Testosterone Modifies Alterations to Detrusor Muscle after Partial Bladder Outlet Obstruction in Juvenile Mice.

Lower urinary tract symptoms secondary to posterior urethral valves (PUV) arise in boys during adolescence. The reasons for this have previously been attributed to increased urine output as boys experience increased growth. Additionally, there are few choices for clinicians to effectively treat these complications. We formed the new hypothesis that increased androgen levels at this time of childhood development could play a role at the cellular level in obstructed bladders. To test this hypothesis, we investigated the role of testosterone on bladder detrusor muscle following injury from partial bladder outlet obstruction (PO) in mice. A PO model was surgically created in juvenile male mice. A group of mice were castrated by bilateral orchiectomy at time of obstruction (CPO). Testosterone cypionate was administered to a group of castrated, obstructed mice (CPOT). Bladder function was assessed by voiding stain on paper (VSOP). Bladders were analyzed at 7 and 28 days by weight and histology. Detrusor collagen to smooth muscle ratio (Col/SM) was calculated using Masson's trichrome stain. All obstructed groups had lower max voided volumes (MVV) than sham mice at 1 day. Hormonally intact mice (PO) continued to have lower MVV at 7 and 28 days while CPO mice improved to sham levels at both time points. In accordance, PO mice had higher bladder-to-body weight ratios than CPO and sham mice demonstrating greater bladder hypertrophy. Histologically, Col/SM was lower in sham and CPO mice. When testosterone was restored in CPOT mice, MVV remained low at 7 and 28 days compared to CPO and bladder-to-body weight ratios were also greater than CPO. Histologic changes were also seen in CPOT mice with higher Col/SM than sham and CPO mice. In conclusion, our findings support a role for testosterone in the fibrotic changes that occur after obstruction in male mice. This suggests that while other changes may occur in adolescent boys that cause complication in boys with PUV, the bladder itself responds to testosterone at the cellular level. This opens the door to a new understanding of pathways that influence bladder fibrosis and could lead to novel approaches to treat boys with PUV.

The effect of minimally invasive prostatectomy on practice patterns of American urologists.

INTRODUCTION AND OBJECTIVES: To determine how robotic prostatectomy affects practice patterns of urologists, we examined the case volume characteristics among certifying urologists for the surgical treatment of prostate cancer. We hypothesized that the utilization of open and robotic prostatectomy as well as lymph node dissection changed dynamically over the last 10 years. METHODS: A total of 6-month case log data of certifying urologists from 2003 to 2013 were obtained for the American Board of Urology. Cases were identified using Current Procedural Terminology codes for open radical prostatectomy (ORP) and laparoscopic or robotic-assisted laparoscopic prostatectomy (RALP) with a corresponding diagnosis of prostate cancer as defined by ICD-9 code 185.0. RESULTS OBTAINED: A total of 6,563 urologists submitted case logs, of which 68% (4,470/6,563) reported performing at least one radical prostatectomy (RP), totaling 46,030 RPs logged. There was a 376% increase in the performance of RALP over the study period with robotic volume increasing from 22% of all RP in 2003 to 85% in 2013. Among surgeons performing ORP, the median number performed was 2; of surgeons who performed RALP, the median number performed was 8 (P<0.001). Overall, 39% of surgeons logging ORP performed 2 or fewer RP, whereas 19% of surgeons who performed RALP performed 2 or less RP (P<0.001). The highest volume robotic surgeons (top 10% surgical volume) performed 41% of all RALP with the highest performing robotic surgeon recording 658 prostatectomies over 6 months. Oncologists represented 4.1% of all surgeons performing RP and performed 15.1% of all RP (P<0.001); general urologists performed the majority of RP (57.8%). When performed open, there was no influence of surgeon specialty on the performance of lymph node dissection (LND); if performed robotically, oncologists were significantly more likely to perform LND compared with general surgeons (47% vs. 25.9%, respectively, P<0.001). CONCLUSIONS: Robotic prostatectomies are performed 5 times more commonly than open prostatectomy and represent 85% of all RP performed by board-certified urologists in 2013. Compared to RALP, ORP are significantly more likely to be performed by lower volume surgeons. Oncologists perform a higher relative percentage of RPs and are significantly more likely to perform LND if performed robotically when compared with general urologists.

