Pedunculated polyp limited surgical intervention such as a diverting stoma or bypass 1299

procedure may be appropriate in patients with stage IV disease

who develop obstruction. Hemorrhage in an unresectable tumor
Invasive ca can sometimes be controlled with angiographic embolization.
Muscularis
mucosa
External beam radiation also has been used for palliation. The
involvement of a palliative care team in the management of
Neck Sessile polyp these patients is critical.116
Stalk

Therapy for Rectal Carcinoma

Principles of Resection. The biology of rectal adenocarci-

CHAPTER 29 COLON, RECTUM, AND ANUS

noma is thought to be similar to the biology of colonic adeno-
carcinoma, and the operative principles of complete resection
of the primary tumor, its lymphatic bed, and any other involved
organ apply to surgical resection of rectal carcinoma. However,
Figure 29-25. Levels of invasive carcinoma in pedunculated and the anatomy of the pelvis and proximity of other structures
sessile polyps. ca = carcinoma. (ureters, bladder, prostate, vagina, iliac vessels, and sacrum)
make resection more challenging and often require a different
approach than for colonic adenocarcinoma. Moreover, it is more
molecular profiling for selecting patients to receive chemother- difficult to achieve negative radial margins in rectal cancers that
apy remains unproven. extend through the bowel wall because of the anatomic limita-
Stage III: Lymph Node Metastasis (Tany, N1, M0) Patients tions of the pelvis. Therefore, local recurrence is higher than
with lymph node involvement are at significant risk for both with similar stage colon cancers. However, unlike the intraperi-
local and distant recurrence, and adjuvant chemotherapy has toneal colon, the relative paucity of small bowel and other radi-
been recommended routinely in these patients. 5-Fluorouracil– ation-sensitive structures in the pelvis makes it easier to treat
based regimens (with leucovorin) and oxaliplatin (FOLFOX) rectal tumors with radiation. Therapeutic decisions, therefore,
reduce recurrences and improve survival in this patient popula- are based on the location and depth of the tumor and its relation-
tion. It is important to note, however, that a subgroup of patients ship to other structures in the pelvis.
with stage III disease will do well without chemotherapy. MSI Local Therapy. The distal 10 cm of the rectum are accessible
status in particular predicts good prognosis. Subset analysis transanally. For this reason, several local approaches have been
from the CRYSTAL trial has shown that patients with MSI- proposed for treating rectal neoplasms. Transanal excision (full
high stage III disease do not benefit from 5-fluorouracil–based thickness or mucosal) is an excellent approach for noncircum-
chemotherapy. Molecular profiling, therefore, may be helpful in ferential, benign, villous adenomas of the rectum. Transanal
determining which stage III patients can safely avoid systemic endoscopic microsurgery (TEM) and transanal minimally
chemotherapy.118 invasive surgery (TAMIS) make use of a specially designed
Stage IV: Distant Metastasis (Tany, Nany, M1) Survival is proctoscope, magnifying system, and instruments similar to
extremely limited in stage IV colon carcinoma. Systemic che- those used in laparoscopy to allow local excision of lesions
motherapy is recommended in almost all cases of distant spread. higher in the rectum (up to 15 cm). Although this technique
However, unlike many other malignancies, highly selected has been used for selected T1, and some T2, carcinomas, local
patients with isolated, resectable metastases may benefit from excision does not allow pathologic examination of the lymph
resection (metastasectomy). The most common site of metasta- nodes and might therefore understage patients. Moreover, local
