Surgery of Colorectal Cancer

By

Professor Ahmed Hussein

Chairman of Unit of Colon and Rectal Surgery University of Alexandria

Incidence
In Egypt, colorectal cancer is the fourth most commonly diagnosed cancer in both men and women.
World Age-adjusted Incidence Rates by Gender Males Females M/F Ratio World 20.1 14.6 1.2 More Developed Countries 40.0 26.6 1.2 Less Developed Countries 10.2 7.7 1.2 Incidence Rates/100,000

The Incidence of CRC in Egypt Egyptian Males Females Total New CRC Cases 2263 2057 4320 Incidence /100,000 6.3 5.3 5.8 Median Age 48.0 48.8 48.4 M/F Ratio 1.1 1.0 1.1 Number of Deaths 1426 1295 2721

Middle East Cancer Consortium (MECC), Egypt

Risk Factors for Colorectal Cancer:

1. Hereditary CRC Syndromes a. Adenomatous polyposis syndromes i. Familial adenoamtous polyposis (FAP) ii. MYH-associated polyposis (MAP) b. Nonpolyposis syndrome i. Hereditary nonpolyposis CRC (HNPCC) c. Hamartomatous polyp syndromes i. Peutz-Jeghers syndrome (PJS) ii. Juvenile polyposis syndrome (JPS) iii. Cowden disease (Bannayan-Ruvalcaba-Riley) 2. Inflammatory Bowel Disease: Ulcerative Colitis 3. Personal History of CRC 4. Family History of CRC 5. Ethnic background: Ashkenazi Jews 6. Age: above 50 years in the western community.

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a. In Egypt the median age of CRC less than 50 years Environmental Factors Increased risk of CRC with a diet high in: 1. Red meat and animal fat 2. Low-fiber diet: low overall intake of fruits and vegetables Lifestyle choices that are associated with increased risk for CRC: 1. Alcohol and tobacco consumption 2. Obesity 3. Sedentary habits Factors associated with lower risk include: 1. Folate intake 2. Calcium intake 3. Estrogen replacement therapy

Genetics of Colorectal Cancer

Genetics does not mean inherited, genetics means pathogenesis. Genetically, colorectal cancer represents a complex disease, and accumulation of genetic alterations is associated with progression from normal epithelial cells or premalignant lesion (adenoma) to invasive adenocarcinoma. Colorectal cancers have several gene expression profiles with different pathogenic (genetic) pathways. Types of Colorectal Cancer Type Sporadic Family History of CRC HNPCC FAP MAP PJS & JP IBD % 75% 18% 5% 1% 1% <1% 1%

The major known mechanisms of genetic instability are chromosomal instability (CIN), which constitute 85% of colon cancer and the other 15% is due to microsatellite instability (MSI, mismatch repair pathway).

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Pathway I CIN (Chromosomal Instability) Acquired (somatic) or inherited (germline) macrogenetic alterations at chromosomal level either in the form of abnormal number (aneuploidy) or gross changes i.e. loss of heterozygosity (LOH). The important genes involved in these chromosome losses are APC (5q), DCC (18q), and TP53 (17p). This pathway is seen in Familial Adenomatous Polyposis (FAP) and adenoma-carcinoma model.
APC K-ras DCC p53

Normal Epithelium

Early Adenoma

Intermediate Adenoma

Late Adenoma

Cancer

Pathway II Microsatellite Instability (MSI) Mismatch Repair Pathway (MMR) Germline or somatic microgenetic (intragenic) mutations of DNA damage-repair genes result in Microsatellite Instability (MSI) i.e. insertion or deletion of nucleotides in one or more alleles. MSI means alterations in repeating units of DNA that occur normally throughout the genome. The important genes involved in this MSI are MMR genes (hMSH2, hMSH6, hMLH1, hMLH3, hPMS1, hPMS2) This pathway is seen in 95% of HNPCC and 18% of sporadic colorectal cancer. Alternative Pathways 1. 2. 3. 4. Flat & depressed adenoma De Novo CRC Colitis induced CRC Serrated Pathway

Alternative pathways are involved in up to 30% of CRC, precursors not easily seen with rapid evolution following genetic instability.

