Journal of Gastroenterology最新文献

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Main genetic factors associated with inflammatory bowel diseases and their consequences on intestinal permeability: involvement in gut inflammation. 与炎症性肠病相关的主要遗传因素及其对肠通透性的影响:参与肠道炎症
IF 5.5 2区 医学
Journal of Gastroenterology Pub Date : 2025-11-01 Epub Date: 2025-08-21 DOI: 10.1007/s00535-025-02289-x
Arthur Mauduit, Emmanuel Mas, Nuria Solà-Tapias, Sandrine Ménard, Frédérick Barreau
{"title":"Main genetic factors associated with inflammatory bowel diseases and their consequences on intestinal permeability: involvement in gut inflammation.","authors":"Arthur Mauduit, Emmanuel Mas, Nuria Solà-Tapias, Sandrine Ménard, Frédérick Barreau","doi":"10.1007/s00535-025-02289-x","DOIUrl":"10.1007/s00535-025-02289-x","url":null,"abstract":"<p><p>Crohn's disease (CD) and ulcerative colitis (UC), the two main subtypes of inflammatory bowel diseases (IBD), are chronic relapsing inflammatory disorders of the gastrointestinal tract. IBD are multifactorial diseases with a complex etiology, involving an intricate interaction between environmental and genetic factors. Since the discovery of NOD2 gene in 2001, genome-wide association studies have reported more than 200 IBD susceptibility loci. The strongest associations highlighted five main pathways as altered in IBD: bacterial sensing (NOD2), autophagy (ATG16L1, IRGM…), endoplasmic reticulum stress (XBP1, ARG2…), Th-17 immune pathway (IL23-receptor), and the vitamin D receptors (VDR). The pathophysiology of IBD results from an abnormal immune response toward an altered gut microbiota. Although the primum movens remains unknown, an increased intestinal permeability is clearly involved in the genesis of this abnormal crosstalk, leading to whole tissue inflammation. Thus, an excessive intestinal permeability, or \"leaky gut\", has been described to precede the development of CD. Moreover, in IBD, intestinal permeability is described to be a sensitive prognostic indicator of relapse in patients with quiescent IBD. Thus, the aim of this review is to highlight the molecular and cellular mechanisms by which the main pathways associated with IBD could contribute to alter the intestinal permeability to favour and/or exacerbate chronic inflammation, leading to debilitating diseases.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1323-1338"},"PeriodicalIF":5.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957135","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}
引用次数: 0
Potential role of Geriatric Nutritional Risk Index as a risk factor for immune-mediated adverse events during durvalumab plus tremelimumab therapy in unresectable hepatocellular carcinoma. 老年营养风险指数作为durvalumab加tremelimumab治疗不可切除肝细胞癌期间免疫介导不良事件的危险因素的潜在作用。
IF 5.5 2区 医学
Journal of Gastroenterology Pub Date : 2025-11-01 Epub Date: 2025-08-20 DOI: 10.1007/s00535-025-02290-4
Hideko Ohama, Atsushi Hiraoka, Toshifumi Tada, Masashi Hirooka, Kazuya Kariyama, Joji Tani, Masanori Atsukawa, Koichi Takaguchi, Ei Itobayashi, Shinya Fukunishi, Kunihiko Tsuji, Toru Ishikawa, Kazuto Tajiri, Hironori Tanaka, Hidenori Toyoda, Chikara Ogawa, Takashi Nishimura, Takeshi Hatanaka, Satoru Kakizaki, Kazuhito Kawata, Atsushi Naganuma, Hisashi Kosaka, Tomomitsu Matono, Hidekatsu Kuroda, Yutaka Yata, Hiroki Nishikawa, Michitaka Imai, Tomoko Aoki, Hironori Ochi, Hideyuki Tamai, Shohei Komatsu, Fujimasa Tada, Shinichiro Nakamura, Yoshiko Nakamura, Teruki Miyake, Osamu Yoshida, Kazuhiro Nouso, Asahiro Morishita, Norio Itokawa, Tomomi Okubo, Taeang Arai, Akemi Tsutsui, Takuya Nagano, Kazunari Tanaka, Takanori Matsuura, Yuichi Koshiyama, Yuki Kanayama, Hidenao Noritake, Hirayuki Enomoto, Kosuke Matsui, Masaki Kaibori, Takumi Fukumoto, Yoichi Hiasa, Masatoshi Kudo, Takashi Kumada
