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  • 李风伟,邹奇飞,薛辉,项红军,夏勇,李俊,阎振林,沈锋,王葵.术前糖类抗原19-9水平评估不同甲胎蛋白水平肝细胞癌肝切除术后患者的预后[J].第二军医大学学报,2018,39(6):603-609    [点击复制]
  • LI Feng-wei,ZOU Qi-fei,XUE Hui,XIANG Hong-jun,XIA Yong,LI Jun,YAN Zhen-lin,SHEN Feng,WANG Kui.Assessment of preoperative carbohydrate antigen 19-9 level for prognosis of hepatocellular carcinoma patients with different levels of α-fetoprotein[J].Acad J Sec Mil Med Univ,2018,39(6):603-609   [点击复制]
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术前糖类抗原19-9水平评估不同甲胎蛋白水平肝细胞癌肝切除术后患者的预后
李风伟1△,邹奇飞1△,薛辉1,项红军1,夏勇2,李俊2,阎振林2,沈锋2,王葵1*
0
(1. 海军军医大学(第二军医大学)东方肝胆外科医院肝外二科, 上海 200438;
2. 海军军医大学(第二军医大学)东方肝胆外科医院肝外四科, 上海 200438
共同第一作者
*通信作者)
摘要:
目的 探讨术前糖类抗原19-9(CA19-9)水平对不同甲胎蛋白(AFP)水平肝细胞癌患者术后预后的影响。方法 前瞻性收集2008年1月4日至2010年12月31日在我院因肝细胞癌首次接受肝切除术治疗的3 791例患者的临床及随访资料。以400 ng/mL为术前AFP水平的截断值,32 U/mL为术前CA19-9水平的截断值,将患者分为双阳性组(DP组)、CA19-9单阳性组[SP(CA19-9)组]、AFP单阳性组[SP(AFP)组]和双阴性组(DN组),比较各组患者的肿瘤学特征。采用Kaplan-Meier法和log-rank检验分析各组患者的总生存(OS)和无瘤生存(DFS)情况。采用Cox回归模型进行单因素和多因素分析,筛选影响肝细胞癌患者预后的危险因素。结果 4组患者有不同的肿瘤学特征。与DN组相比,SP(AFP)组、DP组患者的肿瘤最大径更大、病理EdmondsonSteiner分级为Ⅲ~Ⅳ级的比例和微血管侵犯(MVI)发生率更高(P<0.01),且DP组患者的多发肿瘤比例更高(P<0.05);而SP(CA19-9)组患者的肿瘤最大径更小(P<0.05),多发肿瘤的比例更高(P<0.01)。按DN组、SP(CA19-9)组、SP(AFP)组与DP组的顺序,患者的1年、3年和5年OS率均依次降低(P均<0.01);DN组患者的1年、3年和5年DFS率最高(P<0.01),DP组最低(P<0.01),SP(CA19-9)组与SP(AFP)组差异无统计学意义。术前AFP水平分层分析结果表明,CA19-9<32 U/mL组患者的1年、3年和5年OS率及DFS率均高于CA19-9≥32 U/mL组患者(P<0.05)。多因素分析结果显示,AFP≥400 ng/mL、CA19-9≥32 U/mL、术中出血≥600 mL、肿瘤最大径≥5 cm、肿瘤多发、肿瘤包膜缺如、MVI、Edmondson-Steiner分级为Ⅲ~Ⅳ级是影响患者OS的独立危险因素(P<0.05);乙型肝炎病毒表面抗原(+)、AFP≥400 ng/mL、CA19-9≥32 U/mL、肿瘤最大径≥5 cm、肿瘤多发、肿瘤包膜缺如、MVI是影响患者DFS的独立危险因素(P<0.05)。结论 术前血清AFP≥400 ng/mL和CA19-9≥32 U/mL均是影响肝细胞癌患者OS和DFS的独立危险因素。对于不同术前AFP水平的肝细胞癌患者,术前CA19-9水平是进一步评估预后的重要指标。
关键词:  肝肿瘤  甲胎蛋白  糖类抗原19-9  肝细胞癌  预后  肝切除术
DOI:10.16781/j.0258-879x.2018.06.0603
投稿时间:2017-12-28修订日期:2018-04-11
基金项目:中国传染病重大专项课题(2018ZX10723204),2017年海军军医大学研究型科室和研究型医师建设项目重点突破专病方向(王葵,夏勇),肝胆管结石病外科诊疗规范的建立(201502014).
