Effect of intraoperative secretin on operative outcomes in pancreatic resection: A randomized controlled trial.

BACKGROUND: Objectives: We performed a randomized, double-blind, placebo-controlled trial to determine if using Secretin intra-operatively to identify leaks and subsequently target operative intervention would decrease the frequency of clinically significant post-operative pancreatic fistula formation. METHODS: Patients undergoing pancreaticoduodenectomy or distal pancreatectomy were randomized to receive intra-operative Secretin or placebo intra-operatively following the completed pancreaticojejunostomy or closure of the cut remnant stump. If a potential leak was identified, targeted therapy with directed suture placement was performed. RESULTS: 170 patients were randomized; 83 receiving placebo and 87 receiving Secretin. The rate of clinically significant fistula formation was 3% (3/87) in the Secretin group and 6% (5/83) in the placebo group (p = 0.489). The rate of biochemical leak was 29% (25/87) in the Secretin group and 19% (16/83) in the placebo group (p = 0.157). There were no Grade C post-operative fistula in either group. Of the 9% of patients in the Secretin group who had a targeted intra-operative intervention, none developed a clinically significant fistula. Adverse events were similar between groups. CONCLUSIONS: Compared to placebo, intra-operative Secretin administration was not associated with an overall reduction in clinically significant pancreatic fistula formation. However, patients with an intra-operative leak identified by Secretin may benefit from intervention (clinicaltrials.gov: NCT02160808).

A phase II trial of human secretin infusion for refractory type B pain in chronic pancreatitis.

OBJECTIVE: We aimed to determine if intravenous synthetic human secretin (sHS) improves refractory type B pain in patients with chronic pancreatitis (CP). METHODS: In a phase II dose escalation trial, patients with CP received sHS of varying doses (0.05-0.8 µg/kg) for 3 days. The primary outcomes were changes in the visual analogue pain score (VAS), short form (SF)-36, and opiate use from baseline at 30 days after infusion. RESULTS: Twelve patients (mean age, 42 years, 6 men) were included. Mean pain scores (VAS) were 5.79, 4.80, 4.72, and 4.90, at baseline, day 4, day 10, and day 30, respectively (P = 0.25, 0.19, and 0.27 when compared with baseline, respectively). Daily opiate use (oral morphine equivalents) decreased throughout the study from a baseline value of 136 to 111 mg on day 4 (P = 0.52) and to 104 mg on day 30 (P = 0.34). In subgroup analysis, women had the most improvement (VAS baseline, 5.42 vs. VAS day 30, 3.67; P = 0.07; baseline morphine equivalents, 107 mg vs. 84 mg; P = 0.21). CONCLUSIONS: In patients, especially women, with refractory type B pain from CP, intravenous sHS administration demonstrated a trend toward improvement in self-reported pain and opiate use at 30 days after infusion, although statistical significance was not achieved (clinicaltrials.gov registration number NCT01265875).

Pancreatic duct compliance after secretin stimulation: a novel endoscopic ultrasound diagnostic tool for chronic pancreatitis.

OBJECTIVES: Endoscopic ultrasound (EUS) evaluation of pancreatic duct compliance after secretin stimulation (sEUS) along with EUS morphologic examination (EUS) and duodenal fluid [HCO3] measurement (endoscopic pancreatic function test, ePFT) in 1 endoscopic session has not been reported as a means of evaluating for chronic pancreatitis (CP). We evaluated the feasibility of the combined examination and compared EUS measurements of pancreatic ductal compliance with duodenal fluid [HCO3] for diagnosing CP. METHODS: The study is a prospective case series of patients with suspected CP who underwent a combined EUS, sEUS, and ePFT examination in 1 endoscopic session. The main outcome measures were the feasibility of performing the combination examination and the correlation between ductal compliance and ePFT. RESULTS: All examinations were completed in 1 endoscopic session, and there were no complications in 35 patients. Although there was a trend toward less change from baseline head and body ductal diameter in patients with CP, only the percent change from baseline in the tail was significant (CP 144.3% vs healthy patients 240.9%, P < 0.01). Regression analysis demonstrated fair correlation between maximum change in ductal diameter and duodenal fluid [HCO3] (r = 0.27). CONCLUSIONS: Combined EUS, sEUS, and ePFTs are feasible and safe, with preliminary results demonstrating a positive correlation between pancreatic ductal compliance and duodenal fluid [HCO3].

Intravenous synthetic secretin reduces the incidence of pancreatitis induced by endoscopic retrograde cholangiopancreatography.

OBJECTIVES: This study aimed to evaluate whether synthetic secretin is effective in reducing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. METHODS: This is a single academic medical center, prospective, randomized, double-blind, placebo-controlled trial using secretin (dose of 16 µg) administered intravenously immediately before ERCP. Patients were evaluated for the primary outcome of post-ERCP pancreatitis as diagnosed by a single investigator. RESULTS: A total of 1100 patients were screened, of whom 869 were randomly assigned to receive secretin (n = 426) or placebo (n = 443) before ERCP and were evaluated after the procedure for efficacy of secretin. The incidence of pancreatitis in the secretin group compared with the placebo group was 36 (8.7%) of 413 patients versus 65 (15.1%) of 431 patients, respectively, P = 0.004. In the subgroup analysis, secretin was highly protective against post-ERCP pancreatitis for patients undergoing biliary sphincterotomy (6/129 vs 32/142, P < 0.001), patients undergoing cannulation of the common bile duct (26/339 vs 56/342, P < 0.001), and patients not undergoing pancreatic sphincterotomy (26/388 vs 57/403, P = 0.001). Analysis of the interaction between these groups reveals that the primary effect of secretin prophylaxis was prevention of post-ERCP pancreatitis in patients undergoing biliary sphincterotomy. CONCLUSIONS: Synthetic secretin reduces the risk of post-ERCP pancreatitis, particularly in patients in undergoing biliary sphincterotomy.