Background/Aims : Long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) increases the risk of peptic ulcers. Tegoprazan, a novel potassium-competitive acid blocker, provides rapid and potent inhibition of acid production. This study evaluated whether tegoprazan 25 mg is non-inferior to lansoprazole 15 mg in preventing NSAID-induced peptic ulcer.Methods : In this double-blind, randomized, active-controlled, multicenter phase III trial, patients requiring NSAIDs for up to 24 weeks were randomized (1:1) to the tegoprazan or the lansoprazole group. The primary endpoint was the incidence of peptic ulcer at week 24 in the per-protocol population. Secondary endpoints were NSAID-induced gastrointestinal symptom-free rates. Safety outcomes included adverse drug reactions (ADRs) and serious adverse events (SAEs).Results : A total of 392 patients were randomized, and 269 patients were analyzed in the perprotocol set. Tegoprazan was non-inferior to lansoprazole for the prevention of gastroduodenal ulcers (p=0.0004). The heartburn-free rate at week 12 was higher in the tegoprazan group (p=0.0421), while other symptom-free rates did not differ significantly. In terms of safety, ADR and SAE rates were comparable and not significantly different.Conclusions : Tegoprazan was non-inferior to lansoprazole in preventing NSAID-induced peptic ulcers with excellent tolerance. Tegoprazan represents a clinically effective alternative gastroprotective therapy (ClinicalTrials.gov identifier NCT04840550).

Background/Aims:Proton pump inhibitors (PPIs) effectively reduce bleeding in patients after endoscopic submucosal dissection (ESD). Tegoprazan, a potassium-competitive acid blocker, provides stronger acid suppression than PPIs do; however, its efficacy in preventing post-ESD bleeding has rarely been studied. The aim of this study was to compare the effects of tegoprazan and pantoprazole on post-ESD bleeding. Methods:In this randomized, multicenter trial, patients undergoing ESD for gastric epithelial neoplasms were randomly assigned to two groups; each received tegoprazan (50 mg once daily for 28 days) or pantoprazole (40 mg intravenously for 48 hours and orally once daily for 26 days). Adverse events and serum gastrin levels were assessed as safety outcomes. Results:The per-protocol set comprised 238 patients (117 tegoprazan, 121 pantoprazole). Noninferiority (within an 8.3% margin) in the post-ESD bleeding rates within 4 weeks was confirmed (risk difference, -6.30%; 95% confidence interval [CI], -14.67% to 2.07%; p=0.0003), with rates of 9.40% (11/117) and 15.70% (19/121) for the tegoprazan and pantoprazole groups, respectively. The bleeding rates within 24 hours were 5.98% (7/117) and 10.74% (13/121), respectively (risk difference, -4.76%; 95% CI, -11.75% to 2.23%). No significant differences were observed in adverse events or serum gastrin levels between the groups. Conclusions:Tegoprazan was non-inferior to pantoprazole in its effectiveness in preventing post-ESD bleeding, with comparable safety profiles. Notably, administering oral tegoprazan can potentially shorten the length of hospital stay and reduce medical costs, supporting its potential clinical value. Tegoprazan is expected to replace high-dose intravenous PPI therapy for patients after ESD (CRIS registration: KCT0006850).

