IsoPSA Performance Characteristics are Unaffected by 5-Alpha Reductase Inhibitors or Alpha-Blockers: Results From the IsoPSA Validation Study.

OBJECTIVE: To. determine the impact of 5-α reductase inhibitors or α-blockers on IsoPSA performance for the detection of actionable prostate cancer. MATERIALS AND METHODS: This is a secondary analysis of data from an institutional review board approved, prospective, multicenter(8-sites) study evaluating IsoPSA in men ≥ 50 years of age with a total PSA ≥ 4 ng/mL with planned prostate biopsy who met previously described inclusion and exclusion criteria. Analytic groups included (i)all subjects, (ii-iii)+/- 5-ARI use, (iv-v)+/- α-blocker use. The performance characteristics of IsoPSA in these groups were assessed by ROC curve, sensitivity, and specificity (SP) analysis. RESULTS: A total of 1385 men were recruited with 888 men included in final analysis. Actionable prostate cancer, defined as GG2+, was identified in a total of 316 patients with 40 and 217 patients reporting 5-ARI and α-blocker use respectively. Sensitivity to detect both prostate cancer and actionable cancer was similar between patient subsets (P >.05). SP was similar between patients regardless of 5-ARI(P >.05). Increased SP was noted in patients on α-blockers(GG1+: No-α-blocker: 0.360 vs α-blocker: 0.529, P <.05; GG2+: No-α-blocker: 0.40 vs α-blocker: 0.61, P <.05). ROC analysis demonstrates that IsoPSA performance is unaffected by 5-ARI or α-blocker use for prostate cancer and actionable cancer (GG2+) detection. CONCLUSION: The performance of IsoPSA for detecting any prostate cancer and clinically actionable prostate cancer is unaffected by commonly used medications (5-ARI and α-blockers) for symptoms of benign prostatic hyperplasia.

IsoPSA® Reduces Provider Recommendations for Biopsy and Magnetic Resonance Imaging in Men with Total Prostate Specific Antigen ≥4 ng/ml: A Real-World Observational Clinical Utility Study.

INTRODUCTION: We assessed the impact of the IsoPSA® test for prostate cancer risk assessment on provider patient management decisions in a real-world clinical setting. METHODS: A total of 38 providers, including advanced practice providers, fellowship trained oncologists and general urologists in the Cleveland Clinic health system including both community-based practices and academic locations, enrolled 900 men being evaluated for prostate cancer; 734 met inclusion criteria (age ≥50 years, total serum prostate specific antigen [PSA] ≥4 and <100 ng/ml and no history of prostate cancer) and IsoPSA indication for use. A standard template was used to document biopsy recommendation prior to and after receiving IsoPSA results. The primary outcome was the number of biopsy and magnetic resonance imaging recommendation changes occurring after IsoPSA testing. RESULTS: IsoPSA testing resulted in a 55% (284 vs 638) net reduction in recommendations for prostate biopsy for men with total PSA ≥4 ng/ml. Additionally, a 9% reduction in recommendations for magnetic resonance imaging was observed. There was strong concordance between IsoPSA results and provider recommendations for prostate biopsy, with 87% of patients with an IsoPSA index above the threshold recommended for biopsy and 92% of patients with an IsoPSA index below the threshold not recommended for biopsy. CONCLUSIONS: In a real-world clinical setting, providers from diverse training backgrounds and practice settings readily adopted IsoPSA with substantial reductions in the rate of recommended prostate biopsies in patients with elevated PSA values (≥4 ng/ml). There was a high concordance between recommendation for or against prostate biopsy and the IsoPSA result.

Is treatment of hypogonadism safe for men after a solid organ transplant? Results from a retrospective controlled cohort study.

Male solid organ transplant patients are at increased risk of hypogonadism and the safety of treating these patients for hypogonadism is unknown. We sought to evaluate the safety of treating hypogonadism in the solid organ transplant recipient. To accomplish this, we performed a retrospective review between 2009 and 2017 of patients treated at a single academic urology clinic. Men who underwent a solid organ transplant with a diagnosis of hypogonadism (Testosterone <350 ng/dl) were included. In total, 87 hypogonadal transplant recipients were included (29 no treatment; 58 treated). Treatment modalities included non-testosterone therapies (human chorionic gonadotropin, clomiphene), topical, injectable, and subcutaneous T preparations. There was no difference between groups for baseline characteristics including age, length of follow-up since transplant, baseline testosterone, and transplant type. There was no difference in prostate cancer diagnoses, erythrocytosis, rejection, infections, number of unplanned admissions per patient. While there was no difference in the proportion of deaths in untreated (21%; n = 6) and treated transplant recipients (7%; n = 4; p = 0.08), the median survival was longer in men treated with T (p = 0.03). Treatment of hypogonadism in solid organ recipients did not increase the risk for adverse effects related to treatment of hypogonadism or solid organ transplant.