Centralization of Penile Cancer Management in the United States: A Combined Analysis of the American Board of Urology and National Cancer Data Base.

OBJECTIVE: To assess the potential benefit of centralization of care in penile cancer. Centralization of care in other disease processes standardizes treatment and improves outcomes. Because penile cancer is a rare malignancy with unchanged mortality rates over the last two decades, we hypothesize that there may be a benefit to centralization. METHODS: We identified surgeon, patient, and hospital characteristics captured by the National Cancer Data Base (1998-2012) and American Board of Urology case logs (2003-2013) for all penile cancer cases and procedures. Differences in patient demographics, stage of disease, referral patterns, and surgical quality indicators were assessed between academic and community hospitals. RESULTS: Using case logs to evaluate the distribution of penile cancer care, we found that only 4.1% of urologists performed a penile surgery and 1.5% performed a lymph node dissection (LND). Academic centers treated higher-stage cancers and saw more cases/year than community centers, suggesting informal centralization. Two guideline-based quality indicators demonstrated no difference in use of penile-sparing surgery but a higher likelihood of having an LND performed at an academic center (48.4% vs 26.6%). The total lymph node yield was significantly greater at academic centers (18.5 vs 12.5). Regression modeling demonstrated a 2.29 increased odds of having an LND at an academic center. CONCLUSION: Our data provide the first evidence for centralization of penile cancer in the US. At the time of diagnosis, equal number of patients is treated with penile-sparing surgery but there is greater use of LND and higher lymph node yield at academic centers. Ultimately, longer follow-up is necessary to determine if this improves survival of patients with penile cancer.

Update on the Diagnosis and Management of Renal Angiomyolipoma.

PURPOSE: Advances in minimally invasive therapies and novel targeted chemotherapeutics have provided a breadth of options for the management of renal masses. Management of renal angiomyolipoma has not been reviewed in a comprehensive fashion in more than a decade. We provide an updated review of the current diagnosis and management strategies for renal angiomyolipoma. MATERIALS AND METHODS: We conducted a PubMed(®) search of all available literature for renal or kidney angiomyolipoma. Further sources were identified in the reference lists of identified articles. We specifically reviewed case series of partial nephrectomy, selective arterial embolization and ablative therapies as well as trials of mTOR inhibitors for angiomyolipoma from 1999 to 2014. RESULTS: Renal angiomyolipoma is an uncommon benign renal tumor. Although associated with tuberous sclerosis complex, these tumors occur sporadically. Risk of life threatening hemorrhage is the main clinical concern. Due to the fat content, angiomyolipomas are generally readily identifiable on computerized tomography and magnetic resonance imaging. However, fat poor angiomyolipoma can present a diagnostic challenge. Novel research suggests that various strategies using magnetic resonance imaging, including chemical shift magnetic resonance imaging, have the potential to differentiate fat poor angiomyolipoma from renal cell carcinoma. Active surveillance is the accepted management for small asymptomatic masses. Generally, symptomatic masses and masses greater than 4 cm should be treated. However, other relative indications may apply. Options for treatment have traditionally included radical and partial nephrectomy, selective arterial embolization and ablative therapies, including cryoablation and radio frequency ablation, all of which we review and update. We also review recent advances in the medical treatment of patients with tuberous sclerosis complex associated angiomyolipomas with mTOR inhibitors. Specifically trials of everolimus for patients with tuberous sclerosis complex suggest that this agent may be safe and effective in treating angiomyolipoma tumor burden. A schema for the suggested management of renal angiomyolipoma is provided. CONCLUSIONS: Appropriately selected cases of renal angiomyolipoma can be managed by active surveillance. For those patients requiring treatment nephron sparing approaches, including partial nephrectomy and selective arterial embolization, are preferred options. For those with tuberous sclerosis complex mTOR inhibitors may represent a viable approach to control tumor burden while conserving renal parenchyma.

