title: Irreversible electroporation enhances delivery of gemcitabine to pancreatic adenocarcinoma.
abstract: BACKGROUND
  Irreversible electroporation (IRE) utilizes short, high-voltage pulses to irreversibly permeabilize the cell membrane, resulting in apoptotic cell death. In addition to the irreversible zone, IRE creates a reversible zone that could be utilized for enhanced drug delivery. The hypothesis of this study is that a zone of reversible electroporation exists and allows for increased chemotherapy delivery.
  
  
  METHODS
  Ten immunocompromised mice with orthotopic human pancreatic adenocarcinoma tumors (Panc1) were treated with either IRE between two doses of gemcitabine (15 mg/kg) (ECT) (N = 5) or gemcitabine alone (N = 5). Gemcitabine levels in the serum, liver, and pancreas were analyzed with liquid chromatography/mass spectrometry (LC/MS).
  
  
  RESULTS
  Concentration of gemcitabine within reversibly electroporated pancreatic tissue was higher in mice receiving ECT compared to those receiving gemcitabine alone (13,567 ng/ml vs.4,126 ng/ml; P = 0.0009). Pancreatic gemcitabine levels were 5.52 and 5.96 times higher than liver and serum levels, respectively, in the ECT group compared to 2.85 and 2.53 times higher (P = 0.117, P = 0.058), respectively, in mice receiving gemcitabine alone.
  
  
  CONCLUSIONS
  IRE can potentially reduce local recurrence by allowing increased drug delivery to the tissue in the reversible electroporation zone. This holds significant potential in augmenting efficacy of gemcitabine in treatment of locally advanced and borderline resectable pancreatic adenocarcinoma. J. Surg. Oncol. 2016;114:181-186. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, Kentucky.
authors.forename: Neal
authors.initials: N
authors.lastname: Bhutiani
authors.affiliation: Division of Surgical Oncology, Department of Surgery, University of Texas Medical Branch, Galveston, Texas.
authors.forename: Steven
authors.initials: S
authors.lastname: Agle
authors.affiliation: Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, Kentucky.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, Kentucky.
authors.forename: Suping
authors.initials: S
authors.lastname: Li
authors.affiliation: Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, Kentucky.
authors.forename: Robert C G
authors.initials: RC
authors.lastname: Martin
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000818:Animals; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000032:analysis; D053672:Electrochemotherapy / Q000379:methods*; D016867:Immunocompromised Host; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D000093542:Gemcitabine
keywords: electrochemotherapy; electroporation; gemcitabine; irreversible electroporation; pancreatic cancer; reversible