Search

Colonoscopic screening and surveillance have been very effective tools in the fight against colorectal cancer (CRC). Colonoscopy is more than a cancer screening test; it also can prevent CRC by detecting and removing precancerous lesions. Despite this potential, there has been increasing concern about CRCs that occur after a previous colonoscopy and before the next screening/surveillance examination (interval CRCs). The etiology of interval CRC is thought to be caused mostly by missed or incompletely resected lesions on index colonoscopy with some contribution of rapidly progressive new lesions. If this is true, many interval cancers should be preventable by improving colonoscopy technique. There are a variety of strategies to decrease interval CRC rates including use of a split-dosed bowel preparation, optimizing withdrawal technique, ensuring complete polypectomy, and careful pathologic examination of the tissue removed. Furthermore, there should be an increased emphasis on how endoscopists are trained to cultivate high-quality technique throughout their careers. It is important to inform patients that even high-quality colonoscopy is not perfectly sensitive for the detection of advanced neoplasia. Improving colonoscopy quality can decrease interval CRC rates and further decrease CRC incidence and mortality. [Copyright &y& Elsevier]

Background & Aims: Asymptomatic diverticulosis is commonly attributed to constipation caused by a low-fiber diet, although evidence for this mechanism is limited. We examined the associations between constipation and low dietary fiber intake with risk of asymptomatic diverticulosis. Methods: We performed a cross-sectional study that analyzed data from 539 individuals with diverticulosis and 1569 without (controls). Participants underwent colonoscopy and assessment of diet, physical activity, and bowel habits. Our analysis was limited to participants with no knowledge of their diverticular disease to reduce the risk of biased responses. Results: Constipation was not associated with an increased risk of diverticulosis. Participants with less frequent bowel movements (<7/wk) had reduced odds of diverticulosis compared with those with regular bowel movements (7/wk) (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.40–0.80). Those reporting hard stools also had reduced odds (OR, 0.75; 95% CI, 0.55–1.02). There was no association between diverticulosis and straining (OR, 0.85; 95% CI, 0.59–1.22) or incomplete bowel movement (OR, 0.85; 95% CI, 0.61–1.20). We found no association between dietary fiber intake and diverticulosis (OR, 0.96; 95% CI, 0.71–1.30) in comparing the highest quartile with the lowest (mean intake, 25 vs 8 g/day). Conclusions: In our cross-sectional, colonoscopy-based study, neither constipation nor a low-fiber diet was associated with an increased risk of diverticulosis. [Copyright &y& Elsevier]

Background: Recent genome-wide studies identified a risk locus for colorectal cancer at 18q21, which maps to the SMAD7 gene. Our objective was to confirm the association between SMAD7 SNPs and colorectal cancer risk in the multi-center Colon Cancer Family Registry. Materials and Methods: 23 tagging SNPs in the SMAD7 gene were genotyped among 1,592 population-based and 253 clinic-based families. The SNP-colorectal cancer associations were assessed in multivariable conditional logistic regression. Results: Among the population-based families, both SNPs rs12953717 (odds ratio, 1.29; 95% confidence interval, 1.12–1.49), and rs11874392 (odds ratio, 0.80; 95% confidence interval, 0.70–0.92) were associated with risk of colorectal cancer. These associations were similar among the population- and the clinic-based families, though they were significant only among the former. Marginally significant differences in the SNP-colorectal cancer associations were observed by use of nonsteroidal anti-inflammatory drugs, cigarette smoking, body mass index, and history of polyps. Conclusions: SMAD7 SNPs were associated with colorectal cancer risk in the Colon Cancer Family Registry. There was evidence suggesting that the association between rs12953717 and colorectal cancer risk may be modified by factors such as smoking and use of nonsteroidal anti-inflammatory drugs. [ABSTRACT FROM AUTHOR]

