SSC improves correct use of Very low
cohort use in podiatric antibiotics, reduces SSI’s, and reduces
surgery LOS
Reames et al. (2015) [14] Retrospective 64,891/general SSI, wound Implementation of a checklist tool did Low
cohort complications, all not affect adverse outcomes, potentially
complications, 30 day due to failed implementation
mortality
E.A. Sparks and H.T. Papaconstantinou
Loor et al. (2012) [15] Retrospective 5812/cardiac Reoperation for Implementation of SSC significantly Moderate
cohort bleeding reduces operations for rebleeding
van Klei et al. (2012) [16] Retrospective 25,513/general mortality SSC implementation reduces Moderate
cohort in-hospital mortality, and effect is
related to checklist compliance
Kim et al. (2015) [17] Retrospective 637/general Overall complications, SSC implementation at a resource- Low
cohort hypoxemia, adherence limited hospital improves
to safety processes communication, adherence to safety
processes, and complications with no

reduction in mortality. Improvements
were greater after two years than after 6
months
Dell’Atti et al. (2013) [18] Retrospective 324/urologic All complications, SSC implementation led to a reduction Very low
cohort intrahospital mortality in overall complication rate and
mortality
Haynes et al. (2015) [19] Opinion n/a/general n/a Checklists are effective if barriers to Very low
implementation are overcome
Garg et al. (2013) [20] Opinion n/a/general n/a Intraoperative crisis checklist is Very low
perceived to fascilitate response to
massive hemorrhage
Ladak et al. (2014) [21] Opinion n/a/general n/a Perceived need for checklists to Very low
improve preoperative workup and
planning
Panesar et al. (2009) [22] Opinion n/a/general n/a Adoption of SSC is effective and Very low
should be adopted throughout the UK
455
456
Table 40.2 Question 2: Do surgical checklists offer other benefits?

Quality of
Author/year Study design n/type of procedure Outcome measures Conclusions evidence
Tillman et al. (2013) [9] Prospective cohort 824/general procedures Compliance with SCIP Implementation of SSC Moderate
measures improves compliance with
SSI reduction strategies and
may reduce SSI rates in
colorectal procedures
Kim et al. (2015) [17] Prospective cohort 637/general procedures Overall complications, SSC implementation at a Low
hypoxemia, adherence to resource-limited hospital
safety processes improves communication,
adherence to safety processes,
and complications with no
reduction in mortality.
Improvements were greater
after 2 years than after 6
months
Semel et al. (2010) [24] Prospective cohort n/a Cost of SSC Theoretical hospital cost of Low
implementation SSC implementation is
recovered if five major
complications are prevented
McCarroll et al. (2015) [12] Meta-analysis 89/robotic/laparoscopic 30 day readmission Decreased readmissions Very low
Length of stay Operative (13.5 % vs 4.1 %), no
time difference in LOS or OR time
40 Checklists in Surgery 457
cohort studies of 37,339 patients, concluding that SSC’s significantly reduce post-
operative complications [4]. Van Klei et al. reported a significant reduction in mor-
tality when checklists were fully completed [16]. Lastly, in an attempt to remove
confounders, Haugen et al. described an elaborate protocol for SSC implementa-
tion, finding significant reductions in morbidity and length of stay [8]. Collectively,
these studies indicate that implementation of surgical safety checklists likely
improves post-operative outcomes including mortality rates.
However, the benefits above have not been demonstrated in all studies. Several
investigators have suggested necessary conditions under which morbidity and mor-
tality can be reduced. Surgical safety checklists are designed primarily to prevent
deaths from perioperative errors, which are rare events. Therefore, the intervention
of introducing checklists should be with the expectation of population-level bene-
fits, and that a large cohort size will be required to demonstrate effectiveness.
Second, some authors have demonstrated effectiveness by examining higher-risk
populations (e.g., complicated procedures, unplanned procedures, colorectal opera-
tions, and procedures at limited-resource hospitals [3, 5, 9, 10, 12, 15, 17]) or by
studying more common or impactful outcomes (e.g., re-operation, infection rates,
length of stay [5, 9, 10, 12–18]). Safety culture and attitudes may also play a role in
checklists and patient outcome. Haynes et al. updated their original work with a
survey of attitudes toward the SSC and found essentially a dose-response curve in
which changes in outcomes were directly associated with team perceptions of suc-
cessful checklist implementation [23]. Fidelity of checklist use and completion has
been shown to have a direct correlation with reduction in morbidity [16]. Therefore,
the evidence clearly indicates that checklists reduce morbidity and mortality effec-
tively, as long as they are being used as intended.
Question 2: Do surgical checklists have other costs or benefits?
In addition to preventing morbidity and mortality, other indirect measures of
quality have been shown to improve with SSC use (Table 40.2). Standardized peri-
operative processes of care have been shown to improve outcomes. Performance
measures including antibiotic timing, intraoperative hypothermia management, and
hypoxemia have all been shown to improve with checklist implementation [5, 9, 17].
As a further indication of SSC success, implementation has improved perceptions of
perioperative patient safety and communication among operative teams [17, 23].
The vocal critics who oppose the conception of surgical safety checklists have
expressed concerns and negative perceptions in the form of anecdotal evidence,
surveys, and opinion papers. Some believe that use of a checklist in the operating
room is ineffective, unnecessary, and reduces operating room efficiency [25]. Even
though there are studies that have failed to demonstrate effectiveness, the concerns
brought forth by these critics have not been objectively validated and in some cases
directly refuted. Two cohort studies have shown no difference in operative times
before and after SSC implementation [12, 26]. This seems intuitive since the
checklist itself takes only a few minutes. Results from our institution indicate that
SSC implementation did not affect first-start in room on time performance or same
day cancellations [9]. Furthermore, the cost of SSC has been investigated. Semel
et al. calculated a cost-savings of $103,829 per year assuming prevention of five

major complications during 4000 non-cardiac operations [24]. Therefore, checklists
have the added benefit of improving performance of standardized care, perception
of patient safety, and communication among team members without adversely
affecting operating room efficiency or cost.
Question 3: Are there costs or barriers to use of surgical checklists?
From the inception of checklist utilization, barriers to their use have been present
(Table 40.3). The most obvious of these is non-use or failure to complete the check-
list [6, 27]. However, “checklist mentality” leads to misuse even after a high com-
pletion rate is achieved. Several investigators have audited checklists and team
behavior, universally finding poor checklist fidelity [16, 37, 39]. This may be a
direct result of checkbox fatigue where the process turns from one of patient safety
and benefit to one of mundane automatic (or mindless) checking of a box.
Many specific barriers have been identified which inhibit a culture of SSC com-
pliance. Ineffective education at the time of implementation may hinder adoption,
while educational interventions are capable of improving compliance [38].
Checklist-specific factors including non-redundancy, inclusion of only critical and
actionable items, and ease of use are described most effectively in Atul Gawande’s
“Checklist for Checklists” [43]. In the end, investigators have almost universally
concluded that leadership buy-in remains the most significant barrier to checklist
use [34, 40, 41].
Fundamentally, one may reasonably assume that outcome improvements cannot
be seen without proper use of the checklist. Frequent audits of checklist use with
cyclical user-feedback and re-education are proposed to help overcome these barri-
ers. Although the barriers to ideal checklist use are numerous, they are well-defined
and can be overcome by a carefully designed and implemented checklist process.
Question 4: Do surgical checklists offer specific benefits to colorectal surgery?
Limited data exist to describe the effects of SSC use specific to the field of
colorectal surgery (Table 40.4). Tillman et al. performed a prospective cohort study
demonstrating improvement in compliance with SCIP SSI-reduction strategies in
general surgery patients. In the subpopulation of 183 patients undergoing colec-
tomy, SCIP compliance increased and SSI’s decreased (24.1 % vs 11.5 %, p = 0.03)
after implementation of a surgical safety checklist [9]. O’Mahoney et al. performed
a retrospective descriptive study using a checklist to evaluate operative steps of
laparoscopic colon resections. They demonstrated feasibility/reproducibility of
this tool to identify and document completion of key surgical steps. The authors
propose that this standardization offers easier implementation of quality improve-
ment projects in colorectal surgery [44]. As such, the benefits of checklist use are
likely applicable beyond those specifically attributed to the well-studied WHO
Surgical Safety Checklist. The place of this tool in the field of colorectal surgery is
discussed in further detail in the “personal view of the data” section of this review.
Since checklists are excellent tools to ensure performance of complex tasks; it is
intuitive that their use in multidisciplinary disease management plans can be power-
ful. Rectal cancer is a wonderful example as multiple diagnostic and treatment steps
Table 40.3 Question 3: Are there costs or barriers to use of surgical checklists?
Oak et al. (2015) Prospective 3000/ Pediatric surgery: major 0 major errors, 0.3 % near misses, high rate of incompletion Low
[27] case series general errors, “near misses”, or errors
checklist compliance
Biskup et al. Retrospective 2166/ 30 days complications Checklist does not reduce complication rates, likely due to Low
(2015) [28] cohort plastics checklist item applicability
Haynes et al. Opinion n/a n/a Checklists are effective if barriers to implementation are Very Low
(2015) [19] overcome
Mahmood et al. Retrospective 51/ Checklist compliance Checklist completion overestimates actual practice Low
(2015) [29] case series general compliance.
Johnston et al. Prospective 63/ Checklist compliance Audit tool was successful, compliance with checklist Low
(2004) [30] case series general (audit) standards varied from 0 to 100 %
Shapiro et al. Opinion n/a n/a Checklists are needed for office-based surgeries Very Low
(2013) [31]
Abdel-Rehim Retrospective 90/ Checklist compliance Use of the WHO SSC improves perioperative use of surgical Very Low
et al. (2011) [32] cohort general “Time out”
Mahaffey et al. Opinion n/a n/a Proper use of a checklist is dificult to maintain; SSC’s are Very Low
(2010) [25] distracting and ineffective.
Panesar et al. Opinion n/a n/a Adoption of SSC is effective and should be adopted Very Low
(2009) [22] throughout the UK
de Vries et al. Opinion n/a n/a Checklists should be empoyed in surgical care beyond the Very Low
(2008) [33] operative phase
Kim et al. (2015) Retrospective 637/ Overall complications, SSC implementation at a resource-limited hospital improves Low
[17] cohort general hypoxemia, adherence to communication, adherence to safety processes, and
safety processes complications with no reduction in mortality. Improvements
were greater after 2 years than after 6 months
(continued)
459
460
Russ et al. (2015) Prospective 874/ Compliance with checklist SSC is frequently incompletely or inappropriately performed. Low
[34] case series general steps (audit) Senior leadership performed best and should champion SSC
use
Russ et al. (2015) Survey 119/ Attitudes towards SSC use checklist characteristics, methods of implementation, senior Low
[35] general staff support, and post-implementation monitoring are
important factors to SSC compliance
Putnam et al. Prospective 873/ Checklist compliance Interventions to improve checklist compliance are effective Low
(2014) [36] cohort general
Papaconstantinou Retrospective 35,570/ OR efficiency Implementation of SSC does not negatively impact OR Moderate
et al. (2013) [26] cohort general efficiency
Sparks et al. Retrospective 671/ Checklist compliance Accuracy of checklist completion remains poor after high Low
(2013) [37] cohort general participation and completion rates are achieved
Sheena et al. Prospective 72/ENT checklist compliance Educational intervention improves checklist compliance Moderate
(2012) [38] cohort
Levy et al. Prospective 142/ Checklist fidelity Despite 100 % documentation, process compliance is poorer Moderate
(2012) [39] cohort general (60–97 %).
Conley et al. Survey n/a Preceptions of barriers to SSC success is related to effectiveness of implementation Low
(2011) [40] SSC implementation which hinges on buy-in of leadership
Vats et al. (2010) Opinion n/a n/a SSC use is frequently poor. Barriers to effective SSC Low
[41] implementation include insufficient education, lack of
leadership buy-in, perceived inefficiency, and duplicated
steps.
Terry et al. Opinion n/a n/a Acceptance and implementation of SSC’s is spreading, yet Very Low
(2009) [42] physician resistance remains frequent
Haynes et al. Survey 281/ Attitudes towards SSC use Reduction in complications is directly associated with Low
(2011) [23] general attidues towards SSC use
Table 40.4 Question 4: Do surgical checklists offer specific benefits to colorectal surgery?
n/type of Outcome Quality of
Author/year Study design procedure measures Conclusions evidence
Tillman Prospective 824/general Compliance Implementation of Moderate
et al. (2013) cohort procedures with SCIP SSC improves
[9] Measures compliance with
SSI reduction
strategies and may
reduce SSI rates in
colorectal
procedures
O’Mahoney Retrospective 16/colorectal Compliance Checklists help Low
et al. (2015) cohort procedures with definite and
[44] operative document key steps
steps of laparoscopic
surgery
exist, treating team members are interdependent on each other, and multidisci-
plinary input and communication is crucial to optimal outcomes.
Recommendations from the Data
1. Implementation of surgical safety checklists likely improves post-operative out-

comes including mortality rates (Level 2a). Outcomes at highest risk are the
most likely to see these benefits (Level 2b). Success hinges on achieving high
rates of participation and proper checklist use (Level 2b).
2. Surgical safety checklists do not increase operative times and are not hindrances
to the operative team (Level 2b). These tools likely improve efficiency, multidis-
ciplinary communication, and compliance with universal quality improvement
initiatives in addition to reducing surgical errors (Level 2b).
3. There are a host of physical and cultural barriers to checklist implementation
(Level 2b). These barriers may be overcome by cyclical auditing of checklist use,
feedback, and re-education (Level 2b).
4. Surgical safety checklists may offer specific benefits when applied to colorectal
surgery (Level 2b). Checklists will likely play a broader role as an invaluable
tool for quality improvement in surgery and ensuring proper delivery of care by
complex multidisciplinary teams (Level 5).
Surgical care is becoming more and more complicated. As humans, our memory is
fallible especially in stressful and complex situations. This is clearly true in surgical
patients, and recent efforts to optimize outcomes have become more focused on
standardization of care. Surgical checklists have proven to be an invaluable tool for

standardizing the processes of care and improving performance on quality mea-
sures. They accomplish this directly, by ensuring that specific tasks are accom-
plished, and indirectly, by improving communication among multidisciplinary
teams. Through these effects, checklists clearly have the ability to reduce morbidity
and mortality and improve outcomes.
The checklist, however, does not accomplish these goals by itself; it is not a
magic carpet. Human factors affect adoption and effective use, and incorporate the
patient safety culture, ownership of process, and team member buy-in. In fact,
despite the seemingly simple nature of a checklist, potential pitfalls are numerous.
We have found both anecdotally and based on literature review that the following
steps are crucial for successful checklist implementation and use.
1. Multidisciplinary planned approach to checklist design and content. You must
get buy-in from all stake holders and participants. This will enhance enthusiasm,
performance and successful adoption of the checklist.
2. Development of a checklist which meets the recommendations of “Checklist for
Checklists” Gawande’s “Checklist for Checklists”. The first and perhaps most
important step here is determining that each checklist item is “a critical safety
step and in great danger of being missed”, “not adequately checked by other
mechanisms”, “actionable, with a specific response required”, and “can be
affected by the use of a checklist”. Our opinion is that many checklists which
suffer from checkbox fatigue and poor fidelity, if examined, will fail to meet
many of these requirements.
3. Leadership must “walk the walk and talk the talk”. Physician champions and
leaders must embrace and perform the checklist in the proper fashion. Team
members look to their leader to see how they respond and perform. A highly vis-
ible leader that is perceived as cutting corners or not embracing the checklist and
process severely erodes the acceptance, adoption and performance by the
remainder of the team.
4. Extensive team education and simulation prior to use. Successful adoption of
checklists requires explaining why something is being done, and must be fol-
lowed by showing how it is performed. We have found that simulation is the easi-
est way to show the how and allows for direct and immediate feedback on
performance.
5. Carefully planned and staged implementation strategy. After thorough education
and simulation, the implementation phase is another opportunity to avoid check-
list failure. At our institution, checklists were rolled out in select operating rooms
to gather early feedback prior to making system-wide changes. This controlled
approach appeared to ease cultural adoption of the new procedures.
6. Frequent auditing of checklist participation and fidelity. You get what you
inspect, not what you expect. Regular auditing is vital to sustainability of prac-
tice. Auditing should be active, not passive, with direct feedback to the team on
performance and how to improve. If team members are cutting corners or not
performing the checklist as intended, and this is not pointed out and addressed,
it will be perceived as the way it should be done. This concept of “normalization

of deviance” is likely why many institutions, including our own, have seen per-
formance erode over time after implementation. Feedback of compliance and
outcomes should be shared with the team and augmented with continuing educa-
tion. Celebration of successes is important to improve morale, justify continued
use, and create a positive culture of safety.
7. Iterations of steps 1–6 to continuously improve the checklist and enhance the
involved processes. Checklists need an appropriate balance of flexibility and
rigidity. For flexibility, we consider this adaptation to an ever changing environ-
ment, needs, and evidence of benefit. We believe that checklist change must be a
structured process and requires a formal request for change with appropriate data
to support the change. This is evaluated by physician champions and team lead-
ers with rapid feedback regarding decision with supporting information. The
rigidity is in maintaining the integrity and focus of the checklist. Wide deviations
can erode into the spirit and intent of the checklist eliminating support for “why”
it is being done.
Of all these steps, we have found that investment, support, and exemplary par-
ticipation and performance of physician champions from all teams appear to be the
most critical and most frequently missed step. This chapter focuses significantly on
the surgical safety checklist; however, we believe that checklists play a broader role
for colon and rectal surgeons. Checklists allow standardization of care and data col-
lection for research and quality improvement. Opportunities are present for design
of new checklist tools which help bridge the gaps between scientifically supported
“best practice” and what is actually provided in routine care.
One potential application is the Rectal Cancer Centers of Excellence initiative.
Checklists are perfect for this situation as they provide a strict protocol for guidance
and objective performance data to tie to outcomes. Our goal in this chapter has been
to provide a better understanding of the successes and pitfalls of checklists so that
colon and rectal surgeons become champions of theses quality improvement initia-
tives and consider them a new tool which helps reduce variability in care and pro-
vides an opportunity to improve outcomes.
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surgical safety checklist combined with pulse oximetry in a resource-limited setting: two-year
update from Moldova. JAMA Surg. 2015;150:473–9.
18. Dell’Atti L. Introduction of a checklist to reduce adverse events in urologic surgery: our expe-
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19. Haynes AB, Berry WR, Gawande AA. What do we know about the safe surgery checklist
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Chapter 41
Quality Improvement: Where Are
We with Bowel Preps for Patients Undergoing
Colon Resection?
Anthony J. Senagore
Introduction
Colorectal surgeons have strived for reductions in postoperative septic complica-

tion rates and especially the incidence of anastomotic dehiscence since the incep-
tion of bowel surgery [1]. Bowel antisepsis as a means to this end was first advocated
by Poth in the 1940s [2]. Thirty years later, Barker and Everett advocated for MBP
because of their belief that gross fecal loading of the bowel was associated with an
increased incidence of wound infection [3, 4]. As a result of this work, MBP became
almost uniformly accepted as a dogma going forward [5]. The classic article which
codified the role of mechanical bowel prep with oral antibiotics was the three armed
study performed by Condon et al. They compared oral mechanical bowel prep with
either intravenous cephalothin alone; oral neomycin and erythromycin alone; or
both intravenous and oral regimens [6]. Although the intravenous antibiotic chosen
was limited in bacterial coverage, the combined strategy was superior nonetheless.
Coppa et al. studied 350 patients randomized to intravenous cefoxitin (broader
coverage gram negative and anaerobes) with or without oral neomycin and erythro-
mycin in conjunction with a mechanical bowel prep [7]. The dual regimen was
superior for superficial wound infection (11 % versus 5 %). Finally, Schoetz et al.
performed the reverse study, randomizing 190 patients to receive neomycin and
erythromycin orally with and without intravenous cefoxitin. Wound infection and
leak rates were higher in the group receiving only oral antibiotics [8]. These data led
to the era of combined mechanical bowel prep, with both oral and intravenous pro-
phylactic antibiotics. Over the last decade, the necessity for mechanical bowel prep
A.J. Senagore, MD, MBA

Department of Surgery, UTMB- Galveston, Galveston, TX, USA

DOI 10.1007/978-3-319-40223-9_41
468 A.J. Senagore
has been questioned along with contemporaneous data reinvestigating the relative
role of mechanical prep with or without oral antibiotics.
Patients undergoing colon Bowel No bowel SSI, leak rate, dehiscence,

resection prep prep complications
Search Strategy
Search DATA SOURCES: Embase, PubMed, and the Cochrane Library were
searched using the terms oral, antibiotics/antimicrobial, colorectal/rectal/colon/rec-
tum, and surgery/operation. Time frame 2014–2016.
MAIN OUTCOME MEASURES: Anastomotic leakage, all-cause mortality,
wound infection, peritonitis/intra-abdominal abscess, reoperation, surgical site
infection, quality of life, length of stay, and adverse events were measured.
Patients Intervention Comparator Outcomes

Patients No bowel Mechanical bowel Anastomotic leak, mortality, wound
undergoing prep prep with or without infection, surgical site infection,
colectomy oral antibiotics ileus, reoperation, quality of life,
length of stay, and adverse events.
Results
Contant et al. studied 1431 patients undergoing open colorectal resection random-
ized to intravenous antibiotics (aerobic and anaerobic coverage) with or without
MBP [9]. The data demonstrated a significant increase in the rate of intra-abdominal
abscess without MBP (2.5 % vs 0.3 %), however there was no significant difference
in superficial wound infection (no-MBP-14 % vs MBP- 13.8 %) or anastomotic leak
(no-MBP-5.4 % vs MBP-4.8 %). The authors concluded that mechanical bowel
preparation can be safely avoided. Jungl et al. performed a similarly designed study
of 1505 open colectomy patients and also concluded that there was no significant
difference in wound infection (MBP- 7.8 % vs N-MBP- 6.4 %) or anastomotic leak
(MBP-2 % vs no-MBP 2.6 %) [10]. The recent meta-analysis by Bucher et al.
included 7 RCTs available in the literature. This meta-analysis revealed a higher
incidence of anastomotic dehiscence in patients receiving MBP, 5.6 % (36/642), vs
no MBP 2.8 % (18/655) (P = .03; OR, 1.85 [95 % CI, 1.06–3.22]) [11]. However,
using a number need to treat analysis (NNT) and an incidence of 5 % for anasto-
motic leaks, 32 patients (95 % CI, 19–306) would have to be operated on without
MBP to prevent one leak in a patient receiving MBP before surgery. The rate of
intra-abdominal infection (peritonitis or abscess) was similar in the MBP group,
3.7 % (17/458), compared with the no-MBP group, 2.0 % (9/461) (OR, 1.69 [95 %
41 Quality Improvement: Where Are We with Bowel Preps for Patients 469
CI, 0.76–3.75]; P = .18). The rate of wound infection was slightly higher in patients
receiving MBP, 7.5 % (48/642), vs no MBP, 5.5 % (36/655) (OR, 1.38 [95 % CI,
0.89–2.15]; P = .15). General complication and extra-abdominal morbidity rates
were not significantly different in any of these studies; this finding was confirmed in
the meta-analysis. Because of the significant impact of anastomotic leaks, the
Bucher meta-analysis would favor the avoidance of MBP in terms of mortality rates
(OR, 1.42 [95 % CI, 0.37–5.45]; P = .60). The systematic review performed by
Wille-Jorgenson arrived at the same conclusion [12].
A major limitation of the “no bowel prep” philosophy was the failure to under-
stand that these data were obtained in the absence of the documented superior treat-
ment arm, mechanical bowel prep with oral antibiotics. Therefore, the more
accurate conclusion from these data is that bowel prep without oral antibiotics is
equivalent to no mechanical bowel prep. The recent report from the Michigan
Surgical Quality Consortium which analyzed 2062 elective colectomies between
January 2008 and June 2009 compared 49.6 % of patients with mechanical prep
only to 36.4 % with mechanical prep and oral antibiotics [13]. Patients receiving
oral antibiotics were less likely to have any SSI (4.5 % vs. 11.8 %, p = 0.0001), to
have an organ space infection (1.8 % vs. 4.2 %, p = 0.044) and to have a superficial
SSI (2.6 % vs. 7.6 %, p = 0.001). Interestingly, patients receiving bowel prep with
oral antibiotics were also less likely to have a prolonged ileus (3.9 % vs. 8.6 %,
p = 0.011). Fry recently reviewed the published literature and found MBP alone did
not reduce SSIs in nine prospective randomized trials between 2000 and 2010 [14].
He then performed a meta-analysis of nine randomized clinical trials of MBP
which showed the superiority of oral and intravenous antibiotics versus only intra-
venous antibiotics [odds ratio 0.47 (95 % CI: 0.16–0.77, p < 0.0001)]. Furthermore
the rate of SSIs decreased by 6.18 % (95 % CI: 3.43–8.94) with MBP using oral and
intravenous antibiotics [14].
More recently, there has been a concerted effort to revisit the impact of bowel
prep with antibiotics as part of quality improvement projects. Althumari performed
an analysis of the American College of Surgeons National Surgical Quality
Improvement Program Colectomy Targeted Participant Use Data File for 2012 and
2013 [15]. The analysis of 19,686 patients (25.7 % no bowel prep; 40.7 % received
MBP only; 3.3 % oral antibiotics only; 30.3 % received MBP plus oral antibiotics).
Patients who received MBP plus oral antibiotics had a lower incidence of superficial
SSI, deep SSI, organ space SSI, any SSI, anastomotic leak, postoperative ileus,
sepsis, readmission and reoperation compared with patients who received neither
(all P < 0.01). The reduction in SSI incidence was associated with a reduction in
wound dehiscence, anastomotic leak, pneumonia, prolonged requirement of
mechanical ventilator, sepsis, septic shock, readmission, and reoperation. Kiran
analyzed a portion of the same National Surgical Quality Improvement Program-
targeted colectomy data and also concluded that mechanical bowel prep with oral
antibiotics reduced the rates of SSI, anastomotic leak, and ileus by nearly half [16].
Wick et al. evaluated the impact of the implementation of a pathway designed to
improve patient outcomes which adopted a mechanical bowel preparation with oral
antibiotics at their institution. Compared to a historical control group, there was a
470 A.J. Senagore
significant reduction in SSI (18.8 % vs 7.3 %). Collins et al. analyzed long term data
from a 1999 to 2005 randomized study comparing mechanical bowel preparation
(no oral antibiotics) to no prep and demonstrated that prep was associated with sig-
nificantly fewer recurrences, and better cancer-specific and overall survival in the
MBP group after 10 years [17]. Finally, a more recent meta-analysis assessing seven
randomized controlled trials that consisted of 1769 cases determined that both total
surgical site infection and incisional surgical site infection were significantly reduced
in patients who received oral and systemic antibiotics with a mechanical bowel prep-
aration (total: 7.2 % vs 16.0 %, p < 0.00001; incisional: 4.6 % vs 12.1 %, p < 0.00001)
[18]. Therefore, the current body of data would support the re-introduction (or con-
tinued practice) of the combination of mechanical bowel prep with oral antibiotics
as well as prophylactic intravenous antibiotics for optimal outcomes including surgi-
cal site infection and the related secondary complications in colectomy patients.
Typical risk
Outcome Typical risk MBP/oral Quality of
Study Patients classification No prep ABX evidence
Contant et al. Elective Mechanical Leak 37/684 Leak- High quality
Lancet. 2007; colorectal prep with (5.4 %) 32/670 PRCT;
370(9605): surgical either PEG or (4.8 %) however no
2112–2117 resection magnesium study arm
patients citrate vs no with prep
Prep; and oral
Anastomotic antibiotics
leak
Jung et al. Elective Primary end SSI- 16.1 % SSI- 15.1 % HIgh quality
British Journal colorectal point- SSI; ND in other PRCT;
of Surgery surgical Secondary- periop however no
2007; 94: resection adverse complications study arm
689–695 patients outcomes with prep
and oral
antibiotics
Cochrane Colorectal SSI Oral/IV vs IV RR 0.55 High quality
Review – surgical with comparison
Antimicrobial resection combination of multiple
prophylaxis patients outcomes
for colorectal favoring
surgery MBP and
(Review) oral ABX
2009- [19]
Fry DE. Meta- SSI OR in favor High quality
American analysis of of combined meta analysis
Journal of 9 studies mechanical
Surgery. comparing prep and oral
2011;202(2): MBP with abx for SSI
225–232 and reduction
without
oral
antibiotics
Typical risk
Outcome Typical risk MBP/oral Quality of
Study Patients classification No prep ABX evidence
Englesbe MJ. Propensity SSI risk and SSI- 11.8 % SSI- 4.5 % High quality
Annals of analysis associated Organ Organ audited
Surgery 2010; based on complications Space- 4.2 % Space- 1.8 % database
252(3): quality Superficial- Superficial-
514–520. database of 7.2 % 2.6 %
colorectal Ileus- 8.6 % Ileus- 3.9 %
surgery
patients
Based upon the available data, it appears that the initial rigorous work by Nichols
and Condon as well as other investigators regarding the efficacy of mechanical
bowel preparation, oral antibiotics, and broad spectrum prophylactic intravenous
antibiotics has been reaffirmed. The controversy over the need for mechanical
bowel preparation in recent years was, in retrospect, supported by incomplete stud-
ies which did not include an arm with oral antibiotics. These studies were conceived
on the incorrect assumption that modern, broad spectrum intravenous prophylactic
antibiotics were sufficient to reduce surgical site infection. The importance of selec-
tive GI decontamination is an important component of both enhanced recovery and
quality improvement in colorectal surgery.
Strength of Implications for Implications for Implications for

recommendation patients clinicians policy makers
Strong in favor of Most patients The robust quality data This single
combined undergoing colectomy base studies comparing component (MBP/
mechanical bowel would desire a historical approaches to oral ABX prep) is
preparation and oral combined MBP/oral broad implementation of the most important
antibiotics; The large ABX prep when MBP/oral ABX prep are single aspect of any
PRCT’s advocating offered the informed consistent with single strategy for
equipoise for prep/ consent discussion center studies reducing SSI in
no prep did not regarding the risk of performing quality colectomy. It is low
include the SSI and associated improvement. The cost and high
important complications. This consistent and reward and should
component of oral approach should be significant decrease in be strongly
antibiotics with the part of the patient SSI and related advocated as a
prep education within an complications is process measure
enhanced recovery compelling and should within a greater
program. be widely adopted. enhanced recovery
protocol for
colectomy.
472 A.J. Senagore
A Personal View of the Literature
The journey of initial adoption of a MBP/oral antibiotic strategy based on high qual-
ity prospective randomized studies, followed by the subsequent refutation of that
strategy also based on high quality prospective randomized studies is a an excellent
object lesson for future quality initiatives. If one looks back at the Nichols/Condon
era, all combinations were assessed: no mechanical bowel prep; no prep/oral antibi-
otics; prep alone; and prep with oral antibiotics. Interestingly, the more modern high
quality studies failed to appreciate the strength of the prior research and the need to
at least compare the study arm (i.e., no prep) to the gold standard (prep with oral
antibiotics). The data describes both the journey away from the successful practice
of prep with oral antibiotics with a resulting increase in SSI to the journey back with
improved outcomes. At least for my practice, I have maintained this successful pro-
cess measure as part of a global enhanced recovery protocol with excellent out-
comes. This should be a platform for future quality studies where the gold standard
should be put up against a comparator with a clear definition of the outcomes to be
impacted. Innovation is important but it should be structured in a way that the new
approach is at least equal, if not superior both from an outcome and cost
perspective.
References
1. Halsted W. Circular suture of the intestine: an experimental study. Am J Med Sci.

