早期低分化胃癌淋巴结转移危险因素分析

Predictive factors for lymph node metastasis in patients with poorly differentiated early gastric cancer

目的探讨早期低分化胃癌淋巴结转移的临床病理因素,为选择治疗方法提供依据。方法采用回顾性病例对照研究的方法,收集2012年1月至2016年12月期间、在上海交通大学医学院附属瑞金医院普通外科行胃癌根治术(远端胃大部或全胃切除+D2淋巴结清扫术)、且术后经病理确诊为早期低分化胃癌(包括印戒细胞癌和黏液腺癌)患者的临床资料。排除远处转移、同时存在两处以上恶性肿瘤、残胃癌、术前辅助治疗、既往存在胃部手术史或明确胃周淋巴结切除病史以及混合型肿瘤者。观察患者年龄、性别、是否溃疡型肿瘤、肿瘤大小、肿瘤部位、肿瘤浸润深度、肿瘤分化类型、淋巴管是否侵犯、血管是否侵犯、神经是否侵犯以及HER2表达等指标,单因素及多元逐步logistic回归方法分析影响胃周淋巴结转移的独立危险因素。进一步根据中国临床肿瘤学会(CSCO)胃癌治疗指南(2018年版)中早期低分化胃腺癌内镜黏膜下剥离术(ESD)手术扩大适应证:(1)无溃疡性病灶,病灶最大径>2 cm的分化型黏膜内癌;(2)合并溃疡病灶,病灶最大径≤3 cm的分化型黏膜内癌;(3)无溃疡性病灶,病灶最大径≤2 cm的未分化型黏膜内癌),选出符合上述适应证的患者,对其中出现淋巴结转移者进行分析,了解这部分患者临床病理因素与其淋巴结转移的关系。结果共517例患者纳入研究,年龄21~83(57.1±11.7)岁,其中男性307例,女性210例;有114例(22.0%)术后病理提示存在淋巴结转移。单因素分析结果显示,肿瘤是否为溃疡型(P=0.042)、肿瘤直径(P=0.048)、肿瘤浸润深度(P<0.001)、肿瘤部位(P<0.001)、肿瘤淋巴管侵犯(P=0.009)、血管侵犯(P<0.001)以及神经侵犯(P=0.028)与本组早期低分化胃癌患者出现淋巴结转移有关;而患者年龄、性别、肿瘤分化类型以及HER2表达与之无关(均P>0.05)。多因素分析结果显示,肿瘤直径(OR=1.61,95% CI:1.03~2.52,P=0.037)、肿瘤浸润深度(OR=2.77,95% CI:1.66~4.63,P<0.001)和淋巴管侵犯(OR=14.74,95% CI:1.58~137.36,P=0.018)是早期低分化胃癌患者淋巴结转移的独立危险因素;而肿瘤是否为溃疡型并不是淋巴结转移的危险因素(OR=0.82,95% CI:0.56~1.18,P=0.285)。全组符合CSCO推荐的ESD适应证患者119例(23.0%),无一例发现存在血管、淋巴管或者神经侵犯现象;但其中11.8%(14/119)存在胃周淋巴结转移,分析其临床病理因素与淋巴结转移的关系结果显示,这组患者的性别、肿瘤直径、肿瘤部位、肿瘤分化类型以及Her-2表达均与淋巴结转移无关(均P>0.05)。结论针对早期低分化胃癌患者,建议在精确评估肿瘤直径和浸润深度以及淋巴管侵犯程度的前提下,选择切除手段;采取ESD治疗应慎重。

Objective This study aimed to identify clinicopathological factors predictive of lymph node metastasis in patients with the poorly differentiated early gastric cancer (EGC) to assess the feasibility of using endoscopic submucosal dissection (ESD). Methods The records of patients with poorly differentiated early gastric cancer undergoing gastric radical resection between January 2012 and December 2016 were reviewed in Ruijin hospital. Those with distant metastasis, two or more malignant tumors, remnant gastric cancer, neo adjuvant therapy, previous history of gastric surgery or clear history of perigastric lymphadenectomy, and mixed tumors were excluded. Age, sex, presence of ulcerous lesion, tumor size, tumor location, depth of invasion, type of differentiation, lymphatic vessel invasion, vascular invasion, nerve invasion and HER2 expression were collected. Univariate and multivariate stepwise logistic regression analyses were used to identify the independent risk factors of perigastric lymph node metastasis.According to the Guidelines for the Treatment of Gastric Cancer (2018 edition) of the Chinese Society of Clinical Oncology (CSCO), the expanded indications of ESD for EGC are as follows:(1)no ulcerative lesions, the maximum diameter of lesions >2 cm of differentiated intramucosal cancer;(2)ulcerative lesions, the maximum diameter of lesions ≤3 cm of differentiated intramucosal cancer;(3)no ulcerative lesions, undifferentiated intramucosal carcinoma with diameter ≤2 cm. The relationship between clinicopathological factors and lymph node metastasis was analyzed. Results A total of 517 patients, aged 21-83 (57.1±11.7), including 307 males and 210 females, were enrolled in the study. Among them, 114 (22.0%) patients had lymph node metastasis. Univariate analysis showed that ulcerative lesion (P=0.042), tumor diameter (P=0.048), depth of invasion (P<0.001), location of tumors (P<0.001), lymphatic vessel invasion (P=0.009), vascular invasion (P<0.001) and nerve invasion (P=0.028) were related to lymph node metastasis after radical resection of poorly differentiated early adenocarcinoma. Age, sex, type of differentiation and HER2 expression were not significantly correlated to lymph node metastasis (P>0.05). Multivariate analysis showed that tumor size (OR=1.61, 95% CI: 1.03-2.52, P=0.037), depth of invasion (OR=2.77, 95% CI:1.66-4.63, P<0.001), lymphatic duct invasion (OR=14.74, 95% CI:1.58-137.36, P=0.018) were independent risk factors for lymph node metastasis in poorly differentiated EGC, and ulcerative lesion was not a risk factor for lymph node metastasis (OR=0.82, 95% CI:0.56-1.18,P=0.285). A total of 119 patients with poorly differentiated EGC fully complied with the relative indications of ESD recommended by the Japanese Statute and the criteria for radical resection after ESD. Among them, 14 (11.8%) still had perigastric lymph node metastasis, while the gender, tumor diameter, location, differentiation and HER2 expression were not associated with lymph node metastasis (P>0.05). Conclusion For patients with poorly differentiated EGC, the application of ESD should be carefully weighed with precise assessment of tumor diameter, depth of invasion, and lymphatic duct invasion.