Replacement of intestinal mucosa with urothelium in rat augmented bladders using intravesical photodynamic therapy with 5-aminolaevulinic acid.
OBJECTIVE
We evaluated the efficacy of intravesical aminolevulinic acid (delta-aminolevulinic acid hydrochloride) (Frontier Scientific, Logan, Utah) and photodynamic therapy for the removal of small intestinal mucosa in augmented bladders in a rat model.


METHODS
Enterocystoplasty was performed in 70 female rats using a patch of terminal ileum. A total of 28 were used to determine the pharmacokinetics (0.3, 0.6 and 0.9 M) and dwell time (30, 60 and 90 minutes) of intravesically administered aminolevulinic acid to optimize intestinal mucosal absorption and minimize bladder mucosal absorption. The remaining augmented rats were treated with intravesical photodynamic therapy at light doses of 75, 100 and 125 J. Ileal and bladder tissues were evaluated by light microscopy. Cystometric studies to evaluate bladder volume were measured before and after photodynamic therapy.


RESULTS
The concentration of 0.3 M aminolevulinic acid with a dwell time of 30 minutes resulted in an average +/- SE bowel-to-bladder concentration of 2,156 +/- 269/749 +/- 62 ng/gm (ratio 2.9:1). After photodynamic therapy histology revealed uniform ablation and replacement of the intestinal mucosa with urothelium and minimal damage to the bladder wall at all light doses. Bladder cystometry revealed no significant change in bladder capacity after photodynamic therapy.


CONCLUSIONS
In the rat model intravesical aminolevulinic acid and photodynamic therapy resulted in the replacement of intestinal mucosa with urothelium, leaving the underlying muscular layer intact. This could potentially be a viable option for patients with a preexisting bladder augment.
Baig
Mirza
M
Department of Urology, University of Toledo Health Sciences Campus, Toledo, Ohio 43614, USA. mbaig@meduohio.edu
Miocinovic
Ranko
R
Keck
Rick W
RW
Fynes
Evan M
EM
Strobel
Stephen L
SL
Kropp
Kenneth A
KA
Selman
Steven H
SH
D000283:Administration, Intravesical; D000622:Aminolevulinic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D005260:Female; D007082:Ileum / Q000166:cytology / Q000637:transplantation; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000637:transplantation; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats; D011916:Rats, Inbred F344; D001743:Urinary Bladder / Q000166:cytology / Q000601:surgery*; D019459:Urothelium / Q000254:growth & development*
D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid