Shoichi Tabata

Long-term prophylactic effects of intravesical instillation of thiotepa and oral administration of UFT on the recurrence of superficial bladder cancer after transurethral resection

AbstractBackground. We examined the long-term effects of two chemotherapeutic agents, thiotepa and UFT, a 4 : 1 mixture of uracil and tegafur (a 5-fluorouracil pro-drug), in preventing postoperative recurrence of superficial bladder cancer. Methods. The subjects of the study were 153 patients with newly diagnosed superficial bladder cancer (≦ grade 2, ≦ pT1b) who underwent transurethral resection of bladder tumors (TURbt) between November 1986 and March 1990. The patients were randomized into three groups, group 1 (intravesical instillation of thiotepa), group 2 (oral administration of UFT), and group 3 (no treatment). The initial treatment was maintained until the third recurrence or disease progression. The patients were observed until February 1997 and the findings analyzed statistically. Results. The non-recurrence rate during the 5-year period after TURbt was 85.2% in group 1, 40.3% in group 2, and 53.2% in group 3, with the rate in group 1 significantly higher than that in groups 2 and 3. Analysis of the non-recurrence rate in relation to cancer grade or stage showed that patients with grade 2, stage pT1 tumors in group 1 had a significantly higher non-recurrence rate than patients with grade 2, pT1 in tumors groups 2 and 3. Multivariate analysis by Coxs proportional hazards regression model confirmed that prophylactic treatment was the most important factor affecting the non-recurrence rate. Conclusion. Intravesical thiotepa instillation after TURbt was useful to prevent the recurrence of bladder cancer in patients with grade 2 or pT1 tumor in a 5-year period.

A histopathological mapping study of the urinary bladder tumors induced byN-butyl-N-(4-hydroxybutyl)nitrosamine in dogs

Bladder tumors were induced byN-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in five Beagles and four mongrel dogs. The tumors were observed for long periods and the tumor progression was traced using histopathological mapping. The results indicated (1) that low-dose BBN over a long period induced multiple low-grade (G1-2) and low-stage (pTa-1) papillary tumors, resembling superficial bladder cancer in humans; (2) that high-dose BBN over a short period induced high-grade (G2-3) and high-stage (pT3b) nonpapillary tumors and carcinoma in situ (CIS) resembling invasive cancer and CIS in humans; (3) that beagle dogs required longer periods and higher total doses of BBN as compared with mongrel dogs; (4) that the tumors induced by low-dose BBN in beagles were observed without BBN as long as the animals lived, and neither increasing numbers of tumors nor malignant features such as deep infiltration and metastasis was observed; and (5) that low-dose BBN seems to induce mild dysplasia, which is followed by Brunns nest-like proliferation in the lamina propria and nodular change, eventually leading to the development of papillary noninvasive transitional cell carcinoma (TCC); and that high-dose BBN seems to induce severe dysplasia which leads to CIS and nonpapillary invasive TCC. These results may contribute to clarifying the natural history of human bladder cancer.