{"title":"Novel drug targets for the early treatment of acute pancreatitis: Focusing on calcium signaling","authors":"Jin-Hao Chen , Robert Sutton , Li Wen","doi":"10.1016/j.hbpd.2025.06.001","DOIUrl":"10.1016/j.hbpd.2025.06.001","url":null,"abstract":"<div><div>Acute pancreatitis (AP) is a common but potentially devastating disease characterized at onset pathophysiologically by premature activation of digestive enzymes within the pancreas. Despite an abundance of preclinical research and, until recently, a series of disappointing clinical trials, no specific disease modifying pharmacological treatment has yet been approved for this condition. Recent novel approaches to understanding the molecular pathogenesis of AP provide us with renewed optimism for translational drug discovery. Although digestive enzyme activation is the hallmark of AP, a critical mechanism that initiates AP is intracellular calcium (Ca<sup>2+</sup>) overload in pancreatic parenchymal cells, which triggers mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and impairs autophagic flux. These processes are pivotal to the disease and present a range of drug targets, associated with the inflammatory responses that drive local and systemic inflammation in AP. Progress in translation has now been made, targeting the ORAI channel with the inhibitor zegocractin (Auxora) to reduce pancreatic injury and inflammatory responses in human AP. Herein we evaluated potential drug targets for the early treatment of AP, focused on intra-acinar mechanisms of injury central to the onset and severity of AP. Our analysis highlights the opportunities and progress in translating these molecular insights into clinical therapies.</div></div>","PeriodicalId":55059,"journal":{"name":"Hepatobiliary & Pancreatic Diseases International","volume":"24 4","pages":"Pages 359-370"},"PeriodicalIF":3.6,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144334522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiao-Yan Hu , Zi-Biao Zhong , Wei Wang , Zhi-Ping Xia , Jun-Tao Liang , Zhong-Zhong Liu , Shao-Jun Ye , Qi-Fa Ye
{"title":"Autologous liver transplantation for right liver fragmentation and left lobe ischemia for 46 hours","authors":"Xiao-Yan Hu , Zi-Biao Zhong , Wei Wang , Zhi-Ping Xia , Jun-Tao Liang , Zhong-Zhong Liu , Shao-Jun Ye , Qi-Fa Ye","doi":"10.1016/j.hbpd.2025.05.007","DOIUrl":"10.1016/j.hbpd.2025.05.007","url":null,"abstract":"","PeriodicalId":55059,"journal":{"name":"Hepatobiliary & Pancreatic Diseases International","volume":"24 4","pages":"Pages 462-467"},"PeriodicalIF":3.6,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Heng-Kai Zhu, Hai-Bo Mou, Zhuo-Yi Wang, Wu Zhang, Dan Zhu, Si-Yi Zhong, Shu-Sen Zheng, Li Zhuang
{"title":"Adjuvant chemotherapy improves post-transplant outcome in patients with hepatocellular carcinoma.","authors":"Heng-Kai Zhu, Hai-Bo Mou, Zhuo-Yi Wang, Wu Zhang, Dan Zhu, Si-Yi Zhong, Shu-Sen Zheng, Li Zhuang","doi":"10.1016/j.hbpd.2025.05.004","DOIUrl":"https://doi.org/10.1016/j.hbpd.2025.05.004","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) recurrence following liver transplantation (LT) remains a major challenge. This study aimed to investigate the effect of adjuvant chemotherapy (ACT) with the modified FOLFOX-6 (mFOLFOX-6) regimen on the post-transplant prognosis of HCC patients.</p><p><strong>Methods: </strong>HCC patients who underwent LT at our institution from June 2017 to December 2019 were enrolled. The cohort was divided into the ACT group (n = 57) and the non-ACT group (n = 93). The median post-transplant follow-up period was 54.0 months. The study endpoints were HCC recurrence and patient mortality following LT. The association between ACT and recurrence/mortality were evaluated through univariate and multivariate analyses utilizing a Cox proportional hazards model, propensity score adjustment, propensity score matching, and inverse probability of treatment weighting (IPTW) analyses. A stratification analysis was performed to determine the interaction effects.</p><p><strong>Results: </strong>The ACT group was younger and had worse tumor characteristics including tumor number, tumor size, portal vein tumor thrombosis, pathological differentiation and microvascular invasion (MVI). The ACT group also demonstrated a lower risk of mortality than the non-ACT group (hazard ratio = 0.36, P = 0.017). It was consistent across sensitivity analyses utilizing propensity score adjustment and matching. There was a significant stronger association between ACT and recurrence-free benefit in patients with grade M2 of MVI compared to patients with grade M0/1 (P for interaction = 0.002).</p><p><strong>Conclusions: </strong>ACT with mFOLFOX-6 regimen decreased the recurrence and mortality risks following LT for HCC patients. ACT may be considered in HCC patients with high risk of recurrence and mortality after LT.</p>","PeriodicalId":55059,"journal":{"name":"Hepatobiliary & Pancreatic Diseases International","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dan Wang , Wei An , Jin-Hui Yi , Fan Wang, Zhao-Shen Li, Liang-Hao Hu
