Journal of Gastroenterology最新文献

{"title":"Optimising carotegrast methyl use in ulcerative colitis: patient profiling, predictive biomarkers, and timing of efficacy evaluation (ASPECT study).","authors":"Katsuyoshi Matsuoka, Fumihito Hirai, Kenji Watanabe, Ryota Hokari, Taku Kobayashi, Masayuki Saruta, Hiroshi Nakase, Takahiro Suzuki, Gakuto Yamazaki, Toshifumi Hibi, Mamoru Watanabe, Tadakazu Hisamatsu","doi":"10.1007/s00535-025-02299-9","DOIUrl":"https://doi.org/10.1007/s00535-025-02299-9","url":null,"abstract":"<p><strong>Background: </strong>Carotegrast methyl is approved for treating patients with moderately active ulcerative colitis with inadequate response to 5-aminosalicylic acid agents. However, real-world evidence to guide optimal use is limited. This retrospective study aimed to characterise suitable patient profiles, identify biomarkers predictive of carotegrast methyl efficacy, and determine the appropriate timing for treatment evaluation.</p><p><strong>Methods: </strong>We analysed data from 186 patients enrolled in a phase 3 trial of carotegrast methyl (96 carotegrast methyl, 90 placebo). We assessed biomarkers (leucine-rich α-2 glycoprotein, C-reactive protein, faecal calprotectin, and anti-integrin αvβ6 antibody titres) alongside clinical outcomes and assessed symptom diaries and maintenance therapies.</p><p><strong>Results: </strong>Low disease activity at baseline (partial Mayo score ≤ 5) was associated with higher remission rates (56.1 vs. 33.3%). Anti-integrin αvβ6 antibody titres of < 44.6 U/mL at baseline predicted higher clinical remission rates (49.1 vs. 26.8%). Symptom improvement was detectable from week 2. Faecal calprotectin correlated with the endoscopic subscore at the end of treatment (ρ = 0.566); a faecal calprotectin level of < 387.5 µg/g predicted Mayo endoscopic subscore 0/1. Most patients maintained remission with oral 5-aminosalicylic acid alone; the 1-year maintenance rate was 56.5%.</p><p><strong>Conclusions: </strong>Carotegrast methyl appears most effective in patients with moderately active ulcerative colitis with low disease activity, with week 2 and beyond as an appropriate time point for assessing efficacy. Anti-integrin αvβ6 antibody titre shows promise in predicting response to carotegrast methyl. Faecal calprotectin may serve as a non-invasive surrogate for evaluating endoscopic healing.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113201","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":"Prevalence, characteristics, and screening of spondyloarthritis in Japanese patients with early inflammatory bowel diseases: a prospective multidisciplinary study.","authors":"Sho Fukui, Mitsumasa Kishimoto, Minoru Matsuura, Aika Sakamoto, Keisuke Ono, Satoshi Kobayashi, Soko Kawashima, Noriko Ikegaya, Takahisa Kawakami, Tatsuya Mitsui, Daisuke Saito, Mari Hayashida, Jun Miyoshi, Yoshinori Komagata, Tadakazu Hisamatsu","doi":"10.1007/s00535-025-02301-4","DOIUrl":"https://doi.org/10.1007/s00535-025-02301-4","url":null,"abstract":"<p><strong>Background: </strong>The prevalence and characteristics of inflammatory bowel disease-associated spondyloarthritis (IBD-SpA) in Japan are unclear. Moreover, methods for screening SpA among IBD patients have not been established.</p><p><strong>Methods: </strong>This single-center prospective multidisciplinary study included consecutive patients with IBD, which was newly diagnosed within the past 3 years (early IBD). Board-certified rheumatologists examined the patients for disease history and musculoskeletal manifestations, with imaging studies if needed. Questionnaires assessed patient-reported outcomes and Psoriatic Arthritis Screening and Evaluation (PASE) scores.</p><p><strong>Results: </strong>We identified 85 eligible patients with early IBD, 22 (25.9%) of whom had Crohn's disease, 63 (74.1%) had ulcerative colitis, and 3 (3.5%) had IBD-SpA diagnosed prior to study enrollment. Rheumatologist evaluations identified additional seven SpA cases, resulting in a total of 10 patients (11.8%) with IBD-SpA (1: axial, 9: peripheral). IBD patients without SpA often presented with back pain (52%) and peripheral joint pain (24%), whereas arthritis, cervical and thoracic pain, and inflammatory back pain were more frequent in IBD-SpA. Newly identified IBD-SpA cases tended to have lower-limb arthritis, dactylitis, and enthesitis, compared with previously diagnosed IBD-SpA cases. For patients with active SpA symptoms in the past 6 months, PASE demonstrated that the area under the receiver operating characteristic curve was 0.87 (95% confidence interval: 0.68, 1.00). The optimal cut-off (33 points) had a sensitivity of 0.88 and specificity of 0.88.