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Cullinane C, Devine M, Alazzawi M, Suilleabhain CO, Sullivan AO. "Somatostatin analogues do not reduce the risk of clinically relevant post-operative fistula rates in patients undergoing pancreatic surgery", a systematic review and meta-analysis. HPB (Oxford) 2025:S1365-182X(25)00078-4. [PMID: 40180812 DOI: 10.1016/j.hpb.2025.03.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 03/03/2025] [Accepted: 03/06/2025] [Indexed: 04/05/2025]
Abstract
BACKGROUND The impact of Somatostatin Analogues (SSA) on Post-Operative Pancreatic Fistula (POPF) risk reduction lacks clarity and reports are conflicting. The aim of this study was to perform a systematic review and meta-analysis to explore the effect of SSA on POPF rates. METHODS A systematic review was performed for studies reporting POPF in relation to SSA use following the consensus by the International Study Group of Pancreatic Fistula (ISGPF) to re-define what constitutes a clinically significant POPF in 2015. The primary outcome was the incidence of clinically relevant POPF among patients who received SSA peri-operatively. RESULTS Twenty studies, including 6947 patients, were eligible for inclusion. Overall, SSA use did not significantly lower the risk of developing a POPF(OR 0.89, 95 % CI 0.66-1.20, P = 0.44, I2 = 73 %). Subgroup analysis was performed to determine whether SSA could reduce POPF in high-risk cohorts (soft pancreas, duct <5 mm). SSA did not significantly reduce POPF in the five studies reporting on high-risk cohorts (OR 1.42, 95 % CI 0.60-3.37, P = 0.43, I2 = 73 %). Furthermore, subgroup analysis of both grade B and grade C POPF's did not show any benefit of SSA. CONCLUSION SSA prophylaxis does not reduce the incidence of clinically relevant POPR and should not be routinely administered for pancreatic resections.
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Affiliation(s)
- Carolyn Cullinane
- Department of Hepatobiliary and Pancreatic Surgery, Mercy University Hospital, Cork, Ireland; Department of General Surgery, Royal College of Surgeons, Dublin, Ireland.
| | - Michael Devine
- Department of General Surgery, Royal College of Surgeons, Dublin, Ireland
| | - Mohammed Alazzawi
- Department of General Surgery, Royal College of Surgeons, Dublin, Ireland
| | | | - Adrian O Sullivan
- Department of Hepatobiliary and Pancreatic Surgery, Mercy University Hospital, Cork, Ireland
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Chauhan SSB, Vierra B, Park JO, Pillarisetty VG, Davidson GH, Sham JG. Prophylactic somatostatin analogs for postoperative pancreatic fistulas: a cross-sectional survey of AHPBA surgeons. HPB (Oxford) 2024; 26:1229-1236. [PMID: 38971667 DOI: 10.1016/j.hpb.2024.06.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Revised: 05/13/2024] [Accepted: 06/12/2024] [Indexed: 07/08/2024]
Abstract
BACKGROUND Postoperative pancreatic fistulas lead to substantially increased morbidity, mortality, and healthcare costs after pancreatectomy. Studies have reported conflicting data on the role of prophylactic somatostatin analogs in the reduction of postoperative pancreatic fistula. Current practice patterns, surgeon beliefs, and barriers to using these drugs in the Americas is not known. METHODS An online 26-question cross-sectional survey was distributed via email to the members of the Americas Hepato-Pancreato-Biliary Association in April 2023. RESULTS One hundred and two surgeons responded in spring 2023. 48.0% of respondents reported using prophylactic SSAs during their surgical training, however, only 29.4% do so in their current practice, most commonly when performing Whipple procedures. Octreotide was the most frequently used SSA (34.3%), followed by octreotide LAR (12.7%) and pasireotide (11.8%). Reasons for not prescribing included a lack of high-quality data (62.7%), perception of limited efficacy (34.3%) and high cost (30.4%). CONCLUSION These results highlight key areas for future study including understanding surgeon rationale for patient and drug selection. Variable practice patterns amongst surgeons also underscore the importance of generalizability in the design of future clinical trials in order to maximize impact.
