The incidence of colorectal cancer, the second leading cause of cancer-related deaths in the United States, has increased during the past decade.  Last year alone, it was estimated that 150,000 new cases would be diagnosed and that more than 60,000 related deaths would occur. Despite new treatment strategies, mortality rates for colorectal cancer have changed little during the past decade. Detecting colorectal cancer at an early, more treatable stage offers the best opportunity to reduce cancer deaths. Congress is currently considering legislation to expand Medicare coverage to include colorectal cancer screening. 
This article reviews the pathogenesis of colorectal cancer and discusses current screening methods.
Polyps and Colorectal Cancer
It was recognized over a century ago that colonic polyps have a malignant potential. In the 1930s, Westhues was the first to realize the importance of anatomy and histology in the evaluation of colonic polyps. His illustrations led to a classification system of polyps based on their malignant potential and certain morphologic and histologic features (Table 1). 
Westhues thought that certain polyps have no malignant potential and are not clinically important. These lesions, called hamartomatous polyps, include both juvenile polyps and polyps of Peutz-Jeghers syndrome. Once considered to be completely benign, these polyps are now recognized as having some malignant potential. Other types of polyps are associated with up to a 100 percent risk of cancer, such as those of the classic familial polyposis syndromes, Gardner's syndrome and Turcot syndrome. 
Adenomatous polyps are considered to be of great clinical importance. These polyps may have one of three different histologic patters, each marked by its own degree of malignant potential. The high incidence of colorectal cancer in the United States is thought to be related to the high incidence of colonic adenomas and their propensity for malignant change. While the adenoma-carcinoma sequence is generally accepted, only a minority of adenomas become malignant, and this process may take from five to 25 years. 
Primary and Secondary Prevention
Primary prevention of colorectal cancer requires identification and avoidance of etiologic agents. A diet high in fat and red meat and low in fruits, vegetables and whole grains is the major dietary risk factor for colonic cancer.  The virtual absence of adenomatous polyps and colorectal cancer in persons residing in many parts of Africa and Asia is though to be related to a low intake of saturated fat. Patients should therefore be told that they can reduce the risk of colorectal cancer by increasing their intake of fruits, vegetables and whole grains and decreasing their intake of fat.
A high-fat, low-fiber diet exposes the colonic mucosa to a variety of metabolic insults that may result in polyp genesis. Current evidence suggests that colonic bile acid has a role in this process. Dietary fat enhances cholesterol synthesis by the liver, which leads to increased bile acid
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synthesis and high bile acid levels in the bowel. Bile acid metabolites, probably produced by common intestinal microbes, have been found to be associated with the development of colonic cancer in animal models. 
Secondary prevention, or detection of a condition at an early, more treatable stage, can only be successful if a screening test is available that is both reasonably sensitive and specific. In addition, the prognosis must be improved by early detection and treatment. To justify the screening of large populations, the criteria outlined in Table 2 must be met.
Populations at high risk for colorectal cancer should be screened more frequently than the general population. The genetically transmitted syndromes, such as Gardner's syndrome, Turcot syndrome and familial polyposis syndrome, are well known risk factors. The familial cancer syndrome is characterized by an increased risk of colorectal adenocarcinoma in persons with multiple family members who have had breast, ovarian and/or uterine cancer. This syndrome has an autosomal
Criteria for Screening
as Secondary Prevention
dominant mode of transmission and is associated with a 50 percent increase in the risk of colorectal carcinoma. 
Flexible fiberoptic sigmoidoscopy and fecal occult blood testing are currently the most common used methods for colorectal cancer screening in the United States, and are endorsed by the National Cancer Institute and the American Cancer Society. However, no direct evidence indicates that either screening test reduces mortality from colorectal cancer. 
Fecal Occult Blood Testing
Overt bleeding from the rectum is a common early symptom of polyps and rectosigmoid cancer. Patients with this symptom should be referred for a complete colonoscopic investigation, since almost 25 percent of those over age 60 will have polyps and 10 percent will have colorectal cancer. 
Opinion is divided concerning whether testing of stool for occult blood is effective as a screening tool for early colorectal cancer. In the 1980s, the American Cancer Society and the National Cancer Institute recommended annual fecal occult blood testing in persons 50 years of age or older. However, the Canadian Task Force on the Periodic Health Examination  and the U.S. Preventive Services Task Force  found no evidence that fecal blood testing is an effective method of detecting early colorectal cancer.
However, several recent studies suggest that although fecal occult blood tests are often negative in the presence of colorectal tumors, cancers detected by fecal blood testing may be at a stage amenable to treatment. [11-13] Nevertheless, reports by several authors suggest that 1 to 4 percent of asymptomatic subjects older than 40 years of age will have false-positive results. [13-14] Furthermore, the predictive value of a positive fecal occult blood test for colonic malignancy has been estimated to be only between 20 and 50 percent, depending on the age of the patient. 
The number of false-positive and false-negative results can be reduced if patients are advised to avoid certain medications and foods before the test, such as red meat, parsnips, horseradish, beets and foods containing vitamin C or peroxidase. A high-fiber diet has been recommended as a method of increasing the sensitivity of Hemoccult tests. 
