Pancreatic Cancer Detection in Intraductal Papillary Mucinous Neoplasm (IPMN)-New Insights.

Early diagnosis of pancreatic cancer, particularly in intraductal papillary mucinous neoplasm (IPMN), remains challenging despite advances in imaging and biomarkers. Pancreatic adenocarcinoma (PDAC) has a high mortality rate; therefore, its early detection and adequate interventions are necessary to improve the disease outcome. Most IPMNs are asymptomatic and discovered incidentally. Magnetic resonance imaging (MRI) is a preferred tool for diagnosing malignant IPMNs, with a sensitivity of 90.7-94.1% and a specificity of 84.7-87.2% in detecting mural nodules > 5 mm, a strong predictor of high-risk lesions. Radiomics further enhances diagnostic accuracy (sensitivity 91-96%, specificity 78-81%), especially when combined with CA 19-9, which has lower sensitivity (73-90%) but higher specificity (79-95%). Computed tomography (CT), though less effective for small mural nodules, remains widely used; its accuracy improves with radiomics and clinical variables (sensitivity 90.4%, specificity 74%). Conventional endoscopic ultrasonography (EUS) shows lower performance (sensitivity 60%, specificity 80%), but its advanced variations have improved outcomes. Contrast-enhanced EUS (CE-EUS) visualizes mural nodules with more than 90% sensitivity and involvement of the main pancreatic duct, with a sensitivity of 83.5% and a specificity of 87%. EUS-fine-needle aspiration (EUS-FNA) allows cyst fluid analysis; however, CEA, glucose, and KRAS/GNAS mutations show poor value for malignancy risk. Cytology has low sensitivity (28.7-64.8%) but high specificity (84-94%) in diagnostic malignant changes and strongly affects further management. EUS-through-the-needle biopsy (EUS-TTNB) yields high diagnostic accuracy (sensitivity 90%, specificity 95%) but carries a range of 2-23% adverse events, which limits its wide use. EUS-confocal laser endomicroscopy (EUS-nCLE) provides real-time microscopic evaluation, detecting malignant IPMN with a sensitivity of 90% and a specificity of 73%, though its availability is limited. New emerging biomarkers available in cyst fluid or blood include mucins, miRNA panels (sensitivity 66.7-89%, specificity 89.7-100%), lipidomics, and cancer metabolite profiling, with diagnostic accuracy approaching 89-91%. Pancreatoscopy (POP) enables direct main pancreatic duct (MPD) visualization and biopsy with a sensitivity of 64-100% and a specificity of 75-100%, though adverse events occur in around 12% cases. Combining advanced imaging, EUS-based tissue acquisition, and novel biomarkers holds promise for earlier and more accurate detection of malignant IPMN, potentially improving PDAC outcomes.