Objectives: The indications for endoscopic submucosal dissection (ESD) for gastric adenoma and gastric cancer have expanded, leading to an increase in the number of patients with high procedural complexity. Post-ESD perforations prolong hospital stays and increase costs. However, no studies have focused on detecting micro-perforations during ESD. This study aimed to identify signs of perforation using abdominal ultrasound during gastric ESD. Materials and methods: This pilot study analyzed 50 patients who underwent abdominal ultrasound (VScan Air™, GE Healthcare) during ESD at Samsung Medical Center (March 2023–July 2024). Perforation was assessed via ultrasound, and post-procedure X-rays were performed for three days to detect free air. Results: Among 50 patients (median age 60, 76.1% male), the median procedure time was 60 min. Lesions were most common in the antrum (30.4%) and lesser curvature (17.4%). Pathology revealed 32.6% well-differentiated and 10.9% moderately differentiated adenomas, with 15.2% showing high-grade dysplasia. Free air was detected in three patients after procedures involving the body wall of the stomach. Abdominal US showed indirect signs of perforation, including an abnormal peritoneal line, hyperechoic shadowing, and an absence of normal gas patterns, confirmed by X-ray. Conclusions: Abdominal US is a simple, useful tool for rapid detection of perforation during ESD, enabling timely intervention. Further multicenter studies are needed to confirm these findings.

Purpose: Cigarette smoking is an established risk factor for colorectal cancer (CRC), yet the association between smoking status, including non-combustible nicotine or tobacco product (NNTP) use, and site-specific CRC risk remains unclear. Methods: This population-based retrospective cohort study used data from 4,489,451 participants in the Korean National Health Insurance System database. Smoking status was classified according to combustible cigarette (CC) and NNTP use. Multivariable Cox regression models were used to estimate adjusted hazard ratios (aHRs) for CRC risk. Results: During a mean follow-up of 3.4 ± 0.4 years, 17,538 incident CRC cases occurred. Compared with never smoking, exclusive CC use was associated with the highest CRC risk (aHR 1.29, 95% CI 1.23–1.35), with elevated risks across the colon, rectum, distal colon, and unspecified sites. Rectal cancer risk was higher for switching from CCs to NNTPs (aHR 1.51, 95% CI 1.19–1.92) and concurrent CC and NNTP use (aHR 1.23, 95% CI 1.04–1.45). Compared with exclusive CC use, all other smoking-status groups had lower CRC risks, with subsite variations. Colon cancer risk was lower for switching from CCs to NNTPs and concurrent CC and NNTP use; rectal cancer risk was lowest for exclusive NNTP use; and distal colon cancer risk was lowest for concurrent CC and NNTP use. Stratified analyses showed significant interactions of smoking status with age and alcohol consumption in relation to CRC incidence. Conclusions: CRC risk varied by smoking status and anatomical subsite. Further studies are needed to clarify the long-term effects of NNTP use on CRC risk.

Background/Objectives: Partially covered duodenal stents rapidly relieve malignant gastric outlet obstruction, but tumor overgrowth restenosis limits durability. We compared six preprocedural inflammatory, nutritional, and immune indices for predicting this outcome in patients with gastric cancer. Methods: We retrospectively analyzed 68 consecutive patients from a prospectively maintained cohort. The primary endpoint was endoscopically or radiologically confirmed tumor overgrowth restenosis. Discrimination was assessed using receiver operating characteristic curves (pairwise DeLong tests with Bonferroni correction) and time-dependent areas under the curve (AUCs) accounting for death as a competing risk. Multivariable cause-specific Cox models were restricted to preprocedural covariates; post-stenting chemotherapy or radiotherapy was examined in time-dependent sensitivity analyses. Results: Technical and clinical success rates were 100% and 94.1%. Seventeen patients (25.0%) developed restenosis at a median of 66 days. The C-reactive protein–albumin–lymphocyte (CALLY) index showed the highest AUC (0.859), followed by the C-reactive protein-to-albumin ratio (CAR; 0.822) and neutrophil-to-lymphocyte ratio (0.774); these three indices did not differ significantly. At an exploratory, internally derived cutoff of ≤0.110, CALLY had 76.5% sensitivity and 84.3% specificity and remained associated with restenosis after adjustment for stenosis site and stent length (adjusted hazard ratio, 12.30; 95% confidence interval, 3.89–38.83; C-index, 0.836), with consistent results in continuous, time-dependent, and tumor-covariate-adjusted analyses. The 180-day cumulative incidence was 52.4% with low CALLY versus 4.3% with high CALLY. Conclusions: C-reactive protein-based indices showed the highest numerical discrimination, although pairwise differences among CALLY, CAR, and NLR were not statistically significant. CALLY is a promising exploratory biomarker for restenosis risk stratification, but its cutoff should not guide clinical decisions until externally validated.

