The Journal of Urology

This Month in Adult Urology

William D. Steers — 2013-03-07

Erectile dysfunction is common after radical prostatectomy and often fails to respond to phosphodiesterase type 5 inhibitors. Avanafil, a new short-acting phosphodiesterase type 5 inhibitor with greater affinity than other agents, was tried by Mulhall et al (page 2229) in a phase 3 study of 298 patients with erectile dysfunction lasting as long as 6 months after prostatectomy. The primary outcomes of the study were 1) successful vaginal insertion, 2) ability to complete intercourse and 3) improved responses to the IIEF (International Index of Erectile Function) questionnaire. Ad hoc analysis of the 85% of participants who completed the study indicated clinically significant improvement of 23% in SEP3 (Sexual Encounter Profile), 21% in SEP2 and greater than 4 points for IIEF-EF, respectively, in a statistically significant proportion of patients compared to placebo. The authors conclude from these results that avanafil may be of benefit in this population.

This Month in Pediatric Urology

Michael L. Ritchey — 2013-03-08

The timing and role of surgical intervention for adolescent varicocele continue to be debated, as early surgical intervention is often recommended to prevent future fertility problems. However, long-term outcome data on adolescent varicocele are limited. Bogaert et al (page 2298) from Belgium report on 661 boys between 12 and 17 years old with varicocele, of whom 372 had undergone antegrade sclerotherapy and 289 were followed conservatively. They obtained followup data on 361 patients using written surveys and identified 158 men who had fathered a child. They identified no difference in paternity between those treated for the varicocele vs those who were observed (85% vs 79%, p >0.05). The authors further analyzed patients with a smaller left testis preoperatively and found no difference in paternity rates (82% in the treated group vs 90% in the conservative group, p = 1.0). This study is provocative but is limited by its retrospective nature. The authors conclude that prepubertal screening and treatment have no beneficial effect on subsequent paternity. Although there are some patients who could benefit from early intervention, it is not yet clear how those patients would be identified with just physical examination or imaging findings alone.

This Month in Investigative Urology

Karl-Erik Andersson — 2013-03-18

Since progression-free survival with current therapies for metastatic renal cell carcinoma (RCC) is only 1 to 2 years and existing drugs are associated with high resistance, new pharmacological targets are needed. In this issue of The Journal Inoue et al (page 2317) from Davis, California identified the nuclear exporter protein CRM1 as a potential RCC therapy, and studied the effects of CRM1 blockade with the CRM1 inhibitors KPT-185 and 251. Drug efficacy was tested in RCC cell lines and an RCC xenograft model. Apoptosis and cell cycle arrest were quantified and p53 family protein localization was assessed.

Continuous Review Improvement

William D. Steers — 2013-03-13

Authors' perceptions of journal quality are based on a variety of metrics. Every author demands a fair and high quality critique. Most of our authors also desire a prompt assessment and, if the manuscript is accepted, timely publication.

Epigenetic Changes in Histologically Normal Prostate Tissues

James D. Brooks — 2013-03-04

Cancers arise as a result of accumulated alterations in the DNA of normal cells coupled with changes in the surrounding stroma and influences from the host, including exposure to environmental factors, and innate DNA repair and immune functions. At some point in the path to cancer histologically normal tissues must transition to frank malignancy with possible intervening histological lesions, such as dysplasia or noninvasive intraepithelial neoplasia. These transition events usually do not occur as isolated events in a tissue. Around the time that tobacco was recognized as a carcinogen in the 1950s, the concept of field cancerization or field defect was introduced to explain the frequent clinical observation of multifocal lung cancers in heavy smokers.

Comprehensive Care for Urological Disease: Pediatric Urology and Adult Urology are not Mutually Exclusive

C.D. Anthony Herndon — 2013-03-18

Although a clear demarcation exists between patients served by pediatric and adult urologists, several diseases transcend these traditional models and reinforce the need for a comprehensive treatment program that serves the life of the patient. As opposed to known conditions such as spina bifida that lend themselves to a seamless transition from the pediatric to the adult urologist, in this issue of The Journal 2 articles focus on primary pediatric urology conditions that, although adequately treated, may resurface later in life with new urological symptoms. Other conditions such as voiding dysfunction and posterior urethral valves (PUV) may share similar relationships. These diseases serve as a reminder that treatment of the primary urological condition in childhood may serve as a marker of adult urological disease. These associations should serve as a basis for research endeavors that rely on a collaborative effort among all urologists who focus on treatment as a continuum rather than mutually exclusive pediatric and adult urological disease.

The Adolescent Varicocele—A Shakespearean Tragedy or Much Ado About Nothing?

Thomas F. Kolon — 2013-03-18

In this issue of The Journal Bogaert et al (page 2298) present intriguing findings suggesting that there is no beneficial effect to screening for varicocele since treating the varicocele at diagnosis does not appear to improve later paternity. This retrospective review evaluates the ability to achieve paternity in adults who had been diagnosed with a varicocele in adolescence and were treated with antegrade sclerotherapy (historically 87% to 95% success rate) or “let go” without further treatment (nonrandomized). Data correlating Tanner stage, testicular volume over time and semen analysis were not available.

The Relevance of Social Media and Online Reviews for Urological Practice: Some Questions and Some Answers

Robert Dowling — 2013-03-18

In this issue of The Journal Ellimoottil et al (page 2269) address the subject of online reviews of urologists by patients. The authors report their results of urologists' ratings on 10 popular free physician review websites (PRWs) as well as a smaller number of written comments on one of those sites. They found that approximately 80% of the random sample of 500 urologists had been rated on at least 1 site, and concluded, “We advise physicians and patients to be aware that most urologists are rated on at least 1 PRW, and that while most ratings and reviews are favorable, composite scores are typically based on a small number of reviews and, therefore, can be volatile.” While this particular study may raise more questions about the value of PRWs than it answers, it is fair and reasonable to raise awareness among urologists about the potential impact of social media, patient satisfaction instruments, patient centeredness initiatives and the information empowered patient in today's health care environment.

Suprapubic Tube After Radical Prostatectomy

Sandip M. Prasad, Norm D. Smith, William J. Catalona, Jesse Sammon, Mani Menon — 2013-03-18

In his 2012 lecture on “Avoiding Avoidable Care,” the president of the Institute of Medicine, Dr. Harvey Fineberg noted that the decision to use additional, elective care should include assessment of the 1) benefits, 2) risks and 3) additional resources that must be expended. He chided the medical profession on its “magical thinking” that technology is always good and new technology is always better. He also pointed out the assumption, “more is always better,” is often an obstacle to improvements in health care. Dr. Fineberg's framework to “avoid avoidable care” can be applied to the use of suprapubic tube drainage to facilitate early urethral catheter removal after radical prostatectomy. What are the true risks, benefits and additional resources expended with this approach? Until recently, these assessments could only be made based on retrospective reports, as there are yet no published randomized clinical trials.

Diagnosis and Treatment of Erectile Dysfunction for Reduction of Cardiovascular Risk

2013-01-10

Purpose: We established erectile dysfunction as an often neglected but valuable marker of cardiovascular risk, particularly in younger men and men with diabetes. We also reviewed evidence that lifestyle change, combined with informed prescribing of pharmacotherapies used to mitigate cardiovascular risk, can improve overall vascular health and sexual functioning in men with erectile dysfunction. Materials and Methods: We performed a PubMed® search for articles and guidelines pertinent to relationships between erectile dysfunction and cardiovascular disease, cardiovascular and all cause mortality, and pharmacotherapies for dyslipidemia and hypertension. The clinical guidance presented incorporates the current literature and the expertise of the multispecialty investigator group. Results: Numerous cardiovascular risk assessment tools exist but risk stratification remains challenging, particularly in patients at low or intermediate short-term risk. Erectile dysfunction has a predictive value for cardiovascular events that is comparable to or better than that of traditional risk factors. Interventional studies support lifestyle changes as a means of improving overall vascular health as well as sexual functioning. Statins, diuretics, β-blockers and renin-angiotensin system modifiers may positively or negatively affect erectile function. Furthermore, the phosphodiesterase type 5 inhibitors used to treat erectile dysfunction may have systemic vascular benefits. Conclusions: Erectile dysfunction treatment should be considered secondary to decreasing cardiovascular risk. However, informed prescribing may prevent worsening sexual function in men receiving pharmacotherapy for dyslipidemia and hypertension. As the first point of medical contact for men with erectile dysfunction symptoms, the primary care physician or urologist has a unique opportunity to identify those who require early intervention to prevent cardiovascular disease.

Optimization of Initial Prostate Biopsy in Clinical Practice: Sampling, Labeling and Specimen Processing

2013-02-28

Purpose: An optimal prostate biopsy in clinical practice is based on a balance among adequate detection of clinically significant prostate cancers (sensitivity), assuredness regarding the accuracy of negative sampling (negative predictive value), limited detection of clinically insignificant cancers and good concordance with whole gland surgical pathology results to allow accurate risk stratification and disease localization for treatment selection. Inherent within this optimization is variation of the core number, location, labeling and processing for pathological evaluation. To date, there is no consensus in this regard. The purpose of this review is to 1) define the optimal number and location of biopsy cores during primary prostate biopsy among men with suspected prostate cancer, 2) define the optimal method of labeling prostate biopsy cores for pathological processing which will provide relevant and necessary clinical information for all potential clinical scenarios, and 3) determine the maximal number of prostate biopsy cores allowable within a specimen jar which would not preclude accurate histological evaluation of the tissue. Materials and Methods: A bibliographic search using PubMed® covering the period up to July 2012 yielded approximately 550 articles. Articles were reviewed and categorized based on which of the 3 objectives of this review was addressed. Data were extracted, analyzed and summarized. Recommendations are provided based on this literature review and our clinical experience. Results: The use of 10 to 12-core extended sampling protocols increases cancer detection rates compared to traditional sextant sampling methods and reduces the likelihood of repeat biopsy by increasing negative predictive value, ultimately allowing more accurate risk stratification without increasing the likelihood of detecting insignificant cancers. As the number of cores increases above 12, the increase in diagnostic yield becomes marginal. Only limited evidence supports the use of initial biopsy schemes involving more than 12 cores or saturation. Apical and laterally directed sampling of the peripheral zone increases cancer detection rate, reduces the need for repeat biopsies and predicts pathological features on prostatectomy while transition zone biopsies do not. There are little data to suggest that knowing the exact site of an individual positive biopsy core provides meaningful clinical information. However, determining laterality of cancer on biopsy may be helpful for predicting sites of extracapsular extension and therapeutic planning. Placement of multiple biopsy cores in a single container (greater than 2) appears to compromise pathological evaluation, which can reduce cancer detection rate and increase the likelihood of equivocal diagnoses. Conclusions: A 12-core systematic biopsy that incorporates apical and far-lateral cores in the template distribution allows maximal cancer detection, avoids repeat biopsy, and provides information adequate for identifying men who need therapy and planning that therapy while minimizing the detection of occult, indolent prostate cancers. This literature review does not provide compelling evidence that individual site specific labeling of cores benefits clinical decision making regarding the management of prostate cancer. Based on the available literature, we recommend packaging no more than 2 cores in each jar to avoid reduction of the cancer detection rate through inadequate tissue sampling.

Differential Use of Partial Nephrectomy for Intermediate and High Complexity Tumors May Explain Variability in Reported Utilization Rates

2013-01-10

Purpose: Partial nephrectomy has become a reference standard for tumors amenable to a kidney sparing approach but reported utilization rates vary widely. The R.E.N.A.L. (radius, exophytic/endophytic, nearness of tumor to collecting system or sinus, anterior/posterior, location relative to polar lines and hilar tumor touching main renal artery or vein) nephrometry score was developed to standardize the reporting of tumor complexity with applicability in academic and community based settings. We hypothesized that tumor and surgeon factors account for variable use of partial nephrectomy. Materials and Methods: Clinical and R.E.N.A.L. nephrometry score data were analyzed on 1,433 cases performed between 2004 and 2011 by a total of 19 surgeons with varying partial nephrectomy utilization rates (0% to 100%) who practiced at a total of 2 academic centers and 1 community based health system. Results: Partial nephrectomy use increased during the study period from 36% before 2007 to 73% for 2010 to 2012 (p <0.0001). Increasing proportions of intermediate and high R.E.N.A.L. nephrometry score tumors were treated with partial nephrectomy during this time (35% to 86% and 11% to 36%, respectively, p <0.0001). Partial nephrectomy use was stable for low complexity tumors at 91% overall. Individual surgeons performed partial nephrectomy for 0% to 100% of intermediate complexity and 0% to 45% of high complexity tumors. On multivariable analysis surgery year, tumor size, each R.E.N.A.L. nephrometry score component, surgeon and annual surgeon volume predicted partial vs radical nephrectomy (each p <0.05). On multivariable analysis several surgeon factors, including surgeon volume, setting, fellowship training, and proportional use of minimally invasive and robotic partial nephrectomy, were associated with higher partial nephrectomy use (each p <0.002). Conclusions: Surgeon and tumor factors contribute significantly to the choice of partial nephrectomy. The significant variation in partial nephrectomy use by individual surgeons appears to be caused by differential treatment for intermediate and high complexity tumors. This may be due to surgical volume, training, setting and the use of minimally invasive techniques.

Endoscopic Versus Laparoscopic Management of Noninvasive Upper Tract Urothelial Carcinoma: 20-Year Single Center Experience

2012-12-10

Purpose: We compare the outcomes of endoscopic surgery to laparoscopic nephroureterectomy for the management of specifically noninvasive upper tract urothelial carcinoma. Materials and Methods: A retrospective database review identified consecutive patients with clinically noninvasive upper tract urothelial carcinoma who underwent endoscopic surgery (59, via ureteroscopic ablation or percutaneous resection) or laparoscopic nephroureterectomy (70) at a single center during 20 years (1991 to 2011). Overall survival, upper tract urothelial carcinoma specific survival, upper tract recurrence-free survival, intravesical recurrence-free survival, progression-free survival and renal unit survival were estimated using Kaplan-Meier methods, with differences assessed using the log rank test. Results: Median age and followup were 74.8 years and 50 months, respectively. Overall renal preservation in the endoscopic group was high (5-year renal unit survival 82.5%), although this came at a cost of high local recurrence (endoscopic surgery 5-year recurrence-free survival 49.3%, laparoscopic nephroureterectomy 100%, p <0.0001). For G1 upper tract urothelial carcinoma, endoscopic surgery 5-year disease specific survival (100%) was equivalent to that of laparoscopic nephroureterectomy (100%). However, laparoscopic nephroureterectomy demonstrated superior disease specific survival to endoscopic surgery for G2 disease (91.7% vs 62.5%, p = 0.037) and superior progression-free survival for G3 disease (88.9% vs 55.6%, p = 0.033). Conclusions: For G1 upper tract urothelial carcinoma, endoscopic management can provide effective oncologic control and renal preservation. However, endoscopic management should not be considered for higher grade disease except in compelling imperative cases or in patients with poor life expectancy as oncologic outcomes are inferior to those of laparoscopic nephroureterectomy.

