Pasireotide for postoperative pancreatic fistula.
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.).
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.
Peter J
PJ
Allen
Mithat
M
Gönen
Murray F
MF
Brennan
Adjoa A
AA
Bucknor
Lindsay M
LM
Robinson
Marisa M
MM
Pappas
Kate E
KE
Carlucci
Michael I
MI
D'Angelica
Ronald P
RP
DeMatteo
T Peter
TP
Kingham
Yuman
Y
Fong
William R
WR
Jarnagin
D018784:Abdominal Abscess / Q000453:epidemiology / Q000517:prevention & control*; D000368:Aged; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010180:Pancreatectomy; D010183:Pancreatic Ducts / Q000601:surgery; D010185:Pancreatic Fistula / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D016577:Pancreaticoduodenectomy; D059035:Perioperative Period; D011183:Postoperative Complications / Q000401:mortality / Q000517:prevention & control*; D013004:Somatostatin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
D013004:Somatostatin; C517782:pasireotide