The potent somatostatin analogue vapreotide does not decrease pancreas-specific complications after elective pancreatectomy: a prospective, multicenter, double-blinded, randomized, placebo-controlled trial. Randomized controlled multicentre trial of somatostatin infusion after pancreaticoduodenectomy. [Somatostatin in the prevention of postoperative increase of pancreatic enzyme after pancreatic surgery]. [Effect of somatostatin on basal and stimulated exocrine pancreatic secretion after partial duodenopancreatectomy. A clinical experimental study]. The role of somatostatin in 67 consecutive pancreatectomies: a randomized clinical trial. [Somatostatin prophylaxis following cephalic duodenopancreatectomy]. Effects of somatostatin prophylaxis after pylorus-preserving pancreaticoduodenectomy: increased delayed gastric emptying and reduced plasma motilin. A randomized, prospective trial of postoperative somatostatin analogue in patients with neuroendocrine tumors of the pancreas. Role of octreotide in the prevention of postoperative complications following pancreatic resection.
Pancreatectomy can be complicated by pancreatic anastomotic leakage, causing major morbidity.
                Our aim was to determine if vapreotide, a potent long-acting somatostatin analogue, would decrease pancreas-related complications. This prospective, multicenter, randomized, double-blind, placebo-controlled trial involved 275 patients without preexisting chronic pancreatitis undergoing elective proximal, central, or distal pancreatectomy. Complications were defined by objective criteria before beginning the study.
                One hundred thirty-five patients received vapreotide; 140 patients received placebo. There were no statistically significant differences between vapreotide- and placebo-treated patients in either pancreas-related complications (30.4% versus 26.4%, respectively) or in other complications not directly related to the pancreas (40% versus 42%, respectively).
                The potent somatostatin analogue vapreotide does not appear to decrease postoperative complications after major pancreatectomy in patients without chronic pancreatitis. It remains debatable whether somatostatin can prevent pancreatic fistula and other pancreatic stump-related complications following pancreaticoduodenectomy. This study assessed the effects of somatostatin-14 (S-14) on pancreatic remnant exocrine secretion.
                This was a double-blind, randomized, placebo-controlled trial in patients undergoing pancreaticoduodenectomy for malignancy. Patients received a continuous infusion of S-14 (n = 38) or placebo (n = 37) for 7 days. Pancreatic juice and peripancreatic drainage fluid was collected and measured, and pancreatic enzymes were monitored daily. Postoperative complications were recorded.
                S-14 infusion was associated with a decrease in median daily pancreatic juice and pancreatic amylase output. Amylase concentration and output in the peripancreatic drain fluid were significantly lower after S-14 infusion than in the control group (both P < 0.05). The incidence of clinical pancreatic fistula (two of 38 versus eight of 37; P < 0.05) and total pancreatic stump-related complications (five of 38 versus 12 of 37; P < 0.05) was lower in patients treated with S-14. Duration of hospital stay was shorter after S-14 (18 versus 26 days; P = 0.01).