Editorial Comment

J. Stuart Wolf — 2013-03-21

This report adds to the evidence that endoscopic management of UTUC is an excellent alternative to nephroureterectomy in the setting of low grade malignancy but is associated with inferior oncologic outcomes in the setting of high grade malignancy. The authors attempted to limit their comparison to patients with noninvasive disease. They propose that a greater incidence of invasive disease in the extirpative cohort in prior comparative series (references 9 to 14 in article) had biased those comparisons against extirpative therapy. While this confounding may well be present, their methodology likely has biased their results against endoscopy. To the authors' credit, they admit as much, acknowledging that “a proportion of the higher grade endoscopic cases with clinically noninvasive UTUC may have been under staged, which potentially biases this group to poorer outcomes.” Thus, this report serves as a bookend on the spectrum of comparisons of endoscopic and extirpative treatment of UTUC. The oncologic efficacy of endoscopic treatment may well be overestimated in prior reports, but I suspect that its relative efficacy is underestimated in this report.

Reply by Authors

2013-03-21

It is inevitable that there will always be selection bias to the different arms of studies comparing endoscopic management to nephroureterectomy for several inherent reasons. The rare incidence of nonmuscle invasive UTUC effectively precludes the recruitment of patients with equally matched tumor characteristics to both treatment arms. Endoscopic management naturally selects patients with favorable tumor characteristics (such as small tumor size, unifocality, low grade and stage) as it is principally an ablative rather than extirpative form of surgery. However, the study outcomes do underscore the inherent dangers of treating patients with high grade disease with endoscopic management. It is likely that the poorer outcomes reflect the limitations in the efficacy of ablative surgery and the inevitable risk of under staging in patients with higher grade disease.

Impact of Smoking Status on Bladder Tumor Recurrence After Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma

2013-01-15

Purpose: Although smoking status has a significant association with clinical features in patients with bladder cancer, there are few reports of the impact of smoking on the clinical outcome of upper tract urothelial cancer. We investigated the possible influence of smoking status on bladder tumor recurrence after radical nephroureterectomy. Materials and Methods: We identified a study population of 245 consecutive patients treated surgically for upper tract urothelial cancer at our 3 institutions between 1994 and 2010. We analyzed associations between subsequent bladder tumor recurrence and patient clinicopathological parameters, including smoking status. Results: The 3-year bladder tumor recurrence-free survival rate was 32.6% in current smokers, 37.6% in former smokers and 61.7% in nonsmokers. Multivariate analysis revealed that male gender (HR 1.90, 95% CI 1.15–3.16, p = 0.013) and smoking status (former vs none HR 1.77, 95% CI 1.07–2.93, p = 0.027 and current vs none HR 1.58, 95% CI 1.03–2.42, p = 0.035) were independent risk factors for subsequent bladder tumor recurrence. Also, of patients with a positive smoking history those with 50 pack-years or greater showed a significantly higher incidence of bladder tumor recurrence after radical nephroureterectomy (HR 2.00, p = 0.003). Conclusions: Positive smoking history and male gender were independent risk factors for bladder tumor recurrence after radical nephroureterectomy. A larger number of cigarettes smoked may increase the incidence of bladder tumor recurrence in patients with upper tract urothelial cancer.

Prognostic Interest in Discriminating Muscularis Mucosa Invasion (T1a vs T1b) in Nonmuscle Invasive Bladder Carcinoma: French National Multicenter Study with Central Pathology Review

2012-11-29

Purpose: Predictive factors of T1 nonmuscle invasive bladder cancer evolution that could guide treatment decision making are lacking. We assessed the prognostic value of muscularis mucosa invasion in nonmuscle invasive bladder cancer. Materials and Methods: In a national multicenter study patients with primary T1 nonmuscle invasive bladder cancer were recruited from 6 French hospitals. All patients had undergone transurethral resection of bladder tumor. All T1 tumors were substaged according to muscularis mucosa invasion as T1a—no invasion beyond the muscularis mucosa or T1b—invasion beyond the muscularis mucosa with muscle preservation. Subsequent central pathology review was then done by a single referent uropathologist. Muscularis mucosa invasion was tested as a prognostic factor for survival on univariate and multivariate analysis. Results: A total of 587 patients were enrolled in the study, including 388 (66%) with T1a and 199 (34%) with T1b tumors. Median followup after transurethral resection of bladder tumor was 35 months (IQR 14-54). There was no significant difference between groups T1a and T1b except high tumor grade in T1b cases (p <0.0001). After central review, initial pathological substaging was confirmed in 84% of cases. On multivariate analysis muscularis mucosa invasion (T1b substage) was significantly associated with recurrence-free (p = 0.03), progression-free (p = 0.0002) and cancer specific (p = 0.02) survival. The main study limitation was absent systematic subsequent transurethral resection of bladder tumor. Conclusions: Muscularis mucosa invasion appears to be highly predictive of T1 nonmuscle invasive bladder cancer behavior. Consequently, systematic T1a vs T1b discrimination should be highly advocated by urologists and pathologists. We believe that it could aid in crucial decision making when choosing between conservative management and radical cystectomy remains a moot point.

Results of a Phase 1 Dose Escalation Study of Intravesical TMX-101 in Patients with Nonmuscle Invasive Bladder Cancer

2012-12-03

Purpose: Imiquimod, a toll like receptor 7 (TLR-7) agonist, is effective as a topical treatment for skin malignancies. TMX-101 is a liquid formulation of imiquimod. In this study we establish a safety profile of TMX-101 in patients with nonmuscle invasive bladder cancer. Materials and Methods: We conducted a multicenter phase 1 dose escalation study in patients with nonmuscle invasive bladder cancer. Patients were included in 1 of 4 dose groups (0.05%, 0.1%, 0.2% or 0.4%) and treated with 6 weekly instillations of TMX-101, starting 2 weeks after transurethral resection of bladder tumor. Patients were evaluated weekly, and pharmacokinetic and pharmacodynamic parameters were measured. Results: A total of 16 patients were included in the study with 4 per dose group. Two patients dropped out after instillation 2 in dose groups 1 and 2. Overall, 88 instillations were administered without serious adverse events. There were 118 adverse events, of which 84 were related to the study drug. All adverse events were mild or moderate and number or severity was not correlated with dose group. Of the related adverse events 70% were confined to the genitourinary tract and resolved without intervention. There was a dose dependent systemic uptake with low plasma levels up to dose group 3 (0.2%, 100 mg). Maximum plasma concentration in dose group 4 (0.4%, 200 mg) was 71.7 ng/ml. This is below plasma concentrations of 123 and 128 ng/ml without significant side effects measured in healthy volunteers after subcutaneous (30 mg) or oral intake (100 mg) of imiquimod, respectively. Conclusions: Intravesical treatment with TMX-101 is safe. The side effects are common but mild and mostly limited to the genitourinary tract. There is a low systemic uptake.

Pseudocarcinomatous Urothelial Hyperplasia of the Bladder: Clinical Findings and Followup of 70 Patients

Oleksandr N. Kryvenko, Jonathan I. Epstein — 2012-12-10

Purpose: Pseudocarcinomatous urothelial hyperplasia is rare and almost exclusively described in the pathology literature. Materials and Methods: We reviewed 70 cases during a 9.5-year period. Results: Two specimens were taken from biopsies done at our institution and 68 were from cases referred for consultation. Samples were obtained from a total of 60 men and 10 women with a mean age of 67 years (range 33 to 85). Of 68 patients with information available 52 (76.5%) underwent prior pelvic irradiation, 2 received systemic chemotherapy only, 3 had an indwelling bladder catheter, 2 received intravesical chemotherapy, 1 had been treated with radical prostatectomy, 4 had severe peripheral vascular disease, 1 had an arteriovenous malformation, 1 had sickle cell disease and only 2 (2.9%) had no identifiable contributing factors. Pseudocarcinomatous urothelial hyperplasia developed an average of 54.6 months (range 9 months to 13 years) after prior irradiation. Hematuria was the most common clinical presentation, noted in 45 of 51 patients with data available. Of 48 patients with data endoscopy revealed erythema in 20, a papillary/polypoid lesion in 12, broad-based elevated erythematous lesions in 6, erythematous bullous edema in 5, shallow bleeding ulcers in 4 and prominent trabeculation in 1. Additional findings in the bladder were carcinoma in situ in 3 cases, and dysplasia, low grade papillary urothelial carcinoma and papillary urothelial hyperplasia in 1 each. Three of the 40 patients with an average followup of 27 months (range 1 to 94) subsequently had urothelial carcinoma, including 1 who had prior positive cytology and fluorescence in situ hybridization, 1 with prior high grade papillary urothelial carcinoma and 1 with an unknown history. Conclusions: Although pseudocarcinomatous urothelial hyperplasia mimics invasive urothelial carcinoma clinically and histologically, it is not related to urothelial neoplasms. Almost all patients have causes of bladder ischemia, most commonly a history of remote prior pelvic irradiation.

Re: Comparison of Oncological Outcomes After Segmental Ureterectomy or Radical Nephroureterectomy in Urothelial Carcinomas of the Upper Urinary Tract: Results from a Large French Multicentre Study

M. Pilar Laguna — 2013-02-27

P. Colin, A. Ouzzane, G. Pignot, E. Ravier, S. Crouzet, M. M. Ariane, M. Audouin, Y. Neuzillet, B. Albouy, S. Hurel, F. Saint, J. Guillotreau, L. Guy, P. Bigot, A. De La Taille, F. Arroua, C. Marchand, A. Matte, P. O. Fais and M. Rouprêt; French Collaborative National Database on U.U.T.-U.C.

Re: Ureteroscopic and Extirpative Treatment of Upper Urinary Tract Urothelial Carcinoma: A 15-Year Comprehensive Review of 160 Consecutive Patients

M. Pilar Laguna — 2013-02-27

M. Grasso, A. I. Fishman, J. Cohen and B. Alexander Department of Urology, New York Medical College, Valhalla, New York

Re: Renal Cortical Tumors: Use of Multiphasic Contrast-Enhanced MR Imaging to Differentiate Benign and Malignant Histologic Subtypes

Cary Siegel — 2013-02-27

H. A. Vargas, J. Chaim, R. A. Lefkowitz, Y. Lakhman, J. Zheng, C. S. Moskowitz, M. J. Sohn, L. H. Schwartz, P. Russo and O. Akin Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York

Re: Targeted Delayed Scanning at CT Urography: A Worthwhile Use of Radiation?

Cary Siegel — 2013-02-27

K. Hack, P. A. Pinto and M. J. Gollub Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York

Re: Association of Polymorphisms in Oxidative Stress Genes with Clinical Outcomes for Bladder Cancer Treated with Bacillus Calmette-Guérin

David P. Wood — 2013-02-27

H. Wei, A. Kamat, M. Chen, H. L. Ke, D. W. Chang, J. Yin, H. B. Grossman, C. P. Dinney and X. Wu Department of Epidemiology, University of Texas M. D. Anderson Cancer Center, Houston, Texas

Clinical Implementation of Quality of Life Instruments and Prediction Tools for Localized Prostate Cancer: Results from a National Survey of Radiation Oncologists and Urologists

2012-12-05

Purpose: Although clinical guidelines recommend assessing quality of life, cancer aggressiveness and life expectancy for making localized prostate cancer treatment decisions, it is unknown whether instruments that objectively measure such outcomes have disseminated into clinical practice. In this context we determined whether quality of life and prediction instruments for prostate cancer have been adopted by radiation oncologists and urologists in the United States. Materials and Methods: Using a nationally representative mail survey of 1,422 prostate cancer specialists in the United States, we queried about self-reported clinical implementation of quality of life instruments, prostate cancer nomograms and life expectancy prediction tools in late 2011. The Pearson chi-square test and multivariate logistic regression were used to determine differences in the use of each instrument by physician characteristics. Results: A total of 313 radiation oncologists and 328 urologists completed the survey for a 45% response rate. Although 55% of respondents reported using prostate cancer nomograms, only 27% and 23% reported using quality of life and life expectancy prediction instruments, respectively. On multivariate analysis urologists were less likely to use quality of life instruments than radiation oncologists (OR 0.40, p <0.001). Physicians who spent 30 minutes or more counseling patients were consistently more likely to use quality of life instruments (OR 2.57, p <0.001), prostate cancer nomograms (OR 1.83, p = 0.009) and life expectancy prediction tools (OR 1.85, p = 0.02) than those who spent less than 15 minutes. Conclusions: Although prostate cancer nomograms have been implemented into clinical practice to some degree, the use of quality of life and life expectancy tools has been more limited. Increased attention to implementing validated instruments into clinical practice may facilitate shared decision making for patients with prostate cancer.

Image Guided Hypofractionated Radiotherapy and Quality of Life for Localized Prostate Cancer: Prospective Longitudinal Study in 337 Patients

2013-01-10

Purpose: We prospectively analyzed quality of life in a cohort of patients with prostate cancer undergoing a course of hypofractionated image guided radiotherapy. Materials and Methods: Between August 2006 and January 2011, 337 patients with a median age of 73 years who had cT1-T2N0M0 prostate cancer were eligible for this prospective, longitudinal study of hypofractionated image guided radiotherapy (70.2 Gy/26 fractions) using 1 of 3 image guided radiotherapy modalities (transabdominal ultrasound, x-ray or cone beam computerized tomography) available in our radiation oncology department. Patients completed 4 questionnaires before treatment, and 6, 12 and 24 months later, including the International Index of Erectile Function-5, International Prostate Symptom Score, and EORTC (European Organization for Research and Treatment of Cancer) prostate cancer specific QLQ-PR25 and QLQ-C30. Results: Patient followup was updated to at least the last questionnaire time point. Median followup was 19 months. Significant deterioration in erectile function on the International Index of Erectile Function-5 was documented with time only in patients without androgen deprivation (p = 0.0002). No change with time was observed in urinary symptom related quality of life on the QLQ-PR25 or International Prostate Symptom Score. Slight deterioration in QLQ-PR25 bowel symptom related quality of life was observed (p = 0.02). Overall QLQ-C30 Global Health Status improved with time (p = 0.03). On univariate analysis it significantly correlated with the maximum RTOG (Radiation Therapy Oncology Group)/EORTC urinary and bowel late toxicity scores after radiotherapy. Conclusions: The regimen of hypofractionated image guided radiotherapy with multiple imaging modalities adopted in our radiation oncology department for localized prostate cancer might be a successful strategy for dose escalation with a limited impact on different aspects of quality of life with time.

