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Ⅱ、Ⅲ期胃癌病人术后治疗失败模式及危险因素分析

陆    俊,吴    栋,林    嘉,许斌斌,薛    震,郑朝辉,李    平,谢建伟,王家镔,林建贤,陈起跃,黄昌明   

  1. 福建医科大学附属协和医院胃外科  福建医科大学附属协和医院普外科 福建医科大学消化道恶性肿瘤教育部重点实验室,福建福州 350004 
  • 出版日期:2021-10-01

  • Online:2021-10-01

摘要: 目的    探讨Ⅱ、Ⅲ期胃癌病人的术后治疗失败模式及其影响因素。方法    回顾性分析2010年1月至2013年12月福建医科大学附属协和医院胃外科收治的875例行根治性切除手术的Ⅱ、Ⅲ期胃癌病人的临床资料,其中术后治疗失败407例(治疗失败组),无术后治疗失败468例(无治疗失败组)。术后治疗失败定义为手术后首次发现任何部位复发或任何原因死亡。通过Kaplan-Meier累积风险曲线、COX比例风险模型分析术后治疗失败的影响因素,并用韦恩图和核密度曲线展示术后治疗失败模式。结果    治疗失败组与无治疗失败组病人在远侧胃切除率、术前CA19-9水平、术前癌胚抗原(CEA)水平、肿瘤大小以及pN分期方面差异有统计学意义(P均<0.05)。多因素分析发现,术前CA19-9水平≥37 kU/L、术前CEA水平≥5 μg/L、肿瘤部位、pN分期、严重并发症为影响Ⅱ、Ⅲ期胃癌病人术后治疗失败的独立危险因素,而术后辅助化疗是其独立保护因素。竞争风险分析术后治疗失败模式显示,Ⅱ、Ⅲ期胃癌病人远处器官复发、腹膜复发、局部复发和无复发死亡的3年累积发生率分别为20.4%、10.0%、7.9%和5.1%。根据3个月的时间间隔拟合所有病例的治疗失败风险曲线显示,治疗失败风险率峰值在术后第16.7个月出现,峰值为0.0143,随后逐渐下降,大部分治疗失败事件发生于术后36个月内。分层分析显示,尽管局部复发、腹膜复发和无复发死亡呈现出相似的达峰时间和风险峰值,但远处器官复发的达峰时间最早,且峰值显著高于其他失败类型(达峰时间14.5个月,风险峰值0.0074)。结论    不良的肿瘤学特征与Ⅱ、Ⅲ期胃癌病人术后治疗失败密切相关,而术后辅助化疗是其独立保护因素。对于Ⅱ、Ⅲ期胃癌病人早期随访应重视远处器官复发的筛查。

关键词: 胃癌, 失败模式, 动态风险, 危险因素, 随访

Abstract: Patterns and risk factors of postoperative treatment failure in patients with stage Ⅱ-Ⅲ gastric cancer        LU Jun,WU Dong,LIN Jia,et al. Department of Gastric Surgery/General Surgery,Fujian Medical University Union Hospital;Key Laboratory of Ministry of Education of Gastrointestinal Cancer,Fujian Medical University,Fuzhou 350004,China 
Corresponding author:HUANG Chang-ming,E-mail:hcmlr2002@163.com
Abstract    Objective    To explore the pattern and risk factors of postoperative treatment failure in patients with stage Ⅱ-Ⅲ gastric cancer. Methods    A total of 875 stage Ⅱ-Ⅲ gastric cancer patients who underwent radical resection in the Department of Gastric Surgery of the Union Hospital of Fujian Medical University from January 2010 to December 2013 were retrospectively analyzed. Among them,407 patients endured postoperative treatment failure (46.5%,Failure group,FG) and the remaining 468 patient did not (53.5%,Non-failure group,NFG). Postoperative treatment failure is defined as the initial recurrence of any site or death of any cause after surgery. The competing risk curve and COX proportional hazard regression were used to analyze the risk factors of postoperative treatment failure,and the Venn diagram and kernel density curve were used to show the dynamic failure patterns. Results    Compared with the NFG,significant difference were witnessed in the FG in terms of the distal gastrectomy rate,preoperative CA19-9,preoperative CEA,tumor size and pathological N stage (all P<0.05). Multivariate analysis found that preoperative CA19-9 ≥ 37 kU/L,preoperative CEA ≥ 5 μg/L,tumor location,pN stage and major complication were independent risk factors associated with treatment failure for patients with stage Ⅱ-Ⅲ gastric cancer,however,adjuvant chemotherapy was the independent protective factor. Competing risk curve showed that the 3-year cumulative hazard rate of distant recurrence,peritoneal recurrence,local recurrence,and death without recurrence in patients with stage Ⅱ-Ⅲ gastric cancer was 20.4%,10.0%,7.9%,and 5.1%,respectively. Furthermore,the dynamic hazard rate peaked at 16.7 months (peak rate=0.0143) before gradually declining,most treatment failure events occurred within 36 months after surgery. Similar trend were between local recurrence,peritoneal recurrence and death without recurrence,whereas the earliest peak time and highest hazard rate was seen in distant recurrence compared with other failure types (peak time=14.5 months;peak rate=0.0074). Conclusion    Poor oncological characteristics are closely related to treatment failure in patients with stage Ⅱ-Ⅲ gastric cancer,while adjuvant chemotherapy is the independent protective factor. More intensive surveillance for early detection of distant recurrence should be considered for patients with stage Ⅱ-Ⅲgastric cancer.

Key words: gastric cancer, failure pattern, dynamic hazard, risk factors, surveillance