This Month in Adult Urology

FitzGerald et al (page 2113) report the results of this randomized multicenter trial to determine the efficacy and safety of myofascial pelvic floor therapy. A total of 81 women were randomized to receive either the specific myofascial physical therapy or a nonspecific global therapeutic massage to see which ameliorated the symptoms of interstitial cystitis. The primary outcome measure was the proportion of moderately or markedly improved overall symptoms compared to a baseline 7-point Global Response Assessment. The secondary outcomes included the O'Leary-Sant IC Symptom and Problem Index and reports of adverse events. The efficacy of moderately or markedly improved overall symptoms was 59% in the myofascial physical therapy group vs only 26% in the global therapeutic massage group. Since a significantly higher proportion of women with interstitial cystitis responded to myofascial physical therapy, the authors suggest this therapy may be a beneficial for this syndrome.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

This Month in Pediatric Urology

There has been an increase in the incidence of urolithiasis in children, the reasons for which are likely multifactorial, although some have attributed the upsurge to diet and obesity. Gabrielsen et al (page 2182) from Salt Lake City, Utah analyzed the stone composition data submitted to a large national reference laboratory during the last decade. Information was available on more than 5,000 stones submitted for analysis from patients 1 to 18 years old. Calcium containing stones represented almost 90% of all specimens. There has been an increase in the percentage of stones containing calcium oxalate, whereas the incidence of stones with magnesium phosphate and urate containing stones has decreased. The authors did not identify any difference in stone composition by geographic location but there were differences based on gender and age. Uric acid stones were more common in males and younger girls were more prone to have calcium phosphate stones, although calcium oxalate was predominant in both populations. Further studies are needed to determine the etiology for these differences in stone composition.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

This Month in Investigative Urology

Collagenase Clostridium histolyticum (CCh) is a purified mix of 2 collagenases that has demonstrated safety and efficacy in patients with Peyronie disease (PD) in early clinical studies. In a phase 2b, double-blind, randomized, placebo controlled study Gelbard et al (page 2268) from Burbank, California determined the safety and efficacy of CCh, and assessed a patient reported outcome (PD-PRO) questionnaire. The study included 147 subjects randomized into 4 groups to receive CCh or placebo (3:1) with or without penile plaque modeling (1:1). Two injections of CCh (0.58 mg) were given per treatment cycle 24 to 72 hours apart, and subjects received up to 3 cycles with 6 weeks between cycles. Investigator modeling was performed 24 to 72 hours after the second injection of each cycle. Study assessments included evaluation of penile curvature, PD-PRO responses and adverse event profiles.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Best in Class

Reviewing for any journal is a time-consuming and challenging endeavor. Some reviewers consider it an honor, others a chore or inconvenience. Becoming an outstanding reviewer takes training and practice often through participation in journal clubs as a resident or through mimicking mentors, especially during fellowship training. One can be taught to be a reviewer. Therefore along with my Associate Editors and staff, for years we have offered courses at AUA Section and international meetings on how to review manuscripts. As a minor benefit, I write personal letters on behalf of our reviewers at the time of their academic promotions, citing the quality and timeliness of their work and supporting their national and international stature in the field by virtue of reviewing for a top journal in their specialty.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

The Quest for the Perfect Prostate Biopsy Continues

Until well into the 1980s, biopsy of the prostate often relied on a few cores using a device such as the Vim-Silverman needle digitally guided transperineally or transrectally into a palpably abnormal prostate. In this pre-prostate specific antigen (PSA) era prostate cancers were often detected at an advanced clinical stage. The modern era of prostate biopsy was ushered in during the late 1980s with the development of the spring loaded biopsy needle and the transrectal ultrasound (TRUS) probe. Since that time the state of the art has evolved from the TRUS directed biopsy of suspicious lesions to the sextant and now extended 10 to 12-core biopsy schema using local anesthesia. The decision to perform prostate biopsy today is often based on the interpretation of changes in serum PSA leading to cancer detection in palpably normal prostate glands.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Intermittent Androgen Suppression—Ready for Prime Time?

Canadian prostate cancer researchers have led the field of androgen withdrawal therapy for many years, “boxing above their weight class,” from Nobel prize winner (Halifax born) Charles Huggins in 1940 to Nicholas Bruchovsky's Vancouver team's preclinical and clinical work on intermittent therapy in the early 1990s.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Identifying Biomarkers for Interstitial Cystitis/Bladder Pain Syndrome

A syndrome is a collection of symptoms and/or signs. A person either has them or does not. Therefore, we do not need biomarkers to tell us whether or not a patient has interstitial cystitis/bladder pain syndrome (IC/BPS). On the other hand, we do need biomarkers for research and also for the practical clinical uses discussed below.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

The Role of Uroflowmetry in the Diagnosis of Lower Urinary Tract Disorders in Children

The evaluation, diagnosis and management of functional lower urinary tract disorders in children are time-consuming, tedious and often frustrating for pediatric urologists. Patients present with a constellation of lower urinary tract symptoms such as urgency, frequency, incontinence and dysuria, with or without bona fide evidence of urinary tract infection. Bowel dysfunction is often an additional feature. Although there are some standardized and validated scores to aid in the diagnosis and quantification of the problem, the clinician is usually left to empirically try a variety of pharmacological and behavioral interventions. Patients in whom this approach fails then undergo a series of investigations with an increasing degree of invasiveness, from uroflowmetry and urodynamics to videourodynamics, then spinal magnetic resonance imaging and, in some cases, endoscopy. It would be great if there were a simple, noninvasive investigation that could help diagnose and direct therapy in these challenging cases.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Pro

Urgency urinary incontinence is a symptom of the overactive bladder (OAB) syndrome, although detrusor overactivity (DO) does not occur in all patients with OAB. Acetylcholine is the primary contractile neurotransmitter in the human detrusor. Antimuscarinics are the mainstay of oral OAB treatment, affecting OAB/DO by inhibiting the binding of acetylcholine at muscarinic receptors M2 and M3 which are present on different structures in the bladder wall. One can assume from this method of action that results and side effects will depend on the dosage of antimuscarinic.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Con

Antimuscarinic medications are a cornerstone of treatment for urge urinary incontinence. Clinical trials have demonstrated a clear benefit of these agents over placebo in reducing urge incontinence episodes with cure/improved rates of 50% to 60%. A contrarian may look at these results and point out that 40% to 50% of well chosen and motivated clinical trial subjects will not observe a benefit from treatment. Furthermore, multiple studies have demonstrated that patient compliance with medications over time is poor, with as many as 85% discontinuing treatment after 12 months. The most common reasons for medication discontinuation are lack of efficacy and the presence of intolerable side effects. Therefore, there exists a large population of individuals with urge urinary incontinence in which antimuscarinic medications have proven to be inadequate treatment. Fortunately, a number of therapies exist which have demonstrated efficacy in these refractory patients.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Outcomes of Pregnancy Following Surgery for Stress Urinary Incontinence: A Systematic Review

Purpose: Although few data have been published on the safety of childbearing after surgery for stress urinary incontinence, a large proportion of physicians recommend that women wait to complete childbearing before pursuing surgical treatment for stress urinary incontinence. We systematically reviewed the available literature to examine the safety of pregnancy after stress urinary incontinence surgery, and to measure the effect of such pregnancy on continence outcomes. Materials and Methods: The review was conducted according to the recommendations of the MOOSE (Meta-Analysis of Observational Studies in Epidemiology) group. We performed a systematic review to identify articles published before January 2011 on pregnancy after incontinence surgery. Databases searched include PubMed®, EMBASE® and the Cochrane Review. Our literature search identified 592 titles, of which 20 articles were ultimately included in the review. Results: Data were tabulated from case reports, case series and physician surveys. The final analysis in each category included 32, 19 and 67 patients, respectively. Urinary retention developed during pregnancy in 2 women, 1 of whom was treated with a sling takedown and the other with intermittent catheterization. Of these 2 women 1 also had an episode of pyelonephritis during pregnancy, possibly related to the intermittent catheterization. The incidence of postpartum stress urinary incontinence ranged from 5% to 18% after cesarean delivery and from 20% to 30% after vaginal delivery. Conclusions: Although the data on outcomes in the literature are limited and further studies need to be performed on the subject, the current data suggests that any increase in risks for pregnancy after surgery for stress incontinence may be small. A low risk of urinary retention during pregnancy may exist. Although some data suggest that cesarean deliveries may result in a lower rate of recurrent stress urinary incontinence than vaginal deliveries, a formal analysis could not be performed with the available data.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Conflict of Interest in Urology

Purpose: We provide an overview of the current landscape of conflicts of interest relevant to urology practitioners and researchers. Materials and Methods: We conducted an extensive literature review to gather data to define the current state of conflicts of interest in the urological community and beyond. Results: In this work we examine the history and emergence of conflicts of interest in the public forum. In addition, we elucidate and define the types of conflicts of interest that exist. We examine the effects of conflicts of interest on practice patterns and on peer reviewed literature. We outline the current conflict of interest policies that exist. Finally, we discuss future trends in the management of conflicts of interest that will be important in the urological community. Conclusions: Conflicts of interest in the field of urology are prevalent and are becoming increasingly important to manage.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

The Association of the Human Development Index With Global Kidney Cancer Incidence and Mortality

Purpose: We describe contemporary worldwide age standardized incidence and mortality rates for kidney cancer, and their association with social and economic development metrics. Materials and Methods: We obtained gender specific, age standardized incidence and mortality rates for 184 countries and 16 major world regions from the GLOBOCAN 2008 database. We compared the mortality-to-incidence ratio on the national and regional levels in males and females, and assessed the association with the development level of each country using the United Nations Human Development Index. Results: The age standardized incidence rate varied twentyfold worldwide with the highest rate in North America, and the lowest in Africa and South Central Asia (11.8 vs 1.2 and 1.0/100,000 individuals, respectively). The geographic distribution of the age standardized mortality rate was similar to that of the age standardized incidence rate with the highest rates in Europe and North America (3.1 and 2.6/100,000 individuals, respectively) and the lowest rates in Asian and African regions (0.6 to 1.5). Age standardized incidence and mortality rates were 4.5 and 2.8 times higher, respectively, in more developed countries than in developing countries. However, the mortality-to-incidence ratio was highest in Africa and Asia, and lowest in North America (0.6 to 0.8 vs 0.2/100,000 individuals). There was a strong inverse relationship between the Human Development Index and the mortality-to-incidence ratio (regression coefficient −0.79, p <0.0001). Conclusions: Kidney cancer incidence and mortality rates vary widely throughout the world while the mortality-to-incidence ratio is highest in less developed nations. These observations suggest significant health care disparities and may reflect differences in risk factors, health care access, quality of care, diagnostic modalities and treatment options available. Future research should assess whether the mortality-to-incidence ratio decreases with increasing development.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Volume-Outcome Relationships in the Treatment of Renal Tumors

Purpose: Outcomes of complex surgical procedures tend to be better for high volume providers, although this has not been clearly established for renal cell carcinoma. We determined the relationship of provider volume with partial nephrectomy and morbidity for renal cell carcinoma treatment. Materials and Methods: We performed a population based, observational study using data on 24,579 patients treated surgically for a renal mass from April 1998 to March 2008. Surgeon and hospital volume quartiles were created using the total number of nephrectomies during the 10-year observation period. The effect of provider volume on partial nephrectomy use, complications and mortality was determined by multivariable logistic regression adjusted for covariates. Results: Partial nephrectomy was done by 10.9% of low vs 24.7% of very high volume surgeons (p <0.0001). A modest decrease in complications was observed with increasing surgeon volume (low vs very high 37.6% vs 34.5%, p <0.0001). The effect of in-hospital mortality was more dramatic with a 1.71%, 1.20%, 0.97% and 0.92% rate for low, intermediate, high and very high volume surgeons, respectively (p <0.0001). After adjusting for covariates, compared to low volume surgeons patients treated by very high volume surgeons had 1.54 times the odds of undergoing partial nephrectomy (95% CI 1.37–1.72, p <0.0001), 0.84 times the odds of an in-hospital complication (95% CI 0.77–0.92, p <0.0001) and 0.69 times the odds of in-hospital death (95% CI 0.47–1.01, p = 0.16). Conclusions: Higher volume surgeons perform partial nephrectomy more often, show a lower complication rate and may have a lower in-hospital mortality rate than lower volume surgeons.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Urological Laparoendoscopic Single Site Surgery: Multi-Institutional Analysis of Risk Factors for Conversion and Postoperative Complications

Purpose: We analyzed the incidence of and risk factors for complications and conversions in a large contemporary series of patients treated with urological laparoendoscopic single site surgery. Materials and Methods: The study cohort consisted of consecutive patients treated with laparoendoscopic single site surgery between August 2007 and December 2010 at a total of 21 institutions. A logistic regression model was used to analyze the risks of conversion, and of any grade and only high grade postoperative complications. Results: Included in analysis were 1,163 cases. Intraoperatively complications occurred in 3.3% of cases. The overall conversion rate was 19.6% with 14.6%, 4% and 1.1% of procedures converted to reduced port laparoscopy, conventional laparoscopic/robotic surgery and open surgery, respectively. On multivariable analysis the factors significantly associated with the risk of conversion were oncological surgical indication (p = 0.02), pelvic surgery (p <0.001), robotic approach (p <0.001), high difficulty score (p = 0.004), extended operative time (p = 0.03) and an intraoperative complication (p = 0.001). A total of 120 postoperative complications occurred in 109 patients (9.4%) with major complications in only 2.4% of the entire cohort. Reconstructive procedure (p = 0.03), high difficulty score (p = 0.002) and extended operative time (p = 0.02) predicted high grade complications. Conclusions: Urological laparoendoscopic single site surgery can be done with a low complication rate, resembling that in laparoscopic series. The conversion rate suggests that early adopters of the technique have adhered to the principles of careful patient selection and safety. Besides facilitating future comparisons across institutions, this analysis can be useful to counsel patients on the current risks of urological laparoendoscopic single site surgery.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Is There a Financial Disincentive to Perform Partial Nephrectomy?

