Postoperative Hypophosphatemia as a Prognostic Factor for Postoperative Pancreatic Fistula: A Systematic Review

Background and Objectives: Postoperative pancreatic fistula (POPF) is one of the most challenging complications after pancreatic resections, associated with prolonged hospital stay and high mortality. Early identification of pancreatic fistula is necessary for the treatment to be effective. Several prognostic factors have been identified, although it is unclear which one is the most crucial. Some studies show that post-pancreatectomy hypophosphatemia may be associated with the development of POPF. The aim of this systematic review was to determine whether postoperative hypophosphatemia can be used as a prognostic factor for postoperative pancreatic fistula. Materials and Methods: The systematic literature review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations (PRISMA) and was registered in the International Prospective Register of Systematic Reviews (PROSPERO). The PubMed, ScienceDirect, and Web of Science databases were systematically searched up to the 31st of January 2022 for studies analyzing postoperative hypophosphatemia as a prognostic factor for POPF. Data including study characteristics, patient characteristics, operation type, definitions of postoperative hypophosphatemia and postoperative pancreatic fistula were extracted. Results: Initially, 149 articles were retrieved. After screening and final assessment, 3 retrospective studies with 2893 patients were included in this review. An association between postoperative hypophosphatemia and POPF was found in all included studies. Patients undergoing distal pancreatectomy were more likely to develop severe hypophosphatemia compared to patients undergoing proximal pancreatectomy. Serum phosphate levels on postoperative day 4 (POD 4) and postoperative day 5 (POD 5) remained significantly lower in patients who developed leak-related complications showing a slower recovery of hypophosphatemia from postoperative day 3 (POD 3) through postoperative day 7 (POD 7). Moreover, body mass index (BMI) higher than 30 kg/m², soft pancreatic tissue, abnormal white blood cell count on postoperative day 3 (POD 3), and shorter surgery time were associated with leak-related complications (LRC) and lower phosphate levels. Conclusions: Early postoperative hypophosphatemia might be used as a prognostic biomarker for early identification of postoperative pancreatic fistula. However, more studies are needed to better identify significant cut-off levels of postoperative hypophosphatemia and development of hypophosphatemia in the postoperative period.