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BACKGROUND & AIMS: Colonoscopy reduces colorectal cancer (CRC) incidence and mortality in Lynch syndrome (LS) carriers. However, a high incidence of postcolonoscopy CRC (PCCRC) has been reported. Colonoscopy is highly dependent on endoscopist skill and is subject to quality variability. We aimed to evaluate the impact of key colonoscopy quality indicators on adenoma detection and prevention of PCCRC in LS. METHODS: We conducted a multicenter study focused on LS carriers without previous CRC undergoing colonoscopy surveillance (n = 893). Incident colorectal neoplasia during surveillance and quality indicators of all colonoscopies were analyzed. We performed an emulated target trial comparing the results from the first and second surveillance colonoscopies to assess the effect of colonoscopy quality indicators on adenoma detection and PCCRC incidence. Risk analyses were conducted using a multivariable logistic regression model. RESULTS: The 10-year cumulative incidence of adenoma and PCCRC was 60.6% (95% CI, 55.5%-65.2%) and 7.9% (95% CI, 5.2%-10.6%), respectively. Adequate bowel preparation (odds ratio [OR], 2.07; 95% CI, 1.06-4.3), complete colonoscopies (20% vs 0%; P = .01), and panchromoendoscopy use (OR, 2.14; 95% CI, 1.15-3.95) were associated with significant improvement in adenoma detection. PCCRC risk was significantly lower when colonoscopies were performed during a time interval of less than every 3 years (OR, 0.35; 95% CI, 0.14-0.97). We observed a consistent but not significant reduction in PCCRC risk for a previous complete examination (OR, 0.16; 95% CI, 0.03-1.28), adequate bowel preparation (OR, 0.64; 95% CI, 0.17-3.24), or previous use of high-definition colonoscopy (OR, 0.37; 95% CI, 0.02-2.33). CONCLUSIONS: Complete colonoscopies with adequate bowel preparation and chromoendoscopy use are associated with improved adenoma detection, while surveillance intervals of less than 3 years are associated with a reduction of PCCRC incidence. In LS, high-quality colonoscopy surveillance is of utmost importance for CRC prevention.

BACKGROUND & AIMS: Lynch syndrome is characterized by DNA mismatch repair (MMR) deficiency. Some patients with suspected Lynch syndrome have DNA MMR deficiencies but no detectable mutations in genes that encode MMR proteins-this is called Lynch-like syndrome (LLS). There is no consensus on management of patients with LLS. We collected data from a large series of patients with LLS to identify clinical and pathology features. METHODS: We collected data from a nationwide-registry of patients with colorectal cancer (CRC) in Spain. We identified patients whose colorectal tumors had loss of MSH2, MSH6, PMS2, or MLH1 (based on immunohistochemistry), without the mutation encoding V600E in BRAF (detected by real-time PCR), and/or no methylation at MLH1 (determined by methylation-specific multiplex ligation-dependent probe amplification), and no pathogenic mutations in MMR genes, BRAF, or EPCAM (determined by DNA sequencing). These patients were considered to have LLS. We collected data on demographic, clinical, and pathology features and family history of neoplasms. The chi(2) test was used to analyze the association between qualitative variables, followed by the Fisher exact test and the Student t test or the Mann-Whitney test for quantitative variables. RESULTS: We identified 160 patients with LLS; their mean age at diagnosis of CRC was 55 years and 66 patients were female (41%). The Amsterdam I and II criteria for Lynch syndrome were fulfilled by 11% of cases and the revised Bethesda guideline criteria by 65% of cases. Of the patients with LLS, 24% were identified in universal screening. There were no proportional differences in sex, indication for colonoscopy, immunohistochemistry, pathology findings, or personal history of CRC or other Lynch syndrome-related tumors between patients who met the Amsterdam and/or Bethesda criteria for Lynch syndrome and patients identified in universal screening for Lynch syndrome, without a family history of CRC. CONCLUSIONS: Patients with LLS have homogeneous clinical, demographic, and pathology characteristics, regardless of family history of CRC.

Background & Aims The combination of β-blockers and band ligation is the standard approach to prevent variceal rebleeding, but bleeding recurs and mortality is high. The lipid-lowering drug simvastatin decreases portal pressure, improves hepatocellular function, and might reduce liver fibrosis. We assessed whether adding simvastatin to standard therapy could reduce rebleeding and death after variceal bleeding in patients with cirrhosis. Methods We performed a multicenter, double-blind, parallel trial of 158 patients with cirrhosis receiving standard prophylaxis to prevent rebleeding (a β-blocker and band ligation) in Spain from October 2010 through October 2013. Within 10 days of bleeding, subjects were randomly assigned, but stratified by Child-Pugh class of A or B vs C, to groups given simvastatin (20 mg/d the first 15 days, 40 mg/d thereafter; n = 69) or placebo (n = 78). Patients were followed for as long as 24 months. The primary end point was a composite of rebleeding and death, and main secondary end points were the individual components of the composite (death and rebleeding). Results The primary end point was met by 30 of 78 patients in the placebo group and 22 of 69 in the simvastatin group ( P = .423). Seventeen patients in the placebo group died (22%) vs 6 patients in the simvastatin group (9%) (hazard ratio for adding simvastatin to therapy = 0.39; 95% confidence interval: 0.15–0.99; P = .030). Simvastatin did not increase survival of patients with Child-Pugh class C cirrhosis. Rebleeding occurred in 28% of patients in the placebo group and 25% in the simvastatin group ( P = .583). Serious adverse events occurred in 53% of patients in the placebo group and 49% in the simvastatin group ( P = .752); the percentages of serious adverse events related to therapy were 11% in the placebo group vs 8% in the in the simvastatin group ( P = .599). Two patients in the simvastatin group, each with advanced liver disease, developed rhabdomyolysis. Conclusions In a randomized controlled trial, addition of simvastatin to standard therapy did not reduce rebleeding, but was associated with a survival benefit for patients with Child-Pugh class A or B cirrhosis. Survival was not the primary end point of the study, so these results require validation. The incidence of rhabdomyolysis in patients receiving 40 mg/d simvastatin was higher than expected. European Clinical Trial Database ID: EUDRACT 2009-016500-24; ClinicalTrials.gov ID: NCT01095185.