Re: 11C-Choline PET/CT in Patients with Hormone-Resistant Prostate Cancer Showing Biochemical Relapse After Radical Prostatectomy

Samir S. Taneja — 2013-03-07

F. Ceci, P. Castellucci, M. Mamede, R. Schiavina, D. Rubello, C. Fuccio, V. Ambrosini, S. Boschi, G. Martorana and S. Fanti Nuclear Medicine Unit, Department of Haematology, Oncology and Laboratory Medicine, Azienda Ospedaliero-Universitaria di Bologna, Policlinico Sant'Orsola-Malpighi, University of Bologna, Bologna, Italy

Re: Analysis of Urological Procedures in Men Who Died from Prostate Cancer Using a Population-Based Approach

Samir S. Taneja — 2013-03-13

K. Babaian, M. Truong, J. Cetnar, D. S. Cross, F. Shi, M. A. Ritter and D. F. Jarrard Department of Urology, University of Wisconsin School of Medicine and Public Health, and Departments of Medicine and Human Oncology, University of Wisconsin Carbone Cancer Center, Madison and Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, Wisconsin

Re: 20-Year Survival After Radical Prostatectomy as Initial Treatment for cT3 Prostate Cancer

Samir S. Taneja — 2013-03-13

C. R. Mitchell, S. A. Boorjian, E. C. Umbreit, L. J. Rangel, R. E. Carlson and R. J. Karnes Department of Urology, Mayo Medical School and Mayo Clinic, Rochester, Minnesota

Re: Early Salvage Radiation Therapy Combined with Short-Term Hormonal Therapy in Recurrent Prostate Cancer After Radical Prostatectomy: Single-Institution 4-Year Data on Outcome, Toxicity, Health-Related Quality of Life and Co-Morbidities from 184 Consecutive Patients Treated with 70 Gy

Samir S. Taneja — 2013-03-13

J. R. Cortés-González, E. Castellanos, K. Sandberg, M. H. Eriksson, P. Wiklund, S. Carlsson, G. Cohn-Cedermark, U. Harmenberg, O. Gustafsson, S. H. Levitt, B. Lennernäs, Y. Brandberg, M. Márquez, K. M. Kälkner and S. Nilsson

Re: Socioeconomic Status, Healthcare Density, and Risk of Prostate Cancer Among African American and Caucasian Men in a Large Prospective Study

David F. Penson — 2013-02-28

J. M. Major, M. Norman Oliver, C. A. Doubeni, A. R. Hollenbeck, B. I. Graubard and R. Sinha Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, Maryland

Re: Explaining Racial Differences in Prostate Cancer Mortality

David F. Penson — 2013-03-01

G. B. Taksler, N. L. Keating and D. M. Cutler Department of Medicine, New York University School of Medicine, New York, New York

Re: Active Surveillance for Prostate Cancer Compared with Immediate Treatment: An Economic Analysis

David F. Penson — 2013-03-01

K. A. Keegan, M. A. Dall'Era, B. Durbin-Johnson and C. P. Evans Department of Urologic Surgery, Vanderbilt University, Nashville, Tennessee

Re: Barriers to the Implementation of Surveillance for Stage I Testicular Seminoma

Jerome P. Richie — 2013-02-27

N. D. Arvold, P. J. Catalano, C. J. Sweeney, K. E. Hoffman, P. L. Nguyen, T. A. Balboni, S. D. Fosså, L. R. Travis and C. J. Beard Harvard Radiation Oncology Program, Harvard Medical School, Boston, Massachusetts

A Prospective Study Examining the Incidence of Bacteriuria and Urinary Tract Infection After Shock Wave Lithotripsy with Targeted Antibiotic Prophylaxis

2013-01-02

Purpose: Controversy exists regarding antibiotic prophylaxis before shock wave lithotripsy. The AUA (American Urological Association) guideline recommends universal antibiotic prophylaxis, whereas the EAU (European Association of Urology) guideline recommends prophylaxis only for select patients. We evaluated the use of targeted antibiotic prophylaxis in preventing urinary tract infections in patients undergoing shock wave lithotripsy. Materials and Methods: A prospective single cohort study was performed during 6 months with patients undergoing shock wave lithotripsy. All patients underwent urine dipstick and culture before shock wave lithotripsy. Targeted antibiotic prophylaxis was provided at the discretion of the treating urologist. All patients had a urine culture performed after shock wave lithotripsy and completed a survey documenting fevers or urinary symptoms. The primary outcome was the incidence of urinary tract infections, urosepsis and asymptomatic bacteriuria after shock wave lithotripsy. The secondary outcome was the sensitivity and specificity of urinary dipstick leukocytes and nitrites. Results: A total of 526 patients were enrolled in the study. Of the 389 patients included in the determination of the primary outcome, urinary tract infection developed in only 1 (0.3%), urosepsis did not develop in any patients and asymptomatic bacteriuria developed in 11 (2.8%). Eight (2.1%) patients were administered antibiotic prophylaxis. The specificity of urine dipstick nitrites was high (95%) while the sensitivity was poor (9.7%). Conclusions: In our cohort study using targeted antibiotic prophylaxis the rates of urinary tract infection after shock wave lithotripsy and rates of asymptomatic bacteriuria were extremely low, with no development of urosepsis. This finding questions the need for universal antibiotic prophylaxis before shock wave lithotripsy.

Circumcision and Lifetime Risk of Urinary Tract Infection: A Systematic Review and Meta-Analysis

Brian J. Morris, Thomas E. Wiswell — 2012-11-28

Purpose: Urinary tract infection is common in infant males who are uncircumcised and can lead to renal parenchymal disease of the still growing pediatric kidney. Although the rate of urinary tract infection is highest in the first year of life, the cumulative incidence during the rest of the lifetime is under-recognized, but is expected to be nontrivial. Thus, any intervention that might prevent urinary tract infection would be expected to reduce suffering and medical costs. Materials and Methods: We conducted a meta-analysis of 22 studies examining the single risk factor of lack of circumcision, then determined the prevalence and relative risk of urinary tract infection in different age groups (0 to 1, 1 to 16 and older than 16 years). From these data we estimated the lifetime prevalence. Results: For age 0 to 1 year the relative risk was 9.91 (95% CI 7.49–13.1), for age 1 to 16 years RR was 6.56 (95% CI 3.26–13.2) and for older than 16 years it was 3.41-fold (95% CI 0.916–12.7) higher in uncircumcised males. We then calculated that 32.1% (95% CI 15.6–49.8) of uncircumcised males experience a urinary tract infection in their lifetime compared with 8.8% (95% CI 4.15–13.2) of circumcised males (RR 3.65, 95% CI 1.15–11.8). The number needed to treat was 4.29 (95% CI 2.20–27.2). Conclusions: The single risk factor of lack of circumcision confers a 23.3% chance of urinary tract infection during the lifetime. This greatly exceeds the prevalence of circumcision complications (1.5%), which are mostly minor. The potential seriousness of urinary tract infection supports circumcision as a desirable preventive health intervention in infant males.

A Novel Method for Iatrogenic Vesicovaginal Fistula Treatment: Autologous Platelet Rich Plasma Injection and Platelet Rich Fibrin Glue Interposition

Maliheh Keshvari Shirvan, Daryoush Hamidi Alamdari, Alireza Ghoreifi — 2013-01-02

Purpose: Vesicovaginal fistula remains a challenge in surgical therapy. In this study autologous platelet rich plasma and platelet rich fibrin glue were used as a minimally invasive approach for vesicovaginal fistula closure. Materials and Methods: Data including age, parity, ICIQ-UI (International Consultation on Incontinence Questionnaire-urinary incontinence), ICIQ-QOL (International Consultation on Incontinence Questionnaire-quality of life), duration of leakage, fistula diameter and complications were collected before and after the intervention. Platelet rich plasma and platelet rich fibrin glue were prepared from 12 patients' own blood. De-epithelialization was performed around the fistula until a small hemorrhage occurred. Platelet rich plasma was injected around the fistula into the tissue and platelet rich fibrin glue was interpositioned in the tract. Results: No complications were observed during and after the injection. Mean ± SD patient age was 39.75 ± 8.45 years. At 6-month followup 11 patients considered themselves clinically cured, and transvaginal physical examination and cystography were normal. ICIQ-UI and ICIQ-QOL showed remarkable improvement in 11 patients. One patient had significant improvement but did not consent to the second injection. None of the patients had voiding dysfunction, urinary incontinence, retention or urinary tract infection. Conclusions: Autologous platelet rich plasma injection and platelet rich fibrin glue interposition offer a safe, effective and novel minimally invasive approach for the treatment of vesicovaginal fistula which obviate the need for open surgery. We propose calling this technique the Hamidi-Shirvan method.

Re: α-Blockers, Antibiotics and Anti-Inflammatories have a Role in the Management of Chronic Prostatitis/Chronic Pelvic Pain Syndrome

Edward M. Schaeffer — 2013-03-07

A. Thakkinstian, J. Attia, T. Anothaisintawee and J. C. Nickel Section for Clinical Epidemiology and Biostatistics, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

Re: Continuous Intravesical Lidocaine Treatment for Interstitial Cystitis/Bladder Pain Syndrome: Safety and Efficacy of a New Drug Delivery Device

Edward M. Schaeffer — 2013-03-11

J. C. Nickel, P. Jain, N. Shore, J. Anderson, D. Giesing, H. Lee, G. Kim, K. Daniel, S. White, C. Larrivee-Elkins, J. Lekstrom-Himes and M. Cima Department of Urology, Queen's University, Kingston, Ontario, Canada

Clinical Implications and Applications of the Twinkling Sign in Ureteral Calculus: A Preliminary Study

Gyanendra Sharma, Anshu Sharma — 2012-12-05

Purpose: Twinkling is an artifact seen on color Doppler ultrasound as a rapidly changing mixture of red and blue behind a stationary echogenic structure. We studied the presence or absence of this artifact in ureteral calculi detected on ultrasound and correlated it with clinical parameters. Materials and Methods: We evaluated 284 ureteral calculi seen on color Doppler ultrasound. The twinkling artifact was graded as 0 to 2 and correlated with the presence or absence of pain, symptom duration, degree of hydronephrosis and passage of a Glidewire® guidewire across the ureteral calculus during ureterorenoscopy. Results: The presence or absence of twinkling was not associated with the degree of hydronephrosis. Twinkling was absent in 92% of patients with significant pain and grade 2 twinkling was seen in 69.5% without significant pain. Twinkling was dominantly absent in patients with a recent colic episode, while 77% who presented 2 to 15 days after a colic episode had grade 2 twinkling. The guidewire was difficult to pass in cases with absent twinkling compared to those with grade 2 twinkling, in which the guidewire and ureteral catheter crossed the calculus easily. Conclusions: Absent twinkling is associated with significant pain, a recent colic episode and difficult guidewire passage across the calculus. These findings suggest that absent twinkling implies significant obstruction, while its presence indicates no significant obstruction.

How Much is a Kidney Worth? Cost-Effectiveness of Routine Imaging After Ureteroscopy to Prevent Silent Obstruction

Tori N. Sutherland, Margaret S. Pearle, Yair Lotan — 2013-01-02

Purpose: The 2012 American Urological Association (AUA) Clinical Effectiveness Protocols for Imaging in the Management of Ureteral Calculous Disease recommends routine postoperative imaging after ureteroscopy. We evaluated the cost-effectiveness of routine postoperative imaging after ureteroscopy. Materials and Methods: We searched the literature to determine the risk of complications after routine ureteroscopy for stones, including the incidence of postoperative pain, stricture and silent obstruction. Sequelae of renal loss due to undiagnosed silent obstruction may include chronic kidney disease, end stage renal disease and cardiovascular disease. Imaging and procedure costs were obtained from Medicare reimbursement rates and the literature. The costs and prevalence of lifetime complications associated with silent loss of 1 kidney were obtained from the renal donor transplant literature. A decision tree was constructed to calculate the cost of a strategy of routinely imaging all patients after ureteroscopy vs selective imaging based on postoperative pain. We performed 1-way and 2-way sensitivity analyses. Results: The average cost per patient of a strategy of routine imaging after ureteroscopy in all patients was $5,326 vs $5,196 for a strategy of selective imaging based on postoperative pain. Assuming a 2% rate of silent obstruction, the cost per kidney saved would be $6,262. Conclusions: While routine postoperative imaging carries a $130 per patient incrementally higher cost over that of a strategy of selective imaging in patients with postoperative pain, preventing renal loss and its attendant morbidity justifies the additional modest cost.

Obesity Triples the Radiation Dose of Stone Protocol Computerized Tomography

2012-12-26

Purpose: Patients with recurrent nephrolithiasis are often evaluated and followed with computerized tomography. Obesity is a risk factor for nephrolithiasis. We evaluated the radiation dose of computerized tomography in obese and nonobese adults. Materials and Methods: We scanned a validated, anthropomorphic male phantom according to our institutional renal stone evaluation protocol. The obese model consisted of the phantom wrapped in 2 Custom Fat Layers (CIRS, Norfolk, Virginia), which have been verified to have the same radiographic tissue density as fat. High sensitivity metal oxide semiconductor field effect transistor dosimeters were placed at 20 organ locations in the phantoms to measure organ specific radiation doses. The nonobese and obese models have an approximate body mass index of 24 and 30 kg/m2, respectively. Three runs of renal stone protocol computerized tomography were performed on each phantom under automatic tube current modulation. Organ specific absorbed doses were measured and effective doses were calculated. Results: The bone marrow of each model received the highest dose and the skin received the second highest dose. The mean ± SD effective dose for the nonobese and obese models was 3.04 ± 0.34 and 10.22 ± 0.50 mSv, respectively (p <0.0001). Conclusions: The effective dose of stone protocol computerized tomography in obese patients is more than threefold higher than the dose in nonobese patients using automatic tube current modulation. The implication of this finding extends beyond the urological stone population and adds to our understanding of radiation exposure from medical imaging.

