Journal of Gastroenterology最新文献

{"title":"Acknowledgements.","authors":"","doi":"10.1007/s00535-025-02229-9","DOIUrl":"10.1007/s00535-025-02229-9","url":null,"abstract":"","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"392-395"},"PeriodicalIF":6.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"YAP acts as an independent prognostic marker and regulates growth and metastasis of gastrointestinal stromal tumors via FBXW7-YAP pathway.","authors":"Xiyu Wu, Kohei Yamashita, Chihiro Matsumoto, Weiliyun Zhang, Ming Ding, Kazuto Harada, Keisuke Kosumi, Kojiro Eto, Satoshi Ida, Yuji Miyamoto, Masaaki Iwatsuki","doi":"10.1007/s00535-024-02180-1","DOIUrl":"10.1007/s00535-024-02180-1","url":null,"abstract":"<p><strong>Background: </strong>Although imatinib (IM) and subsequent tyrosine kinase inhibitors (TKIs) significantly improve the prognosis of GIST patients by delaying metastasis and recurrence, most patients experience limited efficacy due to toxicity and secondary resistance. We evaluated Yes-associated protein (YAP), a coactivator of the Hippo pathway accounting for IM resistance and aggressive GIST phenotypes, in GISTs. The degradation of YAP is mediated by FBXW7, and FBXW7 predicts recurrence and IM efficacy for GIST patients. Here, we aimed to identify the potential of YAP as a prognostic marker for patients with GISTs, and the molecular mechanism of FBXW7-YAP pathway in GIST cells.</p><p><strong>Methods: </strong>We measured YAP expression in 167 GIST cases using immunohistochemical staining, correlated its expression levels with clinicopathological features, and the molecular mechanism underlying the FBXW7-YAP pathway was further examined in vitro and in vivo.</p><p><strong>Results: </strong>Compared to 80 (47.9%) cases in the low YAP expression group, 87 (52.1%) cases with high YAP expression associated with a poorer prognosis in terms of overall survival (P = 0.004) and recurrence-free survival (P = 0.003). YAP expression was identified as a significant independent factor affecting the 5-year overall survival (P = 0.005) and recurrence-free survival rates (P = 0.007). Moreover, YAP was directly targeted by FBXW7 to affect proliferation, invasion, and migration in GIST cells. High YAP expression correlated with FBXW7 deficiency, as shown in xenograft and metastasis mouse models.</p><p><strong>Conclusions: </strong>YAP expression serves as a predictive marker of recurrence for GIST patients with curative resection, highlighting its potential as a novel therapeutic target that warrants further investigation.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"275-284"},"PeriodicalIF":6.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation of the Japanese version of the Esophageal Hypervigilance and Anxiety Scale for esophageal symptoms.","authors":"Akinari Sawada, Yoshimasa Hoshikawa, Hiroko Hosaka, Masahiro Saito, Hirotaka Tsuru, Shunsuke Kato, Eikichi Ihara, Tomoyuki Koike, Toshio Uraoka, Kunio Kasugai, Katsuhiko Iwakiri, Daniel Sifrim, John Erik Pandolfino, Tiffany H Taft, Yasuhiro Fujiwara","doi":"10.1007/s00535-024-02193-w","DOIUrl":"10.1007/s00535-024-02193-w","url":null,"abstract":"<p><strong>Background: </strong>The Esophageal Hypervigilance and Anxiety Scale (EHAS) is an English questionnaire created in the USA to assess these factors in all patients with esophageal diseases. The aim of this study was to develop and validate the Japanese version of EHAS and investigate the relationship between EHAS scores and symptoms in untreated disorders of esophagogastric junction (EGJ) outflow.</p><p><strong>Methods: </strong>This prospective study recruited patients who underwent high-resolution manometry (HRM) at six tertiary centers in Japan. The EHAS was translated to Japanese using standard forward and backward translation methods. Patients completed the following questionnaires: the Japanese EHAS, Eckardt score, Gastroesophageal Reflux Disease Questionnaire, and Hospital Anxiety and Depression Scale for assessment of construct validity. Logistic regression analysis identified factors associated with esophageal symptom severity in untreated disorders of EGJ outflow.