{"title":"Potential role of Geriatric Nutritional Risk Index as a risk factor for immune-mediated adverse events during durvalumab plus tremelimumab therapy in unresectable hepatocellular carcinoma.","authors":"Hideko Ohama, Atsushi Hiraoka, Toshifumi Tada, Masashi Hirooka, Kazuya Kariyama, Joji Tani, Masanori Atsukawa, Koichi Takaguchi, Ei Itobayashi, Shinya Fukunishi, Kunihiko Tsuji, Toru Ishikawa, Kazuto Tajiri, Hironori Tanaka, Hidenori Toyoda, Chikara Ogawa, Takashi Nishimura, Takeshi Hatanaka, Satoru Kakizaki, Kazuhito Kawata, Atsushi Naganuma, Hisashi Kosaka, Tomomitsu Matono, Hidekatsu Kuroda, Yutaka Yata, Hiroki Nishikawa, Michitaka Imai, Tomoko Aoki, Hironori Ochi, Hideyuki Tamai, Shohei Komatsu, Fujimasa Tada, Shinichiro Nakamura, Yoshiko Nakamura, Teruki Miyake, Osamu Yoshida, Kazuhiro Nouso, Asahiro Morishita, Norio Itokawa, Tomomi Okubo, Taeang Arai, Akemi Tsutsui, Takuya Nagano, Kazunari Tanaka, Takanori Matsuura, Yuichi Koshiyama, Yuki Kanayama, Hidenao Noritake, Hirayuki Enomoto, Kosuke Matsui, Masaki Kaibori, Takumi Fukumoto, Yoichi Hiasa, Masatoshi Kudo, Takashi Kumada","doi":"10.1007/s00535-025-02290-4","DOIUrl":"10.1007/s00535-025-02290-4","url":null,"abstract":"<p><strong>Background: </strong>Immune-mediated adverse events (imAEs) are a significant concern in patients with unresectable hepatocellular carcinoma (uHCC) undergoing combination immunotherapy with durvalumab and tremelimumab (Dur/Tre). This study aimed to investigate the potential association of risk factors, particularly nutrition and immune markers, associated with the development of imAEs.</p><p><strong>Methods: </strong>Between November 2022 and December 2024, 312 patients with uHCC treated with Dur/Tre were enrolled and retrospectively analyzed. Clinical characteristics, inflammatory markers, and nutritional indices (Geriatric Nutritional Risk Index [GNRI], body mass index, Prognostic Nutritional Index-Onodera, C-reactive protein-to-albumin ratio, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio) were evaluated to identify predictors for imAE development.</p><p><strong>Results: </strong>The imAEs occurred in 122 patients (39.1%), most commonly affecting dermatological, gastrointestinal, and endocrine systems. On multivariate analysis, only normal GNRI (≥ 98) was independently associated with a higher incidence of imAE (odds ratio: 1.99, 95% confidence interval: 1.05-3.79, P = 0.036). Patients with GNRI ≥ 98 also showed better overall survival (OS) than those with GNRI < 98 (not reached vs. 12.5 months, P < 0.001). Among patients who developed imAEs, no significant differences were observed in the imAE types or high-dose steroid use between the GNRI ≥ 98 group (n = 66) and the GNRI < 98 group (n = 56) (40.9% vs. 58.9%, P = 0.069).</p><p><strong>Conclusions: </strong>Normal GNRI status (≥ 98) was associated with an increased risk of imAE development and improved OS in patients with uHCC receiving Dur/Tre therapy. GNRI may be a useful clinical factor for identifying patients at higher risk of developing imAEs.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1427-1436"},"PeriodicalIF":5.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957127","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}
引用次数: 0
Current status of waitlist mortality and transplant probability for adult candidates with chronic end-stage liver disease for deceased donor liver transplantation under the Model for End-Stage Liver Disease score-based allocation policy in Japan. 在日本终末期肝病评分分配政策下,慢性终末期肝病成年患者等待死亡供肝移植的死亡率和移植概率的现状
IF 5.5 2区 医学
Journal of Gastroenterology Pub Date : 2025-11-01 Epub Date: 2025-08-14 DOI: 10.1007/s00535-025-02288-y
