AIM: To investigate the expression of programmed death (PD)-1,PD ligand 1 (PD-L1) and PD-L2 in liver tissues in the context of chronic hepatitis and hepatocellular carcinoma (HCC).METHODS: Liver biopsies and HCC speci...AIM: To investigate the expression of programmed death (PD)-1,PD ligand 1 (PD-L1) and PD-L2 in liver tissues in the context of chronic hepatitis and hepatocellular carcinoma (HCC).METHODS: Liver biopsies and HCC specimens from patients were collected and histologically examined.The expression of PD-1,PD-L1,and PD-L2 in biopsy specimens of chronic hepatitis and HCC specimens was evaluated by immunohistochemical staining.The association between the expression level of PD-1,PD-L1,and PD-L2 and clinical and pathological variables was analyzed statistically.RESULTS: Expression of PD-1 was found in liverinfiltrating lymphocytes.In contrast,PD-L1 and PD-L2 were expressed in non-parenchyma liver cells and tumor cells.The expression of PD-L1 was significantly correlated with hepatitis B virus infection (1.42 ± 1.165 vs 0.50 ± 0.756,P = 0.047) and with the stage of HCC (7.50 ± 2.121 vs 1.75 ± 1.500 vs 3.00 ± 0.001,P = 0.018).PD-1 and PD-Ls were significantly up-regulated in HCC specimens (1.40 ± 1.536 vs 5.71 ± 4.051,P = 0.000;1.05 ± 1.099 vs 4.29 ± 3.885,P = 0.004;1.80 ± 1.473 vs 3.81 ± 3.400,P = 0.020).CONCLUSION: PD-L1 may contribute to negative regulation of the immune response in chronic hepatitis B.PD-1 and PD-Ls may play a role in immune evasion of tumors.展开更多
This study was conducted to compare the feasibility,safety and effectiveness of the combined-laparoscopic splenectomy and esophagogastric devascularization(C-LSED)with open splenectomy and esophagogastric devasculariz...This study was conducted to compare the feasibility,safety and effectiveness of the combined-laparoscopic splenectomy and esophagogastric devascularization(C-LSED)with open splenectomy and esophagogastric devascularization surgery(OSED)in patients with portal hypertension due to liver cirrhosis.From February 2014 to June 2018,68 patients with portal hypertension were diagnosed as having serious gastroesophageal varices and/or hypersplenism in our center.Thirty patients underwent C-LSED and 38 patients received OSED.Results and outcomes were compared retrospectively.No patients of C-LSED group required an intraoperative conversion to open surgery.Significantly shorter operating time,less blood loss,lower transfusion rates,shorter postoperative hospital stay,lower rates of complications were found in C-LSED group than in C-LSED group(P<0.05).No death and rebleeding were documented in both groups during the follow-up periods of one year Postoperative endoscopy revealed that varices in the patients of both groups were alleviated significantly from severe to mild,and in a part of cases,the varices disappeared.The final results suggest that the C-LSED technique is superior to open procedure,due to slightly invasive,simplified operative procedure,significantly shorter operating time,less intraoperative bleeding and lower post-operative complication rates.And C-LSED offers comparable long-term effects to open surgery.展开更多
AIM： To investigate the effect of bromocripUne （BCT） and tumor necrosis factor-α ClNF-α） on hepatocellular carcinoma （HCC） multidrug resistance （MDR） in nude mouse HDR model of liver neoplasm. METHODS： Huma...AIM： To investigate the effect of bromocripUne （BCT） and tumor necrosis factor-α ClNF-α） on hepatocellular carcinoma （HCC） multidrug resistance （MDR） in nude mouse HDR model of liver neoplasm. METHODS： Human hepatocarcinoma cell line HepG2t drug resistant hepatocarcinoma cell line HepG2/adriamycin （ADM） and hepatocarcinoma cell line transfected with TNF-α gene HepG2JADM/TNF were injected into the liver of