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High nuclear ABCG1 expression is a poor predictor for hepatocellular carcinoma patient survival

hepatobiliary & pancreatic Diseases International 2022年第4期21卷 370-377页

作者： Bin Xi Fang-Zhou Luo Bin He Fang Wang Ze-Kuan Li Ming-Chun Lai Shu-Sen Zheng Division of hepatobiliary and pancreatic surgery Department of SurgeryThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of Radiotherapy The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China key laboratory of Combined Multi-organ transplantation Ministry of Public HealthZhejiang UniversityHangzhou 310003China

Background:ATP-binding cassette transporter G1(ABCG1)regulates cellular cholesterol homeostasis and plays a significant role in tumor ***,for hepatocellular carcinoma(HCC),the role of ABCG1 has not been ***,the aim of this study was to evaluate the prognostic value and clinicopathological significance of ABCG1 in ***:One hundred and four adult patients with HCC were enrolled,and ABCG1 expression in paired HCC specimens was determined by *** these patients were stratified by ABCG1 expression,Kaplan-Meier analysis was used to compare the overall survival(OS)and recurrence-free survival(RFS),and Cox regression analysis was used to determine independent predictors of tumor ***:Upregulation of ABCG1 was observed in HCC samples compared to matched tumor-adjacent *** with high nuclear ABCG1 expression had lower OS and RFS(P=0.012 and P=0.020,respectively).High nuclear ABCG1 expression was related to larger tumor size(P=0.004)and tumor recurrence(P=0.027).Although ABCG1 was expressed in the cytoplasm,cytosolic expression could not predict the outcome in patients with HCC.A new stratification pattern was established based on the heterogenous ABCG1 expression pattern:high risk(High^(nucleus)/Low^(cytosol)),moderate risk(High^(nucleus)/High^(cytosol) or Low^(nucleus)/Low^(cytosol)),and low risk(Low^(nucleus)/High^(cytosol)).This ABCG1-based risk stratification could distinguish the different OS and RFS in patients with *** Cox regression analysis indicated that ABCG1 high risk was an independent predictor of poor RFS(P=0.015).Conclusions:High nuclear ABCG1 expression indicates poor prognosis in patients with *** distribution of ABCG1 in the nucleus and cytoplasm may have an important role in tumor recurrence.

关键词： ATP-binding cassette transporter G1 Hepatocellular carcinoma Overall survival Prognostic factor Progression-free survival

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A good prognostic predictor for liver transplantation recipients with benign end-stage liver cirrhosis

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hepatobiliary & pancreatic Diseases International 2017年第2期16卷 164-168页

作者： Qiang Wei Rahmeet Singh Nemdharry Run-Zhou Zhuang Jie Li Qi Ling Jian Wu Tian Shen Lin Zhou Hai-Yang Xie Min Zhang Xiao Xu Shu-Sen Zheng key Lab of Combined Multi-organ transplantation Ministry of Public Health Division of Hepatobiliary and Pancreatic Surgery Department of Surgery First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases Hangzhou 310003 China

BACKGROUND： Post-transplant model for predicting mortality（PMPM, calculated as-5.359＋1.988×ln（serum creatinine [mg/d L]）＋1.089×ln（total bilirubin [mg/d L]）） score has been proved to be a simple and accurate model for predicting the prognosis after liver transplantation（LT） in a single center study. Here we aim to verify this model in a large cohort of ***： A total of 2727 patients undergoing LT with endstage liver cirrhosis from January 2003 to December 2010 were included in this retrospective study. Data were collected from the China Liver Transplant Registry（CLTR）. PMPM score was calculated at 24-h and 7-d following LT. According to the PMPM score at 24-h, all patients were divided into the low-risk group（PMPM score ≤-1.4, n=2509） and the high-risk group（PMPM score 〉-1.4, n=218）. The area under receiver operator characteristic curve（AUROC） was calculated for evaluating the prognostic ***： The 1-, 3-, and 5-year patient survival rates in the low-risk group were significantly higher than those in the high-risk group（90.23%, 88.01%, and 86.03% vs 63.16%, 59.62%, and 56.43%, respectively, P〈0.001）. In the high-risk group, 131 patients had a decreased PMPM score（≤-1.4） at 7-d, and their cumulative survival rate was significantly higher than the other 87 patients with sustained high PMPM score（〉-1.4）（P〈0.001）. For predicting 3-month mortality, PMPM score showed a much higher AUROC than post-transplant MELD score（P〈0.05）.CONCLUSION： PMPM score is a simple and effective tool to predict short-term mortality after liver transplantation in patients with benign liver diseases, and an indicator for prompt salvaging treatment as well.