The Murine Bladder Supports a Population of Stromal Sca-1+/CD34+/lin- Mesenchymal Stem Cells.

Bladder fibrosis is an undesired end point of injury of obstruction and often renders the smooth muscle layer noncompliant. In many cases, the long-term effect of bladder fibrosis is renal failure. Despite our understanding of the progression of this disease, little is known about the cellular mechanisms that lead to a remodeled bladder wall. Resident stem (progenitor) cells have been identified in various organs such as the brain, heart and lung. These cells function normally during organ homeostasis, but become dysregulated after organ injury. Here, we aimed to characterize a mesenchymal progenitor cell population as a first step in understanding its role in bladder fibrosis. Using fluorescence activated cell sorting (FACS), we identified a Sca-1+/ CD34+/ lin- (PECAM-: CD45-: Ter119-) population in the adult murine bladder. These cells were localized to the stromal layer of the adult bladder and appeared by postnatal day 1. Cultured Sca-1+/ CD34+/ lin- bladder cells self-renewed, formed colonies and spontaneously differentiated into cells expressing smooth muscle genes. These cells differentiated into other mesenchymal lineages (chondrocytes, adipocytes and osteocytes) upon culture in induction medium. Both acute and partial obstruction of the bladder reduced expression of CD34 and changed localization of Sca-1 to the urothelium. Partial obstruction resulted in upregulation of fibrosis genes within the Sca-1+/CD34+/lin- population. Our data indicate a resident, mesenchymal stem cell population in the bladder that is altered by bladder obstruction. These findings provide new information about the cellular changes in the bladder that may be associated with bladder fibrosis.

Characteristics of Certifying Urologists Performing Cystectomies in the United States.

INTRODUCTION: The surgical volume and training of the surgeon performing radical cystectomy can have a significant impact on bladder cancer outcomes. We hypothesize significant variability in the training and volume of surgeons performing radical cystectomy in the United States. METHODS: The 6-month case log data of urologists certifying between 2003 and 2013 were obtained from the American Board of Urology. Cases specifying an ICD-9 code for bladder cancer and a CPT code for radical cystectomy were analyzed for surgeon specific variables. RESULTS: A total of 5,335 radical cystectomies in the case log system were performed by 2,102 urologists, with 289 (5.4%) performed laparoscopically or robotically. Median urologist age was 42 years (range 36 to 50). Median number of cystectomies performed was 2 (IQR 1-3) with the top 10% of urologists performing 5 or more cystectomies. Half of cystectomies were performed by a urologist who performed only 1 during the certification period. On multivariable analysis stated specialty of oncology and nonprivate practice type were associated with top 10% cystectomy volume. For minimally invasive cystectomy 54% of surgeons logged only a single minimally invasive cystectomy. Factors predictive of performing minimally invasive cystectomy on multivariable analysis were male gender, more recent certifying year and original certification year, endourology and urolithiasis specialization, and Northeast practice region. CONCLUSIONS: Despite the high level of complexity associated with the surgical management of bladder cancer with radical cystectomy, the majority of cystectomies seem to be performed by low volume surgeons who have most often applied for their first certification with the American Board of Urology.

Contemporary surgical trends in the management of upper tract calculi.

