Gastric Cancer最新文献

{"title":"The relationship between the gastric cancer microbiome and clinicopathological factors: a metagenomic investigation from the 100,000 genomes project and The Cancer Genome Atlas.","authors":"Mary E Booth, Henry M Wood, Mark A Travis, Phil Quirke, Heike I Grabsch","doi":"10.1007/s10120-025-01588-9","DOIUrl":"10.1007/s10120-025-01588-9","url":null,"abstract":"<p><strong>Background: </strong>Findings from previous gastric cancer microbiome studies have been conflicting, potentially due to patient and/or tumor heterogeneity. The intratumoral gastric cancer microbiome and its relationship with clinicopathological variables have not yet been characterized in detail. We hypothesized that variation in gastric cancer microbial abundance, alpha diversity, and composition is related to clinicopathological characteristics.</p><p><strong>Methods: </strong>Metagenomic analysis of 529 GC samples was performed, including whole exome sequencing data from The Cancer Genome Atlas (TCGA) and whole genome sequencing data from the 100,000 Genomes Project. Microbial abundance, alpha diversity, and composition were compared across patient age, sex, tumor location, geographic origin, pathological depth of invasion, pathological lymph node status, histological phenotype, microsatellite instability status, and TCGA molecular subtype.</p><p><strong>Results: </strong>Gastric cancer microbiomes resembled previous results, with Prevotella, Selenomonas, Stomatobaculum, Streptococcus, Lactobacillus, and Lachnospiraceae commonly seen across both cohorts. Within the TCGA cohort, microbial abundance and alpha diversity were greater in gastric cancers with microsatellite instability, lower pathological depth of invasion, intestinal-type histology, and those originating from Asia. Microsatellite instability status was associated with microbiome composition in both cohorts. Sex and pathological depth of invasion were associated with microbiome composition in the TCGA cohort.</p><p><strong>Conclusion: </strong>The intratumoral gastric cancer microbiome appears to differ according to clinicopathological factors. Certain clinicopathological factors associated with favourable outcomes in gastric cancer were observed to be associated with greater microbial abundance and diversity. This highlights the need for further work to understand the underlying biological mechanisms behind the observed microbiome differences and their potential clinical and therapeutic impact.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"358-371"},"PeriodicalIF":6.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11993446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of CD66c as a potential target in gastroesophageal junction cancer for antibody-drug conjugate development.","authors":"Peng Zhang, Changjuan Tao, Hanfei Xie, Liu Yang, Ye Lu, Yun Xi, Shili Yao, Li Yuan, Peng Guo, Xiangdong Cheng","doi":"10.1007/s10120-025-01584-z","DOIUrl":"10.1007/s10120-025-01584-z","url":null,"abstract":"<p><strong>Background: </strong>Gastroesophageal junction (GEJ) cancer exhibits unique biological characteristics and currently lacks specific targeted therapies. Given the clinical efficacy of antibody-drug conjugates (ADCs) in solid tumor treatment, we aimed to identify a novel ADC target and suitable payload for GEJ-targeted therapy.</p><p><strong>Methods: </strong>In this study, we conducted bioinformatic analyses of multi-omics data, including transcriptomics, proteomics, and phosphoproteomics, to identify CD66c as a promising ADC target for GEJ cancer. We then engineered a CD66c-directed antibody-drug conjugate (CD66c-DXd) incorporating a GGFG linker. The preclinical efficacy of CD66c-DXd was determined in multi GEJ xenograft models.</p><p><strong>Results: </strong>Proteomic analyses of 103 cases of GEJ cancer revealed that CD66c expression was significantly higher in tumoral tissues compared to normal tissues. Proteomic and phosphoproteomic analyses identified deruxtecan (DXd) as a potentially potent payload for ADCs targeting GEJ cancer. Furthermore, high CD66c expression in GEJ was associated with a significantly lower proportion of plasma cells. The drug-to-antibody ratio (DAR) of CD66c-DXd was determined to be 3.6. CD66c-DXd effectively and selectively ablated multiple human GEJ cell lines (OE-19, OE33 and SK-GT-4) without affecting non-malignant cells (GES-1) in vitro. Eventually, CD66c-DXd mediated potent and durable tumor regression in vivo with excellent safety profiles.</p><p><strong>Conclusions: </strong>This preclinical study provides a strong rationale for the further development of CD66c-DXd as promising therapeutic candidates to treat advanced GEJ cancer. Additionally, the study demonstrates the robustness of the multi-omics data in identifying novel potential ADC targets and payloads.