Background Lynch syndrome is an autosomal dominantly inherited disorder caused by germline mutations in DNA mismatch repair (MMR) genes. Previous studies have shown that MMR gene mutation carriers are at increased risk of colorectal, endometrial, and several other cancers following an initial diagnosis of colorectal cancer. We estimated cancer risks following an endometrial cancer diagnosis for women carrying MMR gene mutations. Methods We obtained data from the Colon Cancer Family Registry for a cohort of 127 women who had a diagnosis of endometrial cancer and who carried a mutation in one of four MMR genes (30 carried a mutation in MLH1, 72 in MSH2, 22 in MSH6, and 3 in PMS2). We used the Kaplan-Meier method to estimate 10- and 20-year cumulative risks for each cancer. We estimated the age-, country-, and calendar period–specific standardized incidence ratios (SIRs) for each cancer, compared with the general population. Results Following endometrial cancer, women carrying MMR gene mutations had the following 20-year risks of other cancer cancers: colorectal cancer (48%, 95% confidence interval [CI] = 35% to 62%); cancer of the kidney, renal pelvis, or ureter (11%, 95% CI = 3% to 20%); urinary bladder cancer (9%, 95% CI = 2% to 17%); and breast cancer (11%, 95% CI = 4% to 19%). Compared with the general population, these women were at statistically significantly elevated risks of colorectal cancer (SIR = 39.9, 95% CI = 27.2 to 58.3), cancer of the kidney, renal pelvis, or ureter (SIR = 28.3, 95% CI = 11.9 to 48.6), urinary bladder cancer (SIR = 24.3, 95% CI = 8.56 to 42.9), and breast cancer (SIR = 2.51, 95% CI = 1.17 to 4.14). Conclusions Women with Lynch syndrome who are diagnosed with endometrial cancer have increased risks of several cancers, including breast cancer. [ABSTRACT FROM PUBLISHER]

Purpose: The cytochrome P450 2C9 enzyme (CYP2C9) is involved in metabolism of endogenous compounds, drugs, and procarcinogens. Two common nonsynonymous polymorphisms in CYP2C9 are associated with reduced enzyme activity: CYP2C9*2 (rs1799853, R144C) and CYP2C9*3 (rs1057910, I359L).Methods: We investigated whether CYP2C9 genotype was associated with risk of colorectal adenoma and/or modified associations with aspirin treatment or cigarette smoking in a cohort of 928 participants in a randomized trial of aspirin chemoprevention. Generalized linear regression was used to compute relative risks (RRs) and 95 % confidence intervals (95 % CIs). Multiplicative interactions terms were used to assess effect modification.Results: CYP2C9 genotype was associated with increased risks for adenoma recurrence of 29 % (RR = 1.29, 95 % CI 1.09-1.51) for ≥1 variant allele (CYP2C9*2 or *3) and 47 % (RR = 1.47, 95 % CI 1.19-1.83) for ≥1 CYP2C9*3 allele. The risk for advanced lesions or multiple (≥3) adenomas was increased by 64 % (RR = 1.64, 95 % CI 1.18-2.28) for ≥1 variant allele (CYP2C9*2 or *3) and 79 % (RR = 1.79, 95 % CI 1.16-2.75) for ≥1 CYP2C9*3 allele. Genotype modified associations with smoking, but not aspirin treatment. The adenoma risk was increased by 26 % (RR = 1.26, 95 % CI 0.99-1.58) for former smokers and 60 % (RR = 1.60, 95 % CI 1.19-2.15) for current smokers among wild-type individuals, but there was no increased risk among individuals with ≥1 variant allele (CYP2C9*2 or *3) (p (interaction) = 0.04).Conclusions: Carriers of CYP2C9 variants with lower enzyme activity have increased overall risk of colorectal adenoma but reduced adenoma risk associated with cigarette smoking. These results may be due to effects on the synthesis of endogenous eicosanoids and/or reduced activation of procarcinogens in smoke by CYP2C9 variants. [ABSTRACT FROM AUTHOR]

Background: Guidelines from the United Kingdom and the United States on risk stratification after polypectomy differ, as do recommended surveillance intervals.Objective: To compare risk for advanced colorectal neoplasia at 1-year colonoscopy among patients cross-classified by U.S. and U.K. surveillance guidelines.Design: Pooled analysis of 4 prospective studies between 1984 and 1998.Setting: Academic and private clinics in the United States.Patients: 3226 postpolypectomy patients with 6- to 18-month follow-up colonoscopy.Measurements: Rates of advanced neoplasia (an adenoma ≥1 cm, high-grade dysplasia, >25% villous architecture, or invasive cancer) at 1 year, compared across U.S. and U.K. risk categories.Results: Advanced neoplasia was detected 1 year after polypectomy in 3.8% (95% CI, 2.7% to 4.9%) of lower-risk patients and 11.2% (CI, 9.8% to 12.6%) of higher-risk patients by U.S. criteria. According to U.K. criteria, 4.4% (CI, 3.3% to 5.4%) of low-risk patients, 9.9% (CI, 8.3% to 11.5%) of intermediate-risk patients, and 18.7% (CI, 14.8% to 22.5%) of high-risk patients presented with advanced neoplasia; U.K. high-risk patients comprised 12.1% of all patients. All U.S. lower-risk patients were low-risk by U.K. criteria; however, more patients were classified as low-risk, because the U.K. guidelines do not consider histologic features. Higher-risk U.S. patients were distributed across the 3 U.K. categories. Among all patients with advanced neoplasia, 26.3% were reclassified by the U.K. criteria to a higher-risk category and 7.0% to a lower-risk category, with a net 19.0% benefiting from detection 2 years earlier. Overall, substitution of U.K. for U.S. guidelines resulted in an estimated 0.03 additional colonoscopy every 5 years per patient.Limitations: Patients were enrolled 15 to 20 years ago, and quality measures for colonoscopy were unavailable. Patients lacking follow-up colonoscopy or with surveillance colonoscopy after 6 to 18 months and those with cancer or insufficient baseline adenoma characteristics were excluded (2076 of 5302).Conclusion: Application of the U.K. guidelines in the United States could identify a subset of high-risk patients who may warrant a 1-year clearing colonoscopy without substantially increasing rates of colonoscopy.Primary Funding Source: European Union Public Health Programme. [ABSTRACT FROM AUTHOR]

