Background:The survival benefit of postoperative adjuvant transcatheter arterial chemoembolization(PA-TACE)remained controversial.We aimed to investigate the prognosis effect of PA-TACE on the Barcelona Clinic Liver C...Background:The survival benefit of postoperative adjuvant transcatheter arterial chemoembolization(PA-TACE)remained controversial.We aimed to investigate the prognosis effect of PA-TACE on the Barcelona Clinic Liver Cancer(BCLC)early stage multinodular hepatocellular carcinoma(MHCC)patients with/without microvascular invasion(MVI).Methods:Two hundred and seventy-one patients from January 2010 to December 2014 undergoing curative hepatectomy were included in this study.Disease-free survival(DFS)rates and overall survival(OS)rates as well as prognostic factors were analyzed by the Kaplan-Meier method,the log-rank test and the Cox proportional hazard model.Results:Thirty-four point four percent(44/128)MVI positive and 55.2%(79/143)MVI negative patients underwent PA-TACE.Multivariate analysis revealed that HBV DNA load>103 copy/Ml,>three tumors,MVI,and without PA-TACE were independent risk factors for poor DFS.Higher alkaline phosphatase(ALP),three tumors,MVI,and without PA-TACE were independent risk factors for poor OS.Both DFS and OS were significantly improved in patients with MVI who received PA-TACE as compared to those who underwent hepatic resection alone(5-year DFS,26.3%vs.20.7%,P=0.038;5-year OS,73.6%vs.47.7%,P=0.005).No differences were noted in DFS and OS among MVI negative patients with or without PA-TACE(5-year DFS,33.7%vs.33.0%,P=0.471;5-year OS,84.1%vs.80.3%,P=0.523).Early recurrence was more likely to occur in patients without PA-TACE(P=0.001).Conclusions:PA-TACE was a safe intervention and could effectively prevent tumor recurrence and improve the survival of the BCLC early stage MHCC patients with MVI.展开更多
Background:To study the influence of pathological responses(PR)after transcatheter arterial chemoembolization(TACE)on incidences of microvascular invasion(MVI)and early recurrence in hepatocellular carcinoma(HCC)patie...Background:To study the influence of pathological responses(PR)after transcatheter arterial chemoembolization(TACE)on incidences of microvascular invasion(MVI)and early recurrence in hepatocellular carcinoma(HCC)patients.Methods:Between 2013 to 2015,consecutive HCC patients who underwent liver resection with“curative”intent at three hospitals were enrolled in this study.Patients with different areas of PR after preoperative TACE were compared with those without preoperative TACE on the incidences of MVI,early recurrence rates and patterns of recurrence before and after propensity score matching(PSM).Results:Of 1,970 patients,737 patients who received preoperative TACE were divided into three groups according to the areas of PR:≥90%(n=226),60-90%(n=447),and<60%(n=64).PR≥90%was an independent protective factor of incidences of MVI[odds ratio(OR),0.144;95%confidence interval(CI),0.082-0.245,P<0.001)and early recurrence(HR,0.742;95%CI,0.561-0.963,P=0.032);while PR<60%was an independent risk factor of incidences of MVI(OR,6.076;95%CI,3.004-11.728,P<0.001)and early recurrence(HR,1.428;95%CI,1.095-1.929;P=0.009).Furthermore,patients with PR<60%were significantly more likely to develop multiple intrahepatic recurrences involving multiple hepatic segments when compared with patients without preoperative TACE.Conclusions:This study indicated the area of PR after TACE was closely associated with the incidences of MVI and early tumor recurrence.Patients with PR<60%were at significantly higher risks of having more MVI,early and multiple tumor recurrences.展开更多
Aim:Genetic polymorphisms of human leukocyte antigen(HLA)class II molecules are associated with chronic hepatitis B virus(HBV)infection.We aimed to investigate the impacts of HLA-II haplotypes on viral evolution and t...Aim:Genetic polymorphisms of human leukocyte antigen(HLA)class II molecules are associated with chronic hepatitis B virus(HBV)infection.We aimed to investigate the impacts of HLA-II haplotypes on viral evolution and the risks of HBV-caused liver diseases.Methods:HLA-DR-DQ-DP haplotypes were estimated in 1210 healthy controls,296 HBV clearance subjects,301 asymptomatic hepatitis B surface antigen carriers,770 chronic hepatitis B patients,443 HBV-related liver cirrhosis(LC)patients,and 1037 HBV-related hepatocellular carcinoma(HCC)patients.HBV mutations were determined by sequencing.The associations of HLA-DR-DQ-DP haplotypes with viral mutations and the risks of liver diseases were assessed by multivariate