Improving the effectiveness of fecal occult blood screening for colorectal cancer.
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Biomedical subjects
Publications and source records attributed to J H Bond.
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BACKGROUND: In 1993, a randomized controlled trial in Minnesota showed, after 13 years of follow-up, that annual fecal occult blood testing was effective in reducing colorectal cancer mortality by at least 33%. Biennial screening (i.e., every 2 years) resulted in only a 6% mortality reduction. Two European trials (in England and in Denmark) subsequently showed statistically significant 15% and 18% mortality reductions with biennial screening. Herein, we provide updated results-through 18 years of follow-up--from the Minnesota trial that address the apparent inconsistent findings among the trials regarding biennial screening. METHODS: From 1976 through 1977, a total of 46551 study subjects, aged 50-80 years, were recruited and randomly assigned to an annual screen, a biennial screen, or a control group. A screen consisted of six guaiac-impregnated fecal occult blood tests (Hemoccult) prepared in pairs from each of three consecutive fecal samples. Participants with at least one of the six tests that were positive were invited for a diagnostic examination that included colonoscopy. All participants were followed annually to ascertain incident colorectal cancers and deaths. RESULTS: The numbers of deaths from all causes were similar among the three study groups. Cumulative 18-year colorectal cancer mortality was 33% lower in the annual group than in the control group (rate ratio, 0.67; 95% confidence interval [CI] = 0.51-0.83). The biennial group had a 21% lower colorectal cancer mortality rate than the control group (rate ratio, 0.79; 95% CI = 0.62-0.97). A marked reduction was also noted in the incidence of Dukes' stage D cancers in both screened groups in comparison with the control group. CONCLUSION: The results from this study, together with the other two published randomized trials of fecal occult blood screening, are consistent in demonstrating a substantial, statistically significant reduction in colorectal cancer mortality from biennial screening.
Evidence-based guidelines recommend that all asymptomatic, average-risk U.S. citizens >50 years of age be encouraged to undergo screening for colorectal cancer. Those at higher risk should be offered more intensive screening and follow-up surveillance. It is estimated that widespread adoption of these recommendations could reduce mortality from colorectal cancer by >50%. The only screening methods that have been evaluated directly are the fecal occult blood test and flexible sigmoidoscopy. Current guidelines now recommend annual screening for fecal occult blood plus flexible sigmoidoscopy every 5 years for asymptomatic, average-risk men and women >50 years of age. Indirect evidence supports the options of colonoscopy or barium enema x-ray screening for highly motivated individuals, but these methods have not yet been tested in prospective trials. In the future, gene-based screening tests may be developed, and computed tomography of the colon ("virtual colonoscopy") may prove effective and feasible.
BACKGROUND AND METHODS: Laboratory, clinical, and epidemiologic evidence suggests that calcium may help prevent colorectal adenomas. We conducted a randomized, double-blind trial of the effect of supplementation with calcium carbonate on the recurrence of colorectal adenomas. We randomly assigned 930 subjects (mean age, 61 years; 72 percent men) with a recent history of colorectal adenomas to receive either calcium carbonate (3 g [1200 mg of elemental calcium] daily) or placebo, with follow-up colonoscopies one and four years after the qualifying examination. The primary end point was the proportion of subjects in whom at least one adenoma was detected after the first follow-up endoscopy but up to (and including) the second follow-up examination. Risk ratios for the recurrence of adenomas were adjusted for age, sex, lifetime number of adenomas before the study, clinical center, and length of the surveillance period. RESULTS: The subjects in the calcium group had a lower risk of recurrent adenomas. Among the 913 subjects who underwent at least one study colonoscopy, the adjusted risk ratio for any recurrence of adenoma with calcium as compared with placebo was 0.85 (95 percent confidence interval, 0.74 to 0.98; P=0.03). The main analysis was based on the 832 subjects (409 in the calcium group and 423 in the placebo group) who completed both follow-up examinations. At least one adenoma was diagnosed between the first and second follow-up endoscopies in 127 subjects in the calcium group (31 percent) and 159 subjects in the placebo group (38 percent); the adjusted risk ratio was 0.81 (95 percent confidence interval, 0.67 to 0.99; P=0.04). The adjusted ratio of the average number of adenomas in the calcium group to that in the placebo group was 0.76 (95 percent confidence interval, 0.60 to 0.96; P=0.02). The effect of calcium was independent of initial dietary fat and calcium intake. CONCLUSIONS: Calcium supplementation is associated with a significant - though moderate - reduction in the risk of recurrent colorectal adenomas.
