BACKGROUND AND STUDY AIM:Individuals classified as "high-risk" at initial colonoscopy face an elevated risk of metachronous advanced colorectal neoplasms (meta-ACRN), but risk heterogeneity within this group remains unclear. We aimed to stratify meta-ACRN risk among high-risk individuals based on their synchronous neoplastic burden. PATIENTS AND METHODS:This prospective cohort study utilized data from a Taiwanese multicenter trial (NCT03373136). We included participants with conventional high-risk findings (3-10 low-risk adenomas [LRAs] or any high-risk adenoma [HRA]). The primary outcome was meta-ACRN incidence. Adjusted incidence rate ratios (aIRRs) were calculated using multivariable Poisson regression, stratifying patients by baseline synchronous burden, with the 3-4 LRAs group as reference. RESULTS:Among 730 participants undergoing surveillance (mean follow-up 2.4 years), 81 (11.1%) developed meta-ACRN. A single HRA did not significantly increase meta-ACRN risk compared to 3-4 LRAs (aIRR 2.02; 95% confidence interval(CI) 0.83-4.90). However, risk escalated significantly when the index HRA was accompanied by synchronous LRA(s) (aIRR 2.56; 95% CI 1.24-5.39) or synchronous HRA(s) (aIRR 3.93; 95% CI 1.77-8.73) (P for trend = .001). Furthermore, applying a more severe modified advanced adenoma criteria, an identical dose-response pattern emerged, culminating in a >5-fold increased risk for severe metachronous outcomes (aIRR 5.23; 95% CI 1.50-18.22) when accompanied by synchronous HRA(s) . CONCLUSIONS:Meta-ACRN risk within the conventional high-risk population is highly heterogeneous and driven primarily by baseline synchronous neoplastic burden. Surveillance intervals should be personalized, reserving shorter intervals for patients with advanced lesions accompanied by synchronous adenomas.
BACKGROUND AIMS:Multi-target stool DNA (mt-sDNA) is an established stool-based colorectal cancer screening test, yet long-term performance is not well-described. We evaluated follow-up colonoscopy rates & quality, neoplasia yield, and repeat-testing adherence over 10 years with an integrated screening program. METHODS:We assembled a retrospective cohort of mt-sDNA tests (September 2014-July 2025) within a multi-site health system. A validated large-language-model pipeline extracted colonoscopy, pathology, and quality endpoints from free-text reports. Detection outcomes (adenoma detection rate, advanced neoplasia, modified advanced adenoma, sessile serrated lesion (SSL), and negative exams) were calculated among high-quality exams; adenocarcinoma, bowel preparation adequacy, and cecal intubation rate (CIR) used all screening exams. We assessed colonoscopy completion ≤1 year after positive mt-sDNA, follow-up colonoscopy findings, findings by time-to-colonoscopy, and adherence to repeat mt-sDNA after negative result. RESULTS:Among 148,624 tests in 110,410 individuals, positivity was 13.6%. Of 19,506 positives, 65.1% completed colonoscopy within 12 months (median 82 days). Colonoscopy after a positive mt-sDNA had high yield: advanced adenoma diagnosis was 30.7%; adenocarcinoma was 1.3%. Of patients who had colonoscopy within 3 years of a negative mt-sDNA test, 45.2% had adenoma/serrated lesion, 9.3% had advanced adenoma and 0.5% had colon cancer.Adenoma detection rate after positive mt-sDNA (>50%) exceeded specialty society quality benchmarks and increased over time; Longer intervals (>6 months) to colonoscopy after a positive test were associated with higher advanced adenoma (trend P=0.001).After an initial negative mt-sDNA, only 35.3% were screened again by mt-sDNA testing within 3 years. CONCLUSIONS:Over a decade,mt-sDNA screening achieved high colonoscopy qualitybut revealed critical gaps in the care cascade. One-third of positive tests lacked timely follow-up and nearly two-thirds of negative tests were not repeated on schedule, suggesting opportunities for system-level interventions.
