Annals of Gastroenterology

Temporal trends in colorectal cancer mortality in Greece, 2014-2022: a Joinpoint regression analysis

Tommy Rizkala — 2026-06-01

Atrophic gastritis of distinct etiologies: malignant potential in Helicobacter pylori-associated and autoimmune forms

Theodore Rokkas — 2026-06-01

Atrophic gastritis is an important step in the Correa cascading pathway. It forms a pivotal period between chronic inflammation and a biologically-disrupted mucosal epithelial phenotype leading to gastric neoplasia. From a more than superficial perspective, both Helicobacter pylori (H. pylori)- associated atrophic gastritis and autoimmune atrophic gastritis converge on glandular loss and metaplastic reprogramming, but their etiologic pathways, molecular mediators, topographic distribution and neoplastic characteristics differ drastically. H. pylori infection induces multifocal atrophy and incomplete intestinal metaplasia and is the typical path to intestinal-type gastric adenocarcinoma, while autoimmune gastritis results in corpus-restricted oxyntic destruction, severe hypochlorhydria, hypergastrinemia, and a distinctive predisposition to type I gastric neuroendocrine neoplasms. Despite H. pylori eradication, the epigenetic landscape of metaplastic mucosa often persists, requiring risk-adapted surveillance approaches underpinned by histologic systems such as OLGA and OLGIM. This narrative review aggregates mechanistic, epidemiologic and clinical evidence establishing malignant potentials for both etiologies of atrophic gastritis, and offers an integrated framework for surveillance and prevention.

Keywords Atrophic gastritis, Helicobacter pylori, autoimmune gastritis, gastric cancer, intestinal metaplasia

Ann Gastroenterol 2026; 39 (3): 283-293

Vonoprazan–amoxicillin dual therapy improves 14-day eradication and reduces adverse events in patients with Helicobacter pylori infection: an updated landmark systematic review and meta-analysis of 11 randomized trials with subgroup analysis

Urvashi Bharia — 2026-06-01

Background Vonoprazan, a potassium-competitive acid blocker (P-CAB), may enhance Helicobacter pylori (H. pylori) eradication in combination with amoxicillin. With increasing drug resistance, dual therapy is a potential alternative to standard triple and quadruple regimens. This systematic review and meta-analysis evaluated the efficacy and safety of vonoprazan dual therapy (VDT) as first-line treatment for H. pylori infection.

Methods A comprehensive systematic search on PubMed, Embase, Scopus and Cochrane Library identified 11 randomized controlled trials (RCTs) involving 2877 patients (1439 VDT; 1438 control), comparing VDT with standard triple therapy, quadruple therapy or individualized treatment regimens for H. pylori eradication, up to March 2025. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using the Mantel-Haenszel method for dichotomous outcomes. Random or fixed-effects models were applied based on heterogeneity, assessed using the Higgins I2 statistic. A P-value <0.05 was considered statistically significant.

Results VDT significantly improved eradication rates compared to standard therapy (RR 1.06, 95%CI 1.00-1.12; P<0.001), driven primarily by 14-day regimens (RR 1.08, 95%CI 1.01-1.15; P=0.0001); no benefit was seen for 7-day regimens (RR 0.97, 95%CI 0.91-1.04; P=0.30), with low heterogeneity (8.6%). There was no significant difference in drug compliance (RR 1.02, 95%CI 0.99-1.05; P=0.03), with moderate heterogeneity (50.3%). VDT demonstrated significantly fewer adverse events (RR 0.66, 95%CI 0.52-0.84; P<0.001).

Conclusions VDT is as effective as standard therapies overall, but shows clear superiority in 14-day regimens, with no advantage in 7-day durations. The observed heterogeneity was probably due to differences in treatment duration and regional variability in resistance.

Keywords Helicobacter pylori, vonoprazan, dual therapy, triple therapy, amoxicillin

Ann Gastroenterol 2026; 39 (3): 294-302

Incidence of Barrett’s esophagus and esophageal cancer following sleeve gastrectomy versus liraglutide therapy

Edward Butt — 2026-06-01

Background Sleeve gastrectomy has consistently been linked to gastroesophageal reflux disease and Barrett’s esophagus. At the same time, the long-term effects of glucagon-like peptide-1 receptor agonists, particularly short-acting agents such as liraglutide, are less well understood. We compared the incidence of Barrett’s esophagus and esophageal cancer among patients treated with liraglutide vs. those who underwent sleeve gastrectomy.

