P-P39 Perioperative Interventions to Reduce Pancreatic Fistula following Pancreaticoduodenectomy: A Systematic Review and Meta-Analysis

Abstract

Background Many studies evaluate interventions to reduce POPF following PD, but often report conflicting results. Previous meta-analyses have generally included non-randomised trials and not considered novel interventions. Aim To evaluate interventions to reduce postoperative pancreatic fistula (POPF) following pancreatoduodenectomy (PD) with level 1 data. Methods A systematic review and meta-analysis assessed randomised controlled trials (RCTs) evaluating interventions to reduce All-POPF or clinically relevant (CR)-POPF after PD. A post-hoc analysis of negative RCTs assessed whether these had appropriate levels of statistical power. Results Among 22 interventions (n = 7,512 patients, 55 studies), 12 were assessed by multiple studies, and subject to meta-analysis. Of these, external pancreatic duct drainage was the only intervention found to be associated with significantly reduced rates of CR- and all-POPF. In addition, Ulinastatin was associated with significantly reduced rates of CR-POPF, whilst invagination (vs duct to mucosa) pancreatojejunostomy was associated with significantly reduced rates of all-POPF. Review of negative RCTs found the majority to be underpowered, with post-hoc power calculations indicating that interventions would need to reduce the POPF rate to ≤ 1% in order to achieve 80% power in 16/34 (All-POPF) and 19/25 (CR-POPF) studies, respectively. Conclusions Meta-analysis supports a role for several interventions to reduce POPF after PD, although data is often inconsistent and/or based on small trials. Systematic review identifies other interventions which may benefit from further study. However, underpowered trials appear to be a fundamental problem, inherently more so with CR-POPF. Larger trials, or new directions for research are required to further understanding in this field.

Prediction of postoperative pancreatic fistula and pancreatitis after pancreatoduodenectomy or distal pancreatectomy: A review

“…A recent review demonstrated almost all of the randomized-controlled trials (RCTs) evaluating perioperative intervention strategies for POPF after PD to be underpowered. 3 Perhaps, risk stratification could allow for better evaluation of POPF mitigation strategies with future interventions directed to certain risk groups mostly benefiting from them. At any rate, studies examining the utility of the prediction models are warranted.…”

“…3,21 Some mitigation strategies explored have been different modalities of pancreatoenteric anastomosis in PD, stump closure mechanisms in DP, use of internal and external pancreatic stents, and perioperative somatostatin analogues. 3,22 Of these, pasireotide (a type of somatostatin analogue) has shown benefit in randomized controlled trials. 21,23 Individualized POPF risk estimation could provide clinicians and researchers a useful tool for controlling case-mix and assessing the effect of different mitigation strategies in a risk stratified setting.…”

“…1 Still, postoperative morbidity remains high. 2,3 Regardless of the type of resection-pancreatoduodenectomy (PD) or distal pancreatectomy (DP)-most of the severe complications are related to leakage and failure of pancreatic stump, ultimately leading to postoperative pancreatic fistula (POPF). [4][5][6] The 2016 POPF definition by the International Study Group for Pancreatic Surgery (ISGPS) is based on elevated drain fluid amylase on the third postoperative day and the severity is graded according to the gravity of interventions required, with grades B (antibiotics, drainage) and C (reoperation, organ-failure, death) regarded as clinically relevant.…”

“…20 Due to the clear negative impact of POPF on short-and long-term outcomes, there has been a high interest for its prediction, prevention, and mitigation. 3,21 Some mitigation strategies explored have been different modalities of pancreatoenteric anastomosis in PD, stump closure mechanisms in DP, use of internal and external pancreatic stents, and perioperative somatostatin analogues. 3,22 Of these, pasireotide (a type of somatostatin analogue) has shown benefit in randomized controlled trials.…”

Effects of Pancreatic Surgery : Quality of Life, Cost-effectiveness and Postoperative Results

“…Although no specific anastomosis method has ultimately been shown to consistently reduce the rate of clinically significant pancreatic leakage 19 , there is some evidence to suggest that invagination methods are preferable when operating on high-risk patients with a soft pancreas and small pancreatic duct. 20 One international position statement and literature review by the International Study Group of Pancreatic Surgery (ISGPS) published in 2016 on pancreatic anastomoses concluded that after 2 decades of randomized controlled trials (RCTs) and metaanalyses the evidence was still inconclusive.…”