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Colitis induced CRC This pathway is seen in ulcerative colitis and schistosomiasis Japonicum. Chronic inflammation results in free O2 radicals cause DNA damage. Dysplasia-carcinoma model.
Aneuploidy p53 p53 K-ras MSI DCC

Normal Epithelium

Indefinite Dysplasia

Low Grade Dysplasia

High Grade Dysplasia

Cancer

Serrated Pathway: CpG Island Methylator Phenotype (CIMP) Epigenetic factors are mechanisms outside the gene such as a cells exposure to carcinogens or hormones, or genetic variations that modify a gene or its protein by methylation, demethylation, phosphorylation, or dephosphorylation. Genes that must be expressed in all tissues have unmethylated regions, called CpG islands. On the other hand, genes that must be turned off in differentiated tissues have these islands methylated. In this pathway type C tumor suppressor genes silenced by promoter region CpG methylation. This pathway is seen in Juvenile Polyposis, Peutz-Jeghers Syndrome and Serrated adenomas

SurgeryofCRC ProfessorAhmedHussein

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Clinical Picture of Colorectal Cancer

1. 2. 3. 4. Asymptomatic by screening program Primary Lesion Metastases Complications

Screening for Colorectal Cancer Life-Time Risk of CRC Group Life Time Risk of CRC General Population 5% Ashkenazi Jews 6-10% Family History of CRC 10-15% Personal History of CRC 15-20% IBD 15-40% PJS 50% JP 50% HNPCC 70-80% FAP >95% High Risk Group 1. 10-100% lifetime risk according to: a. Family history criteria b. Pathological criteria c. Pathogenic gene mutation 2. Screening Method: in Genetics Centre for formal counseling & mutation analysis Moderate Risk Group 1. First degree relative (FDR) with CRC aged <45yrs or two FDRs 2. Single colonoscopy at age 55yrs. 3. Polyps snared a. If adenomatous, then adenoma surveillance 4. Colon is clear of neoplasia a. Reassured and shift to population risk (FOBT screening) Low Risk Group 1. No family history 2. Population-based screening a. Annual FOBT (Fecal Occult Blood Test) 6

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b. Flexible Sigmoidoscpy / 5 years c. Colonoscopy / 10 years

Clinical Picture of Primary Colorectal Cancer

The most common presenting symptoms associated with colon cancer are abdominal pain, followed by change in bowel habits, rectal bleeding, and occult blood in the stool.

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Cancer Right Colon 1. Change in Bowel Habits a. Diarrhea 2. Pain a. Vague upper abdominal 3. Iron Deficiency Anemia 4. Weight Loss 5. Mass (advanced ) 6. Obstruction Rare Cancer Left Colon 1. Change in Bowel Habits a. Increasing Constipation 2. Pain a. Colicky with distension 3. Weight Loss 4. Mass (advanced or fecal matter) 5. Obstruction common or 1st presentation 6. Bleeding /Rectum 7. Mucous/ Rectum Cancer Rectum Bleeding /Rectum Mucous/ Rectum Tensmus (Sense of incomplete evacuation) Change in Bowel Habits a. Spurious morning diarrhea 5. Pain a. Colicky in rectosigmoid lesions b. Severe pelvic ( advanced due to infiltration) 6. Weight Loss 7. Rare Obstruction in rectosigmoid lesions 1. 2. 3. 4.

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Symptom Change in Bowel Habits Bleeding /Rectum Colicky Pain Mass Mucous/ Rectum Tensmus Incomplete Evacuation Weight Loss Iron Deficiency Anemia

Rt. Side Diarrhea Altered + +++ +++ ++++

Lt. Side Constipation Dark ++++ ++ + + +

Rectum Constipation spurious morning diarrhea Fresh upper 1/3 ++++ +++++ ++ +

Spread of Colorectal Cancer 1. Direct spread a. Intramural i. Circumferential ii. Longitudinal b. Transmural 2. Lymphatic spread 3. Venous spread: Liver & Lung metastases 4. Transperitoneal spread a. Malignant ascites b. Krukenbergs tumor Complications of Colorectal Cancer 1. 2. 3. 4. 5. Intestinal obstruction Penetration (fistula) Bleeding (anemia or hypovolemia) Intussusception: incomplete obstruction Perforation a. Tumor perforation b. Caecal perforation caused by a left-sided colon cancer

Diagnosis
An individualized approach to the diagnosis considers: 1- The patients symptoms 2- Age

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3- Personal history of inflammatory bowel disease, colon polyps, or colorectal cancer 4- Family history of colon cancer or predisposing genetic syndromes (e.g., familial adenomatous polyposis or hereditary nonpolyposis colorectal cancer) Diagnostic Evaluation 1- Colonoscopy: A crucial part of this evaluation is to ensure that the patients entire colon and rectum have been assessed with colonoscopy for the presence of synchronous neoplasms. Colonoscopy allows biopsy and histologic confirmation of the diagnosis. It also allows for identification and endoscopic removal of synchronous polyps. Pre-operative histology should be done in all rectal tumors. 2- Depending on the patients age and health status, a variety of laboratory, radiologic, and cardiorespiratory tests may be appropriate to assess the patients operative risk. Preoperative Assessment 1- Preoperative, carcinoembryonic antigen level: Is beneficial for two reasons: a. Postoperative return to normal of an elevated preoperative CEA is associated with complete tumor resection, whereas persistently elevated values indicate the presence of visible or occult residual disease. b. Elevated preoperative CEA levels have been found to be an independent prognosticator of poor outcome. CEA has never been useful as a screening tool as it is elevated in a variety of conditions, including colorectal cancer, proximal gastrointestinal cancers, lung and breast cancers, benign inflammatory conditions of the gastrointestinal tract, and smoking. 2- Preoperative CT scanning CT scans can be used to evaluate local extension of the tumor and regional lymphadenopathy, as well as for the presence of hepatic metastases. 3- Preoperative chest x-rays or chest CT scanning: to evaluate the lungs for evidence of metastatic disease. 4- PET CT scan is not routinely indicated.