</p><p><strong>Conclusions: </strong>This prospective study found rheumatologist evaluation increased SpA diagnosis and 11.8% of Japanese early IBD patients had IBD-SpA. PASE questionnaires may be effective for screening SpA among IBD patients.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080829","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":"Development of gastric mucosa-associated microbiota in autoimmune gastritis with neuroendocrine tumors.","authors":"Koji Otani, Geicho Nakatsu, Kosuke Fujimoto, Daichi Miyaoka, Noriaki Sato, Yuji Nadatani, Yu Nishida, Hirotsugu Maruyama, Masaki Ominami, Shusei Fukunaga, Shuhei Hosomi, Fumio Tanaka, Seiya Imoto, Satoshi Uematsu, Toshio Watanabe, Yasuhiro Fujiwara","doi":"10.1007/s00535-025-02298-w","DOIUrl":"https://doi.org/10.1007/s00535-025-02298-w","url":null,"abstract":"<p><strong>Background: </strong>Autoimmune gastritis (AIG) is a chronic atrophic gastritis that affects the gastric corpus, leading to achlorhydria, hypergastrinemia, and a precursor of neuroendocrine tumors (NETs). This study aimed to elucidate the underlying mechanisms of gastric NET formation in AIG by analyzing gastric mucosa-associated microbiota and host tissue-derived metabolite profiles.</p><p><strong>Methods: </strong>A total of 19 patients diagnosed with AIG and 12 controls uninfected with Helicobacter pylori underwent gastric mucosal biopsies for microbiome analysis using next-generation sequencing with primers targeting the V3-V4 region of the 16S rRNA gene, and metabolome analysis using capillary electrophoresis time-of-flight mass spectrometry.</p><p><strong>Results: </strong>Microbiome analysis revealed significantly reduced α-diversity indices in patients with AIG when compared with the control group. β-Diversity analysis showed distinct microbial compositions among the control, NET-negative, and NET-positive groups. The NET-positive group exhibited a significantly higher abundance of Proteobacteria and Fusobacteriota, particularly Haemophilus parainfluenzae, Fusobacterium periodonticum, and Fusobacterium nucleatum, whereas Firmicutes, including Streptococcus salivarius and Veillonella atypica, were significantly decreased compared with the NET-negative group. Metabolome analysis revealed a shift away from glycolysis and tricarboxylic acid cycle activity toward alternative metabolic pathways in patients with AIG. Integrated analysis of gastric microbiota signatures (GMS) and tissue metabotypes demonstrated significant associations among GMS, tissue metabotypes, and NET diagnosis.</p><p><strong>Conclusions: </strong>These findings highlight marked shifts in gastric mucosa-associated microbiota profiles in patients with AIG who developed gastric NETs. Tissue-specific metabolic alterations may precede mucosal dysbiosis in patients with AIG and promote the development of a microenvironment implicated in NET formation.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040260","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":"Hic-5 deficiency attenuates MAFLD by inhibiting neutrophils migration via the CXCL1-CXCR2 axis.","authors":"Bingyu Ren, Han Li, Shenglu Liu, Zhiwei Huang, Junjie Bai, Zhonghao Jiang, Tongjie Xu, Boyuan Gu, Wenhao Yu, Lei Sun, Peng Tan, Wenguang Fu","doi":"10.1007/s00535-025-02293-1","DOIUrl":"https://doi.org/10.1007/s00535-025-02293-1","url":null,"abstract":"<p><strong>Background and aims: </strong>Inflammatory cell infiltration in the liver is a hallmark of metabolic dysfunction-associated fatty liver disease (MAFLD). However, the pathological events that trigger the infiltration of inflammatory cells to mediate MAFLD pathogenesis remains poorly understood. This study aims to investigate the function and mechanism of Hic-5 on hepatic inflammation of MAFLD.