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The landscape of 142 Epstein-Barr viral whole genomes in gastric cancer. 胃癌中 142 个 Epstein-Barr 病毒全基因组的分布情况。
IF 6.9 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-11-21 DOI: 10.1007/s00535-024-02170-3
Yuki Kojima, Motoharu Hamada, Azumi Naruse, Kimitoshi Goto, Htet Thiri Khine, Haruto Arai, Yuta Akutsu, Akira Satou, Masato Nakaguro, Seiichi Kato, Yasuhiro Kodera, Yasushi Yatabe, Yuka Torii, Jun-Ichi Kawada, Takayuki Murata, Hiroshi Kimura, Shuji Takiguchi, Hiroshi Inagaki, Hiromi Kataoka, Yusuke Okuno

Background: A substantial portion of gastric cancer (GC) is linked to Epstein-Barr virus (EBV) infection. The characteristics of this viral genome, such as specific viral strains and large structural variations, influence the progression of diseases like nasopharyngeal carcinoma and hematological malignancy. However, the EBV genomes from GC have not been thoroughly characterized.

Methods: Our study involved 849 consecutive GC patients diagnosed at Nagoya City University Hospital, Japan (NCU cohort). We detected EBV from formalin-fixed, paraffin-embedded sections using a novel direct PCR-based rapid detection method. Additionally, we analyzed 142 EBV whole genomes (125 newly sequenced) from GC, comparing them with 205 genomes from other EBV-associated diseases.

Results: We identified 32 (3.8%) patients associated with EBVaGC in the NCU cohort. Moreover, the direct PCR identified several GC specimens containing EBV-infected lymphocytes or their follicles. The dominant viral strain in GC was type 1 EBV, prevalent in most parts of the world, and no GC-specific strain was identified. We found no significant associations between single-nucleotide variants in the viral genome and GC. Structural variations of the EBV genome were infrequent in GC (4 cases, 2.1%), contrasting with EBV-associated hematological malignancy, which frequently carries large deletions.

Conclusions: This study is the first to uncover the genomic variations of EBV in GC. While EBV is definitively linked to GC, the characteristics of its genomes do not strongly correlate with disease development or progression. Our findings on viral genomes supplement the current understanding of human genomes in EBVaGC.

背景:相当一部分胃癌(GC)与 Epstein-Barr 病毒(EBV)感染有关。这种病毒基因组的特征,如特定的病毒株和巨大的结构变异,影响着鼻咽癌和血液恶性肿瘤等疾病的进展。然而,来自 GC 的 EBV 基因组尚未被彻底鉴定:我们的研究涉及在日本名古屋市立大学医院确诊的连续 849 例 GC 患者(NCU 队列)。我们使用一种基于 PCR 的新型直接快速检测方法检测了福尔马林固定、石蜡包埋切片中的 EBV。此外,我们还分析了来自 GC 的 142 个 EBV 全基因组(其中 125 个是新测序的),并将它们与来自其他 EBV 相关疾病的 205 个基因组进行了比较:我们在NCU队列中发现了32名(3.8%)与EBVaGC相关的患者。此外,直接 PCR 还发现了几例含有 EBV 感染淋巴细胞或其滤泡的 GC 标本。GC 中的主要病毒株是 1 型 EBV,流行于世界大部分地区,没有发现 GC 特异性病毒株。我们发现病毒基因组中的单核苷酸变异与 GC 之间没有明显的关联。EBV基因组的结构变异在GC中并不常见(4例,2.1%),这与EBV相关的血液恶性肿瘤形成鲜明对比,后者经常携带大量缺失:本研究首次发现了EBV在GC中的基因组变异。虽然 EBV 与 GC 有明确的联系,但其基因组的特征与疾病的发生或发展并无密切关系。我们对病毒基因组的发现补充了目前对 EBVaGC 中人类基因组的认识。
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引用次数: 0
Association between advanced fibrosis and epigenetic age acceleration among individuals with MASLD. 晚期纤维化与 MASLD 患者表观遗传年龄加速之间的关系。
IF 6.9 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-11-20 DOI: 10.1007/s00535-024-02181-0
Haili Wang, Zhenqiu Liu, Hong Fan, Chengnan Guo, Xin Zhang, Yi Li, Suzhen Zhao, Luojia Dai, Ming Zhao, Tiejun Zhang

Background: The biological process of aging plays an important role in the progress of liver fibrosis. However, epidemiological evidence about the associations between advanced fibrosis and epigenetic age acceleration (EAA) among individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) is limited.

Methods: We utilized publicly available DNA methylation data (GSE180474) for our analysis. Five EAA measures were calculated in this study, including IEAA, PhenoAA, GrimAA, DunedinPACE, and DNAmTLAA. Separate linear regression models were conducted to explore the associations between different fibrosis grades and each measure of EAA.

Results: A total of 325 participants were included in this study, with a mean (± SD) age of 48.56 ± 11.50 years. Of these participants, 64.6% with no fibrosis, 16.9% with bridging fibrosis, 11.1% with incomplete cirrhosis, and 7.4% with cirrhosis. After adjusting for demographics and medication status, MASLD individuals with advanced fibrosis were associated with a 5% increase in the pace of aging (DunedinPACE, β = 0.05, 95% CI: 0.03-0.07) and a 10% decrease in DNAmTLAA (β = -0.10, 95% CI: -0.13 to -0.07) compared those without fibrosis. Similarly, higher stages of fibrosis were associated with an increased pace of aging (DunedinPACE, β = 0.02, 95% CI: 0.01-0.03, Ptrend < 0.001) and decreased DNAmTLAA (β = -0.05, 95% CI: -0.07 to -0.04, Ptrend < 0.001). However, no significant association was found between advanced fibrosis and IEAA, PhenoAA, and GrimAA.

