Timothy B. Boone

Risk Factors for Urinary Incontinence after Radical Prostatectomy

PURPOSE We identified risk factors associated with urinary incontinence after radical retropubic prostatectomy. MATERIALS AND METHODS The time from operation until urinary continence was achieved was determined by chart review and questionnaire in 581 patients who were continent before undergoing radical retropubic prostatectomy between 1983 and 1994. Using univariate and multivariate analyses of data gathered prospectively, we examined risk factors associated with incontinence in these patients. RESULTS The actuarial rate of urinary continence at 24 months was 91% for the entire patient population and 95% for those treated after 1990. Many factors were associated with the risk of incontinence in univariate Cox proportional hazards regression analysis (patient age and weight, degree of obstructive voiding symptoms, prior transurethral resection of the prostate, clinical stage, intraoperative blood loss, resection of neurovascular bundles, postoperative anastomotic stricture and technique of vesicourethral anastomosis). However, in a multivariate analysis the factors that were independently associated with increased chance of regaining continence were decreasing age, a modification in the technique of anastomosis (introduced in 1990), preservation of both neurovascular bundles and absence of an anastomotic stricture. With introduction of the new surgical technique in 1990 the median time to continence decreased from 5.6 to 1.5 months and the rate of continence at 24 months increased from 82 to 95%. CONCLUSIONS While the risk of urinary incontinence after radical prostatectomy is related to the uncontrollable factor of patient age, it is also sensitive to the surgical technique used.

Prospective Randomized Controlled Trial of Extended-Release Oxybutynin Chloride and Tolterodine Tartrate in the Treatment of Overactive Bladder: Results of the OBJECT Study

OBJECTIVE To compare the efficacy and tolerability of extended-release oxybutynin chloride and tolterodine tartrate at 12 weeks in participants with overactive bladder. SUBJECTS AND METHODS The OBJECT (Overactive Bladder: Judging Effective Control and Treatment) study was a prospective, randomized, double-blind, parallel-group study conducted between March and October 2000 at 37 US study sites. Participants who had between 7 and 50 episodes of urge incontinence per week and 10 or more voids in 24 hours received extended-release oxybutynin, 10 mg/d, or tolterodine, 2 mg twice daily. The outcome measures were the number of episodes of urge incontinence, total incontinence, and micturition frequency at 12 weeks adjusted for baseline. RESULTS A total of 315 women and 63 men were randomized and treated, and 332 participants (276 women, 56 men) completed the study. At the end of the study, extended-release oxybutynin was significantly more effective than tolterodine in each of the main outcome measures: weekly urge incontinence (P=.03), total incontinence (P=.02), and micturition frequency episodes (P=.02) adjusted for baseline. Both drugs improved symptoms of overactive bladder significantly from baseline to the end of the study as assessed by the 3 main outcome measures (P<.001). Dry mouth, the most common adverse event, was reported by 28.1% and 33.2% of participants taking extended-release oxybutynin and tolterodine, respectively (P=.32). Rates of central nervous system and other adverse events were low and similar in both groups. CONCLUSIONS Extended-release oxybutynin was more effective than tolterodine as measured by end-of-study urge incontinence, total incontinence, and micturition frequency episodes. Both groups had similar rates of dry mouth and other adverse events.

Efficacy of antimicrobial-impregnated bladder catheters in reducing catheter-associated bacteriuria: a prospective, randomized, multicenter clinical trial

