Michael Belsante

Cumulative number of altered biomarkers in mammalian target of rapamycin pathway is an independent predictor of outcome in patients with clear cell renal cell carcinoma.

OBJECTIVE To evaluate the association of the altered expression of the mammalian target of rapamycin (mTOR) pathway components with oncologic outcomes in patients with nonmetastatic clear cell renal cell carcinoma (ccRCC). MATERIALS AND METHODS Immunohistochemistry for phosphorylated-S6, phosphorylated-mTOR, mTOR, phosphorylated-AKT, hypoxia inducible factor-1α, Raptor, phosphatase and tensin homolog (PTEN), phosphoinositide 3-kinase (PI3K), and phosphorylated 4E-binding protein-1 was performed on tissue microarray constructs of patients treated for nonmetastatic kidney cancer from 1997 to 2010. The relationship between individual altered marker expression and a prognostic marker score (low, intermediate, and high, defined as ≤ 3, 4-5, >5 altered biomarkers, respectively) and oncologic outcome was assessed. RESULTS The study included 419 patients with nonmetastatic ccRCC, with a median follow-up period of 26 months (range 6-150). The tumors were nonorgan confined (pT3-T4) in 86 (20.5%) and high Fuhrman nuclear grade (3-4) in 131 (31%). A low, intermediate, and high prognostic marker score was found in 214 (51%), 152 (36%), and 53 (13%) patients, respectively. Kaplan-Meier analysis demonstrated a statistically significant correlation between the risk groups and disease recurrence and cancer-specific survival. In a multivariate Cox regression analysis controlling for tumor stage and grade, a high marker score was an independent predictor of disease recurrence (hazard ratio 3.3, 95% confidence interval 1.33-8.39, P = .01), and a combination of a high and an intermediate score was an independent predictor of survival (hazard ratio 4.8, 95% confidence interval 1.27-4.78, P = .008). CONCLUSION The cumulative number of aberrantly expressed biomarkers correlated with aggressive tumor biology and inferior oncologic outcomes in patients with ccRCC. Our data support prospective pathway-based exploration of the mTOR signaling cascade to augment current clinicopathologic predictors of oncologic outcomes in patients with ccRCC.

Cost-Effectiveness of Risk Stratified Followup after Urethral Reconstruction: A Decision Analysis

PURPOSE We propose a novel risk stratified followup protocol for use after urethroplasty and explore potential cost savings. MATERIALS AND METHODS Decision analysis was performed comparing a symptom based, risk stratified protocol for patients undergoing excision and primary anastomosis urethroplasty vs a standard regimen of close followup for urethroplasty. Model assumptions included that excision and primary anastomosis has a 94% success rate, 11% of patients with successful urethroplasty had persistent lower urinary tract symptoms requiring cystoscopic evaluation, patients in whom treatment failed undergo urethrotomy and patients with recurrence on symptom based surveillance have a delayed diagnosis requiring suprapubic tube drainage. The Nationwide Inpatient Sample from 2010 was queried to identify the number of urethroplasties performed per year in the United States. Costs were obtained based on Medicare reimbursement rates. RESULTS The 5-year cost of a symptom based, risk stratified followup protocol is

The Artificial Urinary Sphincter is Superior to a Secondary Transobturator Male Sling in Cases of a Primary Sling Failure

430 per patient vs

Prospective evaluation of molecular markers for the staging and prognosis of upper tract urothelial carcinoma.

2,827 per patient using standard close followup practice. An estimated 7,761 urethroplasties were performed in the United States in 2010. Assuming that 60% were excision and primary anastomosis, and with more than 5 years of followup, the risk stratified protocol was projected to yield an estimated savings of

Malleable Penile Prosthesis Is a Cost-Effective Treatment for Refractory Ischemic Priapism

11,165,130. Sensitivity analysis showed that the symptom based, risk stratified followup protocol was far more cost-effective than standard close followup in all settings. Less than 1% of patients would be expected to have an asymptomatic recurrence using the risk stratified followup protocol. CONCLUSIONS A risk stratified, symptom based approach to urethroplasty followup would produce a significant reduction in health care costs while decreasing unnecessary followup visits, invasive testing and radiation exposure.