1887;94:436–61.
2. Poth E. Historical development of intestinal antisepsis. World J Surg. 1982;6:153–9.
3. Barker K, Graham NG, Mason FT, Dombal FT, Goligher JC. The relative significance of pre-
operative oral antibiotics, mechanical bowel preparation, and preoperative peritoneal contami-
nation in the avoidance of sepsis after radical surgery for ulcerative colitis and Crohn’s disease
of the large bowel. Br J Surg. 1971;58:270–3.
4. Everett MT, Brogan TD, Nettleton J. The place of antibiotics in colonic surgery: a clinical
study. Br J Surg. 1969;56:679–84.
5. Nichols RL, Condon RE. Preoperative preparation of the colon. Surg Gynecol Obstet.
1971;132:323–37. Condon RE, Bartlett JG, Nichols RL, et al. Preoperative prophylactic ceph-
alothin fails to control septic complications of colorectal operations: results of a controlled
clinical trial. A Veterans Administration cooperative study. Am J Surg. 1979;137(1):68–74.
6. Coppa GF, Eng KE. Factors involved in antibiotic selection in elective colon and rectal sur-
gery. Surgery. 1988;104(5):853–8.
7. Schoetz DJ, Roberts PL, Murray JJ, et al. Addition of parenteral cefoxitin to regimen of oral
antibiotics for elective oral colorectal operations. A randomized prospective study. Ann Surg.
1990;212(2):209–12.
8. Caroline ME, Contant CME, Hop WCJ, van’t Sant HP, Oostvogel JM, Smeets HJ, Stassen
LPS, Neijenhuis PA, et al. Mechanical bowel preparation for elective colorectal surgery: a
multicentre randomised trial. Lancet. 2007;370:2112–7.
9. Jung B, Påhlman L, Nystrom PO, Nilsson E, Mechanical Bowel Preparation Study Group.
Multicentre randomized clinical trial of mechanical bowel preparation in elective colonic
resection. Br J Surg. 2007;94:689–95.
10. Bucher P, Mermillod BS, Gervaz P, Morel P. Mechanical bowel preparation for elective
colorectal surgery. A meta-analysis. Arch Surg. 2004;139:1359–64.
11. Wille-Jorgensen P, Guenaga K, Castor A, Matos D. Clinical value of preoperative mechanical
bowel cleansing in elective colorectal surgery: a systematic review. Dis Colon Rectum.
2003;46:1013–20.
12. Englesbe MJ, Luchtefeld MA, Kubus J, Lynch J, Velanovich V, Senagore AJ, Eggenberger JC,
Brooks L, Campbell DA. A statewide assessment of surgical site infection (SSI) following
colectomy: the role of oral antibiotics. Ann Surg. 2010;252(3):514–20.
13. Fry DE. Colon preparation and surgical site infection. Am J Surg. 2011;202(2):225–32.
14. Althumairi AA, Canner JK, Gearhart SL, Safar B, Sacks J, Efron JE. Predictors of perineal
wound complications and prolonged time to perineal wound healing after abdominoperineal
resection. World J Surg. 2016;40(7):1755–62.
15. Kiran RP, Murray AC, Chiuzan C, Estrada D, Forde K. Combined preoperative mechanical
bowel preparation with oral antibiotics significantly reduces surgical site infection, anasto-
motic leak, and ileus after colorectal surgery. Ann Surg. 2015;262(3):416–25.
16. Wick EC, Galante DJ, Hobson DB, Benson AR, Lee KH, Berenholtz SM, Efron JE, Pronovost
PJ, Wu CL. Organizational culture changes result in improvement in patient-centered out-
comes: implementation of an integrated recovery pathway for surgical patients. J Am Coll
Surg. 2015;221(3):669–77.
17. Collin Å, Jung B, Nilsson E, Påhlman L, Folkesson J. Impact of mechanical bowel preparation
on survival after colonic cancer resection. Br J Surg. 2014;101(12):1594–600.
18. Chen M, Song X, Chen LZ, Lin ZD, Zhang XL. Benefits of bowel preparation beyond surgical
site infection: a retrospective study. Comparing mechanical bowel preparation with both oral
and systemic antibiotics versus mechanical bowel preparation and systemic antibiotics alone
for the prevention of surgical site infection after elective colorectal surgery: a meta-analysis of
randomized controlled clinical trials. Dis Colon Rectum. 2016;59(1):70–8.
19. Nelson RL, Glenny AM, Song F. Antimicrobial prophylaxis for colorectal surgery (Review)
2009. The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. London, United
Kingdom
Chapter 42
Quality Improvement: Are Fast Track
Pathways for Laparoscopic Surgery Needed?
Avery S. Walker, Michael Keating, and Scott R. Steele
Introduction
Multiple studies have been performed demonstrating the benefits of an enhanced

recovery program following a wide breadth of surgical disciplines, including more
recent reports showing significant benefits of enhanced recovery protocols for
patients undergoing a laparoscopic colectomy. This has held true in both compari-
sons of an open versus minimally invasive approach, as well as when comparing
enhanced recovery pathways to traditional perioperative care strategies. While most
providers are now well versed in the concept of enhanced recovery, the individual
practice and components often vary in number and nature. However, the basic prin-
ciples of ensuring this program spans the preoperative, intraoperative, and postop-
erative settings, along with a multidisciplinary mandated “buy-in”, are necessary to
ensure maximal effectiveness regardless of the institution or procedure.
While enhanced recovery protocols may include anywhere from 8 to 26 different
components, almost all begin with detailed patient education on expectations and
outcomes in the outpatient setting prior to pursuing optimal perioperative tech-
niques, early enteral nutrition, and early mobilization. Initially described by
Disclaimers The results and opinions expressed in this article are those of the authors, and do not
reflect the opinions or official policy of the United States Army or the Department of Defense.
A.S. Walker, MD
Department of Surgery, Brian Allgood Army Community Hospital, Yongsan, South Korea
M. Keating, BA
Case Western Reserve University School of Medicine, Cleveland, OH, USA
S.R. Steele, MD (*)
Department of Colon and Rectal Surgery, Case Western University, Cleveland, OH, USA

DOI 10.1007/978-3-319-40223-9_42
476 A.S. Walker et al.
Professor Kehlet in the setting of open abdominal surgery, the impact that this “fast
track” protocol in the setting of a minimally invasive/laparoscopic approach has
also been questioned. To answer this latter question, this chapter focuses on patients
who undergo laparoscopic colectomy under the tenets of an enhanced recovery
pathway compared to those patients who progress through traditional perioperative
management strategies following a laparoscopic approach. The outcomes we pri-
marily evaluated within these programs include overall length of stay, morbidity,
and readmission rates--all in an effort to accelerate recovery without compromising
patient safety.
Search Strategy
A systematic database search utilizing the Cochrane Collaborative Library, OVID,

and PubMed databases was performed to identify all trials of interest from January
2009 to December 2015. This time period was selected in an effort to provide the
most up-to-date information balanced with allowing enough time from the initiation
and evolution of enhanced recovery programs in the early 2000s. Randomized con-
trolled trials (RCTs) and observational studies were provided the most weight,
though not the sole inclusionary criteria. The following keyword combinations were
used: “fast track”; “enhanced recovery”; “laparoscopic”; “colorectal”; “colon”;
“rectal”; “traditional open surgery”; and “laparotomy”. MeSH terms included “min-
imally invasive”; “laparoscopy*”; “treatment outcome”; “colonic/surgery”; “colec-
tomy/rehabilitation”; “length of stay”; “outcome assessment”; “postoperative care”;
“preoperative care”; “patient readmission”; “laparoscopic colectomy” and
“enhanced recovery pathway”. In addition, we hand-searched reference lists of
related systematic reviews since 2001 to identify relevant additional studies. Final
studies were selected based on the PICO (Population, Intervention, Comparator,
Outcomes) framework as listed in Table 42.1. Although not exclusionary, primary
authors focused on all English language manuscripts and studies of adults. The
primary authors formulated recommendations with the final grade of recommenda-
tion selected using the GRADE system (Table 42.2).
Table 42.1 PICO chart

Patients 1. Laparoscopic- 1. Traditional open Total hospital stay,
undergoing assisted approach surgery postoperative stay,
colorectal or or complications,
surgery 2. Enhanced recovery 2. Conventional readmissions
program/fast track postoperative care
pathway
Note: Studies were included where either (1) a fast track pathway was in place and they compared
open vs. laparoscopic approach or (2) laparoscopic colorectal surgery was being performed and the
analysis focused whether or not the addition of a fast track pathway changed outcomes
42 Quality Improvement: Are Fast Track Pathways for Laparoscopic Surgery Needed? 477
Table 42.2 The GRADE system – grading recommendations

Methodologic quality
Benefit vs. risk of supporting
Description and burdens evidence Implications
1A Strong Benefits RCTs without Strong recommendation,
recommendation, clearly important limitations can apply to most
High quality outweigh risk or overwhelming patients in most
evidence and burdens or evidence circumstances without
vice versa from observational reservation
studies
1B Strong Benefits RCTs with important Strong recommendation,
recommendation, clearly limitations can apply to most
Moderate quality outweigh risk (inconsistent results, patients in most
evidence and burdens or methodologic flaws, circumstances without
vice versa indirect or imprecise) reservation
or exceptionally
strong evidence
from observational
studies
1C Strong Benefits Observational studies Strong recommendation
recommendation, clearly or case series but may change when
Low or very low outweigh risk higher quality evidence
quality evidence and burdens or becomes available
vice versa
2A Weak Benefits RCTs without Weak recommendation,
recommendation, closely important limitations best action may differ
High quality balanced with or overwhelming depending on
evidence risks and evidence from circumstances or
burdens observational studies patients’ or societal
values
2B Weak Benefits RCTs with important Weak recommendation,
recommendations, closely limitations best action may differ
Moderate quality balanced with (inconsistent results, depending on
evidence risks and methodologic flaws, circumstances or
burdens indirect or imprecise) patients’ or societal
or exceptionally values
strong evidence
from observational
studies
2C Weak Uncertainty in Observational studies Very weak
recommendation, the estimates or case series recommendations; other
Low or very low of benefits, alternatives may be
quality evidence risks and equally reasonable
burden;
benefits, risk
and burden
may be closely
balanced
Adapted from Guyatt et al. [1]
Results
The definition of an enhanced recovery pathway for colon and rectal surgery was
established by the Consensus Review of Optimal Perioperative Care in Colorectal
Surgery Group in 2009. This was a succinct and easily adaptable list which describes
the 20 aspects of the enhanced recovery protocol [2]. Our focus was whether adding
an enhanced recovery/fast track pathway to patients undergoing laparoscopic tech-
niques add any benefits when compared to those undergoing laparoscopy in the
absence of a fast track pathway (Table 42.3).
It is well known that using a laparoscopic approach for colorectal surgery is
associated with shorter hospital stays, decreased postoperative complications, and
decreased pain when compared to open surgery [9–12]. It is also well established
that adding an enhanced recovery protocol to open colorectal surgery results in bet-
ter patient outcomes. In theory, the addition of an enhanced recovery protocol
should produce better outcomes for laparoscopic surgery as well; however, the lack
of tier 1 randomized controlled trials makes this presumption difficult to definitively
prove. In reality, most studies are retrospective reviews, underpowered, or lack an
appropriate number of fast track elements.
However, Zhao et al. attempted to strengthen the literature by combining the
data with a meta-analysis in August of 2014 [6].The authors were able to identify
and deem eligible five randomized controlled trials and five clinical controlled tri-
als for a total of 1,317 patients. The patients all underwent laparoscopic colorectal
surgery, with 696 participating in an enhanced recovery protocol and 621 patients
undergoing traditional care. Importantly, all patients underwent a minimally inva-
sive approach. In addition, all studies within the meta-analysis were determined to
range in quality from moderate to high. Primary hospital stay (−1.64 days; 95 % CI,
−2.25 to−1.03; p < 0.001), time to first flatus (−0.40 day; 95 % CI, −0.77 to−0.04;
p = 0.03), time to first bowel movement (−0.98 day; 95 % CI, −1.45 to−0.52;
p < 0.001), and complication rate (RR, 0.67; 95 % CI, 0.56–0.80; p < 0.001) were all
improved when an enhanced recovery program was applied in addition to the lapa-
roscopic technique. Readmission rate and 30-day mortality were found to be non-
significant, which has been consistent with other studies comparing enhanced
recovery protocols within colorectal surgery. Another interesting aspect of this
meta-analysis was that complication rates were found to be significantly reduced--a
finding in which no other meta-analysis had identified before. The authors ulti-
mately concluded that not only can an enhanced recovery protocol be combined
with laparoscopic colorectal surgery to decrease primary hospital stay, increase
time to first flatus and bowel movements, but also that using laparoscopy within
these protocols may actually increase patient safety when compared to traditional
perioperative colorectal care.
When looking at some of the existing primary data, a study by Vlug and col-
leagues provides a closer comparative evaluation. Vlug and associates provided one
of the first studies looking specifically at laparoscopy versus open techniques within
enhanced recovery protocols in the 2011 entitled LAparoscopy and/or FAst track
Table 42.3 GRADE profile for laparoscopic colorectal surgery in enhanced recovery protocols
Quality of
Study year Study type Patients numbers Outcomes evidence
Zhuang et al. Meta-analysis 598 patients Laparoscopic surgery Moderate
(2015) [3] Lap vs. Open in ↓Total hospital stay
ERAS program ↓# of complications
Lei et al. Meta-analysis 714 Patients Lap surgery – shorter Moderate
(2015) [4] 373 FT Lap post op stay and shorter
341 FT Open overall hospital stay
Tiefenthal Prospective 292 Patients ↓Pain control Moderate
et al. (2015) Clinical Trial Lap within ERAS ↓Hospital stay
[5] program
Zhao et al. Meta-analysis 1,317 Patients ↓Primary hospital stay Moderate-
(2014) [6] 696 Lap/ERAS ↓Time to first flatus High
621 LAP/ ↓Time to first bowel
traditional care movement
↓Complications
Vlug et al. RCT 400 Patients Factors ↓ total hospital Low-moderate
(2012) [7] 193 Lap/Open FT stay
207 Lap/Open Female Sex
standard Laparoscopic
resection
Normal diet on POD 1,
2, 3 Enforced
Mobilization
Vlug et al. RCT 400 Patients Laparoscopy within Moderate
(2011) [8] Lap FT ERAS protocol
Lap standard ↓hospital stay to 5 days
Open FT vs. 7 days in the Open
Open standard and ERAS protocol
RCT randomized controlled trial, ERAS enhanced recovery after surgery pathway, Lap laparo-
scopic, FT fast track pathway
multimodal management versus standard care (LAFA trial) [13]. The authors
stratified 400 patients into 4 treatment groups: laparoscopic/fast track, open/fast
track, laparoscopic/standard, and open/standard with the primary goal to find a min-
imum difference of 1 day in hospital stay [13]. They showed a total hospital stay of
5 days in the laparoscopic/fast tract group versus 7 days for the open/fast track
group (p < 0.001), concluding that optimal perioperative treatment includes a lapa-
roscopic resection within an enhanced recovery protocol [13]. On regression analy-
sis, laparoscopy was the only independent predictive factor to reduce hospital stay
and morbidity [13]. When specifically comparing laparoscopic with fast track, ver-
sus laparoscopic with standard perioperative care, the median hospital stay was
lower in the fast track cohort at 5 days (interquartile range: 4–8) versus 6 days
(range: 4.5–9.5). However, secondary outcomes including postoperative hospital
stay, morbidity, reoperation, readmission, in-hospital mortality, and quality of life
did not differ significantly amongst the groups.
In 2012, Vlug and colleagues followed up with a more specific question given the
potentially confounding elements of the enhanced recovery recommendations and
attempted to ferret out which aspects of the enhanced recovery protocol predicted
early recovery after colon cancer surgery [7]. Using patients from the LAFA trial,
all patients who were randomized to fast track care (n = 193) and standard care
(n = 207) were analyzed to determine whether one single item or a set of items inde-
pendently predicted “enhanced recovery” as defined by total postoperative hospital
stay as the primary outcome [7]. Six baseline characteristics (female gender, age,
ASA, BMI, laparoscopic operation, and right-sided resections) along with the
achieved fast-track elements were entered in a univariate linear regression analysis.
Those with a p < 0.100 were subsequently entered in a multivariate linear regression
analysis, which identified female gender, laparoscopic resection, normal diet at
postoperative days 1, 2, and 3, and enforced mobilization at postoperative days 1, 2,
and 3, as independent predictors of total postoperative hospital stay [7]. They con-
cluded that a laparoscopic resection was an independent predictor of decreased
length of stay, in accordance with the results of the earlier LAFA Trial, thus further
validating the improvement in early recovery with the use of laparoscopy within an
enhanced recovery protocol.
Zhuang et al., published an update to their prior meta-analysis regarding ERAS
protocols within colorectal surgery versus traditional care with a more focused
meta-analysis in 2015,evaluating laparoscopic versus open colorectal surgery within
an enhanced recovery program [3, 14].Five randomized clinical trials encompassing
598 patients were included in the final analysis. The nature of their inclusion/exclu-
sion criteria increased the strength of this meta-analysis. They included only RCTs
and all studies must have had at least 7 enhanced recovery interventions.
Laparoscopic colorectal surgery significantly reduced total hospital stay by
1.92 days (95 % confidence interval (CI): 2.61± 1.23 days; p < 0.00001) and number
of complications (RR 0.78; 95 % CI 0.66–0.94; p = 0.007) compared with open sur-
gery in the setting of enhanced recovery programs [3]. Unfortunately, the benefits of
laparoscopic colorectal resection within optimal ERAS programs was not able to be
determined. In part, this was due to the lack of high-quality primary studies. In addi-
tion, there were too few laparoscopic/standard versus laparoscopic/fast track
comparisons.
The effect of the skill level of surgeons performing laparoscopy on final out-
comes within an enhanced recovery protocol has also surfaced amongst these stud-
ies, as many of the prior studies proclaimed that the participating surgeons were
well versed in the technique of laparoscopic colorectal surgery [13, 15]. Tiefenthal
published a study in the summer of 2015 looking at laparoscopic versus open right-
sided colonic resection within an ERAS protocol [5]. They attempted to avoid the
bias introduced in previous laparoscopic research where laparoscopic specialists
performed the surgery. They included surgery performed by low-volume surgeons
and trainees. Their primary outcomes included postoperative recovery and morbid-
ity, with secondary outcomes including preoperative variables that influenced the
selection of patients for laparoscopic or open surgery [5]. The compliance with the
enhanced recovery elements was very high compared to most studies at 87 %, and
on multivariate analysis the authors reported earlier pain control and shorter hospi-
tal stay in the laparoscopic group (2.4 ± 3.2 days vs. 4.2 ± 5.9 p = 0.016; and 4 vs. 6
days (p = 0.002), respectively). The authors concluded that trainees and low-volume
surgeons within a well-performed enhanced recovery protocol program might still
produce the similar results as reported in prior studies.
The most recent evidence supporting laparoscopic colonic resection within an
enhanced recovery protocol was a meta-analysis performed by Lei and colleagues
in 2015, which supports the use of laparoscopic-assisted techniques [4]. This meta-
analysis encompassed seven RCTs and a total of 714 patients: 373 undergoing lapa-
roscopic colonic resections and 341 undergoing an open operation--all within an
enhanced recovery program. The authors found the laparoscopic group demon-
strated a significant decrease in postoperative hospital stay, total hospital stay, and
overall complications when compared to the open operation [4]. The strengths of
this meta-analysis include their inclusion of only RCTs, large number of patients,
and studies only comparing laparoscopic with open colorectal resection within the
setting of an established enhanced recovery program. The downside includes the
lack of comparison evaluating the benefit of laparoscopic plus enhanced recovery
versus simply laparoscopy alone. Despite this drawback, this analysis strongly sup-
ports our recommendation concerning the use of laparoscopic techniques within an
enhanced recovery system in order to reduce the postoperative stay, total hospital
stay, and overall complications without jeopardizing patient’s safety.
Song and colleagues looked at randomized and clinical controlled trials from
2000–2012, and focused this analysis on laparoscopic cases only—identifying 13
trials and 1795 patients. Overall, time to time to passage of flatus (WMD = −1.37, 95
% CI: -1.55 ~ −1.19, P < 0.05), time to resumption of diet/drink (WMD = −2.62, 95
% CI: -2.69 ~ −2.55, P < 0.05), postoperative length of postoperative hospital stay
(WMD = −1.63, 95 % CI: −1.92 ~ −1.34, P < 0.05) and the incidence of postopera-
tive complications (OR = 0.52, 95 % CI: 0.41 ~ 0.67, P < 0.05) were all improved in
the fast track cohort. The authors concluded that enhanced recovery does make a
difference in improving outcomes, even for those patients undergoing a laparoscopic
approach [16]. Taupyk and colleagues followed this in a small blinded controlled
trial of 70 patients with colorectal cancer, all of who munder went conventional
laparoscopic surgery and were then randomized to fast track versus conventional
recovery [17]. The fast track protocol consisted of avoidance of bowel preparation,
early postoperative feeding, and early ambulation. Total length of stay (5.9 vs.
10.9 days), post-operative stay (4.3 vs. 8.0 days), first flatus (1.6 vs. 2.5 days), def-
ecation time (2.2 vs. 4.5 days), and time to resumption of solid diet (1.1 vs. 3.6
days) were all improved in the fast track cohort, as well as lower CRP levels.
Although this was a “bare-bones” fast track system, it does highlight that even sim-
ple things can improve outcomes--even in patients undergoing laparoscopic
surgery.
Improved length of stay with the addition of an enhanced recovery pathway for
all patients undergoing laparoscopic colorectal surgery has also been shown by
Haverkamp and associates. This retrospective chart review looked at those prior to
(n = 77) and after (n = 109) implementation of a fast track program. Whereas they
were unable to show any improvement in postoperative procedure-related compli-
cations, morbidity, readmission, reoperation, or mortality, length of stay was
improved in those with a fast track program (4 vs. 6 days) [18]. These same benefits
with regards to hospital length of stay have been demonstrated in the setting of
minimally invasive approaches for rectal cancer as well [19, 20].
A 2005 Cochrane review confirmed that laparoscopic colorectal resection resulted

in better safety, decreased the postoperative pain, and lessened the duration of post-
operative ileus than open surgery [21]. Around this time, enhanced care protocols
came into the forefront of colorectal surgery, initially making their mark in open
surgery [2]. We feel strongly that this same improvement can be witnessed when
applied to laparoscopic colorectal surgery as well. This improvement in clinical out-
comes seen when combing laparoscopic surgery with the enhanced recovery proto-
col may be due to simply combining the two modalities, which ultimately decreases
postoperative stress, inflammatory response, and leads to a faster recovery. The lit-
erature discussed above only strengthens the recommendation stated in the Cochrane
review: the implementation of an enhanced recovery protocol to a minimally
invasive approach for colorectal surgery should be performed in every possible
instance. This STRONG recommendation would be expected to result primarily in
faster recovery times and decreased length of stay. The effect on decreasing compli-
cations, improving patient satisfaction, and cultivating overall patient safety remains
to be determined, but the majority of the literature suggests (at a minimum) equiva-
lent, and likely better outcomes with adding a fast track program.
1. Adding an enhanced recovery/fast track pathway to laparoscopic-assisted

colorectal surgery is the preferred approach whenever feasible. (Strong recom-
mendation based on moderate-high quality evidence)
2. Patients deemed at high-risk (i.e., elderly, multiple comorbidities, high frailty
index) may still benefit from individual components of an enhanced recovery/
fast track pathway when undergoing laparoscopic colorectal surgery. (Weak rec-
ommendation based on low-quality evidence)
Our review of the data regarding the addition of an enhanced recovery/fast track
pathway even in those well versed in laparoscopic-assisted techniques for colorec-
tal surgery is that it will result in an improvement in outcomes. Anecdotally, this
has definitely been the senior author’s experience. The data seems clear that add-
ing a fast track pathway will result in shorter hospital stays. Although outcomes
such as complications, readmission, quality of life, and reoperations are lower
with fast track pathways when comparing open with laparoscopic approaches, the
majority of data shows equivalent or more modest benefits when limited to lapa-
roscopic cohorts alone. Part of this is obvious--the benefits of a minimally inva-
sive technique (i.e., laparoscopy) for emergent and elective colon and rectal
procedures has been clearly evident based on relatively longstanding literature.
Several meta-analyses have demonstrated not only the impact on decreased length
of stay, morbidity and quality of life, but also improved pain control, earlier return
of bowel function, and lower mortality with the laparoscopic approach. With such
vast improvements in outcomes, the question remains that in the face of a techni-
cally sound laparoscopic approach, what is the impact of an enhanced recovery
program to improve outcomes even further? On one hand, laparoscopic techniques
are increasingly becoming a new “standard of care” within colorectal surgery, and
many institutions have already implemented a majority of fast track tenets within
their “traditional” care pathways. Therefore, many comparisons are “apples to
apples”. However, especially for those without a fast track pathway in place, lapa-
roscopy with the addition of an enhanced recovery program will improve out-
comes. We do need more and higher level data to solidify this recommendation.
As such, we need to gear our future investigations to augment the paucity of lit-
erature evaluating outcomes following laparoscopic colorectal surgery in tradi-
tional postoperative recovery pathway versus outcomes following laparoscopic
colorectal surgery in an enhanced recovery pathway. It seems likely that there is a
symbiotic relationship that results in a meaningful improvement inpatient
outcomes.
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of evidence in clinical guidelines: report from an American College of Chest Physicians Task
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versus open surgery for colorectal cancer. Br J Surg. 2006;93(8):921–8.
13. Vlug MS, Wind J, Hollmann MW, et al. Laparoscopy in combination with fast track multi-
modal management is the best perioperative strategy in patients undergoing colonic surgery: a
randomized clinical trial (LAFA-study). Ann Surg. 2011;254(6):868–75.
14. Zhuang C-L, Ye X-Z, Zhang X-D, Chen B-C, Yu Z. Enhanced recovery after surgery programs
versus traditional care for colorectal surgery: a meta-analysis of randomized controlled trials.
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Chapter 43
Quality Improvement: Enhanced Recovery
Pathways for Open Surgery
W. Conan Mustain and Conor P. Delaney
Introduction
Patients undergoing open colectomy are frequently subjected to severe metabolic

stress and dramatic alterations of their normal physiology during the perioperative
period. These changes contribute to prolonged pain, immobility, and gut dysfunc-
tion which require extended hospitalization. In recent years efforts have been made
to accelerate recovery, by minimizing stress, optimizing pain control, and shorten-
ing the time to resumption of normal activities, with the goal of returning patients to
their normal lives and avoiding perioperative complications. The logical secondary
benefit of decreasing length of stay and complications is a reduction in health care
costs. The combination of multiple modalities to achieve this goal has been referred
to as fast-track surgery, multimodal recovery, enhanced recovery pathways (ERP),
or enhanced recovery after surgery (ERAS).
The general concept of ERP involves a protocol designed to avoid unnecessary
stress, preserve organ function, and promote patient autonomy. This requires a series
of targeted interventions in the preoperative, intraoperative, and immediate postopera-
tive period. The principle areas of an effective ERP and the outlined in Table 43.1. The
specific interventions within each realm that are required for an effective ERP are still
open to debate. Over 20 different possible interventions have been described, with
great variation in their use between institutions. A detailed analysis of the evidence
behind each potential component of an ERP is beyond the scope of this review. For a
W.C. Mustain, MD
Division of Colon and Rectal Surgery, University of Arkansas for Medical Sciences,
Little Rock, AR, USA
C.P. Delaney, MD, PhD (*)
Digestive Disease Institute, Cleveland Clinic,
9500 Euclid Avenue, Cleveland, OH 44195, USA

DOI 10.1007/978-3-319-40223-9_43
486 W.C. Mustain and C.P. Delaney
Table 43.1 Components of an enhanced recovery pathway

Patient information
1. Preoperative information and counseling
2. Preset discharge criteria
3. Stoma marking and education if indicated
4. Optimization (home incentive spirometer, smoking cessation, prehab)
Preservation of bowel function
5. Clear liquids until 2 h before surgery
6. High-carbohydrate beverage morning of surgery
7. Alvimopan, chewing gum, laxatives
8. Early feeding post-operatively
Avoiding organ dysfunction
9. Selective use of bowel prep
10. Antimicrobial and thromboembolic prophylaxis
11. Avoid hypothermia
12. Balanced use of crystalloids to optimize cardiac output and avoid excess fluid
Optimizing pain control
13. Preemptive analgesia started before surgery
14. Local anesthetic, regional blocks, or epidurals
15. Laparoscopy or minimal access incisions
16. Scheduled use of non-opioid analgesics
Promotion of patient autonomy
17. Avoid long-acting sedative premedication
18. Avoid nasogastric tubes and drains
19. Enforced early mobilization
20. Early removal of urinary catheter and IV fluids
comprehensive analysis of the evidence supporting specific pathway components the

reader is referred to the Guidelines for Perioperative Care in Elective Surgery:
Enhanced Recovery After Surgery (ERAS®) Society Recommendations [1].
While the theoretical benefits of ERP are clear, it is necessary to ensure that the
benefits outweigh any undesirable consequences caused by deviations from conven-
tional management. Simply achieving an earlier discharge from the hospital is
insufficient if there are resultant increases in complications from feeding patients
too early, readmissions from sending them out too soon, or dissatisfaction from
patients’ feeling rushed out of the hospital. In this chapter we review the literature
supporting ERP for open colectomy and provide an evidence-based endorsement
for their routine application.
Methods
Following the GRADE approach we began by formulating an appropriate clinical

question, defining the four critical components of patient population, intervention,
comparison, and outcomes of interest, illustrated in a standard PICO table
43 Quality Improvement: Enhanced Recovery Pathways for Open Surgery 487

P (patient population) I (intervention) C (comparator) O (outcomes of interest)
Patients undergoing Enhanced recovery Traditional care Complications
open colectomy pathways (ERP) (TC) Readmissions
Length of Stay
Cost
Quality of Life/
Satisfaction
(Table 43.2) [2]. The patient group of interest was those undergoing open colec-
tomy, with the intervention of treatment by ERP as compared to traditional care
(TC), with the intent to answer, “Should patients undergoing open colectomy be
managed by ERP rather than TC?” The outcomes considered critical in this search
were morbidity, mortality, and readmission rates, recognizing the principle of non-
maleficence (do no harm) as paramount over any effects on hospital stay or costs.
However, because beneficence (acting for the benefit of others), rather than simply
avoidance of harm, should form the foundation of any clinical recommendation
we also considered hospital length of stay (LOS), costs, and patient satisfaction or
quality of life (QoL) as important outcomes. The quality of the evidence was
graded for each outcome and the evidence was used to formulate a recommenda-
tion on the question of interest. The strength of our recommendation is based on
our degree of confidence that the desirable effects outweigh the undesirable
effects, as influenced by the magnitude of the differences between benefit and
harm, the quality of the evidence, and the value placed on the outcomes of
interest.
Search Strategy
A systematic search of the literature was conducted using MEDLINE, PubMed,