Conclusions: Our findings suggest that advanced fibrosis was associated with an accelerated pace of aging, as measured by the third-generation EA measure DunedinPACE, and shorter telomere length, captured by DNAmTLAA, among individuals with MASLD. This finding has potential prognostic implications and suggests EAA may serve as a surrogate marker of therapeutic efficacy in MASLD.

背景:生物衰老过程在肝纤维化的进展过程中起着重要作用。然而,有关代谢功能障碍相关性脂肪性肝病(MASLD)患者肝纤维化晚期与表观遗传年龄加速(EAA)之间关系的流行病学证据却很有限:我们利用公开的 DNA 甲基化数据(GSE180474)进行分析。本研究计算了五种 EAA 测量值,包括 IEAA、PhenoAA、GrimAA、DunedinPACE 和 DNAmTLAA。我们分别建立了线性回归模型,以探讨不同纤维化等级与每种 EAA 指标之间的关联:本研究共纳入 325 名参与者,平均(± SD)年龄为 48.56 ± 11.50 岁。在这些参与者中,64.6%无纤维化,16.9%为桥接纤维化,11.1%为不完全肝硬化,7.4%为肝硬化。在对人口统计学和用药状况进行调整后,与无纤维化者相比,纤维化晚期的 MASLD 患者的衰老速度增加了 5%(DunedinPACE,β = 0.05,95% CI:0.03-0.07),DNAmTLAA 降低了 10%(β = -0.10,95% CI:-0.13 至 -0.07)。同样,纤维化程度越高,衰老速度越快(DunedinPACE,β = 0.02,95% CI:0.01-0.03,Ptrend 趋势结论):我们的研究结果表明,在 MASLD 患者中,晚期纤维化与第三代 EA 测量 DunedinPACE 测定的老化速度加快和 DNAmTLAA 测定的端粒长度缩短有关。这一发现具有潜在的预后意义,并表明 EAA 可作为 MASLD 疗效的替代标志物。
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引用次数: 0
YAP acts as an independent prognostic marker and regulates growth and metastasis of gastrointestinal stromal tumors via FBXW7-YAP pathway. YAP是一种独立的预后标志物,通过FBXW7-YAP通路调控胃肠道间质瘤的生长和转移。
IF 6.9 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-11-18 DOI: 10.1007/s00535-024-02180-1
Xiyu Wu, Kohei Yamashita, Chihiro Matsumoto, Weiliyun Zhang, Ming Ding, Kazuto Harada, Keisuke Kosumi, Kojiro Eto, Satoshi Ida, Yuji Miyamoto, Masaaki Iwatsuki

Background: Although imatinib (IM) and subsequent tyrosine kinase inhibitors (TKIs) significantly improve the prognosis of GIST patients by delaying metastasis and recurrence, most patients experience limited efficacy due to toxicity and secondary resistance. We evaluated Yes-associated protein (YAP), a coactivator of the Hippo pathway accounting for IM resistance and aggressive GIST phenotypes, in GISTs. The degradation of YAP is mediated by FBXW7, and FBXW7 predicts recurrence and IM efficacy for GIST patients. Here, we aimed to identify the potential of YAP as a prognostic marker for patients with GISTs, and the molecular mechanism of FBXW7-YAP pathway in GIST cells.

Methods: We measured YAP expression in 167 GIST cases using immunohistochemical staining, correlated its expression levels with clinicopathological features, and the molecular mechanism underlying the FBXW7-YAP pathway was further examined in vitro and in vivo.

Results: Compared to 80 (47.9%) cases in the low YAP expression group, 87 (52.1%) cases with high YAP expression associated with a poorer prognosis in terms of overall survival (P = 0.004) and recurrence-free survival (P = 0.003). YAP expression was identified as a significant independent factor affecting the 5-year overall survival (P = 0.005) and recurrence-free survival rates (P = 0.007). Moreover, YAP was directly targeted by FBXW7 to affect proliferation, invasion, and migration in GIST cells. High YAP expression correlated with FBXW7 deficiency, as shown in xenograft and metastasis mouse models.

Conclusions: YAP expression serves as a predictive marker of recurrence for GIST patients with curative resection, highlighting its potential as a novel therapeutic target that warrants further investigation.

