腹腔热灌注化疗对BorrmannⅢ/Ⅳ型进展期胃癌疗效及预后的影响

Effect of hyperthermic intraperitoneal chemotherapy on BorrmannⅢ/Ⅳadvanced gastric cancer and its prognosis

目的研究腹腔热灌注化疗(HIPEC)对BorrmannⅢ/Ⅳ型进展期胃癌疗效及预后影响。方法采用前瞻性随机对照研究方法。选取泰安市中心医院2014-06-15-2016-02-24收治的BorrmannⅢ/Ⅳ型进展期胃癌患者86例,采用随机数字表法将其分为对照组和观察组。对照组43例,采用标准胃癌D2根治术治疗;观察组43例,在此基础上术中联合HIPEC治疗。采集手术前后2组患者空腹静脉血,采用流式细胞术检测细胞毒T淋巴细胞相关抗原4(CTLA-4)和CD28阳性细胞数,比较手术前后的免疫功能指标,并比较2组患者的化疗不良反应发生率和术后并发症发生率,同时术后随访5年,比较2组患者术后1、3、5年生存率和复发率,采用单因素和逻辑回归分析患者预后影响因素。结果2组化疗不良反应发生率及分级比较差异均无统计学意义,均P>0.05;2组术后并发症发生率比较差异均无统计学意义,P=0.763;与手术前相比,术后2组CTLA-4水平均降低,差异有统计学意义,P值分别为0.024和0.042;术后2组CD28水平均降低,差异有统计学意义,P值分别为0.013和<0.001;手术后,观察组CTLA-4细胞水平低于对照组(P<0.001),CD28细胞水平高于对照组,P<0.001;术后3年对照组和观察组的生存率分别为39.53%和62.79%,术后5年分别为20.93%和41.86%,术后3、5年观察组生存率高于对照组,P值分别为0.031和0.037;术后3年对照组和观察组的复发率分别为83.72%和65.12%,术后5年分别为88.37%和67.44%,术后3、5年复发率低于对照组,P值分别为0.048和0.019。单因素分析显示,胃癌患者预后与肿瘤大小、淋巴结转移、Borrmann分型、TNM分期、分化程度等有相关性(P<0.01),多因素二分类Logistic回归分析显示,淋巴结转移(HR=3.201,95%CI:2.136~5.204)、Borrmann分型(HR=2.752,95%CI:1.027~3.182)、TNM分期(HR=2.752,95%CI:1.925~2.490)和分化程度(HR=1.963,95%CI:2.051~3.448)均是影响胃癌预后的危险因素,P<0.01。结论HIPEC能改善BorrmannⅢ/Ⅳ型进展期胃癌患者机体免疫功能,延长患者生存期,减少复发风险,且未增加术后并发症,值得在临床推广。

Objective To study the effect of hyperthermic intraperitoneal chemotherapy(HIPEC)on the prognosis of BorrmannⅢ/Ⅳtype advanced gastric cancer.Methods A prospective randomized controlled study was conducted.Totally86patients with BorrmannⅢ/Ⅳadvanced gastric carcinoma from Taian City Central Hospital were randomly allocated to control group and observation group between June 15,2014and February 24,2016,43cases of each group.Patients in control group underwent standard gastric cancer D2radical surgery and the remaining 43patients in observation group underwent HIPEC combined with surgery.The fasting venous blood of patients was collected before and after surgery,the cytotoxic T lymphocyte-associated antigen 4(CTLA-4)and CD28positive cells were detected by flow cytometry to compare the immune function indexes between two groups before and after the operation.The incidence of adverse reaction and postoperative complications in the two groups were analyzed.The survival rates and recurrence rates of 1,3and 5years after surgery were compared between the two groups during a follow-up of 5years.The prognostic factors were analyzed by univariate analysis and logistic regression analysis.Results There was no significant difference in the incidence and grade of side effects of chemotherapy between the two groups(all P>0.05).Both groups had no significant difference in the incidence of postoperative complications(P=0.763).Compared with those in pre-operation,the CTLA-4cell levels in both groups were significantly decreased after the operation(P=0.024,P=0.042).Compared with those in pre-operation,the CD28cell levels in both groups were significantly decreased after the operation(P=0.013,P<0.001).After surgery,the level of CTLA-4cells in the observation group was significantly lower than that in the control group(P=0.001),but the level of CD28cells was significantly higher than that of the control group(P<0.001).After a 3-year follow-up,the survival rate was 39.53%in the control group,and 62.79%in the observation group.After 5years,the survival rate was 20.93%in the control group,and 41.86%in the observation group.Therefore,the survival rate of the patients in the observation group was significantly higher than that in the control group(P=0.031,P=0.037)after a follow-up period of 3years and 5years.The recurrence rate was 83.72%in the control group,and 65.12%in the observation group after 3years;the recurrence rate was 88.37%in the control group,and 67.44%in the observation group after5years.The 3-year and 5-year recurrence rates were significantly lower than those in the control group(P=0.048,P=0.019).Results of univariate analysis showed that the prognosis of gastric cancer is correlated with tumor size,lymph node metastasis,Borrmann classification,TNM staging,differentiation degrees,etc.(P<0.01).Logistic regression analysis showed that lymph node metastasis(HR=3.201,95%CI:2.136-5.204),Borrmann classification(HR=2.752,95%CI:1.027-3.182),TNM staging(HR=2.752,95%CI:1.925-2.490)and differentiation degrees(HR=1.963,95%CI:2.051-3.448)are all risk factors affecting the prognosis of gastric cancer(P<0.01).Conclusions HIPEC can improve the immune function of BorrmannⅢ/Ⅳadvanced gastric cancer,prolong patients’survival rate and reduce the risk of recurrence without increasing the incidence of postoperative complications;therefore,HIPEC may be worth popularizing in clinic.