Despite the scientific controversy, many physicians believe that both symptomatic and asymptomatic persons benefit from screening with fecal occult blood testing. Eddy and colleagues  estimate that annual fecal occult blood testing in patients over 50 years of age could reduce the mortality associated with colorectal carcinoma by as much as 30 percent.
and Air-Contrast Barium Enema
In evaluating patients with a single positive test for fecal occult blood, many physicians use full colonoscopy or a combination of sigmoidoscopy and air-contrast barium enema. In a modified approach, colonic evaluation is delayed until a stool test is repeated after restriction of foods that cause false-positive results (meat, turnips of foods that contain peroxidase, depending on the test used).
Detection of an adenomatous polyp during sigmoidoscopy necessitates a more extensive evaluation, such as colonoscopy, because of the increased likelihood that tumors are present in more proximal regions of the colon.  Patients with adenomatous polyps greater than 3 mm in diameter have a higher risk of developing colorectal carcinoma.  These patients require more intensive surveillance than the general population.
Although colonoscopy and the combination of sigmoidoscopy and air-contrast barium enema are similarly sensitive in the detection of colonic cancer, colonoscopy may have several advantages over the other approach. First, colonoscopy involves only one preparation and procedure for the patient. Second, polyps found during colonoscopy can be removed or samples of suspicious lesions can be obtained. Third, sources of fecal blood not detectable by barium enema, such as vascular lesions, can be identified. One drawback of colonoscopic examination may be its slightly higher risk and cost. However, data comparing the two diagnostic approaches are not yet available.
Although strategies that involve complete visualization of the colon, such as air-contrast barium enema or colonoscopy, are diagnostically the most effective, they add significantly to cost and patient discomfort. The fecal occult blood test provides a simple, convenient and inexpensive method of screening but is comparatively less effective.
Eddy  recently examined various screening methods (Table 3). He suggests that the most effective combination is an annual fecal occult blood test and flexible fiberoptic sigmoidoscopy (60 cm) every three to five years in men and women aged 50 to 75 who are at average risk for colorectal cancer.
While the U.S. Preventive Services Task Force awaits the results of controlled clinical trials currently in progress, the American Cancer Society recommends that sigmoidoscopic examination be performed every three to five years in persons 50 years of age or older. 
It is generally believed that 25 percent of all polyps are detected by rigid sigmoidoscopy, whereas 50 to 60 percent are detected by flexible, 60-cm fiberoptic sigmoidoscopy. The importance of visualizing the entire colon with colonoscopy or a combination of flexible sigmoidoscopy and air-contrast barium enema, rather than performing flexible sigmoidoscopy alone, is supported by the fact that one-fourth to one-third of polyps and/or cancers are found in the right portion of the colon.
The American Cancer Society's recommendations emphasize the importance and perceived effectiveness of regurla screening. Until the results of prospective, long-term controlled clinical trials become available, clinicians must choose an appropriate approach to screening and follow-up when a fecal occult blood test is positive or an adenomatous polyp is found.
We recommend annual fecal occult blood testing in persons older than 50 years of age. If the test is positive, follow-up with either colonoscopy or flexible sigmoidoscopy plus air-contrast barium enema is indicated. Although no consensus exists concerning the use of sigmoidoscopy at regular intervals, persons between 50 and 75 years of age may benefit from screening with flexible fiberoptic sigmoidoscopy at three-to five-year intervals.
Follow-up after removal of adenomas should include colonoscopy or sigmoidoscopy in combination with air-contrast barium enema at annual intervals until no new polyps are found. Once the colon is free of polyps, screening with colonoscopy should be repeated every three years. Annual fecal blood tests should be used in intervening years.
When Biopsy Is Necessary
The decision to obtain a biopsy depends on the size and appearance of the polyp. Most
Screening Tests for Colorectal Polyps and Cancer
small adenomas containing a stalk and branching glands are classified histologically as tubular. They have a low malignant potential. Few cells, if any, demonstrate nuclear atypia. Villous adenomas, which have long, frondlike processes, are usually less differentiated and may contain highly dysplastic cells.
It has been suggested that more than 50 percent of patients found to have hyperplastic polyps will have adenomatous polyps higher in the colon.  However, a recent study suggest that hyperplastic polyps are not strong predictors of the presence of adenomatous polyps. We therefore believe that the finding of a pyperplastic polyp does not appear to justify colonoscopy. 
Adenomatous polyps less than 3 mm in diameter are not likely to be malignant. They may be monitored endoscopically at two -to four-year intervals. Hyperplastic polyps do not need to be followed at regular intervals.
Biopsy and histologic examination are advocated for polyps that are 3 mm in diameter or larger.  Based on several authopsy studies, 0.3 to 2 percent of these polyps can be expected to contain invasive cancer.  The percentage of polyps that contain invasive cancer is higher in patients with large (greater than 3 mm) adenomatous polyps and in those with first-degree relatives who have colonic cancer. Therefore, certain characteristics, such as size, are helpful in determining which polyps should be removed. If the type of polyp visualized by endoscopy is uncertain, biopsy and histologic examination are recommended.
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ROBERT LEVINE, M.D. is a fellow in gastroenterology at George Washington University Medical Center, Washington, D.C. Dr. Levine graduated from Georgetown University School of Medicine, Washington, D.C., and completed a residency in internal medicine at George Washington University.
SCOTT TENNER, M.D., M.P.H. is a resident in the Department of Medicine at George Washington University Medical Center. Dr. Tenner received his medical degree from George Washington University.
HANS FROMM, M.D. is professor of medicine and director of the Division of Gastroenterology and Nutrition at George Washington University Medical Center.
COPYRIGHT 1992 American Academy of Family Physicians
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