Kurt A. McCammon

Comparative quality-of-life analysis after radical prostatectomy or external beam radiation for localized prostate cancer

OBJECTIVES To determine and compare quality-of-life (QOL) evaluations from patients who received external beam radiation therapy or radical prostatectomy for the treatment of localized prostate cancer, and to compare differences in QOL assessments for urinary and sexual function after radical prostatectomy as reported by patient and physician. METHODS Two hundred three patients treated by radical prostatectomy and 257 patients treated by external beam irradiation, all beyond 12-month follow-up after therapy, responded to a QOL questionnaire. The difference in responses with regard to bladder, bowel, and sexual function, overall satisfaction with treatment, and choice of the same treatment were assessed. Satisfaction with and choice of the same treatment were also specifically assessed according to bowel and bladder function and current disease status. The medical records of patients treated by radical prostatectomy were reviewed by an independent data manager to record the physicians assessment of continence and sexual function for comparison with that patients assessment as noted in the questionnaire. RESULTS Problems with urinary continence were more frequent among patients treated by radical prostatectomy; problems with gastrointestinal function were more frequent after irradiation. Sexual dysfunction was similar in both groups, although surgical patients experienced a greater impact on sexual relationships. The physician estimates of urinary continence were more favorable than the patient-reported outcomes. However, the physician estimate of sexual function closely approximated that of the patient. Preservation of sexual function among patients who underwent nerve-sparing surgery was disappointingly low. Only for the response to the question dealing with difficulty in achieving an erection was there a statistically significant benefit for patients receiving nerve-sparing versus non-nerve-sparing procedures. Patient satisfaction with and choice of the same treatment varied according to function and current disease status. Patients who had incontinence or bowel dysfunction or had evidence of recurrent disease were statistically less likely to choose the same treatment again when compared with functional and disease-free counterparts. Because irradiated patients were on average 6 years older than surgical patients, responses were adjusted for age; adjustment for age did not alter results. CONCLUSIONS QOL is determined by the treatment received, by the assessment source, and by the patients function and disease status at the time of assessment. Prospective and longitudinal studies will more accurately quantify immediate and chronic alterations in QOL. Uniformity of evaluation through consolidation of QOL instruments will permit more accurate cross-series and cross-treatment comparisons.

Safety and Tolerability of Solifenacin Add-on Therapy to α-Blocker Treated Men With Residual Urgency and Frequency

PURPOSE VICTOR was a 12-week, double-blind, placebo controlled trial assessing the safety and tolerability of solifenacin plus tamsulosin in men with residual overactive bladder symptoms after tamsulosin monotherapy. Efficacy of solifenacin plus tamsulosin vs placebo plus tamsulosin was also evaluated. MATERIALS AND METHODS A total of 398 men 45 years old or older were randomized to 12 weeks of solifenacin plus tamsulosin or placebo plus tamsulosin once daily. The study population had 8 or more micturitions per 24 hours and 1 or more urgency episode per 24 hours after taking tamsulosin for 4 or more weeks, a total International Prostate Symptom Score of 13 or greater, a Patient Perception of Bladder Condition score of 3 or greater, a post-void residual of 200 ml or less and a peak flow rate of 5 ml per second or greater. Adverse events were monitored throughout the study. The primary efficacy end point was mean change from baseline to week 12 in micturitions per 24 hours. Secondary measures included mean change in urgency episodes per 24 hours, and changes in Patient Perception of Bladder Condition, Urgency Perception Scale and total International Prostate Symptom Scores. RESULTS The most frequent adverse events in the solifenacin plus tamsulosin and placebo plus tamsulosin groups were dry mouth (7% and 3%, respectively) and dizziness (3% and 2%, respectively). Of the patients on solifenacin plus tamsulosin 7 (3%) reported retention and 3 required catheterization. No patients on placebo plus tamsulosin reported retention. Patients on solifenacin plus tamsulosin vs placebo plus tamsulosin showed larger reductions in frequency but not of statistical significance (-1.05 vs -0.67, p = 0.135). However, patients on solifenacin plus tamsulosin vs placebo plus tamsulosin did show statistically significant reductions in urgency (-2.18 vs -1.10, p <0.001). Patient reported outcome measures showed no significant between group differences. CONCLUSIONS Solifenacin plus tamsulosin was well tolerated. There was a low incidence of urinary retention requiring catheterization. At week 12 solifenacin plus tamsulosin decreased daily micturitions and urgency episodes. Only urgency reached statistical significance vs placebo plus tamsulosin.