The Interaction of Thiol Drugs and Urine pH in the Treatment of Cystinuria

Daniel M. Asplin, John R. Asplin — 2012-12-26

Purpose: Pharmacological therapy for cystinuria consists of alkali salts to increase urine pH and thiol drugs to form soluble cysteine-drug complexes. The effect of alkalinizing urine on thiol drug activity has not been well studied. Materials and Methods: Urine samples were obtained from 5 healthy subjects and pH was adjusted (range 6.0 to 8.0) in each urine aliquot. Urine samples were incubated with cystine crystals at 37C for 5, 15 and 60 minutes, and 48 hours. We compared cystine solubility in urine samples spiked with thiol drugs at a final concentration of 2 mM to that in control urine samples at the various pH levels and time points. Results: In samples incubated for 48 hours, which is the standard time frame for solubility studies, cystine solubility more than doubled with thiol drugs compared to control and did not depend on pH. However, when incubation time was shortened to 5 minutes, representing the dwell time of urine in the renal pelvis, the effect of thiol drugs to solubilize cystine greatly depended on urine pH with less cystine dissolved at lower pH. Conclusions: Increasing urine pH greatly increased the efficacy of thiol drugs to solubilize cystine in a clinically relevant time frame. These findings suggest that to maximize the benefit of thiol drugs alkali therapy should be used in conjunction with thiol drugs with the goal of keeping urine pH at 7.5 or above. Clinical trials are needed to confirm these in vitro findings.

Urolithiasis After Ileal Conduit Urinary Diversion: A Comparison of Minimally Invasive Therapies

2012-12-10

Purpose: We report our experience with ureteroscopy, percutaneous nephrolithotomy and shock wave lithotripsy for symptomatic stone disease in patients with ileal conduit urinary diversion. Materials and Methods: We retrospectively reviewed the charts of all patients treated with cystectomy and ileal conduit urinary diversion from 1982 to June 2010 in whom urolithiasis subsequently developed. Results: We identified 77 patients with urolithiasis requiring surgical intervention after ileal conduit urinary diversion. Average age at treatment was 62.5 years (range 30 to 82). Mean followup was 7.1 years (range 0.1 to 24.3). The primary therapy mode was percutaneous nephrolithotomy in 48 patients (62.3%), extracorporeal shock wave lithotripsy in 20 (26.0%) and ureteroscopy in 9 (11.6%). Average stone size was greater in the nephrolithotomy group than in the ureteroscopy and lithotripsy groups (2.1 vs 0.9 and 1.0 cm, respectively, p <0.0001). Total complication rates were similar, including 29% for nephrolithotomy, 30% for lithotripsy and 33% for ureteroscopy (p = 0.9). The incidence of stone-free status was greater in the nephrolithotomy cohort than in the ureteroscopy and shock wave lithotripsy cohorts (83.3% vs 33.3% and 30%, respectively, p <0.0001). The re-treatment rate did not significantly differ among the groups with 66.7% of the ureteroscopy group requiring subsequent procedures compared to 29.2% of the nephrolithotomy and 45% of the lithotripsy groups (p = 0.08). The change in the mean preoperative and current calculated glomerular filtration rate did not significantly differ among the 3 treatment groups. Conclusions: Treatment for urolithiasis in patients with urinary diversion is associated with high re-treatment and complication rates. Percutaneous nephrolithotomy achieves a better stone-free outcome than ureteroscopy or shock wave lithotripsy. However, there is no difference in ancillary procedures or complication rates among the 3 treatment modalities.

Epidemiology of Upper Urinary Tract Stone Disease in a Taiwanese Population: A Nationwide, Population Based Study

2013-01-10

Purpose: We investigated the epidemiology of upper urinary tract stone disease in Taiwan using a nationwide, population based database. Materials and Methods: This study was based on the National Health Insurance Research Database of Taiwan, which contains data on all medical beneficiary claims from 22.72 million enrollees, accounting for almost 99% of the Taiwanese population. The Longitudinal Health Insurance Database 2005, a subset of the National Health Insurance Research Database, contains data on all medical benefit claims from 1997 through 2010 for a subset of 1 million beneficiaries randomly sampled from the 2005 enrollment file. For epidemiological analysis we selected subjects whose claims records included the diagnosis of upper urinary tract urolithiasis. Results: The age adjusted rate of medical care visits for upper urinary tract urolithiasis decreased by 6.5% from 1,367/100,000 subjects in 1998 to 1,278/100,000 in 2010. There was a significantly decreasing trend during the 13-year period in visits from female and all subjects (r2 = 0.86, p = 0.001 and r2 = 0.52, p = 0.005, respectively). In contrast, an increasing trend was noted for male subjects (r2 = 0.45, p = 0.012). The age adjusted prevalence in 2010 was 9.01%, 5.79% and 7.38% in male, female and all subjects, respectively. The overall recurrence rate at 1 and 5 years was 6.12% and 34.71%, respectively. Male subjects had a higher recurrence rate than female subjects. Conclusions: Our study provides important information on the epidemiology of upper urinary tract stone disease in Taiwan, helping to quantify the burden of urolithiasis and establish strategies to decrease the risk of urolithiasis.

Re: The Relation Between Bone and Stone Formation

Dean G. Assimos — 2013-03-06

N. S. Krieger and D. A. Bushinsky Division of Nephrology, Department of Medicine, University of Rochester School of Medicine, Rochester, New York

Re: Determinants of Urolithiasis in Patients with Intestinal Fat Malabsorption

Dean G. Assimos — 2013-03-13

R. Siener, J. Petzold, N. Bitterlich, B. Alteheld and C. Metzner University Stone Centre, Department of Urology, University of Bonn, Bonn, Germany

Re: Review of Penile Prosthetic Reservoir: Complications and Presentation of a Modified Reservoir Placement Technique

Allen F. Morey — 2013-02-28

L. A. Levine and M. P. Hoeh Department of Urology, Rush University Medical Center, Chicago, Illinois

Re: Laparascopic Capsulotomy to Treat Autoinflation of Inflatable Penile Prostheses

Allen F. Morey — 2013-03-01

P. H. Abbosh, M. R. Thom and A. Bullock Division of Urology, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri

Re: Dorsal Penile Nerve Block Prior to Inflatable Penile Prosthesis Placement: A Randomized, Placebo-Controlled Trial

Allen F. Morey — 2013-03-01

M. C. Raynor, A. Smith, S. N. Vyas, J. P. Selph and C. C. Carson, III Division of Urology, University of North Carolina School of Medicine, Chapel Hill, North Carolina

Re: Outcome of Penile Revascularization for Arteriogenic Erectile Dysfunction After Pelvic Fracture Urethral Injuries

Allen Seftel — 2013-03-08

J. M. Zuckerman, K. A. McCammon, B. E. Tisdale, L. Colen, T. Uroskie, P. McAdams and G. H. Jordan Department of Urology, Eastern Virginia Medical School, Norfolk, Virginia

Re: Erectile Dysfunction in Patients with Traumatic Urethral Strictures Treated with Anastomotic Urethroplasty: A Single-Factor Analysis

Allen Seftel — 2013-03-13

C. Y. Tang, Q. Fu, R. J. Cui and X. J. Sun Urethral Disease, Diagnosis and Treatment Center, Department of Urology, Shanghai 6th Hospital, Shanghai Jiaotong University, Shanghai, PR China

Re: Optimal Preoperative Assessment of the Geriatric Surgical Patient: A Best Practices Guideline from the American College of Surgeons National Surgical Quality Improvement Program and the American Geriatrics Society

Richard K. Babayan — 2013-02-27

W. B. Chow, R. A. Rosenthal, R. P. Merkow, C. Y. Ko and N. F. Esnaola; American Geriatrics Society American College of Surgeons National Surgical Quality Improvement Program, Chicago, Illinois

Caffeine Intake and its Association with Urinary Incontinence in United States Men: Results from National Health and Nutrition Examination Surveys 2005–2006 and 2007–2008

2013-01-02

Purpose: Epidemiological studies in women have revealed an association between caffeine intake and urinary incontinence, although evidence among men is limited. Therefore, we evaluated the association between caffeine intake and urinary incontinence in United States men. Materials and Methods: Data were used from male NHANES (National Health and Nutrition Examination Surveys) 2005–2006 and 2007–2008 participants. Urinary incontinence was defined using a standard questionnaire with Incontinence Severity Index scores 3 or greater categorized as moderate to severe. Structured dietary recall was used to determine caffeine consumption (mg per day), water intake (gm per day) and total dietary moisture (gm per day). Stepwise multivariable logistic regression models were used to assess the association between caffeine intake at or above the 75th and 90th percentiles and moderate to severe urinary incontinence, controlling for potential confounders, urinary incontinence risk factors and prostate conditions in men age 40 years or older. Results: Of the 5,297 men 3,960 (75%) were 20 years old or older with complete data. Among these men the prevalence of any urinary incontinence was 12.9% and moderate to severe urinary incontinence was 4.4%. Mean caffeine intake was 169 mg per day. Caffeine intake at the upper 75th percentile (234 mg or more daily) and 90th percentile (392 mg or more per day) was significantly associated with having moderate to severe urinary incontinence (1.72, 95% 1.18–2.49 and 2.08, 95% 1.15–3.77, respectively). In addition, after adjusting for prostate conditions, the effect size for the association between caffeine intake and moderate to severe urinary incontinence remained. Conclusions: Caffeine consumption equivalent to approximately 2 cups of coffee daily (250 mg) is significantly associated with moderate to severe urinary incontinence in United States men. Our findings support the further study of caffeine modification in men with urinary incontinence.

Comparison of Lower Urinary Tract Symptoms Between Women with Detrusor Overactivity and Impaired Contractility, and Detrusor Overactivity and Preserved Contractility

Kobi Stav, Yaniv Shilo, Amnon Zisman, Arie Lindner, Dan Leibovici — 2012-12-05

Purpose: We compared symptoms in women with detrusor overactivity with impaired contractility and women with detrusor overactivity who had preserved contractility. Materials and Methods: The study included 359 consecutive women with detrusor overactivity who underwent multichannel urodynamics at our department between 2009 and 2011. The women were divided into 2 groups, including 151 (42%) with detrusor overactivity and impaired contractility, and 208 (58%) with detrusor overactivity and preserved contractility. We compared the 2 groups. Results: Women with detrusor overactivity and impaired contractility were older (mean ± SD age 73.2 ± 17.3 vs 54.1 ± 20.7 years) with a higher frequency of diabetes mellitus (49% vs 31%, each p <0.001). The prevalence of previous urinary retention and recurrent cystitis was significantly higher in women with impaired contractility (7% vs 1%, p <0.01 and 22% vs 7%, p <0.001, respectively). Mean post-void residual urine was greater in the group with impaired contractility (89 ± 42 vs 21 ± 18 ml) and the mean maximal flow rate was lower (11 ± 6 vs 23 ± 5 ml per second, each p <0.001). The frequency of storage symptoms was similar in the 2 groups. However, voiding symptoms were more common in women with impaired contractility, including a slow stream in 69% vs 42%, an intermittent stream in 72% vs 26%, hesitancy in 35% vs 22%, straining in 84% vs 26%, terminal dribbling in 73% vs 42% and incomplete emptying in 71% vs 49% (p <0.001). Conclusions: Women with detrusor overactivity and impaired contractility are older than women with detrusor overactivity and preserved detrusor contractility. Urinary retention and recurrent cystitis are more frequent in women with detrusor overactivity and impaired contractility, and voiding symptoms are significantly more common.

Sensory Evoked Potentials of the Human Lower Urinary Tract

2012-12-03

Purpose: We investigated the feasibility and reliability of recording sensory evoked potentials after lower urinary tract electrical stimulation. Sensory evoked potentials might reveal improved insights into afferent processing in specific locations of the human lower urinary tract. Materials and Methods: Electrical stimulation (0.5 and 3 Hz) was applied to the bladder dome and trigone, and the proximal and distal urethra using a transurethral catheter. Cortical sensory evoked potentials were recorded at the Cz electrode with reference to the Fz electrode. All measurements were repeated 3 times for reliability assessment using the ICC. Results: Ten healthy female subjects with a mean ± SD age of 23 ± 4 years and a mean height of 168 ± 6 cm were included in the study. The most prominent, consistent sensory evoked potential landmark across different locations was the first negative peak. In all subjects after 0.5 Hz stimulation, the first negative peak was reliably recorded at a mean of 128.8 ± 23.8, 141.9 ± 51.5, 133.1 ± 32.1 and 132.5 ± 33.6 milliseconds (ICC 0.88, 0.83, 0.90 and 0.81) at the bladder dome, trigone, proximal and distal urethra, respectively. After 3 Hz stimulation, no reliable sensory evoked potentials could be recorded. Conclusions: Sensory evoked potentials can be reliably recorded from different lower urinary tract locations after 0.5 Hz stimulation with a characteristic negativity at about 130 milliseconds. These latencies are compatible with a conduction velocity in the range of 3 to 10 m per second, corresponding to transmission by A-δ fibers. The inability to retrieve reliable responses at 3 Hz stimulation might potentially be related to less involvement of fast conduction fibers, ie A-β, in afferent sensation along the human lower urinary tract. The value of a more distinct diagnosis of sensory sensation in lower urinary tract disorders must be evaluated in further studies.

OnabotulinumtoxinA for the Treatment of Patients with Overactive Bladder and Urinary Incontinence: Results of a Phase 3, Randomized, Placebo Controlled Trial

2012-12-14

Purpose: Overactive bladder affects 12% to 17% of the general population and almost a third experience urinary incontinence, which may severely impact health related quality of life. Oral anticholinergics are the mainstay of pharmacological treatment but they are limited by inadequate efficacy or side effects, leading to a high discontinuation rate. We report the results of the first large (557 patients), phase 3, placebo controlled trial of onabotulinumtoxinA in patients with overactive bladder and urinary incontinence inadequately managed with anticholinergics. Materials and Methods: Eligible patients with overactive bladder, 3 or more urgency urinary incontinence episodes in 3 days and 8 or more micturitions per day were randomized 1:1 to receive intradetrusor injection of onabotulinumtoxinA 100 U or placebo. Co-primary end points were the change from baseline in the number of urinary incontinence episodes per day and the proportion of patients with a positive response on the treatment benefit scale at posttreatment week 12. Secondary end points included other overactive bladder symptoms and health related quality of life. Adverse events were assessed. Results: OnabotulinumtoxinA significantly decreased the daily frequency of urinary incontinence episodes vs placebo (–2.65 vs –0.87, p <0.001) and 22.9% vs 6.5% of patients became completely continent. A larger proportion of onabotulinumtoxinA than placebo treated patients reported a positive response on the treatment benefit scale (60.8% vs 29.2%, p <0.001). All other overactive bladder symptoms improved vs placebo (p ≤0.05). OnabotulinumtoxinA improved patient health related quality of life across multiple measures (p <0.001). Uncomplicated urinary tract infection was the most common adverse event. A 5.4% rate of urinary retention was observed. Conclusions: OnabotulinumtoxinA 100 U showed significant, clinically relevant improvement in all overactive bladder symptoms and health related quality of life in patients inadequately treated with anticholinergics and was well tolerated.

