Mark K. Plante

Safety and feasibility of the prostatic urethral lift: a novel, minimally invasive treatment for lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH).

Study Type – Therapy (case series) 
Level of Evidence 4

Ablation of canine prostate using transurethral intraprostatic absolute ethanol injection

OBJECTIVES Despite extensive research involving numerous treatments for benign prostatic hyperplasia (BPH), the ideal modality has yet to be discovered. This study evaluated chemoablation of the prostate using transurethral intraprostatic absolute ethanol injection (AEI) in an in vivo canine model. METHODS Eight mongrel dogs, 7 to 10 years old, underwent transurethral intraprostatic AEI with various ethanol volumes (10 to 26 mL/animal, mean 19.9). Injection was performed using a 20-gauge, passive deflection, hollow-core needle, introduced cystoscopically by way of a perineal urethrotomy. Oral antibiotics were administered perioperatively. Blood alcohol levels were determined. The canines were kept alive for 1 hour (n = 1), 7 days (n = 2), and 21 days (n = 5) after the treatment. The dogs were observed twice daily for a minimum of 30 minutes to determine continence. At least one spontaneous voiding was recorded at each observation. Before the dogs were sacrificed, the prostate and surrounding tissues were harvested, with gross and microscopic examination performed by a single pathologist. RESULTS Seven and 21 days after AEI, the prostates demonstrated necrosis and cavity formation. Deep injection resulted in cavity formation in a subcapsular location. Superficial injection resulted in cavity formation that was confluent with the urethra and resulted in a widened urethral lumen. No complications directly related to AEI were seen, and systemic absorption of ethanol was minimal. CONCLUSIONS AEI can effectively ablate prostatic tissue in canines with minimal systemic absorption. No disruption of the prostatic capsule or injury to the bladder urothelium and urethral sphincter was identified. Human studies of intraprostatic AEI for BPH adenomatous tissue chemoablation are ongoing at our institution.

DIFFERENTIAL EXPRESSION OF BLADDER NEUROTROPHIC FACTOR mRNA IN MALE AND FEMALE RATS AFTER BLADDER OUTFLOW OBSTRUCTION

PURPOSE We validated a male rat model of bladder outflow obstruction and compared the expression of bladder neurotrophic factor mRNA in male and female rats 6 weeks after bladder outlet obstruction. MATERIALS AND METHODS We examined the proximal urethra in male Wistar rats. Urethral lumen reducing ligatures were placed in 15 females and 19 males, while 10 male and 10 female controls underwent sham surgery. Awake cystometry was performed 6 weeks after surgery. Ribonuclease protection assay was used to measure changes in bladder neurotrophic factor mRNA expression in the 2 sexes. RESULTS Average bladder capacity in rats with bladder outlet obstruction increased 3-fold in males and 4.4-fold in females compared with controls, while bladder weight increased 2.2 and 4.3-fold, respectively. Filling and threshold pressure increased significantly and nonvoiding bladder contractions were recorded in 100% of female and 80% of male rats with bladder outlet obstruction. An 8-fold increase in bladder brain derived neurotrophic factor mRNA was noted in each sex after obstruction. A 2-fold increase in bladder nerve growth factor mRNA after obstruction was only observed in females. CONCLUSIONS This male rat model of bladder outlet obstruction was created by placing lumen reducing ligatures at the urethrovesical junction. The dramatic increase in bladder brain derived neurotrophic factor mRNA expression and differential expression of nerve growth factor mRNA in male and female rats with bladder outlet obstruction suggest that additional neurotrophic factors may contribute to the lower urinary tract neuroplasticity associated with bladder outlet obstruction and this contribution may be gender dependent.

Intraprostatic ethanol chemoablation via transurethral and transperineal injection

To further assess the safety and feasibility of prostatic chemoablation with ethanol and to address previous concerns associated with transperineal injection using a canine model.

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.

Injectables in the prostate.

