Jeremy Reese

Role of spinal GABAA receptors in pudendal inhibition of nociceptive and nonnociceptive bladder reflexes in cats.

Picrotoxin, an antagonist for γ-aminobutyric acid receptor subtype A (GABAA), was used to investigate the role of GABAA receptors in nociceptive and nonnociceptive reflex bladder activities and pudendal inhibition of these activities in cats under α-chloralose anesthesia. Acetic acid (AA; 0.25%) was used to irritate the bladder and induce nociceptive bladder overactivity, while saline was used to distend the bladder and induce nonnociceptive bladder activity. To modulate the bladder reflex, pudendal nerve stimulation (PNS) was applied at multiple threshold (T) intensities for inducing anal sphincter twitching. AA irritation significantly (P < 0.01) reduced bladder capacity to 34.3 ± 7.1% of the saline control capacity, while PNS at 2T and 4T significantly (P < 0.01) increased AA bladder capacity to 84.0 ± 7.8 and 93.2 ± 15.0%, respectively, of the saline control. Picrotoxin (0.4 mg it) did not change AA bladder capacity but completely removed PNS inhibition of AA-induced bladder overactivity. Picrotoxin (iv) only increased AA bladder capacity at a high dose (0.3 mg/kg) but significantly (P < 0.05) reduced 2T PNS inhibition at low doses (0.01-0.1 mg/kg). During saline cystometry, PNS significantly (P < 0.01) increased bladder capacity to 147.0 ± 7.6% at 2T and 172.7 ± 8.9% at 4T of control capacity, and picrotoxin (0.4 mg it or 0.03-0.3 mg/kg iv) also significantly (P < 0.05) increased bladder capacity. However, picrotoxin treatment did not alter PNS inhibition during saline infusion. These results indicate that spinal GABAA receptors have different roles in controlling nociceptive and nonnociceptive reflex bladder activities and in PNS inhibition of these activities.

Timing and Predictors for Urinary Drainage in Children with Expectantly Managed Grade IV Renal Trauma

PURPOSE We determined which children sustaining blunt grade IV renal trauma are at greatest risk for failing nonoperative management and in what time frame they will likely present. MATERIALS AND METHODS We retrospectively reviewed children presenting with nonvascular grade IV blunt renal trauma between 2003 and 2012. We compared characteristics on computerized tomography, reasons for intervention, type and timing of surgery, length of hospital stay and need for readmission between children undergoing early intervention (less than 72 hours after admission) and those managed conservatively (with any subsequent intervention undertaken more than 72 hours after admission). RESULTS A total of 26 children were identified with nonvascular grade IV blunt renal trauma. Conservative management was attempted in 16 cases (62%). Seven of these patients (44%) required intervention (ureteral stent and/or percutaneous drain placement), with a mean time to intervention of 11 days. Collecting system clot and larger urinoma (1.45 cm in cases with successful and 4.29 cm in those with failed conservative management) significantly predicted failure of conservative management (p<0.05). Presence of dissociated renal fragments (57% vs 11%) and interpolar contrast extravasation (57% vs 0%) were increased in the early intervention group compared to the conservatively managed group (p>0.05), as was rehospitalization (43% vs 0%), mean length of stay (7.9 vs 5.4 days) and transfusion (14% vs 0%, p>0.05). CONCLUSIONS Collecting system hematoma and urinoma size significantly predicted failure of conservative management, with a mean time to intervention of 11 days. Children with failed conservative management had a greater incidence of dissociated renal fragments and interpolar extravasation. Early identification of these patients may decrease hospital readmissions, length of stay and prolonged morbidity.

Effects of Duloxetine and WAY100635 on Pudendal Inhibition of Bladder Overactivity in Cats

