Journal of Gastroenterology最新文献

Several similarities and differences have been reported in the epidemiology and clinical characteristics of adult eosinophilic esophagitis (EoE) between Japan and Western countries. To review the similarities and differences in adult EoE between Japan and Western countries with respect to asymptomatic cases, the efficacy of proton pump inhibitors (PPIs) and potassium-competitive acid blockers (P-CABs), gene profiles, and disease severity. A PubMed search was performed to identify relevant publications using the following search terms: "eosinophilic esophagitis," "esophageal eosinophilia," "epidemiology," "natural history," "asymptomatic," "PPI," "P-CAB," "Japan," and "Japanese." Asymptomatic EoE has been reported only in Japan, primarily during gastric cancer screening and routine health check-ups, and progression from asymptomatic EoE to symptomatic EoE is uncommon. The efficacy of PPIs and P-CABs for the treatment of EoE appears to be higher in Japan than in Western countries. Severe fibrostenotic cases requiring emergency visits or endoscopic dilation are rare in Japan. The gene expression profile of EoE in Japan is similar to that reported in the United States, and no differences in gene expression have been observed between patients with EoE and those with asymptomatic EoE in Japan. We hypothesize that early detection and diagnosis of adult EoE in Japan may contribute to the high efficacy of PPIs and P-CABs and that early therapeutic intervention may prevent the development of fibrostenosis and severe disease.

Background: In pancreatic ductal adenocarcinoma (PDAC), activation of Yes-associated protein 1 (YAP1) is linked to increased extracellular matrix (ECM) stiffness, yet how YAP1 interacts with cancer-associated fibroblasts (CAFs) and their subtypes to promote stromal remodeling remains unclear.

Methods: Utilizing single-cell RNA sequencing (scRNA-seq) data to identify CAF subsets; validating the role of a specific subset, tumor-like CAFs (tCAFs), in YAP1-dependent promotion of ECM stiffness, epithelial-mesenchymal transition (EMT) combining the YAP1 inhibitor verteporfin with gemcitabine in KPC mouse models to assess effects on tCAF function, stromal stiffness, and survival; and employing magnetic resonance elastography (MRE) to quantify tumor stiffness in PDAC patients and mouse models.

Results: scRNA-seq identified a novel CAF subset (tCAFs) enriched in tumors with high YAP1 activity; tCAFs and mCAFs can mutually differentiate, and this process is regulated by YAP1 activity; in KPC mice, the combination of verteporfin and gemcitabine suppressed tCAF function, reduced stromal stiffness, and improved survival; MRE can accurately quantify tumor stiffness in PDAC patients; elevated YAP1 activity induces a stiffer, more highly cross-linked ECM, which is associated with increased tumor aggressiveness and shortened survival.

Conclusions: YAP1 and tumor-like CAFs (tCAFs) play a pivotal role in driving desmoplasia in PDAC. YAP1 mediates the conversion of mCAFs to tCAFs and remodels the extracellular matrix (ECM), while high YAP1 activity in tCAFs regulates EMT induction to propel disease progression. Targeting the YAP1-tCAF axis can suppress desmoplasia and improve therapeutic outcomes. Magnetic resonance elastography (MRE) holds significant potential for non-invasive monitoring of stromal mechanics, offering a new perspective for stromal therapies in PDAC.

Background: Elastography techniques such as two-dimensional shear wave elastography (2D-SWE) often result in missed or misdiagnoses when distinguishing between intermediate stages of liver fibrosis in clinical practice for patients with chronic hepatitis B (CHB).

Methods: Between January 2020 and August 2023, we prospectively enrolled 964 potentially eligible CHB patients from 6 hospitals who underwent liver biopsy. Finally, 598 patients with 2139 high-frequency ultrasound (HF-US) images were included. LS-Net, a deep learning network based on paired liver-spleen HF-US images was trained for distinguishing different stages of liver fibrosis against a comparison network(L-Net), 2D-SWE, and radiologist. We further simulated potential clinical utility across three clinical guidelines and conducted subgroup analyses for potential confounding factors.

Results: LS-Net demonstrated consistently superior performance for all-stage liver fibrosis classification in the validation set (AUROC: 0.94, 0.87, 0.92; p < 0.05) compared to L-Net, 2D-SWE, and radiologist assessment. In our clinical simulation focused on CHB patients, LS-Net reduced the biopsy rate to 9.9% for cirrhosis detection, increased essential referral by 40.3% for advanced fibrosis, and substantially improved treatment decision-making for significant fibrosis compared to 2D-SWE. The model maintained stable performance across subgroups (BMI, inflammation, ALT, antiviral status).

