Journal of Gastroenterology最新文献

{"title":"B cell receptor-associated protein 31 levels in serum-derived extracellular vesicles are associated with therapeutic response and prognosis in patients with advanced hepatocellular carcinoma receiving atezolizumab plus bevacizumab: a multicenter study.","authors":"Takanori Suzuki, Kentaro Matsuura, Yutaka Hashimoto, Masako Okina, Ryo Sato, Hayato Kawamura, Kiyoto Narita, Kei Fujiwara, Satoshi Narahara, Haruki Uojima, Hiromi Kataoka, Yasuhito Tanaka","doi":"10.1007/s00535-026-02515-0","DOIUrl":"https://doi.org/10.1007/s00535-026-02515-0","url":null,"abstract":"<p><strong>Background: </strong>There remains an unmet need for reliable biomarkers associated with therapeutic response to immune checkpoint inhibitors (ICIs) in hepatocellular carcinoma (HCC). We retrospectively examined protein levels in serum-derived extracellular vesicles (EVs) as candidate biomarkers associated with treatment response in patients with advanced HCC.</p><p><strong>Methods: </strong>A total of 122 patients with advanced HCC treated with atezolizumab plus bevacizumab (ATZ/BEV) were retrospectively selected. The discovery group comprised 12 patients, whose serum-derived EV samples underwent comprehensive proteomic profiling by quantitative data-independent acquisition mass spectrometry. The remaining 110 patients comprised the validation group, in whom selected EV proteins were quantified by parallel reaction monitoring analysis.</p><p><strong>Results: </strong>B cell receptor-associated protein 31 (BAP31) was identified as an exploratory biomarker associated with early treatment response. Receiver operating characteristic analysis of pretreatment log₂ BAP31 levels for distinguishing non-progressive disease from progressive disease at the initial response in the validation group yielded an area under the curve of 0.719 and an optimal cut-off of -14.582. This threshold stratified overall survival (OS) in the entire cohort (44.8 vs 25.3 months for low- vs high-level groups, P = 0.039). Multivariable analysis showed that EV BAP31 levels were independently associated with OS (HR 1.78, P = 0.044); however, this association was attenuated and was no longer statistically significant after propensity score adjustment. No significant association with progression-free survival was observed.</p><p><strong>Conclusions: </strong>Pretreatment BAP31 levels in serum-derived EVs may represent an exploratory biomarker potentially associated with early treatment response and prognosis in patients with advanced HCC receiving ATZ/BEV. Further validation is warranted.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891881","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":"Temporal sequence in chronic kidney disease risk assessment in primary biliary cholangitis.","authors":"Huijuan Cheng, Zhe Zhang, Feng Lu","doi":"10.1007/s00535-026-02512-3","DOIUrl":"https://doi.org/10.1007/s00535-026-02512-3","url":null,"abstract":"","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887401","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":"Extracellular vesicle biomarkers in pancreatic ductal adenocarcinoma: from bulk detection to single-extracellular vesicle profiling and endoscopic liquid biopsy.","authors":"Nana Shimamoto, Kazuki Sumiyama, Yu Fujita","doi":"10.1007/s00535-026-02350-3","DOIUrl":"10.1007/s00535-026-02350-3","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) remains a deadly malignancy owing to its late presentation and the limited sensitivity of current serum biomarkers and imaging for early detection. Extracellular vesicles (EVs), which carry proteins, nucleic acids, and lipids that reflect tumor-stromal interactions, have emerged as promising biomarkers for early diagnosis, disease monitoring, and treatment response. Several EV-derived proteins, microRNAs, long noncoding RNAs, and DNA alterations linked to early carcinogenesis and therapeutic resistance have been identified. However, variability in pre-analytical handling and analytical platforms has hindered reproducibility. Global standardization efforts, such as European Liquid Biopsy Society (ELBS), The Blood Profiling Atlas in Cancer (BloodPAC), International Liquid Biopsy Standardization Alliance (ILSA), and Minimal information for studies of extracellular vesicles (MISEV), are currently helping to unify methodologies for EV isolation and molecular profiling. Advances in analytical technologies have shifted the field from bulk EV measurements to high-resolution single-vesicle approaches. Techniques, such as nanoflow cytometry, super-resolution imaging, Raman spectroscopy, and surface-enhanced Raman