James W. Kikendall

LACK OF EFFECT OF A LOW-FAT, HIGH-FIBER DIET ON THE RECURRENCE OF COLORECTAL ADENOMAS

BACKGROUND We tested the hypothesis that dietary intervention can inhibit the development of recurrent colorectal adenomas, which are precursors of most large-bowel cancers. METHODS 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. RESULTS 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. CONCLUSIONS 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.

Dietary Flavonoids and Colorectal Adenoma Recurrence in the Polyp Prevention Trial

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; Ptrend = 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. (Cancer Epidemiol Biomarkers Prev 2008;17(6):1344–53)

The Polyp Prevention Trial–Continued Follow-up Study: No Effect of a Low-Fat, High-Fiber, High-Fruit, and -Vegetable Diet on Adenoma Recurrence Eight Years after Randomization

The Polyp Prevention Trial (PPT) was a multicenter randomized clinical trial to evaluate the effects of a high-fiber (18 g/1,000 kcal), high-fruit and -vegetable (3.5 servings/1,000 kcal), and low-fat (20% of total energy) diet on the recurrence of adenomatous polyps in the large bowel over a period of 4 years. Although intervention participants reported a significantly reduced intake of dietary fat, and increased fiber, fruit, and vegetable intakes, their risk of recurrent adenomas was not significantly different from that of the controls. Since the PPT intervention lasted only 4 years, it is possible that participants need to be followed for a longer period of time before treatment differences in adenoma recurrence emerge, particularly if diet affects early events in the neoplastic process. The PPT-Continued Follow-up Study (PPT-CFS) was a post-intervention observation of PPT participants for an additional 4 years from the completion of the trial. Of the 1,905 PPT participants, 1,192 consented to participate in the PPT-CFS and confirmed colonoscopy reports were obtained on 801 participants. The mean time between the main trial end point colonoscopy and the first colonoscopy in the PPT-CFS was 3.94 years (intervention group) and 3.87 years (control group). The baseline characteristics of 405 intervention participants and 396 control participants in the PPT-CFS were quite similar. Even though the intervention group participants increased their fat intake and decreased their intakes of fiber, fruits, and vegetables during the PPT-CFS, they did not go back to their prerandomization baseline diet (P < 0.001 from paired t tests) and intake for each of the three dietary goals was still significantly different from that in the controls during the PPT-CFS (P < 0.001 from t tests). As the CFS participants are a subset of the people in the PPT study, the nonparticipants might not be missing completely at random. Therefore, a multiple imputation method was used to adjust for potential selection bias. The relative risk (95% confidence intervals) of recurrent adenoma in the intervention group compared with the control group was 0.98 (0.88-1.09). There were no significant intervention-control group differences in the relative risk for recurrence of an advanced adenoma (1.06; 0.81-1.39) or multiple adenomas (0.92; 0.77-1.10). We also used a multiple imputation method to examine the cumulative recurrence of adenomas through the end of the PPT-CFS: the intervention-control relative risk (95% confidence intervals) for any adenoma recurrence was 1.04 (0.98-1.09). This study failed to show any effect of a low-fat, high-fiber, high-fruit and -vegetable eating pattern on adenoma recurrence even with 8 years of follow-up. (Cancer Epidemiol Biomarkers Prev 2007;16(9):1745–52)

Does Nonsteroidal Anti-inflammatory Drug Use Modify the Effect of a Low-Fat, High-Fiber Diet on Recurrence of Colorectal Adenomas?

The Polyp Prevention Trial was designed to evaluate the effects of a high-fiber (18 g/1,000 kcal), high-fruit and -vegetable (3.5 servings/1,000 kcal), low-fat (20% energy) diet on recurrence of adenomatous polyps. Participants ≥35 years of age, with histologically confirmed colorectal adenoma(s) removed in the prior 6 months, were randomized to the intervention or control group. Demographic, dietary, and clinical information, including use of nonsteroidal anti-inflammatory drugs (NSAID), was collected at baseline and four annual visits. Adenoma recurrence was found in 754 of 1,905 participants and was not significantly different between groups. NSAID use was associated with a significant reduction in recurrence [odds ratio (OR), 0.77; 95% confidence interval (95% CI), 0.63-0.95]. In this analysis, NSAIDs modified the association between the intervention and recurrence at baseline (P = 0.02) and throughout the trial (P = 0.008). Among participants who did not use NSAIDs, the intervention was in the protective direction but did not achieve statistical significance (OR, 0.87; 95% CI, 0.69-1.09). The intervention was protective among males who did not use NSAIDs at baseline (OR, 0.71; 95% CI, 0.54-0.94), but not among NSAIDs users (OR, 1.09; 95% CI, 0.74-1.62). For females, corresponding OR estimates were 1.28 (95% CI, 0.86-1.90) and 2.30 (95% CI, 1.24-4.27), respectively. The protective association observed for NSAID use was stronger among control (OR, 0.63; 95% CI, 0.47-0.84) than for intervention group participants (OR, 0.97; 95% CI, 0.74-1.28). These results should be interpreted cautiously given that they may have arisen by chance in the course of examining multiple associations and Polyp Prevention Trial study participants were not randomly assigned to both dietary intervention and NSAID use. Nevertheless, our results suggest that adopting a low-fat, high-fiber diet rich in fruits and vegetables may lower the risk of colorectal adenoma recurrence among individuals who do not regularly use NSAIDs.

