title: EUS-guided injection of paclitaxel (OncoGel) provides therapeutic drug concentrations in the porcine pancreas (with video).
abstract: BACKGROUND
  OncoGel (ReGel/paclitaxel) is an intralesional injectable formulation of the chemotherapeutic drug, paclitaxel, for local tumor management.
  
  
  OBJECTIVE
  The aim of this study was to determine if a minimally invasive EUS-guided injection of paclitaxel, bound to a thermosensitive gel carrier, would lead to therapeutic tissue concentrations of the chemotherapeutic agent in the porcine pancreas.
  
  
  METHODS
  Eight Yorkshire breed pigs were sedated by general anesthesia and OncoGel was injected, under EUS-guidance, with a 22-gauge needle into the tail of the pancreas.
  
  
  METHODS
  During the 7-day (n = 4) or 14-day (n = 4) observational period, the animals were monitored by serum levels of amylase and lipase, and by a CT on day 4. The outcome was determined by gross and microscopic evidence of inflammation of the pancreas, clinical tolerance, and quantitation of tissue paclitaxel concentrations.
  
  
  RESULTS
  Eight pigs underwent injection of 1, 2, 3, or 4 mL OncoGel (6 mg paclitaxel per 1 mL OncoGel) (n = 2 per group). An intrapancreatic hyperechoic focus, with an average diameter of 2.1 +/- 0.8 cm, was visible by EUS, and a hypodense area in the tail of the pancreas was visible by contrast CT. Clinically, the animals appeared to tolerate the procedure without sequelae. Blood levels of amylase and lipase were normal. At euthanasia, a depot of OncoGel, with an average diameter of 14.7 +/- 5.0 mm), was located both grossly and histologically in the pancreatic tail. After 14 days, clinically significant tissue concentrations of paclitaxel were detected at a distance of 30 to 50 mm from the depot in the animals that underwent an injection of 3 and 4 mL of the agent (n = 2).
  
  
  CONCLUSIONS
  The EUS-guided injection of OncoGel into the pancreas of the pig provided high and sustained localized concentrations of paclitaxel. This technique is a potential minimally invasive local treatment option for unresectable pancreatic tumors.
authors.affiliation: Gastrointestinal Unit, Gastrointestinal Pathology Service, Department of Pathology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Matthes
authors.forename: Mari
authors.initials: M
authors.lastname: Mino-Kenudson
authors.forename: Dushyant V
authors.initials: DV
authors.lastname: Sahani
authors.forename: Nagaraj
authors.initials: N
authors.lastname: Holalkere
authors.forename: Kirk D
authors.initials: KD
authors.lastname: Fowers
authors.forename: Ramesh
authors.initials: R
authors.lastname: Rathi
authors.forename: William R
authors.initials: WR
authors.lastname: Brugge
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D019160:Endosonography / Q000379:methods* / Q000662:veterinary; D005260:Female; D015552:Injections, Intralesional; D008297:Male; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D010179:Pancreas / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism; D013552:Swine; D014057:Tomography, X-Ray Computed; D014741:Video Recording
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel