Adenocarcinoma of the colon and rectum is identified in more than 150,000 men and women in the United States each year, and 60,000 people die from the disease annually. Colorectal is the second leading cause of cancer mortality in the United States. In men, Colorectal is second in prevalence only to lung cancer, and in women it is third behind breast and lung cancer. More than 95% of the cancers are thought to have their origin in a polyp. Adenomatous polyps are found in approximately 33% of the general population by age 50 years and 50% by age 70 years.
Pathogenesis. The term polyp refers to any protrusion into the lumen of the gastrointestinal tract. A sessile polyp is a raised protuberance with a broad base. A pedunculated polyp is attached to the bowel wall by a stalk that is narrower than the body of the polyp.
Polyps may be benign or malignant, although in common usage the term generally has a benign connotation. In the colon, polyps can be described as adenomatous, hamartomatous, hyperplastic, or inflammatory, according to their histopathologic appearance. Adenomatous polyps can be classified as tubular, villous, or tubulovillous, depending on whether their histologic appearance is primarily glandular, villous, or mixed, respectively.
Although most adenomatous polyps are benign, some may contain carcinoma and others may degenerate later to carcinoma. The risk of a polyp containing carcinoma increases directly with the size of the polyp (Table RELATION OF POLYP SIZE TO RISK OF CANCER IN THE POLYP). Cancer is more likely to occur in villous adenomas than the other types, and benign adenomatous polyps may coexist with adenocarcinoma elsewhere in the bowel. In short, a colon that has a tendency to produce polyps also is at higher risk of the development of cancer.
Clinical presentation. Because colonic polyps are so common – some estimates of prevalence are as high as 50% in people over age 50 – they are an important risk factor in the development of Colorectal in the general population.
Most patients with polyps are asymptomatic. In those instances, the polyps remain undiscovered or are diagnosed during surveillance sigmoidoscopy or colonoscopy. Sometimes polyps cause occult or gross bleeding. Occasionally patients complain of abdominal discomfort, which may be caused by tugging on the polyp by peristaltic contractions. If the polyp is large, frank obstruction can occur. Rarely, a polyp causes intussusception of the small or large intestine.
Diagnostic studies. Colonic polyps are identified by barium enema x-ray examination, sigmoidoscopy, or colonoscopy. Often the barium enema has been ordered for symptoms that have no relation to the polyp. If the possibility of a polyp is raised by barium enema findings, complete colonoscopy should be performed. Similarly, identification of a polyp by sigmoidoscopy is justification for colonoscopy because the chance that there is a synchronous polyp in the colon above the reach of the sigmoidoscope exceeds 20%. For discussion of cancer surveillance.
Polypectomy. Sessile polyps should be biopsied, and pedunculated polyps usually can be removed during colonoscopy. Polypectomy is performed by encircling the polyp with a wire snare through which an electrocauterizing current is passed. The bowel should be evacuated thoroughly using a standard colonoscopy preparation to eliminate potentially explosive gases (hydrogen and methane). Electrocautery should not be used during sigmoidoscopy when the bowel preparation has been incomplete. If a polyp is identified at sigmoidoscopy, a biopsy may be taken at the endoscopist’s discretion, but the appropriate time for polypectomy is during a subsequent complete colonoscopy. Tests of blood coagulation, such as a prothrombin time, partial thromboplastin time, and platelet count, and a complete blood count are appropriate before performance of colonoscopic polypectomy.
|TABLE. RELATION OF POLYP SIZE TO RISK OF CANCER IN THE POLYP|
Careful histologic examination of resected polyps is essential for formulating appropriate recommendations for the patient. Nonadenomatous polyps are thought to have little or no malignant potential, and removal of those polyps is sufficient treatment. On the other hand, adenomatous polyps not only predispose to the subsequent development of cancer but also may contain cancer cells at the time of resection. Thus, it is important that all polyps, particularly those larger than 1 cm in diameter, be examined carefully for adenocarcinoma.
Adenocarcinoma may be present in adenomatous polyps in one of four ways.
The cancerous change involves only the mucosa and does not penetrate the muscularis mucosa into the stalk of the polyp. This condition is sometimes called carcinoma in situ. Colonoscopic resection of the polyp in this instance is regarded as curative. No surgical treatment is indicated. The patient is scheduled to return in 1 year for follow-up colonoscopy.
|TABLE. DIAGNOSIS AND TREATMENT OF CANCEROUS ADENOMATOUS POLYPS|
The cancer penetrates the muscularis mucosae of the polyp into the stalk but does not involve blood vessels or lymphatics within the resected portion of the stalk, and the cancer is moderately to well differentiated.
