Joel M. Kaufman

Bladder Cancer and Squamous Metaplasia in Spinal Cord Injury Patients

The influence of long-term indwelling urethral catheterization was studied by random bladder and urethral biopsies in 62 spinal cord injury patients. Six patients (10 per cent) had diffuse squamous cell bladder carcinoma, 4 of whom had no tumor visible endoscopically. Five of the patients with cancer were among 25 patients (20 per cent) managed with an indwelling urethral catheter for more than 10 years (average 21 years, range 15 to 30 years). The other cancer patient had been free of the catheter for 27 years after suprapubic cystotomy for 4 years. Gross and microscopic hematuria was associated with cancer. Squamous metaplasia of the bladder was significantly greater in patients who had been catheterized for more than 10 years (80 per cent), compared to those catheterized for less than 10 years (42 per cent) and patients without catheters (20 per cent). Urethral squamous metaplasia increased slightly in long-term catheterization patients. Urinary infection was universal and did not distinguish patients with inflammation, metaplasia or cancer. Therefore, the duration of indwelling catheterization seems to be the major factor in squamous changes in these patients.

Treatment benefit of dapoxetine for premature ejaculation: results from a placebo‐controlled phase III trial

To evaluate the overall treatment benefit of dapoxetine for premature ejaculation (PE), with specific emphasis on improvements in personal distress and interpersonal difficulty related to ejaculation. Although these factors are key elements of numerous sets of diagnostic criteria for PE, they have rarely been evaluated as outcome measures in clinical trials.

Efficacy and Safety Study of 1.62% Testosterone Gel for the Treatment of Hypogonadal Men

INTRODUCTION Male hypogonadism is a significant and growing problem that can be successfully treated with testosterone replacement therapy. A new formulation of testosterone gel (1.62%) was developed with increased viscosity, reduced volume of application, and increased skin permeation compared with other currently available testosterone gels. AIM To evaluate the efficacy and safety of titrated doses of 1.62% testosterone gel after daily application to the skin of hypogonadal men for 182 days. METHODS This was a multicenter, randomized, double-blind, placebo-controlled study in hypogonadal men (234 active; 40 placebo), 18 to 80 years of age with average serum total testosterone concentrations <300 ng/dL and prostate-specific antigen <2.5 ng/mL. Topical testosterone gel (1.62%), 1.25 g, 2.5 g, 3.75 g, and 5.0 g, or placebo gel was applied once daily to either upper arms/shoulders or abdomen. Dose adjustments were made on days 14, 28, and 42. Main Outcome Measures.  The percentage of subjects with serum total testosterone average concentrations (C(av) ) within the normal range of 300-1,000 ng/dL on study days 14, 56, 112, and 182. RESULTS Following titration, significantly (P < 0.0001) more subjects receiving active treatment had testosterone C(av) values (range 81.6% to 82.5%) within the eugonadal range compared with placebo (range 28.6% to 37.0%) on all study days. The 1.62% gel was safe and well tolerated. CONCLUSIONS In this study, treatment with 1.62% testosterone gel was safe and efficacious, resulting in an acceptable percentage of hypogonadal males achieving eugonadal serum testosterone levels.

IMMEDIATE SALVAGE PROCEDURE FOR INFECTED PENILE PROSTHESIS

PURPOSE The most devastating complication after the insertion of a penile prosthesis is the development of infection. The standard approach involves removing the entire device, treating intensively with antibiotics and attempting to reinsert a prosthesis at a later date, often with a suboptimal result. Based on the encouraging results of others, during the last 24 months we have used in 2 separate private urological practices a salvage procedure for treatment of infected inflatable penile prostheses. MATERIALS AND METHODS The protocol used in 7 men with an infected inflatable penile prosthesis included removal of all device components, a 7-step vigorous intraoperative irrigation with 4 different solutions, including vancomycin, immediate reimplantation of a new inflatable penile prosthesis and postoperative outpatient antibiotics with oral ciprofloxacin or intravenous vancomycin or cefazolin. RESULTS Of the 7 men 6 have experienced excellent results with no infection, minimal morbidity and preservation of penile length. The only failure occurred in a poorly controlled diabetic who required multiple revisions and may have had latent infection for months before it became apparent. CONCLUSIONS We believe that an immediate salvage procedure for an infected inflatable penile prosthesis is an effective treatment for this difficult complication.

Long Acting Testosterone Undecanoate Therapy in Men With Hypogonadism: Results of a Pharmacokinetic Clinical Study

PURPOSE We determined the pharmacokinetics and safety of 750 mg long acting testosterone undecanoate given intramuscularly at 0, 4 and 14 weeks to men with hypogonadism. MATERIALS AND METHODS A 24-week, single arm, open label, multicenter trial in 130 hypogonadal men 18 years or older who were screened for serum total testosterone less than 300 ng/dl was performed at 31 research sites in the United States between March and November 2007. Testosterone undecanoate (750 mg) was administered at baseline, and at weeks 4 and 14. Serum testosterone samples were collected on days 4, 7, 11, 14, 21, 28, 42, 56 and 70 following injection 3. Safety was assessed, eg biochemical markers and adverse events, secondary to testosterone undecanoate treatment. RESULTS Of the 130 patients 116 with a mean +/- SE age of 54.2 +/- 0.90 years completed the 24-week trial. Following the week 14 injection mean +/- SD average serum testosterone was 494.9 +/- 141.46 ng/dl during the 70-day dosing interval and mean +/- SD maximum serum testosterone was 890.6 +/- 345.11 ng/dl with a mean concentration within the young healthy adult male range (300 to 1,000 ng/dl) in 94% of patients and a mean maximum concentration of below 1,500 ng/dl in 92%. Mean +/- SE hematocrit and hemoglobin increased from baseline to week 24 (43.3% +/- 0.32% to 45.7% +/- 0.35% and 14.6 +/- 0.11 to 15.5 +/- 0.13 gm/dl, respectively). Mean +/- SE prostate specific antigen increased from baseline to 24 weeks (1.0 +/- 0.08 to 1.3 +/- 0.10 ng/ml). No prostate cancer or gynecomastia was observed during this 24-week study. CONCLUSIONS This 24-week clinical study demonstrated that 750 mg testosterone undecanoate depot injection administered intramuscularly at 0, 4 and 14 weeks achieves serum testosterone levels in the normal range during a 10-week dosing interval.

