Somatostatin analogues and the risk of post-operative pancreatic fistulas after pancreatic resection - A systematic review & meta-analysis
Introduction
Pancreatic resection is advocated for treating various pancreatic and periampullary pathologies. The common indications for pancreatic resection include pancreatic ductal adenocarcinoma, periampullary tumours and chronic pancreatitis [1]. There are two main types of pancreatic resection. Pancreaticoduodenectomy (PD) is indicated to resect tumours of the pancreatic head, neck and uncinate process [2] and distal pancreatectomy (DP) is indicated to resect pancreatic tail diseases [3]. Less common type of surgery includes enucleation, central pancreatectomy and duct drainage procedures. Post-operative pancreatic fistula (POPF) is a common complication of all forms of pancreatic surgery. POPF is variably defined by authors and hence its incidence has wide ranges from 3 to 30% for both PD and DP [4]. Spectrum of POPF can be mild to severe. The International Study Group of Pancreatic Surgery (ISGPS) stratifies POPF in three risk grades [5]. Grade A POPF is mild and of no clinical importance while Grade B POPF mandates a change in postoperative management or require prolonged drainage for more than three weeks post-surgery and potentially increasing the incidence of infection [6]. Grade C POPF can lead to acute haemorrhage and abdominal sepsis [4], increasing both morbidity and mortality.
The pancreas produces both endocrine and exocrine secretions [7]. Exocrine secretions rich in amylase and lipase are responsible for POPF [8]. Octreotide (SMS 201–995 [9]) is a synthetic somatostatin analogue (SA) that has been used to reduce POPF [10]. Compared to somatostatin, octreotide is more specific [11], has a half-life 30 times longer [12] and up to three times more potent [13]. By reducing the exocrine secretions, it has been proposed that SA would reduce the incidence of POPF [14]. Though previous trials have demonstrated the efficacy of SA prophylaxis in reducing the incidence of POPF [15,16], there has been no unified consensus regarding their routine prophylactic use for preventing POPF. Furthermore, some studies show that SA not only has no effect on the incidence of POPF [17,18], but also incur significant additional costs [19] and hence advocate against routine prophylaxis [19,20]. Lastly, the science of POPF aetiology is emerging and it is now known that anatomical breach in pancreatic anastomotic integrity is just one of the plausible aetiologies amongst the many. Male gender, obesity, pancreatic fat content, texture of pancreas, pancreas duct diameter and more are implicated in POPF and many authors have proposed composite fistula risk scores based on such variables [[21], [22], [23]]. Hence SA prophylaxis alone may not be effective in reducing POPF and therefore more randomized studies continue to be conducted. The primary aim of this systematic review and meta-analysis is to review the current literature concerning the use of prophylactic SA in the prevention of POPF following pancreatic resection. We also analysed the effects of SA prophylaxis on morbidity and mortality.
Section snippets
Materials and methods
The studies selected for this meta-analysis and systematic review adhered to the quality and standards set by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) [24].
Data extraction
A total of 1189 studies were identified regarding SA prophylaxis in prevention of POPF post-pancreatic resection during an initial literature search, of which 508 studies were excluded because of duplication or irrelevance. The title and abstract of the remaining studies were reviewed, of which 592 studies were then excluded for the following reasons: (i) Incomplete data, (ii) Unable to extract relevant data, (iii) SA not used with prophylactic intent. After full text evaluation of 89 studies,
Discussion
Pancreatic anastomosis is the Achilles heel of pancreatic resection and POPF is a common complication [31] following both pancreaticoduodenectomy and distal pancreatectomy [8]. As early as 1979, prevention of POPF through somatostatin infusion was attempted [32]. The potential morbidity and mortality from POPF have prompted researchers to investigate the role of SA in preventing POPF, with mixed results thus far. Lowy et al. [20] and Yeo et al. [19] reported no significant reduction in POPF
Sources of funding
No sources of funding were provided for this study.
Declaration of competing interest
All authors declare no conflicts of interest.
References (67)
- et al.
1423 pancreaticoduodenectomies for pancreatic cancer: a single-institution experience
J Gastrointest Surg
(2006) - et al.
Postoperative pancreatic fistula
The Surgeon
(2011) - et al.
The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 Years after
Surgery
(2017 Mar) - et al.
Chapter 87 - gastrointestinal pharmacology
- et al.
Sms 201-995: a very potent and selective octapeptide analogue of somatostatin with prolonged action
Life Sci
(1982 Sep 13) - et al.
Octreotide does not prevent pancreatic fistula following pancreatoduodenectomy in patients with soft pancreas and non-dilated duct: a prospective randomized controlled trial
J Gastrointest Surg
(2015) - et al.
Randomized controlled study of the effect of octreotide on pancreatic exocrine secretion and pancreatic fistula after pancreatoduodenectomy
Asian J Surg
(2019 Feb) - et al.
Efficacy of octreotide in the prevention of complications after pancreaticoduodenectomy in patients with soft pancreas and non-dilated pancreatic duct: a prospective randomized trial
Hepatobiliary Pancreat Dis Int
(2018 Feb) - et al.
A prospectively validated clinical risk score accurately predicts pancreatic fistula after pancreatoduodenectomy
J Am Coll Surg
(2013 Jan) - et al.
Impact of obesity on short and long term results following a pancreatico-duodenectomy
Int J Surg
(2017 Jun)