The hereditary adenomatous colorectal polyposis syndromes are incurable, systemic, cancer risk predisposition syndromes with substantial morbidity and mortality. They differ in their mode of inheritance, age at disease onset, phenotypic expression, and cancer risk. The most common cancer risks involve the gastrointestinal tract including the colon, rectum, duodenum, ampulla, and stomach. Identifying these syndromes through personal and family history risk assessment and germline genetic testing, along with timely surgical and endoscopic management, can reduce cancer incidence and mortality. These guidelines use the Grading of Recommendations, Assessment, Development, and Evaluation methodology to provide clinical guidance on the selection of individuals who should undergo a risk assessment for a hereditary adenomatous colorectal polyposis syndrome, modality and timing of germline genetic testing, cancer risk mitigation through endoscopic and surgical interventions, and the role of chemoprevention. This document reviews the approach to genetic testing in patients with phenotypic colorectal polyposis and the impact of presymptomatic diagnosis in families with a known familial germline pathogenic variant or clinical features suggestive of a hereditary adenomatous polyposis syndrome. Management strategies for patients based on genetic test results or without genetic testing are provided. We also review colorectal and extracolonic phenotypic benign and malignant manifestations of the known hereditary syndromes with a focus on the 2 most common hereditary colorectal polyposis syndromes: familial adenomatous polyposis and MUTYH-associated polyposis. The document concludes with recommendations on polyposis and cancer risk mitigation strategies and highlights updates to management since the previous guideline was published.
Vibration-controlled transient elastography (VCTE) requires a three-hour fasting period to minimize postprandial increases in liver stiffness measurement (LSM), but this recommendation predates widespread use of glucagon-like peptide-1 receptor agonists (GLP-1-RAs), which alter gastric emptying and postprandial hemodynamics. We evaluated whether current fasting guidance remains valid in 23 participants, including 12 with cirrhosis, receiving GLP-1 RAs who underwent serial LSM following standardized meal ingestion. LSM increased 20.6% at 30-60 minutes but fell back to <10% by 3 hours. Most patients returned to baseline by 3-4 hours, supporting adequacy of a three-hour fast, however, some patients required 4 hours for full return to baseline.
INTRODUCTION:REBYOTA and VOWST are the first FDA-approved live biotherapeutic products for recurrent Clostridioides difficile infection (CDI). Previous FDA safety alerts (2019-2020) regarding invasive infections from investigational fecal microbiota transplantation underscore the need for postmarketing surveillance of these novel products. The aims of this study were to characterize the real-world safety profiles of REBYOTA and VOWST using the FDA Adverse Event Reporting System and compare them against established CDI therapeutics. METHODS:We performed a disproportionality analysis of FDA Adverse Event Reporting System data (Q1; 2020-Q4; 2025). REBYOTA and VOWST were identified as primary suspect drugs using Biologics License Application numbers and drug name matching. Comparators included fidaxomicin, bezlotoxumab, and vancomycin (CDI-filtered). Four methods were applied: reporting odds ratio (ROR), proportional reporting ratio, information component, and empirical Bayes geometric mean. Signals required ≥2 methods agreement. RESULTS:We identified 231 REBYOTA and 813 VOWST primary suspect reports, yielding 18 and 54 disproportionality signals, respectively. Both products' signals were consistent with known gastrointestinal adverse events. No signals were detected for bacteremia, septic shock, or anaphylaxis. Death was reported at lower-than-expected frequency for VOWST (ROR 0.29; 95% confidence interval 0.15-0.53). A VOWST-specific urinary tract infection (UTI) cluster (Klebsiella UTI ROR 405.73; Pseudomonal UTI ROR 168.54) was identified; head-to-head comparison showed no significant UTI difference vs REBYOTA (ROR 1.39, not significant), suggesting stimulated reporting bias rather than a biological signal. Route-dependent adverse event profiles differed between oral VOWST and rectal REBYOTA. DISCUSSION:FDA-approved live biotherapeutic products demonstrate reassuring postmarketing safety profiles without transmitted infection signals. The extreme VOWST UTI signal is likely attributable to FDA-mandated expedited reporting obligations rather than a causal drug effect.
