High-dimensional Cytometry (ExCYT) and Mass Spectrometry of Myeloid Infiltrate in Clinically Localized Clear Cell Renal Cell Carcinoma Identifies Novel Potential Myeloid Targets for Immunotherapy.

Renal Cell Carcinoma (RCC) is one of the most commonly diagnosed cancers worldwide with research efforts dramatically improving understanding of the biology of the disease. To investigate the role of the immune system in treatment-naïve clear cell Renal Cell Carcinoma (ccRCC), we interrogated the immune infiltrate in patient-matched ccRCC tumor samples, benign normal adjacent tissue (NAT) and peripheral blood mononuclear cells (PBMCs isolated from whole blood, focusing our attention on the myeloid cell infiltrate. Using flow cytometric, MS, and ExCYT analysis, we discovered unique myeloid populations in PBMCs across patient samples. Furthermore, normal adjacent tissues and ccRCC tissues contained numerous myeloid populations with a unique signature for both tissues. Enrichment of the immune cell (CD45+) fraction and subsequent gene expression analysis revealed a number of myeloid-related genes that were differentially expressed. These data provide evidence, for the first time, of an immunosuppressive and pro-tumorigenic role of myeloid cells in early, clinically localized ccRCC. The identification of a number of immune proteins for therapeutic targeting provides a rationale for investigation into the potential efficacy of earlier intervention with single-agent or combination immunotherapy for ccRCC.

Selecting Patients with Small Renal Masses for Active Surveillance: A Domain Based Score from a Prospective Cohort Study.

PURPOSE: We sought to identify predictors of active surveillance in a prospective cohort study of patients with a small renal mass demonstrating favorable outcomes. We generated a summary score to discriminate patients selected for active surveillance or primary intervention. MATERIALS AND METHODS: We analyzed the records of 751 patients from 2009 to 2018 who were enrolled in the DISSRM (Delayed Intervention and Surveillance for Small Renal Masses) Registry to compare active surveillance and primary intervention in the domains of demographics, tumor characteristics, comorbidity and patient reported quality of life. Regression models were created to assess univariable and multivariable model discrimination by the AUC and quality by the AIC (Akaike information criterion). The DISSRM score was based on the most predictive combination of variables and validated for its association with overall survival by Kaplan-Meier survival curves and a Cox proportional hazards regression model. RESULTS: Of the patients 410 (55%) elected active surveillance and 341 (45%) elected primary intervention. Of the domains patient age, the Charlson comorbidity index, tumor diameter and the SF-12® Physical Component Score had the greatest discrimination for clinical selection into active surveillance. These domains made up the DISSRM score (AUC 0.801). The maximum DISSRM score was 7. The average score for active surveillance was 4.19 (median 4, IQR 2-6) and 72% of scores were 4 or greater. The average score for primary intervention was 3.03 (median 3, IQR 1-5) and 63% of scores were 3 or less. A higher DISSRM score was associated with worse overall survival, for example a score of 6-7 had a HR of 10.45 (95% CI 1.25-87.49, p = 0.03). CONCLUSIONS: The DISSRM score represents a measure of oncologic and competing risks of death in various important domains in patients with a small renal mass. It could be used to guide the management selection. Patients with intermediate scores that express illness uncertainty may require additional workup, such as confirmatory biopsy, to reach a treatment decision.

Comparative effectiveness of management options for patients with small renal masses: a prospective cohort study.

OBJECTIVES: To explore the comparative effectiveness of partial nephrectomy (PN), radical nephrectomy (RN), ablative therapies (ablation) and active surveillance (AS) for small renal masses (SRMs; tumour diameter ≤4.0 cm) in the domains of survival, renal function and quality of life (QoL) using the prospectively maintained Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) Registry. PATIENTS AND METHODS: Estimated glomerular filtration rate (eGFR) was calculated from creatinine values to determine renal function. QoL was measured using the Short Form 12 (SF-12) questionnaire. The Kaplan-Meier method and Cox proportional hazards regression were used for survival analysis. The mixed-effects model was used for renal function and QoL analysis. RESULTS: Of 638 patients, 231 (36.2%) chose PN, 41 (6.4%) RN, 27 (4.2%) ablation and 339 (53.1%) AS. Cancer-specific survival at 7 years was 98.8% in PN patients and 100% in all other groups. Overall survival (OS) at 7 years was 87.9%, 90.2%, 83.5% and 66.1% in PN, RN, ablation and AS patients, respectively. The OS rate was significantly worse in the AS group than other groups and likely attributable to older age and increased comorbidities. The eGFR was lowest in RN patients but comparable in all other groups. QoL was lowest in AS patients due to lower physical health scores, but mental health scores were similar in all groups. CONCLUSIONS: With excellent oncological outcomes in all groups, nephron-sparing approaches, like PN and ablation, are preferred over RN when intervention is indicated for SRMs. AS is a reasonable option for select patients, given the comparable oncological and mental health outcomes.