{"title":"Treatment of large pancreatic radiolucent stone","authors":"Dan Wang , Wei An , Jin-Hui Yi , Fan Wang, Zhao-Shen Li, Liang-Hao Hu","doi":"10.1016/j.hbpd.2025.05.003","DOIUrl":"10.1016/j.hbpd.2025.05.003","url":null,"abstract":"<div><h3>Background</h3><div>Previous studies have not clarified the treatment of large pancreatic radiolucent stones (≥ 5 mm). The primary objective of this study was to assess the clinical features and therapeutic efficacy in patients with chronic pancreatitis who have large radiolucent stones, and to propose a treatment strategy.</div></div><div><h3>Methods</h3><div>This analysis examined the data of patients with large pancreatic ductal stones (≥ 5 mm) from March 2011 to June 2018. Patients with radiolucent stones were classified as the radiolucent stones group, while those with pancreatic radiopaque stones presented at the same time were randomly selected as controls in a 1:2 ratio. Data on demographics, disease courses and treatment details were retrieved, and stone clearance and pain relief during the follow-up were compared between the two groups.</div></div><div><h3>Results</h3><div>A total of 52 patients with large radiolucent stones and 104 patients with large radiopaque stones were included in the study. Pancreatic extracorporeal shock wave lithotripsy (ESWL) was the initial treatment for large radiopaque stone. Endoscopic retrograde cholangiopancreatography (ERCP) was the first-step treatment for all patients in the radiolucent stones group, of which one patient received medication after failed ERCP cannulation, and four who failed stone extraction were treated with ESWL following the placement of a nasopancreatic catheter. There was no significant difference in the complete stone clearance rate (75.0% vs. 78.8%; <em>P</em> = 0.553) between the two groups. Among the 51 patients in the large radiolucent stones group who were followed up for 5.8 years (range 2.1-12.6), complete pain relief was achieved in 42 patients (82.4%), with no significant difference compared with the radiopaque group (82.4% vs. 76.4%; <em>P</em> = 0.409).</div></div><div><h3>Conclusions</h3><div>ERCP is an effective endotherapy for large radiolucent stone and should be considered the first-step treatment. When stone extraction failed during ERCP, ESWL is recommended following the placement of a nasopancreatic catheter.</div></div>","PeriodicalId":55059,"journal":{"name":"Hepatobiliary & Pancreatic Diseases International","volume":"24 4","pages":"Pages 404-411"},"PeriodicalIF":3.6,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Prevalence and risk factors of skeletal muscle loss and sarcopenia in patients with autoimmune pancreatitis","authors":"Takanori Sano, Kazuhiro Kikuta, Ryotaro Matsumoto, Tetsuya Takikawa, Shin Hamada, Shin Miura, Kiyoshi Kume, Atsushi Masamune","doi":"10.1016/j.hbpd.2025.05.002","DOIUrl":"10.1016/j.hbpd.2025.05.002","url":null,"abstract":"<div><h3>Background</h3><div>Previous studies have highlighted the frequent occurrence of sarcopenia in patients with pancreatic diseases, including chronic pancreatitis. We aimed to clarify the prevalence of skeletal muscle (SM) loss and sarcopenia, and their associations with clinical characteristics, bone mineral density, and pancreatic imaging findings in patients with autoimmune pancreatitis (AIP).</div></div><div><h3>Methods</h3><div>This study included 114 patients with AIP treated at Tohoku University Hospital. The SM index was assessed using a bioelectrical impedance analysis device, grip strength was measured using a hand dynamometer, and bone mineral density was evaluated using dual-energy X-ray absorptiometry. Univariate and multivariate logistic regression analyses were used to analyze factors associated with SM loss and sarcopenia.</div></div><div><h3>Results</h3><div>Among 114 patients, 57 (50.0%) had SM loss, 31 (27.2%) had reduced grip strength, and 27 (23.7%) had both. Patients with SM loss were older and had a lower body mass index, weaker grip strength, higher Controlling Nutritional Status scores, and lower serum lipase and albumin levels compared to those without SM loss. Computed tomography scans revealed a higher prevalence of pancreatic parenchymal atrophy in patients with SM loss. Similar differences were observed between patients with sarcopenia and those without. Osteopathy was observed in 35.6% of patients with SM loss and 38.1% of those with sarcopenia, whereas only 4.1% of patients without SM loss had osteopathy. Low BMI (< 21.0 kg/m<sup>2</sup>) was also found to be an independent risk factor for SM loss in multivariate analysis. Age > 72 years, low BMI (< 20.0 kg/m<sup>2</sup>), and low serum lipase levels (< 13 U/L) were independent risk factors for sarcopenia in multivariate analysis.</div></div><div><h3>Conclusions</h3><div>SM loss and sarcopenia are prevalent in patients with AIP and are associated with aging, poor nutritional status, low serum lipase levels, and pancreatic parenchymal atrophy. In addition to the high risk of osteopathy, careful attention should be paid to maintain muscle health in AIP patients.</div></div>","PeriodicalId":55059,"journal":{"name":"Hepatobiliary & Pancreatic Diseases International","volume":"24 4","pages":"Pages 396-403"},"PeriodicalIF":3.6,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiang-Yi Sun, Bo Yu, Jia Yu, Yuan-Pei Wang, Xian-Bin Li, Ran-Ran Sun, Xin Tian, Quan-Cheng Kan