Percutaneous Tibial Nerve Stimulation for the Long-Term Treatment of Overactive Bladder: 3-Year Results of the STEP Study

2012-12-05

Purpose: We report the long-term efficacy and safety of percutaneous tibial nerve stimulation with the Urgent® PC Neuromodulation System for overactive bladder after 3 years of therapy. Materials and Methods: Fifty participants in the randomized, double-blind SUmiT (Sham Effectiveness in Treatment of Overactive Bladder Symptoms) Trial who met the primary effectiveness end point after 12 weekly percutaneous tibial nerve stimulation treatments were enrolled in this prospective study to assess long-term outcomes with percutaneous tibial nerve stimulation. STEP (Sustained Therapeutic Effects of Percutaneous Tibial Nerve Stimulation) Study patients were prescribed a fixed schedule 14-week tapering protocol followed by a personal treatment plan aimed at sustaining overactive bladder symptom improvement. Overactive bladder and quality of life questionnaires were completed every 3 months and 3-day voiding diaries were completed every 6 months. Results: A total of 29 patients completed the 36-month protocol and received a median of 1.1 treatments per month after a 14-week treatment tapering protocol. A Bayesian model estimated that 77% (95% CI 64–90) of patients maintained moderate or marked improvement in overactive bladder symptoms at 3 years. Compared to baseline, median voids per day decreased from 12.0 (IQR 10.3–13.7) to 8.7 (IQR 7.3–11.3), nighttime voids per night decreased from 2.7 (IQR 1.7–3.3) to 1.7 (IQR 1.0–2.7) and urge incontinence episodes per day decreased from 3.3 (IQR 0.7–6.0) to 0.3 (IQR 0.0–1.0) (all p <0.0001). All quality of life parameters remained markedly improved from baseline through 3 years (all p <0.0001). One patient experienced 2 mild treatment related adverse events of bleeding at the needle site during followup. Conclusions: Most STEP participants with an initial positive response to 12 weekly percutaneous tibial nerve stimulation treatments safely sustained overactive bladder symptom improvement to 3 years with an average of 1 treatment per month.

Re: The Efficacy of Posterior Tibial Nerve Stimulation for the Treatment of Overactive Bladder in Women: A Systematic Review

Alan J. Wein — 2013-03-07

P. J. Levin, J. M. Wu, A. Kawasaki, A. C. Weidner and C. L. Amundsen Duke University, Durham, North Carolina

Re: Association of Overactive Bladder and C-Reactive Protein Levels. Results from the Boston Area Community Health (BACH) Survey

Alan J. Wein — 2013-03-11

V. Kupelian, R. C. Rosen, C. G. Roehrborn, P. Tyagi, M. B. Chancellor and J. B. McKinlay New England Research Institutes, Watertown, Massachusetts

Re: Efficacy and Tolerability of Mirabegron, a β3-Adrenoceptor Agonist, in Patients with Overactive Bladder: Results from a Randomised European-Australian Phase 3 Trial

Alan J. Wein — 2013-03-11

V. Khullar, G. Amarenco, J. C. Angulo, J. Cambronero, K. Høye, I. Milsom, P. Radziszewski, T. Rechberger, P. Boerrigter, T. Drogendijk, M. Wooning and C. Chapple St. Mary's Hospital, Imperial College, London, United Kingdom

Re: OnabotulinumtoxinA Improves Health-Related Quality of Life in Patients with Urinary Incontinence due to Idiopathic Overactive Bladder: A 36-Week, Double-Blind, Placebo-Controlled, Randomized, Dose-Ranging Trial

Alan J. Wein — 2013-03-11

C. J. Fowler, S. Auerbach, D. Ginsberg, D. Hale, P. Radziszewski, T. Rechberger, V. D. Patel, J. Zhou, C. Thompson and J. W. Kowalski National Hospital for Neurology and Neurosurgery, London, United Kingdom

Re: An Evaluation of Bladder Emptying Methods and the Effect of Demographic and Clinical Factors on Spontaneous Voiding Frequency in Stroke Patients

Tomas Griebling — 2013-03-08

M. Ersoz, B. Erhan, Y. Akkoc, M. Zinnuroglu, N. Yildiz, H. Gok, S. Ozdolap, H. Tunc, K. Kaya, E. Alemdaroglu, S. Susuzer, B. Gunduz, A. N. Bardak, S. Ozcan, H. Yesil, K. Uygunol, S. Konukcu, N. Gunes and F. Ege; Turkish Neurogenic Bladder Research Group

Re: Influence of Oxidative Stress on Inducing Micturition Dysfunction Following Chronic Infravesical Obstruction and the Protective Role of an Antioxidant Diet—Association of In Vivo and In Vitro Studies in Rats

Tomas Griebling — 2013-03-13

S. Bisogni, F. T. Ferreira, A. Amstalden Neto, L. O. Chiarelli and V. Ortiz Geriatric Urology Service, Federal University of São Paulo, São Paulo, Brazil

Re: Prevalence and Correlates of Nocturia in Community-Dwelling Older Men: Results from the Korean Longitudinal Study on Health and Aging

Tomas Griebling — 2013-03-13

Y. J. Lee, S. J. Jeong, S. S. Byun, J. J. Lee, J. W. Han and K. W. Kim Department of Urology, Seoul National University College of Medicine, Seoul, Korea

Re: Systematic Review of Care Intervention Studies for the Management of Incontinence and Promotion of Continence in Older People in Care Homes with Urinary Incontinence as the Primary Focus (1966–2010)

Tomas Griebling — 2013-03-13

L. Flanagan, B. Roe, B. Jack, J. Barrett, A. Chung, C. Shaw and K. W. Williams Wirral University Teaching Hospitals NHS Foundation Trust, Arrowe Park Hospital, Wirral, United Kingdom

Re: Risk Factors for Fecal Incontinence in Older Women

Tomas Griebling — 2013-03-13

M. K. Townsend, C. A. Matthews, W. E. Whitehead and F. Grodstein Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts

Re: Involvement of Estrogen Receptors in Prostatic Diseases

Steven A. Kaplan — 2013-03-06

H. Kawashima and T. Nakatani Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan

Re: Sleep Analysis of Patients with Nocturia and Benign Prostatic Obstruction

Steven A. Kaplan — 2013-03-06

K. Bal, S. Ayik, Y. Issi, A. Bolukbasi and G. Akhan Department of Urology, Izmir Ataturk Research and Training Hospital, Izmir, Turkey

Re: Robotic Single Port Suprapubic Transvesical Enucleation of the Prostate (R-Step): Initial Experience

Jeffrey A. Cadeddu — 2013-02-27

K. Fareed, O. M. Zaytoun, R. Autorino, W. M. White, S. Crouzet, R. Yakoubi, G. P. Haber, M. A. White and J. H. Kaouk Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio

Renal Perfusion Pump Vs Cold Storage for Donation After Cardiac Death Kidneys: A Systematic Review

2012-12-05

Purpose: Static cold storage is generally used to preserve kidney allografts from deceased donors. Hypothermic machine perfusion may improve the outcome after transplantation but few studies with limited power have addressed this issue. We reviewed evidence of the effectiveness of storing kidneys from deceased donors after cardiac death before transplantation using cold static storage solution or pulsatile hypothermic machine perfusion. Materials and Methods: We searched electronic databases in September 2011 for systematic reviews and/or meta-analyses, randomized, controlled trials and studies of other designs that compared delayed graft function and graft survival. Sources included The Cochrane Library, PubMed® and EMBASE®. Studies excluded from review included those that did not discriminate between donation after cardiac death and donation from a neurologically deceased donor. Primary outcomes were delayed graft function and 1-year graft survival. Statistical analysis was done using RevMan (http://ims.cochrane.org/revman). Results: Nine studies qualified for review. Pulsatile perfusion pumped kidneys from donation after cardiac death donors had decreased delayed graft function compared to kidneys placed in cold storage (OR 0.64, 95% CI 0.43–0.95, p = 0.03). There was a trend toward improved 1-year graft survival in the pulsatile perfusion group but statistical significance was not attained (OR 0.74, 95% CI 0.48–1.13, p = 0.17). Conclusions: Pulsatile machine perfusion of donation after cardiac death kidneys appears to decrease the delayed graft function rate. We noted no benefit in 1-year graft survival. Due to the great heterogeneity among the trials as well as several confounding factors, the overall impact on allograft function and survival requires more study.

Re: Independent of Nephrectomy, Weaning Immunosuppression Leads to Late Sensitization After Kidney Transplant Failure

David A. Goldfarb — 2013-01-21

J. J. Augustine, K. J. Woodside, A. Padiyar, E. Q. Sanchez, D. E. Hricik and J. A. Schulak Department of Medicine, University Hospitals Case Medical Center, Cleveland, Ohio

Re: Value of Routine Voiding Cystourethrography After Renal Transplantation

David A. Goldfarb — 2013-02-27

M. Margreiter, G. P. Györi, G. A. Böhmig, S. Trubel, F. Mühlbacher and R. Steininger Department of Urology, Medical University Vienna, Vienna, Austria

Childhood Enuresis is Associated with Shorter Intravaginal Ejaculatory Latency Time in Healthy Men

Ahmet Gokce, Fikret Halis — 2012-12-10

Purpose: In our previous study we showed that there was a significant increase in the prevalence of monosymptomatic enuresis among lifelong premature ejaculators. In this study we compared the intravaginal ejaculatory latency time of men with and without a history of monosymptomatic enuresis, and determined the association between the severity and duration of monosymptomatic enuresis and intravaginal ejaculatory latency time in healthy men. Materials and Methods: Between March and September 2012 we designed a prospective study in 49 healthy men who had a history of monosymptomatic enuresis and in age matched 49 control cases without a history of monosymptomatic enuresis. All subjects were asked about their history of monosymptomatic enuresis. Each subject was then evaluated using the premature ejaculation diagnostic tool and asked to measure their intravaginal ejaculatory latency times with their female sexual partner using a calibrated stopwatch. Results: Men with a history of monosymptomatic enuresis and control cases had a mean age of 33.6 (SD 4.7, range 25 to 43) and 33.8 (SD 5.4, range 25 to 48) years, respectively (p = 0.97). Mean/median intravaginal ejaculatory latency times of men with and without a history of monosymptomatic enuresis were 196.9/126.2 and 426.6/343.2 seconds, respectively (p <0.001). Mean/median premature ejaculation diagnostic tool scores of men with and without a history of monosymptomatic enuresis were 7.1/6 and 2.3/2, respectively (p <0.001). In correlation matrix analysis, intravaginal ejaculatory latency times and premature ejaculation diagnostic tool scores were correlated significantly with monosymptomatic enuresis history, duration and severity (p <0.001). Conclusions: We found that intravaginal ejaculatory latency time in men with a history of monosymptomatic enuresis is significantly shorter than that of controls. We have also shown that there is a strong negative correlation between having a history of monosymptomatic enuresis and intravaginal ejaculatory latency time.

A Phase 3, Placebo Controlled Study of the Safety and Efficacy of Avanafil for the Treatment of Erectile Dysfunction After Nerve Sparing Radical Prostatectomy

2012-12-05

Purpose: We evaluated the safety and efficacy of 100 and 200 mg avanafil for the treatment of adult males with erectile dysfunction after bilateral nerve sparing radical prostatectomy. Materials and Methods: This was a double-blind, placebo controlled, parallel group, phase 3 study in males age 18 to 70 years with a history of erectile dysfunction of 6 months or more after bilateral nerve sparing radical prostatectomy. Patients were randomized to 100 or 200 mg avanafil or placebo (taken 30 minutes before sexual activity) for 12 weeks. Primary end points included successful vaginal insertion (Sexual Encounter Profile [SEP] question 2), successful intercourse (SEP3) and change in score on the erectile function domain of the International Index of Erectile Function (IIEF-EF) questionnaire. Results: A total of 298 patients were randomized and 84.6% completed the study. At baseline 16.1% were age 65 years or older and 71.5% had severe erectile dysfunction (mean overall IIEF-EF domain score 9.2). After 12 weeks there were significantly greater increases in SEP2 and SEP3 and change in mean IIEF-EF domain score with 100 and 200 mg avanafil vs placebo (p <0.01). Following dosing with avanafil 36.4% (28 of 77) of sexual attempts (SEP3) at 15 minutes or less were successful vs 4.5% (2 of 44) for placebo (p <0.01). Avanafil was generally well tolerated. No serious adverse events were reported and fewer than 2% of patients discontinued the study due to an adverse event. Conclusions: Avanafil in 100 and 200 mg doses was effective and well tolerated in improving erectile function after prostatectomy. Results suggest a rapid onset of action and sustained duration of effect, with all 3 primary end points being achieved at both dose levels.

How Painful is Adult Circumcision? A Prospective, Observational Cohort Study

Bhavan Prasad Rai, Asim Qureshi, Nourdin Kadi, Roland Donat — 2013-01-02

Purpose: Men are particularly concerned about pain after circumcision. Concerns about pain can be a reason to refuse surgery. We assessed the severity of postoperative pain and investigated factors that may influence postoperative pain. Materials and Methods: We performed a prospective, observational cohort study in patients undergoing circumcision. Patients were asked to complete a questionnaire using a visual analog scale for pain (severity range 0 to 10) on days 1 to 3, 7 and 21, and record the analgesia used, complications and time off work. Other data recorded were patient age, clinical indication for surgery, foreskin retractility, presence of adhesions and histology. Results: Of 211 questionnaires 112 were returned (53.1%). Mean patient age was 46.4 years. The most common clinical indication for circumcision was phimosis (75% of patients). Postoperative pain was scored as mild to moderate, including a mean of 2.4 on days 1 to 3, 2.1 on day 7 and 0.5 on day 21. Patients younger than 35 years (p = 0.025) and patients with wound infection (p = 0.036) had higher pain scores. Only 11 patients (9.8%) had severe pain at any time during recovery, including 8 with wound problems. Average ± SD time off work in the employed population was 6.6 ± 6.5 days, including 5 days for light work and 11 days for heavy physical activity. Conclusions: Pain is mild to moderate after circumcision in adults under general anesthesia with an intraoperative penile block. Severe pain is rare and mostly related to complications. Younger patients generally have more discomfort.