Comparison of Pathological Stage in Patients Treated with and without Neoadjuvant Chemotherapy for High Risk Upper Tract Urothelial Carcinoma.

PURPOSE: High risk upper tract urothelial carcinoma has been associated with poor survival outcomes. Limited retrospective data support neoadjuvant chemotherapy prior to radical nephroureterectomy. To validate prior findings we evaluated differences in the pathological stage distribution in patients with high risk upper tract urothelial carcinoma based on the administration of neoadjuvant chemotherapy before radical nephroureterectomy. MATERIALS AND METHODS: We retrospectively analyzed the records of 240 patients with upper tract urothelial carcinoma at The Johns Hopkins Hospital from 2003 to 2017. Patients with biopsy proven high grade disease and a visible lesion on cross-sectional imaging were offered neoadjuvant chemotherapy prior to radical nephroureterectomy. A control group of a time matched cohort of patients with biopsy proven high grade disease underwent extirpative surgery alone. The chi-square and Fisher exact tests were used to evaluate clinical and pathological variables between the cohorts. RESULTS: There were 32 patients in the study group and 208 in the control group. Significantly lower pathological stage was noted in the study group than in the control group (p <0.001). Significantly fewer patients with pT2 disease or higher were treated with neoadjuvant chemotherapy (37.5% vs 59.6%, p = 0.02). There was a 46.5% reduction in the prevalence of pT3 disease or higher in study group patients without clinically node positive or low volume metastatic disease (25.9% vs 48.4%, p = 0.04). A 9.4% complete remission rate was observed in patients who underwent neoadjuvant chemotherapy. CONCLUSIONS: Patients with high risk upper tract urothelial carcinoma treated with neoadjuvant chemotherapy were noted to have a lower pathological stage distribution than patients treated with radical nephroureterectomy alone.

Growth Kinetics of Small Renal Masses on Active Surveillance: Variability and Results from the DISSRM Registry.

PURPOSE: Active surveillance is emerging as a safe and effective strategy for the management of small renal masses (4 cm or less). We characterized the growth rate and its pertinence to clinical outcomes in a prospective multi-institutional study of patients with small renal masses. MATERIALS AND METHODS: Since 2009, the DISSRM (Delayed Intervention and Surveillance for Small Renal Masses) prospective, multi-institutional registry of patients with small renal masses has enrolled patients who elect primary intervention or active surveillance. Patients who elect active surveillance received regularly scheduled imaging and those with 3 or more followup images were included in the current study to evaluate growth rates. RESULTS: We evaluated 318 patients who elected active surveillance, of whom 271 (85.2%) had 3 or more followup images available with a median imaging followup of 1.83 years. The overall mean ± SD small renal mass growth rate was 0.09 ± 1.51 cm per year (median 0.09) with no variables demonstrating statistically significant associations. The growth rate and variability decreased with longer followup (0.54 and 0.07 cm per year at less than 6 months and greater than 1 year, respectively). No patients had metastatic disease or died of kidney cancer. No statistically significant difference was noted in the growth rate in patients with biopsy demonstrated renal cell carcinoma or in those who died. CONCLUSIONS: Small renal mass growth kinetics are highly variable early on active surveillance with growth rates and variability decreasing with time. Early in active surveillance, especially during the initial 6 to 12 months, the growth rate is variable and does not reliably predict death or adverse pathological features in the patient subset with available pathology findings. An elevated growth rate may indicate the need for further assessment with imaging or consideration of biopsy prior to progressing to treatment. Additional followup will inform the best clinical pathway for elevated growth rates.

Multiple growth periods predict unfavourable pathology in patients with small renal masses.

