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[EN] Pancreatic duct ligation (PDL) in the murine model has been described as an exocrine pancreatic atrophy-inducing procedure. However, its influence has scarcely been described on premalignant lesions. This study describes the histological changes of premalignant lesions and the gene expression in a well-defined model of pancreatic ductal adenocarcinoma by PDL. Selective ligation of the splenic lobe of the pancreas was performed in Ptf1a-Cre((+/ki)); K-ras LSLG12Vgeo((+/ki)) mice (PDL-Kras mice). Three experimental groups were evaluated: PDL group, controls and shams. The presence and number of premalignant lesions (PanIN 1-3 and Atypical Flat Lesions-AFL) in proximal (PP) and distal (DP) pancreas were studied for each group over time. Microarray analysis was performed to find differentially expressed genes (DEG) between PP and PD. Clinical human specimens after pancreaticoduodenectomy with ductal occlusion were also evaluated. PDL-Kras mice showed an intense pattern of atrophy in DP which was shrunk to a minimal portion of tissue. Mice in control and sham groups had a 7 and 10-time increase respectively of risk of high-grade PanIN 2 and 3 and AFL in their DP than PDL-Kras mice. Furthermore, PDL-Kras mice had significantly less PanIN 1 and 2 and AFL lesions in DP compared to PP. We identified 38 DEGs comparing PP and PD. Among them, several mapped to protein secretion and digestion while others such as Nupr1 have been previously associated with PanIN and PDAC. PDL in Ptf1a-Cre((+/ki)); K-ras LSLG12Vgeo((+/ki)) mice induces a decrease in the presence of premalignant lesions in the ligated DP. This could be a potential line of research of interest in some cancerous risk patients.

Irreversible electroporation is a fast-growing liver ablation technique. Although safety has been well documented in small ablations, our aim is to assess its safety and feasibility when a large portion of liver is ablated. Eighty-seven mice were subjected to high voltage pulses directly delivered across parallel plate electrodes comprising around 40% of mouse liver. One group consisted in 55 athymicnude, in which a tumor from the KM12C cell line was grown and the other thirty-two C57-Bl6 nontumoral mice. Both groups were subsequently divided into subsets according to the delivered field strength (1000V/cm, 2000V/cm) and whether or not they received anti-hyperkalemia therapy. Early mortality (less than 24hours post-IRE) in the 2000V/cm group was observed and revealed considerably higher mean potassium levels. In contrast, the animals subjected to a 2000V/cm field treated with the anti-hyperkalemia therapy had higher survival rates (OR=0.1, 95%CI=0.02–0.32, p<0.001). Early mortality also depended on the electric field magnitude of the IRE protocol, as mice given 1000V/cm survived longer than those given 2000V/cm (OR=4.7, 95%CI=1.8–11.8, p=0.001). Our findings suggest that ionic disturbances, mainly due to potassium alterations, should be warned and envisioned when large volume ablations are performed by IRE.