Journal of Gastroenterology最新文献

{"title":"Abnormalities of intracellular organelles in metabolic dysfunction-associated steatotic disease.","authors":"Hidenori Kido, Eishiro Mizukoshi, Masahiro Yanagi, Li Shihui, Takuya Seike, Hidetoshi Nakagawa, Tetsumori Yamashima, Yoshitake Shiraishi, Noriyuki Ozaki, Kenichi Harada, Hikari Okada, Hisanori Goto, Kumi Kimura, Yasuhiko Yamamoto, Taro Yamashita","doi":"10.1007/s00535-025-02257-5","DOIUrl":"10.1007/s00535-025-02257-5","url":null,"abstract":"<p><strong>Background: </strong>The concept of metabolic dysfunction-associated steatotic disease (MASLD) is increasingly being recognized. The mechanisms contributing to hepatocellular injury include oxidative stress owing to mitochondrial dysfunction, endoplasmic reticulum (ER) stress owing to abnormal protein accumulation in the rough ER, and disruption of cellular homeostasis and metabolic regulation to autophagic dysfunction. However, the morphological abnormalities of these intracellular organelles remain unclear.</p><p><strong>Methods: </strong>Liver tissues from model mice of MASLD, patients with MASLD, and respective controls were subjected to histopathological examination using light microscopy, and intracellular organelles were analyzed via transmission electron microscopy (TEM).</p><p><strong>Results: </strong>In model mice of MASLD, the progression of MASLD pathology was associated with abnormalities in mitochondria, glycogen granules, and rough ER. Based on these findings, the electron microscopic observations of these intracellular organelles were classified, weighted, and evaluated in liver tissues of patients with MASLD. The electron microscopic findings were significantly relatively frequent in patients with MASLD and correlated with existing histopathological scoring.</p><p><strong>Conclusions: </strong>Using TEM, we identified characteristic abnormalities in intracellular organelles specific to MASLD. These findings contribute to the understanding of the mechanisms underlying hepatocellular injury in MASLD.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"990-999"},"PeriodicalIF":5.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12289852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028752","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":"Factors associated with actionable gene aberrations in pancreatic cancer based on the C-CAT database.","authors":"Go Endo, Kazunaga Ishigaki, Yousuke Nakai, Hiroto Nishio, Koshiro Fukuda, Kota Ishida, Shinya Takaoka, Yurie Tokito, Rintaro Fukuda, Kensaku Noguchi, Hiroki Oyama, Tatsunori Suzuki, Tatsuya Sato, Tomotaka Saito, Tsuyoshi Hamada, Koji Miyabayashi, Naminatsu Takahara, Yasuyoshi Sato, Hidenori Kage, Katsutoshi Oda, Mitsuhiro Fujishiro","doi":"10.1007/s00535-025-02253-9","DOIUrl":"10.1007/s00535-025-02253-9","url":null,"abstract":"<p><strong>Background: </strong>Comprehensive genomic profiling (CGP) tests are increasingly used to explore the genomically matched therapies for solid tumors. The aim of this study is to investigate factors associated with actionable gene aberrations in pancreatic cancer (PC) using real-world data from the Center for Advanced Cancer Genome Therapy (C-CAT) database.</p><p><strong>Methods: </strong>Among 6768 patients with unresectable and recurrent PC registered in the C-CAT database between June 2019 and July 2023, we identified 4628 patients who underwent tissue-based CGP tests using either FoundationOne^® CDx (F1CDx) or OncoGuide^™ NCC Oncopanel (NOP). We investigated the incidence of actionable gene aberrations and the factors associated with their detection.</p><p><strong>Results: </strong>The cohort included 3,554 patients who underwent F1CDx and 1128 NOP, with surgical specimens in 50% of the cases. Adenocarcinoma was the predominant subtype (95%), and KRAS mutations were found in 90%. The overall incidence of actionable gene aberrations was 27%. The most common gene abnormalities were BRCA2 (3.4%), followed by ATM (2.9%), ERBB2 (2.8%), PIK3 CA (2.5%), and BRAF (1.9%). Multivariable analysis revealed that acinar cell carcinoma (ACC) (Odds ratio [OR] 1.87, 95% confidence interval [CI] 1.00-2.67), KRAS wild type (KRAS_WT) (OR 3.09, 95% CI 2.49-3.85), and use of F1CDx (OR 2.38, 95% CI 1.98-2.85) were significantly associated with actionable gene aberrations.</p><p><strong>Conclusions: </strong>Actionable gene aberrations were more likely in cases of ACC, KRAS_WT, and F1CDx usage. The choice of CGP test should be made on a case-by-case basis, as other factors beyond actionable gene aberrations also need to be considered.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1026-1035"},"PeriodicalIF":5.