The Journal of Urology

This Month in Adult Urology

William D. Steers — 2012-01-23

To our knowledge, no test currently available predicts the response to intravesical bacillus Calmette-Guérin (BCG) after resection in patients with bladder cancer. In this prospective trial Kamat et al (page 862) from Houston, Texas examine whether fluorescent in situ hybridization (FISH) can predict therapy failure. In 26 patients with a median followup of 24 months a third had recurrent tumors and 14% had disease progression. Patients who had a positive FISH test during BCG therapy were 3 to 5 times more likely than those who had a negative FISH test to have recurrent tumors and 5 to 13 times more likely to experience disease progression. Thus, FISH appears to be able to identify patients at higher risk for tumor recurrence and help direct alternative treatments.

This Month in Pediatric Urology

Michael L. Ritchey — 2012-01-23

There have been several studies showing that urinary proteome profiles can identify patients with ureteropelvic junction (UPJ) obstruction. In this multi-institutional study Bandin et al (page 1006) evaluate changes in the urinary proteome in children who either underwent surgical correction of UPJ or were observed without surgery and followed for 5 years. They excluded from study patients with vesicoureteral reflux, solitary kidney, bilateral hydronephrosis or any lower urinary tract anomalies. Patients not treated surgically were divided into those with mild dilatation and those described as having intermediate obstruction. These patients had SFU (Society of Fetal Urology) grade 3 or 4 hydronephrosis but normal differential renal function on diuretic renography. At the 5-year followup the urinary proteome of patients who had undergone surgical correction of the UPJ obstruction was similar to that of age matched controls. In contrast, patients followed nonoperatively had an altered urinary proteome with increased secretion of urinary peptides interpreted to be a result of increased intrarenal collagen turnover. The authors postulate this finding as a sign of ongoing renal remodeling which could potentially lead to clinical problems at a later date. It is important to note that these patients were otherwise clinically similar to the surgically treated patients. Further study and long-term followup of these patients are needed to determine if this alteration of the urinary proteome will have significant clinical implications.

This Month in Investigative Urology

Karl-Erik Andersson — 2012-01-23

To determine the accuracy of a novel 3-dimensional (3-D) transrectal ultrasound (TRUS) system for image based mapping biopsies in a prostate phantom, Ukimura et al (page 1080) from Los Angeles, California tested a system (Urostation®) that is capable of registering the 3-D location of each biopsy track in the 3-D prostate volume data and performing elastic image fusion of TRUS with magnetic resonance (MR) imaging. They used 3 prostate phantoms (CIRS-053) containing 3 hypoechoic lesions to perform ultrasound (US) guided biopsy, and 3 phantoms (CIRS-066) containing 3 isoechoic but MR imaging visible lesions to perform MR fusion guided biopsy. Three targeted biopsies were performed per lesion. Each biopsy tract was injected with gadolinium based MR contrast mixed with india ink. The phantoms were then subjected to 1 mm slice MR imaging and serial step sectioning to assess the accuracy of the targeted biopsy.

Early Adoption of New Devices: Flying on Untested Wings

William B. Rogers, Deborah R. Erickson — 2012-01-16

Greek mythos portrays the fable of Daedalus and his son, Icarus, imprisoned within the Labyrinth on the island of Crete. Daedalus used his great intellect, creativity and technological skill to fashion wings made of feathers and wax. He and his son were to fly on these wings and escape their exile. Before the flight, Daedalus counseled his son to avoid flying too close to the sun because he feared that the untested wings, which had potential faults, might fail. Icarus ignored these warnings and flew too high and close to the sun, causing the wax to melt and the feathers to come undone. He fell to his death in the sea. Some alternate accounts describe Daedalus as the first creator of the sail and Icarus fell overboard as the boat rocked in high winds.

Warming Up to Ischemia

Dipen J. Parekh — 2012-01-16

As a practitioner of urology, it is daunting not to accept the common surgical dogma preached to us for decades that renal ischemia is harmful. The deleterious impact of renal ischemia has been significantly magnified during the last 3 decades. While it was originally accepted that up to 30 minutes of warm ischemia may be safely tolerated, the upper limit of acceptable renal ischemia is now in a downward spiral, with suggestions that every single minute of renal ischemia is harmful in the short and long term. The intolerance shown toward ischemia has even led to significant changes in surgical approaches such as selective clamping of the renal microvasculature alone as well as nonclamping techniques. The obvious question that comes to mind is do we have concrete evidence that temporary, clamp induced renal ischemia in the context of partial nephrectomy translates into adverse long-term renal outcomes? The answer is no.

Management of the High Urogenital Sinus—Risk of Overexposure?

Ricardo González, Barbara Ludwikowski — 2012-01-16

The confluence of the female urethra with the vagina (urogenital [UG] sinus) into a single channel that opens in the vulva or perineum may result from the lack of reabsorption of the distal UG sinus (persistent UG sinus), from alterations in septation (persistent cloaca), or from the influence of endogenous or exogenous androgenic substances. The distinction between the first 2 causes and the latter is crucial because it has a profound influence on the choice of surgical intervention needed to correct the anomaly.

Can We Better Predict and Treat Urinary Incontinence After Prostatectomy?

Daniel S. Elliott — 2012-01-16

Urinary incontinence after prostatectomy is a devastating complication for the patient, and it is and should be an embarrassing complication for the surgeon. Fixing this problem is not always easy and it is always expensive. Several articles in this issue of The Journal highlight the complexity and magnitude of this problem.

Con

Joel B. Nelson — 2012-01-16

Speculation about the future is tricky, and one must be clear about what actually exists and what may eventually exist. If limited to reality (as opposed to conjecture), arguing against currently applied focal therapy as a standard treatment for localized prostate cancer is not a Luddite exercise. The collapse of these technologies can be expected from a growing weight of evidence of their often unnecessary and ineffective interventions.

Pro

Hashim Uddin Ahmed — 2012-01-18

The current diagnostic and therapeutic strategy for localized prostate cancer is not working. As a result of the random nature in which we deploy transrectal biopsies into the prostate, there is inaccuracy in detection, localization and characterization of malignant lesions. Much debate has centered on these inaccuracies but what is clear from level I evidence is that we cannot continue to apply the same principles of treatment as this can lead to significant harm along with little benefit.

Molecular Diagnosis of Prostate Cancer: PCA3 and TMPRSS2:ERG Gene Fusion

Maciej Salagierski, Jack A. Schalken — 2012-01-16

Purpose: Widespread prostate specific antigen screening together with the increase in the number of biopsy cores has led to increased prostate cancer incidence. Standard diagnostic tools still cannot unequivocally predict prostate cancer progression, which often results in a significant overtreatment rate. We present recent findings on PCA3 and TMPRSS:ERG fusion, and describe their clinical implications and performance. Materials and Methods: The PubMed® database was searched for reports on PCA3 (130 articles), TMPRSS:ERG and ETS fusion (180 publications) since 1999. Results: In recent years advances in genetics and biotechnology have stimulated the development of noninvasive tests to detect prostate cancer. Serum and urine molecular biomarkers have been identified, of which PCA3 has already been introduced clinically. The identification of prostate cancer specific genomic aberrations, ie TMPRSS2:ERG gene fusion, might improve diagnosis and affect prostate cancer treatment. Conclusions: Although several recently developed markers are promising, often showing increased specificity for prostate cancer detection compared to that of prostate specific antigen, their clinical application is limited. The only 2 true prostate cancer specific biomarkers identified to date remain PCA3 and TMPRSS2:ERG gene fusion.

Does Prolonged Warm Ischemia After Partial Nephrectomy Under Pneumoperitoneum Cause Irreversible Damage to the Affected Kidney?

2012-01-16

Purpose: We determined the effects of warm ischemia time on the recovery of renal function after partial nephrectomy under pneumoperitoneum. Materials and Methods: In this prospective study 37 consecutive patients who underwent laparoscopic partial nephrectomy or robot-assisted partial nephrectomy between June 2008 and May 2009 to remove a single cT1 renal tumor were evaluated using 99mTc-diethylenetriamine pentaacetic acid renal scintigraphy preoperatively, and at 3 and 12 months postoperatively. Results: The most significant reduction in the glomerular filtration rate of the affected kidney at 3 and 12 months after surgery (p = 0.018, p = 0.036, respectively) was seen for a warm ischemia time cutoff of 28 minutes. The glomerular filtration rate of the affected kidney was consistently and significantly reduced at 3 and 12 months postoperatively (−22.4% to −30.6%, p <0.001) in patients with a warm ischemia time greater than 28 minutes. In contrast, no significant glomerular filtration rate change was seen in patients with a warm ischemia time of 28 minutes or less. In terms of the contributional change of the affected kidney to total renal function, there is a trend toward a recovery after an initial decrease in both groups with a warm ischemia time greater than 28 minutes vs 28 minutes or less. On multivariate analysis warm ischemia time was a strong independent predictor of glomerular filtration rate reduction even 12 months after surgery (β = −1.3; 95% CI −1.8, −0.7; p <0.001). Conclusions: If the warm ischemia time is greater than 28 minutes during laparoscopic partial nephrectomy or robot-assisted partial nephrectomy, the functional damage to the affected kidney progresses even up to 1 year after surgery.