Yusuke Takemura, Yoshihide Ueda, Ryo Takemura, Junya Mita, Juntaro Ashikari, Kaori Kuramitsu, Yasushi Hasegawa, Minoru Kitago, Hideaki Obara, Yuko Kitagawa, Hideki Ohdan, Hiroyuki Yokota
{"title":"Current status of waitlist mortality and transplant probability for adult candidates with chronic end-stage liver disease for deceased donor liver transplantation under the Model for End-Stage Liver Disease score-based allocation policy in Japan.","authors":"Yusuke Takemura, Yoshihide Ueda, Ryo Takemura, Junya Mita, Juntaro Ashikari, Kaori Kuramitsu, Yasushi Hasegawa, Minoru Kitago, Hideaki Obara, Yuko Kitagawa, Hideki Ohdan, Hiroyuki Yokota","doi":"10.1007/s00535-025-02288-y","DOIUrl":"10.1007/s00535-025-02288-y","url":null,"abstract":"<p><strong>Background: </strong>In Japan's deceased-donor liver transplantation (DDLT), a new allocation policy based on the Model for End-Stage Liver Disease (MELD) score, including the exceptional MELD system (Ex-MELD), which periodically assigns additional points to the basal MELD score, was implemented in May 2019. We assessed the current state of this system for adult candidates with chronic end-stage liver disease.</p><p><strong>Methods: </strong>Adult candidates (≥ 18 years) registered in the Japan Organ Transplant Network for DDLT as Status 2 cases (including chronic end-stage liver disease patients) between May 2019 and April 2023 were evaluated. We divided them into the MELD, Ex-MELD (major) [start 16 points, 2 points by 180 days], and Ex-MELD [hepatocellular carcinoma (HCC)] groups. Transplant probability and waitlist mortality rates were compared using competing risk analyses. The annual proportion of DDLT and the transition of median MELD at transplantation were also investigated.</p><p><strong>Results: </strong>There were 757 candidates in MELD,126 in Ex-MELD (major), and 99 in Ex-MELD (HCC) groups. The transplant probability rates were not significantly different (3-year transplant probability rate; MELD: 24.0% vs. Ex-MELD (major): 21.0% vs. Ex-MELD (HCC): 24.1%). The rate in the Ex-MELD (major) increased dramatically as the waiting period lengthened. The waitlist mortality rates in the Ex-MELD (major) group were significantly lower (3-year waitlist mortality rate; MELD: 50.5% vs. Ex-MELD (major): 25.0% vs. Ex-MELD (HCC): 57.0%). Although the proportion of Ex-MELD (major) increased yearly in the transplanted cases, the median MELD at transplantation did not change significantly.</p><p><strong>Conclusions: </strong>We clearly showed the current status of adult Status 2 candidates.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1414-1426"},"PeriodicalIF":5.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855494","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}
引用次数: 0
New potential biomarkers of ulcerative colitis and disease course - integrated metagenomic and metabolomic analysis among Polish patients. 溃疡性结肠炎新的潜在生物标志物和波兰患者病程整合宏基因组学和代谢组学分析
IF 5.5 2区 医学
Journal of Gastroenterology Pub Date : 2025-11-01 Epub Date: 2025-07-04 DOI: 10.1007/s00535-025-02280-6
Oliwia Zakerska-Banaszak, Karolina Ladziak, Dariusz Kruszka, Kacper Maciejewski, Lukasz Wolko, Iwona Krela-Kazmierczak, Agnieszka Zawada, Marie Vibeke Vestergaard, Agnieszka Dobrowolska, Marzena Skrzypczak-Zielinska
