肝细胞癌患者肝移植术后肿瘤复发的多因素分析

Multivariate analysis of recurrence of hepatocellular carcinoma after liver transplantation

目的分析肝细胞癌（HCC）患者临床及肿瘤影像学特征，探讨HCC患者肝移植（LT）术后肿瘤复发的危险因素。方法回顾性分析2003年10月至2009年7月广州中山大学附属第三医院230例（男210例、女20例，中位年龄50岁）因HCC行LT术患者的临床及肿瘤影像学特点，将这些特点视为肿瘤复发的预测因素。运用Kaplan—Meier法计算HCC患者LT术后生存率，绘制不同预测因素水平HCC患者坍术后的无瘤生存曲线。分别运用Log-rank test及Forward Conditional Cox回归分析对预测因素进行单因素分析和多因素分析，得到肿瘤复发相关危险因素和独立危险因素。结果定期随访3—68个月（中位随访时间29个月），230例HCC患者LT术后在随访期间，肿瘤复发患者77例，无肿瘤复发患者153例，死亡63例。1、3、5年累积生存率分别为84％、75％、69％，累积无瘤生存率分别为73％、65％、63％。单因素分析HCC患者LT术后肿瘤复发的相关危险因素为（P〈0．05）：患者年龄〈50岁、超出米兰标准、TNM分期Ⅱ-Ⅲ期、肿瘤数目≥2、活性肿瘤最大直径〉5cm、肝移植术前介入治疗后活性病灶直径减小小于原病灶直径的30％、肿瘤分布〉1叶、肿瘤边界不清晰、肿瘤的病理分级差、术前血清AFP浓度〉400ug／L、活性肿瘤直径总和≥7．7cm及门静脉癌栓。多因素分析肿瘤复发的独立危险因素为（P〈0．05）：肿瘤的病理分级差、术前血清AFP浓度〉400ug／L、活性肿瘤直径总和≥7．7cm及门静脉癌栓。结论HCC患者LT术后肿瘤复发的主要危险因素为：肿瘤的病理分级差、术前血清AFP浓度〉400ug／L、活性肿瘤直径总和≥7．7cm及门静脉癌栓。HCC患者LT术前积极的介入治疗有助于减少患者术后复发。

Objective To explore the prognostic factors for the recurrence of hepatocellular carcinoma （HCC） after liver transplantation （LT） through analyzing the clinical and imaging characteristics of HCC. Methods The preoperative data of 230 consecutive HCC cases undergoing LT were retrospectively collected from our hospital from October 2003 to July 2009. There were 210 males and 20 females with a median age of 50 years. Their survival rates were calculated by Kaplan-Meier method. The disease-free survival curves of different prognostic factors were plotted by Kaplan-Meier method. The prognostic factors were analyzed by Log-rank test and Forward Conditional Cox regression respectively to yield the related risk factors and independent risk factors for the recurrence of HCC after LT. Results The median follow-up period was 29 months （ range ： 3 - 68 ）. The outcomes included recurrence （ n = 77 ）, no recurrence （ n = 153 ） and mortality （n = 63）. Their 1-, 3- and 5-year cumulative survival rates and cumulative disease-free survival rates were 84% , 75% , 69% and 73% , 65%, 63% respectively. Univariate analysis with Logrank test revealed that the following prognostic factors were significant （ P 〈 0. 05 ） ： age 〈 50 years, exceeding Milan-criteria, TNM stages of II -III, number of tumor ≥ 2, the diameter of the largest viable tumor 〉 5 cm, the post-intervention diameter of viable tumor ≥ 30% of entire tumor diameter, tumor distribution 〉 1 lobe, indistinct boundary of tumor, histological differentiation, serum a-fetoprotein level 〉 400 ng/ml, the sum of viable tumor diameters ≥ 7. 7 cm and intrahepatic portal venous thrombosis.Multivariate analysis with a forward conditional Cox hazard model revealed that the following prognostic factors were independently statistically significant （ P 〈 0.05 ） ： histological differentiation, serum a - fetoprotein level 〉400 ng/ml, the sum of viable tumor diameters ≥7.7 cm and intrabepatic portal venous thrombosis. Conclusions Poor histological differentiation, serum a-fetoprotein level 〉 400 ng/ml, the sum of viable tumor diameters ≥ 7. 7 cm and intrahepatic portal venous thrombosis are significant risk factors. Preoperative aggressive interventional therapy may prolong the disease-free survival period of HCC after LT.