title: Effect of slow-release 5-Fluorouracil on capsule formation around silicone breast implants: an experimental study with mice.
abstract: BACKGROUND
  Capsule formation around breast implants, development of tendon adhesions after tendon repair, intestinal brits after laparatomies, hypertrophic scars in skin incisions all are the results of excessive collagen synthesis to the extracellular matrix by fibroblasts. Any intervention that leads to cessation of collagen synthesis in these clinical situations may help to prevent these untoward results of wound healing. Although 5-fluorouracil (5-FU) is used mainly as a cytotoxic drug in chemotherapy protocols, it decreases cellular metabolism and blocks protein synthesis only at lower concentrations. Findings have shown that 5-FU downregulates fibroblast proliferation and differentiation in vitro. It has been used to treat fibroproliferative disorders of the eye and skin and is thought to inhibit thymidylate synthetase, blocking DNA replication.
  
  
  METHODS
  This study used five treatment groups: (1) gelatin only, (2) silicone only, (3) silicone + gelatin, (4) silicone + gelatin containing 1 mg of 5-FU, and (5) silicone + gelatin containing 5 mg of 5-FU. The release kinetics of 5-FU from gelatin have been investigated by means of ultraviolet spectrophotometric analysis. Specimens were obtained on postoperative day 30. Gross evaluation and histopathologic examination were conducted for capsule formation and the development of inflammation.
  
  
  RESULTS
  The silicone group had the most prominent capsule formation among all the groups. The gelatin group was second, and the silicone + gelatin group was third. As compared with the other groups, the 5-FU-containing groups had the least capsule formation. The 5-mg 5-FU-containing group had the most inflammation. The silicone + gelatin group was second in inflammation. Although the silicone, gelatin, and 1-mg 5-FU-containing groups had the same means, the results of the silicone group showed the most divergent data within the group.
  
  
  CONCLUSIONS
  Because 5-FU loaded to a gelatin carrier for its slow release seems to prevent capsule formation around silicone blocks, it may be used to prevent capsule formation around silicone breast implants.
authors.affiliation: Department of Plastic, Reconstructive, and Aesthetic Surgery, Hacettepe University, Faculty of Medicine, Ankara, Turkey. hicanter@gmail.com
authors.forename: Halil
authors.initials: H
authors.lastname: Ibrahim Canter
authors.forename: Ersoy
authors.initials: E
authors.lastname: Konas
authors.forename: Onder
authors.initials: O
authors.lastname: Bozdogan
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Vargel
authors.forename: Bilgen
authors.initials: B
authors.lastname: Ozbatir
authors.forename: Filiz
authors.initials: F
authors.lastname: Oner
authors.forename: Yucel
authors.initials: Y
authors.lastname: Erk
mesh_terms: D000818:Animals; D000963:Antimetabolites / Q000008:administration & dosage / Q000494:pharmacology*; D018427:Breast Implants / Q000009:adverse effects*; D003094:Collagen / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D016326:Extracellular Matrix Proteins / Q000187:drug effects; D005260:Female; D005347:Fibroblasts / Q000187:drug effects*; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology*; D005549:Foreign-Body Reaction / Q000209:etiology / Q000517:prevention & control*; D020007:Implants, Experimental; D051379:Mice; D020034:Silicone Gels / Q000009:adverse effects*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000963:Antimetabolites; D016326:Extracellular Matrix Proteins; D020034:Silicone Gels; D003094:Collagen; D005472:Fluorouracil