Although a small number of patients with this finding have cancerous involvement of the bowel or local lymph nodes, the mortality (< 2%) and morbidity of surgery to resect the portion of the colon that contained the polyp exceed the risk of residual cancer. Thus, additional surgery for these patients is not recommended. Repeated colonoscopy should be scheduled for 1 year later.
The cancer not only penetrates the muscularis mucosae of the polyp but also has invaded blood vessels or lymphatics within the stalk. In these patients, cancer also is likely to be present in the bowel or local lymph nodes. Also in this category are patients with poorly differentiated cancers that do not involve blood vessels or lymphatics. If operative risk is not prohibitive, these patients should undergo resection of the segment of colon that contained the polyp. Repeated colonoscopy to examine the anastomosis for recurrent tumor should be scheduled for 3 to 6 months if residual cancer is found at surgery. If no residual cancer is found, colonoscopy should be scheduled for 6 to 12 months.
The cancer involves the resectional margin of olyp, indicating that residual cancer remains in the patient. If the patient is an operative candidate, segmental resection of the colon is indicated. These patients should undergo follow-up colonoscopy in 3 to 6 months to check for residual tumor at the anastomosis and for other polyps.
Polyposis syndromes differ in their clinical manifestations, pathology, patterns of inheritance, and predisposition to carcinoma (Table POLYPOSIS SYNDROMES).
Familial polyposis and Gardner’s syndrome. These conditions probably are related and expressions of the same genetic syndrome: one that is inherited in an autosomal dominant pattern. Affected individuals have hundreds of colorectal polyps in the first three decades of life. Polyps also may occur in the stomach and small intestine. If the colon is not resected, virtually 100% of the patients eventually develop cancer. Gardner’s syndrome is distinguished by osteomas, fibromas, and other features (Table POLYPOSIS SYNDROMES) in addition to the intestinal polyps. Yearly flexible sigmoidoscopy should begin at age 10 in asymptomatic individuals carrying the gene for Familial polyposis. Colonoscopy may be indicated if flexible sigmoidoscopy is normal. Total proctocolectomy with an ileostomy or an anal sphincter-saving procedure is indicated if the diagnosis of Familial polyposis is made.
Turcot’s syndrome. In this rare disease, colonic polyposis is associated with brain tumors. Both recessive and dominant patterns of genetic transmission have been described. Screening and treatment of affected individuals are the same as for Familial polyposis.
In Peutz-Jeghers syndrome, intussusception, obstruction, or infarction of the polyps may develop with consequent abdominal pain and bleeding. For these reasons, surgery may be indicated. Because the risk of cancer is less than 3%, prophylactic surgery is not indicated.
The other polyposis syndromes are not associated with an increased risk of cancer, although relatives of patients with juvenile polyps may have cancers of the stomach, small intestine, colon, or pancreas. However, patients with these syndromes may have complications of the polyps, such as bleeding and obstruction; if conservative treatment fails, they require surgery.
Familial colon cancer syndrome
Hereditary nonpolyposis colorectal cancer syndrome is a condition that is transmitted in an autosomal dominant fashion with a high degree of penetrance for the development of colorectal carcinoma. Two types are recognized. In type 1, cancers are confined predominantly to the colon. In type 2, cancers occur not only in the colon but also in the female genital tract, breast, brain, small bowel, pancreas, lymph system, and bone marrow. The diagnosis is suspected when Colorectal occurs in a young person with a family history of Colorectal.
Surveillance of family members in kindreds that may be affected should begin when members are age 20. Fecal occult blood should be tested yearly. Total colonoscopy should be performed every 3 years beginning at age 20. Because of the high prevalence of cancers in the proximal colon, flexible sigmoidoscopy is not sufficient. Women with type 2 Hereditary nonpolyposis colorectal cancer syndrome should undergo yearly pelvic examinations. If colon cancer is detected, total or subtotal colectomy is indicated.
|TABLE. MODIFIED DUKE’S CLASSIFICATION TO STAGE COLORECTAL CANCER|
Recommendations for cancer surveillance and follow-up of polyps and cancer
Rationale for Colorectal screening
The overall 5-year survival rate for patients in the United States is approximately 60%. This correlates almost directly with the stage of diagnosis. Early detection of Colorectal can improve outcome significantly. The 5-year survival rate for patients with stage I to II disease is 80% to 90%, whereas it is 60% for those with stage III disease and less than 10% for stage intravenous disease. Studies have shown decreased mortality for Colorectal when screening is performed and the improved survival is associated with a shift to earlier stages at diagnosis.
