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Recent advances in promising drugs for primary prevention of gastroesophageal variceal bleeding with cirrhotic portal hypertension

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hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 4-13页

作者： Ji-Yao Sheng Zi-Fan Meng Qiao Li Yong-Sheng Yang department of hepatobiliary and Pancreatic Surgery the Second Hospital of Jilin UniversityChangchun 130041China Jilin Engineering Laboratory for Translational medicine of hepatobiliary and Pancreatic Diseases the Second Hospital of Jilin UniversityChangchun 130041China

Background:Gastroesophageal variceal bleeding is one of the most severe complications of patients with cirrhosis.Although primary prevention drugs,including non-selectiveβ-blockers,have effectively reduced the incidence of bleeding,their efficacy is limited due to side effects and related contraindications.With recent advances in precision medicine,precise drug treatment provides better treatment efficacy.Data sources:Literature search was conducted in PubMed,MEDLINE and Web of Science for relevant articles published up to May 2022.Information on clinical trials was obtained from https://clinicaltrials.gov/and http://***/.Results:The in-depth understanding of the pathogenesis and advances of portal hypertension has enabled the discovery of multiple molecular targets for promising drugs.According to the site of action,these drugs could be classified into four classes:intrahepatic,extrahepatic,both intrahepatic and extrahepatic targets and others.All these classes of drugs offer advantages over traditional treatments in prevention of gastroesophageal variceal bleeding in patients with cirrhotic portal hypertension.Conclusions:This review classified and summarized the promising drugs,which prevent gastroesophageal variceal bleeding by targeting specific markers of pathogenesis of portal hypertension,demonstrating the significance of using the precision medicine strategy to discover and develop promising drugs for the primary prevention of gastroesophageal variceal bleeding in patients with cirrhotic portal hypertension.

关键词： Cirrhotic portal hypertension Target drug Primary prevention Bleeding

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Laparoscopic anatomical liver resection of segment 7 using a sandwich approach to the right hepatic vein (with video)

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hepatobiliary & Pancreatic Diseases International 2024年第2期23卷 217-220页

作者： Song-Feng Yu Wei-Chen Zhang Jun Yu department of hepatobiliary and Pancreatic Surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Full laparoscopic liver resection has been performed widely since it was introduced in the early 1990s.It has been expanded from initial for partial resection of the anterolateral segments to non-restriction of area of the liver[1–3].Anatomical liver resec-tion is considered to have potential superiority than non-anatomic resection in terms of tumor prognosis,thus it is more often rec-ommended in the treatment of hepatocellular carcinoma[4,5].Recently,laparoscopic segmental liver resection according to the Couinaud classification has been widely performed due to its ad-vantages in minimal invasiveness and tumor prognosis.

关键词： resection liver hepatic

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Concomitant hepatocellular carcinoma recurrence and mantle cell lymphoma

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hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 434-437页

作者： Liang Xue Da-Long Wan Chen Hu Qing-Hong Ke Jie Zhou Yan Shen department of hepatobiliary and Pancreatic Surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

To the Editor:Mantle cell lymphoma(MCL)is a rare subgroup of B-cell nonHodgkin’s lymphoma(NHL)that occurs in approximately 6%of NHL patients.Chronic hepatitis and cirrhosis may promote hepatocellular carcinoma(HCC)de... 详细信息

关键词： lymphoma hepatocellular NHL

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Deep learning-based radiomics allows for a more accurate assessment of sarcopenia as a prognostic factor in hepatocellular carcinoma

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第1期25卷 83-90页

作者： Zhikun LIU Yichao WU Abid Ali KHAN Lun LU Jianguo WANG Jun CHEN Ningyang JIA Shusen ZHENG Xiao XU Key Laboratory of Integrated Oncology and Intelligent medicine of Zhejiang Province Department of Hepatobiliary and Pancreatic SurgeryAffiliated Hangzhou First People’s HospitalZhejiang University School of MedicineHangzhou310006China Zhejiang University School of medicine Hangzhou310058China department of Radiology Easter Hepatobiliary Surgery HospitalNaval Medical UniversityShanghai200438China department of hepatobiliary and Pancreatic Surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou310003China NHC Key Laboratory of Combined Multi-organ Transplantation Hangzhou310003China department of hepatobiliary and Pancreatic Surgery Shulan(Hangzhou)HospitalHangzhou310022China

Hepatocellular carcinoma(HCC)is one of the most common malignancies and is a major cause of cancer-related mortalities worldwide(Forner et al.,2018;He et al.,2023).Sarcopenia is a syndrome characterized by an accelerated loss of skeletal muscle(SM)mass that may be age-related or the result of malnutrition in cancer patients(Cruz-Jentoft and Sayer,2019).Preoperative sarcopenia in HCC patients treated with hepatectomy or liver transplantation is an independent risk factor for poor survival(Voron et al.,2015;van Vugt et al.,2016).