</p><p><strong>Methods: </strong>MAFLD animal models were fed a methionine- and choline-deficient (MCD) diet in Hic-5 knockout mice. Liver tissues were analyzed by immunohistochemical staining, immunofluorescence and flow cytometry, with a particular focus on the impact on the immune microenvironment.</p><p><strong>Results: </strong>Hic-5 deficiency alleviates the severity of MAFLD, particularly the inflammation response. Gain- and loss-of-function experiments revealed that Hic-5 deficiency results in decreased neutrophil proliferation and increased apoptosis, as well as impaired migration. Conversely, Hic-5 overexpression had the opposite effects. This study confirmed that METTL3-mediated methylation of m⁶A stabilizes Hic-5 mRNA and promotes its expression, which in turn regulates the infiltration of neutrophils by the CXCL1-CXCR2 axis.</p><p><strong>Conclusions: </strong>The study reveals the role of Hic-5 in regulating neutrophils and indicates that it may be a potential therapeutic target for MAFLD.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023425","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":"Combination chemotherapy for older patients with unresectable biliary tract cancer: a prospective observational study using propensity-score matched analysis (JON2104-B).","authors":"Satoshi Kobayashi, Kohei Nakachi, Kouji Yamamoto, Makoto Ueno, Yuta Maruki, Kenji Ikezawa, Takeshi Terashima, Satoshi Shimizu, Kotoe Oshima, Kunihiro Tsuji, Yoshiharu Masaki, Hidetaka Tsumura, Taro Shibuki, Masato Ozaka, Naohiro Okano, Yukiyasu Okamura, Kumiko Umemoto, Tatsunori Satoh, Yasushi Kojima, Kazuhiko Shioji, Hiroko Nebiki, Toshifumi Doi, Atsushi Naganuma, Shigeki Kataoka, Emiri Kita, Hiroyuki Asama, Kaoru Tsuchiya, Michiaki Unno, Reiko Ashida, Kazuyuki Matsumoto, Izumi Ohno, Takao Itoi, Yuji Negoro, Yasunari Sakamoto, Shiho Arima, Akinori Asagi, Hiroyuki Okuyama, Yoshito Komatsu, Noritoshi Kobayashi, Hiroaki Nagano, Junji Furuse","doi":"10.1007/s00535-025-02294-0","DOIUrl":"https://doi.org/10.1007/s00535-025-02294-0","url":null,"abstract":"<p><strong>Background: </strong>Systemic chemotherapy with gemcitabine plus S-1 (GEM + S-1), GEM + CDDP plus S-1 (GEM + CDDP + S-1), or gemcitabine plus cisplatin (GEM + CDDP) is standard treatment for advanced biliary tract cancer (aBTC). We aimed to evaluate the efficacy and safety of combination chemotherapy in older patients with aBTC.</p><p><strong>Methods: </strong>This multicenter prospective observational study (JON2104-B, UMIN000045156) included patients aged ≥ 70 years with aBTC. Inverse-probability weighting propensity-score analyses (IPW) were used to compare overall survival (OS) as the primary endpoint and progression-free survival (PFS) across treatment groups.</p><p><strong>Results: </strong>This study included 305 patients between August 2021 and January 2023. Of them, 75, 131, 26, 52, and 10 received GEM + CDDP + S-1, GEM + CDDP, GEM + S-1, gemcitabine, and S-1; their median ages were 74, 75, 77.5, 80, and 80 years, and approximately 24%, 16.8%, 23.1%, 9.6%, and 0% had G-8 scores of > 14, respectively. GEM + CDDP had a safety profile comparable to that of GEM + CDDP + S-1 but was more toxic than gemcitabine. Per IPW, the hazard ratio (HR) for GEM + CDDP + S-1 versus GEM + CDDP was 0.80 for OS (95% confidence interval [CI], 0.55-1.17) and 0.55 for PFS (95% CI 0.38-0.80). The HR for GEM + CDDP versus gemcitabine was 0.74 for OS (95% CI 0.42-1.29) and 0.79 for PFS (95% CI 0.42-1.49).</p><p><strong>Conclusions: </strong>GEM + CDDP + S-1 was associated with longer PFS without additional toxicity than GEM + CDDP for fit older patients. However, the OS for both were not statistically different. The efficacies of GEM + CDDP and gemcitabine for vulnerable older patients did not also differ significantly. These findings highlight the importance of vulnerability in patients with aBTC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006261","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":"VPS45 promotes the progression of hepatocellular carcinoma by recycling β1 integrin to the cell membrane via the endocytic pathway.","authors":"Takashi Ofuchi, Hajime Otsu, Kiyotaka Hosoda, Tomohiko Ikehara, Akinori Tsujimoto, Satoshi Higuchi, Shohei Shibuta, Yuya Ono, Kosuke Hirose, Yasuo Tsuda, Yusuke Yonemura, Takaaki Masuda, Hiromitsu Hayashi, Masaaki Iwatsuki, Koshi Mimori","doi":"10.1007/s00535-025-02278-0","DOIUrl":"10.1007/s00535-025-02278-0","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is a highly aggressive malignancy with poor prognosis, which is often driven by chromosomal amplifications at 1q. Vacuolar sorting protein 45 (VPS45), a gene located on chromosome 1q, is involved in the endocytic recycling pathway; however, its role in HCC remains unclear. In this study, we aimed to investigate the functional significance of VPS45 in the progression of HCC.