Recurrence Of Adenomatous Polyps Research Articles

Recurrences of advanced sessile and lateral spreading colorectal adenoma after endoscopic mucosal resection (EMR) thermal ablation versus no adjuvant therapy (RESPECT): a protocol of an international randomized controlled trial

BackgroundNowadays, large benign lateral spreading lesions (LSLs) and sessile polyps in the colorectum are mostly resected by endoscopic mucosal resection (EMR). A major drawback of EMR is the polyp recurrence rate of up to 20%. Snare tip soft coagulation (STSC) is considered an effective technique to reduce recurrence rates. However, clinical trials on STSC have mainly been conducted in expert referral centers. In these studies, polyp recurrence was assessed optically, and additional adjunctive techniques were excluded. In the current trial, we will evaluate the efficacy and safety of STSC in daily practice, by allowing adjunctive techniques during EMR and the use of both optical and histological polyp recurrence to assess recurrences during follow-up.MethodsThe RESPECT study is a multicenter, parallel-group, international single blinded randomized controlled superiority trial performed in the Netherlands and Germany. A total of 306 patients undergoing piecemeal EMR for LSLs or sessile colorectal polyps sized 20–60 mm will be randomized during the procedure after endoscopic complete polyp resection to the intervention or control group. Post-EMR defects allocated to the intervention group will be treated with thermal ablation with STSC of the entire resection margin. Primary outcome will be polyp recurrence by optical and histological confirmation at the first surveillance colonoscopy after 6 months. Secondary outcomes include technical success and complication rates.DiscussionThe RESPECT study will evaluate if STSC is effective in reducing recurrence rates after piecemeal EMR of large colorectal lesions in daily clinical practice performed by expert and non-expert endoscopists. Moreover, endoscopists will be allowed to use adjunctive techniques to remove remaining adenomatous tissue during the procedure. Finally, adenomatous polyp recurrence during follow-up will be defined by histologic identification.Trial registrationClinicalTrials.gov NCT05121805. Registered on 16 November 2021. Start recruitment: 17 March 2022. Planned completion of recruitment: 31 April 2025.

Expanding endoscopic boundaries: Endoscopic resection of large appendiceal orifice polyps with endoscopic mucosal resection and endoscopic submucosal dissection

Large appendiceal orifice polyps are traditionally treated surgically. Recently, endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) have been utilized as alternative resection techniques. To evaluate the efficacy and safety of endoscopic resection techniques for the management of large appendiceal orifice polyps. This was a retrospective observational study conducted to assess the feasibility and safety of EMR and ESD for large appendiceal orifice polyps. This project was approved by the Baylor College of Medicine Institutional Review Board. Patients who underwent endoscopic resection of appendiceal orifice polyps ≥ 1 cm from 2015 to 2022 at a tertiary referral endoscopy center in the United States were enrolled. The main outcomes of this study included en bloc resection, R0 resection, post resection adverse events, and polyp recurrence. A total of 19 patients were identified. Most patients were female (53%) and Caucasian (95%). The mean age was 63.3 ± 10.8 years, and the average body mass index was 28.8 ± 6.4. The mean polyp size was 25.5 ± 14.2 mm. 74% of polyps were localized to the appendix (at or inside the appendiceal orifice) and the remaining extended into the cecum. 68% of polyps occupied ≥ 50% of the appendiceal orifice circumference. The mean procedure duration was 61.6 ± 37.9 minutes. Polyps were resected via endoscopic mucosal resection, endoscopic submucosal dissection, and hybrid procedures in 5, 6, and 8 patients, respectively. Final pathology was remarkable for tubular adenoma (n = 10) [one with high grade dysplasia], sessile serrated adenoma (n = 7), and tubulovillous adenoma (n = 2) [two with high grade dysplasia]. En bloc resection was achieved in 84% with an 88% R0 resection rate. Despite the large polyp sizes and challenging procedures, 89% (n = 17) of patients were discharged on the same day as their procedure. Two patients were admitted for post-procedure observation for conservative pain management. Eight patients underwent repeat colonoscopy without evidence of residual or recurrent adenomatous polyps. Our study highlights how endoscopic mucosal resection, endoscopic submucosal dissection, and hybrid procedures are all appropriate techniques with minimal adverse effects, further validating the utility of endoscopic procedures in the management of large appendiceal polyps.

