High-Risk Adenomas at Screening Colonoscopy Remain Predictive of Future High-Risk Adenomas Despite an Intervening Negative Colonoscopy.

INTRODUCTION: Limited data inform the current postpolypectomy surveillance guidelines, which suggest a shortened interval to third colonoscopy after a negative second examination if high-risk adenomas (HRA) were present on the initial screening colonoscopy. Therefore, we examined the risk of HRA at third colonoscopy stratified by findings on 2 previous examinations in a prospective screening colonoscopy cohort of US veterans. METHODS: We identified participants who had 3 or more colonoscopies from CSP#380. We examined the risk of HRA on the third examination based on findings from the previous 2 examinations. Multivariate logistic regression was used to adjust for multiple covariates. RESULTS: HRA were found at the third examination in 114 (12.8%) of 891 participants. Those with HRA on both previous examinations had the greatest incidence of HRA at third examination (14/56, 25.0%). Compared with those with no adenomas on both previous examinations, participants with HRA on the first examination remained at significantly increased risk for HRA at the third examination at 3 years after a negative second examination (odds ratio [OR] 3.41, 95% confidence interval [CI] 1.28-9.08), 5 years (OR 3.14, 95% CI 1.49-6.61), and 7 years (OR 2.89, 95% CI 1.08-7.74). DISCUSSION: In a screening population, HRA on the first examination identified individuals who remained at increased risk for HRA at the third examination, even after a negative second examination. This finding supports current colorectal cancer surveillance guidelines, which suggest a shortened, 5-year time interval to third colonoscopy after a negative second examination if high-risk findings were present on the baseline examination.

Proximal and large hyperplastic and nondysplastic serrated polyps detected by colonoscopy are associated with neoplasia.

BACKGROUND & AIMS: The family of serrated lesions includes hyperplastic polyps and sessile serrated adenomas without dysplasia, as well as traditional serrated adenoma with dysplasia. We investigated whether detection of proximal nondysplastic serrated polyps (ND-SP) at screening and surveillance colonoscopies is associated with advanced neoplasia. METHODS: The study included 3121 asymptomatic patients (aged 50-75 years) who had screening colonoscopies; 1371 had subsequent surveillance. The proximal colon was defined as segments proximal to the descending colon. Large ND-SP were defined as ≥ 10 mm. We compared rates of detection of any neoplasia and advanced neoplasia at screening and surveillance colonoscopies (within 5.5 years) in patients with and without proximal or large ND-SP. RESULTS: At baseline screening, 248 patients (7.9%) had at least 1 proximal ND-SP. They were more likely than patients with no proximal ND-SP to have advanced neoplasia (17.3% vs 10.0%; odds ratio [OR], 1.90; 95% confidence interval [CI], 1.33-2.70). Patients with large ND-SP (n = 44) were also more likely to have synchronous advanced neoplasia (OR, 3.37; 95% CI, 1.71-6.65). During surveillance, 39 patients with baseline proximal ND-SP and no neoplasia were more likely to have neoplasia compared with subjects who did not have polyps (OR, 3.14; 95% CI, 1.59-6.20). Among patients with advanced neoplasia at baseline, those with proximal ND-SP (n = 43) were more likely to have advanced neoplasia during surveillance (OR, 2.17; 95% CI, 1.03-4.59). CONCLUSIONS: Detection of proximal and large ND-SP at a screening colonoscopy is associated with an increased risk for synchronous advanced neoplasia. Detection of proximal ND-SP in a baseline colonoscopy is associated with an increased risk for interval neoplasia during surveillance.

Colonoscopy withdrawal time and risk of neoplasia at 5 years: results from VA Cooperative Studies Program 380.

