Kiyoo Koseki

Mutual neoplastic promotion by instillation of mitomycin C and cauterization on rat bladder urothelium.

The authors studied the effect of bladder instillation of mitomycin C (MMC), a potential carcinogen, on the duration and severity of the hyperplasia induced by transurethral fulguration. This experimental system may simulate closely the intravesical chemoprophylaxis of MMC after transurethral resection of bladder cancer. Physiologic saline or MMC was instilled into the rat bladder once on the day of, or 3 or 7 days after cauterization. In all groups instilled with physiologic saline the changes were reversed by day 14. On the other hand, five of nine MMC‐instilled rats developed papillary lesions, and three of these had mild dysplastic epithelium on day 84. Under the scanning electron microscope, the animals of these groups showed pleomorphic microvilli on the luminal surface of the regenerative cells on days 10 and 14 after cauterization. These results may indicate the mutual neoplastic promotion by instillation of MMC and cauterization to a certain extent.

Species differences in regenerative hyperplasia of bladder urothelium after transurethral cauterization

SummaryThe early histological changes in bladder urothelium following transurethral cauterization were sequentially studied in female rats, mice, hamsters and guinea pigs. The changes differed markedly between species: papillary hyperplasia or papilloma in the rats and simple hyperplasia in the mice, hamsters and guinea pigs. The regenerative response to the fulgurative ulcer within a given species was similar to the early response previously observed by others following administration of known bladder carcinogens. This suggests that there may be a regulatory mechanism in the urothelium which is common to urothelial proliferations induced by both carcinogenic and non-carcinogenic stimulations, though differing between animal species.

THE ROLE OF TRANSURETHRAL CAUTERIZATION AND INSTILLATION OF MITOMYCIN-C ON CARCINOGENESIS OF URINARY BLADDER

THE ROLE OF TRANSURETHRAL CAUTERIZATION AND INSTILLATION OF MITOMYCIN-C ON CARCINOGENESIS OF URINARY BLADDER Kiyoo Koseki Department of Urology, Faculty of Medicine, The University of Tokyo (Director: Prof. T. Niijima) Electro-resection of the tumors and prophylactic intravesical chemotherapy are usually performed on patients with superficial bladder tumors. The effects of these transurethral manipulations on the urinary bladder urothelium were studied using rat experimental model systems. Transurethral cauterization induced nodular or papillary hyperplasia of the rat bladder urothelium fed on a normal diet. These lesions became normal urothelium by day 14, whereas intravesically instilled Mitomycin-C (MMC) markedly prolonged these histological changes. Then, transurethral catheterization and cauterization as well as instillation of MMC were performed on the rat bladder urothelium which had been exposed to a carcinogenic initiation by ingestion of 0.05% N-butyl-N(hydroxybutyl) nitrosamine (BBN) for 4 weeks, since this experimental model was thought to simulate well the transurethral manipulations and MMC instillation on the bladder urothelium of patients with superficial bladder tumors. Repeated transurethral catheterization or cauterization showed some roles in the promotion and invasive development of bladder tumors, whereas single manipulation did not show any significant influences on the bladder carcinogenesis in this experimental model systems. Single instillation of MMC did not give any influence in this experimental condition either. It is too eary to adapt these experimental results to human bladder cancer. However, it is important to make an intimate observation on patients with superficial bladder tumors in regard to tumor development and invasiveness when a long term and frequent intravesical chemotherapy is performed.