pasireotide and Pancreatic-Fistula

Pasireotide was recently suggested for the prevention of postoperative pancreatic fistula (POPF) after pancreatic surgery. However, its efficacy remains to be controversially dicussed. Therefore, we conducted a systematic review and meta-analysis to assess the efficacy of pasireotide for preventing POPF after pancreatic surgery.. A systematic literature search was conducted in PubMed, Web of Science, and The Cochrane Library to identify clinical studies investigating the efficacy of pasireotide after pancreatic surgery. The identified studies were critically appraised, and meta-analyses were then performed. The study was performed in accordance with PRISMA guidelines and was registered at the PROSPERO study database (CRD42018112334).. Four studies with a total of 919 patients were included: 418 with pasireotide treatment and 501 controls. Meta-analysis showed that pasireotide could reduce neither clinically relevant POPF rate (OR = 0.78; 95% CI, 0.49-1.24; P = 0.29) nor overall POPF rate (OR = 0.94; 95% CI, 0.60-1.48; P = 0.80) after pancreatic resections. There were no significant differences in delayed gastric emptying, mortality, and postoperative hospital stay after pancreatic surgery. However, pasireotide reduces readmission after pancreatic surgery (OR = 0.61; 95% CI, 0.44-0.85; P = 0.004). Subgroup analyses revealed that prophylactic use of pasireotide did not reduce the incidence of clinically relevant POPF after pancreaticoduodenectomy or distal pancreatectomy compared with the control.. Based on the available evidence, use of pasireotide may not reduce clinically relevant POPF as well as it may not improve postoperative course substantially after pancreatic surgery. Further investigator-initiated high-quality trials are needed.

Topics: Humans; Pancreatectomy; Pancreatic Fistula; Pancreaticoduodenectomy; Postoperative Complications; Somatostatin

A randomized controlled trial (RCT) of routine administration of pasireotide demonstrated decreased incidence of clinically significant postoperative pancreatic fistula (POPF). Recent studies have not replicated these results. A meta-analysis was performed to evaluate its efficacy in this setting.. Prospective trials utilizing pasireotide prophylactically after pancreatectomy were reviewed. The primary outcome was clinically significant POPF. Secondary outcomes included length of stay (LOS), readmission rates, and mortality. Study heterogeneity was assessed.. Five studies totaling 1571 patients were identified. There was no difference in age, sex, or cancer rates. Pasireotide patients had smaller pancreatic ducts (. Routine administration of pasireotide did not decrease POPF rates for all pancreatectomies, but was associated with lower rates for PD and decreased readmission rates. Further prospective, randomized studies are warranted.

Topics: Humans; Pancreatectomy; Pancreatic Fistula; Pancreaticoduodenectomy; Postoperative Complications; Somatostatin

A randomized controlled trial of routine administration of pasireotide demonstrated decreased incidence of clinically significant postoperative pancreatic fistula (POPF). Recent studies have not replicated these results. A meta-analysis was performed to evaluate its efficacy in this setting.. Prospective trials utilizing pasireotide prophylactically after pancreatectomy were reviewed. The primary outcome was clinically significant POPF. Secondary outcomes included length of stay (LOS), readmission rates, and mortality. Study heterogeneity was assessed.. Five studies totaling 1571 patients were identified. There was no difference in age, sex, or cancer rates. Pasireotide patients had smaller pancreatic ducts (. Routine administration of pasireotide did not decrease POPF rates for all pancreatectomies, but was associated with lower rates for PD, and decreased readmission rates. Further prospective, randomized studies are warranted.

Topics: Hormones; Humans; Pancreatectomy; Pancreatic Fistula; Pancreatic Neoplasms; Pancreaticoduodenectomy; Postoperative Complications; Somatostatin