Purpose: Despite the explicit endorsement of the American Urological Association guidelines of partial nephrectomy as the treatment of choice for T1a renal cell carcinoma, a considerable underuse of nephron sparing surgery characterizes general practice patterns in the United States. We explored possible financial disincentives associated with partial nephrectomy that may contribute to this important quality of care deficit. Materials and Methods: A PubMed® query on perioperative outcomes identified 10 series on open or laparoscopic radical nephrectomy and 16 on open, laparoscopic or robot-assisted partial nephrectomy. Mean operative time and hospital length of stay were calculated for each group. Using these data in conjunction with Health Care Financing Administration data on physician work time, which guides the current Resource-Based Relative Value Scale Medicare fee schedule, we calculated global physician time expenditure and hourly Medicare reimbursement rates for each of these 5 surgical services. Results: Mean ± SD operative time for open and laparoscopic radical nephrectomy, and open, laparoscopic and robot-assisted partial nephrectomy was 180.7 ± 24.7 minutes (95% CI 119.3–242.0) in 3 studies, 178.8 ± 16.5 (95% CI 163.5–194.1) in 7, 226.0 ± 36.9 (95% CI 187.2–264.8) in 6, 227.9 ± 40.2 (95% CI 185.8–270.1) in 6 and 227.9 ± 37.8 (95% CI 167.7–288.1) in 4, respectively (p = 0.028). Mean length of stay (days) after open and laparoscopic radical nephrectomy, and open, laparoscopic and robot-assisted partial nephrectomy was 5.8 ± 0.7 days (95% CI 4.0–7.7) in 3 studies, 2.5 ± 1.1 (95% CI 1.4–3.6) in 6, 5.8 ± 0.4 (95% CI 5.3–6.2) in 5, 2.9 ± 0.3 (95% CI 2.6–3.3) in 6 and 2.8 ± 1.0 (95% CI 1.2–4.4) in 4, respectively (p <0.001). The hourly reimbursement rate was calculated at $200.61, $242.03, $185.66, $231.27 and $231.97 for open and laparoscopic radical nephrectomy, and open, laparoscopic and robot-assisted partial nephrectomy, respectively. Hence, open partial nephrectomy emerged as the lowest paying of these procedures. Conclusions: Inferior compensation for open partial nephrectomy relative to that of laparoscopic or open radical nephrectomy may impede the dissemination of nephron sparing surgery for small renal masses. This may occur particularly in a general practice setting, where the expertise required for laparoscopic or robot-assisted partial nephrectomy may be lacking. We propose rectifying this inequity to facilitate wider use of nephron sparing surgery in the clinically appropriate setting.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Perioperative Outcomes of Robotic and Open Partial Nephrectomy for Moderately and Highly Complex Renal Lesions

Purpose: We compared outcomes in patients undergoing robotic vs open partial nephrectomy stratified by moderately and highly complex tumor nephrometry scores. Materials and Methods: Patients treated with partial nephrectomy from 2007 to 2010 were grouped by tumor characteristics into low—nephrotomy score 4 to 6, moderate—7 to 9 and high—10 to 12 anatomical complexity cohorts. Lesions with low complexity were excluded from study. Demographic, surgical and pathological outcomes were compared between patients undergoing robotic vs open partial nephrectomy in the moderately and highly complex cohorts. Results: A total of 281 patients, of whom 63.3% were male, with a mean ± SD age of 58.1 ± 11.7 years and a mean followup of 21.3 ± 16.3 months underwent partial nephrectomy. Moderately complex lesions were noted in 81 robotic and 136 open partial nephrectomy cases with a mean tumor size of 3.8 ± 2.2 cm. Highly complex lesions were noted in 10 robotic and 54 open partial nephrectomy cases with a mean tumor size of 4.8 ± 3.0 cm. There were no differences between the groups in patient age, race, gender, body mass index or American Society of Anesthesiologists classification. Cases treated with open partial nephrectomy for moderately or highly complex lesions were of higher pathological stage (p = 0.02 and 0.01, respectively). The percent change in creatinine and the glomerular filtration rate were similar for robotic and open partial nephrectomy in the moderately and highly complex tumor groups. In patients undergoing robotic vs open partial nephrectomy for moderately complex lesions we noted differences in pathological tumor size (mean 3.2 ± 1.8 vs 4.1 ± 2.3 cm, p <0.0001) and operative time (205.9 ± 52.5 vs 189.5 ± 52.0 minutes, p <0.01) while decreased estimated blood loss (131.3 ± 127.8 vs 256.5 ± 291.3 ml) and hospital length of stay (3.7 ± 1.6 vs 5.6 ± 3.9 days, each p <0.001) were observed in the robotic group. Comparison of highly complex lesions revealed decreased hospital length of stay (2.9 ± 1.4 vs 6.1 ± 4.1days, p <0.0001) in the robotic partial nephrectomy group. Conclusions: In our large institutional series of patients with moderate and highly complex solid renal tumors classified by the nephrometry score robotic partial nephrectomy offered comparable perioperative and functional outcomes with the added benefit of decreased hospital length of stay.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Evaluation of Vitamin E and Selenium Supplementation for the Prevention of Bladder Cancer in SWOG Coordinated SELECT

Purpose: Epidemiological and biological evidence suggests a preventive effect of selenium and vitamin E on bladder cancer. We assessed the effect of selenium and/or vitamin E on bladder cancer development. Materials and Methods: This was a secondary analysis of the randomized, placebo controlled SELECT (Selenium and Vitamin E Cancer Prevention Trial), which included 34,887 men randomly assigned to 4 groups (selenium, vitamin E, selenium plus vitamin E and placebo) in double-blind fashion between August 22, 2001 and June 24, 2004. The primary end point was bladder cancer incidence, as determined by routine clinical management. Results: During a median followup of 7.1 years (IQR 6.4–8.0) 224 bladder cancer cases were recorded. Patients with bladder cancer were older, and more likely to be white and have a smoking history than those without bladder cancer. Most cancers were urothelial and nonmuscle invasive. There was no significant difference in the bladder cancer incidence between the 53 men in the placebo group and the 56 in the vitamin E group (HR 1.05, IQR 0.64–1.73, p = 0.79), the 60 in the selenium group (HR 1.13, 0.70–1.84, p = 0.52) or the 55 in the vitamin E plus selenium group (HR 1.05, 0.63–1.70, p = 0.86). Conclusions: This secondary analysis showed no preventive effect of selenium or vitamin E alone or combined on bladder cancer in this population of men. Further studies are needed to assess the effect in women, and at different doses and formulations.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

The Implications of Hospital Acquired Adverse Events on Mortality, Length of Stay and Costs for Patients Undergoing Radical Cystectomy for Bladder Cancer

Purpose: The incidence of hospital acquired adverse events in radical cystectomy and their implications for hospital outcomes and costs remain poorly described. We describe the incidence of hospital acquired adverse events in radical cystectomy, and characterize its relationship with in-hospital mortality, length of stay and hospitalization costs. Materials and Methods: We identified 10,856 patients who underwent radical cystectomy for bladder cancer at 1,175 hospitals in the Nationwide Inpatient Sample from 2001 to 2008. We used hospital claims to identify adverse events for accidental puncture, decubitus ulcer, deep vein thrombosis/pulmonary embolus, methicillin-resistant Staphylococcus aureus, Clostridium difficile, surgical site infection and sepsis. Logistic regression and generalized estimating equation models were used to test the associations of hospital acquired adverse events with mortality, predicted prolonged length of stay and total hospitalization costs. Results: Hospital acquired adverse events occurred in 11.3% of all patients undergoing radical cystectomy (1,228). Adverse events were associated with a higher odds of in-hospital death (OR 8.07, p <0.001), adjusted prolonged length of stay (41.3%) and total costs ($54,242 vs $26,306; p <0.001) compared to no adverse events on multivariate analysis. The incremental total costs attributable to hospital acquired adverse events were $43.8 million. Postoperative sepsis was associated with the highest risk of mortality (OR 17.56, p <0.001), predicted prolonged length of stay (62.22%) and adjusted total cost ($79,613). Conclusions: With hospital acquired adverse events occurring in approximately 11% of radical cystectomy cases, they pose a significant risk of in-hospital mortality and higher hospitalization costs. Therefore, increased attention is needed to reduce adverse events by improving patient safety, while understanding the economic implications for tertiary referral centers with possible policy changes such as denial of payment for hospital acquired adverse events.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Learning From Our Patients: Complications and the Future of Radical Cystectomy for Bladder Cancer

The scope of minimally invasive laparoscopic and robotic techniques for urological surgery has expanded vastly during the last decade. These techniques hold the promise of applying modern surgical technology to decrease patient morbidity and improve surgical outcomes. Application of minimally invasive techniques in urology may yield the most significant clinical impact for treatment of bladder cancer by potentially decreasing the morbidity traditionally associated with radical cystectomy. Long considered the gold standard for muscle invasive bladder cancer, radical cystectomy has significant morbidity and mortality compared to other urological operations, even when performed by experienced surgeons at tertiary medical centers.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Is Ultrasound Imaging Inferior to Computed Tomography or Magnetic Resonance Imaging in Evaluating Renal Mass Size?

P. Mucksavage, P. Ramchandani, S. B. Malkowicz and T. J. Guzzo Department of Urology, University of California, Irvine School of Medicine, Orange, California

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Multilocular Cystic Renal Cell Carcinoma: Comparison of Imaging and Pathologic Findings

N. M. Hindman, M. A. Bosniak, A. B. Rosenkrantz, S. Lee-Felker and J. Melamed Department of Radiology, New York University School of Medicine, New York, New York

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Accuracy of Multi-Detector Computed Tomography (MDCT) in Staging of Renal Cell Carcinoma (RCC): Analysis of Risk Factors for Mis-Staging and its Impact on Surgical Intervention

A. S. El-Hefnawy, A. Mosbah, T. El-Diasty, M. Hassan and A. A. Shaaban Urology Department, Urology and Nephrology Center, Mansoura University, Mansoura, Egypt

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Bosniak Category IIF and III Cystic Renal Lesions: Outcomes and Associations

A. D. Smith, E. M. Remer, K. L. Cox, M. L. Lieber, B. C. Allen, S. N. Shah and B. R. Herts Section of Abdominal Imaging, Imaging Institute, Glickman Urological and Kidney Institute, and Department of Quantitative Health Sciences, Cleveland Clinic Foundation, Cleveland, Ohio, and Department of Radiology, University of Mississippi Medical Center, Jackson, Mississippi

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Large Prospective Investigation of Meat Intake, Related Mutagens, and Risk of Renal Cell Carcinoma

C. R. Daniel, A. J. Cross, B. I. Graubard, Y. Park, M. H. Ward, N. Rothman, A. R. Hollenbeck, W. H. Chow and R. Sinha Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Rockville, Maryland, AARP, Washington, D. C.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Electromotive Instillation of Mitomycin Immediately Before Transurethral Resection for Patients With Primary Urothelial Non-Muscle Invasive Bladder Cancer: A Randomised Controlled Trial

S. M. Di Stasi, M. Valenti, C. Verri, E. Liberati, A. Giurioli, G. Leprini, F. Masedu, A. R. Ricci, F. Micali and G. Vespasiani Department of Surgery/Urology, Tor Vergata University, Rome, Italy

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Phase III Study of Molecularly Targeted Adjuvant Therapy in Locally Advanced Urothelial Cancer of the Bladder Based on p53 Status

W. M. Stadler, S. P. Lerner, S. Groshen, J. P. Stein, S. R. Shi, D. Raghavan, D. Esrig, G. Steinberg, D. Wood, L. Klotz, C. Hall, D. G. Skinner and R. J. Cote University of Chicago, Chicago, Illinois

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Urinary Bladder: Normal Appearance and Mimics of Malignancy at CT Urography

A. B. Shinagare, C. A. Sadow, V. A. Sahni and S. G. Silverman Division of Abdominal Imaging and Intervention, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Bias Due to Missing SEER Data in D'Amico Risk Stratification of Prostate Cancer

Purpose: We examined the degree of exclusion bias that may occur due to missing data when grouping prostate cancer cases from the SEER (Surveillance, Epidemiology and End Results) database into D'Amico clinical risk groups. Exclusion bias may occur since D'Amico staging requires all 3 variables to be known and data may not be missing at random. Materials and Methods: From the SEER database we identified 132,606 men with incident prostate cancer from 2004 to 2006. We documented age, race, Gleason score, clinical T stage, PSA and geographic region. Men were categorized into D'Amico risk groups. Those with 1 or more unknown tumor variables (prostate specific antigen, T stage and/or Gleason score) were labeled unclassified. We compared the value of the other 2 known clinical variables for men with known vs unknown prostate specific antigen, Gleason score and T stage. Demographics were compared for those with and without missing data. Results were compared using chi-square and logistic regression. Results: Of the men 33% had 1 or more unknown tumor variables with T stage the most commonly missing variable. There was no clinically significant difference in the value of the other 2 known tumor variables when T stage or prostate specific antigen was missing. Men older than 75 years were more likely to have unknown variables than younger men. There was significant geographic variation in the frequency of unclassified D'Amico data. Conclusions: In studies in which the data set is limited to men who can be classified into a D'Amico risk group 33% of eligible patients are excluded from analysis. Such men are older and from certain SEER registries but they have tumor characteristics similar to those with complete data.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Prostate Cancer Foci Detected on Multiparametric Magnetic Resonance Imaging are Histologically Distinct From Those Not Detected