                Although the effect of S-14 on exocrine secretion remains difficult to demonstrate, it did reduce pancreatic juice leakage from the pancreatic remnant. The prophylactic effect of perioperative use of somatostatin on postoperative increase of pancreatic digestive enzymes was investigated in this double blind, randomized study. Thirty three patients undergoing pancreatic surgery because of chronic pancreatitis were divided randomly into two groups. Fifteen patients received somatostatin- (dose 125 micrograms/hour), 18 placebo-infusion, pre- and postoperatively for a total time of 48 hours. The level of serum amylase, lipase, gammaGT, calcium, creatinine and blood glucose was determined every 12 hours. In the placebo group the serum lipase and amylase increased significantly (p less than 0.001), while the calcium decreased. In the somatostatin treated patients only the lipase level increased significantly (p less than 0.01), while the amylase and calcium showed no significant changes compared to their initial values. The postoperative increase in serum enzyme levels is interpreted as being an indicator of pancreatic injury. These results suggest that the perioperative use of somatostatin has beneficial effect for the prevention of pancreatic enzymes increases, associated with pancreatic surgery or its complications in patients with chronic pancreatitis. In a prospective trial 30 patients underwent pancreaticoduodenectomy (Whipple operation) for cancer. They were randomly assigned to receive Somatostatin (SST) (n = 15) or not (n = 15). SST was started at laparotomy with 250 micrograms/h and given over a period of 5 days. A small catheter, which was placed into the duct of the pancreatic remnant, gave access to the pancreatic juice. Volume, amylase, lipase and protein as well as bicarbonate outputs were analyzed. As regards endocrine function, insulin and glucagon plasma levels were measured. The nitrogen balance was calculated. A stimulation test was done on the fifth postoperative day. Six patients (3/3) were assessed as drop-outs. A significant reduction was found for volume, amylase, lipase, protein and bicarbonate with SST, this effect lasting for two days. Lipase however was reduced significantly for 5 days. Pancreatic exocrine function was reduced as well after stimulation, if SST was given. Insulin and glucagon were inhibited with SST, the latter more effectively. We found a positive nitrogen-balance as early as on the second postoperative day in the SST-group, whereas without SST this did not occur before the fourth postoperative day. This findings were significant on the third and fourth postoperative day. The inhibitoric effects of SST, which are demonstrated by our laboratory investigations, conform very well with a more favorable clinical course and a reduction of perioperative morbidity and mortality. Somatostatin has been found to be effective in the prevention of postoperative complications in pancreatic surgery. It can inhibit the pancreatic secretions that, quite often, are responsible for complications during the postoperative period.
                We randomized 67 patients in 2 groups. In the study group (n = 35), somatostatin was administered 30 minutes prior to surgery as well as intraoperatively and postoperatively. No medication was given to the control group (n = 32). Biopsies were taken and processed for electron microscopy and ultrastructural morphometric analysis.
                Administration of somatostatin reduced the exocrine granule number, and the patients suffered from fewer postoperative complications.
                Somatostatin reduces granule number and size of pancreatic cells, which can partially explain the prophylactic effect of the drug on early complications of pancreatic surgery, and which is confirmed by the clinical findings. This study was aimed at assessing the value of prophylactic somatostatin after cephalic duodenopancreatectomy. A randomized prospective study was undertaken using two groups of patients, one with prophylactic somatostatin (4.5 mg daily in continuous perfusion for 7 days postoperatively), known as group I, and group II, which did not receive somatostatin. During a five-year period, from April 1989 to April 1994, we performed 35 duodenopancreatectomies, of which 21 belonged to group I and 14 to group II. We found a lower incidence of pancreatic anastomosis fistulae in group I (9.5% vs 35.7%; p < 0.05). We did not find any correlation between prophylaxis with somatostatin and the appearance of other complications or postoperative mortality. The mean time of fistula closure in group I was 5 days while that of group II was 19.2 days. In conclusion, the administration of prophylactic somatostatin after cephalic duodenopancreatectomy reduces the incidence and duration of pancreatic fistula. Somatostatin inhibits gastroenteropancreatic exocrine secretion and is often used after pancreaticoduodenectomy to reduce pancreatic secretion to minimize tissue damage and pancreatic stump complications. Because our earlier clinical work saw a major increase in delayed gastric emptying (DGE) with somatostatin prophylaxis after pylorus-preserving pancreaticoduodenectomy (PPPD), this small-group study was designed to confirm or disprove that observation. From August 1997 to December 2000, a total of 23 post-PPPD patients were randomized to receive somatostatin prophylaxis [somatostain (+)] (n = 11) or not [somatostatin] (-) (n = 