World Gastroenterology Organisation Global Guidelines: Diet and the Gut.

World Gastroenterology Organisation Global Guidelines: Diet and the Gut.

Abstract CT236: Randomized, double-blind, placebo-controlled trial of preventative MUC1 vaccine in patients with newly diagnosed advanced adenomas: Results from one-year booster

Abstract Background: Immunoprevention via targeting antigens aberrantly expressed on colorectal cancers and adenomatous polyps offers the potential for a less invasive prevention strategy than endoscopic surveillance. Specificity of the immune response and long-term memory provide the potential for prolonged protection. Leveraging the infrastructure of the NCI-funded Cancer Prevention Network (CPN) consortium, we are conducting a double-blind randomized trial in individuals with a diagnosis of advanced colorectal adenomas within the previous year. We are evaluating MUC1 vaccine with the TLR-3 agonist polyICLC as an adjuvant, for its immunogenicity, ability to elicit immune memory and prevent recurrence of colorectal adenomas. Aims: We previously reported on the vaccine immunogenicity at week 12 (vaccine administered at 0, 2, and 10 weeks) compared to placebo. Here we report the ability of the vaccine to elicit long-term memory by measuring increase in anti-MUC1 antibody levels following a booster administered at one year. Methods: Subjects with endoscopically resected advanced adenoma (defined as ≥1cm, tubululovillous or villous histology, or with high grade dysplasia) were randomized. The primary endpoint was the response to the vaccine at week 12 assessed by monitoring anti-MUC1 IgG antibody titer ratio defined as t12/t0, where t0 was the titer pre-vaccination, and t12 was the titer at week 12. The key secondary endpoint was to assess anti-MUC1 IgG response at week 55 to a booster at week 52 in the vaccine arm compared to placebo. Results: 102 eligible subjects were randomized at 6 centers, 52 received MUC1 vaccine and 50 placebo. The mean age was 59.4±7.0 (range 40-70), 60.8% male, 88.2% white, and 18.6% Hispanic or Latino ethnicity. At 12 weeks the IgG ratio was ≥2.0 in 13/52 (25%) of individuals receiving vaccine (ratio range -0.5-17.3), vs. 0/50 in placebo group (2-sided p=.0001), and was ≥1.5 in 19/52 (36.5%) individuals receiving vaccine compared to 1/50 (2%) in placebo group (P<.0001). To evaluate immune memory, 1-year booster data available for 95 patients (51-MUC1, 44-placebo) were analyzed. 10/13 (76.9%) of the week 12 vs. week 0 vaccine responders showed a response at week 52 vs. baseline and 11/13 (84.6%) at week 55 vs. week 52. Using an IgG ratio of 2 (per-protocol), the response rate was 33% for MUC1 vs. 5% for placebo (1-sided p=0.0003). Using a ratio of 1.5 yielded similar results (37% MUC1 vs. 9% Placebo (1-sided p=0.0008). The MUC1 arm had significantly higher IgG at week 52 (1-sided p=0.0294), week 55 (1-sided p=0.0048), and significantly higher week 55 to week 52 IgG ratio values (1-sided p=0.0293). Conclusions: Subjects with a recent history of advanced adenoma receiving a MUC1 vaccine compared with a placebo were significantly more likely to develop an immune response at week 12, confirming the vaccine’s immunogenicity, and to respond again at week 55 to a booster injection on week 52, confirming the vaccine’s ability to elicit immune memory. Follow-up colonoscopy to evaluate the vaccine’s potential to lower adenomatous polyp recurrence rates are in progress. Citation Format: Olivera J. Finn, Lisa Boardman, Marcia Cruz-Correa, Ajay Bansal, David Kastenberg, Chin Hurr, Sharon Kaufman, Colleen Akerley, Lynda Dzubinski, April Felt, Karrie Fursa, L.M. Rodriguez, Ellen Richmond, Asad Umar, Eva Szabo, John McKolanis, Ryan McMurray, Nathan Foster, Andres Salazar, Paul Limburg, Robert Schoen. Randomized, double-blind, placebo-controlled trial of preventative MUC1 vaccine in patients with newly diagnosed advanced adenomas: Results from one-year booster [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT236.

