肝细胞癌根治性切除术后复发伴门静脉癌栓危险因素分析
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摘要
目的探讨肝癌根治性切除时的临床病理因素对术后出现伴有门静脉癌栓(PVTT)复发性肝癌的影响。方法回顾性分析2000年1月至2014年12月在青岛大学附属医院接受原发性肝癌R0切除的206例病人首次切除至肝癌复发期间的临床及病理资料,根据肝癌复发时是否伴有PVTT分为伴有PVTT组和无PVTT组,分析肝癌复发时PVTT形成的危险因素。在伴有PVTT的复发性肝癌病人中,分析影响PVTT形成时间的危险因素。结果单因素分析结果显示,多发病灶、无肿瘤包膜、肝功能Child分级B级的肝癌病人肝癌复发时,伴有PVTT的比例更大。二元Logistic回归分析结果显示,多发病灶、无肿瘤包膜、Child分级B级是影响肝细胞癌根治性切除术后PVTT形成的独立危险因素。以这3个危险因素建立"肝细胞癌根治性切除术后PVTT预测模型",每个危险因素赋值1分,ROC曲线分析结果显示该模型评分对肝细胞癌根治性切除术后是否发生PVTT具有一定的预测价值(P=0.003,95%CI 0.557～0.766),曲线下面积为0.662,Cut-off值为0.5分,约登指数为0.302,敏感度为60.0%,特异度为70.2%。模型得分越高者无瘤生存时间越短(P=0.007),且出现伴有PVTT复发的比例更高(P=0.001)。Kaplan-Meier法(Log-rank检验)及Cox回归模型分析显示,在复发性肝癌且伴有门静脉癌栓病人中,低分化肝癌术后出现肉眼可见的PVTT时间更短(P=0.000)。结论多发癌灶、无肿瘤包膜、肝功能Child分级B级的肝癌病人R0术后更容易出现伴有PVTT的复发,其中肝癌低分化者生长速度更快。对具有高危因素的病人采取更紧密随访或预防性治疗措施,或能改善预后。
Objective To investigate the effect of clinicopathological factors on the recurrent hepatocellular carcinoma(HCC)with portal vein tumor thrombus(PVTT)after radical resection.Methods The data of patients with HCC who underwent radical resection between January 2000 and December 2014 in Affiliated Hospital of Qingdao University were analyzed retrospectively.Clinical and pathological data from first resection to the recurrence of HCC with PVTT were extracted in the form of data tables.All patients were divided into PVTT group and non PVTT group according to the occurence of PVTT at time of HCC recurrence,and the risk factors of PVTT formation were analyzed.Risk factors influencing the formation time,from radical resection to HCC recurrence,were analyzed in recurrent HCC patients with PVTT.Results Univariate analysis results showed that patients having HCC with multiple tumors,no tumor capsule,and Child-pugh B grade had a high proportion of PVTT when HCC recurred.The results of logistic regression analysis showed that multiple tumors,no tumor capsule,and Childpugh B grade were independent risk factors for PVTT formation after radical resection of HCCA predictive model was established on the basis of the three risk factors(1 point for each factor).ROC curve showed the total model score has certain predictive value.The area under the curve was 0.662(P=0.003,95% CI:0.557-0.766),cut-off value was 0.5 points,Youden index was 0.302(sensitivity=60.0%,specificity=70.2%).The higher the model score,the shorter the tumor-free survival time(P=0.007),and the higher the incidence of PVTT recurrence(P=0.001).The results of Kaplan-Meier(log-rank test)and multivariate analysis of Cox regression model showed that lower differentiation of HCC was an independent risk factor influencing the time from radical resection to HCC recurrence with PVTT(P=0.000). Conclusion Patients with multiple tumor foci,no tumor capsule and Child grade B grade liver cancer are more likely to recur with PVTT after RO operation.And among them,the low differentiation of liver cancer grows faster.A closer follow-up or preventive treatment of patients with high-risk factors may improve prognosis.
Objective To investigate the effect of clinicopathological factors on the recurrent hepatocellular carcinoma(HCC)with portal vein tumor thrombus(PVTT)after radical resection.Methods The data of patients with HCC who underwent radical resection between January 2000 and December 2014 in Affiliated Hospital of Qingdao University were analyzed retrospectively.Clinical and pathological data from first resection to the recurrence of HCC with PVTT were extracted in the form of data tables.All patients were divided into PVTT group and non PVTT group according to the occurence of PVTT at time of HCC recurrence,and the risk factors of PVTT formation were analyzed.Risk factors influencing the formation time,from radical resection to HCC recurrence,were analyzed in recurrent HCC patients with PVTT.Results Univariate analysis results showed that patients having HCC with multiple tumors,no tumor capsule,and Child-pugh B grade had a high proportion of PVTT when HCC recurred.The results of logistic regression analysis showed that multiple tumors,no tumor capsule,and Childpugh B grade were independent risk factors for PVTT formation after radical resection of HCCA predictive model was established on the basis of the three risk factors(1 point for each factor).ROC curve showed the total model score has certain predictive value.The area under the curve was 0.662(P=0.003,95% CI:0.557-0.766),cut-off value was 0.5 points,Youden index was 0.302(sensitivity=60.0%,specificity=70.2%).The higher the model score,the shorter the tumor-free survival time(P=0.007),and the higher the incidence of PVTT recurrence(P=0.001).The results of Kaplan-Meier(log-rank test)and multivariate analysis of Cox regression model showed that lower differentiation of HCC was an independent risk factor influencing the time from radical resection to HCC recurrence with PVTT(P=0.000). Conclusion Patients with multiple tumor foci,no tumor capsule and Child grade B grade liver cancer are more likely to recur with PVTT after RO operation.And among them,the low differentiation of liver cancer grows faster.A closer follow-up or preventive treatment of patients with high-risk factors may improve prognosis.