Web of Science, and the Cochrane Collaborative to identify articles related to the
topic of interest. The initial search included Medical Subject Headings terms, as
well as entry terms for relevant interventions and outcomes. Key words included
[“colectomy” OR “colon surgery” OR “colorectal surgery”] AND [“perioperative”
OR “post-operative” OR “post-surgical” OR “rehabilitation”] AND [“enhanced
recovery” OR “ERAS” OR “ERP” OR “fast-track” OR “multimodal”]. The search
was conducted for all dates up to November 2015 and restricted to English language
titles. No age limits were applied. Titles and abstracts were screened for inclusion
based on relevance. In addition, reference lists of retrieved articles were screened
for additional relevant studies. Randomized controlled trials, case control trials, ret-
rospective cohorts, systematic reviews, meta-analyses, reviews, letters, and editori-
als were considered. Emphasis was placed on studies comparing ERP to TC after
open colectomy, with priority given to randomized controlled trials and meta-
analyses where data was available for specific outcomes. For less well-studied out-
comes all sources were considered.
Results
We identified over 300 articles related to the topic of interest, including 15 meta-
analyses and systematic reviews of trials comparing ERP to TC (Table 43.3). These
reviews encompass a total of 32 different randomized controlled trials, controlled
clinical trials, and retrospective reviews, and provide some insight in each of the
outcomes of interest for our clinical question.
Complications
Several large meta-analyses of randomized controlled trials, including a Cochrane

review, have examined morbidity and mortality after colectomy in patients manage
by ERP versus TC (Table 43.3). Mortality is a rare event after colorectal surgery
with consistent rates of around 1 % and no significant difference between ERP and
TC in any series. The three largest and most recent meta-analyses to examine post-
operative complications, by Greco [3], Yin [30], and Zhuang [31] respectively, all
found a significant risk reduction for overall complications with ERP as compared
to TC [Greco RR = 0.60 (95 % CI 0.46 – 0.76); Yin RR = 0.58 (95 % CI 0.43 – 0.77);
Zhuang RR = 0.71 (95 % CI 0.58 – 0.86)]. Some reviews examined sub-categories
of complications. Two studies found a significant decrease in non-surgical, but not
surgical complications [3, 31] with ERP. The Cochrane review by Spanjersberg
et al. found a significant reduction in overall complications with ERP [RR = 0.52
(95 % CI 0.38 – 0.71), though significance did not hold up when examining major
complications or minor complications separately. The definition of complications
and the way in which they were recorded is not constant and many studies fail to
note whether complications occurring after discharge were measured; nonetheless,
the findings remain consistent across multiple large studies and it is unlikely that
major complications were missed.
Readmission
After assuring safety, the most obvious concern with implementing pathways
designed to get patients home sooner, is if this makes them more likely to be read-
mitted to the hospital. In each of the studies cited above there was no difference in
the rate of readmission among patients managed by ERP or TC [3, 30, 31, 41]. In
the largest of these series, including over 1,600 patients, the overall readmission rate
was 4 – 5 % in each group. This outcome is consistent and has very low heterogene-
ity in multiple meta-analyses. There is a risk of observational error if patients were
readmitted to a different hospital, but there is no reason to suspect this phenomenon
more frequently in one group versus the other.
Table 43.3 Meta-analyses and systematic reviews of enhanced recovery pathways vs. traditional
care for colectomy
Inclusion Included Primary Secondary
Author Year Studies criteria studies outcomes outcomes
Greco et al. 2014 RCT Open or Anderson Overall Primary LOS
[3] laparoscopic [4], morbidity Readmission
Minimum 4 Delaney Surgical Mortality
ERAS [5], complications Ileus
elements Garcia- Nonsurgical
Botello [6], complications
Gatt [7],
Ionescu [8],
Khoo [9],
Lee [10],
Muller
[11], Ren
[12],
Serclova
[13], Vlug
[14], Wang
[15], Wang
[16], Wang
[17], Wang
[18], Yang
[19]
Lee et al. 2014 RCT Open or Ren [12], Cost N/A
[20] CCTa laparoscopic Vlug [14],
RRb Minimum 5 Archibald
ERAS [21] a,
elements Bosio [22]a,
Cost data Folkerson
included [23]a,
Jurowich
[24]a,
Kariv [25]a,
King [26]a,
Sammour
[27]a,
Stephen
[28]b
Lemanu 2014 RCT Open or Ren [12], Cost Primary LOS
et al. [29] CCTa laparoscopic Vlug [14] Readmission
RRb No minimum Archibald Morbidity
ERAS [21]a, Kariv
elements [25]a,
Cost data King [26]a,
included Sammour
[27]a,
Stephen
[28]b
(continued)
Yin et al. 2014 RCT Open or Anderson Total LOS
[30] laparoscopic [4], Gatt Readmission
No minimum [7], Morbidity
ERAS Ionescu [8], Mortality
elements Khoo [9], GI function
Muller
[11],
Serclova
[13],
Vlug [14],
Wang [16],
Yang [19]
Zhuang et al. 2013 RCT Open or Anderson Primary LOS Time to first
[31] laparoscopic [4], Total LOS flatus and
Minimum 7 Garcia- Readmission stool
ERAS Botello [6], Total Hospital
elements Gatt [7], complications costs
Ionescu [8], Surgical
Khoo [9], complications
Muller Nonsurgical
[11], Ren complications
[12], Mortality
Serclova
[13], Vlug
[14], Wang
[17], Wang
[18], van
Bree [32],
Yang [19]
Lvet al. [33] 2012 RCT Open surgery Anderson Primary LOS Readmission
only [4], Morbidity
No minimum Delaney Mortality
ERAS [5],
elements Gatt [7],
Khoo [9],
Muller
[11],
Serclova
[13], Vlug
[14]
(continued)
Adamina 2011 RCT Open or Anderson Primary LOS N/A
et al. [34] laparoscopic [4], Readmission
Minimum 4 Delaney [5] Morbidity
ERAS Gatt [7], Mortality
elements Khoo [9],
Muller
[11],
Serclova
[13]
Rawlinson 2011 RCT Open or Anderson Primary LOS N/A
et al. [35] CCTa laparoscopic [4], Total LOS
RRb Minimum 4 Delaney Readmission
ERAS [5], Morbidity
elements Gatt [7], Mortality
Khoo [9],
Muller
[11],
Serclova
[13]
Basse [36]a,
Kariv [25]a,
Polle [37]a,
Raue [38]a,
Teeuwen
[39]a,
Wichmann
[40]a,
Stephen
[28]b
Spanjersberg 2011 RCT Open or Anderson Mortality Operative
et al. [41] laparoscopic [4], Gatt Total time
Minimum 7 [7], Khoo complications Economic
ERAS [9], Major impact
elements Serclova complications QoL
[13] Minor
complications
(continued)
Khan et al. 2010 RCT Open or Anderson QoL
[42] CCTa laparoscopic [4], Patient
No minimum Delaney satisfaction
ERAS [5],
elements Gatt [7],
QoL or Henriksen
satisfaction [43],
data included Basse [36]a,
Jakobsen
[44]a,
King [26]a,
Polle [37]a,
Raue [38]a,
Zargar
[45]a
Varadhan 2010 RCT Open surgery Anderson Primary LOS Readmission
et al. [46] only [4], Morbidity
Minimum 4 Delaney Mortality
ERAS [5],
elements Gatt [7],
Khoo [9],
Muller
[11],
Serclova
[13]
Eskicioglu 2009 RCT Open or Anderson Primary LOS Readmission
et al. [47] laparoscopic [4], Total LOS Morbidity
No minimum Delaney [5] Mortality
ERAS Gatt [7],
elements Khoo [9]
Gouvas et al. 2009 RCT Open or Anderson Primary LOS NG required
[48] CCTa laparoscopic [4], Total LOS Lung
RRb No minimum Delaney Readmission function
ERAS [5], Morbidity Pain, fatigue,
elements Gatt [7], Mortality quality of life
Khoo [9] scores
Basse [36]a,
Bradshaw
[49]a,
Kariv [25]a,
Polle [37]a,
Raue [38]a,
Wichmann
[40]a,
Stephen
[28]b
(continued)
Walter et al. 2009 RCT Open or Anderson Primary LOS Total LOS
[50] CCTa laparoscopic [4], Gatt Readmission
Minimum 5 [7] Morbidity
ERAS Basse [36]a, Mortality
elements Raue [38]a
Wind et al. 2006 RCT Open or Anderson Primary LOS N/A
[51] CCTa laparoscopic [4], Total LOS
Minimum 4 Delaney Readmission
ERAS [5], Morbidity
elements Gatt [7] Mortality
Basse [36]a,
Bradshaw
[49]a, Raue
[38]a
a
CCT controlled clinical trial
b
RR retrospective review
RCT randomized controlled trial, ERAS enhanced recovery after surgery, Primary LOS initial post-
operative length of stay, Total LOS primary LOS + readmission LOS, QoL quality of life, NG naso-
gastric tube
Length of Stay
Perhaps the most consistent positive finding in the literature regarding ERP after
colectomy is a decrease in hospital LOS with ERP as compared to TC. There are
likely differences in the definition of “traditional” care between hospitals, and espe-
cially between countries, as evidenced by the wide variation in mean LOS in the TC
cohorts of many recent series, ranging from 7 to 12 days [11–13, 15, 19]. However,
there is high quality evidence showing a consistent reduction in LOS of around 2
days with implementation of ERP [3, 30, 31, 34, 46]. There is a risk for observer
bias in some studies where discharge criteria were less than explicit and were
assessed by non-blinded investigators.
Cost
Economic and cost-effectiveness analyses of healthcare technologies and systems

are frequently plagued by imprecise and unclear methodology [52]. This is the case
for the limited data available to examine cost-effectiveness of ERP as compared
with TC. In 2014, two systematic reviews [20, 29] on the economic impact of ERP
in colorectal surgery were published encompassing a total of 10 studies, including
two randomized controlled trials (Table 43.3). The authors found significant
heterogeneity in the methods used to the calculate costs and the types of factors
considered. Most studies reported only direct hospital charges with few considering
hospital overhead, cost of implementation of the ERP, or indirect costs such as loss
of productivity by patients or caregivers. In total, eight of the 10 studies reported
lower costs with ERP as compared to TC, including all four American studies [21,
22, 25, 28], two Australasian studies [12, 27], and two out of four European studies
[14, 23, 24, 26]. Lee et al. were able to generate incremental cost-effectiveness
ratios for five of the 10 studies, with all five showing ERP to be dominant (less
costly and more effective) with regard to LOS [20]. Two studies published in 2015
reported cost data from retrospective comparisons of ERP and TC cohorts. Thiele
et al. [53] reported a significant decrease of $7,129/patient in direct costs, while
Ehrlich et al. [54] found a trend toward lower in-hospital costs with ERP that did not
reach statistical significance.
Quality of Life
The impact of ERP on patient satisfaction and QoL remains unclear. It stands to
reason that most patients place a high value on resuming normal activities and
returning to their homes. On the other hand, some patients may have a negative
perception of ERP if they feel rushed out of the hospital before they are ready.
Unfortunately, it is difficult to objectively measure these perceptions and their
relative importance to patients. A systematic review by Khan et al. examined the
available evidence regarding QoL and patient satisfaction of colorectal surgery
patients managed by ERP or TC [42]. The authors included four randomized
controlled trials and six comparative cohort studies, with mostly small numbers
of patients (Table 43.3). There was significant heterogeneity in the instruments
used for assessment, the outcomes examined, and the timing of measurements.
Only two studies used a validated global QoL index [5, 26] with neither finding
a difference between ERP and TC at time of discharge or post-operative day
(POD) 30.
Five studies compared pain scale values [4, 5, 7, 38, 43], though all at different
time periods. Three of these found no difference between the groups in pain scores
at any point [7, 38, 43]. One study found significantly increased pain in the TC
group on POD 1 [4], while another found increased pain at discharge in the ERP
group [5]. In the later study, the day of discharge was significantly earlier in the ERP
group so the discharge pain scores were closer to the date of surgery. Neither study
found a difference in pain scores between the groups at POD 7 or POD 30. Seven
studies assessed fatigue levels between the two approaches, with three finding no
difference at any time point [7, 36, 43] and another four finding increased fatigue in
the TC groups at various points in the early postoperative period [4, 38, 44, 45]. A
single included study reported patient satisfaction scores of ERP vs. TC patients.
The authors reported similar scores (50.4 and 49.8 out of a potential 80; p = 0.84)
between ERP and TC patients on a 16 question satisfaction survey, with an 80 %
Table 43.4 Summary of the evidence evaluating enhanced recovery pathways vs. traditional care
for colectomy
Quality of
Outcome Summary evidence Comment
Complications Consistently decreased with Low Inconsistency
ERP in multiple meta- Small magnitude of
analyses of randomized trials effect
Readmission No increase with ERP in Moderate Study quality
multiple meta-analyses of Publication bias
randomized trials
Length of Stay Consistently decreased with High Imprecision
ERP in multiple meta-
analyses of randomized trials
Cost Consistently decreased with Low Study quality
ERP in all available studies Inconsistency
Imprecision
Publication bias
Quality of Life/Patient No decrease with ERP in any Low Study quality
Satisfaction study; similar or slightly Inconsistency
improved in most studies Small magnitude of
effect
response rate in both groups. The Cochrane review concluded that more research is
necessary to clarify the effect of ERP on QoL [41].
Wang et al. recently published the results of a prospective trial of ERP vs. TC
after open colectomy for cancer [55]. Using validated, cancer-specific QoL instru-
ments, the authors found significantly better scores in multiple domains including
global QoL, physical and emotional functioning, pain, appetite, gastrointestinal
symptoms, and financial difficulties in patients treated by ERP as compared to
TC. The large, multicenter prospective trial by Vlug et al. examined QoL and patient
satisfaction in a four-armed study comparing laparoscopic and open colectomy with
or without ERP and found no differences in either outcome between the four groups
[14]. An ongoing multicenter prospective trial comparing open colectomy plus TC,
open colectomy plus ERP, and laparoscopic colectomy plus ERP aims to assess
QoL as a secondary outcome and may provide additional information [56].
A summary of the findings and grading of the evidence for each outcome is pre-
sented in Table 43.4.
“Patients undergoing open colectomy should be managed by a standardized

Enhanced Recovery Pathway designed to preserve preoperative function, minimize
surgical stress, and hasten return to normal activities.”
Strength of recommendation: strong
Quality of the evidence: low

The strength of this recommendation reflects our confidence that the desirable
effects of ERP outweigh the undesirable effects, as influenced by the magnitude of
the treatment effect, the quality of the evidence, and the value placed on the out-
comes of interest, in accordance with the GRADE approach to developing guide-
lines [57]. We placed a high value on the avoidance of complications and readmission.
While the quality of the evidence regarding complications is low, based on signifi-
cant heterogeneity and a modest treatment effect, there is no data to suggest that
ERP are unsafe or associated with any increase in harm. The safety of ERP is further
supported by numerous trials demonstrating a lack of difference in readmission
when patients are managed by ERP. This is a consistent finding with low heteroge-
neity, though there is a risk for observational error.
If there is no undesirable effect of ERP on patient safety, the question becomes if
there is any improvement in either resource utilization or patient quality of life.
There is abundant evidence that implementation of ERP leads to shorter LOS after
colorectal surgery. Hospital LOS is a reliable, objective, and easy to measure out-
come and the quality of the evidence supporting the positive effect of ERP is high.
Whether this reduction in hospital stay is associated with a reliable decrease in
resource utilization and healthcare system costs is less clear, for the reasons stated
above. The quality of the evidence in this regard is poor, but no studies have sug-
gested that overall expense is increased by the use of ERP, even when costs of
implementing the program are considered [27]. The available literature suggests
that there is no negative effect on QoL or patient satisfaction when patients are man-
aged by ERP.
Despite the shortcomings of the available evidence, there is ample data that the
institution of ERP is associated with a decrease in some postoperative complica-
tions and a reduction in hospital stay, without an increase in readmissions. There is
no data to suggest that patients managed by ERP are dissatisfied with being fed
earlier or allowed to return to their homes sooner. In fact, the limited evidence (and
common sense) would suggest that QoL improves when complications are avoided
and patients are able to return to their normal activities. While health system costs
may be of minimal importance to individual patients, the impact on the practice of
medicine and healthcare economics cannot be overlooked. In an era of diminishing
resources, clinician efforts to be cost-effective are paramount to sustainability.
The concept of “enhanced recovery” and the specific components constituting a
pathway is a moving target. It is frequently assumed that individual interventions,
shown to be beneficial on their own, will have an additive effect when combined
into multidimensional pathways. The inherent problem with this approach however
is that it becomes very difficult to weigh the individual merits of a particular
intervention when multiple variables are instituted at once. This problem is further
compounded by the fact that the literature on ERP rarely includes the degree of
compliance to specific measures within pathways and infrequently uses blinded
data collectors. Furthermore, the natural course of medicine is such that treatments
or interventions which seem radical at first, such as avoiding NG tubes after colec-
tomy, eventually become part of standard practice, thereby altering “traditional
care” and blurring the lines between ERPs and modern surgical management.
We and others believe that a critical part of a successful ERP is the audit of one’s
own data and the willingness to adapt. For various reasons certain components of an
ERP may cease to become efficient or cost-effective in a given setting. A perfect
example in our practice is that of intravenous acetaminophen, which we abandoned
in favor of the oral form when the price of the drug more than doubled. If epidurals
are slow to be placed and poorly managed in a particular hospital, they are unlikely
to have a benefit. Proper education of the staff and adherence to the protocol is para-
mount to success, and deviations from the pathway should be analyzed
periodically.
How We Do It
Since 2000, we have managed patients according to a standardized ERP which has
been modified and refined over time [58–62]. We use a similar protocol for open and
laparoscopic colectomy, except where noted below. In the preoperative phase we
focus on patient education, medical optimization, and avoiding physiologic derange-
ments. Patients are counseled in the office about the details of their procedure and
their anticipated post-operative course. They are provided with printed instructions
for the days leading up to surgery as well as the expected course of recovery and
rehabilitation. Patients with an anticipated need for a stoma are referred to a sepa-
rate appointment with our certified enterostomal therapists for marking and educa-
tion. Pre-anesthesia evaluation and testing is ordered based on the results of a
standardized risk assessment form.
We prescribe gabapentin 300 mg 3 times daily for 3 days prior to surgery and
100 mg of diclofenac for the night before surgery. On the day of surgery patients are
encouraged to drink clear liquids until 2 h before surgery. They are provided with a
high carbohydrate beverage to be consumed on the way to the hospital. We use
mechanical bowel preps selectively. We order mechanical and antibiotic bowel prep
on all rectal cancer patients and in settings where a diverting ostomy is deemed
likely. This is consistent with recommendations from the ERAS Group on rectal and
pelvic surgery [63]. We avoid mechanical bowel prep for right colectomy when
there is no anticipated need for intraoperative colonoscopy. We make a point to
inform our anesthesiologists whether the patient has had mechanical bowel prep to
help them gauge preoperative volume status.
In the preoperative holding area patients are ordered an additional 300 mg gaba-
pentin, appropriate antibiotic and thromboembolic prophylaxis, and alvimopan
12 mg if the procedure is planned as open or has a high risk of conversion. In lapa-
roscopic colectomy using our ERP, the typical LOS is the same or better than the
published median for laparoscopic colectomy with alvimopan, so we have not
appreciated a benefit in these patients [59, 64]. We avoid thoracic epidurals for pain
control, having found no benefit to their use in randomized trials of laparoscopic
and open colectomy [65, 66]. Intraoperatively patients are actively warmed and IV
fluids are given judiciously as determined by our anesthesiologists familiarized with
ERP principles. We routinely perform transversus abdominus plane (TAP) blocks at
the conclusion of laparoscopic and open procedures [67–71]; we do not use NG
tubes or drains after colectomy. Post-operatively patients are ordered IV patient
controlled analgesia (PCA) plus 650 mg of oral acetaminophen every 4 h beginning
immediately after surgery. Gabapentin 300 mg every 8 h and ketorolac 15 mg IV
every 6 h are given for up to 72 h unless there is preexisting renal dysfunction or
high risk of bleeding. Bisacodyl 10 mg daily is given beginning the following day.
Patients are given noncarbonated liquids and chewing gum on the evening of sur-
gery and are walked with the assistance of their nurse.
On post-op day 1, the PCA and Foley catheter are removed. Laparoscopic colec-
tomy patients who have tolerated liquids are given a soft diet on post-op day 1 and
their IV fluids are hep-locked. We continue liquid diets until day 2 after open proce-
dures. Oral narcotics are offered in addition to the other analgesic modalities if
needed. Patients are instructed to walk the halls (roughly 60 m) up to 5 times per
day, sit in a chair between walks, and use an incentive spirometer at regular inter-
vals. Before discharge patients must be passing flatus, tolerating solid food, com-
fortable on oral analgesia, and have adequate home support as assessed by the
discharge planner on the hospital floor. Adherence to our protocol has been greatly
facilitated by trying to keep our patients on a single hospital ward and the hiring of
dedicated nurse practitioners who provide consistency in the face of frequently
changing housestaff and fellows.
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62. Keller DS, Stulberg JJ, Lawrence JK, Delaney CP. Process control to measure process improve-
ment in colorectal surgery: modifications to an established enhanced recovery pathway. Dis
Colon Rectum. 2014;57(2):194–200.
63. Nygren J, Thacker J, Carli F, et al. Guidelines for perioperative care in elective rectal/pelvic
surgery: Enhanced Recovery After Surgery (ERAS((R))) Society recommendations. World
J Surg. 2013;37(2):285–305.
64. Delaney CP, Craver C, Gibbons MM, et al. Evaluation of clinical outcomes with alvimopan in
clinical practice: a national matched-cohort study in patients undergoing bowel resection. Ann
Surg. 2012;255(4):731–8.
65. Zutshi M, Delaney CP, Senagore AJ, et al. Randomized controlled trial comparing the con-
trolled rehabilitation with early ambulation and diet pathway versus the controlled rehabilita-
tion with early ambulation and diet with preemptive epidural anesthesia/analgesia after
laparotomy and intestinal resection. Am J Surg. 2005;189(3):268–72.
66. Senagore AJ, Delaney CP, Mekhail N, Dugan A, Fazio VW. Randomized clinical trial compar-
ing epidural anaesthesia and patient-controlled analgesia after laparoscopic segmental colec-
tomy. Br J Surg. 2003;90(10):1195–9.
67. Keller DS, Ermlich BO, Delaney CP. Demonstrating the benefits of transversus abdominis
plane blocks on patient outcomes in laparoscopic colorectal surgery: review of 200 consecu-
tive cases. J Am Coll Surg. 2014;219(6):1143–8.
68. Keller DS, Ermlich BO, Schiltz N, et al. The effect of transversus abdominis plane blocks on
postoperative pain in laparoscopic colorectal surgery: a prospective, randomized, double-blind
trial. Dis Colon Rectum. 2014;57(11):1290–7.
69. Favuzza J, Delaney CP. Outcomes of discharge after elective laparoscopic colorectal surgery
with transversus abdominis plane blocks and enhanced recovery pathway. J Am Coll Surg.
2013;217(3):503–6.
70. Favuzza J, Delaney CP. Laparoscopic-guided transversus abdominis plane block for colorectal
surgery. Dis Colon Rectum. 2013;56(3):389–91.
71. Favuzza J, Brady K, Delaney CP. Transversus abdominis plane blocks and enhanced recovery
pathways: making the 23-h hospital stay a realistic goal after laparoscopic colorectal surgery.
Surg Endosc. 2013;27(7):2481–6.
Chapter 44
Quality Improvement: Preventing
Readmission After Ileostomy Formation
Najjia N. Mahmoud and Emily Carter Paulson
Introduction
Readmission after surgery is a problem that is increasingly recognized by surgeons,

patients, insurers, and hospitals. It exposes patients to additional risk and increases
expense in a variety of predictable ways. Readmission can occur for a number of
reasons but in colorectal surgery it falls into a few broad categories: complications
related to the operative procedure, functional complications as a result of the proce-
dure, and medical complications unrelated to the procedure but related to hospital-
ization, anesthesia, or patient comorbidities. Relatively common reasons for
readmission following discharge after elective colorectal operation include surgical
site infection (wound infection and anastomotic leak or intra-abdominal abscess),
high ileostomy output and dehydration, and symptomatic venous thrombosis events.
In recent years, a focus on quality metrics has highlighted deficiencies that are pos-
sible to target by planned interventions resulting in improvement in patient clinical
outcomes as well as health system resource allocation. Surgical site infection and
venous thrombosis prevention have been the subject of numerous studies. There are
evidence-based guidelines and recommendations focused on creating pathways and
specific interventions for these issues already and a chapter on evidence and recom-
mendations could easily be written on each of these problems. Acceptable interven-
tions for ileostomy dehydration are not as well studied and therefore consensus is
more difficult.
Readmission following diverting ileostomy in colorectal surgery is a frequent occur-
rence and could serve as a target for future quality improvement programs. A recent
retrospective review of over 75,000 patients undergoing colectomy with either primary
N.N. Mahmoud (*) • E.C. Paulson

Department of Surgery, University of Pennsylvania, Philadelphia, PA, USA

DOI 10.1007/978-3-319-40223-9_44
504 N.N. Mahmoud and E.C. Paulson
anastomosis, colostomy, or ileostomy revealed that ileostomy patients return to the

hospital at a much more frequent rate than those patients who do not have an ileostomy
[1]. In this group, almost 40 % of the ileostomy patients had a hospital-based acute care
encounter within 30 days of their initial discharge. Over 17 % of these encounters were
secondary to either renal failure and/or fluid and electrolyte disorders from dehydra-
tion. This result is consistent with many other studies published in the past 5 years
regarding readmission following ileostomy [1–6]. In these studies, the overall readmis-
sion rate for patients with new ileostomies ranged from 17 % to over 40 %. Dehydration
and/or renal failure accounted for up to 40 % of these readmissions.
Pre-operative stoma education with involvement of enterostomy nurses, includ-
ing preoperative marking of the planned stoma site, have been advocated as a
means to reduce stomal complications. Much of this discussion, however, has
focused on prevention of mechanical stomal problems, such as leakage due to mal-
position, and on the psychosocial preparation required for adapting to life with an
ostomy [7, 8]. There has been little published regarding interventions targeted at
reducing the high rate of readmission following ileostomy, especially readmission
due to the dehydration and electrolyte imbalances that can accompany high ileos-
tomy output. The aim of this chapter is to identify and review the published litera-
ture regarding interventions aimed at reducing readmission following ileostomy
formation.
Search Strategy
We searched the PubMed database from January 1, 2005-January 1, 2016 to identify

studies (including meta-analyses, randomized controlled trials, and retrospective
cohort studies) relevant to readmission following ileostomy formation. The search
terms were: “ostomy” or “ileostomy” or “stoma” and “readmission” or “dehydra-
tion” or “renal failure”. The articles were screened by title and abstract by both
authors. English-only articles were included if they evaluated a specific ostomy-
focused intervention at the time of stoma creation (pre- or post- creation) and
reported on the outcome of interest--readmission.

Patients undergoing Patient education; stoma Traditional Readmission
ileostomy teaching management
Results
Only three articles were identified that specifically discussed stoma-related inter-
ventions and readmission (Table 44.1) [9–11]. The quality of evidence of these stud-
ies is rated as low.
44 Quality Improvement: Preventing Readmission After Ileostomy Formation 505
Table 44.1 Studies of Ileostomies and Readmission Rates

