血清AFP阴性的肝细胞癌患者预后及分期系统分析

目的 初步分析血清AFP阴性(<20ng/ml)肝细胞癌患者的预后及分期系统,并确定影响AFP阴性患者术后生存率的危险因素及临床疗效评价的最佳评分系统。方法 回顾性分析2012年1月-2017年12月在湖北医药学院附属襄阳市第一人民医院行手术切除的188例肝细胞癌患者的临床资料,其中AFP阳性组127例,AFP阴性组61例。比较两组的肿瘤相关因素、手术相关因素和其他临床资料。符合正态分布的计量资料2组间比较采用t检验;非正态分布的计量资料2组间比较采用Mann-WhitneyU检验。计数资料2组间比较采用χ2检验。总体生存率和无复发生存率用Kaplane-Meier生存曲线计算,两组的生存差异用log-rank检验,采用Cox比例风险模型进行单因素和多因素分析确定影响AFP阴性组生存率的危险因素,及TNM系统、巴塞罗那临床肝癌评分系统(BCLC)、意大利肝脏肿瘤评分(CLIP)、国内分期(CS)、日本整体分期评分系统(JIS)和Okuda分期对于AFP阴性组术后生存情况的判断力。结果 肝癌患者中AFP阴性者占32.45%(61/188),相对于AFP阳性患者,阴性组患者趋向于有更完整的包膜(χ2=7.234,P=0.007)、更好的病理分期(χ2=6.698,P=0.01)及更高的生存率(χ2=9.580,P=0.002)和更低的复发率(χ2=8.407,P=0.004)。降低AFP阴性组总体生存率的独立因素是Child-PughB级[危险比(HR)=1.711,95%可信区间(95%CI):1.073~39.921,P=0.001],较高的胆红素值(HR=1.044,95%CI:1.006~1.083,P=0.021)和缺乏肿瘤包膜(HR=7.025,95%CI:1.319~37.401,P=0.022)。增加AFP阴性组肿瘤复发率的危险因素是肿瘤直径>3cm(HR=4.172,95%CI:1.271~13.691,P=0.019)、缺乏肿瘤包膜(HR=8.901,95%CI:2.352~33.693,P=0.001)和血管侵袭性(HR=0.043,95%CI:0.003~0.584,P=0.018)。在这6个被确定的分期系统中,单因素分析显示无论是总体生存还是无复发生存率,TNM、BCLC分期均有统计学意义(P值均<0.05),而CS分期仅对总体生存率有统计学意义(P<0.05);多因素分析显示对于总体生存率,只有BCLC分期具有统计学意义(HR=0.124,95%CI:0.038~0.401,P<0.01),而对于无复发生存率,TNM(HR=0.339,95%CI:0.158~0.952,P=0.039)和BCLC分期(HR=0.177,95%CI:0.058~0.539,P=0.002)均具有统计学意义。结论 AFP阴性患者多具有较好肝脏储备功能、生物学行为以及较高的生存率和无复发生存率。在被确定的6个分期系统中,BCLC分期系统是唯一一个对AFP阴性患者术后总体生存率及无复发生存率均有意义的分期,是评价生存预后的最佳系统。

Prognosis and staging system analysis of hepatocellular carcinoma patients with negative serum alpha-fetoprotein

ObjectiveTo investigate the effect of negative expression of serum alpha-fetoprotein (AFP)(<20 ng/L) on the prognosis and staging of patients with hepatocellular carcinoma (HCC), the risk factors for postoperative survival rate of AFP-negative patients, and the best scoring system for clinical outcome evaluation. MethodsA retrospective analysis was performed for the clinical data of 188 patients with HCC who underwent surgical resection in Xiangyang First People′s Hospital Affiliated to Hubei Medical College from January 2012 to December 2017, among whom 127 had positive AFP (AFP-positive group) and 61 had negative AFP (AFP-negative group). The two groups were compared in terms of tumor-related factors, surgery-related factors, and other clinical data. The t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups;the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier survival curve was used to calculate overall survival rate and relapse-free survival rate, and the log-rank test was used for comparison of survival between two groups. The Cox proportional hazards model was used for univariate and multivariate analyses to identify the risk factors for survival rate in the AFP-negative group and to evaluate the value of TNM system, Barcelona Clinic Liver Cancer (BCLC) system, Cancer of the Liver Italian Program (CLIP) score, Chinese staging (CS) system, Japan Integrated Staging (JIS) score, and Okuda staging system in judging postoperative survival of the AFP-negative group. ResultsOf all 188 HCC patients, 61 (32.45%) had negative AFP. Moreover, compared with the AFP-positive patients, the AFP-negative patients tended to have a more complete capsule (χ 2=7.234, P =0.007), a better pathological stage (χ 2=6.698, P =0.01), a higher survival rate (χ 2=9.580, P =0.002), and a lower recurrence rate (χ 2=8.407, P =0.004). Child-Pugh class B HCC (hazard ratio [HR]=1.711, 95% confidence interval [CI]: 1.073~39.921, P =0.001), a high level of bilirubin (HR=1.044, 95%CI: 1.006-1.083, P =0.021), and absence of tumor capsule (HR=7.025, 95%CI: 1.319-37.401, P =0.022) were independent risk factors for a reduced overall survival rate in the AFP-negative group. Tumor diameter >3 cm (HR=4.172, 95%CI: 1.271-13.691, P =0.019), absence of tumor capsule (HR=8.901, 95%CI: 2.352-33.693, P =0.001), and vascular invasion (HR=0.043, 95%CI: 0.003-0.584, P =0.018) were risk factors for an increased recurrence rate of tumor in the AFP-negative group. The univariate analysis showed that among these six staging systems, the TNM and BCLC staging systems were significantly associated with overall survival rate and relapse-free survival rate (P <0.05) and the CS system was only significantly associated with overall survival rate ( P <0.05);the multivariate analysis showed that only the BCLC stating system was significantly associated with overall survival rate (HR=0.124, 95%CI: 0.038-0.401, P <0.01) and that the TNM staging system (HR=0.339, 95%CI: 0.158-0.952, P =0.039) and the BCLC staging system (HR=0.177, 95%CI: 0.058-0.539, P= 0.002) were significantly associated with relapse-free survival rate. ConclusionAFP-negative patients often have good liver reserve function and biological behavior and high survival rate and relapse-free survival rate. Among the above six staging systems, only the BCLC staging system is significantly associated with both overall survival rate and relapse-free survival rate after surgery, and therefore, it is the best system for evaluating postoperative survival and prognosis in AFP-negative patients.