Mo1190 Differential Diagnosis of Solid Pancreatic Lesions by Using Three-Dimensional Contrast Enhanced Ultrasonography With High Mechanical Index Mode

Abstract

Background: We have shown that pancreas cells undergo an epithelial-to-mesenchymal transition (EMT), invade the stroma, and enter the blood circulation before tumor formation in epithelial lineage-labeled genetic mouse models of PanIN (Rhim et al., DDW 2011). Because EMT and invasion were most prevalent within areas of dense inflammation, we hypothesized that inflammation was required for early acquisition of a malignant phenotype. Methods: We bred Pdx-Cre; LSL-KrasG12D; p53fl/+; Rosa26LSL-YFPmice in which pancreatic epithelial cells were permanently labeled with yellow fluorescent protein (YFP) and aged 22.5 mo (deemed PanIN mice as only precancerous PanIN lesions and no cancer are found on HE Rosa26LSL-YFPmice (CY) were used as controls. Acute cerulein pancreatitis (AC) or main pancreatic duct ligation (PDL) was performed in PanIN and control animals as previously described (Siveke et al, 2008; Scoggins et al, 2000). Animals were analyzed 3 and 7d after AC and PDL, respectively. 2.5mo old control and PanIN mice were also treated with the potent anti-inflammatory agent dexamethasone (Dex, 10mg/kg daily) for 7d and analyzed 24h after the last dose. Results: Using the YFP label, we found that PanIN mice contained pancreas cells that sustained an EMT, invaded the stroma and seeded the blood, as we previously described. However, we found a significant increase in EMT and invasion in PanIN animals with ACand PDL-induced pancreatitis compared to vehicleand sham laparotomy-treated control PanIN mice (p<0.05 for AC v. vehicle and PDL v. Sham (n=12 & 8)). AC in control CY mice led to the emergence of EMT+ cells lining the pancreas capsule. There was a significant 3-fold increase in circulating YFP+ pancreatic cells (CPCs) in the blood of PDL-treated PanIN mice v. Sham-treated PanIN mice by FACS (p<0.04). Surprisingly, after only one week of PDL, 3/4 pancreases were found to have histologic (HE DK060694 to AKR), AGA/FDHN (Fellow to Faculty Transition Award to ADR), and NPF (MR, ADR).