Purpose: We identified histological differences between prostate cancer foci that are detected and missed using multiparametric magnetic resonance imaging. Materials and Methods: A total of 49 patients who underwent multiparametric magnetic resonance imaging, including T2-weighted imaging, including diffusion weighted imaging and dynamic contrast enhanced imaging, before prostatectomy were enrolled in the study. One radiologist identified areas highly suspicious for tumor. One pathologist identified and categorized tumors in terms of size, Gleason score, solid tumor growth, intermixed benign glands, loose stroma, desmoplastic stroma and a high malignant epithelium-to-stroma ratio. Differences between detected and missed tumors were assessed using logistic regression analyses based on generalized estimating equations for correlated data. Results: All histological features showed significant differences between detected and missed tumors on multiparametric magnetic resonance imaging (p <0.0001). Independent predictors of detection on multivariate analysis were size (OR 5.38, p = 0.0077), Gleason score (OR 5.12, p = 0.0094) and solid growth (OR 17.83, p <0.0001). Size, Gleason score and loose stroma were significant predictors of identification with diffusion weighted imaging on univariate analysis (p ≤0.0245), while Gleason score (OR 17.05, p = 0.0212) and solid growth (OR 34.90, p = 0.0103) were independent predictors of identification with diffusion weighted imaging on multivariate analysis. Identification with T2-weighted imaging was associated with size and Gleason score (p ≤0.01876). Identification with dynamic contrast enhanced imaging was associated with intermixed benign epithelium, loose stroma and a high malignant epithelium-to-stroma ratio (p ≤0.0499). No combination of features served as independent predictors on multivariate analysis for T2-weighted imaging or dynamic contrast enhanced imaging. Conclusions: There are fundamental histological differences between detected and missed prostate tumors using magnetic resonance imaging. Insights into these differences may facilitate the prospective role of magnetic resonance imaging in counseling and treatment selection for patients with prostate cancer.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

The Impact of Real-Time Elastography Guiding a Systematic Prostate Biopsy to Improve Cancer Detection Rate: A Prospective Study of 353 Patients

Purpose: We evaluated whether real-time elastography guided biopsy improves prostate cancer detection compared to conventional systematic gray scale ultrasound guidance. Materials and Methods: A total of 353 consecutive patients suspicious for prostate cancer were prospectively randomized for real-time elastography (178) or gray scale ultrasound (175). Each patient enrolled in the study underwent a 10-core prostate biopsy. Six lateral prostate sectors (base, mid, apex) were scanned for cancer suspicious areas, defined as stiffer blue lesions using real-time elastography and hypoechoic lesions using gray scale ultrasound. Suspicious areas were sampled by a single targeted biopsy and considered representative of a defined prostate sector. If real-time elastography or gray scale ultrasound did not visualize a suspicious area in a sector, the biopsy core was taken systematically. Imaging findings were correlated with histopathological reports. Real-time elastography and gray scale ultrasound cases were compared in terms of cancer detection rate and imaging guidance accuracy. Results: Characteristics of patients undergoing real-time elastography and gray scale ultrasound, including age, prostate specific antigen, prostate volume and digital rectal examination, were not significantly different (p >0.05). Prostate cancer was detected in 160 of 353 patients (45.3%). The prostate cancer detection rate was significantly higher in patients who underwent biopsy with the real-time elastography guided approach compared to the gray scale ultrasound guided biopsy at 51.1% (91 of 178) vs 39.4% (69 of 175) (p = 0.027). Overall sensitivity and specificity to detect prostate cancer was 60.8% and 68.4% for real-time elastography vs 15% and 92.3% for gray scale ultrasound, respectively. Conclusions: Sensitivity to visualize and detect prostate cancer improved using real-time elastography in addition to gray scale ultrasound during prostate biopsy. Overall sensitivity did not reach levels to omit a systematic biopsy approach.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Accuracy of Primary Systematic Template Guided Transperineal Biopsy of the Prostate for Locating Prostate Cancer: A Comparison With Radical Prostatectomy Specimens

Purpose: We determined whether systematic template guided transperineal biopsies can accurately locate and sensitively detect prostate cancer. In addition, we reported discrepancies between diagnostic and pathological Gleason scores, and investigated whether prostate size had an effect on the cancer detection rate. Materials and Methods: This retrospective diagnostic accuracy study compares the results of primary transperineal biopsies with the radical prostatectomy pathology of 414 consecutive patients treated at a single institution between November 2002 and August 2010. Results: The average sensitivity and specificity for the detection of cancer in all prostates across all biopsy zones was 48% (95% CI 42.6–53.4) and 84.1% (95% CI 80–88.2), respectively. There was a statistically significant decrease in the sensitivity of transperineal biopsy in larger prostates (t11 = 4.687, p = 0.001). The overall Kappa value was 0.255 (95% CI 0.212–0.298). Grading concordance between biopsy and pathology specimens was achieved in 65.7% of patients. Upgrading of Gleason scores occurred in 25.6% of patients and downgrading occurred in 8.8%. Conclusions: Our current transperineal biopsy method has only demonstrated fair agreement with the histopathology findings of the corresponding radical prostatectomy specimens. This finding is most likely due to the small, multifocal nature of prostate cancer in the patient series. The cancer detection rate was lower in larger prostates. Thus, clinicians may consider increasing the number of cores in larger prostates as a strategy to improve cancer detection.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Editorial Comment

The authors have written an interesting analysis of the accuracy of template guided transperineal prostatic biopsies to diagnose men with prostate cancer. This technique should not be confused with transperineal staging biopsies, which are performed to better select patients for targeted focal therapies or active surveillance.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Reply by Authors

Rove and Crawford raise a number of issues on which we have additional information that may be of interest. We agree with the statement that “men with larger prostates should be considered candidates for increased biopsy count.” In response to the findings of this study, our institution has made adjustments to the biopsy protocol by increasing the number of biopsy cores in larger prostates (with increased sampling in the anterior/transition and lateral peripheral zones in particular).

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Core Length in Prostate Biopsy: Size Matters

Purpose: The diagnostic yield of prostate biopsy is limited. Increasing the number of cores enhances the cancer detection rate by sampling additional sites and obtaining more tissue. An alternative way to inspect more tissue would be to obtain longer cores. However, the impact of biopsy core length on cancer detection rate is an undervalued topic. We assessed the role of biopsy core length in prostate biopsy and determined the minimal tissue length to serve as quality assurance. Materials and Methods: We retrospectively analyzed the records of 331 patients who underwent transrectal ultrasound guided initial prostate biopsy with 12 to 18 cores. The biopsy procedure and pathological evaluation were standardized. Core length was compared in patients with vs without cancer. Statistical analysis was done to determine a minimally acceptable cutoff for biopsy length. Results: We analyzed data on 245 patients. The overall cancer detection rate was 30.2%. Mean core length in patients with vs without cancer was 12.3 ± 2.6 vs 11.4 ± 2.4 mm (p = 0.015). Thus, core length was significantly longer in patients with cancer. Core length greater than 11.9 mm was associated with an increased prostate cancer detection rate (OR 2.57, 95% 1.46–4.52). The cancer detection rate for cores less vs greater than 11.9 mm was 23% vs 39%. Conclusions: Needle core length is an important morphometric parameter of transrectal prostate biopsy that directly influences the cancer detection rate. Results suggest a core length of greater than 11.9 mm as a cutoff for quality assurance.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Are Repeat Prostate Biopsies Safe? A Cohort Analysis From the SEARCH Database

Purpose: Patients question whether multiple biopsy sessions cause worse prostate cancer outcomes. Therefore, we investigated whether there is an association between the number of prior biopsy sessions and biochemical recurrence after radical prostatectomy. Materials and Methods: Men in the SEARCH (Shared Equal Access Regional Cancer Hospital) database who underwent radical prostatectomy between 1988 and 2010 after a known number of prior biopsies were included in the analysis. Number of biopsy sessions (range 1 to 8) was examined as a continuous and categorical (1, 2 and 3 to 8) variable. Biochemical recurrence was defined as a prostate specific antigen greater than 0.2 ng/ml, 2 values at 0.2 ng/ml or secondary treatment for an increased prostate specific antigen. The association between number of prior biopsy sessions and biochemical recurrence was analyzed using the Cox proportional hazards model. Kaplan-Meier estimates of freedom from biochemical recurrence were compared among the groups. Results: Of the 2,739 men in the SEARCH database who met the inclusion criteria 2,251 (82%) had only 1 biopsy, 365(13%) had 2 biopsies and 123 (5%) had 3 or more biopsies. More biopsy sessions were associated with higher prostate specific antigen (p <0.001), greater prostate weight (p <0.001), lower biopsy Gleason sum (p = 0.01) and more organ confined (pT2) disease (p = 0.017). The Cox proportional hazards model demonstrated no association between number of biopsy sessions as a continuous or categorical variable and biochemical recurrence. Kaplan-Meier estimates of freedom from biochemical recurrence were similar across biopsy groups (log rank p = 0.211). Conclusions: Multiple biopsy sessions are not associated with an increased risk of biochemical recurrence in men undergoing radical prostatectomy. Multiple biopsy sessions appear to select for a low risk cohort.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Prostate Specific Antigen Levels and Prostate Cancer Detection Rates in Patients With End Stage Renal Disease

Purpose: Patients with end stage renal disease plus prostate cancer are ineligible to receive a renal transplant at most centers until an acceptable cancer-free period is demonstrated. To our knowledge previously established prostate specific antigen reference ranges have not been validated in patients with end stage renal disease. We determined age stratified 95th percentile prostate specific antigen reference ranges and the prostate cancer detection rate at specific prostate specific antigen intervals for patients with end stage renal disease. Materials and Methods: We retrospectively reviewed the records of 775 male patients with end stage renal disease on the waiting list for a renal transplant who had undergone a serum prostate specific antigen test. Prostate specific antigen was stratified by age at the time of the blood test and 95th percentile reference ranges were calculated for each decade. A total of 80 patients underwent prostate biopsy for increased prostate specific antigen and/or abnormal digital rectal examination. The cancer detection rate was calculated for specific prostate specific antigen reference ranges. Results: The age specific 95th percentile prostate specific antigen references ranges were 0 to 4.0 ng/ml for ages 40 to 49 in 137 patients, 0 to 5.3 ng/ml for ages 50 to 59 in 257, 0 to 10.5 ng/ml for ages 60 to 69 in 265 and 0 to 16.6 ng/ml for ages 70 to 79 years in 69. The cancer detection rate was 44%, 38% and 67% for prostate specific antigen 2.5 to 4.0, 4 to 10 and greater than 10 ng/ml, respectively. Conclusions: In our study population of patients with end stage renal disease age stratified prostate specific antigen was higher than in the general population. The cancer detection rate was increased in our patients with end stage renal disease compared to that in patients with normal renal function at specific prostate specific antigen intervals. Lower prostate specific antigen cutoffs may be appropriate to recommend prostate biopsy in patients with end stage renal disease.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Editorial Comment

These authors provide new, interesting information on PSA in men with ESRD who undergo PCa screening before consideration for renal transplantation. Compared to traditional reference ranges in the general population PSA in men with ESRD is higher across all age groups. This population had a high cancer detection rate since cancer was detected in 44% of men with PSA between 2.5 and 4.0 ng/ml. Similar to findings from published screening studies, these data suggest that there is no single cutoff PSA at which the risk of cancer is minimal and using a value of 2.5 ng/ml may not be appropriate. Unfortunately only 10% of the patients underwent prostate biopsy.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Reply by Author

We agree that PCa screening is a multifaceted, complex issue that urologists and policy makers such as the United States Preventive Services Task Force continue to debate. PSA screening in men with renal failure who may not have 10-year life expectancy without transplantation is even more controversial. Currently PCa screening guidelines from the American Society of Transplantation recommend that annual digital rectal examination and PSA should be offered to men awaiting renal transplantation beginning at age 50 years who have a life expectancy of at least 10 years and to younger men at high risk for PCa. However, there are unique attributes of this patient population that we believe justify PSA screening.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Posttreatment Prostate Specific Antigen Nadir Predicts Prostate Cancer Specific and All Cause Mortality

