Gregory T. Bales

Botulinum toxin type A inhibits calcitonin gene-related peptide release from isolated rat bladder

PURPOSE Increasing evidence suggests that sensory nerve dysfunction may underlie several urological disorders, including interstitial cystitis and sensory urgency. We determined the effect of botulinum toxin type A (Allergan, Irvine, California) on baseline and chemically evoked release of the sensory neuropeptide, calcitonin gene-related peptide in an isolated bladder preparation. MATERIALS AND METHODS Whole rat bladders were incubated in a series of tissue baths containing physiological salt solution. Following bladder equilibration in PSS sequential incubation was performed and this sample was used to measure baseline CGRP release. To evoke CGRP release tissue was subsequently incubated in PSS containing capsaicin (30 nM) and adenosine triphosphate (10 microM). To measure the effect of BTX-A on baseline and evoked CGRP release bladders were incubated for 6 hours in an organ bath containing BTX-A (50 microM) or vehicle prior to bladder equilibration. CGRP release was determined by radioimmunoassay. RESULTS Mean baseline release of CGRP +/- SEM was 346 +/- 44 pg/gm. Adenosine triphosphate/capsaicin application increased CGRP release by 75% over baseline (606 +/- 98 pg/gm, p < 0.005). BTX-A application resulted in a 19% decrease in baseline release of CGRP, although this difference did not achieve statistical significance. BTX-A application significantly decreased evoked CGRP by 62% vs control (606 +/- 98 vs 229 +/- 21 pg/gm, p < 0.005). CONCLUSIONS BTX-A application inhibits the evoked release of CGRP from afferent nerve terminals in isolated rat bladder. This finding suggests a potential clinical benefit of BTX-A for the treatment of interstitial cystitis or sensory urgency.

Botulinum toxin type A inhibits sensory neuropeptide release in rat bladder models of acute injury and chronic inflammation

To determine the effect of botulinum toxin type A (BTX‐A) on the release of the neuropeptides substance P (SP) and calcitonin gene‐related peptide (CGRP) from isolated bladder preparations after acute injury with HCl and the induction of cyclophosphamide (CYP)‐induced cystitis, as neurogenic inflammation has been increasingly identified in urological disorders such as interstitial cystitis.

Short-term outcomes after cryosurgical ablation of the prostate in men with recurrent prostate carcinoma following radiation therapy

OBJECTIVES Cryosurgical ablation of the prostate represents a possibly efficacious method of treating prostate carcinoma in men failing radiation therapy. In addition to eradicating the disease, cryosurgery has the potential to avoid some of the morbidity associated with other treatment modalities. Therefore, a prospective Phase II trial was conducted to determine the safety and efficacy of cryosurgery following radiation therapy in men with local recurrence. METHODS Cryosurgical ablation of the prostate was performed in men with prostate cancer previously treated by radiation therapy. All patients had biopsy-proven recurrent disease and no evidence of metastases. Initial follow-up occurred at approximately 3 months and included repeat biopsy and serum prostate-specific antigen (PSA) determinations. Biochemical disease-free survival defined as a PSA value less than 0.3 ng/mL was assessed using the Kaplan-Meier method. RESULTS Thus far, 23 patients have been treated with cryosurgery with follow-up ranging between 12 and 23 months. Approximately 3 months after treatment, sextant biopsies revealed no cancer in 19 of 22 (86%) of the specimens; however, 10 of 22 (45%) showed small amounts of benign glandular tissue. The PSA at 3 months postoperatively declined in 18 of 22 (82%) patients but reached female levels in only 8 men (36%). Nineteen of 22 (86%) patients followed up a minimum of 1 year after cryotherapy have a PSA level equal to or greater than 0.3 ng/mL. Complications occurred in 100% of the patients with 12 of 22 (55%) requiring at least one transurethral resection of sloughed, necrotic tissue. CONCLUSIONS Our preliminary results suggest that the current cryosurgical technique used in men failing radiation therapy has a low probability of biochemical cure and a high complication rate. Until more data are available, cryosurgery for men with locally recurrent disease after radiation therapy should be considered strictly experimental.

Effect of preoperative biofeedback/pelvic floor training on continence in men undergoing radical prostatectomy.

OBJECTIVES To determine whether preoperative biofeedback training improves urinary continence overall or the rate of return of continence in men undergoing radical prostatectomy. METHODS One hundred men scheduled to undergo radical prostatectomy were randomized to receive graded pelvic muscle exercise training with biofeedback 2 to 4 weeks before surgery or to a control group performing pelvic muscle exercises without biofeedback. The biofeedback group was instructed to continue exercises four times per day until surgery and to resume exercises when the urethral catheter was removed following surgery. The control group received written and brief verbal instructions in pelvic muscle exercises before surgery and again after catheter removal. Urinary continence was assessed by personal or phone interviews. RESULTS Six months following surgery, the continence rates, as defined by the use of one pad or less per day, were 94% (44 of 47) and 96% (48 of 50) in the biofeedback and control groups, respectively (P = 0.596). Also, the rate of return as determined at time points 1, 2, 3, and 4 months after surgery was not significantly different between the two groups. CONCLUSIONS Preoperative biofeedback training did not improve the outcome of pelvic muscle exercises on overall continence or the rate of return of urinary control in men undergoing radical prostatectomy.