sis is the liver. Of patients with systemic disease, approximately recurrence rates are high after transanal excision, and salvage
15% will have metastases limited to the liver. Of these, 20% are surgery, while often curative, has been reported to be associ-
potentially resectable for cure. Survival is improved in these ated with poorer survival than with initial radical surgery. Cur-
patients (20–40% 5-year survival) when compared to patients rent recommendation is to limit local excision of T1 lesions to
who do not undergo resection. Hepatic resection of synchronous patients with well to moderately differentiated small lesions
metastases from colorectal carcinoma may be performed as a (<3 cm) and/or in patients medically unfit for radical resection.
combined procedure or in two stages. The second most com- In general, local excision of any rectal neoplasm should be con-
mon site of metastasis is the lung, occurring in approximately sidered an excisional biopsy because final pathologic examina-
20% of patients with colorectal carcinoma. Although very few tion of the specimen may reveal an invasive carcinoma that then
of these patients will be potentially resectable, among those mandates more radical therapy.120,121
Ablative techniques, such as electrocautery or endocavi-
who are (about 1–2% of all colorectal cancer patients), long-
tary radiation, also have been used. The disadvantage of these
term survival benefit is approximately 30% to 40%. There are
techniques is that no pathologic specimen is retrieved to confirm
limited reports of successful resection of metastases in other
the tumor stage. Fulguration is generally reserved for extremely
sites (ovary and retroperitoneum are most common). Cytore-
high-risk, symptomatic patients with a limited life span who
ductive surgery and intraperitoneal chemotherapy (HIPEC) has
cannot tolerate more radical surgery.120
been suggested for patients with carcinomatosis, but remains
unproven for colorectal cancer and carries high morbidity.119,120 Radical Resection. Radical resection is preferred to local
The remainder of patients with stage IV disease cannot be therapy for most rectal carcinomas. Radical resection involves
cured surgically, and therefore, the focus of treatment should removal of the involved segment of the rectum along with its
be palliation. Methods such as colonic stenting for obstruct- lymphovascular supply. Although any microscopically nega-
ing lesions of the left colon also provide good palliation. More tive margin has been suggested to be adequate, most surgeons
1300 still attempt to obtain a 2-cm distal mural margin for curative to determine the T and N status of a rectal cancer. Ultrasound is
resections. highly accurate at assessing tumor depth, but it is less accurate
Total mesorectal excision (TME) is a technique that uses in diagnosing nodal involvement. Ultrasound evaluation can
sharp dissection along anatomic planes to ensure complete guide choice of therapy in most patients. MRI is useful to assess
resection of the rectal mesentery during low and extended low mesorectal involvement. When the radial margin is threatened
anterior resections. For upper rectal or rectosigmoid resections, or involved, neoadjuvant chemoradiation is recommended.122
a partial mesorectal excision of at least 5 cm distal to the tumor Stage 0 (Tis, N0, M0) Villous adenomas harboring carci-
appears adequate. TME both decreases local recurrence rates noma in situ (high-grade dysplasia) are ideally treated with local
and improves long-term survival rates. Moreover, this tech- excision. A 1-cm margin should be obtained. Rarely, radical
nique is associated with less blood loss and less risk to the pel- resection will be necessary if transanal excision is not techni-
vic nerves and presacral plexus than is blunt dissection. The cally possible (large circumferential lesions).
principles of TME should be applied to all radical resections
PART II