Purpose: We investigated whether the prostate specific antigen nadir predicts prostate cancer specific and all cause mortality in men treated in a randomized trial of radiation with or without 6 months of androgen deprivation therapy. Materials and Methods: The study included 204 men with cT1b-T2bN0M0 prostate adenocarcinoma and at least 1 unfavorable factor, including prostate specific antigen less than 10 to 40 ng/ml, Gleason 7 or greater, or T3 on magnetic resonance imaging. We performed Fine and Gray regression, and Cox multivariable analysis to determine whether an increasing prostate specific antigen nadir was associated with prostate cancer specific and all cause mortality, adjusting for treatment, age, Adult Comorbidity Evaluation 27 score and cancer prognostic factors. Results: At a 6.9-year median followup median prostate specific antigen nadir was 0.7 ng/ml for radiation alone and 0.1 ng/ml for radiation plus androgen deprivation therapy. The prostate specific antigen nadir (adjusted HR 1.18/ng/ml increase, 95% CI 1.07–1.31, p = 0.001) and Gleason 8 or greater (adjusted HR 8.05, 95% CI 1.01–64.05, p = 0.049) significantly predicted increased prostate cancer specific mortality. Moderate/severe comorbidity carried a decreased risk (adjusted HR 0.13, 95% CI 0.02–0.96, p = 0.045). Higher prostate specific antigen nadir (adjusted HR 1.10/ng/ml increase, 95% CI 1.04–1.17), older age (adjusted HR 1.10/year, 95% CI 1.04–1.15) and interaction between comorbidity score and randomization arm (each p <0.001) increased the all cause mortality risk. Men who achieved a prostate specific antigen nadir of the median value or less had lower estimated prostate cancer specific and all cause mortality at 7 years (3.7% vs 18.3%, p = 0.0005 and 31.5% vs 55.0%, p = 0.002). Conclusions: Posttreatment prostate specific antigen nadir is significantly associated with the risk of prostate cancer specific and all cause mortality after radiation with or without androgen deprivation therapy. A suboptimal prostate specific antigen nadir may identify candidates for earlier intervention to prolong survival.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

The FinnProstate Study VII: Intermittent Versus Continuous Androgen Deprivation in Patients With Advanced Prostate Cancer

Purpose: We conducted a randomized trial to compare intermittent and continuous androgen deprivation in patients with advanced prostate cancer. We studied time to progression, overall and prostate cancer specific survival, and time to treatment failure. Materials and Methods: Between May 1997 and February 2003, 852 men with locally advanced or metastatic prostate cancer were enrolled to receive androgen deprivation therapy for 24 weeks. Patients in whom prostate specific antigen decreased to less than 10 ng/ml, or by 50% or more if less than 20 ng/ml at baseline, were randomized to intermittent or continuous androgen deprivation. In the intermittent therapy arm androgen deprivation therapy was withdrawn and resumed again for at least 24 weeks based mainly on prostate specific antigen decrease and increase. Results: There were 298 patients who did not meet the randomization criteria. The remaining 554 patients were randomized, with 274 (49.5%) to intermittent androgen deprivation and 280 (50.5%) to the continuous androgen deprivation arm. Median followup was 65.0 months. Of these patients 392 (71%) died, including 186 (68%) in the intermittent androgen deprivation arm and 206 (74%) in the continuous androgen deprivation arm (p = 0.12). There were 248 prostate cancer deaths, comprised of 117 (43%) in the intermittent androgen deprivation and 131 (47%) in the continuous androgen deprivation arm (p = 0.29). Median times from randomization to progression were 34.5 and 30.2 months in the intermittent androgen deprivation and continuous androgen deprivation arms, respectively. Median times to death (all cause) were 45.2 and 45.7 months, to prostate cancer death 45.2 and 44.3 months, and to treatment failure 29.9 and 30.5 months, respectively. Conclusions: Intermittent androgen deprivation is a feasible, efficient and safe method to treat advanced prostate cancer compared with continuous androgen deprivation.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Pelvic Lymph Node Dissection for Prostate Cancer: Frequency and Distribution of Nodal Metastases in a Contemporary Radical Prostatectomy Series

Purpose: We determined the frequency and distribution of metastases to pelvic lymph nodes in a contemporary American radical prostatectomy series. Materials and Methods: In 642 consecutive patients with clinically localized prostate cancer treated by a single surgeon between 2002 and 2009 pelvic lymph nodes were removed and submitted to the pathologist in separate packets (external iliac, obturator and hypogastric). We assessed the total number of nodes and the number with metastases in each packet. Results: Complete pathological information was available for 427 patients, who had a median of 16 lymph nodes removed. Of the patients 35 (8.2%) had lymph node metastases, including 1.7% with low, 8.6% with intermediate and 23.9% with high risk cancer. Of those with nodal metastases 24 (69%) had positive lymph nodes in only 1 of the 3 areas, including the external iliac in 4 (11%), the obturator in 9 (26%) and the hypogastric in 11 (31%). Only 37% of the patients had positive nodes only in the external iliac area above the obturator nerve while 60% and 49% had at least 1 positive node in the obturator and the hypogastric area, respectively. Of the patients 80% had only 1 (49%) or 2 (31%) positive nodes. Conclusions: In contemporary American patients with clinically localized prostate cancer lymph node metastases were found more often and frequently exclusively in the obturator and hypogastric areas than in the external iliac area. Pelvic lymph node dissection limited to the external iliac area above the obturator nerve would identify and remove lymph node metastases in only a third of the patients with positive nodes found at full pelvic lymph node dissection.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Contemporary Open and Robotic Radical Prostatectomy Practice Patterns Among Urologists in the United States

Purpose: We describe current trends in robotic and open radical prostatectomy in the United States after examining case logs for American Board of Urology certification. Materials and Methods: American urologists submit case logs for initial board certification and recertification. We analyzed logs from 2004 to 2010 for trends and used logistic regression to assess the impact of urologist age on robotic radical prostatectomy use. Results: A total of 4,709 urologists submitted case logs for certification between 2004 and 2010. Of these logs 3,374 included 1 or more radical prostatectomy cases. Of the urologists 2,413 (72%) reported performing open radical prostatectomy only while 961 (28%) reported 1 or more robotic radical prostatectomies and 308 (9%) reported robotic radical prostatectomy only. During this 7-year period we observed a large increase in the number of urologists who performed robotic radical prostatectomy and a smaller corresponding decrease in those who performed open radical prostatectomy. Only 8% of patients were treated with robotic radical prostatectomy by urologists who were certified in 2004 while 67% underwent that procedure in 2010. Median age of urologists who exclusively performed open radical prostatectomy was 43 years (IQR 38–51) vs 41 (IQR 35–46) for those who performed only robotic radical prostatectomy. Conclusions: While the rate was not as high as the greater than 85% industry estimate, 67% of radical prostatectomies were done robotically among urologists who underwent board certification or recertification in 2010. Total radical prostatectomy volume almost doubled during the study period. These data provide nonindustry based estimates of current radical prostatectomy practice patterns and further our understanding of the evolving surgical treatment of prostate cancer.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Editorial Comment

These authors present a retrospective cohort analysis of surgical case logs for 4,709 urologists who sought certification between 2004 and 2010. This study describes the patterns of use of open prostatectomy and RP. It addresses 2 main questions, including 1) whether the proportion of urologists who perform RP has changed since the introduction of robotic technology, and 2) the influence of urologist age on robotic RP use.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Editorial Comment

These authors analyzed contemporary prostatectomy practice in the United States. Case logs submitted to the ABU from 2004 to 2010, which was a period of rapid diffusion of robotic prostatectomy, provide a unique source of descriptive data on patterns of care.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Prediction of Erectile Function Following Treatment for Prostate Cancer

M. Alemozaffar, M. M. Regan, M. R. Cooperberg, J. T. Wei, J. M. Michalski, H. M. Sandler, L. Hembroff, N. Sadetsky, C. S. Saigal, M. S. Litwin, E. Klein, A. S. Kibel, D. A. Hamstra, L. L. Pisters, D. A. Kuban, I. D. Kaplan, D. P. Wood, J. Ciezki, R. L. Dunn, P. R. Carroll and M. G. Sanda

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Prostate Cancer in the Elderly: Frequency of Advanced Disease at Presentation and Disease-Specific Mortality

E. Scosyrev, E. M. Messing, S. Mohile, D. Golijanin and G. Wu Department of Urology, University of Rochester Medical Center, Rochester, New York

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Surrogate Endpoints for Prostate Cancer-Specific Mortality After Radiotherapy and Androgen Suppression Therapy in Men With Localised or Locally Advanced Prostate Cancer: An Analysis of Two Randomised Trials

A. V. D'Amico, M. H. Chen, M. de Castro, M. Loffredo, D. S. Lamb, A. Steigler, P. W. Kantoff and J. W. Denham Department of Radiation Oncology, Brigham and Women's Hospital, and Dana Farber Cancer Institute, Boston, Massachusetts

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Denosumab and Bone-Metastasis-Free Survival in Men With Castration-Resistant Prostate Cancer: Results of a Phase 3, Randomised, Placebo-Controlled Trial

M. R. Smith, F. Saad, R. Coleman, N. Shore, K. Fizazi, B. Tombal, K. Miller, P. Sieber, L. Karsh, R. Damião, T. L. Tammela, B. Egerdie, H. Van Poppel, J. Chin, J. Morote, F. Gómez-Veiga, T. Borkowski, Z. Ye, A. Kupic, R. Dansey and C. Goessl

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: What is the Long-Term Relevance of Clinically Detected Postoperative Anastomotic Urine Leakage After Robotic-Assisted Laparoscopic Prostatectomy?

D. A. Rebuck, S. Haywood, K. McDermott, K. T. Perry and R. B. Nadler Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Global Trends in Testicular Cancer Incidence and Mortality

A. Rosen, G. Jayram, M. Drazer and S. E. Eggener Section of Urology, Department of Surgery, University of Chicago Medical Center, Chicago, Illinois

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Early Aggressive Treatment of Lichen Sclerosus May Prevent Disease Progression

Purpose: When not recognized and treated aggressively, lichen sclerosus may progress and cause debilitating symptoms. It also may result in significant morbidity in patients undergoing treatment for urethral strictures because unrecognized, it may result in rapid and severe recurrence after surgical treatment. We present our experience treating patients with lichen sclerosus in an equal access health care system. Materials and Methods: We performed an institutional review board approved retrospective review of all adult men with lichen sclerosus treated at our institution during a 10-year period. We analyzed all patients diagnosed with lichen sclerosus, and recorded patient demographics and therapies. We recorded characteristics of the disease process including external and internal manifestations. We also recorded the various treatments, and whether the patients experienced recurrence. Results: A total of 43 patients were diagnosed with lichen sclerosus during the review period. Of those patients presenting with more severe (urethral) involvement and undergoing 1 or 2-stage urethroplasties, we noted 7 with recurrence. In the remainder of patients presenting with less severe disease who were treated aggressively with clobetasol and/or minor procedures, no recurrences were noted on followup examination, and all of these patients had documented normal flow patterns on noninvasive urodynamics. Conclusions: Our data suggest that early aggressive topical therapy plus minimally invasive surgical therapy to relieve high pressure voiding may prevent the progression of lichen sclerosus in patients who present with limited disease involving the skin and meatus.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Polysymptomatic, Polysyndromic Presentation of Patients With Urological Chronic Pelvic Pain Syndrome

Purpose: Somatization disorder has been described in several comorbid functional syndromes of urological chronic pelvic pain syndrome, such as irritable bowel syndrome. We investigated whether a subset of patients with urological chronic pelvic pain syndrome may have the polysymptomatic, polysyndromic presentation pattern that is common in somatization disorder. Materials and Methods: A total of 70 male and female patients with urological chronic pelvic pain syndrome and 35 age matched controls without the syndrome completed a 59-item symptom checklist to assess the classic polysymptomatic, polysyndromic symptom pattern. The 2 operational tools used were the Perley-Guze derived symptom checklist and the somatic symptom algorithm used for Diagnostic and Statistical Manual, 4th Edition, Text Revision somatization disorder criteria. Results: Female patients with urological chronic pelvic pain syndrome (interstitial cystitis/bladder pain syndrome) reported significantly more nonpain symptoms and pain symptoms outside the pelvis than control female urology patients (p = 0.0016 and 0.0018, respectively). Female patients with urological chronic pelvic pain syndrome were more likely to endorse a polysymptomatic, polysyndromic symptom pattern than female controls (27% vs 0%, p = 0.0071). In contrast, male patients with urological chronic pelvic pain syndrome (interstitial cystitis/bladder pain syndrome and/or chronic prostatitis/chronic pelvic pain syndrome) did not report more extrapelvic pain than male controls (p = 0.89). Male patients with urological chronic pelvic pain syndrome were not more likely than male controls to have a polysymptomatic, polysyndromic symptom pattern. Conclusions: A subset of female patients with urological chronic pelvic pain syndrome endorses numerous extrapelvic symptoms across multiple organ systems. The checklist may be valuable to assess patients for this polysymptomatic, polysyndromic symptom pattern, which is common in somatization disorder. Recognizing this polysymptomatic, polysyndromic presentation will prompt clinicians to investigate further to determine whether somatization disorder may be an underlying diagnosis in a small subset of patients with urological chronic pelvic pain syndrome who complain of numerous extrapelvic symptoms.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Randomized Multicenter Clinical Trial of Myofascial Physical Therapy in Women With Interstitial Cystitis/Painful Bladder Syndrome and Pelvic Floor Tenderness