Importance:Esophageal squamous cell carcinoma (ESCC) is highly prevalent in Asian populations and carries a poor prognosis. With growing numbers of cancer survivors, the prognostic impact of prior cancer in ESCC remains unclear. Most existing data are derived from Western cohorts dominated by adenocarcinoma, limiting generalizability to Asian populations. Objective:To evaluate whether prior cancer is associated with overall survival (OS) and esophageal cancer-specific mortality (ECSM) in a nationwide Korean ESCC cohort. Design, Setting, and Participants:A retrospective cohort study of patients with newly diagnosed ESCC across 19 tertiary hospitals in Korea from 2005 to 2017 was conducted. Follow-up was completed in 2017. Data were reanalyzed in August 2025. Exclusion criteria were nonsquamous histology (including adenocarcinoma), diagnosis of esophageal cancer within 6 months of a prior cancer, multiple prior cancers, and hematologic cancers. Exposures:History of cancer before the diagnosis of ESCC, classified by cancer type and latency (≤5 years vs >5 years). Main Outcomes and Measures:The primary outcome was OS, and the secondary outcome was esophageal cancer-specific mortality (ECSM). Hazard ratios (HRs) and cause-specific hazard ratios (CSHRs) were estimated after adjustment for clinicopathologic and treatment variables. Propensity score-adjusted Cox regression and competing risk regression models were used. Subgroup analyses were conducted by prior cancer type and latency period. Results:Of the 5557 patients (mean [SD] age, 64.7 [8.9] years; 5168 [93.0%] male), 368 (6.6%) had a prior cancer and were older and more often diagnosed at an earlier stage than those without prior cancer. Patients with a prior cancer had significantly poorer outcomes, with a median OS of 3.58 (95% CI, 2.50-4.92) vs 4.25 (95% CI, 3.83-4.58) years and a 3-year ECSM of 8.35% (95% CI, 4.42%-12.29%) vs 4.98% (95% CI, 4.17%-5.78%) compared with those without a prior cancer. Prior cancer was independently associated with worse OS (HR, 1.25; 95% CI, 1.07-1.47) and ECSM (CSHR, 1.89; 95% CI, 1.09-3.29). Among prior cancer types, patients with a history of stomach, head and neck, or lung cancer demonstrated poorer OS (HR, 1.63; 95% CI, 1.24-2.15; P < .001). A latency of 5 or more years was also associated with reduced OS (HR, 1.27; 95% CI, 1.03-1.57; P = .02). Conclusions and Relevance:In this nationwide Korean cohort study, prior cancer was an independent adverse prognostic factor in ESCC, with stomach, head and neck, and lung cancers associated with the poorest outcomes.

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.

Background/Aims : Zastaprazan (JP-1366) is a novel potassium-competitive acid blocker with a fast onset and prolonged duration. This study aimed to assess the efficacy and safety of zastaprazan versus lansoprazole in patients with gastric ulcers.Methods : A total of 329 subjects with confirmed gastric ulcers participated in a phase 3, multicenter, randomized, double-blind, active-controlled clinical study. Subjects were randomized to receive zastaprazan 20 mg or lansoprazole 30 mg once daily up to 8 weeks. The primary endpoint was the cumulative healing rate of gastric ulcers as confirmed by upper gastrointestinal endoscopy at 8 weeks in patients. Secondary endpoints included ulcer healing rate, symptom recovery, quality of life changes, and safety assessment results.Results : In the per-protocol set, the cumulative healing rate at 8 weeks was 100.00% (146/146) for zastaprazan 20 mg and 97.06% (132/136) for lansoprazole 30 mg, while at week 4, the healing rates were 93.84% (137/146) and 91.91% (125/136), respectively. Zastaprazan was noninferior to lansoprazole in ulcer healing, while the incidence of adverse events was comparable between groups. Gastrin levels increased during the treatment and declined after the treatment in both groups.Conclusions : An 8-week therapy involving zastaprazan 20 mg demonstrated noninferiority to lansoprazole 30 mg in the cumulative rate of healing of gastric ulcers at 8 weeks, and the two demonstrated similar safety profiles. (ClinicalTrials.gov identifier NCT05448001)

PURPOSE:Male sex is a recognized risk factor for colorectal adenoma, yet whether the associations of Helicobacter pylori, atrophic gastritis (AG), and intestinal metaplasia (IM) with colorectal adenoma differ by sex remains unclear. This study evaluated the sex-stratified and combined associations of anti-H. pylori IgG seropositivity, AG, and IM with conventional colorectal adenoma. MATERIALS AND METHODS:This multicenter cross-sectional study included 806 participants from a Korean health-screening cohort who underwent gastroscopy with H. pylori testing and colonoscopy within 3 years. Anti-H. pylori IgG seropositivity was determined by enzyme-linked immunosorbent assay, AG and IM were assessed endoscopically. Multivariable logistic regression models were adjusted for age, sex, body mass index, smoking, and alcohol consumption. RESULTS:Colorectal adenoma was identified in 209 participants (25.6%). Anti-H. pylori IgG seropositivity was independently associated with colorectal adenoma (adjusted odds ratio [aOR], 1.848; 95% confidence interval [CI], 1.323 to 2.581; p<0.001). AG was not significant after adjustment. IM was independently associated in a separate model (aOR, 1.648; 95% CI, 1.125 to 2.415; p=0.010), but showed only borderline significance in the combined model when including H. pylori seropositivity (aOR, 1.440; 95% CI, 0.973 to 2.131; p=0.068), whereas anti-H. pylori IgG seropositivity remained significant. Participants with both H. pylori seropositivity and IM showed the highest odds of colorectal adenoma. In sex-stratified analyses, anti-H. pylori IgG seropositivity was independently associated in males (aOR, 1.811; 95% CI, 1.147 to 2.860; p=0.011) but not in females, whereas IM was independently associated in females (aOR, 2.086; 95% CI, 1.129 to 3.856; p=0.019) but not in males. Formal interaction tests were not statistically significant. CONCLUSIONS:Anti-H. pylori IgG seropositivity and IM were associated with conventional colorectal adenoma, whereas AG was not significant after adjustment. Sex-stratified analyses suggested potential sex-related patterns, with H. pylori seropositivity appearing more prominent in males and IM appearing more prominent in females.

