Pancreatic polypeptide in the diagnosis and follow up of pancreatic neuroendocrine neoplasms – a systematic review

Abstract Introduction Pancreatic polypeptide (PP) is a 36-amino-acid hormone secreted by PP cells located in the uncinate process of the pancreas. While PP can be increased in numerous physiological situations (e.g., prolonged fasting, advancing age, uncontrolled diabetes mellitus and physical exercise), elevated values have been associated with inflammatory processes of the pancreas and are also used as a biomarker for the diagnosis and follow up of non-functioning pancreatic neuroendocrine neoplasms (NF-pNENs). In theory, PP might be particularly important in the context of multiple endocrine neoplasia type 1 (MEN-1). However, current international guidelines (NANETS and ENETS) acknowledge the lack of evidence to recommend PP in routine diagnostic or follow-up protocols for NF-pNENs. In contrast, Swedish national guidelines continue to recommend PP measurement during the follow-up. Method We conducted a systematic review of the literature on PP and its value regarding the diagnosis and follow-up of pancreatic neuroendocrine neoplasms. Result The published literature shows that the diagnostic value of PP is limited because if its low specificity. While PP may be elevated in metastatic disease, studies have not confirmed its reliability for monitoring disease progression. In addition, isolated or intermittent PP elevations often do not correlate with disease progression, leading to unnecessary imaging, extended workup and monitoring as well as increased patient anxiety. Discussion Our review concludes that, given the low specificity and limited diagnostic yield, a reassessment of the Swedish national guidelines is warranted to optimize the use of resources and to reduce clinical uncertainty.