Purpose: We determined the efficacy and safety of pelvic floor myofascial physical therapy compared to global therapeutic massage in women with newly symptomatic interstitial cystitis/painful bladder syndrome. Materials and Methods: A randomized controlled trial of 10 scheduled treatments of myofascial physical therapy vs global therapeutic massage was performed at 11 clinical centers in North America. We recruited women with interstitial cystitis/painful bladder syndrome with demonstrable pelvic floor tenderness on physical examination and a limitation of no more than 3 years' symptom duration. The primary outcome was the proportion of responders defined as moderately improved or markedly improved in overall symptoms compared to baseline on a 7-point global response assessment scale. Secondary outcomes included ratings for pain, urgency and frequency, the O'Leary-Sant IC Symptom and Problem Index, and reports of adverse events. We compared response rates between treatment arms using the exact conditional version of the Mantel-Haenszel test to control for clustering by clinical center. For secondary efficacy outcomes cross-sectional descriptive statistics and changes from baseline were calculated. Results: A total of 81 women randomized to the 2 treatment groups had similar symptoms at baseline. The global response assessment response rate was 26% in the global therapeutic massage group and 59% in the myofascial physical therapy group (p = 0.0012). Pain, urgency and frequency ratings, and O'Leary-Sant IC Symptom and Problem Index decreased in both groups during followup, and were not significantly different between the groups. Pain was the most common adverse event, occurring at similar rates in both groups. No serious adverse events were reported. Conclusions: A significantly higher proportion of women with interstitial cystitis/painful bladder syndrome responded to treatment with myofascial physical therapy than to global therapeutic massage. Myofascial physical therapy may be a beneficial therapy in women with this syndrome.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Single-Dose Antibiotic Prophylaxis for Urinary Catheter Removal Does Not Reduce the Risk of Urinary Tract Infection in Surgical Patients: A Randomized Double-Blind Placebo-Controlled Trial

B. C. van Hees, P. L. Vijverberg, L. E. Hoorntje, E. H. Wiltink, P. M. Go and M. Tersmette Department of Medical Microbiology and Immunology, St. Antonius Hospital, Nieuwegein, The Netherlands

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Clinical Presentation of Urinary Tract Infection (UTI) Differs With Aging in Women

Z. Arinzon, S. Shabat, A. Peisakh and Y. Berner Department of Geriatric Medicine, Meir Medical Center, Kfar Saba and Meuhedet Health Care System, Tel Aviv, Israel

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Candiduria in Those Over 85 Years Old: A Retrospective Study of 73 Patients

T. Fraisse, J. Crouzet, L. Lachaud, A. Durand, S. Charachon, J. P. Lavigne and A. Sotto Department of Geriatrics, Alès-Cévennes Hospital, Alès, France

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Risk Factors of All-Cause In-Hospital Mortality Among Korean Elderly Bacteremic Urinary Tract Infection (UTI) Patients

B. S. Chin, M. S. Kim, S. H. Han, S. Y. Shin, H. K. Choi, Y. T. Chae, S. J. Jin, J. H. Baek, J. Y. Choi, Y. G. Song, C. O. Kim and J. M. Kim Division of Infectious Diseases, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Predictors of In-Hospital Mortality in Elderly Patients With Bacteraemia Admitted to an Internal Medicine Ward

M. Rebelo, B. Pereira, J. Lima, J. Decq-Mota, J. D. Vieira and J. N. Costa Department of Internal Medicine, University Hospital of Coimbra, Coimbra, Portugal

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Antibiotic Use in Long-Term Care Facilities

N. Daneman, A. Gruneir, A. Newman, H. D. Fischer, S. E. Bronskill, P. A. Rochon, G. M. Anderson and C. M. Bell Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Urethroplasty: A Geographic Disparity in Care

Purpose: Urethroplasty is the gold standard for urethral strictures but its geographic prevalence throughout the United States is unknown. We analyzed where and how often urethroplasty was being performed in the United States compared to other treatment modalities for urethral stricture. Materials and Methods: De-identified case logs from the American Board of Urology were collected from certifying/recertifying urologists from 2004 to 2009. Results were categorized by ZIP codes to determine the geographic distribution. Results: Case logs from 3,877 urologists (2,533 recertifying and 1,344 certifying) were reviewed including 1,836 urethroplasties, 13,080 urethrotomies and 19,564 urethral dilations. The proportion of urethroplasty varied widely among states (range 0% to 17%). The ratio of urethroplasty-to-urethrotomy/dilation also varied widely from state to state, but overall 1 urethroplasty was performed for every 17 urethrotomies or dilations performed. Certifying urologists were 3 times as likely to perform urethroplasty as recertifying urologists (12% vs 4%, respectively, p <0.05). Urethroplasties were performed more commonly in states with residency programs (mean 5% vs 3%). Some states reported no urethroplasties during the observation period (Vermont, North Dakota, South Dakota, Maine and West Virginia). Conclusions: To our knowledge this is the first report on the geographic distribution of urethroplasty for urethral stricture disease. There are large variations in the rates of urethroplasty performed throughout the United States, indicating a disparity of care, especially for those regions in which few or no urethroplasties were reported. This disparity may decrease with time as younger certifying urologists are performing 3 times as many urethroplasties as older recertifying urologists.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Penile Fracture Seems More Likely During Sex Under Stressful Situations

A. C. Kramer Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Defining Predictors of Response to Intralesional Verapamil Injection Therapy for Peyronie's Disease

D. J. Moskovic, B. Alex, J. M. Choi, C. J. Nelson and J. P. Mulhall Sexual and Reproductive Medicine Program, Urology Service, Department of Surgery, and Department of Psychiatry and Behavioral Services, Memorial Sloan Kettering Cancer Center, New York, New York

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: The Use of Tissue Expanders for Resurfacing of the Penis for Hypospadias Cripples

T. Mir, R. L. Simpson and M. K. Hanna Long Island Plastic Surgical Group, PC, Garden City, New York

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: The Z-Shaped Ileal Neobladder After Radical Cystectomy: An 18 Years Experience With 329 Patients

Y. Neuzillet, L. Yonneau, T. Lebret, J. M. Herve, M. Butreau and H. Botto Department of Urology, Hopital Foch, Suresnes, France

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Phase 3 Efficacy and Tolerability Study of OnabotulinumtoxinA for Urinary Incontinence From Neurogenic Detrusor Overactivity

Purpose: We assessed the efficacy, safety and effects on quality of life of onabotulinumtoxinA in patients with neurogenic detrusor overactivity. Materials and Methods: In this 52-week, international, multicenter, double-blind, randomized, placebo controlled trial 416 patients with neurogenic detrusor overactivity and urinary incontinence (14 or more episodes per week) resulting from multiple sclerosis (227) and spinal cord injury (189) were treated with intradetrusor injections of onabotulinumtoxinA (200 or 300 U) or placebo. The primary end point was the change from baseline in the mean number of urinary incontinence episodes per week at week 6. Maximum cystometric capacity, maximum detrusor pressure during the first involuntary detrusor contraction and Incontinence Quality of Life total score were secondary end points. Adverse events were monitored. Results: OnabotulinumtoxinA at a dose of 200 U in 135 patients and 300 U in 132 decreased mean urinary incontinence at week 6 by 21 and 23 episodes per week, respectively, vs 9 episodes per week in 149 on placebo (each dose p <0.001). Also, maximum cystometric capacity, maximum detrusor pressure during the first involuntary detrusor contraction and Incontinence Quality of Life score were significantly improved over values in the placebo group (each dose p <0.001). Median time to patient re-treatment request was greater for onabotulinumtoxinA 200 and 300 U than for placebo (256 and 254 days, respectively, vs 92). The most common adverse events were urinary tract infection and urinary retention. Of patients who did not catheterize at baseline 10% on placebo, 35% on 200 U and 42% on 300 U initiated catheterization due to urinary retention. Conclusions: OnabotulinumtoxinA significantly improved neurogenic detrusor overactivity symptoms vs placebo. Clean intermittent catheterization initiation due to urinary retention appeared to increase in a dose dependent fashion. No clinically relevant benefit in efficacy or duration was identified for the 300 U dose over the 200 U dose.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Complex Repetitive Discharges—A Feature of the Urethral Continence Mechanism or a Pathological Finding?

Purpose: We compared the proportion of women with complex repetitive discharges on urethral sphincter electromyography during filling cystometry among women with and without urinary disorders. Materials and Methods: After receiving institutional review board approval we recruited community dwelling women without urinary symptoms and women who presented for urinary incontinence treatment. Participants completed the Pelvic Floor Distress Inventory. Women who responded affirmatively to an inventory item (“Do you have difficulty emptying your bladder?” or “Do you experience a feeling of incomplete bladder emptying?”) were classified with voiding dysfunction. Women with post-void residual urine greater than 100 ml, active urinary tract infection, prolapse greater than stage II or neuromuscular disease were excluded from study. Participants underwent standardized multichannel urodynamics with continuous concentric needle electromyography of the urethral sphincter throughout filling cystometry. Results: In the 31 controls and 56 incontinent participants mean ± SD age was 48 ± 15 years and median vaginal parity was 1 (range 0 to 2). The urodynamic diagnosis in the incontinent group included urodynamic stress incontinence in 31 (56%), detrusor overactivity with incontinence in 17 (30%) and mixed urodynamic stress incontinence with detrusor overactivity in 8 (14%). Of the women 26 (32%) met voiding dysfunction criteria with 96% reporting a feeling of incomplete bladder emptying and 53% reporting difficult bladder emptying. Controls were significantly more likely to have complex repetitive discharges than incontinent women (9 of 30 vs 2 of 56, p <0.002). Conclusions: Complex repetitive discharges occur in about a third of women without urinary symptoms.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Selective Management of the Urethra at Time of Pelvic Organ Prolapse Repair: An Assessment of Postoperative Incontinence and Patient Satisfaction

Purpose: Management of the urethra in women without stress urinary incontinence during pelvic organ prolapse repair can be approached selectively or with a prophylactic suburethral sling. We report on patient satisfaction and outcomes in patients who underwent selective urethral management during pelvic organ prolapse repair. Materials and Methods: Patients undergoing repair of advanced apical and/or anterior compartment pelvic organ prolapse underwent prolapse reduction to screen for stress urinary incontinence. Patients with clinical, occult and urodynamic stress urinary incontinence underwent a sling procedure. Those without stress urinary incontinence did not undergo sling surgery. Patients completed responses to the UDI-6 (Urogenital Distress Inventory, PGI-I (Patient Global Impression of Improvement) and MESA (Medical, Epidemiological, and Social Aspects of Aging). Cost analysis of selective urethral management was completed. Results: A total of 42 patients met the study inclusion criteria and 30 completed responses to all questionnaires. Patients were separated into prolapse repair only (14) and prolapse repair with sling (16) groups. In the prolapse repair only group 1 patient required a subsequent sling. Mean UDI-6, MESA urge and MESA stress scores were 3.71, 1.29 and 3.14 in the prolapse repair only group, and 2.31 (p = 0.219), 2.69 (p = 0.244) and 3.00 (p = 0.918) in the prolapse repair with sling group, respectively. The PGI-I revealed no statistical difference between the groups. A total cost savings of $55,804 was achieved using selective urethral management. Conclusions: Patients undergoing prolapse repair only have continence and satisfaction outcomes that appear equivalent to those who underwent concomitant prolapse repair and sling. The decision to perform a concomitant sling at the time of prolapse repair should be tailored to the patient.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Outcomes Following Artificial Sphincter Implantation After Prior Unsuccessful Male Sling

Purpose: Despite the proven success and durability of the artificial urinary sphincter many patients elect an AdVance® sling as the initial treatment of male stress incontinence. We determined whether sling placement would change the outcome of an ensuing artificial urinary sphincter. Materials and Methods: A total of 29 patients with stress urinary incontinence after failed sling placement were treated with an AMS 800® artificial urinary sphincter between January 2006 and May 2011. A control group of 136 men with a primary artificial urinary sphincter was used for comparison. Preoperative and postoperative evaluation included demographic variables, voiding diary, 24-hour pad weight, urodynamic characteristics, operative time, estimated blood loss, complication rate, followup and cuff selection. Results: There was no statistical difference in urodynamic characteristics, operative variables or the complication rate. Pad use was reported as less than 1 pad daily in 96% of patients (28 of 29) with a secondary artificial urinary sphincter at 3-month followup. At 20.7 months 6.9% of patients (2 of 29) treated with an artificial urinary sphincter after the male sling required revision of the artificial urinary sphincter. The overall complication rate in the control group was 8.8% (12 of 136 patients) with a 2.2% infection rate (3 of 136). The overall complication rate in the artificial urinary sphincter plus male sling group was 6.9% (2 of 29 patients) with a 0% infection rate. Conclusions: Patients who require an artificial urinary sphincter after an initial male sling seem to fare as well as those who undergo primary artificial urinary sphincter implantation.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Detrusor Underactivity: A Plea for New Approaches to a Common Bladder Dysfunction

G. A. van Koeveringe, B. Vahabi, K. E. Andersson, R. Kirschner-Herrmans and M. Oelke Department of Urology and Pelvic Care Center, Maastricht University Medical Centre, Maastricht, The Netherlands

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Neural Control of the Female Urethral and Anal Rhabdosphincters and Pelvic Floor Muscles

K. B. Thor and W. C. de Groat Urogenix, Inc, Durham, North Carolina

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Duloxetine for Mild to Moderate Postprostatectomy Incontinence: Preliminary Results of a Randomised, Placebo-Controlled Trial

J. N. Cornu, B. Merlet, C. Ciofu, S. Mouly, L. Peyrat, P. Sèbe, R. Yiou, G. Vallancien, I. Debrix, K. Laribi, O. Cussenot and F. Haab Department of Urology, Tenon Hospital, University Paris VI, Paris, France

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Cost-Effectiveness Analysis of Sacral Neuromodulation and Botulinum Toxin A Treatment for Patients With Idiopathic Overactive Bladder

R. K. Leong, S. G. de Wachter, M. A. Joore and P. E. van Kerrebroeck Departments of Urology, Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Center, Maastricht, The Netherlands

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Prospective Comparative Study of Endoscopic Management of Bladder Lithiasis: Is Prostate Surgery a Necessary Adjunct?

