Journal of Gastroenterology最新文献

{"title":"Clinical features and endoscopic polyp management of Peutz-Jeghers syndrome: the 2nd nationwide epidemiological survey in Japan.","authors":"Shoko Miyahara, Tomonori Yano, Yoshiko Nakayama, Hideki Kumagai, Hideki Ishikawa, Yuri Matsubara, Yosikazu Nakamura, Junji Umeno, Keisuke Jimbo, Hideyuki Ishida, Okihide Suzuki, Koichi Okamoto, Fumihiko Kakuta, Yuhki Koike, Yuko Kawasaki, Naoki Ohmiya, Kumiko Tanaka, Shiko Kuribayashi, Yusuke Takahashi, Kazuki Kakimoto, Hiroki Yano, Toshiyuki Sakurai, Hirotsugu Sakamoto","doi":"10.1007/s00535-025-02311-2","DOIUrl":"https://doi.org/10.1007/s00535-025-02311-2","url":null,"abstract":"<p><strong>Background: </strong>Peutz-Jeghers syndrome (PJS), a rare genetic disorder characterized by hamartomatous gastrointestinal polyps, poses increased risks of various cancers. Despite the importance of early intervention, the optimal timing for jejunal-ileal polypectomy remains unclear owing to the limited number of comparative studies.</p><p><strong>Methods: </strong>Herein, we conducted a nationwide survey in Japan and analyzed data from 184 patients with PJS identified through a two-stage sampling process. The initial screening of 2912 medical institutions yielded 1748 facilities, of which 1077 responded to the survey. Time-dependent Cox proportional hazards models and logistic regression analyses were used to examine the association between the timing of jejunal-ileal polypectomy and the risk of surgery for intussusception.</p><p><strong>Results: </strong>Among 184 patients (47.0% women; mean age, 33.5 years), intussusception was the most common complication (67.7%). In the Cox proportional hazards analysis excluding surgeries within 1 year of diagnosis, early jejunal-ileal polypectomy was associated with a reduced risk of surgery for intussusception (adjusted hazard ratio, 0.17; 95% confidence interval [CI] 0.04-0.74, p = 0.018). Logistic regression analysis showed higher odds of surgery in the late treatment group compared with the early treatment group (adjusted odds ratio, 4.26; 95% CI 1.38-13.16, p = 0.012).</p><p><strong>Conclusions: </strong>Early jejunal-ileal polypectomy may reduce the risk of intussusception in patients with PJS. However, the need for frequent endoscopic procedures must be balanced considering patient burden. These findings support the importance of early intervention and highlight the need for optimized surveillance strategies that consider clinical effectiveness and patients' quality of life.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145345447","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 overt hepatic encephalopathy increases mortality in patients with cirrhosis: a multicenter retrospective cohort study.","authors":"Taisei Iwasa, Takao Miwa, Yuki Utakata, Mikita Oi, Mayu Asakura, Takumi Onishi, Masashi Aiba, Shinji Unome, Tatsunori Hanai, Makoto Shiraki, Seiji Adachi, Naoki Katsumura, Yasuhiro Kawashima, Shinji Nishiwaki, Masahito Shimizu","doi":"10.1007/s00535-025-02309-w","DOIUrl":"https://doi.org/10.1007/s00535-025-02309-w","url":null,"abstract":"<p><strong>Background: </strong>Overt hepatic encephalopathy (OHE) is a severe complication of liver cirrhosis. However, data on its incidence, prognostic significance, and associated risk factors in patients without OHE at baseline remain limited.</p><p><strong>Methods: </strong>A multicenter retrospective cohort study was conducted by reviewing records of hospitalized patients with cirrhosis at three institutions in Japan. OHE was defined as West Haven grade ≥ 2 and its incidence during the follow-up was estimated using the cumulative incidence function. Prognostic factors were assessed using Cox proportional hazards regression analysis, with OHE and hepatocellular carcinoma (HCC) development treated as time-dependent covariates. Independent predictors for OHE development were analyzed using fine-gray proportional hazards regression analysis.