Perioperative interventions to reduce pancreatic fistula following pancreatoduodenectomy: meta-analysis

Abstract

Background Data on interventions to reduce postoperative pancreatic fistula (POPF) following pancreatoduodenectomy (PD) are conflicting. The aim of this study was to assimilate data from RCTs. Methods MEDLINE and Embase databases were searched systematically for RCTs evaluating interventions to reduce all grades of POPF or clinically relevant (CR) POPF after PD. Meta-analysis was undertaken for interventions investigated in multiple studies. A post hoc analysis of negative RCTs assessed whether these had appropriate statistical power. Results Among 22 interventions (7512 patients, 55 studies), 12 were assessed by multiple studies, and subjected to meta-analysis. Of these, external pancreatic duct drainage was the only intervention associated with reduced rates of both CR-POPF (odds ratio (OR) 0.40, 95 per cent c.i. 0.20 to 0.80) and all-POPF (OR 0.42, 0.25 to 0.70). Ulinastatin was associated with reduced rates of CR-POPF (OR 0.24, 0.06 to 0.93). Invagination (versus duct-to-mucosa) pancreatojejunostomy was associated with reduced rates of all-POPF (OR 0.60, 0.40 to 0.90). Most negative RCTs were found to be underpowered, with post hoc power calculations indicating that interventions would need to reduce the POPF rate to 1 per cent or less in order to achieve 80 per cent power in 16 of 34 (all-POPF) and 19 of 25 (CR-POPF) studies respectively. Conclusion This meta-analysis supports a role for several interventions to reduce POPF after PD. RCTs in this field were often relatively small and underpowered, especially those evaluating CR-POPF.

Comparison of two anastomosis techniques in terms of postoperative pancreatic fistula development: A retrospective cohort study

“…Although each procedure has some advantages and disadvantages, several systematic reviews and meta-analyses failed to show the superiority of either technique [17][18][19]. In the Pancreatic Anastomosis Audit (PARANOIA) study, the authors reported that invagination PJ, compared to the duct-to-mucosa technique, was associated with reduced rates of all POPF, including biochemical leaks and clinically relevant fistula types [17]. The most recent version of the Cochrane review did not find any significant difference between duct-to-mucosa and invagination PJs in terms of the development of Grade B or C POPFs [18].…”

Recent Advances in Pancreatic Ductal Adenocarcinoma: Strategies to Optimise the Perioperative Nutritional Status in Pancreatoduodenectomy Patients

“…One aspect of this is the lack of an accepted 'standardised practice', which means that designing an appropriate control group to minimise the impact of important confounders is challenging. Additionally, pancreatic surgery trials typically struggle with timely recruitment and therefore are frequently underpowered to detect meaningful differences [117]. Clear, standardised outcomes to evaluate the effect of nutritional therapies have also been lacking, making designing and powering clinical trials extremely difficult.…”

Non-Surgical Interventions for the Prevention of Clinically Relevant Postoperative Pancreatic Fistula—A Narrative Review

“…As such, they have been investigated as part of singular and combination strategies for reducing CR-POPF. Ulinastatin, a trypsin inhibitor, has been found to significantly reduce CR-POPF after PD in a meta-analysis combining two studies (Table 5) [30]. Its mechanism of inactivating pancreatic juice may also explain the noted reduction in PPAP after PD [134].…”