Therapeutic Advances in Gastroenterology最新文献

Background: There is no consensus on whether proton pump inhibitor (PPI) or vonoprazan (VPZ) is superior in preventing delayed bleeding (DB) after endoscopic submucosal dissection (ESD) of the stomach.

Objectives: This study aimed to compare the efficacy of combined intravenous and oral PPI versus oral VPZ alone therapy in preventing DB after gastric ESD in a consecutive and large case series.

Design: Retrospective study.

Methods: This study included consecutive patients who underwent gastric ESD at Chiba University Hospital from January 2017 to July 2023. Before 2019, patients received intravenous omeprazole 20 mg in the morning and evening on the day of ESD and the day after. Thereafter, esomeprazole 20 mg was administered orally once daily, which was continued for generally 28 days (defined as the PPI group). From 2020 onward, patients received oral VPZ 20 mg once daily starting on the day of ESD, also typically continued for 28 days (defined as the VPZ group). DB rates between the PPI and VPZ groups were compared using propensity score matching.

Results: There were 720 cases (856 tumors) of gastric ESD during the study period, of which 352 (409 tumors) were in the PPI group and 368 (447 tumors) in the VPZ group. Propensity score matching for 9 covariates related to DB rates for gastric ESD ultimately produced 329 best matches. There was no significant difference in DB rates between the two groups (4.3% vs 3.6%, p = 0.84).

Conclusion: Though further prospective studies are needed to draw definitive conclusions, it was suggested that the easily administered oral VPZ can be an important option for acid suppression after gastric ESD.

Percutaneous biliary drainage and radiofrequency ablation (RFA) have long been used for malignant biliary obstruction (MBO). Endoscopic radiofrequency ablation (eRFA) has been performed for this condition, and it has also been performed in combination with endoscopic biliary stenting, and/or chemotherapy. Although eRFA is apparently being used in a wide variety of applications, there are insufficient reports on its use, and mostly from retrospective studies. This article summarizes and seeks to clarify the status of RFA for MBO. eRFA for MBO with endoscopic biliary stenting was shown in a recent meta-analysis to improve overall survival (OS) at 6 months of follow-up, but there was no improvement of stent patency. A combination of eRFA and chemotherapy reportedly improved OS and progression-free survival, especially for patients with locally-advanced biliary tract cancer. When eRFA was performed for occluded self-expandable metal stents (SEMSs), the time to recurrent obstruction in the eRFA group was significantly longer than that in the patients treated by uncovered SEMS placement alone. eRFA has also been performed for inoperable ampullary tumors, and the median OS was significantly longer in an eRFA group than in a stenting alone group, and there was improvement of obstructive jaundice. eRFA reportedly has a high clinical success rate for patients after endoscopic papillectomy. Future studies should examine the synergistic effects of using immune-checkpoint inhibitors and eRFA together. eRFA has been shown to have therapeutic effects in various applications, but further large prospective research is needed to improve the level of evidence.

Background: Ulcerative colitis (UC) is associated with an increased risk of venous thromboembolism (VTE) and cardiovascular (CV) events, particularly during flares. While concerns have emerged regarding the intrinsic CV and thromboembolic risk of Janus kinase inhibitors, real-world data on baseline risk profiles in UC remain scarce.

Objectives: This study aimed to assess the thromboembolic and cardiovascular risk profiles of UC outpatients initiating advanced therapies and to evaluate the incidence of related clinical events.

Design: We conducted a cross-sectional study with prospective longitudinal follow-up at a single tertiary center.

Methods: Consecutive UC outpatients who initiated an advanced therapy between June 2020 and December 2023 were enrolled. Baseline VTE and CV risk factors were assessed using medical records, a structured online questionnaire, and the International Physical Activity Questionnaire. CV risk was estimated using the Atherosclerotic Cardiovascular Disease and Systematic Coronary Risk Estimation 2 calculators. Patients were monitored for VTE and CV events until December 2024.

Results: The study included 300 patients (median age 44 years; 45.3% female). Most had 0-1 VTE risk factor (61.0%) and elevated C-reactive protein was the most common (45.0%). CV risk stratification showed that most non-elderly patients had low or moderate risk, while elderly patients showed higher risk. During a median follow-up of 27 months (683 person-years), only four events (1.3%, incidence rate 0.59 per 100 P-Y) were recorded: two VTE (both in patients on ustekinumab, one with multiple risk factors and one with cirrhosis) and two CV events (angina and retinal ischemia in low-risk patients on vedolizumab and adalimumab).