OBJECTIVES: Withdrawal time (WT) has been proposed as a quality indicator for colonoscopy based on evidence that it is directly related to the rate of adenoma detection. Our objective was to test the hypothesis that baseline WT is inversely associated with the risk of finding neoplasia at interval colonoscopy. METHODS: In all, 3,121 subjects, aged 50-75 years, had screening colonoscopy between 1994 and 1997 at 13 Veteran Affairs Medical Centers. In all, 1,193 subjects returned by protocol for surveillance within 5.5 years. In the 304 patients without polyps at baseline, we evaluated the contribution of baseline WT to their risk of interval neoplasia using bivariate and logistic regression analysis. We also examined the correlation between mean WT, baseline adenoma detection rate, and interval neoplasia rate at the medical-center level. RESULTS: The average WT at the baseline exam in subjects with neoplasia on follow-up was 15.3 min as compared with 13.2 min in subjects without neoplasia (P=0.18). In a logistic regression model, WT was not associated with the risk of interval neoplasia (P=0.07). At the medical-center level, mean WT was not correlated with the probability of finding interval neoplasia (P=0.61) but was positively correlated with adenoma detection rate at baseline (P=0.03). CONCLUSIONS: In this study with a mean baseline WT &12 min, there was no detectable association between WT and risk of future neoplasia. The medical center-level WT was positively correlated with adenoma detection. Therefore, above a certain threshold, WT may no longer be an adequate quality measure for screening colonoscopy.

Value of fibrosis markers for staging liver fibrosis in patients with precirrhotic alcoholic liver disease.

BACKGROUND: Our aim was to identify markers predictive of fibrosis in alcoholic liver disease (ALD). Percutaneous liver biopsy is the recommended standard for histologic assessment of liver fibrosis. Seven serum markers (tissue inhibitor of matrix metalloproteinase 1 [TIMP1], tenascin, collagen VI, amino-terminal propeptide of type III collagen [PIIINP], matrix metalloproteinases [MMP2], laminin, and hyaluronic acid [HA]) representing various aspects of collagen and extracellular matrix deposition and degradation, have been proposed as noninvasive surrogates for liver biopsy. Moreover, a diagnostic algorithm including 3 serum markers (TIMP1, PIIINP, HA) and age has been proposed to accurately detect fibrosis with acceptable levels of sensitivity/specificity in a chronic hepatitis C subgroup. METHODS: To determine variability of these markers in liver fibrosis with different etiologies, we conducted an evaluation of their correlative properties in a subgroup of patients (n = 247) with biopsy confirmed liver fibrosis resulting from long-term heavy alcohol consumption. Patients were participants in a recently completed VA multicenter clinical trial followed over 2 years with liver biopsy at baseline and 24 months, and with markers assessed every 3 months. RESULTS: Among the markers measured in this alcoholic subgroup all except collagen VI displayed significant correlation with degrees of fibrosis. Three markers, TIMP1, PIIINP and HA adjusted for age, emerged as the most promising predictors of the degree of fibrosis in a population of alcoholics. However, there was little change over time as related to change in fibrosis. The lower than expected accuracy of these markers based on receiver operating curves (ROC) also showed their limited use in this etiologic subgroup. CONCLUSION: In alcoholic patients, various markers have limited value in predicting and diagnosing the stages of fibrosis compared to liver biopsy. Thus, further prospective studies are required to better define the usefulness of each marker or their combination which are possibly affected by alcohol metabolism.

Five-year colon surveillance after screening colonoscopy.

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 > or =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 > or =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.

Aspartate aminotransferase to platelet ratio index in patients with alcoholic liver fibrosis.

OBJECTIVE: Aspartate aminotransferase (AST) to platelet ratio index (APRI) has been proposed as an easily determined and accurate noninvasive marker of liver fibrosis in chronic hepatitis C. To validate APRI in hepatitis C and to determine its usefulness in other liver diseases, we evaluated APRI in patients with liver fibrosis due to excessive alcohol consumption with or without viral hepatitis C. METHODS: A total of 1,308 subjects from two VA cooperative studies of alcoholic liver disease were evaluated. Liver biopsy was available from 781 noncirrhotic patients while a history of decompensation was present in 527. Alcohol intake was determined by self-report. Hepatitis C was confirmed by PCR. RESULTS: Ninety-eight percent were men with a mean age of 51.5 yr. Alcohol intake averaged 19 drinks/day for 20.6 yr. One hundred thirty-three (10.2%) were hepatitis C positive. In the HCV-positive subgroup, APRI had a sensitivity of 35.6% and a specificity of 29.7% for significant fibrosis. Of 64 patients classified as significant fibrosis, 21 (32.8%) were incorrectly classified. In the 507 HCV negative patients with biopsy confirmed fibrosis, the sensitivity of APRI for significant fibrosis was 13.2% and the specificity was 77.6%. Twenty percent were classified incorrectly. CONCLUSION: APRI has low sensitivity and specificity for the diagnosis of significant fibrosis in patients with alcoholic liver disease, including patients who have hepatitis C. Given the frequent history of alcohol use in patients with hepatitis C, APRI may be of limited usefulness in the diagnosis of fibrosis in many patients.