关键词： cancer patients

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Pancreatic giant malignancy simulating a gastrointestinal stromal tumor

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hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 431-433页

作者： Ben-Jie Liu Chen-Hui Jin Yan-Lun Guo Zhi-Gang Ke Jun-Jun Huang Lin-Ping Cao department of hepatobiliary Surgery Department of General SurgeryPujiang Branch of the First Affiliated HospitalZhejiang University School of MedicineJinhua 322200China department of Pathology Pujiang Branch of the First Affiliated HospitalZhejiang University School of MedicineJinhua 322200China department of hepatobiliary and Pancreatic Surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Pancreatic acinar cell carcinoma(PACC)is a rare malignant tumor of pancreatic epithelial cells,which produces pancreatic exocrine enzymes.PACC originates from acinar cells and terminal branches of the pancreatic ducts in the exocrine tissue of the pancreas.PACC accounts for 1%−2%of pancreatic exocrine tumors[1].Herein,we present an elderly woman with PACC who recovered after effective laparoscopic surgery.The tumor was located on the left side of the abdomen;imaging suggested that it was a gastrointestinal stromal tumor of the gastric wall origin,infiltrating the tail of the pancreas and omentum,while postoperative pathology suggested PACC.

关键词： Pancreatic gastrointestinal pancreas

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Middle hepatic vein variation provides a safe path for anterior transection of hepatocellular carcinoma in caudate lobe

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hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 438-440页

作者： Bing-Yi Lin Qi-Jun Zhang Zhe Yang Shu-Sen Zheng department of hepatobiliary and Pancreatic Surgery The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China department of Thyroid Surgery The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Division of hepatobiliary Pancreatic Surgery Shulan(Hangzhou)HospitalZhejiang Shuren University School of MedicineHangzhou 310000China

To the Editor:Hepatocellular carcinoma(HCC)is one of the main causes of cancer related death worldwide,and new cases are expected to continue to increase in future[1].Surgical resection is still the best way to remove the tumor and improve patient’s prognosis.However,resection of caudate lobe often presents a technical challenge,even to accomplished hepatic surgeons.Caudate lobe is located anterior to the inferior vena cava(IVC)and posterior to the bifurcation of the portal vein(PV),generally consists of three regions:the paracaval portion,the left Spiegel lobe and the process portion[2].The anatomy of the paracaval portion includes the liver parenchyma ventral to the hepatic IVC and the area between the Spiegel lobe and the right lobe adjacent to the middle hepatic vein(MHV)ventrally,which was classified by Couinaud as segment IX[3].Here,we presented a case of HCC with successful downstaging therapy,as well as variation of MHV,which provides a safe path for anterior transection of segment IX.

关键词： hepatic anatomy Middle

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Efficacy of ginseng-based Renshenguben oral solution for cancer-related fatigue among patients with advanced-stage hepatocellular carcinoma:A prospective multicenter cohort study

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hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 249-256页

作者： Ming-Da Wang Chen Yuan Ke-Chun Wang Nan-Ya Wang Ying-Jian Liang Hong Zhu Xiang-Min Tong Tian Yang department of hepatobiliary and Pancreatic Surgery General Surgery CenterFirst Hospital of Jilin UniversityChangchun 130021China department of hepatobiliary Surgery Eastern Hepatobiliary Surgery HospitalSecond Military Medical University(Naval Medical University)Shanghai 200438China department of Clinical Laboratory Laboratory Medicine CenterZhejiang Provincial People’s HospitalHangzhou Medical CollegeHangzhou 310000China department of hepatobiliary Surgery First Affiliated Hospital of Harbin Medical UniversityHarbin 150007China department of Medical Oncology First Affiliated Hospital of Soochow UniversitySuzhou 215006China fdepartment of Central Laboratory Affiliated Hangzhou First People’s HospitalWestlake University School of MedicineHangzhou 310006China