Prophylactic administration of somatostatin analogues (SA) to reduce the incidence of post-operative pancreatic fistula (POPF) remains contentious. This meta-analysis evaluated its impact on outcomes following pancreaticoduodenectomy (PD).. The EMBASE, MEDLINE and Cochrane databases were searched for randomised controlled trials (RCTs) investigating prophylactic SA following PD. Comparative effects were summarised as odds ratio and weighted mean difference based on an intention to treat. Quantitative pooling of the effect sizes was derived using the random-effects model.. Twelve RCTs were included involving 1615 patients [SA-treated group (n = 820) and control group (n = 795)]. The SA used included somatostatin-14, pasireotide, vapreotide and octreotide. Pooling of the data showed no significant benefit of its use for the primary outcome measure of all grades of POPF, odds ratio (OR) 0.73 [95% confidence interval (CI), 0.51-1.05, p = 0.09] and clinically relevant POPF, OR 0.48 [95% CI, 0.22-1.06, p = 0.07]. There were no benefits in the secondary outcome measures of delayed gastric emptying, OR 0.98 [95% CI, 0.57-1.69, p = 0.94]; infected abdominal collections, OR 0.80 [95% CI, 0.44-1.43, p = 0.80]; reoperation rates, OR 1.24 [95% CI, 0.73-2.13, p = 0.42]; duration of hospital stay, - 0.23 [95% CI - .59 to 1.13, p = 0.74]; and mortality, 1.78 [95% CI, 0.94-3.39, p = 0.08].. SA did not improve the post-operative outcomes following PD, including reducing the incidence of POPF. The routine administration of SA cannot be recommended following PD.

Topics: Antineoplastic Agents, Hormonal; Gastroparesis; Humans; Length of Stay; Octreotide; Pancreatic Fistula; Pancreaticoduodenectomy; Postoperative Complications; Randomized Controlled Trials as Topic; Reoperation; Somatostatin

Postoperative pancreatic fistula (POPF) is a major determinant of pancreatic surgery outcome, and prevention of POPF is a relevant clinical challenge. The aim of the present study is to compare the cost-effectiveness of octreotide and pasireotide for POPF prophylaxis.. A systematic literature review and meta-analysis and a retrospective patient cohort provided the data. Cost-effectiveness was calculated by the incremental cost-effectiveness ratio (ICER) and by decision tree modelling of hospital stay duration.. Six randomised trials on octreotide (1255 patients) and one trial on pasireotide (300 patients) were included. The median POPF incidence without prophylaxis was 19.6 %. The relative risks for POPF after octreotide or pasireotide prophylaxis were 0.54 or 0.45. Octreotide prophylaxis (21 × 0.1 mg) costs were 249.69 Euro, compared with 728.84 Euro for pasireotide (14 × 0.9 mg) resulting in an ICER of 266.19 Euro for an additional 1.8 % risk reduction with pasireotide. Decision tree modelling revealed no significant reduction of median hospital stay duration if pasireotide was used instead of octreotide.. Prophylactic octreotide is almost as effective as pasireotide but incurs significantly fewer drug costs per case. However, the data quality is limited, because the effect of octreotide on clinically relevant POPF is unclear. Together with the lack of multicentric data on pasireotide and its effectiveness, a current off-label use of pasireotide does not appear to be justified.

Topics: Cost-Benefit Analysis; Hormones; Humans; Length of Stay; Octreotide; Pancreatectomy; Pancreatic Fistula; Postoperative Complications; Retrospective Studies; Somatostatin; Treatment Outcome

The use of somatostatin analogues (SAs) following pancreaticoduodenectomy (PD) is controversial.. Literature databases were searched systematically for relevant articles. A meta-analysis of all randomized controlled trials (RCTs) evaluating prophylactic SAs in PD was performed.. Fifteen RCTs involving 1,352 patients were included. There was a towards reduced incidences of pancreatic fistulas (p = 0.26), clinically significant pancreatic fistulas (p = 0.08), and bleeding (p = 0.05) in prophylactic SAs group. In subgroup analyses, prophylactic somatostatin significantly reduced the incidence of pancreatic fistulas(p = 0.02), with a nonsignificant trend toward reduced incidence of clinically significantly pancreatic fistulas (p = 0.06).Pasireotide significantly reduced the incidence of clinically significantly pancreatic fistulas (p = 0.03). Octreotide had no influence on the incidence of pancreatic fistulas.. The current best evidence suggests prophylactic treatment with somatostatin or pasireotide has a potential role in reducing the incidence of pancreatic fistulas, while octreotide had no influence on the incidence of pancreatic fistulas.High-quality RCTs assessing the role of somatostatin and pasireotide are required for further verification.