关键词： cirrhosis liver transplantation post-transplant model for predicting mortality score prognosis

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When immunotherapy meets liver transplantation for hepatocellular carcinoma: A bumpy but promising road

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Chinese Journal of Cancer Research 2023年第2期35卷 92-107页

作者： Yufeng Gu Shengjun Xu Zhengxin Wang Jiayin Yang Shusen Zheng Qiang Wei Zhikun Liu Xiao Xu The Fourth School of Clinical Medicine Zhejiang Chinese Medical UniversityHangzhou 310053China Department of hepatobiliary and pancreatic surgery Affiliated Hangzhou First People's HospitalZhejiang University School of MedicineHangzhou 310006China Institute of organ transplantation Zhejiang UniversityHangzhou 310003China key laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang province Hangzhou 310006China Department of General surgery Huashan HospitalFudan UniversityShanghai 200040China Department of Liver surgery Liver Transplantation CenterWest China Hospital of Sichuan UniversityChengdu 610044China 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 Westlake laboratory of Life Sciences and Biomedicine Hangzhou 310024China

Liver transplantation(LT)is a highly curative therapy for patients with hepatocellular carcinoma(HCC).However,due to the shortage of donor livers and rapid progression of HCC,a majority of patients are dropped out from the ***,immunotherapy has shown great promise in the treatment of advanced ***,the use of immunotherapy is limited in LT mainly due to the potentially increasing risk of graft *** of the main challenges for researchers is the protection of donor graft from an immunotherapy-boosted immune response mounted by the ***,the safety,availability,and costs of immunotherapy are other challenges that need to be ***,we reviewed the literature involving patients who received immunotherapy prior to transplant to avoid waitlist dropouts and following transplantation to prevent the progression of tumor recurrence and ***,the incidence of rejection was 25.0%pre-transplant and 18.5%*** on the review of these clinical studies,we can conclude that conducting clinical trials on the safety and efficacy of currently available immunotherapy drugs and identifying novel immunotherapy targets through extensive research may be promising for patients who do not meet the selection criteria for LT and who experience post-transplant *** date,the clinical experience on the use of immunotherapy before or after LT comes from individual case *** some of the reported results are promising,they are not sufficient to support the standardized use of immunotherapy in clinical practice.

关键词： Liver transplantation hepatocellular carcinoma immunotherapy immune checkpoint inhibitors adoptive cell therapy

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Irreversible electroporation plus chemotherapy versus chemotherapy alone as treatments for patients with locally advanced pancreatic cancer

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hepatobiliary & pancreatic Diseases International 2022年第1期21卷 69-72页

作者： Shan-Shuo Liu Hai-Yu Wang Ying Sun Ya-Wen Zou Zhi-Gang Ren Xin-Hua Chen Zu-Jiang Yu Department of Infectious Diseases The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Gene Hospital of henan province Precision Medicine CenterThe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Department of hepatobiliary and pancreatic surgery The First Affiliated HospitalZhejiang University School of MedicineKey Laboratory of Combined Multi-organ TransplantationMinistry of Public HealthHangzhou 310003China

pancreatic cancer is a major health problem worldwide,with a high incidence and mortality *** is estimated that it has become the sixth leading cause of cancer-related death in China and the fourth leading cause of cancer-related death globally[1].For patients with locally advanced pancreatic cancer(LAPC),there are no standard treatment options.

关键词： patients chemotherapy mortality

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Predictive value of tumor markers in patients with recurrent hepatocellular carcinoma in different vascular invasion pattern

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hepatobiliary & pancreatic Diseases International 2016年第4期15卷 371-377页

作者： Feng Gao Heng-Kai Zhu Yang-Bo Zhu Qiao-Nan Shan Qi Ling Xu-Yong Wei Hai-Yang Xie Lin Zhou Xiao Xu Shu-Sen Zheng Division of hepatobiliary and pancreatic surgery Department of Surgery First Affiliated Hospital Zhejiang University School of Medicine Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases Zhejiang University key Lab of Combined Multi-organ transplantation Ministry of Public Health First Affiliated Hospital Zhejiang University School of Medicine