scattering, enable the detection of rare, mutation-bearing, or functionally distinct EV subpopulations, which may enhance diagnostic precision. In gastroenterology, a major opportunity lies in integrating single-EV analytics with the endoscopic sampling of tumor-proximal fluids. EVs obtained from pancreatic juice, bile, duodenal fluid, or portal venous blood via endoscopic retrograde cholangiopancreatography (ERCP) or endoscopic ultrasound (EUS) provide spatially enriched molecular information beyond peripheral blood. Combining endoscopic access with particle-level EV characterization may allow real-time, mechanism-informed assessment of tumor biology and premalignant lesions, offering a promising strategy for early detection and risk stratification in PDAC. Together, these developments have positioned EV-based liquid biopsy as a rapidly maturing field with strong translational potential.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1234-1250"},"PeriodicalIF":5.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13506566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132098","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":"A modified Delphi consensus on fusion (laparoscopic and robotic) approaches to colorectal surgery in Asia-Pacific.","authors":"Jun Watanabe, Yoshinori Kagawa, Takashi Nonaka, Hyejin Kim, Siripong Cheewatanakornkul, Peter Chien-Chih Chen, William Tzu-Liang Chen, Ashwin deSouza, Atsushi Hamabe, Hiroyasu Kagawa, Yoon Suk Lee, Simon Siu-Man Ng, Andrew R L Stevenson, Nan Zun Teo, Mamoru Uemura, Kar Yong Wong, James Chi-Yong Ngu","doi":"10.1007/s00535-026-02445-x","DOIUrl":"10.1007/s00535-026-02445-x","url":null,"abstract":"<p><strong>Background: </strong>Fusion surgery, where laparoscopic techniques are purposefully integrated into robotic surgery, is a novel approach that can be used in colorectal surgery. However, a standard definition and practical guidance are lacking. Therefore, this study aimed to generate consensus to standardise the definition of fusion surgery and consequently raise awareness of fusion surgical approaches and their appropriate use cases.</p><p><strong>Methods: </strong>We conducted a two-round modified Delphi study with 17 colorectal surgeons from Asia-Pacific (5 Steering Committee [SC]; 12 Expert Panellists [EP]). Statements were drafted by the SC based on clinical experience, published literature and comments from the EP. The EP rated these statements anonymously on a 5-point Likert scale. A virtual expert meeting was held between voting rounds to discuss the statements. Consensus was predefined as ≥ 75% \"agree\"/\"strongly agree\" or \"disagree\"/\"strongly disagree\".</p><p><strong>Results: </strong>Ultimately, consensus was reached on 23 statements: \"Defining Fusion Surgery in Colorectal Surgery\" (n = 2); \"When to Consider Fusion Surgery in Colorectal Surgery\" (n = 10; 5 statements each on \"Device Factors\" and \"Surgeon Factors\"); \"Task- or Procedure-Specific Considerations in Colorectal Surgery\" (n = 11).</p><p><strong>Conclusion: </strong>The Expert Panel were aligned on the definition of fusion surgery as a procedure where laparoscopic tools and techniques are electively combined with robotic surgery. Fusion surgery may achieve similar safety and effectiveness as fully robotic surgery, whilst potentially offering advantages such as improved ergonomics, shorter operating times and educational opportunities for bedside assistants. This consensus serves as a valuable guide containing considerations for surgeons to encourage the appropriate adoption of fusion approaches in colorectal surgery.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1284-1294"},"PeriodicalIF":5.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13506586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147959800","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":"Regulatory mechanism of the RNF168-SCCA1-MYH9 signaling axis in the response of ulcerative colitis.","authors":"Xuanqi Zhang, Junyan Zhu, Fang Wei, Lingyi Bu, Yingying Xing","doi":"10.1007/s00535-026-02458-6","DOIUrl":"10.1007/s00535-026-02458-6","url":null,"abstract":"<p><strong>Background and aim: </strong>The potential function of E3 ubiquitin ligase RNF168 in inflammatory processes remains largely unexplored. Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) characterized by chronic inflammation and epithelial damage of the intestinal mucosa. The pathophysiology of UC is complex, and its mechanisms remain incompletely understood. This study explores the role of RNF168 in the pathogenesis of experimental colitis.