OBJECTIVE: To use the number of positive growth periods as a characterization of the growth of small renal masses in order to determine potential predictors of malignancy. PATIENTS AND METHODS: Patients who underwent axial imaging at multiple time points prior to surgical resection for a small renal mass were queried. Patients were categorized based on their pathological tumour grade and stage: favourable (benign, chromophobe and low-grade pT1-2 renal cell carcinoma [RCC]) vs unfavourable (high-grade of any stage and low-grade pT3-4 RCC). A positive growth period was counted each time the difference in greatest tumour diameters between two images was positive. The Cochran-Armitage trend test and Somers' D association were used to determine if the number of positive growth periods was correlated with unfavourable pathology. RESULTS: Of the 124 patients, 86 (69.4%) had favourable pathology and 38 (30.6%) had unfavourable pathology. Those who had favourable pathology were younger than those who had unfavourable pathology: median (interquartile range [IQR]) 61.0 (52.2-66.0) vs 68.5 (61.5-77.0); P < 0.001. The overall growth rate was higher in the unfavourable group, but was not statistically significant: mean (sd) 0.7 (1.7) vs 1.6 (2.8) cm/year; P = 0.07. There was a significant trend difference in the number of positive growth periods between favourability groups (P = 0.02). An association between increased number of positive growth periods and unfavourable pathology was observed: 0.15 (95% confidence interval 0.02, 0.29). The ratios of favourable to unfavourable pathology were 1.8, 1.0, 0.66, 0.59 and 0 as the number of positive growth periods increased from 0 to 4, respectively. CONCLUSION: While overall growth rate was not predictive of pathology favourability, there was a positive association between the number of positive growth periods and unfavourable pathology. The number of positive growth periods may be a potential parameter for malignant potential in patients undergoing active surveillance for small renal masses.

Causes, Timing, Hospital Costs and Perioperative Outcomes of Index vs Nonindex Hospital Readmissions after Radical Cystectomy: Implications for Regionalization of Care.

PURPOSE: We compared the timing, causes, hospital costs and perioperative outcomes of index vs nonindex hospital readmissions after radical cystectomy. MATERIALS AND METHODS: The 2013 Nationwide Readmissions Database was queried for patients with bladder cancer undergoing cystectomy. Sociodemographic characteristics, hospital costs and causes of readmission were compared among index and nonindex readmitted patients. Univariable and multivariable logistic regression models were used to identify predictors of nonindex readmissions, mortality during the first readmission and subsequent readmission. RESULTS: Among 4,991 patients identified 29% (1,447) and 11% (571) experienced an index and nonindex readmission, respectively. Compared to index readmissions, nonindex readmissions were more likely late readmissions (p <0.001) of older patients (p=0.047) who underwent cystectomy at higher volume hospitals (p=0.02) and were readmitted to hospitals located in less populated areas (p <0.001). Compared to index readmissions the percentage of nonindex readmissions for cardiovascular complications was higher (7.6% vs 2.9%, p=0.003), while the percentage of nonindex readmissions for gastrointestinal (6.0% vs 11.0%, p=0.04) and wound (5.3% vs 16.7%, p=0.0001) complications was lower. Predictors of nonindex readmission included longer length of stay (OR 1.02; 95% CI 1.001, 1.04), patient location in less populated areas, nonteaching hospital (OR 0.52; 95% CI 0.31, 0.86) and discharge to facility (OR 2.82; 95% CI 1.75, 4.55) or with home health (OR 1.49; 95% CI 1.05, 2.10). Nonindex readmissions had comparable mean readmission hospital costs ($14,147 vs $15,102, p=0.7), in-hospital mortality (OR 1.11; 95% CI 0.42, 2.87) and subsequent readmission (OR 1.32; 95% CI 0.87, 2.00) to index readmissions. CONCLUSIONS: This nationally representative study of patients undergoing radical cystectomy demonstrated comparable perioperative outcomes and hospital costs between index and nonindex readmitted patients, which supports the continued regionalization of cystectomy care.

Evaluation of gender-based disparities in time from initial haematuria presentation to upper tract urothelial carcinoma diagnosis: analysis of a nationwide insurance claims database.