Colonoscopic screening of average-risk women for colorectal neoplasia.

BACKGROUND: Veterans Affairs (VA) Cooperative Study 380 showed that some advanced colorectal neoplasias (i.e., adenomas at least 1 cm in diameter, villous adenomas, adenomas with high-grade dysplasia, or cancer) in men would be missed with the use of flexible sigmoidoscopy but detected by colonoscopy. In a tandem study, we examined the yield of screening colonoscopy in women. METHODS: To determine the prevalence and location of advanced neoplasia, we offered colonoscopy to consecutive asymptomatic women referred for colon-cancer screening. The diagnostic yield of flexible sigmoidoscopy was calculated by estimating the proportion of patients with advanced neoplasia whose lesions would have been identified if they had undergone flexible sigmoidoscopy alone. Lesions were considered detectable by flexible sigmoidoscopy if they were in the distal colon or if they were in the proximal colon in patients who had concurrent small adenomas in the distal colon, a finding that would have led to colonoscopy. The results were compared with the results from VA Cooperative Study 380 for age-matched men and women with negative fecal occult-blood tests and no family history of colon cancer. RESULTS: Colonoscopy was complete in 1463 women, 230 of whom (15.7 percent) had a family history of colon cancer. Colonoscopy revealed advanced neoplasia in 72 women (4.9 percent). If flexible sigmoidoscopy alone had been performed, advanced neoplasia would have been detected in 1.7 percent of these women (25 of 1463) and missed in 3.2 percent (47 of 1463). Only 35.2 percent of women with advanced neoplasia would have had their lesions identified if they had undergone flexible sigmoidoscopy alone, as compared with 66.3 percent of matched men from VA Cooperative Study 380 (P<0.001). CONCLUSIONS: Colonoscopy may be the preferred method of screening for colorectal cancer in women.

Colchicine treatment of alcoholic cirrhosis: a randomized, placebo-controlled clinical trial of patient survival.

BACKGROUND & AIMS: Colchicine improved survival and reversed cirrhosis in several small clinical trials. We compared the efficacy and safety of long-term colchicine, as compared with placebo, in patients with advanced alcoholic cirrhosis. METHODS: Five hundred forty-nine patients with advanced (Pugh B or C) alcoholic cirrhosis were randomized to receive either colchicine 0.6 mg twice per day (n = 274) or placebo (n = 275). Treatment lasted from 2 to 6 years. The primary outcome was all-cause mortality. Secondary outcomes were liver-related morbidity and mortality. Liver biopsy was requested prior to entry and after 24 months of treatment. RESULTS: Attendance at scheduled clinic visits and adherence with study medication were similar in colchicine and placebo groups. Alcohol intake was less than 1 drink per day in 69% of patients. In an intention-to-treat analysis, all-cause mortality was similar in colchicine (49%) and placebo (45%) patients (P = .371). Mortality attributed to liver disease was 32% in colchicine and 28% in placebo patients (P = .337). Fewer patients receiving colchicine developed hepatorenal syndrome. In 54 patients with repeat liver biopsies after 24 or more months of treatment, cirrhosis improved to septal fibrosis in 7 patients (3 colchicine, 4 placebo) and to portal fibrosis in 1 patient (colchicine). CONCLUSIONS: In patients with advanced alcoholic cirrhosis, colchicine does not reduce overall or liver-specific mortality. Liver histology improves to septal fibrosis in a minority of patients after 24 months of treatment, with similar rates of improvement in patients receiving placebo and colchicine. Colchicine is not recommended for patients with advanced alcoholic cirrhosis.

