Tadashi Hiramatsu

Effect of sex hormones on development of urinary bladder tumours in rats induced by N-butyl-N-(4-hydroxybutyl) nitrosamine

SummaryMale and female Wistar strain rats were given 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in their drinking water for 6 weeks and then water without BBN for 18 weeks. Diethylstilboestrol and testosterone were implanted subcutaneously into both intact and gonadectomised animals before or after treatment with BBN to evaluate their effects on the development of bladder tumours. Diethylstilboestrol reduced the incidence of bladder tumours significantly in male rats. The incidence was higher in female rats after spaying and administration of testosterone after BBN treatment, than in the intact female.-These results suggest that diethylstilboestrol inhibits carcinogenesis of the urinary bladder induced by BBN and growth of bladder tumours induced by BBN, in male rats. On the other hand, testosterone seems to stimulate the growth of bladder tumours induced by BBN in female rats.

Prophylactic treatment for superficial bladder cancer following transurethral resection.

SummaryA total of 130 primary cases with superficial bladder cancer were entered in the prospective randomized group study. The prophylactic treatments compared consisted in intravesical instillation of adriamycin (20 mg/40 ml or 30 mg/30 ml), mitomycin C (20 mg/40 ml) or thio-TEPA (30 mg/30 ml), and noninstillation treatments with etretinate or tegafur; control patients were also studied. All agents were administered for 2 years. Recurrences were significantly suppressed in the instillation groups compared with control and non-instillation groups. Significant suppression of recurrence was observed in stage 1 or grade 2 disease treated with prophylactic instillation administered over the first 24 months of a 48-month observation period. These results may indicate the clinical usefulness of prophylactic instillation, but the long-term effect of intravesical instillation is still uncertain. A long-term follow-up study is therefore necessary.

Effects of foreign bodies on development of urinary bladder tumors in rats treated with N-butyl-N-(4-hydroxybutyl) nitrosamine

SummaryThe effects of chronic mechanical stimulation induced by glass balls or paraffin balls on precursor lesions of the urinary bladder of male Wistar strain rats induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in the drinking water were studied.When foreign bodies were present in the bladder, proliferative lesions of the urinary bladder epithelium were found even without administration of carcinogen. When the foreign bodies were implanted into the urinary bladder and then rats were given BBN in the drinking water for the first 4 weeks of the experimental period, a high incidence of tumors of the urinary bladder was observed. The incidence of tumors induced by BBN was increased by the presence of glass balls or paraffin balls in the urinary bladder.These results clearly show that foreign bodies in the urinary bladder have a significant effect in promoting carcinogenesis of the urinary bladder in rats.

Prospective randomized study of prophylaxis of superficial bladder cancer with epirubicin: the role of a central pathology laboratory

The preliminary results of a multi-institutional prospective randomized study of the prophylaxis of superficial bladder cancer using epirubicin (protocol NUORG SBT-003) are reported. The subjects were 129 patients with untreated superficial bladder cancer (≦T1b, ≦G2) who were randomized into 2 groups: a transurethral resection (TUR)-alone group (63 patients) and a TUR+intravesical epirubicin (20 mg/40 ml, 30 times/2 years) group (66 patients). The nonrecurrence rate observed in the epirubicin group was significantly higher than that seen in the control group. To unify the pathological diagnosis, a central pathology laboratory (CPL) was set up for extramural review. The correspondence of the pathological diagnosis of TUR-Bt specimens between the CPL and the local pathology laboratory (LPL) was 70.5% in grading and 51.9% in staging. There was a tendency for overdiagnosis by the LPL for both the grade and the stage of tumors. However, differing interpretations by pathologists seem to exert little influence on the nonrecurrence rate at interim analysis. Further observation will be necessary to clarify the prophylactic efficacy of low-dose, long-term periodic intravesical epirubicin instillation and the influence of the disagreement in pathological findings between the CPL and the LPL on the analysis of the results.