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Affiliation(s)
| | - Benjamin Vierra
- University of Washington Department of Surgery, Seattle, WA, USA
| | - James O Park
- University of Washington Department of Surgery, Seattle, WA, USA; Fred Hutchinson Cancer Center, Seattle, WA, USA
| | - Venu G Pillarisetty
- University of Washington Department of Surgery, Seattle, WA, USA; Fred Hutchinson Cancer Center, Seattle, WA, USA
| | - Giana H Davidson
- University of Washington Department of Surgery, Seattle, WA, USA; Surgical Outcomes Research Center, University of Washington Seattle, WA, USA
| | - Jonathan G Sham
- University of Washington Department of Surgery, Seattle, WA, USA; Surgical Outcomes Research Center, University of Washington Seattle, WA, USA; Fred Hutchinson Cancer Center, Seattle, WA, USA.
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Tarvainen T, Sirén J, Kokkola A, Sallinen V. Effect of Hydrocortisone vs Pasireotide on Pancreatic Surgery Complications in Patients With High Risk of Pancreatic Fistula: A Randomized Clinical Trial. JAMA Surg 2020; 155:291-298. [PMID: 32022887 PMCID: PMC7042940 DOI: 10.1001/jamasurg.2019.6019] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Question Is hydrocortisone noninferior compared with pasireotide in reducing pancreatic surgery complications? Findings In this randomized clinical trial that included 126 patients undergoing partial pancreatectomy, the mean Comprehensive Complication Index score (a measurement of overall postoperative morbidity) was –6.16 points lower in patients receiving pasireotide and the lower limit of the 90% CI crossed the prespecified noninferiority margin (–9). In subgroup analyses of patients undergoing distal pancreatectomy, the mean Comprehensive Complication Index score was significantly lower (10.3 points) in the pasireotide vs hydrocortisone group. Meaning In this study, hydrocortisone is not noninferior compared with pasireotide, and pasireotide may be more effective in reducing postoperative complications in patients undergoing distal pancreatectomy. Importance 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. Objective To assess the noninferiority of hydrocortisone compared with pasireotide in reducing complications after partial pancreatectomy. Design, Setting, and Participants 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. Interventions Treatment included pasireotide, 900 μg, subcutaneously twice a day for 7 days or hydrocortisone, 100 mg, intravenously 3 times a day for 3 days. Main Outcomes and Measures The primary outcome was the Comprehensive Complication Index (CCI) score within 30 days. The noninferiority limit was set to 9 CCI points. Results 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. Conclusions and Relevance 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. Trial Registration ClinicalTrials.gov identifier: NCT02775227; EudraCT identifier: 2016-000212-16
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Affiliation(s)
- Timo Tarvainen
- Department of Gastroenterological Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Jukka Sirén
- Department of Gastroenterological Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Arto Kokkola
- Department of Gastroenterological Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Ville Sallinen
- Department of Gastroenterological Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Department of Transplantation and Liver Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
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Kawaida H, Kono H, Hosomura N, Amemiya H, Itakura J, Fujii H, Ichikawa D. Surgical techniques and postoperative management to prevent postoperative pancreatic fistula after pancreatic surgery. World J Gastroenterol 2019; 25:3722-3737. [PMID: 31391768 PMCID: PMC6676555 DOI: 10.3748/wjg.v25.i28.3722] [Citation(s) in RCA: 113] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Revised: 06/20/2019] [Accepted: 06/26/2019] [Indexed: 02/06/2023] Open
Abstract
Postoperative pancreatic fistula (POPF) is one of the most severe complications after pancreatic surgeries. POPF develops as a consequence of pancreatic juice leakage from a surgically exfoliated surface and/or anastomotic stump, which sometimes cause intraperitoneal abscesses and subsequent lethal hemorrhage. In recent years, various surgical and perioperative attempts have been examined to reduce the incidence of POPF. We reviewed several well-designed studies addressing POPF-related factors, such as reconstruction methods, anastomotic techniques, stent usage, prophylactic intra-abdominal drainage, and somatostatin analogs, after pancreaticoduodenectomy and distal pancreatectomy, and we assessed the current status of POPF. In addition, we also discussed the current status of POPF in minimally invasive surgeries, laparoscopic surgeries, and robotic surgeries.
