Colon Polyps

Colon Cancer

1. Incidence
• lifetime risk of developing colorectal cancer is ~ 5%
• second leading cause of cancer death in the U.S. for men and the third most common cause in women
• incidence rates for patients > 50 years old have been declining at ~ 2% per year
• incidence rates for patients < 50 have been increasing at ~ 2% per year


2. Etiology
• colorectal cancer is a genetic disease caused by alterations in the genetic code
• these alterations in the genetic code may be inherited or acquired


1. Genetic Predisposition
• 10% to 15% of cases are familial


1. Familial Adenomatous Polyposis (FAP)



1. Etiology
• transmitted in autosomal dominant fashion
• the defective gene is the APC gene located on chromosome 5q21
• 25% of patients do not have a family history of FAP (spontaneous germline mutation)


2. Clinical Manifestations
• characterized by hundreds or thousands of colonic adenomatous polyps
• frequency is 1/10,000 patients
• polyps occur at an average age of 15 years; colon cancer develops at an average age of 40
• gastric polyps occur in 50% (no malignant potential); duodenal polyps occur in 90% with a lifetime risk of duodenal cancer of 10%
• desmoid tumors occur in 30% of FAP patients
• Gardner’s syndrome is polyposis accompanied by osteomas, epidermal inclusion cysts, and desmoid tumors
• Turcot’s syndrome is polyposis and brain tumors
• attenuated adenomatous polyposis coli is an attenuated form of FAP in which patients have fewer polyps but retain the high risk of colon cancer


3. Diagnosis and Screening
• genetic testing can be used to diagnose FAP and its variants
• screening by flexible sigmoidoscopy should begin at age 10 to 12 in those at risk for the disease
• upper endoscopy to screen for gastric and duodenal polyps should begin after colonic polyposis develops


4. Treatment
• curative procedure requires removal of all colonic and rectal mucosa to the level of the dentate line
• procedure of choice is a total proctocolectomy with an ileal pouch-anal anastomosis
• proctocolectomy with ileostomy is reserved for patients who are not candidates for a pouch procedure (older, poor sphincter function)
• abdominal colectomy with ileorectal anastomosis leaves rectal mucosa at risk for malignant degeneration and should only be chosen for patients who are not candidates for an ileal pouch procedure and who refuse a permanent ileostomy


2. Hereditary Nonpolyposis Colorectal Cancer (HNPCC)
• autosomal dominant inheritance; average age of cancer diagnosis is 45
• the genetic defect appears to be inherited mutations of mismatch repair genes (genetic proofreading)


1. Definition
• now defined by the modified Amsterdam criteria, which expanded the cancers involved to colorectal, endometrial, pancreatic, small intestine, ureteral, and renal pelvis



2. Diagnosis
• mainstay of diagnosis is a detailed family history
• genetic testing includes analysis of 4 mismatch repair genes in peripheral WBCs


3. Screening
• colorectal cancers develop through the typical adenoma-carcinoma sequence
• since most cancers develop in the proximal colon, a full colonoscopy is necessary for screening
• screening should be done every several years beginning at age 20, and then annually at age 35
• screening for endometrial cancer by endometrial biopsy and ovarian cancer by pelvic ultrasound and CA-125 should also be done periodically


4. Treatment
• most patients should be treated with a subtotal colectomy with ileorectal anastomosis since 20% have a synchronous cancer and 25% will develop a metachronous cancer in the remaining colon
• rectum remains at risk for the development of cancer, and annual proctoscopy is mandatory
• prophylactic colectomy has not been adopted for Lynch syndrome
• for a woman who is done with childbearing, a prophylactic TAH-BSO is recommended at the time of colectomy
• stage for stage, Lynch syndrome patients have a better outcome than non-Lynch syndrome patients


2. Acquired Somatic Defects
• majority of colon cancers arise from acquired genetic mutations that originate in a single cell or group of cells
• tumorigenesis proceeds through a series of genetic alterations involving mutational activation of oncogenes (ras) and mutational inactivation of tumor suppressor genes (APC, p53)
• cumulative total of mutations is more important than their order of appearance