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"422-441"},"PeriodicalIF":6.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11993476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinicopathological significance of JAK2, STAT3, and STAT4 expression in patients with gastric solid-type poorly differentiated adenocarcinoma: a retrospective study.","authors":"Shinya Umekita, Daisuke Kiyozawa, Hitoshi Honma, Kenichi Kohashi, Yoshiaki Taniguchi, Shinichiro Kawatoko, Taisuke Sasaki, Eikichi Ihara, Eiji Oki, Masafumi Nakamura, Yoshihiro Ogawa, Yoshinao Oda","doi":"10.1007/s10120-025-01589-8","DOIUrl":"10.1007/s10120-025-01589-8","url":null,"abstract":"<p><strong>Background: </strong>The role of janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling remains unclear in gastric solid-type poorly differentiated adenocarcinoma. The present study investigates the clinicopathological significance of JAK2, STAT3, and STAT4 expression in solid-type poorly differentiated adenocarcinoma.</p><p><strong>Methods: </strong>We retrospectively enrolled 102 participants with primary solid-type poorly differentiated adenocarcinoma. We categorized participants according to deficient or proficient mismatch repair status (46 and 56 participants, respectively). Expression of phosphorylated JAK2 (pJAK2), phosphorylated STAT3 (pSTAT3), and STAT4 were analyzed via immunohistochemistry. We analyzed differences in protein expression in relation to mismatch repair status, and associations of high/low protein expression with clinicopathological characteristics and prognoses.</p><p><strong>Results: </strong>Deficient mismatch repair was found to be associated with high pJAK2 (p = 0.038) and STAT4 (p = 0.023) expression in contrast to proficient mismatch repair. Log-rank analysis revealed high pSTAT3 and low STAT4 expression to be significantly correlated with reduced overall survival (p = 0.001). Multivariate analysis revealed high pSTAT3 and low STAT4 expression to be independent indicators of unfavorable prognosis (hazard ratio = 2.751, p = 0.030), as was proficient mismatch repair status (hazard ratio = 3.819, p = 0.012).</p><p><strong>Conclusions: </strong>High expression of pJAK2 and STAT4 is more frequent in deficient compared with proficient mismatch repair in solid-type poorly differentiated adenocarcinoma. High pSTAT3 and low STAT4 expression could be a useful prognostic indicator in solid-type poorly differentiated adenocarcinoma.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"455-464"},"PeriodicalIF":6.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial organization of B lymphocytes and prognosis prediction in patients with gastric cancer.","authors":"Ryan Yong Kiat Tay, Manavi Sachdeva, Haoran Ma, Young-Woo Kim, Myeong-Cherl Kook, Hyunki Kim, Jae-Ho Cheong, Lindsay C Hewitt, Katharina Nekolla, Günter Schmidt, Takaki Yoshikawa, Takashi Oshima, Tomio Arai, Supriya Srivastava, Ming Teh, Xuewen Ong, Su Ting Tay, Taotao Sheng, Joseph J Zhao, Patrick Tan, Heike I Grabsch, Raghav Sundar","doi":"10.1007/s10120-025-01593-y","DOIUrl":"10.1007/s10120-025-01593-y","url":null,"abstract":"<p><strong>Background: </strong>Within the tumor microenvironment (TME), the association of B lymphocytes (B cells) with prognosis and therapy response in gastric cancer (GC) remains poorly characterized. We investigated the predictive and prognostic value of B cells, including their spatial organization within the TME, in one of the largest multi-cohort studies to date.</p><p><strong>Methods: </strong>Using CD20 immunohistochemistry, we evaluated B cell density in resection specimens from 977 patients with resectable GC across three cohorts, including the randomized phase III Korean CLASSIC trial. The relationship between CD20 density, clinicopathological characteristics, and overall survival (OS) was analyzed. Digital spatial profiling of 1063 regions of interest from 15 patients was performed to characterize B cell distribution within different regions of interest (ROIs) using the NanoString GeoMx platform.</p><p><strong>Results: </strong>CD20 density was significantly higher in diffuse-type GC compared to intestinal-type (p = 0.000012). Patients with CD20-low diffuse-type GC had the shortest OS in the CLASSIC trial (median OS: 49 vs 62 months, HR: 1.9, 95% CI: 1.2-3.0, p = 0.003) and in a Japanese cohort (median OS: 49 vs 67 months, HR: 2.2, 95% CI: 1.2-4.0, p = 0.011). This survival difference was not seen in patients treated with adjuvant chemotherapy (median OS: 62 vs 63 months, HR: 1.8, 95% CI: 0.88-3.5, p = 0.108). Spatial profiling revealed significant B cell enrichment within tumor ROIs compared to the stroma, particularly in diffuse-type GC.