</p><p><strong>Results: </strong>Among 652 patients, the median age was 67 years, and 53% were male. The median model for end-stage liver disease (MELD) score was 9. During a median follow-up period of 3.2 years, 136 patients (21%) developed OHE and 183 patients (28%) died. The cumulative incidence of OHE at 1, 3, and 5 years was 8%, 16%, and 20%, respectively. Multivariable analysis demonstrated that OHE development (hazard ratio [HR], 3.07; 95% confidence interval [CI], 1.99-4.75) was a significant independent prognostic factor, regardless of age, sex, liver functional reserve, and HCC development. Furthermore, multivariable analysis identified lower body mass index, higher MELD score, lower albumin levels, and higher ammonia levels as independent predictors for OHE development.</p><p><strong>Conclusions: </strong>OHE development is common and increases mortality among patients with cirrhosis. Therefore, close monitoring of high-risk populations is warranted for early management of OHE.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145312931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation of novel scoring systems for acute decompensated cirrhosis identifies PBC as an independent poor prognostic factor: a single-center Japanese cohort study.","authors":"Yukie Nakadai, Keisuke Ojiro, Ryosuke Kasuga, Po-Sung Chu, Makoto Ueno, Takaya Tabuchi, Nobuhito Taniki, Shingo Usui, Yasushi Hasegawa, Yuta Abe, Minoru Kitago, Hideaki Obara, Takanori Kanai, Nobuhiro Nakamoto","doi":"10.1007/s00535-025-02310-3","DOIUrl":"https://doi.org/10.1007/s00535-025-02310-3","url":null,"abstract":"<p><strong>Background: </strong>The Model for End-Stage Liver Disease 3.0 (MELD 3.0) was developed in the United States to improve prioritization for liver transplantation (LT); however, its utility in Japanese patients with liver cirrhosis (LC) and acute decompensation (AD) remains invalidated.</p><p><strong>Methods: </strong>We retrospectively analyzed 312 patients with LC and first-time AD admitted to our institution between 2012 and 2022. Prognostic accuracy of MELD 3.0 was evaluated at 90 and 180 days after admission by comparison with other predictive models. Prognoses according to cirrhosis etiology and contributing factors were also examined.</p><p><strong>Results: </strong>MELD 3.0 demonstrated superior prognostic accuracy at day 180 (C-index: 0.770) compared to the original MELD and MELD Na, although its C-index up to day 90 was comparable to that of MELD and MELD Na. A cut-off value of MELD 3.0 > 20.5 predicted LT or liver-related death at day 180. Patients with primary biliary cholangitis (PBC) had poorer outcomes than non-PBC cases through 180 days and remained an independent risk factor in the Cox proportional hazards model incorporating MELD 3.0. A progressive increase in both MELD 3.0 and total bilirubin from day 0 to day 90 after AD was observed specifically in the PBC group, which may have been associated with the poor prognosis at day 180.</p><p><strong>Conclusions: </strong>MELD 3.0 was effective in predicting 180-day outcomes in Japanese patients with LC and AD. Progressive bilirubin elevation in PBC may be associated with poor prognosis. These findings suggest that early consideration of LT is warranted in patients with PBC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274768","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":"Hepatitis B core-related antigen kinetics predict spontaneous HBeAg seroclearance in chronic hepatitis B patients.","authors":"Hung-Yao Lin, Kuan-Hui Hsin, Chun-Jen Liu, Tung-Hung Su, Wan-Ting Yang, Shang-Chin Huang, Shih-Jer Hsu, Hung-Chih Yang, Chen-Hua Liu, Pei-Jer Chen, Tai-Chung Tseng, Jia-Horng Kao","doi":"10.1007/s00535-025-02306-z","DOIUrl":"https://doi.org/10.1007/s00535-025-02306-z","url":null,"abstract":"<p><strong>Background and aims: </strong>Hepatitis B e antigen (HBeAg) seroclearance is crucial in the natural history of chronic hepatitis B (CHB). Little is known about the role of hepatitis B core-related antigen (HBcrAg) levels in predicting spontaneous HBeAg seroclearance.