title: Pressurized intraluminal aerosol chemotherapy with Dbait in the distal esophagus of swine.
abstract: OBJECTIVE
  A novel therapeutic concept, pressurized intraluminal aerosol chemotherapy (PILAC), and a corresponding device for distributing drugs to the mucosa and submucosa of the distal esophagus are presented.
  
  
  METHODS
  The endoscopic device that was designed consisted of (i) a double-balloon catheter, similar to a Sengstaken-Blakemore tube; (ii) a carbon dioxide (CO2) line, used to create a gaseous, pressurized environment; and (iii) a micropump, used to generate a therapeutic aerosol. The device was inserted into the distal esophagus in three narcotized Landrace pigs. Dbait (short interfering DNA, or siDNA) was aerosolized under pressure (12 mmHg) in CO2 at 37 °C for 30 minutes.
  
  
  RESULTS
  The procedure was well tolerated by all animals. At autopsy, no mucosal or muscular tear was observed. Fluorescence microscopy revealed a homogeneous intramural distribution of Dbait-cyanine 5 in the esophageal wall down to the circular muscular layer (400 - 600 µm).
  
  
  CONCLUSIONS
  PILAC is feasible in a large animal model and appears to be safe. Therapy of the entire "tissue at risk" for the development of cancer in the distal esophagus is possible without the prior endoscopic identification of diseased tissue.
authors.affiliation: Department of Surgery, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
authors.forename: Nadja
authors.initials: N
authors.lastname: Khalili-Harbi
authors.affiliation: DNA Therapeutics, Orsay, France.
authors.forename: Nirmitha
authors.initials: N
authors.lastname: Herath
authors.affiliation: Department of Surgery, St. Mary's Hospital, Ruhr University Bochum, Bochum, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Solass
authors.affiliation: Department of Surgery, St. Mary's Hospital, Ruhr University Bochum, Bochum, Germany.
authors.forename: Urs
authors.initials: U
authors.lastname: Giger-Pabst
authors.affiliation: Institut Curie, Orsay, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Dutreix
authors.affiliation: Department of Surgery, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
authors.forename: Marc Andre
authors.initials: MA
authors.lastname: Reymond
mesh_terms: D000336:Aerosols / Q000008:administration & dosage; D000818:Animals; D004938:Esophageal Neoplasms / Q000175:diagnosis / Q000188:drug therapy*; D004945:Esophagoscopy / Q000379:methods*; D004947:Esophagus; D005240:Feasibility Studies; D008856:Microscopy, Fluorescence; D009374:Neoplasms, Experimental; D011312:Pressure; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D013552:Swine
chemical_list: D000336:Aerosols; D034741:RNA, Small Interfering