Persistent urothelial differentiation changes in the reconstructed exstrophic bladder: Congenital or acquired dysfunction of the epithelial barrier?. Issue 5 (October 2021)

• Record Type: Journal Article
• Authors: Rubenwolf, Peter; Eder, Fabian; Götz, Stefanie; Promm, Martin; Rösch, Wolfgang H.
• Is Part Of: Journal of pediatric urology. Volume 17:Issue 5(2021)
• Page Start: 632.e1
• Page End: 632.e7
• Publication Date: 2021-10
• Subjects: Classic bladder exstrophy -- Urothelium -- Urothelial barrier function -- Urothelial differentiation -- Histological changes; Pediatric urology -- Periodicals; Urologic Diseases -- Periodicals; Urogenital Diseases -- Periodicals; Urologic Surgical Procedures -- Periodicals; Child; Infant; Urologie pédiatrique -- Périodiques; Appareil urinaire -- Maladies -- Périodiques; Pédiatrie; Urologie; Pediatric urology; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); Electronic journals; Periodicals; Electronic journals; 618.926
• DOI: 10.1016/j.jpurol.2021.07.016
• Languages: English
• ISSNs: 1477-5131

Abstract

Summary: Background: We have previously characterised the urothelium from infants with classic bladder exstrophy (CBE) for the expression of urothelial differentiation-associated markers. We found abnormal expression patterns of uroplakin 3a, cytokeratin 13, cytokeratin 20 and claudin 4 in the majority of bladder biopsies taken at the time of primary bladder closure. Abnormal urothelial differentiation results in a compromised urothelial barrier with potential implications on bladder development and the success of reconstructive surgery. Objective: To investigate whether the urothelial differentiation changes observed in the unclosed exstrophic bladder persist after successful primary exstrophy repair. Design, setting and participants: From 2005 to 2018 bladder biopsies from 115 children with CBE obtained at the time of primary bladder closure (n = 67, median age: 8.1 weeks) and during secondary procedures aimed at achieving continence (n = 48, median age: 6.8 years) were prospectively collected. Following histological assessment immunohistochemistry was used to investigate the expression of uroplakin 3a, cytokeratin 13 and 20 and claudin 4, well-characterized markers associated with the terminally-differentiated, fully functional urothelial phenotype. The urothelium from 16 children with VUR and with non-refluxing disorders of the urinary tract served as controls. Results: Tissue specimen from 100 children were included in the analysis. Only 32% of bladder specimens from children having undergone successful primary bladder closure in early infancy displayed a fully differentiated urothelial phenotype with regular expression of all 4 markers. The remaining bladders revealed irregular or absent marker expression suggesting abnormal urothelial differentiation. 86% of the samples had inflammatory, proliferative or metaplastic histological changes. Conclusion: Our results suggest persisting urothelial differentiation changes in two-thirds of exstrophic bladders following successful bladder closure in early infancy. Despite some limitations, the findings provide a platform for translational studies into the role of the urothelium for the developmental potential of the exstrophic bladder and the success of reconstructive surgery. Summary Table % regular expression of urothelial differention markers CK13, CK20, UPK3 and CL4 in bladder specimens before and afte primary exstrophy repair. All values p < 0.05 (for interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article). Summary Table