Risk Factors, Patterns, and Outcomes of Late Recurrence After Liver Resection for Hepatocellular Carcinoma A Multicenter Study From China
Risk Factors, Patterns, and Outcomes of Late Recurrence After Liver Resection for Hepatocellular Carcinoma A Multicenter Study From China
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肝细胞癌肝切除术后晚期复发的危险因素、模式和结果来自中国的多中心研究
DOI：
10.1001/jamasurg.2018.4334
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发表时间：
2019-03-01
期刊：
影响因子：
16.9
通讯作者：
Yang, Tian
中科院分区：
文献类型：
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作者：
Xu, Xin-Fei;Xing, Hao;Yang, Tian
重要性 肝细胞癌 (HCC) 肝切除术后晚期复发（超过 2 年）通常被认为是多中心肿瘤或新发癌症。 目的 探讨 HCC 根治性肝切除术后晚期复发的危险因素、模式和结局。 设计、地点和参与者 本研究是对 2001 年 1 月以来在中国 6 家医院接受根治性 HCC 肝切除术的患者进行的多中心回顾性分析截至2015年12月。在734名切除后2年仍存活且无复发的患者中，303名患者出现晚期复发。分析了 2017 年 6 月至 2018 年 2 月的数据。 干预措施 HCC 肝切除术。 主要结果和措施 晚期复发的危险因素以及晚期复发患者的模式、治疗和长期结果。采用单变量和多变量Cox回归分析来确定晚期复发的独立危险因素。结果纳入的734例患者中，652例（88.8%）为男性，平均（SD）年龄为51.0（10.3）岁。在中位（四分位距）78.0（52.8-112.5）个月的随访中，303 名患者（41.3%）出现晚期复发。多因素分析显示，男性、肝硬化、多发肿瘤、卫星结节、肿瘤大小大于5 cm、宏观和微观血管侵犯是晚期复发的独立危险因素。 303例晚期复发患者中，273例（90.1%）仅发生肝内复发，30例（9.9%）同时发生肝内和肝外复发，无一例仅发生肝外复发。 303 名晚期复发患者中的 165 名（54.5%）接受了潜在治愈性治疗，包括再次切除、移植和局部消融。多变量 Cox 回归分析显示，定期监测术后复发（风险比 [HR]，0.470；95% CI，0.310-0.713；P = .001）、肝硬化（HR，1.381；95% CI，1.049-1.854；P = .02）、门静脉高压（HR，2.424；95% CI， 1.644-3.574；P < .001)，Child-Pugh B 级或 C 级（HR，1.376；95% CI，1.153-1.674；P < .001），巴塞罗那临床肝癌 B 期（HR，1.304；95% CI，1.007-1.708；P = .04）和 C 期（HR，2.037；95% CI，1.583-2.842；P < .001）和潜在治愈性治疗（HR，0.443；95% CI，0.297-0.661；P < .001）是晚期复发患者总生存率的独立预测因素。 结论和相关性 HCC 切除后的晚期复发与性别、肝硬化，以及初始 HCC 的几种侵袭性肿瘤特征。晚期复发的模式表明，手术两年后的复发监测应以肝脏为目标。术后监测提高了潜在治愈性治疗的机会，改善了晚期复发患者的生存结果。
IMPORTANCE Late recurrence (more than 2 years) after liver resection for hepatocellular carcinoma (HCC) is generally considered as a multicentric tumor or a de novo cancer.OBJECTIVE To investigate the risk factors, patterns, and outcomes of late recurrence after curative liver resection for HCC.DESIGN, SETTING, AND PARTICIPANTS This study was a multicenter retrospective analysis of patients who underwent curative liver resection for HCC at 6 hospitals in China from January 2001 to December 2015. Among 734 patients who were alive and free of recurrence at 2 years after resection, 303 patients developed late recurrence. Data were analyzed from June 2017 to February 2018.INTERVENTIONS Liver resection for HCC.MAIN OUTCOMES AND MEASURES Risk factors of late recurrence as well as patterns, treatments, and long-term outcomes of patients with late recurrence. Univariate and multivariate Cox regression analyses were performed to identify independent risk factors of late recurrence.RESULTS Of the included 734 patients, 652 (88.8%) were male, and the mean (SD) age was 51.0 (10.3) years. At a median (interquartile range) follow-up of 78.0 (52.8-112.5) months, 303 patients (41.3%) developed late recurrence. Multivariate analysis revealed that male sex, cirrhosis, multiple tumors, satellite nodules, tumor size greater than 5 cm, and macroscopic and microscopic vascular invasion were independent risk factors of late recurrence. Of the 303 patients with late recurrence, 273 (90.1%) had only intrahepatic recurrence, 30 (9.9%) had both intrahepatic and extrahepatic recurrence, and none had only extrahepatic recurrence. Potentially curative treatments were given to 165 of 303 patients (54.5%) with late recurrence, which included reresection, transplant, and local ablation. Multivariate Cox regression analysis showed that regular surveillance for postoperative recurrence (hazard ratio [HR], 0.470; 95% CI, 0.310-0.713; P = .001), cirrhosis (HR, 1.381; 95% CI, 1.049-1.854; P = .02), portal hypertension (HR, 2.424; 95% CI, 1.644-3.574; P < .001), Child-Pugh grade of B or C (HR, 1.376; 95% CI, 1.153-1.674; P < .001), Barcelona Clinic Liver Cancer stage B (HR, 1.304; 95% CI, 1.007-1.708; P = .04) and stage C (HR, 2.037; 95% CI, 1.583-2.842; P < .001), and potentially curative treatment (HR, 0.443; 95% CI, 0.297-0.661; P < .001) were independent predictors of overall survival for patients with late recurrence.CONCLUSIONS AND RELEVANCE Late recurrence after HCC resection was associated with sex, cirrhosis, and several aggressive tumor characteristics of the initial HCC. The patterns of late recurrence suggested surveillance for recurrence after 2 years of surgery should be targeted to the liver. Postoperative surveillance improved the chance of potentially curative treatments, with improved survival outcomes in patients with late recurrence.