Conclusions: In this development and internal validation study in the CHB patient cohort, LS-Net demonstrated significantly higher diagnostic performance for all-stage liver fibrosis classification compared to L-Net, 2D-SWE and radiologist. Our findings indicate that LS-Net could offer potential clinical value for CHB management by reducing unnecessary biopsy rate, increasing essential referral rate, and promoting timely treatment.

Background: We sought to evaluate the predictive value of protease-3 (PR3)-anti-neutrophil cytoplasmic antibodies (ANCAs) and myeloperoxidase (MPO)-ANCA for primary nonresponse (PNR) to biologic agents in patients with ulcerative colitis (UC).

Methods: A multicenter, prospective cohort study was conducted. Patients with UC who initiated biologic agents (anti-TNF, anti-integrin, or anti-IL12/23 agents) as their first-line therapy were enrolled. PNR was defined as failure to achieve a partial Mayo Score improvement of at least 2 points by weeks 14-16 or necessitating treatment modification. Logistic regression identified PNR predictors.

Results: Among 95 biologic-naïve UC patients, 38 received anti-TNF, 39 received anti-integrin, and 18 received anti-IL12/23 agents. PR3-ANCA positivity was observed in 47.4% of anti-TNF recipients. The PNR rate among PR3-ANCA-positive patients receiving anti-TNF therapy was 66.7%, significantly higher than in PR3-ANCA-negative patients (25.0%, P = 0.02). Multivariate logistic regression confirmed PR3-ANCA as an independent risk factor for PNR to anti-TNF therapy (OR 5.61; 95% CI 1.37-26.82; P = 0.02). By contrast, PR3-ANCA did not predict PNR to anti-integrin therapy, but the platelet-to-lymphocyte ratio (PLR) and the systemic immune-inflammatory index (SII) were identified as significant predictors. Only one of 95 patients tested positive for MPO-ANCA, precluding statistical analysis for its association with PNR.

Conclusion: In patients with UC, PR3-ANCA is a significant predictor of PNR to anti-TNF therapy, but not to anti-integrin therapy. PLR and SII may predict PNR to anti-integrin therapy. PR3-ANCA could aid biologic selection, optimizing personalized UC treatment and healthcare resource utilization.

Background: The long-term local control and effect of photodynamic therapy (PDT) using talaporfin sodium and a diode laser (talaporfin PDT) on overall survival (OS) for local failure after chemoradiotherapy (CRT) for esophageal cancer are unknown. Here, we present a 5-year survival analysis for talaporfin PDT.

Methods: This was a prospective follow-up analysis of an open-label, multicenter, phase 2 study of local failure after CRT or radiotherapy in patients who received talaporfin PDT. The primary endpoint was the overall OS. The secondary endpoints were progression-free survival (PFS), local progression-free survival (L-PFS) with local progression or recurrence and death as events, and local time to progression (L-TTP) with only local progression or recurrence as events.

Results: Between November 2012 and December 2013, 26 patients with oesophageal squamous cell carcinoma underwent talaporfin PDT. The baseline T stages were cT1 in 14 patients, cT2 in 6 patients, and cT3 in 6 patients. Pre-PDT T stages were cT1b for 19 and cT2 for 7 patients, and no lymph nodes or distant metastases were detected. At a median 6.8-year follow-up, the median OS and 5-year OS rates were 4.2 years (95% confidence interval [CI]: 1.6-7.3) and 40.6% (95% CI: 21.7-58.7), respectively. The median PFS and L-PFS were 1.1 and 2.1 years, respectively. The 5-year local progression-free rate was 84.9%. No treatment-related deaths occurred.

Conclusion: Talaporfin PDT for patients with oesophageal cancer with local failure after CRT can achieve long-term local complete response and long-term survival as a minimally invasive salvage treatment.

Trial registration number: UMIN000009184.

Background: Pancreaticobiliary maljunction (PBM) contributes to epithelial hyperplasia and, ultimately, the development of gallbladder cancer (GBC). Despite its clinical significance, the molecular and cellular mechanisms driving carcinogenesis in GBC with PBM remain poorly elucidated. This study investigated the oncogenic mechanisms, biomarkers, and performance associated with Erb-b2 receptor tyrosine kinase 2 (ERBB2)-targeted therapies in GBC with PBM.

