Therapeutic Advances in Gastroenterology最新文献

Disorders of gut-brain interaction (DGBI) are among the commonest contributors to disease burden in children, yet remain difficult to diagnose and treat, in part because available tests inadequately capture underlying mechanisms or link physiology to symptoms. Body surface gastric mapping (BSGM) is a next-generation, noninvasive electrophysiological technology that records high-resolution gastric slow-wave activity with simultaneous symptom logging. This review summarizes emerging evidence that BSGM may fill a key diagnostic gap in pediatric DGBI. After outlining the burden and multifactorial pathophysiology of pediatric DGBI, we compare alternative investigations-including electrogastrography, gastric emptying scintigraphy, and antroduodenal manometry-and highlight their limitations in pediatrics, including regarding reproducibility, accessibility, invasiveness, and symptom correlation. We then describe BSGM methodology, validated spectral metrics, symptom integration, and standardized testing protocols. Early pediatric studies have demonstrated excellent feasibility, particularly in adolescents, established preliminary normative ranges, and identified phenotypes to distinguish neuromuscular disorders, delayed meal responses, and alternative symptom profiles to help inform targeted care. Concordance with antroduodenal manometry is also discussed. Finally, we outline research priorities, including the need for larger multicenter cohort studies, formalization of pediatric-specific reference intervals, and longitudinal studies assessing treatment responses. BSGM shows potential as a valuable noninvasive diagnostic tool for better characterizing pediatric DGBIs, though further validation is required.

Colorectal cancer (CRC) remains the second leading cause of global cancer-related mortality, with serrated colon neoplasia (SCN) accounting for 20%-30% of cases. SCN exhibits distinct clinicopathological and molecular features, whose superficial and pale appearance poses challenges for endoscopic detection. Linked Color Imaging (LCI) significantly improves lesion detection by enhancing color contrast through narrowband preprocessing and post-processing augmentation, demonstrating superior performance in large-lumen examinations. This review synthesizes current knowledge on the clinicopathological and molecular profiles of SCN, elaborates on the technical advantages of LCI over conventional imaging modalities, and highlights its diagnostic utility in SCN screening. Furthermore, we explore the innovative integration of LCI with artificial intelligence for real-time lesion recognition and with biomedical nanomaterials for targeted therapy, proposing a promising "detection-treatment" paradigm that may transform early CRC management.

Background: Anti-tumor necrosis factor (TNF) agents are now accepted as the first-line medical treatment for stricturing Crohn's disease (CD). However, data are lacking about the effectiveness of advanced therapies after anti-TNF failure.

Objectives: To compare the effectiveness of ustekinumab and a second-line anti-TNF agent after failing to respond to a first-line anti-TNF for a symptomatic stricturing CD.

Design: Multicenter retrospective study.

Methods: We included consecutive adult patients with CD treated with ustekinumab or anti-TNF for symptomatic stricture (confirmed on imaging or endoscopy) after prior failure of one anti-TNF for the current stricture. Short-term endpoints were symptomatic remission (composite endpoint) at 6 months, defined as no abdominal pain, no vomiting, no food restriction, no sub-occlusive episode, no steroid, no surgery, and no drug discontinuation or symptomatic response (same definition except for tolerating mild abdominal pain). Long-term endpoints were time to drug discontinuation for treatment failure and to bowel damage progression. The comparisons were performed after using propensity score analysis.

Results: Seventy patients were included (34 on ustekinumab, 36 on anti-TNF). After propensity score adjustment, symptomatic remission at 6 months was achieved in 73.9% of patients receiving ustekinumab compared to 42.7% in the anti-TNF group (p = 0.24), while symptomatic response was observed in 84.0% and 49.5%, respectively (p = 0.13). Predictors of remission in the ustekinumab group were prior bowel resection (p = 0.001) and stricture length <12 cm (p = 0.042). The risk of treatment discontinuation (hazard ratio (HR) = 2.86 (1.33-6.15); p = 0.008) and bowel damage progression (HR = 3.90 (1.64-9.24); p = 0.003) were higher in the anti-TNF group.

Conclusion: Ustekinumab appears more effective than a second-line anti-TNF in patients with symptomatic stricturing CD after failing to respond to a first-line anti-TNF.