P. Philippou, D. Volanis, I. Kariotis, E. Serafetinidis and D. Delakas Department of Urology, Asklipieion General Hospital, Athens, Greece

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Impact of Medical Therapy on Transurethral Resection of the Prostate: Two Decades of Change

J. Izard and J. C. Nickel Department of Urology, Queen's University, Kingston, Ontario, Canada

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Intraprostatic Botulinum Toxin Type A Administration: Evaluation of the Effects on Sexual Function

J. Silva, R. Pinto, T. Carvalho, F. Botelho, P. Silva, C. Silva, F. Cruz and P. Dinis Department of Urology, Institute for Molecular and Cell Biology, Hospital S. João, Porto, Portugal

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

The Influence of Testosterone Suppression and Recovery on Sexual Function in Men With Prostate Cancer: Observations From a Prospective Study in Men Undergoing Intermittent Androgen Suppression

Purpose: We investigated the effects of testosterone change on the sexual function of men with prostate cancer undergoing intermittent maximal androgen deprivation therapy. Materials and Methods: We conducted a phase II cohort study of 250 patients with prostate cancer undergoing intermittent maximal androgen deprivation therapy. Flutamide (Eulexin®) 250 mg 3 times daily and leuprolide (Lucrin®) 22.5 mg were given during a 9-month treatment phase (ONPhase). Therapy was ceased provided that prostate specific antigen was 4 ng/ml or less. Monitoring continued every 3 months for a further 2 years (OFFPhase) unless re-treatment occurred. Sexual function was assessed with the QLQ-PR25 version 3.0 prostate module in conjunction with the QLQ-C30 questionnaire at baseline and every 3 months thereafter. Results: At baseline 46% of patients reported sexual activity with almost half (43%) reporting mild or no erectile problems. Of the men 63% reported an interest in sex (libido), with 28% reporting moderate to high libido. In addition, 26% felt less masculine as a result of illness or treatment. By 3 months of ONPhase all parameters deteriorated, worsening to a low at 9 months. Only 13% of the men reported sexual activity and 10% reported moderate to high libido. The proportion of men feeling less masculine increased to 50%. During the OFFPhase recovery was observed. Of those previously sexually active men 52% resumed sexual activity. Of these patients all reported erectile function returning to baseline. Levels of libido, masculinity and sexual activity recovered but not to baseline levels. Conclusions: Libido, sexual activity and perceptions of masculinity deteriorate during ONPhase. Of the sexually active men at baseline half will resume sexual activity despite 9 months of androgen deprivation therapy.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Editorial Comment

The authors evaluated the influence of testosterone fluctuation and its impact on sexual function in a well conducted phase II cohort study on intermittent ADT. Since ADT has been associated with loss of libido and erectile dysfunction, intermittent ADT, through periods of no treatment, seems to decrease the severity of these side effects. Recovery of sexual function during the treatment off phase has been recently reported, showing that the decrease in side effects is related to testosterone normalization.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Can Sexual Bother After Radical Prostatectomy be Predicted Preoperatively? Findings From a Prospective National Study of the Relation Between Sexual Function, Activity and Bother

E. A. Steinsvik, K. Axcrona, A. A. Dahl, L. M. Eri, A. Stensvold and S. D. Fosså Department of Urology, National Resource Center for Late Effects, Oslo University Hospital, and Division of Surgery and Cancer Medicine, University of Oslo, Oslo, Norway

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Quality of Life of Patients After Retropubic Prostatectomy—Pre- and Postoperative Scores of the EORTC QLQ-C30 and QLQ-PR25

P. Bach, T. Döring, A. Gesenberg, C. Möhring and M. Goepel Department of Urology of Klinikum Niederberg Velbert, University of Duisburg-Essen, Essen, Germany

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: The 5-Year Functional Outcomes After Radical Prostatectomy: A Real-Life Experience in Korea

S. K. Hong, S. H. Doo, D. S. Kim, W. K. Lee, H. Z. Park, J. H. Park, S. J. Jeong, C. Y. Yoon, S. S. Byun and S. E. Lee Department of Urology, Seoul National University Bundang Hospital, Seongnam, Korea

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Shorter Abstinence Decreases Sperm Deoxyribonucleic Acid Fragmentation in Ejaculate

J. Gosálvez, M. González-Martínez, C. López-Fernández, J. L. Fernández and P. Sánchez-Martín Departamento de Biología, Unidad de Genética, Universidad Autónoma de Madrid, Madrid, Spain

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Semen Parameters and Sperm DNA Fragmentation as Causes of Recurrent Pregnancy Loss

S. Brahem, M. Mehdi, H. Landolsi, S. Mougou, H. Elghezal and A. Saad Department of Cytogenetic and Reproductive Biology, Farhat Hached University Teaching Hospital, Sousse, Tunisia

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Sperm Organelle Morphologic Abnormalities: Contributing Factors and Effects on Intracytoplasmic Sperm Injection Cycles Outcomes

D. P. de Almeida Ferreira Braga, A. S. Setti, R. C. Figueira, M. Nichi, C. D. Martinhago, A. Iaconelli, Jr. and E. Borges, Jr. Fertility-Assisted Fertilization Center, São Paulo, Brazil

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Absolute Asthenozoospermia and ICSI: What are the Options?

C. Ortega, G. Verheyen, D. Raick, M. Camus, P. Devroey and H. Tournaye Centre for Reproductive Medicine, University Hospital, Dutch-Speaking Brussels Free University, Brussels, Belgium

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Prospective Blinded Laboratory Assessment of Prophylactic Antibiotic Compliance in a Pediatric Outpatient Setting

Purpose: Prophylactic antibiotics are commonly used to prevent urinary tract infections in children with conditions such as vesicoureteral reflux. Patient compliance with antibiotics is salient, given the effects that noncompliance can have on development of antibiotic resistance and outcomes of clinical trials. Prior series have shown variable compliance (17% to 70%). However, no study has used objective methods. We hypothesized that direct measurement of urine antibiotic levels can reveal poor compliance. Materials and Methods: During a pediatric urology clinic visit patients 0 to 18 years old taking trimethoprim prophylaxis for any urological diagnosis were invited to participate in the study. They were unaware of any potential urine testing before the visit. Urine was sent for chromatography to quantify trimethoprim levels. Parents also completed a compliance self-assessment. Results: Of patients invited to participate 97% consented (54 patients). Of the patients 91% were compliant based on urine levels. Factors not associated with compliance included age, gender, self-report of compliance, duration of time on antibiotics, insurance status and history of breakthrough infection, surgery, pyelonephritis or hospitalization. Conclusions: This study demonstrates the highest compliance reported for children taking prophylactic antibiotics to prevent urinary tract infection. We attribute this unexpected result to the discussion by specialists of 1 problem for the duration of an office visit. All education in this study was part of clinical care. Thus, our results should be generalizable to nonstudy environments. Future studies should confirm whether this high level of compliance can be achieved by nephrologists and pediatricians. If such compliance cannot be achieved at nonsurgical clinics, then early referral to a pediatric urologist may be warranted.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Pediatric Urinary Stone Composition in the United States

Purpose: The incidence of urolithiasis in children is increasing. However, stone composition studies in this population are limited. We sought to determine the effects of age, gender and geographical location on urinary stone composition in the United States pediatric population. Materials and Methods: We obtained composition analyses for all urinary stones submitted to a reference laboratory between 2000 and 2009. Stones were excluded if the patient was younger than 1 year or older than 18 years. Stone composition was determined by Fourier transform infrared spectroscopy. Logistic regression analysis was performed to determine associations between stone composition frequency and age, gender and geographical region. Results: A total of 5,245 stones were included in our analysis. Calcium was found in 89.2% of stones. The percentage of stones containing calcium oxalate increased, while magnesium ammonium phosphate and ammonium acid urate containing stones decreased with age. Calcium oxalate and magnesium ammonium phosphate containing stones were more common in females, while uric acid stones were more common in males. Additionally, significant differences in stone composition frequency were noted between males and females in specific age groups and between age groups within the same gender. Geographical distribution was not significantly associated with stone composition. Conclusions: This series is the largest analysis to date of urinary stone composition in the pediatric population in the United States. Age and gender were significantly associated with stone composition, while geographical region was not significantly associated with stone composition.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Can Staccato and Interrupted/Fractionated Uroflow Patterns Alone Correctly Identify the Underlying Lower Urinary Tract Condition?

Purpose: Worldwide, uroflowmetry without simultaneous electromyography is often the only testing performed during the initial assessment of children with lower urinary tract symptoms. Various alterations in uroflow pattern are thought to indicate particular types of lower urinary tract conditions, specifically staccato uroflow indicating dysfunctional voiding and intermittent/fractionated uroflow indicating detrusor underactivity. We determined how reliable uroflow pattern alone is as a surrogate for simultaneously measured pelvic floor electromyography activity during voiding, and how well staccato and interrupted uroflow actually correlate with the diagnoses they are presumed to represent. Materials and Methods: We reviewed uroflow/electromyography studies performed during the initial evaluation of 388 consecutive neurologically and anatomically normal patients with persistent lower urinary tract symptoms. We identified those with staccato, interrupted/fractionated and mixed uroflow based on current International Children's Continence Society guidelines. Results: A total of 69 girls (58.5%) and 49 boys (41.5%) met inclusion criteria. Staccato uroflow was noted in 60 patients, interrupted/fractionated uroflow in 28 and a combination in 30. An active electromyography during voiding confirmed the diagnosis of dysfunctional voiding in 33.3% of patients with staccato, 46.4% with interrupted/fractionated and 50% with mixed uroflow patterns. Conclusions: Diagnoses based on uroflow pattern appearance without simultaneous electromyography to support them can be misleading, and reliance on uroflow pattern alone can lead to overdiagnoses of dysfunctional voiding and detrusor underactivity. When assessing patients with uroflow, an accompanying simultaneous pelvic floor electromyography is of utmost importance for improving diagnostic accuracy and thereby allowing for the most appropriate therapy.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Editorial Comment

As with most medical treatments, the more we learn, the more we understand the complexity of the entity we are trying to cure. This series reinforces the discussion that has been going on since the release of the documentation study (reference 11 in article). The documentation article was a significant step forward but has major areas of weakness. The definition of dysfunctional voiding represents the largest weakness. It is incorrect to say that dysfunctional voiding is present only when there is a history of staccato voiding. This characterization has led to publication confusion, especially from programs that base their reports on that mistaken definition. We have come to understand that accurately diagnosing the underlying voiding abnormality is essential to provide the appropriate treatment. History or flow pattern alone, no matter how accurate, cannot identify dysfunctional voiding in all patients. The most common dysfunctional voiding pattern is a flattened flow rate with hyperactivity of the pelvic floor. This article provides a complicated diagnosis strategy. We have used EMG and flow patterns since the 1990s with a less complicated successful algorithm.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Urodynamic Findings in Patients With Currarino Syndrome

Purpose: Currarino syndrome is an inherited disorder consisting of a triad of anorectal anomaly, sacrococcygeal defect and presacral mass. We evaluated the urological issues in patients with Currarino syndrome and sought to determine whether spinal cord detethering improves urinary tract function. Materials and Methods: We retrospectively reviewed 14 patients diagnosed with Currarino syndrome. We evaluated urinary signs/symptoms and urodynamic findings before and after spinal cord detethering. Results: All patients with Currarino syndrome having a sacral defect and presacral mass were diagnosed between birth and 6 years. Of the patients 86% had a tethered spinal cord that was surgically detethered between 8 months and 6 years (average 3 years). Overall 10 of 12 children who underwent surgery had voiding complaints postoperatively, including urgency, frequency and incontinence. Five patients had recurrent urinary tract infections, of whom 3 had vesicoureteral reflux that resolved spontaneously. Three patients had mild unilateral hydronephrosis without reflux. Ten of 12 patients who underwent spinal cord detethering underwent comprehensive urodynamic evaluation. Of the 5 patients who underwent preoperative and postoperative urodynamic evaluation 3 showed improvement with resolution of detrusor overactivity or dyssynergia postoperatively, and 2 demonstrated no change. Of the 5 patients who underwent only postoperative urodynamic evaluation 4 had abnormal findings, including small capacity, poor compliance, detrusor overactivity, detrusor sphincter dyssynergia and/or high voiding pressure. No progressive denervation was seen on electromyography preoperatively or postoperatively. Conclusions: Currarino syndrome is a rare congenital disorder with few published reports regarding the long-term implications. Although no solid conclusions could be drawn regarding urodynamic improvement postoperatively due to our small sample size, spinal cord detethering did not lessen ongoing voiding complaints in the study patients.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Abdominopelvic Ultrasound: A Cost-Effective Way to Diagnose Solitary Kidney