Helicobacter pylori (H. pylori) screening reduces the incidence and mortality of gastric cancer (GC). This study evaluated the cost-effectiveness of incorporating H. pylori screening into the Korean National Gastric Cancer Screening Program. A Markov model was developed to evaluate the cost-effectiveness of adding H. pylori screening to the existing national endoscopic screening program. The model simulated a virtual cohort of individuals aged ≥ 40 years and compared the current biennial endoscopy-only strategy (S1) with eight intervention strategies involving one-time or repeated H. pylori eradication at varying ages and intervals. Sensitivity analyses were performed to test the robustness of the results. All intervention strategies resulted in higher QALYs and costs than S1. H. pylori screening at age 40 (S2) was the most cost-effective (ICUR = 3,892,429 KRW/QALY). Other cost-effective strategies included H. pylori screening at ages 40 and 50 years (S5), every 6 years from ages 40 to 60 years (S9), and every 4 years during the same period (S8). Health outcome comparisons showed reductions in both cumulative cancer incidence and mortality with eradication-based strategies. Adding H. pylori screening to Korea’s national endoscopic screening program is a cost-effective strategy for the prevention of gastric cancer. These findings support the potential integration of screening into existing national screening policies, with implications for improving health outcomes and optimizing healthcare resource use.

BACKGROUND:Tegoprazan, a potassium-competitive acid blocker, offers potent and sustained acid inhibition and potentially improves eradication efficacy. AIM:This study aimed to evaluate the efficacy and safety of tegoprazan-based triple therapy with two dosing regimens compared with that of lansoprazole-based therapy for first-line Helicobacter pylori eradication. METHODS:This randomized, double-blind, active-controlled, multicenter trial was conducted at 19 referral hospitals in South Korea (February 2023-April 2024). Treatment-naïve adults with H. pylori infection were randomized 1:1:1 to receive 14-day triple therapy with tegoprazan, 50 mg (TAC1), tegoprazan, 100 mg (TAC2), or lansoprazole, 30 mg (LAC), each combined with amoxicillin 1000 mg and clarithromycin 500 mg, administered twice daily. The primary endpoint was H. pylori eradication rate in the modified intention-to-treat (mITT) population, with a non-inferiority margin of -10%. Secondary endpoints included subgroup analyses based on clarithromycin resistance and safety assessments. RESULTS:Of the 564 screened patients, 382 were randomized. In the mITT analysis (mean age, 54.9 years; 54.3% male), eradication rates were 86.0%, 85.5%, and 78.7% for TAC1, TAC2, and LAC, respectively. Both tegoprazan-based regimens met the non-inferiority criteria. Among clarithromycin-resistant infections, the eradication rates were higher for TAC1 (47.8%) and TAC2 (50.0%) than for LAC (35.5%), although the difference was not statistically significant. Safety profiles were comparable across the groups, with no serious drug-related adverse events. CONCLUSION:Tegoprazan-based triple therapies, at 50- and 100-mg doses, were non-inferior to lansoprazole-based therapy and were well tolerated. Our findings indicated that tegoprazan-based triple therapy is a viable first-line option for H. pylori eradication. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT05933031.

