Long-term histological and mucin alterations in the neobladder mucosa following urinary bladder augmentation or substitution with gastrointestinal segment
Introduction
Urinary bladder augmentation is widely used for conservatively unmanageable urinary incontinence. However, to date, there is no evidence-based consensus in the literature as to which tissue type is the ideal for these operations. The uncertainty is caused by the fact, that after the increasing popularity of the technique in the 1980s and 1990s, long-term complications were identified, which were dependent on the type of the gastrointestinal segment used [1], [2], [3]. These can be grouped as metabolic and non-metabolic (mainly surgical) complications [2]. Malignancy is considered to be one of the most serious in the metabolic group [1], [3]. Literature puts the incidence of bladder cancer at 1.5% per decade after colocystoplasty and 2.8% per decade after gastrocystoplasty [3].
Many factors are suspected to play a role in tumor formation following urinary bladder augmentation. Bacteria living in the urine may transform nitrates into potentially carcinogenic nitrosamines [4]. Urine may exert a direct toxic, DNA damaging effect on the gastrointestinal epithelium [5]. Aberrant signal mechanisms between the bladder mucosa and tissue used for augmentation may also play a role [1].
According to the literature, the average time elapsing between augmentation cystoplasty and first tumor detection is about 17 years [6]. Therefore, regular cystoscopies with mucosal biopsies are strongly recommended by many specialists for early cancer detection [2], [3].
Mucins have been investigated widely in connection with malignancy of various tissues. They are high-molecular-weight glycoproteins containing at least 50% carbohydrate. Their oligosaccharide side chains, which are O-glycosidically linked to an apomucin core peptide, consist of N-acetylgalactosamine, galactose, fucose, N-acetylglucosamine, and syalic acid residues. The apomucin peptides are typically rich in serine, threonine, proline, alanine, and glycine [7], [8]. To date, 19 types of mucin genes have been identified.
Every gastrointestinal epithelium (stomach, small- and large-intestine) has a unique mucin expression pattern, which may change in the case of malignancy [7]. There is evidence in adults that some of these changes in mucin expression happen very early in carcinogenesis. They may even precede the detectable morphological changes that are indicative of malignant transformation [9].
Changes in the levels of MUC1 and MUC2 proteins are associated with various malignancies in humans, as well as urothelial, intestinal, and gastric tumors [10]. MUC1 has barrier and cell signaling functions [11]. Overexpression or changes in glycosylation may result in carcinoma formation [12]. MUC2 protein is a secreted, gel forming protein. Its expression may decrease in colorectal carcinomas [13], and loss of its expression may predict recurrence or worse survival [14].
The aim of our study was to investigate histological changes and MUC1 and MUC2 protein levels and gene expression in the epithelium of the augmented urinary bladder following gastro-, ileo-, and colocystoplasty or bladder substitution.
Section snippets
Materials and methods
All investigations were performed with the approval of the university's local ethical committee and the National Ethical Committee in Hungary.
Between 1988 and 2013, 91 patients underwent urinary bladder augmentation and/or substitution at University of Pecs, Department of Paediatrics, Surgical Unit. We selected patients in whom augmentation had been performed at least 4 years previously, and who could come to control surveys regularly. Thus, 54 patients were recruited for the prospective study.
Results
Table 1 details the results of routine histology of the 54 patients. Metaplasia was found in three patients 8, 10, and 14 years after augmentation. One metaplasia was found in the colonic segment used for augmentation, one in the original bladder part (Fig. 2), and one in the anastomotic line between the bladder and the colonic segment. Dysplasia was observed altogether in six cases, in three patients during their follow-up. Five cases were detected 4 years after bladder augmentation and one
Discussion
The number of reports about tumors arising after urinary bladder augmentation or substitution is increasing [1], [2], [3], [15]. Tumor formation is one of the most insidious complications with many disputes to surveillance and treatment [2], [3], [15], [16]. There are accepted options, which are currently in use for warning in case of bladder cancer in adults [16], [17]. Because of the cancer risk after augmentation cystoplasty, regular cystoscopies are recommended [1], [2], [3], [15]. However,
Conclusion
Detection of changes in MUC1 and MUC2 gene expressions in colonic tissue samples are promising markers for early detection of malignancy in patients with colocystoplasty.
Conflict of interest
None.
Funding
This paper was supported by “PTE ÁOK-KA- 2013/28” (Research Fund for of University of Pecs, Medical School) and János Bolyai Research Scholarship of the Hungarian Academy of Sciences as well as the William J. Fulbright Scholarship.
Acknowledgment
The present scientific contribution is dedicated to the 650th anniversary of the founding of the University of Pécs, Hungary.
References (22)
- et al.
Unique clinicopathologic and molecular characteristics of urinary bladder tumors in children and young adults
Urol Oncol
(2013) - et al.
Mucin gene expression in human urothelium and in intestinal segments transposed into the urinary tract
J Urol
(2000) - et al.
Cell surface-associated mucins in signal transduction
Trends Cell Biol
(2006) - et al.
Long-term follow up of enteric augmentations: the risk for malignancy
J Pediatr Urol
(2008) - et al.
Annual endoscopy and urine cytology for the surveillance of bladder tumors after enterocystoplasty for congenital bladder anomalies
J Urol
(2011) - et al.
Mucins in normal and neoplastic human gastrointestinal tissues
Crit Rev Oncol Hematol
(1994) Malignancy after gastrointestinal augmentation in childhood
Ther Adv Urol
(2009)- et al.
Complications after bladder augmentation or substitution in children: a prospective study of 86 patients
BJU Int
(2011) Long-term risks of bladder augmentation in pediatric patients
Curr Opin Urol
(2008)- et al.
Routine surveillance cystoscopy for patients with augmentation and substitution cystoplasty for benign urological conditions: is it necessary?
BJU Int
(2009)
Late uro-ileal cancer after incorporation of ileum into the urinary tract
J Urol
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Present address. Neonatology Faculty, Department of Paediatrics, University of Alabama at Birmingham, Birmingham, AL, USA.