胃癌伴神经内分泌分化患者临床病理特征及根治术后生存分析

Clinicopathological features and survival analysis of gastric cancer patients with neuroendocrine differentiation after radical resection

目的比较胃腺癌伴与不伴神经内分泌分化(NED)患者的临床病理特征及其接受胃癌根治术+D_(2)淋巴结清扫术后的预后差异。方法采用回顾性队列研究方法,病例纳入标准:(1)接受胃癌根治术+D_(2)淋巴结清扫的患者,术后病理证实为胃腺癌,并接受神经内分泌标记物Syn和(或)CgA的免疫组织化学检查;(2)年龄在20~75岁,各脏器功能正常;(3)术前未接受新辅助化疗或放疗;(4)根据美国癌症联合会(AJCC)第8版肿瘤分期标准,术后病理分期为Ⅰ~Ⅲ期;(5)根据术后病理分期完成规范的术后辅助化疗。排除既往5年内患有其他恶性肿瘤及无法按要求规律随访者。根据上述标准,收集2010年1月至2017年6月期间,确诊为胃癌并在复旦大学附属中山医院接受胃癌根治术+D_(2)淋巴结清扫的患者临床资料,对伴与不伴NED的胃腺癌患者的临床病理特征进行对比。末次随访时间为2020年6月,对比两组无病生存(DFS)和总体生存(OS)情况,并通过Cox比例风险模型校正伴NED对胃腺癌患者预后的影响。采用倾向性评分匹配方法作为敏感性分析。结果共有539例患者符合入组标准,其中胃癌伴NED患者35例,不伴NED患者504例。与不伴NED组患者相比,伴NED组患者的年龄更高[(65.0±7.5)岁比(54.5±11.3)岁,t=-7.681,P<0.001],接受近端胃切除术的比例更高[22.9%(8/35)比7.6%(36/504),χ^(2)=10.335,P=0.006],Lauren分型为肠型的比例更高[77.1%(27/35)比42.5%(214/504),χ^(2)=14.553,P<0.001],术后分期为Ⅲ期的比例更高[65.7%(23/35)比27.6%(139/504),χ^(2)=25.653,P<0.001]。伴NED组和不伴NED组患者的3年DFS分别为48.9%(95%CI:33.8%~70.8%)和37.4%(95%CI:32.9%~42.5%),差异无统计学意义(P=0.44)。伴NED组和不伴NED组患者的3年OS分别为56.1%(95%CI:39.9%~79.1%)和64.3%(95%CI:59.3%~69.7%),差异也无统计学意义(P=0.32)。单因素和多因素分析显示,胃癌伴NED不是影响患者DFS和OS的独立预后危险因素(均P>0.05)。敏感性分析显示,倾向评分匹配后两组间的DFS和OS差异仍无统计学意义(均P>0.05)。结论胃癌伴神经内分泌分化的患者发病年龄更高,接受近端胃切除术的比例更高,Lauren分型多为弥漫型,确诊时的分期较晚,但生存预后与不伴神经内分泌分化的患者相同。

Objective:To compare the clinicopathological characteristics and the prognosis of gastric adenocarcinoma patients with and without neuroendocrine differentiation(NED)after radical gastrectomy plus D_(2)lymph node dissection.Methods:A retrospective cohort study was performed.The inclusion criteria were as follows:(1)patients who underwent radical resection of gastric cancer plus D_(2)lymph node dissection and were confirmed as gastric adenocarcinoma by postoperative pathology and received immunohistochemical examination of neuroendocrine markers Syn and/or CgA;(2)patients aged 20 to 75 years with normal organ function;(3)patients who did not receive neoadjuvant chemotherapy or radiotherapy before operation;(4)patients with postoperative pathological stage I to III according to the 8th edition of tumor staging system of American Joint Committee on Cancer(AJCC);and(5)patients who completed adjuvant chemotherapy according to the postoperative pathological stage.Those who had other malignant tumors in the past 5 years and who could not be followed up according to the required rules were excluded.According to the above criteria,the clinicopathological characteristics of gastric cancer patients who underwent radical resection plus D_(2)lymph node dissection in Zhongshan Hospital of Fudan University from January 2010 to June 2017 were collected and compared.All patients were followed up till June 2020.The disease-free survival(DFS)and overall survival(OS)between the patients with and without NED were compared,and the effect of NED on the prognosis was corrected by Cox proportional hazards model.The propensity score matching method was used for sensitivity analysis.Results:A total of 539 patients were enrolled in this study,including 35 with NED and 504 without NED.Compared with the patients without NED,the patients with NED were older[(65.0±7.5)years vs.(54.5±11.3)years,t=-7.681,P<0.001],had higher proportion of undergoing proximal gastrectomy[22.9%(8/35)vs.7.6%(36/504),χ^(2)=10.335,P=0.006],higher proportion of intestinal-type based on Lauren classification[77.1%(27/35)vs.42.5%(214/504),χ^(2)=14.553,P<0.001],and higher proportion of pathologic stage III[65.7%(23/35)vs.27.6%(139/504),χ^(2)=25.653,P<0.001].The 3-year DFS of patients with NED and those without NED was 48.9%(95%CI:33.8%-70.8%)and 37.4%(95%CI:32.9%-42.5%)respectively,and no significant difference was found(P=0.44).The 3-year OS was 56.1%(95%CI:39.9%-79.1%)and 64.3%(95%CI:59.3%-69.7%)respectively,and no significant difference was found as well(P=0.32).Univariate and multivariate analyses showed that NED was not an independent risk factor for DFS and OS(all P>0.05).Sensitivity analysis showed that there was no significant difference in DFS and OS between the two groups after propensity score matching.Conclusion:Compared with patients without NED,patients with NED were older at onset,had a higher proportion of proximal gastrectomy,intestinal-type,and later diagnostic stage,but the survival prognosis had no significant difference with that of patients without NED.