The article discusses a research for establishing an efficient strategy to identify Lynch Syndrome among the patients suffering from colorectal cancer (CRC). It informs that Lynch Syndrome is the most common form of hereditary CRC which is caused by germ line mutations in DNA mismatch repair (MMR) genes. It suggests that all Lynch Syndrome-associated CRC display MMR deficiency so tumor MMR screening using MMR testing or immunostaining of CRC patients has been proposed by the researchers. It further informs that universal MMR testing among CRC patients has a greater senstivity for the identification of Lynch Syndrome.

Diets high in red meat are established risk factors for colorectal cancer (CRC). Carcinogenic compounds generated during meat cooking have been implicated as causal agents. We conducted a family-based case-control study to investigate the association between polymorphisms in carcinogen metabolism genes ( CYP1A2 -154A>C, CYP1B1 Leu432Val, CYP2E1 -1054C>T, GSTP1 Ile105Val, PTGS2 5UTR -765, EPHX1 Tyr113His, NAT2 Ile114Thr, NAT2 Arg197Gln and NAT2 Gly286Glu) and CRC risk. We tested for gene-environment interactions using case-only analyses ( N = 577) and compared statistically significant results to those obtained using case-unaffected sibling comparisons ( N = 307 sibships). Our results suggested that CYP1A2 -154A>C might modify the association between intake of red meat cooked using high temperature methods and well done on the inside and CRC risk (case-only interaction OR = 1.53; 95% CI = 1.19-1.97; p = 0.0008) and the association between intake of red meat heavily browned on the outside and rectal cancer risk (case-only interaction OR = 0.65; 95% CI = 0.48-0.86; p = 0.003). We also found that GSTP1 Ile105Val might modify the association between intake of poultry cooked with high temperature methods and CRC risk ( p = 0.0035), a finding that was stronger among rectal cancer cases. Our results support a role for heterocyclic amines that form in red meat as a potential explanation for the observed association between diets high in red meat and CRC. Our findings also suggest a possible role for diets high in poultry cooked at high temperatures in CRC risk. [ABSTRACT FROM AUTHOR]

Consensus guidelines of the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology recommend first-degree relatives of individuals diagnosed with an adenoma before age 60 should be screened every 5 years with colonoscopy starting at age 40. This is the identical recommendation for those with a first-degree relative diagnosed with colorectal cancer (CRC) before age 60. There is good evidence that first-degree relatives of individuals diagnosed with CRC before age 60 are at substantially increased risk for developing cancer at a young age. However, it is unclear whether an individual with a first-degree relative with an adenoma diagnosed before age 60 is at increased risk of CRC. Because not all adenomas portend the same cancer risk in the individual who has the adenoma, they would not be expected to portend the same risk in their first-degree relatives. Because of these uncertainties, the US Preventive Services Task Force does not recommend more aggressive screening of first-degree relatives of individuals with an adenoma. The adenoma detection rate for individuals 50 to 59 years old without a first-degree relative with CRC is sufficiently high (approximately 25%–30%) that almost half the population would be high risk on the basis of one first-degree relative having an adenoma. Given the weakness of evidence supporting the guidelines, suboptimal levels of screening in the general population, and lack of resources to comply with the recommendation, first-degree relatives of individuals with adenomas should be screened as average-risk persons until more compelling data are available to justify more aggressive screening. [ABSTRACT FROM AUTHOR]

Recent guidelines for colorectal cancer screening have reached different conclusions on whether computed tomographic colonography (CTC) is an acceptable screening option, and the Centers for Medicare & Medicaid Services recently decided not to cover CTC screening. The rationale against recommending or covering CTC screening includes concerns about radiation exposure, false-negative rates for small polyps, the discovery of extracolonic findings, variability in performance, a lack of targeted studies, a higher adenoma rate in the Medicare-eligible age group, and an absence of evidence that covering CTC would increase overall screening rates. Similar concerns can be raised for other recommended and covered colon cancer screening tests, but it seems that CTC is being held to a new and higher standard. [ABSTRACT FROM AUTHOR]

