Inhibition of implantation of murine bladder tumor by thiotepa in cauterized bladder

Abstract

This study was designed to determine the role of immediate intravesical instillation of single dose thiotepa post transurethral resection of bladder tumor in the prevention of recurrence by tumor implantation, using murine bladder tumor line 2 and 201 C3H/He mice. Previous studies have suggested implantation may take place as early as the first hour and reach its maximum in 24 hours after resection of bladder tumor. An in vitro dose response curve of MBT2 to thiotepa was established by treatment with various concentrations of thiotepa of 0.00, 0.01, 0.21, 0.44, and 1.91 mg./ml. In a group of 201 mice, the bladder was catheterized with a 24G angiocatheter, and a fine copper wire was inserted through the lumen. The bladder was cauterized by touching the wire with a Bovie coagulator for four seconds at the lowest setting. All bladders were instilled with 1 x 10(6) cells of murine bladder tumor line 2, followed by instillation of 1.91 mg./ml. of thiotepa with various time delays per treatment group. The bladder implantation rates were 30.4% (17/56), 3.4% (2/59), 6.5% (2/31) and 26.9% (7/26) in the control, immediate, one-hour delay and 24-hour delay groups, respectively. The urethral implantation rates were 21.4% (12/56), 0% (0/59), 6.5% (2/31) and 0% (2/26), respectively. The overall implantation rates (bladder, urethra, or both) were 42.9% (24/56), 3.4% (2/59), 6.5% (2/31) and 25.9% (7/27), respectively. Implantation rates were significantly higher in the control and 24-hour delay groups than in the immediate and one-hour instillation groups (p less than 0.05, Fisher Exact Test). We conclude from this animal model that intravesical instillation of single dose thiotepa, to be effective, should be initiated within the first hour after tumor resection, since it dramatically decreased the incidence of bladder and urethral implantation.