BACKGROUND： Four tumor markers for hepatocellular carcinoma（HCC）, alpha-fetoprotein（AFP）, glypican-3（GPC3）, vascular endothelial growth factor（VEGF） and des-gammacarboxy prothrombin（DCP）, are closely associated with tumor invasion and patient＇s survival. This study estimated the predictability of preoperative tumor marker levels along with pathological parameters on HCC recurrence after ***： A total of 140 patients with HCC who underwent hepatectomy between January 2012 and August 2012 were enrolled. The demographics, clinical and follow-up data were collected and analyzed. The patients were divided into two groups： patients with macroscopic vascular invasion（Ma VI ＋） and those without Ma VI（Ma VI-）. The predictive value of tumor markers and clinical parameters were evaluated by univariate and multivariate ***： In all patients, tumor size（〉8 cm） and Ma VI were closely related to HCC recurrence after hepatectomy. For Ma VI＋ patients, VEGF（〉900 pg/m L） was a significant predictor for recurrence（RR=2.421; 95% CI： 1.272-4.606; P=0.007）. The 1- and 2-year tumor-free survival rates for Ma VI＋ patients with VEGF ≤900 pg/m L versus for those with VEGF 〉900 pg/m L were 51.5% and 17.6% versus 19.0% and 4.8%（P〈0.001）. For Ma VI- patients, DCP 〉445 m Au/m L and tumor size 〉8 cm were two independent risk factors for tumor recurrence（RR=2.307, 95% CI： 1.132-4.703, P=0.021; RR=3.150, 95% CI： 1.392-7.127, P=0.006; respectively）. The 1- and 2-year tumor-free survival rates for the patients with DCP ≤445 m Au/m L and those with DCP 〉445 m Au/m L were 90.4% and 70.7% versus 73.2% and 50.5% respectively（P=0.048）. The 1-and 2-year tumor-free survival rates for the patients with tumor size ≤8 cm and 〉8 cm were 83.2% and 62.1% versus 50.0% and 30.0%, respectively（P=0.003）.CONCLUSIONS： The Ma VI＋ patients with VEGF ≤900 pg/m L had a relatively high tumor-free survival than those with VEGF 〉900 pg/m L. In the Ma VI- patients, DCP 〉445 m Au/m L and tumor size 〉8

关键词： tumor markers hepatocellular carcinoma recurrence vascular invasion prediction

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Implementing an innovated liver ex-situ machine perfusion technology:The 2018 Joint International Congress of ILTS,ELITA and LICAGE

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hepatobiliary & pancreatic Diseases International 2018年第4期17卷 283-285页

作者： Jun-Jun Jia Jian-Hui Li Hai-Yang Xie Lin Zhoua Shu-Sen Zheng Division of hepatobiliary pancreatic surgery First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China key laboratory of Combined Multi-organ transplantation Ministry of Public HealthFirst Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

The 2018 Joint International Congress of ILTS,ELITA and LICAGE were held in Lisbon,Portugal on May 23–26,*** exciting and innovative program brought together 1144 experts in liver transplantation(LT)such as surgeons,physicians or basic scientists from 61 *** presentations included 110 invited speakers,181 oral presentations,and 545 *** editorial highlights some of the most innovative and impactful presentations in

关键词： NMP WIT DCD Implementing an innovated liver ex-situ machine perfusion technology:The 2018 Joint International Congress of ILTS,ELITA and LICAGE

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Efficacy of hepatitis B immunoglobulin in relation to the gene polymorphisms of human leukocyte Fcy receptor Ⅲ (CD16) in Chinese liver transplant patients

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Chinese Medical Journal 2007年第18期120卷 1606-1610页

作者： WANG Wei-lin ZHANG Guo-liang WU Li-hua YAO Min-ya JIN Jing JIA Chang-ku XIE Hai-yang ZHOU Lin JIANG Zhi-jun ZHENG Shu-sen Department of hepatobiliary pancreatic surgery Key Laboratoryof Organ Transplantation Zhejiang Province Key Lab ofCombined Multi-organ Transplantation Ministry of Public HealthFirst Affiliated Hospital Medical College Zhejiang University310003 Hangzhou China