INTRODUCTION:Colorectal cancer (CRC) incidence is increasing among younger individuals in many countries. We examined CRC incidence and mortality by age group, site, and histology in Canada. METHODS:Data from the Canadian Cancer Registry and the Canadian Vital Statistics Death Database were used to determine CRC incidence from 1992 to 2019 and mortality from 1974 to 2022. We calculated incidence by age group, site, and histology and mortality by age group and site. Annual percent change was calculated using Joinpoint Regression. Age-period-cohort models with splines were run to indicate influence on CRC incidence. RESULTS:CRC incidence was stable for individuals 20-29 years, increased for those 30-49, remained stable for 50-54, and decreased for 55 years and older. Proximal, distal, and rectal cancer incidence was stable or increased for individuals less than 55 and decreased for those over 55. Adenocarcinoma CRCs increased for those less than 55. Mucinous and signet ring cell CRCs decreased or remained stable for all ages. Neuroendocrine CRCs increased for most ages. Age, cohort, and period effects are evident. CRC mortality stopped decreasing in the late 1990s for individuals 20-49 but decreased for those over 50. Proximal and distal CRC mortality decreased for all ages. Rectal cancer mortality increased. DISCUSSION:CRC incidence and mortality in Canada vary by age, site, and histology. In addition to a reduction in the screening start age, CRC screening programs must focus on individuals 50-54 years of age because they have not experienced a decrease in CRC incidence.
INTRODUCTION:Experimental and limited clinical studies suggest that curcumin has chemopreventive activity in the colorectum. This large-scale clinical trial evaluated the efficacy and safety of curcumin in patients with previously endoscopically resected colorectal neoplasia. METHODS:This randomized, double-blind, placebo-controlled multicenter trial enrolled patients with previously resected colorectal neoplasia. Eligible patients were randomly assigned (1:1), using a stratified, computer-generated scheme to receive oral submicron-powdered curcumin (Theracurmin®; 180 mg twice daily) or identical placebo capsules for 2 years. All analyses were performed according to a modified intention-to-treat principle including all randomly assigned patients who underwent the 2-year colonoscopy. RESULTS:Between April 1, 2016, and March 31, 2020, 577 patients were randomly assigned to curcumin (n=287) or placebo groups (n=290). The detection rate of recurrent colorectal adenomas at 2 years, the primary endpoint, did not differ significantly between groups (risk ratio [RR] 0.98; 95% CI 0.82-1.16). However, the detection rate of adenomas ≥6 mm, a prespecified lesion category recommended for endoscopic resection in Japanese guidelines, was significantly lower with curcumin (RR, 0.56; 95% CI, 0.33-0.95; P=0.04). The per-patient number of adenomas ≥6 mm was also significantly lower (P=0.03), and the median size of all detected adenomas was significantly smaller in the curcumin group (P=0.003). The inhibitory effect appeared more pronounced in patients with higher baseline adenoma burden and in men in exploratory analyses. Treatment-related adverse events were infrequent and mild. DISCUSSION:Curcumin inhibited the growth of recurrent colorectal adenomas, despite no significant reduction in the overall incidence of recurrence. This is the first large-scale randomized clinical trial demonstrating the suppressive efficacy of curcumin against colorectal neoplasia, and also highlighting the importance of incorporating growth-related endpoints, in addition to incidence- or detection-based endpoints, in chemoprevention studies. (jRCTs061180079).
INTRODUCTION:Eosinophilic gastritis (EG) and/or eosinophilic duodenitis (EoD; EG/EoD) are rare, chronic inflammatory disorders lacking approved treatments. METHODS:We report a randomized, double-blind, placebo-controlled phase 3 trial evaluating cendakimab, an anti-IL-13 monoclonal antibody, in 48 Japanese patients with EG/EoD. RESULTS:At week 16, cendakimab significantly reduced mean peak gastrointestinal eosinophil counts versus placebo (least squares mean difference -223.2 eosinophils/high-power field; P=0.003), with numerical improvements across symptom domains. Histologic effects were maintained at week 48 and a favorable safety profile was observed. DISCUSSION:These findings highlight IL-13 inhibition as a potential treatment strategy for EG/EoD.