nude mice via orthotopic implantation and MDR model of liver neoplasm in vivo was established （HepG2t ADM, TNF, BCT groups）. Among these groups, BCT group and TNF group were treated with BCT through gastric canal. Each group was divided into control group and chemotherapy group. Size and weight of the tumor were measured. Furthermore, tumor his^logical character and growth of the nude mice were observed and their chemosensitivity was tested. MDR-associated genes and proteins （MRP, LRP） of implanted tumors were detected by immunohistochemistry, reverse transcriptase polymerase chain reaction, and apoptosis rate of hepatocarcinoma cells was detected by TUNEL assay. RESULTS： The nude mouse model of each cell line was inoculated successfully. The tumor growth rate and weight were significantly different among groups. After chemotherapy, abdominal cavity tumor growth inhibition rate was higher in BCT group （67%） compared to ADM and TNF groups, and similar to HepG2group （54%）. MDRI and LRPmRNA could be detected in all groups, but TNF-α was detected only in TNF and BCT groups. Furthermore, MDR1 and LRP protein expression of tumors in TNF and BCT groups was low similar to HepG2 group. The apoptosis rate of hepatocarcinoma cells was much higher in BCT group than in other groups with TUNEL assay. CONCLUSION： BCT and TNF-a can reverse HCC MDR in nude mouse MDR1 model of liver neoplasm. 2005 The WJG Press and Elsevier Inc. All rights reserved展开更多
Cholangiocarcinoma refers to malignant tumors that develop in epithelial lining of biliary system, and it is divided into two categories according to tumor location, intrahepatic cholangiocarcinoma （ICC） and extrahe...Cholangiocarcinoma refers to malignant tumors that develop in epithelial lining of biliary system, and it is divided into two categories according to tumor location, intrahepatic cholangiocarcinoma （ICC） and extrahepatic cholangiocarcinoma （ECC）. ICC occurs from the epithelial cells of the intrahepatic bile duct, its branches and interlobular biliary tree; and ECC is divided into hilar cholangiocarcinoma and distal cholangiocarcinoma by the circumscription at the confluence of cystic duct and the common hepatic duct.展开更多
Background:Adequate evaluation of degrees of liver cirrhosis is essential in surgical treatment of hepatocellular carcinoma(HCC)patients.The impact of the degrees of cirrhosis on prediction of post-hepatectomy liver f...Background:Adequate evaluation of degrees of liver cirrhosis is essential in surgical treatment of hepatocellular carcinoma(HCC)patients.The impact of the degrees of cirrhosis on prediction of post-hepatectomy liver failure(PHLF)remains poorly defined.This study aimed to construct and validate a combined pre-and intra-operative nomogram based on the degrees of cirrhosis in predicting PHLF in HCC patients using prospective multi-center’s data.Methods:Consecutive HCC patients who underwent hepatectomy between May 18,2019 and Dec 19,2020 were enrolled at five tertiary hospitals.Preoperative cirrhotic severity scoring(CSS)and intra-operative direct liver stiffness measurement(DSM)were performed to correlate with the Laennec histopathological grading system.The performances of the pre-operative nomogram and combined pre-and intra-operative nomogram in predicting PHLF were compared with conventional predictive models of PHLF.Results:For 327 patients in this study,histopathological studies showed the rates of HCC patients with no,mild,moderate,and severe cirrhosis were 41.9%,29.1%,22.9%,and 6.1%,respectively.Either CSS or DSM was closely correlated with histopathological stages of cirrhosis.Thirty-three(10.1%)patients developed PHLF.The 30-and 90-day mortality rates were 0.9%.Multivariate regression analysis showed four pre-operative