Accuracy of screening for fecal occult blood on a single stool sample obtained by digital rectal examination: a comparison with recommended sampling practice.

BACKGROUND: Many expert panels recommend colorectal cancer screening for average-risk asymptomatic individuals older than 50 years of age. Recent studies have found that 24% to 64% of primary care providers use only the digital fecal occult blood test (FOBT) as their primary screening test. The effectiveness of a single digital FOBT is unknown. OBJECTIVE: To compare the sensitivity and specificity of digital FOBT and the recommended 6-sample at-home FOBT for advanced neoplasia in asymptomatic persons. DESIGN: Prospective cohort study. SETTING: 13 Veterans Affairs medical centers. PATIENTS: 3121 asymptomatic patients 50 to 75 years of age. INTERVENTION: 2665 patients had 6-sample at-home FOBT and digital FOBT, followed by complete colonoscopy. MEASUREMENTS: We measured the sensitivity of digital and 6-sample FOBT for advanced neoplasia and the specificity for no neoplasia. We calculated predictive values and likelihood ratios for advanced neoplasia, defined as tubular adenomas 10 mm or greater, adenomas with villous histology or high-grade dysplasia, or invasive cancer. RESULTS: Of all participants, 96.8% were men; their average age was 63.1 years. The 6-sample FOBT and the single digital FOBT had specificities of 93.9% and 97.5%, respectively, as defined by studying 1656 patients with no neoplasia. Sensitivities for detection of advanced neoplasia in 284 patients were 23.9% for the 6-sample FOBT and 4.9% for the digital FOBT. The likelihood ratio for advanced neoplasia was 1.68 (95% CI, 0.96 to 2.94) for positive results on digital FOBT and 0.98 (CI, 0.95 to 1.01) for negative results. LIMITATIONS: Most patients were men. CONCLUSIONS: Single digital FOBT is a poor screening method for colorectal neoplasia and cannot be recommended as the only test. When digital FOBT is performed as part of a primary care physical examination, negative results do not decrease the odds of advanced neoplasia. Persons with these results should be offered at-home 6-sample FOBT or another type of screening test.

Risk factors for advanced colonic neoplasia and hyperplastic polyps in asymptomatic individuals.

CONTEXT: Knowledge of risk factors for colorectal neoplasia could inform risk reduction strategies for asymptomatic individuals. Few studies have evaluated risk factors for advanced colorectal neoplasia in asymptomatic individuals, compared risk factors between persons with and without polyps, or included most purported risk factors in a multivariate analysis. OBJECTIVE: To determine risk factors associated with advanced colorectal neoplasia in a cohort of asymptomatic persons with complete colonoscopy. DESIGN, SETTING, AND PARTICIPANTS: Prospective, cross-sectional study of 3121 asymptomatic patients aged 50 to 75 years from 13 Veterans Affairs medical centers conducted between February 1994 and January 1997. All participants had complete colonoscopy to determine the prevalence of advanced neoplasia, defined as an adenoma that was 10 mm or more in diameter, a villous adenoma, an adenoma with high-grade dysplasia, or invasive cancer. Variables examined included history of first-degree relative with colorectal cancer, prior cholecystectomy, serum cholesterol level, physical activity, smoking, alcohol use, and dietary factors. MAIN OUTCOME MEASURES: An age-adjusted analysis was performed for each variable to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) associated with having advanced neoplasia compared with having no polyps. We developed a multivariate logistic regression model to identify the most informative risk factors. A secondary analysis examined risk factors for having hyperplastic polyps compared with having no polyps and compared with having advanced neoplasia. RESULTS: Three hundred twenty-nine participants had advanced neoplasia and 1441 had no polyps. In multivariate analyses, we found positive associations for history of a first-degree relative with colorectal cancer (OR, 1.66; 95% CI, 1.16-2.35), current smoking (OR, 1.85; 95% CI, 1.33-2.58), and current moderate to heavy alcohol use (OR, 1.02; 95% CI, 1.01-1.03). Inverse associations were found for cereal fiber intake (OR, 0.95; 95% CI, 0.91-0.99), vitamin D intake (OR, 0.94; 95% CI, 0.90-0.99), and use of nonsteroidal anti-inflammatory drugs (NSAIDs) (OR, 0.66; 95% CI, 0.48-0.91). In the univariate analysis, the inverse association was found with cereal fiber intake greater than 4.2 g/d, vitamin D intake greater than 645 IU/d, and daily use of NSAIDs. Marginal factors included physical activity, daily multivitamin use, and intake of calcium and fat derived from red meat. No association was found for body mass index, prior cholecystectomy, or serum cholesterol level. Three hundred ninety-one patients had hyperplastic polyps as the worst lesion found at colonoscopy. Risk variables were similar to those for patients with no polyps, except that past and current smoking were associated with an increased risk of hyperplastic polyps. CONCLUSIONS: Our data endorse several important risk factors for advanced colonic neoplasia and provide a rationale for prudent risk reduction strategies. Further study is needed to determine if lifestyle changes can moderate the risk of colorectal cancer.