{"title":"New potential biomarkers of ulcerative colitis and disease course - integrated metagenomic and metabolomic analysis among Polish patients.","authors":"Oliwia Zakerska-Banaszak, Karolina Ladziak, Dariusz Kruszka, Kacper Maciejewski, Lukasz Wolko, Iwona Krela-Kazmierczak, Agnieszka Zawada, Marie Vibeke Vestergaard, Agnieszka Dobrowolska, Marzena Skrzypczak-Zielinska","doi":"10.1007/s00535-025-02280-6","DOIUrl":"10.1007/s00535-025-02280-6","url":null,"abstract":"<p><strong>Background & aim: </strong>The course of ulcerative colitis (UC) involves successive periods of remission and exacerbation but is difficult to predict. Gut dysbiosis in UC has already been intensively investigated. However, are periods of exacerbation and remission associated with specific disturbances in the composition of the intestinal microbiota and its metabolome? Our goal was to answer this question and to identify bacteria and metabolites necessary to maintain the remission.</p><p><strong>Methods: </strong>We enrolled 65 individuals, including 20 UC patients in remission, 15 in exacerbation, and 30 healthy controls. Metagenomic profiling of the gut microbial composition was performed based on 16S rRNA V1-V9 sequencing. Stool and serum metabolic profiles were studied by chromatography combined with mass spectrometry.</p><p><strong>Results: </strong>We revealed significant differences in the gut bacterial and metabolic composition between patients in active UC and those in remission, as well as in healthy controls. As associated with UC remission we have identified following bacteria: Akkermansia, Agathobacter, Anaerostipes, Enterorhabdus, Coprostanoligenes, Colinsella, Ruminococcus, Subdoligranulum, Lachnoclostridium, Coriobacteriales, Erysipelotrichaceae, and Family XII, and compounds - 1-hexadecanol, phytanic acid, squalene, adipic acid, cis-gondoic acid, nicotinic acid, tocopherol gamma, ergosterol and lithocholic acid. Whereas, in the serum lithocholic acid, indole and xanthine were found as potential candidates for biomarkers of UC remission.</p><p><strong>Conclusion: </strong>We have demonstrated that specific bacteria, metabolites, and their correlations could be crucial in the remission of UC among Polish patients. Our results provide valuable insights and a significant source for developing new hypotheses on host-microbiome interactions in diagnosis and course of UC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1384-1399"},"PeriodicalIF":5.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560339","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}
引用次数: 0
STYK1 as a targetable vulnerability enhances the efficacy of anti-PD-L1 therapy in pancreatic cancer. STYK1作为靶向易感性可增强胰腺癌抗pd - l1治疗的疗效。
IF 5.5 2区 医学
Journal of Gastroenterology Pub Date : 2025-11-01 Epub Date: 2025-09-19 DOI: 10.1007/s00535-025-02291-3
Xiao Wang, Yueqin Zhang, Anan Li, Chuanzan Zhou, Sen Xu, Zongting Gu, Wei Wang, Peng Nan, Ran Tao
{"title":"STYK1 as a targetable vulnerability enhances the efficacy of anti-PD-L1 therapy in pancreatic cancer.","authors":"Xiao Wang, Yueqin Zhang, Anan Li, Chuanzan Zhou, Sen Xu, Zongting Gu, Wei Wang, Peng Nan, Ran Tao","doi":"10.1007/s00535-025-02291-3","DOIUrl":"10.1007/s00535-025-02291-3","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with limited treatment options. Immunotherapy, though effective in various tumors, has limited efficacy in PDAC due to immune tolerance. Thus, identifying new targets to enhance immunotherapy response is crucial.</p><p><strong>Methods: </strong>This study used bioinformatics analysis and public database data to identify STYK1 as a potential PDAC biomarker. We analyzed STYK1 expression in PDAC tissues, its link to patient prognosis and immune cell infiltration. In vitro experiments assessed the impact of STYK1 knockdown on PDAC cell proliferation, migration, and invasion. Immunohistochemical analysis was performed on 79 PDAC tissue samples to evaluate CD8<sup>+</sup> T cell infiltration. In vivo studies examined the effects of STYK1 knockdown on tumor growth, T cell infiltration and activation, especially with anti-PD-L1 antibodies. We also investigated the molecular mechanisms of STYK1's regulation of T cell infiltration, focusing on its association with CCL20 and its role beyond the PD-1/PD-L1 pathway.