OBJECTIVES To examine the efficacy of bladder catheters impregnated with minocycline and rifampin in reducing catheter-associated bacteriuria. METHODS A prospective, randomized clinical trial was conducted at five academic medical centers. Patients undergoing radical prostatectomy were randomized to receive intraoperatively either regular silicone bladder catheters (control catheters) or silicone bladder catheters impregnated with minocycline and rifampin (antimicrobial-impregnated catheters). Catheters remained in place for a mean of 2 weeks. Urine cultures were obtained at about 3, 7, and 14 days after catheter insertion. Bacteriuria was defined as the growth of organism(s) in urine at a concentration of 10(4) colony-forming units per milliliter or greater. RESULTS Kaplan-Meier analysis demonstrated that it took significantly longer for patients (n = 56) who received the antimicrobial-impregnated catheters to develop bacteriuria than those (n = 68) who received the control catheters (P = 0.006 by the log-rank test). Patients who received the antimicrobial-impregnated catheters had significantly lower rates of bacteriuria than those in the control group both at day 7 (15.2% versus 39.7%) and at day 14 (58.5% versus 83.5%) after catheter insertion. Patients who received the antimicrobial-impregnated catheters had significantly lower rates of gram-positive bacteriuria than the control group (7.1% versus 38.2%; P <0.001) but similar rates of gram-negative bacteriuria (46.4% versus 47.1%) and candiduria (3.6% versus 2.9%). The antimicrobial-impregnated catheters provided zones of inhibition against Enterococcus faecalis and Escherichia coli, both at baseline and on removal. CONCLUSIONS Bladder catheters impregnated with minocycline and rifampin significantly reduced the rate of gram-positive catheter-associated bacteriuria up to 2 weeks after catheter insertion.

ARTIFICIAL URINARY SPHINCTER FOR POST-PROSTATECTOMY INCONTINENCE IN MEN WHO HAD PRIOR RADIOTHERAPY: A RISK AND OUTCOME ANALYSIS

PURPOSE We retrospectively reviewed our experience with the artificial urinary sphincter for post-prostatectomy incontinence, comparing the outcome of those patients who did and did not receive previous radiation therapy. MATERIALS AND METHODS A total of 86 patients with post-prostatectomy incontinence treated with implantation of artificial urinary sphincter includes 58 who did not (group 1) and 28 who did (group 2) receive prior radiation therapy during treatment of prostate carcinoma. In group 2 radiation was the primary treatment followed by salvage prostatectomy in 5 patients, adjuvant after radical retropubic prostatectomy 20 and after transurethral prostatic resection 3. Mean patient age plus or minus standard deviation was 68.3 +/- 6.6, and 69.7 +/- 6.6 years in groups 1 and 2, respectively. Activation of the sphincter was 4 weeks from the date of surgery, and deactivation at night was not adopted in either group. Patients were followed for a mean period of 31 +/- 23, and 36 +/- 21 months in groups 1 and 2, respectively. Comparison of continence, urodynamic testing, complication rate, overall satisfaction and quality of life was done between both groups. RESULTS Reoperation was required in 13 (22.4%) patients in group 1 and 7 (25%) group 2 (p >0.05). Urethral atrophy and/or inadequate compression was seen in 8 (14%) and 4 (14%) patients, and urethral erosion was observed in 1 (2%) and 2 (7%) in groups 1 and 2, respectively (p >0.5). Infection of the device was observed in 4 (7%) patients in group 1 but none group 2 (p >0.05). Continence status was similar in both groups, with 60% and 64% of patients who wore 0 to 1 pad daily in groups 1 and 2, respectively (p >0.05). Urgency with or without urge incontinence was reported after implantation of artificial urinary sphincter in 47%, and 44% of patients in groups 1 and 2, respectively (p >0.05). On a visual analog scale (range 0 to 5, 0-not satisfied at all, 5-extremely satisfied) for satisfaction with the results of the artificial urinary sphincter 86% and 91% of patients reported 4 or greater in groups 1 and 2, respectively (p >0.05). CONCLUSIONS The artificial urinary sphincter has a similar outcome in patients with post-prostatectomy incontinence whether or not they have received previous radiation therapy. No special precaution needs to be adopted for the men in group 2 with post-prostatectomy incontinence considering implantation of artificial urinary sphincter.

Enhanced ATP release from rat bladder urothelium during chronic bladder inflammation: effect of botulinum toxin A.