</p><p><strong>Conclusions: </strong>Low CD20 positivity, especially in diffuse-type GC, is linked to poor prognosis and may identify patients who could benefit from chemotherapy. These findings underscore the role of B cells in GC.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"384-396"},"PeriodicalIF":6.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11993452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential impact of frailty on surgical and non-surgical site complications in patients with gastric cancer undergoing gastrectomy.","authors":"Katsunobu Sakurai, Naoshi Kubo, Tatsuro Tamura, Tsuyoshi Hasegawa, Yutaka Tamamori, Junya Nishimura, Yasuhito Iseki, Takafumi Nishii, Toru Inoue, Masakazu Yashiro, Yukio Nishiguchi, Tsubasa Bito, Kiyoshi Maeda","doi":"10.1007/s10120-025-01590-1","DOIUrl":"10.1007/s10120-025-01590-1","url":null,"abstract":"<p><strong>Background: </strong>The aim of this study was to determine the differential impact of frailty on surgical site complications (SSCs) and non-surgical site complications (non-SSCs) in gastric cancer (GC) patients undergoing gastrectomy.</p><p><strong>Methods: </strong>In this study, frailty was assessed preoperatively using a frailty index (FI) in 395 patients scheduled for gastrectomy for GC between January 2016 and December 2023. Patients were divided into two groups (high FI vs. low FI) to examine the impact of frailty on SSC and non-SSC.</p><p><strong>Results: </strong>Overall complication and non-SSC rates were significantly higher in the high FI group, but the two groups had similar rates of SSC. In multivariate analysis, high FI, high BMI, and male were independent risk factors for non-SSC. The incidence of non-SSC was 0% in patients with no applicable risk factors, 3.6% in patients with one applicable risk factor, 13.0% in patients with two applicable risk factors, and 37.1% in patients with all three risk factors (Cochran-Armitage trend test, p < 0.001). The area under the curve (AUC) of the risk prediction model using these three variables to predict non-SSC was 0.760.</p><p><strong>Conclusions: </strong>High FI was an independent risk factor for non-SSC in patients undergoing gastrectomy for GC. Our developed non-SSC risk model combining FI, BMI, and sex effectively identifies individuals at increased risk for non-SSC in GC patients.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"501-513"},"PeriodicalIF":6.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lenvatinib suppress FGF19-FGFR4 signaling to enhance antitumor immune response in gastric cancer.","authors":"Yuya Maruyama, Motonobu Saito, Shotaro Nakajima, Katsuharu Saito, Hiroya Suzuki, Ryo Kanoda, Hirokazu Okayama, Hiroyuki Hanayama, Wataru Sakamoto, Zenichiro Saze, Tomoyuki Momma, Kosaku Mimura, Akiteru Goto, Koji Kono","doi":"10.1007/s10120-025-01596-9","DOIUrl":"10.1007/s10120-025-01596-9","url":null,"abstract":"<p><strong>Background: </strong>Fibroblast growth factor receptor (FGFR) 4 is overexpressed in gastric cancer (GC) and is a potential therapeutic target for GC. Since the FGF/FGFR signaling is involved in tumor microenvironment inducing the formation of an immunosuppression, lenvatinib is expected to inhibit FGFR4 leading to reduced tumor PD-L1 levels and regulatory T cell (Treg) infiltration, improving pembrolizumab efficacy. This study explored the background of the molecular mechanisms underlying the therapeutic efficacy of lenvatinib plus pembrolizumab.</p><p><strong>Methods: </strong>Expression of FGFR4 and its specific ligand FGF19 was assessed by immunohistochemical staining and clinicopathological relevance was also examined. The effect of lenvatinib on FGF19-FGFR4 signaling was evaluated using cellular experiments. Lastly, the expression of FGFR4 on Treg cells was evaluated by immunostaining and flow cytometry. The Cancer Genome Atlas cBioPortal and Gene Expression Omnibus microarray databases were accessed to support these results.</p><p><strong>Results: </strong>High FGFR4 expression was associated with histological type and venous invasion and predominantly detected in human epidermal growth factor receptor 2 and Epstein-Barr virus-positive GC. Bioinformatics data suggested that FGF19-FGFR4 signaling was activated in GC, and cellular experiments showed that lenvatinib reduced FGFR4 and PD-L1 expression in GC cells. Results of integrating various analyses suggested that FGFR4 did not seem to be enough expressed on Treg cells in GC.</p><p><strong>Conclusions: </strong>The FGF19-FGFR4 signaling has a pivotal role in gastric tumorigenesis and may be involved in immunosuppression through PD-L1 modification. But, lenvatinib may not regulate immune editing by directly inhibiting FGFR4 on Treg cells.