</p><p><strong>Results: </strong>Elevated STYK1 expression in PDAC tissue is associated with poor prognosis and reduced CD8<sup>+</sup> T cell infiltration. STYK1 knockdown inhibits PDAC cell proliferation, migration, and invasion in vitro. In vivo, it decreases tumor growth and, when combined with anti-PD-L1 antibody treatment, significantly enhances T cell infiltration and activation without affecting PD-L1 expression. STYK1 regulates T cell infiltration via CCL20, independently of the PD-1/PD-L1 signaling pathway.</p><p><strong>Conclusions: </strong>STYK1 is a potential predictive biomarker for immunotherapy response in PDAC, as its regulation of T cell infiltration via CCL20, independent of the PD-1/PD-L1 pathway, may provide a strategy to potentially augment immunotherapy efficacy, pending mechanistic confirmation.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1449-1469"},"PeriodicalIF":5.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085502","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}
引用次数: 0
Ferroptosis: biology and role in liver disease. 下垂铁:生物学及其在肝脏疾病中的作用。
IF 5.5 2区 医学
Journal of Gastroenterology Pub Date : 2025-11-01 Epub Date: 2025-09-18 DOI: 10.1007/s00535-025-02300-5
Keisuke Hino, Sohji Nishina, Izumi Yanatori
{"title":"Ferroptosis: biology and role in liver disease.","authors":"Keisuke Hino, Sohji Nishina, Izumi Yanatori","doi":"10.1007/s00535-025-02300-5","DOIUrl":"10.1007/s00535-025-02300-5","url":null,"abstract":"<p><p>Ferroptosis is a form of nonapoptotic cell death that is driven by iron-dependent lipid peroxidation and is relevant to a wide range of biological processes, such as development, aging, immunity, and cancer. Ferroptosis has also been linked to numerous hepatic metabolic pathways, including the metabolism of iron, fatty acids, and amino acids, such as cysteine. During the last decade, studies on the biology of and molecules regulating ferroptosis have shed light on the role of ferroptosis in liver disease and its implications. The susceptibility of liver cells to ferroptosis determines the extent of liver injury and affects the progression of nonneoplastic diseases, whereas liver cancer cells display intrinsic or acquired resistance to ferroptosis, which promotes cancer progression. These findings indicate that ferroptosis represents a promising target for the prevention and treatment of many forms of liver disease. In this review, we provide an update on the mechanisms regulating ferroptosis, focusing on the peroxidation of phospholipids, the antioxidant pathways that limit lipid peroxidation, and the regulation of the labile iron pool, all of which are closely connected. We also summarize the roles and importance of ferroptosis in the pathogenesis of liver disease, and the therapeutic potential of targeting ferroptosis in liver diseases.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1339-1361"},"PeriodicalIF":5.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080835","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}
引用次数: 0
Investigating tumor-infiltrating lymphocytes as predictors of lymph node metastasis in deep submucosal invasive esophageal squamous cell carcinoma: a retrospective cross-sectional study. 探讨肿瘤浸润淋巴细胞作为深粘膜下浸润性食管鳞状细胞癌淋巴结转移的预测因子:一项回顾性横断面研究。
IF 5.5 2区 医学
Journal of Gastroenterology Pub Date : 2025-11-01 Epub Date: 2025-07-25 DOI: 10.1007/s00535-025-02286-0
Hirona Konishi, Yuji Urabe, Yoshiki Hatsushika, Satoshi Masuda, Takeo Nakamura, Kazuki Ishibashi, Junichi Mizuno, Takeshi Takasago, Hidenori Tanaka, Akiyoshi Tsuboi, Ken Yamashita, Yuichi Hiyama, Yoshihiro Kishida, Hidehiko Takigawa, Akira Ishikawa, Toshio Kuwai, Yoichi Hamai, Yuji Murakami, Shiro Oka