Topics: Gastrointestinal Agents; Humans; Models, Statistical; Octreotide; Pancreatic Fistula; Pancreaticoduodenectomy; Postoperative Complications; Postoperative Hemorrhage; Somatostatin; Treatment Outcome

Both hydrocortisone and pasireotide have been shown in randomized clinical trials to be effective in reducing postoperative complications of pancreatic surgery, but to date no randomized clinical trial has evaluated the effectiveness of pasireotide compared with hydrocortisone.. To assess the noninferiority of hydrocortisone compared with pasireotide in reducing complications after partial pancreatectomy.. A noninferiority, parallel-group, individually randomized clinical trial was conducted at a single academic center between May 19, 2016, and December 17, 2018. Outcome collectors and analyzers were blinded. A total of 281 patients undergoing partial pancreatectomy were assessed for inclusion. Patients younger than 18 years, those allergic to hydrocortisone or pasireotide, patients undergoing pancreaticoduodenectomy with hard pancreas or dilated pancreatic duct, and patients not eventually undergoing partial pancreatectomy were excluded. Modified intention-to-treat analysis was used in determination of the results.. Treatment included pasireotide, 900 μg, subcutaneously twice a day for 7 days or hydrocortisone, 100 mg, intravenously 3 times a day for 3 days.. The primary outcome was the Comprehensive Complication Index (CCI) score within 30 days. The noninferiority limit was set to 9 CCI points.. Of the 281 patients (mean [SD] age, 63.8 years) assessed for eligibility, 168 patients (mean [SD] age, 63.6 years) were randomized and 126 were included in the modified intention-to-treat analyses. Sixty-three patients received pasireotide (35 men [56%]; median [interquartile range] age, 64 [56-70] years) and 63 patients received hydrocortisone (25 men [40%]; median [interquartile range] age, 67 [56-73] years). The mean (SD) CCI score was 23.94 (17.06) in the pasireotide group and 30.11 (20.47) in the hydrocortisone group (mean difference, -6.16; 2-sided 90% CI, -11.73 to -0.60), indicating that hydrocortisone was not noninferior. Postoperative pancreatic fistula was detected in 34 patients (54%) in the pasireotide group and 39 patients (62%) in the hydrocortisone group (odds ratio, 1.39; 95% CI, 0.68-2.82; P = .37). One patient in the pasireotide group and 2 patients in the hydrocortisone group died within 30 days. In subgroup analyses of patients undergoing distal pancreatectomy, the CCI score was a mean of 10.3 points lower (mean [SD], 16.03 [11.94] vs 26.28 [21.76]; 2-sided 95% CI, -19.34 to -2.12; P = .03) and postoperative pancreatic fistula rate was lower (37% vs 67%; P = .02) in the pasireotide group compared with the hydrocortisone group.. In this study, hydrocortisone was not noninferior compared with pasireotide in patients undergoing partial pancreatectomy. Pasireotide may be more effective than hydrocortisone in patients undergoing distal pancreatectomy.. ClinicalTrials.gov identifier: NCT02775227; EudraCT identifier: 2016-000212-16.

Topics: Anti-Inflammatory Agents; Female; Finland; Hormones; Humans; Hydrocortisone; Intention to Treat Analysis; Male; Middle Aged; Pancreatectomy; Pancreatic Fistula; Postoperative Complications; Prospective Studies; Somatostatin

The objective of this study was to determine the costs of clinically significant postoperative pancreatic fistula (POPF) and to evaluate the cost-effectiveness of routine pasireotide use.. We recently completed a prospective randomized trial that demonstrated an 11.7% absolute risk reduction of clinically significant POPF with use of perioperative pasireotide in patients undergoing pancreaticoduodenectomy or distal pancreatectomy [POPF: pasireotide (n = 152), 9% vs placebo (n = 148), 21%; P = 0.006].. An institutional modeling system was utilized to obtain total direct cost estimates from the 300 patients included in the trial. This system identified direct costs of hospitalization, physician fees, laboratory tests, invasive procedures, outpatient encounters, and readmissions. Total direct costs were calculated from the index admission to 90 days after resection. Costs were converted to Medicare proportional dollars (MP$).. Clinically significant POPF occurred in 45 of the 300 randomized patients (15%). The mean total cost for all patients was MP$23,400 (MP$8,000 - MP$202,500). The mean cost for those who developed clinically significant POPF was MP$39,700 (MP$13,800 - MP$202,500) versus MP$20,500 (MP$8,000 - MP$62,900) for those who did not (P = 0.001). The mean cost of pasireotide within the treatment group (n = 152) was MP$3,300 (MP$300 - MP$3,800). The mean cost was lower in the pasireotide (n = 152) group than the placebo (n = 148) group; however, this did not reach statistical significance (pasireotide, MP$22,800 vs placebo, MP$23,900: P = 0.571).. The development of POPF nearly doubled the total cost of pancreatic resection. In this randomized trial, the routine use of pasireotide significantly reduced the occurrence of POPF without increasing the overall cost of care.