A controlled trial of bicalutamide versus castration in patients with advanced prostate cancer

OBJECTIVES Bicalutamide is a new, potent antiandrogen with potential efficacy in the treatment of men with advanced prostate cancer. Although no pure antiandrogen has been well studied versus castration, potentially fewer adverse effects could occur, making such an agent a potentially useful alternative therapy. To date, three randomized controlled trials have been performed comparing these two treatments. In preliminary studies, a dose of 50 mg bicalutamide per day was selected for these trials. In two of the studies (0302, 0303), this drug was compared to either medical or surgical castration, the latter choice being made by the patient. In the third study (0301), bicalutamide was compared to bilateral orchiectomy. METHODS Using an intention-to-treat format, the outcomes assessed were time-to-treatment failure, time-to-objective disease progression, subjective response, and survival time in men with previously untreated metastatic disease. The incidence of breast tenderness, gynecomastia, and hot flushes was also determined in both treatment arms. A quality-of-life questionnaire was administered on multiple occasions after initiation of therapy. RESULTS Based on an analysis of > 1000 patients, the objective and subjective results favored castration over bicalutamide (50 mg/day). The hazard ratios for time-to-treatment failure (1.59), time-to-disease progression (1.62), and median survival (1.44) were all significantly greater in the castration group (P > 0.001). Another difference noted at 3 months was a significantly lower median fall in prostate-specific antigen values in the bicalutamide group (86-88% versus 96-97%). Symptomatic patients receiving bicalutamide were only 0.43 times as likely to have subjective improvement as the patients treated by castration. A comparison of pharmacologic effects showed that only the incidence of hot flushes was lower in the bicalutamide group, whereas breast tenderness and gynecomastia were more common. This difference in hot flushes, however, translated into better quality of life during the first several months with regard to sexual relations and sexual functioning. CONCLUSIONS Bicalutamide monotherapy at 50 mg/day appears inferior to castration in overall objective and subjective response rates. Whether higher doses of bicalutamide can compete more favorably will need to be tested in further clinical trials.

Long-term Follow-up of Single Versus Double Cuff Artificial Urinary Sphincter Insertion for the Treatment of Severe Postprostatectomy Stress Urinary Incontinence

OBJECTIVES To assess the long-term effectiveness and complications associated with single and double cuff artificial urinary sphincter (AUS) implantation for the treatment of severe postprostatectomy stress urinary incontinence (SUI). METHODS We updated the outcomes of 56 men with postprostatectomy SUI who underwent single (28 patients) or double (28 patients) cuff AUS placement. Originally patients in each cohort were matched according to preoperative pad usage, risk factors for complications, and age. Continence, quality of life, and complications were assessed according to the Incontinence Impact Questionnaire Short Form (IIQ-7), postoperative pad usage, chart review, and patient/family interview. RESULTS Updated data were available for 47 men (25 single cuff and 22 double cuff patients). Mean pre-AUS implant age was 67 years for each group. Average follow-up was 74.1 months and 58.0 months for single and double cuff patients, respectively. No statistically significant difference in continence improvement was noted between the two groups according to daily pad usage and overall dry rate. IIQ-7 scores improved from 14.8 to 4.1 after single cuff implants and from 16.3 to 6.4 after double cuff placement (P = 0.34). Men receiving a single cuff AUS reported seven complications requiring further operative intervention. Double cuff patients underwent 12 additional surgeries secondary to complications. CONCLUSIONS Despite our earlier findings, no significant difference in dry rate, overall continence, or quality of life was seen with long-term follow-up of single versus double cuff AUS patients. Furthermore, men receiving double cuff implants may be at higher risk of complications requiring additional surgery.

Saw Palmetto (Serenoa repens) in Men with Lower Urinary Tract Symptoms: Effects on Urodynamic Parameters and Voiding Symptoms