3. Diet
• populations that consume < 5% of their diet as fat have a lower incidence of colorectal cancer, whereas those that consume > 20% of their diet as fat have a greater incidence
• high fiber diets may lower the risk of colorectal cancer


4. Premalignant Conditions
1. Ulcerative Colitis
• risk of cancer is 1% per year after 10 years in patients with pancolitis
• dysplasia is an indication for proctocolectomy
• cancers are difficult to detect and usually present in a more advanced stage


2. Crohn’s Disease
• lower risk than ulcerative colitis


3. Family History
• twofold to threefold increased risk in first degree relatives of patients with sporadic colon cancer


3. Screening
• goals of screening are to detect premalignant lesions (polyps) and to detect cancers at an early stage when they are most amenable to cure


1. Average Risk Patients
• most guidelines recommend starting screening at age 50
• however, since colon cancer is increasing in frequency in younger people, the American Cancer Society recommends beginning screening at age 45
• several different approaches are possible


1. Annual Fecal Occult Blood Test
• patients submit 2 samples from each of 3 consecutive stools
• positive result mandates an examination of the entire colon and rectum with colonoscopy
• test is able to detect blood loss of 20 mL/day
• high rate of both false positives and false negatives


2. Flexible Sigmoidoscopy
• recommended every five years
• will detect ~ 50% of colon cancers
• if adenomatous polyps or a colon cancer is found, then the patient should have a full colonoscopy
• this test is often combined with annual fecal occult blood testing


3. Colonoscopy
• gold standard test – highly sensitive and allows for biopsy and polypectomy
• cost, fear of the procedure, and the need for a bowel prep are major barriers to widespread adoption
• recommended every 10 years


2. High Risk Patients
• screening recommendations vary depending upon the risk category


1. First-Degree Relatives of Patients with Colon Cancer
• screening should begin at age 40
• consider colonoscopy as the screening tool of choice


2. Patients with a History of Adenomatous Polyps
• repeat colonoscopy in 3 years
• if the repeat examination is negative, then subsequent examinations should be every 5 years


3. Patients with a History of Colorectal Cancer
• colonoscopy within 1 year of resection
• colonoscopy 3 years after a negative 1-year examination


4. Patients with a Family History of FAP
• should receive genetic testing to see if they are carriers of the mutant gene
• flexible sigmoidoscopy should be done yearly beginning at puberty


5. Patients with a Family History of HNPCC
• colonoscopy every 1 to 2 years beginning at 20
• yearly colonoscopy beginning at age 35


6. Patients with Ulcerative Colitis
• colonoscopy yearly after 8 years with pancolitis
• dysplasia on random biopsies is an indication for proctocolectomy


4. Staging
• TNM is the standard system used
• clinical staging is based on history, physical exam, endoscopy, and imaging
• pathologic examination of the resected specimen provides a basis for prognosis and the need for adjuvant treatment


5. Clinical Manifestations
1. Subacute Presentation
1. Right Colon Cancers
• usually do not cause change in bowel habits
• often present with iron-deficiency anemia, with resulting fatigue, weakness, and dizziness
• A tumor that obstructs the ileocecal valve may present as a small bowel obstruction


2. Left Colon Cancers
• decrease in stool caliber
• cramping lower abdominal pain
• occasionally present with bright red blood per rectum


2. Acute Presentation
1. Obstruction
• complete obstruction occurs in less than 10% of patients


2. Perforation
• complete obstruction can lead to perforation, often of the cecum
• colon may also perforate at the tumor site and mimic acute diverticulitis
• if the perforation is not contained, then generalized peritonitis results


6. Diagnosis and Preoperative Evaluation
1. Endoscopy
• colonoscopy is the most accurate and complete examination of the colon
• synchronous cancers are found in 4% of patients and synchronous adenomatous polyps in 30% - 50%
• a complete colonoscopy may be technically difficult in some patients, in which case a LGI may be substituted