PRSS50 is a testis protease responsible for proper sperm tail formation and function.

Multiple morphological abnormalities of the sperm flagella (MMAF) are a major cause of asthenoteratozoospermia. We have identified protease serine 50 (PRSS50) as having a crucial role in sperm development, because Prss50-null mice presented with impaired fertility and sperm tail abnormalities. PRSS50 could also be involved in centrosome function because these mice showed a threefold increase in acephalic sperm (head-tail junction defect), sperm with multiple heads (spermatid division defect) and sperm with multiple tails, including novel two conjoined sperm (complete or partial parts of several flagellum on the same plasma membrane). Our data support that, in the testis, as in tumorigenesis, PRSS50 activates NFκB target genes, such as the centromere protein leucine-rich repeats and WD repeat domain-containing protein 1 (LRWD1), which is required for heterochromatin maintenance. Prss50-null testes have increased IκκB, and reduced LRWD1 and histone expression. Low levels of de-repressed histone markers, such as H3K9me3, in the Prss50-null mouse testis may cause increases in post-meiosis proteins, such as AKAP4, affecting sperm formation. We provide important insights into the complex mechanisms of sperm development, the importance of testis proteases in fertility and a novel mechanism for MMAF.

An Infertile Couple's Long and Expensive Path to Varicocele Repair.

OBJECTIVE: To characterize the pathways to care that infertile couples requiring varicocele repair (VR) pursue prior to presenting to a male fertility clinic. METHODS: An IRB-approved single center retrospective review of patients undergoing VR after presentation to an academic male fertility clinic was performed. Patients whose charts included partner histories were assessed for duration of attempting conception, prior workup, and assisted reproductive technology (ART) use. RESULTS: A total of 405 couples were included. At presentation, mean age was 34.4 (SD ± 6.5) years for men and 31.1 (SD ± 4.3) years for women (P < .0001). A couple's first visit to a physician was a gynecologist in 59% (198/334) of couples, a reproductive endocrinologist (REI) in 25% (83/334) of cases, with 14% (47/334) presenting without a previous female workup and were self-referred, and 2% (6/334) seeing both a gynecologist and REI prior to presentation. On average, couples attempted pregnancy for 22.3 (SD ± 21.1, range 0-120) months prior to presentation. Eighteen percent of couples underwent ART prior to presentation. Couples who had undergone ART had lower pre-VR total motile sperm counts compared to couples not pursuing ART prior to presentation (P = 0.031). The majority (70.4%) of females had no abnormality in their workup, making varicocele the only correctable factor for infertility in the couple. CONCLUSIONS: Our findings show a significant delay in referral of infertile men requiring VR. Eighteen percent of couples underwent costly ART prior to an inexpensive male workup. In an era of medical cost containment, early referral to a male infertility specialist is imperative.

Patient-specific Virtual Simulation-A State of the Art Approach to Teach Renal Tumor Localization.

OBJECTIVE: To test whether a novel visuospatial testing platform improves trainee ability to convert two-dimensional to three-dimensional (3D) space. METHODS: Medical students were recruited from Baylor College of Medicine and McGovern Medical School (Houston, TX). We 3D reconstructed 3 partial nephrectomy cases using a novel, rapid, and highly accurate edge-detection algorithm. Patient-specific reconstructions were imported into the dV-Trainer (Mimics Technologies, Seattle, WA) as well as used to generate custom 3D printed physical models. Tumor location was altered digitally to generate 9 physical models for each case, 1 with the correct tumor location and 8 with sham locations. Subjects were randomized 1:1 into the dV-Trainer (intervention) and No-dV-Trainer (control) groups. Each subject completed the following steps: (1) visualization of computed-tomographic images, (2) visualization of the reconstructed kidney and tumor in the dV-Trainer (intervention group only), and (3) selection of the correct tumor location on the 3D printed models (primary outcome). Normalized distances from the correct tumor location were quantified and compared between groups. RESULTS: A total of 100 subjects were randomized for this study. dV-Trainer use significantly improved subjects ability to localize tumor position (tumor localization score: 0.24 vs 0.38, P < .001). However, subjects in the No-dV-Trainer group more accurately assigned R.E.N.A.L. scores. CONCLUSION: Even brief exposure to interactive patient-specific renal tumor models improves a novice's ability to localize tumor location. Virtual reality simulation prior to surgery could benefit trainees learning to localize renal masses for minimally invasive partial nephrectomy.

