Elaine Lanza

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.

Carotenoid content of fruits and vegetables: An evaluation of analytic data

The test of the association between dietary intake of specific carotenoids and disease incidence requires the availability of accurate and current food composition data for individual carotenoids. To generate a carotenoid database, an artificial intelligence system was developed to evaluate data for carotenoid content of food in five general categories, namely, number of samples, analytic method, sample handling, sampling plan, and analytic quality control. Within these categories, criteria have been created to rate analytic data for beta-carotene, alpha-carotene, lutein, lycopene, and beta-cryptoxanthin in fruits and vegetables. These carotenoids are also found in human blood. Following the evaluation of data, acceptable values for each carotenoid in the foods were combined to generate a database of 120 foods. The database includes the food description; median, minimum, and maximum values for the specific carotenoids in each food; the number of acceptable values and their references; and a confidence code, which is an indicator of the reliability of a specific carotenoid value for a food. The carotenoid database can be used to estimate the intake of specific carotenoids in order to examine the association between dietary carotenoids and disease incidence.

A Pooled Analysis of Advanced Colorectal Neoplasia Diagnoses After Colonoscopic Polypectomy

BACKGROUND & AIMS Limited data exist regarding the actual risk of developing advanced adenomas and cancer after polypectomy or the factors that determine risk. METHODS We pooled individual data from 8 prospective studies comprising 9167 men and women aged 22 to 80 with previously resected colorectal adenomas to quantify their risk of developing subsequent advanced adenoma or cancer as well as identify factors associated with the development of advanced colorectal neoplasms during surveillance. RESULTS During a median follow-up period of 47.2 months, advanced colorectal neoplasia was diagnosed in 1082 (11.8%) of the patients, 58 of whom (0.6%) had invasive cancer. Risk of a metachronous advanced adenoma was higher among patients with 5 or more baseline adenomas (24.1%; standard error, 2.2) and those with an adenoma 20 mm in size or greater (19.3%; standard error, 1.5). Risk factor patterns were similar for advanced adenomas and invasive cancer. In multivariate analyses, older age (P < .0001 for trend) and male sex (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.19-1.65) were associated significantly with an increased risk for metachronous advanced neoplasia, as were the number and size of prior adenomas (P < .0001 for trend), the presence of villous features (OR, 1.28; 95% CI, 1.07-1.52), and proximal location (OR, 1.68; 95% CI, 1.43-1.98). High-grade dysplasia was not associated independently with metachronous advanced neoplasia after adjustment for other adenoma characteristics. CONCLUSIONS Occurrence of advanced colorectal neoplasia is common after polypectomy. Factors that are associated most strongly with risk of advanced neoplasia are patient age and the number and size of prior adenomas.

The development and application of a carotenoid database for fruits, vegetables, and selected multicomponent foods

A carotenoid database for individual and multicomponent foods has been compiled that contains values for the five most common carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, lutein) in 2,458 fruits, vegetables, and multicomponent foods containing fruits and vegetables. The database was used to estimate intakes of specific carotenoids for 19- to 50-year-old women (n = 1,102), using food consumption data obtained from dietary recalls in the US Department of Agriculture Continuing Survey of Food Intake by Individuals, 1986. The major contributors of alpha-carotene were carrots consumed as a single food or as an ingredient in multicomponent foods. Carrots, cantaloupe, and broccoli were the main sources of beta-carotene. Orange juices and blends, oranges, and tangerines were important contributors of beta-cryptoxanthin. Tomatoes and tomato products consumed as single foods or as ingredients in multicomponent foods provided most of the dietary lycopene. Contributors of lutein + zeaxanthin included collard, mustard, or turnip greens; spinach; and broccoli. The per capita consumption of total carotenoids (the sum of the five specific carotenoids) among these women was approximately 6 mg/day.

Ongoing Colorectal Cancer Risk Despite Surveillance Colonoscopy: The Polyp Prevention Trial Continued Follow-up Study

BACKGROUND Despite regular colonoscopy, interval colorectal cancer (CRC) may occur. Long-term studies examining CRC rates in patients with previous colonoscopy are lacking. OBJECTIVE We examined the rate of interval CRC in the Polyp Prevention Trial Continued Follow-up Study (PPT-CFS), an observational study of PPT participants that began after the PPT ended. DESIGN Prospective. SETTING A national U.S. community-based polyp prevention trial. MAIN OUTCOME MEASUREMENTS Medical records of patients with CRC were collected, reviewed, and abstracted in a standardized fashion. RESULTS Among 2079 PPT participants, 1297 (62.4%) agreed to participate in the PPT-CFS. They were followed for a median of 6.2 years after 4.3 years of median follow-up in the main PPT. Nine cases of CRC were diagnosed over 7626 person-years of observation (PYO), for an incidence rate of 1.2/1000 PYO. The ratio of CRCs observed compared with that expected by Surveillance, Epidemiology, and End Results was 0.64 (95% CI, 0.28-1.06). Including all CRCs (N = 22) since the beginning of the PPT, the observed compared with expected rate by Surveillance, Epidemiology, and End Results was 0.74 (95% CI, 0.47-1.05). Of patients in whom CRC developed in the PPT-CFS, 78% had a history of an advanced adenoma compared with only 43% of patients who remained cancer free (P = .04). LIMITATION A relatively small number of interval cancers were detected. CONCLUSIONS Despite frequent colonoscopy during the PPT, in the years after the trial, there was a persistent ongoing risk of cancer. Subjects with a history of advanced adenoma are at increased risk of subsequent cancer and should be followed closely with continued surveillance.