The Aspirin/Folate Polyp Prevention Trial found that aspirin, but not folic acid, reduced recurrence of colorectal adenomas. This study examined whether treatment effects on inflammation markers explained the trial results. The trial had a factorial design with three aspirin (placebo, 81, and 325 mg/d) and two folic acid (placebo and 1 mg/d) groups. There were 884 subjects who had colonoscopic evaluation for adenomas at year 3 and plasma levels of C-reactive protein (CRP), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), soluble TNF receptor type II (sTNF-R2), and IL-1 receptor antagonist (IL-1Ra) measured at baseline and year 3. Among individuals not receiving folic acid, there was a 4% decrease (mean ratio of year 3 to baseline levels = 0.96, 95% confidence interval [CI] = 0.82 to 1.14) in CRP for a period of 3 years in the 325 mg of aspirin group vs a 20% increase (mean ratio = 1.20, 95% CI = 1.03 to 1.41) in the placebo group (P = .027). By contrast, the reverse was observed among individuals who also received folic acid (Pinteraction = .013). Changes in inflammation markers were not associated with adenoma recurrence. Low-dose aspirin (325 mg/d) is beneficial in stabilizing CRP levels, which may be abrogated by folate. Nevertheless, inflammation markers do not mediate the chemopreventive effect of aspirin on colorectal adenomas. [ABSTRACT FROM PUBLISHER]

Background: Suggested intervals for postpolypectomy surveillance colonoscopy are currently based on the adenoma findings from the most recent examination. Objective: To determine the risk for clinically significant adenoma recurrence on the basis of the results of 2 previous colonoscopies. Design: Prospective cohort study. Setting: Academic and private centers in North America. Patients: Participants in an adenoma chemoprevention trial in which all participants had 1 or more adenoma found on complete colonoscopy at entry. For this analysis, only participants whose qualifying adenoma was their first were included. All participants then underwent second and third study colonoscopies at roughly 3-year intervals. Measurements: Proportion of patients with high-risk findings at the third study colonoscopy-either at least 1 advanced ( 1 cm or advanced histology) adenoma or multiple ( 3) adenomas. Results: Fifty-eight of 564 participants (10.3%) had high-risk findings at the third study examination. If the second examination showed high-risk findings, then results from the first examination added no significant information about the probability of high-risk findings on the third examination (18.2% for high-risk findings on the first examination vs. 20.0% for low-risk findings on the first examination; P = 0.78). If the second examination showed no adenomas, then the results from the first examination added significant information about the probability of high-risk findings on the third examination (12.3% if the first examination had high-risk findings vs. 4.9% if the first examination had low-risk findings; P = 0.015). Limitation: This observational study cannot specifically examine adenoma recurrence risk at intervals suggested for patients with low-risk adenomas (for example, 5 years vs. 10 years). Conclusion: Information from 2 previous examinations may help identify low-risk populations that benefit little from intense surveillance. Surveillance guidelines might be tailored in selected patients to use information from 2 previous examinations, not just the most recent one. [ABSTRACT FROM AUTHOR]

Background Frequent use of nonsteroidal anti-inflammatory drugs (NSAIDs) has been shown to reduce the risk of colorectal adenomas in randomized trials. We examined the persistence of the protective effect after the cessation of randomized aspirin treatment and whether it is affected by the duration and frequency of subsequent NSAID use. Methods We used data from the Aspirin/Folate Polyp Prevention Study (AFPPS), in which 1121 subjects were randomly assigned to receive placebo or aspirin (81 or 325 mg/d) for 3 years. After the end of treatment and a follow-up colonoscopy, AFPPS participants were invited to remain under follow-up until their next surveillance colonoscopies, scheduled 3-5 years later. Information regarding use of NSAIDs during posttreatment follow-up was gathered periodically via questionnaires. Average weekly NSAID use was classified as sporadic (<2 days per week), moderate (2 to <4 days per week), or frequent (⩾4 days per week). The analysis was stratified according to randomized aspirin groups and posttreatment NSAID use; placebo subjects who later were sporadic NSAID users formed the reference group. The primary outcomes were all adenomas and advanced lesions. Adjusted relative risks and 95% confidence intervals were computed with generalized linear models. All statistical tests were two-sided. Results A total of 850 subjects underwent a posttreatment colonoscopy, on average 4 years after the end of study treatment. The protective effect of 81 mg of aspirin for colorectal adenomas persisted with continued post-treatment NSAID use. The risk of any adenoma among frequent NSAID users was 26.8% vs 39.9% among placebo subjects who later used NSAIDs sporadically (adjusted relative risk = 0.62, 95% confidence inter- val [Cl] = 0.39 to 0.98; Ptrend with NSAID use frequency = .03). The unadjusted absolute risk reduction was 13.1 percentage points (95% Cl = -0.3 to 26.5 percentage points) (P= .07). Results for 325 mg of aspirin were similar, although not statistically significant. For advanced lesions, small numbers of endpoints limited the analysis, but findings among subjects randomly assigned to 81 mg of aspirin suggested a protective association regardless of posttreatment NSAID use. Conclusion Long-term and frequent use of NSAIDs may enhance the chemopreventive effect of aspirin against colorectal neoplasia. [ABSTRACT FROM AUTHOR]

Background & Aims: Hypergastrinemia and Helicobacter pylori (Hp) infection have been associated with an increased risk for colorectal neoplasia in some studies. However, data from large prospective studies of both associations are lacking. The aim of this study was to evaluate whether serum gastrin levels and/or infection with Hp are associated with the subsequent development of colorectal adenomas. Methods: Subjects (all with a history of adenoma formation) were drawn from 2 previously completed adenoma chemoprevention trials. Participants underwent clearing colonoscopy at baseline with follow-up colonoscopy 1 and 4 years after enrollment. We used commercially available assays on fasting blood specimens to measure serum gastrin levels and Hp serologies 1 year after randomization. Risk ratios for adenoma and advanced adenoma development during the subsequent 3 years were computed by generalized linear regression. Results: Of the 1794 subjects randomized in the 2 trials, 685 had available serum and were included in the analyses. Gastrin levels were significantly higher in the 239 subjects with Hp titers indicating infection (mean, 88.3 pg/mL) than in those not infected (mean, 73.9 pg/mL; P < .001). In fully adjusted models, gastrin levels were not associated with incident adenoma development (risk ratio [RR], 1.10; 95% confidence interval [CI], 0.78–1.54) or advanced adenoma formation (RR, 0.82; 95% CI, 0.33–2.03). A positive Hp serology was associated with a decreased risk for adenoma formation (RR, 0.76; 95% CI, 0.60–0.96). Conclusions: Neither hypergastrinemia nor serologic evidence of Hp infection were associated with an increased risk for recurrent adenoma development. These results do not support the notion that gastrin promotes colorectal carcinogenesis, at least at the stage of adenoma development. [Copyright &y& Elsevier]

Background: Stool DNA testing is a new approach to colorectal cancer detection. Few data are available from the screening setting. Objective: To compare stool DNA and fecal blood testing for detection of screen-relevant neoplasia (curable-stage cancer, highgrade dysplasia, or adenomas >1 cm). Design: Blinded, multicenter, cross-sectional study. Setting: Communities surrounding 22 participating academic and regional health care systems in the United States. Participants: 4482 average-risk adults. Measurements: Fecal blood and DNA markers. Participants collected 3 stools, smeared fecal blood test cards and used same-day shipment to a central facility. Fecal blood cards (Hemoccult and HemoccultSensa, Beckman Coulter, Fullerton, California) were tested on 3 stools and DNA assays on 1 stool per patient. Stool DNA test 1 (SDT-1) was a precommercial 23-marker assay, and a novel test (SDT-2) targeted 3 broadly informative markers. The criterion standard was colonoscopy. Results: Sensitivity for screen-relevant neoplasms was 20% by SDT-1, 11% by Hemoccult (P = 0.020), 21% by HemoccultSensa (P = 0.80); sensitivity for cancer plus high-grade dysplasia did not differ among tests. Specificity was 96% by SDT-1, compared with 98% by Hemoccult (P < 0.001) and 97% by HemoccultSensa (P = 0.20). Stool DNA test 2 detected 46% of screen-relevant neoplasms, compared with 16% by Hemoccult (P < 0.001) and 24% by HemoccultSensa (P < 0.001). Stool DNA test 2 detected 46% of adenomas 1 cm or larger, compared with 10% by Hemoccult (P < 0.001) and 17% by HemoccultSensa (P < 0.001). Among colonoscopically normal patients, the positivity rate was 16% with SDT-2, compared with 4% with Hemoccult (P = 0.010) and 5% with HemoccultSensa (P = 0.030). Limitations: Stool DNA test 2 was not performed on all subsets of patients without screen-relevant neoplasms. Stools were collected without preservative, which reduced detection of some DNA markers. Conclusion: Stool DNA test 1 provides no improvement over HemoccultSensa for detection of screen-relevant neoplasms. Stool DNA test 2 detects significantly more neoplasms than does Hemoccult or HemoccultSensa, but with more positive results in colonoscopically normal patients. Higher sensitivity of SDT-2 was particularly apparent for adenomas. [ABSTRACT FROM AUTHOR]

The article reports on results of a study of vitamins B2, B6 and B12 and risk of new colorectal adenomas in a randomized trial of aspirin use and folic acid supplementation. A description of the experimental set-up and measurement method is provided. The study concluded that high levels of pyridoxal 5-phosphate (PLP) and B2 may protect against colorectal adenomas.