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A number of recent publications dealing with colon polyps and cancer emphasize cost-effectiveness and the outcomes of screening and follow-up surveillance of high-risk groups. These groups include patients with either a past personal history or a family history of colorectal adenomas or cancer. Several papers address the effectiveness and compliance with different methods of screening of the asymptomatic, average-risk population for colorectal neoplasia. Other important publications deal with colorectal cancer prevention, the natural history of the adenoma-carcinoma sequence, diagnosis of polyps and cancer, colonoscopic polypectomy, management of the patient with a malignant polyp, and endoscopic treatment of obstructing cancer.
Experimental and observational findings suggest that calcium intake may protect against colorectal neoplasia. To investigate this hypothesis, we conducted a randomized, double-blind trial of colorectal adenoma recurrence. Nine hundred thirty patients with a recent history of colorectal adenomas were randomly given calcium carbonate (3 gm daily; 1200 mg elemental calcium) or placebo, with follow-up colonoscopies one and four years after the qualifying examination. The main analysis focused on new adenomas found after the first follow-up endoscopy, up to (and including) the second follow-up examination. Risk ratios of at least one recurrent adenoma and ratios of the average numbers of adenomas were calculated as measures of calcium effect. There was a lower risk of recurrent adenomas in subjects assigned calcium. Eight hundred thirty-two patients had two follow-up examinations and were included in the main analysis; the adjusted risk ratio of one or more adenomas was 0.81 (95% CI 0.67 to 0.99); the adjusted ratio of the average numbers of adenomas was 0.76 (95% CI 0.60 to 0.96). Among subjects who had at least one follow-up colonoscopy, the adjusted risk ratio of one or more recurrent adenomas was 0.85 (95% CI 0.74 to 0.98). The effect of calcium seemed independent of initial dietary fat and calcium intake. No toxicity was associated with supplementation. These findings indicate that calcium supplementation has a modest protective effect against colorectal adenomas, precursors of most colorectal cancers.
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Occult gastrointestinal bleeding is diagnosed by using one of the commercially available fecal occult blood tests (FOBTs). Guaiac-based slide tests are most frequently used, although the more specific immunochemical methods are promising. The guaiac tests are inexpensive, nonspecific, qualitative measures of stool blood, and their use requires dietary and drug restrictions. Clinicians need to be aware of the causes of false-positive and false-negative test results. Although specific for the presence of human blood, immunochemical tests are more expensive and tend to react also to physiological quantities of blood in fecal specimens. Whichever test is chosen, it must be processed and read correctly. Annual FOBT screening for colorectal cancer, combined with periodic flexible sigmoidoscopy, is a cost-effective method of detecting early, curable colorectal cancer.
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Comprehensive evidence-based guidelines for screening and surveillance for colorectal cancer were published in 1997. Backed by compelling scientific data from recently completed controlled trials and case-control studies, these guidelines recommend annual fecal occult blood test screening plus periodic flexible sigmoidoscopy about every 5 years for asymptomatic, average-risk individuals over 50 years of age. Other screening studies published during the past year refine knowledge about how these screening tests detect early cancer and polyps and assess factors that influence compliance with screening recommendations. Preliminary reports suggest revolutionary new methods of screening that may become clinically feasible in the next millennium.
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Second only to lung cancer in mortality, colon cancer is amenable to cure if detected early. Because fecal occult blood testing and flexible sigmoidoscopy are effective individually but have limitations, both are now recommended for screening. However, after successful polyp removal, surveillance colonoscopy does not need to be performed as often as previously thought.
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