Purpose: Solitary kidneys are detected on approximately 1 of 1,500 prenatal ultrasounds and during evaluation for other urological complaints. Although renal scintigraphy is currently the gold standard for confirming the diagnosis and ruling out renal ectopia, scintigraphy is associated with radiation exposure, placement of an intravenous line and sedation. We hypothesize that ultrasonography alone is sufficient to detect solitary kidneys and that confirmatory renal scintigraphy is unnecessary. Materials and Methods: We reviewed the records of children with a solitary kidney who underwent ultrasound and nuclear scintigraphy at our institution from 2001 to 2010. Radiological findings were compared to assess the accuracy of ultrasound in diagnosing solitary kidneys. Costs were calculated based on 2011 Medicare global reimbursement. Results: A total of 25 children met the inclusion criteria of undergoing ultrasound and renal scintigraphy (dimercapto-succinic acid or mercaptoacetyltriglycine scan). The majority of cases were male (16, 64%) and left sided (17, 68%). Median age was 9 days (range 1 day to 11.6 years) at first ultrasound and 4.4 months (3 weeks to 12 years) at first renal scintigraphy. In 24 patients ultrasound correctly diagnosed a solitary kidney as confirmed by nuclear scan. In 1 patient ultrasound suggested a pelvic kidney but repeat ultrasound was negative, as was dimercapto-succinic acid scan. The diagnostic accuracy of ultrasound was 96%. Medicare reimbursement for dimercapto-succinic acid scan (CPT 78700) is $460 to $720 ($222 plus $240 for radiotracer plus $260 for anesthesia, if used). Conclusions: Our findings suggest that ultrasonography alone is sufficient to make the diagnosis of solitary kidney. Omitting routine renal scintigraphy saves approximately $460 to $720 per case, and avoids radiation and discomfort without sacrificing diagnostic accuracy.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Transurethral Incision of Congenital Obstructive Lesions in the Posterior Urethra in Boys and its Effect on Urinary Incontinence and Urodynamic Study

S. Nakamura, S. Kawai, T. Kubo, T. Kihara, K. Mori and H. Nakai Department of Paediatric Urology, Jichi Medical University, Children's Medical Center, Tochigi, Japan

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Urinary Flow Patterns in Infants With Distal Hypospadias

L. H. Olsen, I. Grothe, Y. F. Rawashdeh and T. M. Jørgensen Paediatric Urology, Department of Urology, Aarhus University Hospital-Skejby, Aarhus, Denmark

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Prenatal Hormones and Childhood Sex Segregation: Playmate and Play Style Preferences in Girls With Congenital Adrenal Hyperplasia

V. Pasterski, M. E. Geffner, C. Brain, P. Hindmarsh, C. Brook and M. Hines University of Cambridge, Cambridge, United Kingdom

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Vaginoplasty in the Female Exstrophy Population: Outcomes and Complications

R. M. Cervellione, T. Phillips, N. Baradaran, H. Asanuma, R. I. Mathews and J. P. Gearhart Division of Pediatric Urology, Brady Urological Institute, Johns Hopkins Hospital, Baltimore, Maryland

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Quality of Life in Children With Vesicoureteral Reflux as Perceived by Children and Parents

D. F. Yao, A. C. Weinberg, F. J. Penna, L. Huang, D. A. Freilich, B. J. Minnillo, J. Shoag, A. B. Retik and H. T. Nguyen Department of Urology, Children's Hospital, Boston, Massachusetts

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Nonspecific Granulomatous Prostatitis

A 72-year-old man with no urological history presented to the urologist with nocturia and a sensation of incomplete bladder emptying. Digital rectal examination revealed a firm nodule in the left upper portion of the prostate. Serum prostate specific antigen (PSA) was 5.0 ng/ml. Transrectal ultrasound showed an enlarged prostate with a homogeneous echotexture of the peripheral zone. Core needle biopsy of the prostate revealed noncaseating granulomatous prostatitis ().

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Renal Primitive Neuroectodermal Tumor

A 54-year-old female presented with right flank pain, gross hematuria and low grade fever. Computerized tomography (CT) of the abdomen showed a 7 cm heterogeneous lesion involving the lower pole of the right kidney (), thrombus in the right renal vein and multiple small pulmonary nodules in the lung bases.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Expression and Role of HMGA1 in Renal Cell Carcinoma

Purpose: Although molecular targeted therapy has improved the clinical outcome of metastatic renal cell carcinoma, a complete response is rare and there are various side effects. Identifying novel target molecules is necessary to improve the clinical outcome of metastatic renal cell carcinoma. HMGA1 is over expressed in many types of cancer and it is associated with metastatic potential. It is expressed at low levels or not expressed in normal tissue. We examined HMGA1 expression and function in human renal cell carcinoma. Materials and Methods: HMGA1 expression in surgical specimen from patients with renal cell carcinoma was examined by immunoblot. HMGA1 expression in 6 human renal cell carcinoma cell lines was examined by immunoblot and immunofluorescence. The molecular effects of siRNA mediated knockdown of HMGA1 were examined in ACHN and Caki-1 cells. Results: Immunoblot using surgical specimen showed that HMGA1 was not expressed in normal kidney tissue but it was expressed in tumor tissue in 1 of 30 nonmetastatic (3%) and 6 of 18 metastatic (33%) cases (p = 0.008). Immunoblot and immunofluorescence revealed significant nuclear expression of HMGA1 in ACHN and Caki-1 cells derived from metastatic sites. HMGA1 knockdown remarkably suppressed colony formation and induced significant apoptosis in ACHN and Caki-1 cells. HMGA1 knockdown significantly inhibited invasion and migration in vitro, and induced anoikis associated with P-Akt down-regulation in ACHN cells. Conclusions: HMGA1 is a potential target for novel therapeutic modalities for metastatic renal cell carcinoma.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Bradeion (SEPT4) as a Urinary Marker of Transitional Cell Bladder Cancer: A Real-Time Polymerase Chain Reaction Study of Gene Expression

Purpose: We evaluated whether Bradeion/SEPT4 gene expression could be used as a potential urinary marker to diagnose bladder transitional cell carcinoma. Materials and Methods: From 2005 to 2007 we collected urine samples from 58 individuals, 17 healthy controls and 41 patients in whom bladder tumors were previously diagnosed by cystoscopy. Urine was collected from all patients before transurethral resection of bladder tumor. We performed real-time reverse transcriptase-polymerase chain reaction to evaluate Bradeion/SEPT4 transcript levels using urine sample mRNA. Statistical analysis was done with the Mann-Whitney test and ROC curves. Results: Pathological examination of bladder tumor specimens revealed transitional cell bladder cancer. According to the 2002 TNM classification stage was Ta in 11 patients, T1 in 18 and T2/T3 in 12. All patients had G2 or G3 tumors according to the 1973 WHO grade classification. Relative quantification analysis of Bradeion transcript showed significantly increased levels compared to controls, namely 21.85 times higher in Ta stage tumors, 7.21 times higher in T1 tumors and 4.36 times higher in grade T2/T3 tumors. We compared each tumor stage group with the control group using the Mann-Whitney test to verify the statistical significance of observed differences. The ROC curve built on the change in threshold cycle revealed that with this method we attained 92.68% sensitivity and 64.71% specificity (AUC 0.798, p = 0.0001). Conclusions: Bradeion/SEPT4 transcript levels are significantly increased in patients with transitional cell bladder cancer compared to healthy controls. Our preliminary study supports the possible usefulness of Bradeion as a urinary marker of urothelial disease.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Anti-Interleukin-10R1 Monoclonal Antibody Enhances Bacillus Calmette-Guérin Induced T-Helper Type 1 Immune Responses and Antitumor Immunity in a Mouse Orthotopic Model of Bladder Cancer

Purpose: Proper induction of the T-helper type 1 immune response is required for effective bacillus Calmette-Guérin immunotherapy for bladder cancer. Interleukin-10 down-regulates the T-helper 1 response and is associated with bacillus Calmette-Guérin failure. We investigated whether blocking interleukin-10 receptor 1 would enhance the bacillus Calmette-Guérin induced T-helper type 1 immune response and anti-bladder cancer immunity in a mouse model. Materials and Methods: Splenocytes were incubated with bacillus Calmette-Guérin or bacillus Calmette-Guérin plus control IgG1, anti-interleukin-10 receptor 1 mAb or anti-interleukin-10 neutralizing mAb, followed by enzyme-linked immunosorbent assay of interferon-γ production. Bladder RNA was extracted after intravesical bacillus Calmette-Guérin plus intraperitoneal IgG1 or anti-interleukin-10 receptor 1 mAb and analyzed by reverse transcriptase and/or quantitative polymerase chain reaction. Urine was collected and analyzed by enzyme-linked immunosorbent assay. Mice bearing a luciferase expressing MB49 orthotopic tumor were treated with intravesical bacillus Calmette-Guérin plus intraperitoneal IgG1 or anti-interleukin-10 receptor 1 mAb. Tumor response was assessed by bioluminescent imaging and bladder weight measurement. Results: Bacillus Calmette-Guérin plus anti-interleukin-10R1 mAb induced significantly higher interferon-γ production by splenocytes than bacillus Calmette-Guérin plus anti-interleukin-10 mAb. Bacillus Calmette-Guérin plus anti-interleukin-10 receptor 1 mAb also induced significantly higher interferon-γ mRNA and protein in bladder and urine, respectively, in a dose dependent manner. Treatment with phosphate buffered saline, bacillus Calmette-Guérin plus control IgG1 and bacillus Calmette-Guérin plus anti-interleukin-10 receptor 1 mAb showed a 0% tumor-free rate with a 20% death rate, a 20% tumor-free rate with a 20% death rate and a 40% tumor-free rate with a 0% death rate, respectively. Bladder weight also revealed the effect of anti-interleukin-10 receptor 1 mAb on the bacillus Calmette-Guérin induced bladder tumor response. Conclusions: Anti-interleukin-10 receptor 1 mAb enhanced the bacillus Calmette-Guérin induced T-helper type 1 immune response and anti-bladder cancer immunity. A humanized form of this mAb warrants future investigation for bacillus Calmette-Guérin treatment of bladder cancer.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Establishment and Characterization of Primary Cell Lines of Squamous Cell Carcinoma of the Penis and its Metastasis

Purpose: We established cell lines from penile squamous cell carcinoma and its lymph node metastasis, and investigated the role of chemokines, chemokine receptors and podoplanin in cancer progression. Materials and Methods: Tumor specimen of primary tumors, and lymph node and distant metastases were cultured in vitro and xenotransplanted in SCID beige mice. Specimens were analyzed by hematoxylin and eosin staining, and immunohistochemistry. Comparative screening for chemokines, chemokine receptors and podoplanin was done by polymerase chain reaction, fluorescence activated cell sorting and enzyme-linked immunosorbent assay. Results: We established 2 cell lines from a primary tumor and its corresponding lymph node metastasis, respectively. Heterotopic xenotransplantation revealed reliable tumor growth in vivo. Morphological and immunohistological analysis showed comparable features for human tumors, cell lines in vitro and xenotransplanted tumors in mice regarding the primary tumor and metastasis. Comprehensive analysis of chemokines and chemokine receptors in the metastasis derived cell line and in the cell line originating from the primary tumor revealed the most pronounced changes for CXCL14. This pattern was confirmed on the protein level. Comparative analysis of podoplanin showed marked down-regulation in the metastatic variant on the mRNA and protein levels. Conclusions: To our knowledge we established the first pair of cell lines of a human primary penile tumor and the corresponding lymph node metastasis. These cell lines offer unique possibilities for further comparative functional investigations in in vitro and in vivo settings. They enable studies of new potential therapeutic agents and other assays to better understand the molecular mechanisms of penile cancer progression.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Urinary Chemokines as Noninvasive Predictors of Ulcerative Interstitial Cystitis

Purpose: Based on basic research findings an increase in chemokines and cytokines (CXCL-1 and 10, nerve growth factor and interleukin-6) is considered responsible for inflammation and afferent sensitization. In this cross-sectional study we tested the hypothesis that select chemokines are increased in the urine of patients with ulcerative and nonulcerative interstitial cystitis/painful bladder syndrome. Materials and Methods: Midstream urinary specimens were collected from 10 patients with ulcerative and nonulcerative interstitial cystitis/painful bladder syndrome, respectively, and from 10 asymptomatic controls. Urinary levels of 7 cytokines were measured by a human cytokine/chemokine assay. Nerve growth factor was measured by enzyme-linked immunosorbent assay. Results: Urinary levels of most chemokines/cytokines were tenfold to 100-fold lower in asymptomatic controls vs patients with ulcerative and nonulcerative interstitial cystitis/painful bladder syndrome. Univariate comparison of 8 tested proteins in the ulcerative vs nonulcerative groups revealed a significant fivefold to twentyfold increase in CXCL-10 and 1, interleukin-6 and nerve growth factor (ANOVA p <0.001). Conclusions: Differential expression of chemokines in ulcerative and nonulcerative subtypes of interstitial cystitis/painful bladder syndrome suggests differences in paracrine signaling between the 2 entities.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Protective Effects of Hydrogen Rich Saline Solution on Experimental Testicular Ischemia-Reperfusion Injury in Rats