The effects of mechanoreceptor stimulation and subsequent ATP release in cyclophosphamide evoked chronic bladder inflammation was examined to demonstrate: (1) whether inflammation modulates ATP release from bladder urothelium and (2) whether intravesical botulinum toxin A administration inhibits urothelial ATP release, a measure of sensory nerve activation. ATP release was measured from rat bladders in a Ussing chamber, an apparatus that allows one to separately measure resting and mechanoreceptor evoked (e.g. hypoosmotic stimulation) ATP release from urothelial and serosal sides of the bladder. Cystometry was utilized to correlate changes in ATP release with alterations in the frequency of voiding and non-voiding bladder contractions, in vivo measures of bladder afferent activity. The resting urothelial release of ATP was not significantly affected by either cyclophosphamide or botulinum toxin A treatment. However, evoked ATP release following hypoosmotic stimulation was significantly increased (i.e. 94%) in chronic cyclophosphamide treated bladder urothelium compared to control bladders. In addition, botulinum toxin A treatment significantly reduced hypoosmotic shock induced ATP release in cyclophosphamide treated animals by 69%. Cystometry revealed that cyclophosphamide and botulinum toxin A treatments altered non-voiding (i.e. cyclophosphamide increased, botulinum toxin A decreased) but not voiding contraction frequency suggesting that alterations in urothelial ATP release selectively diminished underlying bladder C-fiber nerve activity. Finally, intravesical instillation of botulinum toxin A did not affect ATP release from the serosal side implying that its effects were confined to the urothelial side of the bladder preparation.

Urodynamic pattern changes in multiple sclerosis

OBJECTIVES Multiple sclerosis (MS) causes neurologic symptoms to change over time. Voiding dysfunction is common in patients with MS, and few studies have examined the changes in urodynamic patterns in these patients over time. The purpose of this study was to examine the frequency and nature of urodynamic pattern changes in patients with MS who underwent two or more urodynamic studies. METHODS Twenty-two patients (7 men and 15 women) with well-documented MS were referred to one urologist (T.B.B.) for evaluation of lower urinary tract symptoms. All patients had undergone two or more urodynamic evaluations during a 14-year period for persistent or new symptoms, and a retrospective comparison was made among the urodynamic test results. RESULTS Overall, 12 (55%) of 22 patients experienced a change in their urodynamic patterns and/or compliance during a mean follow-up interval of 42 +/- 45 months between the urodynamic studies. Most patients initially had urodynamic patterns showing detrusor hyperreflexia, detrusor external sphincter dyssynergia, or detrusor hypocontractility. Fourteen (64%) of the 22 patients studied had the same or worsening of the same symptoms and 8 (36%) of 22 had new urologic symptoms. Six (43%) of 14 patients with no new symptoms and 6 (75%) of 8 with new symptoms had significant changes found with follow-up urodynamic testing. CONCLUSIONS A significant proportion of patients with MS with and without new urinary symptoms will develop changes in their underlying urodynamic patterns and detrusor compliance. Therefore, urodynamic evaluations should be repeated at regular intervals in symptomatic patients to optimize clinical management, reduce complications, and better enable these patients to manage their neurogenic bladder dysfunction.

Botulinum toxin type A normalizes alterations in urothelial ATP and NO release induced by chronic spinal cord injury

The purpose of this paper was to simultaneously examine changes in urothelial ATP and NO release in normal and spinal cord injured animals as well as in spinal cord injured animals treated with botulinum toxin type A (BoNT-A). Furthermore we correlated changes in transmitter release with functional changes in bladder contraction frequency, and determined the effects of BoNT-A on bladder efferent nerve function. Normal and spinal cord injured rat bladders were injected on day 0 with either vehicle (saline containing bovine serum albumin) or BoNT-A. On day 2, in vitro neurotransmitter release and bladder strip contractility studies as well as in vivo cystometrographic studies were conducted. Resting ATP release was significantly enhanced following spinal cord injury (i.e. 57% increase, p<0.05) and was unaffected by BoNT-A treatment. SCI increased hypoosmotic evoked urothelial ATP release by 377% (p<0.05). BoNT-A treatment reduced evoked ATP release in SCI bladders by 83% (p<0.05). In contrast, hypoosmotic stimulation induced NO release was significantly inhibited following SCI (i.e. 50%, p<0.05) but recovered in SCI rats treated with BoNT-A (i.e. 195% increase in NO release in SCI-BTX-treated rats compared to SCI controls, p<0.01). Changes in urothelial transmitter release coincided with a significant decrease in non-voiding bladder contraction frequency (i.e. 71%, p<0.05) in SCI-BTX rats compared to SCI rats. While no difference was measured between neurally evoked contractile amplitude between SCI and SCI-BTX animals, atropine (1 microM) inhibited contractile amplitude to a greater extent (i.e. 76%, p<0.05) in the SCI-BTX group compared to the SCI group. We hypothesize that alterations in the ratio of excitatory (i.e. ATP) and inhibitory (i.e. NO) urothelial transmitters promote bladder hyperactivity in rat bladders following SCI that can be reversed, to a large extent, by treatment with BoNT-A.

