A randomized, prospective trial of postoperative somatostatin analogue in patients with neuroendocrine tumors of the pancreas. Prospectively randomized trial using perioperative low-dose octreotide to prevent organ-related and general complications after pancreatic surgery and pancreatico-jejunostomy. Effects of somatostatin prophylaxis after pylorus-preserving pancreaticoduodenectomy: increased delayed gastric emptying and reduced plasma motilin. The potent somatostatin analogue vapreotide does not decrease pancreas-specific complications after elective pancreatectomy: a prospective, multicenter, double-blinded, randomized, placebo-controlled trial. Role of octreotide in the prevention of postoperative complications following pancreatic resection. [Effect of somatostatin on basal and stimulated exocrine pancreatic secretion after partial duodenopancreatectomy. A clinical experimental study]. Randomized controlled multicentre trial of somatostatin infusion after pancreaticoduodenectomy. [Prospective and randomized study on the usefulness of octreotide in the prevention of complications after cephalic duodeno-pancreatectomy]. Prophylactic octreotide and delayed gastric emptying after pancreaticoduodenectomy: results of a prospective randomized double-blinded placebo-controlled trial. [Somatostatin prophylaxis following cephalic duodenopancreatectomy]. Efficacy of octreotide in the prevention of complications of elective pancreatic surgery. Italian Study Group. [Somatostatin in the prevention of postoperative increase of pancreatic enzyme after pancreatic surgery]. Does prophylactic octreotide decrease the rates of pancreatic fistula and other complications after pancreaticoduodenectomy? Results of a prospective randomized placebo-controlled trial. Octreotide in the prevention of intra-abdominal complications following elective pancreatic resection: a prospective, multicenter randomized controlled trial. [Somatostatin in duodenocephalopancreatectomy for neoplastic pathology]. The role of somatostatin in 67 consecutive pancreatectomies: a randomized clinical trial. Randomized controlled multicentre study of the prevention of complications by octreotide in patients undergoing surgery for chronic pancreatitis. Efficacy of octreotide in the prevention of pancreatic fistula after elective pancreatic resections: a prospective, controlled, randomized clinical trial.
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. The aim of the present study was to evaluate the influence of low-dose perioperative octreotide on the prevention of complications (pancreatic fistula and general complications) in patients undergoing pancreatic surgery followed by pancreaticojejunostomy. A total of 105 patients were randomized to receive either octreotide 0.1 mg subcutaneously 3 times/day for a total of 7 days or no octreotide. The primary endpoints were the occurrence of a pancreatic fistula and or general complications, including extended length of hospital stay. There were 25 surgical draining procedures performed and 80 duodenopancreatectomies with or without preservation of the pylorus. In all, 25 (23.8%) of the patients were treated for chronic pancreatitis, 8 (7.6%) for benign tumoral disease, and 72 (68.6%) for carcinoma. All patients underwent pancreaticojejunostomy. 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. 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. 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. 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. 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. This study seeks to evaluate the role of the somatostatin analogue Octreotide as postoperative prophylaxis in the prevention of pancreatic fistula following Pancreaticoduodenectomy (PD).
                A prospective and randomized study has been completed in 34 patients undergoing PD. Sixteen patients were randomly assigned to receive Octreotide 0.1 cc (100 mcg) three times daily subcutaneously during the first seven days of the post-operative period and the remaining 18 constituted the control group. All patients were fed parenterally until normal oral feeding was restored (mean 8 days). Fisher's exact test was used to compare complications in both groups. Pancreatic fistula was defined as the persistence of an amylase-rich discharge at least 50 ml daily during a minimum period of two weeks.
                The mortality rate was 3% and the morbidity 26%. No significant differences were observed regarding the total number of complications. The appearance of pancreatic fistula was considerably smaller (p = 0.03) in the Octreotide group than in control group. Postoperative hospital stay and the number of subsequent surgical interventions were significantly higher (p < 0.05) in the control group.
                Octreotide prevents the occurrence of pancreatic fistula after PD when it is administered prophylactically during the immediate postoperative period. To evaluate the impact of prophylactic octreotide on gastric emptying in patients undergoing pancreaticoduodenectomy. Postoperative pancreatic fistula (POPF) and delayed gastric emptying (DGE) are common complications after pancreaticoduodenectomy. Whereas several prospective randomized trials propose the prophylactic use of octreotide to prevent pancreatic fistula formation, somatostatin has, however, been associated with delayed gastric emptying after partial duodenopancreatectomy.