Editorial Comment

Ephrem O. Olweny, Vitaly Margulis — 2012-01-16

In this prospective study the long-term impact of warm ischemia during elective nephron sparing surgery was evaluated using 99mTc-DTPA renal scintigraphy. The main finding was that at 1 year only WIT greater than 28 minutes was associated with a significant and sustained decrease in the absolute GFR of the affected kidney without compensation by the contralateral kidney. It is important to note that accurate interpretation of radioisotope derived quantification of renal function hinges on appropriate corrections for hydration status, differential isotope uptake in different regions of the kidney (eg tumor) and body surface area. Furthermore, alternative isotopes such as 99mTc-mercaptoacetyltriglycine-3 may more accurately estimate GFR, given higher protein binding and, thus, less background signal. A recent prospective study incorporating electron microscopy and biomarkers of renal injury showed no impact on renal ultrastructure or function with WIT up to 60 minutes. Further studies are needed to better inform on this important and timely topic.

Zero Ischemia Anatomical Partial Nephrectomy: A Novel Approach

2012-01-16

Purpose: We present a novel concept of zero ischemia anatomical robotic and laparoscopic partial nephrectomy. Materials and Methods: Our technique primarily involves anatomical vascular microdissection and preemptive control of tumor specific, tertiary or higher order renal arterial branch(es) using neurosurgical aneurysm micro-bulldog clamps. In 58 consecutive patients the majority (70%) had anatomically complex tumors including central (67%), hilar (26%), completely intrarenal (23%), pT1b (18%) and solitary kidney (7%). Data were prospectively collected and analyzed from an institutional review board approved database. Results: Of 58 cases undergoing zero ischemia robotic (15) or laparoscopic (43) partial nephrectomy, 57 (98%) were completed without hilar clamping. Mean tumor size was 3.2 cm, mean ± SD R.E.N.A.L. score 7.0 ± 1.9, C-index 2.9 ± 2.4, operative time 4.4 hours, blood loss 206 cc and hospital stay 3.9 days. There were no intraoperative complications. Postoperative complications (22.8%) were low grade (Clavien grade 1 to 2) in 19.3% and high grade (Clavien grade 3 to 5) in 3.5%. All patients had negative cancer surgical margins (100%). Mean absolute and percent change in preoperative vs 4-month postoperative serum creatinine (0.2 mg/dl, 18%), estimated glomerular filtration rate (−11.4 ml/minute/1.73 m2, 13%), and ipsilateral kidney function on radionuclide scanning at 6 months (−10%) correlated with mean percent kidney excised intraoperatively (18%). Although 21% of patients received a perioperative blood transfusion, no patient had acute or delayed renal hemorrhage, or lost a kidney. Conclusions: The concept of zero ischemia robotic and laparoscopic partial nephrectomy is presented. This anatomical vascular microdissection of the artery first and then tumor allows even complex tumors to be excised without hilar clamping. Global surgical renal ischemia is unnecessary for the majority of patients undergoing robotic and laparoscopic partial nephrectomy at our institution.

Editorial Comment

Steven C. Campbell, Matthew Simmons — 2012-01-16

This article describes a minimally invasive approach to partial nephrectomy that eliminates global ischemia by meticulous dissection of the renal artery out to segmental branches leading into the portion of the kidney containing the tumor. As such, it minimizes what has traditionally been considered the most important modifiable factor influencing renal function after PN, namely warm ischemia time, by driving this to zero for the uninvolved segments of the kidney. The authors are to be congratulated for their efforts to pioneer this procedure even in cases with challenging tumor size and location, and they were able to complete the procedure without hilar clamping in all but 1 instance. The high transfusion rate (21%) is difficult to reconcile with the reported lack of intraoperative or perioperative bleeding events. The long operative times (mean 4.4 hours, range up to 8 hours) reflect the potential difficulty of this dissection, and one can only wonder about the advisability of this approach given emerging data demonstrating that volume loss is in reality the predominant factor responsible for the decline of renal function after PN, presuming the relatively short warm ischemic intervals (less than 20 to 25 minutes) or use of hypothermia that characterize conventional PN. These data now suggest that precision of surgery, with preservation of as much vascularized kidney as possible, while still obtaining negative margins, is the key to optimal renal functional recovery after PN. In reality, a short ischemic interval (or hypothermia) can facilitate surgical precision during PN by providing a bloodless field and, thus, affords the best opportunity to optimize renal function after PN.

Reply by Authors

2012-01-16

Ischemic injury is a relevant issue. Even after adjusting for percent kidney parenchyma excised during PN, minimizing ischemia times correlated with improved function. As to why a “short ischemic interval (or hypothermia)” is “in reality” somehow better than no ischemia for preserving renal function is difficult to comprehend. If the former is acceptable, surely the latter is preferable.

National Trends in the Use of Partial Nephrectomy: A Rising Tide That Has Not Lifted All Boats

2012-01-16

Purpose: Treatment of organ confined renal masses with partial nephrectomy has durable oncologic outcomes comparable to radical nephrectomy. Partial nephrectomy is associated with lower risk of chronic kidney disease and in some series with better overall survival. We report a contemporary analysis on national trends of partial nephrectomy use to determine partial nephrectomy use over time, and whether nontumor related factors such as structural attributes of the treating institution or patient characteristics are associated with the underuse of partial nephrectomy. Materials and Methods: We performed an analysis of the NIS (National Inpatient Sample), which contains 20% of all United States inpatient hospitalizations. We included patients who underwent radical or partial nephrectomy for a renal mass between 2002 and 2008. Survey weights were applied to obtain national estimates of nephrectomy use and to evaluate nonclinical predictors of partial nephrectomy. Results: A total of 46,396 patients were included in the study for a weighted sample of 226,493. There was an increase in partial nephrectomy use from 15.3% in 2002 to 24.7% in 2008 (p <0.001). On multivariate analysis hospital attributes (urban teaching status, nephrectomy volume, geographic region) and patient socioeconomic status (higher income ZIP code and private/HMO payer) were independent predictors of partial nephrectomy use. Conclusions: Since 2002 the national use of partial nephrectomy for the management of renal masses has increased. However, the adoption of partial nephrectomy at smaller, rural and nonacademic hospitals lags behind that of larger hospitals, urban/teaching hospitals and higher volume centers. A lower rate of partial nephrectomy use among patients without private insurance and those living in lower income ZIP code areas highlights the underuse of partial nephrectomy as a quality of care concern.

Comprehensive Assessment of Quality of Life and Psychosocial Adjustment in Patients With Renal Tumors Undergoing Open, Laparoscopic and Nephron Sparing Surgery

2012-01-16

Purpose: We prospectively evaluated the general and cancer specific quality of life, and psychosocial adjustment of patients with a renal mass treated with radical vs partial nephrectomy via a laparoscopic or an open approach. Materials and Methods: A total of 172 patients with renal tumors completed questionnaires before surgery, and 3 weeks, and 2, 3, 6 and 12 months postoperatively. We assessed general quality of life using SF-36™ and cancer specific quality of life using the Cancer Rehabilitation Evaluation System-Short Form, in addition to intrusive thoughts, avoidance behaviors and fear of recurrence. We used mixed model regression analysis to compare these measures across surgery types during the study course, adjusted for tumor size, histology, stage and renal function. Results: The SF-36 physical component score differed significantly by surgery type with time (p = 0.04). Patients treated with laparoscopy improved by month 2 while those treated with open surgery had poorer quality of life until month 3. Better cancer specific quality of life was reported in patients who underwent radical vs partial nephrectomy. Age also had a significant effect on outcomes. Conclusions: We report one of the most comprehensive patient reported prospective quality of life studies in patients with renal cell carcinoma. There were significant differences in quality of life and psychosocial adjustment outcomes during 1 year among patients treated with 1 of 4 commonly accepted surgical renal procedures. These outcomes must be evaluated in the context of tumor characteristics, cancer specific outcomes and renal function. These quality of life issues may be important to consider when choosing surgical procedures for patients with renal tumors.

Chemokine and Chemokine Receptor Expression in Kidney Tumors: Molecular Profiling of Histological Subtypes and Association With Metastasis

2012-01-16

Purpose: Molecular characterization of renal cell carcinoma may help differentiate benign oncocytoma from malignant renal cell carcinoma subtypes and predict metastasis. Chemokines, eg IL-8 and chemokine receptors such as CXCR4 and 7, promote inflammation and metastasis. SDF-1 is a CXCR4 and 7 ligand with 6 known isoforms. We evaluated the expression of these chemokines and chemokine receptors in kidney specimens. Materials and Methods: Using quantitative polymerase chain reaction we measured mRNA levels of IL-8, CXCR4 and 7, and SDF1 isoforms α, β and γ in a total of 166 specimens from 86 patients, including 86 tumor samples and 80 matched normal kidney samples. Mean ± SD followup was 18.9 ± 12 months (median 19.5). Renal cell carcinoma specimens included the clear cell, papillary and chromophobe subtype in 65, 10 and 5 cases, respectively, and oncocytoma in 6. A total of 17 cases were positive for metastasis. Results: Median CXCR4 and 7, and SFD1-γ levels were increased twofold to tenfold. SDF1-α and β were unchanged or lower in clear cell renal cell carcinoma and papillary tumors than in normal tissue. Median SDF1-γ, IL-8, and CXCR4 and 7 were increased threefold to fortyfold in chromophobe tumors compared to oncocytoma. CXCR4 and 7 were increased in tumors less than 4 cm (mean 3,057 ± 2,230 and 806 ± 691) compared to oncocytoma (336 ± 325 and 201 ± 281, respectively, p ≤0.016). On multivariate analysis CXCR4 (p = 0.01), CXCR7 (p = 0.02) and SDF1-β (p = 0.005) were independently associated with metastasis. Combined CXCR7 plus SDF1-α and CXCR7 plus IL-8 markers showed the highest sensitivity (71% to 81%) and specificity (75% to 80%) of all individual or combined markers. Conclusions: Chemokines and chemokine receptors differentiate renal cell carcinoma and oncocytoma. Combined SDF1-α plus CXCR7 and IL-8 plus CXCR7 markers have about 80% accuracy for predicting renal cell carcinoma metastasis.

