摘要
目的探讨肝移植前行经导管动脉化疗栓塞术(TACE)疗效对肝细胞癌预后的影响。方法采用回顾性队列研究方法。收集2005年1月至2012年12月解放军总医院第三医学中心收治的311例肝移植前行TACE的肝细胞癌患者临床病理资料;男276例, 女35例;中位年龄为52岁, 年龄范围为47~59岁。所有患者肝移植前行TACE。观察指标:(1)肝细胞癌患者行TACE不同疗效及其与临床病理因素的关系。(2)随访情况。(3)肝细胞癌患者肝移植预后影响因素分析。采用门诊或电话方式进行随访。肝移植后前3个月每2~4周复查1次, 此后每1~3个月复查1次, 了解肿瘤复发及转移情况、患者生存情况和移植物丢失情况。随访时间截至2017年12月。正态分布的计量资料以x±s表示, 组间比较采用t检验;偏态分布的计量资料以M(范围)或M(Q1, Q3)表示, 组间比较采用Mann-WhitneyU检验。计数资料以绝对数或百分比表示, 组间比较采用χ^(2)检验。等级资料比较采用非参数秩和检验。采用COX回归模型进行单因素和多因素分析。采用Kaplan-Meier法绘制生存曲线并计算生存率, 采用Log-rank检验进行生存分析。结果 (1)肝细胞癌患者行TACE不同疗效及其与临床病理因素的关系:311例患者行TACE, 57例为病理学完全缓解(pCR), 254例为病理学部分缓解(pPR)。pCR患者甲胎蛋白(<20 μg/L、20~400 μg/L、>400 μg/L), 微血管侵犯, 肿瘤数目单发, 肿瘤分布右半肝, 肿瘤供血动脉管径>1 mm分别为26、26、5, 51, 6, 43, 46例;pPR患者上述指标分别为87、64、103, 158, 59, 125, 159例, 两者比较, 差异均有统计学意义(Z=3.35, χ^(2)=4.54, 15.71, 12.89, 6.79, P<0.05)。(2)随访情况:311患者均获得随访, 随访时间为47.0~59.0个月, 中位随访时间为44.6个月。57例pCR患者中, 肿瘤复发11例、转移11例;254例pPR患者中, 肿瘤复发96例、转移66例。311例患者1、3、5年肿瘤无复发生存率(RFS)分别为98.2%、91.1%、80.3%, 57例pCR患者1、3、5年RFS分别为100.0%、91.1%、80.3%, 254例pPR患者1、3、5年RFS分别为82.0%、68.4%、59.4%, 两者生存情况比较, 差异有统计学意义(χ^(2)=13.47, P<0.05)。57例pCR患者中, 11例移植物丢失;254例pPR患者中, 96例移植物丢失, 两者比较, 差异有统计学意义(χ^(2)=7.06, P<0.05)。(3)肝细胞癌患者肝移植预后影响因素分析:单因素分析结果显示性别、基础疾病(丙型病毒性肝炎)、甲胎蛋白(20~400 μg/L、>400 μg/L)、米兰标准、微血管侵犯、肿瘤数目、肿瘤分布、肿瘤供血动脉管径、TACE次数、TACE疗效是影响肝细胞癌患者肝移植预后的相关因素(风险比=0.49, 3.97, 1.78、1.84, 2.41, 1.96, 3.00, 1.76, 0.19, 2.01, 3.07, 95%可信区间为0.30~0.81, 2.23~7.05, 1.03~3.06、1.18~2.85, 1.63~3.56, 1.28~3.01, 2.04~4.40, 1.20~2.59, 0.13~0.28, 1.28~3.14, 1.63~5.76, P<0.05)。多因素分析结果显示:甲胎蛋白>400 μg/L、超出米兰标准、肿瘤数目多发、TACE疗效为pPR是影响肝细胞癌患者肝移植预后的独立危险因素(风险比=1.59, 2.06, 1.99, 2.05, 95%可信区间为1.22~2.07, 1.35~3.13, 1.29~3.07, 1.02~4.10, P<0.05);肿瘤供血动脉管径>1 mm是影响肝细胞癌患者肝移植预后的独立保护因素(风险比=0.10, 95%可信区间为0.05~0.19, P<0.05)。结论 TACE疗效与甲胎蛋白、微血管侵犯、肿瘤数目、肿瘤分布、肿瘤供血动脉管径有关。甲胎蛋白>400 μg/L、超出米兰标准、肿瘤数目多发、TACE疗效为pPR是影响肝细胞癌患者肝移植预后的独立危险因素;肿瘤供血动脉管径>1 mm是影响肝细胞癌患者肝移植预后的独立保护因素。
Objective To investigate the influence of effects of transarterial chemoembo-lization(TACE)before liver transplantation on the prognosis of hepatocellular carcinoma.Methods The retrospective cohort study was conducted.The clinicopathological data of 311 hepatocellular carcinoma patients undergoing TACE before liver transplantation who were admitted to the Third Medical Center of Chinese PLA General Hospital from January 2005 to December 2012 were collec-ted.There were 276 males and 35 females,aged from 47 to 59 years,with a median age of 52 years.All the 311 patients underwent TACE before liver transplantation.Observation indicators:(1)effects of hepatocellular carcinoma patients undergoing TACE and its relationship with clinicopathological factors;(2)follow-up;(3)influencing factors for prognosis of hepatocellular carcinoma patients after liver transplantation.Follow-up was conducted using outpatient examination or telephone interview to detect recurrence and metastasis of tumor and survival and graft loss of patients up to December 2017.The patients were followed up every 2 to 4 weeks within 3 months after liver transplantation,and once every 1 to 3 months thereafter.Measurement data with normal distri-bution were represented as Mean±SD,and comparison between groups was analyzed using the t test.Measurement data with skewed distribution were represented as M(range)or M(Q1,Q3),and comparison between groups was analyzed using the Mann-Whitney U test.Count data were described as absolute numbers or percentages,and comparison between groups was analyzed using the chi-square test.Comparison of ordinal data was analyzed using the nonparametric rank sum test.The COX regression model was used for univariate and multivariate analyses.The Kaplan-Meier method was used to draw survival curves and calculate survival rates,and the Log-rank test was used for survival analysis.Results(1)Effects of hepatocellular carcinoma patients undergoing TACE and its relationship with clinicopathological factors.Of the 311 patients undergoing TACE,57 cases had pathologic complete response(pCR)and 254 cases had pathologic partial response(pPR),respectively.Cases with alpha fetoprotein(AFP)<20μg/L,20‒400μg/L,>400μg/L,cases with microvascular invasion,cases with tumor number as single nodule,cases with tumor distribution at right lobe of liver,cases with tumor caliber of feeding artery(CFA)>1 mm were 26,26,5,51,6,43,46 in patients with pCR,versus 87,64,103,158,59,125,159 in patients with pPR,showing significant differences in the above indicators(Z=3.35,χ²=4.54,15.71,12.89,6.79,P<0.05).