                In this prospective, randomized, double-blinded, placebo-controlled trial we analyzed the influence of prophylactic octreotide on delayed gastric empting after pancreaticoduodenectomy. Patients were randomized to the placebo group (n=32) and the octreotide group (n=35). Primary endpoint was the incidence of delayed gastric emptying, secondary endpoints included perioperative morbidity other than DGE. DGE was measured by clinical signs, gastric scintigraphy and the hydrogen breath test. Risk factors for DGE other than octreotide were analyzed by univariate and multivariate analyses.
                DGE measured by clinical signs was similar between both groups studied ( approximately 20% of the patients). Gastric scintigraphy (T(1/2)) was 76.3+/-15.2 min in the octreotide group and 86.7+/-18.0 min in controls at day 7, respectively. The H(2) breath test was 65.0+/-6.5 min in octreotide treatment group and 67.0+/-5.7 min in controls at day 8. POPF grade C occurred in approximately 3% of the patients, although prophylactic treatment of octreotide did not reduce the incidence of POPF. Multivariate analysis showed that postoperative intraabdominal bleeding and infection were independent risk factors for DGE. Furthermore preoperative biliary stenting reduced postoperative DGE after partial duodenopancreatectomy.
                Prophylactic octreotide has no influence on gastric emptying and does not decrease the incidence of postoperative pancreatic fistula after pancreaticoduodenectomy. 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. A placebo-controlled double-blind multicentre study, with randomization into parallel groups, was performed to determine whether perioperative subcutaneous administration of octreotide 0.1 mg every 8 h reduces the rate of complications specifically related to pancreatic surgery. In all, 252 patients were evaluated (153 men, 99 women; mean(s.e.m.) age 53.1(0.8) years) who had pancreatic or periampullary tumour or other duodenal disease (157 patients) or chronic pancreatitis (95) and were undergoing elective pancreatic resection (100 Whipple's procedure, 60 distal resection, 12 others), pancreaticojejunostomy (66) or enucleation of pancreatic lesions (14). The proportion of patients with complications was significantly lower in the group treated with octreotide than in the placebo group (15.6 versus 29.2 per cent, P = 0.01). Octreotide thus appears to reduce substantially the risk of complications related to elective pancreatic surgery. Moreover, treatment acceptability was high. 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. To evaluate the endpoints of complications (specifically pancreatic fistula and total complications) and death in patients undergoing pancreaticoduodenectomy.
                Four randomized, placebo-controlled, multicenter trials from Europe have evaluated prophylactic octreotide (the long-acting synthetic analog of native somatostatin) in patients undergoing pancreatic resection. Each trial reported significant decreases in overall complication rates, and two of the four reported significantly lowered rates of pancreatic fistula in patients receiving prophylactic octreotide. However, none of these four trials studied only pancreaticoduodenal resections, and all trials had high pancreatic fistula rates (>19%) in the placebo group. A fifth randomized trial from the United States evaluated the use of prophylactic octreotide in patients undergoing pancreaticoduodenectomy and found no benefit to the use of octreotide. Prophylactic use of octreotide adds more than $75 to the daily hospital charge in the United States. In calendar year 1996, 288 patients received octreotide on the surgical service at the authors' institution, for total billed charges of $74,652.
                Between February 1998 and February 2000, 383 patients were recruited into this study on the basis of preoperative anticipation of pancreaticoduodenal resection. Patients who gave consent were randomized to saline control versus octreotide 250 microg subcutaneously every 8 hours for 7 days, to start 1 to 2 hours before surgery. The primary postoperative endpoints were pancreatic fistula, total complications, death, and length of hospital stay.
                Two hundred eleven patients underwent pancreaticoduodenectomy with pancreatic-enteric anastomosis, received appropriate saline/octreotide doses, and were available for endpoint analysis. The two groups were comparable with respect to demographics (54% male, median age 66 years), type of pancreaticoduodenal resection (60% pylorus-preserving), type of pancreatic-enteric anastomosis (87% end-to-side pancreaticojejunostomy), and pathologic diagnosis. The pancreatic fistula rates were 9% in the control group and 11% in the octreotide group. The overall complication rates were 34% in the control group and 40% in the octreotide group; the in-hospital death rates were 0% versus 1%, respectively. The median postoperative length of hospital stay was 9 days in both groups.
