Supplementary Material for: Biochemical early detection of postoperative pancreatic fistula

Introduction: Clinically relevant postoperative pancreatic fistula (CR-POPF) is a severe complication following pancreatic surgery, leading to increased mortality, morbidity, and healthcare burden. This review focuses on the role of drain amylase and lipase as biomarkers for predicting and diagnosing CR-POPF and explores perspectives considering novel markers and their clinical applicability. Methods: A comprehensive literature review was conducted using Medline via PubMed, Scopus via Elsevier and Web of Science via Clarivate, selecting studies from 2019 to 2024. Search terms included pancreatic fistula, drainage, amylase, lipase and biomarkers and corresponding MeSH terms. Studies were screened and selected for their assessment of biomarker accuracy, sensitivity, specificity, and postoperative timing of drain fluid collection. Results: A total of 13 studies met the inclusion criteria, analyzing amylase, lipase, or other biomarkers in drain fluid for CR-POPF prediction. Both amylase and lipase consistently showed high diagnostic accuracy, with AUC values above 0.8. However, variability in optimal cut-off values across studies complicated standardization. Other drain biomarkers such as CRP or drain fluid culture positivity as well as amylase/lipase ratio and the temporal drain amylase level progression were found to be promising predictors of CR-POPF. Conclusion: Drain fluid amylase and lipase remain valuable diagnostic tools for CR-POPF, though variabilities and inconsistencies still pose challenges. Combining these with dynamic biomarker progression analysis and emerging markers as well as standardizing protocols could advance prediction and management. Further research is needed to verify the usefulness of supplementary novel biomarkers and to establish their clinical application in order to improve postoperative outcomes.