</p><p><strong>Methods: </strong>This retrospective cohort study included 484 treatment-naïve HBeAg-positive CHB patients with an extended follow-up period at National Taiwan University Hospital. The primary endpoint was spontaneous seroclearance of HBeAg. The association between baseline HBcrAg levels and their kinetic patterns with spontaneous HBeAg seroclearance was assessed.</p><p><strong>Results: </strong>Of 484 patients with a mean follow-up period of 7.80 years, 331 (68.4%) achieved spontaneous HBeAg seroclearance, corresponding to an annual rate of 8.76%. Lower baseline HBcrAg levels correlated with an increased likelihood of HBeAg seroclearance (log-rank P < .001). When HBcrAg kinetics were assessed based on baseline and year 3 levels, patients with HBcrAg levels persistently < 10⁵ KU/mL (HR: 2.66; 95% CI: 1.75-4.04) and those declining to < 10⁵ KU/mL (HR: 2.31; 95% CI: 1.50-3.55) had an increased likelihood of HBeAg seroclearance when compared to those with persistently high HBcrAg levels. This association remained statistically significant in multivariate analysis after adjusting for baseline viral factors. In addition, HBcrAg kinetics were consistently associated with HBeAg seroclearance in immune-tolerant patients.</p><p><strong>Conclusions: </strong>HBcrAg < 10⁵ KU/mL, or a decline to this threshold, identified HBeAg-positive CHB patients with higher likelihood of spontaneous HBeAg seroclearance. Persistently high HBcrAg may indicate earlier CHB phases and inform management strategies.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274706","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":"Inhibition of integrin α3 suppresses gastric cancer progression via STAT3-mediated regulation of SLC1A5-dependent glutamine uptake.","authors":"Weiwei Zhu, Siwei Pan, Jingli Xu, Yuqi Wang, Zhenjie Fu, Xiao Han, Yanqiang Zhang, Qianyu Zhao, Ruolan Zhang, Can Hu, Zhiyuan Xu","doi":"10.1007/s00535-025-02305-0","DOIUrl":"https://doi.org/10.1007/s00535-025-02305-0","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) remains one of the most lethal malignancies, primarily due to limited treatment efficacy and its strong metastatic potential. The identification of new molecular targets is therefore crucial for enhancing therapeutic strategies and improving clinical outcomes.</p><p><strong>Methods: </strong>The expression of ITGA3 was investigated in clinical GC tissue samples, and its association with patient prognosis was evaluated. Both in vitro and in vivo assays were employed to investigate the functional role of ITGA3 in GC cell proliferation and invasion. To uncover the underlying molecular mechanisms, integrated proteomic and transcriptomic analyses were performed. Mechanistic validation was subsequently carried out using Western blotting, immunofluorescence, nuclear-cytoplasmic fractionation, dual-luciferase reporter, and chromatin immunoprecipitation (ChIP) assays.</p><p><strong>Results: </strong>Elevated ITGA3 expression was strongly correlated with an unfavorable prognosis in GC patients. Functional studies revealed that ITGA3 promotes tumor cell proliferation and invasion. Multi-omics analyses revealed that ITGA3 modulates glutamine metabolism by regulating the amino acid transporter SLC1A5 and engages the JAK-STAT3 signaling pathway. Silencing ITGA3 significantly reduced STAT3 nuclear translocation, suppressing SLC1A5 transcription and decreasing glutamine uptake. Both dual-luciferase reporter and ChIP assays confirmed that STAT3 directly binds to the promoter region of SLC1A5.