Clinically relevant postoperative pancreatic fistula (CR-POPF) has continued to compromise patient recovery post-pancreatectomy despite decades of research seeking to improve risk prediction and diagnosis. The current diagnostic criteria for CR-POPF requires elevated drain fluid amylase to present alongside POPF-related complications including infection, haemorrhage and organ failure. These worrying sequelae necessitate earlier and easily obtainable biomarkers capable of reflecting evolving CR-POPF. Drain fluid has recently emerged as a promising source of biomarkers as it is derived from the pancreas and hence, capable of reflecting its postoperative condition. The present review aims to summarise the current knowledge of CR-POPF drain fluid biomarkers and identify gaps in the field to invigorate future research in this critical area of clinical need. These findings may provide robust diagnostic alternatives for CR-POPF and hence, to clarify their clinical utility require further reports detailing their diagnostic and/or predictive accuracy.
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