BACKGROUND Vonoprazan consistently demonstrates superior Helicobacter pylori eradication (HPE) rates compared to other potassium-competitive acid blockers (P-CABs), yet the pharmacological basis for this heterogeneity remains unclear. We hypothesized that the acid dissociation constant (pKa) – which determines acid stability and parietal cell accumulation – may explain the differential efficacy among individual P-CABs. AIM To examine whether pKa values predict clinical efficacy of P-CABs for HPE and erosive esophagitis healing. METHODS A systematic review and network meta-analysis were conducted. Randomized controlled trials (RCTs) comparing P-CABs with proton pump inhibitors (PPIs) were identified from core databases (up to January 2026). Risk of bias was assessed using RoB 2.0 and certainty of evidence using GRADE. RESULTS Thirty RCTs (7639 patients) were included for HPE. High-pKa P-CABs (vonoprazan of 9.06, keverprazan of 9.12) achieved 82%-84% eradication in clarithromycin-resistant infections vs 32%-40% with PPIs, while low-pKa P-CAB achieved only 47.8% (not significant vs PPI). For erosive esophagitis (10 RCTs; 4196 patients), high-pKa zastaprazan (9.95) achieved 100% Los Angeles classification grade C/D healing vs 83.3% with esomeprazole, whereas low-pKa P-CABs showed inferior outcomes. Spearman correlation analysis revealed a positive association between pKa and efficacy (ρ = 0.80). However, fexuprazan (pKa of 9.04) showed PPI-equivalent outcomes despite high-pKa, highlighting pKa as necessary but not sufficient for clinical efficacy. Network ranking confirmed high-pKa P-CABs as top-ranked agents. No publication bias was detected. CONCLUSION P-CAB efficacy may not be uniform across the class. High-pKa P-CABs (≥ 9.0) were associated with higher eradication rates in clarithromycin-resistant infections and superior healing in severe esophagitis, whereas low-pKa P-CABs showed limited advantages over PPIs. The pKa may serve as a hypothesis-generating pharmacological parameter, though all P-CAB comparisons were indirect and prospective validation is needed.

For the treatment of advanced colorectal neoplasms, colon endoscopic submucosal dissection (ESD) is a crucial technique, although it is time-consuming. The purpose of this study was to evaluate the efficacy of a recently developed one-step knife (OSK) in colon ESD and compare its performance with that of a conventional knife (CK). Between July 2020 and November 2021, patients scheduled to undergo colorectal ESD were randomly assigned to either the OSK group or the CK group. The primary outcome was the total submucosal injection time. Additionally, total procedure time, treatment outcomes, adverse events, and operator convenience were analyzed. Data from 53 patients (28 in the OSK group and 25 in the CK group) were analyzed. The mean total injection time was lower in the OSK group than in the CK group (186 s [IQR, 116.8–249.5] vs. 265 s [IQR, 130.5–553.0]), but the difference was not statistically significant (P = 0.082). The total procedure time tended to be shorter in the OSK group than in the CK group (15.5 min [IQR, 11.3–22.8] vs. 20 min [IQR, 13.5–42.5], P = 0.110). Resection rates and adverse events did not differ between the two groups. A greater proportion of endoscopists expressed high satisfaction with the OSK, particularly regarding submucosal injection. Compared to the CK, OSK use led to shorter injection and procedure times, though not statistically significant. The use of this newly developed endoscopic knife can potentially enhance the effectiveness and efficiency of colorectal ESD (Clinical Research Information Service: KCT0005123).

BACKGROUND:Bacteroides-centric gut dysbiosis reported to exacerbates liver cirrhosis via inflammation and fibrosis, therefore utilizing Bacteroides species as microbiome-based therapeutic logical to mitigate disease progression. MATERIALS AND METHODS:Feces were collected from 52 Healthy and 144 Liver cirrhosis individuals for V3-V4 dependent 16rRNA-bsed comparative metagenomics analysis, followed a by microbiome depleted and non-depleted DDC mice model to explain the role of Bacteroidetes phylum classified microbial species P. plebeius in liver fibrosis pathophysiological pathways. RESULTS:Bacteroides presented cirrhosis-dependent decrease in human and animal microbiome, and negatively correlated to key molecular pattern associated with cirrhosis. P. plebeius significantly reduced in abundance and identified as a microbial biomarker for cirrhosis (AUC = 0.73) and treatment with P. plebeius significantly improved the levels of cirrhosis-related phenotypical and biochemical markers in the microbiome-depleted cirrhosis group. P. plebeius decrease the expression of S100a9, CCR1, ADAM8, TREM2, ITGAM, and MYO5A which are primarily responsible for inducing inflammation in liver cirrhosis. P. plebeius downregulated the fibrosis related genes expression including CD51, PLAT, ITGA3, CXCR4, and TGFBR1 and gene related to extracellular matrix formation including COL1A1, LTBP2, S100A6, and SMCO2. Additionally, P. plebeius treatment decreased the expression of hepatotoxicity-related genes including LPL, KRT18, ALDOA, and MCM10, and increased the expression of FABP1 and RDX. Additionally, P. plebeius normalized the expression of genes connected to two pathophysiological process including TIMP4, TGFB3, S100A8, PLSCR1, MMP8, CXCL4, and BMP. CONCLUSIONS:Our study revealed P. plebeius as a multifaceted bio-therapeutic candidate that normalized dysregulated gene expression and reversed hepatic inflammation, fibrogenesis, and hepatotoxicity.