M1036 Real World Clinical Outcomes Observed After Adoption of CTC in a Gastroenterology Practice Setting

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer, and survival in African Americans (AAs) is worse than Caucasians. Some studies suggest that the incidence of CRC is higher in AA patients below the age of 50 when compared to Caucasians. This study aims to confirm the higher prevalence of CRC in an AA population within the age groups of 40-49, and its implications to the screening guidelines. METHOD: In a retrospective study demographic data, indication and outcome of colonoscopy, and biopsy data were collected at Howard University Hospital over a period of 38 years (1970-2007). All of the study patients were (AA), and cases were classified either symptomatic average risk, 692 (91%); or high risk (family history, IBD), 69 (9%). Distribution of variables were studied by mean (standard deviation) or number (%) . RESULTS: A total of 8851 patients who had colonoscopy were analyzed. Female comprise 56%, and the mean (SD) for age was 60.3 (14.9). Out of the total, 965 (11%) were in the age group of 40-49, of which 409 (42%) had adenoma, and 45 (4.8%) had CRC. The location of 86% of the 409 adenomas were obtained. Two-hundred six (59%) adenomas were on the left side, and 144 (41%) were right sided. The histology of the adenomas included, 264 tubular adenomas (64.5%), 83 hyperplastic lesions (0.3%), 44 villous adenomas (10.8%), and 18 other histology (4.4%). When patients from age 40-44 (378) were compared for the prevalence of adenoma and CRC to those age 45-49 (587), the 40-44 age group had 148 (39.2%) adenomas and 18 (4.8%) CRC, vs. the 45-49 age group had 349 (59.4%) adenomas and 28.1(4.8%) CRC. Twenty four (68.5%) cancers were on the left side, and 11(31.5%) were right sided. Females had higher CRC rates 27 (61%), compared to males 18(39%). CONCLUSION: Our data showed a very high burden of colorectal adenoma and CRC in young AAs (<45). CRC rate of (4.8%) was seen for both the age group of 40-44, and 45-49, which indicates cancer in AAs may starts at younger age than predicted (<45). The American College of Gastroenterology recommends to start screening of AAs at age of 45, but this may not cover many high risk people who are younger than 45. Further study is needed on AAs to confirm these findings.

