title: Long-term histological and mucin alterations in the neobladder mucosa following urinary bladder augmentation or substitution with gastrointestinal segment.
abstract: BACKGROUND
  Bladder augmentation is widely used to treat otherwise unmanageable urinary incontinence. However, it is associated with a large number of complications, of which tumor formation is the most severe. Mucin proteins and MUC genes are linked, among others, to malignancies of the urinary bladder and the gastrointestinal system.
  
  
  OBJECTIVE
  To investigate histological alterations as well as changes in expression of MUC1 and MUC2 genes and proteins following different types of urinary bladder augmentation or substitution performed in children and adolescents.
  
  
  METHODS
  Between 1988 and 2013, 91 patients underwent urinary bladder augmentation or substitution at the study institute. Patients were included on whom cystoplasty had been performed 4 years previously or earlier, and could have been followed-up prospectively. Thus, 54 patients were involved in the study. In eight patients gastrocystoplasty was performed, in 17 patients ileocystoplasty, and in 22 patients colocystoplasty. Seven patients underwent bladder substitution using a colonic-segment. Biopsies were taken via cystoscopy from the native bladder, from the gastrointestinal segment used for augmentation, and from the anastomotic line between these two. One part of the samples was fixed in formaldehyde for routine histological processing. The other part of the biopsies was embedded into OCT medium, then cryosectioned and fluorescently double-immunostained for MUC1 and MUC2 proteins. Samples from the microscopically dysplastic lesions and from the 15-year-old or older biopsies were processed by laser capture microdissection, and then real-time PCR was done. Data were statistically analyzed by ANOVA and ordinary least squares regression tests.
  
  
  RESULTS
  One adenocarcinoma was found in a female patient, 11 years after colocystoplasty. There were no significant changes in the level of MUC1 and MUC2 proteins and gene expression in the urothelium and in the gastrointestinal segment used for augmentation following ileocystoplasty and gastrocystoplasty. Significant increase in MUC1 and decrease in MUC2 protein levels were detected following colocystoplasty in the large bowel segment used for augmentation, both with qualitative and quantitative methods (p < 0.05) (Figure). The uroepithelium showed no significant change. RT-PCR revealed progressive increase in MUC1 gene expression and decrease in MUC2 gene expression after colocystoplasty in the course of time. It also showed highly increased MUC1 gene expression and decreased MUC2 gene expression in the samples of patients.
  
  
  CONCLUSIONS
  Alterations in gene expression of MUC1 and MUC2 might serve as promising markers for early detection of histological changes after colocystoplasty.
authors: Surgical Unit, Department of Paediatrics, University of Pécs, Hungary; Department of Paediatric and Adolescent Surgery-Medical University of Graz, Graz, Austria. Electronic address: zachary22@gmail.com.
authors: Zoltan Farkas
authors: ZF
authors: Kispal
authors: Surgical Unit, Department of Paediatrics, University of Pécs, Hungary. Electronic address: kardos.daniel@pte.hu.
authors: Daniel
authors: D
authors: Kardos
authors: The Evanston Hospital, Northshore University Healthsystem, Evanston, IL, USA. Electronic address: tjilling@peds.uab.edu.
authors: Tamas
authors: T
authors: Jilling
authors: Department of Pathology, University of Pécs, Hungary. Electronic address: laszlo.kereskai@aok.pte.hu.
authors: Laszlo
authors: L
authors: Kereskai
authors: The Evanston Hospital, Northshore University Healthsystem, Evanston, IL, USA. Electronic address: marlaissac2011@u.northwestern.edu.
authors: Marla
authors: M
authors: Isaacs
authors: Surgical Unit, Department of Paediatrics, University of Pécs, Hungary. Electronic address: radibutz@gmail.com.
authors: Daniel L
authors: DL
authors: Balogh
authors: Surgical Unit, Department of Paediatrics, University of Pécs, Hungary. Electronic address: pinter.andras@pte.hu.
authors: Andrew B
authors: AB
authors: Pinter
authors: Department of Paediatric and Adolescent Surgery-Medical University of Graz, Graz, Austria. Electronic address: holger.till@medunigraz.at.
authors: Holger
authors: H
authors: Till
authors: Surgical Unit, Department of Paediatrics, University of Pécs, Hungary. Electronic address: vajda.peter@pte.hu.
authors: Peter
authors: P
authors: Vajda
mesh_terms: D000293:Adolescent; D000714:Anastomosis, Surgical; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D003106:Colon / Q000601:surgery*; D015870:Gene Expression; D006801:Humans; D007082:Ileum / Q000601:surgery*; D018396:Mucin-1 / Q000096:biosynthesis* / Q000235:genetics; D055262:Mucin-2 / Q000096:biosynthesis* / Q000235:genetics; D009092:Mucous Membrane / Q000473:pathology*; D011446:Prospective Studies; D013270:Stomach / Q000601:surgery*; D013997:Time Factors; D001743:Urinary Bladder / Q000601:surgery*; D016476:Urinary Reservoirs, Continent; D013520:Urologic Surgical Procedures / Q000379:methods; D055815:Young Adult
chemical_list: C060192:MUC1 protein, human; C524625:MUC2 protein, human; D018396:Mucin-1; D055262:Mucin-2
keywords: MUC genes; Neoplasia; Urinary bladder augmentation