Conclusion: In our cohort, both thromboembolic and CV risks were overall low. CV risk was higher in elderly patients. The incidence of VTE and CV events during follow-up was low. These findings suggest that concerns regarding the intrinsic VTE and CV risks associated with Janus kinase inhibitors may not fully apply to UC patients.

Background: The impact of dynamic changes in alpha-fetoprotein (AFP) levels on the prognosis of hepatocellular carcinoma (HCC) remains controversial.

Objectives: This review aims to clarify the prognostic value of dynamic changes in AFP levels in patients with HCC treated with immune checkpoint inhibitors (ICIs).

Data sources and methods: PubMed, EMBASE, Cochrane Library, and Web of Science were searched to collect eligible studies published up to July 29, 2024. The Newcastle-Ottawa Scale score was used to assess the quality of included studies, and Stata 15.1 statistical software was used for statistical analysis.

Results: This review included 23 studies involving 2860 patients with HCC. Following treatment with ICIs, a dynamic decrease in AFP levels was significantly associated with improved overall survival (OS; hazard ratio (HR) 0.40, 95% confidence interval (CI), 0.34-0.48) and progression-free survival (PFS; HR 0.39, 95% CI, 0.34-0.45). Conversely, dynamically increased AFP levels were linked to poorer OS (HR 2.34, 95% CI, 1.69-3.23) and PFS (HR 2.62, 95% CI, 1.92-3.56). Subgroup analyses revealed that while the association with OS was influenced by factors such as treatment regimen and sample size, the prognostic value of AFP changes for PFS appeared more consistent across various subgroups.

Conclusion: This review demonstrates that dynamic changes in AFP levels are significantly associated with OS and PFS in HCC patients treated with ICIs, particularly in those receiving combination ICI regimens.

Trial registration: PROSPERO registration number CRD42024599795.

Background: Inflammatory digestive diseases can majorly impact the physical and mental well-being of affected patients.

Objectives: This meta-analysis aimed to assess the efficacy of psychological interventions (including psychotherapy, mindfulness, cognitive-behavioral therapy, relaxation techniques, meditation, stress management, self-help strategies, psychoeducation, motivational interviewing, hypnotherapy, solution-based therapy, and counseling) on mental parameters and disease-related outcomes in this population.

Design: This was a systematic review and meta-analysis.

Data sources and methods: The systematic search was conducted on July 31, 2025. Randomized controlled trials (RCTs) were eligible. Outcomes were assessed at the end of therapy and at various time points during the follow-up period (short-, mid-, and long-term follow-up). Owing to the differences in scales and questionnaires, the standardized mean difference (SMD) was used to pool effect sizes, along with corresponding 95% confidence interval (CI). Higgins and Thompson's I ² statistics were used to assess heterogeneity.

Results: We included 24 RCTs that investigated the effect of psychological interventions on depressive symptoms in inflammatory digestive diseases, totaling 1572 participants. The pooled analysis found that psychological interventions resulted in a moderate reduction of depression compared to controls (SMD -0.46; CI: -0.75; -0.18). Data from 19 RCTs with 1593 patients also demonstrated a moderate reduction in anxiety symptoms in subjects undergoing psychological interventions (SMD -0.58; CI: -0.94; -0.22). The pooled analysis of 13 RCTs with 772 participants found that psychological therapy was associated with a moderate decrease in stress (SMD -0.53; CI: -1.04; -0.03). The additional analysis of follow-up data showed that benefits resulting from treatment gradually decreased, showing no significant difference at the end of the long-term follow-up period.

Conclusion: Psychological interventions effectively improve mental health-related outcomes in patients with inflammatory digestive diseases. Since benefits from therapy seem to decrease during the follow-up period, repeated interventions may be necessary.

Trial registration: The study protocol was prospectively registered on PROSPERO (CRD42021282965).

Background: Patients with inflammatory bowel disease (IBD) are at heightened risk of infection for several reasons.

Objectives: To evaluate the factors predisposing IBD patients to gastrointestinal (GI) infections, the elements influencing the severity of these infections and the likelihood of hospitalization, and the impact of GI bacterial infections on the progression of IBD.

Design: Retrospective, single-center, case-control study of IBD patients with GI infection and matched controls.