Abstract LB-305: Randomized, double-blind, placebo-controlled immunoprevention trial with MUC1 vaccine in patients with newly diagnosed advanced adenomas

Abstract Background: Immunotherapy targeting tumor-associated antigens aberrantly expressed on colorectal cancers and adenomatous polyps offers the potential for a relatively non-invasive and non-toxic prevention strategy, and because of the specificity of the immune response and its long-term memory, the potential for prolonged protection. In a double-blind randomized trial in patients with a diagnosis of advanced colorectal adenomas within the previous year, we are evaluating MUC1 vaccine with the TLR-3 agonist polyICLC (Hiltonol®) as an adjuvant, for its immunogenicity and effect on colorectal adenoma recurrence at follow up colonoscopy. Aim: We report on a primary endpoint, MUC1 immunogenicity at week 12 (following vaccine or placebo administration at 0, 2, and 10 weeks), and on determinants of the immune response and vaccine toxicity. Methods: Subjects with an advanced adenoma (defined as ≥1cm, tubulovillous or villous histology, or with HGD) were randomized. Response to the vaccine was assessed by monitoring IgG anti-MUC1 antibody titer ratio; defined as t12/t0, where t0 is the initial titer measured prior to vaccination, and t12 is the titer drawn at 12 weeks. A ratio of 2.0 was used as the primary definition of a significant immune response. T Regulatory and myleoid derived suppressor cell (MDSC) levels at baseline were assessed in relation to vaccine response. Adverse events (AEs) were recorded according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Results: 102 subjects were randomized at 6 centers, 52 received MUC1 vaccine and 50 placebo. Subjects had a mean age of 59.4±7.0 (range 40-70) years, 60.8% were male, 88.2% were white, and 18.6% Hispanic or Latino. At 12 weeks the IgG ratio was ≥2.0 in 13/52 (25%) of patients receiving vaccine (ratio range 2.9-17.3), vs. 0/50 in placebo group (P=.0001), and was ≥1.5 in 19/52 (36.5%) of patients receiving vaccine compared to 1/50 (2%) in placebo group (P<.0001). In the vaccinated group, the IgG ratio was ≥2.0 in 45% of women (9/20) vs. 12.5% of men (4/32) (P=0.009) and ≥1.5 in 55% of women (11/20) vs. 25% of men (8/32) (P=0.03). In the vaccinated group, reduced levels of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) pre-vaccination were associated with response, 0.2±0.1 among responders (n=13) vs. 0.8±1.1 among non-responders (N=39) (p=0.0006) whereas monocytic MDSC and T regulatory cells (CD4+CD25, Foxp3) were not. There were no grade 3 adverse events (AE) possibly or probably related to the vaccine. The most common AE was an injection site reaction (grade 1 or 2) which occurred in 80.8% (n=42/52) in vaccine group vs. 6.0% in the placebo group (3/50). Conclusions: Subjects with an advanced adenoma receiving MUC1 vaccine compared with a placebo are significantly more likely to develop an anti-IgG MUC1 immune response at 12 weeks. Women and subjects with lower circulating PMN-MDSC levels at baseline were more likely to respond. The vaccine was well tolerated. Follow up for the effect of the vaccine on adenomatous polyp recurrence is ongoing. Citation Format: Robert E. Schoen, Lisa A. Boardman, Marcia Cruz-Correa, Ajay Bansal, Pamela L. Beatty, David Kastenberg, Chin Hur, Lynda Dzubinski, Luz Rodriguez, Andres Salazar, John McKolanis, Drew Seisler, Nathan R. Foster, May-Yin Polley, Paul J. Limburg, Olivera J. Finn. Randomized, double-blind, placebo-controlled immunoprevention trial with MUC1 vaccine in patients with newly diagnosed advanced adenomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-305.

