Contemporary practice patterns in the treatment of pediatric stone disease.

INTRODUCTION: To compare endourology versus pediatric urology exposure to pediatric stone cases during fellowship, comfortability in treating pediatric stone cases, and access to pediatric surgical equipment. MATERIALS AND METHODS: A survey was distributed to all pediatric urology fellowship programs and the Endourological Society. Age was stratified into < 12 months old, 12 months-4 years, 5-12 years, and 13-18 years. Exposure and comfortability performing extracorporeal shock wave lithotripsy (SWL), ureteroscopy (URS) and percutaneous nephrolithotomy (PCNL) were assessed across age groups. Exposure was assessed as 'yes/no' and comfortability was scaled from 1-5 ('would not do' to 'very comfortable'). RESULTS: Seventy-two surveys met inclusion criteria, with 23 (31.9%) from pediatric urologists and 49 (68.1%) by endourologists. During fellowship, pediatric urologists had more exposure to SWL in toddlers (p = 0.03) and school age children (p = 0.045), URS in toddlers (p = 0.012) and school age children (p = 0.002), and PCNL in infants (p = 0.031) and school age children (p = 0.025) compared to endourologists. Pediatric urologists were significantly more comfortable performing SWL in toddlers (p = 0.04), URS in toddlers (p = 0.04) and school age children (p = 0.04), and PCNL in school age children (p = 0.02) compared to endourologists. Endourologists were significantly more uncomfortable than pediatric urologists in performing URS in toddlers (p = 0.03) and PCNL in infants (p = 0.04) and school age children (p = 0.03). There were no differences in availability of pediatric equipment. CONCLUSIONS: Pediatric urologists, have significantly more exposure than endourologists during fellowship and are more comfortable performing surgical treatment for urolithiasis in most pediatric ages. Endourology fellowships may benefit from greater exposure to pediatric patients with stones.

Disparities in the Use of Continent Urinary Diversions after Radical Cystectomy for Bladder Cancer.

BACKGROUND: Radical cystectomy (RC) with ileal conduit (IC) or continent diversion (CD) is standard treatment for high-risk non-invasive and muscle-invasive bladder cancer. OBJECTIVE: Our aim is to study contemporary trends in the utilization of ICs and CDs in patients undergoing RC. METHODS: Using the National Inpatient Sample 2001-2012, we identified all patients diagnosed with a malignant bladder neoplasm who underwent RC followed by IC or CD. Patient demographics, comorbidities, length of stay (LOS), and in-hospital complications, mortality, and costs were compared. Multivariable logistic regression analysis, Chi square, and t-tests were used for analysis. RESULTS: Between 2001-2012, approximately 69,049 ICs and 6,991 CDs were performed. CDs increased from 2001 to 2008, but declined after 2008 (p < 0.0001). Patients of all ages received ICs at a higher rate than CDs (40-59 years: 79.5% vs. 20.5%; 60-69 years: 88.0% vs. 12.0%; p < 0.0001). There was a difference in males vs. females (10.2% vs. 4.0%; OR 2.36) and Caucasians vs. African Americans (9.0% vs. 6.7%; OR 1.49) when comparing CD rates. CD rates were highest in the West, urban teaching centers, and large hospitals (p < 0.001). ICs were associated with higher rates of overall postoperative complications (p = 0.0185) including infection (p = 0.002) and mortality (p < 0.0001). In-hospital costs were greater for the CD group. CONCLUSIONS: The number of CDs has declined recently. Patients of all ages are more likely to receive ICs than CDs. Gender, racial, and geographic disparities exist among those receiving CDs. CDs are associated with lower rates of in-hospital complications and mortality, but higher in-hospital costs.

Use of Fluoroscopy and Potential Long-Term Radiation Effects on Cataract Formation.

INTRODUCTION: The lens of the eye is extremely susceptible to radiation and long-term exposure can induce cataract formation. Our objective was to explore the risk of cataract formation for urologists at our institution. METHODS: A retrospective review of a multisurgeon database of fluoroscopic cases between October 2013 to December 2014 was queried. Procedures were performed by different subspecialties and ranged from stent insertion/ureteroscopy to percutaneous nephrolithotomy. Fluoroscopic parameters were recorded from all cases and the radiation dosimetry was calculated through methods described by the National Council on Radiation Protection. The data were extrapolated to determine the risk of cataract formation. The technical specifications of the GE OEC 990 mobile C-arm unit were used for calculations. RESULTS: A total of 780 cases were analyzed, of which 182 were endourology cases. Average fluoroscopic time was 34.86 seconds per case. Average tube potential and current were 86.84 kV and 1.95 mA, respectively. Pediatric urologists utilized fluoroscopy the least, 11.84 seconds per case (p = 0.0022). Endourology trained faculty had fluoroscopy exposure of 68.35 seconds per case (p < 0.0001), whereas others were exposed 26.24 seconds per case (p < 0.0001). For the highest exposed urologist, the estimated dose to the eyes was 5.64 µGy per case. Total estimated cumulative dose over the study timeframe was 997.58 µGy, or 748.19 µGy per year. CONCLUSIONS: The defined threshold in the absorbed dose for cataract formation is 0.5 Gy. Resident exposure was the highest, at 11% of the annual limit, and the most exposed urologists had an estimated dose of 5% of the annual limit. At current exposure levels, it would not be feasible to reach the stated safety limit during 50 to 60 years of practice. However, changing exposure guidelines could result in stricter safety limits.

