新辅助治疗行胃癌根治术患者术后并发症及其对预后的影响因素分析

目的探讨新辅助治疗后行胃癌根治术的患者术后并发症发生情况及其预后的影响因素。方法采用回顾性病例队列研究方法。病例纳入标准:(1)组织病理学证实为胃腺癌;(2)术前影像学检查无远处转移或腹膜种植转移;(3)行新辅助治疗后接受胃癌根治术加D2淋巴结清扫术;(4)临床病理及随访资料完整。根据以上标准,回顾性收集2008年1月至2018年12月期间,于中国医学科学院北京协和医学院肿瘤医院行胃癌根治术的490例胃癌患者的临床资料,其中男性358例,女性132例,年龄(55.0±10.6)岁。新辅助治疗方案包括SOX(替吉奥+奥沙利铂)151例,XELOX(希罗达+奥沙利铂)105例,FLOT(多西他赛+奥沙利铂+氟尿嘧啶)66例以及DOS(多西他赛+奥沙利铂+替吉奥)68例;术前行同步放化疗患者100例,采用SOX方案2-4周期诱导化疗加同步放化疗(三维适形调强放疗+替吉奥)。术后并发症指术后出现的手术相关并发症,主要包括术后出血、吻合口漏、术后梗阻、术后狭窄、肺部感染、腹腔感染等。根据Clavien-Dindo法评定术后并发症分级。采用log-rank检验进行预后单因素分析,采用Cox回归模型进行预后模型的多因素分析。结果全组患者术后总并发症的发生率为17.8%(87/490,总计101例次),其中发生严重并发症者(Clavien-Dindo Ⅲ-Ⅴ级)29例,非严重并发症者(Clavien-Dindo Ⅰ-Ⅱ级)58例。多因素分析结果显示,年龄>65岁(HR=3.077,95% CI:1.827-5.184,P<0.001)和胃切除范围(HR=1.735,95% CI:1.069-2.814,P=0.026)是新辅助治疗胃癌根治术患者术后并发症发生的独立危险因素(均P<0.05)。全组患者随访时间0.7-131.8(中位数21.5)个月,5年生存率为47.4%。并发症组(87例)与无并发症组(403例)5年总体生存率分别为33.2%和50.9%(P=0.001)。多因素分析结果显示,年龄(HR=1.906,95% CI:1.248-2.913,P=0.003)、ypTNMⅡ-Ⅲ期(Ⅱ期:HR=5.853,95% CI:1.778-19.260,P=0.004;Ⅲ期:HR=10.800,95% CI:3.411-34.189,P<0.001)、手术时间>3.5 h(HR=1.492,95% CI:1.095-2.033,P=0.011)、全胃切除(HR=1.657,95% CI:1.216-2.257,P=0.001)以及术后并发症(HR=1.614,95% CI:1.125-2.315,P=0.009)是影响本组患者预后的独立危险因素,术后行辅助治疗(HR=0.578,95% CI:0.421-0.794,P=0.001)是本组患者预后的独立保护因素。结论新辅助治疗行胃癌根治术患者并发症的发生与患者年龄和手术切除范围密切相关,重视减少并发症的损害及加强辅助治疗,有利于改善新辅助治疗胃癌根治术患者的预后。

Postoperative complications and their influence on the prognosis factors in gastric cancer patients receiving neoadjuvant treatment

Objective To investigate postoperative complications of patients undergoing neoadjuvant therapy followed by radical gastrectomy,and to analyze their influence on the prognosis.Methods A retrospective case-control study was used.Case inclusion criteria:(1)gastric adenocarcinoma confirmed by histopathology;(2)preoperative imaging examination showed no distant metastasis or peritoneal dissemination;(3)undergoing radical gastrectomy and D2 lymph node dissection after neoadjuvant therapy;(4)complete clinicopathological and follow-up data.According to the above criteria,clinical data of 490 gastric cancer patients who underwent radical gastrectomy in the Cancer Hospital of Chinese Academy of Medical Sciences,Peking Union Medical College from January 2008 to December 2018 were retrospectively collected,including 358 males and 132 females with mean age of(55.0±10.6)years.Neoadjuvant chemotherapy regimens included SOX(S-1+oxaliplatin,n=151),XELOX(capecitabine+oxaliplatin,n=155),FLOT(docetaxel+oxaliplatin+fluorouracil,n=66),and DOS(docetaxel+oxaliplatin+S-1,n=68).Preoperative concurrent chemoradiotherapy was performed in 100 patients.SOX regimen was used for 2-4 cycles as induction chemotherapy plus concurrent chemoradiotherapy(3D IMRT+S-1).Postoperative complications were defined as surgery-related complications,mainly including hemorrhage,anastomotic leakage,obstruction,anastomotic stenosis,pulmonary infection,abdominal infection,etc.Postoperative complications were graded according to Clavien-Dindo classification.Log-rank test and Cox regression model were used for univanriate multivariate prognostic analysis,respectively.Results A total of 101 complications ocaured after operation in 87(17.8%)patients,including 29 cases of major complications(Clavien-Dindo Ⅲ to Ⅴ),and 58 cases of minor complications(Clavien-Dindo I to Ⅱ).Multivariate analysis showed that age>65 years(HR=3.077,95%CI:1.827-5.184,P<0.001)and total gastrectomy(HR=1.735,95%CI:1.069-2.814,P=0.026)were independent risk factors for postoperative complications in patients with gastric cancer undergoing neoadjuvant therapy and radical gastrectomy(both P<0.05).The follow-up period was 0.7 to 131.8 months(median 21.5 months),and the 5-year overall survival rate was 47.4%.The 5-year overall survival rates of the complication group(87 cases)and the non-complication group(403 cases)were 33.2%and 50.9%,respectively(P=0.001).Multivariate analysis showed that age(HR=1.906,95%CI:1.248-2.913,P=0.003),ypTNM Ⅱ to Ⅲ stage(Ⅱ stage:HR=5.853,95%CI:1.778-19.260,P=0.004;Ⅲ stage:HR=10.800,95%CI:3.411-34.189,P<0.001),surgery time>3.5 h(HR=1.492,95%CI:1.095-2.033,P=0.011),total gastrectomy(HR=1.657,95%CI:1.216-2.257,P=0.001)and postoperative complications(HR=1.614,95%CI:1.125-2.315,P=0.009)were independent risk factors for prognosis,and postoperative adjuvant therapy(HR=0.578,95%CI:0.421-0.794,P=0.001)was an independent protective factor for prognosis.Conclusions The occurrence of postoperative complications in gastric cancer patients undergoing neoadjuvant therapy is closely related to the age of the patients and the range of surgical resection.It is beneficial to improve the prognosis for these patients by paying more attention to the prevention of postoperative complications and the reinforcement of postoperative adjuvant therapy.