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Ischemic preconditioning enhances hepatocyte proliferation in the early phase after ischemia under hemi-hepatectomy in rats

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hepatobiliary & pancreatic Diseases International 2012年第5期11卷 521-526页

作者： Li-Ming Jin, Shui-Fang Jin, Yuan-Xing Liu, Lin Zhou, Hai-Yang Xie, Sheng Yan, Xiao Xu , Shu-Sen Zheng Department of General surgery and Intensive Care Unit, First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou 310006, China key laboratory of Combined Multi-organ transplantation, Ministry of Public Health, key laboratory of organ transplantation, Zhejiang province, and Division of hepatobiliary and pancreatic surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China [a] Department of General surgery First Affiliated Hospital Zhejiang Chinese Medical University Hangzhou 310006 Hangzhou China [b] Intensive Care Unit First Affiliated Hospital Zhejiang Chinese Medical University Hangzhou 310006 Hangzhou China [c] key laboratory of Combined Multi-organ transplantation Ministry of Public Health Key Laboratory of Organ Transplantation Zhejiang Province and Division of Hepatobiliary and Pancreatic Surgery First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 Hangzhou China

BACKGROUND: Ischemia/reperfusion (I/R) injury is an important barrier to liver surgery and transplantation because it impairs remnant liver/reduced-size-graft regeneration. Ischemic preconditioning (IPC), as an effective measure to overcome I/R injury, has been shown to enhance the regenerative capacity of hepatocytes. However, investigations have always focused on regeneration in the late phase after reperfusion. This study aimed to investigate whether IPC enhances hepatocyte proliferation in the early phase after reperfusion and possible underlying mechanisms. METHODS: A total of 90 rats were divided into three groups: hemi-hepatectomy alone (PHx group), 60 minutes of ischemia plus hemi-hepatectomy (I/R group), and a cycle of 10 minutes of alternating I/R prior to 60 minutes of ischemia plus hemi-hepatectomy (IPC group). Each group was divided into five subgroups sacrificed after 0.5, 2, 6, 12 or 24 hours (n=6/ subgroup). Subsequently, serum concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) were measured; caspase-3 and proliferating cell nuclear antigen (PCNA) proteins were also determined by Western blotting. Furthermore, PCNA was detected by immunohistochemistry to identify the expression ***: Serum ALT and AST levels after 2-24 hours of reperfusion in the PHx and IPC groups were remarkably decreased compared to the I/R group, and the serum TNF-α was relatively lower. A significant increase of serum IL-6 levels was found in the PHx and IPC groups compared with the I/R group at each time point. Furthermore, PCNA expression was remarkably increased in the IPC group after 6-12 hours of reperfusion, and in the earlier 0.5 and 6 hours time points after reperfusion have shown the massive PCNA-positive hepatocytes. At the same time, the expression of liver p-JNK was higher in the IPC group in the early phase after reperfusion than that of the I/R group and its expre

关键词： reperfusion injury ischemic preconditioning hepatocytes proliferation hemi-hepatectomy

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Aspirin in hepatocellular carcinoma:Is it an out-of-date or promising treatment?

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iLIVER 2022年第1期1卷 55-64页

作者： Xun Qiu Fengqiang Gao Kai Wang Zhensheng Zhang Chuxiao Shao 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 Westlake laboratory of Life Sciences and Biomedicine Hangzhou310024China NHC key laboratory of Combined Multi-organ transplantation Hangzhou310003China Institute of organ transplantation Zhejiang UniversityHangzhou310003China Department of hepatobiliary and pancreatic surgery Affiliated Lishui HospitalZhejiang University School of MedicineLishui323000China

Hepatocellular carcinoma(HCC)is one of the most aggressive human malignancies with a dismal survival *** strategies can effectively prevent the occurrence of *** immunotherapy has significantly improved HCC-related survival in recent years,this systemic therapy is very expensive and lays a heavy burden on most HCC ***,which is currently one of the most widely used medications in analgesic and cardiovascular diseases,is reported to have anti-tumor effects on *** importantly,long-term administration of low-dose aspirin does not significantly increase the risk of gastrointestinal *** to its costeffectiveness and wide use,aspirin can be easily applied as an HCC treatment and is affordable for a wide range of ***,deeper understanding and more attention are needed to extend the frontline of aspirin's preventive and therapeutic potential into cancer research and *** this review,we discuss the preventive effect of aspirin on HCC in the context of different etiological factors,including hepatitis B or hepatitis C virus infection,non-alcoholic fatty liver disease,and alcohol-associated liver *** therapeutic role of aspirin in resectable or unresectable HCC management is also ***,the mechanisms underlying the anti-cancer effects of aspirin on HCC are fully reviewed and discussed in the following two aspects:the effect of aspirin on multi-oncogenic signaling pathways in HCC(e.g.,AMPK,Wnt/β-catenin,NF-κB)and aspirinmediated immunometabolic responses in liver *** findings indicate aspirin is a promising agent for populations at risk and HCC patients to prevent or treat HCC.