(2)Follow-up.All the 311 patients were followed up for 47.0 to 59.0 months,with a median follow-up time of 44.6 months.There were 11 cases undergoing tumor recurrence and 11 cases undergoing tumor metastasis in the 57 patients with pCR,and there were 96 cases undergoing tumor recurrence and 66 cases under-going tumor metastasis in the 254 patients with pPR.The 1-,3-,5-year tumor recurrence free rates were 98.2%,91.1%,80.3%in the 311 patients,respectively.The 1-,3-,5-year tumor recurrence free rates were 100.0%,91.1%,80.3%in the 57 patients with pCR,versus 82.0%,68.4%,59.4%in the 254 patients with pPR,showing significant differences in the above indicators(χ²=13.47,P<0.05).Cases with graft loss were 11 and 96 in the 57 patients with pCR and the 254 patients with pPR,respectively,showing a significant difference(χ²=7.06,P<0.05).(3)Influen-cing factors for prognosis of hepatocellular carci-noma patients after liver transplantation.Results of univariate analysis showed that gender,basic diseases as viral hepatitis C,AFP(20‒400μg/L,>400μg/L),Milan criteria,microvascular invasion,tumor number,tumor distribution,tumor CFA,times of TACE,effects of TACE were related factors influencing prognosis of hepatocellular carcinoma patients after liver transplantation(hazard ratio=0.49,3.97,1.78,1.84,2.41,1.96,3.00,1.76,0.19,2.01,3.07,95%confidence interval as 0.30‒0.81,2.23‒7.05,1.03‒3.06,1.18‒2.85,1.63‒3.56,1.28‒3.01,2.04‒4.40,1.20‒2.59,0.13‒0.28,1.28‒3.14,1.63‒5.76,P<0.05).Results of multi-variate analysis showed that AFP>400μg/L,exceeding Milan criteria,tumor number as multiple nodule,effects of TACE as pPR were independent risk factors influencing prognosis of hepatocellular carcinoma patients after liver transplantation(hazard ratio=1.59,2.06,1.99,2.05,95%confidence interval as 1.22‒2.07,1.35‒3.13,1.29‒3.07,1.02‒4.10,P<0.05)and tumor CFA>1 mm was an independent protective factor influencing prognosis of hepatocellular carcinoma patients after liver transplantation(hazard ratio=0.10,95%confidence interval as 0.05‒0.19,P<0.05).Conclusions The effects of TACE are related to AFP,microvascular invasion,tumor number,tumor distribution and tumor CFA.AFP>400μg/L,exceeding Milan criteria,tumor number as multiple nodule,effects of TACE as pPR are independent risk factors influencing prognosis of hepatocellular carcinoma patients after liver transplantation and tumor CFA>1 mm is an independent protective factor influencing prognosis of hepatocellular carcinoma patients after liver transplantation.
作者
朱雄伟
李自强
田彦
游波
杨洋
路宾
武泽昊
张庆
舒清明
Zhu Xiongwei;Li Ziqiang;Tian Yan;You Bo;Yang Yang;Lu Bin;Wu Zehao;Zhang Qing;Shu Qingming(Department of Organ Transplantation,the Third Medical Center of Chinese PLA General Hospital,Beijing 100039,China;Department of Organ Transplantation Management,the Third Medical Center of Chinese PLA General Hospital,Beijing 100039,China;Department of Clinical Epidemiology and Evidence-based Medicine Center,Beijing Children′s Hospital,Capital Medical University,Beijing 100045,China;Department of Pathology,the Third Medical Center of Chinese PLA General Hospital,Beijing 100039,China)
出处
《中华消化外科杂志》
CAS
CSCD
北大核心
2022年第2期256-264,共9页
Chinese Journal of Digestive Surgery
基金
国家自然科学基金(81372595)
首都临床特色应用研究(Z121107001012168)。
关键词
肝肿瘤
动脉化疗栓塞
病理学反应
肝移植
无复发存活
预后
Liver neoplasms
Transarterial chemoembolization
Pathological response
Liver transplantation
Recurrence-free survival
Prognosis