The Impact of Microsurgical Repair of Subclinical and Clinical Varicoceles on Total Motile Sperm Count: Is There a Difference?

OBJECTIVE: To determine if subclinical varicocele repair produces similar results to palpable varicocele repair. METHODS: Retrospective review was performed on 190 infertile men who underwent a microsurgical varicocele repair by two surgeons from 2009 to 2017. Improvement in total motile sperm count (TMC) that enables men limited to in vitro fertilization (IVF) or intrauterine insemination (IUI) to undergo IUI or natural conception (upgrade) is clinically meaningful. Using TMC, men were grouped into three pre- and postoperative categories: IVF, (TMC < 5 million), IUI (TMC 5-9 million), or natural pregnancy (TMC > 9 million). Changes in category after varicocele repair were assessed. We compared the proportion of men in each category with clinical varicoceles to those with subclinical varicoceles. RESULTS: Men with clinical and subclinical varicoceles had improvements in TMC after surgery (change in TMC of 9.3 ± 19.5, 7.7 ± 22.6 million, P < 0.001 for both, respectively). There was no difference in TMC improvement between men with clinical and subclinical varicoceles (P = 0.66). Of men initially limited to IVF, 11% improved to IUI, and 38% to natural pregnancy. Of patients starting in IUI category, 22% transitioned to natural pregnancy category. No difference exists in the proportion of men who "upgraded" between palpable or subclinical varicoceles. CONCLUSION: Men with subclinical varicoceles have similar, clinically meaningful improvement in TMC after varicocele repair compared with men with palpable varicoceles.

Percent of Tracer Clearance at 40 Minutes in MAG3 Renal Scans Is More Sensitive Than T1/2 for Symptomatic Ureteropelvic Junction Obstruction.

OBJECTIVE: To increase the diagnostic sensitivity of standard MAG3 diuretic renal scans for ureteropelvic junction obstruction (UPJO) by exploring the utility of an alternative measurement P40, the percentage of maximal tracer counts present at 40 minutes. MATERIALS AND METHODS: Patients with strong clinical and anatomic evidence for UPJO may have a normal T1/2, making definitive diagnosis difficult. We reviewed the charts of 142 consecutive patients who underwent successful laparoscopic or robotic-assisted laparoscopic pyeloplasty for UPJO between 2005 and 2015. Both pre- and postoperative renal scan images were available for 37 symptomatic patients with primary unilateral UPJO and 2 kidneys. We defined P40 as the percentage of maximal tracer counts present at 40 minutes. We identified the upper limit of normal (97.5th percentile, +2SD) for P40 using the preoperative renal scans from the unaffected kidney. We compared the sensitivity of P40 to T1/2 to identify symptomatic UPJO. RESULTS: In our cohort, 51% of symptomatic patients (n = 19) had a normal T1/2 (median 8.9 minutes; interquartile range: 7.5 minutes) and 49% (n = 18) had an abnormal T1/2 (median: 40 minutes; interquartile range: 0 minute). None of the patients had an abnormal P40 on their unaffected kidney. All patients with an abnormal T1/2 also had an abnormal P40. P40 increased the sensitivity of the renal scan from 49% (n = 18 of 37) to 73% (n = 27 of 37) when compared to T1/2. The majority of patients (95%) demonstrated an improvement in P40 after pyeloplasty. CONCLUSION: P40 markedly increases the sensitivity of a renal scan for diagnosing symptomatic UPJO and may be another valuable marker in addition to T1/2 to document functional improvement in drainage after pyeloplasty.

Impaired Sleep Quality is Associated With More Significant Lower Urinary Tract Symptoms in Male Shift Workers.