关键词： Hepatocellular carcinoma Aspirin Chemoprevention Cancer therapy Oncogenic signaling Immunometabolic response

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Lower mean platelet volume is a risk indicator of hepatocellular carcinoma recurrence following liver transplantation

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hepatobiliary & pancreatic Diseases International 2019年第3期18卷 223-227页

作者： Ai-Bin Zhang Zhi-Hao Zhang Jie Zhang Bing-Yi Lin Lei Geng Zhe Yang Xiao-Ning Feng Shu-Sen Zheng Division of hepatobiliary and pancreatic surgery Department of Surgery The First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China key laboratory of Combined Multi-organ transplantation Ministry of Public Health The First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China Department of hepatobiliary surgery The First Hospital of Jiaxing Jiaxing University Jiaxing 314000 China

Background: Lower mean platelet volume(MPV) is an indicator of platelet activity in the setting of tumor development. This study was to assess the relationship between preoperative MPV and survival outcomes of patients with hepatocellular carcinoma(HCC) following liver transplantation(LT). Methods: The demographic and clinical characteristics of 304 HCC patients following LT were retrieved from an LT database. All the patients were divided into the normal and lower MPV groups according to the median MPV. The factors were first analyzed using a Kaplan–Meier survival analysis, then the factors with P < 0.10 were selected for multivariate Cox regression analysis and were used to define the independent risk factors for poor prognosis. Results: The 1-, 3-, and 5-year tumor free survival was 95.34%, 74.67% and 69.29% in the normal MPV group, respectively, and 95.40%, 59.97% and 42.94% in the lower MPV group, respectively( P < 0.01). No significant difference was observed in post-LT complications between the normal and lower MPV groups. Portal vein tumor thrombosis(PVTT)[hazard ratio(HR = 2.24;95% confidence interval: 1.46–3.43;P < 0.01) and lower MPV(HR = 1.58;95% confidence interval: 1.05–2.36;P = 0.03) were identified as independent prognostic risk factors for recipient survival. Conclusion: Preoperative lower MPV is a risk indicator of HCC patients survival outcomes after LT.

关键词： Hepatocellular carcinoma Mean platelet volume Liver transplantation Platelet Prognosis

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Recent advances in immunotherapy for hepatocellular carcinoma

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hepatobiliary & pancreatic Diseases International 2021年第6期20卷 511-520页

作者： Abid Ali Khan Zhi-Kun Liu Xiao Xu Division of hepatobiliary and pancreatic surgery Department of SurgeryThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China key Lab of Combined Multi-organ transplantation Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesMinistry of Public HealthHangzhou 310003China Department of hepatobiliary and pancreatic surgery Affiliated Hangzhou First People's HospitalZhejiang University School of MedicineHangzhou 310006China

Background:Treatment of hepatocellular carcinoma(HCC)is challenging as most patients are diagnosed at advanced stage with underlying chronic liver *** systemic chemotherapy has failed in HCC,and the clinical efficacy of FDA-approved molecular targeted agents such as sorafenib and lenvatinib remains *** sources:Literature search was conducted in Pub Med for relevant articles published before January *** search aimed to identify recent developments in immune-based treatment approaches for *** of clinical trials was obtained from https://***/.Results:Two immune checkpoint inhibitors(ICIs),nivolumab and pembrolizumab were approved as monotherapies,which has revolutionized HCC ***,combination ICIs have also got accelerated FDA approval ***-based therapies have challenged targeted drugs owing to their safety,tolerability,and survival *** addition to the significant success in ICIs,other immunotherapeutic strategies such as cancer vaccine,chimeric antigen receptor T-cells,natural killer cells,cytokines,and combination therapy,have also shown promising outcomes in clinical *** diagnostic and prognostic biomarkers have been identified which can help in clinical decision making when starting treatment with ***:Immunotherapy has emerged as one of the mainstream treatment modalities for advanced HCC in recent ***,challenges such as low response rate and acquired resistance in previously respondent patients still *** research is needed to understand the unique resistance mechanism to immunotherapy and to discover more predictive biomarkers to guide clinical decision making.

