高原地区术中低体温对非肌层浸润性膀胱癌患者术后免疫功能和远期复发的影响

Effect of intraoperative hypothermia on postoperative immune function and long-term recurrence in patients with non-muscle invasion bladder cancer in plateau area

目的探讨术中低体温对非肌层浸润性膀胱癌(NMIBC)患者术后免疫功能和远期复发的影响。方法试验设计属于前瞻性研究,以2015年1月至2019年12月期间符合条件的337例NMIBC患者为研究对象。根据术中最低体温36℃为界将患者分为低体温组和对照组。于麻醉诱导前1 h(T0)、手术结束时(T1)及术后24 h(T2)抽取外周静脉血检测Thl/Th2型细胞内细胞因子。长期随访以电话随访为主,失效事件为膀胱癌复发。结果337例参与者中,158例(46.9%)患者出现术中低体温。与对照组相比,低体温组T1时的IFN-γ水平和IFN-γ/IL-4显著降低,低体温组T2时的IFN-γ水平和IFN-γ/IL-4显著降低,而IL-4水平显著升高。对照组有102例出现膀胱癌复发,无复发生存时间为15(3~48)个月;低体温组有97例出现膀胱癌复发,无复发生存时间为12(3~60)个月,两组之间无复发生存曲线差异无统计学意义(χ^(2)=0.533,P=0.465)。对于T1期患者,对照组有28例出现膀胱癌复发,无复发生存时间为10.5(3~48)个月;低体温组有36例出现膀胱癌复发,无复发生存时间为10.5(3~45)个月,两组之间的无复发生存曲线差异有统计学意义(χ^(2)=5.261,P=0.022)。对于非T1期患者,对照组有74例出现膀胱癌复发,无复发生存时间为15(3~48)个月;低体温组有61例出现膀胱癌复发,无复发生存时间为12(3~60)个月,两组之间的无复发生存曲线差异无统计学意义(χ^(2)=0.199,P=0.656)。多因素Cox回归分析表明术中低体温是影响复发的独立危险因素之一[HR:1.153(1.055~3.984),P=0.039]。结论术中低体温能抑制NMIBC患者术后的细胞免疫功能,并且是T1期患者术后复发的危险因素之一,术中保温对于进一步改善NMIBC患者的预后具有一定的意义。

Objective To explore the effect of intraoperative hypothermia on postoperative immune function and long-term recurrence in patients with non-muscle invasion bladder cancer(NMIBC).Methods This study was a prospective study which included 337 NMIBC patients meeting the conditions between January 2015,and December 2019.Patients were divided into hypothermia group and control group according to the lowest body temperature(36℃)during operation.Peripheral venous blood was taken to detect Thl/Th2 intracellular cytokines at 1 h before induction of anesthesia(T0),the end of surgery(T1)and 24 h after operation(T2).The main form of follow-up was telephone follow-up.Endpoint was bladder cancer recurrence.Results Of the 337 participants,158 cases(46.9%)showed intraoperative hypothermia.Compared with the control group,the hypothermia group had a significantly lower level of IFN-γand IFN-γ/IL-4 at T1,and a significantly lower level of IFN-γand IFN-γ/IL-4 and a significantly higher level of IL-4 at T2.In the control group,102 patients had recurrence of bladder cancer,and the recurrence-free survival time was 15(3-48)months.In the hypothermia group,97 patients had bladder cancer recurrence,and the recurrence-free survival time was 12(3-60)months.There was no significant difference in the recurrence-free survival curve between the 2 groups(χ^(2)=0.533,P=0.465).For patients with T1,28 patients had recurrence of bladder cancer,and the recurrence-free survival time was 10.5(3-48)months in the control group,36 patients had recurrence of bladder cancer,and the recurrence-free survival time was 10.5(3-45)months in the hypothermia group.There was a significant difference in the recurrence-free survival curves between the 2 groups(χ^(2)=5.261,P=0.022).For non-T1 patients,74 patients had bladder cancer recurrence in the control group,and the recurrence-free survival time was 15(3-48)months.61 patients had bladder cancer recurrence in the hypothermia group,and the recurrence-free survival time was 12(3-60)months.There was no significant difference in the recurrence-free survival curve between the 2 groups(χ^(2)=0.199,P=0.656).Multivariate Cox regression analysis showed that intraoperative hypothermia was one of the independent risk factors for recurrence[HR:1.153(1.055-3.984),P=0.039].Conclusions Intraoperative hypothermia inhibits postoperative cellular immune function in patients with NMIBC is one of risk factors for postoperative recurrence in NMIBC patients with T1.Intraoperative warming has a certain significance for further improving the prognosis of patients with NMIBC.