Stage I: Localized Rectal Carcinoma (T1-2, N0, M0)

for rectal cancer.
Although local excision has been used for small, favorable ses-
Recurrence of rectal cancer generally has a poor prog-
sile uT1N0 and uT2N0 rectal cancers, local recurrence rates
nosis. Extensive involvement of other pelvic organs (usually
may be as high as 20% and 40%, respectively. Local excision
occurring in the setting of tumor recurrence) may require a
increasingly is offered to patients with small, low-risk lesions,
pelvic exenteration. The rectal and perineal portions of this
SPECIFIC CONSIDERATIONS

but it does not allow physicians to assess regional lymph nodes.

operation are similar to an APR, but en bloc resection of the
For this reason, radical resection is recommended in all good-
ureters, bladder, and prostate or uterus and vagina are also per-
risk patients. Lesions with unfavorable histologic characteristics
formed. A permanent colostomy and an ileal conduit to drain
and those located in the distal third of the rectum, in particular,
the urinary tract may be necessary. The sacrum may also be
are prone to recurrence. In high-risk patients and in patients
resected if necessary (sacrectomy) up to the level of the S2-S3
who refuse radical surgery because of the risk of need for a
junction. These operations are best performed in tertiary centers
permanent colostomy, local excision may be adequate, but
with multidisciplinary teams consisting of a colon and rectal
strong consideration should be given to adjuvant or neoadju-
surgeon, urologist, neurosurgeon, and plastic surgeon.
vant chemoradiation to improve local control. The efficacy of
Stage-Specific Therapy (Fig. 29-26). Pretreatment staging adjuvant or neoadjuvant chemoradiation followed by transanal
of rectal carcinoma often relies on endorectal ultrasound or MRI excision in patients who can tolerate radical surgery has been