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12289854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983495","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":"Letter to \"The potential of an artificial intelligence for diagnosing MRI images in rectal cancer: multicenter collaborative trial\".","authors":"Haoxun Mao, Sheng Li","doi":"10.1007/s00535-025-02255-7","DOIUrl":"10.1007/s00535-025-02255-7","url":null,"abstract":"","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1047-1048"},"PeriodicalIF":6.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029544","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":"Post-marketing surveillance of tofacitinib in patients with ulcerative colitis in Japan: a final report of safety and effectiveness data.","authors":"Katsuyoshi Matsuoka, Satoshi Motoya, Takayuki Yamamoto, Minoru Matsuura, Toshimitsu Fujii, Shinichiro Shinzaki, Yohei Mikami, Shoko Arai, Junichi Oshima, Yutaka Endo, Hirotoshi Yuasa, Masato Hoshi, Keiko Sato, Tadakazu Hisamatsu","doi":"10.1007/s00535-025-02249-5","DOIUrl":"10.1007/s00535-025-02249-5","url":null,"abstract":"<p><strong>Background: </strong>We present the final analysis of a tofacitinib post-marketing surveillance (PMS) study in Japanese patients with ulcerative colitis (UC).</p><p><strong>Methods: </strong>Safety/effectiveness data were evaluated (through Sept/30/2022). All patients with UC in Japan receiving tofacitinib were registered (60-week observation period). Adverse events (AEs) were recorded. Per protocol, several AEs were identified as clinically important/potential risks; all treatment-period data were used to calculate incidence rates (IRs; unique patients with events/100 patient-years [PY] of exposure). Effectiveness was assessed (partial/total Mayo score), with last observation carried forward for imputation of missing data.</p><p><strong>Results: </strong>Overall, 2043 patients were enrolled (safety analysis set: n = 1982/effectiveness analysis set: n = 1969). Data were excluded for 13 patients from two hospitals from which consent was not obtained for publication and which, therefore, were not permitted for publication. AEs and serious AEs were observed in 33.4% and 5.2% of patients, respectively; one death occurred (intestinal abscess). Herpes zoster (HZ; non-serious and serious) was the most reported infection (n = 92 [IR 5.93/100 PY, 95% confidence interval 4.78, 7.27]). Serious infection, malignancy, cardiovascular and venous thromboembolic events IRs were 1.51/100 PY, 0.62/100 PY, 0.13/100 PY, and 0.31/100 PY, respectively. Overall, 52.4% of patients discontinued treatment, mostly due to inadequate clinical response (48.9%). At Week 60, 1151/1969 patients (58.5%) achieved partial Mayo score remission.</p><p><strong>Conclusion: </strong>The overall safety profile was generally comparable with tofacitinib data from PMS reports from Japan, worldwide and the tofacitinib UC clinical program. However, HZ IR was higher than in the tofacitinib UC clinical program. Tofacitinib effectiveness was consistent with data from the tofacitinib UC clinical program.</p><p><strong>Clinicaltrials: </strong>GOV: NCT03643211.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"979-989"},"PeriodicalIF":5.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12289845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969795","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":"Response to Letter to the Editor 'Comments on the potential of an artificial intelligence for diagnosing MRI images in rectal cancer: multicenter collaborative trial' by Mao and Li.","authors":"Atsushi Hamabe, Ichiro Takemasa","doi":"10.1007/s00535-025-02256-6","DOIUrl":"10.1007/s00535-025-02256-6","url":null,"abstract":"","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1049-1050"},"PeriodicalIF":6.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584135","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":"Current status and trends in ERCP and post-ERCP pancreatitis in Japan: a nationwide observational study.","authors":"Tomoo Manaka, Tetsuya Takikawa, Kunio Tarasawa, Kazuhiro Kikuta, Ryotaro Matsumoto, Yu Tanaka, Takanori Sano, Shin Hamada, Shin Miura, Kiyoshi Kume, Kenji Fujimori, Kiyohide Fushimi, Atsushi Masamune","doi":"10.1007/s00535-025-02254-8","DOIUrl":"10.1007/s00535-025-02254-8","url":null,"abstract":"<p><strong>Background: </strong>Endoscopic retrograde cholangiopancreatography (ERCP) is indispensable for the management of biliary and pancreatic diseases but carries a high risk of post-ERCP pancreatitis (PEP). This study aimed to clarify the current status and temporal trends of ERCP and PEP in Japan, including preventive measures.</p><p><strong>Methods: </strong>We conducted a retrospective, population-based cohort study using the Diagnosis Procedure Combination database from April 1, 2016, to March 31, 2023. Trend analyses were performed for ERCP, PEP, nonsteroidal anti-inflammatory drugs (NSAIDs), and protease inhibitors. Additionally, factors associated with PEP and severe PEP were evaluated.