This Month in Clinical Urology

Article Outline

• Antifibrinolytic Agents and Bacillus Calmette-Guerin for Superficial Bladder Cancer
• Papaverine Hydrochloride for the Treatment of Renal Colic
• Terazosin for Female Lower Urinary Tract Symptoms
• Incidence and Predictors of Urinary Incontinence in Older Adults
• Buccal Mucosa vs Acellular Bladder Matrix Grafts for Complex Anterior Urethral Strictures
• Urodynamic Measures Do Not Always Predict Stress Continence Outcomes After Surgery
• Asymptomatic Men With Testicular Microlithiasis
• Radical Retropubic Prostatectomy in Immunosuppressed Transplant Recipients
• Use of Sevelamer Hydrochloride as an Oxalate Binder
• Questionnaire Versus Pedigree Analysis for Genetic Risk Assessment for Infertility
• Copyright

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Antifibrinolytic Agents and Bacillus Calmette-Guerin for Superficial Bladder Cancer 

It is appreciated that 20% to 50% of patients who receive intravesical bacillus Calmette-Guerin (BCG) for superficial transitional cell carcinoma of the bladder are still at risk for recurrent tumors. In some of these patients disease even progresses to muscle invasive bladder cancer. The first requisite step to initiate the antitumor effect of BCG is the attachment of the BCG organisms to the extracellular matrix, particularly fibronectin, at sites of urothelial disruption. This process directly correlates with antitumor activity. Pan et al (page 1307) from Shanghai present intriguing pilot data on patients, based on preliminary data on animals, that co-administration of para-aminomethyl benzoic acid or epsilon aminocaproic acid plus BCG increased the probability of a recurrence-free state. This observation even held true at reduced doses of BCG. Although serious adverse effects were low overall, and even lower in the group treated with antifibrinolytic agents, they failed to attain statistical significance. It is important to note that the majority of patients in the study were in the low risk category. The results warrant further evaluation of the potential of antifibrinolytic agent co-therapy with BCG for bladder cancer.

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Papaverine Hydrochloride for the Treatment of Renal Colic 

Papaverine hydrochloride is a nonselective phosphodiesterase (PDE) inhibitor known to possess direct relaxant effects on smooth muscle. Unbeknownst to many clinicians renal colic is a registered indication for the use of this agent, yet studies evaluating its efficacy are lacking. Snir et al (page 1411) from Tel Aviv performed a prospective single-blind comparative trial of 86 patients with acute renal colic. The patients were randomized to receive either 120 mg papaverine hydrochloride, 75 mg sodium diclofenac or a combination of both drugs. Papaverine was as effective as sodium diclofenac in relieving pain within a 20 to 30-minute period. However, further analgesia was required in the papaverine group due to its shorter drug half-life. This study suggests that in patients who are poor candidates for nonsteroidal anti-inflammatory drugs (ulcer disease, reduced renal function) papaverine might work just as well to relieve renal pain. Results with this nonselective PDE inhibitor raise the intriguing possibility that selective PDE inhibitors targeting PDE 1, 2, 4 and 5 that are expressed by ureteral and renal pelvic smooth muscle would exert a similar effect. It would be particularly interesting to know if PGE-5 inhibitors used to treat erectile dysfunction, lower urinary tract symptoms of benign prostatic hyperplasia and nonurological disorders could possess a similar effect to reduce renal colic.

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Terazosin for Female Lower Urinary Tract Symptoms 

Use of α-1 adrenergic antagonists to treat lower urinary tract symptoms in women remains controversial. Low et al (page 1461) from Penang, Malaysia performed a randomized, double-blind, placebo controlled study of terazosin during a 14-week period in 100 women with an International Prostate Symptom Score (I-PSS) score of 8. The end point was reduction in the I-PSS Quality of Life (QOL) score to 2 or less. The secondary end point was reduction of I-PSS score to 7 or less at the end of treatment. In per-protocol and intent to treat analyses the authors showed that terazosin was more effective than placebo in women with lower urinary tract symptoms, with reduction in the I-PSS QOL assessment index. It should be noted that the specific symptoms of “urinary frequency” and “straining to urinate” were especially relieved by terazosin. In the absence of urodynamic studies it is difficult to determine the mechanism of this effect.

Other studies performed more than a decade ago in men in whom symptom relief was seen but whose flow rates were unchanged on terazosin suggested that alpha-adrenergic blockers may work at sites other than the bladder outlet to achieve reduction in symptoms. Furthermore, although the frequency of urination was reduced, a 2 mg dose of terazosin twice daily may be insufficient for significant action at all α-1 adrenergic receptors. The results of this study should stimulate investigators to study potential mechanisms of action of alpha-adrenergic blockers for lower urinary tract symptoms in women, including other alpha-adrenergic antagonists currently in use.