</p><p><strong>Methods: </strong>RNF168-knockout murine models were employed. The functional impact of RNF168 was determined by assessing colitis severity and susceptibility in these mice through a comprehensive evaluation of disease activity index, histological scoring, and pro-inflammatory cytokine levels. The molecular mechanism was explained using co-immunoprecipitation combined with mass spectrometry to identify and confirm downstream effectors.</p><p><strong>Results: </strong>We identified RNF168 as a susceptibility gene for colonic inflammation in mouse models and cell lines. RNF168 downregulation in colonic inflammation reduces SCCA1 ubiquitination, leading to SCCA1 accumulation. Increased SCCA1 contribute to inflammation by suppresses the MYH9-p53 signaling pathway, subsequently reduces the expression of p53 and phosphorylated p53 (p-p53), thereby exacerbating the inflammatory response. Administration of the small-molecule SCCA1 inhibitor 1-PPA alleviated colonic inflammation pathology. Our findings reveal a novel ubiquitination-dependent pathway and identify SCCA1 as a promising therapeutic target for colonic inflammation.</p><p><strong>Conclusions: </strong>Our findings reveal a novel ubiquitination-dependent pathway in experimental colitis pathogenesis and identify SCCA1 as a promising therapeutic target for colitis. Elucidating these mechanisms opens avenues for developing therapies targeting inflammatory responses in UC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1295-1311"},"PeriodicalIF":5.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148264860","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":"Covert hepatic encephalopathy as a multi-organ syndrome: the gut-liver-muscle-brain axis, diagnosis, treatment, and multidisciplinary care.","authors":"Takao Miwa, Cynthia L Hsu, Masahito Shimizu, Patricia P Bloom, Bernd Schnabl","doi":"10.1007/s00535-026-02425-1","DOIUrl":"10.1007/s00535-026-02425-1","url":null,"abstract":"<p><p>Covert hepatic encephalopathy (CHE) is a highly prevalent complication of liver cirrhosis. Despite the absence of overt symptoms, CHE is strongly associated with impaired quality-of-life, overt hepatic encephalopathy, and mortality. Over the past two decades, evidence regarding the pathophysiology, diagnosis, and treatment of CHE has accumulated considerably, and clinical guidelines recommend screening in patients with cirrhosis. Nevertheless, diagnostic and therapeutic algorithms have not been fully implemented in real-world practice, and many patients remain undiagnosed and untreated. Understanding the natural history of CHE is essential to improve cirrhosis care, as it provides a framework for appropriate screening, treatment decision-making, and patient counseling. CHE is a multi-organ syndrome with complex interactions between the liver, gut, skeletal muscle, kidneys, and brain, with impaired ammonia handling and systemic inflammation acting as central drivers of this organ crosstalk. Hyperammonemia induces astrocytic dysfunction, brain edema, and neuroinflammation, while systemic inflammation, oxidative stress, sarcopenia, gut dysbiosis, and altered microbial metabolites, including bile acids and short-chain fatty acids, further modulate disease expression. In this review, we summarize current understanding of CHE pathophysiology, diagnostic testing, including psychometric batteries and point-of-care tools, such as the Stroop test and animal naming test, and therapeutic options, ranging from lactulose and rifaximin to microbiome-targeted approaches, including fecal microbiota transplantation. We also highlight major challenges in CHE management, including limited implementation of testing, inadequate biomarkers, diagnostic difficulties in geriatric cirrhosis, and unmet needs in fall and driving risk management, and emphasize the importance of multidisciplinary team-based approaches to improve patient outcomes.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1217-1233"},"PeriodicalIF":5.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13506657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838944","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":"Reelin level in serum-derived extracellular vesicles predicts regression of M2BPGi-defined liver fibrosis following hepatitis C virus eradication by direct-acting antiviral agents.","authors":"Takanori Suzuki, Kentaro Matsuura, Yutaka Hashimoto, Masako Okina, Mayumi Hojo, Hayato Kawamura, Kei Fujiwara, Katsuya Nagaoka, Takehisa Watanabe, Hiromi Kataoka, Yasuhito Tanaka","doi":"10.1007/s00535-026-02454-w","DOIUrl":"10.1007/s00535-026-02454-w","url":null,"abstract":"<p><strong>Background: </strong>We investigated serum-derived extracellular vesicle (EV)-associated proteins as predictors of liver fibrosis (LF) regression following sustained virological responses (SVR) in individuals with chronic hepatitis C (CHC) managed using direct-acting antiviral (DAA) therapy.