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TNM Staging
T Tx: Incomplete information Tis: It involves only the mucosa T1: Extends into the submucosa T2: Extends into the muscularis propria T3: Extends into subserosa T4a: Penetrates visceral peritoneum T4b: Tumor invades other organs or structures N Nx: Incomplete information N0: No LN involvement N1: In 1- 3 regional LNs. N1a: in 1 regional LNs N1b: in 2- 3 regional LNs N1c: Tumor Deposits in subserosa, mesentry, nonperitonealized pericolic or perirectal tissues without regional LNs metastasis N2: In 4 or more regional LNs N2a: in 4-6 regional LNs N2b: in 7 or more regional LNs M M0: No distant Metastasis M1: Distant Metastasis M1a: Metastasis confined to one organ or site (Liver, lung, ovary, non-regional LNs) M1b: Metastasis in more than one organ/site or peritonium

Stage 0 Stage I Stage IIA IIB IIC Stage IIIA IIIB

IIIC

Stage IVA IVB

Tis T1 T2 T3 T4a T4b T1-2 T1 T3-4 T2-T3 T1-T2 T4a T3-T4a T4b Any T Any T

TNM N0 N0 N0 N0 N0 N0 N1/N1c N2a N1/N1c N2a N2b N2a N2b N1-N2 Any N Any N

M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M1a M1b

Dukes A A B B B C C C C C C C C -

5-years Survival Stage I 92% Stage II 73% IIA 85% IIB 72% Stage III 56% IIIA 83% IIIB 64% IIIC 44% Stage IV 8%

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Preparation for Operation A. Informed Consent All patients who are to undergo surgery for colon cancer need to be clearly informed of the reasons for and the extent of the proposed resection, the likely outcome of the surgery, the pertinent complications and their likelihood of occurring, expected length of hospitalization and recovery, alternatives to the proposed surgery, and prognosis. B. Mechanical Bowel Preparation Mechanical bowel preparation is nearly universally used in elective surgery. Despite its nearly universal use, the literature does not support a defined benefit for preoperative mechanical preparation of the bowel. The persistence in using a preoperative bowel preparation may be justified simply on the basis of the advantages it affords in ease of handling the prepared colon, the proven safety of the methods used for bowel cleansing, and the relatively low cost. Outpatient bowel preparation (the day before surgery) is generally safe and cost effective. C. Prophylactic Antibiotics Prophylactic antibiotics have proven effectiveness in decreasing the rate of infection, mortality, and cost of hospitalization after colonic resection. There are a wide variety of antibiotic regimens that are effective. Regardless which parenteral antibiotic regimen is selected, it is agreed that it must be given before the start of the operation to be effective. D. Blood Cross Match and Transfusion Blood transfusion should be based on physiologic need. The need for transfusion is primarily based on the starting hemoglobin, the patients physiologic status, and extent of intraoperative blood loss. The immunosuppressive effect of transfusion is well established. Patients who receive perioperative blood transfusions have a greater incidence of infection. However, recently it was found that the immunosuppressive effect of transfusion does not increase the rate of cancer recurrence. Other factors (extent of resection required, location of tumor, and experience of surgeon) in patients requiring transfusion may actually be the cause for the increased recurrence rate. E. Thromboembolism Prophylaxis All patients undergoing surgery for colon cancer should receive prophylaxis against thromboembolic disease. Patients undergoing colon resection for cancer have a high incidence of venous thromboembolism, including deep venous thrombosis and pulmonary embolism. 12

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Operative Issues
A. Operative Technique The extent of resection of the colon should correspond to the lymphovascular drainage of the site of the colon cancer. The determinant of adequate bowel resection for colon cancer is removal of the primary feeding arterial vessel and its corresponding lymphatics. Tumors located in border zones should be resected with the neighboring lymphatic regions to encompass both possible directions of spread. The length of bowel resected is usually governed by the blood supply to that segment. Ligation of the origin of the primary feeding vessel ensures the inclusion of the apical nodes, which may convey prognostic significance for the patient. There is much concern regarding intraoperative manipulation of the tumor with shedding of cancer cells into the portal circulation. However, the value of the no touch technique has not been proven, although there is a theoretic basis for its use.

