MP26-20 INTRAVESICAL INSTILLATION OF LIPOSOMAL-TACROLIMUS (LP-10) IS AN EFFECTIVE TREATMENT FOR CHRONIC RADIATION CYSTITIS (2016)

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder II1 Apr 2016MP26-20 INTRAVESICAL INSTILLATION OF LIPOSOMAL-TACROLIMUS (LP-10) IS AN EFFECTIVE TREATMENT FOR CHRONIC RADIATION CYSTITIS Bernadette Zwaans, Sarah Bartolone, Michael Chancellor, Peter Levanovich, Sarah Krueger, Brain Marples, and Laura Lamb Bernadette ZwaansBernadette Zwaans More articles by this author , Sarah BartoloneSarah Bartolone More articles by this author , Michael ChancellorMichael Chancellor More articles by this author , Peter LevanovichPeter Levanovich More articles by this author , Sarah KruegerSarah Krueger More articles by this author , Brain MarplesBrain Marples More articles by this author , and Laura LambLaura Lamb More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2957AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Radiation cystitis (RC) is a severe inflammatory condition of the bladder resulting from radiation therapy (RT) to the pelvic area. Current treatment options are inadequate due to poor treatment response and high recurrence rates. In a recent study, we demonstrated that intravesical instillation of the tacrolimus delivered in liposomal formulation in an acute rat RC model improved bladder function. Furthermore, in a compassionate use case study, the use of tacrolimus proved to be effective in treating a severe case of radiation-induced hemorrhagic cystitis. The goal of this study was to develop a chronic mouse RC model and determine the effect of intravesical Liposomal-Tacrolimus. METHODS 40 HCN3 mice were included in the study, of which 20 received a single dose of 20Gy radiation delivered specifically to the whole bladder using a Small Animal Radiation Research Platform. Weekly micturition patterns were measured and mice were tested for the development of hematuria. After 20 weeks, the bladders were instilled with saline, liposomes or liposomal-tacrolimus (LP-10, Lipella Pharmaceuticals). Mice were sacrificed 25 weeks after study initiation and damage to the bladder was analyzed extensively through histology. RESULTS Bladder irradiation was well tolerated as no signs of skin irritation or weight loss were detected up to 12 weeks post RT. By the end of the study, mild hematuria, weight loss and reduced micturition frequency was only observed in mice previously instilled with saline. No changes in overall health or micturition pattern were observed in the other treatment groups. Intravesical instillation of tacrolimus did not alter white blood cell count 24 and 72 hours post instillation. Bladder radiation resulted in collagen deposition, immune infiltration, damaged blood vessels, thinning of the urothelial wall and edema. Treatment with liposomal-tacrolimus significantly improved radiation-induced damage without side effect. CONCLUSIONS We have developed a chronic mouse radiation cystitis model that closely mimics the human condition. Furthermore, we demonstrate that intravesical instillation of liposomal formulated tacrolimus prevents adverse systemic effects and is proving to be a promising treatment for patients suffering from radiation cystitis. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e361 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Bernadette Zwaans More articles by this author Sarah Bartolone More articles by this author Michael Chancellor More articles by this author Peter Levanovich More articles by this author Sarah Krueger More articles by this author Brain Marples More articles by this author Laura Lamb More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...