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Incidence and Predictors of Urinary Incontinence in Older Adults 

Examination of risk factors may provide insights into the pathophysiology and thereby lead to preventive strategies. Most epidemiological data regarding risk factors for urinary incontinence are derived from cross-sectional studies examining prevalence rather than longitudinal studies which can establish temporal relationships. Goode et al (page 1449) from Birmingham, Alabama present the results of the University of Alabama-Birmingham’s Study of Aging, which examined the potential risk factors associated with the development of incontinence during a 3-year period. Urinary incontinence data were derived from trained interviewers using a structured questionnaire. Patients were asked if they leaked even a small amount of urine during the previous 6 months. Incontinence was defined only if they reported urinary leakage at least once a month. Data were obtained from 490 women and 496 men.

Of the women 41% at baseline noted urinary incontinence compared to 27% of men. The overall incidence of new incontinence during the 3-year period was 29% in women and 24% in men. Just as important, the remission rates in 3 years were 39% for women and 55% for men. Factors predictive of incontinence in women during the study period included a history of stroke, postmenopausal estrogen use, fecal incontinence, urinary incontinence less frequent than monthly and high geriatric depression scores. Factors predictive of urinary incontinence in men during the study period included falls, poor vision, poor concentration, incontinence less frequent than monthly and high geriatric depression scores. The study continues to add to the evidence that depression is highly associated with urinary incontinence. Evidence on the effect of hormone replacement therapy on incontinence is also becoming stronger. This study suggests that there may be modifiable risk factors that can be addressed to reduce the incidence of urinary incontinence in older women.

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Buccal Mucosa vs Acellular Bladder Matrix Grafts for Complex Anterior Urethral Strictures 

Prospective randomized trials in reconstructive surgery are rare. Buccal mucosa has been widely accepted as the standard for graft procedures to treat anterior urethral strictures. El Kassaby et al (page 1432) from Egypt and North Carolina compared acellular bladder matrix to buccal mucosa in a prospective, randomized study. Thirty patients were enrolled in the study, and assessed postoperatively with ascending and voiding urethrography and uroflow rates 3 months after repair, every 3 months for the first year and every 6 months for the second year. Patients were followed for 32 months with a mean followup of 25 months. Outcomes with human acellular bladder matrix from cadaveric donors were similar to buccal mucosa except in patients who were preoperatively determined to have an unhealthy urethral bed due to multiple prior operations. The authors conclude that acellular bladder matrix is a viable “off-the-shelf” option. Unfortunately this small study is not powered to detect significant differences and followup is still short (less than 5 years). Future randomized studies to evaluate procedures, materials for urethral stricture disease and surgical experience are desperately needed.

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Urodynamic Measures Do Not Always Predict Stress Continence Outcomes After Surgery 

Several guidelines state that urodynamics are optional for the evaluation of stress urinary incontinence. However, most experts agree that in certain patients urodynamic studies provide valuable insights. Some specialty societies advocate routine use of urodynamics. Nager et al (page 1470) report results of the UITN (Urinary Incontinence Treatment Network) SISTEr (Stress Incontinence Surgical Treatment Efficacy) trial showing that urodynamics failed to predict overall stress incontinence cures in women undergoing either a Burch colposuspension or a pubovaginal fascial sling procedure. However, we must recognize that the patients potentially most able to benefit from urodynamic evaluation such as those with increased residual urine, neurological disorders or multiple previous surgeries were either not included in the trial or only small numbers were evaluated. This study is the largest report to evaluate the usefulness of urodynamics in predicting outcomes of stress incontinence surgery. Although these conclusions cannot be extrapolated to other surgical approaches, the results will fuel the debate of who tends to benefit from expensive and invasive testing before surgical correction of stress urinary incontinence.

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Asymptomatic Men With Testicular Microlithiasis 

Testicular microlithiasis has been regarded as a risk factor for development of testicular carcinoma. In 2000 the Madigan Army Medical Center conducted a large screening of 1,504 men, of whom 84 (5.6%) had testicular microlithiasis. At 2-year followup 63 of the 84 men had no evidence of testicular cancer or scrotal masses.

DeCastro et al (page 1420) from the same medical center now present followup results of the 63 men 5 years later in regard to the development of testicular cancer. Only 1 of the 63 men was diagnosed with testicular cancer. Based on this solitary case in their cohort, the authors calculate the odds of cancer in asymptomatic healthy men with testicular microlithiasis to be 317 (95% confidence interval 36–2,756) compared to the general population. The development of testicular cancer in a single subject did imply an increased risk in men with testicular microlithiasis compared to the general population, in which the incidence is 5.3/100,000 men. The authors argue that despite these findings all young men do not warrant routine sonographic screening since testicular carcinoma did not develop in 98.4% of men with testicular microlithiasis during the 5-year study period. Screening 80 million American men for this would cost $7.8 billion. Patient testicular self-examination remains the most cost-effective modality. However, men with classic testicular microlithiasis should be followed with periodic ultrasound and vigilant self-examinations.