Arterial Supply of the Colon and Rectum

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Site of the Lesion Appendix Cecum Ascending Colon Hepatic Flexure

Operation Right Hemicolectomy with ileotransverse anastomosis Extended Right Hemicolectomy with ileotransverse anastomosis Transverse colectomy with anastomosis between the ascending and descending colons Extended Left Hemicolectomy with anastomosis between transverse and sigmoid colons Left Hemicolectomy with anastomosis between transverse and sigmoid colons or (Rectum) Sigmoidectomy With anastomosis between left colon and upper rectum Tumor Specific Mesorectal Excision With anastomosis between descending colon and middle third rectum If the anastomosis above the peritoneal reflection = Anterior Resection If the anastomosis below the peritoneal reflection = Low Anterior Resection Total Mesorectal Excision With anastomosis between descending colon and anal canal (coloanal anastomosis)

Vessels Ileocolic Right Colic Rt. branch of middle colic Ileocolic Right Colic Middle Colic Middle Colic

Transverse Colon

Splenic Flexure

Inferior Mesenteric Left branch of the middle colic Inferior Mesenteric

Excised Parts Cecum, appendix, ascending colon and the right third of the transverse colon Cecum, appendix, ascending colon and the right two thirds of the transverse colon Transverse colon including both hepatic and splenic flexures greater omentum in T4 lesions Descending Colon and Left half of the transverse colon Descending Colon and Left third of the transverse colon sigmoid colon Sigmoid Colon

Descending Colon

Sigmoid Colon

Inferior Mesenteric

Upper Third Rectum

Inferior Mesenteric

Sigmoid Colon and upper third Rectum with distal safety margin of 5 cm

Middle and lower Third Rectum down to > 2 cm from the dentate line

Inferior Mesenteric Middle Rectal

Sigmoid Colon and total proctectomy with distal safety margin at least 2 cm

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SurgeryofCRC ProfessorAhmedHussein = Ultra-Low Anterior Resection Total Mesorectal Excision with Abdominoperineal Excision of the Rectum (APER) with permanent colostomy

< 2 cm from the dentate line or lesion infiltrating the anal sphincter or the pelvic floor muscles

Inferior Mesenteric Middle Rectal Inferior Rectal

Sigmoid Colon, total proctectomy, anal canal, anal sphincters and pelvic floor muscles

Right Hemicolectomy

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Left Hemicolectomy

Total Colectomy & Ileorectal Anastomosis

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Sigmoid Colectomy

Sigmoid Colectomy with End colostomy and Hartmanns pouch

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B. Synchronous Colon Cancer Synchronous colon cancers can be treated by two separate resections or subtotal colectomy. C. Contiguous Organ Attachment Colon cancers adherent to adjacent structures should be resected en bloc. Fifteen percent of patients with colon cancer will have tumors adherent to adjacent organs. At the time of surgery, it often is impossible to distinguish between malignant and inflammatory adhesions. Because it has been demonstrated that these adhesions harbor malignant cells at least 40 percent of the time, an en bloc excision is necessary to achieve a tumor-free resection. D. Synchronous Resection of Liver Metastases Resection of synchronous liver metastases may be reasonable to perform at the time of the initial colon resection. Between 10 and 20 percent of patients will have liver metastases at the time of their colon resection. Surgical excision or ablation of these tumors, when amenable, remains the only means of obtaining long-term survival in this group of patients. It is generally believed that such anatomic resections are best performed at a later date after recovery from the initial colonic resection. However, if at the time of the primary colon resection the patient is found to have limited metastatic disease in the liver, which is amenable to subsegmental resection or metastasectomy, it may be preferable to proceed with this additional procedure at the time of colectomy. Removal of the metastasis can proceed if the following conditions are met: 1) colon resection has proceeded with minimal blood loss or contamination, 2) the medical condition of the patient will permit combining both procedures, 3) resection can be accomplished with at least 1-cm margin, 4) the incision is appropriate for hepatic resection, and 5) the surgeon is comfortable with performing the hepatic resection. E. Role of Oophorectomy Bilateral oophorectomy is advised when one or both ovaries are grossly abnormal or involved with contiguous extension of the colon cancer. However, prophylactic oophorectomy is not recommended. F. Role of Laparoscopic Resection

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Laparoscopic resection of colon cancer is feasible but requires specific surgical expertise. Adherence to oncologic principles is possible and adequate lymphadenectomy with disease-free margins can be achieved comparable to open surgery.