Lymphovascular invasion in clear cell renal cell carcinoma—Association with disease-free and cancer-specific survival

PURPOSE We compared continence outcomes in patients with post-prostatectomy stress urinary incontinence treated with a salvage artificial urinary sphincter vs a secondary transobturator sling. MATERIALS AND METHODS We retrospectively reviewed the records of patients undergoing salvage procedures after sling failure from 2006 to 2012. Postoperative success was defined as the use of 0 or 1 pad, a negative stress test and pad weight less than 8 gm per day. We performed the Wilcoxon test and used a Cox regression model and Kaplan-Meier survival analysis. RESULTS A total of 61 men presenting with sling failure were included in study, of whom 32 went directly to an artificial urinary sphincter and 29 received a secondary sling. Of the artificial urinary sphincter cohort 47% underwent prior external beam radiation therapy vs 17% of the secondary sling cohort (p = 0.01). Average preoperative 24 hour pad weight and pad number were higher in the artificial urinary sphincter cohort. Median followup in artificial urinary sphincter and secondary sling cases was 4.5 (IQR 4-12) and 4 months (IQR 1-5), respectively. Overall treatment failure was seen in 55% of patients (16 of 29) with a secondary sling vs 6% (2 of 32) with an artificial urinary sphincter (unadjusted HR 7, 95% CI 2-32 and adjusted HR 6, 95% CI 1-31). CONCLUSION In this cohort of patients with post-prostatectomy stress urinary incontinence and a failed primary sling those who underwent a secondary sling procedure were up to 6 times more likely to have persistent incontinence vs those who underwent artificial urinary sphincter placement. These data are useful for counseling patients and planning surgery. We currently recommend placement of an artificial urinary sphincter for patients in whom an initial sling has failed.

The contemporary management of urethral strictures in men resulting from lichen sclerosus

The prognostic utility of biomarkers is well studied in bladder cancer with tissue-based molecular markers demonstrating the ability to predict disease progression in non–muscle-invasive tumors and pathologic and clinical outcomes in patients treated with radical cystectomy [1–4]. In this study we prospectively evaluated the utility of a tissue biomarker panel of cell cycle regulators (p53, p21, p27, cyclin E) and a proliferative marker (Ki-67) in patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU). This investigation was undertaken with University of Texas Southwestern Medical Center institutional review board (IRB) authorization. The study population included all patients (n = 73) between January 2007 and October 2011 receiving open or laparoscopic RNU with or without regional lymphadenectomy for clinically localized biopsy-proven high grade UTUC of the renal pelvis or ureter. Systemic chemotherapy was administered to 15 patients in an adjuvant or neoadjuvant setting (5 neoadjuvant, 7 adjuvant, and 3 both). Each patient was seen at least every 3–4 mo in the first postoperative year, semiannually for the second year, and then annually. Comprehensive clinical and pathologic data were maintained in an IRB-approved database. Tumor histology, grade, stage, presence of carcinoma in situ, lymphovascular invasion (LVI), necrosis, and architecture (papillary vs sessile) were assessed in a standardized manner by a genitourinary pathologist. The 2010 American Joint Committee on Cancer TNM staging system was used. All final pathology specimens were prospectively assessed with immunohistochemical staining of viable representative primary tumor tissue. Cyclin E, p53, p21, Ki-67, and p27 immunohistochemical staining using sections from the paraffin-embedded tissue was performed. Staining and scoring protocols for cyclin E, p53, p21, p27, and Ki-67 were previously described [1–3,5,6]. Outcomes were measured by time to disease recurrence or to UTUC-specific mortality from time of RNU. Univariable recurrence and survival probabilities were analyzed using the Kaplan-Meier method. Univariable and multivariable Cox regression models with known predictors of outcomes and incorporation of prognostic marker score addressed cancer-specific mortality after RNU. The maximum altered

