Injection therapy for prostatic disease: A renaissance concept.

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.

Diffusion properties of transurethral intraprostatic injection.

OBJECTIVES: To evaluate the location and extent of diffusion that occurs when liquid is injected transurethrally into the prostate gland, by correlating real-time fluoroscopy and gross pathology, and to quantify the variables that influence intraprostatic diffusion during chemoablation of the prostate. MATERIALS AND METHODS: A solution of diatrizoate meglumine (Hypaque, Nycomed, Princeton, NJ) gentamicin and methylene-blue dye (HGM) was injected transurethrally into the prostate in six dogs, using a passive-deflection needle injection system. The intraprostatic diffusion characteristics were evaluated during each injection using real-time C-arm fluoroscopy, and following each injection by gross examination of methylene blue staining within the prostatic tissues. HGM back-flow into the urethra at the time of injection was assessed by measuring gentamicin levels in the collected bladder irrigant after each injection, using a standard dilution formula. RESULTS: There was variability in the intraprostatic diffusion both fluoroscopically and grossly. The needle occasionally assumed a straighter trajectory than its intended curve. Intraprostatic diffusion was detected in 12 of 36 injections (33%). Using standard manipulations of various devices increased the intraprostatic diffusion in these injections to almost 80%. There was less intraprostatic diffusion when the injection resistance was either extremely high or absent. There was no extraprostatic extravasation of HGM beyond the prostatic capsule. CONCLUSION: Current methods of transurethral intraprostatic injection are variable for both the diffusion of HGM solution and in needle deployment. The gross diffusion patterns with the HGM solution were consistent with the diffusion patterns documented in our previous research using absolute ethanol. These and other factors may partly explain the variability of the lesions produced with ethanol injection. Therefore, more research is needed to further elucidate the diffusion characteristics of solutions injected intraprostatically using the transurethral approach.

Minimally invasive therapies for prostatitis.

A plethora of reports describe a number of promising new minimally invasive treatment modalities available to patients with chronic prostatitis. This article reviews these studies, with most evaluating treatments using heat or intraprostatic injection. The results are difficult to compare because of the inconsistencies in study design, modalities of treatment, and outcome measures. Standard criteria for assessing symptom severity in chronic prostatitis recently have been developed and prospective clinical trials are underway to evaluate minimally invasive therapies for this debilitating condition. Until definitive data from these trials are available, minimally invasive therapies most likely will continue to be empirical and not a standard of care.

Prostatic tissue ablation by injection: a literature review.

PURPOSE: Most men 50 to 80 years old will have development of some degree of benign prostatic hyperplasia (BPH). Many who experience lower urinary tract symptoms (LUTS) will be treated medically. However, significant numbers will have more severe and progressive disease requiring surgery. Transurethral resection of the prostate is the current gold standard of treatment for BPH. Minimally invasive therapies for symptomatic BPH emerge and fade continuously. However, intraprostatic injection for BPH has been used for more than 100 years and may be on the verge of a rebirth. The goal of this review is to familiarize the reader with the origins and history of intraprostatic injection, and its evolution using transperineal, transrectal and transurethral routes with multiple injectants. Initially used to treat urinary retention in men with BPH, its primary indication is now for LUTS. MATERIALS AND METHODS: We performed a structured MEDLINE review of the literature on intraprostatic injections from 1966 to 2003, augmented with relevant articles from select journals and documents dating to 1832. RESULTS: In patients with BPH transperineal and transurethral injections have the most systematic evaluation. Most injectants will cause localized prostatic necrosis and gland volume reduction with varying degrees of LUTS relief. Anhydrous ethanol is the most widely studied injectable to date. There are advantages and disadvantages associated with each route of injection. CONCLUSIONS: Examined for more than a century, the potential for using injectables for prostatic tissue ablation remains significant. More systematic laboratory research and clinical trials, currently ongoing, need to be completed.

Increased expression of neuronal nitric oxide synthase in bladder afferent cells in the lumbosacral dorsal root ganglia after chronic bladder outflow obstruction.

Nitric oxide (NO), a neurotransmitter in autonomic reflex pathways, plays a role in functional neuroregulation of the lower urinary tract. Upregulation of the levels of neuronal nitric oxide synthase (nNOS), the enzyme system responsible for NO synthesis, has been documented in the peripheral, spinal and supraspinal segments of the micturition reflex in diseases such as cystitis, bladder/sphincter dyssynergia following spinal cord injury and bladder overactivity after cerebral infarction. These observations suggest that NO might play a role in the development of bladder overactivity. In this study, nNOS-immunoreactivity (IR) was evaluated in bladder afferent and spinal neurons following bladder outflow obstruction (BOO) in male and female rats. Chronic BOO was induced by placing lumen reducing ligatures around the proximal urethra. Six weeks following the obstructive or sham surgery, bladder function was evaluated by awake cystometry. Bladder afferent neurons in L1, L2, L6 and S1 dorsal root ganglia (DRG) were identified by retrograde neuronal labeling with injection of Fast Blue into the bladder smooth muscle. A differential distribution of nNOS-IR was subsequently evaluated in bladder afferent neurons in the DRG and in the associated spinal cord segments. The percentage of bladder afferent neurons expressing nNOS-IR was increased in L6 (1.8-fold in males and 1.9-fold in females) and S1 (2.8-fold in males and 5.3-fold in females) DRG. In contrast, no changes in nNOS-IR in neurons or fiber distribution were observed in any spinal cord segments examined.