Development of bladder urothelial hyperplasia and carcinoma in portacaval shunted rats is not dependent upon urolithiasis.
The pathogenesis of bladder tumors is poorly understood, possibly due to the lack of a suitable experimental model that is drug-free. The aim of the present study was to determine whether bladder tumors could be reproduced reliably in portacaval anastomosis (PCS) rats and whether induction is due to urolithiasis from the development of bladder stones. Eighteen male Sprague-Dawley rats were anaesthetised with isoflurane. Twelve were subjected to portacaval anastomosis and allowed to recover for 38 weeks and the remaining 6 underwent sham control procedures. They were then re-anaesthetised, the anastomosis checked for patency and the bladders and livers excised, fixed, block-mounted, sectioned and stained with haematoxylin and eosin staining for histological examination. None of the control rats developed bladder wall abnormalities of any recognisable nature. However, 5 (42%) of the PCS group had urothelial lesions and bladder stones present and a further 5 (42%) had urothelial lesions alone with no recognisable evidence of bladder stone formation. One PCS rat had bladder stones alone and the remaining PCS rat had an apparently normal bladder epithelium and no stones. Thus, 10 (83%) of the 12 PCS rats developed epithelial lesions and half of these did not display evidence of bladder stone formation. This represented a highly significant difference between the development of bladder stones and the occurrence of urothelial lesions in PCS rats (P > 1.0, chi(2) analysis). Urothelial lesions, therefore, can be reproduced in PCS rats. Their occurrence appears independent of bladder stone formation.