variables[HBV-DNA level,ICG-R15,prothrombin time(PT),and CSS],and one intra-operative variable(DSM)to be independent risk factors of PHLF.The pre-operative nomogram was constructed based on these four pre-operative variables together with total bilirubin.The combined pre-and intra-operative nomogram was constructed by adding the intra-operative DSM.The pre-operative nomogram was better than the conventional models in predicting PHLF.The prediction was further improved with the combined pre-and intra-operative nomogram.Conclusions:The combined pre-and intra-operative nomogram further improved prediction of PHLF when compared with the pre-operative nomogram.展开更多
Background:We aim to investigate the prevalence,patterns,risk factors,and outcomes of peritoneal metastases(PM)after curative laparoscopic hepatectomy(LH)for hepatocellular carcinoma(HCC).Methods:A multicenter cohort ...Background:We aim to investigate the prevalence,patterns,risk factors,and outcomes of peritoneal metastases(PM)after curative laparoscopic hepatectomy(LH)for hepatocellular carcinoma(HCC).Methods:A multicenter cohort of 2,138 HCC patients who underwent curative LH from August 2010 to December 2016 from seven hospitals in China was retrospectively analyzed.The incidence of PM following LH was evaluated and compared with that in open hepatectomy(OH)after 1:1 propensity score matching(PSM).Results:PM prevalence was 5.1%(15/295)in the early period[2010-2013],2.6%(47/1,843)in the later period[2014-2016],and 2.9%(62/2,138)in all LH patients,which was similar to 4.0%(59/1,490)in the OH patients.The recurrence patterns,timing,and treatment did not significantly vary between the LH and OH patients(P>0.05).Multivariate logistic regression revealed that tumor diameter>5 cm,non-anatomical resection,presence of microvascular invasion,and lesions<2 cm from major blood vessels were independent risk factors of PM after LH.Of the 62 cases with PM,26(41.9%)had PM only,34(54.9%)had intrahepatic recurrence(IHR)and PM,and 2(3.2%)had synchronous extraperitoneal metastases(EPM).Patients with resectable PM had a 5-year overall survival(OS)of 65.0%compared to 9.0%for unresectable PM(P=0.001).Conclusions:The prevalence,patterns and independent risk factors of PM were identified for HCC patients after LH.LH was not associated with increased incidence of PM in HCC patients for experienced surgeons.Surgical re-excision of PM was associated with prolonged survival.展开更多
The rising global prevalence of metabolic diseases has increased the prevalence of non-alcoholic fatty liver disease(NAFLD),leading to an increase in cases of NAFLD-related hepatocellular carcinoma(HCC).To provide an ...The rising global prevalence of metabolic diseases has increased the prevalence of non-alcoholic fatty liver disease(NAFLD),leading to an increase in cases of NAFLD-related hepatocellular carcinoma(HCC).To provide an updated literature review detailing epidemiology,risk factors,pathogenic pathways,and treatment strategies linked to NAFLD-related HCC,we conducted a literature search on PubMed from its inception to December 31,2021.About 25%of the global population suffers from NAFLD.The annual incidence of HCC among NAFLD patients is approximately 1.8 per 1,000 person-years.Older age,male sex,metabolic comorbidities,unhealthy lifestyle habits(such as smoking and alcohol consumption),physical inactivity,genetic susceptibility,liver fibrosis,and degree of cirrhosis in NAFLD patients are important risk factors for NAFLD-related HCC.Therefore,low-calorie diet,moderate-intensity exercise,treatment of metabolic comorbidities,and cessation of smoking and alcohol are the main measures to prevent NAFLD-related HCC.In addition,all patients with advanced NAFLD-related fibrosis or cirrhosis should be