Intracrine androgen biosynthesis in renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) is one of the most lethal genitourinary cancers. The presence of androgen receptor (AR) in RCC has recently been shown to be associated with higher tumour stage irrespective of gender. Because the clinical context of androgens in female RCC patients is similar to that of prostate cancer patients undergoing androgen-deprivation therapy, mechanisms underlying the emergence of castration-resistant prostate cancer (CRPC) may be at play in AR-positive RCC cells. Therefore, we hypothesized that AR-positive RCC has intratumoral steroidogenesis and that anti-androgen therapy may result in tumour suppression. METHODS: Mice were injected with an AR-positive RCC cell line. When tumours became palpable, surgical castration was performed and tumour volume was measured. Using ELISA, the levels of intracellular testosterone and dihydrotesterone were measured in AR-positive human RCC cell lines. Lastly, male mice containing xenografts were treated with enzalutamide or abiraterone acetate (AA) for 3 weeks to measure tumour volume. RESULTS: We first observed in vivo that castration retards the growth of AR-positive RCC tumour xenograft in mice. Next, AR-positive human RCC cell lines and tissues were found to have elevated levels of testosterone and dihydrotestosterone and express key enzymes required for intracellular androgen biosynthesis. A mouse xenograft study with AR-positive RCC cell line using the commonly used anti-androgen therapies showed significant tumour suppression (P<0.01). CONCLUSIONS: Intracrine androgen biosynthesis is a potential source of androgen in AR-positive RCC and that the androgen signaling axis is a potential target of intervention in RCC.

Pharmacokinetic drug evaluation of atezolizumab for the treatment of locally advanced or metastatic urothelial carcinoma.

INTRODUCTION: Muscle invasive bladder cancer (MIBC) is difficult to manage for patients who progress during or after initial chemotherapy regimens. Current regimens offer low response rates with high toxicities. The advent of immune checkpoint inhibitors may represent a new opportunity for effective management of these patients. Areas covered: Atezolizumab is an engineered humanized monoclonal immunoglobulin G1 antibody that binds selectively to PD-L1 and prevents its interaction with PD-1 and B7-1. It is administered intravenously and is given every 3 weeks as long as there is no evidence of tumor progression. Phase I trials confirmed antitumor activity of atezolizumab in patients with advanced or metastatic urothelial carcinoma. Phase II trials showed an improved response rate and a longer durable response than current conventional therapy. Phase III trials are currently underway with an estimated accrual end date of 2017. Expert opinion: MIBC is a high-risk disease, and after progression on current chemotherapy regimens, second-line treatments leave much to be desired. Emerging evidence of efficacy and safety and a recent accelerated approval by the FDA presents atezolizumab as a promising treatment option. Current clinical challenges include the details of disease progression and determining where immune checkpoint inhibition will reside in the treatment algorithm.

Long-Term Outcomes of Using Hyaluronic Acid-Carboxymethylcellulose Adhesion Barrier Film on the Neurovascular Bundle.

INTRODUCTION/OBJECTIVE: We hypothesize that the use of hyaluronic acid-carboxymethylcellulose (HACM) adhesion barrier at the neurovascular bundle may hasten the return of erectile function after robot-assisted laparoscopic prostatectomy. MATERIALS AND METHODS: A retrospective review identified 462 consecutive patients who underwent a nerve-sparing prostatectomy between 2009 and 2012. The first 246 patients were administered the barrier film, while the next 216 patients, the control group, did not receive HACM. Postoperative erectile function and oncologic outcomes were compared. Independent t-test and Kaplan-Meier analysis were conducted, p < 0.05 was considered significant. RESULTS: The two groups were well matched, without significant differences in age, weight, operative time, prostate size, preoperative prostate-specific antigen, sexual health inventory for men (SHIM), or AUA symptom scores. The mean SHIM was significantly higher for the experimental group at 6 months (6.39 vs 4.75, p = 0.008), 9 months (7.32 vs 5.44, p = 0.006), 1 year (8.52 vs 6.90, p = 0.049), and 18 months (10.01 vs 7.60, p = 0.018). This effect was not noted beyond 18 months. A subgroup analysis of patients with initial SHIM scores 22 or greater demonstrated a higher rate of return to the preoperative SHIM score for the barrier film group, 23% vs 12% (p = 0.046). There was no significant difference in biochemical recurrence between groups, with a median follow-up duration of 18 months. CONCLUSIONS: HACM application at the neurovascular bundle during prostatectomy may decrease the time to return of erectile function, with improved SHIM at 6 to 18 months after surgery. This effect is more pronounced in patients with better baseline erectile function. There is no significant effect on biochemical recurrence.