I. Veterans Affairs Cooperative Study of polyenylphosphatidylcholine in alcoholic liver disease: effects on drinking behavior by nurse/physician teams.

BACKGROUND: This multicenter prospective, randomized, double-blind placebo-controlled trial was designed to evaluate the effectiveness of polyenylphosphatidylcholine against the progression of liver fibrosis toward cirrhosis in alcoholics. Seven hundred eighty-nine alcoholics with an average intake of 16 drinks per day were enrolled. To control excessive drinking, patients were referred to a standard 12-step-based alcoholism treatment program, but most patients refused to attend. Accordingly, study follow-up procedures incorporated the essential features of the brief-intervention approach. An overall substantial and sustained reduction in drinking was observed. Hepatic histological and other findings are described in a companion article. METHODS: Patients were randomized to receive daily three tablets of either polyenylphosphatidylcholine or placebo. Monthly follow-up visits included an extensive session with a medical nurse along with brief visits with a study physician (hepatologist or gastroenterologist). A detailed physical examination occurred every 6 months. In addition, telephone consultations with the nurse were readily available. All patients had a liver biopsy before entry; a repeat biopsy was scheduled at 24 and 48 months. RESULTS: There was a striking decrease in average daily alcohol intake to approximately 2.5 drinks per day. This was sustained over the course of the trial, lasting from 2 to 6 years. The effect was similar both in early dropouts and long-term patients, i.e., those with a 24-month biopsy or beyond. CONCLUSIONS: In a treatment trial of alcoholic liver fibrosis, a striking reduction in alcohol consumption from 16 to 2.5 daily drinks was achieved with a brief-intervention approach, which consisted of a relative economy of therapeutic efforts that relied mainly on treatment sessions with a medical nurse accompanied by shorter reinforcing visits with a physician. This approach deserves generalization to address the heavy drinking problems commonly encountered in primary care and medical specialty practices.

