One-year outcomes of the ARTISAN-SNM study with the Axonics System for the treatment of urinary urgency incontinence

Aims: Sacral neuromodulation (SNM) is a guideline-recommended treatment for voiding dysfunction including urgency, urge incontinence, and nonobstructive retention as well

Ambulatory and cystometric response following single versus multiple onabotulinumtoxina detrusor injections in a rat model of overactive bladder induced by intravesical acetic acid

Introduction: Intradetrusor onabotulinumtoxinA (BTX) chemo-denervation is an established therapy for appropriately selectedpatients who fail first and second-line treatments for overactive bladder. There has been much variability regarding injectionpatterns and concentration of BTX described in the literatureincluding templates which generally deliver the toxin to the posterior and lateral walls of the bladder. The physiologic effect of different injection patterns deserves further investigation. Methods: Thirty-six adult female rats were divided into six (n = 6) groups. Treatment animals received intradetrusor injection of 7.5 units (in 25 μL saline) BTX to the bladder: intact control (no injection); saline vehicle control (five aliquots); trigone (one aliquot); posterior and lateral walls (three aliquots); whole bladder (five aliquots); unilateral (one aliquot). Animals were acclimated and micturition frequency and volume were assessed using metabolic cages at baseline (day 0, 7) and following injection (day 14, 21, 28). On day 7, animals underwent detrusor injection via midline incision. On day 28, overactive bladder was inducedwith acetic acid bladder instillation (0.25%, 30-minutes). Bladder function was assessed using anesthetized cystometry before and after acid instillation. Results: All but one animal survived until final testing. One rat in the trigone group expired during recovery from anesthesia after injection. Ambulatory urinary frequency and mean voided volume show consistent trends, with stable voided volume demonstrated over timein all groups.Each animal demonstrated a consistent voiding pattern at each of the five metabolic cage time points; however there was wide variability from animal to animal. All controls developed obvious detrusor overactivity when challenged with acetic acid. In contrast, BTX resulted in increased threshold pressure immediately prior to spontaneous micturition and was successful in suppressing detrusor overactivity in treated rats that underwent instillation of acetic acid. Overall bladder contractility was preserved to a greater degree in the unilateral single aliquot injection group compared to the multiple injection treatment groups. Conclusion: With equal total toxin delivery, the various BTX injection patterns did not result in clear physiologic differences in our rat model of overactive bladder. The only exception was that unilateral single aliquot BTX injection appeared to preserve bladder contractility compared to multiple BTX injections. Funding Source: SUFU Foundatio

Ambulatory and cystometric response following single versus multiple onabotulinumtoxina detrusor injections in a rat model of overactive bladder induced by intravesical acetic acid

Introduction: Intradetrusor onabotulinumtoxinA (BTX) chemo-denervation is an established therapy for appropriately selectedpatients who fail first and second-line treatments for overactive bladder. There has been much variability regarding injectionpatterns and concentration of BTX described in the literatureincluding templates which generally deliver the toxin to the posterior and lateral walls of the bladder. The physiologic effect of different injection patterns deserves further investigation. Methods: Thirty-six adult female rats were divided into six (n = 6) groups. Treatment animals received intradetrusor injection of 7.5 units (in 25 μL saline) BTX to the bladder: intact control (no injection); saline vehicle control (five aliquots); trigone (one aliquot); posterior and lateral walls (three aliquots); whole bladder (five aliquots); unilateral (one aliquot). Animals were acclimated and micturition frequency and volume were assessed using metabolic cages at baseline (day 0, 7) and following injection (day 14, 21, 28). On day 7, animals underwent detrusor injection via midline incision. On day 28, overactive bladder was inducedwith acetic acid bladder instillation (0.25%, 30-minutes). Bladder function was assessed using anesthetized cystometry before and after acid instillation. Results: All but one animal survived until final testing. One rat in the trigone group expired during recovery from anesthesia after injection. Ambulatory urinary frequency and mean voided volume show consistent trends, with stable voided volume demonstrated over timein all groups.Each animal demonstrated a consistent voiding pattern at each of the five metabolic cage time points; however there was wide variability from animal to animal. All controls developed obvious detrusor overactivity when challenged with acetic acid. In contrast, BTX resulted in increased threshold pressure immediately prior to spontaneous micturition and was successful in suppressing detrusor overactivity in treated rats that underwent instillation of acetic acid. Overall bladder contractility was preserved to a greater degree in the unilateral single aliquot injection group compared to the multiple injection treatment groups. Conclusion: With equal total toxin delivery, the various BTX injection patterns did not result in clear physiologic differences in our rat model of overactive bladder. The only exception was that unilateral single aliquot BTX injection appeared to preserve bladder contractility compared to multiple BTX injections. Funding Source: SUFU Foundatio

ISOLATED TRIGONE ONABOTULINUMTOXINA INJECTION DOES NOT ADVERSELY CHANGE AMBULATORY VOIDING FUNCTION IN A RAT MODEL OF OVERACTIVE BLADDER