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Affiliation(s)
- Hiromichi Kawaida
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan
| | - Hiroshi Kono
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan
| | - Naohiro Hosomura
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan
| | - Hidetake Amemiya
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan
| | - Jun Itakura
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan
| | - Hideki Fujii
- Department of Surgery, Kofu Manicipal Hospital, Yamanashi 400-0832, Japan
| | - Daisuke Ichikawa
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan
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Elliott IA, Dann AM, Ghukasyan R, Damato L, Girgis MD, King JC, Hines OJ, Reber HA, Donahue TR. Pasireotide does not prevent postoperative pancreatic fistula: a prospective study. HPB (Oxford) 2018; 20:418-422. [PMID: 29398424 DOI: 10.1016/j.hpb.2017.10.018] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2017] [Revised: 10/11/2017] [Accepted: 10/24/2017] [Indexed: 02/09/2023]
Abstract
BACKGROUND 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. METHODS 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). RESULTS 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. CONCLUSIONS In an appropriately-powered, single-institution prospective study, pasireotide was not validated as a preventive measure for pancreatic fistula.
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Affiliation(s)
- Irmina A Elliott
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Amanda M Dann
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Razmik Ghukasyan
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Lauren Damato
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Mark D Girgis
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Jonathan C King
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - O J Hines
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Howard A Reber
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Timothy R Donahue
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
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Abstract
BACKGROUND Pancreatic anastomosis is the Achilles heel of pancreatic surgery. Despite substantial progress in surgical techniques the rate of postoperative pancreatic fistulas remains very high. For this reason various supportive measures to secure pancreatic anastomoses are of continuing interest. OBJECTIVE This review presents the newest evidence-based data on supportive measures designed to secure a pancreatic anastomosis. MATERIAL AND METHODS The most recent meta-analyses, randomized controlled trials and the largest retrospective studies on the role of pancreatic duct stenting, double loop reconstruction, autologous patches and drainage in pancreaticoduodenectomy were taken into account. The value of somatostatin analogues, perioperative nutrition and fluid management is critically discussed. RESULTS The existing body of evidence on supportive measures is insufficient and remains controversial. The use of somatostatin analogues, drainages and restrictive perioperative fluid management has proven effective. In contrast, routine stenting of the pancreatic duct cannot be recommended. Other approaches, such as double loop reconstruction and use of autologous patches lack sufficient evidence. CONCLUSION Meticulous surgical technique and surgeon experience remain the cornerstones of performing a safe pancreatic anastomosis; however, some additional supportive measures seem to have significant potential and should be further investigated in large and well-designed prospective clinical trials.
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Affiliation(s)
- O Belyaev
- Klinik für Allgemein- und Viszeralchirurgie, St. Josef-Hospital, Ruhr-Universiät Bochum, Gudrunstr. 56, 44791, Bochum, Deutschland.