Purpose of review Benign prostatic hyperplasia with associated symptoms and morbidity is increasingly common among aging men. Medical treatment of lower urinary tract symptoms is the mainstay of therapy with progressive disease requiring more invasive intervention. Transurethral resection of the prostate remains a widely applied gold standard therapy. Numerous minimally invasive surgical therapy options have arisen and subsequently faded over recent years. Those remaining in use are largely positioned between pharmacological treatment and transurethral resection of the prostate. Intraprostatic injection therapy, the oldest minimally invasive surgical therapy, has been investigated for over 100 years with renewed interest recently. This review will provide some history of intraprostatic injection for benign prostatic hyperplasia including the most recent reports using transperineal, transrectal and transurethral routes with different injectables. Recent findings For benign prostatic hyperplasia, transperineal and transurethral injection routes have received the most systematic evaluation. Intraprostatic injection of botulinum toxin type A has received much recent attention with regards to mechanism of action and efficacy. Anhydrous ethanol remains the most extensively studied injectable to date. Summary Injection therapy remains a very promising minimally invasive surgical therapy for benign prostatic hyperplasia with increased attention from the urologic community in recent years. Further experience both with systematic laboratory and clinical trials investigation will be necessary before widespread clinical adoption.

WATER: A Double-Blind, Randomized, Controlled Trial of Aquablation® vs Transurethral Resection of the Prostate in Benign Prostatic Hyperplasia

Purpose: We compared the safety and efficacy of Aquablation and transurethral prostate resection for the treatment of lower urinary tract symptoms related to benign prostatic hyperplasia. Materials and Methods: In a double‐blind, multicenter, prospective, randomized, controlled trial 181 patients with moderate to severe lower urinary tract symptoms related to benign prostatic hyperplasia underwent transurethral prostate resection or Aquablation. The primary efficacy end point was the reduction in International Prostate Symptom Score at 6 months. The primary safety end point was the development of Clavien‐Dindo persistent grade 1, or 2 or higher operative complications. Results: Mean total operative time was similar for Aquablation and transurethral prostate resection (33 vs 36 minutes, p = 0.2752) but resection time was lower for Aquablation (4 vs 27 minutes, p <0.0001). At month 6 patients treated with Aquablation and transurethral prostate resection experienced large I‐PSS improvements. The prespecified study noninferiority hypothesis was satisfied (p <0.0001). Of the patients who underwent Aquablation and transurethral prostate resection 26% and 42%, respectively, experienced a primary safety end point, which met the study primary noninferiority safety hypothesis and subsequently demonstrated superiority (p = 0.0149). Among sexually active men the rate of anejaculation was lower in those treated with Aquablation (10% vs 36%, p = 0.0003). Conclusions: Surgical prostate resection using Aquablation showed noninferior symptom relief compared to transurethral prostate resection but with a lower risk of sexual dysfunction. Larger prostates (50 to 80 ml) demonstrated a more pronounced superior safety and efficacy benefit. Longer term followup would help assess the clinical value of Aquablation.

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.

Diffusion properties of transurethral intraprostatic injection

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.

Comparison of Intraprostatic Ethanol Diffusion Using a Microporous Hollow Fiber Catheter Versus a Standard Needle

PURPOSE Transurethral intraprostatic ethanol chemoablation of the prostate has shown promising preliminary clinical results for benign prostatic hyperplasia with some variability in clinical outcome. This is likely due to the uneven prostate diffusion caused by varying resistance of the tissue type in which the tip of the needle is embedded. We examined whether the distribution of the injectable in the canine prostate could be improved using a microporous hollow fiber catheter (Twin Star Medical, Minneapolis, Minnesota). MATERIALS AND METHODS The prostate was exposed in 9 mongrel dogs. A single injection of 98% ethanol was delivered in each lobe using a microporous hollow fiber catheter and a standard needle. Prostates were harvested and fixed in 10% formalin. After injection 2.5 mm step sections were obtained and scanned. The ethanol induced tissue lesions were traced on hematoxylin and eosin sections. Three-dimensional reconstructions were created and the volume of each prostate lesion was calculated using stereology. RESULTS Ethanol induced tissue changes were seen bilaterally in 8 of 9 ethanol injected prostates. In all cases the lesion created by microporous hollow fiber catheter injection was larger than that in the contralateral lobe injected with the control needle. When data were pooled, the hollow fiber catheter injection produced significantly greater tissue changes than the control needle injection (p = 0.03). CONCLUSIONS Improved distribution and absent backflow were seen when using the microporous hollow fiber catheter, supporting its potential as a new method to treat prostate disease.