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"397-408"},"PeriodicalIF":6.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of histologically poorly cohesive phenotype as a prognostic factor in patients with pStage II/III gastric cancer undergoing adjuvant chemotherapy.","authors":"Chikara Kunisaki, Sho Sato, Kohei Kasahara, Tsutomu Sato, Akikazu Yago, Yuko Tamura, Hiroki Kondo, Masanori Oshi, Takashi Kosaka, Hirotoshi Akiyama, Itaru Endo","doi":"10.1007/s10120-025-01599-6","DOIUrl":"10.1007/s10120-025-01599-6","url":null,"abstract":"<p><strong>Background: </strong>Few studies have focussed on using histological phenotype to evaluate prognostic factors after adjuvant chemotherapy (AC) in patients with pStage II/III gastric cancer. We evaluated the impact of histological type based on the World Health Organization classification.</p><p><strong>Methods: </strong>Overall, 348 patients with pStage II/III advanced gastric cancer undergoing R0 gastrectomy without neoadjuvant chemotherapy were included. Of these, 143 underwent AC. Univariate and multivariate analyses for prognostic factors of relapse-free survival (RFS) and overall survival (OS) were performed in all patients and patients receiving AC. Moreover, long-term survivals were compared by histological phenotype between patients with and without AC.</p><p><strong>Results: </strong>Multivariate analysis in all patients revealed that histologically poorly cohesive carcinoma with not otherwise specified and signet ring cell subtype (PCC-NOS/SRC) and pN 2/3 independently and adversely affected RFS. Alternatively, male sex, poor PS and pN 2/3 adversely affected OS. In multivariate analysis of patients receiving AC, longer tumour size (≥ 80 mm), histologically PCC-NOS/SRC phenotype and pN 3 independently influenced RFS. Multivariate analysis in this population for OS revealed that pN 3 and poor postoperative immune-nutritional status significantly induced worse OS. Comparison of RFS and OS by histological phenotype between patients with and without AC showed that AC had no efficacy for improving long-term survivals in histologically PCC phenotype.</p><p><strong>Conclusions: </strong>Histologically PCC phenotype by WHO classification, particularly PCC-NOS/SRC phenotypes, showed poor long-term RFS even after AC in patients with pStage II and III gastric cancer. An effective chemotherapeutic regimen needs to be developed for this specific subtype of gastric cancer.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"478-492"},"PeriodicalIF":6.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel ypN-TRG staging system for gastric cancer patients after neoadjuvant therapy based on the metro-ticket paradigm: a multicenter and large sample retrospective analysis.","authors":"Cai-Ming Weng, Qing Zhong, Yu-Qin Sun, Zhi-Yu Liu, Yu-Bin Ma, Zhi-Quan Zhang, Hao-Xiang Zhang, Ji-Yun Zhu, Wen Ye, Ju Wu, He Du, Chao-Hui Zheng, Ping Li, Qi-Yue Chen, Chang-Ming Huang, Jian-Wei Xie","doi":"10.1007/s10120-025-01586-x","DOIUrl":"10.1007/s10120-025-01586-x","url":null,"abstract":"<p><strong>Background: </strong>Conventional ypT category evaluates the depth of invasion after neoadjuvant therapy (NAT) for gastric cancer (GC) and has limited prognostic value. Tumor regression grade (TRG) measures the extent of tumor response to treatment, and when combined with the ypN category, it may enhance the prediction of patient outcomes. This study aims to develop a new staging system by integrating TRG and ypN category to better evaluate the prognosis of GC patients receiving NAT.</p><p><strong>Methods: </strong>This retrospective analysis included 962 patients who underwent radical gastrectomy after NAT, with 513 in the development cohort (from one center) and 449 in the external validation cohort (from five centers). The ypN-TRG staging system was established by calculating the distance from the origin on a cartesian plane incorporating the ypN (x-axis) stage and TRG (y-axis) grade, and five sub-stages were delineated.</p><p><strong>Results: </strong>In the development cohort, 3-year overall survival rates according to ypN-TRG stage I, IIA, IIB, IIIA, IIB were 87.6%, 80.2%, 70.7%, 47.3%, 21.5%, p < 0.01. Compared with ypTNM, the ypN-TRG staging system performed better in terms of the prognostic discrimination power (C-index), goodness-of-fit (AIC, BIC), model improvement (NRI, IDI), and model stability (time-AUC). Multivariate Cox regression analysis confirmed the superiority of ypN-TRG over ypTNM staging. In the external validation cohort, ypN-TRG staging was a better predictor of OS and DFS in patients with GC.</p><p><strong>Conclusions: </strong>The ypN-TRG staging system is superior to the AJCC eighth edition ypTNM staging system in accurately assessing the prognosis of patients with GC after NAT.