Updates and Critical Evaluation on Novel Biomarkers for the Malignant Progression of Intraductal Papillary Mucinous Neoplasms of the Pancreas

Intraductal papillary mucinous neoplasms (IPMNs) are presumed to evolve from low-grade dysplasia to high-grade dysplasia to invasive carcinoma. Resection of lesions before the development of pancreatic cancer may prevent the development of an incurable process as, once IPMNs progress to invasive cancer, the prognosis may be as poor as resected conventional pancreatic ductal adenocarcinoma. Resection of IPMNs, particularly in the setting of high-grade dysplasia, is presumed to provide a survival benefit. IPMNs also present many challenges as the identification of high-grade dysplasia and early invasive carcinoma and the timing and frequency of malignant progression are not yet established. The limited predictive accuracy presents a challenge as pancreatic resection is associated with a risk of substantial morbidity and mortality; 20-30% and 2-4%, respectively. Diagnostic armamentarium contains pancreas-protocol computed tomography (CT) scan, gadolinium-enhanced magnetic resonance imaging (MRI) with or without magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound (EUS). The most promising method is endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) as this technique allows analysis of cyst fluid using biomarkers. Until now, in clinical practice, we utilize two biomarkers, carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9); however, DNA analysis of pancreatic cystic fluid and genomic analysis could offer new tools to the diagnosis and administration of IPMNs. Novel genomic and serum biomarkers could play an important future role to identify those individuals who will benefit from an early operation and those who will benefit from watchful waiting approach. More prospective studies are needed.