Effect of sulindac on sporadic colonic polyps. A randomized trial of a low fat high fibre diet in the recurrence of colorectal polyps. Toronto Polyp Prevention Group. Sulindac causes regression of rectal polyps in familial adenomatous polyposis. Dietary flavonoids and colorectal adenoma recurrence in the Polyp Prevention Trial. Implementation of a 4-y, high-fiber, high-fruit-and-vegetable, low-fat dietary intervention: results of dietary changes in the Polyp Prevention Trial. Lack of effect of a low-fat, high-fiber diet on the recurrence of colorectal adenomas. Polyp Prevention Trial Study Group. Primary chemoprevention of familial adenomatous polyposis with sulindac. Daily soluble aspirin and prevention of colorectal adenoma recurrence: one-year results of the APACC trial.
We sought to determine in a double-blinded, placebo-controlled study if the nonsteroidal anti-inflammatory drug sulindac causes regression of sporadic colonic polyps. The impetus for this study is the profound regressive effect of sulindac on polyps in familial adenomatous polyposis.
                Asymptomatic patients undergoing routine screening flexible sigmoidoscopy were enrolled if they had polyps of < or = 1 cm in size. Of 162 patients screened, 22 patients were randomly enrolled to take 150 mg of sulindac twice daily, and 22 patients took a placebo. Treatment duration was 4 months and was followed by colonoscopy with removal of all polyps.
                Four patients were dropped from the study (sulindac group) due to urosepsis (1 patient), heartburn (2 patients), and anemia (1 patient). Compliance (determined by monthly pill counting), mean age, and the effect of sulindac vs. placebo on polyp regression or size were not statistically different in the two treatment groups. Analysis of our data indicated that there is only a 0.8% chance that the probability of polyp regression with sulindac is as large as 50%.
                Four months of treatment with sulindac does not result in a clinically significant regression of sporadic colonic polyps, although a small effect may not have been detected by the size of our study. Our data suggest that the biological response of sporadic and familial polyposis polyps to sulindac is different. After polypectomy for adenomatous colorectal polyps, 201 persons were randomized to receive counselling on a diet low in fat (the lesser of 50 g/day or 20% of energy) and high in fibre (50 g/day) (LFHF), or to follow a normal western diet (ND), high in fat and low in fibre. After 12 months of counselling, fat consumption was about 25% of energy in the LFHF group and 33% in the ND group; fibre consumption was 35 g and 16 g respectively. After an average of two years of follow-up, an intention to treat analysis led to a ratio of cumulative incidence rates of 1.2 (95% CL 0.6-2.2) for recurrence of neoplastic polyps, a finding which suggests no significant difference between dietary groups over the period of observation. An exploratory analysis conducted among 142 persons with substantial diet counselling indicated a reduced risk of neoplastic polyp recurrence in women (RR = 0.5), associated with reduced concentrations of faecal bile acids while on the LFHF diet, but indicated an increased risk of recurrence in men (RR = 2.1), associated with increased faecal bile acids. Although a larger study would be needed to rule out the role of chance, these findings of gender-specific associations between diet counselling and both faecal bile acid concentrations and recurrence of colorectal neoplasia are consistent with recently published evidence of differences between genders. In familial adenomatous polyposis, sulindac-induced polyp regression has been reported by several authors. In this study, the goal was to confirm these results by a randomized, placebo-controlled, double-blind crossover study in 10 patients with rectal polyps that had been previously treated by colectomy and ileorectal anastomosis. Patients received sulindac, 300 mg/day, or placebo during two 4-month periods separated by a 1-month wash-out phase. One patient was not compliant and was excluded. With sulindac, the authors observed a complete (6 patients) or almost complete (3 patients) regression of the polyps. With placebo, the authors observed an increase (5 patients), no change (2 patients), and a relative decrease (2 patients) in the number of polyps. The difference between sulindac and placebo was statistically significant (P less than 0.01). In biopsy specimens of polyps and normal rectal mucosa of 6 patients, the authors conducted an immunohistochemical study of the cellular proliferation index using the Ki 67 monoclonal antibody (Ki 67 index), at the beginning and at the end of each treatment period. They were not