logistic regression.Results:Compared to HBV-free subjects,the haplotypes CCAACG,CCGACG,TCAATA,and TCGATA were associated with decreased HCC risk,with an odds ratio(OR)[95%confidence interval(CI)]of 0.62(0.40-0.95),0.60(0.39-0.92),0.73(0.54-0.98),and 0.58(0.42-0.78),respectively.CCAACG,CCGACG,and TCAATA were significantly associated with decreased frequencies of the HCC-risk HBV mutations:preS1 deletion,APOBECsignature HBV mutations in the core promoter and preS regions,A51C/T,G104C/T,and G146C/T.TCGATA and TTAACG were associated with increased LC risk,with an OR(95%CI)of 1.54(1.03-2.30)and 2.23(1.50-3.33),respectively.However,TCGATA and TTAACG were not consistently associated with the cirrhosis-risk HBV mutations.Conclusion:CCAACG,CCGACG,and TCAATA are inversely associated with HCC risk,possibly because they are involved in creating an immune microenvironment attenuating the generation of HCC-risk HBV mutations.TCGATA and TTAACG might predispose the polarity of immunity towards Th17 isotype related to LC.展开更多
Intrahepatic cholangiocarcinoma(ICC)is the second most common liver cancer.Chemotherapy remains the main therapeutic strategy for advanced ICC patients,but chemosensitivity varies individually.Here,we applied cytometr...Intrahepatic cholangiocarcinoma(ICC)is the second most common liver cancer.Chemotherapy remains the main therapeutic strategy for advanced ICC patients,but chemosensitivity varies individually.Here,we applied cytometry by time-of-flight(CyTOF)to establish the immune profile of peripheral blood mononuclear cells(PBMCs)on the single-cell level at indicated time points before,during,and after chemotherapy.Multiplex immunofluorescence staining was applied to examine the spatial distribution of certain immune clusters.Tissue microarrays(TMAs)were used for prognostic evaluation.A total of 20 ICC patients treated with gemcitabine(GEM)were enrolled in our study,including eight cases with good response(R)and 12 cases with non-response(NR).Tremendous changes in PBMC composition,including an increased level of CD4/CD8 double-positive T cells(DPT),were observed after chemotherapy.Patients with higher level of CD4^(+)CD45RO^(+)CXCR3^(+)T cells before treatment had a favorable response to chemotherapy.Our study identified a positive correlation between the percentage of T cell subpopulations and clinical response after chemotherapy,which suggests that it is practical to predict the potential response before treatment by evaluating the proportions of the cell population in PBMCs.展开更多
Background:For patients with a large but resectable solitary hepatocellular carcinoma(HCC)of>5 cm in diameter,it is often difficult to achieve a sufficient resection margin.There is still no study on whether a two-...Background:For patients with a large but resectable solitary hepatocellular carcinoma(HCC)of>5 cm in diameter,it is often difficult to achieve a sufficient resection margin.There is still no study on whether a two-stage hepatectomy to increase a narrow resection margin would be beneficial.Methods:From August 2014 to February 2017,patients with a large but resectable solitary HCC of>5 cm and a preoperative estimated resection margin of<1.0 cm were retrospectively studied.They were divided into one-and two-stage resection groups.A retrospective analysis was performed,followed by propensity score matching(PSM)analysis.Disease recurrence,survival,intraoperative and postoperative data were compared.Results:Before PSM,the 1-,2-,3-and 4-year recurrence-free survival rates for the one-and two-stage groups were 44.3%,31.7%,24.3%,19.2%versus 60.6%,45.4%,43.5%,32.3%,respectively(P=0.007).The corresponding OS rates were 61.0%,45.2%,43.8%,38.4%versus 69.6%,62.5%,60.7%,57.3%,respectively(P=0.029).After PSM,the 1-,2-,3-and 4-year recurrence-free survival rates for the one-and two-stage groups were 44.0%,31.5%,27.3%,21.0%versus 60.6%,45.4%,43.5%,32.3%,respectively(P=0.013).The corresponding OS rates were 62.5%,41.1%,41.1%,37.5%versus 69.6%,62.5%,60.7%,57.3%,respectively(P=0.038).Differences in the resection margins between the one-and two-stage groups before[0.3(0-0.5)versus 1.2(0.8-2.2)cm]and after[0.2(0-0.5)versus 1.2(0.8-2.2)cm]PSM were also significant.Conclusions:Two-stage hepatectomy allowed a wider resection margin for patients with a resectable but solitary HCC of>5 cm,and resulted in significantly better long-term survival outcomes after partial hepatectomy.展开更多
基金National Natural Science Foundation of China(grant No.81472278)Funds for Creative Research Groups of National Natural Science Foundation of China(grant No.81521091).
