Abstract
Pancreatic cystic neoplasms (PCNs) are a highly prevalent disease of the pancreas. Among PCNs, Intraductal Papillary Mucinous Neoplasms (IPMNs) are common lesions that may progress from low-grade dysplasia (LGD) through high-grade dysplasia (HGD) to invasive cancer. Accurate discrimination of IPMN-associated neoplastic grade is an unmet clinical need. Targeted (semi)quantitative analysis of 100 metabolites and >1000 lipid species were performed on peri-operative pancreatic cyst fluid and pre-operative plasma from IPMN and serous cystic neoplasm (SCN) patients in a pancreas resection cohort (n = 35). Profiles were correlated against histological diagnosis and clinical parameters after correction for confounding factors. Integrated data modeling was used for group classification and selection of the best explanatory molecules. Over 1000 different compounds were identified in plasma and cyst fluid. IPMN profiles showed significant lipid pathway alterations compared to SCN. Integrated data modeling discriminated between IPMN and SCN with 100% accuracy and distinguished IPMN LGD or IPMN HGD and invasive cancer with up to 90.06% accuracy. Free fatty acids, ceramides, and triacylglycerol classes in plasma correlated with circulating levels of CA19-9, albumin and bilirubin. Integrated metabolomic and lipidomic analysis of plasma or cyst fluid can improve discrimination of IPMN from SCN and within PMNs predict the grade of dysplasia.
Highlights
Pancreatic cystic neoplasms (PCNs) are a highly prevalent disease of the pancreas
The pre-operative diagnostic accuracy to distinguish between the various benign ormalignant PCNs, such as Intraductal Papillary Mucinous Neoplasms (IPMNs), is low, and there are no methods available to discriminate between the different grades of dysplasia associated with IPMNs
Compared to serous cystic neoplasm (SCN), IPMN low-grade dysplasia (LGD) and high-grade dysplasia (HGD) showed no significant elevation of circulating CA19-9, HbA1c, amylase, albumin, bilirubin, or white blood cell count
Summary
Pancreatic cystic neoplasms (PCNs) are a highly prevalent disease of the pancreas. Among PCNs, Intraductal Papillary Mucinous Neoplasms (IPMNs) are common lesions that may progress from lowgrade dysplasia (LGD) through high-grade dysplasia (HGD) to invasive cancer. The development of a population-based screening program is challenged by two factors: on one hand the costs of lifelong surveillance, on the other hand the low pre-operative diagnostic accuracy for pancreatic cystic lesions These two problems partly overlap, as due to the low diagnostic yield of conventional radiology, many patients will undergo unnecessary lifelong follow-up with magnetic resonance imaging and/or endoscopic ultrasound with associated high health care costs that might become unsustainable in the near future[11]. The pre-operative diagnostic accuracy to distinguish between the various benign or (pre-)malignant PCNs, such as IPMNs, is low, and there are no methods available to discriminate between the different grades of dysplasia associated with IPMNs. Correctly identifying PCNs and their risk for progression to cancer is clinically crucial; as such, novel biomarkers from blood or cyst fluid may allow for a more accurate definition of IPMNs and improve their management and treatment[17,18,19,20]
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