奥曲肽预防胰十二指肠切除术后胰瘘疗效的前瞻性研究

Prospective study on the effect of prophylactic octreotide administration in preventing pancreatic fistula after pancreatoduodenectomy

目的评估预防性使用奥曲肽对胰十二指肠切除术(PD)后临床相关胰瘘、总手术并发症、围术期死亡和术后住院天数的影响。方法招募2020年1月至2021年8月间上海交通大学医学院附属仁济医院胆胰外科行PD的148例患者, 单中心进行前瞻性、随机、对照、双盲临床研究。患者按随机数字表法分为奥曲肽组(74例)和对照组(74例), 奥曲肽组患者于术前麻醉后皮下注射奥曲肽0.1 mg(1 ml), 术后同剂量每8 h注射1次, 持续5 d共16剂。对照组患者以同法注射等容积生理盐水1 ml, 记录两组患者相关临床资料和指标。主要研究终点为术后临床相关胰瘘, 次要终点为术后总并发症发生率、围术期死亡率和术后住院天数。采用单因素及多因素logistic回归分析筛选PD后临床相关性胰瘘的危险因素。结果最终有效入组120例, 其中奥曲肽组61例, 对照组59例。奥曲肽组和对照组的患者年龄、性别构成比、体重指数、术前减黄手术率、术前主要生物化学指标及手术时间、术中出血量、胰管直径、胰腺质地、病理类型构成比等差异均无统计学意义。临床相关胰瘘总体发生率为8.3%, 奥曲肽组和对照组的生化漏(4.9%比8.5%, P=0.435)、B级瘘(4.9%比8.5%, P=0.435)和C级瘘(1.6%比1.7%, P=0.981)发生率差异均无统计学意义;术后两组总并发症发生率(24.5%比28.8%, P=0.601)、围术期死亡率(0比3.3%, P=0.147)、术后住院天数[(20.6±11.1)d比(19.5±12.2)d, P=0.633]差异均无统计学意义。单因素分析结果显示, 术前血清白蛋白水平<30 g/L(P<0.001)和病理学类型为胰腺导管腺癌(P=0.036)是PD后发生临床相关性胰瘘的独立危险因素。多因素分析结果未发现有统计学意义的危险因素。结论生长抑素类似物奥曲肽不能预防和减少PD后临床相关胰瘘的发生, 不能降低PD后总体并发症的发生率和围术期死亡率, 也不能减少术后住院天数, 但对于术前存在低蛋白血症和(或)病理类型为胰腺导管腺癌的患者, 行PD时及术后预防性使用奥曲肽可能减少临床相关胰瘘的发生。

Objective To evaluate the effect of prophylactic octreotide administration on pancreaticoduodenectomy(PD)associated postoperative pancreatic fistula(POPF),total complications,peri-operative death and postoperative in-hospital days.Methods From January 2020 to August 2021,148 patients who underwent PD in the Department of Biliary-Pancreatic Surgery in Ren Ji Hospital affiliated with School of Medicine of Shanghai Jiao Tong University were recruited into this single-center randomized control double-blinded clinical trial.Patients were randomly assigned into octreotide group(n=74)and control group(n=74).Octreotide group was subcutaneously injected with 0.1 mg(1 ml)octreotide after preoperative anesthesia,and was subcutaneously injected with the same dose every 8 hours for 5 days,with a total of 16 doses.Control group was injected with 1 ml normal saline in the same way,and relevant clinical data and indicators of the two groups were recorded.The primary endpoint was clinically relevant pancreatic fistula,and the secondary endpoints were total complications,perioperative death and postoperative in-hospital days.Univariate and multivariate logistic regression analysis were used to screen the risk factors of clinically related POPF after PD.Results 120 patients were finally enrolled,including 61 in octreotide group and 59 in control group.There were no significant differences on age,gender ratio,body mass index,preoperative surgery rate of jaundice reduction,preoperative major biochemical indicators,operation time,intraoperative blood loss,pancreatic duct diameter,pancreatic texture and pathological type composition ratio.The total incidence of clinical relevant POPF was 8.3%,and there were no significant differences on biochemical leakage(4.9%vs 8.5%,P=0.435),grade B fistula(4.9%vs 8.5%,P=0.435)and grade C fistula(1.6%vs 1.7%,P=0.981).The total complication incidence(24.5%vs 28.8%,P=0.601),perioperative mortality(0 vs 3.3%,P=0.147)and postoperative in-hospital days(20.6±11.1 d vs 19.5±12.2 d,P=0.633)were not significantly different between two groups.Univariate analysis showed that preoperative serum albumin level<30 g/L(P<0.001)and pathological type of pancreatic ductal adenocarcinoma(P=0.036)were independent risk factors for POPF after PD,while multivariate analysis found no statistically significant risk factors.Conclusions Octreotide can neither reduce the incidences of POPF,total complications and postoperative mortality,nor shorten postoperative in-hospital days.However,for patients with preoperative hypoproteinemia and(or)the pathological type of pancreatic duct adenocarcinoma,the prophylactic use of octreotide during PD and after PD may reduce the occurrence of POPF.