Background Although the use of hepatitis B immunoglobulin （HBIG） may lead to a significant reduction in recurrent hepatitis B virus （HBV） infection and improve the survival of patients who have undergone liver transplantation （LT） for hepatitis B-related diseases, the recurrence of the disease still remains at a lower level. Different clinical curative effects were observed in patients with the same HBV-related diseases and the same therapy. This study was undertaken to investigate whether the efficacy of HBIG is associated with FCGR3A gene polymorphisms in Chinese liver transplant patients. Methods Altogether 77 patients who had received liver transplantation for hepatitis B-related diseases with more than one-year survival after surgery were studied. The recurrence of HBV was characterized by the appearance of HBsAg in serum after the operation. The FCGR3A genotyping was performed using genomic DNA sequencing （ABI 3037）. Single nucleotide polymorphism at nucleotide 559 was detected by Polyphred. Results Of the 77 patients, 14 were complicated with HBV recurrence post-transplant. The FCGR3A at nucleotide 559 TT was observed in 35 （45.5%0） subjects, whereas TG in 31（40.3%） and GG in 11（14.3%）. In the 559G carrier group （n=42, 54.5%）, the risk of HBV recurrence was 9.5%, and 1- and 2-year recurrence-free survival rates were 95.2% and 88.7%, respectively. In the 559G noncarrier group （n=35, 45.5%）, the risk of HBV recurrence was 28.6%, and 1- and 2-year recurrence-free survival rates were 74.3% and 69.3%, respectively. The risk of HBV recurrence and the recurrence-free survival rate were both statistically different between the 559G carrier and noncarrier groups （P〈0.05）. Conclusions A single nucleotide polymorphism （T/G） at position 559 of the FCGR3A gene was found in Chinese patients. The efficacy of HBIG in prophylaxis of HBV recurrence after LT is associated with the gene polymorphism, so detectina FCGR3A aenotypes can be a clinical reference, of the HBIG

关键词： Fc gamma RIII polymorphism immunoglobulin hepatitis B recurrence

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Prognostic implication of early posttransplant hypercholesterolemia in liver transplantation for patients with hepatocellular carcinoma

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hepatobiliary & pancreatic Diseases International 2023年第3期22卷 228-238页

作者： Rong-Li Wei Guang-Han Fan Chen-Zhi Zhang Kang-Chen Chen Wen-Hui Zhang Chang-Biao Li Si-Yi Dong Jun-Li Chen Sun-Bin Ling Shu-Sen Zheng Xiao Xu Department of hepatobiliary and pancreatic surgery The Center for Integrated Oncology and Precision MedicineAffiliated Hangzhou First People’s HospitalZhejiang University School of MedicineHangzhou 310006China Department of hepatobiliary and pancreatic surgery The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Institute of organ transplantation Zhejiang UniversityHangzhou 310003China National Center for Healthcare Quality Management in Liver Transplant Hangzhou 310003China Department of hepatobiliary and pancreatic surgery Shulan(Hangzhou)HospitalHangzhou 310022China

Background: Hyperlipidemia is a common complication after liver transplantation(LT) and develops mostly in the early posttransplant period. Recently, some studies have reported a positive correlation between hyperlipidemia and favorable prognosis in patients with hepatocellular carcinoma(HCC) undergoing hepatectomy. This study aimed to evaluate the possibility of predicting prognosis in HCC patients receiving LT by early posttransplant dyslipidemia. Methods: From January 2015 to December 2017, a total of 806 HCC patients from China Liver Transplant Registry database were retrospectively enrolled. The prognostic relevance of early posttransplant hypertriglyceridemia or hypercholesterolemia was examined using survival analysis, and subgroup analysis was implemented based on LT criteria. Results: Early posttransplant hypercholesterolemia(EPHC) was independently inversely associated with the risk of recurrence [hazard ratio(HR) = 0.630;P = 0.022], but was not significantly correlated with the mortality. However, early posttransplant hypertriglyceridemia was not related to prognosis. Intriguingly, with further classification, we found that borderline EPHC(B-EPHC), instead of significant EPHC, was a predictor of lower risk for both recurrence(HR = 0.504;P = 0.006) and mortality(HR = 0.511;P = 0.023). Compared with non-EPHC patients, B-EPHC patients achieved significantly superior 1-year and 3-year tumor-free survival(89.6% and 83.7% vs. 83.8% and 72.7% respectively;P = 0.023), and 1-year and 3-year overall survival(95.8% and 84.8% vs. 94.6% and 77.6% respectively;P = 0.039). In the subgroup analysis, BEPHC remained an independent predictor of better prognosis in patients beyond Milan criteria and those within Hangzhou criteria;whereas there was no significant relationship between B-EPHC and prognosis in patients within Milan criteria and those beyond Hangzhou criteria. More interestingly, patients beyond Milan criteria but within Hangzhou criteria were identified as the c