背景:尽管伊马替尼(IM)和后续的酪氨酸激酶抑制剂(TKIs)通过延缓转移和复发显著改善了GIST患者的预后,但由于毒性和继发性耐药性,大多数患者的疗效有限。我们评估了GISTs中的Yes-相关蛋白(YAP),它是Hippo通路的辅助激活剂,导致IM耐药和侵袭性GIST表型。YAP的降解由FBXW7介导,而FBXW7可预测GIST患者的复发和IM疗效。在此,我们旨在确定YAP作为GIST患者预后标志物的潜力,以及FBXW7-YAP通路在GIST细胞中的分子机制:我们采用免疫组化染色法检测了167例GIST病例中YAP的表达,将其表达水平与临床病理特征相关联,并在体外和体内进一步研究了FBXW7-YAP通路的分子机制:结果:与 YAP 低表达组的 80 例(47.9%)相比,YAP 高表达组的 87 例(52.1%)在总生存期(P = 0.004)和无复发生存期(P = 0.003)方面预后较差。YAP表达被认为是影响5年总生存率(P = 0.005)和无复发生存率(P = 0.007)的重要独立因素。此外,FBXW7 直接靶向 YAP,影响 GIST 细胞的增殖、侵袭和迁移。正如异种移植和转移小鼠模型所示,YAP的高表达与FBXW7的缺乏有关:结论:YAP的表达可作为治愈性切除术后GIST患者复发的预测标志物,突出了其作为新型治疗靶点的潜力,值得进一步研究。
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引用次数: 0
Anti-integrin αvβ6 autoantibody in primary sclerosing cholangitis: a Japanese nationwide study. 原发性硬化性胆管炎中的抗整合素αvβ6自身抗体:一项日本全国性研究。
IF 6.9 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-11-16 DOI: 10.1007/s00535-024-02169-w
Muneji Yasuda, Masahiro Shiokawa, Takeshi Kuwada, Yoshihiro Nishikawa, Risa Nakanishi, Ikuhisa Takimoto, Koki Chikugo, Masataka Yokode, Yuya Muramoto, Shimpei Matsumoto, Takeharu Nakamura, Sakiko Ota, Tomoaki Matsumori, Keiko Kuroda, Takahisa Hachiya, Hajime Yamazaki, Norimitsu Uza, Yuzo Kodama, Tsutomu Chiba, Toshio Fujisawa, Atsumasa Komori, Masanori Abe, Izumi Yamaguchi, Fumihiko Matsuda, Hiroyuki Isayama, Atsushi Tanaka, Hiroshi Seno

Background: Although specific biomarkers for primary sclerosing cholangitis (PSC) are required, no such biomarkers have been identified. We previously reported that patients with PSC had anti-integrin αvβ6 autoantibodies at only two hospitals. In this study, we aimed to validate the accuracy of the autoantibodies in diagnosing PSC using the newly developed Anti-integrin αvβ6 enzyme-linked immunosorbent assay (ELISA) Kit, which enables quantitation and comparison of antibodies among different facilities.

Methods: Overall, 81 patients with PSC in a Japanese PSC registry recruited from 17 medical centers and hospitals, and 358 controls were enrolled. We retrospectively assessed anti-integrin αvβ6 autoantibodies using the Anti-integrin αvβ6 ELISA Kit and in-house ELISA.

Results: Anti-Integrin αvβ6 ELISA Kit and in-house ELISA exhibited a significant correlation (r = 0.97, P < 0.001). Anti-integrin αvβ6 autoantibodies were detected in 67 of 81 (82.7%) patients with PSC and 20 of 358 (5.6%) controls, resulting in a sensitivity of 82.7% and specificity of 94.4% for PSC, using the anti-integrin αvβ6 ELISA Kit. When focusing on the presence or absence of inflammatory bowel disease (IBD), the sensitivities for PSC with ulcerative colitis, Crohn's disease, unclassified-IBD, and without IBD were 97.8% (43/44), 100% (1/1), 80.0% (8/10), and 53.8% (7/13), respectively. Antibody concentrations were significantly higher in PSC patients without IBD than in controls (P < 0.001).

Conclusions: We validated that anti-integrin αvβ6 autoantibodies have high sensitivity and specificity for diagnosing PSC. This study provides further evidence that anti-integrin αvβ6 autoantibodies are a useful biomarker for diagnosing PSC.

