Evidence of Nonuniformity in Urothelium Barrier Function between the Upper Urinary Tract and Bladder

Abstract

To our knowledge we report for the first time that the upper urinary tract and bladder show differing permeability to a single drug. Ex vivo porcine ureter is significantly more permeable to mitomycin C than bladder urothelium and consequently higher mitomycin C tissue concentrations can be achieved after topical application. Data in this study correlate with the theory that mammalian upper tract urothelium represents a different cell lineage than that of the bladder and it is innately more permeable to mitomycin C.

Intravesical radiofrequency induced hyperthermia enhances mitomycin C accumulation in tumour tissue

“…The tissue MMC concentrations found in our study are substantially lower than values published by others [13,14,24], which probably is methodology derived. In two pharmacokinetic studies, MMC concentrations in normal human bladder tissue after cold MMC instillation pre-cystectomy were on average 15-40 times higher [13,24].…”

“…The bladder urothelium is a highly impermeable barrier to luminal molecules, also when compared to pelvic or ureteral urothelium, thus protecting underlying tissue from excreted fluid and molecules [14]. Our results suggest that RF-CHT N/A 41,6 (41.0-41.8, n ¼ 5) a n < 5 due to incomplete documentation of this characteristic.…”

“…This is most likely the consequence of impaired cell-cell contact, leading to enhanced MMC accumulation. It has been well established that malignant cells lose their original functional properties such as the urothelial barrier function, and cell-cell contact may be impaired as they dedifferentiate [14,[16][17][18][19].…”

“…Studies with cold MMC instillations show six-fold higher MMC concentrations in the urothelium and lamina propria interface, and threefold higher MMC concentrations in the lamina propria compared to the muscularis layer [13,14]. However, how tumour or normal tissue drug concentrations relate after cold and warm intravesical application of MMC is unknown.…”