Topics: Adult; Aged; Aged, 80 and over; Cost-Benefit Analysis; Double-Blind Method; Female; Follow-Up Studies; Health Care Costs; Hormones; Humans; Male; Middle Aged; Models, Economic; New York City; Pancreatectomy; Pancreatic Fistula; Pancreaticoduodenectomy; Postoperative Complications; Prospective Studies; Somatostatin; Treatment Outcome

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

Topics: Abdominal Abscess; Aged; Double-Blind Method; Female; Humans; Injections, Subcutaneous; Male; Middle Aged; Pancreatectomy; Pancreatic Ducts; Pancreatic Fistula; Pancreaticoduodenectomy; Perioperative Period; Postoperative Complications; Somatostatin

Postoperative pancreatic fistulas (POPFs) remain common; POPFs frequently require intervention, termed clinically-relevant POPFs (crPOPFs). Pasireotide is increasingly used to prevent POPF, however, risk factors for POPF in this population remain unexplored.. Patients undergoing pancreatectomy with perioperative pasireotide from 2013 to 2020 were identified from our institutional National Surgical Quality Improvement Project database. Logistic regression was utilized to identify risk factors associated with POPF.. One-hundred patients were identified; 26 (26%) underwent distal pancreatectomy with the remainder undergoing pancreaticoduodenectomy. Thirty (30%) experienced POPF, with 21 crPOPFs. Only current smoking was significantly associated with crPOPF (OR 3.79, p = 0.04). Of 30 patients with a firm gland, none experienced crPOPF. Twenty-five received a partial course of pasireotide; 7/25 (28%) crPOPFs occurred versus 14/75 (19%) in patients receiving a full course (p = 0.38).. Shortened courses of pasireotide do not increase crPOPF risk; selective discontinuation may be suitable in low-risk patients. Smoking cessation should be encouraged.

Topics: Humans; Pancreatectomy; Pancreatic Fistula; Pancreaticoduodenectomy; Postoperative Complications; Retrospective Studies; Risk Factors; Somatostatin

Postoperative pancreatic fistula (POPF), a difficult complication after surgery, can cause peripancreatic fluid collection and infections in the operative area. In addition, pancreatic fluid is corrosive and can lead to postoperative bleeding. Clinically significant grade B and C fistulas (CR-POPF) increase postoperative morbidity, resulting in a prolonged hospital stay. Delaying adjuvant therapy due to fistula formation in cancer patients can affect their prognosis. In this study, we aimed to determine if pasireotide affects fistula formation, and the severity of other complications in patients following pancreatic distal resections.. Between 2000 and 2016, 258 distal pancreatectomies were performed at Helsinki University Hospital and were included in our analysis. Pasireotide was administered to patients undergoing distal resections between July 2014 and December 2016. Patients received 900-μg pasireotide administered twice daily perioperatively. Other patients who received octreotide treatment were analyzed separately. Complications such as fistulas (POPF), delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), reoperations, and mortality were recorded and analyzed 90 days postoperatively.. Overall, 47 (18%) patients received pasireotide and 31 (12%) octreotide, while 180 patients (70%) who received neither constituted the control group. There were 40 (16%) clinically relevant grade B and C POPFs: seven (15%) in the pasireotide group, three (10%) in the octreotide group, and 30 (17%) in the control group (p = 0.739). Severe complications categorized as Clavien-Dindo grade III or IV were recorded in 64 (25%) patients: 17 (27%) in the pasireotide group, 4 (6%) in the octreotide group, and 43 (67%) in the control group (p = 0.059). We found no 90-day mortality.. In this study, pasireotide did not reduce clinically relevant POPFs or severe complications following pancreatic distal resection.