</p><p><strong>Methods: </strong>VPS45 expression was analyzed using public databases, clinical HCC samples, and cell lines. Functional assays, including VPS45 knockout and rescue experiments, were conducted to assess the effect on tumor progression in vitro and in vivo. The molecular mechanisms underlying VPS45 function, particularly its role in β1 integrin recycling and FAK-AKT signaling activation, were also explored.</p><p><strong>Results: </strong>VPS45 expression was significantly elevated in HCC owing to DNA copy number amplification and correlated with poor prognosis. Moreover, VPS45 knockout suppressed cell proliferation, migration, and invasion, while promoting apoptosis. VPS45 interacted with syntaxin16 and rabenosyn-5 to facilitate the recycling of β1 integrin to the cell membrane, thereby activating FAK-AKT signaling, which promotes oncogenic phenotypes. In xenograft models, VPS45 knockout significantly suppressed tumor growth, further supporting its role in HCC progression.</p><p><strong>Conclusions: </strong>VPS45 is a key oncogene in HCC that promotes tumor progression by enhancing β1 integrin recycling and activating FAK-AKT signaling. Given its strong association with poor prognosis and tumor malignancy, VPS45 may serve as a promising prognostic biomarker and a potential therapeutic target for HCC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1157-1173"},"PeriodicalIF":5.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333267","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":"SEC61G promotes colorectal cancer progression by regulating cytosolic Ca²⁺ concentration.","authors":"Satoshi Higuchi, Hajime Otsu, Takaaki Masuda, Masahiro Hashimoto, Yusuke Nakano, Kiyotaka Hosoda, Kosuke Hirose, Tomohiko Ikehara, Takashi Ofuchi, Yasuo Tsuda, Yusuke Yonemura, Mamoru Uemura, Hidetoshi Eguchi, Yuichiro Doki, Koshi Mimori","doi":"10.1007/s00535-025-02259-3","DOIUrl":"10.1007/s00535-025-02259-3","url":null,"abstract":"<p><strong>Background: </strong>Intracellular calcium (Ca²⁺) signaling regulates key cancer processes. Research findings suggest that the SEC61 complex, involved in protein translocation, contributes to calcium leakage from the endoplasmic reticulum. However, the mechanism by which SEC61 Translocon Subunit Gamma (SEC61G), a component of this complex, influences colorectal cancer (CRC) progression remains unclear.</p><p><strong>Methods: </strong>Bioinformatics analysis was performed using The Cancer Genome Atlas data sets to identify candidate genes on chromosome 7p, examine their association with DNA copy number amplification. In addition, SEC61G expression in CRC cells and tissues was validated using reverse-transcription quantitative polymerase chain reaction and immunohistochemistry. Moreover, in vitro and in vivo experiments were performed to investigate the effects of SEC61G overexpression and knockdown on CRC cell proliferation. Furthermore, publicly available single-cell RNA sequencing (scRNA-seq) and spatial transcriptome sequencing (ST-seq) data were used to validate the role of SEC61G in CRC.</p><p><strong>Results: </strong>SEC61G was significantly upregulated in CRC tissues and was correlated with poor prognosis in patients with CRC. SEC61G overexpression enhanced cell proliferation and activated the EGFR pathway, promoting cell cycle progression from the G1 to S phase. In addition, SEC61G overexpression increased cytosolic Ca²⁺ levels, which activated EGFR signaling via calmodulin. Moreover, analyses of scRNA-seq and ST-seq data confirmed that SEC61G expression was higher in tumor epithelial cells and that it was co-expressed with EGFR pathway-related genes.