Operative IssuesEmergency
A. Obstructing Colon Cancer a. Patients with an obstructing right or transverse colon cancer should undergo a right or extended right colectomy. A primary ileocolic anastomosis can be performed in the appropriate clinical setting. b. Patient with a left-sided colonic obstruction, the procedure selected should be individualized from a variety of appropriate operative approaches. i. Resection with end colostomy and Hartmanns pouch ii. Resection with on-table colonic lavage and primary anastomosis iii. Subtotal colectomy with ileorectal anastomosis. iv. Insertion of colonic Stent to relieve the acute obstruction thereby permitting an elective colonic oral lavage, colonoscopy, and subsequent resection with primary anastomosis. The three-stage approach of performing proximal diversion, then resection, then colostomy closure is generally thought to be less advantageous because of its high mortality and morbidity rates. B. Colonic Perforation The site of a colonic perforation caused by colon cancer should be resected, if at all possible. a. Right-sided colon perforation from a right colon cancer should be resected. If there is a free perforation with peritonitis, an anastomosis may be unwise and the patient is probably best left with an end ileostomy. The distal end may be brought out as a mucous fistula or stapled off as a Hartmanns pouch. Alternatively, if there is limited fecal spillage, the surgeon may choose to reanastomose the bowel with or without fecal diversion. b. When a left colon cancer perforates resulting in peritonitis, a Hartmanns resection is the indicated operation in most settings. In cases in which there is massive proximal colonic distention and/or ischemia, a subtotal colectomy may be the best choice. If there is a limited degree of peritoneal contamination, the surgeon may choose to perform an ileorectal or ileosigmoid anastomosis with a diverting loop ileostomy. c. In the case of a right colon perforation caused by a left-sided colon cancer, most experts advocate a subtotal colectomy. Whether an anastomosis or a loop 19

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ileostomy to protect the anastomosis are performed is dependent on the surgeons judgment about the degree of contamination and the patients clinical status. C. Massive Colonic Bleeding Acutely bleeding colon cancers that require emergent resection should be removed following the same principles as in elective resection. Because of the cathartic effect of the bleeding, the bowel has been effectively cleansed of the bulk of fecal matter and a primary anastomosis can be considered. Whether to proceed with an anastomosis or elect to perform an end stoma and mucous fistula (or Hartmanns pouch) is based on the surgeons judgment about the current clinical condition of the patient. In cases in which the site of the bleeding cannot be identified, a subtotal colectomy is the preferred procedure. POSTOPERATIVE STAGING OF COLON CANCER a. Colon cancers should be staged using the TNM staging system. b. It is important that accurate pathologic evaluation of the radial margin of resection be performed. Each operation is given a resection code to denote completeness of resection: R0: Complete tumor resection with all margins negative R1: Incomplete tumor resection with microscopic involvement of the margin R2: Incomplete tumor resection with gross residual tumor that was not resected. c. Other factors that have an impact on the patients risk of recurrence and survival. i. Microscopic venous or lymphatic invasion within the specimen worsen the prognosis for every stage. ii. Histologic grade and histologic type iii. Serum CEA Lymph node numbers: To be properly evaluated, one should strive to have a minimum of 15 lymph nodes examined microscopically. The accuracy of colon cancer staging improves with increasing the number of lymph nodes evaluated microscopically. Ten or more lymph nodes can be found in 98 percent of colon specimens and 13 or more lymph nodes can be found in 91 percent of specimens without using fat-clearing techniques.

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Adjuvant Therapy
A. Chemotherapy Postoperative adjuvant systemic chemotherapy has a proven benefit in Stage III colon cancer and may be beneficial in certain high risk Stage II patients. Patients with Stage III colon cancer are recognized to be at high risk for recurrence, and administration of 5-fluorouracil (5-FU)/leucovorin for six months postoperatively has proven benefit in decreasing recurrence and improving survival. Patients with Stage II colon cancer who are considered at higher risk for recurrence include those with one or more of the following characteristics: tumor perforation, adherence, or invasion of adjacent organs; nondiploidy by flow cytometry; poorly differentiated tumor; or venous, lymphatic, and perineural invasion. It may be advantageous for these patients to receive adjuvant chemotherapy. The oral chemotherapy agent, capecitabine: Capecitabine is an oral fluoropyrimidine carbamate preferentially converted to 5-FU in tumor cells. B. Immunotherapy The value of immunotherapy for colon cancer is undetermined. Its use is recommended within the setting of a clinical trial. C. Intraperitoneal/Intraportal Chemotherapy Intraperitoneal and intraportal infusions of chemotherapy are recommended only in the confines of a clinical trial. D. Radiation Therapy The role for radiation therapy in colon cancer is limited. Radiation is rarely used in the treatment of colon cancer. Radiations potential for injury to the abdominal viscera limits its usefulness.