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Radical Retropubic Prostatectomy in Immunosuppressed Transplant Recipients 

Management of localized prostate cancer in patients undergoing renal transplantation is problematic. External beam radiation therapy could put the renal allograft at risk for radiation fibrosis or lead to ureteral stenosis. Furthermore, immunosuppression associated with organ transplantation may lead to higher rates of malignancies such as prostate cancer. Thus, it is of interest to examine the outcomes of renal and nonrenal transplant patients undergoing surgical management of prostate cancer. Thompson et al (page 1349) from Rochester, Minnesota present a retrospective analysis of 17 patients who underwent organ transplantation followed by radical retropubic prostatectomy between 1988 and 2005 compared to 7,178 nontransplant patients treated with radical retropubic prostatectomy between 1994 and 2005. Surgical technique was relatively similar. However, in the renal transplant cases there was a tendency to avoid ipsilateral pelvic lymph node dissection.

Postoperative wound infection rates were higher in the 17 renal, heart and lung transplant cases (11.8%) versus the nontransplant cases (2.4%). Myocardial infarction (5.9% versus 0.1%) and hematoma (5.9% versus 1.1%) were more common in the post-transplant compared to the nontransplant cases, respectively. Median followup was 4.9 years during which biochemical recurrence developed in only 1 case. However, 4 patients died of nonprostate cancer related causes at a mean of 3.8 years after prostatectomy. This series raises the issue of potentially higher morbidity and a somewhat lower life expectancy in patients treated with prostatectomy after organ transplantation. However the small number of transplant patients was insufficient to reach statistical validity. Given these findings, examination of a national database may provide more robust data for counseling patients with localized prostate cancer on the best approach to management with active surveillance, radiation or surgery.

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Use of Sevelamer Hydrochloride as an Oxalate Binder 

The management of enteric hyperoxaluria leading to recurrent nephrolithiasis is a significant challenge. Sevelamer hydrochloride is a cationic nonabsorbable polymer used in end stage renal disease as a phosphate binder. It may also be useful to bind oxalate, to absorb bile acids and to bind phosphate-free additional enteric calcium to act as an oxalate binder. Lieske et al (page 1407) from Rochester, Minnesota conducted an open label pilot study of patients with enteric hyperoxaluria to determine whether this agent would be of use in reducing urinary oxalate. A 24-hour urine concentration of oxalate was collected. Patients served as their own controls. After a week of sevelamer hydrochloride 24-hour urine concentration was again collected and urinary oxalate decreased by only 17% compared to pretreatment levels. Urinary calcium increased by 25%, urinary citrate decreased by 23% and urinary phosphorus decreased by 44%. The authors conclude that sevelamer hydrochloride is not an ideal agent for correcting hyperoxaluria. The study raises the issue of whether the drug may be useful for treating calcium phosphate stones. A significant warning accompanies the study, however, in that serum phosphate also decreased. The safety of this approach would need to be determined by long-term trials with careful attention to phosphorus homeostasis. The investigators also note that lack of a rigorously controlled diet in the clinical setting was a weakness of this study.

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Questionnaire Versus Pedigree Analysis for Genetic Risk Assessment for Infertility 

Because a significant proportion of male infertility arises from an underlying genetic component, medical and family history is a key component of an infertility evaluation. A comprehensive family history can reveal genetic etiologies of infertility and indicate possible inherited risks for offspring. Danziger Kaplan et al (page 1499) from San Francisco, California compared the use of a genetic questionnaire to a rigorous 4-generation pedigree constructed by board certified genetic counselors in men with either oligospermia or azoospermia. The questionnaire was based on standard questions from the American College of Obstetrics and Gynecology prenatal genetic screening tool. Of the patients 80% failed to report significant family history on the questionnaire that was obtained by the genetic pedigree. In particular, the routine questionnaires documented fewer than 25% of recurrent miscarriages, stillborn births, heart defects, birth defects and developmental disability issues. The sensitivity of the questionnaire for listing these 5 family history elements was low, suggesting that the authors’ questionnaire failed to capture the majority of the family history information revealed by the pedigree. This study has significant implications for the evaluation of the infertile male. It demonstrates that at this time questionnaires cannot supplant a detailed pedigree analysis by qualified examiners. The authors acknowledge that the questionnaire was administered first, which may have introduced a recall bias favoring the pedigree analysis. However, the discordance was so high that it suggests the need to be careful when using questionnaires to obtain family genetic history.