引文
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[18]孙琦蛮,樊嘉,周俭,等.肝细胞肝癌侵袭性及门静脉癌栓形成与ezrin[J].中华肝胆外科杂志,2005,11(12):802-805.
[19]Fukuda S,Itamoto T,Nakahara H,et al.Clinicopathologic features and prognostic factors of resected solitary small-sized hepatocellular carcinoma[J].Hepatogastroenterology,2005,52:1163-1167.
[20]Cucchetti A,Vivarelli M,Piscaglia F,et al.Tumor doubling time predicts recurrence after surgery and describes the histological pattern of hepatocellular carcinoma on cirrhosis[J].JHepatol,2005,43:310-316.
[21]Atsuo J.Pathological study of hepatocellular carcinoma:a study of tumor thrombus of the portal vein[J].Acta Hepatologica Japonica,1983,24(6):641
[2]MaluccioM,CoveyA.Recent progressinunderstanding,diagnosing,and treating hepatocellular carcinoma[J].CA Cancer J Clin,2012,62:394-399.
[3]Sangiovanni A,Colombo M.Treatment of hepatocellular carcinoma:beyound international guidelines[J].Liver Int,2016,36(1):124-129.
[4]Dai WC,Cheung TT.Strategic overview on the best treatment option for intrahepatocellular carcinoma recurrence[J].Expert Rev Anticancer Therapy,2016,16(10):1063-1072.
[5]Akamatsu N,Cillo U,Cucchetti A,et al.Surgery and hepatocellular carcinoma[J].Liver Cancer,2016,6(1):44-50.
[6]孙居仙,石洁,程树群.肝癌合并门静脉癌栓诊治难点与对策[J].中国实用外科杂志,2016,36(6):614-617.
[7]张修平,王康,程树群.原发性肝细胞癌合并门静脉癌栓非手术治疗进展[J].中国实用外科杂志,2016,36(6):702-705.
[8]童颖,杨甲梅.原发性肝癌门静脉癌栓的形成及治疗[J].中国实用外科杂志,2003,23(6):373-375.
[9]陈孝平,裘法祖,吴在德,等.肝细胞癌门静脉癌栓形成的分子生物学机制研究[J].中国实验外科杂志,2005,22(9):1056-1058.
[10]Liu Shupeng,Guo Weixing,Shi Jie,et al.MicroRNA-135a contributes to the development of portal vein tumor thrombus by promoting metastasis in hepatocellular carcinoma[J].JHepatol,2012,56:389-396.
[11]Zhang ZM,Lai EC,Zhang C,et al.The strategies for treating primary hepatocellular carcinoma with portal vein tumor thrombus[J].Int J Surg,2015,20:8-16.
[12]Akamatsu N,Cillo U,Cucchetti A,et al.Surgery and hepatocellular carcinoma[J].Liver Cancer,2016,6(1):44-50.
[13]Poon RT,Fan ST,Ng IO,et al.Different risk factors and prognosis for early and late intrahepatic reccurence after resection of hepatocellular carcinoma[J].Cancer,2000,89(3):500-507.
[14]Zhou J,Tang ZY,Fan J,et al.The potential of plasma thrombomodulin as a biomarker of portal vein tumor thrombus of hepatocellular carcinoma[J].J Cancer Res Clin Oncol,2001,127(9):559-564.
[15]Shimizu Y,Minemura M,Tsukishiro T,et al.Serum concentration of intercellular adhesion molecule-1 in patients with hepatocellular carcinoma is a marker of the disease progression and prognosis[J].Hepatology,1995,22(2):525-531.
[16]Genda T,Sakamoto M,Ichida T,et al.Cell motility mediated by rho and rho-associated protein kinase plays a critical role in intrahepatic metastasis of human hepatocellular carcinoma[J].Hepatology,1995,30(4):1027-1036.
[17]Ercolani G,Grazi GL,Ravaioli M,et al.Liver resection for hepatocellular carcinoma on cirrhosis:univariate and multivariate analysis of risk factors for intrahepatic recurrence[J].Ann Surg,2003,237(4):536-543.
[18]孙琦蛮,樊嘉,周俭,等.肝细胞肝癌侵袭性及门静脉癌栓形成与ezrin[J].中华肝胆外科杂志,2005,11(12):802-805.
[19]Fukuda S,Itamoto T,Nakahara H,et al.Clinicopathologic features and prognostic factors of resected solitary small-sized hepatocellular carcinoma[J].Hepatogastroenterology,2005,52:1163-1167.
[20]Cucchetti A,Vivarelli M,Piscaglia F,et al.Tumor doubling time predicts recurrence after surgery and describes the histological pattern of hepatocellular carcinoma on cirrhosis[J].JHepatol,2005,43:310-316.
[21]Atsuo J.Pathological study of hepatocellular carcinoma:a study of tumor thrombus of the portal vein[J].Acta Hepatologica Japonica,1983,24(6):641