screened for HCC.Immune suppression disorders and changes in the liver microenvironment may be the main pathogenesis of NAFLD-related HCC.Hepatic resection,liver transplantation,ablation,transarterial chemoembolization,radiotherapy,targeted drugs,and immune checkpoint inhibitors are used to treat NAFLD-related HCC.Lenvatinib treatment may lead to better overall survival,while immune checkpoint inhibitors may lead to worse overall survival.Given the specific risk factors for NAFLD-related HCC,primary prevention is key.Moreover,the same treatment may differ substantially in efficacy against NAFLD-related HCC than against HCC of other etiologies.展开更多
基金Supported by Grants from the National Mega Research Program of China,No.2008ZX10002-011the National Key Basic Research Program of China,No.2001CB510008,2005CB522901,2007CB512804 and 2009CB522500the Deutsche Forschun-gsgemeinschaft (SFB/Transregio 60)
文摘AIM: To investigate the expression of programmed death (PD)-1,PD ligand 1 (PD-L1) and PD-L2 in liver tissues in the context of chronic hepatitis and hepatocellular carcinoma (HCC).METHODS: Liver biopsies and HCC specimens from patients were collected and histologically examined.The expression of PD-1,PD-L1,and PD-L2 in biopsy specimens of chronic hepatitis and HCC specimens was evaluated by immunohistochemical staining.The association between the expression level of PD-1,PD-L1,and PD-L2 and clinical and pathological variables was analyzed statistically.RESULTS: Expression of PD-1 was found in liverinfiltrating lymphocytes.In contrast,PD-L1 and PD-L2 were expressed in non-parenchyma liver cells and tumor cells.The expression of PD-L1 was significantly correlated with hepatitis B virus infection (1.42 ± 1.165 vs 0.50 ± 0.756,P = 0.047) and with the stage of HCC (7.50 ± 2.121 vs 1.75 ± 1.500 vs 3.00 ± 0.001,P = 0.018).PD-1 and PD-Ls were significantly up-regulated in HCC specimens (1.40 ± 1.536 vs 5.71 ± 4.051,P = 0.000;1.05 ± 1.099 vs 4.29 ± 3.885,P = 0.004;1.80 ± 1.473 vs 3.81 ± 3.400,P = 0.020).CONCLUSION: PD-L1 may contribute to negative regulation of the immune response in chronic hepatitis B.PD-1 and PD-Ls may play a role in immune evasion of tumors.
基金grants from Liver Surgery Medical Research Center Project in Hubei Province and China National Key Projects for Infectious Diseases(No.2008ZX10002-025).
文摘This study was conducted to compare the feasibility,safety and effectiveness of the combined-laparoscopic splenectomy and esophagogastric devascularization(C-LSED)with open splenectomy and esophagogastric devascularization surgery(OSED)in patients with portal hypertension due to liver cirrhosis.From February 2014 to June 2018,68 patients with portal hypertension were diagnosed as having serious gastroesophageal varices and/or hypersplenism in our center.Thirty patients underwent C-LSED and 38 patients received OSED.Results and outcomes were compared retrospectively.No patients of C-LSED group required an intraoperative conversion to open surgery.Significantly shorter operating time,less blood loss,lower transfusion rates,shorter postoperative hospital stay,lower rates of complications were found in C-LSED group than in C-LSED group(P<0.05).No death and rebleeding were documented in both groups during the follow-up periods of one year Postoperative endoscopy revealed that varices in the patients of both groups were alleviated significantly from severe to mild,and in a part of cases,the varices disappeared.The final results suggest that the C-LSED technique is superior to open procedure,due to slightly invasive,simplified operative procedure,significantly shorter operating time,less intraoperative bleeding and lower post-operative complication rates.And C-LSED offers comparable long-term effects to open surgery.