In the United States, compliance with colorectal cancer (CRC) screening recommendations remains suboptimal. Professional organizations advocate use of shared decision making in screening test discussions, but strategies to facilitate informed choice in CRC screening have not been well elucidated. The objectives of the study were to determine screening test preference among colonoscopy-naïve adults after considering a detailed, written presentation of fecal occult blood testing (FOBT) and colonoscopy and to assess whether their preferences are associated with demographic characteristics, attitudes, and knowledge. The design of the study was a cross-sectional survey. Colonoscopy-naïve supermarket shoppers age 40–79 in low- and middle-income, multiethnic neighborhoods in Denver, CO, reviewed a detailed, side-by-side description of FOBT and colonoscopy and answered questions about test preference, strength of preference, influence of physician recommendation, basic knowledge of CRC, and demographic characteristics. Descriptive statistics characterized the sample, and bivariate and multivariable logistic regression analyses identified correlates of screening test preference. In a diverse sample of 323 colonoscopy-naïve adults, 53% preferred FOBT, and 47% preferred colonoscopy for CRC screening. Individuals of Latino ethnicity and those with lower educational attainment were more likely to prefer FOBT than non-Latino whites and those with at least some college. Almost half of the respondents felt “very strongly” about their preferences, and one third said they would adhere to their choice regardless of physician recommendation. After considering a detailed, side-by-side comparison of the FOBT and colonoscopy, a large proportion of community-dwelling, colonoscopy-naïve adults prefer FOBT over colonoscopy for CRC screening. In light of professional guidelines and time-limited primary care visits, it is important to develop improved ways of facilitating informed patient decision making for CRC screening. [ABSTRACT FROM AUTHOR]

Background & Aims: Orlistat is a weight management agent that selectively inhibits gastrointestinal lipase activity. Because of orlistat’s mode of action, increased fecal fat is presented to the colonic mucosa, and fecal bile acid and free fatty acid composition may be altered during treatment. Our aim was to assess the effect of treatment of obese subjects with orlistat 120 mg 3 times a day for 6 weeks on fecal lipid and bile acid parameters and colonic mucosal cell proliferation. Methods: Twenty-four obese (body mass index, 30–40 kg/m2) but otherwise healthy male and female subjects were enrolled in a single-center, randomized, double-blind, placebo-controlled, parallel-group study. Participants were hospitalized during days 1–3 and 33–42 of treatment and were treated as outpatients for the remaining days. Results: Treatment with orlistat for 6 weeks resulted in significantly greater increases in fecal weight, total fecal fat, and fecal free fatty acids than placebo. Total fecal bile acid amounts decreased slightly with orlistat, and increased significantly with placebo treatment (P < .05 between-group difference). Orlistat did not alter colonic cell proliferation as assessed by the 3 proliferative indices (5-bromo-2-deoxyuridine, whole crypt mitotic count, and proliferating cell nuclear antigen). Conclusions: Biochemical changes in fecal composition related to the pharmacodynamic mode of action of orlistat are not accompanied by altered colonic cell proliferation, a putative biomarker of colon cancer risk. [Copyright &y& Elsevier]

Background & Aims: Outcomes of colon surveillance after colorectal cancer screening with colonoscopy are uncertain. We conducted a prospective study to measure incidence of advanced neoplasia in patients within 5.5 years of screening colonoscopy. Methods: Three thousand one hundred twenty-one asymptomatic subjects, age 50 to 75 years, had screening colonoscopy between 1994 and 1997 in the Department of Veterans Affairs. One thousand one hundred seventy-one subjects with neoplasia and 501 neoplasia-free controls were assigned to colonoscopic surveillance over 5 years. Cohorts were defined by baseline findings. Relative risks for advanced neoplasia within 5.5 years were calculated. Advanced neoplasia was defined as tubular adenoma greater than ≥10 mm, adenoma with villous histology, adenoma with high-grade dysplasia, or invasive cancer. Results: Eight hundred ninety-five (76.4%) patients with neoplasia and 298 subjects (59.5%) without neoplasia at baseline had colonoscopy within 5.5 years; 2.4% of patients with no neoplasia had interval advanced neoplasia. The relative risk in patients with baseline neoplasia was 1.92 (95% CI: 0.83–4.42) with 1 or 2 tubular adenomas <10 mm, 5.01 (95% CI: 2.10–11.96) with 3 or more tubular adenomas <10 mm, 6.40 (95% CI: 2.74–14.94) with tubular adenoma ≥10 mm, 6.05 (95% CI: 2.48–14.71) for villous adenoma, and 6.87 (95% CI: 2.61–18.07) for adenoma with high-grade dysplasia. Conclusions: There is a strong association between results of baseline screening colonoscopy and rate of serious incident lesions during 5.5 years of surveillance. Patients with 1 or 2 tubular adenomas less than 10 mm represent a low-risk group compared with other patients with colon neoplasia. [Copyright &y& Elsevier]