Quality
Outcome of Traditional Enhanced of
Study Study design Patients interest management education evidence
Nagle Uncontrolled 203 Readmission 35.4 % 21.4 % Low
[9] before and Loop or rates
(2012) after end
ileostomy
Younis Uncontrolled 240 Readmission 2.5 % 0 % Low
[10] before and Loop or rates
(2012) after end
ileostomy
Phatak Systematic NA Readmission NA NA Low
[11] Review rates
(2014)
In 2012, Nagel et al. published the results of a non-randomized before-and-

after trial examining the impact of a well-defined ileostomy pathway on readmis-
sion following formation of a new ileostomy [9]. Their pathway included
preoperative education, standardized ileostomy teaching materials, in-hospital
teaching including direct patient engagement with their ileostomy, and strict post-
discharge tracking of fluid input and output.. The authors compared readmission
rate for new ileostomy patients over the 7 months after implementation of the
pathway (n = 42) to the rate for new ileostomy patients for the 4 years prior
(n = 161). The overall readmission rate dropped from 35.4 to 21.4 % after the
pathway was initiated, but this was not statistically significant (p = 0.28). The
readmission rate for dehydration, however, dropped from 15.5 to 0.0 % with
adoption of the ileostomy pathway (p = 0.02). These authors conclude that their
overall decrease in readmissions was almost exclusively “due to preemptive man-
agement of potential diarrhea and dehydration by patient’s self-management of
their input and output.”
In 2012, Younis et al. published the results of a non-randomized trial evaluating
the impact of focused preoperative patient stoma education on post-ileostomy out-
comes [10]. In this study, the stoma intervention was included as part of a larger
enhanced recovery program (ERP) being evaluated. Patients in their ERP received
a stoma instructional DVD and a “practice pack” to allow them to practice ileos-
tomy care preoperatively. Prior to ERP, the patients at their institution had only
received routine information and counselling at their surgical preoperative visit. The
authors compared 120 patients who underwent ileostomy after institution of the
ERP to 120 patients who underwent ileostomy in the 2 years prior to ERP. They
found that delay in hospital discharge caused by delay in independent stoma man-
agement was reduced from 17.5 % in the pre-ERP group to 0.8 % in the ERP group
(p < 0.001). Their readmission rate was very low compared to almost all other pub-
lished studies. Only 2.5 % of the pre-ERP patients were readmitted, compared to
0 % of the ERP group, although this was not a statistically significant difference
(p = 0.001)
Finally, in 2014, Phatak et al. published a systematic review of educational inter-

ventions for ostomates [11].This group only identified 3 articles, two of which are
discussed above, that reported rates of readmission following new ostomy from a
total of 7 articles that evaluated any stoma education intervention. They conclude
that the quality of evidence regarding educational interventions and readmission
following ostomy surgery is low. Of note, the third article identified in this review
was a randomized-trial published by Delaney et al. in 2003 evaluating the impact of
a postoperative care pathway using controlled rehabilitation with early ambulation
and diet (CREAD) on outcome after intestinal resection. Upon review of this article,
there is no clear description of specific stoma-related interventions. The authors do
mention that CREAD patients received “supporting written information document-
ing the expected post-operative milestones.” As such, it is hard to draw any conclu-
sions related to stoma-specific interventions and readmission from this trial, which
is why it is not included in our review.
It should be quite obvious that the data related to specific ileostomy pathways for
prevention of readmission, and specifically readmission for dehydration, is quite
sparse. Furthermore, the data that is available is low quality. Even so, there are many
institutions that have implemented ad hoc ileostomy counseling and have encour-
aged pathway development in an effort to prevent the well-known complication of
post-discharge dehydration and readmission.
There is good reason to believe from the study by Nagle et al., that an appro-
priately powered, prospective study would likely show that a programmatic
approach to providing specific counselling to prevent dehydration results in a
reduction of readmissions. But there are also compelling reason to believe that
the additional benefits of counselling new ostomates obviates the need for level
1 data In reality, stoma interventions including pre- and post-operative counsel-
ling and education and patient-driven pathways to track and balance post-dis-
charge fluid management pose minimal risk to new ostomates. The benefits,
however, can improve quality of life and decrease readmission and cost of care.
Our practice includes, when possible, preoperative stoma site marking and coun-
selling with an enterostomal therapist, in-hospital counselling and education,
and post-discharge visiting nursing.
Preoperative ileostomy marking can ensure that the planned ileostomy is in a
position that enables the avoidance of leakage, skin excoriation, and facilitates pat-
ent self-care. It is also an opportunity to counsel, educate, and reassure. New osto-
mates desire and require preoperative education to set expectations and alleviate
anxiety. They need to know what to expect both in the hospital and afterwards. Data
in the field of education supports the fact that repetitive exposure to the same set of
educational objectives reinforces desirable behaviors and, in this case, helps com-
pliance. The patient should be reassured that they will receive stoma education
44 Quality Improvement: Preventing Readmission After Ileostomy Formation 507
again prior to discharge and be helped and supervised in the care of their own
ostomy prior to discharge.
Personal Recommendations Based on the Data
While published data is scarce, the basics of post-discharge ileostomy management

is actually quite simple. In our practice, prior to hospital discharge, patients should
be able to:
1 . Change their own appliance.
2. Make daily measurements of output and record 24 h totals until the first office
visit.
3. Be aware of dietary restrictions.
4. Be familiar with 2–3 interventions for reducing output.
5. Have recourse to contact help if confused or ill.
Specific interventions include:
1. An ileostomy checklist reviewed, point-by-point, with a caregiver prior to dis-
charge. Review with both patient and family members can help reinforce
compliance.
2. A 24 h chart for documenting output.
3. Ensuring that the patient can participate in his or her own care by viewing a
change of appliance in the hospital.
4. A list of foods to avoid in the post-operative period.
5. A graduated measuring vessel and a specific 24 h total ileostomy output to
target.
6. A list of interventions and medications to try if output exceeds the target.
7. A reliable call-in number for the patient to reach out to the office in the event of
questions or concerns that will be answered within several hours.
Other interventions that may be offered that are quite valuable and improve
patient satisfaction include routine and automatic referral to visiting nurse services
for new ostomates, calls from the office in the early discharge period to reinforce
checklist, measurement, and dietary compliance, and reminder texts and emails via
secure medical portals to ensure that directions are followed.
Although it seems logical that program like this should reduce readmissions, it is
also likely that overall institutional and practitioner compliance is poor. Improvement
in our ability to administer complex pathways is dependent upon diffusion of
knowledge of goals of care to all members of the team including floor nurses and
social workers and home nurses, and empowerment of ancillary providers to pro-
vide counselling and materials for ileostomy care postoperatively. A pathway such
as the one outlined is not difficult to organize, it is simply hard to routinely admin-
ister. Providing alternative means (data pushed out via electronic medical records
and secure portals) and empowering personnel (floor nurses, advanced p ractitioners,
stoma therapists, social workers) may allow us to improve the efficacy of these
pathways in the future.
References
1. Tyler JA, Fox JP, Dharmarajan S, et al. Acute health care resource utilization for ileostomy
patients is higher than expected. Dis Colon Rectum. 2014;57(12):1412–20.
2. Åkesson O, Syk I, Lindmark G, Buchwald P. Morbidity related to defunctioning loop ileos-
tomy in low anterior resection. Int J Colorectal Dis. 2012;27(12):1619–23.
3. Hayden DM, Pinzon MC, Francescatti AB, et al. Hospital readmission for fluid and electrolyte
abnormalities following ileostomy construction: preventable or unpredictable? J Gastrointest
Surg. 2013;17(2):298–303.
4. Paquette IM, Solan P, Rafferty JF, Ferguson MA, Davis BR. Readmission for dehydration or
renal failure after ileostomy creation. Dis Colon Rectum. 2013;56(8):974–9.
5. Messaris E, Sehgal R, Deiling S, et al. Dehydration is the most common indication for read-
mission after diverting ileostomy creation. Dis Colon Rectum. 2012;55(2):175–80.
6. Campos-Lobato LF, Alves-Ferreira PC, Oliveira PG, Sousa JB, Vogel JD. What are the risk
factors for readmission in patients with an ileostomy? J Coloproctol. 2013;33(4):203–9.
7. McKenna LS, Taggart E, Stoelting J, Kirkbride G, Forbes GB. The impact of preoperative
stoma marking on health-related quality of life: a comparison cohort study. J Wound Ostomy
Continence Nurs. 2016;43(1):57–561.
8. Person B, Ifargan R, Lachter J, Duek SD, Kluger Y, Assalia A. The impact of preoperative
stoma site marking on the incidence of complications, quality of life, and patient’s indepen-
dence. Dis Colon Rectum. 2012;55(7):783–7.
9. Nagle D, Pare T, Keenan E, Marcet K, Tizio S, Poylin V. Ileostomy pathway virtually elimi-
nates readmissions for dehydration in new ostomates. Dis Colon Rectum.
2012;55(12):1266–72.
10. Younis J, Salernoa G, Fanto D, Hadjipavlou M, Chellar D, Trickett JP. Focused preoperative
patient stoma education, prior to ileostomy formation after anterior resection, contributes to a
reduction in delayed discharge within the enhanced recovery programme. Int J Colorectal Dis.
2012;27:43–7.
11. Phatak UR, Li LT, Karanjawala B, Chang GJ, Kao LS. Systematic review of educational inter-
ventions for ostomates. Dis Colon Rectum. 2014;57(4):529–37.
Part VIII
Technique
Chapter 45
Trans-anal Endoscopic Surgery vs.
Conventional Transanal Surgery
Theodore J. Saclarides
The treatment of rectal cancer has evolved substantially over the years. Treatment
options available to the patient and surgeon over the years have been determined by
available instrumentation and technology as well as the ability to care for the sick
patient in terms of anesthetic techniques and knowledge of critical care medicine
and antisepsis. Prior to 1908, transanal and posterior approaches dominated and, by
today’s standards, these choices were oncologically inadequate. In 1908, Sir Ernest
Miles published his report of an operation which now bears his name and with his
technique; radical removal not only of the tumor bearing segment of bowel was
performed, but also the regional lymphatics of the rectum.
Although radical resection remains the oncologic standard for the treatment of
patients with rectal cancer, there is substantial morbidity due to both the pelvic dissec-
tion and the stoma when necessary. Complications related to the former include genito-
urinary dysfunction (e.g., impotence and urinary retention) and to the latter include
hernias and skin issues. It has been questioned whether taking on this morbidity is justi-
fied for very early tumors where possibly more conservative surgery could achieve simi-
lar oncologic outcomes, but without the higher morbidity and mortality. This has been
debated for decades and the debate will continue. Further, many patients are not medi-
cally fit for radical surgery; consequently alternative surgical methods have been sought
and even combined with adjuvant therapy in some instances. As such, transanal resec-
tion of rectal cancer remains an important aspect of the surgeon’s armamentarium.
Conventional transanal resection involves using a variety of hand held or self
retaining retractors to gain exposure. The patient is usually positioned in the exag-
gerated prone jack-knife position and the overhead lights are directed into the
T.J. Saclarides, MD
The Section of Colon and Rectal Surgery, Loyola University School of Medicine,
Maywood, IL, USA

DOI 10.1007/978-3-319-40223-9_45
512 T.J. Saclarides
rectum; the surgeon may also wear a headlight for illuminating the surgical field.
Standard surgical instruments are the norm. The lesion is visualized, surrounding
tissue is grasped, and stay sutures are placed around the lesion in order to bring it
down into view. The lesion is removed while attempting to avoid fragmentation of
the specimen, obtain negative margins, and to handle complications that arise such
as bleeding or entry into the peritoneal cavity or vagina. Limited upward reach and
poor exposure have restricted the surgeon to the distal-most rectal lesions. Yet for
even such tumors, being able to remove the lesion in one piece with negative mar-
gins has remained a challenge. Reported recurrence rates as high as 30 % have
restricted wholesale acceptance of transanal excision of rectal cancers [1].
In order to circumvent the limitations posed by conventional instruments,
Professor Gerhard Buess pioneered and developed Transanal Endoscopic
Microsurgery (TEM) in the mid 1980’s during the dawn of the era of minimally
invasive surgery. His equipment utilizes a closed, air-tight system that insufflates
carbon dioxide into the rectum where it is retained and distends the rectal vault.
Visibility is obtained through a fiberoptic scope that has an extended field of view
relative to standard laparoscopes. The scope is inserted through a rigid rectoscope
which is 40 cm in diameter and sealed with an airtight face piece. The scope may be
connected to an adapter to enable viewing on a video screen. This “pneumorectum”,
combined with the high definition optics and the long shafted instruments, has
extended the application of transanal surgery to larger and more proximal lesions.
The instruments are inserted through working ports in the sealed facepiece and are
manipulated in parallel. The most important component of the system is the endo-
surgical unit which regulates four different functions at once: carbon dioxide insuf-
flation, irrigation, suction, and monitoring of the intrarectal pressure. Once the
system is setup and the surgeon verifies there is no air leak within the system, cau-
tery points are placed around the lesion such that at least a one centimeter margin of
normal tissue is obtained surrounding the lesion. The tumor is removed by dissect-
ing either within the submucosal plane or by traversing the full thickness of the
rectal wall into the perirectal fat. Most surgeons routinely close the rectal wall in a
transverse fashion. The specimen is submitted for histologic analysis and decisions
are made whether or not additional therapy is needed. Occasionally, the treating
physicians decide that radical surgery is needed because of the presence of unfavor-
able features. Complications include bleeding, wound dehiscence, entry into the
peritoneal cavity, rectovaginal fistula, and fecal soilage, which is short lived and
temporary in the majority of cases.
Recently, industry has entered the fray and a variety of different platforms are
available for the surgeon who wishes to practice Transanal Endoscopic Surgery
(TES). There are distinct differences in the systems, yet they all share certain unify-
ing features. First, this surgery is an endoscopic, intraluminal operation aided by the
insufflation of carbon dioxide. Secondly, visibility is obtained with the use of fiber-
optic laparoscopes or scopes specifically designed for this purpose instead of direct
vision as with conventional transanal surgery. Thirdly, long shafted instruments
allow excision of lesions beyond the reach of conventional instruments. Many reports
describe being able to remove lesions beyond 15 cm from the anal canal. Fourth,
TES is technically demanding and advanced training is required, although a skilled
45 Trans-anal Endoscopic Surgery vs. Conventional Transanal Surgery 513
laparoscopist can master TES in a short time. Lastly, because of the extended utility
of this type of surgery, many of the lesions referred for excision are the recurrent or
persistent tumors that failed successful management with conventional instruments.
Publications describing TEM appeared sparsely in the medical literature in the
1980’s. In fact, most of the papers were written by Buess himself. Over the next
three decades, more manuscripts were written and range in character from small
series describing a novel application of the technology to large meta-analyses. It is
difficult to compare TEM/TES with other conservative operations for rectal cancer
not only for the reasons mentioned above, but also because once surgeons master
the technique, they cannot resort to older methods simply for the sake of a compara-
tive research study. This is certainly the case for this author. Nevertheless, it will be
the focus of this chapter to review the literature comparing TES platforms with
other methods. The specific factors that will be assessed are whether TES is more
likely to obtain negative margins, cause less tissue fragmentation, produce fewer
complications, and yield better outcomes with respect to tumor recurrence. The
articles chosen for this review were found using a PubMed computer search using
the terms “transanal excision” and “transanal endoscopic microsurgery” from 2003
to 2016. Alternative methods to TES include conventional transanal excision, pos-
terior approaches such as the Kraske operation, and endoscopic mucosal (EMS) and
submucosal dissection (ESD). Table 45.1 outlines the objectives of the study.
Results
Table 45.2 summarizes the literature. The table is organized to reflect those factors
for which TEM/TES (collectively referred to as TES) has advantages to, is equal to,
or is disadvantageous compared to the alternative techniques. Overall there is a
paucity of manuscripts comparing these techniques with the other methods of local
excision. As stated above, a randomized prospective study is not likely to appear
because once the technique is mastered, some form of TES will become the pre-
ferred approach for surgeons. There is only one prospective, randomized study and
excision of only adenomas is considered. [2] Of the remaining studies, there are 3
meta-analyses, [3–5] one systematic review, [6] and several retrospective series
[7–14] where the control groups are within the same institution, other institutions,
or literature based. Study designs are generally flawed.
Table 45.1 PICO Table

Patients TES Patients undergoing Negative margins, tumor
undergoing conventional transanal fragmentation, recurrence
transanal excision, posterior approach, rates, perioperative
endoscopic or endoscopic submucosal or outcomes
surgery (TES) mucosal resection
(alternative methods)
Table 45.2 Analyzed studies
514
Results
Level of Alternative >
Author (year) Study type evidence Patients TES > alternativea TES=alternative TESb
Clancy (2015) [4] Systematic review 492 TES, 435 Negative margins Complication rate
conventional Less tissue
transanal excision fragmentation
Recurrence rate
Moore (2008) [9] Retrospective 82 TES, 89 Negative margins Complications
conventional Less fragmentation
Recurrence rate
Winde (1996) [2] Prospective 90 TEX, 98 Local recurrence
randomized conventional;
adenomas only
Sgourakis (2011) [3] Meta-analysis TES vs conventional Negative margins
for T1 and T2 cancers Disease free survival
Han (2012) [8] Case controlled 53 TES, 76 Local recurrence Operative time
conventional Distance from anus
de Graaf (2010) [7] Case controlled 216 TES, 43 Operative time
conventional; all complications
adenomas Negative margins
Less fragmentation
Local recurrence
Lebedyev (2009) Retrospective 24 TES, 18 Negative margins
[10] conventional; all T1 complications
cancer recurrence
Christoforidis (2009) Retrospective 42 TES, 129 Negative margins Disease free survival
[1] conventional; fragmentation for tumors ≥ 5 cm
postoperative
adjuvant therapy
T.J. Saclarides
Langer (2003) [11] Retrospective 79 TES, 76 Local recurrence 2 year survival
conventional; T1 and
T2 cancers and
adenomas
Nakagoe (2003) [12] Case controlled 45 TES, 26 posterior Operative time, blood
approach; adenomas loss, length of stay
and cancer analgesic need
complications
Hitzler (2015) [6] Systematic review TES vs Endoscopic In European literature:
Submucosal Negative margins
Dissection. European Fragmentation
and Japanese Complications
Literature
Lin (2006) [13] Retrospective 31 TEM, 51 Length of stay Mortality
Posterior Approach Time to oral intake Resection margins
different hospitals, Analgesic need Recurrence
benign and malignant
Arezzo (2014) [5] Systematic review 1407 TEM, 490 ESD En bloc resection Complications
benign and RO resection Recurrence rate for
malignanty adenoma
Kawaguti (2014) Retrospective review 13 TEM, 11 ESD En bloc resection
[14] Operative time
Hospital stay
45 Trans-anal Endoscopic Surgery vs. Conventional Transanal Surgery
a
Advantage in favor of TES
b
Alternative methods superior to TES
515
516 T.J. Saclarides
Regarding complications, there are no differences when comparing TES with

conventional transanal excision; however TES generally has fewer complications
when compared to the posterior approach [12] and in Hitzler’s study of patients
undergoing ESD [6]. Compared to conventional transanal surgery, TES is associ-
ated with longer operative times but this may be due to the time required for patient
positioning, equipment set up, and troubleshooting carbon dioxide leaks when they
occur [8]. Other potential disadvantages include the need for advanced training,
mastering the learning curve and the cost of the equipment, but no comparative
studies exist regarding these issues. Because of these factors, combined with the
technical difficulty of performing TES, it is not likely that TES will be performed
by the surgeon whose practice has a low volume of patients with suitable lesions.
TES has definite advantages compared to conventional transanal resection, and
these are consistently noted in the manuscripts. TES is superior with respect to
being able to obtain negative margins surrounding the lesion [1, 3, 4, 7, 9], and
being able to remove the lesion en bloc, intact and without fragmentation [1, 4, 7,
9]. These advantages are directly related to improved visibility because of the pneu-
morectum and the high definition optics. The end result is being able to provide the
pathologist with a better specimen to study, and since this often drives decisions
regarding whether or not additional treatment is necessary, this is extremely impor-
tant. In the meta-analysis provided by Clancy et al., a lower recurrence rate with
TES was noted, along with a lower incidence of positive margins and tumor frag-
mentation [4]. In the meta-analysis of patients with T1 and T2 cancers by Sgourakis
et al., an improved disease free survival was noted [3]. A lower incidence of positive
resection margins and tumor fragmentation was noted in the majority of the retro-
spective series as well.
There has been debate as to who “owns” the rectal adenoma or the superficial
cancer; the surgeon or the gastroenterologist. If the lesion is persistent or recurrent
following endoscopic resection (ESD), the patient should be referred to a TES sur-
geon after one attempt. All too often, patients are referred only after multiple polyp-
ectomies, laser or argon plasma coagulations, or ESD have been performed and
such practices can render the subsequent TES operation more technically difficult
and/or make it harder to close the wound. Certainly, if the lesion has a central ulcer-
ation or depression or does not lift well with saline injection, consideration should
be given to prompt referral to a TES surgeon without attempting to remove it with
alternative endoscopic methods.
Author’s View of the Data
TES and alternative methods of local excision are different operations and it is
incorrect to compare the two. TES requires advanced training, the equipment is
more expensive, the learning curve must be mastered, and surgeon volume must
support maintaining skills. Having said that, TES is the preferred method of local
excision because it enhances our ability to obtain negative margins and remove the
lesion without fragmentation. In some series, this leads to a lower recurrence rate,
45 Trans-anal Endoscopic Surgery vs. Conventional Transanal Surgery 517
however, the strength of the data is suspect. The debate will continue and will not
likely be answered with an adequately powered, prospective randomized study in
the future.
References
1. Christoforidis D, Cho HM, Dixon MR, Mellgren AF, Madoff RD, Finne CO. Transanal endo-
scopic microsurgery versus conventional transanal excision for patients with early rectal can-
cer. Ann Surg. 2009;249:776–82.
2. Winde G, Schmid KW, Reers B, Bunte H. Microsurgery in prospective comparison with con-
ventional transanal excision or anterior rectum resection in adenomas and superficial carcino-
mas. Langenbecks Arch Chir Suppl Kongressbd. 1996;113:265–8.
3. Sgourakis G, Lanitis S, Gockel I, Kontovounisios C, Karaliotis C, Tsiftsi K, Tsiamis A,
Karaliotas CC. Transanal endoscopic microsurgery for T1 and T2 rectal cancers: a meta-
analysis and meta-regression analysis of outcomes. Am Surg. 2011;77:761–72.
4. Clancy C, Burke JP, Albert MR, O’Connell PR, Winter DC. Transanal endoscopic microsur-
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Surg Endosc. 2014;28:1173–9.
Chapter 46
Laparoscopic Versus Robotic Versus Open
Surgery for Rectal Cancer
Campbell S. Roxburgh and Martin R. Weiser
Clinical Scenario A 64-year-old male completed neo-adjuvant chemo-radiotherapy

for a cT3bN+ adenocarcinoma at 11 cm from the anal verge 5 weeks ago. Repeat
MRI demonstrates tumor downsizing. He is aware that surgery involves open or
minimally invasive approaches. He wants to return to work as soon as possible but
above all wants surgery with the highest chance of “cure.”
Question Which of the surgical approaches for rectal cancer resection (open vs.
laparoscopic vs. robotic) results in the best outcomes?
Background When choosing among operative approaches, outcome measures fall

into two broad categories: (1) those related to short and long-term sequelae of the
radical resection (surgical morbidity, return to function, and quality of life), and (2)
those related to the disease process (recurrence, disease-free and overall survival).
Both open and minimally invasive (laparoscopic and robotic) techniques may be
employed to perform total mesorectal excision (TME) for rectal cancer. Here we
aim to review outcomes for each approach to aid decision making.
We make two comparisons:
A. Compared with open surgery, does laparoscopic surgery result in better out-
comes after rectal cancer treatment? (Table 46.1a)
B. Compared with laparoscopic surgery, does robotic-assisted surgery result in bet-
ter outcomes after rectal cancer treatment? (Table 46.1b)
C.S. Roxburgh
Memorial Sloan Kettering Cancer Center, New York, NY, USA
M.R. Weiser, MD (*)
1275 York Avenue, New York, NY 10065, USA

DOI 10.1007/978-3-319-40223-9_46
520 C.S. Roxburgh and M.R. Weiser
Table 46.1 (a) Laparoscopic versus open surgery for rectal cancer and (b) robotic versus
laparoscopic surgery for rectal cancer – PICO tables
(a) Patient Intervention Comparator Outcomes studied
population
Rectal cancer, Laparoscopically Open TME Procedure related
post neoadjuvant performed TME morbidity
chemo- Length of stay,
radiotherapy complications – grade 3/4/5,
anastomotic leak, reoperation
Oncologic
CRM involvement, distal
resection margin
involvement, distance to
CRM, distance to distal
resection margin, LN yield,
completeness of TME
Disease specific survival,
overall survival, local
recurrence
(b) Patient Intervention Comparator Outcomes studied
population
Rectal cancer, Robotically Laparoscopically Procedure related
post neoadjuvant performed TME performed TME Length of stay,
chemo- complications – grade 3/4/5,
radiotherapy anastomotic leak,
reoperation, cost, open
conversion
Oncologic
CRM involvement, distal
resection margin
involvement, distance to
CRM, distance to distal
resection margin, LN yield,
completeness of TME
Disease specific survival,
overall survival, local
recurrence
Methods/Search Strategy Studies reporting short- and long-term results for rectal
cancer surgery in which a proportion of patients received neoadjuvant treatment
were reviewed. Rectal cancer was defined as a tumor 15 cm or less from the anal
verge. Laparoscopic surgery was defined as completion of the pelvic dissection
using laparoscopic instruments. Non-conventional laparoscopic techniques were
excluded (e.g., hand-assisted or single-port surgery). Robotic surgery was defined
as completion of the pelvic dissection using a robotic platform. PubMed, Ovid, Web
of Science and Cochrane databases were searched using terms “rectal cancer”, “lap-
aroscopy”, “open”, “robot”, and “robotic” for studies up to December 1, 2015. We
sought to review the highest quality evidence with emphasis on Level 1/2 data. For
46 Laparoscopic Versus Robotic Versus Open Surgery for Rectal Cancer 521
comparison (A), five multicenter RCTs have reported data pertinent to this question
and therefore the meta-analysis focused on their results. For comparison (B), no
prospective randomized data is available. If multiple reports were published from
one institution, the most recent series was evaluated.
esults: (A): Laparoscopic Surgery Versus Open Surgery

R
for Rectal Cancer
Description of Studies Five multicenter RCTs have been undertaken to evaluate

laparoscopic surgery versus open surgery in rectal cancer: the CLASICC, COREAN,
COLOR II, ACOSOG Z6051 and ALaCaRT trials [1–5]. Trial characteristics and
results are summarized in Table 46.2. Long-term outcomes are reported by
CLASICC, COREAN and COLOR II. Each trial was designed with a slightly dif-
ferent rationale for power calculation and outcome reporting. CLASICC recruited
413 colon and 381 rectal cancer patients and was powered not by an outcome
assessment; but on the need to evaluate laparoscopic colorectal surgery in a trial
setting by examining differences between treatment arms for a range of endpoints
[1]. The COREAN trial recruited 170 patients per arm with tumors ≤10 cm from the
anal verge after neoadjuvant chemoradiotherapy [2]. The trial assessed non-
inferiority of laparoscopic surgery based on 3-year disease-free recurrence. COLOR
II recruited 1044 patients (699 laparoscopic vs. 345 open) with tumors ≤15 cm from
the anal verge to assess non-inferiority of laparoscopic surgery based on 3-year
local recurrence rates [3]. ACOSOG Z6051 recruited 462 patients (240 laparoscopic
vs. 222 open) with tumors ≤12 cm from the anal verge after neoadjuvant treatment
[4]. The trial was powered to detect non-inferiority of laparoscopic surgery based on
a composite pathological endpoint: completeness of TME, negative circumferential
margin (CRM) and negative distal resection margin (DRM). ALaCaRT had a simi-
lar design, recruiting 475 patients (238 laparoscopic vs. 237 open) with tumors
≤15 cm from the anal verge to assess non-inferiority of laparoscopic surgery based
on a composite pathological endpoint [5].
Short Term Outcomes

Length of hospital stay (LOS) No differences in LOS were seen in the COREAN,
ACOSOG Z6051, or ALaCaRT trials. In contrast, CLASICC and COLOR II
reported lower LOS in the laparoscopic group (CLASICC: 11 vs. 13 days; COLOR
II: 8 vs. 9 days). The COREAN trial demonstrated a trend towards reduced LOS in
the laparoscopic arm (8 vs. 9 days P = 0.056), but unlike ALaCaRT and ACOSOG
Z6051, consistently better short-term outcomes were also observed for the laparo-
scopic group (e.g. earlier passing of flatus, earlier defecation, and resumption of
normal diet). The equivocal short-term outcomes for treatment groups in ACOSOG
Table 46.2 Perioperative and oncologic outcomes from published multicenter randomized controlled trials comparing laparoscopic versus open surgery for
522
rectal cancer (laparoscopic/open)

CLASICC (Rectal
Trial cancers) COREAN COLOR II ACOZOG Z6051 ALaCaRT
Design Phase 3 multicenter Non-inferiority phase Non-inferiority phase Non-inferiority phase Non-inferiority phase
RCT 3 multicenter RCT 3 multicenter RCT 3 multicenter RCT 3 multicenter RCT
Number of centers 27 3 30 35 24
Location United Kingdom South Korea Europe North America Australia and NZ
Number (lap/open) 253/128 (ITT) 170/170 699/345 240a/222 238/235
160/132 (ATG)
Time period 1996–2002 2006–2009 2004–2010 2008–2013 2010–2014
Site of tumors Mid-low rectum ≤15 cm of AV ≤12 cm from AV Within 15 cm of AV
<10 cm from AV
Treatment group Lap Open Lap Open Lap Open Lap Open Lap Open
% receiving neoadjuvant 58 60 100 100 59 58 100 100 50 49
treatment
BMI median (meanb) 26 25b 24.1 24.1 26.1 26.5b 26.4 26.8b 27 26
Perioperative outcomes
Conversion 34 1 16 11 9
LOS (days) 11 13 8 9 8 9 7.3 7.0 8 8b
Mean operative time (min) 244 197 240 188 266 220 210 190b
Complications 0.0 0.0 1.1 1.7 21.7 21.1 18.5 26.4
Grade 3/4 (%) 0.8 0.9 0.4 0.8
Grade 5 (%)
Anastomotic leak (%) 10 7 1.2 0 13 10 2.1 2.3 3 3
Reoperation (%) 1.8 1.8 6 6 5 2.3
Oncological outcomes
CRM negative ≤1 mm (%) 84 86 97.1 95.9 93 91 87.9 92.3 93 97
DRM negative (%) No difference 98.3 98.2 99 99
C.S. Roxburgh and M.R. Weiser
Complete/nearly complete TME 91.8 88.2 97 98 92.1 95.1 97 99
(%)
Composite endpoint 82 87 82 89
Mean LN yield 17 18 13 14 17.9 16.5
Distance DRM (mm) 20 20 30 30b 32 31b 26 30
Distance to CRM (mm) 9 8 10 10b 10.5 12.8b 10 12
3 year DFS 70.9 70.4 79.2 72.5 74.8 70.8
OS 74.6 66.7 91.7 90.4 86.7 83.6
LR 9.7 10.1 2.6 4.9 5.0 5.0
Data presented as median unless otherwise stated
RCT randomized controlled trial, NZ New Zealand, TME total mesorectal excision, AV anal verge, BMI body mass index, LOS length of stay, ITT intention to
treat, ATG actual treatment group, CRM circumferential resection margin, DRM distal resection margin, LN lymph node, DFS disease free survival, OS overall
survival, LR local recurrence
a
Includes 34 Robot assisted procedures
b
Mean
46 Laparoscopic Versus Robotic Versus Open Surgery for Rectal Cancer
523
Z6051 and ALaCaRT may relate to the use of hybrid approaches permitted in the
open arms.
Complications, Anastomotic Leak and Reoperation Rates Clavien-Dindo grade

3/4/5 complication were comparable for open and laparoscopic surgery in the
ACOSOG Z6051 and ALaCaRT trials. The COREAN and COLOR II trials reported
similar rates of infectious and noninfectious complications and short-term mortality
in each trial arm. CLASICC reported higher perioperative morbidity and mortality
in patients converted from laparoscopic to open surgery. Complication rates for
laparoscopic, open and converted rectal cancer operations were 32 %, 37 % and
59 %, respectively. No trial reported a difference in anastomotic leak or reoperation
rates.
Short Term Outcomes Summary Mean LOS after rectal cancer surgery ranged
from 7 to 9 days across the treatment arms. Although two trials reported reduced
LOS with laparoscopic surgery, we conclude that LOS is comparable for each
approach. Rates of complications, anastomotic leaks and reoperation are also
equivocal.
Conclusion
The assessed short-term outcomes are comparable for laparoscopic and open
surgery.
GRADE: HIGH QUALITY
Oncologic Outcomes
Circumferential resection margin involvement Excepting CLASICC, all trials

reported non-involved CRM rates in excess of 87 %, underlining the technical skills
of the surgeons participating in this study. No trial was powered based solely on
CRM assessment. Clear CRM rates were comparable in all five trials (Table 46.2).
In a subgroup analysis of anterior resections, CLASICC reported a nonsignificant
trend towards higher CRM involvement for laparoscopy (12 % vs. 6 % based on 16
positive CRMs in 129 laparoscopic versus 4 positive CRMs in 64 open resections).
Distance to CRM was comparable in COREAN, COLOR II and ALaCaRT. However,
ACOSOG Z6051 reported reduced distance to CRM with laparoscopy (10.8 vs.
12.8 mm, P = 0.03).
Distal margin DRM involvement was low (1–2 %) and incidence was equivalent
where it was reported (Table 46.2) [1, 4, 5].
Complete/nearly complete TME No differences in rates of complete/nearly com-

plete TME were reported where this outcome was assessed (Table 46.2) [1–5].
Composite pathological outcomes Both ACOSOG Z6051 and the ALaCaRT trials
used a composite pathological assessment as their primary outcome measure. Both
trials were powered based on the assumption that 90 % of rectal cancer resections are
oncologically complete (CRM negative, DRM negative, and complete/nearly com-
plete TME). ACOSOG Z6051 stated non-inferiority would be declared if the lower
border of the 95 % CI for difference between groups was >6 %. ALaCaRT set a simi-
lar non-inferiority threshold of >8 %. In ACOSOG Z6051, a complete specimen was
achieved in 81.7 % of laparoscopic versus 86.9 % of open resections (5.2 % differ-
ence, lower bound 95 %, CI −10.8). For ALaCaRT, a complete specimen was
achieved in 82 % of laparoscopic versus 89 % of open resections (7.0 % difference,
lower bound 95 %, CI −12.4). For each trial, non-inferiority was not established.
Lymph node (LN) yield No trial reported a difference in number of LNs retrieved
between treatment arms for laparoscopic versus open surgery (Table 46.2).
Long-term oncologic outcomes Three trials (CLASICC, COREAN, COLOR II)

published long-term outcomes [6–9]. CLASICC reported a trend towards increased
CRM involvement with laparoscopic surgery but this failed to translate into detect-
able difference in terms of local recurrence (LR) (9.7 % vs. 10.1 %), disease-free
survival (DFS) (70.9 % vs. 70.4 %) and overall survival (OS) (74.6 % vs. 66.7 %) at
3 years. CLASICC also reported a non-significant trend towards improved OS and
DFS in Stage I rectal cancer in the laparoscopic arm. The COREAN trial reported
3-year DFS rates of 79.2 % vs. 72.5 % (6.7 % difference, 95 % CI −15.8 to 2.4).
Laparoscopic surgery therefore was deemed non-inferior. No differences were
reported between groups for 3-year OS or LR rates (Table 46.2). COLOR II reported
no difference in 3-year LR (5 % vs. 5 %), concluding laparoscopy is non-inferior.
However, the results favored slightly improved outcomes for laparoscopic surgery
in terms of 3-year DFS (74.8 % vs. 70.8 %) and OS (86.7 % vs. 83.6 %). The most
pronounced difference between groups was seen in Stage III disease (DFS 64.9 %
vs. 52 %).
Oncologic Outcomes Summary No trial has demonstrated a statistically mean-

ingful difference between techniques for CRM and DRM involvement, TME com-
pleteness or LN yield. ACOSOG Z6051 reported reduced distance to CRM with
laparoscopic surgery, an observation not repeated elsewhere. Using a composite
pathological assessment, two trials reported open surgery had higher rates of “onco-
logically complete” resections. Results from three trials demonstrated comparable
long-term oncologic outcomes.
Conclusion
The assessed oncologic and long term outcomes are comparable for laparo-
scopic and open surgery.
GRADE: HIGH QUALITY
esults: Robotic Surgery Versus Laparoscopic Surgery

R
for Rectal Cancer
Description of Studies We identified 43 studies in which outcomes for both

robotic and laparoscopic surgery were reported between 2006 and 12/1/15, 28 of
which were published in the last 3 years, with 17 published in 2015 alone. Most
studies originated in Korea (19) and the United States (10), followed by Italy (3)
Spain (2), Japan (2), Taiwan (2) Turkey (2), Switzerland (1), Romania (1) and
Canada (1). No prospective randomized trials have been published evaluating the
role of robotic surgery versus laparoscopic surgery for rectal cancer. Three early
studies were small, randomized pilot series which aimed to evaluate feasibility of
robotic surgery (Baik et al., 2008, n = 18 and Patriti et al., 2009, n = 29, Jimenez
Rodriguez et al., 2010, n = 6) [10–12]. Two studies report audit outcomes from the
American College of Surgeons (ACS) National Cancer Database (NCDB) [13, 14].
The remainder (38 studies) are single/multicenter case series, the majority of which
(n = 26) analyze outcomes from <50 robotic cases. Of 12 series in which ≥50 robotic
cases are reported, several originate from the same center, reported at different time
points. Outcomes from the six largest series are presented in Table 46.2 [15–20].
Finally, seven meta-analyses have reviewed between 7 and 17 studies to assess
robotic versus laparoscopic surgery for rectal cancer [21–27].
Short Term Outcomes
Length of hospital stay Based on pooled data from published meta-analyses in

addition to reported data from the ACS NCDB, LOS is comparable for robotic and
laparoscopic surgery for rectal cancer [13, 14, 21, 22, 24, 26, 27].
Complications, anastomotic leak and reoperation rates Published meta-

analyses report no differences in complications rates between the techniques [21–
24, 26, 27]. Furthermore, rates of anastomotic leak or reoperation are comparable.
ACSNCDB data also report comparable Grade III/IV complications and short-term
mortality after robotic (n = 1217) and laparoscopic (n = 4700) resections [14].
Cost Robotic surgery is more expensive in comparison to laparoscopic surgery.