Utilization and Yield of Surveillance Colonoscopy in the Continued Follow-Up Study of the Polyp Prevention Trial

BACKGROUND AND AIMS Prospective information on the use and yield of surveillance colonoscopy is limited. We examined the use and yield of surveillance colonoscopy among participants in the Polyp Prevention Trial (PPT) after the 4-year dietary intervention trial ended. METHODS We followed a cohort of 1297 participants. We calculated the cumulative probability of posttrial colonoscopy and investigated the yield and predictive factors for adenoma and advanced adenoma recurrence over a mean time of 5.9 years. RESULTS Seven-hundred seventy-four subjects (59.7%) had a repeat colonoscopy. Among 431 subjects with low-risk adenomas (1-2 nonadvanced adenomas) at baseline and no adenoma recurrence at the end of the PPT (lowest-risk category), 30.3% underwent a repeat colonoscopy within 4 years. Among 55 subjects who had high-risk adenomas (advanced adenoma and/or > or =3 nonadvanced adenomas) at baseline and again at the final PPT colonoscopy (highest-risk category), 41.3% had a colonoscopy within 3 years and 63.5% had an examination within 5 years. The cumulative yield of advanced adenoma through 6 years was 3.6% for the lowest-risk category, 38.9% for the highest-risk category, and ranged from 6.6% to 13.8% for intermediate-risk categories. An advanced adenoma at the final PPT colonoscopy was associated significantly with an advanced adenoma recurrence during surveillance (hazard ratio, 6.2; 95% confidence interval, 2.5-15.4). CONCLUSIONS Surveillance colonoscopy was overused for low-risk subjects and underused for high-risk subjects. Advanced adenoma yield corresponded with the adenoma risk category. Resource consumption can be better managed by aligning use with the risk of adenoma recurrence.

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)

Non-steroidal anti-inflammatory drug use is associated with reduction in recurrence of advanced and non-advanced colorectal adenomas (United States).

Objective: To prospectively examine the association between non-steroidal anti-inflammatory drugs (NSAIDs) use (including dose and dosage schedule) and the recurrence of colorectal adenomas among individuals who were diagnosed with an adenoma at entry into a clinical trial. Methods: For this analysis, participants who completed the full follow-up (n = 1905) for the Polyp Prevention Trial (PPT) were evaluated. Information on current use and dose of NSAIDs and other drugs was obtained at baseline and at each subsequent study visit over the duration of the trial. The study endpoint was the recurrence of colorectal adenomas in the 3 years between the 1-year trial colonoscopy (T1) and the end of the trial colonoscopy (T4). Results: There was a significant reduction in overall adenoma recurrence among NSAIDs users (odds ratio [OR] = 0.77; 95% confidence interval [CI]: 0.63–0.95), with the greatest effect seen in advanced polyps (OR = 0.51; CI: 0.33–0.79). Among aspirin users, we observed a significant dose response for overall adenoma recurrence, with a 40% reduction in the OR association (OR = 0.56; 95% CI: 0.31–0.99) among those taking more than 325 mg per day. Conclusion: This prospective study provides further evidence that NSAIDs may play an important role in the chemoprevention of recurrent colorectal adenomas, even those with advanced features.

Lack of Effect of a Low-Fat, High-Fruit, -Vegetable, and -Fiber Diet on Serum Prostate-Specific Antigen of Men Without Prostate Cancer: Results From a Randomized Trial

PURPOSE To determine whether a diet low in fat and high in fruits, vegetables, and fiber may be protective against prostate cancer by having an impact on serial levels of serum prostate-specific antigen (PSA). METHODS Six hundred eighty-nine men were randomized to the intervention arm and 661 to the control arm. The intervention group received intensive counseling to consume a diet low in fat and high in fiber, fruits, and vegetables. The control group received a standard brochure on a healthy diet. PSA in serum was measured at baseline and annually thereafter for 4 years, and newly diagnosed prostate cancers were recorded. RESULTS The individual PSA slope for each participant was calculated, and the distributions of slopes were compared between the two groups. There was no significant difference in distributions of the slopes (P =.99). The two groups were identical in the proportions of participants with elevated PSA at each time point. There was no difference in the PSA slopes between the two groups (P =.34) and in the frequencies of elevated PSA values for those with elevated PSA at baseline. Incidence of prostate cancer during the 4 years was similar in the two groups (19 and 22 in the control and intervention arms, respectively). CONCLUSION Dietary intervention over a 4-year period with reduced fat and increased consumption of fruits, vegetables, and fiber has no impact on serum PSA levels in men. The study also offers no evidence that this dietary intervention over a 4-year period affects the incidence of prostate cancer during the 4 years.