Androgen Receptor Expression Relationship with Semen Variables in Infertile Men with Varicocele

2012-11-28

Purpose: Androgen receptor, a member of the nuclear receptor superfamily, has important roles in male reproductive function. It is required for sexual differentiation, pubertal development, spermatogenesis regulation, meiosis completion and spermatocyte transition to haploid round spermatids. We assessed the association of androgen receptor expression and semen variables in infertile men with varicocele. Materials and Methods: A total of 299 men were grouped into healthy, fertile controls, infertile men without varicocele and men with infertility associated with varicocele. A history was obtained, clinical examination and semen analysis were done and reproductive hormones were estimated. Androgen receptor expression and the acrosome reaction were determined in recovered spermatozoa. Results: Androgen receptor expression was significantly decreased in infertile men with varicocele more than in infertile men without varicocele compared to fertile controls. Androgen receptor correlated positively with sperm count, motility, normal forms, velocity, linear velocity, acrosome reaction and α-glucosidase. It correlated negatively with serum follicle-stimulating hormone and estradiol. Multiple stepwise regression analysis of androgen receptor expression revealed that the sperm acrosome reaction and linearity index were the most affected independent variables. Conclusions: Androgen receptor expression was significantly decreased in infertile men with varicocele more than in infertile men without varicocele compared to fertile men. Androgen receptor expression correlated positively with sperm count, motility, normal forms, velocity, linear velocity and acrosome reaction.

Compliance with Semen Analysis

Jon Duplisea, Thomas Whelan — 2013-01-28

Purpose: We calculated the compliance rate and determined which population of men would be more or less likely to be compliant with semen analysis followup based on demographic information and complication rates. Materials and Methods: We retrospectively reviewed the records of 946 consecutive patients who underwent vasectomy at an ambulatory clinic, as performed by 1 urologist. Standard followup consisted of a telephone call or prebooked appointment 2 months after vasectomy and 2 semen analyses 4 months after vasectomy. Results: Average ± SD patient age was 33.6 ± 5.4 years. Of the 946 study patients 47.9% did not submit a negative semen sample, 15.7% submitted 1 and 36.4% submitted the required 2 negative samples to confirm successful vasectomy according to the sampling protocol. Mean time to semen analysis was 4.53 ± 2.14 months. Complications included infection in 1.9% of cases, hematoma in 1% and sperm granuloma in 0.5%. Men 34 years or younger, men with 3 or more children and men without complications were more likely to be noncompliant with semen analysis. Conclusions: The number of men who provided samples for semen analysis in this study was low, although they were given written and verbal reminders. This poor patient compliance is similar to that in previous studies. We identified a subset of patients with poor compliance, which may allow urologists to target preprocedure counseling more appropriately.

Re: A Multivariate Twin Study of Female Sexual Dysfunction

Allen Seftel — 2013-03-08

A. Burri, C. Greven, M. Leupin, T. Spector and Q. Rahman Department of Twin Research and Genetic Epidemiology, King's College London, St. Thomas' Hospital, London, United Kingdom

Re: Is Female Sexual Function Related to the Male Partners' Erectile Function?

Allen Seftel — 2013-03-13

B. P. Jiann, C. C. Su and J. Y. Tsai Division of Basic Medical Research, Department of Medical Education and Research, Division of Urology, Department of Surgery, Kaohsiung Veterans General Hospital and Department of Urology, Yuan's General Hospital, Kaohsiung and School of Medicine, National Yang-Ming University, Taipei, Taiwan

Re: Cognitive Performance in Healthy Women During Induced Hypogonadism and Ovarian Steroid Addback

Allen Seftel — 2013-03-13

P. J. Schmidt, P. A. Keenan, L. A. Schenkel, K. Berlin, C. Gibson and D. R. Rubinow Section on Behavioral Endocrinology, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland

Re: Testosterone Implants in Women: Pharmacological Dosing for a Physiologic Effect

Allen Seftel — 2013-03-13

R. Glaser, S. Kalantaridou and C. Dimitrakakis Millennium Wellness Center, Dayton, Ohio

Re: A Case-Control Study on the Association Between Chronic Prostatitis/Chronic Pelvic Pain Syndrome and Erectile Dysfunction

Edward M. Schaeffer — 2013-03-07

S. D. Chung, J. J. Keller and H. C. Lin Division of Urology, Department of Surgery, Far Eastern Memorial Hospital, Ban Ciao, Taiwan

Re: Relationship of Sex Hormones and Nocturia in Lower Urinary Tract Symptoms Induced by Benign Prostatic Hyperplasia

Steven A. Kaplan — 2013-04-12

M. K. Kim, C. Zhao, S. D. Kim, D. G. Kim and J. K. Park Department of Urology, Chonbuk National University Medical School, Jeonju, Korea

Re: Association Between Lower Urinary Tract Symptoms and Sexual Dysfunction Assessed Using the Core Lower Urinary Tract Symptom Score and International Index of Erectile Function-5 Questionnaires

Steven A. Kaplan — 2013-04-12

M. Nakamura, T. Fujimura, M. Nagata, C. Hosoda, M. Suzuki, H. Fukuhara, Y. Enomoto, H. Nishimatsu, H. Kume, Y. Igawa and Y. Homma Department of Urology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan

Re: Dietary Patterns and Semen Quality in Young Men

Craig Niederberger — 2013-03-07

A. J. Gaskins, D. S. Colaci, J. Mendiola, S. H. Swan and J. E. Chavarro Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts

Re: Micronutrients Intake is Associated with Improved Sperm DNA Quality in Older Men

Craig Niederberger — 2013-03-13

T. E. Schmid, B. Eskenazi, F. Marchetti, S. Young, R. H. Weldon, A. Baumgartner, D. Anderson and A. J. Wyrobek Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California

Re: South African Plants and Male Reproductive Healthcare: Conception and Contraception

Craig Niederberger — 2013-03-13

H. S. Abdillahi and J. Van Staden University of KwaZulu-Natal Pietermaritzburg, Research Centre for Plant Growth and Development, School of Life Sciences, Scottsville, South Africa

Re: Epigenetic Disruption of the PIWI Pathway in Human Spermatogenic Disorders

Craig Niederberger — 2013-03-13

H. Heyn, H. J. Ferreira, L. Bassas, S. Bonache, S. Sayols, J. Sandoval, M. Esteller and S. Larriba Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, L'Hospitalet de Llobregat, Barcelona, Catalonia, Spain

Re: Clinical Characteristics and Reproductive Outcomes in Infertile Men with Testicular Early and Late Maturation Arrest

Craig Niederberger — 2013-03-13

M. C. Tsai, Y. S. Cheng, T. Y. Lin, W. H. Yang and Y. M. Lin Department of Urology, National Cheng Kung University Hospital, National Cheng Kung University College of Medicine, Tainan, Taiwan

Autoimmune Disease and Subsequent Urological Cancer

2012-12-10

Purpose: We examined the subsequent risk and prognosis of urological cancer in individuals diagnosed with autoimmune disease. Materials and Methods: We systematically analyzed the risk and prognosis of prostate, kidney and bladder cancers in individuals diagnosed with any of 33 autoimmune diseases based on a national Swedish database for 1964 through 2008. The SIR and HR were calculated for subsequent urological cancers between 1964 and 2008 in individuals hospitalized for autoimmune disease. Results: An increased SIR for urological cancer was recorded after 26 autoimmune diseases. An increased HR for cancer specific survival was noted after 4 autoimmune diseases and for overall survival after 18. The highest SIRs were seen for kidney cancer after polyarteritis nodosa (2.85) and polymyositis/dermatomyositis (2.68), and for bladder cancer after polymyositis/dermatomyositis (2.45). The highest risk of prostate cancer (1.70) was observed after polyarteritis nodosa. SIRs were lower during followup from 1990 to 2008 compared to the previous period. Individuals diagnosed with prostate and kidney cancers showed an improved cancer specific prognosis, in contrast to the poorer overall prognosis for all 3 urological cancers. Conclusions: The risk of urological cancer was increased after all autoimmune diseases. The most significant changes after individual autoimmune diseases were toward higher risk. Survival data were reassuring since autoimmune disease only marginally influences the prognosis of cancer specific mortality. However, overall survival was decreased for the 3 types of cancer.

Online Reviews of 500 Urologists

Chandy Ellimoottil, Alissa Hart, Kristin Greco, Marcus L. Quek, Ahmer Farooq — 2012-12-10

Purpose: Patient demand for easily accessible information about physician quality has led to the development of physician review websites. These sites concern some physicians who argue that ratings can be misleading. In this study we describe the landscape of online reviews of urologists by looking at a sample of ratings and written reviews from popular physician review websites. Materials and Methods: A total of 500 urologists were randomly selected from a database of 9,940. Numerical ratings from 10 popular physician review websites were collected for each physician and analyzed. Written reviews from a single physician review website were also collected and then categorized as extremely negative/positive, negative/positive or neutral. Results: Our sample consisted of 471 male and 29 female urologists from 39 states including small and large cities and 4 census regions. There were 398 (79.6%) urologists who had at least 1 rating on any of the 10 physician review websites (range 0 to 64). On average the composite rating was based on scores from only 2.4 submitted ratings. Most physicians had positive ratings (86%), with 36% having highly positive ratings. No difference was seen in the median number of reviews when gender (p = 0.72), region (p = 0.87) and city size (p = 0.87) were compared. Written reviews were mostly positive or extremely positive (53%). Conclusions: We advise physicians and patients to be aware that most urologists are rated on at least 1 physician review website, and while most ratings and reviews are favorable, composite scores are typically based on a small number of reviews and, therefore, can be volatile.

Hypospadias Repair at a Tertiary Care Center: Long-Term Followup is Mandatory to Determine the Real Complication Rate

2013-01-09

Purpose: The field of reconstructive surgery for hypospadias is lacking standard techniques and followup. Most published series include complication rates after a short followup. We report and analyze the long-term outcome of primary hypospadias repair at a single tertiary care center. Materials and Methods: We reviewed 1,061 operations performed at our institution between 1997 and 2010 and registered as hypospadias repair. The operations were performed in 543 patients born between June 1997 and June 2005. A retrospective database was created with information about hypospadias characteristics, surgery and followup. Results: A total of 474 primary repairs were selected, excluding incomplete/incorrect files. Distal penile hypospadias was reported in 366 patients (77.2%), mid penile hypospadias in 54 (11.4%) and proximal hypospadias in 54 (11.4%). Initial repair technique was based on incised plate in 189 patients (39.9%), meatal advancement in 171 (36%), onlay flap in 82 (17.3%) and other or combined techniques in 25 (5.3%). Insufficient information was reported for 7 patients (1.5%). Mean age at first operation was 22.6 months (range 4 to 134) and mean followup after first operation was 34.0 months (0 to 145). Of the children 360 (75.9%) had a good long-term outcome and required only 1 procedure. Reoperation was needed in 114 patients (24.1%), of whom 54 (47.4%) underwent reoperation in the first year of followup. Conclusions: Overall a good long-term outcome without further complication was achieved in 75.9% of our cases. Of the 24.1% of patients who needed reoperation only 47.4% presented within the first year postoperatively, indicating the need for long-term followup when reporting outcomes of hypospadias repair.

Short Pelvic Floor Electromyographic Lag Time: A Novel Noninvasive Approach to Document Detrusor Overactivity in Children with Lower Urinary Tract Symptoms

Andrew J. Combs, Jason P. Van Batavia, Mark Horowitz, Kenneth I. Glassberg — 2013-01-10

Purpose: Noninvasive uroflow with simultaneous electromyography can measure electromyographic lag time, ie the interval between the start of pelvic floor relaxation and the start of urine flow (normally 2 to 6 seconds). Intuitively one would expect that in patients experiencing urgency secondary to detrusor overactivity the lag time would be short or even a negative value. We studied whether short electromyographic lag time on uroflow with electromyography actually correlates with documented detrusor overactivity on urodynamics. Materials and Methods: We reviewed 2 separate and distinct cohorts of 50 neurologically and anatomically normal children with persistent lower urinary tract symptoms who were evaluated by uroflow with simultaneous electromyography and videourodynamics. Group 1 consisted of 30 boys and 20 girls (mean age 7.8 years, range 4 to 19) selected based on electromyographic lag time of 0 seconds or less on screening uroflow with electromyography who subsequently underwent videourodynamics. Group 2 consisted of 14 boys and 36 girls (median age 8.4 years, range 5 to 18) selected based on the presence of detrusor overactivity on videourodynamics whose screening uroflow with electromyography was then reviewed. Correlations between short electromyographic lag time and videourodynamically proved detrusor overactivity were analyzed. Results: For group 1 urodynamics confirmed the presence of detrusor overactivity in all patients with an electromyographic lag time of 0 seconds or less. For group 2 mean ± SD electromyographic lag time was 0.1 ± 1.7 seconds, and 35 patients (70%) with urodynamically proved detrusor overactivity had a lag time of 0 seconds or less. Conclusions: In patients with lower urinary tract symptoms an electromyographic lag time of 0 seconds or less is 100% predictive of detrusor overactivity. This short electromyographic lag time has 100% specificity and 70% sensitivity for diagnosing detrusor overactivity (88% if less than 2 seconds). Thus, diagnosing the presence or absence of detrusor overactivity in most children with lower urinary tract symptoms and a quiet pelvic floor during voiding can be done reliably via uroflow with simultaneous electromyography.

Models of Care for Vesicoureteral Reflux With and Without an End Point of Reflux Resolution: A Computer Cost Analysis

Gaayana A. Raju, Andrew J. Marks, Ronald M. Benoit, Steven G. Docimo — 2012-12-26

As providers increasingly believe in a more benign natural history of childhood vesicoureteral reflux, many have adopted a noninterventional approach, reserving aggressive therapy for select patients. On the other hand, the availability of subureteral injection has caused many to question whether indications for correction of vesicoureteral reflux should be more liberal than in the past.