2. Radiology
1. CT Scan
• preoperative chest, abdomen, and pelvis CT scans can reveal local tumor extension, regional nodal disease, and distant metastases
• if the scans cannot be done prior to resection, then they can be done in the postop period







2. PET Scans
• should not be done for routine preoperative evaluation
• if a patient has isolated liver or lung metastases, then a PET scan is valuable to look for additional disease that would exclude surgical excision


3. Blood Tests
1. Liver Function Tests
• elevated alkaline phosphatase, transaminases, and bilirubin can suggest liver metastases
• often used in the postoperative follow up period


2. CEA
• not useful in screening or diagnosis since it is nonspecific for colon cancer
• preoperative CEA level is an independent predictor of survival in stage I – III disease
• a rising CEA level postop is worrisome for recurrent disease


7. Treatment
1. General Principles
• all non-emergent cases should have a standard mechanical bowel prep
• surgical resection involves resection of the involved segment of the colon as well as its draining lymphatics
• the lymphatics follow the arterial supply of the colon and so resection requires removal of the segmental blood supply of the colon
• adequate staging requires that at least 12 lymph nodes be removed
• if the tumor invades an adjacent organ, it should be resected en bloc with the colon







1. Laparoscopic Colectomy
• has several potential advantages: decreased pain, better cosmesis, and shorter hospital stay
• hand-assist ports can facilitate the procedure
• laparoscopic and open resection are associated with similar 5-year disease-free and overall survival


2. Right Hemicolectomy
• used to treat tumors of the cecum and ascending colon
• involves ligation of the ileocolic, right colic, and right branch of the middle colic arteries
• lesions near the hepatic flexure will require division of the middle colic
• 5 to 10 cm of the terminal ileum is also removed



3. Transverse Colectomy
• requires ligation of the middle colic artery
• if it is technically difficult to perform an anastomosis between the ascending and descending colons, then an ‘extended’ right hemicolectomy may be performed with an anastomosis between the ileum and the descending colon



4. Left Hemicolectomy
• used for splenic flexure and descending colon tumors
• involves ligation of the left colic artery with anastomosis of the transverse colon to the sigmoid colon



5. Sigmoid Colectomy
• involves ligation of the inferior mesenteric artery distal to the takeoff of the left colic artery, which removes the sigmoidal and superior rectal arteries
• the anastomosis is created between the descending colon and the upper rectum



6. Subtotal Colectomy
• involves an ileosigmoid or ileorectal anastomosis
• should be performed for patients with synchronous cancers, metachronous cancers, or Lynch Syndrome
• also has a role in obstructing or perforated cancers



7. Emergency Operations
1. Obstruction
• several different options to choose from:
• three stage procedure involving an initial defunctioning stoma, definitive resection and anastomosis, ostomy closure
• Hartmann’s type procedure involving resection with creation of a proximal ostomy and either a Hartmann’s pouch or mucous fistula
• subtotal colectomy with primary anastomosis
• resection and anastomosis with or without a diverting loop ileostomy, with or without an on-table bowel lavage


• the clinical condition of the patient is an important determining factor in deciding which operation to choose


2. Perforated Colon Cancer
• goal of surgery is to remove the diseased, perforated segment
• most common operation chosen is a Hartmann’s type procedure
• in stable patients, can consider a subtotal colectomy with primary anastomosis
• when a left colon cancer produces perforation of the right colon, a subtotal colectomy should be performed


8. Adjuvant Therapy
• patients with node-positive disease (stage III) benefit from adjuvant therapy with infusional 5-FU, leucovorin, Oxaliplatin (FOLFOX)
• oral capecitabine (Xeloda) may be substituted for 5-FU
• treatment course is 6 months, and recurrence rates are reduced by at least 40%
• high-risk stage II patients may also benefit from adjuvant chemotherapy (T4, obstruction/perforation, lymphatic or vascular invasion, < 12 nodes removed)
• addition of targeted therapy – monoclonal antibodies against growth factors or growth factor receptors – does not improve survival over chemotherapy alone in the adjuvant setting
• no role for adjuvant chemotherapy in stage I patients
• no role for adjuvant radiation therapy in colon cancer