© 2008 THE AUTHORS 704 JOURNAL COMPILATION © 2 0 0 8 B J U I N T E R N A T I O N A L | 1 0 2 , 7 0 4 – 7 0 6 | doi:10.1111/j.1464-410X.2008.07740.x 2008 The Authors; Journal compilation 2008 BJU International Original Article BLADDER BOTULINUM TOXIN A INJECTION CHUANG et al. Bladder botulinum toxin A injection can benefit patients with radiation and chemical cystitis Yao-Chi Chuang, Dae Kyung Kim*, Po-Hui Chiang and Michael B. Chancellor † Department of Urology, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Chang Gung University College of Medicine, Taiwan, *Department of Urology, Eulji University School of Medicine, Daejeon, Korea, and † Department of Urology, William Beaumont Hospital, Royal Oak, MI, USA Accepted for publication 31 January 2008 sedation or local anaesthesia, BoNT-A was injected through a cystoscope into 20 sites submucosally in the trigone and floor of the bladder. RESULTS There were no side-effects or retention after BoNT-A injection. In five of the six patients with radiation cystitis there was a moderate to significant improvement; the mean ( SD) bladder capacity increased from 105 (25) mL to 250 (35) mL and the urinary frequency decreased from 14 (2) to 11 (1) episodes per day. In the two patients with BCG cystitis both reported significant symptomatic improvement; the mean (SD) bladder capacity increased from 110 (23) to 230 (23) mL, the urinary frequency decreased from 16 (1) to 12 (1) episodes per day, and using a 10-point visual analogue pain scoring system, the perceived pain score decreased from 8 to 2. Microscopically, the bladder tissue at 1 month after BCG injection showed marked acute and chronic inflammation with eosinophilic infiltration and focal granulomatous formation. At 2 months after BoNT-A injection, there was only a mild degree of chronic inflammation with few eosinophils. CONCLUSION These preliminary results suggest that BoNT- A injected into the bladder is a promising treatment for patients with refractory radiation and BCG cystitis. KEYWORDS botulinum toxin, radiation cystitis, chemical cystitis Study Type – Therapy (case series) Level of Evidence 4 OBJECTIVE To investigate the potential utility of botulinum toxin A (BoNT-A) bladder injections in patients with radiation cystitis and bacillus Calmette-Guérin (BCG)-induced chemical cystitis. PATIENTS AND METHODS In all, six patients with refractory radiation cystitis were treated with 200 U bladder BoNT-A injections and two patients with refractory cystitis after intravesical BCG therapy were treated with 100 U bladder BoNT-A injections. All the patients were refractory to anticholinergic agents. Under INTRODUCTION Radiotherapy is inevitably associated with normal tissue side-effects. Pelvic radiotherapy is not infrequently complicated with radiation cystitis, which is characterized by dysuria and increased urinary frequency [1,2]. Similarly, intravesical BCG therapy for superficial bladder cancer often compromises bladder storage function [3,4]. Several different treatments have been proposed for severe cystitis, such as antimuscarinic agents, empirical antibiotic therapy, or NSAIDs. Nevertheless, the therapeutic effects are limited for these patients [4]. Botulinum toxin A (BoNT-A) was originally known to block acetylcholine release at neuromuscular junctions and have therapeutic effects on muscular hypercontraction [5,6]. The utility of BoNT-A, initially used in treating urological disorders including hyper-reflexic bladder and detrusor-sphincter dyssynergia due to spinal cord injury [7], has expanded to the treatment of patients with multiple sclerosis and non-neurogenic voiding and storage disorders [8,9]. Recent research has shown that BoNT-A blocks exocytosis of neurotransmitters including acetylcholine, sensory neuropeptides and inhibits transient receptor potential vanilloid subfamily 1 and P2X 3 receptors [10–12]. BoNT-A may also inhibit cyclooxygenase-2 (COX-2) expression and suppress inflammatory reactions [13]. Persistent voiding symptoms after radiation and intravesical instillation of BCG can be difficult to manage. In the present study, our aim was to assess whether BoNT-A was safe, well tolerated and improved the quality of life in patients with radiation and chemical cystitis. PATIENTS AND METHODS We conducted a retrospective review of eight patients, with a mean (SD) aged of 67.8 (3.1) years, who had moderate to severe storage symptoms, i.e. frequency, urgency, and/or bladder pain, and who had failed conventional therapy for at least 2 months, and then had undergone bladder BoNT-A injections. BoNT-A bladder injections were performed by injecting 100–200 U of BoNT-A diluted in 10–20 mL sterile saline into the bladder wall with a cystoscopic injection needle. Targeted sites included the posterior and lateral wall of the bladder. Care was taken to raise a 0.5–1.0 mL submucosal bleb with each injection, facilitating visualization of the targeted site, avoiding the risks of perforation, damage to surrounding structures, and wastage of toxin. BJUI BJU INTERNATIONAL