Background/Objectives: Glucagon-like peptide-1 (GLP-1) receptor agonists and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists are used long term for obesity and diabetes, but their oesophageal safety is uncertain: weight loss may reduce Barrett’s oesophagus and adenocarcinoma risk, whereas delayed gastric emptying may worsen reflux. We performed a genetic assessment of target-mediated oesophageal safety. Methods: Two-sample drug-target Mendelian randomisation used cis-expression quantitative trait loci for both receptors (31,684 participants). Outcomes were European genome-wide association studies of gastro-oesophageal reflux disease and the Barrett’s oesophagus/oesophageal adenocarcinoma axis, with a trans-ancestry squamous cell carcinoma comparator. A prespecified gated workflow required positive-control validation, and target specificity required genetic colocalisation (posterior probability of a shared causal variant ≥ 0.70). Candidate metabolic mediators were examined in two-step analyses, and findings were replicated in an independent Finnish population (FinnGen R12). Results: Genetically proxied GLP-1 receptor expression was not associated with reflux disease (odds ratio 0.97, 95% confidence interval 0.85–1.11), arguing against a substantial target-mediated reflux liability; the GIP receptor estimate was not estimable. For the Barrett’s oesophagus/adenocarcinoma endpoint, estimates were near the null for both receptors (GLP-1R 0.96, 0.47–1.96; GIPR 1.00, 0.42–2.37); colocalisation was uninformative because the outcome loci carried no detectable association signal, and wide intervals did not exclude moderate effects. The null reflux findings were reproduced in FinnGen. Adiposity showed the most consistent pathway association, whereas glycaemic traits did not, including when HbA1c was instrumented from a population-based genome-wide association study providing an order of magnitude more variants. Conclusions: GLP-1 receptor perturbation was not associated with reflux disease, providing cautious genetic reassurance. For the Barrett’s oesophagus/adenocarcinoma axis, no target-specific association was demonstrated, but colocalisation was uninformative because the outcome loci carried no detectable signal, and imprecision precludes firm safety conclusions; larger adenocarcinoma-specific studies are warranted.

Background/Objectives: Observational studies in East Asia have not shown increased gastric cancer risk in ulcerative colitis, whereas a previous genetic analysis reported a positive association. Because both diseases have major histocompatibility complex (MHC) signals, we assessed whether the association was most apparent in MHC variants under ancestry-matched instrument selection. Methods: We performed a two-stage, two-sample Mendelian randomization study of 12 East Asian datasets (11 immune-related phenotypes) and a gastric cancer genome-wide association study (7921 cases; 159,201 controls), with instruments selected against the 1000 Genomes East Asian panel. For ulcerative colitis, we compared all, MHC, and non-MHC variants, evaluated signal overlap at HLA-DQA1/DQB1, and assessed cross-disease specificity. Results: Ulcerative colitis was the only phenotype associated with gastric cancer after false-discovery-rate correction (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.09–1.24; q = 1.37 × 10⁻⁴). The MHC estimate was similar (OR 1.18, 95% CI 1.11–1.26), whereas the non-MHC estimate was close to 1 but rested on only two variants and remained imprecise (OR 1.00, 95% CI 0.86–1.17). The traits showed overlapping signals at HLA-DQA1/DQB1, and the MHC variants were associated with several other immune diseases. Conclusions: The positive association was most apparent in MHC variants that were not specific to ulcerative colitis. The association therefore appears to be largely carried by pleiotropic MHC variants, although these data cannot establish the pathway that explains it.