Park et al. reported the cost of robotic rectal cancer surgery was 2.4 times that of
laparoscopic surgery per patient episode [28]. Other recent reports suggest the dis-
parity in cost is not as great; Ramji et al. (n = 70) reported costs of $18,273 for
robotic vs. $11,493 for laparoscopic rectal surgery per episode [29], and Kim et al.
reported costs of $15,965 vs. $11,933 per hospital episode [30].
Conversion Meta-analyses report consistently lower rates of conversion to open

surgery for robotic (1.1–3 %) versus laparoscopic (6–7.5 %) surgery [22, 24, 26,
27]. The odds ratios for the reduction in risk of conversion using robotic versus
laparoscopic surgery were 0.26 (95 % CI 0.12–0.57, P < 0.001) reported by Trastulli
(2011) and 0.23 (95 % CI 0.10–0.52, P < 0.001) reported by Xiong in 2013 [21, 26].
Short Term Outcomes Summary Based on meta-analyses of non-randomized

studies and audit series, short-term outcomes are equivalent for robotic and laparo-
scopic surgery. Robotic surgery has lower rates of conversion to open and is consid-
erably more expensive.
Conclusion
The assessed short-term outcomes are comparable for robotic and laparo-
scopic surgery.
GRADE: LOW QUALITY
Oncologic Outcomes
CRM involvement Across the six larger series reviewed, low rates of CRM
involvement were reported, ranging from 0 to 8 % for robotic surgery and 1–12 %
for laparoscopic surgery. No series demonstrated a statistically lower rate of CRM
involvement with robotic surgery, consistent with pooled results from meta-analyses
[21–24]. ACSNCDB data also report equivalent rates for CRM involvement (5 %)
[13, 14]. However, one meta-analysis of eight studies, published in 2014, reported
lower CRM involvement with robotic surgery (2.7 % vs. 5.8 %) [25].
DRM involvement One meta-analysis published in 2011 reported lower rates of

DRM involvement with robotic surgery [24], but later meta-analyses published in
2012 and 2014 reported no difference [21, 23, 25]. Equivalent DRM rates were seen
in the six larger series detailed in Table 46.3 [15–20]. ACS NCDB data also reported
equivalent rates for DRM involvement (5 %) with both techniques [14].
Complete/nearly complete TME One small study by Baik reported higher rates
of complete/nearly complete TME after robotic surgery [31].
Lymph node yield No differences in lymph node yield in resection specimens

were reported in meta-analyses [21, 23, 24, 26, 27] or ACS NCDB reports [13, 14].
Long-term oncologic outcomes Two large case series from Korea reported data
on long-term outcomes at 3 and 5 years, revealing comparable OS, DFS and LR
rates for the two techniques [15, 18]. Using ACS NCDB data, Sun et al. observed
comparable OS at 3 years (1217 robotic vs. 4700 laparoscopic resections) [14].
Oncologic Outcomes Summary Based on meta-analyses of non-randomized

studies and audit studies, measures of pathological quality and long-term outcomes
appear to be comparable for both robotic and laparoscopic surgery for rectal
cancer.
Conclusion
The assessed long-term outcomes are comparable for robotic and laparo-
scopic surgery.
GRADE: LOW QUALITY
Recommendations
A. After neoadjuvant treatment, patients with non-margin-threatening rectal cancer

may be managed by either open or laparoscopic TME as long-term outcomes for
each technique appear comparable (Evidence Strong; strong
recommendation).
B. Although data from prospective, randomized studies is awaited, robotic surgery
does not appear to be inferior to laparoscopic surgery for TME in terms of short
and long-term outcomes (Evidence Weak, weak recommendation)
Personal View The implementation of MIS in colorectal cancer treatment has
brought with it reduced surgical trauma and stress with a more rapid return to func-
tion and is widely regarded as the major development in colorectal surgery in the
past 20 years. Rectal cancer surgery requires technical competence and outcomes
are improved by surgical specialization and increased case volume [32]. This is
especially critical for TME performed using MIS techniques. To date, equivalent
long-term oncologic outcomes are reported with both laparoscopic and open TME;
some subgroup analyses suggesting improved outcomes with the laparoscopic tech-
nique. Questions over the oncologic adequacy for laparoscopic TME have arisen
from analyses of surrogate pathological endpoints. This is the case in the ALaCaRT
and ACOSOG Z6051 studies, which employed a novel composite pathological
assessment. The endpoint was based on retrospective studies correlating these path-
ological characteristics with recurrence. Interestingly, no differences between the
individual components of the composite score (CRM and DRM clearance and com-
pleteness of TME) were seen between the treatment groups in each study. This
composite has not been validated to date as a risk assessment for recurrence, but was
employed by these studies to enable early analysis. Long-term results with recur-
rence data are ultimately required to draw final conclusions on its prognostic impor-
tance. This is especially relevant given CLASICC initially reported higher CRM
involvement after laparoscopic TME, a finding that failed to translate into a mean-
ingful difference in long-term oncologic outcome beyond 5 years [7].
Colorectal surgeons are faced with several RCTs which draw somewhat conflict-
ing conclusions. The most mature data demonstrates no difference in long-term
outcomes and significant weighting should be afforded to these studies. Nonetheless,
Table 46.3 Perioperative and oncologic outcomes from largest published studies comparing robotic versus laparoscopic surgery for rectal cancer (robotic/
laparoscopic)
Yamaguchi
Study Park JS (2011) D’Annibale (2013) Ielpo (2015) Cho MS (2015) Park JS (2015) (2015)
Design Retrospective case Retrospective case Retrospective case Case matched Multicenter case Prospective case
series comparison series comparison series comparison retrospective matched series comparison
retrospective
Number of centers 1 1 1 1 7 1
Location South Korea Italy Spain South Korea South Korea Japan
Time period 2007–2009 2004–2012 2012–2013 2007–2011 2008–2011 2010–2015
Site of tumors ≤15 cm from AV Patients undergoing ≤15 cm from AV Patients undergoing Patients undergoing Transection
TME TME ISS with CAA below peritoneal
refection
Treatment group Rob Lap Rob Lap Rob Lap Rob Lap Rob Lap Rob Lap
Number 52 123 50 50 56 87 278 278 106 106 203 239
% neoadjuvant 23.1 8.1 68 56 82 81 67.3 78.8 64.2 56.6 0.5 0
treatment
BMI median 23.7 23.6 22.8 23.7 23.5 23.5 24.3 23.8 23.4 23.1
Perioperative outcomes
Conversion (%) 0 0 0 6 1.8 9.2 0.7 0.4 0.9 1.9 0 1.8
LOS (days) 10.4 9.8 8/10 10 13 10 10.4 10.7 9.9/ 1.7 7.3 9.3
Mean operative 233 158 270 280 309 252 361 272 271 232 232 227
46 Laparoscopic Versus Robotic Versus Open Surgery for Rectal Cancer
time (min)
Complications 7.7 4.9 7.1 5.7 12.2 12.2 6.6 11.3 0 0
30 days 0 0 0 0 0 0.4 0 0
Grade 3/4 (%)
Grade 5 (%)
(continued)
529
530
Yamaguchi
Study Park JS (2011) D’Annibale (2013) Ielpo (2015) Cho MS (2015) Park JS (2015) (2015)
Anastomotic leak 9.6 5.6 10 14 9.5 4.5 10.4 10.8 3.8 5.7 1.5 2.9
(%)
Reoperation (%) 5.3 3.4
Oncologic outcomes
CRM ≥1 mm (%) 98.1 97.6 100 88 96.4 97.7 95.0 95.3 92 91 100 99
DRM negative (%) 100 100 99 97 98.8 98.8 100 100
Mean LN yield 19.4 15.9 16.5 13.8 10 9 15.2 16 13.2 15.2 30 29
Distance to DRM 28 32 30 30 20 22 12 12 28 32
(mm)
Distance to CRM 7.9 8.2 6.9 7.2
(mm)
3 year 5 year 5 year 89.6 90.5
DFS 81.8 79.6 93.8 94.8
OS 92.2 93.1 6.7 5.7
LR 5.9 3.9
Data presented as median unless otherwise stated
TME total mesorectal excision, AV anal verge, ISS intesphincteric dissection, CAA coloanal anastomosis, BMI body mass index, LOS length of stay, CRM cir-
cumferential resection margin, DRM distal resection margin, LN lymph node, DFS disease free survival, OS overall survival, LR local recurrence
CRM <2 mm
C.S. Roxburgh and M.R. Weiser
surgeons should be prepared to make treatment decisions and recommendations

based on both patient and tumor characteristics, respecting the patient’s own
informed choices. To conclude, no data exists to suggest that long term outcomes
are worse with laparoscopy. Providing the surgeon is competent to perform the lapa-
roscopic TME, both open and laparoscopic techniques can be offered based on indi-
vidual treatment considerations.
Robotic rectal cancer surgery is evolving and to date, meta-analyses suggest
equivocal short-term outcomes to laparoscopic techniques. The UK MRC ROLARR
trial is the first multicenter RCT examining robotic surgery compared with laparo-
scopic surgery for rectal cancer and outcomes are eagerly awaited [33]. No published
results are available but preliminary data presented at the American Society of
Colon and Rectal Surgeons Annual Meeting in 2015 reported low CRM involve-
ment (5 %) and a complete/near complete TME in 89 % in the robotic arm. If con-
firmed in the final report, this data is comparable to published data for laparoscopic
surgery. The published literature consistently demonstrates lower rates of open con-
version with robotic surgery, suggesting robotic platforms may enhance ability to
complete more challenging cases with minimally invasive techniques (e.g. high
BMI; narrow pelvis; low, locally advanced tumor).
We favor the use of the robotic platform for MIS in rectal cancer. This stance is
based on the perceived benefits of robotic surgery, improved visualization and
increased dexterity of the instruments. These benefits in our view enable the opera-
tor to perform a more precise and detailed dissection with greater ease than conven-
tional laparoscopic surgery alone.
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Chapter 47
Reservoir Construction After Low Anterior
Resection: Who and What?
David A. Liska and Matthew F. Kalady
Introduction
The two key major outcomes after surgical treatment of rectal cancer are oncologic
and functional. Improved understanding of tumor biology and advanced surgical
techniques have led to improved oncologic results and also increased rates of
sphincter-preserving procedures for low rectal cancers. This trend, however, has
brought to light the functional consequences following low anterior resection (LAR)
with total mesorectal excision (TME) and coloanal anastomosis (CAA). Many
patients who have undergone sphincter-preserving low or ultra-low anterior resec-
tions with a straight CAA experience defecatory symptoms that can include fre-
quency, urgency, clustering, incomplete evacuation, constipation, diarrhea, and
incontinence [1]. This collection of symptoms, also known as low anterior resection
syndrome (LARS),is partially attributable to the loss of the reservoir function of the
rectum.
In an attempt to improve functional outcomes, different surgical techniques have
been devised for the creation of a neo-rectal reservoir in lieu of a straight
CAA. Lazorthes et al. [2] and Parc et al. [3]initially described a neo-rectal reservoir
creation in the form of a colonic J pouch in 1986. Due to anatomic constraints in
some patients (especially obese male patients with a narrow pelvis), a low anasto-
mosis with a J-pouch is sometimes not technically feasible. Therefore, other reser-
voir options in addition to the colonic J pouch have been described and evaluated,
including transverse coloplasty, and side-to-end CAA. Each of these options has its
distinct advantages and disadvantages when compared to a straight CAA. This
chapter reviews the literature on this topic comparing the different types of reservoir
D.A. Liska, MD • M.F. Kalady, MD (*)

Department of Colorectal Surgery, Cleveland Clinic, Cleveland, OH, USA

DOI 10.1007/978-3-319-40223-9_47
536 D.A. Liska and M.F. Kalady
Table 47.1 Structure of the analysis performed to evaluate different techniques of reservoir
construction
Patient population Intervention Comparators Outcomes studied
Rectal cancer patients Colonic reservoir Straight coloanal Postoperative
undergoing low creation: J-pouch, anastomosis morbidity and
anterior resection with transverse coloplasty, functional outcomes
coloanal anastomosis or side-to-end
anastomosis
construction and formulates clinical recommendations. A summary of the structure

of this analysis is provided in Table 47.1
Search Strategy
A systematic literature search was conducted in the following bibliographic data-

bases: MEDLINE (using PubMed) and the Cochrane Library since the inception of
the databases until October 2015. In addition, reference lists of published system-
atic reviews were searched manually. Publications not written in English were
excluded. Given the availability of multiple randomized controlled trials (RCTs),
non-randomized trials were excluded. Only trials comparing two reconstructive
procedures were included for review. Studies reporting on results with less than
6 months follow up were excluded with regards to functional outcomes. No restric-
tions were applied with regard to publication date. Titles and abstracts of retrieved
studies were screened for relevance and eligibility. Results from the most recent
meta-analyses were also included in this review. Full texts of all eligible studies
were retrieved and reviewed.
Results
Our literature search retrieved 20 RCTs that prospectively compared outcomes with
a straight CAA to one of the colonic reservoirs or compared outcomes between dif-
ferent types of colonic reservoirs (Table 47.2). We reviewed ten RCTs comparing a
straight anastomosis (SA) to a colonic J pouch (JP), six studies comparing a JP to a
transverse coloplasty (CP), four studies comparing a JP to a side-to-end anastomo-
sis (STE), and one study comparing a SA to a CP. The vast majority of studies used
a circular stapled technique for the coloanal anastomosis. The largest published
RCT, by Fazio et al. [18],randomized patients in whom a JP was technically feasible
to receive either a JP or a CP, and if a JP was not feasible to receive either a SA or a
CP. For clarity sake, this study was treated as two separate studies in Table 47.2. Our
review also included one well-designed, recently published meta-analysis [25] and
the most recent Cochrane systematic review published in 2008 [26].
47 Reservoir Construction After Low Anterior Resection: Who and What? 537
Table 47.2 Summary of randomized controlled trials included in this review

Anastomotic Follow-up
Study N leak (months) BM/24 h Continence Urgency
SA JP SA JP SA JP SA JP SA JP
Straight coloanal (SA) vs. colonic J pouch (JP)
Seow Chen 20 20 0 0 6 4 2*
(1995) [4] 12 2 2 − +* − +
Ortiz (1995) 19 19 2 2 12 11a 5a* − + − +
[5]
Hallbook 52 45 8 1* 2 6.4 2* − +* − +*
(1996) [6] 12 3.5 2* − +* − +*
Lazorthes 19 18 2 1 3 ~5 ~2* − + − +*
(1997) [7] 12 ~4.5 ~2* − + − +
24 ~3.5 ~2* = = + −
Ho (2000, 19 16 0 0 6 15b 6b* − +* = =
2001) [8, 9] 12 7.1 4.6* − + + −
24 7b 3b − + = =
Furst (2002) 37 37 3 3 6 4.7 2.5* − +* − +
[10]
Oya (2002) 21 20 0 0 6 4 3 − + = =
[11] 12 3 2.5 − + = =
Sailer 32 32 4 3 3 1.2c 1.2c − +* = =
(2002) [12] 12 1.3 c 1.3 c = = = =
Park (2005) 26 24 0 0 3 ~11 ~5* − +*
[13] 12 ~6 ~5 − +*
Liang 24 24 0 0 3 7 4* − + + −
(2007) [14] 6 6.5 4* − + + −
Colonic J pouch (JP) vs. transverse coloplasty (CP)
Ho (2002) 44 44 0 7* 4 4.5 4.6 − +* − +*
[15] 12 3 3.4 − + = =
Pimentel 15 15 1 2 3 4.1 3.9 + − − +
(2003) [16] 6 3.4 3.1 + − − +
12 2.8 2.1 + − = =
Furst (2003) 15 20 = = 6 2.75 2 − + − +
[17]
Fazio (2007) 137 131 4 6 4 3 4* + −* + −
[18] 12 3 3* + − + −
24 2 3* + −* + −
Ulrich 68 76 6 6 1
(2008) [19]
Biondo 54 52 1 1 6 29b 31b = = = =
(2013) [20] 36 9b 10b = = + −
(continued)
Anastomotic Follow-up
Study N leak (months) BM/24 h Continence Urgency
SA JP SA JP SA JP SA JP SA JP
Straight coloanal (SA) vs. transverse coloplasty (CP)
Fazio (2007) 49 47 5 4 4 6 5.5 − +* − +
[18] 12 4 4 = = − +
24 3 2.5 = = − +
Colonic J pouch (JP) vs. side-to-end (STE)
Huber 29 30 3 2 3 2.2 5.4* + − + −
(1999) [21] 6 2.2 3.1* = = + −
Machado 50 50 4 5 6 3.4 3.4 = = + −
(2003) [22] 12 3.1 3.0 = = + −
Jiang (2005) 24 24 0 0 3 4 4 = = = =
[23] 12 2.3 1.9 = = = =
24 1.9 2 = = = =
Doeksen 55 52 10 9 4 28 42d + −*
(2011) [24] 12 21 30d + −*
+ Indicates better function (i.e., better continence and less urgency)
*p < 0.05
a
Number of patients with >3 BM per day
b
Number of patients with >4 BM per day
c
Mean result of two point score > 5 BM = 0, 3–5 BM = 1, 1–2 BM = 0
d
Mean of transformed score (0–100) with higher scores indicating worse bowel function
There were some design shortcomings and risks for bias in many of the included
studies. Due to the nature of these trials, a double-blinded design—including blind-
ing of the surgeon—is not feasible. However, it is unfortunate that the majority of
trials do not clearly state if the patients and other study personnel were blinded.
Considering that functional outcomes depend on self reported variables, non-blinding
of patients can lead to significant bias. The majority, but not all of the included trials,
describe appropriate randomization and allocation methods. Attrition and losses to
follow-up were relatively low in most studies. Most of the studies did not specifically
address the experience of the participating surgeons and, as such, allow for some ele-
ment of bias. In all trials, randomization achieved groups that were well-matched in
terms of important preoperative variables that could affect outcomes such as gender,
preoperative bowel function, height of the tumor, and neoadjuvant chemoradiation.
Overall, despite the relatively small number of patients enrolled in each study and the
mentioned design shortcomings, the reviewed RCTs and meta-analyses provide us
with moderate to high quality evidence with relatively low risk of bias [25].
The outcomes reported in the reviewed trials generally include surgical outcomes
in terms of perioperative morbidity and mortality and specifically those related to
anastomotic dehiscence. Some trials supply further, more detailed, perioperative
variables in terms of morbidity, operative times, and length of stay. Except for the
study by Ulrich et al. [19], which only reports short-term perioperative outcomes,
all studies included report outcomes with regards to bowel function. Bowel function
is longitudinally assessed at different time points, which in patients with diverting

ostomies is measured following restoration of intestinal continuity. There is signifi-
cant variability among the different trials in the time points chosen at which bowel
function is assessed. Furthermore, there is great heterogeneity among the different
trials in terms of the specific functional parameters evaluated, questionnaires used
to collect data, and scoring systems used to report outcomes such as incontinence
and urgency. This variability makes it difficult to directly compare results from one
trial to the other. Future research would greatly benefit from the uniform use of a
validated scoring system at defined time points to assess post-operative function in
rectal cancer patients [27].
While all trials assessing functional outcomes document self-reported variables
such as bowel frequency, continence, and urgency, a significant number of trials also
report data from anorectal physiologic assessments conducted in these patients.
Interestingly, differences between the reconstructive options in terms of functional
parameters such as bowel frequency, urgency, and incontinence did often not cor-
relate with anorectal manometric or volumetric measurements. The explanation for
this finding proposed by Furst et al. [10]is that a colonic reservoir such as a J pouch
does not improve function by providing a more capacious reservoir, but is predomi-
nantly related to decreased propulsive motility in the pouch. This theory has gained
widespread acceptance as many investigators have noted minimal or no correlation
between differences in anorectal physiologic measurements and functional
outcomes.
Perioperative Outcomes
Straight CAA Versus Colonic J Pouch
When comparing perioperative complications between a straight CAA and a colonic

J pouch, there was a statistically non-significant trend towards fewer complications
with a colonic J pouch. With regards to anastomotic leaks, only the study by
Hallbook et al. [6] had a significant difference in postoperative complications, with
a reduced rate of anastomotic leaks in patients with a JP compared to patients with
a SA (2 % vs. 15 %, p = 0.03). It is noteworthy that the 15 % leak rate is higher than
most reports in the literature and could account for the statistical difference. The
trial by Jiang et al. [23], in which all procedures were done by laparoscopic-assisted
technique, had similar perioperative outcomes between the JP and SA groups, but
significantly longer operative times for the JP group (274.4 ± 34.0 vs.
202.0 ± 28.0 min, p < 0.001). The other studies reported no significant difference in
operative times. On pooled analyses there was no statistically significant difference
with regards to anastomotic leaks or overall complications between patients with a
JP reconstruction versus a straight anastomosis. It is hypothesized that despite the
additional staple lines required for a colonic JP, the risk for leaks is actually lower
in the JP due to better blood supply to the anastomosis and reduced “dead space” in
the pelvic cavity [13].
Colonic J Pouch Versus Transverse Coloplasty
When comparing perioperative outcomes between colonic J pouch and transverse

coloplasty patients, only the study by Ho et al. [15]showed a statistically significant
difference in the incidence of anastomotic leaks. In that study, seven patients (15.9 %)
in the CP group developed anastomotic leaks compared to zero patients in the JP
group. All leaks in this study developed at the anterior portion of the stapled coloanal
anastomosis below the site of the coloplasty which was made 4 cm proximal to the
anastomosis. In subsequent RCTs, the leak rate in CP patients ranged from 1.9 to
13 %, without any statistically significant differences when compared to JP patients.
Of note, in the study by Fazio et al., comparing CP to a straight CAA reconstruction,
there was also no difference in anastomotic leak rates. It is possible that the increased
leak rate with the CP reservoir found by Ho et al. [15]was due to the contributing
surgeons still being early on the learning curve for this procedure. On meta-analysis
there was no significant increase in leak rates with a transverse CP reconstruction [25].
Side-to-End Versus Colonic J Pouch
In trials comparing STE anastomoses to colonic JP reconstruction, there was no

statistically significant difference in overall complications or anastomotic leaks.
The study by Huber et al. [21] showed significantly shorter operative times for STE
patients compared to JP patients (149 vs. 167 min, p < 0.05), with similar trends in
other trials. On meta-analysis there was again no significant difference with STE
reconstruction in terms of perioperative complications.
In summary, there is no significant difference in perioperative outcomes between the
different reconstructive options assessed by the included trials. There is a trend towards
decreased anastomotic leaks with a colonic JP and STE anastomoses compared to
transverse CP and straight CAA that does not reach statistical significance [25].
Functional Outcomes
Straight CAA Versus Colonic J Pouch
When comparing the functional results following a straight CAA versus a colonic JP
reconstruction, most studies show significantly improved results with a JP, espe-
cially in the first 6–12 months after restoration of intestinal continuity. When specifi-
cally assessing bowel frequency, eight of the ten included RCTs showed significantly
decreased bowel frequency with the JP. In trials assessing functional outcomes at
12 months, the majority of studies still found significantly reduced bowel frequency
with a JP reconstruction. In the study by Lazorthes et al. [7] this held true even at
2 years post restoration of intestinal continuity. However, the study by Ho et al. [8]
demonstrated that at 2 years, in patients with a straight CAA, there was colonic
conduit adaptation and marked reduction of bowel frequency, so that there was no
longer a significant difference compared to patients with a JP. In terms of functional
outcomes related to continence and urgency, the majority of trials demonstrated sig-
nificantly better function with a JP. These benefits however were less pronounced
and usually not significantly different when assessed at 12 months and beyond. On
meta-analysis of the data amenable to pooling, bowel frequency was significantly
lower with a JP at early and intermediate time points, while other measures of bowel
function were not significantly different between the groups [25].
Colonic J Pouch Versus Tranverse Coloplasty
Functional outcomes following a transverse (CP) compare well to those observed

with a JP in most studies. However, the study with the largest number of patients, by
Fazio et al. [18], demonstrated that patients with a JP had significantly lower bowel
frequency and better continence (as measured by the Fecal Incontinence Severity
Index) in the early postoperative months and at 2 years. In that study, 27 % of
patients were ineligible for a JP and were randomized to either a CP or straight
anastomosis. Except for improved continence with a CP in the early postoperative
period, there were no significant functional differences between the CP and the SA
groups. This study was excluded from the meta-analysis due to unclear patient num-
bers at the different follow-up points. The remaining studies comparing a JP versus
CP reconstruction that were included in the meta-analysis did not show any signifi-
cant functional differences [25].
Side-to-End Versus Colonic J Pouch
There are only few RCTs comparing functional outcomes of a STE anastomosis
with colonic JP reconstruction. Only the study by Huber et al. [21]showed signifi-
cantly decreased bowel frequency with a JP, with the longest follow-up being only
6 months. The more recent study by Doeksen et al. [24] found better continence
scores with a JP at 4 and 12 months but similar results with respect to other func-
tional parameters. The other studies and data included in the meta-analysis showed
that functional results following a STE compare well with those of a JP.
Summary of Comparisons
In summary, functional results after a colonic JP are significantly improved when

compared to a straight anastomosis. These benefits are most pronounced in the early
postoperative months, and according to some studies are still apparent at 2 years
following restoration of intestinal continuity. While there is no high-quality data

directly comparing a side-to-end anastomosis to a straight anastomosis, the reviewed
studies demonstrate that functional results following a STE compare relatively well
to those seen with a JP. We therefore would expect a STE anastomosis to provide
better function than a SA. Most studies also suggest that a transverse coloplasty
provides functional benefits similar to a JP. However the transverse coloplasty study
with the largest number of patients, demonstrated significantly better function with
a JP and minimal benefit when comparing TC to a straight anastomosis.
For rectal cancer patients treated by low anterior resection and restoration of the
gastrointestinal tract via CAA, a colonic J pouch should be constructed for the anas-
tomosis as opposed to a straight CAA. There is no difference in perioperative mor-
bidity between the two techniques, but the J pouch reconstruction results in improved
postoperative functional outcomes. This is a strong recommendation based on high
quality evidence. In patients with anatomy not suitable for a colonic J pouch, recon-
struction with a side-to-end anastomosis or transverse coloplasty should be consid-
ered instead of a straight coloanal anastomosis due to improved functional results
As there is limited direct evidence comparing straight coloanal anastomosis to side-
to-end anastomosis or coloplasty, this is a conditional recommendation based on
moderate data.
In our opinion, there is strong evidence based on randomized controlled trials sup-
porting the use of a colonic JP for coloanal anastomosis after low anterior resection
for rectal cancer. This should be the default option for reconstruction as opposed to
a straight coloanal anastomosis. Although there is some bias in the randomized tri-
als, the total body of work overwhelmingly supports this recommendation. We rec-
ognize that there are some clinical situations where creation of a colonic J pouch for
reconstruction is not technically feasible due to the patients anatomy; e.g., an obese
male with a narrow pelvis may not be able to accommodate a colonic J pouch reser-
voir. In these situations, a side-to-end coloanal anastomosis or a transverse colo-
plasty are preferred reconstructions compared to a straight coloanal anastomosis.
Although data directly comparing these latter techniques to a straight coloanal anas-
tomosis are limited, the literature supports similar functional outcomes when
directly comparing colonic J pouch, side-to-end, or transverse coloplasty anastomo-
ses. Therefore, it is logical to expect superior functional outcomes with these tech-
niques as compared to a straight coloanal anastomosis. Therefore in clinical practice,
the authors primarily use a colonic J pouch, but have no reservations using a
side-to-end anastomosis if a colonic J pouch is not feasible. Although a transverse

coloplasty is acceptable, it is not routinely used in our practice.
Abstract of Recommendation
Patients with rectal cancer treated by proctectomy with restoration of bowel conti-
nuity via coloanal anastomosis should receive a colonic J pouch reservoir recon-
struction if technically feasible (strong recommendation; high quality evidence). If
a colonic J pouch to anal anastomosis is not possible, then a side-to-end anastomo-
sis or transverse coloplasty should be performed (conditional recommendation,
moderate quality evidence).
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colonic J-pouch for rectal cancer--a comparative study. Colorectal Dis. 2003;5(5):465–70.
17. Furst A, Suttner S, Agha A, Beham A, Jauch KW. Colonic J-pouch vs. coloplasty following
resection of distal rectal cancer: early results of a prospective, randomized, pilot study. Dis
Colon Rectum. 2003;46(9):1161–6.
18. Fazio VW, Zutshi M, Remzi FH, et al. A randomized multicenter trial to compare long-term
functional outcome, quality of life, and complications of surgical procedures for low rectal
cancers. Ann Surg. 2007;246(3):481–8; discussion 488–90.
19. Ulrich AB, Seiler CM, Z’graggen K, Loffler T, Weitz J, Buchler MW. Early results from a
randomized clinical trial of colon J pouch versus transverse coloplasty pouch after low anterior
resection for rectal cancer. Br J Surg. 2008;95(10):1257–63.
20. Biondo S, Frago R, Codina Cazador A, et al. Long-term functional results from a randomized
clinical study of transverse coloplasty compared with colon J-pouch after low anterior resec-
tion for rectal cancer. Surgery. 2013;153(3):383–92.
21. Huber FT, Herter B, Siewert JR. Colonic pouch vs. side-to-end anastomosis in low anterior
resection. Dis Colon Rectum. 1999;42(7):896–902.
22. Machado M, Nygren J, Goldman S, Ljungqvist O. Similar outcome after colonic pouch and
side-to-end anastomosis in low anterior resection for rectal cancer: a prospective randomized
trial. Ann Surg. 2003;238(2):214–20.
23. Jiang JK, Yang SH, Lin JK. Transabdominal anastomosis after low anterior resection: a pro-
spective, randomized, controlled trial comparing long-term results between side-to-end anas-
tomosis and colonic J-pouch. Dis Colon Rectum. 2005;48(11):2100–8; discussion 2108–10.
24. Doeksen A, Bakx R, Vincent A, et al. J-pouch vs side-to-end coloanal anastomosis after pre-
operative radiotherapy and total mesorectal excision for rectal cancer: a multicentre random-
ized trial. Colorectal Dis. 2012;14(6):705–13.
25. Huttner FJ, Tenckhoff S, Jensen K, et al. Meta-analysis of reconstruction techniques after low
anterior resection for rectal cancer. Br J Surg. 2015;102(7):735–45.
26. Brown CJ, Fenech DS, McLeod RS. Reconstructive techniques after rectal resection for rectal
cancer. Cochrane Database Syst Rev. 2008;(2):CD006040.
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bowel function after sphincter-preserving surgery for rectal cancer. Dis Colon Rectum.
2005;48(7):1353–65.
Chapter 48
Conventional vs Single Port Approaches
to Laparoscopic Colectomy
H. Hande Aydinli and Meg Costedio
Introduction
Multiple multicentered randomized clinical trials confirming the safety, efficacy

and benefits of laparoscopy have arguably made minimally invasive surgery the new
standard of care for colon resection. Both European and American multicenter ran-
domized clinical trials (RCT) demonstrate improved short-term and comparable
long-term outcomes with laparoscopic versus open colon resection [1–7].
It is now established that laparoscopic colorectal resection is associated with less
intraoperative blood loss (EBL) despite a longer operating time, less postoperative
narcotic use, earlier return of bowel function and equal or shorter hospital stay
(LOS) when compared with open surgery [2, 3]. In the early stages of laparoscopy,
skepticism existed about whether laparoscopic colon resection was safe for onco-
logic procedures, both technically as well as the possibility of cancer seeding from
carbon dioxide insufflation. Studies show no difference in the lymph node yield or
the length of resected bowel between laparoscopic and open surgery. The 3 and
5 year follow up publications of RCT’s demonstrate comparable outcomes with
resection margins, mean number of lymph nodes harvested, overall survival,
disease-free survival, and local and distant recurrence [5–7].
As most studies show a longer operative time and an increased cost associated with
laparoscopy, it was initially hypothesized that laparoscopy would not be cost effective
when compared to an open surgical procedure. Multiple RCT’s and a case-matched
study confirm that the total cost, including the treatment of postoperative complica-
H. Hande Aydinli, MD • M. Costedio, MD