Topics: Humans; Octreotide; Pancreatectomy; Pancreatic Fistula; Pancreaticoduodenectomy; Postoperative Complications; Somatostatin

Topics: Humans; Hydrocortisone; Pancreatic Fistula; Pancreaticoduodenectomy; Somatostatin

Post-operative pancreatic fistula (POPF) is a feared complication after a pancreaticoduodenectomy. Previously in a randomized trial found fewer clinically relevant fistulas (CR-POPF) accompanying administration of perioperative pasireotide. Our hospital previously found that the risk for CR-POPF reached 7% in pancreaticoduodenectomy patients. Here, we aimed to determine the CR-POPF rate accompanying prophylactic pasireotide in patients with a normal pancreas at resection level.. In this clinical study, perioperative pasireotide was administered to pancreaticoduodenectomy patients treated between 1 July 2014 and 30 April 2016. High-risk individuals were defined preoperatively by the surgeon based on the following: no dilatation of the pancreatic duct, suspected soft pancreas and a cystic or neuroendocrine tumor at the head of the pancreas. If the pancreas was considered hard at surgery, thereby carrying a lower risk for fistula, pasireotide was discontinued following one preoperative 900-μg dose. Among high-risk patients, pasireotide was continued for one week or until discharge from the hospital.. During the study period, 153/215 pancreatic operations were pancreaticoduodenectomies, 58 (38%) of which were considered high risk for developing clinically significant pancreatic fistula. Among these, 4 (2.6%) developed a grade B or C fistula: 2 in the pasireotide group [3.5%, 95% confidence interval (CI) 0.4-11.9%], 1 in the low-risk group (1.2%, 95% CI 0.0-6.4%; difference: 2.3%, 95% CI -6.4-17.3%) and 1 in the discontinued group (10%).. We found similar rates of CR-POPF among high- and low-risk patients undergoing pancreaticoduodenectomy when using prophylactic perioperative pasireotide in high-risk patients.

Topics: Aged; Female; Humans; Male; Neuroendocrine Tumors; Pancreatic Cyst; Pancreatic Ducts; Pancreatic Fistula; Pancreatic Neoplasms; Pancreaticoduodenectomy; Postoperative Complications; Somatostatin

Pasireotide was shown in a randomized trial to decrease the rate of postoperative pancreatic fistula (POPF). However, retrospective series from other centers have failed to confirm these results.. Patients who underwent pancreatoduodenectomy or distal pancreatectomy between January 2014 and February 2019 were included. Patients treated after November 2016 routinely received pasireotide and were compared to a retrospective cohort. Multivariate analysis was performed for the outcome of clinically relevant POPF (CR-POPF), with stratification by fistula risk score (FRS).. Ninety-nine of 300 patients received pasireotide. The distribution of high, intermediate, low, and negligible risk patients by FRS was comparable (P = .487). There were similar rates of CR-POPF (19.2% pasireotide vs 14.9% control, P = .347) and percutaneous drainage (12.1% vs 10.0%, P = .567), with greater median number of drain days in the pasireotide group (6 vs 4 days, P < .001). Multivariate modeling for CR-POPF showed no correlation with operation or pasireotide use. Adjustment with propensity weighted models for high (OR, 1.02, 95% CI, 0.45-2.29) and intermediate (OR, 1.02, CI, 0.57-1.81) risk groups showed no correlation of pasireotide with reduction in CR-POPF.. Pasireotide administration after pancreatectomy was not associated with a decrease in CR-POPF, even when patients were stratified by FRS.

Topics: Aged; Female; Humans; Male; Middle Aged; Multivariate Analysis; Pancreatectomy; Pancreatic Fistula; Pancreatic Neoplasms; Pancreaticoduodenectomy; Postoperative Complications; Precancerous Conditions; Randomized Controlled Trials as Topic; Retrospective Studies; Risk; Somatostatin

Topics: Humans; Hydrocortisone; Pancreatic Fistula; Pancreaticoduodenectomy; Somatostatin