This study was aimed at determining the effect of duloxetine (a serotonin-norepinephrine reuptake inhibitor) on pudendal inhibition of bladder overactivity. Cystometrograms were performed on 15 cats under α-chloralose anesthesia by infusing saline and then 0.25% acetic acid (AA) to induce bladder overactivity. To inhibit bladder overactivity, pudendal nerve stimulation (PNS) at 5 Hz was applied to the right pudendal nerve at two and four times the threshold (T) intensity for inducing anal twitch. Duloxetine (0.03–3 mg/kg) was administered intravenously to determine the effect on PNS inhibition. AA irritation significantly (P < 0.01) reduced bladder capacity to 27.9 ± 4.6% of saline control capacity. PNS alone at both 2T and 4T significantly (P < 0.01) inhibited bladder overactivity and increased bladder capacity to 83.6 ± 7.6% and 87.5 ± 7.7% of saline control, respectively. Duloxetine at low doses (0.03–0.3 mg/kg) caused a significant reduction in PNS inhibition without changing bladder capacity. However, at high doses (1–3 mg/kg) duloxetine significantly increased bladder capacity but still failed to enhance PNS inhibition. WAY100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide; a 5-HT1A receptor antagonist, 0.5–1 mg/kg i.v.) reversed the suppressive effect of duloxetine on PNS inhibition and significantly (P < 0.05) increased the inhibitory effect of duloxetine on bladder overactivity but did not enhance the effect of PNS. These results indicate that activation of 5-HT1A autoreceptors on the serotonergic neurons in the raphe nucleus may suppress duloxetine and PNS inhibition, suggesting that the coadministration of a 5-HT1A antagonist drug might be useful in enhancing the efficacy of duloxetine alone and/or the additive effect of PNS-duloxetine combination for the treatment of overactive bladder symptoms.

Role of glycine in nociceptive and non-nociceptive bladder reflexes and pudendal afferent inhibition of these reflexes in cats.

This study examined the role of glycinergic transmission in nociceptive and non‐nociceptive bladder reflexes and in inhibition of these reflexes by pudendal nerve stimulation (PNS).

Role of spinal metabotropic glutamate receptor 5 in pudendal inhibition of the nociceptive bladder reflex in cats

This study examined the role of spinal metabotropic glutamate receptor 5 (mGluR5) in the nociceptive C-fiber afferent-mediated spinal bladder reflex and in the inhibtion of this reflex by pudendal nerve stimulation (PNS). In α-chloralose-anesthetized cats after spinal cord transection at the T9/T10 level, intravesical infusion of 0.25% acetic acid irritated the bladder, activated nociceptive C-fiber afferents, and induced spinal reflex bladder contractions of low amplitude (<50 cmH2O) and short duration (<20 s) at a smaller bladder capacity ∼80% of saline control capacity. PNS significantly (P < 0.01) increased bladder capacity from 85.5 ± 10.1 to 137.3 ± 14.1 or 148.2 ± 11.2% at 2T or 4T stimulation, respectively, where T is the threshold intensity for PNS to induce anal twitch. MTEP {3-[(2-methyl-4-thiazolyl)ethynyl]pyridine; 3 mg/kg iv, a selective mGluR5 antagonist} completely removed the PNS inhibition and significantly (P < 0.05) increased bladder capacity from 71.8 ± 9.9 to 94.0 ± 13.9% of saline control, but it did not change the bladder contraction amplitude. After propranolol (3 mg/kg iv, a β1/β2-adrenergic receptor antagonist) treatment, PNS inhibition remained but MTEP significantly (P < 0.05) reduced the bladder contraction amplitude from 18.6 ± 2.1 to 6.6 ± 1.2 cmH2O and eliminated PNS inhibition. At the end of experiments, hexamethonium (10 mg/kg iv, a ganglionic blocker) significantly (P < 0.05) reduced the bladder contraction amplitude from 20.9 ± 3.2 to 8.1 ± 1.5 cmH2O on average demonstrating that spinal reflexes were responsible for a major component of the contractions. This study shows that spinal mGluR5 plays an important role in the nociceptive C-fiber afferent-mediated spinal bladder reflex and in pudendal inhibition of this spinal reflex.

Safety and Surgical Outcomes of Same-day Anterior Urethroplasty

OBJECTIVE To evaluate the safety and feasibility of same-day anterior urethroplasty at our institution and define predictors of postoperative admission and surgical failure. METHODS We retrospectively reviewed the charts of 118 consecutive anterior urethroplasties performed at a tertiary care center. Data were analyzed to detect predictors of postoperative admission and urethroplasty failure. The 30-day complications and long-term outcomes were compared between same-day and admitted patients. RESULTS Ninety-two patients (78%) were discharged on the day of surgery. A penile stricture location compared with a bulbar stricture location (odds ratio: 13.4, P = .009) and having undergone more than 3 prior endoscopic stricture interventions (odds ratio: 10.2, P = .001) were significantly associated with postoperative admission. Patients with a ventral onlay approach were more likely to be discharged home (P = .03), whereas patients with combined repairs were more likely to be admitted (P = .04). Same-day urethroplasty did not increase 30-day postoperative complications, patient emergency room visits, unplanned clinic visits, or phone calls. Success rates did not differ between same-day (89%) and admitted (79%) cohorts, and no individual stricture characteristic was predictive of urethroplasty failure. CONCLUSION Same-day anterior urethroplasty is safe and feasible and could help increase utilization of urethroplasty for urethral stricture disease.