</p><p><strong>Conclusions: </strong>SEC61G promotes CRC progression by regulating cytosolic Ca²⁺ concentration, EGFR activation, and cell cycle progression, highlighting its potential as a prognostic biomarker and therapeutic target in CRC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1091-1107"},"PeriodicalIF":5.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142458","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":"Pretreatment serum angiopoietin-2 predicts prognosis and liver functional reserve after successful HCV eradication with sofosbuvir and velpatasvir in patients with HCV-related decompensated cirrhosis.","authors":"Naoki Kawagishi, Goki Suda, Yuki Tahata, Hayato Hikita, Takahiro Kodama, Satoshi Mochida, Nobuyuki Enomoto, Seiichi Mawatari, Hidekatsu Kuroda, Daiki Miki, Masayuki Kurosaki, Yoichi Hiasa, Norifumi Kawada, Taro Yamashita, Hiroshi Yatsuhashi, Hitoshi Yoshiji, Naoya Kato, Taro Takami, Hisamitsu Miyaaki, Kentaro Matsuura, Yasuhiro Asahina, Yoshito Itoh, Ryosuke Tateishi, Yasunari Nakamoto, Eiji Kakazu, Shuji Terai, Masahito Shimizu, Yoshiyuki Ueno, Norio Akuta, Masatsugu Ohara, Naoya Sakamoto, Tetsuo Takehara","doi":"10.1007/s00535-025-02275-3","DOIUrl":"10.1007/s00535-025-02275-3","url":null,"abstract":"<p><strong>Background: </strong>Direct-acting-antivirals (DAAs) achieve high sustained-virologic response (SVR) rates, even in patients with hepatitis C virus (HCV)-related decompensated liver cirrhosis (LC). However, predictors of post-treatment liver function improvement and survival remain unclear. This study evaluated pretreatment angiopoietin-2 (Ang2) levels as a predictor of prognosis and liver functional reserve after DAA treatment.</p><p><strong>Methods: </strong>This multicenter retrospective study included 123 patients with HCV-related decompensated LC treated with sofosbuvir/velpatasvir. Serum Ang2 levels were quantified, and liver function was assessed using the Child-Pugh grading at baseline and 12 weeks after the end of treatment (SVR12). Factors associated with prognosis and post-SVR liver functional reserve (Child-Pugh grade C) were investigated.</p><p><strong>Results: </strong>Multivariate Cox regression analysis revealed that, in addition to age and creatinine levels at SVR12, baseline Ang2 levels (hazard ratio [HR] = 1.151 per 1000 pg/mL, P = 0.033) and Child-Pugh grade C at SVR12 (HR = 11.765, P < 0.001), but not baseline Child-Pugh grade C, were significantly associated with the overall survival. Multivariate analysis revealed that baseline Ang2 levels and baseline Child-Pugh grade C were significantly and independently associated with Child-Pugh grade C at SVR12. The combination of elevated baseline Ang2 levels (≥ 8684 pg/mL; 1 point) and baseline Child-Pugh grade C (1 point) effectively stratified patients with a high likelihood of having Child-Pugh Grade C at SVR12. The incidence rates were as follows: 0 points, 2.1% (2/96); 1 point, 37.5% (9/24); and 2 points, 100% (2/2) (P < 0.001).</p><p><strong>Conclusions: </strong>Pretreatment Ang2 levels predict survival and liver functional reserve after SVR in HCV-related decompensated LC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1145-1156"},"PeriodicalIF":5.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336615","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":"Noninvasive prediction of the clinical benefit of immunotherapy in hepatocellular carcinoma.","authors":"Atsushi Ono, C Nelson Hayes, Ryoichi Miura, Tomokazu Kawaoka, Masataka Tsuge, Shiro Oka","doi":"10.1007/s00535-025-02251-x","DOIUrl":"10.1007/s00535-025-02251-x","url":null,"abstract":"<p><p>Long-term survival following a diagnosis of hepatocellular carcinoma (HCC) is greatly diminished when transplantation and surgical resection are ruled out. Fortunately, the advent of immune checkpoint inhibitors (ICIs) has revolutionized the treatment of advanced unresectable HCC (uHCC), prolonging median survival by over a year. T lymphocytes normally eliminate neoplastic cells, but some tumors suppress this response by binding to immune checkpoint receptors. Blocking this interaction via ICIs restores immune-mediated targeting of cancer cells. While ICI-based combination immunotherapy is currently recommended as the first-line systemic therapy for uHCC, the objective radiological response rate remains limited to 20-30%, as not all tumors exploit this