Methods: Patients with ulcerative colitis (UC) or Crohn's disease who tested positive for Campylobacter spp., Yersinia spp., Salmonella spp., or enterohemorrhagic Escherichia coli were enrolled. Clostridioides difficile was excluded due to its distinct epidemiology. For each patient with a GI bacterial infection, a control patient with IBD but without the infection was matched by sex and proximity in calendar age. Data were collected from electronic patient records spanning from January 2008 to June 2023. Various risk factors for medical consultations and hospitalizations due to GI bacterial infections were evaluated. Fisher's exact test and logistic regression were used to assess the associations between GI infections and clinical outcomes.

Results: Of the 5194 IBD patients in the IBD registry, 123 patients had a confirmed GI infection, the majority having UC (n = 79, 64%). Patients who experienced GI infection had a higher likelihood of experiencing an IBD flare within 1-6 months post-infection, often requiring intensification of medication, than the control group. However, such factors as age, IBD phenotype, disease activity, comorbidities, IBD pharmacological treatment, and prior travel to countries with lower hygiene standards did not increase the risk of severe bacterial infection or the likelihood of requiring hospitalization.

Conclusion: Our study indicates that IBD patients diagnosed with GI infections may be at elevated risk of experiencing an IBD flare within 1-6 months post-infection, often necessitating the intensification of their pharmacological treatment.

Background: Upadacitinib (UPA) is a new small-molecule drug for treating inflammatory bowel disease (IBD); however, its therapeutic use in China remains limited.

Objectives: This study aimed to explore Chinese physicians' treatment preferences for UPA in IBD and analyze experience-related decision-making differences.

Design: A nationwide cross-sectional study conducted among Chinese physicians.

Methods: The study was conducted among Chinese physicians using a 69-item questionnaire on physicians' backgrounds and UPA preferences, covering (1) Physician backgrounds (12 items), (2) Therapeutic preferences regarding physicians' attention to different characteristics of UPA and physicians (24 items), and (3) clinical application practices (33 items). Physicians were categorized into experienced and inexperienced groups, and preference differences were compared and analyzed using chi-square or Fisher's exact tests.

Results: Of 583 participating physicians, 182 were classified as experienced and 401 as inexperienced. Safety and efficacy were prioritized by 63.8% and 61.6% of physicians, respectively. UPA was preferred for patients with IBD aged 18-60 years (452/583, 77.5%) and with moderate-to-severe disease activity (486/583, 83.4%). For clinical application, experienced physicians preferred efficacy assessments at week 8 (63/182, 34.6%), while inexperienced physicians preferred week 12 (133/401, 33.2%) for patients with ulcerative colitis. Both groups preferred week 12 for efficacy assessments (251/583, 43.0%) and evaluation of perianal involvement (269/583, 46.1%) and extraintestinal manifestations (271/583, 46.5%) in Crohn's disease. Safety concerns included thrombosis, opportunistic infections, and severe infections, with discontinuation recommended for severe infections, cardiovascular events, or thrombosis.

Conclusion: This was the first nationwide cross-sectional study to investigate the therapeutic preferences of Chinese physicians for UPA in patients with IBD. These findings provide evidence-based support for UPA applications in China but require further real-world validation.

Background: Magnetic resonance enterography (MRE) is a noninvasive and radiation-free option for managing Crohn's disease (CD), for which various predictors have been reported to show significant prognostic value.

Objectives: The aim of this review was to summarize MRE predictors that indicated poor prognosis, including surgeries, complications, relapses, therapeutic escalations, and persistent pathological changes in patients with CD.

Design: Systematic review with meta-analysis.

Data sources and methods: Web of Science and PubMed were systematically searched for articles exploring the predictive performance of MRE in patients with luminal CD, with the latest search performed on July 21, 2025. Pooled analyses of odds ratios (OR) and hazard ratios for predicting poor prognosis were conducted using a random-effects model when available.

Results: Thirty articles were included in this study. Meta-analysis identified five significant MRE predictors for predicting CD poor prognosis over 12 months, including inflammation (OR 3.40, 95% confidence interval (CI 1.96-5.89)), bowel wall thickening (OR 2.88, 95% CI (1.95-4.25)), strictures (OR 4.95, 95% CI (1.99-12.34)), edema (OR 2.67, 95% CI (1.25-5.69)), and fistula (OR 5.15, 95% CI (2.72-9.76)). Furthermore, scoring systems, such as the Magnetic Resonance Index of Activity (MaRIA) and Clermont scores, showed significant predictive values.