CKD-495 is a newly developed drug extracted from Cinnamomum cassia Presl. This phase II study assessed the clinical benefits of CKD-495 in the treatment of acute and chronic gastritis. This study randomly assigned 250 patients with endoscopically-proven gastric mucosal erosion to five groups. The groups received either 75 mg or 150 mg of CKD-495, 100 mg of rebamipide, 60 mg of Artemisiae argyi folium 95% ethanol ext. (20 ⟶ 1) (Stillen; Dong-A ST Co., Ltd., Seoul, Korea), or placebo for 2 weeks, respectively. The primary endpoint was the erosion improvement rate, and the secondary endpoints were erosion cure rates, improvement rates of gastrointestinal symptoms, edema, redness, and hemorrhage. Drug-related adverse events were evaluated. The endoscopic erosion improvement rate was significantly higher in the 75 mg CKD-495 group than in the other groups in both the full analysis set (73% vs. 41%, 45%, 52%, 48% for the 75 mg CKD-495, 150 mg CKD-495, placebo, 60 mg Stillen, and 100 mg rebamipide groups, respectively) and the per-protocol set (PPS) (75% vs. 37%, 45%, 51%, 50%). The cure rate of gastric erosion was significantly higher in the 75 mg CKD-495 group than in the other groups. The improvement rates of hemorrhage erosion were significantly higher in the 150-mg CKD-495 group. No significant differences were observed in the safety profiles. No serious adverse events or drug reactions were observed. These results demonstrate that 75 mg of CKD-495 has excellent efficacy for the treatment of endoscopic and symptomatic improvements for acute and chronic gastritis. Trial Registration: ClinicalTrials.gov identifier: NCT03437785.

BackgroundIn Korea, the National Cancer Screening Program (NCSP) was implemented in 1999 and provides biennial endoscopy for adults aged ≥40 years. The NCSP has contributed to the early detection of gastric cancer and reduction of associated mortality in Korea. Helicobacter pylori is the main cause of gastric cancer. Screening for and eradication of H pylori reduces the incidence and mortality of gastric cancer. Previous studies have reported that screening for H pylori is a cost-saving intervention that can significantly decrease gastric cancer burden in areas with a high prevalence of H pylori infection. However, no study has examined whether incorporating H pylori screening into national endoscopic screening is cost effective. ObjectiveThis study aims to evaluate the cost-effectiveness of incorporating H pylori screening into Korea’s National Gastric Cancer Screening Program. MethodsWe have developed a Markov model to compare two strategies: (1) endoscopy screening every 2 years starting at the age of 40 years (conventional screening), and (2) H pylori screening at the age of 40 years followed by continuous endoscopy screening every 2 years. We will also conduct a comparative analysis by varying the age at which the H pylori screening is performed. The primary outcome is the incremental cost-utility ratio (ICUR), calculated by dividing the incremental cost by the incremental quality-adjusted life-years (QALYs) between the two strategies. A probabilistic sensitivity analysis will be performed to test the uncertainty of the cost-effectiveness results. A sensitivity analysis will identify the most influential variables for cost-effectiveness. ResultsThe primary outcome parameter is the cost-effectiveness of adding H pylori testing to the current NCSP, which is expressed as the ICUR. Costs and utilities are discounted at an annual rate of 4.5%. The ICUR threshold is set at KRW 50 million (US $36,719), which is the South Korean gross domestic product per capita. This research has been funded by a Patient-Centered Clinical Research Coordinating Center grant from the Ministry of Health & Welfare, Republic of Korea (grant RS-2024-00398474). This study will analyze and synthesize previously published information and is thus exempt from institutional review board approval. Data collection started in June 2024 and was completed in May 2025. Study results will be published in peer-reviewed journals and presented at national and international conferences throughout 2025. ConclusionsWe will examine whether introducing H pylori testing and eradication therapy into the NCSP is a more cost-effective strategy for reducing gastric cancer risk than conventional endoscopy-based screening. Our study also examines the optimal age for H pylori screening, as well as the optimal screening frequency. International Registered Report Identifier (IRRID)DERR1-10.2196/72228