</p><p><strong>Conclusions: </strong>ITGA3 acts as an oncogenic driver in GC by facilitating glutamine uptake via the STAT3-SLC1A5 signaling axis. These findings suggest that therapeutic targeting of this pathway could represent a promising approach for the clinical management of GC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251577","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":"Molecular insights into HER2/ERBB2 amplification and carcinogenesis in gallbladder cancer associated with pancreaticobiliary maljunction.","authors":"Ming Zhu, Daisuke Douchi, Keigo Murakami, Taito Itoh, Shusuke Migita, Naoki Rikiyama, Shuichiro Hayashi, Takashi Kokumai, Hideaki Sato, Shingo Yoshimachi, Akiko Kusaka, Mitsuhiro Shimura, Shun Nakayama, Shuichi Aoki, Masahiro Iseki, Takayuki Miura, Shimpei Maeda, Masaharu Ishida, Hideo Ohtsuka, Masamichi Mizuma, Kei Nakagawa, Atsushi Masamune, Toru Furukawa, Michiaki Unno","doi":"10.1007/s00535-025-02303-2","DOIUrl":"https://doi.org/10.1007/s00535-025-02303-2","url":null,"abstract":"<p><strong>Background: </strong>Pancreaticobiliary maljunction (PBM) contributes to epithelial hyperplasia and, ultimately, the development of gallbladder cancer (GBC). Despite its clinical significance, the molecular and cellular mechanisms driving carcinogenesis in GBC with PBM remain poorly elucidated. This study investigated the oncogenic mechanisms, biomarkers, and performance associated with Erb-b2 receptor tyrosine kinase 2 (ERBB2)-targeted therapies in GBC with PBM.</p><p><strong>Methods: </strong>Overall, 127 surgically treated patients were stratified as follows: Group A, normal gallbladder; Group B, PBM; Group C, GBC without PBM; and Group D, GBC with PBM. We performed whole-exome sequencing (WES) for Group D and human epidermal growth factor receptor 2 immunohistochemistry (HercepTest) for the entire cohort. Fluorescence in situ hybridization (FISH) was used to clarify human epidermal growth factor receptor 2 (HER2) expression in cases with equivocal HercepTest results.</p><p><strong>Results: </strong>ERBB2 amplification was detected in 50% of Group D patients. The proportion of HER2 protein expression scores ≥ 2 + was highest in Group D compared with that in the other groups (50.0% vs. 0% in Groups A and B and 15.6% in Group C) (P = 0.006, chi-squared test). Finally, 37.5% and 13.3% of cases in Groups D and C, respectively, showed HER2 overexpression (P = 0.037, chi-squared test).</p><p><strong>Conclusions: </strong>This is the first evaluation of HER2/ERBB2 expression in GBC with PBM based on WES, HercepTest, and FISH. The significant increase in ERBB2 expression, driven by the synergistic interplay between GBC and PBM, underscores a critical molecular interaction that may inform the development of targeted therapeutic strategies.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228331","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":"GPAM upregulation enhances hepatic fat deposition and reduces visceral adipose tissue in response to trans-fatty acids.","authors":"Teruki Miyake, Osamu Yoshida, Shinya Furukawa, Yusuke Sato, Yoshimasa Murakami, Ayumi Kanamoto, Masumi Miyazaki, Akihito Shiomi, Hironobu Nakaguchi, Mitsuhito Koizumi, Takao Watanabe, Yoshio Tokumoto, Masashi Hirooka, Masanori Abe, Bunzo Matsuura, Yoichi Hiasa","doi":"10.1007/s00535-025-02297-x","DOIUrl":"https://doi.org/10.1007/s00535-025-02297-x","url":null,"abstract":"<p><strong>Background: </strong>Dietary fatty acids are involved in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD). We examined the mechanism by which dietary fatty acid composition affects MASLD pathogenesis.</p><p><strong>Methods: </strong>The MASLD mouse model was developed by feeding a high-fat diet (HFD) rich in palmitic acid (PA), trans-fatty acids (TFAs), or oleic acid (OA). For in vitro experiments, Hepa 1-6 cells were exposed to PA, elaidic acid (a representative TFA), and OA. Glycerol-3-phosphate acyltransferase 1 (GPAM) expression in Hepa 1-6 cells was manipulated using a plasmid encoding GPAM and GPAM-specific siRNAs. In addition, GPAM depletion in the liver of HFD-fed mice was achieved using a pH-sensitive multifunctional envelope-type nanodevice as a siRNA carrier. Liver specimens from patients with MASLD were also analyzed.</p><p><strong>Results: </strong>The TFA group displayed higher serum alanine-aminotransferase and hepatic triglyceride content but lower serum fasting triglyceride and visceral adipose tissue (VAT) compared with that in the PA and OA groups. Hepatic GPAM expression in the TFA group was higher than in the PA group. Consistently, TFA-treated Hepa 1-6 cells showed a greater GPAM increase than that with OA and PA. GPAM-overexpressing Hepa 1-6 cells showed increased triglyceride accumulation, whereas GPAM-deficient cells failed to accumulate triglyceride. Hepatic GPAM knockdown in HFD-fed mice suppressed steatosis and increased VAT. Notably, hepatic GPAM gene expression was higher in patients with severe steatosis than in those with non-severe steatosis.</p><p><strong>Conclusions: </strong>A TFA-rich HFD increased hepatic GPAM expression, exacerbated steatosis, and decreased VAT. Therefore, GPAM may regulate systemic fat accumulation in the body.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228342","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":"Posttreatment serum CXCL10 level stratifies survival in compensated and decompensated cirrhotic patients due to chronic hepatitis C virus infection after direct-acting antiviral therapy.","authors":"Takanori Suzuki, Kentaro Matsuura, Yuki Tahata, Hayato Hikita, Ryotaro Sakamori, Norifumi Kawada, Nobuyuki Enomoto, Daiki Miki, Hiroshi Yatsuhashi, Hidekatsu Kuroda, Taro Yamashita, Hitoshi Yoshiji, Masayuki Kurosaki, Seiichi Mawatari, Hisamitsu Miyaaki, Yasuhiro Asahina, Yoichi Hiasa, Satoshi Mochida, Yasunari Nakamoto, Taro Takami, Takahiro Kodama, Tomohide Tatsumi, Tetsuo Takehara","doi":"10.1007/s00535-025-02282-4","DOIUrl":"10.1007/s00535-025-02282-4","url":null,"abstract":"<p><strong>Aim: </strong>We investigated the usefulness of serum CXCL10 levels for predicting prognosis in hepatitis C virus (HCV)-infected patients with compensated and decompensated cirrhosis (cLC and dLC) after direct-acting antiviral (DAA) therapy.</p><p><strong>Methods: </strong>This nationwide multicenter study enrolled 212 HCV-associated LC patients, consisting of 113 cLC and 99 dLC patients, receiving DAA therapy, who had preserved serum samples. Serum CXCL10 levels were measured at pretreatment (pre-CXCL10) and posttreatment (12 or 24 weeks after the end of treatment: EOT12W or EOT24W) (post-CXCL10). We evaluated the relationship between these levels and liver transplantation (LT)-free overall survival (OS) and clinical outcomes.</p><p><strong>Results: </strong>During the observational period (median: 37 months), 27 patients developed dLC events and 20 died. The post-CXCL10 levels were significantly higher in dLC than in cLC (P = 0.006) and among patients who died than those who survived (P < 0.001). The cutoff value of serum post-CXCL10 level for discriminating the occurrence of death (345 pg/mL) could predict LT-free OS in groups of all, cLC, and dLC patients (P < 0.001, P = 0.007, and P < 0.001, respectively). Multivariate analysis on factors associated with LT-free OS demonstrated that age (HR 1.076; P = 0.013), Child-Pugh score at EOT12W (HR 1.575; P = 0.009), and serum post-CXCL10 level (HR 1.003; P = 0.001) were independent factors.</p><p><strong>Conclusions: </strong>The serum post-CXCL10 level was independently related to survival in HCV-associated LC patients.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1272-1283"},"PeriodicalIF":5.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540501","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":"Distinct age-related effects of homologous recombination deficiency on genomic profiling and treatment efficacy in gastric cancer.","authors":"Yoshie Maki, Yoshiyasu Kono, Toshiki Ozato, Hideki Yamamoto, Akira Hirasawa, Daisuke Ennishi, Shuta Tomida, Shinichi Toyooka, Kenta Hamada, Masaya Iwamuro, Seiji Kawano, Motoyuki Otsuka","doi":"10.1007/s00535-025-02267-3","DOIUrl":"10.1007/s00535-025-02267-3","url":null,"abstract":"<p><strong>Background: </strong>The incidence of gastric cancer among younger patients is increasing globally, with growing attention being paid to the role of homologous recombination deficiency (HRD). However, the effect of HRD on treatment outcomes and prognosis in this population remains unclear.