mechanism. Consequently, strategies are being explored to modulate the immune microenvironment into a \"hot\" environment more responsive to ICIs by combining local therapies such as transarterial chemoembolization, ablation, and radiation therapy. Therapeutic options have also expanded beyond ICIs, emphasizing the importance of selecting the most appropriate treatment. Therefore, the development of biomarkers capable of predicting the efficacy of immunotherapy is a priority. Direct evaluation of immune cell infiltration through biopsy is currently the most effective method but involves issues such as invasiveness and susceptibility to sampling bias. In this review, we aim to highlight promising non-invasive biomarkers and scoring systems that have the potential to improve treatment outcomes, including blood-based biomarkers such as lymphocyte ratios, cytokines, C-reactive protein, and alpha-fetoprotein; imaging biomarkers such as MRI, ultrasound, and contrast-enhanced CT; and other clinical indicators such as sarcopenia, grip strength, and diversity of the gut microbiome.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1053-1069"},"PeriodicalIF":5.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12378506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187137","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":"Asia Pacific Gastroesophageal Cancer Congress (APGCC) 2024 consensus statement on stage 2 and 3 locally advanced gastric and Siewert 3 junctional adenocarcinoma.","authors":"Yoshio Masuda, Kang Ler Fong, Danson Yeo, Charleen Yeo, Koy Min Chue, Said Bani Araba, Chiew Woon Lim, Baldwin Yeung, June Lee, Jinlin Lin, Claramae Chia, Matthew Ng, Kennedy Ng, Jens Samol, Daryl Chia, Jun Liang Teh, Raghav Sundar, Wei-Peng Yong, Hon Lyn Tan, Kei Muro, Florian Lordick, Zev Wainburg, Bo Chuan Tan, Guowei Kim, Koichi Suda, Simon Law, Takeshi Sano, Ramesh Gurunathan, Philip Chiu, Emile Woo, Cuong Duong, Han-Kwang Yang, Vo Duy Long, Hyung Ho Kim, Han Alexander Mahendren, Hyuk Joon Lee, Inian Samarasam, Takuji Gotoda, Reis Liew, Asim Shabbir, Myint Oo Aung, Masanori Terashima, Edward Cheong, Jimmy So, Jeremy Tan","doi":"10.1007/s00535-025-02266-4","DOIUrl":"10.1007/s00535-025-02266-4","url":null,"abstract":"<p><strong>Background: </strong>While the development in multimodal therapies has helped improve treatment outcomes for patients with locally advanced gastric adenocarcinoma (LAGC), there still exist disparities in opinion with an optimal treatment plan. This consensus hopes to provide clinicians with structured guidelines to aid in the decision-making for treatment options for LAGC.</p><p><strong>Methods: </strong>The consensus statement was initiated by establishing a taskforce in collaboration with the Asia Pacific Gastroesophageal Cancer Congress (APGCC) and a multidisciplinary expert panel was selected. Clinical questions on LAGC where perceived variance in practice or opinion may exist were formulated. Studies involving patients with Stage 2 or 3 gastric or Siewert 3 junctional cancers with treatment arms of perioperative chemotherapy, neoadjuvant chemotherapy, adjuvant chemotherapy, immunotherapy and surgery were included. A total of two rounds of voting were performed. Consensus was determined to be reached when a single answer or a combination of either \"strongly agree/agree\" or \"strongly disagree/disagree\" responses exceeded 75%.</p><p><strong>Results: </strong>A total of thirteen clinical questions were developed. They were identified through five main categories: Distal LAGC, Proximal LAGC, Deficient mismatch repair tumors, Chemotherapy and Immunotherapy, and Elderly/Unfit patients. After two rounds of voting by our multidisciplinary expert panel, eleven out of a total thirteen clinical questions had reached consensus. No consensus was reached for two clinical questions.</p><p><strong>Conclusion: </strong>The APGCC consensus statement aims to guide clinicians in the treatment options for LAGC and Siewert 3 junctional cancer and has clarified some of the roles of perioperative chemotherapy and immunotherapy.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1079-1090"},"PeriodicalIF":5.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293862","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}