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投稿时间：2021-02-09 网络发布日期：2021-09-20
投稿时间：2021-02-09 网络发布日期：2021-09-20
中文摘要: 目的 研究肝细胞癌（HCC）微血管侵犯（MVI）对于患者肝切除术后预后的影响，评价术前γ-谷氨酰转肽酶-淋巴细胞比值（GLR）对MVI的预测价值。方法 回顾性分析2004年7月至2016年8月南京鼓楼医院肝胆外科收治的455例因HCC行肝切除术患者的临床资料，采用单因素及多因素Cox比例风险模型分析影响患者无病生存期（DFS）及总生存期（OS）的独立危险因素;通过受试者工作特征（ROC）曲线分析GLR对于MVI的诊断价值，并确定最佳临界值;使用单因素及多因素Logistic回归分析简单术前临床指标中肝细胞癌MVI的独立危险因素，建立预测评分模型。结果 多因素Cox回归分析显示，肝硬化（HR=1.435，P<0.05）、切缘<1 cm（HR=1.691，P<0.01）、MVI阳性（HR=1.471，P<0.05）是DFS的独立危险因素，MELD评分≥9（HR=1.551，P<0.05）、切缘<1 cm（HR=2.477，P<0.01）、MVI阳性（HR=1.833，P<0.01）及TNM分期Ⅲ~Ⅳ期（HR=1.622，P<0.05）是OS的独立危险因素。MVI阳性组手术切缘≥1 cm的患者术后DFS及OS均显著优于切缘<1 cm者（P<0.01），而MVI阴性组手术切缘对DFS及OS无显著影响（P>0.05）。ROC曲线分析提示，术前GLR对于MVI具有诊断价值（AUC=0.600，P<0.01），最佳临界值为42.75。多因素Logistic分析显示，肿瘤直径≥5 cm（OR=2.763，P<0.01）、多发肿瘤（OR=1.742，P<0.05）、甲胎蛋白（AFP）≥400 μg/L（OR=1.817，P<0.01）、GLR≥42.75（OR=1.698，P<0.05）是MVI阳性的独立危险因素。以上述四危险因素构成的评分系统显示对于MVI有良好预测价值（AUC=0.696，P<0.01）。结论 MVI阳性是HCC肝切除术后预后不佳的独立危险因素，较宽的切缘对于改善MVI阳性HCC患者预后具有重要意义。术前GLR是存在MVI的独立危险因素，与肿瘤直径、肿瘤数目及AFP共同组成的预测模型对于术前预估是否存在MVI，从而指导手术规划具有一定的参考意义。
中文关键词: 肝细胞癌 γ-谷氨酰转肽酶-淋巴细胞比值 微血管侵犯 预后
Abstract:Objective To investigate the influences of microvascular invasion (MVI) on the prognosis of hepatectomy and evaluate the predictive value of gamma-glutamyl transpeptidase to lymphocyte count ratio (GLR) in hepatocellular carcinoma (HCC) patients with MVI. Methods A retrospective analysis was performed on the clinical data of 455 HCC patients undergoing liver resection from July 2004 to August 2016. Univariate and multivariate Cox proportional hazard regression models were used to identify the independent risk factors of disease-free survival (DFS) and overall survival (OS). Receiver operating characteristics (ROC) curve analysis was employed to determine the diagnostic value of GLR and the optimal cut-off value for MVI. Univariate and multivariate Logistic regression analysis were used to determine the independent risk factors of MVI, and a prediction model was developed using readily-available preoperative parameters. Results Cox regression analysis showed that cirrhosis (HR=1.435, P<0.05), surgical margin <1 cm (HR=1.691, P<0.01) and positive MVI (HR=1.471, P<0.05) were the independent risk factors of DFS. MELD score ≥9 (HR=1.551，P<0.05), surgical margin <1 cm (HR=2.477，P<0.01), MVI (HR=1.833，P<0.01) and TNM stage Ⅲ～Ⅳ (HR=1.622，P<0.05) were the independent risk factors of OS. In MVI-positive group, DFS and OS in the patients with surgical margin ≥1 cm were significant better than those in the patients with surgical margin <1 cm (P<0.01). There was no significant association between surgical margin and DFS or OS in MVI-negative group (P>0.05). ROC analysis demonstrated that preoperative GLR had diagnostic value on MVI (AUC=0.600, P<0.01), and its optimal cut-off value was 42.75. Multivariate logistic analysis showed that tumor diameter ≥5 cm (OR=2.763, P<0.01), multiple tumors (OR=1.742, P<0.05), alpha-fetoprotein (AFP) ≥ 400 μg/L (OR=1.817, P<0.01) and GLR≥42.75 (OR=1.698, P<0.05) were the independent risk factors for positive MVI. The scoring system based on the above four risk factors demonstrated a good predictive value on MVI (AUC=0.696，P<0.01). Conclusion Positive MVI is an independent risk factor for the poor prognosis of HCC patients after hepatectomy. Wide surgical margin has important significance on improving the prognosis of MVI-positive patients. Preoperative GLR is an independent risk predictor of MVI. The prediction model based on GLR, AFP level, tumor diameter and multiple tumors has certain reference significance for preoperative prediction of MVI and guidance of operation planning.
keywords: Hepatocellular carcinoma Gamma-glutamyl transpeptidase Lymphocyte count Microvascular invasion Prognosis
文章编号： 中图分类号： 文献标志码：A
基金项目:国家自然科学基金青年基金（81602093）;湖北陈孝平科技发展基金会肝胆胰恶性肿瘤研究基金（CXPJJH12000001-2020318）;南京市医学科技发展一般项目（YKK18241）
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引用文本：
强光辉,曹胤,张广,等.肝癌微血管侵犯对预后的影响及基于γ-谷氨酰转肽酶-淋巴细胞比值预测评分模型的建立[J].中国临床研究,2021,34(9):1164-1170.
强光辉,曹胤,张广,等.肝癌微血管侵犯对预后的影响及基于γ-谷氨酰转肽酶-淋巴细胞比值预测评分模型的建立[J].中国临床研究,2021,34(9):1164-1170.