Rectal adenocarcinoma

Staging evaluation
CT chest/abdomen/pelvis
Endorectal U/S
+/– MRI
Colonoscopy/CT colonography (if possible)

Stage I Stage II Stage III Stage IV

(T1-2, N0, M0) (T3-4, N0, M0) (Tany, N1-3, M0) (Tany, Nany, M1)

High risk or Low risk and Asymptomatic Symptomatic

refuses radical accepts radical
resection resection
Neoadjuvant Neoadjuvant
Chemotherapy
chemoradiation chemoradiation

Restage

Restage Restage
Unresectable/ Resectable/single
multiple metastatic site
metastatic
No metastases No metastases sites
Chemoradiation
vs. palliative
Transanal Radical Radical Radical Continue Consider procedure
excision +/– resection resection resection chemotherapy resection stent, laser
neoadjuvant or ablation, stoma,
adjuvant resection
chemoradiation

Figure 29-26. Diagnostic algorithm for rectal cancer. CT = computed tomography; MRI = magnetic resonance imaging; U/S = ultrasound.
controversial. Early results from ACOSOG Z6041, in which or involved by the cancer or if anal sphincter or other local 1301
patients with T2 rectal cancers received neoadjuvant chemo- organ invasion is present. In the United States, chemoradia-
radiation followed by transanal excision, showed a pathologic tion therapy is still recommended for all patients with stage III
complete response rate of 44%.123 At 3 years, disease-free sur- disease and the majority of patients with stage II disease. In
vival was 88%, which is comparable to cancer outcomes after a select patients with T3 tumors, favorable histology, and nega-
formal resection. However, population-based data suggests that tive radial margins, chemoradiation may not be necessary, but
survival after local excision for rectal cancer is suboptimal and larger prospective studies are required before this approach can
should not be offered as a matter of routine.124 be recommended.125-127
Appropriate timing of chemoradiation for locally
Locally Advanced Rectal Cancer (Stages II and III) advanced rectal cancer has been debated. Historically, preopera-
Stage II: Localized Rectal Carcinoma (T3-4, N0, M0). Larger