able to show a sulindac-induced modification of the Ki 67 index. The authors conclude that sulindac is effective in inducing the regression of rectal polyps in familial adenomatous polyposis. Two recent case-control studies suggested that some flavonoid subgroups may play a role in preventing colorectal cancer. Previous prospective cohort studies generally reported no association; however, only a small subset of flavonoids was evaluated and partial flavonoid databases were used. We used the newly constructed U.S. Department of Agriculture flavonoid database to examine the association between consumption of total flavonoids, 6 flavonoid subgroups, and 29 individual flavonoids with adenomatous polyp recurrence in the Polyp Prevention Trial. The Polyp Prevention Trial was a randomized dietary intervention trial, which examined the effectiveness of a low-fat, high-fiber, high-fruit, and high-vegetable diet on adenoma recurrence. Intakes of flavonoids were estimated from a food frequency questionnaire. Multivariate logistic regression models (adjusted for age, body mass index, sex, regular non-steroidal anti-inflammatory use, and dietary fiber intake) were used to estimate odds ratios and 95% confidence intervals for both any and advanced adenoma recurrence within quartiles of energy-adjusted flavonoid intake (baseline, during the trial, and change during the trial). Total flavonoid intake was not associated with any or advanced adenoma recurrence. However, high intake of flavonols, which are at greater concentrations in beans, onions, apples, and tea, was associated with decreased risk of advanced adenoma recurrence (4th versus 1st quartile during the trial; odds ratio, 0.24; 95% confidence interval, 0.11, 0.53; P(trend) = 0.0006). Similar inverse associations were observed to a smaller extent for isoflavonoids, the flavonol kaempferol, and the isoflavonoids genistein and formononetin. Our data suggest that a flavonol-rich diet may decrease the risk of advanced adenoma recurrence. The Polyp Prevention Trial (PPT) was a multicenter randomized clinical trial designed to determine the effects of a high-fiber (4.30 g/MJ), high-fruit-and-vegetable (0.84 servings/MJ), low-fat (20% of energy from fat) diet on the recurrence of adenomatous polyps in the large bowel.
                Our goal was to determine whether the PPT intervention plan could effect change in 3 dietary goals and to examine the intervention's effect on the intake of other food groups and nutrients.
                Participants with large-bowel adenomatous polyps diagnosed in the past 6 mo were randomly assigned to either the intervention (n = 1037) or the control (n = 1042) group and remained in the trial for 4 y. Three dietary assessment instruments were used to measure dietary change: food-frequency questionnaires (in 100% of the sample), 4-d food records (in a 20% random cohort), and 24-h dietary recalls (in a 10% random sample).
                Intervention participants made and sustained significant changes in all PPT goals as measured by the dietary assessment instruments; the control participants' intakes remained essentially the same throughout the trial. The absolute differences between the intervention and control groups over the 4-y period were 9.7% of energy from fat (95% CI: 9.0%, 10.3%), 1.65 g dietary fiber/MJ (95% CI: 1.53, 1.74), and 0.27 servings of fruit and vegetables/MJ (95% CI: 0.25, 0.29). Intervention participants also reported significant changes in the intake of other nutrients and food groups. The intervention group also had significantly higher serum carotenoid concentrations and lower body weights than did the control group.
                Motivated, free-living individuals, given appropriate support, can make and sustain major dietary changes over a 4-y period. We tested the hypothesis that dietary intervention can inhibit the development of recurrent colorectal adenomas, which are precursors of most large-bowel cancers.
                We randomly assigned 2079 men and women who were 35 years of age or older and who had had one or more histologically confirmed colorectal adenomas removed within six months before randomization to one of two groups: an intervention group given intensive counseling and assigned to follow a diet that was low in fat (20 percent of total calories) and high in fiber (18 g of dietary fiber per 1000 kcal) and fruits and vegetables (3.5 servings per 1000 kcal), and a control group given a standard brochure on healthy eating and assigned to follow their usual diet. Subjects entered the study after undergoing complete colonoscopy and removal of adenomatous polyps; they remained in the study for approximately four years, undergoing colonoscopy one and four years after randomization.