Background:Cancer-related fatigue(CRF)is a common and debilitating symptom experienced by patients with advanced-stage cancer,especially those undergoing antitumor therapy.This study aimed to evaluate the efficacy and safety of Renshenguben(RSGB)oral solution,a ginseng-based traditional Chinese medicine,in alleviating CRF in patients with advanced hepatocellular carcinoma(HCC)receiving antitumor treatment.Methods:In this prospective,open-label,controlled,multicenter study,patients with advanced HCC at BCLC stage C and a brief fatigue inventory(BFI)score of≥4 were enrolled.Participants were assigned to the RSGB group(RSGB,10 mL twice daily)or the control group(with supportive care).Primary and secondary endpoints were the change in multidimensional fatigue inventory(MFI)score,and BFI and functional assessment of cancer therapy-hepatobiliary(FACT-Hep)scores at weeks 4 and 8 after enrollment.Adverse events(AEs)and toxicities were assessed.Results:A total of 409 participants were enrolled,with 206 assigned to the RSGB group.At week 4,there was a trend towards improvement,but the differences were not statistically significant.At week 8,the RSGB group exhibited a significantly lower MFI score(P<0.05)compared to the control group,indicating improved fatigue levels.Additionally,the RSGB group showed significantly greater decrease in BFI and FACT-Hep scores at week 8(P<0.05).Subgroup analyses among patients receiving various antitumor treatments showed similar results.Multivariate linear regression analyses revealed that the RSGB group experienced a significantly substantial decrease in MFI,BFI,and FACT-Hep scores at week 8.No serious drug-related AEs or toxicities were observed.Conclusions:RSGB oral solution effectively reduced CRF in patients with advanced HCC undergoing antitumor therapy over an eight-week period,with no discernible toxicities.These findings support the potential of RSGB oral solution as an adjunctive treatment for managing CRF in this patient population.

关键词： Cancer-related fatigue Hepatocellular carcinoma Renshenguben oral solution Efficacy Safety Ginseng

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HSP110 aggravates ischemia-reperfusion injury after liver transplantation by promoting NF-κB pathway

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hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 344-352页

作者： Qing-Zhi Hu Zhen-Rui Cao Wei-Xiong Zheng Min-Jie Zhao Jun-Hua Gong Cong Chen Zhong-Jun Wu Rui Tao department of hepatobiliary Surgery Bishan Hospital of Chongqing Medical UniversityChongqing 402760China department of Cardiothoracic Surgery the First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China c department of hepatobiliary Surgery the First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China department of hepatobiliary Surgery the Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China

Background:Ischemia-reperfusion injury(IRI)poses a significant challenge to liver transplantation(LT).The underlying mechanism primarily involves overactivation of the immune system.Heat shock protein 110(HSP110)functions as a molecular chaperone that helps stabilize protein structures.Methods:An IRI model was established by performing LT on Sprague-Dawley rats,and HSP110 was silenced using siRNA.Hematoxylin-eosin staining,TUNEL,immunohistochemistry,ELISA and liver enzyme analysis were performed to assess IRI following LT.Western blotting and quantitative reverse transcription-polymerase chain reaction were conducted to investigate the pertinent molecular changes.Results:Our findings revealed a significant increase in the expression of HSP110 at both the mRNA and protein levels in the rat liver following LT(P<0.05).However,when rats were injected with siRNAHSP110,IRI subsequent to LT was notably reduced(P<0.05).Additionally,the levels of liver enzymes and inflammatory chemokines in rat serum were significantly reduced(P<0.05).Silencing HSP110 with siRNA resulted in a marked decrease in M1-type polarization of Kupffer cells in the liver and downregulated the NF-κB pathway in the liver(P<0.05).Conclusions:HSP110 in the liver promotes IRI after LT in rats by activating the NF-κB pathway and inducing M1-type polarization of Kupffer cells.Targeting HSP110 to prevent IRI after LT may represent a promising new approach for the treatment of LT-associated IRI.

