{"title":"Clinical factors to predict changes of esophagogastric varices after sustained viral response with direct-acting antiviral therapy.","authors":"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","doi":"10.1007/s00535-024-02174-z","DOIUrl":"10.1007/s00535-024-02174-z","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"222-234"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639186","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":"Association between homologous recombination deficiency and time to treatment failure to platinum-based chemotherapy for pancreatic cancer by using the C-CAT database.","authors":"Kazunaga Ishigaki, Yurie Tokito, Naminatsu Takahara, Hiroto Nishio, Go Endo, Koshiro Fukuda, Kota Ishida, Rintaro Fukuda, Shinya Takaoka, Hiroki Oyama, Kensaku Noguchi, Tatsunori Suzuki, Tatsuya Sato, Tomotaka Saito, Tsuyoshi Hamada, Koji Miyabayashi, Yasuyoshi Sato, Yousuke Nakai, Hidenori Kage, Katsutoshi Oda, Mitsuhiro Fujishiro","doi":"10.1007/s00535-024-02173-0","DOIUrl":"10.1007/s00535-024-02173-0","url":null,"abstract":"<p><strong>Background: </strong>Since homologous recombination deficiency (HRD) is relatively uncommon in pancreatic cancer (PC), its impact on time-to-treatment failure (TTF) among patients undergoing systemic chemotherapy for unresectable and recurrent PC remains uncertain.</p><p><strong>Methods: </strong>Among patients with unresectable and recurrent PC enrolled in the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database by July 2023, a total of 1394 patients who underwent first-line chemotherapy with either gemcitabine plus nab-paclitaxel (GnP) or FOLFIRINOX (FFX) and received tissue-based CGP tests after disease progression were included in this study. HRD was defined as the presence of germline or somatic genetic mutations in homologous recombination repair (HRR)-related genes such as ATM, BARD1, BRIP1, BRCA1/2, CHEK2, CDK12, PALB, and RAD51C/D. We investigated the correlation between HRD and TTF among patients treated with GnP and FFX.</p><p><strong>Results: </strong>First-line chemotherapy consisted of GnP in 69% of the cases and FFX in 31%. The CGP tests used were NCC OncoPanel and FoundationOne CDx in 26% and 74%, respectively. HRR-related genetic abnormalities were identified in 107 patients (7.6%): BRCA2 (n = 51), ATM (n = 34), BRCA1 (n = 9), PALB2 (n = 9), among others. In the GnP cohort, the median TTF was comparable between the HRD and non-HRD groups (5.3 vs 4.6 months, P = 0.44). Conversely, in the FFX cohort, it was significantly longer in the HRD group compared to the non-HRD group (7.3 vs. 4.7 months, p < 0.01).</p><p><strong>Conclusions: </strong>Our findings suggest that HRR-related genetic abnormalities might be predictive of TTF in platinum-based chemotherapy for PC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"247-256"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681996","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}
Zi Cao, Yichen Yang, Shasha Liu, Lin Sun, Yanxue Liu, Ye Luo, Jian Wang, Yan Sun
{"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":"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":"235-246"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","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}
{"title":"Comprehensive pathological evaluation of risk factors for metastasis after endoscopic resection of superficial esophageal squamous cell carcinoma.","authors":"Ryu Ishihara, Hiroshi Kawachi, Kaoru Nakano, Tomohiro Kadota, Kenshi Matsuno, Ayumu Takizawa, Takashi Matsunaga, Akiyoshi Ishiyama, Tomonori Yano, Hiroaki Takahashi, Satoshi Fujii","doi":"10.1007/s00535-024-02189-6","DOIUrl":"10.1007/s00535-024-02189-6","url":null,"abstract":"<p><strong>Background: </strong>Esophageal cancer is a major cause of cancer mortality worldwide. Endoscopic resection (ER) is a curative treatment for esophageal squamous cell carcinoma (ESCC). Predicting risk of metastasis is crucial for post-ER management. In this study, we aimed to identify predictors of metastasis by examining endoscopically resected specimens.