title: Ultrastructural and immunohistopathological evaluation of intravesical ureters via electron and light microscopy in children with vesicoureteral reflux.
abstract: OBJECTIVE
  We used immunohistochemical methods and transmission electron microscopy to investigate the cytokine profiles and ultrastructural changes in the ureterovesical junction of children with primary vesicoureteral reflux.
  
  
  METHODS
  A total of 39 distal intravesical ureters were obtained from 23 children who underwent ureteroneocystostomy for primary vesicoureteral reflux. Ureteral wall smooth muscle organization and transforming growth factor-β1, vascular endothelial growth factor and CD34 were evaluated immunohistochemically and compared to controls, which consisted of 10 age matched autopsy specimens. Ultrastructural evaluations and morphological descriptions were performed semiquantitatively and compared to the published data.
  
  
  RESULTS
  Of the patients 6 (26%) were male and 17 (74%) were female, and mean ± SD age was 73.2 ± 34.3 months (range 12 to 168). There was no correlation between reflux grade and age (p = 0.39). Smooth muscle disorganization score differed significantly between patients with intravesical ureters and controls (p = 0.01). Transforming growth factor-β1 levels were significantly higher (p = 0.001) and vascular endothelial growth factor levels and microvessel densities were significantly lower in the patients with reflux compared to controls (both p <0.001). Vascular endothelial growth factor, CD34 and transforming growth factor-β1 levels did not correlate with reflux grades (p = 0.84, p = 0.76 and p = 0.10, respectively). Urothelium, lamina propria and tunica adventitia appeared normal in the specimens for all grades of vesicoureteral reflux using transmission electron microscopy. Damage was observed in the muscular layers of the ureterovesical junction, especially in patients with grade IV or V reflux.
  
  
  CONCLUSIONS
  Primary refluxing ureters exhibit immunohistopathological abnormalities compared to normal ureters irrespective of reflux grade, and ultrastructural changes are especially severe in cases of high grade reflux. These abnormalities can hinder the normal ureteral valve mechanism, and may lead to reflux due to smooth muscle dysfunction and microvascular alterations.
authors.affiliation: Department of Urology, Faculty of Medicine, University of Çukurova, Adana, Turkey.
authors.forename: Volkan
authors.initials: V
authors.lastname: Izol
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Çukurova, Adana, Turkey.
authors.forename: Arbil Avci
authors.initials: AA
authors.lastname: Acikalin
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, University of Çukurova, Adana, Turkey.
authors.forename: Yurdun
authors.initials: Y
authors.lastname: Kuyucu
authors.affiliation: Department of Urology, Faculty of Medicine, University of Çukurova, Adana, Turkey.
authors.forename: Mutlu
authors.initials: M
authors.lastname: Deger
authors.affiliation: Department of Urology, Faculty of Medicine, University of Çukurova, Adana, Turkey.
authors.forename: Ibrahim Atilla
authors.initials: IA
authors.lastname: Aridogan
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, University of Çukurova, Adana, Turkey.
authors.forename: Sait
authors.initials: S
authors.lastname: Polat
authors.affiliation: Department of Urology, Faculty of Medicine, University of Çukurova, Adana, Turkey.
authors.forename: Nihat
authors.initials: N
authors.lastname: Satar
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D008853:Microscopy; D046529:Microscopy, Electron, Transmission; D014513:Ureter / Q000473:pathology* / Q000648:ultrastructure*; D001743:Urinary Bladder / Q000473:pathology* / Q000648:ultrastructure*; D014718:Vesico-Ureteral Reflux / Q000473:pathology*
keywords: child; electron; microscopy; ureter; vesico-ureteral reflux