Methods We conducted a retrospective cohort study using a large electronic health record database. Adults with obesity treated with liraglutide were compared to those who underwent sleeve gastrectomy. Propensity score matching was used to balance demographics, comorbidities, medication use and body mass index. The primary outcome was the incidence of Barrett’s esophagus without dysplasia diagnosed 3 years or more after treatment. Secondary outcomes involved esophageal cancer and Barrett’s esophagus with dysplasia. Risk ratios (RR) and 95%
confidence intervals (CI) were calculated.

Results We analyzed 10,048 sleeve gastrectomy and 10,048 liraglutide patients. Barrett’s esophagus without dysplasia was more frequent in the sleeve (0.3%) than in the liraglutide (0.1%) group, with a risk difference of 0.2% (95%CI 0.1-0.3%) and RR 2.70 (95%CI 1.31-5.56). Barrett’s esophagus with dysplasia was also more common in the sleeve group (0.1% vs. 0%). No significant difference in esophageal cancer was observed.

Conclusions Sleeve gastrectomy is associated with a higher risk of Barrett’s esophagus compared to liraglutide, though esophageal cancer rates did not differ. Liraglutide may offer a safe option for patients at risk of esophageal complications.

Keywords Barrett’s esophagus, cancer, liraglutide, sleeve, obesity

Ann Gastroenterol 2026; 39 (3): 303-309

Liver fibrosis severity evaluated by shear-wave elastography is associated with procoagulant and systemic inflammatory activity in patients with cirrhosis

George Kalambokis — 2026-06-01

Background Hemostatic and inflammatory pathways may drive liver fibrogenesis. We investigated whether coagulation and systemic inflammatory activities influence liver fibrosis severity in patients with cirrhosis and thrombocytopenia.

Methods Two patient groups were evaluated according to liver stiffness measurement (LSM) through shear wave elastography: ≥25 kPa (n=100) vs. <25 kPa (n=100). Anti-hemostatic parameters (platelet count, factors II, V, VII, IX, X, XI, XII, and XIII, fibrinogen, and a2-antiplasmin), pro-hemostatic parameters (factor VIII [FVIII], protein C [PC], protein S, antithrombin, von Willebrand factor-antigen [vWf-Ag], plasminogen, and plasminogen activator inhibitor-1), the FVIII-to-PC ratio as procoagulant imbalance index, and systemic inflammation markers (serum lipopolysaccharide-binding protein [LBP], tumor necrosis factor [TNF]-α, and interleukin [IL]-6) were measured. Cirrhosis severity was evaluated by model for end-stage liver disease (MELD) score.

Results Patients with LSM≥25 kPa exhibited significantly higher decompensation rates, MELD score, FVIII-to-PC ratio, and levels of FVIII, PC, protein S, vWf-Ag, LBP, TNF-α, and IL-6, and significantly lower levels of anti-hemostatic parameters than those with LSM<25 kPa. In multivariate analysis evaluating coagulation parameters alone or alongside inflammatory markers, FVIII-to-PC ratio (P=0.01/P=0.03) and LBP (P=0.01) were linked to LSM≥25 kPa after adjusting for MELD score and prior decompensation. LSM correlated significantly with FVIII-to-PC ratios, and levels of FVIII, PC, vWf-Ag, LBP, TNF-α and IL-6, in both the total cohort and patients with LSM≥25 kPa. LBP, TNF-α and IL-6 levels correlated significantly with the FVIII-to-PC ratios and vWf-Ag levels in both LSM subgroups.

Conclusion Higher procoagulant and systemic inflammatory activities are associated with greater liver fibrosis severity in cirrhotic patients.

Keywords Liver fibrosis, cirrhosis, systemic inflammation, prothrombotic activity, shear wave elastography

Ann Gastroenterol 2026; 39 (3): 310-318

Sociodemographic disparities in documented nonadherence to medication for hepatic encephalopathy: a National Inpatient Sample analysis

Christopher Behrend — 2026-06-01

Background Medication nonadherence is often cited as a precipitant of hepatic encephalopathy. However, the underlying reasons and clinical implications of medication nonadherence in this population are understudied.

Methods This was a retrospective cross-sectional analysis of hospitalization for hepatic encephalopathy within the National Inpatient Sample from 2016-2022. Multivariate logistic regression analysis was used to assess for patient factors associated with documented nonadherence; results were presented as adjusted odds ratios (aOR) and 95% confidence intervals (CI). Additionally, analysis was performed to assess for associations between documented nonadherence and clinical outcomes.