</p><p><strong>Methods: </strong>We retrospectively analyzed 107 CHC patients with pretreatment Mac-2 binding protein glycosylation isomer (M2BPGi) levels ≥ 2.0 cut-off index (COI). Two years after the end of treatment (EOT), participants were grouped according to the M2BPGi levels: regression group (M2BPGi < 1.76 COI) and non-regression group (M2BPGi ≥ 1.76 COI). Twelve patients were selected for the discovery cohort, where comprehensive protein profiling of serum-derived EVs was performed at 12-24 weeks post-EOT using quantitative mass spectrometry for label-free quantification. The remaining 95 patients formed the validation group, in which the identified EV proteins were further assessed via protein quantification using parallel reaction monitoring.</p><p><strong>Results: </strong>Reelin (RELN) and oncoprotein-induced transcript 3 (OIT3) protein had potential role as predictors of fibrosis regression in both groups. Multivariate analysis incorporating clinical parameters indicated that levels of RELN and OIT3 were associated with fibrosis regression (odds ratio [OR] = 1.510; P = 0.022 for log₂ RELN, and OR = 0.297; P = 0.001 for log₂ OIT3). In cases with advanced fibrosis (baseline M2BPGi ≥ 3.3 COI), RELN showed a borderline significant result (OR = 1.550; P = 0.050 for log₂ RELN).</p><p><strong>Conclusions: </strong>Serum-derived EV levels of RELN show promise as predictor of LF regression in CHC patients following SVR.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1322-1333"},"PeriodicalIF":5.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148138260","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":"Clinical significance of gadoxetate sodium-enhanced MRI for detecting liver metastasis in patients with pancreatic cancer: decadal real-world data analysis in Japan.","authors":"Atsushi Oba, Tomoyuki Taguchi, Naoto Fujikawa, Suguru Okami, Takashi Tsuji, Alexander Michel, Satoshi Goshima","doi":"10.1007/s00535-026-02431-3","DOIUrl":"10.1007/s00535-026-02431-3","url":null,"abstract":"<p><strong>Background: </strong>Precise, early diagnosis of liver metastasis improves clinical outcomes in patients with pancreatic cancer. While gadoxetate sodium-enhanced magnetic resonance imaging (EOB-MRI) may offer additional benefits in detecting liver metastases in patients with pancreatic cancer, it is still unclear whether the addition of this imaging modality to contrast-enhanced computed tomography (CE-CT) confers clinical benefits regarding prognosis and access to appropriate treatments. The objective is to evaluate the treatment pathway of patients with or without EOB-MRI after a pancreatic cancer diagnosis and examine whether the addition of EOB-MRI is associated with improved survival.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted using a Japanese hospital-based administrative database. Patients aged ≥ 18 years and diagnosed with pancreatic cancer between 2011 and 2021 with any record of CE-CT or MRI were included. Patients were stratified based on a record of EOB-MRI (EOB-MRI vs. non-EOB-MRI). Main outcomes were treatment pathway and overall survival (OS). OS was compared between the EOB-MRI and non-EOB-MRI groups using Cox proportional hazard regression models in the propensity-score-matched cohort.</p><p><strong>Results: </strong>A total of 39,624 patients were included. The proportion of neoadjuvant chemotherapy increased to 13.4% during recent years (2019-2021) in the EOB-MRI group versus 7.8% in the non-EOB-MRI group. Significantly longer OS in the matched cohort was observed (HR [95% CI] = 0.88 [0.83-0.94]) in the EOB-MRI group (1,442 days [1275-1604]) versus the non-EOB-MRI group (1,293 days [1187-1440]).</p><p><strong>Conclusions: </strong>The addition of EOB-MRI was associated with increased survival times in patients with pancreatic cancer.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1334-1345"},"PeriodicalIF":5.