PURPOSE: Upper tract nephrolithiasis is a common surgical condition that is treated with multiple surgical techniques, including shock wave lithotripsy, ureteroscopy and percutaneous nephrolithotomy. We analyzed case logs submitted to the ABU by candidates for initial certification and recertification to help elucidate the trends in management of upper tract urinary calculi. MATERIALS AND METHODS: Annualized case logs from 2003 to 2012 were analyzed. We used logistic regression models to assess how surgeon specific attributes affected the way that upper tract stones were treated. Cases were identified by the CPT code of the corresponding procedure. RESULTS: A total of 6,620 urologists in 3 certification groups recorded case logs, including 2,275 for initial certification, 2,381 for first recertification and 1,964 for second recertification. A total of 441,162 procedures were logged, of which 54.2% were ureteroscopy, 41.3% were shock wave lithotripsy and 4.5% were percutaneous nephrolithotomy. From 2003 to 2013 there was an increase in ureteroscopy from 40.9% to 59.6% and a corresponding decrease in shock wave lithotripsy from 54% to 36.3%. For new urologists ureteroscopy increased from 47.6% to 70.9% of all stones cases logged and for senior clinicians ureteroscopy increased from 40% to 55%. Endourologists performed a significantly higher proportion of percutaneous nephrolithotomies than nonendourologists (10.6% vs 3.69%, p <0.0001) and a significantly smaller proportion of shock wave lithotripsies (34.2% vs 42.2%, p = 0.001). CONCLUSIONS: Junior and senior clinicians showed a dramatic adoption of endoscopic techniques. Treatment of upper tract calculi is an evolving field and provider specific attributes affect how these stones are treated.

Completely intracorporeal robotic-assisted laparoscopic augmentation enterocystoplasty with continent catheterizable channel.

OBJECTIVE: To report our results from series of robotic-assisted laparoscopic augmentation enterocystoplasty (RALAE) performed in a completely intracorporeal fashion. METHODS: Patients who underwent RALAE with or without the creation of a catheterizable channel between 2006 and 2011 at the University of Texas, Houston and Northwestern Memorial Hospital were identified. Perioperative and follow-up data were analyzed. Preoperative and postoperative urodynamic data were analyzed when available. RESULTS: Twenty-two patients with neurogenic bladder underwent RALAE with or without the creation of a catheterizable channel. Fifteen patients underwent robotic augmentation enterocystoplasty alone, and 7 patients had creation of a catheterizable channel (4 Monti and 3 Mitrofanoff). There was 1 conversion to an open procedure in a patient undergoing concomitant creation of an appendicovesicostomy. Mean follow-up was 38.9 months (range, 6.2-72.1 months). Mean operative time was 365 minutes (range, 220-788 minutes); mean estimated blood loss was 110 mL (range, 30-250 mL). Median time to return of bowel function was 5 days (range, 2-17 days). Preoperative and postoperative urodynamic data were available for 13 patients. Mean cystometric capacity increased by 52%, and mean maximal bladder pressures decreased by 40. There were 5 minor complications (Clavien grade 1-2) and 4 major complications (Clavien grade 3-4). No patient experienced a wound infection. CONCLUSION: RALAE is a feasible approach that provides potential benefits over open bladder reconstruction in the neurogenic voiding dysfunction population.

Patterns of performance of retroperitoneal lymph node dissections by American urologists: most retroperitoneal lymph node dissections in the United States are performed by low-volume surgeons.

OBJECTIVE: To characterize the current patterns of retroperitoneal lymph node dissection (RPLND) performance among practicing US urologists. METHODS: Six-month case log data of urologists certifying between 2003 and 2013 were obtained from the American Board of Urology. Cases specifying both an International Classification of Diseases, Ninth Revision code for testis cancer and a Current Procedural Terminology code for RPLND were analyzed for surgeon-specific variables. RESULTS: Among 8545 certifying urologists, 290 (3.4% of all) urologists logged 553 RPLNDs in the case log system with 21 (3.6%) performed laparoscopically. Median number of RPLNDs logged annually was 1 (range, 1-59; interquartile range, 1-1) with 3 urologists performing 23% of all RPLNDs. Seventy-five percent of urologists logged a single RPLND. Urologists who logged 2 RPLNDs in a year were in the top 25% of performers with over half (52%) of all RPLNDs performed by urologists who logged 1 or 2 RPLND. On univariate regression analysis, oncology specialization (odds ratio, 5.1 [95% confidence interval, 2.2-11.6; P = .0001]) and non-private practice type (odds ratio, 2.8 [95% confidence interval, 1.1-7.1; P = .03]) were predictive of top 10% (≥ 3 cases) surgeon RPLND volume. CONCLUSION: Despite the critical importance of the surgical quality for outcomes of patients with testis cancer, the majority of surgeons performing RPLND are certifying for the first time and log only 1 RPLND.