</p><p><strong>Methods: </strong>The cohort of this retrospective multicenter study comprised 422 patients who had undergone ER for ESCC from 1994 to 2017. Inclusion required a histological diagnosis of pT1a-muscularis mucosa or pT1b-submucosa (SM) cancer. Central pathological review comprehensively evaluated depth of invasion, lymphovascular invasion (LVI), droplet infiltration (DI), infiltrative growth pattern, histological differentiation, intraductal and intraglandular involvement, solitary nest, resected margin, and other factors. Logistic regression was used to identify predictors of metastasis.</p><p><strong>Results: </strong>Metastases were identified in 103 patients. Univariate analysis identified LVI, depth of invasion, and DI as significant predictive factors. Multivariate analysis identified LVI, depth of invasion pT1b-SM2 (odds ratio 2.72) and indeterminate (positive vertical margin) (odds ratio 3.63) compared with the reference category of pT1b-SM1 as independent predictors of metastasis. Conversely, there were no significant associations between metastasis and lesion size, differentiation, cytological atypia, or infiltration pattern. Subgroup analysis showed that both the number and layer of LVI were associated with metastasis risk. In addition, four or more foci of DI was an independent predictor of LVI.</p><p><strong>Conclusions: </strong>LVI and depth of invasion were significant predictors of metastasis in ESCC. Detailed pathological evaluation and standardized criteria are essential for accurately assessing risk of metastasis and guiding post-ER treatment strategies.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"131-140"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716396","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":"Novel subharmonic-aided pressure estimation for identifying high-risk esophagogastric varices.","authors":"Hidekatsu Kuroda, Tamami Abe, Naohisa Kamiyama, Takuma Oguri, Asami Ito, Ippeki Nakaya, Takuya Watanabe, Hiroaki Abe, Kenji Yusa, Yudai Fujiwara, Hiroki Sato, Akiko Suzuki, Kei Endo, Yuichi Yoshida, Takayoshi Oikawa, Keisuke Kakisaka, Kei Sawara, Akio Miyasaka, Takayuki Matsumoto","doi":"10.1007/s00535-024-02161-4","DOIUrl":"10.1007/s00535-024-02161-4","url":null,"abstract":"<p><strong>Background: </strong>Subharmonic-aided pressure estimation (SHAPE) is a technique for determining changes in ambient pressure. We aimed to analyze a novel SHAPE integrated into ultrasound diagnostic equipment to predict patients with liver cirrhosis at high risk of esophagogastric varices (EV).</p><p><strong>Methods: </strong>This prospective study included 111 patients with liver cirrhosis diagnosed between 2020 and 2023. We obtained liver stiffness measurements (LSM) and spleen stiffness measurements (SSM) using shear wave elastography and hepatic vein-portal vein (HV-PV) gradient using the SHAPE method. The EV risk was determined either as null, low, or high by esophagoscopy and Child-Pugh stage.</p><p><strong>Results: </strong>HV-PV gradient increased concordantly with the increase in EV risk (- 7.0 dB in null-risk, - 4.4 dB in low-risk, and - 2.0 dB in high-risk) with statistically significant difference among any two groups. The most appropriate cut-off value of the HV-PV gradient was - 3.5 dB, and sensitivity, specificity, and positive and negative predictive values were 80.0%, 89.0%, 80.0%, and 88.0%, respectively. The areas under the curve values for predicting the high-risk EV were 0.920, 0.843, and 0.824 for the HV-PV gradient, LSM, and SSM, respectively.</p><p><strong>Conclusions: </strong>The novel SHAPE system demonstrated high accuracy in identifying patients with liver cirrhosis at a high risk of EV.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"187-196"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545888","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":"Histological improvement of fibrosis in patients with hepatitis C who achieved a 5-year sustained virological response to treatment with direct-acting antivirals.","authors":"Takayuki Iwamoto, Yasutoshi Nozaki, Takanori Inoue, Takahiro Suda, Rui Mizumoto, Yuki Arimoto, Takashi Ohta, Shinjiro Yamaguchi, Yoshiki Ito, Yoshiko Sudo, Michiko Yoshimura, Machiko Kai, Yoichi Sasaki, Yuki Tahata, Hayato Hikita, Tetsuo Takehara, Hideki Hagiwara","doi":"10.1007/s00535-024-02165-0","DOIUrl":"10.1007/s00535-024-02165-0","url":null,"abstract":"<p><strong>Background: </strong>The histological improvement in liver fibrosis in patients with hepatitis C who achieved a sustained virological response (SVR) to direct-acting antiviral (DAA) treatment has not been comprehensively investigated. Therefore, we assessed the histological changes in liver fibrosis among patients with hepatitis C who underwent long-term follow-up after achieving SVR to treatment with DAA.