{"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}
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":"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}
{"title":"Impact of ursodeoxycholic acid treatment on Fontan-associated liver disease.","authors":"Tomomi Kogiso, Yuri Ogasawara, Makiko Taniai, Eriko Shimada, Kei Inai, Katsutoshi Tokushige, Yousuke Nakai","doi":"10.1007/s00535-024-02168-x","DOIUrl":"10.1007/s00535-024-02168-x","url":null,"abstract":"<p><strong>Background: </strong>Fontan-associated liver disease (FALD) is a type of progressive liver fibrosis that occurs following Fontan surgery and can be complicated by hepatocellular carcinoma (HCC). Established treatments for FALD are lacking. Therefore, we investigated the efficacy of ursodeoxycholic acid (UDCA) in patients with FALD.</p><p><strong>Methods: </strong>This single-center retrospective study was conducted from 2003 to 2024 and involved 220 patients (103 men, 46.8%) who had been diagnosed with FALD. UDCA was administered to 113 patients presenting with liver or biliary enzyme abnormalities. We evaluated the patients' liver enzyme levels 3, 6, and 12 months after treatment. HCC developed in 10.5% and the mortality rate was 4.5%. Survival and cumulative incidence of HCC were compared between patients with and without UDCA treatment using Kaplan-Meier curves and propensity-matched analysis (n = 68 per group).</p><p><strong>Results: </strong>UDCA treatment significantly reduced the aspartate aminotransferase (AST), alanine transaminase (ALT), and gamma-glutamyl transferase (GGT) levels at 3 months. The mean pretreatment AST/ALT/GGT levels were 26/22/323 U/L, respectively, and decreased to 19/15/102 U/L at 3 months, 18/12/88 U/L at 6 months, and 16/19/64 U/L at 12 months. However, the total bilirubin level and platelet count did not show significant differences. The survival rate was higher and the HCC rate was lower in patients with than without UDCA treatment. The 5-year incidence rate of HCC was 5.6% in the UDCA group and 24.2% in the untreated group.</p><p><strong>Conclusions: </strong>UDCA treatment significantly reduced liver enzyme levels, including GGT, and mitigated the progression of HCC. UDCA may be beneficial for patients with FALD.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"210-221"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142729600","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}
Hong Wang, Beili Zhao, Lei Huang, Xiangbin Zhu, Na Li, Can Huang, Zhen Han, Kunfu Ouyang
{"title":"Conditional deletion of IP<sub>3</sub>R1 by Islet1-Cre in mice reveals a critical role of IP<sub>3</sub>R1 in interstitial cells of Cajal in regulating GI motility.","authors":"Hong Wang, Beili Zhao, Lei Huang, Xiangbin Zhu, Na Li, Can Huang, Zhen Han, Kunfu Ouyang","doi":"10.1007/s00535-024-02164-1","DOIUrl":"10.1007/s00535-024-02164-1","url":null,"abstract":"<p><strong>Background and aims: </strong>Inositol 1,4,5-trisphosphate receptor type 1 (IP<sub>3</sub>R1) has been proposed to play a physiological role in regulating gastrointestinal (GI) motility, but the underlying cell-dependent mechanism remains unclear. Here, we utilized cell-specific IP<sub>3</sub>R1 deletion strategies to address this question in mice.</p><p><strong>Methods: </strong>Conditional IP<sub>3</sub>R1 knockout mice using Wnt1-Cre, Islet1-Cre mice, and smMHC-Cre<sup>EGFP</sup> were generated. Cell lineage tracing was performed to determine where gene deletion occurred in the GI tract. Whole-gut transit assay and isometric tension recording were used to assess GI function in vivo and in vitro.