Preventive effects of low-dose aspirin on colorectal adenoma growth in patients with familial adenomatous polyposis: double-blind, randomized clinical trial.

There are several reports of clinical trials of aspirin in sporadic colon cancer. However, only one double-blind trial of aspirin in patients with familial adenomatous polyposis (FAP) has been reported to date. This double-blind, randomized, placebo-controlled clinical trial was therefore performed to evaluate the influence of low-dose aspirin enteric-coated tablets (100 mg/day for 6-10 months) in 34 subjects with FAP (17 each in the aspirin and placebo groups). The increase in mean diameter of colorectal polyps tended to be greater in the placebo group compared with the aspirin group, which showed a response ratio, that is, aspirin response rate (number of subjects with reduced polyps/total)/placebo response rate (number of subjects with reduced polyps/total), of 2.33 (95% confidence interval: 0.72-7.55). Subgroup analysis revealed that the number of subjects with a mean baseline polyp diameter of ≤2 mm, and the diameter and number of polyps after intervention showed a significant reduction in the aspirin group. Adverse effects of aspirin, such as anastomotic ulcer, aphtha in the large intestine, and progression of anemia, occurred in three subjects. Moreover, none of the subjects developed colorectal cancer. The results thus indicated a potential for aspirin to reduce colorectal adenoma development in patients with FAP, but careful follow-up is needed to avoid or rapidly counter severe adverse effects.

Excessive fat restriction might promote the recurrence of colorectal tumors.

The incidence of colorectal cancer is rapidly increasing in Japan. This trend has been suggested to be caused by an increasing fat intake as a result of the Westernized diet among Japanese. We investigated whether dietary instruction optimizing the fat energy ratio suppresses the recurrence of colorectal tumors. The subjects, 373 men and women, were the participants in a randomized clinical trial of colorectal cancer prophylaxis. At entry, each participant completed a 3-consecutive-day food record on which dietary instruction was given to restrict fat energy ratio to 18-22%. Data obtained before and after the intervention were examined by cohort analysis. The primary endpoint was the presence or absence of colorectal tumor(s) at colonoscopy after 4 yr. Unexpectedly, the recurrence of tumor increased as the subjects reduced their fat intake. The lowest tumor recurrence among the men was observed in the group with 23.8-26.4% fat energy ratio after the intervention. Furthermore, in men, the risk of tumors decreased significantly as the intake of linoleic acids per body weight increased. For women, similar trends were observed. These results suggest that extreme fat restriction is highly likely to promote the recurrence of colorectal tumors, which may be partly attributable to linoleic acid deficiency.

Randomized trial of dietary fiber and Lactobacillus casei administration for prevention of colorectal tumors.

The epidemiologic evidence that dietary fiber protects against colorectal cancer is equivocal. No large-scale clinical study of the administration of Lactobacillus casei has been reported. We examined whether dietary fiber and L. casei prevented the occurrence of colorectal tumors. Subjects were 398 men and women presently free from tumor who had had at least 2 colorectal tumors removed. Subjects were randomly assigned to 4 groups administered wheat bran, L. casei, both or neither. The primary end point was the presence or absence of new colorectal tumor(s) diagnosed by colonoscopy after 2 and 4 years. Among 380 subjects who completed the study, 95, 96, 96 and 93 were assigned to the wheat bran, L. casei, both and no treatment groups, respectively. Multivariate adjusted ORs for occurrence of tumors were 1.31 (95% CI 0.87-1.98) in the wheat bran group and 0.76 (0.50-1.15) in the L. casei group compared to the control group. There was a significantly higher number of large tumors after 4 years in the wheat bran group. The occurrence rate of tumors with a grade of moderate atypia or higher was significantly lower in the group administered L. casei. No significant difference in the development of new colorectal tumors was observed with administration of either wheat bran or L. casei. However, our results suggest that L. casei prevented atypia of colorectal tumors.

Study of Prevention of Colorectal Cancer through Lifestyle Modification: an Introduction to the Protocol.

Previous epidemiological studies have suggested that lack of exercise and a high fat diet increase the risk of colorectal cancer. We planned a clinical trial to test these propositions, using subjects with multiple colorectal adenomas and/or carcinomas. Enrolment in this study was conducted in two stages. First, patients were invited to participate in the dietary modification part of the study. Those agreeing to participate were given dietary advice, and 3 months later all subjects to whom the exercise exclusion criteria do not apply were invited to participate in the exercise part of the study. The subjects were randomized to two groups. A total of two hundred and eleven patients meeting the entry criteria have been invited to join the trial, of whom 165 (78%) consented to participate in the dietary modification part of the study. After excluding those unsuitable according to the exclusion criteria for the exercise regimen, the remaining 124 subjects were further invited to participate in the exercise regimen part of the study. One hundred and three (83%) subjects have given their consent. Obtaining informed consent in two stages and the free provision of lifestyle modification measures were factors that contributed to this favorable participation rate.