                A total of 1905 of the randomized subjects (91.6 percent) completed the study. Of the 958 subjects in the intervention group and the 947 in the control group who completed the study, 39.7 percent and 39.5 percent, respectively, had at least one recurrent adenoma; the unadjusted risk ratio was 1.00 (95 percent confidence interval, 0.90 to 1.12). Among subjects with recurrent adenomas, the mean (+/-SE) number of such lesions was 1.85+/-0.08 in the intervention group and 1.84+/-0.07 in the control group. The rate of recurrence of large adenomas (with a maximal diameter of at least 1 cm) and advanced adenomas (defined as lesions that had a maximal diameter of at least 1 cm or at least 25 percent villous elements or evidence of high-grade dysplasia, including carcinoma) did not differ significantly between the two groups.
                Adopting a diet that is low in fat and high in fiber, fruits, and vegetables does not influence the risk of recurrence of colorectal adenomas. Familial adenomatous polyposis is caused by a germ-line mutation in the adenomatous polyposis coli gene and is characterized by the development of hundreds of colorectal adenomas and, eventually, colorectal cancer. Nonsteroidal antiinflammatory drugs can cause regression of adenomas, but whether they can prevent adenomas is unknown.
                We conducted a randomized, double-blind, placebo-controlled study of 41 young subjects (age range, 8 to 25 years) who were genotypically affected with familial adenomatous polyposis but phenotypically unaffected. The subjects received either 75 or 150 mg of sulindac orally twice a day or identical-appearing placebo tablets for 48 months. The number and size of new adenomas and side effects of therapy were evaluated every four months for four years, and the levels of five major prostaglandins were serially measured in biopsy specimens of normal-appearing colorectal mucosa.
                After four years of treatment, the average rate of compliance exceeded 76 percent in the sulindac group, and mucosal prostaglandin levels were lower in this group than in the placebo group. During the course of the study, adenomas developed in 9 of 21 subjects (43 percent) in the sulindac group and 11 of 20 subjects in the placebo group (55 percent) (P=0.54). There were no significant differences in the mean number (P=0.69) or size (P=0.17) of polyps between the groups. Sulindac did not slow the development of adenomas, according to an evaluation involving linear longitudinal methods.
                Standard doses of sulindac did not prevent the development of adenomas in subjects with familial adenomatous polyposis. Epidemiologic and experimental studies have suggested that aspirin intake reduces the risk for colorectal carcinogenesis. However, the available data are not sufficient to serve as the basis for firm recommendations.
                We randomly assigned 272 patients with a history of colorectal adenomas (at least one more than 5 mm in diameter, or more than 3) to daily lysine acetylsalicylate (160 or 300 mg/day) or placebo for 4 years. The primary end points were adenoma recurrence after 1 and 4 years. These results are those of the year 1 colonoscopy.
                Among the 238 patients who completed the year 1 colonoscopy, at least one adenoma was observed in 38 patients of the 126 (30%) in the aspirin group and in 46 of the 112 (41%) in the placebo group; relative risk was 0.73 (95% confidence interval [CI]: 0.52-1.04; P = 0.08). At least one adenoma of more than 5 mm diameter was observed in 13 patients (10%) in the aspirin group and 26 (23%) in the placebo group (P = 0.01). The corresponding numbers for adenomas more than 10 mm in diameter were one (1%) and 7 (6%) (P = 0.05). Stepwise regression showed that independent factors associated with lower adenoma recurrence are aspirin treatment (adenoma >5 mm, P = 0.01), absence of personal history of adenoma before the entry colonoscopy (P = 0.01), and initial adenomatous polyp burden less than 10 mm (P = 0.001).
                Daily soluble aspirin is associated with a reduction in the risk for recurrent adenomas found at colonoscopy 1 year after starting treatment.
There was evidence from three pooled RCTs that ASA significantly reduces the recurrence of sporadic adenomatous polyps after one to three years. There is evidence from short-term studies to support regression, but not elimination or prevention of CRAs in FAP.