CHAPTER 29 COLON, RECTUM, AND ANUS

tive chemoradiation has been advocated based on tumor shrink-
rectal tumors, especially if located in the distal rectum, are age/downstaging, improved resectability, and the possibility of
more likely to recur locally. There are two schools of thought, performing a sphincter-sparing operation in some patients. In
each differing in their approach, concerning how to control addition, the absence of small bowel adhesions in the pelvis
local recurrences. Advocates of total mesorectal resection sug- may decrease toxicity. However, preoperative radiation therapy
gest that optimization of operative technique will obviate the may increase operative complications and impairs wound heal-
need for any adjuvant chemoradiation to control local recur- ing. Although preoperative endorectal ultrasound and MRI have
rence after resection of stages I, II, and III rectal cancers. The improved our ability to stage rectal cancer, clinical “overstag-
opposing school suggests that stages II and III rectal cancers ing” can be problematic, and neoadjuvant therapy may there-
will benefit from chemoradiation. They argue that such therapy fore overtreat patients with pT1-2, N0 tumors. Advocates of
reduces local recurrences and prolongs survival whether given postoperative radiation therapy cite more accurate pathologic
preoperatively or postoperatively. The advantages of preopera- staging and fewer operative/postoperative complications. How-
tive chemoradiation include tumor shrinkage, increased likeli- ever, large, bulky tumors may be unresectable or require a more
hood of resection and of a sphincter-sparing procedure, tumor extensive operation (APR, pelvic exenteration) without preop-
downstaging by treating locally involved lymph nodes, and erative therapy. In addition, postoperative pelvic radiation may
decreased risk to the small intestine. Disadvantages include compromise function of the neorectum.
possible overtreatment of early-stage tumors, impaired wound Comparisons of perioperative toxicity and oncologic out-
healing, and pelvic fibrosis increasing the risk of operative com- come have been addressed by the German CAO/ARO/AIO-94
plications. Postoperative radiation allows accurate pathologic trial. In this study, pre- and postoperative chemoradiation were
staging of the resected tumor and lymph nodes and avoids the associated with equivalent acute toxicity and equivalent post-
wound healing problems associated with preoperative radiation. operative complication rates. Postoperative chemoradiation,
However, bulky tumors, tumors involving adjacent organs, and however, doubled the risk of postoperative stricture forma-
very low rectal tumors may be much more difficult to resect tion. In addition, preoperative chemoradiation halved the risk
without preoperative radiation and may require a more exten- of local recurrence (6% vs. 12%). Based on these data, most
sive operation.124-127 surgeons consider preoperative chemoradiation to be the most
Stage III: Lymph Node Metastasis (Tany, N1, M0). Many appropriate therapy for locally advanced rectal cancer.126 In the
surgeons now recommend chemotherapy and radiation either United States, this generally consists of 5-FU based chemother-
pre- or postoperatively for node-positive rectal cancers. The apy and 5 to 6 weeks of external beam radiation (“long course”)
advantages and disadvantages are similar to those listed for followed by surgery 6 to 8 weeks later. It is important to note,
stage II disease, except that the likelihood of overtreating an however, that many European centers utilize a “short course”
early-stage lesion is considerably less. preoperative radiation regimen consisting of 5 days of radia-
Over the past two decades, a wide variety of studies have tion followed by surgery within 1 to 2 weeks. At present, these
addressed the issue of adjuvant and neoadjuvant therapy for modalities have not been compared in any randomized, prospec-
locally advanced rectal cancer. Many of these studies demon- tive trial.125,127
strated both improved local control and prolonged survival and With advances in chemoradiation, an increasing number
resulted in the 1990 National Institutes of Health (NIH) con- pf patients with locally advanced rectal cancer will have com-
sensus conference recommendation for postoperative chemo- plete shrinkage of their tumor (a clinical complete response;
radiation therapy in these patients. There is little controversy cCR). In light of the potential morbidity of proctectomy, it has
regarding chemoradiation therapy for stage III (node-positive) been suggested that select patients can be managed nonopera-
disease. However, advances in surgical technique, such as TME, tively (“watch and wait”). However, data from current stud-
for locally advanced node-negative cancers (T3-4, N0; stage II) ies are contradictory and concern remains about the ability to
have improved local control with surgery alone, prompting some predict which patients with clinical complete response actually
to abandon adjuvant chemoradiation in these patients, especially have a pathologic complete response.128 Patients selected for
for those with cancers in the proximal rectum. Although the nonoperative management must be examined by a surgeon at a
data from these studies are intriguing, other reports have shown frequent intervals. Additional adjuvant chemotherapy adminis-
that chemoradiation improves local control and survival even tered after the decision for a nonoperative approach is another
in patients who undergo TME. Thus, most colorectal surgeons important consideration.128,129 At present, this approach is not
in the United States continue to recommend adjuvant or neo- recommended outside of a specialty center and/or clinical trial.
adjuvant therapy for patients with locally advanced disease.
Many European surgeons now rely heavily on MRI staging to Stage IV: Distant Metastasis (Tany, Nany, M1) Like
determine the need for neoadjuvant chemoradiation. They use stage IV colon carcinoma, survival is limited in patients with
neoadjuvant chemoradiation if the radial margin is threatened distant metastasis from rectal carcinoma. Isolated hepatic
1302 and/or pulmonary metastases are rare, but when present may be liver or lungs. Resection of other involved organs may be nec-
resected for cure in selected patients.119,120 Some patients will essary. Recurrence of rectal cancer can be considerably more
require palliative procedures. Radical resection may be required difficult to manage because of the proximity of other pelvic
to control pain, bleeding, or tenesmus, but highly morbid pro- structures. If the patient has not received chemotherapy and
cedures such as pelvic exenteration and sacrectomy should radiation, then adjuvant therapy should be administered prior
generally be avoided in this setting. Local therapy using cau- to salvage surgery. Radical resection may require extensive
tery, endocavitary radiation, or laser ablation may be adequate resection of pelvic organs (pelvic exenteration with or without
to control bleeding or prevent obstruction. Intraluminal stents sacrectomy). Ideally, the aim of a salvage operation should be
may be useful in the uppermost rectum but often cause pain and to resect all of the tumor with negative margins. However, if
tenesmus lower in the rectum. Occasionally, a proximal divert- the ability to achieve a negative margin is in question, the addi-
ing colostomy will be required to alleviate obstruction. A mucus tion of intraoperative radiation therapy (usually brachytherapy)
fistula should be created if possible to vent the distal colon. It can help improve local control. Pelvic MRI is useful for identi-
PART II