INTRODUCTION AND OBJECTIVES: OnabotulinumtoxinA (BTX) chemodenervation is an established third-line therapy for overactive bladder. The aim of our study was to further characterize the physiologic effect of various BTX injection distributions on ambulatory and cystometric voiding function in conscious awake rats. METHODS: Adult female rats (n=36) were divided into six groups. Treatment animals received injection of 7.5 units BTX (in 25-125 µL saline; 25 µL/aliquot): intact control, saline vehicle control, unilateral BTX, trigone BTX, posterior-lateral BTX, whole bladder BTX. Micturition frequency and volume were assessed using metabolic cages at baseline (day 0, 7) and following injection (day 14, 21, 28). Bladder function was then assessed using anesthetized acetic acid cystometry. RESULTS: There was no overall correlation between rat weight and mean voided volume (r = -0.02, p = 0.81). Small volume voids were significantly associated with increased food intake (r = -0.21, p = 0.006) and greater stool output (r = -0.23, p = 0.003). Mean nocturnal voided volume was similar in control, vehicle, trigone and posterior-lateral groups. The ability to void small volumes was preserved in both the control and treatment groups with the exception of unilateral and whole bladder injection which demonstrated increased minimum voided volumes. On cystometry, mean voided volume was the greatest in the control and trigone groups prior to acetic acid. Increased threshold pressure was noted in both unilateral and whole bladder injection groups. Post void residual was decreased in all groups after acetic acid. The lowest number of voids and longest interval between voids was noted after unilateral and whole bladder BTX injection. Cystometric intercontractile interval correlated with increased nocturnal mean voided volume before (r = 0.33, p = 0.05) and after (r = 0.24, p = 0.17) acetic acid. Cystometric mean voided volume correlated with ambulatory nocturnal voided volume, however was almost 10-fold lower after saline instillation (r = 0.18, p = 0.30), and more closely approximated ambulatory voiding after acetic acid instillation (r = 0.30, p = 0.08). CONCLUSIONS: Unilateral and whole bladder BTX injection resulted in elevated ambulatory nocturnal mean voided volumes, with higher pressure and smaller volume voids noted on cystometry. Trigone and posterior-lateral BTX injection patterns appear to preserve contractility, with threshold and peak contraction pressures similar to control animals

PERFORMANCE ASSESSMENT AND VALIDATION OF AN ENHANCED 12-RAT METABOLIC CAGE EQUIPPED WITH A NOVEL 100-GRAM LOAD CELL SENSOR INTERFACE

Introduction: The metabolic cage is an important noninvasive tool used to assess ambulatory voiding function in conscious rodents. Other standardized assessments of lower urinary tract (LUT) function in the rat include the 2-hour filter paper test and bladder cystometry, however these tests are labor intensive and represent a single point in time.We sought to validate our enhanced metabolic cage with a novel 12-channel load cell sensor interface, which allows for realtime automated assessment of LUT function. Methods: LUT function of female Sprague-Dawley rats were assessed at multiple time points with: A) two-hour filter paper test (n = 35, 129 samples), B) Metabolic cage (n = 35, 129 cage cycles) and C) Anesthetized bladder cystometry (n = 6). Twelve rats were simultaneously housed in metabolic cages (Tecniplast, Model 3701M081) during each cage cycle (18–24 hr). For the first two hours of each cage cycle, voided volume was measured using filter paper. Urine output for each animal was then measured using twelve 100-gramWheatstone bridge load cells connected to three 4-channel bridge amplifier USB transducers (Phidgets Inc., Model 1046) and data recorded continuously at one-second intervals (DSP Robotics, FlowBotics Studio v3.0.8). Anesthetized cystometry was then performed using urethane sedation (1.2 g/kg). Results: Load cell sensor performance was assessed using a micropipette which demonstrated accurate correlation with known droplet weight (sensitivity range 100–3,000 μL), as well as urine droplet weight after passing through both clean and dirty metabolic cages (sensitivity range 200–3,000 μL). The 2-hour filter paper test demonstrated voided urine droplet volumes which significantly correlated (Pearson r = 0.55, p \u3c 0.001, alpha = 0.05) with daytime voided volumes obtained by metabolic cage. Voided volume demonstrated a non-significant (n = 6) positive correlation with cystometric mean voided volume (Pearson r = 0.48, p = 0.33, alpha = 0.05), and was consistently greater in ambulatory conscious rats (mean 1,014 μL, range 577–2,223) compared to anesthetized cystometry (mean 126 μL, range 20–211). Conclusion: Metabolic cage assessment of LUT function correlated with voided volumes using the filter paper test and anesthetized bladder cystometry. Rat bladder function and behavior patterns may be reliably assessed over time with our enhanced metabolic cage, without the need for anesthesia or terminal bladder cystometry. Funding Source: SUFU Foundatio

Transvaginal ultrasound guided trigone and bladder injection: A cadaveric feasibility study for a novel route of intradetrusor chemodenervation

Purpose: OnabotulinumtoxinA (BTX) detrusor chemodenervation is an efficacious third-line treatment for overactive bladder. Despite high clinical efficacy rates for BTX injection, many patients refuse initial or repeat treatment due to the invasiveness of the cystoscopic route of delivery. We assess the feasibility of injecting the trigone and posterior bladder wall via a transvaginal route under ultrasound guidance using a human cadaveric model. Materials and Methods: Eight de-identified anonymous fresh female deceased donor cadaver pelvises were placed in supine split leg position. A transvaginal ultrasound probe guided injections of India ink into the trigone in 3 sites and the posterior wall in 2 sites. Full thickness bladder biopsies were then obtained and histologic analysis was performed to confirm presence of India ink in the detrusor layer. Results: The mean time from day of death was 11.0 days (range, 4.0–23.0 days). Three to five bladder biopsies were obtained per cadaver, for a total of 34 specimens (20 trigone, 14 posterior wall). Histologic analysis revealed presence of India ink within the detrusor layer in 8/8 (100.0%) of cadavers. The surgeon's perception of appropriate targeting under ultrasound guidance was confirmed in 8/8 cadavers (100.0%) involving the bladder trigone, and 7/8 (87.5%) involving the posterior wall. Of injections that were believed to have appropriately targeted the detrusor layer, 22/34 specimens (64.7%) demonstrated the presence of India ink under histologic analysis. Conclusions: Intradetrusor injection of the bladder trigone and posterior wall under transvaginal ultrasound guidance is feasible and has acceptable accuracy