Department of Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic,
Cleveland, OH, USA

DOI 10.1007/978-3-319-40223-9_48
546 H.H. Aydinli and M. Costedio
tions and additional hospital stay, are comparable to open surgery [1, 8–12]. Long term
hernia rates were also found to be comparable or lower when laparoscopy was per-
formed [8, 11, 13]. The cosmetic benefits of laparoscopy have never been in question.
As surgeons and technology have advanced, laparoscopy is being attempted in
more complex situations and surgeons are using less ports and advanced instrumen-
tation. Multiple new techniques are being introduced to further minimize trauma to
the patient as well as increase minimally invasive options for complex procedures.
The single incision laparoscopic surgery (SILS) technique for colectomy was first
described by Remzi et al. in 2008, and minimizes the incision solely to the extrac-
tion site, sparing multiple laparoscopic port sites. Since colorectal surgeons almost
uniformly have at least 2–3 cm specimen or are creating a stoma, SILS is particu-
larly applicable to colorectal surgery. Considerable clinical experience has been
accumulated with SILS, but this technique has been scrutinized for many of the
same concerns that were conveyed with conventional laparoscopy (CL) [14].
The aim of this evidence-based chapter is to discuss and answer questions related
to the following issues; (a) what is the evidence regarding safety and feasibility of
SILS in patients who are undergoing laparoscopic colorectal resection and (b) is
there a difference in perioperative complications, cost, postoperative pain, cosmetic
outcomes, hernia formation, or oncological outcomes between SILS and conven-
tional laparoscopy.

Patients undergoing SILS ‘Conventional Perioperative outcomes,
minimally invasive laparoscopy’ cost, pain, cosmetic
colorectal resection outcomes, hernia formation,
oncological outcomes
Search Strategy
PubMed was queried using Medical Subject Headings (MESH); “Colon/surgery”,

“Rectum/surgery”, “laparoscopy”, and search terms; “single site”, “single inci-
sion”, “single port” in combination with the Boolean operators AND or OR. English
language, adult: 19+ years and humans filters were used. Relevant articles’ refer-
ences were also reviewed.
Results
Among the 23 papers reviewed from the literature, there was only one RCT compar-
ing the outcomes between SILS and CL in colorectal surgery to our knowledge, and
this study was limited by sample size. One systematic review (SR), four propensity
48 Conventional vs Single Port Approaches to Laparoscopic Colectomy 547
score-matched (PSM) studies, and four case-matched (CM) studies with adequate
sample sizes compared and reported the short-term, long-term and oncological out-
comes between the patients underwent SILS and CL in the context of colorectal
surgery. Eight retrospective cohort (RC), three case–control (CC), and two case-
series (CS) were also reviewed, and the results were added to the study (Table 48.1).
Perioperative Outcomes
Multiple case-matched and case series studies demonstrate that the perioperative out-
comes after SILS colectomy appear to be at least equal to CL [15, 16, 18–30, 32,
34–37]. Katsuno et al. compared 107 patients who underwent SILS colectomy with
107 patients who underwent CL in a propensity score-matched study design and no
differences were found in operative time, EBL, LOS or postoperative complications
[15]. In the largest case-matched study to date comparing 318 CL cases with 308
SILS cases, no significant differences were found in terms of elective or emergent
status, operative time, or conversion to laparotomy. This study did show a significant
decrease in EBL in favor of the SILS group. This study also demonstrated a signifi-
cant decrease in superficial surgical site infections, 11.3 % vs. 5.8 % in the SILS
group with a similar LOS between the groups [29].
Of the 23 studies reviewed, 21 report on LOS. 13 of the studies (3 PSM, 3 CM,
2 CC and 5 RC studies) show a comparable LOS between groups. The other 8
papers (1 RCT, 1 SR, 1 PSM, 1 CM, 1 CC and 3 RC studies) report a shorter LOS
favoring SILS.
Overall 20 papers reported on operative time, 13 of these (4 PSM, 1 RCT and
SR, 2 CM, 3 RC and 2 CC studies) report no significant difference in terms of
operative time between SILS and CL. In one PSM study where they compared 61
patients who underwent SILS with 61 patients who underwent CL for colon cancer,
they distinguished total operation time from net operation time (procedure time).
The total operation time was significantly shorter in SILS group but the total proce-
dure time was not statistically different. This indicates that port placement and clo-
sure are likely to be quicker in SILS [35].
A total of ten papers reported on EBL. Seven studies found a comparable EBL
after SILS and CL (3 PSM, 3 CM, and 1 RCT), while three studies found decreased
EBL after SILS.
Cost
Stewart et al. evaluated the cost in patients undergoing laparoscopic surgery in four
groups including CL converted to open and SILS converted to open groups. This
study included 149 CL and 111 SILS cases. As expected, patients who were
Table 48.1 Study size, type, nature of disease, summary of outcomes, and quality of evidence summarized for all studies
548
Study Results’ Quality of

Study Patient Benign/malign/mixed typea SILS > CLb SILS = CLb CL > SILSb evidence
Katsuno (2015) [15] SILS (n = 107), CL Malign PSM Pain, Incision Op time, EBL, LOS, Moderate
(n = 107), pts w CRC length complication, 5-year
DFS and OS, LN
Lee (2011) [16] SILS (n = 46), CL Mixed CM Cosmesis Op time, LOS, Moderate
(n = 46) incision length,
body image score,
complication
Markar (2014) [17] SILS (n = 1312), CL Mixed SR EBL, LOS Op time, Moderate
(n = 1862) Complication,
mortality, Hernia,
LN
Poon (2012) [18] SILS (n = 25), CL Mixed RCT LOS, pain Op time, EBL, Moderate
(n = 25) complications, LN,
narcotic
Takemasa (2014) [19] SILS (n = 150), CL Malign PSM Pain Op time, EBL, LN, Moderate
(n = 150) hernia, mortality,
LOS
Champagne (2012) [20] SILS (n = 165), CL Mixed CC EBL, pain Op time, LOS, Low
(n = 165) complication
Chew (2013) [21] SILS (n = 40), CL Mixed RC Op time, Low
(n = 40) Complication, LN,
incision length,
pain, narcotic, LOS
D’Hondt (2014) [22] SILS (n = 20), CL Benign CM Pain, cosmesis EBL, LOS, hernia Op time, Low
(n = 40), cost
Sigmoidectomy for
diverticulitis
H.H. Aydinli and M. Costedio
Keshava (2013) [23] SILS (n = 75), CL Mixed RC LOS, incision Complication Low
(n = 74), pts length
underwent R
hemi-colectomy
Kim (2011) [24] SILS (n = 73), CL Malign RC Narcotic, LOS Complication, LN, Op time Low
(n = 106)
Kim (2015) [25] SILS (n = 120), CL Malign PSM Incision length, Op time, EBL, LOS, Low
(n = 120), pts w pain complication, LN,
sigmoid tm 3-year DFS and OS
Osborne (2013) [26] SILS (n = 55), CL Mixed RC Op time, LOS, Complication, pain, Low
(n = 327) LN hernia
Papaconstantinou SILS (n = 39), HALS Mixed CM Pain, LOS Op time, EBL, Low
(2011) [27] (n = 39), CL (n = 39), incision length,
pts undergoing complication,
Right colectomy
Rosati (2013) [28] SILS (n = 50), CL Mixed CC LOS Op time, Low
(n = 50), pts complication, LN
undergoing Right
colectomy
Sangster (2015) [29] SILS (n = 308), CL Mixed RC EBL, LN, Op time, LOS, Low
(n = 318) complication hernia, mortality
Stewart (2014) [30] SILS (n = 111), CL Mixed RC Op time LOS, cost Low
(n = 149)
48 Conventional vs Single Port Approaches to Laparoscopic Colectomy
Sulu (2014) [31] SILS (n = 95), CL Mixed CM Op time EBL, LOS, cost, Low
(continued)
549
550
Study Results’ Quality of

Study Patient Benign/malign/mixed typea SILS > CLb SILS = CLb CL > SILSb evidence
Velthuis (2012) [32] SILS (n = 50), CL Mixed CC Op time Complication, LOS, Low
(n = 50), pts LN, hernia
undergoing Right
colectomy
Waters (2012) [33] SILS (n = 100), pts Mixed CS Short term Low
underwent Right outcomes,
hemi-colectomy oncological
outcomes
Yun (2013) [34] SILS (n = 66), CL Malign RC Op time, LOS, Low
(n = 99), pts complication, LN
underwent Right
hemi-colectomy
Yun (2015) [35] SILS (n = 61), CL Malign PSM LOS, total op Net procedure time, Low
(n = 61) time complication, LN,
DFS, OS
Kanakala (2012) [36] SILS (n = 40), CL Mixed RC LN Op time, LOS, Very low
Vestweber (2013) [37] SILS (n = 224) Benign CS Short term Very low
outcomes
DFS disease free survival, OS overall survival, LN number of lymph node cleared, Pain postoperative complaining frequency of pain, Narcotic postoperative
narcotic use
a
CC: Case-controlled study, CM: Case-matched study, CS: Case-series, RC: Retrospective cohort study, PSM: Propensity score-matched study, SR: Systemic
review
b
SILS ≥ CL: Variables with a better outcome in SILS group, SILS = CL: Comparable outcomes, CL ≥ SILS: Variables with a better outcome in CL group
H.H. Aydinli and M. Costedio
converted to open were found to have a higher cost but no significant difference was
found between patients who underwent CL and SILS in terms of total cost [30].
Sulu et al. found total cost including operating room, nursing, pharmacy, radiology,
professional and pathology/laboratory costs to be comparable in patients undergo-
ing SILS (n = 90) and CL (n = 90) colorectal resections in a case-matched study
design. The anesthesia costs were significantly lower in the SILS group (p = 0.003)
which was related to the significantly longer operating time in the CL group
(p < 0.001) [31]. On the other hand, D’Hondt et al. reported a higher total dispos-
able cost (2599.02 ± 127.28 vs. 2320.13 ± 116.40, p < .0001) in a case-matched
study where they compared 20 SILS patients with 40 CL patients who underwent
sigmoidectomy for diverticulitis. Since the cost they reported did not include the
hospital stay and complication costs, the results are limited in terms of the applica-
bility [22].
Pain
Lesser postoperative pain is a theoretical advantage of SILS that should lead to a

decrease in narcotic use, and in turn, decreased length of stay. There are many case-
matched studies showing that patients who underwent SILS colectomy had better
postoperative pain control with less frequent use of parenteral narcotics [15, 18–20,
22, 24, 25, 27]. Papaconstantinou et al. compared SILS with CL as well as hand
assisted laparoscopy in patients undergoing laparoscopic right colectomy. Twenty
nine patients were included in each group and the maximum pain scores on postopera-
tive day 1 and 2 were significantly lower in the SILS group compared with both CL
and the hand assist group. Since adequate pain control is a widely accepted discharge
criteria, LOS was found to be one day shorter in SILS group when compared to CL in
this study [27]. In a retrospective cohort study by Kim et al., they evaluated the short-
term outcomes in 179 patients (SILS n = 106, CL n = 73) with colorectal cancer.
Results showed a significantly decreased use of parenteral narcotics; accompanied by
a significantly shorter LOS (9.6 ± 9.6 vs 15.5 ± 9.8 days, p = 0.000) favoring the SILS
group [24].
Cosmetic Outcomes
Another obvious benefit of SILS over CL is cosmesis. This has proven to be a dif-
ficult outcome to measure as patients are unaware of the cosmetic results of other
procedures, and are often pleased with their cosmetic result. As expected, studies do
not always show a significant difference in the length of incision between SILS and
CL as often the length of incision is based on the size of the specimen [27]. Keshava
et al. reports the mean length of extraction incision to be less than 1 cm smaller
(p < 0.001),when comparing 75 patients who underwent SILS right hemi-colectomy
vs. 74 patients with CL [23]. Lee et al. compared the body image and cosmesis
scores 3 months from the surgery in a case-matched study of 92 patients, where they
found the incision was 1 cm shorter in the SILS group. The body image scale mea-
sured the patients’ perception of and satisfaction with their own body; the cosmetic
scale on the other hand assessed the degree of satisfaction of patients in terms of the
physical appearance of the scar. While the body image score was found to be com-
parable between groups, there was a significant difference in the cosmetic score
favoring the SILS group [16]. D’Hondt et al. measured an overall satisfaction and a
cosmetic result evaluation on a scale ranging from 0 to 10 in 60 case-matched
patients underwent sigmoidectomy for diverticulitis. They reported comparable
overall satisfaction rates but an improved cosmetic results for SILS group [22]. The
incision length was reported to be 4 cm (3.3 ± 0.6 vs 7.7 ± 0.7 cm) longer in CL
group when they compared 180 patients with sigmoid colon cancer (SILS N = 60,
CL N = 120) in a propensity score-matching setting [25].
Hernia Formation
In the 23 studies reviewed, 6 reported a hernia rate separate from the overall com-
plication rates. Neither the definition, criteria for diagnosis of hernia nor the follow
up time until diagnosis, was were clear in four of the studies. Sangter et al. reported
comparable 60-day incisional hernia rates according to the clinicians’ judgment,
but they excluded 40 patients with a stoma due to the increased risk for hernia [29].
Markar et al. reported comparable 30-day port site hernia rates [17]. There was no
consistency in the literature in terms of types of the hernias reported (2 ‘hernia’, 2
‘incisional hernia’, 2 ‘port site hernia’ terms were used). The data does not support
a difference in hernia rates between SILS and CL [17, 19, 22, 26, 29, 32].
Oncologic Outcomes
Fourteen papers reported the number of lymph nodes in the specimen and 10
papers commented on the comparable safety and feasibility of the SILS in cancer
cases (1 RCT, SR, CC, CS, 4 PSM and 2RC studies) [15, 17–19, 24, 25, 28, 33–
35]. The number of harvested lymph nodes was comparable between SILS and
CL for colorectal cancers in a RCT and multiple CM/PSM studies [15, 18, 19,
35]. There were no significant differences in terms of overall survival rates (one
study 24 months 3-year and 5- year) or disease free survival rates (one study
24 months, 3-year and 5- year) [15, 25, 34]. Long-term results are still pending,
as this technique has only been described for colorectal procedures for approxi-
mately 7 years.
Recommendations
Single incision surgery is still evolving, and high quality comparative evidence is
still lacking. These studies are likely affected by selection bias, where patients with
optimal anatomy and BMI would be chosen for SILS over CL. This could lead to
results skewed towards the SILS group with regards to perioperative outcomes. It is
a common finding that operative time is shorter in the SILS group and this is likely
a combination of decreased port insertion and closure times as well as the fact that
the many advanced laparoscopic surgeons choose to perform SILS. Overall, based
on the available literature, SILS is operatively and oncologically safe and feasible in
advanced laparoscopic hands for selected patients. If the surgeon feels that they can
perform the operation using the SILS technique the same way they perform it using
CL, then it is appropriate for the patient. Cosmetic outcomes and pain scores are
improved with SILS. But prolonged oncologic and hernia outcomes need to be
assessed with well-designed trials. Data are lacking to demonstrate a benefit of
SILS over CL and large well-designed RCT’s are needed.
Our personal view is that SILS colectomy is comparable to CL in experienced hands.

Cosmesis is improved, which is particularly beneficial in young patients. It is difficult
to obtain adequate traction/counter traction required for rectal cancer surgery and the
authors choose not to use SILS for this indication. A common misconception is that
conversion to multiport laparoscopy is a failure of the SILS technique. The authors
would counter that starting with the extraction site allows the surgeon to inspect
intraabdominal adhesive disease early and make decisions about the need for added
ports or conversion to open prior to unnecessary adhesiolysis solely for port place-
ment. So whether the surgeon utilizes the pure SILS technique or a reduced port tech-
nique, this potentially saves time intraoperatively while making the procedure safer.
Recommendations
• If the surgeon feels that they can perform the operation using the SILS technique
the same way they perform it using CL, then it is safe and feasible for the patient.
(Evidence quality is moderate, weak strength)
• Overall based on the available literature SILS is operatively and oncologically
safe and feasible in advanced laparoscopic hands in selected patients. Cosmetic
outcomes are improved with SILS and pain scores are decreased. (Evidence
quality low; weak strength).
• Prolonged oncologic and hernia outcomes need to be assessed with well-designed
trials. Data is lacking to demonstrate a benefit of SILS over CL. (Evidence qual-
ity low; no recommendation)
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2013;27(2):434–42.
Chapter 49
Anastomotic Leak Management Following
Low Anterior Resections
Nathan R. Smallwood and James W. Fleshman
Introduction
Anastomotic leaks commonly occur after low anterior resections (LAR) and are
among the most feared complications encountered by surgeons. Although, overall
mortality rates remain low (~2 %) following LAR, one-third of all postoperative
deaths occur in patients with anastomotic leak [1] Anastomotic leaks also result in
increased rates of patient morbidity, permanent stomas, as well as poor bowel func-
tion and incontinence in those patients managed without a permanent stoma [2–4].
Despite an extensive amount of literature addressing risk factors and methods of
prevention, the number of anastomotic leaks following low anterior resections has
remained the same for the last 40 years [5].
The creation of standardized treatment strategies to manage anastomotic leaks are
commonly built on expert opinion and consensus, as there are only a limited number
of studies focusing on anastomotic leak management [6, 7]. As a result, these prior
treatment strategies are largely empiric and based upon very little evidence. Further,
recommended options are often broken down according to the site of the anastomo-
sis (intraperitoneal vs. extraperitoneal) or size of the anastomotic defect (minor vs.
major),and typically result in an overly complex treatment algorithm [6].
N.R. Smallwood, MD
Division of Colon and Rectal Surgery, Baylor University Medical Center, Dallas, TX, USA
J.W. Fleshman, MD (*)
Department of Surgery, Baylor University Medical Center, Dallas, TX, USA
Texas A&M Healthsciences, Dallas, TX, USA

DOI 10.1007/978-3-319-40223-9_49
558 N.R. Smallwood and J.W. Fleshman
The appropriate management of anastomotic leaks following LAR is best simpli-

fied by focusing on two primary questions:
1. What is needed to obtain source control? Specifically, what intervention is
needed that will provide effective drainage and eradication of the infectious
source while also preventing recurrence of local sepsis?
2. What interventions/measures can be performed to help reestablish intestinal
continuity?
PICO table
Patient population Intervention Comparator
Patients with Anastomotic Anastomotic Morbidity, mortality,
anastomotic leak salvage takedown and end functional outcomes
following LAR stoma
Search Strategy
Relevant studies published between January 2000 and December 2016 were identi-
fied from the search of the Medline databases and Cochrane databases. The follow-
ing search terms were used: rectal, rectum, proctectomy and leakage, failure,
integrity, insufficiency, breakdown, defect, separation, dehiscence. Further articles
were then selected based upon a review of the citations found in selected papers
from the first search. All English language publications which primarily focused on
the management of anastomotic leaks following low anterior resections were
selected. Exclusion criteria included: (1) studies primarily focusing on risk factors,
prevention, recurrence, or the treatment of other types of complications; (2) studies
in which the majority of leaks were not involving a rectal anastomosis (ileo-colic,
colo-colonic, ileo-anal); (3) non-English papers; (4) animal or laboratory studies.
To avoid redundant studies, all of the authors and organizations, community of
patients and study dates were routinely checked. When a study reporting the same
patient cohort was included in several publications, only the most recent or com-
plete study was selected.
The patients that are the most in need of infectious source control are those with
generalized peritonitis and/or sepsis. Most surgeons would agree on the need for
fluid resuscitation, antibiotics and operative intervention to drain and divert.
However, aside from gross ischemia or complete dehiscence, there continues to be
controversy over whether the anastomosis should be taken down or salvaged. We
specifically wanted to know whether or not anastomotic salvage leads to inferior
source control and therefore higher mortality rates as compared to anastomotic
takedown. Also, as has been suggested in prior studies, does anastomotic salvage
provide any benefits over takedown in terms of the ability to re-establish intestinal
continuity and prevent the number of permanent stomas?
There is very little consensus regarding the best methods for preserving or rees-
tablishing intestinal continuity. Despite the high rates of permanent stomas and poor
49 Anastomotic Leak Management Following Low Anterior Resections 559
rectal function in patients with anastomotic leak, many surgeons continue to rely on
a wait and see approach. Definitive treatment to allow for complete closure is there-
fore delayed in the hopes of spontaneous healing. Ultimately, this approach has
been and will continue to be challenged by the emergence of active therapies to treat
anastomotic leaks.
At our institution we have used endoluminal vacuum (E-Vac) therapy in the
treatment of anastomotic leaks. While this therapy is not commonly utilized in the
US, it has been used primarily in Germany since around 2002 [8]. Without any
established gold standard for comparison, we decided to create PICO tables that
compared E-Vac therapy to redo surgery, and conservative management (including
the “wait and see approach,”). Other methods such as endoscopic stent placement
will be less formally reviewed as it was anticipated that available studies concerning
these methods would be limited.
A manual search was also performed focusing on the search terms endoluminal
vacuum therapy, endoscopic vacuum therapy, endo-SPONGE, endosponge, endo
sponge, and endoluminal negative pressure therapy. Additional articles were found
using a Google Scholar search using the same search terms as well as from a review
of the citations of selected articles. All studies evaluating the use of E-Vac therapy
were reviewed and assessed for treatment related complications. Only studies
including ten or more patients treated with E-Vac therapy were used in comparing
outcomes between interventions. One final manual search was performed for a bet-
ter evaluation of the baseline risk of permanent stoma in patients with and without
anastomotic leak. Keywords used were “permanent stoma,” “definitive stoma,”
“permanent ostomy”, “definitive ostomy.”
Traditionally the treatment of choice for a leaking colorectal anastomosis has been
resection with end colostomy. This is despite the limited evidence to support this
practice (Table 49.1a, b). In fact, one of the commonly referenced studies which
emphasized the need for anastomotic takedown contained only three patients so
treated [13]. More recently, the need for anastomotic takedown has been questioned
and the trend continues to be moving away from this approach and towards per-
forming anastomotic salvage.
Comparisons between anastomotic takedown and salvage were limited to four
studies reporting on two of the four important outcomes. Patients treated with anas-
tomotic salvage had statistically significant fewer postoperative deaths [9] and per-
manent stomas [9, 12] compared to patients treated with anastomotic takedown.
Patients treated with anastomotic takedown as compared to anastomotic salvage
also had more episodes of recurrent sepsis [22.7 % (5/22) vs. 0 % (0/10)] [12] and
underwent an additional laparotomy more often [18.5 % (10/54) vs. 7.7 % (3/39)]
[9], respectively.
Table 49.1 Outcomes following anastomotic takedown compared to anastomotic salvage for the
treatment of anastomotic leak
(a) Mortality
№ of Risk of Publication bias Outcome Overall
participants bias Anastomotic Anastomosis quality of
(studies) salvage takedown evidence
125 (1 Very Very strong 15.4 %b (6/39 37.0 % (20/54 Very low
observational seriousa association. patients) patients)
study) [9] Residual
confounding
would reduce
demonstrated
effect.
(b) Need for permanent soma
134 (4 Very Very strong 5.6 %c (4/71) 61.9 % (39/63) Low
observational seriousa association.
studies) [9, 10, Residual
11, 12] confounding
would reduce
demonstrated
effect.
a
In the selected studies, the choice between anastomotic takedown or salvage was not randomized
or controlled
b
Statistically significant p <0.05
c
All four studies showed reduced number of permanent stomas in patients treated with anastomotic
salvage. Only two of four studies assessed for statistical significance with both showing a statisti-
cally significant decrease (p < 0.05) in permanent stomas in patients treated with anastomotic sal-
vage
These differences must be analyzed with caution based upon the overall quality
of the studies (low to very low). Treatment bias may result in severe leakage (larger
defects, colon necrosis etc.) being treated with anastomotic takedown, but remains
unlikely account for differences in outcomes.
urgical Management of Anastomotic Leakage

S
Following LAR in Patients with Generalized Peritonitis and/or
Sepsis
1. In the absence of bowel ischemia/necrosis and/or major dehiscence, patients

should be managed without resection or takedown the anastomosis and given a
proximal diverting stoma. (Strong recommendation based upon low or very low-
quality evidence)
The authors of all four included studies reported favoring the use of anastomotic
salvage [9, 10, 12, 11]. In three of the four studies, anastomotic takedown with
Table 49.2 Outcomes of re-do surgery compared to endoluminal vacuum therapy in restoring
intestinal continuity
(a) Permanent stoma
№ of Risk of Publication bias Need for permanent stoma Overall
participants bias Redo surgery E-vac therapy quality of
(studies) evidence
349 (12 Seriousa Publication bias 15.0 % (21/140) 18.9 % Very low
observational strongly (18/95)
studies) 1 suspected ≤ 6 weeks
[15–22, 8, 23, 15.9 %
22] (10/63)
+ diversion
7.70 % (1/13)
(b) Complete closure
№ of Risk of Publication bias Complete closure Overall
(studies) evidence
293 (11 Seriousa Publication bias 77.1 % (91/118) 85.7 % Very low
observational strongly (150/175)
studies; 8 suspected. ≤ 6 weeks
E-Vac, 3 Redo) Residual 92.1 %
[20, 22, 19, 17, confounding (70/76)
21, 16, 15, 24, would reduce + diversion
23, 8, 18] the demonstrated 93.8 %
effect (75/80)
(c) Rectal function
№ of Risk of Publication bias Rectal function Overall
(studies) evidence
160 (4 Seriousa Publication bias No Not reported Very low
observational strongly incontinence
studies; 4 Redo) suspected 78 % (60/77)
[14, 17, 16, 15] LARS Score
22 ± 9 (n = 17
patients)
Wexner score 8
(0–17) (n = 43
patients)
Risk of bias secondary to study design and no control group
a
creation of an end stoma was only favored in the management of anastomoses

with ≥ 50–100 % dehiscence or in the presence of bowel ischemia or necrosis [9,
11, 12]. In the absence of the above criteria, diverting ostomy and salvage of the
anastomosis is an effective method of controlling peritoneal sepsis resulting from
leakage of both intraperitoneal and extraperitoneal rectal anastomoses. Anastomotic
salvage and diversion is also the favored approach when anastomoses are
inaccessible or poorly visualized as a result of significant inflammation, exudate,
and/or adhesions.
eestablishing Intestinal Continuity in Patients