The Ohmmeter Identifies the Site of Fluid Leakage during Artificial Urinary Sphincter Revision Surgery

INTRODUCTION Refractory ischemic priapism (RIP) can be difficult to treat, consuming significant healthcare-related resources. Acute insertion of a malleable penile prosthesis (MPP) has been reported as an effective therapy that treats the priapism and restores sexual function. AIM We report our 6-year, urban public hospital experience with acute insertion of MPP in patients with RIP. METHODS We retrospectively reviewed the records of patients receiving MPPs for RIP from 2007 to 2013. Data analyzed included duration of erection, number of emergency room (ER) visits, hospital admissions, days of hospitalization, and postoperative course. Costs were estimated using standard Medicare reimbursement rates. MAIN OUTCOME MEASURE Healthcare-related costs of treatment of RIP episodes in men presenting to our institution. RESULTS During the study period, 14 men underwent MPP placement acutely for refractory priapism. Thirteen presented with RIP, and one had stuttering priapism over a 14-day hospitalization. Etiologies included sickle cell anemia (4/13, 29%), medication-induced (3/14, 21%), and idiopathic (7/14, 50%). Average preoperative duration of RIP was 82 hours with considerable consumption of health-care resources (average US

Intraurethral Steroids are a Safe and Effective Treatment for Stricture Disease in Patients with Biopsy Proven Lichen Sclerosus.

83,818 estimated cost, 4 ER visits [range 1-27], 2 hospital admissions [range 1-5], 1.5 shunt procedures [range 1-3], 5 irrigation and drainage procedures using phenylephrine injection [range 2-20], and 5 hospital admission days [range 2-14]). All patients were discharged within 24 hours of MPP surgery. CONCLUSIONS The management of RIP is associated with multiple ER visits, prolonged hospital admissions, and significant resource utilization. MPP insertion is efficacious for the immediate resolution of refractory priapism, with potential cost and resource benefits.

Mechanism of Action of the Transobturator Sling for Post-Radical Prostatectomy Incontinence: A Multi-institutional Prospective Study Using Dynamic Magnetic Resonance Imaging

OBJECTIVES The objective is to evaluate the effect of lymphovascular invasion (LVI) on disease-free survival (DFS) and cancer-specific survival (CSS) in patients with clinically localized clear cell renal cell carcinoma (ccRCC). METHODS Patients with ccRCC who were treated surgically in 1997 to 2010 were identified. Retrospective chart review was performed to identify clinical outcomes. Independent pathologic re-review was performed by a single pathologist to confirm LVI status. Pathologic features were correlated with clinical outcomes using Kaplan-Meier and Cox regression analyses. RESULTS Four hundred and nineteen patients with nonmetastatic ccRCC comprised the study cohort. Three hundred and thirty-three of these patients had an organ-confined (pT1-2, N any, and M0) disease. LVI was present in 14.3% of all nonmetastatic patients. In all patients with nonmetastatic ccRCC, presence of LVI was correlated with significantly shorter DFS (P <0.001) and CSS (P = 0.001) on Kaplan-Meier analysis. In cases of organ-confined, nonmetastatic ccRCC, presence of LVI was a significant predictor of DFS (hazard ratio = 4.0, P = 0.026) and CSS (hazard ratio = 12.7, P = 0.01) on multivariate analysis. Patients with organ-confined RCC who were LVI positive had similar DFS (P = 0.957) and CSS (P = 0.799) to patients with locally advanced tumors (pT3-pT4, N any, and M0) on Kaplan-Meier analysis. CONCLUSIONS The presence of LVI is an independent predictor of both DFS and CSS in organ-confined, nonmetastatic ccRCC. LVI positivity in patients with otherwise pathologically organ-confined ccRCC confers oncologic outcomes similar to those of patients with locally advanced disease. If confirmed by others, future revisions to the tumor-node-metastasis staging system may incorporate LVI status into the prognostic algorithm of patients with RCC.