| | - W Uhl
- Klinik für Allgemein- und Viszeralchirurgie, St. Josef-Hospital, Ruhr-Universiät Bochum, Gudrunstr. 56, 44791, Bochum, Deutschland
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Wang C, Zhao X, You S. Efficacy of the prophylactic use of octreotide for the prevention of complications after pancreatic resection: An updated systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore) 2017; 96:e7500. [PMID: 28723761 PMCID: PMC5521901 DOI: 10.1097/md.0000000000007500] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND The use of octreotide prophylaxis in the prevention of complications after pancreatic resection remains controversial. The aim of this systematic review and meta-analysis was to evaluate the efficacy of octreotide prophylactic treatment to prevent complications after pancreatic resection. METHODS Five databases (PubMed, Medline, SinoMed, Embase, and Cochrane Library) were searched for eligible studies from 1980 to November 2016 with the limitation of human subjects and randomized controlled trials (RCTs). Data were extracted independently and were analyzed using RevMan statistical software version 5.3 (Cochrane Collaboration, http://tech.cochrane.org/revman/download). Weighted mean differences (WMDs), risk ratios (RRs), and 95% confidence intervals (CIs) were calculated. Cochrane Collaboration risk of bias tool was used to assess the risk of bias. RESULTS Twelve RCTs comprising 1902 patients were identified as eligible. The methodological quality of the trials ranged from low to moderate. A pooled analysis of effectiveness based on the data from each study revealed that octreotide could significantly reduce the rate of pancreatic fistula (PF) after pancreatic resection (RR = 0.75, 95% CI = 0.57-0.98, P = .04). The same findings were discovered in multicenter and European subgroups with a subgroup analysis; no obvious differences were noted in American, Asian, and single-center subgroup analyses. An equal effect was observed between the use or non-use of octreotide groups regarding mortality (RR = 1.24, 95% CI = 0.77-2.02, P = .38). Octreotide had no advantages in regards to mortality improvement. The total numbers of complications associated with the use or non-use of octreotide were similar (RR = 0.77, 95% CI = 0.58-1.03, P = .08). Among the high-risk group, octreotide was more effective in reducing complications (RR = 0.61, 95% CI = 0.46-0.82, P = .0009). Compared with the patients who did not receive prophylactic treatment, the patients who underwent pancreatic resection benefited from octreotide because it had better efficacy in preventing fluid collection and postoperative pancreatitis. CONCLUSION The prophylactic use of octreotide is suitable for preventing postoperative complications, especially PF and fluid collection as well as postoperative pancreatitis. However, no obvious differences were noted regarding mortality. In view of the clinical heterogeneity and varying definitions of PF, whether these conclusions are broadly applicable should be further determined in future studies.
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Affiliation(s)
- Chunli Wang
- Department of General Surgery, Tianjin Medical University General Hospital
| | - Xin Zhao
- Nankai Clinical School, Tianjin Medical University, Tianjin, China
| | - Shengyi You
- Department of General Surgery, Tianjin Medical University General Hospital
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Perioperative application of somatostatin analogs for pancreatic surgery-current status in Germany. Langenbecks Arch Surg 2016; 401:1037-1044. [PMID: 27628685 DOI: 10.1007/s00423-016-1502-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2016] [Accepted: 08/19/2016] [Indexed: 12/20/2022]
Abstract
BACKGROUND The most common major complication after pancreatic resection is the postoperative pancreatic fistula (POPF). Somatostatin analogs can reduce POPF, but the use of somatostatin analogs is still controversial. The aim of this study was to assess treatment algorithms for pancreatic surgery in Germany with a special focus on the application of somatostatin analogs. METHODS A questionnaire evaluating the perioperative management-especially the use of somatostatin analogs-and postoperative complications after pancreatic surgery was developed and sent to 209 German hospitals performing >12 pancreatoduodenectomies per year (the requirement for certification as a pancreas center). Statistical analysis was carried out using SPSS 21. RESULTS The final response rate was 77 % (160/209), 14.5 % of hospitals never, 37 % always, and 45 % occasionally apply somatostatin analogs after pancreatic surgery. A (standard) drug of choice was defined in 64 % of hospitals. When standard and occasional usage was analyzed, it appeared that hospitals favored somatostatin (69 %) > sandostatin (50 %) > pasireotide (5 %). A relation between the usage of the different somatostatin analogs and morbidity (POPF) or mortality (84 and 16 % of hospitals reported <5 and 5-10 %, respectively) was not seen. Eighty-seven percent of hospitals were interested in participating in future studies analyzing somatostatin use. CONCLUSION This is the first national survey in Germany evaluating the perioperative application of somatostatin analogs for pancreatic surgery. Despite controversial results in the literature, the majority of German pancreas surgeons apply somatostatin analogs perioperatively. The ideal drug to reduce POPF is still unclear. This uncertainty has aroused significant interest and prompted surgeons to participate in future studies in order to elucidate this issue.
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