Abstract IA10: Precision chemoprevention with aspirin

Abstract Remarkably consistent experimental and epidemiologic evidence demonstrates that aspirin is associated with a lower risk of colorectal cancer. Five placebo-controlled randomized controlled trials (RCTs) among individuals with a history of colorectal neoplasia showed that aspirin reduced the risk of recurrent adenomatous polyps, the precursors of the vast majority of cancers. Additionally, data from long-term follow-up of a RCT of aspirin among individuals with the Lynch hereditary colorectal cancer syndrome and a RCT of aspirin among women for primary prevention of cardiovascular disease and cancer demonstrated a lower risk of colorectal cancer associated with randomized aspirin treatment. As a reflection of the strength of the evidence, the U.S. Preventative Services Task Force (USPSTF) updated its primary prevention guidelines for aspirin in 2016. The USPSTF provided low-dose aspirin (81 mg/day) with a recommendation for chronic disease prophylaxis, including colorectal cancer prevention, among U.S. adults between ages 50-59, and possibly ages 60-69, with a greater than 10% ten-year risk of cardiovascular events. The new USPSTF recommendation represents a significant milestone for the field of preventive medicine. With the exception of tamoxifen for women at high-risk for breast cancer, this is the first medication recommended for cancer prevention by USPSTF guidelines. Despite this advance, broader recommendations for aspirin chemoprevention are limited by concerns about risk-benefit profile in view of the established association of aspirin with gastrointestinal bleeding. Thus, in concert with broader efforts to tailor prevention strategies, our group has led several studies into the mechanistic basis of aspirin's anti-cancer effect that has led to the development of intratumoral, germline, and circulating molecular correlates of outcomes. Such biomarkers can be exploited for risk stratification to more effectively target aspirin chemoprevention for those with more favorable risk-benefit profiles. In this presentation, we will review the evidence supporting a role for aspirin in the prevention and treatment of cancer, with a focus on novel strategies for molecular risk stratification. Citation Format: Andrew T. Chan. Precision chemoprevention with aspirin. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr IA10.

Dietary fibre for the prevention of recurrent colorectal adenomas and carcinomas.