文摘Background:The survival benefit of postoperative adjuvant transcatheter arterial chemoembolization(PA-TACE)remained controversial.We aimed to investigate the prognosis effect of PA-TACE on the Barcelona Clinic Liver Cancer(BCLC)early stage multinodular hepatocellular carcinoma(MHCC)patients with/without microvascular invasion(MVI).Methods:Two hundred and seventy-one patients from January 2010 to December 2014 undergoing curative hepatectomy were included in this study.Disease-free survival(DFS)rates and overall survival(OS)rates as well as prognostic factors were analyzed by the Kaplan-Meier method,the log-rank test and the Cox proportional hazard model.Results:Thirty-four point four percent(44/128)MVI positive and 55.2%(79/143)MVI negative patients underwent PA-TACE.Multivariate analysis revealed that HBV DNA load>103 copy/Ml,>three tumors,MVI,and without PA-TACE were independent risk factors for poor DFS.Higher alkaline phosphatase(ALP),three tumors,MVI,and without PA-TACE were independent risk factors for poor OS.Both DFS and OS were significantly improved in patients with MVI who received PA-TACE as compared to those who underwent hepatic resection alone(5-year DFS,26.3%vs.20.7%,P=0.038;5-year OS,73.6%vs.47.7%,P=0.005).No differences were noted in DFS and OS among MVI negative patients with or without PA-TACE(5-year DFS,33.7%vs.33.0%,P=0.471;5-year OS,84.1%vs.80.3%,P=0.523).Early recurrence was more likely to occur in patients without PA-TACE(P=0.001).Conclusions:PA-TACE was a safe intervention and could effectively prevent tumor recurrence and improve the survival of the BCLC early stage MHCC patients with MVI.
基金the National Natural Science Foundation of China(U21A20376,82102871,81988101,81903184,81790633,and 81830054)the Innovation Program of Shanghai Municipal Education Commission(2019-01-07-00-07E00065)+1 种基金the National Science Foundation of Shanghai(21XD1404600,21JC1406600,and 22140901000)the China Postdoctoral Science Foundation(2020M671007).
基金the Institutional Ethics Committees of the Eastern Hepatobiliary Surgery Hospital,940 Hospital of PLA Joint Logistic Support Force,and Hai Nan Hospital of Chinese PLA General Hospital(No.EHBHKY2020-K-056)。
文摘Background:To study the influence of pathological responses(PR)after transcatheter arterial chemoembolization(TACE)on incidences of microvascular invasion(MVI)and early recurrence in hepatocellular carcinoma(HCC)patients.Methods:Between 2013 to 2015,consecutive HCC patients who underwent liver resection with“curative”intent at three hospitals were enrolled in this study.Patients with different areas of PR after preoperative TACE were compared with those without preoperative TACE on the incidences of MVI,early recurrence rates and patterns of recurrence before and after propensity score matching(PSM).Results:Of 1,970 patients,737 patients who received preoperative TACE were divided into three groups according to the areas of PR:≥90%(n=226),60-90%(n=447),and<60%(n=64).PR≥90%was an independent protective factor of incidences of MVI[odds ratio(OR),0.144;95%confidence interval(CI),0.082-0.245,P<0.001)and early recurrence(HR,0.742;95%CI,0.561-0.963,P=0.032);while PR<60%was an independent risk factor of incidences of MVI(OR,6.076;95%CI,3.004-11.728,P<0.001)and early recurrence(HR,1.428;95%CI,1.095-1.929;P=0.009).Furthermore,patients with PR<60%were significantly more likely to develop multiple intrahepatic recurrences involving multiple hepatic segments when compared with patients without preoperative TACE.Conclusions:This study indicated the area of PR after TACE was closely associated with the incidences of MVI and early tumor recurrence.Patients with PR<60%were at significantly higher risks of having more MVI,early and multiple tumor recurrences.
基金supported by the National Natural Science Foundation of China(91529305,81520108021,and 81673250 to GC)the National Key Basic Research Program of China(973 program)(2015CB554006 to GC).