Surveillance
1. 2. 3. 4. History & Physical Examination: Every 3-6 m for 2 y then every 6 m for a total of 5 yrs Serum CEA: Every 3-6 m for 2 y then every 6 m for a total of 5 yrs CT scan of abdomen & pelvis: Annually for 3 years Colonoscopy: At 1 year then as clinically indicated

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Rectal Cancer
Any cancer whose distal margin is 15 cm or less from the anal verge using a rigid sigmoidoscope should be classified as rectal. Rectal cancer comprises approximately 25 percent of the malignancies arising in the large bowel. Anatomically, the rectum is the distal 15-cm of the large bowel leading to the anal canal. Cancers of the intraperitoneal rectum behave like colon cancers with regard to recurrence patterns and prognosis. By contrast, the extraperitoneal rectum resides within the confines of the bony pelvis; it is this distal 10 to 12 cm that constitutes the rectum from the oncologic standpoint. Rectal Cancer is a challenging disease because: 1. 2. 3. 4. 5. Common malignancy Difficult dissection Treatment not infrequently entails a permanent stoma Sexual and urinary morbidity Local recurrence

PREOPERATIVE ASSESSMENT An individualized approach to the diagnosis considers: 1- The patients symptoms 2- Age 3- Personal history of inflammatory bowel disease, colon polyps, or colorectal cancer 4- Family history of colon cancer or predisposing genetic syndromes (e.g., familial adenomatous polyposis or hereditary nonpolyposis colorectal cancer) I. DIAGNOSTIC EVALUATION 1- Colonoscopy: A crucial part of this evaluation is to ensure that the patients entire colon and rectum have been assessed with colonoscopy for the presence of synchronous neoplasms. Colonoscopy allows biopsy and histologic confirmation of the diagnosis. It also allows for identification and endoscopic removal of synchronous polyps. 2- Depending on the patients age and health status, a variety of laboratory, radiologic, and cardiorespiratory tests may be appropriate to assess the patients operative risk. 3- When an ostomy is a consideration, preoperative counseling with an enterostomal therapist should be offered when available. 4- Digital rectal examination and rigid proctosigmoidoscopy 22

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a. Digital rectal examination enables detection and assessment of the size and degree of fixation of mid and low rectal tumors. b. Rigid proctosigmoidoscopy and digital rectal examination allow the most precise assessment of tumor location and the distance of the lesions from the anal verge. These issues are critical in optimizing preoperative planning. 5- Abdominal and pelvic CT scans often used to evaluate local extension of the tumor and regional lymphadenopathy, as well as for the presence of hepatic metastases. However, its role in local staging is limited. 6- Transrectal ultrasound (TRUS) is the diagnostic modality of choice for preoperative local staging of mid and distal rectal cancers. TRUS may be more accurate in defining earlier-stage lesions (T1, T2). 7- Pelvic Magnetic Resonance Imaging: MRI is more accurate in assessing T3 and T4 lesions. MRI has the added advantage of a multiplanar and larger field of view of the mesorectal fascia and more accurately predicts the likelihood of obtaining a tumorfree circumferential resection margin. 8- Preoperative routine chest radiographs or chest CT scanning: Rectal cancer is more likely than colon cancer to be associated with lung metastases without liver metastases. 9- Carcinoembryonic antigen (CEA) level is most useful when found to be elevated preoperatively and then normalizes after resection of the tumor. Subsequent elevations suggest recurrence or metastatic disease. Because of a lack of sensitivity and specificity, it is not used as a screening test. 10- PET CT scan is not routinely indicated TREATMENT CONSIDERATIONS Informed opinion of the (MDT) Multidisciplinary Team (Radiologist, Pathologist, Medical Oncologist and Colorectal Surgeon). The patient and family should have the opportunity to ask questions and to have important information repeated. The patient should have an access to treatment within 31 days of discussion with MDT. Surgery is the mainstay of treatment for rectal cancer. The risk of recurrence is dependent on the TNM stage. Early stage cancer can be treated by surgical resection alone. More advanced lesions require adjuvant therapy to increase the probability of cure. The surgeon is a critical variable with respect to morbidity, sphincter preservation rate, and local recurrence.

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SURGICAL THERAPY Resection Margin The proximal resection margin is determined by blood supply considerations. For upper third rectal cancers both the rectum and mesorectum are divided not less than 5 cm below the lower margin of the tumor. A 2-cm distal margin is adequate for most low rectal cancers. In smaller cancers of the low rectum without adverse histologic features, a 1-cm distal margin is acceptable.
Site of the Lesion Upper Third Rectum Operation Tumor Specific Mesorectal Excision With anastomosis between descending colon and middle third rectum If the anastomosis above the peritoneal reflection = Anterior Resection If the anastomosis below the peritoneal reflection = Low Anterior Resection Total Mesorectal Excision With anastomosis between descending colon and anal canal (coloanal anastomosis) = Ultra-Low Anterior Resection Total Mesorectal Excision with Abdominoperineal Excision of the Rectum (APER) with permanent colostomy Vessels Inferior Mesenteric Excised Parts Sigmoid Colon and upper third Rectum with distal safety margin of 5 cm