Results Medication nonadherence was documented in 44,685 of the 250,755 (17.8%) hospitalizations for hepatic encephalopathy. Nonadherence was documented more in Black (aOR 1.35, 95%CI 1.24-1.47; P<0.001) and Hispanic (aOR 1.20, 95%CI 1.12-1.28; P<0.001) patients compared to White patients. Substance use diagnoses (aOR 1.36, 95%CI 1.29-1.43; P<0.001) and housing insecurity (aOR 2.47, 95%CI 2.11-2.90; P<0.001) were both associated with documented nonadherence. Discharge against medical advice was more frequent in patients with documented nonadherence (33.8% vs. 18.8%, P<0.001), whereas mortality, need for mechanical ventilation, cost, and length of stay were all less.

Conclusions Marginalized populations have higher rates of documented medication nonadherence in cases of hospitalization for hepatic encephalopathy. Structural barriers and provider bias could both be contributing to the documented medication nonadherence in this population.

Keywords Medication adherence, patient discharge, retrospective studies, socioeconomic disparities in health

Ann Gastroenterol 2026; 39 (3): 319-325

Predictors of self-care among informal caregivers of patients with inflammatory bowel disease: a cross-sectional study

Daniele Napolitano — 2026-06-01

Background Informal caregivers of individuals with inflammatory bowel disease (IBD) face unpredictable responsibilities that may compromise their health. While caregiver burden and psychological distress are well-documented, little is known about caregivers’ self-care practices and their determinants.

Methods A multicenter cross-sectional study was conducted across 9 Italian IBD Units between April and June 2024. Caregivers completed validated measures of self-care (Self-Care of Informal Caregivers Inventory), caregiver burden (Zarit Burden Interview), and psychological distress (Depression Anxiety Stress Scales–21). Logistic regression models were used to identify predictors of inadequate self-care behaviors.

Results A total of 229 caregivers were included (mean age 52.2±13.6 years; 59% women). Adequate self-care was high for routine behaviors such as daily hygiene (98.7%) and regular meals (87.8%), but low for emotionally and socially demanding behaviors, including professional counseling (18.3%), asking for assistance (12.2%), and accepting help (20.6%). Being unpartnered was associated with a higher likelihood of inadequate physical activity (odds ratio [OR] 2.38, 95% confidence interval [CI] 1.32-4.17). Higher anxiety was related to inadequate attention to bodily discomfort (OR 1.32, 95%CI 1.11-1.56), whereas higher caregiver burden and depression were associated with a lower likelihood of inadequate emotional wellbeing strategies (OR 0.97, 95%CI 0.95-0.99), and inadequate help-seeking (OR 0.80, 95%CI 0.68-0.93), respectively.

Conclusions Caregivers maintain basic health habits but show marked vulnerabilities in emotional and social self-care domains. Psychological distress and relational factors play a key role, underscoring the need for caregiver-centered interventions that promote emotional wellbeing, resilience, and help-seeking.

Keywords Caregiver burden, caregiving relationships, inflammatory bowel disease, psychological distress, self-care

Ann Gastroenterol 2026; 39 (3): 326-335

Temporal trends in colorectal cancer mortality in Greece, 2014-2022: a Joinpoint regression analysis

Vasilios Papastergiou — 2026-06-01

Background Colorectal cancer (CRC) is the second most deadly cancer worldwide; however, data on CRC mortality in Greece remain scarce. This study aimed to evaluate temporal trends in CRC mortality in Greece between 2014 and 2022, focusing on sex- and age-groups.

Methods CRC mortality and demographics were gathered from the Hellenic Statistical Authority (ELSTAT). Age-adjusted mortality rates (AAMRs) were calculated, using age-specific mortality rates standardized to the WHO standard population. For age subgroups, crude mortality rates were analyzed. Temporal trends were established using Joinpoint regression with estimation of annual percent change (APC).

Results During the study period, there were 24,973 CRC-related deaths (14,201 men, 56.8%). The overall AAMRs were 10.7 [95% confidence interval (CI) 10.3-11.1] per 100,000 population in 2014 and 10.2 (95%CI 9.7-10.6) in 2022, exhibiting no significant change (APC -0.62, 95%CI -1.34 to 0.13; P=0.11). Men had consistently higher AAMRs than women throughout the study. The AAMRs for women significantly declined between 2014 and 2022 (APC -1.02, 95%CI -1.98 to -0.03; P=0.03). Contrarily, the decline was not significant in men (APC -0.35, 95%CI -1.34 to 0.67; P=0.48). All age subgroups for both sexes exhibited declining trends, except for men 45-59 years who showed a non-significant uptrend throughout the study, and men <45 years who showed a significant increase between 2017 and 2022.