Prognostic Value of the Leibovich Prognosis Score Supplemented by Vascular Invasion for Clear Cell Renal Cell Carcinoma

2012-01-16

Purpose: We assessed whether supplementing the Leibovich prognosis score with vascular invasion would improve prognostic value to predict metastatic disease in patients with nonmetastatic clear cell renal cell carcinoma. Materials and Methods: We retrospectively evaluated the pathology records of 1,754 patients with nonmetastatic clear cell renal cell carcinoma treated with surgery between 1984 and 2006 at a single tertiary academic center. The Leibovich prognosis score was supplemented by additional scoring for vascular invasion. Metastasis-free survival was assessed using the Kaplan-Meier method for each score category. A Cox regression model was used for multivariate testing. Predictive accuracy was determined by the Harrell concordance index and decision curve analysis. Results: Median followup was 84 months. Ten-year metastasis-free survival probability for a score of 0 to 1 and 2 to 8 or greater was 95%, 83%, 78%, 81%, 69%, 51%, 15% and 13%, respectively. The concordance index was 0.792 compared to 0.778 from our external validation of the Leibovich prognosis score using routine pathological findings (p <0.05). Decision curve analysis also favored the predictive ability of the novel model. Conclusions: Adding vascular invasion improved the predictive accuracy of our validation data by 1.4% over that of the Leibovich prognosis score. Patients with a score of 7 or greater had a more than 85% probability of metastatic disease at 10 years. Thus, they could be considered candidates for adjuvant treatment trials.

External Validation of a Biomarker Based Pre-Cystectomy Algorithm to Predict Nonorgan Confined Urothelial Cancers

2012-01-16

Purpose: The role of neoadjuvant chemotherapy before surgery in patients with muscle invasive bladder cancer remains debated and the need for tools to identify patients who would benefit from chemotherapy is pertinent. We previously published a preoperative algorithm to predict nonorgan confined disease. This algorithm included tumor markers (CEA, CA 125 and CA 19–9) as well as clinical parameters. In this study we validated the accuracy of this algorithm in an independent, external cohort. Materials and Methods: We used the Toronto Biobank to measure preoperative serum levels of CEA, CA 125 and CA 19–9 in 76 consecutive patients with clinically organ confined bladder cancer (cT2 or less) who underwent radical cystectomy. Clinical parameters were retrieved from our prospective bladder information system database and incorporated into our marker based algorithm. A numerical score was generated for each patient and a previously published cutoff was used to predict the presence of nonorgan confined disease. The accuracy of the model was quantified with the area under the curve, and the positive and negative predictive values were calculated. Results: On pathological evaluation 38 patients (50%) had nonorgan confined tumors. The AUC of the algorithm was 0.79 (95% CI 0.69–0.89). The positive and negative predictive values were 79% (95% CI 71–87) and 74% (95% CI 66–82), respectively. Conclusions: We externally validated a pre-cystectomy model to predict pathological stage. The algorithm may possibly aid in selecting patients who would benefit from neoadjuvant chemotherapy before cystectomy.

Prognostic Value of Extranodal Extension and Other Lymph Node Parameters in Patients With Upper Tract Urothelial Carcinoma

2012-01-16

Purpose: We assessed the prognostic value of extranodal extension and other lymph node parameters in a large multicenter cohort of patients with lymph node metastasis after radical nephroureterectomy. Materials and Methods: We retrospectively analyzed the records of 222 patients with lymph node metastasis treated with radical nephroureterectomy for upper tract urothelial carcinoma without neoadjuvant therapy. Each lymph node metastasis was microscopically evaluated for extranodal extension. Results: A median of 4 lymph nodes (IQR 8) was removed. Two lymph nodes (IQR 2) were positive. Lymph node density was 51.3% (IQR 71.7%). Overall 110 patients (49.5%) had extranodal extension, which was associated with more advanced pT stage (p = 0.026). On multivariable analysis extranodal extension was associated with disease recurrence (p = 0.01) and cancer specific mortality (p = 0.013). When stratified by a 30% cutoff, lymph node density was associated with disease recurrence and cancer specific mortality on univariable but not multivariable analysis (p = 0.048 and 0.049, respectively). Adding extranodal extension to a multivariable model including pT stage and tumor architecture improved predictive accuracy for disease recurrence from 70.3% to 74.5% (p <0.001). Adding extranodal extension to a multivariable model including age, pT stage and tumor architecture improved predictive accuracy for cancer specific mortality from 70.6% to 74.4% (p <0.001). Conclusions: Extranodal extension is a powerful predictor of clinical outcomes in patients with upper tract urothelial carcinoma with lymph node metastasis. While other lymph node parameters seem to have limited clinical value, extranodal extension could help risk stratify patients with upper tract urothelial carcinoma and lymph node metastasis for better counseling and clinical trial design.

Plasmacytoid Carcinoma of the Bladder: A Urothelial Carcinoma Variant With a Predilection for Intraperitoneal Spread

2012-01-16

Purpose: Bladder plasmacytoid carcinoma is an invasive urothelial carcinoma subtype that is emphasized for its morphological overlap with plasma cells and metastatic carcinoma. Our experience suggests frequent intraperitoneal spread that is not typical of conventional urothelial carcinoma. Materials and Methods: We identified cases of plasmacytoid urothelial carcinoma diagnosed on radical cystectomy. Patient age, gender, American Joint Committee on Cancer (7th edition) stage, metastatic spread/recurrence sites and clinical disease status at last followup were recorded. Results: A total of 10 male and 5 female patients 42 to 81 years old were identified. One tumor was pT2, 11 pT3 and 3 pT4. Six of 15 patients (40%) presented with lymph node metastasis and 5 (33%) had intraperitoneal metastasis at cystectomy. These initial sites of metastatic spread included the prerectal space, ovary and vagina, ovary and fallopian tube, bowel serosa, and omentum and bowel serosa in 1 case each. Three patients had subsequent metastasis involving the prerectal space, pleural fluid and small bowel serosa, and bowel serosa in 1 each. Eight patients had followup information available, including 3 who died of disease, 3 with disease and 2 with no evidence of disease. Conclusions: Of the patients 33% with the plasmacytoid variant of urothelial carcinoma presented with intraperitoneal disease spread and 20% had subsequent metastasis involving serosal surfaces. The possibility of noncontiguous intraperitoneal spread involving serosal surfaces should be recognized to ensure proper intraoperative staging and clinical followup for patients with plasmacytoid carcinoma.

Long-Term Impact of Arsenic in Drinking Water on Bladder Cancer Health Care and Mortality Rates 20 Years After End of Exposure

Mario I. Fernández, J. Francisco López, Bruno Vivaldi, Fernando Coz — 2012-01-16

Purpose: In this study we assessed bladder cancer health care and mortality trends in recent decades in a well studied arsenic exposed area in Northern Chile. Materials and Methods: Arsenic levels in the affected region were obtained for the last 60 years, and correlated with bladder cancer hospital discharge and mortality rates in recent decades. Results: Bladder cancer hospital discharge rates were significantly higher in the affected region (peak RR 3.6, 95% CI 3.0–4.7). Mortality rates for bladder cancer showed a trend of increase during the period analyzed, reaching peak mortality rates of 28.4 per 100,000 for men and 18.7 per 100,000 for women in the last 10 years. Poisson regression models showed an increased mortality risk in the studied region compared to the rest of the country until the present for men (IRR 5.3, 95% CI 4.8–5.8) and women (IRR 7.8, 95% CI 7.0–8.7). Mean age at cancer specific death was significantly lower in the exposed region (69.6 years, 95% CI 68.4–70.7 vs 73.7 years, 95% CI 73.3–74.2, p <0.01). Conclusions: Exposure to arsenic is related to a significant need for bladder cancer health care and to high mortality rates even 20 years after having controlled arsenic levels in drinking water. Affected individuals should be aware of the significant impact of this ecological factor. Further research is required to identify strategies for the management of bladder cancer in arsenic exposed populations.