This article presents research on the use of folic acid for the prevention of colorectal adenomas. The object of the study was to assess the safety and efficacy of folic acid supplements for preventing colorectal adenomas. The study found that folic acid a 1mg/d does not reduce colorectal adenoma risk in patients with a recent history of adenomas and there was no evidence of benefit among subgroups that might be considered sensitive to the chemopreventive effects of foliate. The authors say that further research is need to investigate the possibility that folic acid supplements might increase the risk of colorectal neoplasia.

Background: Even when primary care physicians have face-to-face discussions with patients before referring them for screening colonoscopy, patient nonadherence can be substantial. Often, primary care physicians lack sufficient time to educate patients and address their potential misconceptions and fears about this procedure.Objective: To test whether an informational brochure sent to patients' home addresses after referral for screening colonoscopy would increase patient completion of the procedure.Design: Randomized, controlled trial.Setting: 2 general internal medicine practices affiliated with the University of Colorado Health Sciences Center.Patients: 781 consecutive patients 50 years of age or older referred by their primary care physicians for screening colonoscopy.Intervention: Patients were randomly assigned to receive usual care (control group) versus usual care plus an informational brochure (intervention group). The brochure was mailed within 10 days of referral for screening colonoscopy; it mentioned the name of the patient's primary care physician and encouraged patients to schedule a procedure. It also described colorectal cancer and polyps and the similar lifetime risks for colorectal cancer for men and women, colonoscopy and risk for perforation, the nature of bowel preparation for the procedure, and alternative screening tests.Measurements: Rates of adherence to screening colonoscopy in the 2 study groups.Results: The overall adherence rate was 11.7 percentage points (95% CI, 5.1 to 18.4 percentage points) greater in the intervention group than in the control group (70.7% vs. 59.0%). Older patients were more adherent than younger patients. Patients with low-income insurance plans, such as Medicaid, were less adherent despite being sent a brochure.Limitations: The small number of clinical practices and minority patients may limit generalizability. In addition, it was not possible to determine the degree to which adherence was influenced by a reminder to schedule a procedure versus detailed information about colonoscopy.Conclusions: An inexpensive mailed brochure is an effective way to increase patient adherence to primary care physician referral for screening colonoscopy. [ABSTRACT FROM AUTHOR]

Background: Previous research suggests that the G315A single-nucleotide polymorphism in the ornithine decarboxylase (ODC) gene may be a genetic marker for risk of colorectal neoplasia and may also modify the association of aspirin use with risk. Methods: We tested these hypotheses among participants in the Aspirin/Folate Polyp Prevention Study who were randomly assigned to placebo or to aspirin treatment (81 or 325 mg daily) and followed for 3 years for the occurrence of new adenomas. Genomic DNA from 973 subjects was analyzed for ODC genotype. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated to test the association between ODC genotype and adenoma occurrence and interactions with aspirin treatment. All statistical tests were two-sided. Results: Of the 973 subjects, 54% were homozygous wild-type (GG), 7% were homozygous variant (AA), and 39% were heterozygous individuals; the allele frequencies varied statistically significantly by race and ethnicity. Among these subjects, the absolute risk of any adenoma was 45% and the risk of an advanced lesion was 10%. Overall, no association was found between ODC genotype and the occurrence of new adenomas, but genotype did modify the effect of aspirin on adenoma risk. Although aspirin treatment had no protective effect among subjects with a GG genotype, among subjects with at least one A allele, it was associated with statistically significant reduced risks of any adenoma (RR = 0.77, 95% CI = 0.63 to 0.95; P = .02, Pinteraction = .04) and of advanced lesions (RR = 0.51, 95% Cl = 0.29 to 0.90; P = .02, Pinteraction = .02). Among subjects with at least one A allele, 40.8% who took aspirin versus 52.9% who took placbo developed adenomas; 7.1% versus 14.0% developed advanced lesions. Conclusion: ODC genotype may modify the response to aspirin treatment for colorectal adenoma prevention. [ABSTRACT FROM AUTHOR]