This is an update of the Cochrane review published in 2002.Colorectal cancer (CRC) is a major cause of morbidity and mortality in industrialised countries. Experimental evidence has supported the hypothesis that dietary fibre may protect against the development of CRC, although epidemiologic data have been inconclusive. To assess the effect of dietary fibre on the recurrence of colorectal adenomatous polyps in people with a known history of adenomatous polyps and on the incidence of CRC compared to placebo. Further, to identify the reported incidence of adverse effects, such as abdominal pain or diarrhoea, that resulted from the fibre intervention. We identified randomised controlled trials (RCTs) from Cochrane Colorectal Cancer's Specialised Register, CENTRAL, MEDLINE and Embase (search date, 4 April 2016). We also searched ClinicalTrials.gov and WHO International Trials Registry Platform on October 2016. We included RCTs or quasi-RCTs. The population were those having a history of adenomatous polyps, but no previous history of CRC, and repeated visualisation of the colon/rectum after at least two-years' follow-up. Dietary fibre was the intervention. The primary outcomes were the number of participants with: 1. at least one adenoma, 2. more than one adenoma, 3. at least one adenoma greater than or equal to 1 cm, or 4. a new diagnosis of CRC. The secondary outcome was the number of adverse events. Two reviewers independently extracted data, assessed trial quality and resolved discrepancies by consensus. We used risk ratios (RR) and risk difference (RD) with 95% confidence intervals (CI) to measure the effect. If statistical significance was reached, we reported the number needed to treat for an additional beneficial outcome (NNTB) or harmful outcome (NNTH). We combined the study data using the fixed-effect model if it was clinically, methodologically, and statistically reasonable. We included seven studies, of which five studies with 4798 participants provided data for analyses in this review. The mean ages of the participants ranged from 56 to 66 years. All participants had a history of adenomas, which had been removed to achieve a polyp-free colon at baseline. The interventions were wheat bran fibre, ispaghula husk, or a comprehensive dietary intervention with high fibre whole food sources alone or in combination. The comparators were low-fibre (2 to 3 g per day), placebo, or a regular diet. The combined data showed no statistically significant difference between the intervention and control groups for the number of participants with at least one adenoma (5 RCTs, n = 3641, RR 1.04, 95% CI 0.95 to 1.13, low-quality evidence), more than one adenoma (2 RCTs, n = 2542, RR 1.06, 95% CI 0.94 to 1.20, low-quality evidence), or at least one adenoma 1 cm or greater (4 RCTs, n = 3224, RR 0.99, 95% CI 0.82 to 1.20, low-quality evidence) at three to four years. The results on the number of participants diagnosed with colorectal cancer favoured the control group over the dietary fibre group (2 RCTS, n = 2794, RR 2.70, 95% CI 1.07 to 6.85, low-quality evidence). After 8 years of comprehensive dietary intervention, no statistically significant difference was found in the number of participants with at least one recurrent adenoma (1 RCT, n = 1905, RR 0.97, 95% CI 0.78 to 1.20), or with more than one adenoma (1 RCT, n = 1905, RR 0.89, 95% CI 0.64 to 1.24). More participants given ispaghula husk group had at least one recurrent adenoma than the control group (1 RCT, n = 376, RR 1.45, 95% CI 1.01 to 2.08). Other analyses by types of fibre intervention were not statistically significant. The overall dropout rate was over 16% in these trials with no reasons given for these losses. Sensitivity analysis incorporating these missing data shows that none of the results can be considered as robust; when the large numbers of participants lost to follow-up were assumed to have had an event or not, the results changed sufficiently to alter the conclusions that we would draw. Therefore, the reliability of the findings may have been compromised by these missing data (attrition bias) and should be interpreted with caution. There is a lack of evidence from existing RCTs to suggest that increased dietary fibre intake will reduce the recurrence of adenomatous polyps in those with a history of adenomatous polyps within a two to eight year period. However, these results may be unreliable and should be interpreted cautiously, not only because of the high rate of loss to follow-up, but also because adenomatous polyp is a surrogate outcome for the unobserved true endpoint CRC. Longer-term trials with higher dietary fibre levels are needed to enable confident conclusion.

Retrospective Analysis of Site and Pathological Characteristics of Recurrence in Patients with Adenomatous Colonic Polyps

Aim: The benefits of colonoscopy surveillance in reducing the incidence and mortality of colorectal cancer are known. However, benefit may be driven by early detection of left side colon lesions to a greater extent than right side counterparts. The correlation between initial (“index”) adenoma(s) location, recurrent polyp(s) and their respective pathologic grade is not well understood. The Original Research Article Chahla et al.; BJMMR, 9(4): 1-7, 2015; Article no.BJMMR.17521 2 purpose of this study was to determine if index colonic adenoma polypectomy location (right vs. left) correlated with recurrent adenoma location and polyp pathology. Methodology: Retrospective review of patient medical records including all cases of completely resected adenomatous polyp(s) without evidence of dysplasia at initial colonoscopy with repeat follow-up study between November 1998 and August 2009 was performed at a tertiary level academic hospital. The splenic flexure was used to discriminate right vs. left side colon polyps. Results: Records of 112 patients (53.6% males) with index adenomatous colonic polyps who had follow-up complete colonoscopy with polypectomy were reviewed. Mean (SD) time of follow-up colonoscopy was 43.3 (22.6) months. The mean age at presentation was 59.5 years. Initial polyp site was found on the right in 46 patients (41.1%), left in 38 (33.9%), and both right and left in 28 patients (25.0%). Patients with right side index adenomas were significantly older compared to those with left side lesions, with a mean (SD) age of 61.2 (9.9) vs. 55.6 (7.3) years respectively (p=0.008). Polyp pathology on follow-up colonoscopy revealed 16 (14.3%) hyperplastic, 84 (75.0%) adenomatous, 6 (5.4%) tubulovillous, 5 (4.5%) high grade dysplasia (HGD), and 1 (0.9%) cancer case. 28 of 39 right side index adenomas (71.8%), and 24 of 33 left side index adenomas (72.7%) had same side adenomatous or higher grade pathologic recurrence. Ipsilateral recurrence proved to be statistically significant (p<0.001). In addition, right side index adenomatous polyps had higher rates of adenomatous polyp recurrence (44/46, 95.7%) compared to left side index ones (26/38, 68.4%), independent of recurrence site (p<0.001). Conclusion: Initial adenomatous polyp side may predict recurrent adenomatous location and polyp pathologic grade. Follow-up endoscopic surveillance methods and intervals should consider side of previous adenomatous polyp location.

