规范化外科手术与多学科综合治疗对胃癌患者预后的影响:一项单中心队列研究报告

Effect of standardized surgical treatment and multidisciplinary treatment strategy on the prognosis of gastric cancer patients: report of a single-center cohort study

目的探讨规范化外科手术以及多学科诊疗模式的开展对胃癌外科患者治疗结局的影响。方法采用单中心队列研究方法,自四川大学华西医院胃癌专病数据库收集2000-2016年行胃癌外科手术治疗的4516例原发性胃癌患者的临床病理及预后资料,依据治疗时间段分为第1时期段组(2000-2006年,胃癌规范化外科治疗探索阶段,967例);第2时期段组(2007-2012年,胃癌规范化外科治疗应用阶段,1962例);第3时期段组(2013-2016年,胃癌规范化外科治疗策略优化与多学科治疗体系应用阶段,1587例)。比较分析3组患者之间临床、病理及预后的差异。随访预后信息更新截止至2020年1月1日。全组病例最终随访率88.9%(4016/4516),中位随访时间51.58个月。生存曲线采用Kaplan-Meier法进行绘制,log-rank检验进行生存曲线间的比较。采用Cox比例风险模型进行单因素生存分析及多因素生存分析。结果第1、第2和第3时期段组D2/D2+淋巴结清扫比例分别为14.4%(139/967)、47.2%(927/1962)和75.4%(1197/1587),3组比较,差异有统计学意义(χ^2=907.210,P<0.001);近端胃切除比例分别为19.8%(191/967)、16.6%(325/1962)和8.2%(130/1587),差异也有统计学意义(χ^2=100.020,P<0.001);中位术中出血量分别为300 ml、100 ml和100 ml,差异同样具有统计学意义(H=1126.500,P<0.001)。同时还发现,中位淋巴结清扫数目第1、第2和第3时期段组分别为14枚、26枚及30枚,3组呈显著增加趋势(H=987.100,P<0.001)。生存分析显示,第1、第2和第3时期段组患者预期术后5年总体生存率分别为55.3%、55.2%和62.8%,且第3时期段组与第1时期段组的差异有统计学意义(P=0.004)。多因素生存分析结果显示,治疗时期段(第3时期段组比第1时期段组,HR=0.820,95%CI:0.708~0.950,P=0.008)、接受术后辅助治疗(HR=0.696,95%CI:0.631~0.768,P<0.001)以及非上部肿瘤(HR=0.884,95%CI:0.804~0.973,P=0.011)是影响患者预后的积极因素,而患者发病年龄≥65岁(HR=1.189,95%CI:1.084~1.303,P<0.001)、姑息性手术切除(HR=1.538,95%CI:1.333~1.776,P<0.001)、肿瘤长径≥5 cm(HR=1.377,95%CI:1.239~1.529,P<0.001)、肿瘤大体分型为Ⅲ~Ⅳ型(HR=1.165,95%CI:1.063~1.277,P<0.001)及肿瘤TNM分期Ⅱ~Ⅳ期(Ⅱ/Ⅰ:HR=1.801,95%CI:1.500~2.162,P<0.001;Ⅲ/Ⅰ:HR=3.588,95%CI:3.028~4.251,P<0.001;Ⅳ/Ⅰ:HR=6.114,95%CI:4.973~7.516,P<0.001)为预后独立危险因素。结论通过规范化外科手术治疗技术的实施以及多学科诊疗模式的开展,提高了胃癌外科诊疗质量,改善了胃癌患者的治疗预后。

Objective To explore the effect of standardized surgical treatment and multidisciplinary treatment strategy on the treatment outcomes of gastric cancer patients.Methods A single-center cohort study was carried out.Clinicopathological and long-term follow up data of primary gastric cancer patients were retrieved from the database of Surgical Gastric Cancer Patient Registry(SGCPR)in West China Hospital of Sichuan University.Finally,4516 gastric cancer patients were included and were divided into three groups according to time periods(period 1 group:exploration stage of standardized surgical treatment,2000 to 2006,967 cases;period 2 group:application stage of standardized surgical treatment,2007 to 2012,1962 cases;period 3 group:optimization stage of standardized surgical treatment and application stage of multidisciplinary treatment strategy,2013 to 2016,1587 cases).Differences in clinical data,pathologic features,and prognosis were compared among 3 period groups.Follow-up information was updated to January 1,2020.The overall follow-up rate was 88.9%(4016/4516)and median follow-up duration was 51.58 months.Survival curve was drawn by Kaplan-Meire method and compared with log-rank test.Univariate and multivariate analyses were performed by Cox proportional hazards model.Results There were significant differences among period 1,period 2 and period 3 groups in the rates of D2/D2+lymphadenectomy[14.4%(139/967)vs.47.2%(927/1962)vs.75.4%(1197/1587),χ^2=907.210,P<0.001],in the ratio of proximal gastrectomy[19.8%(191/967)vs.16.6%(325/1962)vs.8.2%(130/1587),χ^2=100.020,P<0.001],and in the median intraoperative blood loss(300 ml vs.100 ml vs.100 ml,H=1126.500,P<0.001).Besides,the increasing trend and significant difference were also observed in the median number of examined lymph nodes among period 1,period 2 and period 3 groups(14 vs.26 vs.30,H=987.100,P<0.001).Survival analysis showed that the 5-year overall survival rate was 55.3%in period 1,55.2%in period 2 and 62.8%in period 3,and significant difference existed between period 3 and period 1(P=0.004).The Cox proportional hazards model analysis showed that treatment period(period 3,HR=0.820,95%CI:0.708 to 0.950,P=0.008),postoperative chemotherapy(HR=0.696,95%CI:0.631 to 0.768,P<0.001)and mid-low gastric cancer(HR=0.884,95%CI:0.804 to 0.973,P=0.011)were good prognostic factors.Whereas old age(≥65 years,HR=1.189,95%CI:1.084 to 1.303,P<0.001),palliative resection(R1/R2,HR=1.538,95%CI:1.333 to 1.776,P<0.001),large tumor size(≥5 cm,HR=1.377,95%CI:1.239 to 1.529,P<0.001),macroscopic type III to IV(HR=1.165,95%CI:1.063 to 1.277,P<0.001)and TNM stage II to IV(II/I:HR=1.801,95%CI:1.500~2.162,P<0.001;III/I:HR=3.588,95%CI:3.028~4.251,P<0.001;IV/I:HR=6.114,95%CI:4.973~7.516,P<0.001)were independent prognostic risk factors.Conclusion Through the implementation of standardized surgical treatment technology and multidisciplinary treatment model,the quality of surgery treatment and overall survival increase,and prognosis of gastric cancer patients has been improved.