Evaluation of an orthotopic rat bladder urothelial cell carcinoma model by cystoscopy.
OBJECTIVE
To enable preclinical testing of intravesical therapies against non-muscle-invasive bladder cancer (NMIBC) in an orthotopic rat bladder tumour model, augmented by the use of serial cystoscopy for in vivo tumour assessment and follow-up.


METHODS
Fischer F344 rats had a 16-G transurethral cannula placed. The bladder mucosa was conditioned with an acid rinse, followed by a 1-h instillation of 1.5 x 10(6) AY-27 rat bladder urothelial cell carcinoma (UCC) cells (day 0). Cystoscopy (1 mm) was done on day 0 (control) and at 3, 4, 5, 6, 7, 10, 13 and 17 days. At the scheduled times the rats were killed after cystectomy (four at each time) for histopathological examination of the bladder.


RESULTS
Overall, tumour establishment was >80%, with predominantly carcinoma in situ preceding or concomitant with invasive tumour growth. All tumours were formed at 3-5 days, and remained non-muscle-invasive up to 5 days. From 6 days, tumours progressed to muscle-invasive disease in 40% of the rats. Visibility at cystoscopy was excellent and tumours were apparent in >90% of rats from 5 days on, with a specificity and sensitivity of >90%. Cystoscopy could not distinguish NMIBC from muscle-invasive disease.


CONCLUSIONS
This is a reliable model of orthotopic rat bladder UCC, with early high-grade NMIBC growth, immediately followed by muscle-invasive growth, i.e. the recommended time to start intravesical therapy would be 5 days after tumour cell inoculation. Tumour growth can easily be monitored by cystoscopy, but cannot be used to distinguish NMIBC from muscle-invasive bladder cancer.
Hendricksen
Kees
K
Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Molkenboer-Kuenen
Janneke
J
Oosterwijk
Egbert
E
Hulsbergen-van de Kaa
Christina A
CA
Witjes
J Alfred
JA
D000818:Animals; D002295:Carcinoma, Transitional Cell / Q000473:pathology*; D002455:Cell Division; D003558:Cystoscopy / Q000379:methods*; D005260:Female; D009368:Neoplasm Transplantation; D051381:Rats; D011916:Rats, Inbred F344; D012680:Sensitivity and Specificity; D001749:Urinary Bladder Neoplasms / Q000473:pathology*