BACKGROUND: Colonoscopy has become a preferred cob rectal cancer (CRC) screening modality. Little is known about why patients who are referred for colonoscopy do not complete the recommended procedures. Prior adherence studies have evaluated colonoscopy only in combination with flexible sigmoidoscopy, failed to differentiate between screening and diagnostic procedures, and have examined cancellations/no-shows, but not nonscheduling, as mechanisms of nonadherence. METHODS: Sociodemographic predictors of screening completion were assessed in a retrospective cohort of 647 patients referred for colonoscopy at a major university hospital. Then, using a qualitative study design, a convenience sample of patients who never completed screening after referral (n=52) was interviewed by telephone, and comparisons in reported reasons for nonadherence were made by gender. RESULTS: Half of all patients referred for colonoscopy failed to complete the procedure, overwhelmingly because of nonscheduling. In multivariable analysis, female sex, younger age, and insurance type predicted poorer adherence. Patient-reported barriers to screening completion included cognitive-emotional factors (e.g., lack of perceived risk for CRC. fear of pain, and concerns about modesty and the bowel preparation), logistic obstacles (e.g., cost, other health problems, and competing demands), and health system barriers (e.g., scheduling challenges, long waiting times). Women reported more concerns about modesty and other aspects of the procedure than men. Only 40% of patients were aware of alternative screening options. CONCLUSIONS: Adherence to screening colonoscopy referrals is sub-optimal and may be improved by better communication with patients, counseling to help resolve logistic barriers, and improvements in colonoscopy referral and scheduling mechanisms. [ABSTRACT FROM AUTHOR]

Colorectal cancer is second to lung cancer as the most common cause of cancer death in the United States. both environmental (diet, physical activity) and genetic (family history, mutations, polymorphisms) factors are related to colon cancer risk. Epidemiologic, animal model, and clinical studies all suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) are potent preventive agents for colon cancer. Most epidemiologic studies (case control, and cohort) are consistent with a protective effect of regular, long-term use of aspirin use, although the prospective Physicians Health Study failed to find a significant protective effect. The entire class of NSAIDs appear to be effective in preventing carcinogen induced colon cancer in animal models. Clinical trials using the NSAID sulindac have shown dramatic regression of colonic adenomas in patients with Familial Polyposis. The biologic and biochemical mechanisms of the putative chemopreventive activity of the NSAIDs is under intense investigation. These drugs can induce cell cycle arrest and apoptosis in colon cancer cell lines through a mechanism that is fundamentally different from the apoptosis caused by cancer chemotherapeutic agens. Sulindac and its metabolites also appear to induce apoptosis in colonic adenomas in vivo. The clinically used NSAIDs are anti-inflammotory due to their ability to decrease prostaglandin synthesis by inhibiting the cyclooxygenase (COX) enzymes. Cyclooxygenase inhibition, particularly COX 2 inhibition, is one putative biochemical target of the chemopreventive activity of NSAIDs. However, recent reports of chemopreventive activity of NSAID deriviatives that no longer have COX inhibitory activity suggest that there are other biochemical targets as well. [ABSTRACT FROM AUTHOR]

Looks at the p53 gene in colorectal carcinogenesis. Evidence which suggest that the normal p53 protein functions to suppress cell replication and induce cell death under specific circumstances; Expression of p53 protein by immunohistochemistry; Possible indicator that stabilizing types of p53 gene mutations do occur earlier in adenomatous polyposis coli.

The authors discus the relation of risk to the initiation of colon carcinogenesis or to the increased velocity of carcinogenesis. They emphasize that an elevated risk of initiation without acceleration of carcinogenesis should not per se dictate increased frequency as the lesions will not develop rapidly when initiated. They indicate that colonoscopic screening and surveillance guidelines for patients at risk for colorectal cancer (CRC) vary depending on the estimates of risk.

An introduction to the journal is presented in which the editor discusses the Veterans Health Administration (VHA), the two performance measures that have been incorporated in the VHA quality-improvement program, and colonoscopy in older patients.

Statins are among the most widely prescribed drugs in the United States. In addition to their established lipid-lowering and cardiovascular protective effect, some case–control studies have suggested that statins could have chemopreventive effects for colorectal cancer (CRC). In this issue of the Journal, Singh et al. examined this question using a potentially powerful population-based “electronic cohort” design, which essentially eliminates many of the biases inherent in case–control and traditional cohort studies. They found no evidence of a chemoprotective effect of statin use, a finding that is consistent with previous cohort and interventional studies that have addressed this issue. We conclude that the best-designed studies of the issue indicate that statin use is neither a major risk factor nor a protective factor for CRC and that we have come very near to the end of the road for the hypothesis relating statins to CRC risk. [ABSTRACT FROM AUTHOR]