关键词： Liver transplantation Hepatocellular carcinoma Hypercholesterolemia Prognosis

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SNHG16 promotes hepatocellular carcinoma development via activating ECM receptor interaction pathway

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hepatobiliary & pancreatic Diseases International 2022年第1期21卷 41-49页

作者： Qi-Jun Zhang Da-Zhi Li Bing-Yi Lin Lei Geng Zhe Yang Shu-Seng Zheng Department of Thyroid surgery The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China NHC key laboratory of Combined Multi-organ transplantation The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of hepatobiliary and pancreatic surgery Shulan(Hangzhou)HospitalZhejiang Shuren University School of MedicineHangzhou 310000China

Background:Accumulating data have suggested that long non-coding RNAs(lncRNAs)play important roles in regulating tumor cell *** study was designed to investigate the role of SNHG16 in hep-atocellular carcinoma(HCC).Methods:SNHG16 expression was detected with real-time polymerase chain reaction(PCR).The cut-offvalue of SNHG16 for tumor-free survival(TFS)was determined with receiver operating characteristic curve *** interfering RNA was used to inhibit the expression of SNHG16 in HCC cell *** biologic behavior of HCC cell was determined with cell viability assay and Transwell assay in *** potential predictive value of SNHG16 on prognosis was analyzed by Kaplan-Meier curves and Cox proportional hazards regression ***:SNHG16 expression was upregulated in tumor tissues and HCC cell *** expression of SNHG16 was associated with tumor recurrence and poor prognosis after *** analysis revealed that SNHG16 was an independent prognostic factor for poor recurrence-free ***,inhibition of SNHG16 in HepG2,Hep3B,and BEL-7402 cells significantly reduced cell invasiveness and *** analyses indicated that the ECM-receptor interaction pathway was remarkably activated by ***:SNHG16 might be a promising biomarker for predicting tumor recurrence in HCC patients after surgery and a potential therapeutic target for HCC.

关键词： Hepatocellular carcinoma SNHG16 ECM-receptor interaction pathway Long non-coding RNA

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Expert consensus on management of metabolic disease in Chinese liver transplant recipients

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World Journal of Gastroenterology 2020年第27期26卷 3851-3864页

作者： Tian Shen Li Zhuang Xiao-Dong Sun Xiao-Sheng Qi Zhi-Hui Wang Rui-Dong Li Wen-Xiu Chang Jia-Yin Yang Yang Yang Shu-Sen Zheng Xiao Xu Department of hepatobiliary and pancreatic surgery The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina Department of hepatobiliary and pancreatic surgery Shulan(Hangzhou)HospitalHangzhou 310003Zhejiang ProvinceChina Department of hepatobiliary and Pancreas surgery The First HospitalJilin UniversityChangchun 130021Jilin ProvinceChina Department of General surgery Shanghai First People's HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200080China Department of hepatobiliary and pancreatic surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina Department of General surgery and Liver Transplant Center Huashan HospitalFudan UniversityShanghai 200040China Department of Nephrology Tianjin First Center HospitalTianjin 300384China Department of Liver surgery and Liver transplantation Center West China Hospital of Sichuan UniversityChengdu 610041Sichuan ProvinceChina Department of Hepatic surgery and Liver transplantation Center The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630Guangdong ProvinceChina

Metabolic disease,including diabetes mellitus,hypertension,dyslipidemia,obesity,and hyperuricemia,is a common complication after liver transplantation and a risk factor for cardiovascular disease and *** development of metabolic disease is closely related to the side effects of ***,optimization of the immunosuppressive regimen is very important for the prevention and treatment of metabolic *** Chinese Society of organ transplantation has developed an expert consensus on the management of metabolic diseases in Chinese liver transplant recipients based on recent *** is placed on the risk factors of metabolic diseases,the effect of immunosuppressants on metabolic disease,and the prevention and treatment of metabolic diseases.

关键词： Liver transplantation Metabolic disease Diabetes mellitus Hypertension Dyslipidemia Hyperuricemia Obesity Immunosuppressive agents Consensus

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