{"title":"YBX1 is required for maintaining PD-L1 expression in intrahepatic cholangiocarcinoma by regulating STAT1 stability in an m5C-dependent manner.","authors":"Xiang-Yi Sun, Bo Yu, Jia Yu, Yuan-Pei Wang, Xian-Bin Li, Ran-Ran Sun, Xin Tian, Quan-Cheng Kan","doi":"10.1016/j.hbpd.2025.05.001","DOIUrl":"https://doi.org/10.1016/j.hbpd.2025.05.001","url":null,"abstract":"<p><strong>Background: </strong>Intrahepatic cholangiocarcinoma (ICC) is the second most frequent primary liver cancer. The involvement of Y-box binding protein 1 (YBX1) in tumor advancement is well-documented. However, its function in ICC is not fully understood. This study aimed to explore the function and regulatory mechanism of YBX1 in ICC and provide evidence for YBX1 as a potential new approach for immunotherapy in ICC.</p><p><strong>Methods: </strong>Tissue immunohistochemistry, TCGA, and GEO databases were used to analyze the expression of YBX1 in ICC. The expression of YBX1 was silenced and overexpressed in cell lines. Both in vitro and in vivo assays were conducted to examine the antitumor T-cell responses. Actinomycin D, RNA immunoprecipitation, and methylated RNA immunoprecipitation assays were used to identify mechanism of YBX1 on downstream genes. Immunofluorescence assay was used to validate the association between YBX1 and relevant genes in clinical specimens of ICC.</p><p><strong>Results: </strong>The research findings indicated that ICC exhibited high levels of YBX1 expression, which was strongly associated with unfavorable outcomes. YBX1 promoted tumor progression by suppressing antitumor T-cell responses. YBX1 enhanced signal transducer and activator of transcription 1 (STAT1) translation by serving as a 5-methylated cytosine (m5C) reader and activating the STAT1/PD-L1 pathway. Mouse experiments and clinical samples of ICC confirmed the strong correlation between the levels of YBX1, STAT1, and PD-L1 expression.</p><p><strong>Conclusions: </strong>YBX1 regulates STAT1 stability in an m5C dependent manner and maintains PD-L1 expression in ICC.</p>","PeriodicalId":55059,"journal":{"name":"Hepatobiliary & Pancreatic Diseases International","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"New-onset diabetes worsens prognosis of patients with pancreatic ductal adenocarcinoma after R0 resection: A multicenter study.","authors":"Peng-Jiong Liu, Zhi-Peng Zhou, Guan-Yu Wang, Shuai Xu, Wei Wang, Xiong Chen, Xiao-Dong Tan, Zhong-Hua Liu, Zhi-Ming Zhao, Yuan-Xing Gao, Xiu-Ping Zhang, Rong Liu","doi":"10.1016/j.hbpd.2025.04.008","DOIUrl":"https://doi.org/10.1016/j.hbpd.2025.04.008","url":null,"abstract":"<p><strong>Background: </strong>The risk of pancreatic ductal adenocarcinoma (PDAC) is increased in patients with diabetes mellitus (DM), particularly in new-onset diabetes (NOD). This study aimed to analyze the effect of NOD on the outcomes of patients with PDAC after R0 resection.</p><p><strong>Methods: </strong>PDAC patients from six centers in China undergoing R0 resection from 2015 to 2022 were included. Patients were categorized as long-term diabetes (LTD), NOD, or non-diabetes mellitus (non-DM) based on the timing of diagnosis relative to pancreatic resection. We compared the effects of diabetes status on perioperative and oncological outcomes of PDAC.</p><p><strong>Results: </strong>Of 1211 patients, 602 (49.7%), 127 (10.5%), and 482 (39.8%) were in the non-DM, LTD, and NOD groups, respectively. Patients with NOD suffered from higher rates of fatty pancreas and postoperative pancreatic fistula (POPF) (both P < 0.05). When compared with the non-DM group, the NOD group had worse median overall survival (OS) (24.6 vs. 29.4 months, P < 0.001) and recurrence-free survival (RFS) (13.3 vs. 15.8 months, P < 0.001); and the LTD group also had worse median OS (25.2 vs. 29.4 months, P = 0.041) and RFS (13.8 vs. 15.8 months, P = 0.007) compared with non-DM group. However, there were no significant differences in survival between the NOD and the LTD groups. Multivariate analysis indicated that NOD, LTD, largest tumor size, and poor tumor differentiation were independently associated with worse OS and RFS (all P < 0.05).</p><p><strong>Conclusions: </strong>Patients with PDAC undergoing R0 resection experienced a higher probability of POPF in the presence of concurrent NOD. Long-term survival prognosis was worse in NOD or LTD patients than in non-DM patients.</p>","PeriodicalId":55059,"journal":{"name":"Hepatobiliary & Pancreatic Diseases International","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}