title: 5-Fluorouracil ointment for the treatment of otitis media with effusion.
abstract: OBJECTIVE
  Our aim was to evaluate the combined effect of 5-fluorouracil (5-FU) and myringotomy for the treatment of otitis media with effusion (OME). OME is usually treated with medication, myringotomy, or insertion of a ventilation tube (VT). Except for VT insertion, however, treatment effects are short-lived. VT insertion has numerous sequelae: increased susceptibility to infection, large perforation of the tympanic membrane, cholesteatoma, and eventual hearing deterioration. We estimated the depressant action of 5-FU on normal cell proliferation in vitro. In addition, clinically, we assessed whether 5-FU has the potential to prolong the effect of myringotomy.
  
  
  METHODS
  An in vitro study and a clinical study were conducted.
  
  
  METHODS
  In study I, fibroblasts harvested from the peritoneum of three green fluorescent protein transgenic mice were cultured with different doses of 5-FU. After 2 weeks, their proliferation rates were compared. In study II, patients (54 males, 47 females) were selected randomly from a group of patients with intractable OME. Myringotomy with or without a single dose of 5-FU ointment (approximately 0.10-0.30 mg) was performed in group I (n = 64) and group II (n = 37), respectively. The natural closure rates of the tympanic membrane were assessed in both groups.
  
  
  RESULTS
  In vitro, 5-FU inhibited the growth of fibroblasts in a dose-dependent manner. The average time to tympanic membrane closure was 20.5 days in group I and 8.1 days in group II. No adverse events were observed in either group.
  
  
  CONCLUSIONS
  Topical application of 5-FU ointment is useful in prolonging the effect of myringotomy. 5-FU ointment therapy is easy, safe, and cost-effective and may be of wide application.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery Graduate School of Medicine, Kyoto University, Kyoto, Japan. kanemaru@ent.kuhp.kyoto-u.ac.jp
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Kanemaru
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Nakamura
authors.forename: Masaru
authors.initials: M
authors.lastname: Yamashita
authors.forename: Akhmar
authors.initials: A
authors.lastname: Magrfov
authors.forename: Koichi
authors.initials: K
authors.lastname: Omori
authors.forename: Juichi
authors.initials: J
authors.lastname: Ito
mesh_terms: D000287:Administration, Topical; D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000963:Antimetabolites / Q000008:administration & dosage / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002648:Child; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use*; D005500:Follow-Up Studies; D049452:Green Fluorescent Proteins; D006801:Humans; D049408:Luminescent Agents; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D009824:Ointments; D010034:Otitis Media with Effusion / Q000188:drug therapy*; D010537:Peritoneum / Q000166:cytology; D013396:Suction; D014432:Tympanic Membrane / Q000601:surgery
chemical_list: D000963:Antimetabolites; D049408:Luminescent Agents; D009824:Ointments; D049452:Green Fluorescent Proteins; D005472:Fluorouracil