Elsevier

Pancreatology

Volume 20, Issue 2, March 2020, Pages 158-168
Pancreatology

Somatostatin analogues and the risk of post-operative pancreatic fistulas after pancreatic resection - A systematic review & meta-analysis

https://doi.org/10.1016/j.pan.2019.12.015Get rights and content

Abstract

Background

Post-operative pancreatic fistula (POPF) is a common complication of pancreatic resection. Somatostatin analogues (SA) have been used as prophylaxis to reduce its incidence. The aim of this study is to appraise the current literature on the effects of SA prophylaxis on the prevention of POPF following pancreatic resection.

Methods

The review of the literature was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data from studies that reported the effects of SA prophylaxis on POPF following pancreatic resection were extracted, to determine the effect of SA on POPF morbidity and mortality.

Results

A total of 15 studies, involving 2221 patients, were included. Meta-analysis revealed significant reductions in overall POPF (Odds ratio: 0.65 (95% CI 0.53–0.81, p < 0.01)), clinically significant POPF (Odds ratio: 0.53 (95% CI 0.34–0.83, p < 0.01)) and overall morbidity (OR: 0.69 (95% CI: 0.50–0.95, p = 0.02)) following SA prophylaxis. There is no evidence that SA prophylaxis reduces mortality (OR: 1.10 (95%CI: 0.68–1.79, p = 0.68)).

Conclusion

SA prophylaxis following pancreatic resection reduces the incidence of POPF. However, mortality is unaffected.

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.

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