Feasibility of Increased Navy Bean Powder Consumption for Primary and Secondary Colorectal Cancer Prevention.

Introduction:Emerging evidence supports that increased consumption of dry beans (Phaseolus vulgaris L.) reduces both the incidence and recurrence of adenomatous polyps or precancerous growths. Navy beans have been studied for dietary colorectal cancer (CRC) chemoprevention in animal models. Our main objectives were to assess the feasibility of increased navy bean consumption in adults with and without history of CRC and to achieve intake amounts associated with chemoprevention. Methods:Seven meals and six snacks were developed for both the absence and inclusion of cooked navy bean powder (35grams/day). Sixteen healthy adults (7 non-cancer and 9 CRC survivors) completed the placebo-controlled, randomized, single-blinded dietary intervention trial. Participants consumed one study-provided meal and snack daily for 28 days, which accounted for approximately one-third of their total recommended caloric intake (meals = 202-483 kcal and snacks = 194-401 kcal). Participants also recorded three-day dietary food logs each week.Results:The addition of 35g of cooked navy bean powder (NBP) into foods provided 5-8% daily caloric intake. The compliance to the meal and snack intervention ranged from 89-100%. Non-cancer participants in the NBP group had a significant decrease in total caloric intake after week 4 (p≤0.0001). CRC survivors in the NBP group significantly increased total fiber intake by week 4 (p≤0.0001). Conclusions:NBP are feasible to include in meals for increased total fiber intake and for consuming the amount that is associated with CRC chemoprevention outcomes. These findings warrant further evaluation of NBP consumption in clinical nutrition trials for CRC control and prevention.

Tu1499 Recurrence of Adenomatous Polyps After Incomplete Resection: Follow-up of the Complete Adenoma Resection (CARE) Study

Tu1499 Recurrence of Adenomatous Polyps After Incomplete Resection: Follow-up of the Complete Adenoma Resection (CARE) Study

The role of aspirin in cancer prevention

Clinical guidelines for prophylactic aspirin use currently only consider the cardiovascular benefits of aspirin, weighed against the potential harm from aspirin-induced bleeding. Daily aspirin use has been convincingly shown to reduce the risk of colorectal cancer and recurrence of adenomatous polyps, but in average-risk populations, these benefits alone do not outweigh harms from aspirin-induced bleeding. Recently published secondary analyses of cardiovascular trials provide the first randomized evidence that daily aspirin use may also reduce the incidence of all cancers combined, even at low doses (75-100 mg daily). This Review considers the general mechanism of action that defines aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) as a class, the specific advantages of aspirin over other NSAIDs for prophylactic use, the current evidence concerning the main health outcomes affected by aspirin use, and the hypothesis that inhibition of platelet activation may mediate both the cardioprotective and cancer-preventive effects of low-dose aspirin. It also considers how even a 10% reduction in overall cancer incidence beginning during the first 10 years of treatment could tip the balance of benefits and risks favourably in average-risk populations.