基金Supported by the Clinical Key Program Point Subject Foundation of Ministry of Public Health, No. 2001-2003
文摘AIM： To investigate the effect of bromocripUne （BCT） and tumor necrosis factor-α ClNF-α） on hepatocellular carcinoma （HCC） multidrug resistance （MDR） in nude mouse HDR model of liver neoplasm. METHODS： Human hepatocarcinoma cell line HepG2t drug resistant hepatocarcinoma cell line HepG2/adriamycin （ADM） and hepatocarcinoma cell line transfected with TNF-α gene HepG2JADM/TNF were injected into the liver of nude mice via orthotopic implantation and MDR model of liver neoplasm in vivo was established （HepG2t ADM, TNF, BCT groups）. Among these groups, BCT group and TNF group were treated with BCT through gastric canal. Each group was divided into control group and chemotherapy group. Size and weight of the tumor were measured. Furthermore, tumor his^logical character and growth of the nude mice were observed and their chemosensitivity was tested. MDR-associated genes and proteins （MRP, LRP） of implanted tumors were detected by immunohistochemistry, reverse transcriptase polymerase chain reaction, and apoptosis rate of hepatocarcinoma cells was detected by TUNEL assay. RESULTS： The nude mouse model of each cell line was inoculated successfully. The tumor growth rate and weight were significantly different among groups. After chemotherapy, abdominal cavity tumor growth inhibition rate was higher in BCT group （67%） compared to ADM and TNF groups, and similar to HepG2group （54%）. MDRI and LRPmRNA could be detected in all groups, but TNF-α was detected only in TNF and BCT groups. Furthermore, MDR1 and LRP protein expression of tumors in TNF and BCT groups was low similar to HepG2 group. The apoptosis rate of hepatocarcinoma cells was much higher in BCT group than in other groups with TUNEL assay. CONCLUSION： BCT and TNF-a can reverse HCC MDR in nude mouse MDR1 model of liver neoplasm. 2005 The WJG Press and Elsevier Inc. All rights reserved
文摘Cholangiocarcinoma refers to malignant tumors that develop in epithelial lining of biliary system, and it is divided into two categories according to tumor location, intrahepatic cholangiocarcinoma （ICC） and extrahepatic cholangiocarcinoma （ECC）. ICC occurs from the epithelial cells of the intrahepatic bile duct, its branches and interlobular biliary tree; and ECC is divided into hilar cholangiocarcinoma and distal cholangiocarcinoma by the circumscription at the confluence of cystic duct and the common hepatic duct.
基金supported by the grants from the Major Special Science and Technology Project of Hubei Province(grant number 2021BCA115)the National Science and Technology Major Project of China(grant number 2017ZX10203207-002)to Z.Y.H.+2 种基金the grants from the Project of Science and Technology in Hubei Province(grant number 2018ACA137)General Project of Health Commission of Hubei Province(grant number WJ2021M108)to X.P.C.the grant from National Natural Science Foundation of China(No.81902839)to E.L.Z.
文摘Background:Adequate evaluation of degrees of liver cirrhosis is essential in surgical treatment of hepatocellular carcinoma(HCC)patients.The impact of the degrees of cirrhosis on prediction of post-hepatectomy liver failure(PHLF)remains poorly defined.This study aimed to construct and validate a combined pre-and intra-operative nomogram based on the degrees of cirrhosis in predicting PHLF in HCC patients using prospective multi-center’s data.Methods:Consecutive HCC patients who underwent hepatectomy between May 18,2019 and Dec 19,2020 were enrolled at five tertiary hospitals.Preoperative cirrhotic severity scoring(CSS)and intra-operative direct liver stiffness measurement(DSM)were performed to correlate with the Laennec histopathological grading system.The performances of the pre-operative nomogram and combined pre-and intra-operative nomogram in predicting PHLF were compared with conventional predictive models of PHLF.Results:For 327 patients in this study,histopathological studies showed the rates of HCC patients with no,mild,moderate,and severe cirrhosis were 41.9%,29.1%,22.9%,and 6.1%,respectively.Either CSS or DSM was closely correlated with histopathological stages of cirrhosis.Thirty-three(10.1%)patients developed PHLF.The 30-and 90-day mortality rates were 0.9%.Multivariate regression analysis showed four pre-operative variables[HBV-DNA level,ICG-R15,prothrombin time(PT),and CSS],and one intra-operative variable(DSM)to be independent risk factors of PHLF.The pre-operative nomogram was constructed based on these four pre-operative variables together with total bilirubin.The combined pre-and intra-operative nomogram was constructed by adding the intra-operative DSM.The pre-operative nomogram was better than the conventional models in predicting PHLF.The prediction was further improved with the combined pre-and intra-operative nomogram.Conclusions:The combined pre-and intra-operative nomogram further improved prediction of PHLF when compared with the pre-operative nomogram.