文摘Aim:Genetic polymorphisms of human leukocyte antigen(HLA)class II molecules are associated with chronic hepatitis B virus(HBV)infection.We aimed to investigate the impacts of HLA-II haplotypes on viral evolution and the risks of HBV-caused liver diseases.Methods:HLA-DR-DQ-DP haplotypes were estimated in 1210 healthy controls,296 HBV clearance subjects,301 asymptomatic hepatitis B surface antigen carriers,770 chronic hepatitis B patients,443 HBV-related liver cirrhosis(LC)patients,and 1037 HBV-related hepatocellular carcinoma(HCC)patients.HBV mutations were determined by sequencing.The associations of HLA-DR-DQ-DP haplotypes with viral mutations and the risks of liver diseases were assessed by multivariate logistic regression.Results:Compared to HBV-free subjects,the haplotypes CCAACG,CCGACG,TCAATA,and TCGATA were associated with decreased HCC risk,with an odds ratio(OR)[95%confidence interval(CI)]of 0.62(0.40-0.95),0.60(0.39-0.92),0.73(0.54-0.98),and 0.58(0.42-0.78),respectively.CCAACG,CCGACG,and TCAATA were significantly associated with decreased frequencies of the HCC-risk HBV mutations:preS1 deletion,APOBECsignature HBV mutations in the core promoter and preS regions,A51C/T,G104C/T,and G146C/T.TCGATA and TTAACG were associated with increased LC risk,with an OR(95%CI)of 1.54(1.03-2.30)and 2.23(1.50-3.33),respectively.However,TCGATA and TTAACG were not consistently associated with the cirrhosis-risk HBV mutations.Conclusion:CCAACG,CCGACG,and TCAATA are inversely associated with HCC risk,possibly because they are involved in creating an immune microenvironment attenuating the generation of HCC-risk HBV mutations.TCGATA and TTAACG might predispose the polarity of immunity towards Th17 isotype related to LC.
基金This work was supported by the National Research Program of China(2017YFA0505803 and 2017YFC0908100)the State Key Project for Infectious Diseases(2018ZX10732202-001)+2 种基金National Natural Science Foundation of China(81790633,81672860,61922047,81422032,and 81902412)National Natural Science Foundation of Shanghai,China(17ZR143800)National Science Foundation for Distinguished Young Scholars of China(81702298).
文摘Intrahepatic cholangiocarcinoma(ICC)is the second most common liver cancer.Chemotherapy remains the main therapeutic strategy for advanced ICC patients,but chemosensitivity varies individually.Here,we applied cytometry by time-of-flight(CyTOF)to establish the immune profile of peripheral blood mononuclear cells(PBMCs)on the single-cell level at indicated time points before,during,and after chemotherapy.Multiplex immunofluorescence staining was applied to examine the spatial distribution of certain immune clusters.Tissue microarrays(TMAs)were used for prognostic evaluation.A total of 20 ICC patients treated with gemcitabine(GEM)were enrolled in our study,including eight cases with good response(R)and 12 cases with non-response(NR).Tremendous changes in PBMC composition,including an increased level of CD4/CD8 double-positive T cells(DPT),were observed after chemotherapy.Patients with higher level of CD4^(+)CD45RO^(+)CXCR3^(+)T cells before treatment had a favorable response to chemotherapy.Our study identified a positive correlation between the percentage of T cell subpopulations and clinical response after chemotherapy,which suggests that it is practical to predict the potential response before treatment by evaluating the proportions of the cell population in PBMCs.
基金supported by:Science Fund for Creative Research Groups,NSFC,China(81521091)State Key Infection Disease Project of China(2018ZX10732202-002-005)+2 种基金Shanghai Rising Star Program(20QA1412000)National Natural Science Foundation of China(81702734)Natural Science Foundation of Shanghai Municipal Commission of Health and Family Planning(Y20170006,2017Y0109).
文摘Background:For patients with a large but resectable solitary hepatocellular carcinoma(HCC)of>5 cm in diameter,it is often difficult to achieve a sufficient resection margin.There is still no study on whether a two-stage hepatectomy to increase a narrow resection margin would be beneficial.Methods:From August 2014 to February 2017,patients with a large but resectable solitary HCC of>5 cm and a preoperative estimated resection margin of<1.0 cm were retrospectively studied.They were divided into one-and two-stage resection groups.A retrospective analysis was performed,followed by propensity score matching(PSM)analysis.Disease recurrence,survival,intraoperative and postoperative data were compared.Results:Before PSM,the 1-,2-,3-and 4-year recurrence-free survival rates for the one-and two-stage groups were 44.3%,31.7%,24.3%,19.2%versus 60.6%,45.4%,43.5%,32.3%,respectively(P=0.007).The corresponding OS rates were 61.0%,45.2%,43.8%,38.4%versus 69.6%,62.5%,60.7%,57.3%,respectively(P=0.029).After PSM,the 1-,2-,3-and 4-year recurrence-free survival rates for the one-and two-stage groups were 44.0%,31.5%,27.3%,21.0%versus 60.6%,45.4%,43.5%,32.3%,respectively(P=0.013).The corresponding OS rates were 62.5%,41.1%,41.1%,37.5%versus 69.6%,62.5%,60.7%,57.3%,respectively(P=0.038).Differences in the resection margins between the one-and two-stage groups before[0.3(0-0.5)versus 1.2(0.8-2.2)cm]and after[0.2(0-0.5)versus 1.2(0.8-2.2)cm]PSM were also significant.Conclusions:Two-stage hepatectomy allowed a wider resection margin for patients with a resectable but solitary HCC of>5 cm,and resulted in significantly better long-term survival outcomes after partial hepatectomy.