Metabolic syndrome is associated with increased risk of recurrent colorectal adenomas in Korean men

Because of the high incidence of recurrent colorectal adenomas, regular surveillance by colonoscopy is recommended. However, there is still a shortage of information on the factors that influence the incidence of recurrent colorectal adenomas in patients with a history of these lesions. The aim of this study was to determine the association between the development of recurrent colorectal adenomas, metabolic syndrome and obesity. The hospital-based cohort was composed of 193 patients who had recurrent colorectal adenomas removed between January 2002 and December 2003. The Cox proportional hazard model was used to determine hazard ratio (HR) and 95% confidence interval (CI) between obesity, metabolic syndrome and other factors, and the incidence of recurrent adenomatous polyps. The mean follow-up period was 4.8 person-years. In all, 78 of the patients (40.4%) had recurrent colorectal adenomas. In the overall recurrent adenoma group, significant associations between metabolic syndrome (HR, 1.33; 95% CI, 1.02-1.73), waist circumference (WC) ≥ 90 cm (HR, 1.42; 95% CI, 1.06-1.90) and waist-hip ratio (WHR) ≥ 0.9 (HR, 2.03; 95% CI, 1.55-2.68) were found. Moreover, advanced adenomas were significantly associated with metabolic syndrome (HR, 2.81; 95% CI, 1.86-4.25), body mass index ≥ 25 kg m(-2) (HR, 2.69; 95% CI, 1.64-4.42), WC (HR, 2.16; 95% CI, 1.31-3.54) and WHR (HR, 1.99; 95% CI, 1.28-3.11). In addition, current smoking (HR, 2.60; 95% CI, 1.09-6.25) and alcohol consumption (HR, 2.20; 95% CI, 1.10-4.39) were also significantly associated with recurrent advanced adenoma. Metabolic syndrome and obesity were significantly associated with the development of recurrent colorectal adenomas in Korean adult males. Furthermore, these associations were more strongly associated with advanced adenomas.

Statin use does not prevent recurrent adenomatous polyp formation in a VA population

To evaluate whether statin use was associated with recurrent adenomatous polyps. We conducted a retrospective cohort study. We used electronic health records to evaluate veterans who underwent polypectomy between January 1, 1999 and December 31, 2001 and surveillance colonoscopy by December 2006. We obtained data on pathology, demographics, body mass index, comorbidity, habits, family history, and medications. We used multivariate proportional hazards regression models to analyze data. We evaluated 197 eligible patients from among 821 who underwent colonoscopy during this period; their mean (SD) age was 63.1 (8.8) years, 192 (98%) were men, and 80 (41%) non-Hispanic white. Surveillance colonoscopy was performed after a mean (SD) 1207 (452) days and 108 (55%) patients had recurrent adenomas. During follow-up, 88 (47%) of patients received statins, but use was not protective against recurrent adenomas (hazard ratio = 1.36, 95% CI 0.35-8.27). Only number of polyps at initial colonoscopy predicted recurrent adenomas (1.98, 95% CI 1.27-3.08). The use of statins was not protective against the recurrence of adenomatous polyps.

Vitamin Supplements and Cancer Prevention: Where Do Randomized Controlled Trials Stand?

Vitamin Supplements and Cancer Prevention: Where Do Randomized Controlled Trials Stand?

Longitudinal Assessment of Air Conduction Audiograms in a Phase III Clinical Trial of Difluoromethylornithine and Sulindac for Prevention of Sporadic Colorectal Adenomas

A phase III clinical trial assessed the recurrence of adenomatous polyps after treatment for 36 months with difluoromethylornithine (DFMO) plus sulindac or matched placebos. Temporary hearing loss is a known toxicity of treatment with DFMO, thus a comprehensive approach was developed to analyze serial air conduction audiograms. The generalized estimating equation method estimated the mean difference between treatment arms with regard to change in air conduction pure tone thresholds while accounting for within-subject correlation due to repeated measurements at frequencies. Based on 290 subjects, there was an average difference of 0.50 dB between subjects treated with DFMO plus sulindac compared with those treated with placebo (95% confidence interval, -0.64 to 1.63 dB; P = 0.39), adjusted for baseline values, age, and frequencies. In the normal speech range of 500 to 3,000 Hz, an estimated difference of 0.99 dB (-0.17 to 2.14 dB; P = 0.09) was detected. Dose intensity did not add information to models. There were 14 of 151 (9.3%) in the DFMO plus sulindac group and 4 of 139 (2.9%) in the placebo group who experienced at least 15 dB hearing reduction from baseline in 2 or more consecutive frequencies across the entire range tested (P = 0.02). Follow-up air conduction done at least 6 months after end of treatment showed an adjusted mean difference in hearing thresholds of 1.08 dB (-0.81 to 2.96 dB; P = 0.26) between treatment arms. There was no significant difference in the proportion of subjects in the DFMO plus sulindac group who experienced clinically significant hearing loss compared with the placebo group. The estimated attributable risk of ototoxicity from exposure to the drug is 8.4% (95% confidence interval, -2.0% to 18.8%; P = 0.12). There is a <2 dB difference in mean threshold for patients treated with DFMO plus sulindac compared with those treated with placebo.