Outcomes Following Fecal Continence Procedures in Patients with Neurogenic Bowel Dysfunction

Nathan Y. Hoy, Peter Metcalfe, Darcie A. Kiddoo — 2012-12-26

Purpose: Malone antegrade continence enema and cecostomy button improve quality of life in patients with neurogenic bowel. However, they have not been compared regarding fecal continence outcomes. We compared these 2 procedures with respect to continence, complications and conversions. Materials and Methods: We retrospectively reviewed the charts of patients who underwent Malone antegrade continence enema or cecostomy at the University of Alberta between January 2006 and January 2011. A total of 26 patients underwent Malone antegrade continence enema, of whom 20 underwent concomitant Monti procedure and bladder augmentation, 5 a laparoscopically assisted procedure and 1 concomitant ileovesicostomy. A total of 23 patients underwent cecostomy, of whom 1 underwent ileovesicostomy, 1 bladder augmentation, 1 a Monti procedure with bladder augmentation and 1 laparoscopic cecostomy. Continence was defined as ability to wear underwear with no accidents at most recent annual followup, which was a minimum of 1 year postoperatively. Results: Fecal continence rates were 84.6% for Malone antegrade continence enema and 91.3% for cecostomy. There were no statistically significant differences in continence based on procedure (p = 0.48), age (p = 0.97) or gender (p = 0.54). Of patients who underwent cecostomy 8.7% switched to the Malone antegrade continence enema, while 11.5% with Malone antegrade continence enema switched to cecostomy. Mean length of hospital stay for patients undergoing cecostomy vs laparoscopically assisted Malone antegrade continence enema was 4.0 vs 5.2 days (p = 0.15). Complications included stomal pain (23.1% of patients) and difficulty with catheterizing (19.2%) following Malone antegrade continence enema, and difficulty flushing (26.1%) following cecostomy. Conclusions: There were no significant differences between Malone antegrade continence enema and cecostomy button with respect to fecal continence or complication rates. Each approach poses unique challenges, suggesting that patients and families need to understand the differences to make an individualized choice.

Pubertal Screening and Treatment for Varicocele do not Improve Chance of Paternity as Adult

Guy Bogaert, Christophe Orye, Gunter De Win — 2012-12-26

Purpose: We investigated the eventual positive effects of early screening and treatment for varicocele in pubertal boys without symptoms to determine their chance of paternity later in life. It has not been proved if the presence of varicocele during puberty has an influence on later fertility or paternity. However, since an influence is believed to exist, beginning in 1987 the Belgian Society of Pediatrics has recommended screening all boys 12 to 17 years old during their yearly medical examination and referral for followup or treatment if varicocele is detected. At our clinic patients and their parents were informed about and able to choose between varicocele treatment (antegrade sclerotherapy) and observation. We subsequently contacted these patients, who are now older than 30 years, and inquired about their paternity. Materials and Methods: We selected for this study pubertal boys 12 to 17 years old with a varicocele who were referred by screening pediatricians to our pediatric urology clinic between 1989 and 2005. We excluded patients with bilateral or unilateral right varicocele and patients with other medical problems that could influence fertility. A total of 661 patients were eligible for the study. Minimally invasive treatment of varicocele, ie antegrade sclerotherapy (with the patient under local or general anesthesia), was offered but not required. Of the patients 372 underwent treatment (mean age 15.3 years, median 15.6) and 289 were followed conservatively (mean age 17.1, median 16.4). All patients were contacted twice by letter and, if no response was received, once by telephone. Patients were asked about paternity, time to conception and whether they had visited a fertility center. Results: Of the 361 respondents 158 (43%) had an active desire to have a child. Paternity was achieved in 85% of the conservatively followed group and 78% of the active treatment group (p >0.05). Conclusions: There is no beneficial effect of pubertal screening and treatment for varicocele regarding chance of paternity later in life.

Editorial Comment

Steven J. Skoog — 2013-03-21

The authors have provided survey data on paternity suggesting that surgical intervention to treat adolescent boys with varicocele is no better than observation of these patients. The paternity rate in both groups was approximately 80% when the mean age of paternity was 30 years. This finding is remarkably similar to the adult data suggesting that 15% to 20% of males with varicocele will seek medical attention for infertility (reference 14 in article), implying that 80% do not have a fertility problem. Should this information preclude us from treating adolescents with varicocele? I believe not. What it suggests is that we need better selection criteria for intervention in adolescents to find the 20% who will have subsequent problems with fertility. The mere presence of a varicocele in insufficient to recommend surgical intervention.

Re: Unilateral Multicystic Dysplastic Kidney: Does Initial Size Matter?

Douglas A. Canning — 2013-02-28

W. N. Hayes and A. R. Watson; Trent and Anglia MCDK Study Group Children's Renal and Urology Unit, Nottingham Children's Hospital, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom

Re: Desmopressin and Oxybutynin in Monosymptomatic Nocturnal Enuresis: A Randomized, Double-Blind, Placebo-Controlled Trial and an Assessment of Predictive Factors

Douglas A. Canning — 2013-03-01

P. Montaldo, L. Tafuro, M. Rea, V. Narciso, A. C. Iossa and R. Del Gado Department of Pediatrics, Second University of Naples, Naples, Italy

Re: Ileal Bladder Augmentation and Vitamin B12: Levels Decrease with Time After Surgery

Douglas A. Canning — 2013-03-01

S. C. Blackburn, S. Parkar, M. Prime, L. Healiss, D. Desai, I. Mustaq, P. Cuckow, P. Duffy and A. Cherian Department of Urology, Great Ormond Street Hospital for Children, London, United Kingdom

Re: Predictive Factors and Management of Steinstrasse After Shock Wave Lithotripsy in Pediatric Urolithiasis—A Multivariate Analysis Study

Dean G. Assimos — 2013-03-06

B. Onal, S. Citgez, N. Tansu, C. Demirdag, C. Dogan, B. Gonul, O. Demirkesen, C. Obek and A. Erozenci Department of Urology, University of Istanbul Cerrahpasa Medical Faculty, Istanbul, Turkey

Re: Ureteroscopy in Pediatric Patients with Spinal Abnormalities

Dean G. Assimos — 2013-03-11

C. J. Colangelo, G. W. Kaplan, N. Holmes, K. Palazzi-Churas and G. Chiang UC San Diego, San Diego, California

Inflammatory Myofibroblastic Tumor of the Kidney

Lawrence C. Jenkins, Elizabeth Whittington, Gaetano Ciancio, Merce Jorda — 2013-03-18

A 61-year-old man presented with 2 weeks of back pain and hematuria. Ultrasound and computed tomography revealed a 4.5 cm heterogeneous mass involving the lower pole of the left kidney and enlarged lymph nodes medial to the mass highly suggestive of renal cell carcinoma. He then underwent a left laparoscopic radical nephrectomy with regional lymphadenectomy.

High Flow Priapism on Color Doppler Ultrasound

Jawad M. Qureshi, Hadley Wood, Myra Feldman — 2013-03-07

A 25-year-old male patient presented with a 3-day history of persistent, painless semirigid erection. He had no history of recent trauma, hematological disease or drug use (recreational, psychotropic or oral supplement). On examination the penile shaft was turgid and nontender. Diffuse ecchymosis was noted along the shaft and scrotum. Arterial blood gas analysis from cavernous aspirate showed pH 7.45, pCO2 36.9, pO2 71.8 and HCO3 24.3. Complete blood count and urinalysis were normal. The clinical findings were consistent with arterial, nonischemic (high flow) priapism.

CRM1 Blockade by Selective Inhibitors of Nuclear Export Attenuates Kidney Cancer Growth

2012-10-17

Purpose: Renal cell carcinoma often presents asymptomatically and patients are commonly diagnosed at the metastatic stage, when treatment options are limited and survival is poor. Since progression-free survival using current therapy for metastatic renal cell carcinoma is only 1 to 2 years and existing drugs are associated with a high resistance rate, new pharmacological targets are needed. We identified and evaluated the nuclear exporter protein CRM1 as a novel potential therapy for renal cell carcinoma. Materials and Methods: We tested the efficacy of the CRM1 inhibitors KPT-185 and 251 in several renal cell carcinoma cell lines and in a renal cell carcinoma xenograft model. Apoptosis and cell cycle arrest were quantified and localization of p53 family proteins was assessed using standard techniques. Results: KPT-185 attenuated CRM1 and showed increased cytotoxicity in renal cell carcinoma cells in vitro with evidence of increased apoptosis as well as cell cycle arrest. KPT-185 caused p53 and p21 to remain primarily in the nucleus in all renal cell carcinoma cell lines, suggesting that the mechanism of action of these compounds depends on tumor suppressor protein localization. Furthermore, when administered orally in a high grade renal cell carcinoma xenograft model, the bioavailable CRM1 inhibitor KPT-251 significantly inhibited tumor growth in vivo with the expected on target effects and no obvious toxicity. Conclusions: The CRM1 inhibitor protein family is a novel therapeutic target for renal cell carcinoma that deserves further intensive investigation for this and other urological malignancies.

The Role of c-FLIP in Cisplatin Resistance of Human Bladder Cancer Cells

Sangchul Lee, Cheol Yong Yoon, Seok-Soo Byun, Eunsik Lee, Sang Eun Lee — 2013-01-10

Purpose: We investigated the mechanisms underlying cisplatin resistance in human bladder cancer cells to provide novel molecular targets for the treatment of cisplatin resistant bladder cancer. Materials and Methods: The differential gene expression of cisplatin sensitive (T24) and resistant (T24R2) human bladder cancer cell lines was analyzed and validated by microarray and Western blot analysis. Changes in cisplatin sensitivity by c-FLIP knockdown and related mechanisms in T24R2 cells were assessed using the Cell Counting Kit-8 assay (Dojindo Molecular Technologies, Gaithersburg, Maryland) and Western blot. siRNA oligonucleotides that specifically target c-FLIP were prepared and siRNA transfection was done. Results: Microarray analysis revealed that the expression of 1,086 and 322 genes showed more than twofold and fourfold changes in the T24R2 and T24 cell lines, respectively. Especially genes involved in the c-FLIP related death receptor apoptosis pathway, including caspase 2 and 9, NF-kB, BID, c-FLIP, XIAP, and cIAP1 and 2, showed differential expression in the 2 cell lines. Western blot demonstrated complete cisplatin mediated suppression of c-FLIP expression in T24 cells but no change in c-FLIP expression was observed in T24R2 cells after cisplatin treatment in the same dose range. Suppression of c-FLIP expression in T24R2 cells by siRNA transfection rendered these cells significantly more sensitive to cisplatin treatment than untransfected T24R2 cells (p <0.05). Conclusions: Results reveal that c-FLIP has an important role in the cisplatin resistance of human bladder cancer cells and c-FLIP modulation may at least partially reverse cisplatin resistance in bladder cancer cells.

Using the Epigenetic Field Defect to Detect Prostate Cancer in Biopsy Negative Patients

2012-11-16

Purpose: We determined whether a novel combination of field defect DNA methylation markers could predict the presence of prostate cancer using histologically normal transrectal ultrasound guided biopsy cores. Materials and Methods: Methylation was assessed using quantitative Pyrosequencing® in a training set consisting of 65 nontumor and tumor associated prostate tissues from University of Wisconsin. A multiplex model was generated using multivariate logistic regression and externally validated in blinded fashion in a set of 47 nontumor and tumor associated biopsy specimens from University of Washington. Results: We observed robust methylation differences in all genes at all CpGs assayed (p <0.0001). Regression models incorporating individual genes (EVX1, CAV1 and FGF1) and a gene combination (EVX1 and FGF1) discriminated nontumor from tumor associated tissues in the original training set (AUC 0.796-0.898, p <0.001). On external validation uniplex models incorporating EVX1, CAV1 or FGF1 discriminated tumor from nontumor associated biopsy negative specimens (AUC 0.702, 0.696 and 0.658, respectively, p <0.05). A multiplex model (EVX1 and FGF1) identified patients with prostate cancer (AUC 0.774, p = 0.001) and had a negative predictive value of 0.909. Comparison between 2 separate cores in patients in this validation set revealed similar methylation defects, indicating detection of a widespread field defect. Conclusions: A widespread epigenetic field defect can be used to detect prostate cancer in patients with histologically negative biopsies. To our knowledge this assay is unique, in that it detects alterations in nontumor cells. With further validation this marker combination (EVX1 and FGF1) has the potential to decrease the need for repeat prostate biopsies, a procedure associated with cost and complications.

Expression of Vesicular Glutamate Transporters in Sensory and Autonomic Neurons Innervating the Mouse Bladder

2012-11-15

Purpose: VGLUTs, which are essential for loading glutamate into synaptic vesicles, are present in various neuronal systems. However, to our knowledge the expression of VGLUTs in neurons innervating the bladder has not yet been analyzed. We studied VGLUT1, VGLUT2 and VGLUT3 in mouse bladder neurons. Materials and Methods: We analyzed the expression of VGLUT1, VGLUT2 and calcitonin gene-related peptide by immunohistochemistry in the retrograde labeled primary afferent and autonomic neurons of BALB/c mice after injecting fast blue in the bladder wall. To study VGLUT3 we traced the bladder of transgenic mice, in which VGLUT3 is identified by enhanced green fluorescent protein detection. Results: Most bladder dorsal root ganglion neurons expressed VGLUT2. A smaller percentage of neurons also expressed VGLUT1 or VGLUT3. Co-expression with calcitonin gene-related peptide was only observed for VGLUT2. Occasional VGLUT2 immunoreactive neurons were seen in the major pelvic ganglia. Abundant VGLUT2 immunoreactive nerves were detected in the bladder dome and trigone, and the urethra. VGLUT1 immunoreactive nerves were discretely present. Conclusions: We present what are to our knowledge novel data on VGLUT expression in sensory and autonomic neurons innervating the mouse bladder. The frequent association of VGLUT2 and calcitonin gene-related peptide in sensory neurons suggests interactions between glutamatergic and peptidergic neurotransmissions, potentially influencing commonly perceived sensations in the bladder, such as discomfort and pain.