Urodynamic Changes and Initial Results of the AdVance Male Sling

OBJECTIVES To present the urodynamic changes and early results associated with the AdVance male sling. The AdVance male sling is a treatment option for postprostatectomy incontinence (PPI), with the goal of eliminating urinary incontinence without affecting voiding parameters. A concern of any procedure in treating men with PPI is whether the treatment induces obstruction and causes retention. METHODS Data were prospectively collected from 13 patients undergoing AdVance male sling placement for PPI. Urodynamic testing was performed at baseline and repeated at 6 months postoperatively. A 24-hour pad test and the Incontinence Quality of Life questionnaire were completed preoperatively and at 3 and 6 months postoperatively. RESULTS The median age at the procedure was 63.3 years (range 44.7-74.7). The mean preoperative and 6-month postoperative patient-reported pad use was 4.52 and 1.04, respectively (2-tailed t test, P = .0009). The 24-hour pad test, performed preoperatively and at 6 months postoperatively, yielded a pad weight of 779.3 and 67.6 g, respectively (P = .03). The Valsalva leak point pressure improved significantly (P = .032), but the detrusor voiding pressure, postvoid residual urine volume, and maximal and average flow rates remained relatively unchanged. At 3 and 6 months postoperatively, the Incontinence Quality of Life scores had improved significantly compared with the preoperative scores (P <.01). CONCLUSIONS These results are encouraging, because this series has demonstrated a significant improvement in patient-reported pad use, 24-hour pad test weights, and Valsalva leak point pressure without signs of obstruction. The improvement in incontinence was accompanied without any changes in the other voiding parameters and with significant improvement in the quality-of-life measures. Ongoing studies with longer follow-up are pending to compare their results with these promising early results.

Rapid effects of estrogen and progesterone on tone and spontaneous rhythmic contractions of the rabbit bladder.

Abstract Previous studies indicate that bladder instability in man may be associated with increased spontaneous rhythmic contractile activity. Ca2+ influx plays a central role in smooth muscle contractions, and recent evidence suggests that steroid hormones rapidly affect Ca2+ influx. Therefore we tested the hypothesis that estrogen and progesterone modulates spontaneous rhythmic detrusor contractions. Tissues were secured to isometric force (F) transducers in tissue baths and length-adjusted until K+-depolarization produced maximum contractions (Fo). Spontaneous rhythmic contractions (SRC) were sampled before and immediately after addition of estradiol or progesterone (10−5 M) to tissue baths. The average frequency and amplitude of SRC were, respectively, 0.156 Hz and 0.053 F/Fo (n = 24). Estradiol caused an immediate reduction in SRC, such that by 10 min, tone, frequency and amplitude were each reduced by, respectively, 36%, 46% and 47% (n = 7, P < 0.05). However, progesterone caused an immediate weak contraction, and at steady state (10 min), progesterone increased frequency of SRC by 152% but decreased SRC amplitude by 50% (n = 10, P < 0.05). Novel therapies using unique steroids that do not interact with genomic receptors may potentially reduce bladder smooth muscle activity, thereby reducing detrusor instability.

Dependency of detrusor contractions on calcium sensitization and calcium entry through LOE-908-sensitive channels.

The subcellular mechanisms regulating stimulus‐contraction coupling in detrusor remain to be determined. We used Ca2+‐free solutions, Ca2+ channel blockers, cyclopiazonic acid (CPA), and RhoA kinase (ROK) inhibitors to test the hypothesis that Ca2+ influx and Ca2+ sensitization play primary roles. In rabbit detrusor, peak bethanechol (BE)‐induced force was inhibited 90% by incubation for 3 min in a Ca2+‐free solution. By comparison, a 20 min incubation of rabbit femoral artery in a Ca2+‐free solution reduced receptor‐induced force by only 5%. In detrusor, inhibition of sarcoplasmic reticular (SR) Ca2+ release by 2APB, or depletion of SR Ca2+ by CPA, inhibited BE‐induced force by only 27%. The CPA‐insensitive force was abolished by LaCl3. By comparison, 2APB inhibited receptor‐induced force in rabbit femoral artery by 71%. In the presence of the non‐selective cation channel (NSCC) inhibitor, LOE‐908, BE did not produce an increase in [Ca2+]i but did produce weak increases in myosin phosphorylation and force. Inhibitors of ROK‐induced Ca2+ sensitization, HA‐1077 and Y‐27632, inhibited BE‐induced force by ∼50%, and in combination with LOE‐908, nearly abolished force. These data suggest that two principal muscarinic receptor‐stimulated detrusor contractile mechanisms include NSCC activation, that elevates [Ca2+]i and ROK activation, that sensitizes cross bridges to Ca2+.