                These data demonstrate that the prophylactic use of perioperative octreotide does not reduce the incidence of pancreatic fistula or total complications after pancreaticoduodenectomy. Prophylactic octreotide use in this setting should be eliminated, at a considerable cost savings. Prophylactic administration of octreotide acetate decreases the rate of postoperative intra-abdominal complications (IACs) after elective pancreatic resection.
                Single-blind, controlled, randomized trial.
                Multicenter (N = 20) trial in France.
                Of 230 randomized patients undergoing pancreatoduodenectomy and pancreatic enteric anastomosis or distal pancreatectomy for either malignant or benign tumor or chronic pancreatitis, 122 were allotted intraoperatively to receive octreotide; 108 served as controls.
                All 230 patients were analyzed. Both groups were comparable except that significantly more patients in the octreotide group had biological glue injected into the main pancreatic duct alone (P<.001) or reinforcing the pancreatic enteric anastomosis (68% [83/122] vs 39% [42/108]; P =.002). Fewer patients (P =.08) in the octreotide group sustained 1 or more IACs (22% vs 32%). In subgroup analysis, octreotide significantly reduced the rate of patients sustaining 1 or more IACs when the main pancreatic duct diameter was less than 3 mm (P<.02), when pancreatojejunostomy was performed (P<.02), or both (P<.02). No significant differences were found regarding IAC severity. Twenty-three patients (10%) died postoperatively, 16 (70% of deaths) of whom had 1 or more IACs. The only independent risk factor for IACs found on multivariate analysis was pancreatoduodenectomy compared with distal pancreatectomy (P<.01) (odds ratio, 3.54 [95% confidence interval, 1.44-8.65]).
                Our results suggest that octreotide is not necessary for all patients undergoing pancreatic resection; it could be useful when the main pancreatic duct is less than 3 mm in diameter and when pancreatoduodenectomy is completed by pancreatojejunostomy. nan 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. A randomized double-blind placebo-controlled multicentre trial was carried out in 247 patients undergoing major elective surgery for chronic pancreatitis to clarify whether the perioperative application of octreotide prevents postoperative complications. Eleven complications were defined, including death, anastomotic leakage, pancreatic fistula, abscess, fluid collection, shock, sepsis, bleeding, pulmonary insufficiency, renal insufficiency and postoperative pancreatitis. A total of 124 patients underwent pancreatic head resection, 55 left resection, 61 pancreaticojejunostomy and seven had other procedures. The overall mortality rate was 1.2 per cent (octreotide group 1.6 per cent, placebo group 0.8 per cent [corrected] (P not significant)). The postoperative complication rate in the octreotide group was 16.4 per cent (20 of 122 patients) and in the placebo group 29.6 per cent (37 of 125) (P < 0.007). The perioperative application of octreotide substantially reduces the risk of postoperative complications in patients undergoing major pancreatic surgery for chronic pancreatitis. A prospective, randomized controlled clinical trial was conducted in 33 Italian surgical departments with the aim of evaluating the efficacy of octreotide in the prevention of pancreatic fistula after elective pancreatic resections.
                Between July 1990 and May 1992, 278 patients were enrolled in the study. Fifty-four dropped out because of unresectable disease and six were excluded because of protocol violation; the remaining 218 were randomly assigned to the octreotide group (n = 111) or to the placebo group (n = 107). There were 131 men and 87 women with a mean age of 58.2 +/- 11.7 yrs. Pancreaticoduodenectomy was the most common operation performed (n = 143), sixty-four percent of patients had a pancreatic or periampullary cancer; chronic pancreatitis accounted for 8.2% of cases.
                Mortality rate was 6.9%. A pancreatic fistula occurred in 31 patients (14.2%), 9% in the octreotide group and 19.6% in the placebo group (p < 0.05). Morbidity rate was significantly lower in the octreotide (21.6%) than in the placebo group (36.4%) (p < 0.05). When specific pancreatic complications were grouped together and evaluated, they occurred less frequently in the treated (15.3%) than in the placebo group (29.9%) (p < 0.05).
                Octreotide was able to reduce significantly the incidence of pancreatic fistula after elective pancreatic resections.
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.