Use of Fluorescence In Situ Hybridization to Predict Response to Bacillus Calmette-Guérin Therapy for Bladder Cancer: Results of a Prospective Trial

2012-01-16

Purpose: No reliable methods currently exist to predict patient response to intravesical immunotherapy with bacillus Calmette-Guérin given after transurethral resection for high risk nonmuscle invasive bladder cancer. We initiated a prospective clinical trial to determine whether fluorescence in situ hybridization results during bacillus Calmette-Guérin immunotherapy can predict therapy failure. Materials and Methods: Candidates for standard of care bacillus Calmette-Guérin were offered participation in a clinical trial. Fluorescence in situ hybridization was performed before bacillus Calmette-Guérin, and at 6 weeks, 3 months and 6 months during bacillus Calmette-Guérin therapy with maintenance. Cox proportional hazards regression was used to assess the relationship between fluorescence in situ hybridization results and tumor recurrence or progression. The Kaplan-Meier product limit method was used to estimate recurrence-free and progression-free survival. Results: A total of 126 patients participated in the study. At a median followup of 24 months 31% of patients had recurrent tumors and 14% experienced disease progression. Patients who had positive fluorescence in situ hybridization results during bacillus Calmette-Guérin therapy were 3 to 5 times more likely than those who had negative fluorescence in situ hybridization results to experience recurrent tumors and 5 to 13 times more likely to have disease progression (p <0.01). The timing of positive fluorescence in situ hybridization results also affected outcomes. For example, patients with a negative fluorescence in situ hybridization result at baseline, 6 weeks and 3 months demonstrated an 8.3% recurrence rate compared to 48.1% for those with a positive result at all 3 points. Conclusions: Fluorescence in situ hybridization results can identify patients at risk for tumor recurrence and progression during bacillus Calmette-Guérin immunotherapy. This information may be used to counsel patients about alternative treatment strategies.

Potential Years of Life Lost Due to Urogenital Cancer in the United States: Trends From 1972 to 2006 Based on Data From the SEER Database

Mohamed H. Kamel, Page C. Moore, Nabil K. Bissada, Samy M. Heshmat — 2012-01-16

Purpose: Urogenital cancer is a major health problem in the United States. We assessed potential years of life lost secondary to genitourinary cancer in the United States from 1972 to 2006 using the SEER (Surveillance, Epidemiology and End Results) database. We report trends in potential years of life lost during the same period. Materials and Methods: Potential years of life lost were calculated to assess premature mortality trends for ureter, bladder, kidney and renal pelvis, penis, testis and prostate cancers. Calculations were based on SEER cancer mortality data. Potential years of life lost up to and including age 75 years were calculated by and across genders in 5-year increments between 1972 and 2006. Results: A total of 7,733,235 potential years of life were lost in men and women. In each gender the greatest potential loss was for kidney and renal pelvis cancer related mortality. In each gender no improvement in the potential loss due to ureteral and bladder cancer related mortality was observed during 3 decades. In males the greatest decrease in potential years of life lost was for testicular cancer, followed by prostate cancer. Conclusions: There has been an increasing trend in potential years of life lost related to urogenital cancer during the last 35 years for males and females. This trend is mainly due to an increase in kidney cancer. The continued increase in potential years of life lost due to renal cancer and the lack of a decrease in the loss in those with bladder cancer should alert urologists and health care policy makers to deficient areas that most need to be addressed.

Re: Familial Renal Cell Carcinoma From the Swedish Family-Cancer Database

Samir S. Taneja — 2012-01-16

H. Liu, J. Sundquist and K. Hemminki Division of Molecular Genetic Epidemiology, German Cancer Research Centre, Heidelberg, Germany

Re: Metastatic Potential in Renal Cell Carcinomas ≤7 cm: Swedish Kidney Cancer Quality Register Data

Samir S. Taneja — 2012-01-16

E. Guðmundsson, H. Hellborg, S. Lundstam, S. Erikson and B. Ljungberg; Swedish Kidney Cancer Quality Register Group Department of Urology, Uppsala University Hospital, Uppsala, Sweden

Re: Survival of Patients With Kidney Cancer in Central and Northern Denmark, 1998–2009

Samir S. Taneja — 2012-01-16

T. Pelant, E. H. Larsen, L. Lund, M. Borre, R. Erichsen, M. Nørgaard and J. B. Jacobsen Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark

Re: Prognostic Model for Survival in Patients With Metastatic Renal Cell Carcinoma: Results From the International Kidney Cancer Working Group

Samir S. Taneja — 2012-01-16

J. Manola, P. Royston, P. Elson, J. B. McCormack, M. Mazumdar, S. Négrier, B. Escudier, T. Eisen, J. Dutcher, M. Atkins, D. Y. Heng, T. K. Choueiri, R. Motzer and R. Bukowski; International Kidney Cancer Working Group

Re: Percutaneous Cryoablation of Renal Tumors: Patient Selection, Technique, and Postprocedural Imaging

Cary Siegel — 2012-01-18

B. C. Allen and E. M. Remer Imaging Institute, Cleveland Clinic, Cleveland, Ohio

Re: Comparison of CT Urography and Excretory Urography in the Detection and Localization of Urothelial Carcinoma of the Upper Urinary Tract

Cary Siegel — 2012-01-18

M. Jinzaki, K. Matsumoto, E. Kikuchi, K. Sato, Y. Horiguchi, Y. Nishiwaki and S. G. Silverman Department of Diagnostic Radiology, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo, Japan

Re: First in Man Renal Transplantation After Ex Vivo Normothermic Perfusion

David A. Goldfarb — 2012-01-18

S. A. Hosgood and M. L. Nicholson Department of Infection, Immunity and Inflammation, Transplant Group, Leicester General Hospital, University of Leicester, Leicester, United Kingdom

Re: Cytoreductive Nephrectomy in the Elderly: A Population-Based Cohort From the USA

Tomas L. Griebling — 2012-01-18

M. Sun, F. Abdollah, J. Schmitges, M. Bianci, Z. Tian, S. F. Shariat, K. Zorn, D. Pharand, H. Widmer, M. Graefen, F. Montorsi, P. Perrotte and P. I. Karakiewicz Cancer Prognostics and Health Outcomes Unit, and Department of Urology, University of Montreal Health Center, Montreal, Quebec, Canada, Department of Urology, Vita Salute San Raffaele University, Milan, Italy, Martini-Clinic, Prostate Cancer Center Hamburg-Eppendorf, Hamburg, Germany, and Department of Urology, Weill Medical College, Cornell University, New York, New York

Re: Persistent Overuse of Radical Nephrectomy in the Elderly

Tomas L. Griebling — 2012-01-18

M. Kates, G. Badalato, M. Pitman and J. McKiernan Department of Urology, Columbia University College of Physicians and Surgeons, New York, New York

Re: Diminished Efficacy of Bacille Calmette-Guérin Among Elderly Patients With Nonmuscle Invasive Bladder Cancer

Tomas L. Griebling — 2012-01-18

D. Margel, S. S. Alkhateeb, A. Finelli and N. Fleshner Division of Urology, Department of Surgical Oncology, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada

Re: Neoadjuvant Systemic Therapy or Early Cystectomy? Single-Center Analysis of Outcomes After Therapy for Patients With Clinically Localized Micropapillary Urothelial Carcinoma of the Bladder

David P. Wood — 2012-01-18

I. A. Ghoneim, R. Miocinovic, A. J. Stephenson, J. A. Garcia, M. C. Gong, S. C. Campbell, D. E. Hansel and A. F. Fergany Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio

Re: Bacillus Calmette-Guérin Osteomyelitis Mimicking Spinal Metastasis From Urothelial Cell Carcinoma of the Bladder

David P. Wood — 2012-01-18

A. R. Patel, E. S. Sabanegh, J. S. Jones, S. M. Gordon, M. Ballin, P. M. Ruggieri and A. J. Stephenson Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio

Re: Phase II Trial of Cisplatin, Gemcitabine, and Bevacizumab as First-Line Therapy for Metastatic Urothelial Carcinoma: Hoosier Oncology Group GU 04-75

David P. Wood — 2012-01-18

N. M. Hahn, W. M. Stadler, R. T. Zon, D. Waterhouse, J. Picus, S. Nattam, C. S. Johnson, S. M. Perkins, M. J. Waddell and C. J. Sweeney; Hoosier Oncology Group Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, Indiana

Impact of Distance to a Urologist on Early Diagnosis of Prostate Cancer Among Black and White Patients

2012-01-16

Purpose: We examined whether an increased distance to a urologist is associated with a delayed diagnosis of prostate cancer among black and white patients, as manifested by higher risk disease at diagnosis. Materials and Methods: North Carolina Central Cancer Registry data were linked to Medicare claims for patients with incident prostate cancer diagnosed in 2004 to 2005. Straight-line distances were calculated from the patient home to the nearest urologist. Race stratified multivariate ordinal logistic regression was used to examine the association between distance to a urologist and prostate cancer risk group (low, intermediate, high or very high/metastasis) at diagnosis for black and white patients while accounting for age, comorbidity, marital status and diagnosis year. An overall model was then used to examine the distance × race interaction effect. Results: Included in analysis were 1,720 white and 531 black men. In the overall cohort the high risk cancer rate increased monotonically with distance to a urologist, including 40% for 0 to 10, 45% for 11 to 20 and 57% for greater than 20 miles. Correspondingly the low risk cancer rate decreased with longer distance. On race stratified multivariate analysis longer distance was associated with higher risk prostate cancer for white and black patients (p = 0.04 and <0.01, respectively) but the effect was larger in the latter group. The distance × race interaction term was significant in the overall model (p = 0.03). Conclusions: Longer distance to a urologist may disproportionally impact black patients. Decreasing modifiable barriers to health care access, such as distance to care, may decrease racial disparities in prostate cancer.

Editorial Comment

Jared M. Whitson — 2012-01-16

These authors present an analysis of data from the North Carolina Central Cancer Registry linked to Medicare claims that suggest an association between increased distance to a urologist and more advanced prostate cancer at presentation. This barrier may disproportionately affect black compared to white patients. However, as they describe in the limitations, the database did not have information on individual socioeconomic indicators and, thus, they could not adjust for several potential confounders, such as income and education.