背景:尽管原发性硬化性胆管炎(PSC)需要特异性生物标志物,但目前尚未发现此类生物标志物。我们以前曾报道过,只有两家医院的 PSC 患者有抗整合素 αvβ6 自身抗体。在本研究中,我们旨在使用新开发的抗整合素αvβ6酶联免疫吸附试验(ELISA)试剂盒验证自身抗体在诊断PSC方面的准确性:从 17 家医疗中心和医院招募了 81 名日本 PSC 登记处的 PSC 患者和 358 名对照者。我们使用抗整合素αvβ6 ELISA试剂盒和内部ELISA对抗整合素αvβ6自身抗体进行了回顾性评估:结果:抗整合素αvβ6 ELISA试剂盒和内部ELISA显示出显著的相关性(r = 0.97,P 结论:抗整合素αvβ6 ELISA试剂盒和内部ELISA显示出显著的相关性(r = 0.97,P 结论):我们验证了抗整合素αvβ6自身抗体对诊断PSC具有较高的灵敏度和特异性。这项研究进一步证明,抗整合素αvβ6自身抗体是诊断PSC的有效生物标记物。
{"title":"Anti-integrin αvβ6 autoantibody in primary sclerosing cholangitis: a Japanese nationwide study.","authors":"Muneji Yasuda, Masahiro Shiokawa, Takeshi Kuwada, Yoshihiro Nishikawa, Risa Nakanishi, Ikuhisa Takimoto, Koki Chikugo, Masataka Yokode, Yuya Muramoto, Shimpei Matsumoto, Takeharu Nakamura, Sakiko Ota, Tomoaki Matsumori, Keiko Kuroda, Takahisa Hachiya, Hajime Yamazaki, Norimitsu Uza, Yuzo Kodama, Tsutomu Chiba, Toshio Fujisawa, Atsumasa Komori, Masanori Abe, Izumi Yamaguchi, Fumihiko Matsuda, Hiroyuki Isayama, Atsushi Tanaka, Hiroshi Seno","doi":"10.1007/s00535-024-02169-w","DOIUrl":"https://doi.org/10.1007/s00535-024-02169-w","url":null,"abstract":"<p><strong>Background: </strong>Although specific biomarkers for primary sclerosing cholangitis (PSC) are required, no such biomarkers have been identified. We previously reported that patients with PSC had anti-integrin αvβ6 autoantibodies at only two hospitals. In this study, we aimed to validate the accuracy of the autoantibodies in diagnosing PSC using the newly developed Anti-integrin αvβ6 enzyme-linked immunosorbent assay (ELISA) Kit, which enables quantitation and comparison of antibodies among different facilities.</p><p><strong>Methods: </strong>Overall, 81 patients with PSC in a Japanese PSC registry recruited from 17 medical centers and hospitals, and 358 controls were enrolled. We retrospectively assessed anti-integrin αvβ6 autoantibodies using the Anti-integrin αvβ6 ELISA Kit and in-house ELISA.</p><p><strong>Results: </strong>Anti-Integrin αvβ6 ELISA Kit and in-house ELISA exhibited a significant correlation (r = 0.97, P < 0.001). Anti-integrin αvβ6 autoantibodies were detected in 67 of 81 (82.7%) patients with PSC and 20 of 358 (5.6%) controls, resulting in a sensitivity of 82.7% and specificity of 94.4% for PSC, using the anti-integrin αvβ6 ELISA Kit. When focusing on the presence or absence of inflammatory bowel disease (IBD), the sensitivities for PSC with ulcerative colitis, Crohn's disease, unclassified-IBD, and without IBD were 97.8% (43/44), 100% (1/1), 80.0% (8/10), and 53.8% (7/13), respectively. Antibody concentrations were significantly higher in PSC patients without IBD than in controls (P < 0.001).</p><p><strong>Conclusions: </strong>We validated that anti-integrin αvβ6 autoantibodies have high sensitivity and specificity for diagnosing PSC. This study provides further evidence that anti-integrin αvβ6 autoantibodies are a useful biomarker for diagnosing PSC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644285","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
Cancer pathways in serrated polyposis syndrome: is conventional more crucial than serrated? 锯齿状息肉病综合征的致癌途径:传统的比锯齿状的更重要吗?
IF 6.9 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-11-16 DOI: 10.1007/s00535-024-02177-w
Munehiro Ikeda, Yuki Nakanishi, Hiroshi Seno
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引用次数: 0
Clinical factors to predict changes of esophagogastric varices after sustained viral response with direct-acting antiviral therapy. 预测直接作用抗病毒疗法持续病毒应答后食管胃静脉曲张变化的临床因素。
IF 6.9 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-11-15 DOI: 10.1007/s00535-024-02174-z
Takao Watanabe, Yoshio Tokumoto, Hironori Ochi, Toshie Mashiba, Fujimasa Tada, Atsushi Hiraoka, Yoshiyasu Kisaka, Yoshinori Tanaka, Sen Yagi, Seiji Nakanishi, Kotaro Sunago, Kazuhiko Yamauchi, Makoto Higashino, Kana Hirooka, Masaaki Tange, Atsushi Yukimoto, Makoto Morita, Yuki Okazaki, Masashi Hirooka, Masanori Abe, Yoichi Hiasa

Background: The clinical course of esophagogastric varices (EGV) after sustained virological response (SVR) with direct-acting antiviral (DAA) therapy has not been clearly elucidated. The predictors for the worsening/improvement of EGV after SVR with DAA therapy were investigated.

Methods: Of the cirrhosis patients who achieved SVR with DAA therapy, 328 patients who underwent endoscopic examinations both before and after DAA therapy were enrolled. The predictors of EGV worsening or improvement were investigated.

Results: Multivariate analysis identified a history of ascites retention, albumin at baseline, and MELD score at baseline as independent factors that contributed to EGV exacerbation. On multivariate analysis, two factors, BMI and platelet count, were related to EGV improvement. An integrated scoring system was created using these risk factors with or without weighting according to each hazard ratio, and the patients were divided into three groups. A scoring system with weighting of each factor appeared to be more useful, with fewer intermediate patients and more cases classified into the low-risk and high-risk groups.

Conclusion: Esophagogastric varices after SVR have a varied clinical course. Using this scoring system that can accurately predict EGV outcomes in clinical settings, it may be feasible to establish a risk-based EGV surveillance plan following SVR.

背景:直接作用抗病毒药物(DAA)治疗持续病毒学应答(SVR)后食管胃静脉曲张(EGV)的临床过程尚未明确阐明。本研究调查了直接作用抗病毒药物治疗 SVR 后 EGV 恶化/改善的预测因素:在接受 DAA 治疗获得 SVR 的肝硬化患者中,有 328 名患者在接受 DAA 治疗前后均接受了内镜检查。结果:多变量分析确定了肝硬化患者的内镜检查病史:多变量分析发现,腹水潴留史、基线白蛋白和基线 MELD 评分是导致 EGV 恶化的独立因素。通过多变量分析,BMI 和血小板计数这两个因素与 EGV 改善有关。利用这些风险因素创建了一个综合评分系统,根据每个危险比加权或不加权,并将患者分为三组。对每个因素进行加权的评分系统似乎更有用,中间型患者更少,更多病例被分为低风险组和高风险组:结论:SVR 后食管胃底静脉曲张的临床过程多种多样。该评分系统可在临床环境中准确预测食管胃底静脉曲张的预后,因此在 SVR 后建立基于风险的食管胃底静脉曲张监测计划是可行的。
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引用次数: 0
Liver transplantation for gastroenteropancreatic neuroendocrine liver metastasis: optimal patient selection and perioperative management in the era of multimodal treatments. 胃肠胰神经内分泌肝转移的肝移植:多模式治疗时代的最佳患者选择和围手术期管理。
IF 6.9 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-11-15 DOI: 10.1007/s00535-024-02166-z
Yosuke Kasai, Takashi Ito, Toshihiko Masui, Kazuyuki Nagai, Takayuki Anazawa, Yoichiro Uchida, Takamichi Ishii, Koji Umeshita, Susumu Eguchi, Yuji Soejima, Hideki Ohdan, Etsuro Hatano

