Mouse models of pancreatic cancer

Pancreatic cancer is one of the most lethal of human malignancies ranking 4th among cancer-related death in the western world and in the United States,and potent therapeutic options are lacking.Although during the last few years there have been important advances in the understanding of the molecular events responsible for the development of pancreatic cancer,currently specific mechanisms of treatment resistance remain poorly understood and new effective systemic drugs need to be developed and probed.In vivo models to study pancreatic cancer and approach this issue remain limited and present different molecular features that must be considered in the studies depending on the purpose to fit special research themes.In the last few years,several genetically engineered mouse models of pancreatic exocrine neoplasia have been developed.These models mimic the disease as they reproduce genetic alterations implicated in the progression of pancreatic cancer.Genetic alterations such as activating mutations in KRas,or TGFb and/or inactivation of tumoral suppressors such as p53,INK4A/ARF BRCA2 and Smad4 are the most common drivers to pancreatic carcinogenesis and have been used to create transgenic mice.These mouse models have a spectrum of pathologic changes,from pancreatic intraepithelial neoplasia to lesions that progress histologically culminating in fully invasive and metastatic disease and represent the most useful preclinical model system.These models can characterize the cellular and molecular pathology of pancreatic neoplasia and cancer and constitute the best tool to investigate new therapeutic approaches,chemopreventive and/or anticancer treatments.Here,we review and update the current mouse models that reproduce different stages of human pancreatic ductal adenocarcinoma and will have clinical relevance in future pancreatic cancer developments.

Polysorb^R(an absorbable lactomer) staples, a safe closure technique for distal pancreatic resection

AIM:To investigate twenty-year experience evaluated the use of the PolysorbR(an absorbable lactomer)staples for distal pancreatic resection.METHODS:The data on 150 patients[92 men,58women,mean age 52(24-72)years]who underwent distal pancreatectomy(DP)in the last 20 years were collected prospectively from an electronic database.The diagnosis was confirmed by endoscopic retrograde cholangiopancreatography,sonography,computed tomography and/or magnetic resonance imaging.The indications for DP were focal pancreatic necrosis,spontaneous pancreatic fistulas,abscesses,pseudocysts,segmental chronic obstructive pancreatitis in the tail,traumatic disruption,and benign(cystadenomas,insulinomas,or glucagonomas)or malignant tumours.The distal resections were performed without splenectomy in 29 of the 150 patients(19%).In the event of splenectomy,the splenic artery and vein were individually ligated,the TA-55 Auto Suture stapler,loaded with Premium PolysorbR 55 staples(5.5mm),was placed across the gland,and the trigger was pulled,the action of which produced two staggered absorbable suture lines.The gland distal to the stapler wasthen amputated with a scalpel on the TA-55 stapler and the two rows of staples were left in the proximal pancreatic stump.After the distal resection,a drainage tube was inserted into the pancreatic bed.RESULTS:The average duration of the operation was150 min(range:90-210 min)and no transfusion was indicated during the operation.After DP in one patient a type B fistula was diagnosed,which was treated successfully by conservative treatment comprising of 12-d octreotide medication(3×0.1 mg/d)and jejunal feeding.The incidence of postoperative pancreatic fistula was therefore0.6%.Another 2 patients suffered postoperative pancreatitis,which was also conservatively treated.Reoperations were performed in 2 patients on the first or second postoperative day,necessitated by bleeding from the retroperitoneal region.The morbidity was 3.3%(5 patients),but no mortality occurred in the postoperative period.Overall,the postoperative period was uneventful without any complications(pancreatic fistula,abscess,bleeding or wound infection)in 145 patients.The length of the postoperative stay ranged between 8 and 16 d.For the 145 patients who had no any postoperative complications,the hospital stay was 8 or 9 d.No mortality occurred in the follow-up period(6 or 12 mo postoperatively);but 6 mo after surgery one patient suffered a pseudocyst following recurrent pancreatitis and was treated with cystojejunostomy.CONCLUSION:Our clinical results demonstrated that the application of absorbable lactomer staples for distal pancreatic resection is a safe alternative to the standard closure technique.