</p><p><strong>Results: </strong>Overall, we analyzed 432 patients. Their main symptoms were dysphagia and reflux. The most common HRM diagnosis was normal (35.9%), followed by achalasia (29.4%). The Japanese EHAS demonstrated excellent reliability, and construct validity, with two subscales similar to the original EHAS. Total EHAS score moderately correlated to Eckardt score (r = 0.545, p < 0.001). In 113 patients with untreated disorders of EGJ outflow, multivariable analysis demonstrated that younger age, type II achalasia, and higher EHAS score were independently associated with higher Eckardt score.</p><p><strong>Conclusions: </strong>The Japanese EHAS is a reliable and valid questionnaire. Its subscale scores can be used as in the original version with some caution. Future studies are warranted to assess the appropriateness of factor loading.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"265-274"},"PeriodicalIF":6.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Refining risk assessment in Barrett's esophagus: addressing follow-up and diagnostic limitations.","authors":"Jing Jia, Ying He, Ling Hu","doi":"10.1007/s00535-024-02207-7","DOIUrl":"10.1007/s00535-024-02207-7","url":null,"abstract":"","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"385-386"},"PeriodicalIF":6.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revisiting the relationship between thyroid function and metabolic dysfunction-associated steatotic liver disease in the era of resmetirom.","authors":"Sadatsugu Sakane, Hayato Hikita","doi":"10.1007/s00535-025-02214-2","DOIUrl":"10.1007/s00535-025-02214-2","url":null,"abstract":"","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"389-391"},"PeriodicalIF":6.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estimating cancer risk in immune-mediated inflammatory diseases exposed to varying doses of tumour necrosis factor inhibitors.","authors":"Shinji Okabayashi, Takahiro Itaya, Hajime Yamazaki, Ryo Yanai, Masaaki Isshiki, Yosuke Yamamoto","doi":"10.1007/s00535-024-02190-z","DOIUrl":"10.1007/s00535-024-02190-z","url":null,"abstract":"<p><strong>Background: </strong>The safety profile of high doses of tumour necrosis factor inhibitors (TNFi) therapy for cancer risk in immune-mediated inflammatory diseases (IMIDs) remains uncertain. We evaluated the risk of cancer development in patients with IMIDs exposed to standard and high doses of TNFi compared with those never exposed to TNFi.</p><p><strong>Methods: </strong>A cohort study was conducted using the Japanese claims database encompassing over 4.6 million individuals from 2013 to 2021. The study included patients aged 16 years or older with new-onset IMIDs, such as inflammatory bowel disease, rheumatoid arthritis, or psoriasis, who had no cancer history. The subdistribution hazard ratios (SHR) for cancer risk in TNFi standard and high dose groups comparing with TNFi unexposed group were estimated using a Fine and Gray model that accounted for the competing risk of death unrelated to cancer. The high dose of TNFi was defined as either a dose escalation or shortening of the intervals during administrations from the standard dose treatment.</p><p><strong>Results: </strong>We identified a total of 42,006 patients with new-onset IMIDs (40,573 in TNFi unexposed, 876 in TNFi standard dose, and 557 in TNFi high dose) and 1211 (2.8%) patients developed cancer, yielding an incidence rate of 787.8 (739.9-828.1) per 100,000 person-years. Neither the standard nor high doses of TNFi significantly increased the cancer risk (TNFi standard dose vs. TNFi unexposed, adjusted SHR, 0.65 [0.40-1.08]; TNF high dose vs. TNFi unexposed, adjusted SHR, 1.12 [0.67-1.87]).</p><p><strong>Conclusions: </strong>There is no association between varying doses of TNFi therapy and cancer risk in IMIDs.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"285-293"},"PeriodicalIF":6.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between advanced fibrosis and epigenetic age acceleration among individuals with MASLD.","authors":"Haili Wang, Zhenqiu Liu, Hong Fan, Chengnan Guo, Xin Zhang, Yi Li, Suzhen Zhao, Luojia Dai, Ming Zhao, Tiejun Zhang","doi":"10.1007/s00535-024-02181-0","DOIUrl":"10.1007/s00535-024-02181-0","url":null,"abstract":"<p><strong>Background: </strong>The biological process of aging plays an important role in the progress of liver fibrosis. However, epidemiological evidence about the associations between advanced fibrosis and epigenetic age acceleration (EAA) among individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) is limited.