Racial Differences in Bone Mineral Density and Fractures in Men Receiving Androgen Deprivation Therapy for Prostate Cancer

2012-01-16

Purpose: Whether race influences bone loss and fracture risk during androgen deprivation therapy for prostate cancer is unknown. Using data from a prospective clinical trial we compared bone mineral density and fracture between African-American and Caucasian men receiving androgen deprivation therapy. Materials and Methods: A total of 516 subjects were in the placebo group of a 2-year randomized placebo controlled fracture prevention trial, and were African-American (68) or Caucasian (448). We compared baseline characteristics, changes in bone mineral density and rates of new fractures between races. Results: Compared to Caucasian men, African-American men had higher baseline hip bone mineral density (mean ± SD 0.98 ± 0.15 vs 0.91 ± 0.15 gm/m2, p = 0.001) and similar spine bone mineral density (1.09 ± 0.22 vs 1.11 ± 0.22, p = 0.51). There was no difference in prevalent vertebral fractures between African-American and Caucasian men (7.4% vs 15.0%, p = 0.13). The percentage change in hip bone mineral density at 2 years was similar between African-American and Caucasian men (mean ± SE -2.21% ± 0.59% vs -2.54% ± 0.26%, p = 0.65). Changes in bone mineral density of the lumbar spine were also similar between African-American and Caucasian men (-1.74% ± 0.69% vs -1.30% ± 0.33%, p = 0.64). No new vertebral fractures were reported in African-American men but 2 fractures were reported in Caucasian men. Conclusions: In a clinical trial African-American men receiving androgen deprivation therapy for prostate cancer have a greater hip bone mineral density and tended to have fewer prevalent vertebral fractures than Caucasian men. Despite a lower baseline risk of osteoporosis and fracture, African-American men experience a decrease in bone mineral density similar to that of Caucasian men.

Pretreatment Expectations of Patients Undergoing Robotic Assisted Laparoscopic or Open Retropubic Radical Prostatectomy

2012-01-16

Purpose: We previously found that patients undergoing robotic assisted laparoscopic radical prostatectomy vs radical retropubic prostatectomy had a higher likelihood of not being satisfied, independent of side effect profile. We hypothesized that differential preoperative expectations might contribute to this finding. In the current study we compared expectations of patients undergoing robotic assisted laparoscopic radical prostatectomy vs radical retropubic prostatectomy. Materials and Methods: A questionnaire on expectations regarding recovery was administered to 171 patients electing to undergo robotic assisted laparoscopic radical prostatectomy or radical retropubic prostatectomy from 2008 to 2010. We prospectively collected data on patient expectations before surgery. Differences between patients undergoing robotic assisted laparoscopic radical prostatectomy vs radical retropubic prostatectomy were assessed with adjusted proportional odds models. Results: Patients who underwent robotic assisted laparoscopic radical prostatectomy (97) did not differ significantly from those treated with radical retropubic prostatectomy (74) in age, race, income, time between survey and surgery, and prostate specific antigen (p ≥0.4). Patients who underwent radical retropubic prostatectomy had significantly higher clinical stage and Gleason grade disease (p ≤0.007). After adjusting for socioeconomic factors, clinical stage and grade on multivariate analysis, patients who underwent robotic assisted laparoscopic radical prostatectomy expected a significantly shorter length of stay (OR 0.07, p <0.001) and earlier return to physical activity (OR 0.36, p = 0.005). The choice of robotic assisted laparoscopic radical prostatectomy (OR 0.41, p = 0.012), younger age (OR 0.49, p = 0.001) and higher preoperative International Index of Erectile Function–5-item version score (OR 0.60, p = 0.017) were independently associated with the expectation of earlier return of erections but not of continence on multivariate analysis. Conclusions: The body of evidence surrounding robotic assisted laparoscopic radical prostatectomy supports shorter hospitalization but there is no conclusive evidence that the robotic approach results in earlier return to physical activity or improved disease specific outcomes. Nonetheless we found that patients who underwent robotic assisted laparoscopic radical prostatectomy had higher expectations regarding these outcomes, particularly that of erectile function recovery, than did their radical retropubic prostatectomy counterparts.

p16INK4a is a Marker of Good Prognosis for Primary Invasive Penile Squamous Cell Carcinoma: A Multi-Institutional Study

Sven Gunia, Andreas Erbersdobler, Oliver W. Hakenberg, Stefan Koch, Matthias May — 2012-01-16

Purpose: We assessed the prognostic role of p16INK4a expression in penile cancer with respect to cancer specific survival. Materials and Methods: Based on a multi-institutional collaboration wax embedded tissues from 92 surgically treated patients, including 27 with total and 65 with partial penectomy, were retrospectively evaluated. After a central histopathological review by 1 pathologist a tissue microarray was constructed for p16INK4a immunostaining. Two independent pathologists evaluated p16INK4a expression, which was correlated with cancer specific survival. The κ statistic was used to assess interobserver variability. Univariate and multivariate Cox proportional hazards analysis was applied to assess the independent effects of prognostic factors on cancer specific survival during a median postoperative followup of 32 months (IQR 6–66). Results: The κ statistic revealed excellent interobserver agreement (κ 0.934, p <0.001). Two and 5-year cancer specific survival rates for the entire study cohort were 86% and 74%, respectively. The 2 and 5-year rates for patients without and with p16INK4a expression differed significantly (73% and 57% vs 95% and 85%, respectively, p = 0.011). Univariate analysis revealed p16INK4a expression as a significant prognostic factor with respect to cancer specific survival (p = 0.018). Multivariate analysis identified koilocytosis (HR 0.24, 95% CI 0.07–0.83, p = 0.024), p16INK4a expression (HR 0.44, 95% CI 0.23–0.84, p = 0.013), and histological stage (HR 3.54, 95% CI 1.88–6.67, p <0.001) and grade (HR 2.47, 95% CI 1.00–6.09, p = 0.049) as independent prognostic factors for cancer specific survival. Conclusions: Results show that p16INK4a seems to be a prognostic parameter for primary invasive penile cancer with excellent interobserver reproducibility. At pathology laboratories without antibodies against p16INK4a conventional histological determination of koilocytosis by the pathologist also appears to provide important prognostic information for cancer specific survival.

Re: Preoperative Characteristics of Men With Unfavorable High-Gleason Prostate Cancer at Radical Prostatectomy

Patrick C. Walsh — 2012-01-19

P. M. Pierorazio, B. M. Lin, J. K. Mullins, M. E. Hyndman, E. M. Schaeffer, M. Han, A. W. Partin and C. P. Pavlovich Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland

Re: Long-Term Quality of Life Outcome After Proton Beam Monotherapy for Localized Prostate Cancer

Patrick C. Walsh — 2012-01-19

J. J. Coen, J. J. Paly, A. Niemierko, E. Weyman, A. Rodrigues, W. U. Shipley, A. L. Zietman and J. A. Talcott Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts

Re: Radiotherapy and Short-Term Androgen Deprivation for Localized Prostate Cancer

Patrick C. Walsh — 2012-01-19

C. U. Jones, D. Hunt, D. G. McGowan, M. B. Amin, M. P. Chetner, D. W. Bruner, M. H. Leibenhaut, S. M. Husain, M. Rotman, L. Souhami, H. M. Sandler and W. U. Shipley Radiological Associates of Sacramento, Sacramento, California

Re: Perineural Invasion Predicts Increased Recurrence, Metastasis, and Death From Prostate Cancer Following Treatment With Dose-Escalated Radiation Therapy

Patrick C. Walsh — 2012-01-19

F. Y. Feng, Y. Qian, M. H. Stenmark, S. Halverson, K. Blas, S. Vance, H. M. Sandler and D. A. Hamstra University of Michigan Medical Center and Ann Arbor Veteran Affairs Medical System, Ann Arbor, Michigan

Re: Contemporary Experience With Ketoconazole in Patients With Metastatic Castration-Resistant Prostate Cancer: Clinical Factors Associated With PSA Response and Disease Progression

Patrick C. Walsh — 2012-01-19

D. Keizman, P. Huang, M. A. Carducci and M. A. Eisenberger Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland

Re: Presence of Teratoma in Orchiectomy Specimen Increases the Need for Postchemotherapy RPLND

Jerome P. Richie — 2012-01-18

K. Inci, H. S. Dogan, B. Akdogan, D. E. Baydar, A. Ergen and H. Ozen Department of Urology, Hacettepe University, Faculty of Medicine, Ankara, Turkey

Optimal Power Settings for Holmium:YAG Lithotripsy

2012-01-19

Purpose: We determined the optimal Ho:YAG lithotripsy power settings to achieve maximal fragmentation, minimal fragment size and minimal retropulsion. Materials and Methods: Stone phantoms were irradiated in water with a Ho:YAG laser using a 365 μm optical fiber. Six distinct power settings were tested, including 0.2 to 2.0 J and 10 to 40 Hz. For all cohorts 500 J total radiant energy were delivered. A seventh cohort (0.2 J 40 Hz) was tested post hoc to a total energy of 1,250 J. Two experimental conditions were tested, including with and without phantom stabilization. Total fragmentation, fragment size and retropulsion were characterized. In mechanism experiments using human calculi we measured crater volume by optical coherence tomography and pressure transients by needle hydrophone across similar power settings. Results: Without stabilization increased pulse energy settings produced increased total fragmentation and increased retropulsion (each p <0.0001). Fragment size was smallest for the 0.2 J cohorts (p <0.02). With stabilization increased pulse energy settings produced increased total fragmentation and increased retropulsion but also increased fragment size (each p <0.0001). Craters remained symmetrical and volume increased as pulse energy increased. Pressure transients remained modest at less than 30 bars even at 2.0 J pulse energy. Conclusions: Holmium:YAG lithotripsy varies as pulse energy settings vary. At low pulse energy (0.2 J) less fragmentation and retropulsion occur and small fragments are produced. At high pulse energy (2.0 J) more fragmentation and retropulsion occur with larger fragments. Anti-retropulsion devices produce more efficient lithotripsy, particularly at high pulse energy. Optimal lithotripsy laser dosimetry depends on the desired outcome.