R
with Symptomatic Anastomotic Leakage Following LAR
1. E-Vac therapy is an effective early treatment option for anastomotic leaks with
an associated abscess cavity, with or without diverting stomas. (Table 49.2).
Strong recommendation based upon low or very low-quality evidence.
Only studies reporting ≥ 10 patients treated with E-Vac therapy were included.
Studies were excluded (Keskin et al.) if the described method of E-Vac therapy dif-
fered greatly from the original description by Weidenhagen et. al. [25, 26]. The
study by von Koperen et al. was excluded because delay in starting of E-Vac led to
worse outcomes [27]. In the majority of studies, E-Vac therapy was the treatment of
choice for anastomotic leaks involving the rectum, associated with a cavity in
patients without generalized peritonitis. E-Vac therapy resulted in very high com-
plete closure rates and low permanent stoma rates. The highest closure rates and
lowest permanent stoma rates could be seen in the subgroup of patients with proxi-
mal diverting stomas and/or early treatment (<6 weeks). No deaths related to E-Vac
therapy or anastomotic leak occurred following the start of therapy. Only a limited
number of complications thought to be related to E-Vac therapy occurred (recurrent
abscesses, fistulas, bleeding).
Compared to E-Vac therapy, redo surgery resulted in slightly lower permanent
stoma rates despite decreased complete closure rates. No postoperative deaths
occurred following redo surgery despite major intraoperative complications and
postoperative morbidity requiring further surgery in 10.3 % of patients. Redo sur-
gery is technically demanding, often requiring adjunctive surgical methods includ-
ing advanced colon mobilization and anastomotic techniques. Authors of these
studies recommend redo surgery only in patients with minimal to no comorbidities
and after multiple other measures have failed.
E-Vac therapy can safely and effectively close anastomotic leaks ultimately
allowing for intestinal continuity to be reestablished in the majority of patients,
especially in patients treated early and those who have a diverting stoma. E-Vac
therapy can be performed in the endoscopy suite, intensive care unit or operating
room, does not require general anesthesia, and in some patients, continued on an
outpatient basis. However, patients should be counseled and informed on the
expected number of endoscopic sponge changes [7–11] and treatment duration (18–
34 days) needed to allow for leak closure. A diverting stoma should be considered
in patients being treated with E-Vac therapy since it is associated with increased
ease of use and higher anastomotic leak closure rates.
Unfortunately, a number of important barriers exist which may severely limit the
feasibility of implementing E-Vac therapy in the US. Due to the inaccessibility and
increased cost seen with the Endosponge device, E-Vac therapy requires adaptation
of current negative pressure devices. Adoption of this new method by surgeons will
likely be slow and challenging at the present time until the collective experience
increases.
2. Reoperative surgery is a treatment option in patients with chronic leaks, minimal

to no comorbidities, and in whom other less invasive methods have failed. (Weak
recommendation based upon low or very low-quality evidence)
Patients with a failed colorectal anastomosis from anastomotic leaks or fistulas
who have failed other therapies can successfully be treated with reoperative or
“redo” surgery. Redo surgery in this setting is highly demanding procedure and
associated with high intraoperative and postoperative morbidity. Therefore, reoper-
ative surgery should only be considered in patients with minor comorbidities and a
very low risk of postoperative mortality. Pelvic recurrence must be excluded in
patients whose primary surgery was for cancer. Patients must also be counseled on
the increased risk of complications that could occur and the potential need for fur-
ther interventions, including the need for further surgery. Patients must also under-
stand that even with a successful redo surgery, their functional result may be poor.
Finally surgeons who are considering performing redo surgery must have experi-
ence with advanced techniques that often are needed for colon mobilization and
anastomotic creation.
3. E-Vac therapy should be considered in selected patients who are highly commit-
ted to having their stoma closed. (Strong recommendation based upon low or
very low-quality evidence)
Despite the low level of evidence, we believed a strong recommendation was
warranted based upon a number of factors. The desire to avoid a permanent stoma
is important to most patients. There is likely to be a moderate to large reduction in
permanent stoma rates with the use of E-Vac therapy as compared to conservative
management. The undesirable effects associated with the use of E-Vac therapy are
likely to be minimal. The present logistic barriers to usage are not likely to be per-
manent, but do require a surgeon or endoscopist experienced in its use.
The first recommendation for a patient with an anastomotic leak from non-diverted
anastomosis, is that they should be given a diverting ostomy. Proximal diversion
limits the flow of stool into the pelvis/abdomen, limits inflammation around the
anastomosis and greatly enhances the ability to employ other adjunctive treatment
methods. Even in the setting of peritonitis, the anastomosis does not typically need
to be resected.
Most patients with a leak will have been given a diverting stoma at the time of
their index operation. Assuming that the leak can be controlled and the patient does
not have diffuse peritonitis and/or septic shock, the first step is usually to perform a
CT of the pelvis with rectal contrast. Imaging indicates the size of the leak, the
extent of potential spread (contained or not), the distance of the separated ends of the
colon and rectal stump, any involvement of the surrounding organs (rectovaginal
fistula, colovesical fistula, coloenteric fistula) and the potential burden of contamina-
tion associated with the defective anastomosis. Each of these must be considered as
the plan is made for treatment. Endoscopic evaluation of the anastomosis demon-
strates the size of the defect, position of the leak along the circumference of the
circular stapleline, the condition of the tissue at the anastomotic site (viable or isch-
emic or ragged), the volume of the extraluminal abscess cavity, the pliability of the
tissue on each side of the stapleline and the distance of the defect from the anal
verge.
The options for the treatment can now be considered and critically compared.
Complete disruption of the anastomosis is generally the worst situation, but on rare
occasions be temporized with a covered stent placed across the defect combined
with external drainage of the pelvis. There must be a landing zone for the distal end
of the stent above the anal sphincter to avoid severe tenesmus and erosion of the
stent into the anal mucosa. The likelihood of successful healing of an intact func-
tioning anastomosis is low, but the stent may buy valuable time so a definitive trans-
abdominal repair can be done later under elective conditions in the setting of a clean
pelvis.
Partial disruption of the anastomosis, with greater than 50 % of the circumfer-
ence intact, has a better chance of local repair when the anastomosis is within the
reach of an anoscope. Once again the external component of the leak must be man-
aged with a percutaneous drain or endosponge placed through the separation in the
anastomosis. Clearing the abscess cavity of fecal and purulent material is critical to
eventual anastomotic healing and the functionality of the pelvic floor. As the cavity
contracts and the area becomes clean, consideration can be given to either placing
full thickness sutures across the defect to close the opening, or endoscopic clips can
be placed to pull the lateral edges together and reduce the opening to a smaller
diameter. The expense of the clips makes this approach less attractive. Suture place-
ment can be facilitated by endoluminal suturing techniques borrowed from laparos-
copy and transanal endoscopic microsurgery. The endosponge is then placed within
the lumen of the bowel at the anastomosis to enhance healing at the sutureline. The
vacuum created by the suction applied to the sponge collapses the lumen of the
rectum and seals at the anus without extra maneuvers. The vacuum acts to remove
bacteria, mucus and debris, encourage blood flow into the tissue and reduce edema
of the adjacent tissue.
An alternative to suture repair of the anastomosis is to place the endosponge
through the opening in the anastomosis to fill the external cavity. As the cavity
shrinks, the sponge can be shaped to fit the cavity and over time is withdrawn from
the cavity during subsequent sponge changes. The last phase involves leaving the
sponge in the lumen of the bowel to completely obliterate the external cavity and
draw the edges of the defect together.
E-Vac therapy requires patience on the part of the surgeon and compliance on the
part of the patient. Numerous endoscopic changes will be required under sedation,
and at times under general anesthesia. The sponges that are used to contract the
pelvic abscess cavity must be changed more frequently to avoid in-growth of the
tissue and excessive bleeding during removal of the sponge. In addition, the
endosponge loses its suctioning power and effectiveness overtime due to a buildup
of secretions. Generally, endoscopic changes are done every 3–4 days, but can
safely be extended up to 7 days, especially if the sponge is placed only within the
lumen. Several months of treatment may be required depending on the extent of
disruption of the anastomosis. However, if the leak can be diagnosed and treated
earlier, leaks healing times may be much quicker [28]. As with all low rectal anas-
tomoses, a final check of healing with an endoscopy and contrast enema prior to
closure of the diverting loop ileostomy is prudent [29].
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Chapter 50
Management of the Unhealed Perineal Wound
After Proctectomy
Jesse Moore and Sean Wrenn
Introduction
Abdominoperineal resection is the surgical standard for low rectal cancers when
sphincter salvage is not possible, and has proven to be a life-saving procedure for
patients who need it. Otherindications for abdominoperineal resection include
inflammatory bowel disease (IBD), and salvage surgery for persistent or recurren-
tanal cancer [1]. An unhealed perineal wound after oncologic surgery was first
described by Miles in 1908 and it remains an ongoing issue for patients to this day
[2]. As surgical approaches have become more aggressive, i.e., extralevator abdomi-
noperineal excision of the rectum to reduce positive circumferential margins,
patients have become more susceptible to wound complications. The increased use
of perioperative chemoradiation further impairs local healing. For these reasons the
unhealed perineal wound is a common complication following proctectomy [3].
The presence of an unhealed perineal wound can delay adjuvant chemotherapy or
radiation therapy. It can also result in severely diminished quality of life following
the operation owing to frequent outpatient visits, prolonged hospital stays, frequent
dressing changes, further operations, and increased healthcare costs [1, 4].
An unhealed perineal wound is classified as a persistent perineal sinus (PPS) if it
persists for greater than 6 months following surgery [5]. The incidence of PPS is up
to 30 % of patients after abdominoperineal resection (APR) for low rectal cancer,
and after surgery for inflammatory bowel disease can be as high as 70 % [5] As
many as 33 % of cases of PPS have not healed by 1 year, and chronic PPS becomes
increasingly unlikely to heal spontaneously without aggressive intervention [6].
J. Moore, MD, FACS, FASCRS (*) • S. Wrenn, MD

University of Vermont Medical Center, University of Vermont College of Medicine,
Burlington, VT, USA

DOI 10.1007/978-3-319-40223-9_50
568 J. Moore and S. Wrenn
In the case of PPS, the sizeof the defect may dictate whether conservative or aggres-
sive treatment strategies will be more appropriate.
Patients with inflammatory bowel disease, particularly Crohn’s disease, are par-
ticularly susceptibile to perineal wound related complications [7]. Diabetes melli-
tus, tobacco use, malnutrition, and obesity are also well-recognized risk factors for
inadequate perineal wound healing [8]. It is important to evaluate, address and con-
trol all patient risk factors (ideally prior to the initial operation) in order to maxi-
mize wound healing potential. In the setting of proctectomy for perineal Crohn’s
Disease, one should assess for the presence of any new or ongoing enteric fistulas
that could prohibit local wound healing [9]. One should also rule out foreign body
reaction and recurrent or de novo carcinoma in these chronic wounds [8].
In order to determine optimal treatment for unhealed perineal wounds and PPS,
it is important to understand the anatomical predisposition created following pel-
vic exenteration and radical extirpations of the anorectum. The pelvic cavity is
bound anteriorly by the urogenital organs (in the female the uterus, cervix and
vagina, and in the male the prostate, seminal vesicles, and bladder [10]), postero-
laterally by the coccyx, sacrum, and the two ischia, and superiorly by the pelvic
peritoneum [5]. These well defined landmarks are generally immobile, except for
downward migration of pelvic peritoneum. The postoperative vacancy leads to an
intrinsic susceptibility for postoperative fluid collections. Bacterial contamination
can result in secondary infection of this fluid, abscesses, inflammation, and fibro-
sis. These processes actively hinder further healing and can progress to perineal
sepsis.
Several of the most effective treatment strategies have addressed the anatomical
defect left following proctectomy, and have utilized tissue autografts or implants to
further close the pelvic space. Historically it was observed that closure of the peri-
toneum resulted in higher incidence of PPS, likely due to the fact that closure inhib-
ited bowel passively filling into the defect [1]. However the filling of the defect with
bowel can prove to be problematic due to an unacceptably high incidence of adhe-
sions and resultant bowel obstructions [11]. This chapter will review the alternative
methods utilized to promote healing and closure of the perineal sinus.
PICO/clinical question
Patient population Patients with unhealed perineal wounds/PPS following proctectomy
Intervention Surgical advancement flap
Comparator Non-operative strategy/local wound care
Outcome Primary perineal wound healing
Literature Search Strategy
All studies evaluating the management of perineal wounds following proctectomy

were considered for inclusion. Inclusion was not restricted to study design, and all
types of studies (retrospective vs. prospective, randomized vs. non-randomized,
observational, etc.) were eligible for consideration. Studies were identified via search
50 Management of the Unhealed Perineal Wound After Proctectomy 569
of the Pubmed database (1991–2015) with the following MeSH terms: “postoperative
complications”, “perineum”, and “wound healing”. The results were then evaluated
for relevancy to the topic, and citation lists of relevant papers were reviewed for fur-
ther references. All papers were evaluated for the quality of their evidence and rec-
ommendations via the GRADE approach (Grades of Recommendation, Assessment,
Development, and Evaluation). Papers were classified in quality as high, moderate,
low, or very low based on multiple factors including methodology, consistency, pre-
cision of results, and directness of the evidence given [12, 13].
Non-operative Strategies
Conservative approaches for the management of the unhealed perineal wound

include local wound care, topical medications and antibiotics, chemical debride-
ment agents, fibrin glue, and negative pressure wound therapy [5]. Perineal wounds
allowed to heal by secondary intention, which was the historical standard prior to
the adoption of primary closure, can often result in a prolonged healing course [14].
Important factors to consider for optimizing wound healing include nutritional sta-
tus, blood supply, and immune function. Ongoing infection within the wound will
impair the healing process, as will devitalized tissue such as necrotic material or
fibrinous exudate. The removal of such devitalized tissues via surgical debridement
and control of any localized sepsis has been shown to accelerate healing.
Debridement
Debridement refers to the surgical removal of devitalized tissue, with the goal to
promote the growth of the underlying healthy tissue. Various forms of debridement
include sharp debridement, biosurgical debridement, chemical debridement,
mechanical debridement, enzymatic debridement, and autolytic debridement [14].
Sharp debridement, typically using either a scalpel or scissors, can be performed
either in the operating room or at the bedside, depending on the extent of the wound
debridement and patient pain control. The wet to dry dressing, frequently applied
within the realm of postsurgical care, utilizes both mechanical and autolytic debride-
ment. Comparisons of modern dressings (alginates, hydrocolloids, polyurethane
foam, silicone foam) to traditional gauze dressings seem to suggest a modest
improvement in wound healing with modern dressings, though these studies have
been criticized for small sample sizes and methodological flaws [14].
Local Antibiotic Agents
As ongoing perineal sepsis is a risk factor for PPS and a major cause of delayed
wound healing, many agents have been developed to target local pathogenic
bacterial populations with the goal of preventing deep space infection and promot-
ing healing. There are multiple delivery agents for local antibiotics, including
sponges, fleeces, injections, and beads. Some agents appear to confer some benefit
due to their space filling potential, with decreased seroma incidence and improved
hemostasis [15]. A prospective trial found that gentamicin absorbable fleeces used
following APR reduced postoperative wound infection to 6 % compared to 21 % of
controls, but this did not translate into a statistically significant improvement in rates
of wound healing [16]. A large multicenter randomized control trial comparing
gentamicin-collagen fleeces following APR to standard care failed to demonstrate
any reduction in perineal wound complications [17]. Due to the lack of consistent
evidence demonstrating benefit, we do not recommend the routine use of local anti-
biotic agents. This advice is consistent with a large systemic review on the use of
local gentamicin which did not support its use following APR [15].
Negative Pressure Wound Therapy
Vacuum assisted closure (VAC) is typically performed with foam wound dressings
(either packed or at the skin surface) under negative pressure, and has become an
increasingly common tool used for difficult surgical wounds to expedite the sec-
ondary intention healing process [18]. Its proposed mechanism decreases bacterial
colonization within the wound, as well as tissue edema and wound tension, while
increasing blood flow to the wound area [19]. Further, the device may confer ben-
efit by creating a mechanical stimulus at the wound site, stimulating neo-angiogen-
esis, and enhancing granulation tissue production [20]. The tight seal associated
with the VAC equipment additionally prevents exogenous contamination between
dressings. Some frequent issues with these devices include their high costs, bulky
size (which prevents patient mobility), and increased expertise required for dress-
ing changes and device management [20]. It also should be avoided in patients
susceptible to fistula formation [21]. Maintaining the necessary tight seal of the
appliance may also be difficult due to the contours of the perineal space [22].
Recent improvements in technology including smaller, battery-operated vacuum
canisters that have allowed increased patient mobility and more frequent use in the
outpatient setting [22].
While there is considerable literature on negative pressure therapy, there is little
data on the use in persistent perineal wounds other than a few small case series [19,
22]. Fujino et al. reported four cases, two to prevent and two to treat perineal wounds
following proctectomy. All of these cases were successful without noted complica-
tion [19]. Yousaf et al. reported a single case of a large PPS (extending up to S2 via
sinogram) following proctocolecotmy for IBD, which healed successfully with
VAC therapy after 15 days [22]. This therapy has proven to be a safe and effective
modality for wound healing and has shown promise in both the prevention and clo-
sure of complex perineal wounds [18].
Endoscopic Approaches: Sinusoscopy
The use of an endoscope to visualize and washout the perineal sinus cavity is a novel
technique described by Al-Sheikh et al. [21]. They describe successful closure of three
perineal sinus cavities, between 55 and 655 days old, with a technique that involves
introduction of a pediatric gastroscope into the perineal sinus cavity. The gastroscope
is used to irrigate the cavity with a hydrogen peroxide and saline mixture under direc-
tion visualization followed by endoscopic breakdown of loculations and curettage.
This has the added benefit of allowing for monitoring for cancer recurrence with biop-
sies. This procedure is not recommended unless the perineal sinus is well developed,
and may have the risk of causing sepsis or intraperitoneal air. There is little evidence
on the safety of this technique and no additional studies to validate its efficacy.
Hyperbaric Oxygen Therapy
The use of hyperbaric oxygen therapy has demonstrated efficacy in improving heal-
ing in difficult, chronic wounds such as diabetic foot ulcers [6]. A small case series
featuring IBD patients with persistent “extreme” PPS following proctectomy
showed complete healing in all four patients with preoperative hyperbaric oxygen
(25–30 sessions, 2.2–2.4 atm) combined with rectus abdominus muscle (RAM) flap,
despite having previously failed multiple surgical interventions [6]. While this paper
showed promising results with rapid wound healing of severe and chronic sinuses,
further large and prospective studies are required to investigate any potential role of
hyperbaric oxygen in the setting of perineal wounds.
Operative Strategies
The goals of reconstruction of the perineum following APR, as suggested by Sinna

et al., include: avoid tumor recurrence, fill the dead space, and obtain skin healing
[1]. The decision to reconstructa perineal wound, either immediately following APR
or after development of PPS, is complex and multifactorial. The available evidence
for the most common approaches will be outlined below. Prior to any additional
operative intervention it is critical to evaluate patient anatomy, patient surgical risk
factors, and patient care goals.
Omental Pedicle Grafts
The significant anatomical vacancy left following proctectomy leaves a space that can
fill with fluid and become infected. One strategy is the use of omental pedicle grafts to
fill the defect. Technically this can be accomplished via creation of a vascular pedicle
(typically based off the right or left gastro-epiploicvessels), with pelvic delivery via
either a retrocolic or paracolic approach [20]. This graft can typically be performed
with a laparoscopic approach, and is not as time-intensive or invasive as other autolo-
gous tissue grafts. A systemic review of omental pedicle flaps evaluated 14 studies
including 891 patients. Primary perineal wound healing was 67 % with an average
time of 24 days for patients receivingo mental pedicle flaps compared to 50 % with an
average time of 79 days for patients without omental pedicle flap. Importantly, operat-
ing time was only minimally increased and there were few reported complications to
the procedure [20]. One disadvantage to this technique in the setting of an unhealed
perineal wound is the necessity of an additional major abdominal operation [23]. It is
for this reason that the majority of such omental pedicle grafts are performed as imme-
diate reconstructions during the abdominal portion of APR or proctocolectomy.
Wide Excision and Split Thickness Skin Grafts
The use of wide excision of the sinus followed by split thickness skin grafting of the
perineum is an operative intervention that has the advantage of less donor site mor-
bidity and ease of procurement of the graft compared to a muscle flap or omental
flap. McLeod et al. reported healing in five of nine patients with this technique in a
small case series [24]. Due to a difficult wound environment in the perineum, with
high levels of sheering forces, the split thickness skin graft is now rarely utilized in
perineal wounds when other grafts are available [8].
Gracilis Muscle Flap
The gracilis muscle flap is performed with a longitudinal incision in the medial
thigh to harvest a gracilis muscle vascular pedicle (from the medial circumflex fem-
oral artery), and subsequently transposing the pedicle to the perineal defect [3]. The
loss of gracilis muscle, either unilaterally or bilaterally, does not cause significant
functional limitations. This advancement flap is most successful when the sinus to
be filled is relatively narrow, and is less ideal when there is an extensive pelvic space
for which it may be less than sufficient [3]. The gracilis flap has a high partial skin
necrosis rate which may compromise the flap and cause further morbidity [25].
Rectus Abdominus Myocutaneous Flap
The rectus abdominus muscle (RAM) flap can be harvested in various configura-
tions with a pedicle derived from the superior or inferior epigastric arteries [26].
This can be performed with multiple variations at the donor site including a vertical
harvest (VRAM), transverse approach (TRAM), and oblique orientation (Taylor’s

Flap) [27]. Noted advantages to this flap include its availability within the operative
field, ability to be harvested extraperitoneally, and its reliability. It can provide sub-
stantial bulk when a large pelvic defect needs to be closed. However as laparoscopic
approaches become more common for the abdominal portion of the operation, the
RAM may create unwanted abdominal sequelae such as increased postoperative
pain and pulmonary complications [27]. Additionally a major potential drawback
with the use of the rectus abdominus muscle in the setting of colorectal surgery is
the loss of potential sites for ostomy creation [3]. Other potential donor site morbid-
ity include the possibility of ventral hernias at the donor site due to weakening of the
abdominal wall, which may be ameliorated with propylene mesh placement at the
procurement site [26]. Other variations intended to decrease the donor site morbid-
ity include the muscle sparing VRAM (ms-VRAM), the deep inferior epigastric
perforator flap, as well as fascial-sparing techniques [27].
GRADE of
Intervention References Study design evidence Summary of recommendations
Debridement Lewis et al. Review and Moderate Some modern dressings (i.e.,
and curettage (2001) [14] metanalysis hydrocolloid, alginate, and
foam dressings) may improve
secondary intention wound
healing compared to traditional
gauze, however many trails
suffered from methodological
flaws and may be prone to bias.
Local Collin et al. Multicenter High No significant differences in
antibiotic (2013) [17] RCT (7 perineal wound healing were
agents hospitals, noted between those who
n = 102) received local gentamicin-
collagen and those who did not.
Negative Fujino et al. Case series Very low VAC therapy appears to be a
pressure (2015) [19] (n = 4) useful adjunct to speed perineal
(VAC) wound wound healing by secondary
therapy intention.
Endoscopic Al-sheikh Case series Very low Patients tolerate the procedure
approaches et al. (2015) (n = 3) safely without serious
[21] complication, and exhibited
perineal wound healing. Further
evidence is needed with larger
trials prior to further
recommendation.
Hyperbaric Chan et al. Case series Very low Hyperbaric oxygen therapy,
oxygen (2014) [6] (n = 4) followed by PPS excision and
RAM flap, led to complete
wound healing in all patients in
study. Appears to be a safe
treatment modality for extreme
and persistent perineal wounds
GRADE of
Intervention References Study design evidence Summary of recommendations
Omental Killeen et al. Review and Moderate Omental mobilization, transfer,
pedicle grafts (2013) [20] metanalysis and buttressing of primary
(14 studies) perineal repair following
protectomy reduces perineal
wound morbidity with minimal
additional operating time or
flap-associated morbidity.
Studies
Gracilis Menon et al. Case series Low A gracilis transposition is
muscle flap (2005) [10] (n = 17) relatively simple operation with
minimal morbidity useful for
superficial sinuses not requiring
much bulk.
Rectus Chessin et al. Prospective Moderate RAM flaps, when compared to
Abdominus (2005) [28] cohort primary closure alone, had a
Muscle significantly lower rate of
(RAM) flap perineal wound complications,
relative to the control group.
Donor site morbidity should be
taken into account when using
the RAM flap.
Pudendal flap Bodinet al. Case series Very low Advantages to this flap include
(2015) [25] (n = 6) less donor site morbidity, rich
blood supply, immediate
proximity to wound, and
complete supra-fascial
procurement.
Gluteus Haapamaki Prospective Moderate There are significant functional
maximus flap et al. (2011) cohort limitations following gluteus
[29] (n = 19) maximus flap. Functional
deficits should be discussed
with the patient and be taken
into account prior to use.
Biologic Foster et al. Review and Moderate There was no significant
mesh (2012) [30] metanalysis difference in the rates of
implants perineal wound complications
of perineal hernia formation
when comparing biological
mesh repair to flap repair.
Pudendal Flaps
Flaps derived from branches of the internal pudendal artery have been reported with
success in the literature, under various names such as pudendal flaps, lotus flaps,
gluteal fold flaps, and Singapore flaps [27]. These reconstructive approaches have
been used frequently in the gynecologic surgery realm for pelvic reconstruction fol-
lowing pelvic exenteration [25].
One example is the supra-fascial lotus petal flap, named for the lotus petal shape
of the resected donor sites. Advantages include effective coverage and healing with-
out muscle harvesting or decrease in function, the option for unilateral or bilateral
flaps, and improved cosmesis (as the flaps are procured from within the gluteal
fold). When APR is performed in the prone position, no repositioning is required.
Further, the flaps benefit from a rich blood supply derived from terminal branches
of the internal pudendal arteries. The flap remains innervated from pudendal nerves
and can be released safely without the underlying fascia. A small case series of six
patients with chronic perineal wounds (four after APR) demonstrated no wound
complications and a mean wound healing time of 35 days [25].
Gluteus Maximus Flap
The gluteus maximus flap is a local flap which provides ample tissue for filling the
desired defect, and can be performed in either a bilateral or unilateral fashion [31].
This strategy provides a bulky and reliable flap immediate adjacent to the wound
site, and avoids the abdomen entirely. A case series by Baird et al. demonstrated
50 % (8/16 patients) uncomplicated healing rates with this technique [32].
Unfortunately, the loss of gluteus maximus function cannot be understated. As a
major hip extensor, the gluteus maximus plays an important role in posture, gait, and
balance [1]. One study investigating performance status in patients who had under-
gone proctectomy with gluteal flap coverage found significantly decreased function
with gait and balance, and high levels of pain while seated [29].
Similar to the RAM flap, various alterations of this flap have been devised to
decrease the donor morbidity (and in this case functional impairment) of the donor
site. Perforator flaps designed to spare the underlying gluteus maximus muscle such
as the VY-perforator flap, the inferior gluteal artery perforator flap, and the superior
gluteal artery perforator flap [27]. These adapted flaps are more technically chal-
lenging and are smaller tissue flaps than a full gluteus flap.
Meshes and Biological Implants
To avoid the morbidity of the previously mentioned myocutaneous flaps (or in centers
with limited access to reconstructive plastic surgery expertise) while still expediting
natural closure of the sinus cavity, one can turn to various meshes and biological scaf-
folds. Human acellular dermal matrix has been proposed for reconstruction as it is
more biologically compatible than synthetic meshes, and was shown in a small case
series to have excellent primary healing rates, with 11 of 12 patients achieving com-
plete primary perineal wound healing at 2 weeks post surgery. The most common
complications noted after this procedure were seroma formation and chronic perineal
pain, occurring in 8 % and 33 % of the patients in this series respectively [33].
Harries et al. (2014) examined the immediate use of a similar porcine collagen
implant (Permacol) following extralevator APR and also noted high rates of primary
wound healing (73.9 % at 4 weeks, 90.9 % at 6 months) [15]. There is little data to
date on the use of these scaffolds for chronic wounds. A review comparing evidence
for immediate reconstruction with myocutaneous flaps versus prophylactic biological
mesh showed no significant differences in perineal healing rates, however these
studies were criticized for methodological flaws and small sample sizes [30]. A
large multicenter randomized controlled trial comparing biologic mesh closure to
primary perineal closure is currently underway to further investigate mesh perineal
closure following extralevator APR [34].
While some synthetic meshes have been suggested to promote adhesion forma-
tion with higher incidence of bowel obstruction, Kusunoki et al. demonstrated that
the use of hyaluronic acid impregnated (Seprafilm®) absorbable mesh to recon-
struct the perineum may prevent adhesions [11].
Conclusions
The persistent perineal wound after proctectomy is a complex problem that results
in morbidity for patients following surgery. The treatment strategies available to
these patients range greatly in their complexity and cost. There are many patient and
disease specific factors that must be considered when determining which approach
to take. It is important to assess the impact of the unhealed wound on the patient’s
quality of life to determine the most appropriate treatment. We recommend evaluat-
ing the patient’s wound healing capacity and optimizing all augmentable factors.
Nutrition should be optimized, serum glucose should be under control and all efforts
to stop smoking should be made. Infection and sepsis should be treated appropri-
ately and fluid collections drained appropriately. The patient’s anatomy should be
clearly delineated by physical examination, intraoperative evaluation, and with rel-
evant imaging modalities.
For small wounds with a minimal impact on the patient we recommend debride-
ment of any devitalized tissue as needed. Depending on the size of the remaining
defect, local wound care and healing by secondary intention may be all that is nec-
essary. Negative pressure wound therapy is a useful adjunct to speed secondary
intention healing. Additional novel and emerging therapies, including hyperbaric
oxygen, and sinusoscopy lack sufficient evidence for recommendation.
For large sinuses, excision with an autograft may be necessary to close the space.
Multiple factors must be taken into account when choosing a flap for your patient,
and collaboration with a plastic surgeon may be beneficial [35]. The required volume
of tissue necessary to fill the defect, the presence of absence of a rectus abdominus
stoma, a patient’s functional and performance status, patient cosmetic concerns, and
presence of vascular disease should all be considered when selecting the ideal flap.
Prophylactic measures can be taken at the time of initial proctectomy to mini-
mize the risk of perineal wound complication. Extralevator APR, or any rectal
excisions that leave large perineal cavities, remain at particularly high risk for
potential wound complication. Strong consideration should therefore be taken to
immediate reconstruction with either a flap or mesh approach.
Finally, evaluation of the current evidence makes it clear there are many promis-
ing and innovative therapies in this field with only minimal evidence to support.
There is a need for high quality, large randomized trials to improve the strength of
current recommendations. Until that time, controversies in treatment strategy will
remain and management based on anectodal evidence.
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Dis. 2012;14(9):1052–9. doi:10.1111/j.1463-1318.2012.03169.x.
31. Nisar PJ, Scott HJ. Myocutaneous flap reconstruction of the pelvis after abdominoperineal
excision. Colorectal Dis. 2009;11(8):806–16. doi:10.1111/j.1463-1318.2008.01743.x.
32. Baird WL, Hester T, Nahai F, Bostwick III J. Management of perineal wounds following
abdominoperineal resection with inferior gluteal flaps. Arch Surg. 1990;125(11):1486–9.
doi:10.1001/archsurg.1990.01410230080014.
33. Han JG, Wang ZJ, Gao ZG, et al. Pelvic floor reconstruction using human acellular dermal
matrix after cylindrical abdominoperineal resection. Dis Colon Rectum. 2010;53:219–23.
34. Musters G, Bemelman W, Bosker R, et al. Randomized controlled multicentre study compar-
ing biological mesh closure of the pelvic floor with primary perineal wound closure after
extralevator abdominoperineal resection for rectal cancer (BIOPEX-study). BMC Surg.
2014;14(1):58. doi:10.1186/1471-2482-14-58.
35. Arnold P, Lahr C, Mitchell M, et al. Predictable closure of the abdominoperineal resection
defect: a novel two-team approach. J Am Coll Surg. 2012;214(4):726–32. doi:10.1016/j.
jamcollsurg.2011.12.035.
Index
A recurrence rates, 351–352

Abdominal vs. perineal approach, rectal 5-aminosalicylic acid (5-ASA) medications
prolapse colorectal cancer, 89
function and quality of life, 350 for post-operative Crohn’s patient, 103
morbidity and mortality, 351 Anal dysplasia/cancer
recurrence rates, 348–349 abnormal pap smear, in HIV positive
Abdominoperineal resection (APR) patients, 267–271
local antibiotic agents, 569–570 AIN 3, 257–264
operative strategies, 571 Anal fissure
PPS incidence, 567 botulinum toxin, 383
Abnormal pap smear, in HIV positive patients, calcium channel blockers, 383
267–271 degree of incontinence, 388
ACTH stimulation, steroid-treated patients etiology, 383
with IBD, 75, 81 fiiber supplement, 388
Acute large bowel obstruction nonsurgical therapies, 388
emergency surgery, 122 recommendations, 387
endoscopic stenting, 121, 129 recurrence after LIS
patient approach, 129 botulinum toxin, 398–399
search strategy, 122 recommendations, 398
self-expanding metal stents search strategy, 396–397
as bridge to surgery, 125–128 studies on, 397–398
as definitive palliation, 123–125 treatment options, 396
safety and efficacy, 123 search strategy, 384
vs surgery, 130–134 studies on, 384–387
Adalimumab Anal fistula, transsphincteric
for fistulizing disease, 23 advancement flaps, 365–366
for post-operative Crohn's patient, 104 biologic products, 366
Adenoma-like mass/lesion (ALM), 90, 92–93 fistulotomy, 362, 364
AIN 3. See Anal intraepithelial neoplasia III LIFT procedure, 367, 368
(AIN III) management, 361, 364
Altemeier vs. Delorme’s procedure, rectal Parks classification system, 361, 362
prolapse search strategy, 362
function and quality of life, 352 setons, 365
morbidity and mortality, 352, 353 studies on, 363