Controversies in Robotics: Open Versus Robotic Radical Cystectomy.

Open radical cystectomy (ORC) remains the gold standard for treatment of muscle-invasive bladder cancer and certain cases of high-risk noninvasive bladder cancer. However, ORC is associated with significant morbidity, and there is promise of improved outcomes with the emergence of minimally invasive surgery. Because of the increased adoption of robotic radical cystectomy (RRC), we sought to review the current literature on the robotic approach. We explored the surgical techniques, perioperative and postoperative complications, oncologic and functional outcomes, and quality of life of patients with RRC versus ORC. Current data appear to favor RRC in perioperative outcomes and patient recovery, although RRC continues to be associated with longer surgical times and higher costs. Oncologic data are also promising, however data on long-term oncologic outcomes are insufficient. To date, there is evidence of similar functional outcomes between RRC and ORC continence, but there is a paucity of rigorous, standardized studies on health-related quality of life for continent versus incontinent diversion. Even as use of RRC steadily grows, there is a lack of consensus on the type of approach and urinary diversion that is optimal. We assessed the influence of surgeon experience on the totally intracorporeal urinary diversion and its feasibility to be widely adopted. We aimed to answer the question of whether there are significant benefits to RRC, and furthermore, of the effect of the approach on the choice of urinary diversion.

Regional Cost Variations of Robot-Assisted Radical Prostatectomy Compared With Open Radical Prostatectomy.

INTRODUCTION: The purpose of the study was to evaluate the cost differences between robot-assisted radical prostatectomy (RARP) and open radical prostatectomy (ORP) in various census regions of the United States because RARP has been reported to be more expensive than ORP with significant regional cost variations in radical prostatectomy (RP) cost across the United States. PATIENTS AND METHODS: International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify patients with prostate cancer who underwent RARP or ORP from the Nationwide Inpatient Sample (NIS) database from 2009 to 2011. Hospital costs were compared using the Wilcoxon rank sum test and multivariable linear regression analysis adjusting for age, sex, race, comorbidities, and hospital characteristics. RESULTS: From the NIS database, 24,636 RARP and 13,590 ORP procedures were identified and evaluated. The lowest cost overall was in the South; the highest cost RARP was in the West and for ORP in the Northeast. In multivariable analysis, adjusted according to patient and hospital characteristics, RARP was 43.3% more costly in the Midwest, 37.2% more costly in the South, and 39.1% more costly in the West (P < .0001 for all). In contrast, the cost for RARP in the Northeast was 12.8% less than for ORP (P < .0001). CONCLUSION: Cost for RP significantly varies within the nation and in most regions it is significantly greater for RARP than for ORP. ORP in the Northeast is more costly than RARP. Further research is needed to delineate the reason for these differences and to optimize the cost of RP.

Pharmacokinetics, pharmacodynamics and clinical efficacy of abiraterone acetate for treating metastatic castration-resistant prostate cancer.

INTRODUCTION: Androgen signaling axis (ASA) continues to play a crucial role in castration-resistant prostate cancer (CRPC). One of the proposed mechanisms is the activation of ASA by adrenal and intratumoral androgens. Targeted therapy to deplete such androgen sources should be effective in treating men with CRPC. AREAS COVERED: Abiraterone acetate (AA) is a selective irreversible inhibitor of CYP 17. It is orally administered and is converted to its active metabolite abiraterone by the liver. Increased adrenocorticotrophic hormone drive, however, results in increased risks of hypertension and hypokalemia. In Phase III trials, AA with prednisone was shown to improve survivals in men with metastatic CRPC (mCRPC). The overall tolerability and safety profiles were acceptable. EXPERT OPINION: It is now accepted that CRPC is not independent of androgen signaling, and targeted therapies to suppress ASA have recently been developed. With multiple high-level evidences of efficacy and safety, AA is considered a breakthrough in the treatment of mCRPC. Current clinical challenge, however, is to better delineate the mechanisms of the disease progression for developments of resistance to targeted therapies. Identification of the drug-resistance patterns would allow better patient selection for each treatment modality.

Large cell differentiation of metastatic prostate cancer after androgen deprivation therapy.

We present a case of a 75-year-old male with a history of high risk prostate cancer who underwent androgen deprivation therapy and palliative radiation treatments for his disease. Subsequently, he presented with gross hematuria and severe lower urinary tract symptoms. A palliative transurethral resection of the prostate (TURP) at that time, demonstrated large cell differentiated neuroendocrine carcinoma with metastasis to the lung. We review the limited literature on this rare form of disease and present current treatment strategies.