{"title":"Investigating tumor-infiltrating lymphocytes as predictors of lymph node metastasis in deep submucosal invasive esophageal squamous cell carcinoma: a retrospective cross-sectional study.","authors":"Hirona Konishi, Yuji Urabe, Yoshiki Hatsushika, Satoshi Masuda, Takeo Nakamura, Kazuki Ishibashi, Junichi Mizuno, Takeshi Takasago, Hidenori Tanaka, Akiyoshi Tsuboi, Ken Yamashita, Yuichi Hiyama, Yoshihiro Kishida, Hidehiko Takigawa, Akira Ishikawa, Toshio Kuwai, Yoichi Hamai, Yuji Murakami, Shiro Oka","doi":"10.1007/s00535-025-02286-0","DOIUrl":"10.1007/s00535-025-02286-0","url":null,"abstract":"<p><strong>Background: </strong>Various subtypes of tumor-infiltrating lymphocytes (TILs) are associated with prognosis in various cancer types. In esophageal squamous cell carcinoma (ESCC), TILs have been associated with prognosis in advanced stages of the disease. However, their significance in superficial esophageal squamous cell carcinoma (SESCC) remains unknown. In this study, we investigated the role of TILs in SESCC.</p><p><strong>Methods: </strong>First, we included 212 SESCC lesions with a diameter of 10-20 mm (65 pT1a-EP, 74 pT1a-LPM,40 pT1a-MM, and 33 pT1b-SM lesions) that were resected at our hospital from November 2007 to December 2019. We then examined changes in TILs related to tumor invasion. We evaluated the phenotype and number of TILs using triple immunofluorescence staining for CD4, CD8, and FoxP3. In addition, we selected 97 consecutive pT1b-SM lesions treated during the same period. These specimens were used to examine the association between TILs and lymph node metastasis (LNM) in pT1b-SM cases.</p><p><strong>Results: </strong>The number of CD4 + , CD8 + , and FoxP3 + TILs infiltrating the tumor increased significantly with increasing invasion depth. In pT1b-SM lesions, CD4 + , CD8 + , and FoxP3 + TIL counts were significantly higher in the invasive front (IF) than in the tumor center (CT). Moreover, in patients undergoing surgical resection or endoscopic submucosal dissection (regardless of additional chemoradiotherapy), the number and ratio of FoxP3 + TILs in IF were significantly higher in patients with LNM than in those without, suggesting their potential utility as predictive biomarkers.</p><p><strong>Conclusions: </strong>The number and ratio of FoxP3 + TILs in the IF may be an indicator of LNM risk in SESCC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1362-1371"},"PeriodicalIF":5.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144707766","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}
引用次数: 0
The pivotal role of SFRP2 in promoting glycolysis and progression in the high-risk group based on the glycometabolism prognostic model for colorectal cancer. 基于糖代谢预后模型的结直肠癌高危人群中,SFRP2在促进糖酵解和进展中的关键作用
IF 5.5 2区 医学
Journal of Gastroenterology Pub Date : 2025-11-01 Epub Date: 2025-07-29 DOI: 10.1007/s00535-025-02281-5
Feng Du, Xu Ji, Jiayi Su, Chuntao Liu, Junxiong Wang, Tingting Ning, Nan Zhang, Junxuan Xu, Si-An Xie, Si Liu, Li Min, Jing Wu, Shutian Zhang, Shuilong Guo, Shengtao Zhu, Peng Li
{"title":"The pivotal role of SFRP2 in promoting glycolysis and progression in the high-risk group based on the glycometabolism prognostic model for colorectal cancer.","authors":"Feng Du, Xu Ji, Jiayi Su, Chuntao Liu, Junxiong Wang, Tingting Ning, Nan Zhang, Junxuan Xu, Si-An Xie, Si Liu, Li Min, Jing Wu, Shutian Zhang, Shuilong Guo, Shengtao Zhu, Peng Li","doi":"10.1007/s00535-025-02281-5","DOIUrl":"10.1007/s00535-025-02281-5","url":null,"abstract":"<p><strong>Background: </strong>Reprogramming glucose metabolism is a hallmark of human cancer during its occurrence and development. However, the comprehensive glycometabolism signature and underlying mechanism in CRC prognosis and immune response remind to be elucidated.