Localized Delivery Of Chemotherapy Through The Bile Duct Using A Double Balloon Catheter - PowerPoint Presentation

1. Localized Delivery Of Chemotherapy Through The Bile Duct Using A Double Balloon Catheter In A Porcine Model1Christopher Laing, MD, 2Joseph Paraschac, 3Nariman Nezami, MD, 4Paula Novelli MD, 5Eugene Breznock, DVM, PhD, DACVS, 2Carter Hultman, 2Ramtin Agah, MD, FACC1Sutter Health, 2RenovoRx, Inc., 3University of Maryland, 4University of Pittsburgh Medical Center, 5Biosurg Inc. IntroductionIntra-arterial delivery of chemotherapeutic agents to treat localized solid tumors is mainstay of interventional oncology. However, other vesicular approaches (beyond the artery) can be promising.For cholangiocarcinoma, direct delivery of drug through the bile duct offers promise for enhanced local effect.Using a double-balloon occlusion catheter in a porcine model we explore the feasibility and efficacy of trans-biliary delivery of small molecule agents (gemcitabine and methylene blue) locally into the peri-ductal tissue.Pig gallbladder (n=3) was accessed percutaneously either directly (n=1) or after placement of gastropexy anchors (n=2). Cholangiography was performed to assess anatomy and guidewire passed through the cystic duct into the intestine. RenovoCath® dual balloon infusion catheter (RenovoRx, Inc) was advanced into the common bile duct and both balloons inflated to isolate the target segment of common bile duct between the balloons. Laparotomy was then performed to expose the hepatoduodenal ligament. Occlusion was confirmed fluoroscopically; in 2 animals 5mL of methylene blue was subsequently infused between the balloons under direct visualization followed by resection and histological assessment.In 1 of 3 animals, 1 g/m2 of gemcitabine was given at 6mL/min over 20 min; the serum gemcitabine pharmacokinetic levels were measured in addition to post-infusion harvesting of peri-ductal tissue to assess localized tissue concentration.ResultsMethodsConclusion/DiscussionReferencesContact InformationThis poster is presented at the 2022 Global Embolization Oncology Symposium Technologies, May 19-22, New York CityRamtin Agah (ragah@renovorx.com)Percutaneous trans-ductal delivery of small molecules (dye and chemotherapeutic agents) into the peri-biliary interstitial tissue failed in this model. The structure of the bile duct likely inhibits translocation of drugs through the ductal wall. Presumably, the inability to deliver molecules trans-vascularly in the bile duct is due to lack of gap junctions which allows for drug diffusion in arterial vessels This approach may be clinically useful for small subset of localized intraductal tumors, but for the majority of hepatobiliary cancers it appears to have little clinical applicability.The peak serum levels of gemcitabine were found to be significantly less with local drug delivery (0.49 nM/mL) compared to historical control1 for intravenous infusion (32nM/mL); however, there was modest tissue level of gemcitabine (3.8 ng/mg) outside the duct. This is all consistent with localization of drug within the duct and poor penetration outside of the ductal tissue1 Ciccolini J, Serdjebi C, Peters GJ, Giovannetti E. Pharmacokinetics and pharmacogenetics of Gemcitabine as a mainstay in adult and pediatric oncology: an EORTC-PAMM perspective. Cancer Chemother Pharmacol. 2016 Jul;78(1):1-12. doi: 10.1007/s00280-016-3003-0. Epub 2016 Mar 23. PMID: 27007129; PMCID: PMC4921117.Splenic Artery InfusionDye Penetration in Bile DuctBile Duct InfusionIn animals infused with methylene blue, inspection of resected bile duct demonstrated scant dye penetration beyond the biliary epithelial monolayer into the immediate periductal tissue (as shown to the left) In comparison, intra-arterial infusion shows local tissue penetration (as shown above)