</p><p><strong>Methods: </strong>We utilized publicly available DNA methylation data (GSE180474) for our analysis. Five EAA measures were calculated in this study, including IEAA, PhenoAA, GrimAA, DunedinPACE, and DNAmTLAA. Separate linear regression models were conducted to explore the associations between different fibrosis grades and each measure of EAA.</p><p><strong>Results: </strong>A total of 325 participants were included in this study, with a mean (± SD) age of 48.56 ± 11.50 years. Of these participants, 64.6% with no fibrosis, 16.9% with bridging fibrosis, 11.1% with incomplete cirrhosis, and 7.4% with cirrhosis. After adjusting for demographics and medication status, MASLD individuals with advanced fibrosis were associated with a 5% increase in the pace of aging (DunedinPACE, β = 0.05, 95% CI: 0.03-0.07) and a 10% decrease in DNAmTLAA (β = -0.10, 95% CI: -0.13 to -0.07) compared those without fibrosis. Similarly, higher stages of fibrosis were associated with an increased pace of aging (DunedinPACE, β = 0.02, 95% CI: 0.01-0.03, P_trend < 0.001) and decreased DNAmTLAA (β = -0.05, 95% CI: -0.07 to -0.04, P_trend < 0.001). However, no significant association was found between advanced fibrosis and IEAA, PhenoAA, and GrimAA.</p><p><strong>Conclusions: </strong>Our findings suggest that advanced fibrosis was associated with an accelerated pace of aging, as measured by the third-generation EA measure DunedinPACE, and shorter telomere length, captured by DNAmTLAA, among individuals with MASLD. This finding has potential prognostic implications and suggests EAA may serve as a surrogate marker of therapeutic efficacy in MASLD.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"306-314"},"PeriodicalIF":6.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"WWP1 inhibition suppresses the proliferation of pancreatic cancer cells by regulating the PI3K-AKT pathway.","authors":"Genso Notoya, Takahiro Kishikawa, Kengo Yasugi, Takuma Iwata, Takahiro Seimiya, Koji Miyabayashi, Ryota Takahashi, Keisuke Yamamoto, Hideaki Ijichi, Motoyuki Otsuka, Mitsuhiro Fujishiro","doi":"10.1007/s00535-024-02192-x","DOIUrl":"10.1007/s00535-024-02192-x","url":null,"abstract":"<p><strong>Background: </strong>The proto-oncogene WWP1 is overexpressed in various cancers and contributes to tumor growth and poor prognosis. Recently, WWP1 inhibition was reported to suppress tumor development and cell proliferation by activating the PTEN function. However, the expression profiles and clinical significance of WWP1 in pancreatic ductal adenocarcinoma (PDAC) tissues remain undetermined. Therefore, this study aimed to evaluate the WWP1 expression in PDAC and investigate the therapeutic potential of WWP1 inhibition.</p><p><strong>Methods: </strong>Cellular proliferation assays were performed using a doxycycline-inducible shWWP1 expression system. Transcriptome analyses were conducted to identify the altered pathways in WWP1-depleted cells. PTEN ubiquitination by WWP1 was confirmed using immunoprecipitation assays. In vivo xenograft and drug screening assays were performed to evaluate the clinical significance of WWP1 inhibition.</p><p><strong>Results: </strong>WWP1 was significantly upregulated in PDAC tissues and associated with poor prognosis. WWP1 depletion significantly reduced the proliferation of PDAC cell lines, correlating with the suppression of the PI3K-AKT pathway. Mechanistically, as reported in other cancer types, PTEN is a target of WWP1 in PDAC cells. PTEN silencing abrogated the growth-inhibitory effects in WWP1-depleted cells, suggesting that the anti-tumor effects of WWP1 inhibition are mediated through PTEN activation. In vivo xenograft studies confirmed that WWP1 depletion substantially inhibited tumor growth. Moreover, drug screening assays revealed that WWP1 depletion had an additive effect with the PI3K-AKT pathway inhibitors on hindering tumor growth.</p><p><strong>Conclusion: </strong>WWP1 inhibition enhances the anti-tumor effects of PI3K-AKT pathway inhibitors through PTEN activation. Thus, WWP1 could be a potential therapeutic target in PDAC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"370-384"},"PeriodicalIF":6.