OBJECTIVES To assess the effects of saw palmetto on voiding symptoms and urodynamic parameters in men with lower urinary tract symptoms (LUTS) presumed secondary to benign prostatic hyperplasia (BPH). METHODS Fifty men with previously untreated LUTS and a minimum International Prostate Symptom Score (IPSS) of 10 or greater were treated with a commercially available form of saw palmetto (160 mg twice per day) for 6 months. The initial evaluation included measurement of peak urinary flow rate, postvoid residual urine volume, pressure-flow study, and serum prostate-specific antigen (PSA) level. Patients completed an IPSS, serum PSA was determined, and flow rate was measured every 2 months during the course of the study. A urodynamic evaluation was repeated at the completion of the 6-month trial. RESULTS The mean IPSS (+/-SD) improved from 19.5+/-5.5 to 12.5+/-7.0 (P <0.001) among the 46 men who completed the study. Significant improvement in the symptom score was noted after treatment with saw palmetto for 2 months. An improvement in symptom score of 50% or greater after treatment with saw palmetto for 2, 4, and 6 months was noted in 21% (10 of 48), 30% (14 of 47), and 46% (21 of 46) of patients, respectively. There was no significant change in peak urinary flow rate, postvoid residual urine volume, or detrusor pressure at peak flow among patients completing the study. No significant change in mean serum PSA level was noted. CONCLUSIONS Saw palmetto is a well-tolerated agent that may significantly improve lower urinary tract symptoms in men with BPH. However, we were unable to demonstrate any significant improvement in objective measures of bladder outlet obstruction. Placebo-controlled trials of saw palmetto are needed to evaluate the true effectiveness of this compound.

AN ANALYSIS OF WATCHFUL WAITING FOR CLINICALLY LOCALIZED PROSTATE CANCER

PURPOSE We reviewed recent series of watchful waiting for prostate cancer to place this management strategy in appropriate perspective MATERIALS AND METHODS We reviewed the literature and analyzed the 9 articles on watchful waiting published in leading medical journals in the last decade. RESULTS Watchful waiting is probably the best treatment option for men with well and perhaps moderately differentiated, low volume prostate cancer who have a life expectancy of less than 10 years. However, the conclusions derived from watchful waiting studies of older men cannot and should not be applied to younger, healthier men or to those with more advanced or aggressive disease. If treated ineffectively, many of these men will die of prostate cancer. CONCLUSIONS Most men with prostate cancer who have a life expectancy greater than 10 to 15 years should be treated with curative intent.

Use of new technology in endourology and laparoscopy by American urologists: Internet and postal survey

OBJECTIVES To assess the use of new technology by American urologists. METHODS Using the American Urological Association directory, surveys were sent via the U.S. postal service to 1000 randomly selected American urologists and 3065 urologists who had an Internet address listed in the directory. RESULTS Responses were received from 601 urologists (415 postal, 186 Internet). Overall, 81% of survey respondents reported performing fewer or the same number of percutaneous procedures as compared with 3 to 4 years ago and 84% reported carrying out more or the same number of ureteroscopic procedures in the treatment of patients with stone disease. Open dismembered pyeloplasty (43%) and Acucise endopyelotomy (42%) were most frequently reported as the preferred treatment for adult patients with symptomatic ureteropelvic junction obstruction. Although 60% of respondents reported that they have taken a laparoscopy course, 67% currently do not perform any laparoscopy in their practice. In addition, only 7% of urologists stated that laparoscopy comprises more than 5% of their practice. When stratified by the number of years in practice, those in practice less than 10 years were more likely than those in practice 10 to 20 years and those in practice longer than 20 years to have performed an endopyelotomy (77%, 60%, and 48%, respectively, P <0.001) and to be currently performing laparoscopy (49%, 36%, and 18%, respectively, P <0.001). CONCLUSIONS Compared with 3 to 4 years ago, American urologists are performing more ureteroscopy and fewer percutaneous stone procedures. Although most urologists have taken laparoscopy courses, this modality has not been widely incorporated into their practices at present.

Practice patterns in the treatment of female urinary incontinence: a postal and internet survey

OBJECTIVES To survey American urologists to assess practice patterns in treating female incontinence. Advances in the treatment of female incontinence have changed the way urologists practice. METHODS Postal and e-mail surveys were sent to 2502 members of the American Urological Association. RESULTS From the postal group (n = 1000), 419 (42%) responses were obtained; from the e-mail group (n = 1502), 160 (11%) responses were obtained. For types I, II, and III stress urinary incontinence (SUI), 239 (44%) of 546, 388 (68%) of 570, and 512 (94%) of 547 urologists, respectively, recommended a sling procedure. For type I SUI, 75 (53%) of the 143 respondents in practice for less than 10 years recommended a sling procedure. The sling was recommended by 62 (35%) of the 176 respondents in practice for longer than 20 years (P <0.001). Most urologists (75%, 358 of 480) referred patients with significant vaginal prolapse to a gynecologist; however, urologists in full-time academic practice were more likely to offer surgical treatment (56%, 29 of 52). Most urologists recommended medical treatment for urge incontinence (94%, 461 of 491), and the medications most commonly selected were tolterodine (41%, 202 of 491), oxybutynin (26%, 129 of 491), and extended-release oxybutynin (25%, 125 of 491). CONCLUSIONS Overall, a sling procedure was the most commonly recommended surgical procedure for all types of SUI. Most urologists referred patients with significant vaginal prolapse to a gynecologist. For type I SUI, older urologists were more likely than younger urologists to perform needle bladder neck suspension.