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816154","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":"Conversion surgery for unresectable pancreatic ductal adenocarcinoma with liver metastasis at initial diagnosis: a nationwide multicenter study.","authors":"Daisuke Hashimoto, Tsukasa Ikeura, Aya Maekawa, Takayoshi Nakajima, Keinosuke Ishido, Aoi Hayasaki, Toshimichi Asano, Masamichi Hayashi, Isaku Yoshioka, Hiromichi Ishii, Akifumi Kimura, Hideki Motobayashi, Masaaki Murakawa, Kenjiro Okada, Toshiya Abe, Yoshiki Hirooka, Masafumi Imamura, Keiko Kamei, Shogo Kobayashi, Toru Maruo, Joe Matsumoto, Katsuyuki Miyabe, Minako Nagai, Shinsuke Nakashima, Yoshitaro Shindo, Makoto Shinzeki, Shuji Suzuki, Tatsunori Suzuki, Masayuki Tanaka, Satoshi Tanno, Tomoyuki Yokota, Kenta Murotani, Yousuke Nakai, Yosuke Inoue, Masamichi Mizuma, Michiaki Unno, Ippei Matsumoto, Tsutomu Fujii, Kenichiro Uemura, Masayuki Sho, Satoshi Hirano, Sohei Satoi, Atsushi Masamune, Yoshifumi Takeyama","doi":"10.1007/s00535-026-02432-2","DOIUrl":"10.1007/s00535-026-02432-2","url":null,"abstract":"<p><strong>Background: </strong>With recent advances in chemotherapy for unresectable pancreatic ductal adenocarcinoma (PDAC) with liver metastasis (LM), attempts have been made to resect the primary tumor in patients showing favorable responses to anti-cancer treatment (so-called \"conversion surgery\"; CS). This study aimed to clarify the outcomes of CS for PDAC with LM in a nationwide multicenter study.</p><p><strong>Methods: </strong>This retrospective, multicenter study was conducted as a project study of the Japan Pancreas Society and included patients with PDAC with LM at initial diagnosis, diagnosed radiologically or intraoperatively (occult LM), who underwent CS after at least 4 months of chemotherapy between 2010 and 2022. Survival outcomes and prognostic factors were analyzed.</p><p><strong>Results: </strong>90 patients were enrolled from 31 Japanese institutions. Median duration of preoperative chemotherapy was 10.4 (range, 4.2-58.5) months, and gemcitabine plus nab-paclitaxel was the most common first-line regimen, followed by folinic acid, 5-fluorouracil, irinotecan, and oxaliplatin. Liver metastasectomy was performed in 27 patients (30%). 82 patients (91.1%) initiated adjuvant chemotherapy, and 41 (45.6%) completed it. Overall survival (OS) from initial treatment was 53.1 (95% CI 41.6-65.7) months; OS after CS was 39.7 (95% CI 24.4-55.9) months, and disease-free survival was 14.7 (95% CI 9.3-23.4) months. Preoperative normalization of carbohydrate antigen 19-9 and pathologic negative lymph node metastasis were independent prognostic factors for OS.</p><p><strong>Conclusion: </strong>CS may provide a survival benefit for highly selected patients with PDAC and LM, including those with occult lesions, who respond well to multidisciplinary treatment.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1346-1360"},"PeriodicalIF":5.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816115","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":"Selective IL-23 inhibitors in ulcerative colitis: current evidence and perspectives for multimodal personalized treatment: a narrative review.","authors":"Ichitaro Horiuchi, Akira Horiuchi, Ken Sugimoto","doi":"10.1007/s00535-026-02429-x","DOIUrl":"10.1007/s00535-026-02429-x","url":null,"abstract":"<p><p>The heterogeneity of ulcerative colitis (UC) results in variable biological responses. Although anti-tumor necrosis factor (anti-TNF) agents remain a cornerstone of therapy, 30-40% of patients experience primary non-response, which is often linked to persistent activation of the interleukin-23 (IL-23) pathway. There is increasing evidence that the IL-23-Th17-neutrophil axis plays a central role in mucosal inflammation and treatment resistance. Phase II and III trials of selective IL-23 inhibitors for UC have demonstrated high rates of endoscopic and histologic remission, with safety profiles comparable to those of anti-TNF agents. These agents have demonstrated efficacy in various patient subgroups, including those with a history of anti-TNF failure. This supports their potential as effective alternatives to existing biologics. Based on these data, we propose a multimodal framework for personalized treatment selection that integrates three diagnostic pillars: (1) noninvasive biomarkers, such as serum leucine-rich alpha-2 glycoprotein and fecal calprotectin, to differentiate between systemic and mucosal inflammation, (2) the Mayo Endoscopic Subscore to guide therapeutic intensity, and (3) quantitative histopathology, specifically the Komagane subclassification of Geboes Grade 3, to identify IL-23-Th17-dominant activity. This integrative approach may enable predicting biologic responses, risk stratification, and the individualized use of selective IL-23 inhibitors. We propose this strategy as a model for generating hypotheses for future personalized medicine studies in UC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1207-1216"},"PeriodicalIF":5.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816228","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}