240例胃神经内分泌肿瘤的临床病理特征及预后分析

目的探讨胃神经内分泌肿瘤(G⁃NEN)的临床病理特征并分析影响预后的因素。方法采用回顾性病例对照研究方法,分析2000年1月至2018年6月期间在解放军总医院经病理检查并确诊为G⁃NEN患者的临床病理资料,排除合并脏器病变、其他脏器原发性肿瘤、精神疾病及临床病理资料不完整者后,共纳入240例患者的病例资料。采用“胃癌专病数据库系统”进行临床及随访数据资料采集。汇总患者体格检查信息、肿瘤特征和病理特征,并采用Cox回归模型分析影响G⁃NEN患者预后的危险因素。采用Kaplan⁃Meier法绘制生存曲线,并用log⁃rank检验分析组间生存率的差异。结果240例G⁃NEN患者年龄(60.3±10.1)岁,男性181例(75.4%),女性59例(24.6%)。肿瘤直径(4.2±2.8)cm,神经内分泌瘤(NET)51例(21.2%),神经内分泌癌(NEC)139例(57.9%),混合性腺神经内分泌癌(MANEC)50例(20.8%);G1低级别28例(11.7%),G2中级别34例(14.2%),G3高级别178例(74.2%);肿瘤浸润深度T1~4分别为44例(18.3%)、27例(11.2%)、60例(25.0%)和109例(45.4%);163例(67.9%)发生淋巴结转移,46例(19.2%)发生远处转移;Ⅰ~Ⅳ期患者分别为55例(22.9%)、42例(17.5%)、94例(39.2%)和53例(22.1%)。240例G⁃NEN患者中,223例(92.9%)获得随访,中位生存时间为39.2(95%CI:29.1~47.5)个月。单因素分析结果显示,年龄≥60岁、肿瘤直径≥4.2 cm、肿瘤分级为G3、淋巴结转移、远处转移、肿瘤分期(Ⅲ~Ⅳ)均是影响G⁃NEN患者预后的危险因素(均P<0.05);多因素分析结果显示,淋巴结转移(HR=1.783,95%CI:1.007~3.155,P=0.047)和远处转移(HR=2.288,95%CI:1.307~4.008,P=0.004)是影响G⁃NEN患者生存的独立危险因素。进一步亚组分析本组G3高级别G⁃NEN显示,NET⁃G3的5年生存率为76.19%,高于NEC⁃G3和MANEC⁃G3(分别为15.60%和24.73%,P=0.012),差异有统计学意义。结论G⁃NEN患者在诊断时,多已处于进展期,存在淋巴结转移和远处转移提示患者预后较差。高增殖NET⁃G3患者的预后好于NEC⁃G3及MANEC⁃G3,是一类值得进一步关注的分类。

Clinicopathologic features and prognostic analysis of 240 patients with gastric neuroendocrine neoplasms

Objective To investigate clinicopathological features and prognostic factors of gastric neuroendocrine tumors(G⁃NEN).Methods Clinical and pathological data of patients with G⁃NEN diagnosed by pathological examination in Chinese PLA General Hospital from January 2000 to June 2018 were retrospectively analyzed in this case⁃control study.Patients with complicated visceral lesions,other visceral primary tumors,mental disorders and incomplete clinicopathological data were excluded.Finally,240 hospitalized patients who met the inclusion criteria were enrolled.Physical examination information,tumor characteristics and pathological characteristics of patients were summarized.The Cox regression models were used to analyze the risk factors affecting G⁃NEN and the survival conditions were described by Kaplan⁃Meier survival curves and log⁃rank test.Results In 240 patients with G⁃NEN,the mean age was(60.3±10.1)years;181 were male(75.4%)and 59 females(24.6%);mean tumor diameter was(4.2±2.8)cm;51 cases(21.2%)were neuroendocrine tumor(NET),139 cases(57.9%)neuroendocrine carcinoma(NEC),50 cases(20.8%)mixed neuroendocrine carcinoma(MANEC);28 cases(11.7%)were G1 low grades,34 cases(14.2%)G2 medium grades,and 178 cases(74.2%)G3 high grades;tumor infiltration depth T1 to T4 were 44 cases(18.3%),27 cases(11.2%),60 cases(25.0%)and 109 cases(45.4%)respectively;163 cases(67.9%)developed lymphatic metastasis and 46 patients(19.2%)distant metastasis;tumor stage from stage I to stage IV were 55 cases(22.9%),42 cases(17.5%),94 cases(39.2%)and 53 cases(22.1%)respectively.Of the 240 G⁃NEN patients,223 cases(92.9%)were followed up.The median survival time of the patients was 39.2(95%CI:29.1 to 47.5)months.Univariate survival analysis showed that age≥60 years,tumor diameter≥4.2 cm,tumor grade G3,lymphatic metastasis,distant metastasis,and tumor stage III⁃IV were risk factors for G⁃NEN patients.Multivariate survival analysis revealed that lymphatic metastasis(HR=1.783,95%CI:1.007⁃3.155,P=0.047)and distant metastasis(HR=2.288,95%CI:1.307⁃4.008,P=0.004)were independent risk factors of the prognosis.Further analysis of the G3 subgroup of G⁃NEN showed that the 5⁃year survival rate of NET⁃G3 was 76.19%,which was significantly higher than that of NEC⁃G3 and MANEC⁃G3(15.60%and 24.73%,P=0.012).Conclusions Most G⁃NEN patients are in advanced stage at diagnosis.Lymphatic metastasis and distant metastasis indicate poor prognosis.The prognosis of high proliferation NET⁃G3 patients is better as compared to those of NEC⁃G3 and MANEC⁃G3.This classification is worth further attention.