关键词： Ischemia-reperfusion injury Liver transplantation Inflammation HSP110 Heat shock proteins NF-κB

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Acute suppurative terminal cholangitis:Clinical characteristics of a new subtype of acute cholangitis

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hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 293-299页

作者： Rong-Tao Zhu Ye Li Chi-Xian Zhang Wei-Jie Wang Ruo-Peng Liang Jian Li Kai Bai Yu-Ling Sun department of hepatobiliary and Pancreatic Surgery the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Zhengzhou Key Laboratory of hepatobiliary and Pancreatic Diseases Zhengzhou 450052China Institute of hepatobiliary and Pancreatic Diseases Zhengzhou UniversityZhengzhou 450052China department of Pathology the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China

Background:Acute suppurative terminal cholangitis(ASTC)is rarer than acute obstructive cholangitis and is not well studied.To explore this subtype of acute cholangitis,we described our clinical experience with ASTC.Methods:We performed a retrospective review of patients with ASTC admitted to our center from September 2014 to August 2020.We analyzed their clinical characteristics,including etiology,clinical manifestations,imaging features,treatment and prognosis.Results:A total of 32 ASTC patients were included in the analysis.The majority of the patients had a history of biliary operations,and clinical manifestations were occult and atypical.The positive rate of bacterial culture was 46.9%.All the patients had typical imaging features on computed tomography and magnetic resonance imaging.Treatment with effective antibiotics was provided as soon as diagnosis was established.After treatment,most patients had a good outcome.Elevated levels of total bilirubin,aspartate aminotransferase,procalcitonin and gamma-glutamyltransferase were the characteristics of critically ill patients and were associated with relatively poor prognosis.Conclusions:Our results demonstrated that ASTC should be recognized as a new subtype of acute cholangitis,and that earlier diagnosis and more personalized treatments are needed.

关键词： Acute suppurative terminal cholangitis Acute cholangitis Gram-negative bacterial infections Diagnosis Treatment

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High-frequency repetitive transcranial magnetic stimulation promotes neural stem cell proliferation after ischemic stroke

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Neural Regeneration Research 2024年第8期19卷 1772-1780页

作者： Jing Luo Yuan Feng Zhongqiu Hong Mingyu Yin Haiqing Zheng Liying Zhang Xiquan Hu department of Rehabilitation medicine The Third Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina department of hepatobiliary Surgery The Third Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina

Prolife ration of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage.Transcranial magnetic stimulation(TMS)has recently emerged as a tool for inducing endogenous neural stem cell regeneration,but its underlying mechanisms remain unclea r In this study,we found that repetitive TMS effectively promotes the proliferation of oxygen-glucose deprived neural stem cells.Additionally,repetitive TMS reduced the volume of cerebral infa rction in a rat model of ischemic stro ke caused by middle cerebral artery occlusion,im p roved rat cognitive function,and promoted the proliferation of neural stem cells in the ischemic penumbra.RNA-sequencing found that repetitive TMS activated the Wnt signaling pathway in the ischemic penumbra of rats with cerebral ischemia.Furthermore,PCR analysis revealed that repetitive TMS promoted AKT phosphorylation,leading to an increase in mRNA levels of cell cycle-related proteins such as Cdk2 and Cdk4.This effect was also associated with activation of the glycogen synthase kinase 3β/β-catenin signaling pathway,which ultimately promotes the prolife ration of neural stem cells.Subsequently,we validated the effect of repetitive TMS on AKT phosphorylation.We found that repetitive TMS promoted Ca2+influx into neural stem cells by activating the P2 calcium channel/calmodulin pathway,thereby promoting AKT phosphorylation and activating the glycogen synthase kinase 3β/β-catenin pathway.These findings indicate that repetitive TMS can promote the proliferation of endogenous neural stem cells through a Ca2+influx-dependent phosphorylated AKT/glycogen synthase kinase 3β/β-catenin signaling pathway.This study has produced pioneering res ults on the intrinsic mechanism of repetitive TMS to promote neural function recove ry after ischemic stro ke.These results provide a stro ng scientific foundation for the clinical application of repetitive TMS.Moreover,repetitive TMS treatment may not only be an efficient and potential approach to support neurogenesis for

关键词： AKT/β-catenin signaling brain stimulation Ca2+influx cell proliferation ischemic stroke middle cerebral artery occlusion neural stem cells neurological rehabilitation repetitive transcranial magnetic stimulation

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