Objective: To explore the clinicopathological features, treatment strategy and to analysis of prognosis-related risk factors of gastric neuroendocrine neoplasms(G-NEN). Methods: In this study, a retrospective observational study method was used to collect the clinicopathological data of patients diagnosed with G-NEN by pathological examination in the First Medical Center of PLA General Hospital from January 2000 to December 2021. The basic information of the patients, tumor pathological characteristics, and treatment methods were entered, and the treatment information and survival data after discharge were followed up and recorded. The Kaplan-Meier method was used to construct survival curves, and the log-rank test to analyze the differences in survival between groups. Cox Regression model analysis of risk factors affecting the prognosis of G-NEN patients. Results: Among the 501 cases confirmed as G-NEN, 355 were male and 146 were female, and their median age was 59 years. The cohort comprised 130 patients (25.9%) of neuroendocrine tumor (NET) G1, 54 (10.8%) of NET G2, 225 (42.9%) of neuroendocrine carcinoma (NEC), and 102 cases (20.4%) of mixed neuroendocrine-non-neuroendocrine(MiNEN). Patients NET G1 and NET G2 were mainly treated by endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR). The main treatment for patients with NEC/MiNEN was the same as that for gastric malignancies, namely radical gastrectomy+lymph node dissection supplemented with postoperative chemotherapy. There were significant differences in sex, age, maximum tumor diameter, tumor morphology, tumor numbers, tumor location, depth of invasion, lymph node metastasis, distant metastasis, TNM staging and expression of immunohistological markers Syn and CgA among NET, NEC, and MiNEN patients (all P<0.05). Further for NET subgroup analysis, there were significant differences between NET G1 and NET G2 in the maximum tumor diameter, tumor shape and depth of invasion(all P<0.05). 490 patients (490/501, 97.8%) were followed up with a median of 31.2 months. 163 patients had a death during follow-up (NET G1 2, NET G2 1, NEC 114, MiNEN 46). For NET G1, NET G2, NEC and MiNEN patients,the 1-year overall survival rates were 100%, 100%, 80.1% and 86.2%, respectively; the 3-year survival rates were 98.9%, 100%, 43.5% and 55.1%, respectively. The differences were statistically significant (P<0.001). Univariate analysis showed that gender, age, smoking history, alcohol history, tumor pathological grade, tumor morphology, tumor location, tumor size, lymph node metastasis, distant metastasis, and TNM stage were associated with the prognosis of G-NEN patients (all P<0.05). Multivariate analysis showed that age ≥60 years, pathological grade of NEC and MiNEN, distant metastasis, and TNM stage III-IV were independent factors influencing the survival of G-NEN patients (all P<0.05). 63 cases were stage IV at initial diagnosis. 32 of these were treated with surgery and 31 with palliative chemotherapy. Stage IV subgroup analysis showed that the 1-year survival rates were 68.1% and 46.2% in the surgical treatment and palliative chemotherapy groups, respectively, and the 3-year survival rates were 20.9% and 10.3%, respectively; the differences were statistically significant (P=0.016). Conclusions: G-NEN is a heterogeneous group of tumors. Different pathological grades of G-NEN have different clinicopathological features and prognosis. Factors such as age ≥ 60 years old, pathological grade of NEC/MiNEN, distant metastasis, stage III, IV mostly indicate poor prognosis of patients. Therefore, we should improve the ability of early diagnosis and treatment, and pay more attention to patients with advanced age and NEC/MiNEN. Although this study concluded that surgery improves the prognosis of advanced patients more than palliative chemotherapy, the value of surgical treatment for patients with stage IV G-NEN remains controversial.
目的： 探讨胃神经内分泌肿瘤（G-NEN）的临床病理特征和治疗模式，并进行预后分析。 方法： 采用回顾性观察性研究方法，收集2000年1月至2021年12月期间，在解放军总医院第一医学中心经病理检查确诊为G-NEN患者的临床病理资料，包括患者基本信息、肿瘤病理特征、治疗方法，随访并记录患者出院后治疗信息和生存资料等。采用Kaplan-Meier法绘制生存曲线，Log-rank检验来比较分析不同病理类型组间G-NEN患者生存率差异，Cox回归模型分析影响G-NEN患者预后的危险因素。 结果： 共计纳入501例G-NEN患者，其中男355例，女146例；中位年龄为59岁。神经内分泌瘤（NET）G1、NET G2、神经内分泌癌（NEC）、混合性神经内分泌-非神经内分泌肿瘤（MiNEN）分别为130例（25.9%）、54例（10.8%）、215例（42.9%）和102例（20.4%）。NET G1/G2患者治疗方式主要是以内镜下切除为主，包括内镜黏膜下剥离术（ESD）和内镜黏膜切除术（EMR），NEC和MiNEN患者主要治疗方式同胃部恶性肿瘤，为根治性胃切除+淋巴结清扫辅以术后化疗。NET、NEC与MiNEN这3组患者在性别、年龄、肿瘤最大径、肿瘤形态、肿瘤个数、肿瘤部位、肿瘤浸润深度、淋巴结转移、远处转移、肿瘤TNM分期、免疫组织化学标记物Syn和CgA表达方面的差异均有统计学意义（均P<0.05）。NET亚组分析结果显示：NET G1与NET G2两组患者在肿瘤最大径、肿瘤形态和肿瘤浸润深度方面差异有统计学意义（均P<0.05）。490例（97.8%，490/501）患者获得随访，中位随访时间为31.2个月。163例患者随访期间发生死亡事件（NET G1 2例，NET G2 1例，NEC 114例，MiNEN 46例）。NET G1、NET G2、NEC和MiNEN患者1年生存率分别为100%、100%、80.1%和86.2%；3年生存率分别为98.9%、100%、43.5%和55.1%；其生存比较，差异有统计学意义（P<0.001）。单因素分析结果显示，性别、年龄、吸烟史、饮酒史、肿瘤病理分级、肿瘤形态、肿瘤位置、肿瘤最大径、淋巴结转移、远处转移、TNM分期均与G-NEN患者生存预后有关（均P<0.05）。多因素分析结果显示，≥60岁、病理分级为NEC和MiNEN、远处转移、TNM分期为Ⅲ~Ⅳ期是影响G-NEN患者生存的独立因素。63例初诊时已处于Ⅳ期，其中32例行手术治疗、31例行姑息性化疗；Ⅳ期亚组分析显示，手术治疗组与姑息性化疗组的1年生存率分别为68.1%和46.2%；3年生存率分别为20.9%和10.3%，其差异有统计学意义（P=0.016）。 结论： G-NEN是一组异质性的肿瘤，不同病理分级的G-NEN具有不同的临床病理学特征和预后；年龄≥60岁，病理分级为NEC/MiNEN、远处转移、分期为Ⅲ~Ⅳ期多提示患者较差的预后，因此应提高早诊早治的能力，同时对于高龄患者和NEC/MiNEN患者更多的关注。尽管本研究认为手术比姑息性化疗更能提高晚期患者的预后，但是手术治疗对于Ⅳ期G-NEN患者的价值仍存在争议。.