II. Veterans Affairs Cooperative Study of polyenylphosphatidylcholine in alcoholic liver disease.

BACKGROUND: Polyenylphosphatidylcholine (PPC) has been shown to prevent alcoholic cirrhosis in animals. Our aims were to determine the effectiveness of PPC in preventing or reversing liver fibrosis in heavy drinkers and to assess the extent of liver injury associated with the reduced drinking achieved in these patients. METHODS: This randomized, prospective, double-blind, placebo-controlled clinical trial was conducted in 20 Veterans Affairs Medical Centers with 789 patients (97% male; mean age, 48.8 years) averaging 16 drinks per day (1 drink = 14 g of alcohol) for 19 years. A baseline liver biopsy confirmed the presence of perivenular or septal fibrosis or incomplete cirrhosis. They were randomly assigned either PPC or placebo. Liver biopsy was repeated at 24 months, and the main outcome measure was the stage of fibrosis compared with baseline. Progression was defined as advancing to a more severe stage. RESULTS: The 2-year biopsy was completed in 412 patients. PPC did not differ significantly from placebo in its effect on the main outcome. Alcohol intake was unexpectedly reduced in both groups to approximately 2.5 drinks per day. With this intake, 21.4% advanced at least one stage (22.8% of PPC patients and 20.0% of placebo patients). The hepatitis C virus-positive subgroup exhibited accelerated progression. Improvement in transaminases and bilirubin favoring PPC was seen at some time points in other subgroups (hepatitis C virus-positive drinkers or heavy drinkers). CONCLUSIONS: PPC treatment for 2 years did not affect progression of liver fibrosis. A trend in favor of PPC was seen for transaminases and bilirubin (in subgroups). One of five patients progressed even at moderate levels of drinking, and thus health benefits commonly associated with moderate drinking do not necessarily extend to individuals in the early stages of alcoholic liver disease.

First-degree relatives of patients with advanced colorectal adenomas have an increased prevalence of colorectal cancer.

BACKGROUND & AIMS: The risk of colorectal cancer in relatives of patients with adenomatous colonic polyps is not well defined. This study assessed whether finding colonic neoplasia during screening colonoscopy was related to the family history of colorectal cancer among the participants' parents and siblings. METHODS: Self-reported family history of colorectal cancer was recorded for all participants in a screening colonoscopy study. The size and location of all polyps were recorded before their removal and histologic examination. Participants were grouped according to the most advanced lesion detected. RESULTS: Three thousand one hundred twenty-one patients underwent complete colonoscopic examination. Subjects with adenomas were more likely to have a family history of colorectal cancer than were subjects without polyps (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.09-1.70). The finding of a small (<1 cm) tubular adenoma as the most advanced lesion was associated with only a modest increase in the OR of colorectal cancer in family members (OR, 1.26; 95% CI, 0.99-1.61), but the presence of an advanced adenoma was associated with a higher OR (OR, 1.62;5% CI, 1.16-2.26). Younger age of adenoma diagnosis was not related to a higher prevalence of a family history of colorectal cancer. CONCLUSIONS: Relatives patients with advanced colorectal adenomas have an increased risk of colorectal cancer. Individuals with advanced colorectal adenomas should be counseled about the increased risk of colorectal cancer among their relatives.

Procedural success and complications of large-scale screening colonoscopy.

BACKGROUND: Indirect evidence and modeling analyses suggest that colonoscopy may be the most cost-effective way to screen the average-risk population for colorectal neoplasia. However, the success and safety of primary colonoscopic screening has not been prospectively evaluated in a multicenter trial. METHODS: Asymptomatic subjects age 50 to 75 years who had not undergone examination of the colon within 10 years were recruited from the general medicine clinics of 13 Department of Veterans Affairs Medical Centers. Eligible patients underwent colonoscopy by study coinvestigators, at which time all polyps were measured, photographed, and removed. Patients were contacted at 24 hours and 1 week to track procedure-related complications. RESULTS: Primary screening colonoscopy was performed in a cohort of 3196 asymptomatic subjects. A "good" preparation was reported in 81% of patients, and colonoscopy to the cecum was successful in 97.2% of cases. Mean insertion time to the cecum and total procedure times were 10.5 (8.7) and 30.6 (19.1) minutes, respectively. No preprocedural patient characteristics were identified that were predictive of an incomplete procedure. At least one polyp was resected in 1672 patients. There was no perforation and no death attributed to colonoscopy. Major morbidity considered to be definitely related to colonoscopy occurred in 9 of 3196 procedures (0.3%): lower GI bleeding requiring intervention (6), myocardial infarction and/or cerebrovascular accident (2), and thrombophlebitis (1). In subjects undergoing only diagnostic procedures, the major complication rate was 0.1%. CONCLUSIONS: Screening colonoscopy can be performed in multiple centers with a high degree of success and safety in large numbers of asymptomatic, average-risk men.