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Behçet's disease: incidence, prevalence, and real-word data on the use of biologic agents in Japan.","authors":"Tadakazu Hisamatsu, Makoto Naganuma, Philippe Pinton, Mitsuhiro Takeno","doi":"10.1007/s00535-024-02191-y","DOIUrl":"10.1007/s00535-024-02191-y","url":null,"abstract":"<p><strong>Background: </strong>Behçet's disease (BD) is an autoinflammatory disease that can affect multiple organs, including the gastrointestinal tract. Conventional management comprises anti-inflammatory drugs such as glucocorticoids (GCs) and/or immunomodulators that alleviate symptoms. The introduction of biological agents that target tumor necrosis factor α (TNF-α) has improved disease management. The goal of this work was to analyze the current prevalence and incidence of total BD and gastrointestinal Behçet's disease (GIBD) in Japan, and examine treatment trends, especially regarding the use of TNF-α inhibitors (TNFαi).</p><p><strong>Methods: </strong>We performed a retrospective descriptive observational study in which BD and GIBD demographic trends, medical treatment patterns, and reported adverse events (AEs) were assessed among patients with data recorded between 2017 and 2021 in the Japan Medical Data Center Claims Database (now JMDC Inc.).</p><p><strong>Results: </strong>Prevalence of BD and GIBD in Japan during the observation period increased at an annual rate of + 3% and + 4%, respectively, while incidence decreased by - 5% and - 2%, with a more prominent decline in confirmed GIBD cases (- 15%). Although GCs were the most common initial treatment administered, use of TNFαi for BD and GIBD management increased by + 5.6% and + 8.1%, respectively. Severe AEs (mainly pneumonia and GI-associated AEs) were reported in 40% of patients receiving TNFαi; however, a high retention rate (of up to 80%) was observed 3 years after treatment initiation.</p><p><strong>Conclusion: </strong>The use of TNFαi for GIBD treatment has increased in Japan in recent years. Additional research is necessary to further evaluate TNFαi effectiveness in GIBD and other BD subtypes.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"294-305"},"PeriodicalIF":6.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fungal mycobiome dysbiosis in choledocholithiasis concurrent with cholangitis.","authors":"Zhiyuan Hao, Yiting Lu, Yarong Hao, Yuanyuan Luo, Kaiming Wu, Changpeng Zhu, Peimei Shi, Feng Zhu, Yong Lin, Xin Zeng","doi":"10.1007/s00535-024-02183-y","DOIUrl":"10.1007/s00535-024-02183-y","url":null,"abstract":"<p><strong>Background: </strong>The gut mycobiome might have an important influence on the pathogenesis of choledocholithiasis concurrent with cholangitis (CC). The aim of this study was to characterize the fungal mycobiome profiles, explore the correlation and equilibrium of gut interkingdom network among bacteria-fungi-metabolites triangle in CCs.</p><p><strong>Methods: </strong>In a retrospective case-control study, we recruited patients with CC (n = 25) and healthy controls (HCs) (n = 25) respectively to analyze the gut fungal dysbiosis. Metagenomic sequencing was employed to characterize the gut mycobiome profiles, and liquid chromatography/mass spectrometry (LC/MS) analysis was used to quantify the metabolites composition.</p><p><strong>Results: </strong>The Shannon index displayed a reduction in fungal α-diversity in CCs compared to HCs (p = 0.041), and the overall fungal composition differed significantly between two groups. The dominant 7 fungi species with the remarkable altered abundance were identified (LDA score > 3.0, p < 0.05), including CC-enriched Aspergillus_niger and CC-depleted fungi Saccharomyces_boulardii. In addition, the correlations between CC-related fungi and clinical variables in CCs were analyzed. Moreover, the increased abundance ratio of Basidiomycota-to-Ascomycota and a dense linkage of bacteria-fungi interkingdom network in CCs were demonstrated. Finally, we identified 30 markedly altered metabolites in CCs (VIP > 1.0 and p < 0.05), including low level of acetate and butyrate, and the deeper understanding on the complexity of bacteria-fungi-metabolites triangle involving bile inflammation was verified.</p><p><strong>Conclusion: </strong>Our investigation demonstrated a distinct gut fungal dysbiosis in CCs and proposed that, beyond bacteria, the more attention should be paid to significantly potential influence of fungi and bacteria-fungi-metabolites triangle interkingdom interactions on pathogenesis of CC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"340-355"},"PeriodicalIF":6.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}