Incidence of rectosigmoid adenomatous polyps in subjects without prior colorectal adenoma or cancer: a prospective cohort study.
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BACKGROUND: Subjects without known colorectal adenomas or cancer constitute a large majority of the population where 85% of all cases of colorectal cancer are thought to occur. Consequently these people should be considered for screening to decrease mortality from colorectal cancer in the general population. AIMS: To estimate the incidence rate of rectosigmoid adenomas in these subjects. METHODS: Subjects without adenomas or cancer at a previous examination which had visualised the rectosigmoid underwent a fibre endoscopy every three years. Endoscopic data and population characteristics were collected prospectively. RESULTS: A total of 450 subjects fulfilled the selection criteria; 287 (64%) underwent at least two examinations, and 163 had three or more. At the second examination, with a mean delay of 39 months, the incidence rate of rectosigmoid adenomas was 1.50% per patient year. The rate was 1.75% per patient year (95% CI 0.80-3.33) at the third endoscopy with an additional mean delay of 38 months. The cumulative incidence rate at six years was 7.3% (95% CI 4.3-10.3), representing a mean of 1.2% per patient year. This rate increased with age and was higher for men than for women after age adjustment (p< 0.03). CONCLUSIONS: The incidence rates are very low compared with those of patients with prior adenomas. These results should be considered in establishing rectosigmoid adenoma screening strategies. (+info)
Dietary determinants of colorectal proliferation in the normal mucosa of subjects with previous colon adenomas.
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Dietary determinants of colorectal mucosa proliferation were studied in 69 subjects previously operated for at least two sporadic colon adenomas. Information on recent dietary habits was collected by a validated food frequency questionnaire, and proliferation was measured by [3H]thymidine incorporation in colorectal biopsies by determining the labeling index (LI) and the percentage of LI in the upper part of the crypt, two parameters that are increased in subjects at high risk of colon cancer. The LI was significantly higher in women as compared with men (P = 0.01). Diet showed several associations with colorectal mucosa proliferation: (a) subjects in the highest tertile of fish consumption had a significantly lower LI (P = 0.0013) compared with those in the lower tertiles [5.20 +/- 1.87 versus 6.80 +/- 2.18 (mean +/- SD)]; (b) subjects with a low red meat consumption had lower proliferation in the upper part of the crypt [2.38 +/- 2.10, 5.30 +/- 4.62, and 5.89 +/- 4.82 in the low, middle, and high tertile of consumption, respectively (mean +/- SD); P = 0.0093]; (c) according to estimated nutrient intakes, the LI was lower in subjects reporting a high intake of starch (P = 0.006) and higher in subjects with a low intake of beta-carotene (P = 0.002). The results show that subjects reporting a diet rich in fish, starch, and beta-carotene and low in red meat had lower colorectal mucosa proliferation and a normal pattern of proliferation along the crypt. Given the correlation between colorectal proliferative activity and colon cancer risk, such a dietary pattern might be beneficial for subjects at high risk of colon cancer. (+info)
Flat adenomas exist in asymptomatic people: important implications for colorectal cancer screening programmes.
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BACKGROUND: Flat adenomas are non-exophytic with a flat top or central depression and histologically the depth of dysplastic tissue is never more than twice the mucosal thickness. Flat adenomas frequently contain severely dysplastic tissue, and may progress rapidly through the adenoma-carcinoma sequence. Flat lesions have never been described in a British asymptomatic population. AIMS: To determine whether flat adenomas exist in an asymptomatic population participating in a large randomised controlled trial of flexible sigmoidoscopy screening. PATIENTS: A total of 3000 subjects (aged 55-64 years) underwent screening by flexible sigmoidoscopy. METHODS: All polyps were removed and sent for histology. The number of polyps with endoscopic and histological features of flat adenomas was recorded. RESULTS: Three subjects had a total of four flat lesions--that is, one per 1000 people screened. Three contained severely dysplastic tissue, one a focus of adenocarcinoma. Three of the four lesions were less than 5 mm in size and the fourth was 15 mm in diameter. CONCLUSIONS: Flat lesions with severe dysplasia exist in the asymptomatic population. This has major implications for gastroenterologists who should be trained to identify them. Their existence is of importance to molecular biologists and epidemiologists investigating the aetiology of colorectal cancer. (+info)
Effect of aspirin on prostaglandin E2 formation and transforming growth factor alpha expression in human rectal mucosa from individuals with a history of adenomatous polyps of the colon.