is critical that the morbidity of any procedure be realistically fying tumor extension that would prevent successful resection
weighed against potential benefit in these patients with limited (extension of tumor into the pelvic sidewall, involvement of the
life expectancy. The assistance of a palliative care team can be iliac vessels or bilateral sacral nerves, sacral invasion above the
invaluable in this setting.116 S2-S3 junction). Patients should also undergo a thorough pre-
operative evaluation to identify distant metastases (CT of chest,
SPECIFIC CONSIDERATIONS

Follow-Up and Surveillance abdomen, and pelvis, and PET scan) before undergoing such an
Patients who have been treated for one colorectal cancer are extensive procedure. Nevertheless, radical salvage surgery can
at risk for the development of recurrent disease (either locally prolong survival in selected patients.
or systemically) or metachronous disease (a second primary
tumor). In theory, metachronous cancers should be preventable Minimally Invasive Techniques for Resection
by using surveillance colonoscopy to detect and remove polyps Laparoscopic colectomy for cancer has been controversial.
before they progress to invasive cancer. For most patients, a Early reports of high port site recurrence dampened enthusiasm
colonoscopy should be performed within 12 months after the for this technique.130 The ability to perform an adequate onco-
diagnosis of the original cancer (or sooner if the colon was not logic resection for cancer has also been questioned. Several tri-
examined in its entirety prior to the original resection). If that als have laid to rest many of these fears. The Clinical Outcomes
study is normal, colonoscopy should be repeated every 3 to of Surgical Therapy (COST) Study Group, the Colon Car-
5 years thereafter. 6 cinoma Laparoscopic or Open Resection (COLOR) trial,
The optimal method of following patients for recurrent and the United Kingdom Medical Research Council Conventional
cancer remains controversial. The goal of close follow-up versus Laparoscopic-Assisted Surgery in Colorectal Cancer
observation is to detect resectable recurrence and to improve (CLASSICC) trial all have shown oncologic equivalence between
survival. Re-resection of local recurrence and resection of dis- open and laparoscopic techniques. In these multi-institutional
tant metastasis to liver, lung, or other sites are often technically studies, the rates of cancer recurrence, survival, and quality of life
challenging and highly morbid, with only a limited chance of were similar, suggesting that, in the hands of an appropriately
achieving long-term survival. Thus, only selected patients who trained surgeon, laparoscopic colectomy is appropriate for colon
would tolerate such an approach should be followed intensively. cancer.131-136 The recent introduction of robotic surgery offers an
Because most recurrences occur within 2 years of the original additional minimally invasive approach. Early studies suggest
diagnosis, surveillance focuses on this time period. Patients who that robotic surgery may be the oncologic equivalent to laparo-
have undergone local resection of rectal tumors also should scopic surgery for colon cancer.137
be followed with frequent endoscopic examinations (every Laparoscopic surgery for rectal cancer has been more
3–6 months for 3 years, then every 6 months for 2 years). CEA controversial. Multiple studies of laparoscopic total mesorectal
is often followed every 3 to 6 months for 2 years. CT scans are excision for rectal cancer have demonstrated decreased blood
often performed annually for 5 years, but there are few data loss, earlier return of bowel function and shorter length of stay
to support this practice. More intensive surveillance is appro- compared with open TME. While a laparoscopic approach to
priate in high-risk patients such as those with possible Lynch mobilization of the left colon and splenic flexure can be used in
syndrome or T3, N+ cancers. Although intensive surveillance rectal resection procedures, laparoscopic TME refers to comple-
improves detection of resectable recurrences, it is important to tion of the pelvic dissection laparoscopically and not through the
note that a survival benefit has never been proven. Therefore, abdominal extraction site. Technical challenges in the retraction
the risks and benefits of intensive surveillance must be weighed of the rectum and surrounding soft tissues and transection of the
and treatment individualized. distal rectum mandate careful evaluation oncologic outcomes.
Two recent randomized controlled trials from the United States
Treatment of Recurrent Colorectal Carcinoma (ACOSOG Z6051)138 and Australia and New Zealand (ALaC-
Between 20% and 40% of patients who have undergone cura- aRT: Australasian Laparoscopic Cancer of the Rectum Trial)139
tive intent surgery for colorectal carcinoma will eventually have shown that laparoscopic surgery is not superior to open
develop recurrent disease. Most recurrences occur within the surgery in this regard. When the totality of evidence from nine
first 2 years after the initial diagnosis, but preoperative chemo- randomized trials is evaluated, CRM was positive in 7.9% of
radiation therapy may delay recurrence. While most of these laparoscopic and 6.1% of open rectal resections, a difference
patients will present with distant metastases, a small propor- that was not statistically significant.17 In trials that reported the
tion will have isolated local recurrence and may be considered completeness of mesorectal excision (n = 5), inadequate TME
for salvage surgery. Recurrence after colon cancer resection was significantly more likely in laparoscopic (13.2%) com-
usually occurs at the local site within the abdomen or in the pared with open (10.4%) resections. Long-term recurrence and
survival data from ACOSOG and ALaCaRT studies will be Carcinoid carcinoma of the colon and rectum should be treated 1303
needed to determine what role laparoscopy should play in rectal according to the same oncologic principles as followed for man-
cancer surgery. Two earlier trials, COLOR (COlon cancer Lapa- agement of adenocarcinoma.
roscopic or Open Resection) II134 and COREAN (Comparison
Lipomas. Lipomas are benign lesions that occur most com-
of Open versus laparoscopic surgery for mid and low Rectal
monly in the submucosa of the colon and rectum. The major-
cancer After Neoadjuvant chemoradiotherapy),135 have shown
ity of lipomas are asymptomatic and discovered incidentally.
equivalent 3-year recurrence and survival. It is possible that spe-
Small asymptomatic lesions do not require resection. However,
cific subsets of patients are more appropriate for open surgery.
larger lesions may occasionally cause bleeding, obstruction, or
For example, ALaCaRT authors thought laparoscopic surgery
intussusception, especially when greater than 2 cm in diameter.
may be less successful in patients who had neoadjuvant therapy,
Larger lipomas should be resected by colonoscopic techniques