Gastroenteropancreatic neuroendocrine tumors (NET) often metastasize to the liver. Although curative liver resection provides a favorable prognosis for patients with neuroendocrine liver metastasis (NELM), with a 5-year survival rate of 70-80%, recurrence is almost inevitable, mainly in the remnant liver. In Western countries, liver transplantation (LT) has been performed in patients with NELM, with the objective of complete removal of macro- and micro-NELMs. However, prognosis had been unsatisfactory, with 5-year overall survival and recurrence-free survival rates of approximately 50 and 30%, respectively. In 2007, the Milan criteria were proposed as indications for LT for NELM. The criteria included: (1) confirmed histology of NET-G1 or G2; (2) a primary tumor drained by the portal system and all extrahepatic diseases removed with curative resection before LT; (3) liver involvement ≤50%; (4) good response or stable disease for at least 6 months before LT; (5) age ≤ 55 years. A subsequent report demonstrated outstanding LT outcomes for NELM within the Milan criteria, with 5-year overall survival and recurrence rates of 97 and 13%, respectively. In Japan, living donor LT (LDLT) for NELM has been performed sporadically in only 16 patients by 2021 in Japan; however, no consensus has been reached on the indications or perioperative management of LDLT. This article presents the outcomes of these 16 patients who underwent LDLT in Japan and reviews the literature to clarify optimal indications and perioperative management of LDLT for NELM in the era of novel multimodal treatments.

胃肠胰神经内分泌肿瘤(NET)经常转移到肝脏。虽然肝脏根治性切除术为神经内分泌肝转移(NELM)患者提供了良好的预后,5年生存率高达70-80%,但复发几乎不可避免,主要是在残余肝脏。在西方国家,已对 NELM 患者实施了肝移植手术(LT),目的是彻底清除巨型和微小 NELM。然而,预后并不令人满意,5 年总生存率和无复发生存率分别约为 50% 和 30%。2007 年,米兰标准被提出作为 NELM LT 的适应症。这些标准包括(1)组织学确诊为NET-G1或G2;(2)原发肿瘤由门静脉系统引流,LT前所有肝外疾病均已治愈性切除;(3)肝脏受累≤50%;(4)LT前至少6个月反应良好或病情稳定;(5)年龄≤55岁。随后的一份报告显示,符合米兰标准的 NELM LT 疗效显著,5 年总生存率和复发率分别为 97% 和 13%。在日本,截至 2021 年,仅有 16 例患者零星接受了针对 NELM 的活体器官移植手术(LDLT);然而,关于 LDLT 的适应症和围手术期管理尚未达成共识。本文介绍了在日本接受 LDLT 的这 16 位患者的治疗结果,并回顾了相关文献,以明确在新型多模式治疗时代 NELM LDLT 的最佳适应症和围手术期管理。
{"title":"Liver transplantation for gastroenteropancreatic neuroendocrine liver metastasis: optimal patient selection and perioperative management in the era of multimodal treatments.","authors":"Yosuke Kasai, Takashi Ito, Toshihiko Masui, Kazuyuki Nagai, Takayuki Anazawa, Yoichiro Uchida, Takamichi Ishii, Koji Umeshita, Susumu Eguchi, Yuji Soejima, Hideki Ohdan, Etsuro Hatano","doi":"10.1007/s00535-024-02166-z","DOIUrl":"https://doi.org/10.1007/s00535-024-02166-z","url":null,"abstract":"<p><p>Gastroenteropancreatic neuroendocrine tumors (NET) often metastasize to the liver. Although curative liver resection provides a favorable prognosis for patients with neuroendocrine liver metastasis (NELM), with a 5-year survival rate of 70-80%, recurrence is almost inevitable, mainly in the remnant liver. In Western countries, liver transplantation (LT) has been performed in patients with NELM, with the objective of complete removal of macro- and micro-NELMs. However, prognosis had been unsatisfactory, with 5-year overall survival and recurrence-free survival rates of approximately 50 and 30%, respectively. In 2007, the Milan criteria were proposed as indications for LT for NELM. The criteria included: (1) confirmed histology of NET-G1 or G2; (2) a primary tumor drained by the portal system and all extrahepatic diseases removed with curative resection before LT; (3) liver involvement ≤50%; (4) good response or stable disease for at least 6 months before LT; (5) age ≤ 55 years. A subsequent report demonstrated outstanding LT outcomes for NELM within the Milan criteria, with 5-year overall survival and recurrence rates of 97 and 13%, respectively. In Japan, living donor LT (LDLT) for NELM has been performed sporadically in only 16 patients by 2021 in Japan; however, no consensus has been reached on the indications or perioperative management of LDLT. This article presents the outcomes of these 16 patients who underwent LDLT in Japan and reviews the literature to clarify optimal indications and perioperative management of LDLT for NELM in the era of novel multimodal treatments.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639188","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
FGFR2 fusions assessed by NGS, FISH, and immunohistochemistry in intrahepatic cholangiocarcinoma. 通过 NGS、FISH 和免疫组化评估肝内胆管癌中的 FGFR2 融合。
IF 6.9 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-11-13 DOI: 10.1007/s00535-024-02175-y
Zi Cao, Yichen Yang, Shasha Liu, Lin Sun, Yanxue Liu, Ye Luo, Jian Wang, Yan Sun

Background: FGFR2 fusion has become a promising therapeutic target in iCCAs; however, the procedure for screening FGFR2 fusion has not been conventionally developed.