Differentiation of Calcium Oxalate Monohydrate and Calcium Oxalate Dihydrate Stones Using Quantitative Morphological Information from Micro-Computerized and Clinical Computerized Tomography

2012-11-09

Purpose: We differentiated calcium oxalate monohydrate and calcium oxalate dihydrate kidney stones using micro and clinical computerized tomography images. Materials and Methods: A total of 22 calcium oxalate monohydrate and 15 calcium oxalate dihydrate human kidney stones were scanned using a commercial micro-computerized tomography scanner with a pixel size of 7 to 23 μm. Under an institutional review board approved protocol, image data on 10 calcium oxalate monohydrate and 9 calcium oxalate dihydrate stones greater than 5 mm were retrieved from a total of 80 patients who underwent clinical dual energy computerized tomography for clinical indications and had stones available for infrared spectroscopic compositional analysis. Micro and clinical computerized tomography images were processed using in-house software, which quantified stone surface morphology with curvature based calculations. A shape index was generated as a quantitative shape metric to differentiate calcium oxalate monohydrate from calcium oxalate dihydrate stones. Statistical tests were used to test the performance of the shape index. Results: On micro-computerized tomography images the shape index of calcium oxalate monohydrate and calcium oxalate dihydrate stones significantly differed (ROC curve AUC 0.92, p <0.0001). At the optimal cutoff sensitivity was 0.93 and specificity was 0.91. On clinical computerized tomography images a significant morphological difference was also detected (p = 0.007). AUC, sensitivity and specificity were 0.90, 1 and 0.73, respectively. Conclusions: On micro and clinical computerized tomography images a morphological difference was detectable in calcium oxalate monohydrate and calcium oxalate dihydrate stones larger than 5 mm. The shape index is a highly promising method that can distinguish calcium oxalate monohydrate and calcium oxalate dihydrate stones with reasonable accuracy.

In Vitro Study of the Revised Ultrasound Based Real-Time Tracking of Renal Stones for Shock Wave Lithotripsy: Part 1

2012-11-28

Purpose: Extracorporeal shock wave lithotripsy has been popular since the 1980s. Only 30% to 50% of the shock waves of all conventional lithotripters are focused on stones. We developed an ultrasound based, real-time stone tracking system (version 1) to improve accuracy and treatment efficiency. However, some problems remained. We revised the existing system (version 2) and tested its reliability and performance. Materials and Methods: We revised the system by adding more algorithms to decrease renal stone misidentification. We verified the advanced system by 2 tests using no tracking and tracking with 13 stone trajectories for versions 1 and 2. We performed the coincidence test to evaluate the accuracy of targeting the stone within the effective focal area and the stone fragmentation efficiency test to clarify the decrease in the number of shocks needed for stone fragmentation. Results: In the coincidence test the mean ± SD results of the nontracking system, and tracking versions 1 and 2 were 68.8% ± 18.8%, 89.9% ± 5.2% and 94.3% ± 4.5%, respectively. Version 2 was statistically significantly better than version 1 (p = 1.5 × 10−4). In the stone fragmentation efficiency test the mean results of the nontracking system, and versions 1 and 2 were 49.5% ± 14.2%, 85.1% ± 4.5% and 89.5% ± 4.2%, respectively. Version 2 was statistically significantly better than version 1 (p = 1.9 × 10−8). Conclusions: The revised tracking system is better than version 1. It improves treatment efficiency, decreases stone misidentification and can shorten treatment time.

Spinal Cord FAAH in Normal Micturition Control and Bladder Overactivity in Awake Rats

2012-12-04

Purpose: We assessed whether spinal inhibition of the cannabinoid degrading enzyme FAAH would have urodynamic effects in normal rats and rats with bladder overactivity induced by partial urethral obstruction or prostaglandin E2. We also determined the expression of FAAH, and the cannabinoid receptors CB1 and CB2 in the sacral spinal cord. Materials and Methods: We used 44 rats for functional (cystometry) and Western blot experiments. The FAAH inhibitor oleoyl ethyl amide (3 to 300 nmol) was administered intrathecally (subarachnoidally) or intravenously. The expression of FAAH and CB1/CB2 receptors was determined by Western blot. Results: Oleoyl ethyl amide given intrathecally affected micturition in normal rats and rats with bladder overactivity but effects were more pronounced in the latter. In normal rats oleoyl ethyl amide only decreased micturition frequency, while it decreased frequency and bladder pressures in rats with bladder overactivity. Intravenous oleoyl ethyl amide (3 to 300 nmol) had no urodynamic effect. FAAH and CB1/CB2 receptors were expressed in the rat sacral spinal cord. The expression of CB1/CB2 receptors but not FAAH was higher in obstructed than in normal rats. Conclusions: FAAH inhibition in the sacral spinal cord by oleoyl ethyl amide resulted in urodynamic effects in normal rats and rats with bladder overactivity. The spinal endocannabinoid system may be involved in normal micturition control and it appears altered when there is bladder overactivity.

Effects of Coenzyme Q10 on Bladder Dysfunction Induced by Chronic Bladder Ischemia in a Rat Model

Jong Wook Kim, Hoon Ah Jang, Jae Hyun Bae, Jeong Gu Lee — 2013-01-09

Purpose: We investigated the protective effects of coenzyme Q10 on bladder dysfunction in a rat model of atherosclerosis induced chronic bladder ischemia. Materials and Methods: A total of 24 male Sprague-Dawley® rats at age 16 weeks were divided into 4 groups of 6 each, including group 1—untreated, sham operated rats, group 2—coenzyme Q10 treated, sham operated rats, group 3—untreated rats with chronic bladder ischemia and group 4—coenzyme Q10 treated rats with chronic bladder ischemia. Groups 3 and 4 received an endothelial injury to the iliac arteries and were fed a 2% cholesterol diet for 8 weeks. Groups 2 and 4 were treated with coenzyme Q10 and the others were treated with vehicle for 4 weeks. Eight weeks postoperatively we performed continuous in vivo cystometry, an in vitro detrusor muscle strip study and a malondialdehyde assay. Histological examination of the bladder walls and iliac arteries was also done. Results: In vivo cystometry revealed that coenzyme Q10 administration after the induction of chronic bladder ischemia prolonged micturition frequency and the intercontraction interval, and increased bladder capacity compared to those in untreated rats with chronic bladder ischemia. In the detrusor muscle strip study coenzyme Q10 administration after the induction of chronic bladder ischemia increased contractile responses compared to those in untreated rats with chronic bladder ischemia. Rats with chronic bladder ischemia also showed higher malondialdehyde in bladder tissue and serum than the other groups. Chronic bladder ischemia induced submucosal fibrosis of the bladder walls and a degenerative change in the blood vessel tunical media, as shown on histological examination. Conclusions: Our study suggests that coenzyme Q10 acts as an antioxidant to protect bladder function in this chronic bladder ischemia model.

Rapamycin Attenuates Bladder Hypertrophy During Long-Term Outlet Obstruction In Vivo: Tissue, Matrix and Mechanistic Insights

2013-01-10

Purpose: Previous molecular studies showed that the mTOR inhibitor rapamycin prevents bladder smooth muscle hypertrophy in vitro. We investigated the effect of rapamycin treatment in vivo on bladder smooth muscle hypertrophy in a rat model of partial bladder outlet obstruction. Materials and Methods: A total of 48 female Sprague-Dawley® rats underwent partial bladder outlet obstruction and received daily subcutaneous injections of rapamycin (1 mg/kg) or vehicle commencing 2 weeks postoperatively. A total of 36 rats underwent sham surgery and received rapamycin or vehicle. Rats were sacrificed 3, 6 and 12 weeks after surgery. Before sacrifice, voiding was observed in a metabolic cage for 24 hours. Bladder-to-body weight in gm bladder weight per kg body weight and post-void residual urine were assessed. We evaluated Col1a1, Col3a1, Eln and Mmp7 mRNA expression and histology. Two-factor ANOVA and the post hoc t test were applied. Results: Bladder outlet obstruction caused a significant increase in bladder weight in all obstructed groups. Three weeks postoperatively (1 week of treatment) there was no difference in the bladder-to-body weight ratio in the obstructed group. However, at 6 and 12 weeks (4 and 10 weeks of treatment, respectively) the bladder-to-body weight ratio of rats with obstruction plus rapamycin was significantly lower than that of rats with obstruction plus vehicle. Post-void residual urine volume after 6 and 12 weeks of obstruction was lower in obstructed rats with rapamycin compared to that in obstructed rats with vehicle. Rapamycin decreased the obstruction induced expression of Col1a1, Col3a1, Eln and Mmp7. Conclusions: Rapamycin prevents mechanically induced hypertrophy in cardiovascular smooth muscle. In vivo mTOR inhibition may attenuate obstruction induced detrusor hypertrophy and help preserve bladder function.

Comprehensive Gene Expression Changes Associated with Mouse Postnatal Kidney Development

Bo Wu, Debashis Sahoo, James D. Brooks — 2012-12-06

Purpose: To provide a portrait of the molecular alterations in renal growth that occur in mice postnatally, we performed gene expression profiling at discrete time points during the first 5 weeks of life. Materials and Methods: Kidneys were harvested from C57BL/6 mice at embryonic day 19.5, and postnatal days 1, 3, 5, 7, 10, 14, 21, 28 and 35. Total RNA was extracted and gene expression profiling was done using microarrays (Agilent Technologies, Santa Clara, California). Transcripts whose expression levels changed during the study course were identified using StepMiner software (http://chicory.stanford.edu/sahoo/public/StepMiner/). Biological functions of the modulated genes were identified using IPA® software. Results: Postnatal kidney growth and development are associated with widespread changes in gene expression with 6,949 transcripts significantly up-regulated and 6,696 down-regulated during the first 5 weeks of life. Pathway analysis showed progressive down-regulation of pathways associated with cell growth and embryonic development (postnatal days 5 to 7). This was followed by increased expression of transcripts associated with lipid/energy metabolism and molecular transport (postnatal days 10 to 14), and down-regulation of genes related to DNA replication, cell cycle, tissue development, protein trafficking and cell morphology (postnatal days 14 to 21). Conclusions: To our knowledge we report the most comprehensive temporal survey of postnatal kidney development to date. This data set provides a framework for interpreting nephropathy, such as that induced by congenital obstruction.

Re: Protease Nexin 1 Inhibits Hedgehog Signaling in Prostate Adenocarcinoma

Anthony Atala — 2013-02-28

C. M. McKee, D. Xu, Y. Cao, S. Kabraji, D. Allen, V. Kersemans, J. Beech, S. Smart, F. Hamdy, A. Ishkanian, J. Sykes, M. Pintile, M. Milosevic, T. van der Kwast, G. Zafarana, V. R. Ramnarine, I. Jurisica, C. Mallof, W. Lam, R. G. Bristow and R. J. Muschel

Re: Both Osteopontin-c and Osteopontin-b Splicing Isoforms Exert Pro-Tumorigenic Roles in Prostate Cancer Cells

Anthony Atala — 2013-03-01

T. M. Tilli, K. D. Mello, L. B. Ferreira, A. R. Matos, M. T. Accioly, P. A. Faria, A. Bellahcène, V. Castronovo and E. R. Gimba Coordenação de Pesquisa, Programa de Medicina Experimental, Instituto Nacional de Câncer, Rio de Janeiro, Brazil

Re: Inhibition of Ca2+-Activated Cl- Channel ANO1/TMEM16A Expression Suppresses Tumor Growth and Invasiveness in Human Prostate Carcinoma

Anthony Atala — 2013-03-01

W. Liu, M. Lu, B. Liu, Y. Huang and K. Wang Department of Neurobiology, Neuroscience Research Institute, Peking University Health Science Center, Beijing, China

Re: Diagnostic Potential of Urinary α1-Antitrypsin and Apolipoprotein E in the Detection of Bladder Cancer: V. Urquidi, S. Goodison, S. Ross, M. Chang, Y. Dai and C. J. RosserJ Urol 2012; 188: 2377–2383

Omer Dizdar, Samed Rahatli, Muhammet Fuat Ozcan — 2013-01-14

We read with great interest this article on the diagnostic usefulness of various biomarkers for bladder cancer (BCa) in urine. The authors found α1-antitrypsin and apolipoprotein E levels but not osteopontin (OPN) to be highly specific and sensitive for aiding in the diagnosis of bladder cancer. OPN has previously been shown to be indicative of a poor prognosis in several cancers. A strong association has been found between high OPN in tumor and plasma measurements and decreased mean survival time. OPN immunohistochemistry score is closely related with TNM stage and grade in more than 10 types of cancer, including bladder cancer. OPN was revealed to favor tumor invasion in vitro and in vivo, as reported previously. Therefore, theoretically OPN is a good candidate as a urinary biomarker for BCa.

Re: Distal Intramural Urethral Pathology in Women: A. N. Romman, F. Alhalabi and P. E. ZimmernJ Urol 2012; 188: 1218–1223

Tony Bazi, Yasser El-Hout — 2013-01-15

Romman et al introduce 2 not so classic concepts. First, they report on a select group of women with lower urinary tract symptoms (LUTS) who had a narrowed urethra due exclusively to intramural pathology, which may or may not be associated with intramural fibrosis on magnetic resonance imaging. Furthermore, dilation of the urethra in this group, and preferably splitting the urethral walls with a 41Fr dilator, cured the majority of lower urinary tract symptoms in at least half of these women.

Reply by Authors

2013-03-20

We agree with the comment that intramural pathology is not a common condition but one that is often overlooked and can be simply suspected on a true lateral voiding study in a woman with LUTS and no apparent neurological deficit. Postoperative VCUG was only obtained when thought to be clinically relevant, as in patients who had improvement of symptoms for a significant period but then had symptom recurrence. Those in the success group did not warrant repeat VCUG. A total of 13 patients underwent VCUG after urethral dilation, with the majority (8) having no change in distal urethral configuration.

Erratum

2013-04-12

Volume 189, Number 4, Pages 1 and 3: On page 1 in the Abstract in Results postoperative hospital stay is median 3 vs 4 days. On page 3 in Results between the PkEP vs B-TURP groups operative time is median 94 vs 98 minutes, p=0.105, perioperative hemoglobin concentration decrease is mean 0.9±0.4 vs 1.7±0.6 gm/dl, p <0.01 and postoperative hospital stay is median 3 vs 4 days, p <0.01. On page 3 in Table 1 median minutes operative time for the B-TURP group is 98.

Ja-Hong Kim — 2013-03-07

In this textbook the global leaders in voiding dysfunction present a well edited and comprehensive overview of the evaluation and management of nocturia. The first half of the book is devoted to clearly defining and classifying nocturia as a symptom, as well as describing its intimate association with various medical conditions and sleep disorders. The authors also review the highest quality literature on the epidemiology and socioeconomic impact of nocturia. One particular chapter delves deeply into the powerful relationship between sleep and nocturia, and the astounding negative effect the condition can have on morbidity, mortality and long-term health outcomes.

The Journal of Urology® Home Study Course 2013 Volume 189/190

2013-03-18

2012 Journal of Urology Consultants

William D. Steers — 2013-03-13

Below is a list of consultants who reviewed manuscripts for The Journal of Urology® in 2012. 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 individuals a debt and our thanks.

Editorial Board

2013-06-01