Determination of Patient Radiation Dose During Ureteroscopic Treatment of Urolithiasis Using a Validated Model

2012-01-19

Purpose: We measured organ specific radiation dose rates and determined effective dose rates during simulated ureteroscopy using a validated model. To calculate the effective dose, patients were exposed to ureteroscopic management of stones at our institution. Materials and Methods: A validated anthropomorphic male phantom was placed on a fluoroscopy table and underwent simulated ureteroscopy. High sensitivity metal oxide semiconductor field effect transistor dosimeters were placed at 20 organ sites in the phantom and used to measure organ specific radiation doses. These dose rates were multiplied by the appropriate tissue weighting factor and summed to calculate effective dose rates. Also, we retrospectively reviewed the charts of patients who underwent ureteroscopy at our institution. A total of 30 nonobese males with data on fluoroscopy time were included in analysis. The median effective dose was determined by multiplying median fluoroscopy time by the effective dose rate. Results: The skin entrance was exposed to the highest absorbed dose rate, followed by the small intestine (mean ± SD 0.3286 ± 0.0054 and 0.1882 ± 0.0194 mGy per second, respectively). The mean effective dose rate was 0.024 ± 0.0019 mSv per second. Median fluoroscopy time was 46.95 seconds (range 12.9 to 298.8). The median effective dose was 1.13 mSv (range 0.31 to 7.17). Conclusions: The fluoroscopy used during ureteroscopy contributes to overall radiation exposure in patients with nephrolithiasis. Nonobese males are exposed to a median of 1.13 mSv during ureteroscopy, similar to that of abdominopelvic x-ray. More data are needed to determine clinical implications but urologists must be aware and decrease patient radiation during ureteroscopy.

Editorial Comment

Roger L. Sur — 2012-01-19

These authors evaluated the risk of radiation exposure that patients receive from fluoroscopy during ureteroscopic kidney surgery. Baseline organ specific radiation doses were estimated using a validated phantom model. Results revealed a median ED of 1.13 mSv. One patient received an alarmingly high dose of 7.17 mSv, which is more than one receives for renal stone protocol CT. This study provides novel information on the additive risk of this procedure with other imaging modalities that places patients with kidney stones at risk for radiation exposure. As urologists, we should continue to minimize patient radiation exposure without compromising surgical outcomes.

Re: Defining Hypercalciuria in Nephrolithiasis

Dean Assimos — 2012-01-19

C. Y. Pak, K. Sakhaee, O. W. Moe, J. Poindexter, B. Adams-Huet, M. S. Pearle, J. E. Zerwekh, G. M. Preminger, M. R. Wills, N. A. Breslau, F. C. Bartter, D. C. Brater, H. J. Heller, C. V. Odvina, C. L. Wabner, J. S. Fordtran, M. Oh, A. Garg, J. A. Harvey, R. J. Alpern, W. H. Snyder and P. C. Peters

Re: Biochemical Determinants of Severe Lithogenic Activity in Patients With Idiopathic Calcium Nephrolithiasis

Dean Assimos — 2012-01-19

M. A. Arrabal-Polo, M. Arrabal-Martin, T. de Haro-Muñoz, A. Poyatos-Andujar, F. Palæo-Yago and A. Zuluaga-Gomez Department of Urology, San Cecilio University Hospital, Granada, Spain

Re: Primary Hyperoxaluria Type III Gene HOGA1 (Formerly DHDPSL) as a Possible Risk Factor for Idiopathic Calcium Oxalate Urolithiasis

Dean Assimos — 2012-01-19

C. G. Monico, S. Rossetti, R. Belostotsky, A. G. Cogal, R. M. Herges, B. M. Seide, J. B. Olson, E. J. Bergstrahl, H. J. Williams, W. E. Haley, Y. Frishberg and D. S. Milliner Hyperoxaluria Center, Divisions of Nephrology and Hypertension, Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota

Re: Changing Composition of Renal Calculi in Patients With Musculoskeletal Anomalies

Dean Assimos — 2012-01-19

E. Gnessin, J. A. Mandeville, S. E. Handa and J. E. Lingeman Department of Urology, Indiana University Health Physicians, Indianapolis, Indiana

Re: Impact of Insulin Resistance, Insulin and Adiponectin on Kidney Stones in the Japanese Population

Dean Assimos — 2012-01-19

R. Ando, S. Suzuki, T. Nagaya, T. Yamada, A. Okada, T. Yasui, K. Tozawa, S. Tokudome and K. Kohri Department of Nephro-Urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

Re: Laparoendoscopic Single-Site (LESS) Surgery Versus Conventional Laparoscopic Surgery: Comparison of Surgical Port Performance in a Surgical Simulator With Novices

Jeffrey A. Cadeddu — 2012-01-23

B. Brown-Clerk, A. E. de Laveaga, C. A. LaGrange, L. M. Wirth, B. R. Lowndes and M. S. Hallbeck Department of Industrial and Management Systems Engineering, University of Nebraska-Lincoln, Lincoln, Nebraska

Re: A Randomized Prospective Study of Single-Port and Four-Port Approaches for Hysterectomy in Terms of Postoperative Pain

Jeffrey A. Cadeddu — 2012-01-23

Y. W. Jung, M. Lee, G. W. Yim, S. H. Lee, J. H. Paek, H. Y. Kwon, E. J. Nam, S. W. Kim and Y. T. Kim Department of Obstetrics and Gynecology, CHA Gangnam Medical Center, CHA University, Seoul, Korea

Race and Insurance Status are Risk Factors for Orchiectomy Due to Testicular Trauma

Marc A. Bjurlin, Lee C. Zhao, Sandra M. Goble, Courtney M.P. Hollowell — 2012-01-19

Purpose: Race and insurance status independently predict outcome disparities after trauma. Black patients, Hispanic patients, uninsured patients and patients who live farther from trauma centers have a worse outcome after trauma than others. To our knowledge it is unknown whether these factors have a role in the testicular salvage rate after testicular trauma. We used NTDB (National Trauma Data Bank®) to investigate whether socioeconomic status, race and rural location predict testicular salvage. Materials and Methods: Patients who sustained testicular trauma were identified in NTDB, version 9.1. Procedure codes for orchiectomy vs testicular repair were used to determine the risk of testicular salvage. Rural location was determined by matching the injury with the urban influence code. Univariate analysis of the influence of patient age, injury severity, race, insurance status and rural location was performed. Multivariate longitudinal analysis was done to identify orchiectomy predictors. Results: Of 635,013 trauma cases 980 (0.2%) involved testicular injury. Of these patients 108 (11.0%) underwent orchiectomy and 58 (5.9%) underwent testicular repair. Self-paying patients had a statistically higher rate of orchiectomy than those with private insurance (79.2% vs 48.0%, p = 0.006). Black patients had a statistically higher rate of orchiectomy than white patients (75.8% vs 53.7%, p = 0.009). No difference in the orchiectomy rate was seen between Hispanic and nonHispanic patients (68.0% vs 65.8%, p = 0.84). In terms of rurality the incidence location was similar for orchiectomy and testicular repair, including urban 46.3% and 39.7%, rural 6.5% and 3.5%, suburban 2.8% and 1.7%, and wilderness 0.9% and 3.5%, respectively (p = 0.55). No statistically significant differences were found in age (31 vs 29 years, p = 0.42), injury severity score (5.8 vs 5.8, p = 0.99), hospital stay (8.4 vs 6.7 days, p = 0.41), intensive care unit stay (14.4 vs 9.6 days, p = 0.41) or ventilator days (18.2 vs 10.2, p = 0.24) for orchiectomy and testicular repair cases. Conclusions: Although age, injury severity score, hospital stay, intensive care unit stay and days of ventilator support are similar for patients who underwent orchiectomy vs testicular repair, the orchiectomy rate was higher for uninsured and black patients. Further studies are needed to elucidate the reasons for this disparity. Standardized protocols to manage testicular injury may decrease these disparities.