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; 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.

Difluoromethylornithine Plus Sulindac for the Prevention of Sporadic Colorectal Adenomas: A Randomized Placebo-Controlled, Double-Blind Trial

Preclinical studies of chemoprevention drugs given in combination at low doses show remarkable efficacy in preventing adenomas with little additional toxicities, suggesting a strategy to improve risk to benefit ratios for preventing recurrent adenomas. Three hundred seventy-five patients with history of resected (> or =3 mm) adenomas were randomly assigned to receive oral difluoromethylornithine (DFMO) 500 mg and sulindac 150 mg once daily or matched placebos for 36 months, stratified by use of low-dose aspirin (81 mg) at baseline and clinical site. Follow-up colonoscopy was done 3 years after randomization or off-study. Colorectal adenoma recurrence was compared among the groups with log-binomial regression. Comparing the outcome in patients receiving placebos to those receiving active intervention, (a) the recurrence of one or more adenomas was 41.1% and 12.3% (risk ratio, 0.30; 95% confidence interval, 0.18-0.49; P < 0.001); (b) 8.5% had one or more advanced adenomas, compared with 0.7% of patients (risk ratio, 0.085; 95% confidence interval, 0.011-0.65; P < 0.001); and (c) 17 (13.2%) patients had multiple adenomas (>1) at the final colonoscopy, compared with 1 (0.7%; risk ratio, 0.055; 0.0074-0.41; P < 0.001). Serious adverse events (grade > or =3) occurred in 8.2% of patients in the placebo group, compared with 11% in the active intervention group (P = 0.35). There was no significant difference in the proportion of patients reporting hearing changes from baseline. Recurrent adenomatous polyps can be markedly reduced by a combination of low oral doses of DFMO and sulindac and with few side effects.

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).

High Dry Bean Intake and Reduced Risk of Advanced Colorectal Adenoma Recurrence among Participants in the Polyp Prevention Trial

Adequate fruit and vegetable intake was suggested to protect against colorectal cancer and colorectal adenomas; however, several recent prospective studies reported no association. We examined the association between fruits and vegetables and adenomatous polyp recurrence in the Polyp Prevention Trial (PPT). The PPT was a low-fat, high-fiber, high-fruit, and vegetable dietary intervention trial of adenoma recurrence, in which there were no differences in the rate of adenoma recurrence in participants in the intervention and control arms of the trial. In this analysis of the entire PPT trial-based cohort, multiple logistic regression analysis was used to estimate the odds ratio (OR) of advanced and nonadvanced adenoma recurrence within quartiles of baseline and change (baseline minus the mean over 3 y) in fruit and vegetable intake, after adjustment for age, total energyy intake, use of nonsteroidal anti-inflammatory drugs, BMI, and gender. There were no significant associations between nonadvanced adenoma recurrence and overall change in fruit and vegetable consumption; however, those in the highest quartile of change in dry bean intake (greatest increase) compared with those in the lowest had a significantly reduced OR for advanced adenoma recurrence (OR = 0.35; 95% CI, 0.18-0.69; P for trend = 0.001). The median in the highest quartile of change in dry bean intake was 370% higher than the baseline intake. The PPT trial-based cohort provides evidence that dry beans may be inversely associated with advanced adenoma recurrence.

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 > or =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.