DOI 10.1007/978-3-319-40223-9
582 Index
Anal intraepithelial neoplasia, 267 B

Anal intraepithelial neoplasia III (AIN III) Benign anal disease
clinical trials, 256 anal fissures
electrocautery, 258 botulinum toxin, 383
expectant management, 261 calcium channel blockers, 383
high-resolution anoscopy, 256 degree of incontinence, 388
infrared coagulation, 258 etiology, 383
prevention, 257 fiiber supplement, 388
recommendations, 261–264 nonsurgical therapies, 388
search strategy, 256 recommendations, 387
treatment, 257–261 search strategy, 384
Anal sphincter repair studies on, 384–387
fecal incontinence, 440 hemorrhoids
outcome prediction, 441–442 control of symptoms, 405–406
QOL, 440 cost, 407–408
repeat sphincteroplasty outcomes, expert opinion, 409–410
442–443 grade I/II, 403
reporting and comparing outcomes, 443 grade III, 403, 409
sacral nerve stimulation, 443–444 lifestyle, 407
Anal squamous cell carcinoma (ASCC), 255 post-treatment pain and complications,
electrocautery, 258 406–407
incidence, 267 recommendations, 408–409
prevention, 257 search strategy, 404
Anastomosis studies on, 404–405
CD recurrence, 100 recurrent anovaginal/rectovaginal fistula
ileoanal, 35 collagen matrix biomesh, 377
Anastomotic leak management gracilis flaps, 380
after LAR, 233, 235–238, 558 greater omentum mobilization, 378
peritonitis, 560–561 LIFT procedure, 380
reestablishing intestinal continuity, recommendations, 379
562–563 rectal sleeve advancement, 377
sepsis, 560–561 search strategy, 371–372
anastomotic takedown vs. salvage, 560 studies on, 372–379
endoluminal vacuum (E-Vac) sacral nerve stimulation (see Sacral nerve
therapy, 559 stimulation (SNS))
ostomy, 563 Biological therapy
partial disruption, 564 for post-operative Crohn's patient, 104
primary anastomosis, 315 pouch vaginal fistula, 57
proximal diversion, 563 Bowel obstruction, 121. See also Acute large
re-do surgery vs. endoluminal vacuum bowel obstruction
therapy, 561 Bowel preparation, colon resection, 467
sepsis, 559 limitation, 469
stomas, 559 oral antibiotic strategy, 472
surgical management, 560–561 recommendations, 471
ulcerative colitis, 38 search strategy, 468
Anti-TNF medications studies on, 468–471
perianal fistulas with Crohn’s disease, BRAF gene mutation, 168
22–23 British Columbia Cancer Agency (BCCA), 166
for post-operative Crohn's patient, 105
ulcerative colitis, 39
Antibiotics C
Clostridium difficile colitis, 279 CEA testing, colorectal cancer, 117–118
for post-operative Crohn's patient, Cecum, large sessile adenomas of. See Large
103–104 sessile cecal polyps
Index 583
Checklists, surgery randomized controlled trials, 144

benefits, 456–458 recommendations, 148–149
benefits to colorectal surgery, 458, 461 risk factor, 89
cost, 458–460 search strategy, 116, 140–144
implementation, 461–462 surveillance and diagnosis, 115
perioperative mortality and mortality rate, survival and quality, 142–143
453–455 systemic inflammation and primary
recommendations, 461 resection, 147–148
search strategy, 452 unresectable metastatic, 144
studies on, 452 Computed tomography (CT)
Clostridium difficile colitis (CDC) colorectal cancer, 119
diverting loop ileostomy, 280 local recurrent rectal cancer, 242
morbidity and mortality, 275, 277 T1 rectal cancer, 180
non-surgical options, 276 Controlled rehabilitation with early
recommendations, 279–280 ambulation and diet
search strategy, 276 (CREAD), 506
studies, 277–279 Conventional laparoscopy (CL), 546
surgical management, 276 Conventional transanal resection,
Colectomy 511–512
conventional laparoscopy, 546 Corticosteroids
laparoscopic (see Laparoscopic inflammatory bowel disease, 73, 74
colectomy) for post-operative Crohn's patient, 103
SILS, 546 Crohn’s colitis
Coloanal anastomosis (CAA), 535 bowel continuity restoration, 65
Colonoscopy recommendations, 69–70
colorectal cancer, 118 risk factors, 69
Crohn’s disease, 105–106 search strategy, 66
Hinchey III diverticulitis, 302 studies, 66–68
ulcerative colitis, 90 Crohn’s disease (CD)
Colorectal cancer (CRC) post-operative prophylaxis
acute large bowel obstruction, 5-ASA, 103
121–134 antibiotics, 103–104
acute surgery during chemotherapy, 147 biological therapy, 104
age of onset, 89 clinical recurrence, 97, 98
CEA testing, 117–118 corticosteroids, 103
chemotherapy, 142–143 disease behavior, 99
chemotherapy and survival, 145–146 endoscopic assessment, 100–101
colonoscopy, 118 immunomodulators, 103–104
cost-effectiveness, of surveillance non-invasive assessment, 101–102
programs, 119 patient factors, 99
CT scan, 119 probiotics, 103
disease duration and extent, 89 recommendations, 105–106
family history, 89 surgical factors, 99–100
flexible sigmoidoscopy or proctoscopy, 118 Crohn’s Disease Activity Index
history and physical examination, 117 (CDAI), 101
incidences, 84
intensive postoperative surveillance
programs, 116 D
metastatic disease burden and Defective MMR (dMMR), 166, 167
survival, 146 Delorme's procedure, 352
MRI and PET scans, 119 Diverticular abscess, percutaneous drainage of
patient population, 140, 142–143 recommendations, 287–288
postoperative complications, 147 search strategy, 283–284
PRISMA guidelines, 141 studies, 284–287
584 Index
Diverticulitis, 319 Endoscopic mucosal resection

acute, 307 (EMR), 155
anastomotic leak, 315 Endoscopic submucosal dissection (ESD),
ASCRS guidelines, 328 153, 155–156
choice of surgery, 316 Enhanced recovery pathways (ERP)
chronic, 328 complications, 488
complicated, 327, 329 components, 485, 486
database studies, 312–313 cost, 493–494
DILALA Trial, 297 GRADE approach, 486
with end stage renal disease (ESRD), 331 length of stay, 493
Hinchey III, 292 meta-analyses and systematic reviews,
Hinchey IV, 292 488–493
LADIES trial, 300 PICO table, 486–487
Markov model, 328 pre-anesthesia evaluation and testing,
meta-analyses, 311–312 497–498
mortality data, 313–315 QoL, 496
outcomes, 321–324 quality of life, 494–495
quality of life, 325–326 readmission, 488–493
randomized control trials (RCTs), 311 recommendations, 495–496
randomized-controlled trials, 297–300 search strategy, 487
recommendations, 301–302, 315, 331 studies on, 488
recurrence rates, 303, 327–328 theoretical benefits, 486
resection after complication, 332 Evidence
retrospective/prospective cohort studies, 313 initial evaluation, 8
SCANDIV trial, 300 methodological limitations, 10
search strategy, 292, 308, 320 quality rating
sigmoid, 307 downgrading evidence, 12–13
special populations, 330–331 strength of recommendation, 15
stoma formation, 302 upgrading evidence, 13–14
studies on, 293–297, 308–310 random error, 9–10
uncomplicated, 320 stratifying evidence, 8
Diverting ileostomy, 40, 60, 503 systematic error, 9, 10
Doppler-guided hemorrhoidal artery ligation Evidence based medicine(EBM)
(DGHAL), 403, 405–406 evolution of, 5
Dysplasia associated lesion or mass historical datas, 3–4
(DALM), 92 model for, 5, 6
Dysplasia, in UC transitional era of, 3
ALMs, 92–93 Excisional hemorrhoidectomy (EH), 403,
classification, 89–90 405–406
DALMS, 92
flat LGD, 91
high grade dysplasia, 91–92 F
incidences, 84 Familial adenomatous polyposis (FAP)
neoplastic progression, 90–91 IPAA, 340
recommendations, 93–94 IRA, 340
search strategy, 84 outcomes of surgery, 338–339
studies, 85–88 quality of surgery, 339
recommendation, 341–343
surgical options, 338
E Fast track protocol, laparoscopic surgery
Electrocautery, 258 GRADE system, 477
Endoluminal vacuum (E-Vac) therapy, 559, 561 outcomes, 483
Endorectal advancement flap (ERAF), 361 PICO chart, 476
perianal fistulas, 23 recommendations, 482
Index 585
search strategy, 476–477 levels of evidence and definitions, 11

studies on, 478–482 perianal fistulas with Crohn's
Fecal calprotectin (FC), 101–102, 105 disease, 21
Fecal incontinence (FI) rating quality of evidence, 7, 12
anal sphincter repair, 439 surgical checklist, 452
anal ultrasound, 417 Grafts, omental pedicle, 571–572
balloon inflation, rectum, 417
definition, 423
diagnostic workup, 413 H
etiology, 423, 439 Hartmann’s procedure, 307
noninvasive therapies, 439 Harvey-Bradshaw index, 101
recommendations, 416 Hemorrhoids
search strategy, 413 control of symptoms, 405–406
studies on, 414–416 cost, 407–408
surgical approaches, 440 expert opinion, 409–410
Fibrin glue, 23 grade I/II, 403
Fissures and skin tags with CD grade III, 403, 409
identifications, 29 lifestyle, 407
medical management, 32, 33 post-treatment pain and complications,
PICO table, 30 406–407
quality of evidence, 31 recommendations, 408–409
recommendations, 30 search strategy, 404
search strategy, 30 studies on, 404–405
Fistula. See Anal fistula, transsphincteric; High-dose steroids, IBD, 73
Pouch vaginal fistula (PVF) High grade dysplasia, 91–92
Fistula plug, 23 High-grade squamous intraepithelial lesion
Fistulectomy, 57 (HSIL), 255
Fistulotomy, 22, 362, 364 expectant management, 261
Flaps treatment, 257, 259–260
transsphincteric anal fistula, High-resolution anoscopy (HRA), 256
365–366 incidence, 269
unhealed perineal wound recommendations, 270
gluteus maximus, 575 surveillance strategies, 269
gracilis muscle, 572 HIV-infected MSM, 267
pudendal, 574–575 meta-analysis, 269
rectus abdominus myocutaneous, recommendations, 270–271
572–574 screening, 268
Fluorouracil (5-FU) search strategy, 268
AIN 3 treatments, 258 Human papilloma virus (HPV), 255
for synchronous colorectal liver
metastasis, 216
T2 N0 rectal cancer, 188 I
Ileal pouch anal anastomosis (IPAA)
Crohn's colitis
G cost-effectiveness, 68
Gracilis muscle interposition flap, 58–59 intentional use, 68
Graciloplasty, 378 proctitis or rectal stenosis, 67
GRADE (Grading of Recommendations strict inclusion criteria, 67
Assessment, Development and technical approach, 70
Evaluation) for ulcerative colitis, 35, 39
diverticulitis, 293 Immunomodulators, 103–104
enhanced recovery pathways, 486 Imprecision, 12
fast track protocol, laparoscopic Inconsistency, 12–13
surgery, 477 Indirectness, 13
586 Index
Inflammatory bowel disease (IBD) vs. open rectopexy, 355

Crohn’s colitis, 65–70 LAR. See Low anterior resections (LAR)
Crohn’s disease (CD), 97–106 Large sessile cecal polyps
dysplasia in UC colonoscopic polypectomy method, 156
incidences, 84 endoscopic mucosal resection (EMR), 155
patients and interventions, 84 endoscopic submucosal dissection (ESD),
recommendations, 93–94 153, 155–156
search strategy, 84 incidence, 153
studies, 85–88 laparoscopic full thickness resection, 156–157
fissures and skin tags with CD, 29–33 polyp characteristics, 158
perianal fistulas with Crohn’s disease, 20–26 standard segmental bowel resection, 157
pouch vaginal fistula, 53–61 surgical removal by, 153–154
steroid management treatment algorithm, 157–159
adverse effects, 73 treatment options, 155
high-dose steroids, 73 tumor location, 158
hypotension, 75 Western gastroenterologists, 154
perioperative steroid dosing, 76–78 Lateral internal sphincterotomy (LIS)
during proctocolectomy, 80 anal fissure, 395
randomized-controlled studies, 79 anal fissure recurrence after
recommendations, 80–81 botulinum toxin, 398–399
renal transplant recipients, 79 recommendations, 398
retrospective study, 75 search strategy, 396–397
search strategy, 74 studies on, 397–398
stress-dose steroids, 73–74 treatment options, 396
studies, 75–80 fissures with CD, 30
ulcerative colitis, 35–41, 45–49 LIFT procedure, 367, 368
Inflammatory Bowel Disease Questionnaire perianal fistulas, 23
(IBDQ), 46 Ligation of the intersphincteric fistula tract
Infliximab procedure (LIFT), 361
for post-operative Crohn's patient, 104 Local recurrent rectal cancer
ulcerative colitis, 39 chemotherapy and radiation, 243
Infrared coagulation, 258 classification, 242–243
imaging techniques, 242
intraoperative radiotherapy, 244
K multimodal treatment approach, 244
Kono-S anastomosis, 100 neoadjuvant chemoradiotherapy, 246
KRAS gene mutation, 168 R0, R1 and R2 resections, 244, 246
recommendations, 245–247
search strategy, 242
L stages of invasion, 243
Laparoscopic colectomy studies, 242–245
cosmetic outcomes, 551–552 Locally advanced rectal cancer (LARC)
cost, 547, 551 imaging techniques, 193
hernia formation, 552 local recurrence, 192
oncologic outcomes, 552 neoadjuvant chemoradiotherapy
pain, 551 clinically complete responses, 194
perioperative outcomes, 547 tumor response to, 192–194
randomized clinical trials (RTC), 545 non-operative management
recommendations, 552 in elderly patients, 200
Laparoscopic methods evidence, 194, 196–197
for large sessile cecal polyps functional outcomes and toxicity, 199
colonoscopic polypectomy method, 156 local regrowth and salvage therapy, 197
endoscopic mucosal resection (EMR), 155 oncological outcomes, 195
endoscopic submucosal dissection stoma rates and operative mortality,
(ESD), 155–156 197–199
full thickness resection, 156–157 operative management, 196–197
Index 587
pathologic complete response search strategy, 283–284

Low anterior resection (LAR), 535 studies, 284–287
anastomotic leak, 233, 235–238 Perianal fistulas with Crohn’s disease
anastomotic leaks, 557 anti-TNF therapy, 22–23
diverting ostomy, 238 complex fistula and no macroscopic rectal
fecal diversion, 234–235 disease, 24–26
intraoperative assessment, of anastomosis, endorectal advancement flap, 23
237 fibrin glue, 23
randomized trials, 236 fistula and macroscopic rectal disease,
recommendations, 235 22–24, 26
reservoir construction (see Reservoir fistula plug, 23
construction) LIFT procedure, 23
search strategy, 234 medical therapy and surgical therapy, 24
Low anterior resection syndrome (LARS), 535 randomized clinical trials, 22
Low grade dysplasia, 90, 91 recommendations for, 25
search strategy, 20
simple fistula and no macroscopic rectal
M disease, 20, 22, 25
Magnetic resonance imaging (MRI) studies, 20
colorectal cancer, 119 Peritonitis
local recurrent rectal cancer, 247 anastomotic leak management after LAR,
pouch-vaginal fistulas, 55 560–561
rectal cancer, 206 Hinchey III disease, 292, 300
T2 N0 rectal cancer, 183, 184 Persistent perineal sinus (PPS)
Mechanical bowel prep (MBP), 4, 466, 467. abdominoperineal resection, 567
See also Bowel preparation, colon endoscopic approaches, 571
resection hyperbaric oxygen therapy, 571
Men who have sex with men (MSM), 267 local antibiotic agents, 569–570
Microsatellite instability (MSI), 166 negative pressure wound therapy, 570
Mismatch repair (MMR), 166 operative strategies, 571
PICO table
bowel obstruction with colorectal
N cancer, 122
National Cancer Center Network (NCCN), 148 Clostridium difficile colitis, 276
Neoadjuvant chemoradiotherapy, LARC colorectal cancer, 115
clinically complete responses, 194 Crohn’s colitis, 66
tumor response to, 192–194 diverticulitis, 292, 320
Neoadjuvant chemotherapy endoluminal vacuum (E-Vac) therapy, 559
rectal cancer, 220 enhanced recovery pathways, 486–487
synchronous colorectal liver metastasis, 207 fast track protocol, laparoscopic
surgery, 476
fissures with CD, 30
O local recurrent rectal cancer, 242
Obstructing colorectal cancers. See also Acute percutaneous drainage of diverticular
large bowel obstruction abscess, 284
perianal fistulas with Crohn's disease, 21
PPS, 568
P rectal prolapse, 348
Painful fissure and skin tags. See Fissure and robotic vs. laparoscopic surgery, rectal
skin tags with CD cancer, 520
Parks classification system, 361, 362 stage II colon cancer, 163
Percutaneous drainage, of diverticular abscess steroid-treated patients with IBD, 74
elective colectomy, 287, 288 surgical checklist, 452
morbidity rate, 284 transanal endoscopic surgery, 512
outcomes after, 286 ulcerative colitis requiring operation, 45
recommendations, 287–288 Pneumorectum, 512
588 Index
Polyps, large sessile cecal. See Large sessile controlled rehabilitation with early
cecal polyps ambulation and diet, 506
Positron emission tomography (PET), 119 enhanced recovery program (ERP), 505
Post-operative Crohn’s patient. See Crohn's pre-operative stoma education, 504
disease (CD); post-operative recommendations, 506–507
prophylaxis search strategy, 504
Posterior rectopexy without/with resection stoma intervention, 505
function and quality of life, 354 Rectal cancer
morbidity and mortality, 354 laparoscopic vs. open surgery, 520
recurrence rates, 353–354 ACOSOG Z6051 trial, 521
Pouch vaginal fistula (PVF) ALaCaRT trial, 521
abdominoperineal approach anastomotic leak, 524
diverting ileostomy, 60 CLASICC trial, 521
surgical options, 59 COLOR II trial, 521
clinical examination, 55 complications, 524
double stapled technique, 53, 54 COREAN trial, 521
imaging, 55 length of hospital stay (LOS), 521, 524
patient counseling, 60 oncologic outcomes, 524–525
pelvic sepsis, 54 perioperative and oncologic outcomes,
perineal approach 522–523
biological therapy, 57 reoperation rates, 524
fistulectomy, 57 studies on, 521
gracilis muscle interposition flap, 58–59 low anterior resection
seton drain, 56–57 anastomotic leak, 233, 235–238
transanal ileal advancement flap, 57–58 diverting ostomy, 238
transanal pouch advancement, 59 fecal diversion, 234–235
transvaginal repair, 58 recommendations, 235
recommendations, 60–61 search strategy, 234
search strategy, 55 robotic surgery vs. laparoscopic surgery
studies, 56 anastomotic leak, 526
surgical technique, 53 complications, 526
symptoms, 54 conversion, 526–527
treatment algorithm, 61 cost, 526
PPS. See Persistent perineal sinus (PPS) length of hospital stay, 526
Primary sclerosing cholangitis (PSC), 89 oncologic outcomes, 527–528
Primary sclerosis cholangitis, 49 recommendations, 528–531
Probiotics, for post-operative Crohn's patient, reoperation rates, 526
103 studies on, 526
Proctectomy robotic vs. laparoscopic surgery, 520
anatomical defect, 568 total mesorectal excision (TME), 519
GRADE approach, paper evaluation, 569 Rectal prolapse
omental pedicle grafts, 571–572 abdominal vs. perineal approach
perineal Crohn’s Disease, 568 function and quality of life, 350
perineal wounds, 568 morbidity and mortality, 351
Proctocolectomy, 47 recurrence rates, 348–349
steroid-treated patients with IBD, 80 Altemeier vs. Delorme’s procedure
Proctoscopy, for colorectal cancer, 118 function and quality of life, 352
Publication bias, 13 morbidity and mortality, 352, 353
recurrence rates, 351–352
laparoscopic vs. open rectopexy, 355
R posterior rectopexy without/with resection
Random error, 9–10 function and quality of life, 354
Readmission morbidity and mortality, 354
enhanced recovery pathways (ERP), 488–493 recurrence rates, 353–354
and ileostomies PROSPER trial, 347
colorectal surgery, 503 randomized control trials (RCT), 347
Index 589
recommendations, 355–356 anastomotic leak management after LAR,

search strategy, 348 560–561
two nonrandomized control trials (NRCT), pelvic sepsis, 54
347 ulcerative colitis, 38, 39
ventral rectopexy, 355 Setons, 365
Recurrent anovaginal/rectovaginal fistula pouch vaginal fistula, 56–57
collagen matrix biomesh, 377 Sigmoid diverticulitis, 307. See also
gracilis flaps, 380 Diverticulitis
greater omentum mobilization, 378 Sigmoidoscopy, colorectal cancer, 118
LIFT procedure, 380 Single incision laparoscopic surgery (SILS)
recommendations, 379 technique, 546
rectal sleeve advancement, 377 Sinusoscopy, 571
search strategy, 371–372 Skin tags with CD, 29. See also Fissure and
studies on, 372–379 skin tags with CD
Reservoir construction Sphincteroplasty, 441
after LAR, 535 outcomes, repeat, 442–443
functional outcomes Stage II colon cancer
colonic J pouch vs. transverse chemotherapy, 165
coloplasty, 541 clinical and pathologic factors, 164, 166
side-to-end vs. colonic J pouch, 541 dMMR status, 167
straight CAA vs. colonic J pouch, 540–541 gene expression profiling, 168
perioperative outcomes molecular factors, 166
colonic J pouch vs. transverse MOSAIC study, 166
coloplasty, 540 non-risk stratified patients, 164
side-to-end vs. colonic J pouch, 540 QUASAR trial, 164
straight CAA vs. colonic J pouch, 539 recommendations, 169
recommendations, 542 search strategy, 163–164
search strategy, 536 Stoma avoidance, 291
studies on, 536–539 Stress-dose steroids, IBD, 73–74
techniques, 536 Surgical safety checklist (SSC), 451
Restorative proctocolectomy. See Ileal pouch benefits, 456–458
anal anastomosis (IPAA) benefits to colorectal surgery, 458, 461
Rubber band ligation (RBL), 403, 405–406 cost, 458–460
Rutgeerts’ scoring system, 100, 101 implementation, 461–462
perioperative mortality and mortality rate,
453–455
S recommendations, 461
Sacral nerve stimulation (SNS) search strategy, 452
anal sphincter defect, 430–431 studies on, 452
anal sphincter repair, 443–444 Synchronous colorectal liver metastasis
percutaneous nerve evaluation (SCRLM)
(PNE), 432 imaging techniques, 206
permanent implantation, 426–429 liver biopsy, 207
recommendations, 425, 432 neoadjuvant chemotherapy, 207
search strategy, 424 patient evaluation, 206–207, 221
studies on, 424–425 recommendations, 219–222
See Anovaginal/rectovaginal fistula, recurrent, search strategy, 206
Recurrent anovaginal/rectovaginal treatment
fistula liver-first approach, 217
Self-expanding metal stents (SEMS), acute multimodality treatment, 207
large bowel obstruction oncologic outcomes, 211–213
as bridge to surgery, 125–128 rectum-first approach, 215–216
as definitive palliation, 123–125 simultaneous resections, 217–218
safety and efficacy, 123 surgical approaches, 208–210,
vs surgery, 130–134 214–215, 218–219
Sepsis Systematic error, 9, 10
590 Index
T U
T2 N0 rectal cancer Ulcerative colitis (UC)
diagnostic imaging, 183 dysplasia in
local excision, 184, 188 classification, 89–90
neoadjuvant chemoradiation, 188 incidences, 84
oncologic interventions, 186 management, 91–93
patient factors, 183 recommendations, 93–94
recommendations, 185–189 search strategy, 84
search strategy, 185 studies, 85–88
stoma rates, 187 operative management
surgical decision making, 185 liver transplantation, 49
surgical treatment, 184 primary sclerosis cholangitis, 49
tumor location and staging, 183 recommendations, 47–48
T1 rectal cancer search strategy, 45–46
distant metastasis, 176 sphincter-sparing procedure, 48
evidence based recommendations, 179 sphincter resting pressures, 49
local excisional approaches, 178 studies, 46–47
local recurrence, 176 surgical management
meta-analysis studies, 177, 178 diverting loop ileostomy, 36–39
quality of life, 178 ileoanal pouch procedure, 35
recommendations, 179–180 initial colectomy, 39–40
search strategy, 176 recommendations, 40–41
studies, 176–179 risk factors, surgical outcomes, 35
transabdominal radical resection, search strategy, 36
175, 178 total colectomy, 36
T4 tumor, 166 Unhealed perineal wound
Total mesorectal excision (TME), 535 bacterial contamination, 568
Trans-anal endoscopic surgery vs. debridement, 569
conventional transanal surgery endoscopic approaches, 571
advantages, 516 gluteus maximus flap, 575
complications, 516 gracilis muscle flap, 572
methods of local excision, 516–517 meshes and biological implants, 575–576
studies on, 513–515 non-operative strategies, 569
Transanal endoscopic microsurgery (TEM), persistent perineal sinus, 567
512 pudendal flaps, 574–575
T2 N0 rectal cancer, 188–189 rectus abdominus myocutaneous flap,
T1 rectal cancer, 178 572–574
Transanal endoscopic surgery (TES), 512 split thickness skin grafting, 572
Transanal excision (TAE), 178 vacuum assisted closure, 570
Transanal ileal advancement flap, 57–58 wide excision, 572
Transanal pouch advancement, 59
Transsphincteric anal fistula
advancement flaps, 365–366 V
biologic products, 366 Vacuum assisted closure (VAC), 570
fistulotomy, 362, 364 Validated EuroQol Group’s EQ-5D-3 L
LIFT procedure, 367, 368 questionnaire, 46
management, 361, 364 Validated Short Form (SF)-36 Health Survey, 46
Parks classification system, 361, 362
search strategy, 362
setons, 365 W
studies on, 363 Wireless capsule endoscopy (WCE), 102
Transvaginal repair, 58 Wound healing, vacuum assisted closure, 570

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Difficult Decisions in Surgery:

For further volumes:

ISSN 2198-7750 ISSN 2198-7769 (electronic)

Library of Congress Control Number: 2016959469

© Springer International Publishing Switzerland 2017

Printed on acid-free paper

This Springer imprint is published by Springer Nature

I dedicate this book to my parents Yakov and

Chicago, IL, USA Neil Hyman

We gratefully acknowledge the talents, expertise, and assistance of Ms. Abby

3 IBD: Management of Symptomatic Anal Fistulas

10 IBD: Management of Dysplasia in Patients with

Part II Colon Cancer

12 Follow-Up in Patient’s After Curative Resection

Part III Rectal Cancer

17 Rectal Cancer: Management of T1 Rectal Cancer ������������������������������ 175

22 Selection Factors for Reoperative Surgery

Part IV Anal Dysplasia/Cancer

23 Anal Dysplasia/Cancer: Management

Part V Benign Colon Disease

25 Indications for Surgery in Patients with Severe

Part VI Benign Anal Disease

32 Optimal Management of the Transsphincteric Anal Fistula �������������� 361

34 Benign Anal Disease: When to Operate on the Patient with

Part VII Quality Improvement

40 Checklists in Surgery������������������������������������������������������������������������������ 451

Part VIII Technique

45 Trans-anal Endoscopic Surgery vs. Conventional

Maher A. Abbas Digestive Disease Institute, Cleveland Clinic Abu Dhabi,

James Church, MBChB, FRACS Department of Colorectal Surgery, Sandford

Woon Kyung Jeong Colorectal Service, Department of Surgery, Memorial

Nitin Mishra, MD Mayo Clinic College of Medicine, Rochester, MN, USA

Patricia L. Roberts, MD Division of Surgery, Lahey Hospital and Medical

Avery S. Walker, MD Department of Surgery, Brian Allgood Army Community

Where is the wisdom we have lost in knowledge? Where is the

Tell Me a Story. The Importance of an Anecdote

Information Literacy. Learning the New Language

© Springer International Publishing Switzerland 2017 1

Fig. 1.1 PubMed entries with keywords ‘evidence based medicine’

Fig. 1.2 Current model of

Patient preferences Research evidence

expertise encompasses the patient’s clinical state and surrounding circumstances,

Why This Book?

Evidence can be defined in the broadest sense as “… any empirical observation,

W.D. Buie, MD, MSc, FRCSC

© Springer International Publishing Switzerland 2017 7

Evaluation of evidence begins with a well-constructed clinical question including a

Once the evidence is collected, it is initially stratified by study methodology. Well

Health Care Question (PICO)

Outcomes OC1 OC2 OC3 OC4

Rate the quality of evidence for each outcome, across studies

Rate overall quality of evidence

Decide on the direction (for/against) and grade strength (strong/weak*)

Random Error and Systematic Error (Bias)

Methodological Limitations (Bias)

Table 2.1 GRADE: levels of evidence and definitions

Table 2.2 Study limitations in randomized trials

A summary of GRADE’s approach to rating quality of evidence

explain the variability between studies based on differences in populations, inter-

Chicago, IL, USA Neil Hyman

3 IBD: Management of Symptomatic Anal Fistulas

10 IBD: Management of Dysplasia in Patients with

12 Follow-Up in Patient’s After Curative Resection

17 Rectal Cancer: Management of T1 Rectal Cancer �� 175

22 Selection Factors for Reoperative Surgery

23 Anal Dysplasia/Cancer: Management

25 Indications for Surgery in Patients with Severe

32 Optimal Management of the Transsphincteric Anal Fistula �� 361

34 Benign Anal Disease: When to Operate on the Patient with

40 Checklists in Surgery�� 451

45 Trans-anal Endoscopic Surgery vs. Conventional

Tell Me a Story. The Importance of an Anecdote

Information Literacy. Learning the New Language

Why This Book?

Random Error and Systematic Error (Bias)

Methodological Limitations (Bias)

Large Magnitude of Effect

Dose Response Gradient

Overall Quality Rating

cenario 1: The Patient with a Simple Fistula and No

cenario 2: The Patient with Either a Simple or a Complex

cenario 3: The Patient with a Complex Fistula and No

Recommendations Based on the Data

A Personal View of the Data

Personal View of the Data

Diverting Loop Ileostomy

Initial Colectomy Prior to IPAA

Recommendations Based on the Data

A Personal View of the Data

Search Strategy (See Table 7.1)

Transanal Ileal Advancement Flap

Gracilis Muscle Interposition Flap

Transanal Pouch Advancement

Personal View of the Data

Recommendations Based on the Data

A Personal View of the Data