Topics: Humans; Hydrocortisone; Malus; Pancreatic Fistula; Pyrus; Somatostatin

Morbidity after pancreatectomy is commonly due to leakage of exocrine secretions resulting in abscess or pancreatic fistula (PF). Previously, we authored a double-blind randomized controlled trial demonstrating that perioperative pasireotide administration lowers abscess or PF formation by >50%. Accordingly, we adopted pasireotide use as standard practice after pancreatectomy in October 2014 and hypothesized a similar PF/abscess rate reduction would be observed.. A prospectively maintained database was queried for all patients who underwent pancreatectomy between October 2014 and July 2017. Pasireotide was administered preoperatively and twice daily for 7 days postoperatively or until discharge. The primary end point was clinically relevant PF/abscess requiring procedural intervention, identical to the earlier trial outcomes. Logistic regression was used to compare outcomes with the placebo arm of the earlier randomized trial and to control known PF risk factors.. During the 34-month study period, 652 patients underwent pancreatectomy (211 distal pancreatectomy, 441 pancreaticoduodenectomy). Compared with the historical placebo group (n = 148), the observational group had an increased prevalence of higher American Society of Anesthesiologists scores (69% vs 54%; p < 0.001) and high-risk cases (small duct and soft gland, 47% vs 36%; p = 0.030). The primary end point occurred in 13.3% of patients receiving pasireotide vs 20.9% in the placebo arm of the earlier trial trial (odds ratio 0.58; 95% CI 0.37 to 0.92; p = 0.020). Biliary leakage was lower in those receiving pasireotide (0.6% vs 3.4%; p = 0.014), and other morbidity was unchanged. No subpopulation was identified more likely to benefit from pasireotide.. At our center, adoption of pasireotide has allowed us to achieve a clinically significant abscess or pancreatic leak rate of 13.3%, approximating the effect observed in the randomized trial of pasireotide during routine surgical practice.

Topics: Abdominal Abscess; Adolescent; Adult; Aged; Aged, 80 and over; Anastomotic Leak; Drug Administration Schedule; Female; Hormones; Humans; Logistic Models; Male; Medication Adherence; Middle Aged; Pancreatectomy; Pancreatic Fistula; Pancreaticoduodenectomy; Perioperative Care; Postoperative Complications; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Factors; Somatostatin; Treatment Outcome; Young Adult

Topics: Humans; Pancreatectomy; Pancreatic Fistula; Pancreaticoduodenectomy; Postoperative Complications; Somatostatin

Topics: Humans; Pancreatic Fistula; Pancreaticoduodenectomy; Postoperative Complications; Prospective Studies; Somatostatin; Treatment Outcome

Topics: Humans; Pancreas; Pancreatic Fistula; Postoperative Period; Somatostatin

Pasireotide is a newer generation somatostatin analogue that led to a significant reduction in pancreatic fistula after pancreatectomy in a single-center randomized controlled trial. We sought to determine if pasireotide reduces the incidence of pancreatic fistula and other complications after pancreaticoduodenectomy at our high volume center.. All patients undergoing pancreaticoduodenectomy between April 2011 and January 2017 were prospectively followed, and their complications were graded using the Modified Accordion Grading System (MAGS) in our institutional complications database. For 18 months, 5 pancreatic surgeons used pasireotide routinely in patients undergoing pancreaticoduodenectomy. Patients receiving pasireotide were then propensity score-matched to patients who did not receive pasireotide, and their outcomes were compared.. There were 459 patients who underwent pancreaticoduodenectomy, and 127 patients (28%) received pasireotide. Patients who received pasireotide were significantly more likely to have dilated pancreatic ducts and have a drain left at the time of surgery. Patients who received pasireotide had no difference in pancreatic fistula, overall complications, 90-day readmission, or 90-day mortality. However, patients who received pasireotide had a significantly reduced rate of postoperative bleeding/anemia (8.7% vs 16.9%, p = 0.03). Among 112 propensity score-matched pairs, patients who received pasireotide did not have significantly different rates of pancreatic fistula, and the rates of severe (MAGS grades 3 to 6) pancreatic fistula were identical between the 2 groups (7.1% vs 7.1%, p = 1.00). Matched patients who received pasireotide had significantly decreased postoperative bleeding/anemia (9.8% vs 19.6%, p = 0.04).. Pasireotide did not reduce the incidence or severity of pancreatic fistulas after pancreaticoduodenectomy, but was associated with a decrease in postoperative bleeding/anemia. A multicenter randomized trial is needed to accurately define the role of pasireotide in the postoperative management of pancreaticoduodenectomy patients.

