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Purpose: Microhematuria is a prevalent condition and the American Urological Association has developed a new risk-stratified approach for the evaluation of patients with microhematuria. Our objective was to provide the first evaluation of this important guideline., Materials and Methods: This multinational cohort study combines contemporary patients from 5 clinical trials and 2 prospective registries who underwent urological evaluation for hematuria. Patients were stratified into American Urological Association risk strata (low, intermediate or high risk) based on sex, age, degree of hematuria, and smoking history. The primary end point was the incidence of bladder cancer within each risk stratum., Results: A total of 15,779 patients were included in the analysis. Overall, 727 patients (4.6%) were classified as low risk, 1,863 patients (11.8%) were classified as intermediate risk, and 13,189 patients (83.6%) were classified as high risk. The predominance of high risk patients was consistent across all cohorts. A total of 857 bladder cancers were diagnosed with a bladder cancer incidence of 5.4%. Bladder cancer was more prevalent in men, smokers, older patients and patients with gross hematuria. The cancer incidence for low, intermediate and high risk groups was 0.4% (3 patients), 1.0% (18 patients) and 6.3% (836 patients), respectively., Conclusions: The new risk stratification system separates hematuria patients into clinically meaningful categories with differing likelihoods of bladder cancer that would justify evaluating the low, intermediate and high risk groups with incremental intensity. Furthermore, it provides the relative incidence of bladder cancer in each risk group which should facilitate patient counseling regarding the risks and benefits of evaluation for bladder cancer.

Purpose: Patients presenting with microhematuria represent a heterogeneous population with a broad spectrum of risk for genitourinary malignancy. Recognizing that patient-specific characteristics modify the risk of underlying malignant etiologies, this guideline sought to provide a personalized diagnostic testing strategy., Materials and Methods: The systematic review incorporated evidence published from January 2010 through February 2019, with an updated literature search to include studies published up to December 2019. Evidence-based statements were developed by the expert Panel, with statement type linked to evidence strength, level of certainty, and the Panel's judgment regarding the balance between benefits and risks/burdens., Results: Microhematuria should be defined as ≥ 3 red blood cells per high power field on microscopic evaluation of a single specimen. In patients diagnosed with gynecologic or non-malignant genitourinary sources of microhematuria, clinicians should repeat urinalysis following resolution of the gynecologic or non-malignant genitourinary cause. The Panel created a risk classification system for patients with microhematuria, stratified as low-, intermediate-, or high-risk for genitourinary malignancy. Risk groups were based on factors including age, sex, smoking and other urothelial cancer risk factors, degree and persistence of microhematuria, as well as prior gross hematuria. Diagnostic evaluation with cystoscopy and upper tract imaging was recommended according to patient risk and involving shared decision-making. Statements also inform follow-up after a negative microhematuria evaluation., Conclusions: Patients with microhematuria should be classified based on their risk of genitourinary malignancy and evaluated with a risk-based strategy. Future high-quality studies are required to improve the care of these patients.

Purpose: We investigated the clinical and prognostic impact of variant histologies on upper tract urothelial carcinoma outcomes after radical nephroureterectomy., Materials and Methods: Data on 1,648 patients with upper tract urothelial carcinoma treated with radical nephroureterectomy without preoperative chemotherapy or radiotherapy were reviewed for histological differentiation and variants. We analyzed differences between pure upper tract urothelial carcinoma and upper tract urothelial carcinoma with variant histology, and differences in the histological variants using different stratifications., Results: A total of 398 patients (24.2%) had histological upper tract urothelial carcinoma variants. The most common variants were squamous cell and glandular differentiation in 9.9% and 4.4% of cases, respectively. Histological variants were associated with advanced tumor stage, tumor multifocality, sessile tumor architecture, tumor necrosis, lymphovascular invasion and lymph node metastasis compared to pure upper tract urothelial carcinoma (p ≤0.031). On univariable analysis variant histology was associated with disease recurrence (p = 0.002) and cancer specific mortality (p = 0.003). In 174 patients treated with adjuvant chemotherapy there was no difference in disease recurrence or survival between variant histology and pure upper tract urothelial carcinoma (p = 0.42 and 0.59, respectively). On multivariable analysis adjusted for the effects of standard clinicopathological characteristics variant histology was not associated with either end point., Conclusions: Almost 25% of patients with upper tract urothelial carcinoma treated with radical nephroureterectomy harbored histological variants. Variant histology was associated with features of biologically aggressive upper tract urothelial carcinoma. While variant histology is associated with worse outcomes on univariable analysis but this effect did not remain significant on multivariable analysis., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We evaluated the concurrent and predictive validity of a novel robotic surgery simulator in a prospective, randomized study., Materials and Methods: A total of 24 robotic surgery trainees performed virtual reality exercises on the da Vinci® Skills Simulator using the da Vinci Si™ surgeon console. Baseline simulator performance was captured. Baseline live robotic performance on ex vivo animal tissue exercises was evaluated by 3 expert robotic surgeons using validated laparoscopic assessment metrics. Trainees were then randomized to group 1-simulator training and group 2-no training while matched for baseline tissue scores. Group 1 trainees underwent a 10-week simulator curriculum. Repeat tissue exercises were done at study conclusion to assess performance improvement. Spearman's analysis was used to correlate baseline simulator performance with baseline ex vivo