Conclusion: MRE is effective in predicting the prognosis of patients with CD, with significant predictors including inflammation, bowel wall thickening, strictures, edema, fistula, and MaRIA score.

Trial registration: The study protocol was registered in the International Prospective Register of Systematic Reviews (registration number: CRD42022365965).

Background: Optimal management of peptic ulcer bleeding remains a clinical challenge.

Objectives: To evaluate the efficacy and safety of endoscopic glue injection (EGI) for acute peptic ulcer bleeding.

Design: Single-center retrospective study.

Methods: This study (October 2015-December 2024) included adults (⩾18 years) with high-risk peptic ulcer bleeding (Forrest Ia-IIa) treated with EGI using n-butyl α-cyanoacrylate ester or standard endoscopic treatment (SET) involving contact thermal therapy and hemoclips. The primary endpoint was the rebleeding within 7 days, and the secondary endpoints included rebleeding within 30 days, 30-day all-cause mortality rate, occurrence of adverse events (AEs), and length of hospital stay and intensive care unit (ICU) stay. Risk factors for rebleeding within 7 days were also analyzed.

Results: A total of 148 patients were included (EGI: 57; SET: 91). The rates of rebleeding within 7 days were 8.77% (EGI) versus 20.88% (SET; p = 0.067), and within 30 days were 8.77% versus 21.98%, respectively (p = 0.043). The 30-day all-cause mortality rate was 0.0% for EGI versus 1.1% for SET (p = 1.000). AEs-including Mallory-Weiss syndrome, esophageal blood blister, pulmonary embolism, hemorrhagic shock, cardiovascular or cerebrovascular events, infections, multiple organ failure, and lower limb thrombosis-did not differ significantly between groups (all p > 0.05). Mean hospital stay was shorter in the EGI group (10.91 ± 12.40 vs 15.38 ± 10.91 days; p = 0.002); ICU stay was similar (p = 0.153). Forrest classification Ia (odds ratio (OR) = 8.294; p = 0.013) and kidney disease (OR = 24.257; p = 0.003) were independent risk factors for rebleeding within 7 days.

Conclusion: EGI may be an effective and safe treatment for acute peptic ulcer bleeding, significantly reducing 30-day rebleeding and shortening hospital stay compared with SET. Clinicians should exercise heightened vigilance and consider more intensive monitoring or preventive strategies for patients with Forrest classification Ia ulcers or underlying kidney disease, who are at increased risk of early rebleeding.

Background: Esophageal distensibility, measured by endoluminal functional lumen imaging probe (EndoFLIP), identifies esophageal fibrostenotic changes and is impaired in patients with eosinophilic esophagitis (EoE). Early-phase clinical trials suggested dupilumab could increase esophageal distensibility. However, there are limited data on the long-term impact of dupilumab treatment on fibrostenosis.

Objectives: To evaluate the long-term efficacy of dupilumab, including its impact on esophageal fibrostenotic progression, in adult patients with EoE.

Design: The phase IV study is comprised of a randomized, double-blind, placebo-controlled trial period for 24 weeks, followed by an open-label extension for 104 weeks.

Methods and analysis: In total, 69 adult patients with endoscopically and histologically active EoE have been recruited from 30 global sites and randomized 2:1 to receive dupilumab 300 mg once weekly (qw) or placebo during the double-blind treatment period. Eligible patients continuing into the open-label extension period will receive dupilumab 300 mg qw. The primary endpoint is absolute change from baseline in esophageal distensibility plateau at week (W)24 measured by EndoFLIP. Secondary endpoints include change in esophageal distensibility plateau at W76 and W128; histologic, endoscopic, and molecular features of EoE at W24, W76, and W128; and long-term safety. After the double-blind treatment period, endpoints will be summarized with descriptive statistics.

Ethics: REMODEL will be conducted in accordance with the Declaration of Helsinki, the Council for International Organizations of Medical Sciences international ethical guidelines, and the International Council for Harmonisation Good Clinical Practice guidelines. The protocol was approved by an institutional review board before study initiation.

Discussion: REMODEL will address whether long-term dupilumab treatment can mitigate fibrostenotic progression in patients with EoE and may provide new insights into the roles of interleukin-4 and -13 in the pathophysiology and progression of EoE.

Trial registration: All patients will provide informed consent. REMODEL was registered on ClinicalTrials.gov (NCT06101095) on October 19, 2023.