Conclusions In Greece, CRC mortality significantly declined between 2014 and 2022 in women, although not in men. Increasing trends observed in younger men warrant further consideration, aiming to optimize prevention and outcomes of CRC.

Keywords Colorectal cancer, mortality, temporal trends, Joinpoint regression, Greece

Ann Gastroenterol 2026; 39 (3): 336-343

Investigating the relationship between vitamin D levels and immune-mediated colitis

Varun Vemulapalli — 2026-06-02

Background The aim of this study was to evaluate the potential association between serum vitamin D levels and the incidence and severity of immune-mediated colitis (IMC), and to explore the potential role of vitamin D supplementation as a preventative or therapeutic intervention.

Methods This was a single-center study in which we retrospectively reviewed patients who received immune checkpoint inhibitor (ICI) treatment, had serum vitamin D levels measured within 6 months before or after starting treatment, and subsequently developed IMC.

Results A total of 179 patients were included in the study. Patients were stratified by serum vitamin D levels: 121 (67.6%) had levels ≤40 ng/mL, and 58 (32.4%) had levels >40 ng/mL. Individuals with vitamin D levels ≤40 ng/mL had more severe diarrhea (65.0%) and severe colitis (48.0%), both defined as common terminology criteria for adverse events grade ≥2, compared to those with vitamin D levels >40 ng/mL (45.6% and 28.6%, respectively; P=0.022 and P=0.034). Univariate analysis revealed that patients receiving vitamin D during ICI therapy had ~1.9 times higher odds of requiring steroid treatment (odds ratio [OR] 1.899, 95% confidence interval [CI] 1.0338-3.474; P=0.038). Patients with grade ≥2 diarrhea had 11 times higher odds of requiring steroids (OR 11.11, 95%CI 5.35-22.73; P<0.001). Patients with colitis grade ≥2 had 3 times higher odds of steroid use (OR 3.08, 95%CI 1.54-6.13; P=0.001).

Conclusions This study suggests that there is a relationship between serum vitamin D levels and IMC. Vitamin D deficiency in those with IMC was associated with more severe disease, and those with more severe disease were more likely to require steroid therapy.

Keywords Immune checkpoint inhibitor, immune mediated colitis, vitamin D

Ann Gastroenterol 2026; 39 (3): 344-351

Evaluating outcomes of alternative pathologic terminology in high-grade dysplastic colorectal lesions

Shaman Dalal — 2026-06-02

Background Pathologists occasionally classify colorectal adenomas with dysplastic mucosal invasion as intramucosal carcinoma (IMC), or carcinoma in situ (CIS), instead of high-grade dysplasia (HGD), potentially leading to earlier surveillance colonoscopies and inappropriate surgical referrals. We aimed to analyze differences in the management of patients with these diagnoses, and examined the factors that may lead to inappropriate early interval (IEI) follow-up recommendations for surveillance.

Methods We reviewed 870 colonoscopy and pathology reports from 2015-2022, excluding cases of colorectal cancer, inflammatory bowel disease, and lesions not amenable to endoscopic resection. Surveillance appropriateness was defined in accordance with the 2020 US Multi Society Task Force (USMSTF) guidelines. ANOVA and Fisher’s exact tests were used to compare patient groups, while binary logistic regression identified predictors of IEI.

Results Among 233 patients analyzed, 86% had HGD, 12% IMC and 2% CIS. IMC (odds ratio [OR] 4.09, 95% confidence interval [CI] 1.52-11.5; P=0.01) and CIS (OR 3.70, 95%CI 0.57-29.7; P=0.17) had significantly higher IEI rates relative to HGD. Predictors of IEI included Black race (OR 2.39, 95%CI 1.17 - 5.03; P=0.02), en bloc resection (OR 10.9, 95%CI 3.53-49.0; P<0.001), and IMC (OR 4.09, 95%CI 1.52-11.50; P=0.01). No differences in surveillance outcomes were observed.

Conclusions Endoscopic resection is curative for dysplasia confined to the mucosa in completely resected colonic adenomas. Labeling these lesions as “carcinoma” increases IEI recommendations without improving outcomes. Our findings support the 2020 USMSTF guidelines to standardize all dysplastic colorectal lesion terminology as HGD to ensure appropriate follow-up intervals.