PD29-06 PREDICTING ENDOSCOPIC TREATMENT SUCCESS FOR POST-PROSTATECTOMY BLADDER NECK CONTRACTURE: LONG-TERM TIME-TO-RECURRENCE ANALYSIS

beam radiotherapy, 38.3% had brachytherapy and 5.8% had combined radiation modalities. The most common complications were urethral stricture/stenosis (88.3%), refractory storage LUTS (88.3%), incontinence (45.8%), erectile dysfunction (60.0%), radiation cystitis (50.8%), acute urinary retention (50.0%) and hematuria (42.5%). Other notable complications included prostate necrosis/abscess (14.2%), pubic osteomyelitis/prostatosymphyseal fistula (3.3%), de novo cancer (5.8%), and rectourethral fistula (0.8%). Patients required a mean of 7.4 4.4 (130) treatments for radiation related complications over the study period and 49.2% of patients required major urologic surgery. Required procedures included urethral dilation/urethrotomy (77.5%), urethral reconstruction (44.2%), incontinence surgery (6.7%), transurethral resection (prostate, bladder, contracture) (43.3%), cystolithopaxy (11.7%) and urinary diversion (6.7%). 13.3% of patients were treated with an indwelling suprapubic catheter. Patients with complications related to combined radiotherapy had more complications (7.0 vs. 5.0; p1⁄40.016) including incontinence (85.7% vs. 44.2%; p1⁄40.04), de novo malignancy (28.6% vs. 4.4%; p1⁄40.05), pubic osteomyelitis (28.6% vs. 1.8%; p1⁄40.02), and tended to require a higher number of procedures (10.1 vs. 7.2; p1⁄40.08). CONCLUSIONS: Lower urinary tract complications related to radiotherapy are very seldom an isolated problem and require a tremendous amount of resources and urologic intervention. Patients with combined radiotherapy complications have a higher number of complications and typically require more interventions.

MP55-04 PERINEPHRIC VERSUS SINUS FAT INVASION IN PT3A TUMORS MANAGED BY PARTIAL NEPHRECTOMY

INTRODUCTION AND OBJECTIVES: We assessed the impact of papillary renal cell carcinoma (RCC) on oncological outcomes after partial nephrectomy compared to clear cell RCC in patients with pathologic T1a RCC. METHODS: After excluding patients with synchronous multiple renal tumors, familial renal cell carcinoma, pathologic T1b or greater disease, and metastatic disease, 759 patients with clear cell and 84 patients with papillary RCC were included for the analysis. We compared the impacts of papillary RCC with clear cell RCC on oncologic outcomes. Median follow-up duration was 67 months. RESULTS: There was no differences in patient and tumor characteristics between the 2 groups except for Fuhrman grade (p1⁄40.006). In Kaplan-Meier analysis, 5-year recurrence free survival was 98.7% in patients with clear cell RCC and 95.6% in patients with papillary RCC. However, 10-year recurrence free survival in patients with clear cell and papillary RCC was 96.1% and 73.0%, respectively (p<0.001). Median time to recurrence was 31 months in patients with clear cell RCC and 77 months in patients with papillary RCC although statistical significance was not achieved (p1⁄40.190). In multivariate analysis, papillary RCC (HR; 5.309, p1⁄40.001) was determined as a significant risk factor for recurrence after partial nephrectomy in pathologic T1a RCC patients in addition to tumor size (HR; 1.861, p1⁄40.038) and Fuhrman grade (1⁄43) (HR; 5.176, p1⁄40.003). CONCLUSIONS: Recurrence after partial nephrectomy was more commonly occurred in pathologic T1a papillary RCC compared to clear cell RCC. Because median time to recurrence in papillary RCC was greater than 5-year after surgery, longer follow-up is needed for patients with papillary RCC even though pathologic stage is T1a.