OBJECTIVE: To investigate the length of time from initial haematuria presentation to upper tract urothelial carcinoma (UTUC) diagnosis and the effect of gender on this duration. PATIENTS AND METHODS: Patients with haematuria claims in the year prior to UTUC diagnosis were identified from the MarketScan database (2010-2014). Delayed diagnosis was defined as >90 days from haematuria presentation to UTUC diagnosis. Multivariable Poisson regression models were used to determine factors associated with delayed UTUC diagnosis. RESULTS: Among 1 326 patients with UTUC, 469 (35.4%) experienced delayed diagnosis. Men (n = 866) had a longer median interval from haematuria to diagnosis than women (60 vs 49 days; P = 0.04). In the multivariable model, male gender (relative risk [RR] 1.13, 95% confidence interval [CI] 0.95-1.34) was not associated with delayed diagnosis, while urinary tract infection (UTI; RR 1.52, 95% CI 1.32-1.76), nephrolithiasis (RR 1.23, 95% CI 1.06-1.44), new (RR 1.37, 95% CI 1.12-1.66) and recurrent prostate-related diagnoses (RR 1.61, 95% CI 1.23-2.10) were. For men presenting to non-urologists, UTI (RR 1.44, 95% CI 1.22-1.71), nephrolithiasis (RR 1.25 95% CI 1.05-1.49), new (RR 1.41, 95% CI 1.12-1.78) and recurrent prostate-related diagnoses (RR 1.94, 95% CI 1.45-2.58) were associated with delayed diagnosis; however, for men presenting to urologists, nephrolithiasis (RR 1.08 95% CI 0.78-1.49), new (RR 1.15, 95% CI 0.79-1.68) and recurrent prostate-related diagnoses (RR 1.17, 95% CI 0.69-1.97) were not associated with delayed diagnosis, while UTI diagnosis (RR 1.74, 95% CI 1.31-2.31) was still associated with delayed diagnosis. CONCLUSION: A UTUC diagnosis was made >90 days after haematuria presentation in approximately one-third of patients. Men experienced a longer median interval from haematuria to UTUC diagnosis compared with women, but male gender was not an independent predictor of delayed diagnosis. Benign diagnoses during haematuria evaluation were strongly associated with delayed diagnosis, especially among patients initially seen by non-urologists. Future interventions should focus on development of non-invasive techniques to improve clinical risk stratification of patients presenting with haematuria and to educate practitioners, especially non-urologists, with regard to the importance of a thoughtful haematuria evaluation and the common mimickers of UTUC, to help reduce delays in diagnosis.

Distinguishing malignant and benign renal masses with composite models and nomograms: A systematic review and meta-analysis of clinically localized renal masses suspicious for malignancy.

Solid renal masses and cystic lesions with solid components are suspicious for renal cell carcinoma. Without an effective screening test, composite models and nomograms rely on patient and tumor characteristics to stratify the risk of benign disease versus malignant disease. To guide decisions about the use of renal mass sampling or excision, a systematic review and meta-analysis of the ability of composite models to predict the likelihood of malignancy on the basis of preoperative clinical variables was performed. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from January 1, 1997, through May 1, 2015, according to the Preferred Reporting Items for Systematic Review and Meta-Analyses statement. Composite models necessarily included imaging results and at least 1 element from the following to be compared with surgical pathology: demographic characteristics, clinical characteristics, and blood or urine tests. Two independent reviewers screened citations and extracted data. Quality Assessment Tool for Diagnostic Accuracy Studies 2 was used to assess the risk of bias. The strength of evidence was graded with the scheme recommended by Methods Guide for Effectiveness and Comparative Effectiveness Reviews. Twenty studies (12,149 patients) were included in this review. The only significant predictors of malignancy in the composite models were tumor size (effect size, 1.33-fold increased risk per centimeter; 95% confidence interval [CI], 1.22-1.43) and male sex (effect size, 2.71; 95% CI, 2.39-3.02). The results were inconclusive or not significant for tumor characteristics, age, body mass index, and incidental presentation. In conclusion, composite models currently have a limited ability to distinguish malignant renal masses from benign renal masses, with increased tumor size and male sex associated with malignancy. Cancer 2016;122:3267-3276. © 2016 American Cancer Society.

Management of Renal Masses and Localized Renal Cancer: Systematic Review and Meta-Analysis.

