Histopathological effects and recovery rate of rat bladders following intravesical instillation of thiotepa, doxorubicin and mitomycin C.

A study was made of the local reactions and systemic effects induced by intravesical instillations of thiotepa, doxorubicin and mitomycin C in rats. The control group received normal saline. In the 1-dose short-term experiments, rats treated with doxorubicin and mitomycin C had a high incidence of chemical reactions, including congestion of the mucosa with methylene blue stain, increased bladder weight with oedematous changes either in the mucosa (doxorubian) or the muscle layer (mitomycin C), and infiltration of polymorphonuclear cells 3 days after instillation. These local changes disappeared within 10 days. In long-term experiments with weekly instillations of chemotherapeutic drugs, the rats showed no significant change in weight, methylene blue staining or mucosal congestion. A high percentage of pyuria and microscopic haematuria with submucosal/muscular fibrosis was noted in rats receiving doxorubicin or mitomycin C. A severe dysplastic change in the urothelium was noted in rats treated with mitomycin C. These results suggest that careful follow-up is required in patients receiving intravesical doxorubicin or mitomycin C because of possible severe side effects in the bladder.