复发时甲胎蛋白的不同水平对肝癌预后的影响

Prognosis of recurrent hepatocellular carcinoma with different α-fetoprotein levels when recurring

目的:观察肝细胞肝癌(简称肝癌)复发时甲胎蛋白(AFP)的不同水平对其预后的影响。方法:回顾性分析我医院821例经根治性手术切除的复发性HCC病人。根据复发时AFP水平分为:A组(阴性组),AFP≤20 ng/mL(n=412);B组(低浓度组),AFP 21～400 ng/mL(n=264);C组(高浓度组),AFP>400 ng/mL(n=145)。分析3组病人的一般临床病理特点、复发后生存率以及影响复发后生存的其他危险因素。结果:相比于A组和B组,C组存在更多的原发肿瘤包膜无/不完整(P<0.001)、更多的微血管侵犯(P<0.001)、更差的肿瘤分级(P<0.001)、复发肿瘤直径更大(P=0.001)以及至复发时间(TTR)更短(P<0.001)。单因素分析发现原发肿瘤最大直径、术中是否输血、肿瘤包膜形成、微血管侵犯、肿瘤病理分级、复发时肿瘤最大直径及数目、TTR、复发后治疗的选择和复发后AFP的血清学水平对复发后生存率存在显著的统计学差异。经COX模型多因素分析,原发肿瘤直径>5 cm、复发肿瘤直径>3 cm、复发肿瘤数目≥2枚、复发时AFP高水平以及复发后非手术治疗是影响肝癌复发生存率的预后危险因素。其中,B组相比于A组的HR值为1.46(95%CI:1.06～2.01,P=0.021);C组相比于A组的HR值为2.77(95%CI:1.89～4.05,P<0.001)。结论:复发时AFP的血清学水平与肿瘤的侵袭性指标相关;复发时AFP浓度越高,预后越差。AFP是判断HCC根治术复发后生存的重要指标。

Objective To identify the clinical outcomes of patients with recurrent hepatocellular carcinoma （HCC） with different α-fetoprotein （AFP） levels when recurring. Methods 821 patients with recurrent HCC who initially underwent curative hepatectomy from Eastern Hepatobiliary Surgery Hospital were studied retrospectively. There were 3 groups according to AFP levels when recurring： group A （negative group）, AFP≤20 ng/mL （n=412）; group B（mildly elevated group）, AFP 21-400 ng/mL （n=264）; and group C （highly elevated group）, AFP〉400 ng/mL （n=145）. The clinical characteristics, recurrence-to-death survival rates, and other risk factors influencing prognosis were compared. Results Compared to those in group A and B, group C tended to present more without / incomplete primary tumor capsule （P〈 0.001）,more microvascular invasion （P〈O.001）, poorer tumor differentiation （P〈0.001）, greater recurrent tumor diameter （P= 0.001） as well as shorter time-to-recurrence （P〈0.001）. Univariate analysis revealed that primary tumor diameter, blood transfusion, tumor capsule, microvascular invasion, recurrent tumor diameter, recurrent tumor number, time-to-recurrence interval, treatment modalities at recurrence, and recurrent AFP level were the factors to affect on recurrence-to-death survival rates （P〈0.05）. With COX model multivariate analysis, primary tumor diameter 〉5 cm, recurrent tumor diameter 〉3 cm, recurrent tumor number≥ 2, high recurrent AFP level, and non-surgical treatment at recurrence were the risk factors of recurrence-to-death survival rates. The hazard ratio （HR） for recurrence-to-death survival in group B compared with that of group A was 1.46 （95%CI： 1.06-2.01 ,P=0.021）. The HR for recurrence-to-death survival in group C compared with that of group A was 2.77 （95%CI： 1.89-4.05 ,P〈0.001）. Conclusions Recurrent AFP level correlated with clinicopathologic characteristics of tumor invasive. The higher AFP level at recurrent, the poorer the recurrence-to-death survival is. AFP is considered as an important prognostic indicator for patients with recurrent HCC who initially underwent curative hepatectomy.