PURPOSE: Several options exist for management of clinically localized renal masses suspicious for cancer, including active surveillance, thermal ablation and radical or partial nephrectomy. We summarize evidence on effectiveness and comparative effectiveness of these treatment approaches for patients with a renal mass suspicious for localized renal cell carcinoma. MATERIALS AND METHODS: We searched MEDLINE®, Embase® and the Cochrane Central Register of Controlled Trials from January 1, 1997 through May 1, 2015. Paired investigators independently screened articles to identify controlled studies of management options or cohort studies of active surveillance, abstracted data sequentially and assessed risk of bias independently. Strength of evidence was graded by comparisons. RESULTS: The search identified 107 studies (majority T1, no active surveillance or thermal ablation stratified outcomes of T2 tumors). Cancer specific survival was excellent among all management strategies (median 5-year survival 95%). Local recurrence-free survival was inferior for thermal ablation with 1 treatment but reached equivalence to other modalities after multiple treatments. Overall survival rates were similar among management strategies and varied with age and comorbidity. End-stage renal disease rates were low for all strategies (0.4% to 2.8%). Radical nephrectomy was associated with the largest decrease in estimated glomerular filtration rate and highest incidence of chronic kidney disease. Thermal ablation offered the most favorable perioperative outcomes. Partial nephrectomy showed the highest rates of urological complications but overall rates of minor/major complications were similar among interventions. Strength of evidence was moderate, low and insufficient for 11, 22 and 30 domains, respectively. CONCLUSIONS: Comparative studies demonstrated similar cancer specific survival across management strategies, with some differences in renal functional outcomes, perioperative outcomes and postoperative harms that should be considered when choosing a management strategy.

Diagnostic Accuracy and Risks of Biopsy in the Diagnosis of a Renal Mass Suspicious for Localized Renal Cell Carcinoma: Systematic Review of the Literature.

PURPOSE: Clinical practice varies widely on the diagnostic role of biopsy for clinically localized renal masses suspicious for renal cell carcinoma. Therefore, we performed a systematic review of the available literature to quantify the accuracy and rate of adverse events of renal mass biopsy. MATERIALS AND METHODS: MEDLINE®, Embase® and the Cochrane databases were searched (January 1997 to May 2015) for relevant studies. The systematic review process established by the Agency for Healthcare Research and Quality was followed. Nondiagnostic biopsies were excluded from diagnostic accuracy calculations. RESULTS: A total of 20 studies with 2,979 patients and 3,113 biopsies were included in the study. The overall nondiagnostic rate was 14.1% with 90.4% of those undergoing surgery found to have malignancy. Repeat biopsy led to diagnosis in 80% of patients. The false-positive rate was low (4.0%), histological and renal cell carcinoma subtype concordance was substantial, and Fuhrman upgrading notable (16%) from low grade (1 to 2) to high grade (3 to 4). Core biopsy was highly sensitive (97.5%, CI 96.5-98.5) and specific (96.2%, CI 90.7-100) when a diagnostic result was obtained, but most patients (∼80%) did not undergo surgery after a benign biopsy. Among patients undergoing extirpation 36.7% with a negative biopsy had malignant disease on surgical pathology (negative predictive value 63.3%, CI 52.4-74.2). Direct complications included hematoma (4.9%), clinically significant pain (1.2%), gross hematuria (1.0%), pneumothorax (0.6%) and hemorrhage (0.4%). CONCLUSIONS: Diagnostic accuracy was generally high for biopsy of localized renal masses with a low complication rate, but the nondiagnostic rate and negative predictive value were concerning. Renal mass sampling should be used judiciously as further research will determine its true clinical utility.

SPINK1 Defines a Molecular Subtype of Prostate Cancer in Men with More Rapid Progression in an at Risk, Natural History Radical Prostatectomy Cohort.

PURPOSE: Prostate cancer is clinically and molecularly heterogeneous. We determined the prognosis of men with ERG-ETS fusions and SPINK1 over expression. MATERIALS AND METHODS: Men were identified with intermediate or high risk localized prostate cancer treated with radical prostatectomy and no therapy before metastasis. A case-cohort design sampled a cohort (262) enriched with metastasis from the entire cohort and a cohort (213) enriched with metastasis from patients with biochemical recurrence. We analyzed transcriptomic profiles and subtyped tumors as m-ERG+, m-ETS+, m-SPINK1+ or Triple Negative (m-ERG─/m-ETS─/m-SPINK1─), and multivariable logistic regression analyses, Kaplan-Meier and multivariable Cox models were used to evaluate subtypes as predictors of clinical outcomes. RESULTS: Overall 36%, 13%, 11% and 40% of prostate cancer was classified as m-ERG+, m-ETS+, m-SPINK1+ and Triple Negative, respectively. Univariable analysis demonstrated that m-SPINK1+ tumors were more common in African-American men (OR 5, 95% CI 1.6-16) but less commonly associated with positive surgical margins (OR 0.16, 95% CI 0.03-0.69) compared to the m-ERG+ group. Compared to the Triple Negative group, m-SPINK1+ showed similar associations with race and surgical margins in univariable and multivariable analyses across the entire cohort. Survival analyses did not show significant differences among m-ERG+, m-ETS+ and Triple Negative cases. m-SPINK1+ independently predicted prostate cancer specific mortality after metastasis (HR 2.48, 95% CI 0.96-6.4) and biochemical recurrence (HR 3, 95% CI 1.1-8). CONCLUSIONS: SPINK1 over expression is associated with prostate cancer specific mortality in at risk men with biochemical and clinical recurrence after prostatectomy. ERG-ETS alterations are not prognostic for outcome.