基金supported by grants from National Natural Science Foundation of China(Nos.81874149,82003403).
文摘Background:We aim to investigate the prevalence,patterns,risk factors,and outcomes of peritoneal metastases(PM)after curative laparoscopic hepatectomy(LH)for hepatocellular carcinoma(HCC).Methods:A multicenter cohort of 2,138 HCC patients who underwent curative LH from August 2010 to December 2016 from seven hospitals in China was retrospectively analyzed.The incidence of PM following LH was evaluated and compared with that in open hepatectomy(OH)after 1:1 propensity score matching(PSM).Results:PM prevalence was 5.1%(15/295)in the early period[2010-2013],2.6%(47/1,843)in the later period[2014-2016],and 2.9%(62/2,138)in all LH patients,which was similar to 4.0%(59/1,490)in the OH patients.The recurrence patterns,timing,and treatment did not significantly vary between the LH and OH patients(P>0.05).Multivariate logistic regression revealed that tumor diameter>5 cm,non-anatomical resection,presence of microvascular invasion,and lesions<2 cm from major blood vessels were independent risk factors of PM after LH.Of the 62 cases with PM,26(41.9%)had PM only,34(54.9%)had intrahepatic recurrence(IHR)and PM,and 2(3.2%)had synchronous extraperitoneal metastases(EPM).Patients with resectable PM had a 5-year overall survival(OS)of 65.0%compared to 9.0%for unresectable PM(P=0.001).Conclusions:The prevalence,patterns and independent risk factors of PM were identified for HCC patients after LH.LH was not associated with increased incidence of PM in HCC patients for experienced surgeons.Surgical re-excision of PM was associated with prolonged survival.
基金supported by the Specific Research Pro-ject of Guangxi for Research Bases and Talents(GuiKe AD22035057)the Natural Science Foundation of Guangxi Province(2020GXNSFAA159022)+2 种基金Bagui Scholars Programs of Guangxi Zhuang Autonomous Region(2019AQ20)the National Natural Science Foundation of China(82060510)Guangxi Undergraduate Training Program for Innovation and Entrepreneurship(202110598178 and 202110598073).
文摘The rising global prevalence of metabolic diseases has increased the prevalence of non-alcoholic fatty liver disease(NAFLD),leading to an increase in cases of NAFLD-related hepatocellular carcinoma(HCC).To provide an updated literature review detailing epidemiology,risk factors,pathogenic pathways,and treatment strategies linked to NAFLD-related HCC,we conducted a literature search on PubMed from its inception to December 31,2021.About 25%of the global population suffers from NAFLD.The annual incidence of HCC among NAFLD patients is approximately 1.8 per 1,000 person-years.Older age,male sex,metabolic comorbidities,unhealthy lifestyle habits(such as smoking and alcohol consumption),physical inactivity,genetic susceptibility,liver fibrosis,and degree of cirrhosis in NAFLD patients are important risk factors for NAFLD-related HCC.Therefore,low-calorie diet,moderate-intensity exercise,treatment of metabolic comorbidities,and cessation of smoking and alcohol are the main measures to prevent NAFLD-related HCC.In addition,all patients with advanced NAFLD-related fibrosis or cirrhosis should be screened for HCC.Immune suppression disorders and changes in the liver microenvironment may be the main pathogenesis of NAFLD-related HCC.Hepatic resection,liver transplantation,ablation,transarterial chemoembolization,radiotherapy,targeted drugs,and immune checkpoint inhibitors are used to treat NAFLD-related HCC.Lenvatinib treatment may lead to better overall survival,while immune checkpoint inhibitors may lead to worse overall survival.Given the specific risk factors for NAFLD-related HCC,primary prevention is key.Moreover,the same treatment may differ substantially in efficacy against NAFLD-related HCC than against HCC of other etiologies.