Re: Comparison of a New Length Measurement Technique for Inflatable Penile Prosthesis Implantation to Standard Techniques: Outcomes and Patient Satisfaction

Allen F. Morey — 2012-01-23

G. Henry, L. Houghton, D. Culkin, J. Otheguy, R. Shabsigh and D. A. Ohl Department of Urology, Regional Urology, Shreveport, Louisiana

Re: Penile Fracture: Long-Term Results of Surgical and Conservative Management

Allen F. Morey — 2012-01-23

W. M. Gamal, M. M. Osman, A. Hammady, M. Z. Aldahshoury, M. M. Hussein and M. Saleem Department of Urology, Sohag University, Sohag, Egypt

Re: Modified Hospital Elder Life Program: Effects on Abdominal Surgery Patients

Richard K. Babayan — 2012-01-23

C. C.-H. Chen, M.-T. Lin, Y.-W. Tien, C.-J. Yen, G.-H. Huang and S. K. Inouye Department of Nursing, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan

Weight Loss Prevents Urinary Incontinence in Women With Type 2 Diabetes: Results From the Look AHEAD Trial

2012-01-19

Purpose: We determined the effect of weight loss on the prevalence, incidence and resolution of weekly or more frequent urinary incontinence in overweight/obese women with type 2 diabetes after 1 year of intervention in the Look AHEAD (Action for Health in Diabetes) trial.Materials and Methods: Women in this substudy (2,739, mean ± SD age 57.9 ± 6.8 years, body mass index 36.5 ± 6.1 kg/m2) were randomized into an intensive lifestyle weight loss intervention or a diabetes support and education control condition.Results: At baseline 27% of participants reported urinary incontinence on a validated questionnaire (no significant difference by intensive lifestyle intervention vs diabetes support and education). After 1 year of intervention the intensive lifestyle intervention group in this substudy lost 7.7 ± 7.0 vs 0.7 ± 5.0 kg in the diabetes support and education group. At 1 year fewer women in the intensive lifestyle intervention group reported urinary incontinence (25.3% vs 28.6% in the diabetes support and education group, p = 0.05). Among participants without urinary incontinence at baseline 10.5% of intensive lifestyle intervention and 14.0% of diabetes support and education participants experienced urinary incontinence after 1 year (p = 0.02). There were no significant group differences in the resolution of urinary incontinence (p >0.17). Each kg of weight lost was associated with a 3% reduction in the odds of urinary incontinence developing (p = 0.01), and weight losses of 5% to 10% reduced these odds by 47% (p = 0.002).Conclusions: Moderate weight loss reduced the incidence but did not improve the resolution rates of urinary incontinence at 1 year among overweight/obese women with type 2 diabetes. Weight loss interventions should be considered for the prevention of urinary incontinence in overweight/obese women with diabetes.

Recovery of Urinary Function After Radical Prostatectomy: Predictors of Urinary Function on Preoperative Prostate Magnetic Resonance Imaging

2012-01-19

Purpose: We determined whether pelvic soft tissue and bony dimensions on endorectal magnetic resonance imaging influence the recovery of continence after radical prostatectomy, and whether adding significant magnetic resonance imaging variables to a statistical model improves the prediction of continence recovery. Materials and Methods: Between 2001 and 2004, 967 men undergoing radical prostatectomy underwent preoperative magnetic resonance imaging. Soft tissue and bony dimensions were retrospectively measured by 2 raters blinded to clinical and pathological data. Patients who received neoadjuvant therapy, who were preoperatively incontinent or had missing followup for continence were excluded from study, leaving 600 patients eligible for analysis. No pad use defined continent. Logistic regression was used to identify variables associated with continence recovery at 6 and 12 months. We evaluated whether the predictive accuracy of a base model was improved by adding independently significant magnetic resonance imaging variables. Results: Urethral length and urethral volume were significantly associated with the recovery of continence at 6 and 12 months. Larger inner and outer levator distances were significantly associated with a decreased probability of regaining continence at 6 or 12 months, but they did not reach statistical significance for other points. Addition of these 4 magnetic resonance imaging variables to a base model including age, clinical stage, prostate specific antigen and comorbidities marginally improved the discrimination (12-month AUC improved from 0.587 to 0.634). Conclusions: Membranous urethral length, urethral volume, and an anatomically close relation between the levator muscle and membranous urethra on preoperative magnetic resonance imaging are independent predictors of continence recovery after radical prostatectomy. The addition of magnetic resonance imaging variables to a base model improved the predictive accuracy for continence recovery, but the predictive accuracy remains low.

Complex Artificial Urinary Sphincter Revision and Reimplantation Cases—How do They Fare Compared to Virgin Cases?

H. Henry Lai, Timothy B. Boone — 2012-01-19

Purpose: We compared artificial urinary sphincter complication rates, overall reoperative rates, and continence results in virgin cases, revision cases and secondary reimplant cases (with prior erosion or infection). Materials and Methods: Only male patients with post-prostatectomy stress incontinence with AMS 800™ placement in the bulbar urethra by a single surgeon were included in the study. A total of 169 virgin cases (no prior artificial urinary sphincter surgery), 37 revision cases (eg cuff revision for urethral atrophy, revision of failed components) and 21 secondary reimplant cases (eg after prior explant from urethral erosion or infection) were compared. Results: Secondary artificial urinary sphincter reimplant cases (eg after prior explant from urethral erosion or infection) had fourfold higher future erosion rates compared to virgin cases (p = 0.02, 14.3% vs 3.6%, RR 4.02). In addition, there was no difference in the rates of other complications (device infection, urethral atrophy, mechanical failure, leaks), overall reoperation rates and postoperative continence outcomes (measured by daily pad use) compared to virgin cases. Artificial urinary sphincter revision cases did not have higher complication rates (including subsequent urethral erosion), reoperation rates or worse postoperative continence outcomes compared to virgin cases. Although the difference was not statistically significant, a trend toward higher future device leak rates (10.8% vs 3.6%, RR 3.05, p = 0.063) and higher urethral atrophy rates (16.2% vs 8.9%, RR 1.83, p = 0.18) was noted in artificial urinary sphincter revision cases compared to virgin implant cases. Conclusions: Patients with a history of artificial urinary sphincter explant have a fourfold increased risk of future cuff erosion. Nevertheless, a good functional outcome with an acceptable complication rate may be achieved in most complex reoperative artificial urinary sphincter cases.

Initial Experience and Results With a New Adjustable Transobturator Male System for the Treatment of Stress Urinary Incontinence

Jürgen Seweryn, Wilhelm Bauer, Anton Ponholzer, Paul Schramek — 2012-01-19

Purpose: We report on our initial experience in terms of efficacy and safety with a new, self-anchoring adjustable transobturator male system (A.M.I.® ATOMS System) for the treatment of male stress urinary incontinence after prostate surgery. Materials and Methods: In this prospective, nonrandomized single center study conducted between March and December 2009, patients with stress urinary incontinence secondary to prostatic surgery were treated with the ATOMS device. Urethroscopy, filling and voiding cystometry were performed preoperatively for all patients. In addition, incontinence symptoms were assessed, and a physical examination, 24-hour pad test and 24-hour pad count were performed before and after surgery. Results: A total of 38 patients were included in the study (36 after radical prostatectomy, 2 after benign prostatic hyperplasia surgery). No intraoperative complications occurred. Mean number of adjustments during followup was 3.97 (range 0 to 9). At a mean followup of 16.9 months (range 13 to 21) the overall success rate was 84.2%. Of the successful cases 60.5% were considered dry (0 to 1 pad and less than 15 ml/24-hour pad test) and 23.7% improved (more than 1 pad per 24 hours but more than 50% decrease in pad use and less than 100 ml per 24-hour pad test). In 15.8% of the patients the treatment was considered to have failed (more than 2 pads daily and greater than 100 ml on 24-hour pad test). Conclusions: The treatment of male stress urinary incontinence with the ATOMS is safe and effective. It is an excellent first or second line treatment for mild to moderate male stress urinary incontinence, even after external irradiation. The option of long-term, minimally invasive adjustment to respond to patient needs is a significant advantage of this new implant.

Re: Current Status of Urodynamics for Evaluation of Incontinence

Alan J. Wein — 2012-01-23

B. M. Whittam, M. R. Kaufman and R. R. Dmochowski Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee

Re: Abnormal Diurnal Rhythm of Urine Output Following Renal Transplantation: The Impact of Blood Pressure and Diuretics

Alan J. Wein — 2012-01-23

K. Alstrup, C. Graugaard-Jensen, S. Rittig and K. A. Jørgensen Department of Nephrology, Aarhus University Hospital, Skejby, Denmark

Re: How Well Informed are Women Who Undergo Urodynamic Testing?

David F. Penson — 2012-01-23

E. G. Neustaedter, J. Milne, K. Shorten, B. Weckman, A. Tse and S. Tange Pelvic Floor Clinic, Women's Health Center, Foothills Medical Centre, Calgary, Alberta, Canada

Re: Physician Documentation of Fluoroscopy Time in Voiding Cystourethrography Reports Correlates With Lower Fluoroscopy Times: A Surrogate Marker of Patient Radiation Exposure

David F. Penson — 2012-01-23

S. Darling, M. Sammer, T. Chapman and M. T. Parisi Department of Radiology, University of Washington, Seattle, Washington

Re: Urologist Compliance With AUA Best Practice Guidelines for Benign Prostatic Hyperplasia in Medicare Population

David F. Penson — 2012-01-23

S. A. Strope, S. P. Elliott, C. S. Saigal, A. Smith, T. J. Wilt and J. T. Wei; Urologic Diseases in America Project Division of Urologic Surgery, Washington University School of Medicine, St. Louis, Missouri

Re: Does Better Quality of Care for Falls and Urinary Incontinence Result in Better Participant-Reported Outcomes?