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Colorectal cancer is the second-most frequent cause of cancer mortality in the United States. Human epidemiology and laboratory studies indicate that aspirin may be an effective colorectal cancer chemopreventive agent. This study was designed to determine whether treatment with 81 mg of aspirin per day for 3 months would alter two putative surrogate end point biomarkers of chemoprevention of colorectal cancer [i.e., mucosal prostaglandin E2 (PGE2) formation and transforming growth factor alpha (TGF-alpha) expression] in normal-appearing rectal mucosa from individuals with a history of adenomatous polyps. Rectal biopsies were obtained by flexible sigmoidoscopy at three sequential time points: (a) after a 1-month placebo run-in period (baseline), (b) after 3 months of ingesting 81 mg of aspirin (as a single tablet) once per day, and (c) after 3 months of ingesting a placebo tablet once per day (washout period). Daily aspirin significantly suppressed PGE2 formation, but this significant suppression was completely reversed when aspirin was withdrawn. The extent of TGF-alpha staining in rectal crypts was also reduced significantly (P = 0.039) by daily aspirin. After a 3-month placebo-washout period, however, the mean extent of TGF-alpha staining was not significantly different from either baseline or the aspirin time point. Thus, 81 mg of aspirin daily significantly reduced rectal mucosal PGE2 formation and TGF-alpha expression in patients with a history of adenomatous polyps. These putative surrogate end point biomarkers may be useful intermediate end points in future colorectal cancer chemoprevention trials. (+info)
Evaluation of 5-aminosalicylic acid (5-ASA) for cancer chemoprevention: lack of efficacy against nascent adenomatous polyps in the Apc(Min) mouse.
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Recent experimental and epidemiological evidence suggests that nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in the prevention of colorectal cancer. However, the toxicity associated with the long-term use of most classical NSAIDs has limited their usefulness for the purpose of cancer chemoprevention. Inflammatory bowel disease (IBD) patients, in particular, are sensitive to the adverse side effects of NSAIDs, and these patients also have an increased risk for the development of intestinal cancer. 5-Aminosalicylic acid (5-ASA) is an anti-inflammatory drug commonly used in the treatment of IBD and may provide protection against the development of colorectal cancer in these patients. To directly evaluate the ability of 5-ASA to suppress intestinal tumors, we studied several formulations of 5-ASA (free acid, sulfasalazine, and Pentasa) at multiple oral dosage levels [500, 2400, 4800, and 9600 parts/million (ppm)] in the adenomatous polyposis coli (Apc) mouse model of multiple intestinal neoplasia (Min). Although the ApcMin mouse is not a model of colitis-associated neoplasia, it is, nonetheless, a useful model for assessing the ability of anti-inflammatory agents to prevent tumor formation in a genetically preinitiated population of cells. We used a study design in which drug was provided ad libitum through the diet beginning at the time of weaning (28 days of age) until 100 days of age. We included 200 ppm of piroxicam and 160 ppm of sulindac as positive controls, and the negative control was AIN-93G diet alone. Treatment with either piroxicam or sulindac produced statistically significant reductions in intestinal tumor multiplicity (95% and 83% reductions in tumor number, respectively; P < 0.001 versus controls). By contrast, none of the 5-ASA drug formulations or dosage levels produced consistent dose-progressive changes in polyp number, distribution, or size, despite high luminal and serum concentrations of 5-ASA and its primary metabolite N-acetyl-5-ASA. Thus, 5-ASA does not seem to possess direct chemosuppressive activity against the development of nascent intestinal adenomas in the ApcMin mouse. However, because intestinal tumor development in the ApcMin mouse is driven by a germline mutation in the Apc gene rather than by chronic inflammation, we caution that these findings do not definitively exclude the possibility that 5-ASA may exert a chemopreventive effect in human IBD patients. (+info)
A case-control study of colorectal adenomatous polyps and consumption of foods containing partially hydrogenated oils.
