759 Effects of High Comorbidity in Patients With Intraductal Papillary Mucinous Neoplasms: A Single Center Analysis of 725 Patients

Abstract

Pancreas features extensive ductal and neurovascular networks in association with acini and islets to perform exocrine and endocrine functions. However, due to the dispersed nature of the network architecture, the standard microtome-based histology cannot provide a globe view of the pancreatic tissue networks in health and disease. To overcome this challenge, we prepared transparent pancreatic specimens by optical clearing (use of immersion solution of high refractive index to promote tissue photon penetration; Tang et al., Diabetes, Obesity and Metabolism, 2014, doi: 10.1111/dom.12342) and performed 3-D microscopy with tile scanning to reveal the spatial features of the pancreatic ductal and neurovascular networks with high definition. Mouse pancreatic intraepithelial neoplasia (PanIN) was induced by activation of oncogenic Kras in acinar cells and/or caerulein injections (chronic pancreatitis). Taking advantage of the transparent tissue, we simultaneously revealed the 3-D PanIN microstructure and the associated neurovascular environment in an integrated fashion. Perilesional neural tissue outgrowth (sympathetic neurite outgrowth and gliosis) and an increase in pericyte marker density were identified via in-depth image projection, indicating the reactivity of the pancreatic neurovascular tissues in response to lesion formation. Overall, the global characterization of duct lesions highlights the advantage of using 3-D microscopy to explore the unknown details of the pancreatic microenvironment in PanIN development.