Tomas L. Griebling — 2012-01-23

L. C. Min, D. B. Reuben, J. Adams, P. G. Shekelle, D. A. Ganz, C. P. Roth and N. S. Wenger Division of Geriatrics, University of Michigan Medical School, Ann Arbor, Michigan

Re: Prevalence and Effect on Health-Related Quality of Life of Overactive Bladder in Older Americans: Results From the Epidemiology of Lower Urinary Tract Symptoms Study

Tomas L. Griebling — 2012-01-23

C. C. Sexton, K. S. Coyne, C. Thompson, T. Bavendam, C. I. Chen and A. Markland Center for Health Outcomes Research, United BioSource Corp., Bethesda, Maryland

Re: Major Depression Drives Severity of American Urological Association Symptom Index

Steven A. Kaplan — 2012-01-23

T. V. Johnson, A. Abbasi, S. S. Ehrlich, R. S. Kleris, S. L. Chirumamilla, E. D. Schoenberg, A. Owen-Smith, C. L. Raison and V. A. Master Department of Urology, Emory University School of Medicine, Atlanta, Georgia

Re: Nocturic Episodes in Patients With Benign Prostatic Enlargement May Suggest the Presence of Obstructive Sleep Apnea

Steven A. Kaplan — 2012-01-23

H. Tandeter, S. Gendler, J. Dreiher and A. Tarasiuk Department of Family Medicine, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel

Re: Increased Risk of Benign Prostatic Enlargement Among Patients With Liver Cirrhosis: A Nationwide Population-Based Study

Steven A. Kaplan — 2012-01-23

S. D. Chung and H. C. Lin Division of Urology, Department of Surgery, Far Eastern Memorial Hospital, Ban Ciao and Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan

Empirical Medical Therapy for Idiopathic Male Infertility: A Survey of the American Urological Association

Edmund Y. Ko, Kashif Siddiqi, Robert E. Brannigan, Edmund S. Sabanegh — 2012-01-19

Purpose: We determined empirical medical therapy practice patterns for idiopathic infertility. Materials and Methods: We performed a survey of 7,745 practicing American Urological Association members from July to November 2010. Respondents were questioned on empirical medical therapy use, patient evaluation and selection, and preferred medications. Results: A total of 387 urologists (5%) participated in the survey, of whom 16% had infertility fellowship training, two-thirds used empirical medical therapy and 78% treated with empirical medical therapy and surgery. Laboratory values important for identifying ideal candidates include sperm concentration, serum follicle-stimulating hormone and serum testosterone. The most common medications used were clomiphene citrate, human chorionic gonadotropin and anastrozole. Of respondents 25% would treat infertile males with testosterone while the patient actively pursued pregnancy. Overall 60.5% of respondents would treat with empirical therapy for 3 to 6 months. Of fellowship trained and general urologist respondents 70% and 47%, respectively, counseled patients that empirical medical therapy has unknown effects on pregnancy and sperm count. Conclusions: Empirical medical therapy is used by two-thirds of survey respondents for idiopathic male infertility. There is no clear, universal pattern to the evaluation or identification of the ideal patient for such therapy among those surveyed. There is no consensus on the optimal medication and considerable ambiguity exists as to perceived effects on fertility. Of concern is that 25% of respondents use exogenous testosterone, a medication known for its contraceptive potential, for male infertility treatment. These findings confirm the need for additional studies to establish recommendations on the empirical use of medical therapy in the setting of male infertility.

Improved Fertility Preservation Care for Male Patients With Cancer After Establishment of Formalized Oncofertility Program

2012-01-19

Purpose: Survival to reproductive age among men with cancer has steadily increased and yet cancer therapy and cancer itself may carry the risk of infertility. Since 2006, we have used a formalized fertility preservation program with expedited fertility care at our institution. We assessed the impact of this program by comparing the frequency of sperm cryopreservation and patient characteristics before and after its implementation. Materials and Methods: Men 18 to 55 years old diagnosed with cancer at our institution from 2002 to 2010 were included in our study. We retrospectively reviewed patient charts to identify those who were offered and subsequently used fertility preservation services before and after program formalization. Results: From 2002 to 2010 at our institution 4,818 men 18 to 55 years old were diagnosed with cancer, of whom 411 were offered fertility preservation consultation and 249 underwent sperm cryopreservation. Since program implementation, the annual number of men receiving fertility preservation consultation and undergoing sperm cryopreservation increased by 2.4 and 2.7-fold, respectively, while the total number diagnosed with cancer remained fairly constant. Upon substratifying patients into the more conventional reproductive age range of 18 to 40 years 23.4% of all men with cancer in this group were offered consultation before formalization vs 43.3% after formalization (p <0.05). The overall sperm use and discard rates were 8.4% and 14.8%, respectively. Conclusions: A formalized institutional fertility preservation program significantly increased the overall number and percent of male patients with cancer who received fertility preservation consultation and pursued sperm cryopreservation. These increases were seen in men with all types of cancer and across all demographics assessed at our institution.

The Effect of Radiation on Semen Quality and Fertility in Men Treated With Brachytherapy for Early Stage Prostate Cancer

2012-01-19

Purpose: We determined the effects of prostatic brachytherapy on semen parameters and sperm DNA integrity, and the potential impact on fertility. Materials and Methods: Five screened patients treated with brachytherapy participated in a pilot study visit to undergo early morning blood collection for serum hormone evaluation and semen collection for semen analysis and DNA integrity assay by sperm chromatin structure assay. Data on 7,617 infertile men, each with at least 1 semen analysis and sperm DNA integrity assay, were obtained from an institutional database for comparison. Published data on fertile men were compared to data on those with brachytherapy for DNA fragmentation analysis. Results: All brachytherapy cases had normal serum luteinizing hormone, follicle-stimulating hormone and testosterone. Specific semen parameters, such as semen volume (p <0.0005), total sperm concentration (p <0.0004) and percent sperm motility (p <0.004), were significantly lower than normal reference values. As measured by the DNA fragmentation index, the mean sperm DNA fragmentation of 46.4% in brachytherapy cases was significantly higher than in the fertile group (13.3%, p <0.0003), the total infertile group (20.4%, p <0.0002) and the age matched infertile group 45 to 53 years old (27.9%, p <0.03). All men with brachytherapy had an abnormal sperm DNA fragmentation index, indicating likely infertility in all. Conclusions: Infertility may well be a long-term adverse effect of brachytherapy for localized, low grade prostate cancer. All men who undergo brachytherapy should be counseled about its potential impact on fertility.

Re: Efficacy and Safety of Tadalafil Once Daily in the Treatment of Men With Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia: Results of an International Randomized, Double-Blind, Placebo-Controlled Trial

Allen D. Seftel — 2012-01-19

H. Porst, E. D. Kim, A. R. Casabé, V. Mirone, R. J. Secrest, L. Xu, D. P. Sundin and L. Viktrup; LVHJ Study Team Eur Urol 2011; 60: 1105–1113.

Re: Combined Tadalafil and α-Blocker Therapy for Benign Prostatic Hyperplasia in Patients With Erectile Dysfunction: A Multicenter, Prospective Study

Allen D. Seftel — 2012-01-19

J. Y. Lee, S. Y. Park, T. Y. Jeong, H. S. Moon, Y. T. Kim, T. K. Yoo, H. Y. Choi, H. Y. Park and S. W. Lee J Androl 2011; Epub ahead of print.

Re: Erectile Dysfunction can Improve the Effectiveness of the Current Guidelines for the Screening for Asymptomatic Coronary Artery Disease in Diabetes

Allen D. Seftel — 2012-01-19

C. Gazzaruso, A. Coppola, T. Montalcini, C. Valenti, A. Garzaniti, G. Pelissero, F. Salvucci, P. Gallotti, A. Pujia, C. Falcone, S. B. Solerte and A. Giustina Internal Medicine, Diabetes, Endocrine-Metabolic Diseases and Cardiovascular Prevention Unit, Centre for Applied Clinical Research, Clinical Institute Beato Matteo, Vigevano, Pavia, Italy

Re: The Effect of Surgical Intervention for Stress Urinary Incontinence (UI) on Post-Prostatectomy UI During Sexual Activity

Allen D. Seftel — 2012-01-19

R. Jain, S. Mitchell, J. Laze and H. Lepor Department of Urology, New York University School of Medicine, New York, New York

Re: Technique of Traction-Free Nerve-Sparing Robotic Prostatectomy: Delicate Tissue Handling by Real-Time Penile Oxygen Monitoring

Allen D. Seftel — 2012-01-19

A. Tewari, A. Srivastava, P. Sooriakumaran, S. Grover, P. Dorsey and R. Leung LeFrak Institute of Robotic Surgery and Prostate Cancer Institute, James Buchanan Brady Foundation, Department of Urology, New York-Presbyterian Hospital, Weill Cornell Medical College, New York, New York

Re: Long-Term Results of the Surgical Treatment of Peyronie's Disease With Egydio's Technique: A European Multicentre Study

Allen D. Seftel — 2012-01-19

S. Sansalone, G. Garaffa, R. Djinovic, S. Pecoraro, M. Silvani, G. Barbagli, A. Zucchi, G. Vespasiani and C. Loreto Department of Urology, School of Medicine, Tor Vergata University of Rome, Rome, Italy

Re: In Vitro Propagation of Human Prepubertal Spermatogonial Stem Cells