Purpose: We examined the effectiveness of hydrogen rich saline solution on the prevention of testicular damage induced by ischemia/reperfusion in rats. Materials and Methods: Male Sprague-Dawley® rats were divided randomly into 4 groups, including group 1—sham operated, group 2—torsion-detorsion, group 3—torsion-detorsion plus saline and group 4—torsion-detorsion plus hydrogen rich saline solution. Testicular torsion was performed by rotating the left testis 720 degrees clockwise for 4 hours. Reperfusion was allowed for 4 hours. Hydrogen rich saline solution (5 ml/kg) was injected intraperitoneally in rats in group 4 15 minutes before the start of detorsion. Rats were sacrificed after 4-hour initiation of detorsion. Left orchiectomy was done for histopathological examination and biochemical assay. Results: The testicular injury score in groups 2 and 3 was significantly lower than in sham operated group 1 but higher in group 4 with hydrogen rich saline than in group 2 with torsion-detorsion. The apoptosis index was significantly increased in groups 2 and 3. Hydrogen rich saline solution treatment significantly decreased the apoptosis index. A significant increase in malondialdehyde and a decrease in superoxide dismutase activity were observed in groups 2 and 3. In group 4 malondialdehyde was significantly lowered and superoxide dismutase activity was significantly improved compared with groups 2 and 3. Conclusions: Results provide a biochemical and histopathological basis for the action of hydrogen rich saline solution as a therapeutic agent for testicular damage induced by ischemia/reperfusion injury.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Nitric Oxide Signaling Pathways Involved in the Inhibition of Spontaneous Activity in the Guinea Pig Prostate

Purpose: We investigated nitric oxide mediated inhibition of spontaneous activity recorded in young and aging guinea pig prostates. Materials and Methods: Conventional intracellular microelectrode and tension recording techniques were used. Results: The nitric oxide donor sodium nitroprusside (10 μM) abolished spontaneous contractions and slow wave activity in 5 young and 5 aging prostates. Upon adding the nitric oxide synthase inhibitor L-NAME (10 μM) the frequency of spontaneous contractile and electrical activity was significantly increased in each age group. This increase was significantly larger in 4 to 8 preparations of younger vs aging prostates (about 40% to 50% vs about 10% to 20%, 2-way ANOVA p <0.01). Other measured parameters, including the duration, amplitude and membrane potential of spontaneous electrical and contractile activity, were not altered from control values. The guanylate cyclase inhibitor ODQ (10 μM) significantly increased the frequency of spontaneous activity by 10% to 30% in 6 young guinea pig prostates (Student paired t test p <0.05). However, it had no effect on aging prostates. The cGMP analogue 8-Br-GMP (1 μM) and the PDE5 inhibitor dipyridamole (1 μM) significantly decreased the frequency of contractile activity by about 70% in 4 to 9 young and older prostates (Student paired t test p <0.05). Conclusions: The decrease in the response to L-NAME in spontaneous contractile and slow wave activity in aging prostate tissue compared to that in young prostates suggests that with age there is a decrease in nitric oxide production. This may further explain the increase in prostatic smooth muscle tone observed in age related prostate specific conditions, such as benign prostatic hyperplasia.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Serum Neutrophil Gelatinase Associated Lipocalin During the Early Postoperative Period Predicts the Recovery of Graft Function After Kidney Transplantation From Donors After Cardiac Death

Purpose: Kidneys procured from donors after cardiac death hold great potential to expand the donor pool. However, they have not yet been fully used, in part due to the high incidence of delayed graft function. Although urine neutrophil gelatinase-associated lipocalin is a well-known early biomarker for renal injury after kidney transplantation, its usefulness is limited in cases with delayed graft function because of the unavailability of a urine sample. We evaluated serum neutrophil gelatinase-associated lipocalin as a potential biomarker to predict the functional recovery of kidneys transplanted from donors after cardiac death. Materials and Methods: Consecutive patients transplanted with a kidney from a living related (39), brain dead (1) or post-cardiac death (27) donor were retrospectively enrolled in the study. Serum samples were collected serially before and after kidney transplantation. Serum neutrophil gelatinase-associated lipocalin was measured using the ARCHITECT® assay. Results: Average serum neutrophil gelatinase-associated lipocalin was markedly high during the pre transplantation period. It decreased rapidly after transplantation. The slope of the decrease correlated well with the recovery period. By analyzing ROC curves we determined cutoffs to predict immediate, slow or delayed graft function requiring hemodialysis for longer than 1 week with high sensitivity and specificity. Conclusions: These data suggest that serial monitoring of serum neutrophil gelatinase-associated lipocalin may allow us to predict graft recovery and the need for hemodialysis after kidney transplantation from a donor after cardiac death.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Phase 2b Study of the Clinical Efficacy and Safety of Collagenase Clostridium Histolyticum in Patients With Peyronie Disease

Purpose: Collagenase Clostridium histolyticum is an investigational nonsurgical treatment for Peyronie disease. In this phase 2b, double-blind, randomized, placebo controlled study we determined the safety and efficacy of collagenase C. histolyticum and assessed a patient reported outcome questionnaire. Materials and Methods: A total of 147 subjects were randomized into 4 groups to receive collagenase C. histolyticum or placebo (3:1) with or without penile plaque modeling (1:1). Per treatment cycle 2 injections of collagenase C. histolyticum (0.58 mg) were given 24 to 72 hours apart. Subjects received up to 3 cycles at 6-week intervals. When designated, investigator modeling was done 24 to 72 hours after the second injection of each cycle. We evaluated penile curvature by goniometer measurement, patient reported outcomes and adverse event profiles. Results: After collagenase C. histolyticum treatment significant improvements in penile curvature (29.7% vs 11.0%, p = 0.001) and patient reported outcome symptom bother scores (p = 0.05) were observed compared to placebo. In modeled subjects 32.4% improvement in penile curvature was observed in those on collagenase C. histolyticum compared to 2.5% worsening of curvature in those on placebo (p <0.001). Those treated with collagenase C. histolyticum who underwent modeling also showed improved Peyronie disease symptom bother scores (p = 0.004). In subjects without modeling there were minimal differences between the active and placebo cohorts. Most adverse events in the collagenase C. histolyticum group occurred at the injection site and were mild or moderate in severity. No treatment related serious adverse events were reported. Conclusions: Collagenase C. histolyticum treatment was well tolerated. We noted significant improvement in penile curvature and patient reported outcome symptom bother scores, suggesting that this may be a safe, nonsurgical alternative for Peyronie disease.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Generation of a Mouse Model of Von Hippel-Lindau Kidney Disease Leading to Renal Cancers by Expression of a Constitutively Active Mutant of HIF1α

L. Fu, G. Wang, M. M. Shevchuk, D. M. Nanus and L. J. Gudas Department of Pharmacology, Weill Cornell Cancer Center, Weill Cornell Medical College of Cornell University, New York, New York

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Cancer Cells Promote Survival Through Depletion of the von Hippel-Lindau Tumor Suppressor by Protein Crosslinking

D. S. Kim, Y. B. Choi, B. G. Han, S. Y. Park, Y. Jeon, D. H. Kim, E. R. Ahn, J. E. Shin, B. I. Lee, H. Lee, K. M. Hong and S. Y. Kim Cancer Cell and Molecular Biology Branch, Division of Cancer Biology, Research Institute, Goyang, Korea

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Targeting PIM Kinase Enhances the Activity of Sunitinib in Renal Cell Carcinoma

D. Mahalingam, C. M. Espitia, E. C. Medina, J. A. Esquivel, II, K. R. Kelly, D. Bearss, G. Choy, P. Taverna, J. S. Carew, F. J. Giles and S. T. Nawrocki Department of Medicine, Institute for Drug Development, Cancer Therapy and Research Center, University of Texas Health Science Center, San Antonio, Texas

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: A Double-Blind Randomized Controlled Clinical Trial to Assess the Effect of Doppler Optimized Intraoperative Fluid Management on Outcome Following Radical Cystectomy: P. Pillai, I. McEleavy, M. Gaughan, C. Snowden, I. Nesbitt, G. Durkan, M. Johnson, J. Cosgrove and A. Thorpe J Urol 2011; 186: 2201–2206

In this randomized controlled trial assessing esophageal Doppler monitoring of intraoperative fluid management during open radical cystectomy the authors conclude this intervention in 32 cases led to significant improvements in outcomes such as recovery of bowel function, ileus, wound infection and length of hospital stay. While optimal fluid management during major surgery makes surgical common sense, the differences in outcomes observed in this series may not necessarily have been a result of the intervention studied. One important variable the authors failed to address was the significantly longer operative times in the control vs intervention group (mean 351 vs 302 minutes). Indeed, the shortest operation in the control group (328 minutes) was still longer than the longest operation in the study group (326 minutes). This important distinction may have contributed to the differences in recovery of bowel function and ileus between groups.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Reply by Authors

We thank Ghani et al for their interest in our study. They have raised a couple of pertinent issues. First, we only studied patients with ASA grades 1 and 2 physical status because at the inception of our study the wholesale use of the transesophageal Doppler probe had not been nationally recognized by the National Institute for Health and Clinical Excellence. Therefore, we based our ethics submission on the series published by Noblett et al (also from our institution), which dealt with fluid optimization in patients with ASA grades 1 and 2 physical status undergoing elective colorectal surgery. Our ethics committee agreed that this was the best way forward at the time. We now routinely use the probe for patients with ASA grades 1, 2 and 3 physical status undergoing radical cystectomy. At our institution patients with ASA grade 4 muscle invasive bladder cancer are not routinely offered cystectomy but, through our multidisciplinary team, referred for radical radiotherapy. The calculations for sample size, power, etc were also partly based on the study by Noblett et al, and this issue was, in fact, addressed in our correspondence with the editor.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Increased Risk of Diabetes in Patients With Urinary Calculi: A 5-Year Followup Study: S.-D. Chung, Y.-K. Chen and H.-C. Lin J Urol 2011; 186: 1888–1893

This large, population based, case-control study demonstrates that patients diagnosed with urinary calculi are at increased risk for diabetes mellitus at 5-year followup, suggesting a role of insulin resistance in the pathogenesis of urolithiasis. Does this also mean that patients with diabetes are at increased risk for urinary calculi formation?

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Implications of Pacemakers and Implantable Cardioverter Defibrillators in Urological Practice: S. S. Ubee, V. S. Kasi, D. Bello and R. Manikandan J Urol 2011; 186: 1198–1205

I read with great interest this article regarding the safety of urological surgery in patients with implantable pacemakers and defibrillators. Our patients are aging, and the presence of these lifesaving devices is ever more common. More and more, procedures are now being performed at doctor offices. This shift is due to many different causes, including technology, patient comfort, economics and time.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Reply by Authors

We are thankful to Kauder for his interest in our article and appreciate his valuable comments. One of the objectives while writing this review article was to keep a universal appeal and deal with devices and procedures that are common to urologists across the continents. Targis and other devices based on microwave technology have been shown to have promising results in management of benign prostatic obstruction, although they are still being used only at selected centers. Also, the amount of information and the number of devices discussed were limited by the permitted word length of the article, hence our decision to be selective about the devices covered.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Alterations in Connective Tissue Metabolism in Stress Incontinence and Prolapse: B. Chen and J. Yeh J Urol 2011; 186: 1768–1772

Chen and Yeh have taken the integral theory statement regarding urinary stress incontinence (USI) and pelvic organ prolapse (POP) to a more fractal level, with an excellent review of the metabolic processes of connective tissue. According to the original statement, “Prolapse, symptoms of stress, urge, abnormal emptying and some types of pelvic pain mainly derive, for different reasons, from laxity in the vagina or its supporting ligaments, a result of altered collagen/elastin.”

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Re: Baseline Urodynamic Predictors of Treatment Failure 1 Year After Mid Urethral Sling Surgery: C. W. Nager, L. Sirls, H. J. Litman, H. Richter, I. Nygaard, T. Chai, S. Kraus, H. Zyczynski, K. Kenton, L. Huang, J. Kusek and G. Lemack for the Urinary Incontinence Treatment Network J Urol 2011; 186: 597–603

Based on previous ultrasound and urodynamic experiments, including intraoperative pressure measurements during tension-free mid urethral sling operations, it is possible to conclude that the length of the recreated pubourethral ligament (PUL) is the critical factor in restoration of the musculoelastic closure mechanisms, not any preoperative urodynamic parameters. We believe that when high failure rates are experienced, they have little to do with individual surgeon skill, but rather the uncertainty of how restoration of the elastic tape to its original shape plays out in an individual patient. If the tape is too tight, retention may occur. If it is too loose, surgical failure may occur, more so in patients with poor intrinsic continence mechanisms such as low maximum urethral closure pressure (MUCP) and low Valsalva leak point pressure (VLPP). Use of a nonstretch tape may provide greater certainty in tensioning the mid urethral sling.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Reply by Authors

We were surprised to receive this letter regarding our article because it has almost nothing to do with our study. Petros, a codeveloper of tension-free vaginal tape, provides some historical background on the development of the mid urethral sling, cites his integral theory and mentions the high rejection rates with his early nonstretch Mersilene tape. He suggests that the “high” failure rate reported in our article is due to “the uncertainty of how restoration of the elastic tape to its original shape plays out in an individual patient,” and he advocates the use of nonstretch tape. Currently all mid urethral slings are made of type 1 polypropylene mesh, and all of the slings in this study were made of this material. This was not a comparative trial with different mesh materials. As such, our results cannot be used either to support or to refute the theory about failure being caused by the elastic nature of the sling material.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Erratum

Volume 187, Number 4, Page 1183: The name of the third author is Ramy F. Youssef.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

The Journal of Urology® Home Study Course 2012 Volume 187/188

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

2011 Journal of Urology Consultants

Below is a list of consultants who reviewed manuscripts for The Journal of Urology® in 2011. Our peer reviewers give their time, expertise and advice generously and objectively to the editors and authors. All participants in the process benefit from this interchange, and the readers benefit from the improved communications that result. We all owe these consultants a debt and our thanks.

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.

Editorial Board

The Journal of Urology 187, 6 (2012)

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© 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc All rights reserved.