tissue performance (concurrent validity) and final tissue performance (predictive validity). The Kruskal-Wallis test was used to compare group performance., Results: Groups 1 and 2 were comparable in pre-study surgical experience and had similar baseline scores on simulator and tissue exercises (p >0.05). Overall baseline simulator performance significantly correlated with baseline and final tissue performance (concurrent and predictive validity each r = 0.7, p <0.0001). Simulator training significantly improved tissue performance on key metrics for group 1 subjects with lower baseline tissue scores (below the 50th percentile) than their group 2 counterparts (p <0.05). Group 1 tended to outperform group 2 on final tissue performance, although the difference was not significant (p >0.05)., Conclusions: Our study documents the concurrent and predictive validity of the Skills Simulator. The benefit of simulator training appears to be most substantial for trainees with low baseline robotic skills., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We evaluated the face, content and construct validity of the novel da Vinci® Skills Simulator™ using the da Vinci Si™ Surgeon Console as the surgeon interface., Materials and Methods: We evaluated a novel robotic surgical simulator for robotic surgery using the da Vinci Si Surgeon Console and Mimic™ virtual reality. Subjects were categorized as novice-no surgical training, intermediate-surgical training with fewer than 100 robotic cases or expert-100 or more primary surgeon robotic cases. Each participant completed 10 virtual reality exercises with 3 repetitions and a questionnaire with a 1 to 10 visual analog scale to assess simulator realism (face validity) and training usefulness (content validity). The simulator recorded performance based on specific metrics. The performance of experts, intermediates and novices was compared (construct validity) using the Kruskal-Wallis test., Results: We studied 16 novices, 32 intermediates with a median surgical experience of 6 years (range 1 to 37) and a median of 0 robotic cases (range 0 to 50), and 15 experts with a median of 315 robotic cases (range 100 to 800). Participants rated the virtual reality and console experience as very realistic (median visual analog scale score 8/10) while expert surgeons rated the simulator as a very useful training tool for residents (10/10) and fellows (9/10). Experts outperformed intermediates and novices in almost all metrics (median overall score 88.3% vs 75.6% and 62.1%, respectively, between group p<0.001)., Conclusions: We confirmed the face, content and construct validity of a novel robotic skill simulator that uses the da Vinci Si Surgeon Console. Although it is currently limited to basic skill training, this device is likely to influence robotic surgical training across specialties., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We evaluated the value of hydronephrosis, ureteroscopic biopsy grade and urinary cytology to predict advanced upper tract urothelial carcinoma., Materials and Methods: We reviewed the charts of 469 patients with upper tract urothelial carcinoma treated with radical nephroureterectomy or distal ureterectomy. Complete data on hydronephrosis (present vs absent), ureteroscopic grade (high vs low) and urinary cytology (positive vs negative) were available in 172 patients. The outcome was muscle invasive (pT2-pT4) or nonorgan confined (pT3 or greater, or lymph node metastasis) upper tract urothelial carcinoma., Results: Of the patients 92 (54%) had hydronephrosis, 74 (43%) had high grade disease on ureteroscopic biopsy and 137 (80%) had positive cytology. On univariate analysis hydronephrosis (p <0.001), high ureteroscopic grade (p <0.001) and positive cytology (p = 0.03) were associated with muscle invasive and nonorgan confined disease. On multivariate analysis adjusting for tumor site, gender and age hydronephrosis and high ureteroscopic grade were associated with muscle invasive carcinoma (HR 12.0 and 4.5, respectively, each p <0.001) but cytology was not (HR 2.3, p = 0.17). However, all 3 variables were independently associated with nonorgan confined disease (HR 5.1, p <0.001; HR 3.9, p <0.001; and HR 3.1, p = 0.035, respectively). Combining these 3 tests incrementally improved the prediction of upper tract urothelial carcinoma stage. Abnormality of all 3 tests had 89% and 73% positive predictive value for muscle invasive and nonorgan confined upper tract urothelial carcinoma, respectively, but when all tests were normal, the negative predictive value was 100%., Conclusions: Preoperative evaluation for hydronephrosis, ureteroscopic grade and cytology can identify patients at risk for advanced upper tract urothelial carcinoma. Such knowledge may impact surgery choice and extent as well as the need for perioperative chemotherapy regimens., (Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: There is relatively little literature on adjuvant chemotherapy after radical nephroureterectomy in patients with upper tract urothelial carcinoma. We determined the incidence of adjuvant chemotherapy in high risk patients and the ensuing effect on overall and cancer specific survival., Materials and Methods: Using an international collaborative database we identified 1,390 patients who underwent nephroureterectomy for nonmetastatic upper tract urothelial carcinoma between 1992 and 2006. Of these cases 542 (39%) were classified as high risk (pT3N0, pT4N0 and/or lymph node positive). These patients were divided into 2 groups, including those who did and did not receive adjuvant chemotherapy, and stratified by gender, age group, performance status, and tumor grade and stage. Cox proportional hazard modeling and Kaplan-Meier analysis were used to determine overall and cancer specific survival in the cohorts., Results: Of high risk patients 121 (22%) received adjuvant chemotherapy. Adjuvant chemotherapy was more commonly administered in the context of increased tumor grade and stage (p <0.001). Median survival in the entire cohort was 24 months (range 0 to 231). There was no significant difference in overall or cancer specific survival between patients who did and did not receive adjuvant chemotherapy. However, age, performance status, and tumor grade and stage were significant predictors of overall and cancer specific survival., Conclusions: Adjuvant chemotherapy is infrequently used to treat high risk upper tract urothelial carcinoma after nephroureterectomy. Despite this finding it appears that adjuvant chemotherapy confers minimal impact on overall or cancer specific survival in this group.