Middle and lower Third Rectum down to > 2 cm from the dentate line

Inferior Mesenteric Middle Rectal

Sigmoid Colon and total proctectomy with distal safety margin at least 2 cm

< 2 cm from the dentate line or lesion infiltrating the anal sphincter or the pelvic floor muscles

Inferior Mesenteric Middle Rectal Inferior Rectal

Sigmoid Colon, total proctectomy, anal canal, anal sphincters and pelvic floor muscles

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Total Mes sorectal Ex xcision (TM ME)

Tum mor Specific c Mesorecta al Excision (TSME)

T TME with APER A 25

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Level of Proximal Vascular Ligation Proximal lymphovascular ligation at the origin of the superior rectal artery is adequate for most rectal cancers. There is no demonstrable survival advantage for a high ligation of the inferior mesenteric artery at its origin. In patients with lymph nodes thought to be involved clinically, removal of all suspicious nodal disease up to the origin of inferior mesenteric artery is recommended. High ligation of the inferior mesenteric vessels may be helpful to provide additional mobility of the left colon, as often is required for a low colorectal anastomosis. Circumferential Resection Margin For distal rectal cancers, total mesorectal excision (TME) is recommended. For upper rectal cancers, a tumor-specific mesorectal resection is adequate. The mesorectum is the fatty tissue that encompasses the rectum. It contains lymphovascular and neural elements. Surgical excision of the mesorectum is accomplished by sharp dissection in the plane between the fascia propria of the rectum and the presacral fascia. Radial clearance of mesorectal tissue enables the en bloc removal of the primary rectal cancer with any associated lymphatic, vascular, or perineural tumor deposits. Total mesorectal excision is associated with the lowest reported local recurrence rates. Pathologic assessment of rectal cancer specimens suggests that distal mesorectal spread may occur up to 4 cm away from the primary tumor. Thus, a cancer in the distal rectum should be treated with a total mesorectal excision in most cases. Upper rectal cancers may be treated with a tumor-specific mesorectal resection with distal safety margin of 5 cm. Circumferential margin involvement in the presence of an intact mesorectal specimen is a strong predictor for local recurrence. A margin of 2 mm between tumor and the mesorectal fascia was considered positive and was associated with a higher local recurrence rate. Furthermore, patients who had a margin 1 mm had an increased risk of distant metastases En Bloc Resection of Adherent (T4) Tumors Rectal cancers with adjacent organ involvement should be treated by en bloc resection. Tumors may be adherent to adjacent organs by malignant invasion or inflammatory adhesions. Locally invasive rectal cancer (T4) is removed by an en bloc resection to include any adherent tissues. If a tumor is transected at the site of local adherence, 26

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resection is deemed incomplete, because it is associated with a higher incidence of local recurrence. Inadvertent Perforation Inadvertent perforation of the rectum worsens oncologic outcome and should be documented. This should be considered in postoperative adjuvant treatment decisions and outcome measurements. Other Operative Considerations 1. Role of Oophorectomy Bilateral oophorectomy is advised when one or both ovaries are grossly abnormal or involved with contiguous extension of the colon cancer. However, prophylactic oophorectomy is not recommended.. 2. Laparoscopic-assisted resection of rectal cancer is feasible but requires specific surgical expertise. 3. Emergency intervention: Hemorrhage, obstruction, and bowel perforation are the most common indications for emergency intervention for rectal cancer. Appropriate management must be individualized with options, including resection with anastomosis and proximal diversion, or diversion alone followed by radiation. Self-expandable metallic stents can be used to relieve obstruction by a proximal rectal cancer.

Preoperative Clinical Staging

1. 2. 3. 4. 5. T1-2,N0 T3, N0 OR T any, N1-2 T4 and/or locally unresectable primary T any, N any, M1 resectable metastases T any, N any, M1 unresectable metastases or medically in operable

Treatment of T1-2, N0, M0 Transanal Resection 1. 2. 3. 4. 5. Conventional resection or Transanal Microsurgery Full thickness excision through the bowel wall into the perirectal fat T1N0 Small (<3 cm) Grade 1-2 27

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6. 7. 8. 9.

within 8 cm of AV < 30% of rectal circumference Negative (> 3 mm) deep & mucosal margins No Tumor fragmentation

According to histopathology of the resected specimen, either Surveillance would be sufficient or further radical surgery might be indicated Transabdominal Radical Resection is indicated if Unfavorable histological features: 1. 2. 3. 4. LVI + PNI+ Grade 3-4 Positive Margins T2