Colonoscopic Screening of Average-Risk Women for Colorectal Neoplasia

ABSTRACT This investigation was performed as a tandem to the Veterans Affairs (VA) Cooperative Study 380, which compared the results of colonoscopy screening with the estimated results of screening with flexible sigmoidoscopy in a mostly male population. The study population for this series consisted of asymptomatic women referred for routine colorectal cancer screening whose colonoscopy was complete to the cecum. Estimates of diagnoses with flexible sigmoidoscopy were made by assuming that advanced lesions in the distal colon (defined as the rectum and the sigmoid colon) would be detected and that small adenomas in the distal colon, which were concurrent with advanced neoplasia in the proximal colon, would have triggered colonoscopy and therefore a correct diagnosis. All asymptomatic women 50 to 79 years of age at average risk for developing colorectal cancer who were screened at one of 4 military centers between July 1999 and December 2002 were eligible for the study. In addition, women with an elevated risk for colorectal cancer (first-degree relative with colon cancer) who were 40 years of age or older were included. Colonoscopy was complete to the cecum in 1463 participants, including 230 (15.7%) who had an elevated risk for colorectal cancer. Neoplastic lesions were identified in 299 women. Seventy-two (4.9%) patients were diagnosed with advanced neoplasia, including 46 women with tubular adenoma 1 cm or more in size, 26 with villous adenoma, 9 who had an adenoma with high-grade dysplasia, and one woman with invasive colorectal cancer. Advanced neoplasia was present in 16 (7.0%) of the 230 high-risk participants. Small or nonadvanced adenomas were seen in 227 women, including 60 high-risk patients. Older women were the most likely to have advanced disease. Nearly 12% (19 of 162) of those 70 to 79 years of age had advanced neoplasia compared with 3.3% (26 of 786) of women in the 50- to 59-year-old group (P = .002). In the 60- to 69-year age group, 5.5% (23 of 420) participants had advanced lesions. Of the 72 women with advanced lesions, 25 (34.7%) had neoplasia in the distal colon, which would have been identified by flexible sigmoidoscopy screening. Forty-seven women positive for advanced neoplasia in the proximal colon had no lesions in the distal colon (65.3%) and would have been missed with sigmoidoscopy. In the entire screening population, 1.7% (25 of 1463) women would have been diagnosed correctly with advanced neoplasias, and 3.2% (47 of 1463) would have been undetected if screening had been performed with flexible sigmoidoscopy. Stratification according to age or family history did not affect the estimated yield of sigmoidoscopy screening. When the distal colon was defined as the rectum and sigmoid colon, a total of 6.3% of participants had neoplastic lesions in the distal colon. Among the 1367 women with no lesions in the distal colon, 47 (3.4%) had advanced disease in the proximal colon and would not have been detected with flexible sigmoidoscopy done to the junction of the sigmoid and descending colon. The incidence of advanced neoplasia in the proximal colon with no lesions in the distal colon was similar for women with and without a family member with colorectal cancer (3.1% and 3.9%, respectively). Among high-risk patients, more advanced lesions were seen in the proximal colon in women with no neoplasia in the distal colon than in women with disease in the distal colon (5.2% vs. 0%, P = .32). When the definition of the distal colon was further expanded to include the descending colon as well as the rectum and sigmoid colon, no neoplasia was found in the distal colon of 1324 (90.6%) women, and small adenomas or advanced neoplasia were seen in 138 (9.4%) patients. Under this definition, 36 (2.7%) women had advanced lesions in the proximal colon but no lesions in the distal colon. Only 3 women (2.2%) had disease in both the proximal and distal colon. The results of this study were compared with the data from the men in the VA Cooperative Study 380. Men under 70 years of age with a negative occult blood test and negative family history who underwent colonoscopy screening were diagnosed with advanced neoplasia nearly twice as often as their female counterparts (15.5% vs. 7.9%). However, in the older age range, 70 to 79 years, the rate of advanced lesions was greater in women than in men (11.8% vs. 10.6%). Overall, the rate of advanced neoplasia was 8.6% in men and 4.5% in women. Screening with flexible sigmoidoscopy would have correctly identified two thirds (126 of 190, 66.3%) of all men with advanced neoplasia. In contrast, sigmoidoscopy screening would not have detected advanced disease in nearly two thirds of all women (64.8%, 10 of 54) who had advanced neoplasia in the proximal colon.

Is colonoscopy needed for the nonadvanced adenoma found on sigmoidoscopy

BACKGROUND & AIMS The need for colonoscopy when small tubular adenomas with low-grade dysplasia are found on sigmoidoscopy is uncertain. The aim of this study was to examine the prevalence and characteristics of proximal adenomas in patients with distal adenomas. METHODS We studied 981 subjects with distal adenomas found on the index colonoscopy before randomization in the Polyp Prevention Trial. RESULTS Four hundred sixty patients (46.9%) had >/=1 distal adenoma that was pathologically advanced (villous component, high-grade dysplasia, or >/=1 cm); 21.5% (211 of 981) had any proximal adenoma; and 4.3% (42 of 981) (95% confidence interval [CI], 3.0-5.5) had an advanced proximal adenoma. A greater percentage of patients with an advanced distal adenoma (5.9%) (95% CI, 3.7-8.0) had an advanced proximal adenoma compared with those with a nonadvanced distal adenoma (2.9%) (95% CI, 1.4-4.3) (OR, 2.1; 95% CI, 1.1-4.3; P = 0.03). Not performing a colonoscopy in patients with a nonadvanced distal adenoma would have missed 36% (15 of 42) of the advanced proximal adenomas. CONCLUSIONS Patients with an advanced distal adenoma are twice as likely to have an advanced proximal adenoma as patients with a nonadvanced distal adenoma. However, eschewing a colonoscopy in patients with a nonadvanced distal adenoma would result in not detecting a sizeable percentage of the prevalent advanced proximal adenomas. These data support performance of a colonoscopy in patients with a nonadvanced distal adenoma. Confirmation of these results in asymptomatic subjects undergoing screening sigmoidoscopy is advisable.