title: Persistent histological changes in the exstrophic bladder after primary closure-a cause for concern?
abstract: OBJECTIVE
  We investigated bladder biopsies from patients with classic bladder exstrophy for the histological features and discuss the potential clinical significance of the findings.
  
  
  METHODS
  Bladder tissues were collected from patients with bladder exstrophy between 2004 and 2011. These specimens were obtained at primary bladder closure (group 1, 29 patients), during secondary reconstructive procedures (group 2, 27) or during cystectomy for failed reconstruction (group 3, 15). All tissue specimens were investigated for inflammatory, proliferative, metaplastic and dysplastic changes. Expression of urothelial differentiation markers CK13 and CK20 was determined by immunohistochemical analysis.
  
  
  RESULTS
  Inflammatory, proliferative and metaplastic changes were found in bladder specimens of all subgroups. Neither dysplasia nor neoplasia was present. Severe epithelial changes such as cystitis glandularis and intestinal metaplasia were observed in up to 62% of bladders several years after primary closure. Aberrant expression patterns of CK13 and CK20 suggesting abnormal urothelial differentiation were shown to be present in the urothelium of all subgroups.
  
  
  CONCLUSIONS
  Our findings provide prima facie evidence that the epithelial changes observed in the unclosed bladder template persist or even progress in a subset of bladders after primary closure. Although the malignant potential of cystitis glandularis and intestinal metaplasia is controversial, some patients may be at increased risk for dysplasia/neoplasia in the long term. Since the natural history of these lesions in the exstrophic bladder is unknown, these patients require lifelong surveillance.
authors.affiliation: Department of Pediatric Urology, University Medical Center Regensburg, Regensburg, Germany. peter.rubenwolf@unimedizin-mainz.de
authors.forename: Peter C
authors.initials: PC
authors.lastname: Rubenwolf
authors.forename: Fabian
authors.initials: F
authors.lastname: Eder
authors.forename: Anne-Karoline
authors.initials: AK
authors.lastname: Ebert
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Hofstaedter
authors.forename: Christopher R J
authors.initials: CR
authors.lastname: Woodhouse
authors.forename: Wolfgang H
authors.initials: WH
authors.lastname: Roesch
mesh_terms: D000293:Adolescent; D000328:Adult; D001706:Biopsy; D001746:Bladder Exstrophy / Q000473:pathology* / Q000601:surgery*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D011183:Postoperative Complications / Q000473:pathology*; D011446:Prospective Studies; D055815:Young Adult