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      Injection therapy for prostatic disease: A renaissance concept

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          Abstract

          Purpose:

          Initially conceived as an intervention for prostatic infection, injection therapy has been used to alleviate urinary retention, and is now primarily investigated for the treatment of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). For over a century, intraprostatic injection has been used as a minimally invasive surgical therapy (MIST), and is on the verge of a rebirth. This review will familiarize the reader with the origins and history of intraprostatic injection, and its evolution using transperineal, transrectal and transurethral routes with multiple injectants.

          Materials and Methods:

          A MEDLINE review of the literature on intraprostatic injections published between 1966 and 2007 was performed, augmented with articles and documents dating back to 1832.

          Results:

          Transperineal and transurethral injections have the most systematic evaluation in patients. There are advantages and disadvantages associated with each route. Most injectants consistently produce localized coagulative necrosis and gland volume reduction with varying degrees of LUTS relief. Anhydrous ethanol (AE) is the most extensively studied injected agent to date.

          Conclusions:

          Injection therapy is a promising minimally invasive treatment option for various prostatic conditions and has been examined for over 100 years. Further experience in systematic laboratory research and completion of currently ongoing clinical trials is necessary before widespread clinical application.

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          Most cited references 45

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          Botulinum toxin type A improves benign prostatic hyperplasia symptoms in patients with small prostates.

          To expand the clinical use of botulinum toxin A (BTX-A) in treating patients with small prostates and symptomatic benign prostatic hyperplasia (BPH). BTX-A injection into the prostate in patients with voiding dysfunction and large prostates has been reported. Sixteen men with symptomatic BPH, a prostate volume less than 30 cm3, peak flow rate less than 12 mL/s, and with refractory disease after at least 1 month of alpha-blocker treatment received BTX-A 100 U injection into the prostate transperineally under transrectal ultrasound guidance. The clinical effects were evaluated at baseline and after treatment. No significant local or systemic side effects were observed in any of the patients. All patients reported subjective improvement starting at approximately 1 week and achieved a maximal effect after 1 month that was maintained at 3 and 6 months. At 6 to 12 months (mean 10) of follow-up, no patient had symptom recurrence. The mean prostate volume, symptom score, and quality-of-life index were significantly reduced by 13.3% (from 19.6 +/- 1.2 to 17.0 +/- 1.1 cm3), 52.6% (from 18.8 +/- 1.6 to 8.9 +/- 1.9), and 44.7% (from 3.8 +/- 0.3 to 2.1 +/- 0.3), respectively. The maximal flow rate increased significantly by 39.8% (from 7.3 +/- 0.7 to 11.8 +/- 0.8 mL/s). In 2 patients who underwent biopsy 1 month after BTX-A injection, terminal deoxynucleotidyl-mediated deoxyuridine triphosphate nick end labeling staining demonstrated an increase in apoptotic activity, not only in the glandular component, but also in the stromal component of the prostatic tissue. BTX-A injected into the prostate is a promising treatment for patients with small prostates and symptomatic BPH.
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            Novel action of botulinum toxin on the stromal and epithelial components of the prostate gland.

            Intraprostatic injection of BTX-A has demonstrated clinical improvement in men with bladder outlet obstruction. We investigated the mechanisms of action of BTX-A on the prostate. Adult male Sprague-Dawley rats were injected with varying doses of BTX-A into the prostate and the prostates were harvested after 1 or 2 weeks. The effects of BTX-A on prostate histology, and the proliferative and apoptotic indexes were determined using hematoxylin and eosin staining, proliferative cell nuclear antigen staining and TUNEL staining, respectively. Changes in alpha(1A) adrenergic receptor and androgen receptor were evaluated by Western blotting. One week after BTX-A injection generalized prostate atrophy was observed. There was a significant increase in apoptotic cells (12, 16 and 22-fold), and decrease in proliferative cells (38%, 77% and 80%) and alpha(1A) adrenergic receptor (13%, 80% and 81%) for 5, 10 and 20 U, respectively. There was no significant change in androgen receptors. The effects were decreased 2 weeks after BTX-A treatment. BTX-A injection into the prostate alters cellular dynamics by inducing apoptosis, inhibiting proliferation and down-regulating alpha(1A) adrenergic receptors. BTX-A may potentially be the drug that has dual actions on the static and dynamic components of benign prostatic hyperplasia.
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              Intraprostatic injection of botulinum toxin type- A relieves bladder outlet obstruction in human and induces prostate apoptosis in dogs

              Background With the increasing interest with botulinum toxin – A (BTX-A) application in the lower urinary tract, we investigated the BTX-A effects on the canine prostate and also in men with bladder outlet obstruction (BOO) due to benign prostatic hyperplasia (BPH). Methods Transperineal injection into the prostate using transrectal ultrasound (TRUS) was performed throughout the study. Saline with or without 100 U of BTX-A was injected into mongrel dogs prostate. One or 3 months later, the prostate was harvested for morphologic and apoptotic study. In addition, eight BPH patients refractory to α-blockers were treated with ultrasound guided intraprostatic injection of 200 U of BTX-A. Results In the BTX-A treated dogs, atrophy and diffuse apoptosis was observed with H&E stain and TUNEL stain at 1 and 3 months. Clinically, the mean prostate volume, symptom score, and quality of life index were significantly reduced by 18.8%, 73.1%, and 61.5% respectively. Maximal flow rate significantly increased by 72.0%. Conclusion Intraprostatic BTX-A injection induces prostate apotosis in dogs and relieves BOO in humans. It is therefore a promising alternative treatment for refractory BOO due to BPH.
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                Author and article information

                Journal
                Indian J Urol
                IJU
                Indian Journal of Urology : IJU : Journal of the Urological Society of India
                Medknow Publications (India )
                0970-1591
                1998-3824
                Jul-Sep 2008
                : 24
                : 3
                : 329-335
                Affiliations
                Division of Urology, Department of Surgery, University of Vermont, Burlington, Vermont, USA
                Author notes
                For correspondence: Dr. Mark K Plante, University of Vermont College of Medicine, Department of Surgical Research, 89 Beaumont Ave, Given Building, D-319C, Burlington, Vermont 05405, USA. E-mail: mark.plante@ 123456uvm.edu
                Article
                IJU-24-329
                10.4103/0970-1591.42613
                2684358
                19468462
                © Indian Journal of Urology

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Categories
                Review Article

                Urology

                injection, prostatic disease, prostate, benign prostatic hyperplasia

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