title: Effect of vocal fold injection of cidofovir and bevacizumab in a porcine model.
abstract: OBJECTIVE
  Recurrent respiratory papillomatosis (RRP) is a common and often chronic disorder. Intralaryngeal bevacizumab has gained recent interest as an adjuvant therapy for RRP. However, no histologic model has been published describing the effects of bevacizumab on the vocal fold.
  
  
  OBJECTIVE
  To investigate the histologic effects of bevacizumab injections into the vocal fold and compare these findings with those for cidofovir and saline control injections.
  
  
  METHODS
  In vivo animal study involving eighteen 1-year-old Yorkshire crossbreed pigs, with a blinded review of pathologic findings conducted in a veterinary research laboratory.
  
  
  METHODS
  The pigs were randomly divided into six study groups receiving 2.5 or 5.0 mg of cidofovir or bevacizumab alone or in combination. Each pig received an injection of 0.5 mL of the test drug in the right vocal fold and 0.5 mL of saline in the left vocal fold. These injections were performed 4 times during the course of 8 weeks. One pig from each group was killed humanely and the larynges harvested 2 weeks after the last injection. The remaining pigs were killed 4 months after the last injection on the remaining pigs. The vocal folds were fixed and stained with hematoxylin-eosin and trichrome and reviewed for histologic changes by 3 blinded pathologists.
  
  
  METHODS
  Histologic changes to the vocal folds.
  
  
  RESULTS
  Minimal inflammation, edema, and atypia were found in all treatment groups. No appreciable histologic differences were found among the 3 treatment groups and their controls. No difference was seen in the vocal folds that were harvested late (4 months) vs early (2 weeks) after last injection. No fibrosis was found in any of the specimens.
  
  
  CONCLUSIONS
  No histologic evidence suggests that intralaryngeal cidofovir or bevacizumab alone or in combination resulted in significant changes to the porcine vocal fold. Future studies may build on this model to test higher dosages and/or may combine injections with potassium titanyl phosphate laser therapy.
authors.affiliation: Department of Otolaryngology, San Antonio Military Medical Center, Ft Sam Houston, Texas.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Connor
authors.affiliation: Department of Pathobiology, 59th Clinical Research Division, Lackland Air Force Base, Texas.
authors.forename: Ammon
authors.initials: A
authors.lastname: Brown
authors.affiliation: Department of Pathology, San Antonio Military Medical Center, Ft Sam Houston, Texas.
authors.forename: Mitzi
authors.initials: M
authors.lastname: Palazzolo
authors.affiliation: Department of Pathology, San Antonio Military Medical Center, Ft Sam Houston, Texas.
authors.forename: Julie
authors.initials: J
authors.lastname: Kunkel
authors.affiliation: Department of Otolaryngology, Lakenheath Air Force Base, England.
authors.forename: Robert
authors.initials: R
authors.lastname: Eller
authors.affiliation: Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts.
authors.forename: Christopher
authors.initials: C
authors.lastname: Hartnick
authors.affiliation: Department of Otolaryngology, San Antonio Military Medical Center, Ft Sam Houston, Texas6Uniformed Services University of the Health Sciences, Bethesda, Maryland.
authors.forename: Stephen
authors.initials: S
authors.lastname: Maturo
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D000068258:Bevacizumab; D001707:Biopsy, Needle; D000077404:Cidofovir; D003596:Cytosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D007150:Immunohistochemistry; D015552:Injections, Intralesional; D023421:Models, Animal; D063065:Organophosphonates / Q000494:pharmacology*; D011897:Random Allocation; D012680:Sensitivity and Specificity; D034421:Sus scrofa; D013552:Swine; D014827:Vocal Cords / Q000187:drug effects* / Q000473:pathology*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D063065:Organophosphonates; D000068258:Bevacizumab; D003596:Cytosine; D000077404:Cidofovir