</p><p><strong>Methods: </strong>We analyzed clinical and genomic data from the Center for Cancer Genomics and Advanced Therapeutics database. Younger patients (≤ 39 years, n = 140) were compared with older patients (≥ 65 years, n = 1118) diagnosed with gastric cancer. This study focused on mutations in homologous recombination repair (HRR) genes and their association with tumor mutation burden (TMB), microsatellite instability (MSI), and treatment outcomes.</p><p><strong>Results: </strong>In older patients, HRD was associated with higher TMB and microsatellite instability-high (MSI-H) status, whereas no such correlations were observed in younger patients. Notably, MSI-H status was not observed in the younger group. Younger patients with HRD had a significantly shorter time to treatment failure (TTF) and overall survival (OS) than those without HRD. Conversely, in older patients, there was no significant difference in TTF or OS based on HRD status.</p><p><strong>Conclusion: </strong>HRR gene mutations influence genomic profiling, TMB, and MSI differently depending on the age of gastric cancer onset, suggesting potential effects on treatment efficacy and prognosis.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1232-1241"},"PeriodicalIF":5.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12450818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293863","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":"The PNPLA3 I148M variant is associated with immune cell infiltration and advanced fibrosis in MASLD: a prospective genotype-phenotype study.","authors":"Jaejun Lee, Jung Hoon Cha, Hee Sun Cho, Keungmo Yang, Hyun Yang, Heechul Nam, Mi Young Byun, Seok Keun Cho, Jinsung Park, Hyuk Wan Ko, Seong Wook Yang, Pil Soo Sung, Si Hyun Bae","doi":"10.1007/s00535-025-02285-1","DOIUrl":"10.1007/s00535-025-02285-1","url":null,"abstract":"<p><strong>Background: </strong>Increasing evidence reveals that immune cells significantly contribute to metabolic dysfunction-associated steatotic liver disease (MASLD) progression. The patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M variant has been linked to hepatic inflammation and fibrosis; however, its role in immune cell infiltration and activation within the liver remains unclear.</p><p><strong>Methods: </strong>Seventy patients with MASLD were prospectively enrolled. Genomic DNA was extracted from buccal swabs or liver biopsy samples, followed by single nucleotide polymorphism genotyping to determine the rs738409 SNP genotype at codon 148 of PNPLA3. Immunohistochemistry was conducted using CD3 and CD68 antibodies to quantify T cell and macrophage infiltration, respectively. Total RNA extracted from biopsy specimens was used for quantitative reverse transcription polymerase chain reaction to assess the expression of specific markers associated with immune cell activation.</p><p><strong>Results: </strong>Among the 70 patients with MASLD, 34 had the GG genotype, whereas 21 and 15 had the GC and CC genotypes, respectively. The GG genotype group showed a higher proportion of advanced fibrosis (F3 or F4) than the GC + CC group (P = 0.051). GG genotype carriers exhibited significantly higher CD3⁺ and CD68⁺ cell counts in the periportal region than the GC/CC carriers (P < 0.05). The transcriptomic analysis revealed elevated expression of markers associated with chronic antigen stimulation and immune cell activation (CD8A, GZMB, CCL2, and TIMP1) in GG carriers compared with those of GC and CC (P < 0.05). Furthermore, correlations among various markers, including inflammatory, steatosis-associated, and fibrosis-associated markers, exhibited consistent positive correlations.</p><p><strong>Conclusions: </strong>Our findings revealed that the PNPLA3 I148M variant and increased immune cell infiltration and activation were significantly correlated within the MASLD liver. Further studies are needed to elucidate the mechanistic links between this genetic variant and liver inflammation.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1284-1295"},"PeriodicalIF":5.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682722","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}