Methods: FGFR2 fusion was identified using DNA + RNA-based NGS and FISH, and the concordance between DNA + RNA-based NGS, FISH, and IHC was compared.

Results: FGFR2 fusions were detected in 9 out of 76 iCCAs (11.8%). The consistency of FISH and DNA + RNA-based NGS for FGFR2 fusions was high (κ value = 0.867, P = 0.001), while the consistency of IHC and DNA + RNA-based NGS was lower (κ value = 0.464, P = 0.072). All nine FGFR2 fusion-positive iCCAs were MSS with a median TMB of 2.1 mut/Mb, and only one had a CPS (PD-L1) above 5. Two FGFR2 fusion-positive iCCA patients were treated with and benefited from FGFR inhibitor therapy.

Conclusions: FGFR2 fusion should be assessed for advanced iCCA patients. We recommend DNA + RNA-based NGS as the preferred option to supply all possible therapeutic targets. FISH should be preferred if the tumor sample is insufficient for NGS or if the patient is inclined to receive FGFR inhibitors promptly. Although IHC is not the preferred method to identify FGFR2 fusion, it might be used as preliminary screening for FGFR2 alterations if the hospital cannot offer NGS or FISH, and the results need to be validated before FGFR2 inhibitors treatment.

背景:表皮生长因子受体2(FGFR2)融合已成为iCCA中一个有前景的治疗靶点;然而,筛选FGFR2融合的程序尚未形成惯例:采用基于 DNA + RNA 的 NGS 和 FISH 方法鉴定 FGFR2 融合,并比较基于 DNA + RNA 的 NGS、FISH 和 IHC 的一致性:76例iCCA中有9例(11.8%)检测到FGFR2融合。FISH 和基于 DNA + RNA 的 NGS 检测 FGFR2 融合的一致性很高(κ值 = 0.867,P = 0.001),而 IHC 和基于 DNA + RNA 的 NGS 的一致性较低(κ值 = 0.464,P = 0.072)。所有九例 FGFR2 融合阳性 iCCA 均为 MSS,中位 TMB 为 2.1 mut/Mb,只有一例的 CPS(PD-L1)高于 5。两名FGFR2融合阳性iCCA患者接受了FGFR抑制剂治疗并从中获益:结论:晚期iCCA患者应进行FGFR2融合评估。我们建议首选基于 DNA + RNA 的 NGS,以提供所有可能的治疗靶点。如果肿瘤样本不足以进行 NGS,或患者倾向于及时接受 FGFR 抑制剂,则应首选 FISH。虽然 IHC 并非鉴别 FGFR2 融合的首选方法,但如果医院无法提供 NGS 或 FISH,且在 FGFR2 抑制剂治疗前需要验证结果,则 IHC 可用作 FGFR2 改变的初步筛查。
{"title":"FGFR2 fusions assessed by NGS, FISH, and immunohistochemistry in intrahepatic cholangiocarcinoma.","authors":"Zi Cao, Yichen Yang, Shasha Liu, Lin Sun, Yanxue Liu, Ye Luo, Jian Wang, Yan Sun","doi":"10.1007/s00535-024-02175-y","DOIUrl":"https://doi.org/10.1007/s00535-024-02175-y","url":null,"abstract":"<p><strong>Background: </strong>FGFR2 fusion has become a promising therapeutic target in iCCAs; however, the procedure for screening FGFR2 fusion has not been conventionally developed.</p><p><strong>Methods: </strong>FGFR2 fusion was identified using DNA + RNA-based NGS and FISH, and the concordance between DNA + RNA-based NGS, FISH, and IHC was compared.</p><p><strong>Results: </strong>FGFR2 fusions were detected in 9 out of 76 iCCAs (11.8%). The consistency of FISH and DNA + RNA-based NGS for FGFR2 fusions was high (κ value = 0.867, P = 0.001), while the consistency of IHC and DNA + RNA-based NGS was lower (κ value = 0.464, P = 0.072). All nine FGFR2 fusion-positive iCCAs were MSS with a median TMB of 2.1 mut/Mb, and only one had a CPS (PD-L1) above 5. Two FGFR2 fusion-positive iCCA patients were treated with and benefited from FGFR inhibitor therapy.</p><p><strong>Conclusions: </strong>FGFR2 fusion should be assessed for advanced iCCA patients. We recommend DNA + RNA-based NGS as the preferred option to supply all possible therapeutic targets. FISH should be preferred if the tumor sample is insufficient for NGS or if the patient is inclined to receive FGFR inhibitors promptly. Although IHC is not the preferred method to identify FGFR2 fusion, it might be used as preliminary screening for FGFR2 alterations if the hospital cannot offer NGS or FISH, and the results need to be validated before FGFR2 inhibitors treatment.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621965","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
Determination of optimal cutoff value of ulcerative colitis intestinal ultrasound index to estimate endoscopic improvement in ulcerative colitis. 确定溃疡性结肠炎肠道超声指数的最佳临界值,以估计溃疡性结肠炎的内镜改善情况。
IF 6.9 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-11-11 DOI: 10.1007/s00535-024-02172-1
Haruka Komatsu, Hiromu Morikubo, Yoko Kimura, Chihiro Moue, Hiromi Yonezawa, Minoru Matsuura, Jun Miyoshi, Tadakazu Hisamatsu

Background: The ulcerative colitis intestinal ultrasound (UC-IUS) index (UII) has been reported as a sonographic scoring system correlating with the Mayo endoscopic subscore (MES). Endoscopic improvement (EI) of UC (MES ≤ 1) is a crucial therapeutic target in clinical practice. However, the cutoff value for estimating EI using the UII has not been established.

