Hemostatic spray as a therapy for pancreatic stump bleeding after cephalic duodenopancreatectomy.

A 70-year-old man with a cholangiocarcinoma underwent a cephalic duodenopancreatectomy. On the 2nd postoperative day, he had hematemesis without hemodynamic instability. Upper endoscopy (EGD) revealed a massive clot at the pancreatic stump, suspected as the source of hemorrhage. After partial clot removal, no active bleeding was found and no therapy was performed. Pancreaticogastric and gastrojejunal anastomoses, as well as the efferent-limb, showed no suspicious lesions. Octreotide was initiated and heparin prophylaxis was temporarily stopped. Bleeding from pancreatic stump following pancreatoduodenectomy is a rare but a life-threatening condition. Conventional endoscopic therapies, including clip placement and cautery, are mostly ineffective and with high risk of pancreatitis. We report the second case of hemostatic powder as a safe and successful therapy in this scenario.

A Mouse Intra-Intestinal Infusion Model and its Application to the Study of Nanoparticle Distribution.

The oral route is the most preferable one when it comes to drug administration. Different animal models have been used to characterize the fate of potential medicines upon oral delivery but fail to clarify specific events occurring at localized sites of the gastrointestinal tract, particularly at the small intestine. We developed a new mouse intra-intestinal infusion model that enabled the direct administration of substances (such as drugs or nanoparticle drug carriers) in the small intestine through an implanted catheter, which can be maintained for prolonged periods of time. The location of catheter insertion can be previously determined as more proximal or distal, allowing to test specific portions of the intestine. Since the model is presumably able to maintain normal physiological characteristics, namely the mucus coating of the intestinal wall, it allowed studying the distribution of different nanoparticles upon localized intra-intestinal administration. The hereby proposed mouse model has the potential to be useful in other types of studies, namely in clarifying localized processes occurring at specific sites of the intestine.

Modified-chitosan/siRNA nanoparticles downregulate cellular CDX2 expression and cross the gastric mucus barrier.

Development of effective non-viral vectors is of crucial importance in the implementation of RNA interference in clinical routine. The localized delivery of siRNAs to the gastrointestinal mucosa is highly desired but faces specific problems such as the stability in gastric acidity conditions and the presence of the mucus barrier. CDX2 is a transcription factor critical for intestinal differentiation being involved in the initiation and maintenance of gastrointestinal diseases. Specifically, it is the trigger of gastric intestinal metaplasia which is a precursor lesion of gastric cancer. Its expression is also altered in colorectal cancer, where it may constitute a lineage-survival oncogene. Our main objective was to develop a nanoparticle-delivery system of siRNA targeting CDX2 using modified chitosan as a vector. CDX2 expression was assessed in gastric carcinoma cell lines and nanoparticles behaviour in gastrointestinal mucus was tested in mouse explants. We show that imidazole-modified chitosan and trimethylchitosan/siRNA nanoparticles are able to downregulate CDX2 expression and overpass the gastric mucus layer but not colonic mucus. This system might constitute a potential therapeutic approach to treat CDX2-dependent gastric lesions.