Transabdominal Radical Resection: 1. Mid to upper rectum a. TSME (LAR) 5 cm below distal edge of Tumor + colorectal anastomosis. 2. Low rectal lesions a. Tumor Within 2 cm above the dentate line i. APER ii. ISRR If T1 & T2 b. Tumor Above 2 cm from the dentate line i. TME with coloanal anastomosis ii. Spare autonomic nerves Adjuvant Chemotherapy If the pathology review after transabdominal resection revealed 1. T3N0 2. T1-3 N1-2 Regimens over 6 months 1. 5-FU +/- LV or FOLFOX or Capecitabine ( 1 Cycle) 2. Concurrent 5-FU/RT or capecitabine/RT 3. 5-FU +/-LV or FOLFOX or capecitabine (2 Cycles) T3, N0 / T any, N1-2, M0 Preoperative (NeoAdjuvant) Therapy is a MUST 1. Continuous 5-FU/RT 2. Alternatives : bolus 5-FU/LV/RT or Capecitabine/RT 28

SurgeryofCRC ProfessorAhmedHussein

Operative Transabdominal approach only, performed 5-10 weeks after completion of neoadjuvant therapy Postoperative Adjuvant Therapy 1. 5-FU +/- LV 2. Alternatives : FOLFOX or Capecitabine All patients receiving preoperative (Neoadjuvant) therapy should receive postoperative adjuvant therapy for 6 months T4 and/or locally unresectable primary Resectable case = anticipated negative (R0) microscopic circumferential resection margin Preoperative (NeoAdjuvant) Therapy 1. Continuous 5-FU/RT 2. Alternatives : bolus 5-FU/LV/RT or Capecitabine/RT Operative More Radical (multi-organ) approach, complete removal of tumor and involved viscera with R0 margins. Postoperative Adjuvant Therapy 1. 5-FU +/- LV 2. Alternatives : FOLFOX or Capecitabine 3. All patients receiving preoperative (Neoadjuvant) therapy should receive postoperative adjuvant therapy for 6 months T any, N any, M1 resectable metastases 1. Combination chemotherapy: a. FOLFOX/FOLFIRI/capeOX +/- Bevacizumab b. FOLFIRI/FOLFOX +/- cetuximab (KRAS wild-type gene only) 2. Staged or synchronous resection of metastases and rectal lesion 3. Adjuvant Therapy: a. Continuous IV 5FU/ RT b. Bolus 5FU+leucovorin/ RT c. Capecitabine/RT

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SurgeryofCRC ProfessorAhmedHussein T any, N any, M1 unresectable metastases or medically inoperable

1. Role of palliative surgery a. Only If Obstruction, Perforation or Bleeding 2. Symptomatic Treatment a. Chemotherapy alone b. Combind modality i. 5FU/RT or Capecitabine /RT. c. Resection of involved rectal segment + CT d. Intraluminal Stent + CT e. Diverting colostomy + CT

Pathologic Evaluation of Rectal Cancer

Gross: Tumor & Specimen Grade LVI & PNI T Stage Number of regional LNs evaluated N Stage: Number of +ve LNs M Stage a. Other organs b. Peritoneum c. Nonregional lymph nodes 8. Proximal, distal, & CRM 9. p = pathologic staging 10. yp = pathologic staging following neoadjuvant therapy 1. 2. 3. 4. 5. 6. 7.

Surveillance
1. History & Physical Examination a. Every 3-6 months for 2 years b. Then every 6 months for a total of 5 years 2. CT scan of abdomen & pelvis Annually for 3 years 3. Colonoscopy At 1 year then as clinically indicated

ADJUVANT THERAPY Neoadjuvant Therapy (Preoperative chemoradiation) should be offered to patients with Stage II and III rectal cancers. 1

It is given as long course (45-50 Gy in 25-28 fractions) 30

SurgeryofCRC ProfessorAhmedHussein

2- 5-FU based chemotherapy should delivered concurrently with radiation 3- All patients receiving preoperative (Neoadjuvant) therapy should receive postoperative adjuvant therapy for 6 months Rationale for Neoadjuvant Therapy 1. Avoids irradiation of neorectum & small bowel 2. Systemic Therapy early a. Less burden of disease b. Better drug perfusion i. Nonsurgically manipulated tumor ii. Well vascularized oxygenated tissue 3. As Radiosensitizers a. Enhanced rates of downstaging & pathologic complete response (ypCR)

Site

AtDL

<2cmDL >2cmDL

PedunculatedPolyp LVI,G12 SessilePolyporLVI+, G34 T1,LVI,G12 SCRT +APR T1,LVI+,G34,orT2 SCRT+ APR GoodT3 CRT+ APR BadT3 CRT+APR T4a T4b CRT+APR CRT+APR

Mid Rectum Polypectomy&Observe RadicalSurgery

UpperRectum

APR/ Local CRT+ISRR Excision APR/ TME CRT+ISRR CRT+APR TME

Local Excision/ TME TME TME

TSME

TSME TSME CRT+TSME CRT+TSME CRT+TSME

CRT+APR CRT+TME CRT+TME CRT+APR CRT+TME CRT+TME CRT+APR CRT+TME CRT+TME

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