Topics: Aged; Anemia; Female; Hormones; Humans; Male; Middle Aged; Pancreatic Diseases; Pancreatic Fistula; Pancreaticoduodenectomy; Postoperative Hemorrhage; Propensity Score; Prospective Studies; Somatostatin

Pancreatic fistula is a major cause of morbidity after pancreas surgery. In 2014, a single-center, randomized-controlled trial found pasireotide decreased pancreatic fistula rates. However, this finding has not been validated, nor has pasireotide been widely adopted.. A single-arm study in 111 consecutive patients undergoing pancreatic resection April 2015-October 2016 was conducted. Beginning immediately before surgery, patients received 900 μg subcutaneous pasireotide twice daily for up to seven days. Fistula rates were compared to 168 historical controls from July 2013 to March 2015. The primary outcome was Grade B/C fistula, as defined by the International Study Group on Pancreatic Fistula (ISGPF).. There were no significant differences between the pasireotide group and historical controls in demographics, comorbidities, operation type, malignancy, gland texture, or pancreatic duct size. Pasireotide did not reduce fistula rate (15.5% control versus 17.1% pasireotide, p = 0.72). In subgroup analyses of pancreaticoduodenectomy or distal pancreatectomy, or patients with soft gland texture and/or small duct size, there was no decrease in fistulas. Thirty-nine patients (38%) experienced dose-limiting nausea.. In an appropriately-powered, single-institution prospective study, pasireotide was not validated as a preventive measure for pancreatic fistula.

Topics: Aged; Case-Control Studies; Drug Administration Schedule; Female; Humans; Injections, Subcutaneous; Male; Middle Aged; Pancreatectomy; Pancreatic Fistula; Pancreaticoduodenectomy; Prospective Studies; Risk Factors; Somatostatin; Time Factors; Treatment Outcome

In a single trial, perioperative pasireotide demonstrated reduction in postoperative pancreatic fistula (POPF) following pancreatectomy, yet recent studies question the efficacy of this drug.. All patients who underwent pancreatic resection between January 2014 and August 2017 at a single institution were prospectively followed. Starting in February 2016, pasireotide was administered to all pancreatectomies. Pancreaticoduodenectomy (PD) patients were additionally risk-stratified using a validated clinical risk score. The primary endpoint was the development of clinically relevant POPF (CR-POPF), and was compared between patients who received pasireotide and controls.. Of 116 patients, 87 patients (75%) underwent PD, and 43 patients (37.1%) received pasireotide. CR-POPF occurred in 28.4% patients. The use of pasireotide was not associated with reduced CR-POPF among the total cohort (25.6% vs. 30.1%, P = 0.599), distal pancreatectomy patients (P = 0.339), PD (P = 0.274), or PD patients with elevated risk scores (P = 0.073). Pasireotide did not decrease hospital length of stay, use of parenteral nutrition, delayed gastric emptying, surgical site wound infection, or readmission rate.. Use of pasireotide after pancreatic resection does not decrease CR-POPF, nor is it associated with reduced length of stay or postoperative complications. A multi-center randomized trial is warranted to study its true effect on outcomes after pancreatectomy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Databases, Factual; Female; Gastrointestinal Agents; Humans; Length of Stay; Los Angeles; Male; Middle Aged; Pancreatectomy; Pancreatic Fistula; Pancreaticoduodenectomy; Patient Readmission; Prospective Studies; Risk Factors; Somatostatin; Time Factors; Treatment Outcome; Young Adult

Topics: Humans; Pancreatic Fistula; Pancreaticoduodenectomy; Postoperative Complications; Prospective Studies; Somatostatin

To determine the cost-effectiveness of perioperative administration of pasireotide for reduction of pancreatic fistula (PF).. PF is a major complication following pancreaticoduodenectomy (PD), associated with significant morbidity and healthcare-related costs. Pasireotide is a novel multireceptor ligand somatostatin analogue, which has been demonstrated to reduce the incidence of PF following pancreas resection; however, the drug cost is significant. This study sought to estimate the cost-effectiveness of routine administration of pasireotide to patients undergoing PD, compared with no intervention from the perspective of the hospital system.. A decision-analytic model was developed to compare costs for perioperative administration of pasireotide versus no pasireotide. The model was populated using an institutional database containing all PDs performed 2002 to 2012 at a single institution, including data regarding clinically significant PF (International Study Group on Pancreatic Fistula Grade B or C) and hospital-related inpatient costs for 90 days following PD, converted to 2014 $USD. Relative risk of PF associated with pasireotide was estimated from the published literature. Deterministic and probabilistic sensitivity analyses were performed to test robustness of the model.. Mean institutional cost of index admissions was $67,417 and $31,950 for patients with and without PF, respectively. Pasireotide was the dominant strategy, associated with savings of $1685, and a mean reduction of 1.5 days length of stay. Univariate sensitivity analyses demonstrated cost-savings down to a PF rate of 5.6%, up to a relative risk of PF of 0.775, and up to a drug cost of $2817. Probabilistic sensitivity analysis showed 79% of simulations were cost saving.. Pasireotide appears to be a cost-saving treatment following PD across a wide variation of clinical and cost scenarios.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cost-Benefit Analysis; Decision Support Techniques; Female; Hormones; Hospital Costs; Humans; Male; Middle Aged; Models, Economic; Ontario; Pancreatic Fistula; Pancreaticoduodenectomy; Perioperative Care; Postoperative Complications; Retrospective Studies; Somatostatin; Treatment Outcome; Young Adult