</p><p><strong>Results: </strong>In the mouse GI tract, Islet1-Cre targeted smooth muscle cells (SMCs) and interstitial cells of Cajal (ICCs), but not enteric neurons. IP<sub>3</sub>R1 deletion by Islet1-Cre (isR1KO) caused a phenotype of intestinal pseudo-obstruction (IPO), evidenced by prolonged whole-gut transit time, enlarged GI tract, abdominal distention, and early lethality. IP<sub>3</sub>R1 deletion by Islet1-Cre not only reduced the frequency of spontaneous contractions but also decreased the contractile responses to the muscarinic agonist carbachol (CCh) and electrical field stimulation (EFS) in colonic circular muscles. By contrast, smMHC-Cre<sup>EGFP</sup> only targeted SMCs in the mouse GI tract. Although IP<sub>3</sub>R1 deletion by smMHC-Cre<sup>EGFP</sup> (smR1KO) also reduced the contractile responses to CCh and EFS in colonic circular muscles, the frequency of spontaneous contractions was less affected, and neither global GI abnormalities nor early lethality was found in smR1KO mice.</p><p><strong>Conclusions: </strong>IP<sub>3</sub>R1 deletion in both ICCs and SMCs but not in SMCs alone causes an IPO phenotype, suggesting that IP<sub>3</sub>R1 in ICCs plays an essential role in regulating GI motility in vivo.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"152-165"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545887","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":"Impact of long-term trends on outcomes in the management of colonic diverticular bleeding: mediation analyses in a large multicenter study.","authors":"Kazuyuki Narimatsu, Naoki Ishii, Atsuo Yamada, Tomonori Aoki, Katsumasa Kobayashi, Atsushi Yamauchi, Jun Omori, Takashi Ikeya, Taiki Aoyama, Naoyuki Tominaga, Yoshinori Sato, Takaaki Kishino, Tsunaki Sawada, Masaki Murata, Akinari Takao, Kazuhiro Mizukami, Ken Kinjo, Shunji Fujimori, Takahiro Uotani, Minoru Fujita, Hiroki Sato, Sho Suzuki, Toshiaki Narasaka, Junnosuke Hayasaka, Tomohiro Funabiki, Yuzuru Kinjo, Akira Mizuki, Shu Kiyotoki, Tatsuya Mikami, Ryosuke Gushima, Hiroyuki Fujii, Yuta Fuyuno, Takuto Hikichi, Yosuke Toya, Noriaki Manabe, Koji Nagaike, Tetsu Kinjo, Yorinobu Sumida, Sadahiro Funakoshi, Kiyonori Kobayashi, Tamotsu Matsuhashi, Yuga Komaki, Ryota Hokari, Mitsuru Kaise, Naoyoshi Nagata","doi":"10.1007/s00535-024-02178-9","DOIUrl":"10.1007/s00535-024-02178-9","url":null,"abstract":"<p><strong>Background: </strong>Despite accumulating evidence and recommendations for management of colonic diverticular bleeding (CDB), the changes in its clinical management and outcomes remain unknown.</p><p><strong>Methods: </strong>We performed a retrospective tendency analysis on a biennial basis, a propensity score-matched cohort study between the first and latter half groups, and mediation analyses to compare the diagnostic and treatment methods between January 2010 and December 2019 (CODE BLUE-J Study).</p><p><strong>Results: </strong>A total of 6575 patients with CDB were included. While the use of colonoscopy as the initial diagnostic procedure declined, the use of computed tomography (CT) increased in both the trend test and before-and-after comparisons. In hemostasis therapy, the use of endoscopic clips declined and band ligation increased. Interventional radiology remained unchanged; however, the number of surgeries decreased over time. The stigmata of recent hemorrhage (SRH) detection rate and length of hospital stay (LOS) improved significantly. Mediation analyses showed that use of a distal attachment and water-jet scope contributed to an improved SRH detection rate, and use of band ligation contributed to preventing rebleeding within 30 days.</p><p><strong>Conclusions: </strong>Management strategies for CDB have changed in the past decade, particularly regarding the increased use of CT and decreased need for surgery. However, the main outcomes, except for the SRH detection rate and LOS, did not improve. The widespread use of distal attachment, water-jet scope, and band ligation could improve outcomes in CDB management.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"174-186"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895458","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}