胃癌根治术中食管切缘跳跃转移30例临床特征分析

Skip metastasis at the esophageal resection margin in radical gastrectomy:clinical characteristics of 30 cases

目的总结分析胃癌根治术中食管切缘跳跃转移病例的临床特征。方法采用描述性病例系列研究的方法,收集2006—2022年期间南京大学医学院附属鼓楼医院和东部战区总医院两家大型胃癌诊治中心的病例资料,总结分析患者的肿瘤特征和手术情况以及肿瘤的免疫组织化学检测特点及病理分期,并进一步分析食管侧吻合圈残留癌的细胞及组织层面分布特点。食管切缘跳跃转移定义为食管切缘阴性、但食管侧吻合圈阳性。结果双中心共有30例(0.33%,30/8972)胃癌患者根治术中发现食管切缘跳跃转移,其中男性24例(80.0%),年龄(63.9±11.0)岁。乳头状或管状腺癌17例(56.7%),其中低分化13例(43.3%),中分化4例(13.3%);印戒细胞癌4例(13.3%);黏液腺癌4例(13.3%);混合性腺癌3例(10.0%),其中2例为低分化管状腺癌混杂印戒细胞癌及黏液腺癌,1例为低分化管状腺癌混杂印戒细胞癌;特殊类型癌2例(6.7%),其中1例为腺鳞癌,1例为未分化癌。肿瘤位于胃小弯侧26例(86.7%),位于贲门24例(80.0%)。肿瘤长径中位数6.6 cm,距食管切缘中位数1.5 cm,肿瘤侵犯齿状线、神经及脉管的比例分别为80.0%(24/30)、86.7%(26/30)和93.3%(28/30)。术中淋巴结清扫(20.4±8.9)枚。术后病理分期T4期18例(60.0%),N3期21例(70.0%)。Ki-67指数中位数为52.7%,HER2、表皮生长因子受体(EGFR)、血管内皮生长因子受体(VEGFR)、E-cadherin和细胞程序性死亡配体1(PD-L1)的阳性比例分别为40.0%(12/30)、46.7%(14/30)、80.0%(24/30)、86.7%(26/30)和16.7%(5/30)。食管侧吻合圈残留癌在细胞层面,癌细胞以“小灶区”、“细胞团”、“癌栓”分布形式为主,极少见大量广泛分布的异型细胞;在组织层面,癌细胞位于黏膜层7例(23.3%),黏膜下层18例(60.0%),肌层5例(16.7%),无一例残留于外膜。在7例黏膜层病例中,5例位于黏膜固有层,2例位于黏膜肌层,无一例残留于黏膜上皮层。结论胃癌食管切缘跳跃转移患者的肿瘤生物学行为较差,增殖指数较高,病理分期较晚,残留癌多位于黏膜下层。

Objective To summarize the clinical characteristics of patients with skip metastasis at esophageal resection margin during radical gastrectomy.Methods This is a descriptive study of case series.Relevant data from 2006 to 2022 were collected from two major gastric cancer consultation and treatment centers:Nanjing Drum Tower Hospital and Jinling Hospital.Characteristics,surgical approach,number of dissected lymph nodes,immunohistochemical staining,and pathological staging were summarized and analyzed.The distribution of residual tumor cells at the esophageal margins was further analyzed at the cellular and tissue levels.Skip metastasis at the esophageal resection margin was defined as a negative esophageal margin with a positive margin in the cephalad donut.Results Thirty(0.33%,30/8972)eligible patients,24(80.0%)of whom were male,were identified in the two centers.The mean age was 63.9±11.0 years.Seventeen(56.7%)of these patients had papillary or tubular adenocarcinomas,including 13(43.3%)poorly-and four(13.3%)moderately-differentiated tumors;four(13.3%)had signet-ring cell carcinomas;four(13.3%)mucinous adenocarcinomas;three(10.0%)mixed adenocarcinomas,including two with poorly-differentiated tubular adenocarcinomas mixed with signet-ring cell carcinoma and mucinous adenocarcinoma;and one had a poorly differentiated tubular adenocarcinoma mixed with signet-ring cell carcinoma.Two patients(6.7%)had other types of cancer,namely adenosquamous carcinoma in one patient and undifferentiated carcinoma in the other one.The predominant tumor sites were the lesser curvature(n=26,86.7%)and the cardia(n=24,80.0%).The mean tumor diameter was 6.6 cm,mean distance between tumor and esophageal resection margin was 1.5 cm,and proportions of tumor invasion into the dentate line,nerves,and vessels were 80.0%(24/30),86.7%(26/30),and 93.3%(28/30),respectively.The mean number of lymph nodes resected was 20.4±8.9.The pathological stage was mainly T4(n=18,60.0%)and N3(n=21,70.0%),the median Ki67 was 52.7%,and the rates of positivity for HER2,EGFR,VEGFR,E-cadherin and PD-L1 were 40.0%(12/30),46.7%(14/30),80.0%(24/30),86.7%(26/30)and 16.7%(5/30),respectively.At the cellular level,cancer cells were mainly distributed in small focal areas,as cell masses,or as tumor thrombi;large numbers of widely distributed atypic cells were seldom observed.At the tissue level,cancer cells were located in the mucosal layer in seven patients(23.3%),in the submucosal layer in 18(60.0%),and in the muscular layer in five(16.7%);no cancer cells were identified in the outer membrane.Five of the seven tumors were located in the lamina propria,two in the muscularis mucosae,and none in the mucosal epithelium.Conclusion Patients with skip metastasis at the esophageal resection margin at radical gastrectomy have unfavorable tumor biology and a high proliferation index,are at a late pathological stage,and the residual cancer is mostly located in the submucosa.