Functional striated sphincter component at the bladder neck: clinical implications.

Anatomical proximal extension of the striated urethral sphincter muscle towards the bladder neck was assessed functionally in normal male subjects and in patients with upper motor neuron lesions. Synchronous cystosphincterometric studies were performed and urethral pressure responses were studied (contraction complexes) at the vesicourethral junction, the supramontane prostatic urethra and the membranous urethra to repeated bulbocavernosus stimuli. All subjects demonstrated positive responses at the membranous urethra. Contraction complexes with amplitudes of less magnitude were elicited at the vesicourethral junction and at the supramontane prostatic urethra in 48 and 71 per cent of the total number of subjects, respectively. The functional significance of the striated muscle component at the bladder neck in patients with detrusor-striated sphincter dyssynergia is described.

Urodynamics in stress urinary incontinence.

Stress urinary incontinence was evaluated urodynamically in 86 women in private urologic practice. While 31 patients had failed prior surgical repairs and 58 patients (67.4 per cent) reported irritative symptoms of frequency, nocturia, urgency and urge incontinence unstable bladders were found in only 5 women (5.8 per cent) over-all, in 6.5 per cent of those patients failing a previous operation and in 8.6 per cent of those patients with irritative symptoms. Urethral pressure profiles were decreased mildly in patients with, compared to those without, stress urinary incontinence but considerable overlap existed and no improvement was seen in 20 patients cured with an operation. Excretory urography, post-voiding residual urine volumes and sphincter electromyography usually were normal. Women with stress urinary incontinence consistently showed poor transmission of cough to the urethra so that the intravesical pressure exceeded the intraurethral pressure.

Operative management of stress urinary incontinence.

A total of 132 women with stress urinary incontinence underwent thorough radiographic and urodynamic evaluation in private urologic practice. With heavy reliance on the readily available technique of bead-chain cystography to differentiate between types I and II abnormalities, and to demonstrate the extent of bladder neck descent, the surgical success rates were 95.8 per cent over-all and 97.3 per cent using the Marshall-Marchetti-Krantz procedure. Postoperative complications were minimal and infrequent except for urinary retention in 31.7 per cent, which was managed easily by intermittent self-catheterization that allowed early hospital discharge without an indwelling catheter.

One‐Year Efficacy and Safety Study of a 1.62% Testosterone Gel in Hypogonadal Men: Results of a 182‐Day Open‐Label Extension of a 6‐Month Double‐Blind Study

INTRODUCTION A new formulation of testosterone gel (1.62% testosterone gel) with increased viscosity and reduced volume of application has been shown to be safe and efficacious after 182 days of use in a phase 3, double-blind study in adult hypogonadal males. AIM The objective of this study was to evaluate the efficacy and safety of the 1.62% testosterone gel after daily application to the skin in a 182-day (6-month) open-label extension of the initial 182-day double-blind study. METHODS One hundred and sixty-three subjects, aged 26 to 77 years, continued on active (Continuing Active subjects) 1.62% testosterone gel for the remainder of the study (364 days total). In 28 subjects who had previously received placebo (Formerly Placebo subjects), the dose was titrated to normal levels of serum total testosterone (300-1,000 ng/dL). Dose adjustments for both groups were allowed at specific visits to maintain serum testosterone within a normal range. MAIN OUTCOME MEASURE The main outcome measure was the percentage of subjects with serum total testosterone average concentrations (C(av) ) within the normal range at day 364. RESULTS On day 364, 77.9% (95% confidence interval: 70.0, 84.6) of the Continuing Active subjects and 87.0% (66.4, 97.2) of the Formerly Placebo subjects had C(av) values within the eugonadal range. The 1.62% testosterone gel was safe and well tolerated in this study. CONCLUSION Treatment with 1.62% testosterone gel for up to 1 year (182 days for the Formerly Placebo subjects, 364 days for the Continuing Active subjects) was safe and efficacious, resulting in >77% of treated subjects achieving normal serum testosterone levels at final visit.

ORIGINAL RESEARCH—SURGERY: Cylinder Aneurysm of Parylene‐Coated American Medical System (AMS) 700CX Penile Prosthesis

INTRODUCTION Cylinder aneurysms and leakages are uncommon with three-layered American Medical System (AMS) CX cylinders. Since 2001, an additional parylene coating improves cylinder wear. AIM To report two patients in whom major cylinder aneurysms developed less than 4 years after implantation. METHODS Two patients in separate urologic private practices developed significant cylinder aneurysms requiring reoperation. RESULTS Both patients developed aneurysms in 21-cm parylene-coated CX cylinders just short of 4 years of inflatable penile prosthesis (IPP) placement. Both did well after the explantation and insertion of Coloplast Titan IPP (Coloplast; Minneapolis, MN, USA). CONCLUSION Longer AMS CX IPP cylinders may develop aneurysms more than 3 years after insertion.