Background: Endoscopic submucosal dissection (ESD) enables en bloc resection of large colorectal lesions, but it remains challenging due to thin walls and poor operability. Traction devices like SureClip traction band (SCTB, Micro-tech) and SO clip (SO-C, Zeon Medical Inc.) are used to address this. This study compared the differences in ESD outcomes between SCTB and SO-C.

Objective: Comparative analysis of the efficacy of SO-C and SCTB for various therapeutic results, including procedure time in colorectal ESD.

Design: A single-center retrospective study reviewed 982 colorectal ESD procedures for lesions 20-49 mm performed at Kyoto Prefectural University of Medicine from January 2015 to November 2024.

Methods: Patients were categorized into no-traction, SCTB, and SO-C groups. Propensity score matching was performed to minimize baseline differences. The primary outcome was ESD procedure time, and secondary outcomes assessed various therapeutic results.

Results: After matching, there were no differences in procedure time (56.0 ± 31.2 vs 59.8 ± 30.6 min, p = 0.206), en bloc resection (97.7% vs 98.3%, p = 0.589), and perioperative perforation (0.3% vs 1.4%, p = 0.101) between the traction (SCTB + SO-C) and no-traction groups. Regarding the comparison between the SCTB and SO-C groups after matching, there were no significant differences regarding ESD procedure time (58.7 ± 37.4 vs 59.1 ± 31.9 min, p = 0.469), en bloc resection (97.4% vs 97.4%, p = 1.000), and perioperative perforation (0% vs 0.9%, p = 0.316). The SCTB deployment was significantly faster than the SO-C (6.3 ± 3.8 vs 9.3 ± 5.9 min, p = 0.004).

Conclusion: There were no significant differences in ESD therapeutic results between SCTB and SO-C, while the SCTB had a faster deployment time.

Balloon endoscopy-assisted endoscopic retrograde cholangiopancreatography (BE-ERCP) has become an essential modality for managing pancreaticobiliary diseases in patients with surgically altered anatomy (SAA). This review summarizes the current evidence and technical advances in BE-ERCP, with a focus on insertion strategies tailored to specific reconstructive surgical techniques. Recent developments in short-type balloon endoscopes have improved maneuverability and device compatibility, enabling the widespread use of standard ERCP accessories. In addition, innovative tools, such as highly rotatable sphincterotomes, helical stone retrieval baskets, and newly introduced slim cholangioscopes, have expanded the diagnostic and therapeutic potential of BE-ERCP. Papillary interventions, including endoscopic sphincterotomy, endoscopic papillary balloon dilation (EPBD), large balloon dilation (EPLBD), and combined approaches (ESBD), are discussed with respect to their feasibility and safety in SAA. Furthermore, the clinical efficacy of stone removal and lithotripsy techniques, including peroral cholangioscopy-guided electrohydraulic lithotripsy, is reviewed. Finally, we address the emerging role of interventional endoscopic ultrasound as a complementary or alternative strategy to BE-ERCP. Taken together, this review provides a comprehensive update on current techniques and evolving strategies for endoscopic management of bile duct stones in patients with altered anatomy.

Inflammatory bowel diseases (IBD) are chronic and recurrent conditions of the gastrointestinal tract. IBD is often challenging to manage due to the complex etiology and involvement of multiple dysregulated immune pathways. Current treatments, including biologics and immunosuppressants, are associated with significant risks and side effects, highlighting the need for safer alternatives. Human milk oligosaccharides (HMOs), a group of bioactive carbohydrates found in human breast milk, play a crucial role in shaping the infant gut microbiome, modulating microbial metabolism and immune responses, and reducing inflammation. Notably, HMOs have no nutritional value for the infant and travel undigested through the upper gastrointestinal tract, serving as selective substrates for beneficial gut bacteria and supporting intestinal epithelial health. Among these, 2'-fucosyllactose (2'-FL) is the most abundant and well-studied HMO, functioning as a trisaccharide prebiotic. Emerging evidence suggests that the benefits of HMOs extend beyond infancy, with potential therapeutic applications in modulating immune responses, promoting epithelial health, and reducing inflammation in IBD. This review summarizes current research on the role of 2'-FL in inflammation and colitis, exploring its potential role in treating IBD.

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.