CHAPTER 29 COLON, RECTUM, AND ANUS

larger T3 tumors, or higher BMIs, but their study was under-
or by a colotomy and enucleation or limited colectomy.144
powered to make definitive conclusions in these patients. A
laparoscopic approach should not be considered for T4 tumors. Lymphoma. Gastrointestinal lymphoma may be primary or
The inferior quality of laparoscopic rectal cancer surgery generalized/secondary. Primary GI lymphomas occur most fre-
suggested by recent randomized trials is attributed to techni- quently in the terminal ileum and cecum. Lymphoma involv-
cal limitations, leading to the suggestion that robotic surgery, ing the colon and rectum is rare, but it accounts for about 10%
with its wristed instruments, fixed platform, and potentially of all gastrointestinal lymphomas. Presentation, treatment and
improved visualization could offer an improvement. The results prognosis differ between patients with lymphoma occurring as
of the ROLARR (Robotic vs Laparoscopic Resection for Rectal a localized entity in the colon and rectum versus those inoccur-
Cancer) randomized trial will offer more data on the quality of ing in patients who have generalized lymphoma with colorectal
TME and margins after robotic surgery; however, a trial com- involvement. Symptoms in isolated rectal lymphoma include
paring open to robotic dissection will also be important.141 bleeding, obstruction, and pain, and these tumors may be clini-
cally indistinguishable from adenocarcinomas. The cecum is most
often involved, probably as a result of spread from the terminal
OTHER NEOPLASMS ileum. Symptoms include bleeding and obstruction. Bowel resec-
Rare Colorectal Tumors tion is the treatment of choice for isolated colorectal lymphoma.
Adjuvant therapy may be given based on the stage of disease.144
Neuroendocrine Tumors. Neuroendocrine tumors occur most
commonly in the gastrointestinal tract, and up to 25% of these Leiomyoma and Leiomyosarcoma. Leiomyomas are benign
tumors are found in the rectum. Well-differentiated neuroendo- tumors of the smooth muscle of the bowel wall and occur most
crine tumors (also known as carcinoid tumors) are commonly commonly in the upper gastrointestinal tract. Most patients
identified on colonoscopy as small (<1 cm) nodules and have a are asymptomatic, and lesions are often diagnosed inciden-
benign clinical course, with overall survival is greater than 80%. tally when a mass is seen on endoscopy or felt on digital rec-
However, the risk of malignancy increases with size, and more tal examination. However, large lesions can cause bleeding or
than 60% of tumors greater than 2 cm in diameter are associated obstruction. Because it is difficult to differentiate a benign leio-
with distant metastases. Rectal neuroendocrine tumors appear to myoma from a malignant leiomyosarcoma, these lesions should
be less likely to secrete vasoactive substances than carcinoids be resected. Recurrence is common after local resection, but
in other locations, and carcinoid syndrome is uncommon in the most small leiomyomas can be adequately treated with limited
absence of hepatic metastases. Small carcinoids can be locally resection. Lesions larger than 5 cm should be treated with radi-
resected transanally. Larger tumors, poorly differentiated tumors cal resection because the risk of malignancy is high.
(such as small cell or large cell neuroendocrine carcinomas), Leiomyosarcoma is rare in the gastrointestinal tract. When
and those with obvious invasion into the muscularis require this malignancy occurs in the large intestine, the rectum is the
more radical surgery. Neuroendocrine tumors in the proximal most common site. Leiomyosarcoma of the rectum is usually
colon are less common and are more likely to be malignant. Size low grade, and, as such, can be difficult to differentiate from
also correlates with risk of malignancy, and tumors less than leiomyoma. Definitive diagnosis is usually made after resection.
2 cm in diameter rarely metastasize. However, the majority of Symptoms, when they occur, are usually bleeding or obstruc-
neuroendocrine tumors in the proximal colon present as bulky tion. A radical resection is indicated for most of these tumors.
lesions, and up to two-thirds of patients will have metastatic Despite complete resection, recurrence is not uncommon, and
spread at the time of diagnosis. These tumors should usually prognosis is generally poor.144
be treated with radical resection. Because well-differentiated Gastrointestinal Stromal Tumor (GIST). Gastrointestinal
neuroendocrine tumors are typically slow growing, patients Stromal Tumors (GIST) are most common in the proximal
with distant metastases may expect reasonably long survival. GI tract but do occasionally occur in the colorectum (5–10%)
Symptoms of carcinoid syndrome can often be alleviated with and may be mistaken for leiomyomas. GISTs are mesenchy-
somatostatin analogues (octreotide) and/or interferon-α. Tumor mal tumors that arise from the interstitial cells of Cajal. The
debulking can offer effective palliation in selected patients.142-144 vast majority (>95%) of GISTs express CD117 (KIT), and as
Mixed Adenoneuroendocrine Carcinomas. Mixed adeno- such, are sensitive to tyrosine kinase inhibitors (TKIs), such
neuroendocrine carcinomas, also known as composite carcinoid as imatinib mesylate and sunitinib malate. Risk stratification
carcinomas, adenocarcinoids tumors, amphicrine or collision is based on tumor size and mitotic activity, and 30% to 50%
tumors, have histologic features of both neuroendocrine tumors are malignant. Although small GISTs may be asymptomatic
and adenocarcinomas. The natural history of these tumors more and discovered incidentally, larger lesions can cause bleeding,
closely parallels that of adenocarcinomas than neuroendocrine obstruction, or abdominal pain. Treatment of choice is surgi-
tumors, and regional and systemic metastases are common. cal resection (either local excision or radical resection) with