</p><p><strong>Methods: </strong>A prognostic model derived from 297 glycometabolism-related genes (GRGs) was developed using LASSO-Cox and nomogram algorithms. Immune dysfunction between high-risk (Risk<sup>H</sup>) and low-risk (Risk<sup>L</sup>) groups was compared using CIBERSORT, TIMER, and TIDE analyses. The expression and function of key genes, including secreted frizzled-related protein 2 (SFRP2), were validated using PCR, western blotting, immunohistochemistry, transwell assays, and metastatic model in mice. Luciferase reporter and chromatin immunoprecipitation were used to determine the transcription regulation of ENO2 by TCF4.</p><p><strong>Results: </strong>More than half of the GRGs (152 out of 297) showed differential expression, mainly those associated with glycolysis and biosynthesis. The GRG-risk score outperformed other clinical indicators (AUC = 0.810) and served as an independent risk predictor (P < 0.001, HR = 3.180). The Risk<sup>H</sup> group showed increased infiltration of immune cells and higher immune checkpoint expression. Mechanistically, SFRP2, a key gene in Risk<sup>H</sup>, promoted CRC glycolysis and metastasis via enolase 2 (ENO2) activation through the TCF4/β-catenin axis. Inhibiting ENO2 reversed SFRP2-induced metastasis. Coexpression of SFRP2 and ENO2 correlated with poorer survival and higher recurrence.</p><p><strong>Conclusion: </strong>The Risk<sup>H</sup> group is characterized by glycolysis overactivation and immune exclusion. SFRP2 and ENO2 have emerged as promising treatment targets for high-risk CRC patients.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1400-1413"},"PeriodicalIF":5.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144731719","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}
引用次数: 0
Nationwide epidemiological survey of acute pancreatitis in Japan, 2021: the impact of the COVID-19 pandemic and revised clinical guidelines. 2021年日本急性胰腺炎全国流行病学调查:COVID-19大流行的影响和修订的临床指南
IF 5.5 2区 医学
Journal of Gastroenterology Pub Date : 2025-11-01 Epub Date: 2025-07-31 DOI: 10.1007/s00535-025-02284-2
Yuichi Tanaka, Atsushi Masamune, Ryotaro Matsumoto, Tetsuya Takikawa, Yu Tanaka, Shin Hamada, Shin Miura, Kiyoshi Kume, Yoshifumi Takeyama, Kazuhiro Kikuta
{"title":"Nationwide epidemiological survey of acute pancreatitis in Japan, 2021: the impact of the COVID-19 pandemic and revised clinical guidelines.","authors":"Yuichi Tanaka, Atsushi Masamune, Ryotaro Matsumoto, Tetsuya Takikawa, Yu Tanaka, Shin Hamada, Shin Miura, Kiyoshi Kume, Yoshifumi Takeyama, Kazuhiro Kikuta","doi":"10.1007/s00535-025-02284-2","DOIUrl":"10.1007/s00535-025-02284-2","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to clarify the current clinico-epidemiological characteristics of acute pancreatitis (AP) in Japan.</p><p><strong>Methods: </strong>We conducted a two-stage nationwide survey of patients with AP treated at selected hospitals in 2021, during the COVID-19 pandemic. The first stage estimated the total number of AP patients, while the second collected detailed clinical data.</p><p><strong>Results: </strong>The estimated number of AP patients requiring hospitalization was 61,080, with an overall incidence rate of 49 per 100,000 persons, decreasing from 78,450 in 2016. Detailed clinical data were obtained for 4,375 patients, including 1,362 (31.1%) classified as severe. The male-to-female ratio was 2.0, with mean ages at onset of 60.1 years for males and 65.4 years for females. The three major causes were alcohol (31.2%), gallstones (22.5%), and idiopathic etiology (22.1%). The AP-associated in-hospital mortality rate was 2.1% in all AP and 5.3% in severe cases, down from 6.1% in the 2016 survey. Antibiotics were administered to 61.2% of mild cases, a significant reduction from 94.5% in 2016. Enteral nutrition was provided to 56.9% of severe cases, up from 31.8% in 2016. Among 124 patients undergoing interventional drainage for walled-off necrosis, 57 were treated using a step-up approach. Notably, no patients underwent upfront surgery as the initial treatment.