Keywords High-grade dysplasia, intramucosal carcinoma, carcinoma in situ, surveillance colonoscopy, colorectal cancer

Ann Gastroenterol 2026; 39 (3): 352-359

Risk of colorectal cancer incidence and mortality after removals of polyps: a cohort study using the UK Biobank

Ziqi Wan — 2026-06-02

Background Colorectal cancer (CRC) is a leading cause of cancer death worldwide, however, the risk of newly-diagnosed CRC and its related mortality after polypectomy have not been conclusively determined.

Methods Prospective cases with polypectomy were identified in the UK Biobank. The age- and sexstandardized incidence ratio (SIR) and standardized mortality ratio (SMR) were calculated to assess the risk of CRC between the removal group and both the non-index-colonoscopy group (no record of diagnostic colonoscopy) from the UK Biobank and the general population in England. We also estimated the effect of removal compared with the polyp-free group using a competing risk model.

Results During a median follow up of 10 (1-44) years (51,136 person-years), 78 incident CRCs (153/100,000 person-years), and 16 CRC-specific deaths (31/100,000 person-years) were identified in the removal group. Compared with the general population in England, the removal group had a similar risk of incident CRC (SIR 0.81, 95% confidence interval [CI] 0.64-1.01; P=0.060), whereas the CRC-specific mortality was 52% lower (SMR 0.48, 95%CI 0.28-0.78; P=0.004). Compared with the non-index-colonoscopy group, CRC-specific deaths after polyp removal were not significantly different (SMR 1.64, 95%CI 0.94-2.66; P=0.050). Compared with the polyp-free group, the risks of incidence and mortality in the removal group were both greater (incidence: adjusted hazard ratio [HR] 6.17, 95%CI 4.36-8.74; P<0.001; mortality: adjusted HR 3.25, 95%CI 1.65-6.41; P<0.001).

Conclusion Polypectomy reduced but not eliminated the risk of CRC for polyp-positive participants to the level of the general population, reinforcing the importance of procedural quality and tailored surveillance strategies.

Keywords Polypectomy, colorectal cancer, incidence, mortality, UK Biobank

Ann Gastroenterol 2026; 39 (3): 360-371

Postpartum nonsteroidal anti-inflammatory drug exposure does not increase risk for flare in patients with inflammatory bowel disease

Loren G. Rabinowitz — 2026-06-02

Background Postpartum pain management is an important part of maternal healthcare. Nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen are typically offered as firstline pharmacologic therapies for postpartum pain. There is a belief that NSAIDs may play a role in exacerbating inflammatory bowel disease (IBD); as a result, some obstetricians avoid NSAIDs for postpartum pain management in patients with IBD. However, data concerning the relationship between short-term NSAID use and IBD flares are inconsistent. The aim of this study was to assess whether hospital postpartum NSAID use is associated with postpartum IBD flare within 9 months from delivery.

Methods This single-center retrospective cohort study included patients with IBD, aged 18 years or older, who had singleton live births between January 1, 2016, and November 30, 2023. Chart review data for each eligible patient were collected for a 9-month postpartum period.

Results Among the 187 patients included in the study, there was no difference between NSAID-exposed and non-exposed patients in postpartum IBD flare: 10/114 (9%) vs. 10/73 (14%), respectively, P=0.335. Based on multivariate regression analysis, NSAID exposure was not associated with postpartum IBD flare, adjusted for active disease at conception and IBD flare during pregnancy: adjusted odds ratio (aOR) 0.6, 95% confidence interval (CI) 0.2-1.7; P=0.327. The same was true for mode of delivery and inpatient opioid exposure: aOR 0.6, 95%CI 0.1-1.5; P=0.291.

Conclusions Postpartum NSAID use for pain control is not associated with IBD flare 9 months after delivery. Large prospective studies are needed to confirm this finding.

Keywords Nonsteroidal anti-inflammatory drugs, pregnancy, inflammatory bowel disease, flare

Ann Gastroenterol 2026; 39 (3): 372-377

Methodological concerns in evaluating water exchange combined with distal attachments for adenoma detection

Selim Coskun — 2026-06-02

Authors’ reply

Felix W. Leung — 2026-06-02

Comments on modeling strategy and data handling in a meta-analysis of anti-integrin αvβ6 for primary sclerosing cholangitis

Javier Arredondo Montero — 2026-06-02

Authors’ reply

Alexandra Argyrou — 2026-06-02