MP20-17 INTRAVESICAL LIPOSOMAL TACROLIMUS PROTECTS AGAINST RADIATION CYSTITIS INDUCED BY 3-BEAM TARGETED BLADDER RADIATION (2015)

You have accessJournal of UrologyInfections/Inflammation of the Genitourinary Tract: Kidney & Bladder II1 Apr 2015MP20-17 INTRAVESICAL LIPOSOMAL TACROLIMUS PROTECTS AGAINST RADIATION CYSTITIS INDUCED BY 3-BEAM TARGETED BLADDER RADIATION Bharathi Raja Rajaganapathy, Joseph Janicki, Peter Levanovich, Pradeep Tyagi, Jason Hafron, Michael Chancellor, Sarah Krueger, and Brian Marples Bharathi Raja RajaganapathyBharathi Raja Rajaganapathy More articles by this author , Joseph JanickiJoseph Janicki More articles by this author , Peter LevanovichPeter Levanovich More articles by this author , Pradeep TyagiPradeep Tyagi More articles by this author , Jason HafronJason Hafron More articles by this author , Michael ChancellorMichael Chancellor More articles by this author , Sarah KruegerSarah Krueger More articles by this author , and Brian MarplesBrian Marples More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.989AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Radiation cystitis (RC), a rare but serious complication with no effective pharmacotherapy, can occur as a result of radiation therapy for pelvic malignancies. Small Animal Radiation Research Platform (SARRP) was used for targeted irradiation of rat bladder. Use of the platform mimics clinical settings and permits quantitation of the radiation dosages that lead to RC. Changes in rat micturition patterns were used as an outcome measure for radiation dose selection in subsequent studies involving the evaluation of therapeutic potential of tacrolimus encapsulated liposomes (LP-10). METHODS In phase I, 16 adult female Sprague-Dawley rats were split into 4 groups and their micturition patterns were analyzed before and after irradition with 20, 30, and 40 Gy's using the 3-beam SARRP. Histological analysis was performed for the clinical symptoms of RC. In phase II, irradiated rats were randomly assigned to receive a single instillation of either saline or LP-10. Voiding studies were performed for 2 weeks after treatment. RESULTS The dose of 40 Gy induced statistically significant reductions in inter-micturition intervals (IMI) compared to those recorded at lower radiation doses. Histological analysis of the bladder irradiated at 40 Gy indicated degenerative type epithelial changes, urothelial swelling, and ulceration with evidence of pseudocarcinomatous epithelial hyperplasia (red arrow). 40 Gy was therefore chosen for phase II efficacy studies. There was no measurable change in total voided urine volume after irradiation or after instillation of LP-10 or saline. LP-10 treatment significantly increased the post-irradiation IMI values by approximately 30 minutes (p < 0.000001) back to baseline levels. The saline treatment group did not show a statistically significant change in the IMI. CONCLUSIONS 3-beam SAARP is an effective method to induce RC while mimicking clinical radiation therapy for pelvic cancer. The RC rat model demonstrated a dose-dependent decrease in inter-micturition intervals without inducing acute skin or gastrointestinal damage. This study demonstrated that liposomal formulation of tacrolimus (LP-10) may be a promising new intravesical therapy for radiation cystitis. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e230 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Bharathi Raja Rajaganapathy More articles by this author Joseph Janicki More articles by this author Peter Levanovich More articles by this author Pradeep Tyagi More articles by this author Jason Hafron More articles by this author Michael Chancellor More articles by this author Sarah Krueger More articles by this author Brian Marples More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...