关键词： Hepatocellular carcinoma Immunotherapy Immune checkpoint inhibitor Adoptive cellular therapy Immune evasion Combination therapy Predictive biomarkers

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Foreign body retained in liver long after gauze packing

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World Journal of Gastroenterology 2013年第21期19卷 3364-3368页

作者： Jian Xu Heng Wang Zheng-Wei Song Miao-Da Shen Shao-Hua Shi Wei Zhang Min Zhang Shu-Sen Zheng Division of hepatobiliary and pancreatic surgery Department of SurgeryFirst Affiliated HospitalSchool of MedicineZhejiang University key laboratory of Combined Multi-organ transplantation Ministry of Public HealthFirst Affiliated HospitalSchool of MedicineZhejiang University VIP Department Red Cross Hospital

This case report describes a foreign body retained in the liver long after perihepatic gauze packing. A 64-year-old female patient had suffered a rib fracture and liver rupture during a traffic accident in 1973. She discovered a mass in her right hypochondrium. Her hepatic ultrasonography showed a round mass (20.3 cm × 17.3 cm × 16.0 cm in size) with fluid echogenicity in the right lobe of her liver, and a hepatic cystic-solid mass (19.7 cm × 18.5 cm × 15.6 cm in size) was identified in an abdominal computerized tomography scan. Several pieces of gauze were extracted, and brown pus from the hepatic mass was suctioned during her exploratory laparotomy. Histology documented gauze remnants with necrotic material inclusions and fibrotic capsules. To our knowledge, this patient's case represents the longest time for which a foreign body has been retained in the liver. In addition, we conducted a comprehensive literature review of foreign bodies retained in the liver. Foreign bodies may be introduced into the liver via penetrating trauma, surgical procedures or the ingestion of foreign bodies (which then migrate from the gut). Thus, they can be classified into the following three categories: penetrating, medical and migrated foreign bodies. The details of the case are thoroughly described.

关键词： Liver Foreign bodies Foreign-body migration Foreign-body reaction Surgical sponges

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TNFR2 is a potent prognostic biomarker for post-transplant lung metastasis in patients with hepatocellular carcinoma

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Chinese Journal of Cancer Research 2023年第1期35卷 66-80页

作者： Huigang Li Zuyuan Lin Jianyong Zhuo Modan Yang Wei Shen Zhihang Hu Yichen Ding Hao Chen Chiyu He Xinyu Yang Siyi Dong Xuyong Wei Beicheng Sun Shusen Zheng Ren Lang Di Lu Xiao Xu Zhejiang University School of Medicine Hangzhou 310058China 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 MedicineHangzhou 310006China The Institute for organ Repair and Regenerative Medicine of Hangzhou Hangzhou 310006China Institute of organ transplantation Zhejiang UniversityHangzhou 310003China National Center for Healthcare Quality Management in Liver Transplant Hangzhou 310003China Department of hepatobiliary surgery the Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing 210008China Department of hepatobiliary and pancreatic surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of hepatobiliary and pancreatic surgery Shulan(Hangzhou)HospitalHangzhou 311112China NHC key laboratory of Combined Multi-organ transplantation Hangzhou 31003China Department of hepatobiliary surgery Beijing Chaoyang Hospital Affiliated to Capital Medical UniversityBeijing 100020China

Objective:Lung metastasis is a common and fatal complication of liver transplantation for hepatocellular carcinoma(HCC).The precise prediction of post-transplant lung metastasis in the early phase is of great ***:The mRNA profiles of primary and paired lung metastatic lesions were analyzed to determine key signaling *** enrolled 241 HCC patients who underwent liver transplantation from three *** microarrays were used to evaluate the prognostic capacity of tumor necrosis factor(TNF),tumor necrosis factor receptor 1(TNFR1),and TNFR2,particularly for post-transplant lung ***:Comparison of primary and lung metastatic lesions revealed that the TNF-dependent signaling pathway was related to lung metastasis of *** expression of TNF was degraded in comparison to that in para-tumor tissues(Pkey receptors in the TNF-dependent signaling pathway,TNFR1 and TNFR2,was higher in HCC tissues than in para-tumor tissues(P<0.001).TNF and TNFR1 showed no relationship with patients’outcomes,whereas elevated TNFR2 in tumor tissue was significantly associated with worse overall survival(OS)and increased recurrence risk(5-year OS rate:31.9%vs.62.5%,P<0.001).Notably,elevated TNFR2 levels were also associated with an increased risk of post-transplant lung metastasis(hazard ratio:1.146;P<0.001).Cox regression analysis revealed that TNFR2,Hangzhou criteria,age,and hepatitis B surface antigen were independent risk factors for post-transplant lung metastasis,and a novel nomogram was established *** nomogram achieved excellent prognostic efficiency(area under time-dependent receiver operating characteristic=0.755,concordance-index=0.779)and was superior to conventional models,such as the Milan ***:TNFR2 is a potent prognostic biomarker for predicting post-transplant lung metastasis in patients with HCC.A nomogram incorporating TNFR2 deserves to be a helpful prognostic tool in liver transplantatio

关键词： Lung metastasis hepatocellular carcinoma liver transplantation nomogram

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Potential of extracellular vesicles and exosomes as diagnostic markers for cholangiocarcinoma

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hepatobiliary surgery and Nutrition 2022年第3期11卷 436-438页

作者： Linping Cao Jiawei Hong Jian Wu Division of hepatobiliary and pancreatic surgery Department of SurgeryFirst Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouChina key Lab of Combined Multi-organ transplantation Ministry of Public HealthHangzhouChina

Cholangiocarcinoma(CCA),a malignant carcinoma originating from biliary epithelium,is the second largest primary liver malignancy,accounting for 10-15%of hepatobiliary ***,CCA is a fatal malignancy,with a 5-year survival rate of less than 10%(1).The lack of typical symptoms and signs makes early CCA difficult to identify and diagnose by early health *** diagnosis of CCA mainly relies on radiography,tumor biomarkers,invasive diagnosis,as well as pathological examination,which results in the majority of patients being detected in the middle and late stages,and only about one-third of CCA patients have access to treatment(1).

关键词： diagnosis epithelium malignancy

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Isolated anti-HBc is an independent risk factor for tumor recurrence in intrahepatic cholangiocarcinoma after curative resection

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hepatobiliary & pancreatic Diseases International 2022年第5期21卷 472-478页

作者： Xiao-Bo Xu Chen Hu Han-Jin Yang Shu-Sen Zheng Department of hepatobiliary and pancreatic surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China key laboratory of Pulsed Power Translational Medicine of Zhejiang province Hangzhou 310012China Department of Pathology the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China key Lab of Combined Multi-organ transplantation Ministry of Public HealthHangzhou 310003China

Background:Intrahepatic cholangiocarcinoma(ICC)is a poorly understood and aggressive malignancy with increasing incidence and *** B virus(HBV)infection is recognized as one of the important risk factors of *** are few reports focusing on whether isolated antibody to hepatitis B core antigen(isolated anti-HBc,IAHBc)have prognostic role in ICC,while positive hepatitis B surface antigen(HBsAg)has been reported to be associated with the prognosis of *** aim of this study was to investigate the prognostic value of IAHBc in ICC patients after curative resection,in order to identify those who have the high risk of ICC recurrence in the early ***:We divided 209 ICC patients who underwent curative resection into 4 groups:groupⅠ(n=40),HBsAg(-)/antibody to hepatitis B surface antigen(anti-HBs)(-)/anti-HBc(+);groupⅡ(n=70),HBsAg(+)/anti-HBc(-);groupⅢ(n=55),HBsAg(-)/anti-HBs(+)/anti-HBc(+);and groupⅣ(n=44),HBsAg(-)/anti-HBc(-).We compared the recurrence-free survival(RFS)and overall survival(OS)among these four ***:The median follow-up time was 16.93 months(range 1-34.6 months).The 1-and 2-year RFS and OS rates were 60%and 42%,and 78%and 63%respectively in all *** to the whole non-IAHBc patients(groupⅡ+groupⅢ+groupⅣ),IAHBc patients(groupⅠ)showed significantly lower RFS at 1 year(39.8%vs.64.4%,P=0.001)and 2 years(20.7%vs.46.7%,P=0.001).When compared to other three individual groups,IAHBc patients(groupⅠ)also had the lowest *** did not find significant difference in OS among the four *** multivariate analysis revealed that IAHBc was an independent risk factor of ***:IAHBc is an independent poor prognostic factor for tumor recurrence in ICC patients after curative resection.