PD66-05 USE OF INTRAOPERATIVE MANNITOL DURING PARTIAL NEPHRECTOMY FAILS TO PROVIDE SHORT-TERM OR LONG-TERM RENAL FUNCTION BENEFIT – EVEN IN HIGH RISK POPULATIONS

INTRODUCTION AND OBJECTIVES: Mannitol has been shown in animal models to have a renoprotective effect during warm ischemia, but these potential benefits have yet to be demonstrated in clinical studies. Despite this, mannitol is still used in about 75% of partial nephrectomies (PN). Using the largest PN series to date, we sought to identify any short-term or long-term preservation in renal function through the use of intraoperative mannitol, with a particular focus on high risk groups. METHODS: We retrospectively reviewed 1,415 robotic and open PN patients over a period of 6 years. Doubly robust inverse probability of treatment weighting (DR-IPTW) was applied to attempt to equilibrate treatment groups with regards to clinicodemographic characteristics. Acute kidney injury (AKI) was defined as a change in preop GFR >25% within 72 hours of surgery, or stage 1 of the RIFLE criteria. GFR preservation (GFR-P) was defined as 100*GFR at 3-12 months/ Preop GFR. A propensity-weighted adjusted logistic regression was employed to determine the relationship between the treatment group, renal functional outcomes, and baseline covariates. Subgroup analyses were performed on patients with baseline CKD, prolonged ischemia time (>25 vs <25 min), cold and warm ischemia, and solitary kidneys. RESULTS: 73.5% of patients received mannitol. After weighting, there were no statistical differences in baseline characteristics (p>0.05). In the cohort at large, 34.8% developed AKI and global GFRP was 90.4% at a median 6 month follow-up. There were no differences in the outcomes of AKI (OR 1.14 [95% CI, 0.84-1.54]) and GFR-P (b 1⁄4 1.34 [95% CI, -1.41-4.09]) between treatment groups. In subgroup analyses, there were no differences in the outcomes of AKI (OR 1.03 [95% CI, 0.51-2.10]) or GFR-P (b 1⁄41.28 [95% CI, -9.77-7.21]) in patients with preexisting CKD, prolonged ischemia time (AKI, OR 1.16 [95% CI, 0.64-2.11] ; GFR-P, b 1⁄41.76 [95% CI, -3.96-7.47]), cold ischemia (AKI, OR 1.02 [95% CI, 0.54-1.91] ; GFR-P, b 1⁄41.39 [95% CI, -4.62-7.40]), warm ischemia (AKI, OR 1.14 [95% CI, 0.77-1.69] ; GFRP, b 1⁄41.16 [95% CI, -2.10-4.42]), and in solitary kidneys (AKI, OR 0.21 [95% CI, 0.24-1.20] ; GFR-P, b 1⁄413.2 [95% CI, -5.73-32.2]). CONCLUSIONS: Mannitol use in PN failed to provide any short-term or long-term renoprotective benefit. This held true within subgroup analyses including patients with preexisting CKD, prolonged ischemia times, cold and warm ischemia groups and in solitary kidneys. Despite evidence from animal models, there does not appear to be a role for mannitol use clinically during PN.

MP12-07 THE ROLE OF GLYCINE IN PUDENDAL NERVE STIMULATION AND BLADDER OVERACTIVITY

INTRODUCTION AND OBJECTIVES: Recent fMRI studies revealed supraspinal networks in response to bladder filling involved in perception and processing of bladder distension. However significance of supraspinal network activity and network localizations varied largely due to the different filling protocols. Therefore, our aim was to standardize filling paradigms using a MR-synchronized pump system for accurate timing and filling volume. METHODS: 31 right-handed healthy subjects, 16 women and 15 men, mean age 34 years (range 19e54) with no history of urinary urgency and/or urinary incontinence were included, were prospectively investigated using a 3 Tesla Phillips scanner. After catheterization, bladder was pre-filled until a persistent desire to void was perceived by each subject. The scan paradigm comprised automated, repetitive bladder filling of 100 mL body warm saline over 15sec by using a MRcompatible pump system, i.e. block design study. Neuroimaging data was analyzed with SPM8. Blood-oxygenation-level dependent signal analysis during bladder filling was compared to rest, i.e. pre-filled bladder. Second-level random effects group analysis was corrected for gender, age and total intracranial volume and was performed to account for between-subject variability, i.e. within-group results at P1⁄40.05 familywise error rate (FWE). RESULTS: 3 subjects, 2 women and 1 man, were excluded from further analysis due to excessive head motions. Within-group results from the remaining 28 subjects revealed activation in the following brain regions: bilateral insula, left inferior parietal lobe (BA40) and right frontal inferior operculum (BA44). CONCLUSIONS: Automated, repetitive bladder filling of body warm saline elicited robust brain activity on a high significance level in specific areas known to be involved in supraspinal lower urinary tract control.