OBJECTIVE: To determine the association between sleep quality and severity of lower urinary tract symptoms (LUTS) in men working nonstandard shifts, a population at risk of poor sleep quality. METHODS: Men who presented to a single andrology clinic between July and October 2014 and worked nonstandard shifts completed the International Prostate Symptom Score (IPSS) and responded to questions regarding their work habits, sleep quality, and physical or cognitive function. We assessed the relationship between age, sleep quality, physical or cognitive function, and severity of LUTS. RESULTS: A total of 228 men with a mean ± standard deviation age of 41.8 ± 5.7 (range 21-76) years reported working nonstandard shifts, with the majority working these shifts for more than 1 year (81%). Men with difficulties falling asleep reported more severe LUTS than men who did not have difficulty falling asleep (IPSS score 9 vs 6, P <.001). Men who reported difficulty staying asleep or falling back asleep after awakening also reported more severe LUTS (IPSS scores 6 vs 13, P = .004; 5 vs 13, P <.001, respectively). Men with a decreased sense of well-being or decreased physical or cognitive function also reported more severe LUTS (IPSS score 6 vs 9, P <.0010; 6 vs 10, P = .016, respectively). All findings were independent of subject age. CONCLUSION: Men working nonstandard shifts who have difficulty falling asleep, staying asleep, and falling back asleep report more severe LUTS than men without similar sleep difficulties. Men with a decreased sense of well-being or decreased physical or cognitive function also report worse LUTS. These findings implicate sleep quality as a possible risk factor for LUTS symptom severity.

Utility of patient-specific silicone renal models for planning and rehearsal of complex tumour resections prior to robot-assisted laparoscopic partial nephrectomy.

OBJECTIVE: To describe our experience using patient-specific tissue-like kidney models created with advanced three-dimensional (3D)-printing technology for preoperative planning and surgical rehearsal prior to robot-assisted laparoscopic partial nephrectomy (RALPN). PATIENTS AND METHODS: A feasibility study of 10 patients with solid renal masses who underwent RALPN after preoperative rehearsal using 3D-print kidney models. A single surgeon performed all surgical rehearsals and procedures. Using standard preoperative imaging and 3D reconstruction, we generated pre-surgical models using a silicone-based material. All surgical rehearsals were performed using the da Vinci® robotic system (Intuitive Surgical Inc., Sunnyvale, CA, USA) before the actual procedure. To determine construct validity, we compared resection times between the model and actual tumour in a patient-specific manner. Using 3D laser scanning in the operating room, we quantified and compared the shape and tumour volume resected for each model and patient tumour. RESULTS: We generated patient-specific models for 10 patients with complex tumour anatomy. R.E.N.A.L. nephrometry scores were between 7 and 11, with a mean maximal tumour diameter of 40.6 mm. The mean resection times between model and patient (6:58 vs 8:22 min, P = 0.162) and tumour volumes between the computer model, excised model, and excised tumour (38.88 vs 38.50 vs 41.79 mm3 , P = 0.98) were not significantly different. CONCLUSIONS: We have developed a patient-specific pre-surgical simulation protocol for RALPN. We demonstrated construct validity and provided accurate representation of enucleation time and resected tissue volume. This simulation platform can assist in surgical decision-making, provide preoperative rehearsals, and improve surgical training.

WITHDRAWN: Re: Vasectomy and Prostate Cancer Incidence and Mortality in a Large US Cohort.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.eururo.2016.11.008. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Comparison of the Effects of Testosterone Gels, Injections, and Pellets on Serum Hormones, Erythrocytosis, Lipids, and Prostate-Specific Antigen.