关键词： Cholangiocarcinoma Hepatitis B virus Isolated antibody to hepatitis B core antigen Occult hepatitis B infection

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Protective effect of probiotics on intestinal barrier function in malnourished rats after liver transplantation

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hepatobiliary & pancreatic Diseases International 2011年第5期10卷 489-496页

作者： Zhi-Gang Ren, Hui Liu, Jian-Wen Jiang, Li Jiang, Hui Chen, Hai-Yang Xie, Lin Zhou and Shu-Sen Zheng key laboratory of Combined Multi-organ Transplan- tation, Ministry of Public Health, and Department of hepatobiliary and pancreatic surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China and Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China [a] key laboratory of Combined Multi-organ transplantation Ministry of Public Health and Department of Hepatobiliary and Pancreatic Surgery First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China [b] Institute of Immunology Zhejiang University School of Medicine Hangzhou 310058 China

BACKGROUND: Most patients waiting for liver transplantation have end-stage liver diseases with malnutrition, which is prone to induce intestinal barrier dysfunction after liver transplantation. We aimed to study the effect of probiotics on intestinal barrier function in malnourished rats following liver transplantation with long-term antibiotics. METHODS: Twelve Lewis rats were selected as donors. Twelve BN rats, which served as recipients, were subjected to malnutrition by semi-starvation for 4-5 weeks. They were randomly divided into two groups: a control group which received phosphate-buffered saline and a probiotics group which received Bifidobacterium and Lactobacillus. All recipients were injected with intramuscular imipenem and subcutaneous cyclosporine A. Furthermore, six normal BN rats without any drugs or operations served as a normal group. Eight days after operation, all rats were sacrificed for examination of the following parameters: serum levels of endotoxin and TNF-α, bacterial translocation, intestinal microflora, ileocecal sIgA, lymphocyte numbers, and phenotypes (CD4, CD8, αβTCR, γδTCR)ofPeyer’spatches. RESULTS: In recipients subjected to malnutrition, weight decreased by 20% and they survived until 8 days after operation. Compared with the normal group, all recipients on postoperative day 8 showed increased levels of serum endotoxin and TNF-α as well as increased counts oftranslocated bacteria. Meanwhile, there were decreases in counts of Bifidobacterium and Lactobacillus in the ileocecum, sIgA concentration, and lymphocytes of Peyer’s patches. Moreover, partial alteration in lymphocyte phenotypes was evidenced by elevated ratios of CD8 + and γδTCR + lymphocytes. In contrast, compared to the control group, supplementation with probiotics reduced the levels of serum endotoxin, TNF-α and bacterial translocation, increased the counts of Bifidobacterium and Lactobacillus, the concentration of sIgA and lymphocytes of Peyer’s patches, and also slightly

关键词： liver transplantation probiotics intestinal microflora intestinal barrier function

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Applications of neural networks in liver transplantation

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iLIVER 2022年第2期1卷 101-110页

作者： Jinwen Meng Zhikun Liu 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 Westlake laboratory of Life Sciences and Biomedicine Hangzhou310024China NHC key laboratory of Combined Multi-organ transplantation Hangzhou310003China Institute of organ transplantation Zhejiang UniversityHangzhou310003China

The use of neural networks(NNs)as a cutting-edge technique in the medical field has drawn considerable *** models“learn”from a large amount of data and then find corresponding clinical patterns that are challenging for clinicians to *** this study,we focus on liver transplantation(LT),which is an effective treatment for end-stage liver *** management before and after LT produces a massive quantity of medical data,which can be fully processed by *** describe recent progress in the clinical application of NNs to LT in five respects:pre-transplantation evaluation of the donor and recipient,recipient outcome prediction,allocation system development,operation monitoring,and post-transplantation complication *** review provides clinicians and researchers with a description of forefront applications of NNs in the field of LT and discusses prospects and pitfalls.

关键词： Artificial intelligence Liver transplantation Machine learning Neural network Deep learning

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