</p><p><strong>Conclusions: </strong>During the pandemic, the estimated number of AP cases requiring hospitalization declined for the first time in nearly four decades. Mortality in severe cases improved, and adherence to clinical guidelines on prophylactic antibiotics and enteral nutrition also improved, indicating enhanced management of AP in Japan.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1437-1448"},"PeriodicalIF":5.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760307","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}
引用次数: 0
Forecasting age-standardized incidence rates of gastric cancer from 1990-2050 in Japan according to H. pylori prevalence and eradication scenarios. 根据幽门螺杆菌流行和根除情况预测1990-2050年日本胃癌年龄标准化发病率
IF 5.5 2区 医学
Journal of Gastroenterology Pub Date : 2025-11-01 Epub Date: 2025-09-19 DOI: 10.1007/s00535-025-02296-y
Byron Sigel, Eiko Saito, Daisuke Yoneoka, Tomohiro Matsuda, Kota Katanoda
{"title":"Forecasting age-standardized incidence rates of gastric cancer from 1990-2050 in Japan according to H. pylori prevalence and eradication scenarios.","authors":"Byron Sigel, Eiko Saito, Daisuke Yoneoka, Tomohiro Matsuda, Kota Katanoda","doi":"10.1007/s00535-025-02296-y","DOIUrl":"10.1007/s00535-025-02296-y","url":null,"abstract":"<p><strong>Background: </strong>This study examines the influence of H. pylori eradication policies on gastric cancer incidence rates in Japan utilizing nationally representative registry data. It evaluates the impact of the H. pylori eradication policies introduced in 2000 and 2013, along with future eradication scenarios, on age-standardized gastric cancer rates.</p><p><strong>Methods: </strong>Data from prefectural cancer registries and national health surveys were analyzed using Poisson regression and autoregressive integrated moving average models. Predictors such as H. pylori prevalence, alcohol consumption, salt intake, body mass index, and smoking prevalence were included. The study assessed past policies by comparing incidence rates with and without the policy changes of 2000 and 2013. Future policies were evaluated through five scenarios, incorporating the cumulative impact of eradication efforts from 2000 and 2013, and a projected 75% reduction by 2050. The evaluation also compared eradication targets for age groups 40-69 and 20-39.</p><p><strong>Results: </strong>Past H. pylori eradication policies were associated with decreased age-standardized gastric cancer incidence rates in Japan, reducing the rate from a projected 39.3 per 100,000 without the 2000 and 2013 policies to 24.9 per 100,000 under current policies. Future policies, integrating the cumulative effects of the 2000 and 2013 eradication efforts and projecting a 75% reduction in H. pylori prevalence, were projected to further reduce gastric cancer incidence.</p><p><strong>Conclusion: </strong>The H. pylori eradication policies of 2000 and 2013 have significantly reduced gastric cancer incidence rates in Japan. Model projections suggest that expanded eradication efforts could lead to additional reductions, further lowering the future burden of gastric cancer in Japan.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1372-1383"},"PeriodicalIF":5.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085183","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}
引用次数: 0
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