Purpose: We examined the impact of lymphadenectomy on the clinical outcomes of patients with upper tract urothelial cancer treated with radical nephroureterectomy., Materials and Methods: Data were collected on 1,130 consecutive patients with pT1-4 upper tract urothelial cancer treated with radical nephroureterectomy at 13 centers worldwide. Patients were grouped according to nodal status (pN0 vs pNx vs pN+). The choice to perform lymphadenectomy was determined by the treating surgeon. All pathology slides were reevaluated by dedicated genitourinary pathologists. Univariable and multivariable Cox regression models measured the association of nodal status (pN0 vs pNx vs pN+) with cancer specific survival., Results: Overall 412 patients (36.5%) had pN0 disease, 578 had pNx disease (51.1%) and 140 had pN+ disease (12.4%). The 5-year cancer specific survival estimate was lower in patients with pN+ compared to those with pNx disease (35% vs 69%, p <0.001), which in turn was lower than that in those with pN0 disease (69% vs 77%, p = 0.024). In the subgroup of patients with pT1 disease (345) cancer specific survival rates were not different in those with pN0 and pNx. In pT2-4 cases (813) cancer specific survival estimates were lowest in pN+, intermediate in pNx and highest in pN0 (33% vs 58% vs 70%, p = 0.017). When adjusted for the effects of standard clinicopathological features pN+ was an independent predictor of cancer specific survival (p <0.001). pNx was significantly associated with worse prognosis than pN0 in pT2-4 upper tract urothelial cancer only., Conclusions: Nodal status is a significant predictor of cancer specific survival in upper tract urothelial cancer. pNx is significantly associated with a worse prognosis than pN0 in pT2-4 tumors. Patients expected to have pT2-4 disease should undergo lymphadenectomy to improve staging and thereby help guide decision making regarding adjuvant chemotherapy.

Purpose: We assessed the efficacy of cryoablation of the prostate with an emphasis on finding predictive factors that lead to improved outcome., Materials and Methods: A total of 187 patients with locally recurrent prostate cancer after radiotherapy underwent salvage cryoablation of the prostate, and were studied after a mean followup of 39 months. Survival analysis was performed with the Kaplan-Meier method. Several variables were tested for predictive value using the Cox regression model including serum prostate specific antigen before radiotherapy, serum prostate specific antigen at cryoablation, clinical stage before radiotherapy, Gleason score before radiotherapy, Gleason score at cryoablation, number of positive biopsy cores and use of neoadjuvant hormonal therapy before cryoablation., Results: Serum prostate specific antigen at cryoablation was a predictive factor for biochemical recurrence on univariate and multivariate analysis (p <0.001). Patients with pre-cryoablation prostate specific antigen less than 4 ng/ml had a 5 and 8-year biochemical recurrence-free survival of 56% and 37%, respectively. In contrast, patients with pre-cryoablation prostate specific antigen 10 ng/ml or greater had a 5 and 8-year biochemical recurrence-free survival of only 1% and 7%, respectively. Patients with pre-cryoablation prostate specific antigen from 4 to 9.99 ng/ml had intermediate survival outcomes. Of the patients 32% were started on hormonal therapy for disease progression at a mean of 31 months postoperatively. Overall 5 and 8-year survival was 97% and 92%, respectively., Conclusions: Salvage cryoablation is a viable treatment option for patients with prostate cancer in whom radiation therapy has failed. Salvage cryoablation should be performed when serum prostate specific antigen is still relatively low because in these patients the procedure may potentially be curative. Even when cryoablation fails to eradicate the disease in some patients, it allows hormonal therapy to be deferred for a significant period of time in that cohort.