Differential effects of sex hormones and phytoestrogens on peak and steady state contractions in isolated rabbit detrusor.

PURPOSE Recent evidence suggests that sex steroids may produce rapid inhibition of voltage operated Ca2+ channels (VOCCs). Detrusor smooth muscle is highly dependent upon Ca2+ influx for receptor-activated contractions. Thus, we examined the relative effectiveness of a select group of sex steroids and dietary phytoestrogens to relax detrusor contracted with the muscarinic receptor agonist, bethanechol (BE) and the purinergic P2X receptor agonist, alpha,beta-methylene ATP (alpha,beta-MeATP). MATERIALS AND METHODS Isolated strips of rabbit detrusor were secured to isometric force transducers in a tissue bath and length-adjusted until maximum contractions were achieved. Peak (P) contractile responses were recorded for alpha,beta-MeATP (P(ATP)) and BE (P(BE)) and steady-state (SS) responses were recorded for BE (SS(BE)) in the presence and absence of selected sex steroids and phytoestrogens (10 microM, unless indicated). RESULTS The L-type VOCC inhibitor, nifedipine (1 to 10 microM), completely inhibited P(ATP) but reduced SS(BE) by approximately 50%, whereas the VOCC and non-VOCC inhibitor, SKF 96365, inhibited SS(BE) by approximately 95%, suggesting that P(ATP) was entirely dependent on L-type VOCCs, but (BE)-induced contractions depended also on activation of non-VOCCs. 17Beta-estradiol (estradiol) and progesterone inhibited P(ATP) by approximately 60% and 20%, respectively, and 32 microM estradiol and ethinyl estradiol inhibited SS(BE) by approximately 80 and 95%, respectively. Inhibition by estradiol was potentiated, rather than blocked, by the nuclear estrogen receptor antagonist, tamoxifen. Moreover, tamoxifen alone nearly completely relaxed SS(BE). The inactive metabolite of estradiol, 17alpha-estradiol, inhibited both P(ATP) and P(BE) by approximately 40%. Testosterone had no effect on P(ATP) and P(BE). The phytoestrogen and tyrosine kinase inhibitor, genistein, inhibited SS(BE) by 44%, whereas daidzein, a phytoestrogen without tyrosine kinase inhibitory activity, produced only a 7% inhibition. None of the phytoestrogens examined inhibited P(BE), whereas all inhibited P(ATP) by approximately 20 to 35%. A comparison of inhibition of (BE) and alpha,beta-MeATP-induced contractions by selected estrogen isomers showed some distinct differences. For example, estrone did not inhibit P(BE) or SS(BE), but inhibited P(ATP) by approximately 20%, whereas DES inhibited SS(BE) by nearly 90%, but P(ATP) by a lesser degree (approximately 70%). CONCLUSIONS Our data support the hypothesis that 17beta-estradiol, ethinyl estradiol, DES, tamoxifen and genistein may relax detrusor contractions by inhibition of both VOCCs and non-VOCCs. Moreover, our data show that genistein, a dietary phytoestrogen with tyrosine kinase inhibitory activity, selectively reduced alpha,beta-MeATP-induced peak and BE-induced steady-state contractions, sparing the maximum response to BE. Lastly, the inactive isomer, 17alpha-estradiol, inhibited both BE- and alpha,beta-MeATP-induced contractions. These data suggest that certain dietary phytoestrogens (for example, genistein) or sex steroids, especially those with weak activity at the nuclear steroid site (for example, 17alpha-estradiol), or tamoxifen may prove therapeutically useful in treating overactive bladder caused by elevated muscarinic and purinergic receptor activation.