Contemporary national comparison of open, laparoscopic, and robotic-assisted laparoscopic pediatric pyeloplasty.

OBJECTIVE: We sought to determine current and longitudinal trends in the usage of open (OP), laparoscopic (LP), and robotic pyeloplasties. (RALP) Furthermore, we aimed to describe patient and hospital level characteristics associated with the use of minimally invasive pyeloplasties (MIP) and to compare basic utilization metrics for each approach. MATERIALS/METHODS: The 2000, 2003, 2006, and 2009 Kid's Inpatient Databases (KID) were used to determine current and longitudinal trends. As a result of a specific billing code for robotic surgery introduced in 2008, the 2009 KID database was used for analysis of RALP. Patient and hospital characteristics examined included: age, gender, race, insurance status, hospital location, and academic status. Utilization metrics of length of stay (LOS) and cost were determined from each modality. RESULTS: In 2009, there were 3354 pediatric pyeloplasties performed in the USA (85% OP, 3% LP, 12% RP). Compared with 2000, this represents an 11.7% decrease in the overall number of pyeloplasties but a progressive increase in MIP from 0.34% in 2000 to 11.7%. Mean patient age was 3.7 years for OP, 9.3 years for LP and 9.9 years for RALP. MIP was more commonly performed in females, Caucasians, patients with private insurance, at urban hospitals and at teaching hospitals. Although length of stay (LOS) in days was statistically lower for MIP (3.46 OP, 2.86 LP, 1.96 RP, p < 0.001), total cost between the groups was not statistically different. On multivariable logistic regression analysis, age (OR 1.17, p < 0.001) increased the odds of MIP whereas lack of private insurance decreased the odds of MIP (OR 0.62, p = 0.002). CONCLUSION: Although utilization of MIP is increasing in the USA, especially in older children, OP remains predominant. MIP was associated with a decrease in LOS. The odds of MIP were higher in older children, whereas the lack of private insurance decreased the odds of MIP.

Nationwide emergency department visits for priapism in the United States.

INTRODUCTION: The epidemiology of priapism is not well characterized. A small number of studies based on inpatient data or small population samples have estimated the incidence to range from 0.34 to 1.5 cases per 100,000 males. AIM: To estimate the current epidemiology and impact on resource utilization of priapism in the United States (US). MAIN OUTCOME MEASURES: Rate of emergency department encounters for priapism in the US. METHODS: Emergency department (ED) visits for priapism were analyzed using discharge data from the Nationwide Emergency Department Sample (NEDS), Healthcare Cost and Utilization Project (HCUP). Priapism encounters were identified by ICD9 code. Priapism encounters were analyzed for patient and hospital characteristics, associated diagnoses, and hospital charge. Established weighting in the sample was used to calculate nationwide estimates. RESULTS: A total of 8,738 ED encounters for priapism were identified between 2006 and 2009 in the NEDS. This translated to an estimated 39,964 encounters out of a total of 496,195,793 ED visits, or 8.05 per 100,000 ED visits (95% confidence interval [CI] 7.59-8.51). 21.1% of patients had a concurrent diagnosis of sickle cell disease (SCD). 72.1% of all patients were discharged home from the ED, while only 49.6% of patients with SCD were discharged home. A concurrent diagnosis of SCD was associated with an odds ratio (OR) of 3.84 (95% CI 3.65-4.05) for admission to the hospital when controlling for age, region, hospital and payer type. The mean hospital charge was $1,778 per encounter if discharged home and $41,909 per encounter if admitted. The estimated mean total annual charge for priapism was $123,860,432 with 86.8% of charges attributed to inpatient admissions. CONCLUSIONS: Our estimate of the rate of ED visits for priapism was significantly higher than prior estimates with a SCD concurrence rate lower than previously estimated.

Hemiscrotal agenesis: new variation in a rare anomaly.