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"465-477"},"PeriodicalIF":6.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple metachronous foveolar-type gastric adenomas in a Helicobacter pylori-naïve patient with long-term use of a proton pump inhibitor: a case report.","authors":"Yoichi Miyaoka, Kotaro Shibagaki, Ryoji Kushima, Taisuke Omachi, Takanobu Hino, Aya Fujiwara, Kousuke Tsukano, Sayaka Ogawa, Satoshi Yamanouchi, Masaki Tanaka, Tatsuya Miyake, Hirofumi Fujishiro, Naruaki Kohge, Hideyuki Ohnuma, Norihisa Ishimura, Tsuyoshi Mishiro, Shunji Ishihara","doi":"10.1007/s10120-025-01595-w","DOIUrl":"10.1007/s10120-025-01595-w","url":null,"abstract":"<p><p>A 69-year-old man undergoing long-term administration of a proton-pump inhibitor (PPI) underwent upper endoscopy, which found a small, whitish, flat lesion in the fundic gland (oxyntic) mucosa. The patient had never received treatment for Helicobacter pylori (Hp) infection, and diagnostic testing for Hp was negative, suggesting an Hp-naïve status. Two years later, the lesion appeared markedly enlarged and was endoscopically resected. Histological examination revealed a low-grade foveolar-type gastric adenoma (FGA), predominantly expressing MUC5AC by immunohistochemistry. Two years later, while PPI therapy was continued, three new flat lesions were found. These were endoscopically resected and histologically diagnosed as low-grade FGAs as before, suggesting that multiple metachronous tumors had developed in a short period of time during long-term PPI administration. A KRAS mutation and a CTNNB1 mutation were identified in the tumor. To our best knowledge, this is the first report of potentially PPI-associated multiple metachronous FGAs in an Hp-naïve patient. Here we report a case of multiple foveolar-type gastric adenomas with rapid metachronous recurrences during long-term use of a proton pump inhibitor in Helicobacter pylori-naïve patient.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"537-543"},"PeriodicalIF":6.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11993507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Minimum resection length to ensure a pathologically negative distal margin and a larger remnant stomach for esophagogastric junction cancer.","authors":"Qingjiang Hu, Manabu Ohashi, Motonari Ri, Rie Makuuchi, Tomoyuki Irino, Masaru Hayami, Takeshi Sano, Souya Nunobe","doi":"10.1007/s10120-025-01581-2","DOIUrl":"10.1007/s10120-025-01581-2","url":null,"abstract":"<p><strong>Background: </strong>Ensuring a pathologically negative distal margin (DM) and preserving a larger remnant stomach is important for proximal gastrectomy (PG) in patients with esophagogastric junction (EGJ) cancer. However, the minimum DM length for ensuring negative margins has not been identified.</p><p><strong>Methods: </strong>We enrolled patients undergoing PG or total gastrectomy for EGJ cancer. A parameter ΔDM, representing the pathological extension distally beyond the gross tumor boundary, was evaluated. The maximum ΔDM, which indicates the minimum length ensuring a pathologically negative DM, was determined in all patients. Subgroup analyses were performed according to factors associated with ΔDM > 10 mm. The possible incidences of pathologically positive DM based on gross DM length were also calculated.</p><p><strong>Results: </strong>Among 253 eligible patients, the maximum ΔDM was 55 mm. Growth and pathological types were significantly associated with ΔDM > 10 mm. In subgroup analyses, the maximum ΔDM was 30/20/55 mm for the superficial/expansive/infiltrative growth types, and 55/40 mm for the differentiated/undifferentiated types. In the infiltrative growth type alone, the maximum ΔDM remained 55/40 mm for the differentiated/undifferentiated types. However, even if the gross DM length was reduced to 30 mm, the possible incidence of pathologically positive DM only increased to 2.6% in the infiltrative differentiated type.</p><p><strong>Conclusion: </strong>We recommend a minimum DM length of 30/20/55 mm for the superficial/expansive/ infiltrative growth types. Specifically in the infiltrative growth type, we alternatively recommend 30/40 mm for the differentiated/undifferentiated types, with a mandatory intraoperative frozen section analysis. Mini-abstract This study proposes a distal margin length for safe resection of esophagogastric junction cancer, ensuring pathologically negative margins while preserving a larger remnant stomach, based on growth and pathological types.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"493-500"},"PeriodicalIF":6.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}