培高利特治疗术后胰瘘。

Pasireotide for postoperative pancreatic fistula.

机构信息

From the Division of Hepatopancreatobiliary Surgery (P.J.A., M.F.B., A.A.B., L.M.R., M.M.P., K.E.C., M.I.D., R.P.D., T.P.K., Y.F., W.R.J.), and the Department of Epidemiology and Biostatistics (M.G.), Memorial Sloan-Kettering Cancer Center, New York.

出版信息

N Engl J Med. 2014 May 22;370(21):2014-22. doi: 10.1056/NEJMoa1313688.

DOI:10.1056/NEJMoa1313688

PMID:24849084

Abstract

BACKGROUND

Postoperative pancreatic fistula is a major contributor to complications and death associated with pancreatic resection. Pasireotide, a somatostatin analogue that has a longer half-life than octreotide and a broader binding profile, decreases pancreatic exocrine secretions and may prevent postoperative pancreatic fistula.

METHODS

We conducted a single-center, randomized, double-blind trial of perioperative subcutaneous pasireotide in patients undergoing either pancreaticoduodenectomy or distal pancreatectomy. We randomly assigned 300 patients to receive 900 μg of subcutaneous pasireotide (152 patients) or placebo (148 patients) twice daily beginning preoperatively on the morning of the operation and continuing for 7 days (14 doses). Randomization was stratified according to the type of resection and whether the pancreatic duct was dilated at the site of transection. The primary end point was the development of pancreatic fistula, leak, or abscess of grade 3 or higher (i.e., requiring drainage).

RESULTS

The primary end point occurred in 45 of the 300 patients (15%). The rate of grade 3 or higher postoperative pancreatic fistula, leak, or abscess was significantly lower among patients who received pasireotide than among patients who received placebo (9% vs. 21%; relative risk, 0.44; 95% confidence interval [CI], 0.24 to 0.78; P=0.006). This finding was consistent among 220 patients who underwent pancreaticoduodenectomy (10% vs. 21%; relative risk, 0.49; 95% CI, 0.25 to 0.95) and 80 patients who underwent distal pancreatectomy (7% vs. 23%; relative risk, 0.32; 95% CI, 0.10 to 0.99), as well as among 136 patients with a dilated pancreatic duct (2% vs. 15%; relative risk, 0.11; 95% CI, 0.02 to 0.60) and 164 patients with a nondilated pancreatic duct (15% vs. 27%; relative risk, 0.55; 95% CI, 0.29 to 1.01).

CONCLUSIONS

Perioperative treatment with pasireotide decreased the rate of clinically significant postoperative pancreatic fistula, leak, or abscess. (Funded by Novartis Pharmaceuticals; ClinicalTrials.gov number, NCT00994110.).

摘要

背景

术后胰瘘是与胰腺切除术相关的并发症和死亡的主要原因。生长抑素类似物帕瑞肽半衰期长于奥曲肽，结合谱更广，可减少胰腺外分泌，可能预防术后胰瘘。

方法

我们进行了一项单中心、随机、双盲的围手术期皮下注射帕瑞肽的试验，该试验纳入了行胰十二指肠切除术或胰体尾切除术的患者。我们将 300 例患者随机分为两组，分别接受皮下注射 900μg帕瑞肽（152 例）或安慰剂（148 例），每天两次，术前于手术当日早晨开始，共 7 天（14 剂）。随机分组根据手术类型和胰管在切断部位是否扩张进行分层。主要终点是发生 3 级或更高级别的胰瘘、漏或脓肿（即需要引流）。

结果

300 例患者中有 45 例（15%）发生了主要终点事件。与接受安慰剂的患者相比，接受帕瑞肽治疗的患者术后发生 3 级或更高级别的胰瘘、漏或脓肿的发生率显著降低（9% vs. 21%；相对风险，0.44；95%置信区间[CI]，0.24 至 0.78；P=0.006）。在 220 例行胰十二指肠切除术的患者（10% vs. 21%；相对风险，0.49；95%CI，0.25 至 0.95）和 80 例行胰体尾切除术的患者（7% vs. 23%；相对风险，0.32；95%CI，0.10 至 0.99）、136 例胰管扩张的患者（2% vs. 15%；相对风险，0.11；95%CI，0.02 至 0.60）和 164 例胰管未扩张的患者（15% vs. 27%；相对风险，0.55；95%CI，0.29 至 1.01）中，这一发现也是一致的。