Methods: We established test and validation cohorts comprising patients with UC undergoing IUS and endoscopy within a 15-day interval at our institution. IUS findings (bowel wall thickness, bowel blood flow, bowel wall structure, haustrations, and inflammatory fat) and endoscopic activity (MES) of each colon segment (ascending, transverse, descending, and sigmoid colon) were assessed.

Results: In the test cohort (74 segments), UII was correlated with MES (r = 0.645, p < 0.0001). The median UII was 1.0 and 6.0 among participants with MES ≤ 1 and MES ≥ 2, respectively. A UII of 2 was identified as the threshold for estimating MES ≤ 1 with receiver operating characteristic analysis. In the validation cohort (122 segments), UII was correlated with MES (r = 0.675, p < 0.0001) and the estimation ability of UII ≤ 2 for EI had a positive predictive value of 85.4% and negative predictive value of 79.0%. This estimation ability of UII for EI was numerically lower but not statistically different from the previously reported Milan Ultrasound Criteria and Kyorin Ultrasound Criterion for UC.

Conclusion: UII ≤ 2 can be a simple, feasible criterion for estimating EI. Correlation with MES is an advantage of the UII compared with other criteria. Proper use of various sonographic criteria is important.

背景:据报道,溃疡性结肠炎肠道超声(UC-IUS)指数(UII)是一种与梅奥内镜评分(MES)相关的超声评分系统。UC 的内镜改善(EI)(MES ≤ 1)是临床实践中的一个重要治疗目标。然而,使用 UII 估算 EI 的临界值尚未确定:方法:我们建立了测试和验证队列,包括在本院接受 IUS 和内镜检查的间隔时间为 15 天的 UC 患者。我们评估了 IUS 检查结果(肠壁厚度、肠道血流、肠壁结构、肿块和炎性脂肪)以及每个结肠段(升结肠、横结肠、降结肠和乙状结肠)的内镜活动度(MES):结果:在测试组群(74 个结肠节段)中,UII 与 MES 相关(r = 0.645,p 结论:UII ≤ 2.5%;MES ≤ 2.5%;UII ≤ 2.5%;UII ≤ 2.5%):UII≤2 可以作为估计 EI 的一个简单可行的标准。与其他标准相比,UII 与 MES 的相关性是其优势所在。正确使用各种超声标准非常重要。
{"title":"Determination of optimal cutoff value of ulcerative colitis intestinal ultrasound index to estimate endoscopic improvement in ulcerative colitis.","authors":"Haruka Komatsu, Hiromu Morikubo, Yoko Kimura, Chihiro Moue, Hiromi Yonezawa, Minoru Matsuura, Jun Miyoshi, Tadakazu Hisamatsu","doi":"10.1007/s00535-024-02172-1","DOIUrl":"https://doi.org/10.1007/s00535-024-02172-1","url":null,"abstract":"<p><strong>Background: </strong>The ulcerative colitis intestinal ultrasound (UC-IUS) index (UII) has been reported as a sonographic scoring system correlating with the Mayo endoscopic subscore (MES). Endoscopic improvement (EI) of UC (MES ≤ 1) is a crucial therapeutic target in clinical practice. However, the cutoff value for estimating EI using the UII has not been established.</p><p><strong>Methods: </strong>We established test and validation cohorts comprising patients with UC undergoing IUS and endoscopy within a 15-day interval at our institution. IUS findings (bowel wall thickness, bowel blood flow, bowel wall structure, haustrations, and inflammatory fat) and endoscopic activity (MES) of each colon segment (ascending, transverse, descending, and sigmoid colon) were assessed.</p><p><strong>Results: </strong>In the test cohort (74 segments), UII was correlated with MES (r = 0.645, p < 0.0001). The median UII was 1.0 and 6.0 among participants with MES ≤ 1 and MES ≥ 2, respectively. A UII of 2 was identified as the threshold for estimating MES ≤ 1 with receiver operating characteristic analysis. In the validation cohort (122 segments), UII was correlated with MES (r = 0.675, p < 0.0001) and the estimation ability of UII ≤ 2 for EI had a positive predictive value of 85.4% and negative predictive value of 79.0%. This estimation ability of UII for EI was numerically lower but not statistically different from the previously reported Milan Ultrasound Criteria and Kyorin Ultrasound Criterion for UC.</p><p><strong>Conclusion: </strong>UII ≤ 2 can be a simple, feasible criterion for estimating EI. Correlation with MES is an advantage of the UII compared with other criteria. Proper use of various sonographic criteria is important.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621963","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
Prognostic factors of second-line nivolumab monotherapy for unresectable or metastatic esophageal cancer: a multi-institutional cohort study for 184 cases. 不可切除或转移性食管癌二线nivolumab单药治疗的预后因素:一项针对184例病例的多机构队列研究。
IF 6.9 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-11-01 Epub Date: 2024-08-17 DOI: 10.1007/s00535-024-02141-8
Sho Sato, Takashi Suzuki, Takashi Chinen, Hironori Yamaguchi, Yusuke Suzuki, Nobukazu Hokamura, Zenichiro Saze, Koji Kono, Keita Takahashi, Fumiaki Yano, Tsutomu Sato, Takashi Kosaka, Itaru Endo, Yasushi Ichikawa, Yutaka Miyawaki, Hiroshi Sato, Hideaki Shimada

Background: The real-world efficacy, prognostic factors, and adverse events of second-line nivolumab monotherapy and subsequent third-line therapy for unresectable or metastatic esophageal cancer have not been fully evaluated.