Assessment of preoperative carbohydrate antigen 19-9 level for prognosis of hepatocellular carcinoma patients with different levels of α-fetoprotein
LI Feng-wei1△,ZOU Qi-fei1△,XUE Hui1,XIANG Hong-jun1,XIA Yong2,LI Jun2,YAN Zhen-lin2,SHEN Feng2,WANG Kui1*
(1. Department of Hepatic Surgery(Ⅱ), Eastern Hepatocellular Surgery Hospital, Navy Medical University(Second Military Medical University), Shanghai 200438, China;
2. Department of Hepatic Surgery(Ⅳ), Eastern Hepatocellular Surgery Hospital, Navy Medical University(Second Military Medical University), Shanghai 200438, China
Co-first authors.
* Corresponding author)
Abstract:
Objective To investigate the effect of preoperative carbohydrate antigen 19-9 (CA19-9) levels on the prognosis of hepatocellular carcinoma (HCC) patients with different α-fetoprotein (AFP) levels. Methods The medical records and follow-up data of 3 791 HCC patients undergoing hepatectomy in our hospital from Jan. 4, 2008 to Dec. 31, 2010 were prospectively collected. When 400 ng/mL was taken as the cut-off value of preoperative AFP level and 32 U/mL as the cut-off value of preoperative CA19-9 level, the patients were divided into four groups:double positive group (DP group), CA19-9 single positive group[SP (CA19-9) group], AFP single positive group[SP (AFP) group] and double negative group (DN group). The tumor characteristics of the patients in the four groups were compared. Kaplan-Meier analysis and log-rank test were used to analyze the overall survival (OS) and disease-free survival (DFS) of each group. Univariate and multivariate analyses were performed using Cox proportional hazards model to screen the independent factors influencing the prognosis of HCC patients. Results Patients in the four groups had different tumor characteristics. Compared with the DN group, the tumor maximal diameters of patients in the SP (AFP) and DP groups were significantly larger, the percentages of patients with Edmondson-Steiner grade Ⅲ-Ⅳ were significantly higher and the positive rates of microvascular invasion (MVI) were significantly higher (P<0.01), and the proportion of multiple tumor in the DP group was significantly higher (P<0.05); while the tumor maximal diameter in the SP (CA19-9) group was significantly smaller (P<0.05), and the proportion of multiple tumor was significantly higher (P<0.01). The 1-, 3- and 5-year OS rates of patients in the DN group, SP (CA19-9) group, SP (AFP) group and DP group were decreased successively (P<0.01). The 1-, 3- and 5-year DFS rates of patients in the DN group were the highest (P<0.01), while those in the DP group were the lowest (P<0.01); there were no significant differences in the 1-, 3- or 5-year DFS rates between the SP (CA19-9) and SP (AFP) groups. The stratified analysis of preoperative AFP levels showed that the 1-, 3- and 5-year OS rates and DFS rates in the CA19-9<32 U/mL group were significantly higher than those in the CA19-9 ≥ 32 U/mL group. Multivariable analysis showed that AFP ≥ 400 ng/mL, CA19-9 ≥ 32 U/mL, intraoperative bleeding ≥ 600 mL, tumor maximal diameter ≥ 5 cm, multiple tumor, absence of tumor capsule, MVI, and Edmondson-Steiner grade Ⅲ-Ⅳ were independent risk factors of OS (P<0.05); hepatitis B surface antigen (+), AFP ≥ 400 ng/mL, CA19-9 ≥ 32 U/mL, tumor maximal diameter ≥ 5 cm, multiple tumor, absence of tumor capsule, and MVI were independent risk factors of DFS (P<0.05). Conclusion Preoperative serum AFP ≥ 400 ng/mL and CA19-9 ≥ 32 U/mL are independent risk factors of OS and DFS in HCC patients. Preoperative CA19-9 level is an important indicator to further assess the prognosis of HCC patients with different AFP levels.
Key words:  liver neoplasms  alpha-fetoprotein  carbohydrate antigen 19-9  hepatocellular carcinoma  prognosis  hepatectomy