INTRODUCTION: Numerous testosterone (T) formulations are available, each with differing effects on serum parameters. AIM: The aim of this study was to compare the long-term effects of topical, injectable, and implantable pellet T formulations in hypogonadal men. METHODS: Retrospective review of hypogonadal men treated with a single T formulation was performed: 47 men on T gels, 57 on injectable T, and 74 on T pellets were identified. Total T (TT), calculated free T (FT), estradiol (E), hemoglobin (Hgb), hematocrit (Hct), prostate-specific antigen (PSA), total cholesterol (Tchol), triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol were evaluated at baseline and every 3-6 months for 3 years. Serum parameters were compared using a mixed model linear regression for repeated measures. MAIN OUTCOME MEASURES: Effects of topical, injectable, and pellet T formulations on serum hormone levels, Hgb, Hct, lipid parameters and PSA. RESULTS: Men in the injectable T group were younger (42.5 ± 12.3 years) than in the gel (54.1 ± 9.8 years) or pellet groups (53.8 ± 13.0 years), and baseline FT, Hgb, and Hct were higher in the injectable T group than in gel or pellet groups. Increases in TT and FT were observed throughout follow-up in all groups. Increases in E were observed at in all T groups and throughout follow-up in injectable and gel groups. No PSA increases were observed. Erythrocytosis (Hct > 50%) was more common with injectable T (66.7%) than with T gels (12.8%) or pellets (35.1%, P < 0.0001). Transient changes in cholesterol, TG, and LDL were observed, and no significant changes were seen in HDL for any group. CONCLUSIONS: All T formulations increase serum T and FT. More significant increases in E occur with injectable T and T gels. Changes in Hgb and Hct are most significant with injectable T, and effects on lipids are variable and inconsistent. Selection of T formulations must account for individual patient preferences and the effects of each formulation.

A nephropleural fistula complicated by distal ureteral obstruction results in tension hydrothorax after percutaneous nephrostolithotomy.

We present the case of a patient with nephrocalcinosis and chronic kidney disease who underwent percutaneous nephrostolithotomy via a mid-pole access. After nephroureteral stent removal, the patient developed a tension hydrothorax due to the rare combination of a nephropleural fistula and ipsilateral distal ureteral obstruction. This complication was managed by percutaneous nephrostomy and thoracostomy placement and subsequent thoracoscopic surgery without further sequelae.

Transurethral use of a nephroscope significantly AIDS in the surgical management of an intrauterine device eroding into the bladder.

BACKGROUND: Intravesical migration of an intrauterine device (IUD) is a rare occurrence. The IUD becomes the nidus for calcification. Three approaches to remove the device include the use of open cystolithotomy, transurethral grasping forceps, or minimally invasive laparoscopy. CASE: A 50-year-old woman presented with vague abdominal pain and recurrent urinary tract infections. She was found to have an intravesical migration or malplacement of an IUD which was unretrievable 20 years ago and was encrusted with a calculus formation. We removed the foreign body through a transurethral approach aided by the use of a nephroscope which allowed for easy access of laparoscopic scissors and grasping forceps. CONCLUSIONS: The transurethral approach with the use of a nephroscope significantly aids in the removal of an IUD embedded into the bladder wall.

Testosterone supplementation versus clomiphene citrate for hypogonadism: an age matched comparison of satisfaction and efficacy.

PURPOSE: We compared satisfaction and treatment efficacy in men with symptomatic hypogonadism who received clomiphene citrate or testosterone supplementation therapy. MATERIALS AND METHODS: Men treated with clomiphene citrate, or testosterone injections or gels for symptomatic hypogonadism (total testosterone less than 300 ng/dl) reported satisfaction with the current treatment regimen using the qADAM questionnaire. RESULTS: A total of 93 men on testosterone injections (31) or gels (31), or clomiphene citrate (31) were age matched from a retrospective cohort of 1,150 on testosterone supplementation therapy. We compared men who received testosterone supplementation therapy to 31 not on such therapy, who served as controls. Median serum testosterone increased from pretreatment levels in all men regardless of therapy with clomiphene citrate, and testosterone injections and gels (from 247 to 504, 224 to 1,104 and 230 to 412 ng/dl, respectively, p <0.05). Final median serum total testosterone in men on clomiphene citrate (504 ng/dl) was lower than in men receiving testosterone injections (1,014 ng/dl, p <0.01) but similar to that in men on testosterone gels (412 ng/dl, p = 0.31). Despite different serum testosterone levels men on all 3 therapies reported similar satisfaction on qADAM, including a score of 35 for clomiphene citrate, 39 for testosterone injections, 36 for testosterone gels and 34 for control treatment (p >0.05). Men receiving testosterone injections reported greater libido than men on clomiphene citrate (4 vs 3, p = 0.04) or testosterone gels (4 vs 3, p = 0.04), or controls (4 vs 3, p <0.01). CONCLUSIONS: Testosterone supplementation regimens and clomiphene citrate are efficacious for improving serum total testosterone. No difference in overall hypogonadal symptoms was noted among men on any testosterone supplementation therapy. Despite lower serum total testosterone, men on clomiphene citrate and testosterone gels reported satisfaction similar to that of men treated with testosterone injections.