12). The incidence of DGE, scintographic solid-phase emptying results on day 14 postoperatively, and sequential fasting plasma motilin levels were compared, as motilin levels are related to both gastric motility and somatostatin levels. The somatostatin(+) group exhibited greatly increased patient complaints of DGE: 9 of 11 (82%) versus 3 of 12 (25%) in the somatostatin(-) group. Radiologic scintography showed somatostatin prophylaxis prolonged the half-time (T(1/2)) of solid-phase emptying: 144.5 +/- 51.4 minutes for somatostatin(+) versus 89.0 +/- 59.9 minutes for somatostatin(-) (p < 0.001). Comparing pre-PPPD and post-PPPD plasma motilin levels prior to somatostatin infusion, motilin decreased 80% in reaction to the surgery. For somatostatin(-) patients, motilin levels oscillated, or "rang," postoperatively, reaching a higher level on day 3, declined to a new record minimum on day 7, and by day 21 were 50% of the original and the slope of the recovery curve was increasing well. In somatostatin(+) patients the same ringing pattern was observed but decreased with motilin levels 30% to 70% lower than in the somatostatin(-) patients. By day 21 somatostatin(+) motilin levels were recovering but still only 20% original levels, and the slope of the recovery curve was not optimistic. On postoperative day 14 the plasma motilin levels (below approximately 6 bg/ml) correlated strongly with DGE for both groups. Despite the small sample size, the results indicated that (1) somatostatin prophylaxis significantly decreases fasting plasma motilin; (2) somatostatin prophylaxis produces lingering suppression of plasma motilin; (3) PPPD surgery itself significantly reduces fasting motilin levels with recovery to 50% normal at day 21; (4) the mechanism of somatostatin-induced DGE seems related to reduced fasting plasma motilin levels. Pancreatic surgery is not uncommonly complicated by prolonged pancreatic drainage and fistula. Octreotide decreases pancreatic exocrine function and has been reported to improve closure of pancreatic and intestinal fistulae. This randomized, prospective trial was designed to evaluate the efficacy of postoperative octreotide in reducing pancreatic drainage and complications after resection of neuroendocrine tumors of the pancreas.
                Patients with neuroendocrine tumors of the pancreas were entered into the study and randomized after operation to receive octreotide 150 micrograms subcutaneously every 8 hours or saline solution subcutaneously every 8 hours in a double-blinded fashion. Daily pancreatic drainage, total drainage, number of days to drain removal, and complications were recorded.
                Ten patients were given octreotide; eleven patients were given saline solution. The number of days to drain removal, daily drainage, and total drainage were not significantly different. Complications related to pancreatic drainage were not significantly different.
                Octreotide is not indicated for the routine postoperative management of patients with neuroendocrine tumors of the pancreas. Though morbidity and mortality rates following pancreatic resection have improved in recent years, they are still around 35% and 5%, respectively. Typical complications, such as pancreatic fistula, abscess, and subsequent sepsis, are chiefly associated with exocrine pancreatic secretion. In order to clarify whether the perioperative inhibition of exocrine pancreatic secretion prevents complications, we assessed the efficacy of octreotide, a long-acting somatostatin analogue. We conducted a randomized, double-blind, placebo-controlled, multicenter trial in 246 patients undergoing major elective pancreatic surgery. Patients were stratified into a high-risk stratum (limited to patients with pancreatic and periampullary tumors) or low-risk stratum (patients with chronic pancreatitis). Patients received octreotide (3 x 100 micrograms) or placebo subcutaneously for 7 days perioperatively. Eleven complications were defined: death, leakage of anastomosis, pancreatic fistula, abscess, fluid collection, shock, sepsis, bleeding, pulmonary insufficiency, renal insufficiency, and postoperative pancreatitis. Two hundred patients underwent pancreatic head resection, 31 patients underwent left resection, and 15 patients had other procedures. The overall mortality rate within 90 days was 4.5%, with 3.2% in the octreotide group and 5.8% in the placebo group. The complication rate was 32% in the patients receiving octreotide (40 of 125 patients) and 55% in patients receiving placebo (67 of 121 patients) (p less than 0.005). In the patients in the high-risk stratum, complications were observed in 26 of the 68 (38%) patients treated with octreotide and in 46 of 71 (65%) patients given placebo (p less than 0.01). Whereas in patients in the low-risk stratum, the complication rate was 25% (14 of 57 patients) in those treated with octreotide and 42% (21 of 50 patients) in patients given placebo (p = NS). The perioperative application of octreotide reduces the occurrence of typical postoperative complications after pancreatic resection, particularly in patients with tumors.
Somatostatin analogues may reduce perioperative complications but do not reduce perioperative mortality. Further adequately powered trials with low risk of bias are necessary. Based on the current available evidence, somatostatin and its analogues are recommended for routine use in people undergoing pancreatic resection.