INTRODUCTION:Current guidelines suggest swallowable capsule-sponge devices with biomarkers can be used as alternatives to endoscopy for detecting Barrett's Esophagus (BE) in at-risk patients. We analyzed the screening performance of capsule-sponge with Trefoil-Factor-3 (TFF3) in patients with symptomatic acid reflux and assessed test performance across individual risk factors. METHODS:The study protocol was registered in PROSPERO (CRD420250652091). Eligible studies reported results for both capsule-sponge-TFF3 and endoscopic assessment in adults with reflux symptoms and no history of BE. A systematic search was conducted through August 29, 2025. Two reviewers independently screened and extracted data using COVIDENCE. Risk of bias was assessed via QUADAS-2. Sensitivity and specificity were estimated in SAS v9.4 using bivariate mixed models allowing estimation of likelihood ratios, diagnostic odds ratios, and predictive values; meta-regression models were estimated for individual risk factors, acid suppressant use and BE prevalence. RESULTS:We identified six studies involving 1,454 participants in our meta-analysis. Pooled sensitivity for BE was 0.87 (95% CI: 0.80-0.94), specificity was 0.88 (95% CI: 0.80-0.95), negative predictive value at 20% prevalence was 0.96 (95% CI: 0.95-0.98), and the diagnostic odds ratio was 47.82 (95% CI: 44.99-50.83). Smoking and acid suppressant use were associated with increased specificity. DISCUSSION:Overall, our findings show that capsule-sponge-TFF3 is an effective minimally invasive screening tool for patients at risk of BE. Increased specificity in smokers may help reduce unnecessary endoscopies in this higher-risk group.
Background and objectives: Biliary drainage(BD)in distal malignant biliary obstruction(DMBO)is often hampered by difficult biliary cannulation(DBC)during endoscopic retrograde cholangiopancreatography(ERCP). Advanced cannulation techniques(aERCP)may overcome DBC but still fail in up to 15% of cases, increasing the risk of adverse events(AEs). Early endoscopic ultrasound-guided BD(eEUS-BD)is a potential alternative. The aim of this study is to directly compare safety and efficacy of EUS-BD and aERCP. Methods: This is a retrospective, multicentric study(29 centres in United States, Canada, Europe), including patients with DMBO and common bile duct(CBD)diameter >12 mm, treated up to 2024. DBC cases managed with either eEUS-BD or aERCP were analysed. A 1:2 propensity score-matched cohort was generated to ensure comparability, with regression modeling and inverse probability of treatment weighting(IPTW)performed as sensitivity analyses. AEs rate was the primary outcome; secondary outcomes included BD failure and clinical success. Results: Standard cannulation failed in 2066/10,738(19.2%)ERCPs. aERCP and eEUS-BD were attempted in 1733 and 333 cases, respectively. After matching, 313 patients per EUS-BD group and 626 patients per aERCP group were analyzed. AEs occurred in 18.2% of aERCPs and 9.3% of eEUS-BD(p<0.01), with post-procedural pancreatitis the most frequent AE after aERCP(55 cases, 12.0%). Both regression and IPTW confirmed the robustness of these findings on the entire cohort. Technical success was significantly lower with aERCP(82.0% vs. 95.9%, p<0.01), clinical success was comparable(94.5% vs. 96.4%, p=0.89). Conclusions: In patients with DMBO and dilated CBD, eEUS-BD is associated with fewer AEs and higher technical success than aERCP, supporting its role as a safer, more effective option in DBC.
Rome V marks a paradigm shift in pediatric disorders of gut-brain interaction (DGBI). The new Rome V criteria introduced new, updated, and refined definitions for pediatric DGBI. A central feature of this framework is the shift toward anchoring diagnoses more firmly in pathophysiology and anatomic regions rather than age groups. Accordingly, the criteria are now organized into two major categories: upper gastrointestinal DGBI and lower gastrointestinal and biliary DGBI. Several new disorders have been added, including esophageal, feeding, and discomfort disorders, along with additional pain-related conditions. Existing criteria have been further refined, and emerging biomarkers are incorporated to support diagnoses. Finally, there is greater harmony between adult and pediatric diagnoses to support a seamless transition across the age continuum.
The liver cirrhosis network (LCN) developed a pragmatic clinical consensus definition for cirrhosis that we aimed to validate with natural language processing in 2 large VA centers. Of the 5465 patients identified with ICD codes for cirrhosis, 42.7% met the LCN definition. Meeting the LCN definition increased the probability of a liver-related event (LRE; new ascites, SBP, hepatic encephalopathy, HCC or variceal bleed) by 44% in multivariable analysis despite adjustment versus patients who did not meet these criteria. Each additional component of the LCN criteria increased the risk of LREs by 43%, which was led by FIB-4 and platelet counts.