Methods: Overall, 127 surgically treated patients were stratified as follows: Group A, normal gallbladder; Group B, PBM; Group C, GBC without PBM; and Group D, GBC with PBM. We performed whole-exome sequencing (WES) for Group D and human epidermal growth factor receptor 2 immunohistochemistry (HercepTest) for the entire cohort. Fluorescence in situ hybridization (FISH) was used to clarify human epidermal growth factor receptor 2 (HER2) expression in cases with equivocal HercepTest results.

Results: ERBB2 amplification was detected in 50% of Group D patients. The proportion of HER2 protein expression scores ≥ 2 + was highest in Group D compared with that in the other groups (50.0% vs. 0% in Groups A and B and 15.6% in Group C) (P = 0.006, chi-squared test). Finally, 37.5% and 13.3% of cases in Groups D and C, respectively, showed HER2 overexpression (P = 0.037, chi-squared test).

Conclusions: This is the first evaluation of HER2/ERBB2 expression in GBC with PBM based on WES, HercepTest, and FISH. The significant increase in ERBB2 expression, driven by the synergistic interplay between GBC and PBM, underscores a critical molecular interaction that may inform the development of targeted therapeutic strategies.

The clinical landscape of chronic liver disease has changed with effective antiviral therapies, enabling the eradication of hepatitis C virus and the durable suppression of hepatitis B virus replication. Despite these advances, patients remain at risk for hepatocellular carcinoma (HCC) and other liver-related complications, but the growing burden of metabolic dysfunction-associated steatotic liver disease (MASLD) has created new challenges for clinical practice. These trends emphasize the need for reliable, noninvasive biomarkers that can stratify risk and guide long-term management across diverse etiologies. Growth differentiation factor 15 (GDF15), a stress-inducible cytokine, has attracted increasing interest as a promising biomarker. Its expression is induced by metabolic, oxidative, and inflammatory stress, and circulating levels increase with disease progression. Elevated serum GDF15 is consistently associated with fibrosis severity, HCC risk, hepatic decompensation, and mortality. Importantly, GDF15 is not merely a surrogate of fibrosis; rather, it integrates hepatocellular and stromal stress pathways and captures residual risk beyond fibrosis stage, liver function scores, and conventional biomarkers. In addition to its prognostic association, GDF15 has diverse biological effects. It may act as a protective response by limiting inflammation and cellular injury; yet, in other contexts, it contributes to fibrogenesis, tumor progression, immunosuppression, and cachexia. These dual roles highlight both the potential and the complexity of targeting GDF15 in therapeutic strategies. Collectively, the results of the current study indicate that GDF15 represents a promising biomarker in chronic hepatic diseases and is clinically independent of hepatic fibrosis. Further work is needed to clarify the underlying mechanisms, validate the prognostic utility, and determine whether GDF15 can be developed as a therapeutic target within precision medicine approaches.

Background and aims: The potential for recompensation and its defining criteria in patients with decompensated cirrhosis due to primary biliary cholangitis (PBC) remain poorly defined. Therefore, our study aimed to explore the criteria for etiological suppression and provide preliminary insights into PBC recompensation.

Methods: In this retrospective-prospective study, we enrolled hospitalized patients with PBC cirrhosis from January 2014 to June 2023. Recompensation was defined according to the Baveno VII criteria. In addition, expanded recompensation criteria were evaluated for patients on low-dose diuretics and/or lactulose/rifaximin with resolution of decompensation and stable improvement of liver function. We explored whether the biochemical responses to UDCA could serve as surrogates for etiological suppression.

Results: We enrolled 240 patients with PBC cirrhosis (122 compensated and 118 decompensated). With a median follow-up of 50.0 (31.0, 72.0) months, 18 (15.3%) out of 118 decompensated patients achieved recompensation and 31 (26.3%) achieved the expanded recompensation. Both recompensated and expanded recompensated patients showed similar long-term outcomes to compensated patients (recompensation: hazard ratio [HR]: 0.70, p = 0.735; expanded recompensation: HR: 0.83, p = 0.814). Patients with variceal hemorrhage as index decompensation had higher potential of recompensation. Fulfillment of the Paris II and Momah/Lindor criteria was linked to better further decompensation-free survival and long-term stabilization of liver function reserve.

Conclusion: Regression to a recompensated stage is possible in PBC patients with decompensated cirrhosis, especially when portal hypertension is the main driver of index decompensation. The Paris II and Momah/Lindor criteria are potentially useful as surrogate indicators for etiological suppression.