Artificial urinary sphincter for post-prostatectomy incontinence: A review

The artificial urinary sphincter remains the gold standard for treatment of post‐prostatectomy urinary incontinence. The AMS 800 (American Medical Systems, Minnetonka, MN, USA) is the most commonly implanted artificial urinary sphincter. Having been on the market for almost 40 years, there is an abundance of literature regarding its use, but no recent review has been published. We reviewed the current literature regarding the indications, surgical principles, outcomes and complications of artificial urinary sphincter implantation for stress urinary incontinence after prostatectomy. A PubMed search was carried out for articles on the artificial urinary sphincter from 1995 to present. The review was centered on articles related to the use of the AMS 800 for stress urinary incontinence in males after prostatectomy. Relevant articles were reviewed. The majority of patients will achieve social continence (1 pad per day) after artificial urinary sphincter implantation; however, rates of total continence (no pad usage) are significantly lower. Patient satisfaction outcomes average greater than 80% in most series. Potential complications requiring reoperation include infection (0.5–10.6%) and urethral erosion (2.9–12%). Revision surgeries are most commonly as a result of urethral atrophy, which ranges from 1.6 to 11.4%. The 5‐year Kaplan–Meier freedom from reoperation ranges from 50 to 79%, while the 10‐year Kaplan–Meier freedom from mechanical failure is 64%. The artificial urinary sphincter is a reliable device with good outcomes. As expected with any prosthetic device, complications including mechanical failure, infection, erosion and recurrent incontinence remain significant concerns. Despite known complications, the patient satisfaction rates after artificial urinary sphincter implantation remain high. Appropriate patient counseling and adherence to surgical principles are imperative.

INTRAVESICAL DIMETHYL SULFOXIDE FOR PRIMARY AMYLOIDOSIS OF THE BLADDER

Primary bladder amyloidosis is a rare disease. Treatment recommendations are necessarily anecdotal. We report a case of a 52-year-old woman treated successfully with intravesical dimethyl sulfoxide instillation.

Extended Outcomes in the Treatment of Male Stress Urinary Incontinence With a Transobturator Sling

OBJECTIVE To review extended patient outcomes after male transobturator sling placement for stress urinary incontinence. METHODS A retrospective review of a prospectively maintained database for patients with at least 12 months of postoperative follow-up after AdVance male sling placement was performed. Success was defined as a dry safety pad or less (cured) or >50% improvement in pads used per day and patient satisfaction (improved). Patients requiring repeat continence procedures were considered failures. RESULTS We reviewed data from 102 patients with a minimum of 12 months of follow-up (mean ± standard deviation 36.2 ± 16.5 months). The mean age at surgery was 66.1 years, and 86.4% had previously undergone a prostatectomy. At 12 months, 24 months, and final follow-up, success rates were 74%, 63%, and 62%, respectively. Although cure rates also declined over time, 40% of patients experienced a durable cure with no complaints of wet pads at final follow-up. Complications were minimal and similar with previous reports. Multivariate Cox regression analysis revealed detrusor overactivity and an elevated detrusor pressure and peak flow negatively predicted being cured using sling placement. CONCLUSION AdVance sling placement continues to represent a viable option in the treatment of male stress incontinence. Although a decrease in efficacy over time was observed, a substantial portion of patients can expect a durable cure.

SIU/ICUD Consultation on Urethral Strictures: Anterior Urethra—Lichen Sclerosus

We reviewed the current literature on lichen sclerosus as it related to urethral stricture disease using MEDLINE and PubMed (U.S. National Library of Medicine, National Institutes of Health) up to the current time. We identified 65 reports, 40 of which were considered relevant and form the basis of this review. Lichen sclerosus is now the accepted term, and balanitis xerotica obliterans is no longer acceptable. This common chronic inflammatory skin condition, mainly affecting the genitalia, remains an enigma, with uncertain etiology, varied presentation, and multiple treatments. In the early stages of the condition, a short course of steroids may be beneficial for some patients. If persistent, patients need long-term surveillance because of the potential development of squamous cell carcinoma. If diagnosed early, lichen sclerosus can be controlled, preventing progression. But once the disease has progressed, it is very difficult to treat. Surgical treatment by circumcision can be curative if the disease is treated early when still localized. Once progression to urethral involvement has occurred, treatment is much more difficult. Meatal stenosis alone is likely to require meatotomy or meatoplasty. Treatment of the involved urethra requires urethroplasty. Single-stage and multiple-stage procedures using oral mucosa have both been reported to give acceptable results, but the use of skin, genital or nongenital, is not recommended, because being skin, it remains prone to lichen sclerosus. With extensive disease, affecting the full length of the urethra, consideration should be given to perineal urethrostomy. A significant number of patients may prefer this simpler option.