title: Effects of botulinum toxin type a in the bladder wall of children with neurogenic bladder dysfunction: a comparison of histological features before and after injections.
abstract: OBJECTIVE
  Botulinum toxin type A has gained popularity in urology. Most reported studies have been in adults at urology centers and most have addressed long-term safety. Since botulinum toxin type A treatment for neurogenic bladder dysfunction requires repeat injections, verifying that such treatment does not induce fibrosis in children seems essential.
  
  
  METHODS
  The study was approved by the institutional review board and patients were enrolled after we obtained written consent. Patients with neurogenic bladder dysfunction not responding to conventional treatment (anticholinergics and clean intermittent catheterization) were treated with 10 IU/kg botulinum toxin type A up to a maximum of 300 IU. Endoscopic cold cup biopsies were obtained from the posterolateral bladder wall 1.5 to 2 cm above the ureteral orifice. Bladder wall findings were categorized into 3 groups, including inflammatory infiltration, edema and fibrosis. Each criterion was then graded as mild or severe and analyzed by Fisher's exact test (p <0.05).
  
  
  RESULTS
  A total of 46 bladder wall biopsies were obtained from 40 patients 2 to 18 years old. Biopsies were evaluated in groups 1 and 2, including group 1-20 from patients with no botulinum toxin type A injection and group 2-20 after botulinum toxin type A injection. Group 2 was subdivided into group 3-10 biopsies after 1 injection and group 4-10 after multiple injections. Six patients underwent biopsy twice, that is before the first and second treatments. Histological changes were present in all biopsies. When comparing groups 1 and 2, there was no statistically significant difference in inflammation and edema. However, there was a significant difference in fibrosis between groups 1 and 4 (p <0.05) with apparently decreased fibrosis after multiple injections.
  
  
  CONCLUSIONS
  In our experience repeat botulinum toxin type A injections into the detrusor in children do not lead to increased fibrosis in the bladder wall. This study confirms the long-term safety of botulinum toxin type A in the pediatric population.
authors.affiliation: Department of Nephro-Urology, Bambino Gesù Pediatric and Research Hospital, Piazza S. Onofrio 4, Rome, Italy.
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Pascali
authors.forename: Giovanni
authors.initials: G
authors.lastname: Mosiello
authors.forename: Renata
authors.initials: R
authors.lastname: Boldrini
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Salsano
authors.forename: Enrico
authors.initials: E
authors.lastname: Castelli
authors.forename: Mario
authors.initials: M
authors.lastname: De Gennaro
mesh_terms: D000283:Administration, Intravesical; D000293:Adolescent; D001706:Biopsy; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005260:Female; D005355:Fibrosis / Q000139:chemically induced; D006801:Humans; D008297:Male; D009465:Neuromuscular Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001743:Urinary Bladder / Q000187:drug effects* / Q000473:pathology*; D001750:Urinary Bladder, Neurogenic / Q000188:drug therapy* / Q000473:pathology*
chemical_list: D009465:Neuromuscular Agents; D019274:Botulinum Toxins, Type A