</p><p><strong>Methods: </strong>This retrospective study enrolled 71 patients with hepatitis C who achieved SVR to treatment with DAA. Changes in histological liver fibrosis and fibrosis biomarkers (hyaluronic acid, type 4 collagen 7S, Mac-2 binding protein glycosylation isomer, autotaxin, and Fibrosis-4 index) were assessed before and 5 years after treatment. Transient elastography using the FibroScan® device was performed 5 years after treatment. Advanced fibrosis and cirrhosis were defined as Ishak fibrosis scores of ≥ 4 and ≥ 5, respectively.</p><p><strong>Results: </strong>Histological liver fibrosis significantly regressed after SVR. Fibrosis biomarkers were significantly reduced after SVR. Transient elastography was the most helpful after evaluating the predictive performance of advanced fibrosis and cirrhosis after SVR, with an area under the receiver operating characteristic curve of 0.965 and a cut-off value of 6.75 kPa. The cut-off values of serum fibrosis biomarkers for identifying advanced fibrosis and cirrhosis after SVR were lower than those before treatment.</p><p><strong>Conclusions: </strong>Long-term SVR to treatment with DAA ameliorated histological liver fibrosis. Noninvasive tests helped predict the degree of liver fibrosis after SVR, but their cut-off values should be redefined to avoid underestimation of liver fibrosis.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"197-209"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710427","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":"Development and validation of a claims-based algorithm to identify incidents and determine the progression phases of gastric cancer cases in Japan.","authors":"Takahiro Inoue, Nobukazu Agatsuma, Takahiro Utsumi, Yukari Tanaka, Yoshitaka Nishikawa, Takahiro Horimatsu, Takahiro Shimizu, Mitsuhiro Nikaido, Yuki Nakanishi, Nobuaki Hoshino, Yoshimitsu Takahashi, Takeo Nakayama, Hiroshi Seno","doi":"10.1007/s00535-024-02167-y","DOIUrl":"10.1007/s00535-024-02167-y","url":null,"abstract":"<p><strong>Background: </strong>Although health insurance claims data can address questions that clinical trials cannot answer, the uncertainty of disease names and the absence of stage information hinder their use in gastric cancer (GC) research. This study aimed to develop and validate a claims-based algorithm to identify and determine the progression phases of incident GC cases in Japan.</p><p><strong>Methods: </strong>The gold standard for validation in this retrospective observational study was medical records of patients with incident GC who underwent specific treatments, defined by the claim codes associated with GC treatment. The algorithm was developed and refined using a cohort from two large tertiary care medical centers (April-September 2017 and April-September 2019) and subsequently validated using two independent cohorts: one from different periods (October 2017-March 2019 and October 2019-March 2021) and the other from a different institution (a community hospital). The algorithm identified incident cases based on a combination of the International Classification of Diseases, 10th Revision diagnosis codes for GC (C160-169), and claim codes for specific treatments, classifying them into endoscopic, surgical, and palliative groups. Positive predictive value (PPV), sensitivity of incident case identification, and diagnostic accuracy of progression phase determination were evaluated.</p><p><strong>Results: </strong>The developed algorithm achieved PPVs of 90.0% (1119/1244) and 95.9% (94/98), sensitivities of 98.0% (1119/1142) and 98.9% (94/95) for incident case identification, with diagnostic accuracies of 94.1% (1053/1119) and 93.6% (88/94) for progression phase determination in the two validation cohorts, respectively.</p><p><strong>Conclusions: </strong>This validated claims-based algorithm could advance real-world GC research and assist in decision-making regarding GC treatment.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"141-151"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716397","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}
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