23Background. A large animal model of pancreatic cancer would permit development of 24

Five-year survival of pancreatic cancer (PC) remains low. Murine models may not adequately mimic human PC and can be too small for medical device development. A large animal PC model could address these issues. We induced and characterized pancreatic tumors in Oncopigs (transgenic swine containing KRASG12D and TP53R167H). Oncopigs underwent injection of adenovirus expressing Cre recombinase (AdCre) into one of the main pancreatic ducts. Resultant tumors were characterized by histology, cytokine expression, exome sequencing and transcriptome analysis. Ten out of fourteen Oncopigs (71%) had gross tumor within three weeks. At necropsy all of these subjects had gastric outlet obstruction secondary to pancreatic tumor and phlegmon. Oncopigs with injections without Cre recombinase and wild type pigs with AdCre injection did not show notable effect. Exome and transcriptome analysis of the porcine pancreatic tumors revealed similarity with the molecular signatures and pathways of human PC. While further optimization and validation of this porcine PC model would be beneficial, it is anticipated that this model will be useful for focused research and development of diagnostic and therapeutic technologies for PC.

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BackgroundIn patients with short bowel syndrome, an elevated pre-resection Body Mass Index may be protective of post-resection body composition. We hypothesized that rats with diet-induced obesity would lose less lean body mass after undergoing massive small bowel resection compared to non-obese rats.MethodsRats (CD®IGS; age = 2 mo; N = 80) were randomly assigned to either a high-fat (obese rats) or a low-fat diet (non-obese rats), and fed ad lib for six months. Each diet group then was randomized to either underwent a 75% distal small bowel resection (massive resection) or small bowel transection with re-anastomosis (sham resection). All rats then were fed ad lib with an intermediate-fat diet (25% of total calories) for two months. Body weight and quantitative magnetic resonance-determined body composition were monitored.ResultsPreoperative body weight was 884 ± 95 vs. 741 ± 75 g, and preoperative percent body fat was 35.8 ± 3.9 vs. 24.9 ± 4.6%; high-fat vs. low fat diet, respectively (p < 0.0001); preoperative diet type had no effect on lean mass. Regarding total body weight, massive resection produced an 18% vs. 5% decrease in high-fat vs. low-fat rats respectively, while sham resection produced a 2% decrease vs. a 7% increase, respectively (p < 0.0001, preoperative vs. necropsy data). Sham resection had no effect on lean mass; after massive resection, both high-fat and low-fat rats lost lean mass, but these changes were not different between the latter two rat groups.ConclusionThe high-fat diet and low-fat diet induced obesity and marginal obesity, respectively. The massive resection produced greater weight loss in high-fat rats compared to low-fat rats. The type of dietary preconditioning had no effect on lean mass loss after massive resection. A protective effect of pre-existing obesity on lean mass after massive intestinal resection was not demonstrated.