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The trans fatty acids produced by partially hydrogenating vegetable oils may cause colorectal neoplasia by interfering with cell membrane function or eicosanoid synthesis. This possibility provides a rationale for looking at the relation between colorectal adenomatous polyps and consumption of foods containing partially hydrogenated vegetable oils (PHVOs). A total of 516 cases and 551 controls who underwent screening sigmoidoscopy from 1991-1993 were recruited from a prepaid Los Angeles health plan. Subjects were interviewed and given a self-administered food frequency questionnaire. Food items containing PHVOs were divided into four groups characterized by principal ingredients and preparation methods: sweetened baked goods, candy bars, oils and condiments, and french fries and chips. After adjusting for age, sex, physical activity, body mass index, smoking, total energy, and red meat and vegetable intake, there was a positive association between polyps and sweetened baked goods [350+ versus <50 kcal/day (odds ratio, 2.1; 95% confidence interval, 1.3-3.5)]. No association was found with the other food groups after adjustment for dietary and nondietary covariates. Neither was total dietary trans fatty acid associated with adenomas after adjustment for sweetened baked goods and other covariates. These results do not support the hypothesis that eating foods containing PHVOs increases the risk of colorectal adenomas, but they are consistent with the hypothesis that foods high in fat and sugar and low in fiber and correlated micronutrients increase the risk of adenomas. (+info)
Reliability and validity of a self-administered food frequency questionnaire in a chemoprevention trial of adenoma recurrence.
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Various chemoprevention trials have assessed dietary intake by means of food frequency questionnaires. However, it is important to assess the degree to which such questionnaires can measure diet. We conducted reproducibility and validity analyses of our Arizona Food Frequency Questionnaire (AFFQ) in our recently completed, randomized, Phase III chemoprevention trial testing the effects of a wheat bran fiber supplement on colorectal adenoma recurrence. A total of 139 individuals provided a baseline and year 1 AFFQ and a set of 4-day dietary records collected over a period of 1 month. The reproducibility analyses of the AFFQ administered 1 year apart showed a mean intraclass correlation of 0.54 for unadjusted nutrients and 0.48 for energy-adjusted nutrients. The relative validity of the AFFQ, as compared with the average of the 4-day diet records, showed a mean deattenuated correlation of 0.49 (range, 0.22-0.65) for the baseline AFFQ and 0.49 (range, 0.25-0.67) for the year 1 AFFQ. When data from both AFFQs were combined and compared with the diet records, there was a slight improvement in the overall deattenuated correlations (mean, 0.56; range, 0.33-0.71). The correlations we observed for macro- and micronutrient intake were within the overall range of those reported in the literature. Reliability and validity studies of dietary instruments are feasible in the setting of a chemoprevention trial and should be conducted when the instrument's performance has not been previously assessed in the target population. (+info)
Patterns of proliferative changes in crypts bordering colonic tumors: zonal histology and cell cycle marker expression.
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Proliferative crypt changes have been noted in mucosa bordering colonic carcinomas, but their biological significance is disputed. We anticipated that zonal patterning of histological changes and cell cycle marker expression would provide clues to the pathogenesis of these border changes. 81 specimens were examined including carcinomas, adenomatours polyps, adenomas with early carcinoma, flat adenomas and aberrant crypt foci. The spatial distribution and frequency of micro-architectural features, and mucosal thickness were determined in a border domain of 150 300 sequential crypts/specimen. Immunocytochemical expression of Ki67 and p53 antigens in crypts also was semi-quantitatively examined. We found that in 100% of carcinomas two histologically abnormal zones (Proximate and Middle) separated tumor from normal mucosa. Differences in the feature frequency between zones were statistically significant (p<0.05). Both zones showed mild increases in crypt cell expression of Ki67, with a statistically significant relationship to zonal patterning (p<0.005). Weak expression of p53 only appeared in rare cells. Crypt elongation with mucosal thickening (1.9x normal, p<0.001) in the Proximate and Middle zones distinguished carcinomas from border changes in all benign lesions, except flat adenomas. Since this change occurs in all cases of carcinoma, there is no correlation with tumor stage or grade. Also in carcinomas, elaborate complexes of attached crypts (connected crypt structures) were characteristic of the Middle zone, so that proximate zone was always architecturally simpler. We conclude, that despite continuous carcinoma growth, the invaded border mucosa maintains a prototypical zonal organization of molecular and histological crypt changes This spatially organized reaction pattern is likely to reflect an interplay between regulated growth and destructive processes in response to advancing carcinoma. Compared to the edges of benign colonic tumors, the edges of carcinomas are distinctive and consistent enough to be diagnostically useful. (+info)