</p><p><strong>Results: </strong>Among the 1,073,513 ERCP cases, PEP and severe PEP incidences were 85,212 (7.9%) and 4841 cases (0.5%), respectively. The mortality rate was 0.5% for severe PEP and 0.2% for non-severe cases. The number of ERCP procedures and the proportion of therapeutic ERCP increased over time. The incidence of PEP declined from 9.1% in the fiscal year 2016-2017 to 6.4% in the fiscal year 2022, while the incidence of severe PEP decreased from 0.5 to 0.33% over the same period. The usage rate of rectal NSAIDs increased from 16.4 to 27.6%, whereas that of protease inhibitors decreased from 70.5 to 53.5%. The administration of rectal NSAIDs at doses of 20-25 mg and 50 mg was associated with a reduced risk of severe PEP.</p><p><strong>Conclusions: </strong>The number of ERCP procedures and the proportion of therapeutic ERCP have increased, whereas the incidences of PEP and severe PEP have decreased. Rectal NSAIDs may prevent the progression of PEP to severe disease.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1036-1046"},"PeriodicalIF":5.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12289747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144064045","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":"Interaction of neuropilin-1 and hepatocyte growth factor/C-Met pathway in liver fibrosis progression in hepatocyte-specific NRP-1 knockout mice.","authors":"Han Ding, Huanran Lv, Minghao Sui, Xinyu Wang, Yanning Sun, Miaomiao Tian, Shujun Ma, Yuchan Xue, Miao Zhang, Xin Wang, Jianni Qi, Le Wang, Qiang Zhu","doi":"10.1007/s00535-025-02262-8","DOIUrl":"10.1007/s00535-025-02262-8","url":null,"abstract":"<p><strong>Background: </strong>Hepatocyte growth factor (HGF)/c-Met signaling critically influences liver fibrosis, but its interaction with neuropilin-1 (NRP-1) in hepatocytes remains unclear. We investigated the role of hepatocyte-specific NRP-1 deletion in liver fibrosis progression and its relationship with the HGF/c-Met pathway.</p><p><strong>Methods: </strong>Hepatocyte-specific NRP-1 knockout mice were generated using the Cre-lox system, and liver fibrosis was induced by carbon tetrachloride injections or a methionine- and choline-deficient diet. Fibrosis severity, hepatocyte injury, and cytokine secretion were evaluated via histology, biochemical assays, and molecular analyses in isolated hepatocytes. In vitro experiments were conducted in primary hepatocytes and Huh7 cells using lentiviral overexpression and knockdown of NRP-1. Chromatin immunoprecipitation and dual-luciferase reporter assays were performed to analyze transcription factor binding to the NRP-1 promoter.</p><p><strong>Results: </strong>Hepatocyte NRP-1 expression increased significantly during liver fibrosis and was positively correlated with HGF/c-Met expression and fibrosis severity. In vivo, NRP-1 inhibition reduced extracellular matrix accumulation and abnormal angiogenesis in Alb-Cre NRP-1^f/f mice. In vitro, NRP-1 blockade inhibited c-Met activation and reduced transforming growth factor-beta and vascular endothelial growth factor secretion in hepatocytes. NRP-1 functioned as a co-receptor for HGF/c-Met, with HGF upregulating NRP-1 expression at transcript and protein levels. NRP-1 promoted fibrosis through the Met/extracellular signal-regulated kinase pathway. Furthermore, HGF increased retinoic acid receptor alpha expression, promoting NRP-1 transcription.</p><p><strong>Conclusions: </strong>HGF-induced upregulation of hepatocyte NRP-1, mediated by RARA binding to its promoter, drives liver fibrosis through c-Met pathway activation, highlighting NRP-1 as a potential therapeutic target for liver fibrosis.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1000-1013"},"PeriodicalIF":5.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12289806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150774","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":"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":"https://doi.org/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":""},"PeriodicalIF":5.5,"publicationDate":"2025-07-31","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}

{"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":"https://doi.org/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^H) and low-risk (Risk^L) 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^H group showed increased infiltration of immune cells and higher immune checkpoint expression. Mechanistically, SFRP2, a key gene in Risk^H, 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^H 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":""},"PeriodicalIF":5.5,"publicationDate":"2025-07-29","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}

{"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":"https://doi.org/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":""},"PeriodicalIF":6.9,"publicationDate":"2025-07-25","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}