Topics: Kidney; Pancreatectomy; Pancreatic Fistula; Somatostatin

In a randomized trial, pasireotide significantly decreased the incidence and severity of postoperative pancreatic fistula (POPF). Subsequent analyses concluded that its routine use is cost-effective. We hypothesized that selective administration of the drug to patients at high risk for POPF would be more cost-effective.. Consecutive patients who did not receive pasireotide and underwent pancreatoduodenectomy (PD) or distal pancreatectomy (DP) between July 2011 and January 2014 were distributed into groups based on their risk of POPF using a multivariate recursive partitioning regression tree analysis (RPA) of preoperative clinical factors. The costs of treating hypothetical patients in each risk group were then computed based upon actual institutional hospital costs and previously published relative risk values associated with pasireotide.. Among 315 patients who underwent pancreatectomy, grade B/C POPF occurred in 64 (20%). RPA allocated patients who underwent PD into four groups with a risk for grade B/C POPF of 0, 10, 29, or 60% (P < 0.001) on the basis of diagnosis, pancreatic duct diameter, and body mass index. Patients who underwent DP were allocated to three groups with a grade B/C POPF risk of 14, 26, or 44% (P = 0.05) on the basis of pancreatic duct diameter alone. Although the routine administration of pasireotide to all 315 patients would have theoretically saved $30,892 over standard care, restriction of pasireotide to only patients at high risk for POPF would have led to a cost savings of $831,916.. Preoperative clinical characteristics can be used to characterize patients' risk for POPF following pancreatectomy. Selective administration of pasireotide only to patients at high risk for grade B/C POPF may maximize the cost-efficacy of prophylactic pasireotide.

Topics: Aged; Body Mass Index; Cost-Benefit Analysis; Female; Hormones; Humans; Male; Middle Aged; Organ Size; Pancreatectomy; Pancreatic Ducts; Pancreatic Fistula; Pancreaticoduodenectomy; Patient Selection; Postoperative Complications; Risk Assessment; Risk Factors; Somatostatin

Pasireotide decreases leak rates after pancreatic resection, though significant drug cost may be prohibitive. We conducted a cost-effectiveness analysis to determine whether prophylactic pasireotide possesses a reasonable cost profile.. A cost-effectiveness model compared pasireotide administration after pancreatic resection versus usual care, populated by probabilities of clinical outcomes from a randomized trial and hospital costs (2013 US$) from a university pancreatic disease center. Sensitivity analyses were performed to identify influential clinical components of the model.. With the cost of pasireotide included, per patient costs of pancreatectomy, including those for readmission, were lower in the intervention arm (41,769 versus 42,159$; net savings of 390$, or 1%). This was associated with a 56% reduction in pancreatic fistula/pancreatic leak/abscess (PF/PL/A; 21.9-9.2%). Pasireotide cost would need to increase by over 15.4% to make the intervention strategy more costly than usual care. Sensitivity analyses exploring variability of key model inputs demonstrated that the three strongest drivers of cost were (i) cost of pasireotide; (ii) probability of readmission; and (iii) probability of PF/PL/A.. Prophylactic pasireotide administration following pancreatectomy is cost savings, reducing expensive post-operative sequealae (major complications and readmissions). Pasireotide should be utilized as a cost-saving measure in pancreatic resection. J. Surg. Oncol. 2016;113:784-788. © 2016 Wiley Periodicals, Inc.

Topics: Abdominal Abscess; Anastomotic Leak; Cost Savings; Cost-Benefit Analysis; Decision Trees; Drug Administration Schedule; Hormones; Hospital Costs; Humans; Models, Economic; Ohio; Pancreatectomy; Pancreatic Fistula; Postoperative Complications; Somatostatin; Treatment Outcome