COMBINED STENT AND ARTIFICIAL URINARY SPHINCTER FOR MANAGEMENT OF SEVERE RECURRENT BLADDER NECK CONTRACTURE AND STRESS INCONTINENCE AFTER PROSTATECTOMY: : A LONG-TERM EVALUATION

Purpose: Concurrent incontinence and severe recurrent bladder neck contracture following radical prostatectomy are difficult to manage. Recurrent anastomotic strictures following repeat transurethral incisions and resections, and the need for frequent instrumentation are contraindications for artificial urinary sphincter placement. Usually treatment alternatives for these patients consist of some form of urinary diversion or chronic catheter drainage. We evaluated our results using a UroLume‡ ‡American Medical Systems, Inc., Minnetonka, Minnesota. stent across the bladder neck contracture followed by placement of an artificial urinary sphincter.Materials and Methods: After failed multiple (mean incisions 4.4) attempts at conservative management of anastomotic stricture 9 men were treated with a UroLume urethral stent across the contracture followed by artificial urinary sphincter placement after appropriate epithelialization of the stent was confirmed.Results: All patients were followed for a mean of 17.5...

Pharmacotherapy for neurogenic detrusor overactivity.

Chancellor MB, Anderson RU, Boone TB: Pharmacotherapy for neurogenic detrusor overactivity. Am J Phys Med Rehabil 2006;85:536–545. Patients with neurogenic detrusor overactivity are a heterogeneous group with voiding dysfunction secondary to neurologic injury or disease. The neurogenic detrusor overactivity syndrome, which may include urinary frequency, urgency, and incontinence, frequently contributes to a loss of independence, or even institutionalization. Urodynamic assessment provides the best method of quantifying and classifying neurogenic detrusor overactivity dysfunction in patients with primary diagnoses as diverse as Parkinson’s disease, cerebral palsy, multiple sclerosis, spinal cord injury, and spina bifida. For many patients, management of urinary symptoms includes pharmacotherapy with an anticholinergic agent. Several novel approaches to managing neurogenic detrusor overactivity, including intravesical instillation of anticholinergic agents, vanilloids, and neurotoxins, are being investigated. For most patients, however, flexible dosing with an anticholinergic agent, with clean intermittent catheterization when indicated, has been shown to reduce the risks of urologic complications, improve levels of continence, and enhance patient quality of life in both children and adults.

Disruption of the Caveolin-1 Gene Impairs Renal Calcium Reabsorption and Leads to Hypercalciuria and Urolithiasis

Using LoxP/Cre technology, we generated a knockout mouse homozygous for a null mutation in exon 2 of Cav1. In male Cav1-/- animals, we observed a dramatic increase in the incidence of urinary calcium stone formation. In 5-month-old male mice, the incidence of early urinary calculi was 67% in Cav1-/- mice compared to 19% in Cav1+/+ animals. Frank stone formation was observed in 13% of Cav1-/- males but was not seen in Cav1+/+ mice. Urine calcium concentration was significantly higher in Cav1-/- male mice compared to Cav1+/+ mice. In Cav1-/- mice, distal convoluted tubule cells were completely devoid of Cav1 and the localization of plasma membrane calcium ATPase was disrupted. Functional studies confirmed that active calcium absorption was significantly reduced in Cav1-/- compared to Cav1+/+ male mice. These results demonstrate that disruption of the Cav1 gene promotes the progressive steps required for urinary calcium stone formation and establish a new mouse model for urinary stone disease.