Scrotal agenesis is a rarely encountered developmental anomaly of the scrotum, with only 6 cases of complete agenesis reported in published studies. We report, to our knowledge, the first case of hemiscrotal agenesis. The specific embryologic basis of scrotal agenesis is unknown but is likely multifactorial, involving localized androgen insensitivity, localized 5α-reductase deficiency, and/or failure of labioscrotal fold formation.

Recurrent rectal prolapse following primary surgical treatment.

PURPOSE: The management of recurrent rectal prolapse following initial surgical procedures remains unclear. We present a series of pediatric patients with rectal prolapse and describe their surgical management, and the subsequent care for those children developing recurrence. METHODS: The records of 29 pediatric patients with rectal prolapse refractory to conservative medical management who were managed with primary modified Thiersch procedures over a 14-year period were reviewed. Initial surgical management consisted of a modified version of the Thiersch anal encirclement procedure, which involved a combination of injection sclerotherapy, linear cauterization, and placement of a Thiersch anal encirclement absorbable stitch. Age at initial procedure, predisposing conditions, complications, recurrence, time to recurrence, and subsequent procedures utilized were reviewed. RESULTS: Of 29 patients, 22 (71%) were male with a mean age at time of first Thiersch procedure of 7.1 years (range 3 months to 19 years). Seven patients were lost to follow-up. Nineteen patients (90%) experienced resolution of their prolapse following one or two modified Thiersch procedures; 14 (67%) following an initial Thiersch and 5 (23%) following a subsequent Thiersch. One additional child experienced recurrence after an initial Thiersch procedure, and underwent a perineal resection of redundant rectum (modified Altemeier procedure). Two patients developed a recurrence after their second Thiersch. These cases both required a modified Altemeier procedure. Mean follow-up for all patients was 1.5 years. CONCLUSION: For pediatric rectal prolapse refractory to conservative medical therapy, the modified Thiersch procedure appears reasonable. Initial recurrences are not uncommon, and their incidence increases with the age of the child. Recurrences should be initially managed by a repeat Thiersch procedure. However, subsequent recurrences should be treated with a modified Altemeier.

Laparoscopic partial nephrectomy for multiple ipsilateral renal tumors using a tailored surgical approach.

BACKGROUND AND PURPOSE: Laparoscopic partial nephrectomy (LPN) is safe and effective for solitary renal masses, but its application to multiple ipsilateral renal tumors has been reported infrequently. We review our experience with LPN for multiple ipsilateral renal tumors to assess its role in current practice. MATERIALS AND METHODS: We have managed seven patients with multiple ipsilateral renal tumors with LPN. Of the patients, four had an imperative indication for nephron-sparing surgery. RESULTS: Among the 16 tumors resected, with a mean size of 2.1 cm, 9 (in five patients) were renal cell carcinoma on final pathology. LPN was performed without hilar clamping in four patients (no-clamp group), and with hilar clamping and a sutured bolster in three patients (clamp-suture group). The no-clamp group had a lower mean operative time than the clamp-suture group (185 vs. 225 minutes), similar mean estimated blood loss (363 vs. 417 mL), and shorter hospital stay (1.8 vs. 3 days). The only complication was an intraoperative hemorrhage necessitating blood transfusion, and there was one focal-positive margin, both in patients in the clamp-suture group. Among the five patients with cancer, there have been no local recurrences or metastases during a mean radiographic follow-up of 48 months. CONCLUSIONS: LPN, with a tailored approach that spares some patients from renal ischemia, appears to be safe and effective in this small series of selected patients with multiple ipsilateral renal tumors.

Management of a traumatic hepatic artery pseudoaneurysm and arterioportal fistula with a combination of a stent graft and coil embolization using flow control with balloon remodeling.

We describe a child who presented with a traumatic hepatic artery pseudoaneurysm and arterioportal fistula, which were subsequently managed with an endovascular stent graft and coil embolization using flow control with balloon remodeling. This case demonstrates a rarely seen condition in the pediatric population and a novel management strategy, which should be considered in the management of this complex injury.