The relatively long duration of adenoma-to-cancer sequence provides a period of predisease time during which early detection may be effective. Most sporadic CRCs arise from adenomatous polyps and the progression from normal mucosa through polyp formation and subsequent development of cancer is a process that occurs over a 5- to 15-year period. Consideration of this time frame is important when deciding what intervals are optimal for repeated screening.
Tests available for cancer screening
Digital rectal examination. Most physicians are able to examine the rectum digitally to a depth of 7 to 9 cm. This should detect about 10% of CRCs. An infiltrating cancer feels hard and irregular, whereas a benign polyp is more likely to be soft and pliable.
Test for occult blood in the stool. Because bleeding is the most common sign of Colorectal, testing for occult blood in the stool is valuable in cancer surveillance. Currently available guaiac-impregnated cards have low false-negative and false-positive rates when used properly. Patients should adhere to a special diet (Table DIET FOR FECAL OCCULT BLOOD TESTING) for 48 hours before the stool is tested for occult blood. The diet eliminates foods and agents that are likely to give a false-negative or false-positive result but includes «roughage,» which is believed to stimulate bleeding from existing bowel lesions. The most reliable method of testing for occult blood is to obtain two smears per day from different parts of the stool for 3 days. A report by Mandel and associates indicates that annual fecal occult blood testing decreased the 13-year cumulative mortality from Colorectal by 33%.
Colonoscopy, sigmoidoscopy, and barium enema x-ray examination.
In the general population.
In patients with colonic polyps.
For people with a family history of Colorectal. People who have a parent, a sibling, or a second-degree relative with colorectal carcinoma are at higher risk of development of Colorectal, albeit much less than those who have familial colon
cancer syndrome. Such people also are at higher risk of the development of Colorectal and polyps. People who have one first-degree relative with Colorectal should undergo Colorectal screening (preferably with colonoscopy) starting at age 40, or 10 years before the age of the onset in the affected relative. For people with two affected first-degree relatives, or one first-degree relative and one or more second-degree relatives, initial colonoscopy at age 40 may be justified, followed by routine yearly stool occult blood testing and periodic colonoscopy every 3 to 5 years.
|Table. DIET FOR FECAL OCCULT BLOOD TESTING|
For postoperative colonoscopic follow-up of patients with resected Colorectal. Patients who have had a colorectal carcinoma are at greater risk of the development of another colorectal carcinoma. Patients who have had resection of the colon for cancer should undergo colonoscopy 6 months after surgery to look for recurrence at the anastomosis and elsewhere in the colon. Subsequent colonoscopic examinations should be yearly.
Chemoprevention of prevention of Colorectal. Compliance to screening programs for Colorectal remains poor and alternative approaches are being sought. Chemoprevention of Colorectal involves the long-term use of a variety of oral agents to prevent the development of adenomatous polyps and their subsequent progression to Colorectal. Molecular analyses of adenomas and CRCs have led to a genetic model of colon carcinogenesis in which the development of cancer results from the accumulation of a number of genetic alterations. By interfering with these molecular events, chemoprevention could inhibit or reverse the development of adenomas or the progression from adenoma to cancer. Recent observations suggest that patients taking aspirin and other nonsteroidal antiinflammatory drugs, supplemental folate, calcium, and estrogen, as seen in postmenopausal women taking hormone replacement therapy, experience a chemopreventive benefit. However, because the value of these prophylactic strategies has not yet been confirmed in double-blind, placebo-controlled, randomized studies, chemoprevention cannot be accepted as standard medical practice.
Chemoprevention should not replace periodic fecal occult-blood tests and endoscopic screening as well as modification in known risk factors of Colorectal such as reduction in the intake of red meat, appropriate exercise, smoking cessation, and weight control. In addition to more selective NSAIDS such as cyclooxygenerase-2 (COX-2) inhibitors such as celecoxib and rofecoxib, other potential chemopreventive agents as ursodiol, eflornithine, and oltipraz are undergoing evaluation in clinical studies.