Methods: This multi-institutional retrospective cohort study evaluated 184 consecutive patients treated with second-line nivolumab monotherapy for esophageal cancer between March 2021 and December 2022. We assessed tumor response, adverse events, long-term survival, and prognostic factors.

Results: Among 128 patients with measurable lesions, the response rate was 23% and the disease control rate for all enrolled patients was 45%. The incidence of grade 3 or higher adverse events was 14%, but no treatment-related deaths presented. Median progression-free survival was 5.1 months and overall survival was 14 months, respectively. C-reactive protein level and performance status were identified as significant prognostic factors of overall survival through Cox proportional hazards analysis. The group with two favorable prognostic factors showed better overall survival than the groups with either one or zero prognostic factors (median overall survival: 22, 15, and 4.4 months, respectively). Among 69 patients who received third-line taxane anticancer agents, the progression-free survival was 6.7 months.

Conclusions: Our study demonstrated that the real-world outcomes of second-line nivolumab monotherapy were comparable to those of previous randomized clinical trials in terms of tumor response, safety, and long-term survival. Furthermore, a good performance status and low C-reactive protein levels may identify patients who are likely to benefit from therapy. Third-line chemotherapy after nivolumab treatment may have an enhanced effect; however, further prospective studies are required to confirm this finding.

背景:目前尚未对不可切除或转移性食管癌二线nivolumab单药治疗和后续三线治疗的实际疗效、预后因素和不良事件进行全面评估:这项多机构回顾性队列研究评估了2021年3月至2022年12月期间接受二线nivolumab单药治疗的184例食管癌连续患者。我们评估了肿瘤反应、不良事件、长期生存和预后因素:在128例有可测量病灶的患者中,反应率为23%,所有入组患者的疾病控制率为45%。3级或以上不良反应发生率为14%,但没有出现与治疗相关的死亡病例。中位无进展生存期为5.1个月,总生存期为14个月。通过考克斯比例危险分析,C反应蛋白水平和表现状态被确定为总生存期的重要预后因素。有两个有利预后因素的组别比只有一个或零个预后因素的组别有更好的总生存期(中位总生存期分别为22个月、15个月和4.4个月)。在接受三线紫杉类抗癌药治疗的69名患者中,无进展生存期为6.7个月:我们的研究表明,在肿瘤反应、安全性和长期生存方面,二线nivolumab单药治疗的实际结果与之前的随机临床试验结果相当。此外,良好的表现状态和较低的C反应蛋白水平可识别出可能从治疗中获益的患者。nivolumab治疗后的三线化疗可能会有更好的疗效,但这一结果还需要进一步的前瞻性研究来证实。
{"title":"Prognostic factors of second-line nivolumab monotherapy for unresectable or metastatic esophageal cancer: a multi-institutional cohort study for 184 cases.","authors":"Sho Sato, Takashi Suzuki, Takashi Chinen, Hironori Yamaguchi, Yusuke Suzuki, Nobukazu Hokamura, Zenichiro Saze, Koji Kono, Keita Takahashi, Fumiaki Yano, Tsutomu Sato, Takashi Kosaka, Itaru Endo, Yasushi Ichikawa, Yutaka Miyawaki, Hiroshi Sato, Hideaki Shimada","doi":"10.1007/s00535-024-02141-8","DOIUrl":"10.1007/s00535-024-02141-8","url":null,"abstract":"<p><strong>Background: </strong>The real-world efficacy, prognostic factors, and adverse events of second-line nivolumab monotherapy and subsequent third-line therapy for unresectable or metastatic esophageal cancer have not been fully evaluated.</p><p><strong>Methods: </strong>This multi-institutional retrospective cohort study evaluated 184 consecutive patients treated with second-line nivolumab monotherapy for esophageal cancer between March 2021 and December 2022. We assessed tumor response, adverse events, long-term survival, and prognostic factors.</p><p><strong>Results: </strong>Among 128 patients with measurable lesions, the response rate was 23% and the disease control rate for all enrolled patients was 45%. The incidence of grade 3 or higher adverse events was 14%, but no treatment-related deaths presented. Median progression-free survival was 5.1 months and overall survival was 14 months, respectively. C-reactive protein level and performance status were identified as significant prognostic factors of overall survival through Cox proportional hazards analysis. The group with two favorable prognostic factors showed better overall survival than the groups with either one or zero prognostic factors (median overall survival: 22, 15, and 4.4 months, respectively). Among 69 patients who received third-line taxane anticancer agents, the progression-free survival was 6.7 months.</p><p><strong>Conclusions: </strong>Our study demonstrated that the real-world outcomes of second-line nivolumab monotherapy were comparable to those of previous randomized clinical trials in terms of tumor response, safety, and long-term survival. Furthermore, a good performance status and low C-reactive protein levels may identify patients who are likely to benefit from therapy. Third-line chemotherapy after nivolumab treatment may have an enhanced effect; however, further prospective studies are required to confirm this finding.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"979-985"},"PeriodicalIF":6.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995899","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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Journal of Gastroenterology
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