年龄对胰腺神经内分泌肿瘤患者术后生存的影响

Impact of age upon the prognosis of patients with pancreatic neuroendocrine tumors

目的研究和评价手术治疗胰腺神经内分泌肿瘤（pNETs）患者年龄与预后的关系。方法回顾性分析复旦大学附属中山医院1999年1月至2010年12月102例手术治疗pNETs患者的临床资料，通过镜下形态学以及对神经内分泌标记物嗜铬粒蛋白A、突触素和神经元特异性烯醇化酶等标志物免疫组织化学染色证实其为胰腺神经内分泌肿瘤。按照有丝分裂计数和Kj-67增殖指数确定肿瘤的分级；ENETSTNM系统确定肿瘤的分期；按年龄是否〉60岁将患者分为低龄组（H60岁，77例）和高龄组（〉60岁，25例）。采用寿命表法估计生存函数和计算生存率；Kaplan—Meier法绘制生存曲线；生存情况的比较用Log—rank检验；Kaplan—Meier法进行单因素生存分析；单因素COX分析计算风险率；COX比例风险模型筛选预后因素。结果全组患者总的中位生存时间为139．8个月；1、2、5及10年生存率分别为96％、93％、90％和80％。行根治术pNETs低龄组患者的术后生存时间显著优于高龄组患者（X^2=4．717，P〈0．05）。WHO分级较高（G2、G3级）和TNM分期较高（Ⅲ、Ⅳ期）的pNETs高龄组患者手术治疗的预后较低龄组差（X^2=11．158，5．375，P〈0．05）。多因素分析结果显示，年龄和大血管侵犯是影响患者预后的独立因素（艘=8．626，12．795，P〈0．05）。结论年龄〉60岁是影响pNETs患者术后预后的重要独立危险因素。肿瘤病理分期、分级与其预后有密切联系。

Objective To analyze the relationship between age and the prognosis of patients with pancre- atic neuroendocrine tumors （pNETs）. Methods The clinical data of 102 patients with pNETs who were admitted to the Zbongshan Hospital of Fudan University from January 1999 to December 2010 were retrospectively analyzed. The properties of the tumors were determined by morphology and immunohistochemical staining of chromogranin A, synaptophysin and neuron-specific enolase. Preoperative grading of the tumors was done by mitotic count and Ki-67 proliferation index, and the staging of the tumors was done by ENETS TNM system. All patients were divided into younger group （age≤60 years, 77 patients） and older group （age 〉 60 years, 25 patients）. The survival of the patients was estimated using the life table, and the survival curve was drawn by the Kaplan-Meier method. The survival of the 2 groups was compared using the Log-rank test. Multivariate analysis was performed with the COX proportional hazards model. Results The median survival time was 139.8 months. The overall 1-, 2-, 5-, and 10-year survival rates were 96% , 93% , 90% and 80% , respectively. The postoperative survival time of patients in the younger group was significantly longer than that in the older group （ X^2 = 4.717, P 〈 0.05 ）. The prognosis of patients with higher tumor grades （ G2, G3 ） and higher TNM stages （Ⅲ,Ⅳ ） in the older group was signifi-cantly poorer than those in the younger group （X^2 = 11. 158, 5. 375, P 〈 0.05 ）. The results of multivariate analysis showed that age and major vascular invasion were the independent predictors for survival （RR = 8. 626, 12. 795, P 〈 0.05）. Conclusions Age above 60 years is an important independent factor influencing the prognosis of pNETs patients. Tumor grading and TNM staging are highly correlated with the prognosis of the pNETs patients.