A Prospective, Comparative Study of Quality of Life among Patients with Small Renal Masses Choosing Active Surveillance and Primary Intervention.

PURPOSE: To our knowledge quality of life has not been evaluated in rigorous fashion in patients undergoing active surveillance for small renal masses. The prospective, multi-institutional DISSRM (Delayed Intervention and Surveillance for Small Renal Masses) Registry was opened on January 1, 2009, enrolling patients with cT1a (4.0 cm or less) small renal masses who elected primary intervention or active surveillance. MATERIALS AND METHODS: Patients were enrolled following a choice of active surveillance or primary intervention. The active surveillance protocol includes imaging every 4 to 6 months for 2 years and every 6 to 12 months thereafter. The SF12® quality of life questionnaire was completed at study enrollment, at 6 and 12 months, and annually thereafter. MCS (Mental Component Summary), PCS (Physical Component Summary) and overall score were evaluated among the groups and with time using ANOVA and linear regression mixed modeling. RESULTS: At 82 months among 3 institutions 539 patients were enrolled with a mean ± SD followup of 1.8 ± 1.7 years. Of the patients 254 were on active surveillance, 285 were on primary intervention and 21 were on active surveillance but crossed over to delayed intervention. A total of 1,497 questionnaires were completed. Total and PCS quality of life scores were better for primary intervention at enrollment through 5 years. There were generally no differences in MCS scores among the groups and there was a trend of improving scores with time. CONCLUSIONS: In a prospective registry of patients undergoing active surveillance or primary intervention for small renal masses those undergoing primary intervention had higher quality of life scores at baseline. This was due to a perceived benefit in the physical health domain, which persisted throughout followup. Mental health, which includes the domains of depression and anxiety, was not adversely affected while on active surveillance, and it improved with time after selecting a management strategy.

Urinary fistula after robot-assisted partial nephrectomy: a multicentre analysis of 1 791 patients.

OBJECTIVE: To evaluate the incidence of and risk factors for a urine leak in a large multicentre, prospective database of robot-assisted partial nephrectomy (RPN). PATIENTS AND METHODS: A database of 1 791 RPN from five USA centres was reviewed for urine leak as a complication of RPN. Patient and tumour characteristics were compared between patients with and those without postoperative urine leaks. Fisher's exact test was used for qualitative variables and Wilcoxon sum-rank tests were used for quantitative variables. A review of the literature on PN and urine leak was conducted. RESULTS: Urine leak was noted in 14/1 791 (0.78%) patients who underwent RPN. The mean (sd) nephrometry score of the entire cohort was 7.2 (1.9), and 8.0 (1.9) in patients who developed urine leak. The median (range) postoperative day of presentation was 13 (3-32) days. Patients with urine leak presented in delayed fashion with fever (two of the 14 patients, 14%), gastrointestinal complaints (four patients, 29%), and pain (five patients, 36%). Eight of the 14 patients (57%) required admission, while eight (57%) and nine (64%) had a drain or stent placed, respectively. Drains and stents were removed after a median (range) of 8 (4-13) days and 21 (8-83) days, respectively. Variables associated with urine leak included tumour size (P = 0.021), hilar location (P = 0.025), operative time (P = 0.006), warm ischaemia time (P = 0.005), and pelvicalyceal repair (P = 0.018). Upon literature review, the historical incidence of urine leak ranged from 1.0% to 17.4% for open PN and 1.6-16.5% for laparoscopic PN. CONCLUSION: The incidence of urine leak after RPN is very low and may be predicted by some preoperative factors, affording better patient counselling of risks. The low urinary leak rate may be attributed to the enhanced visualisation and suturing technique that accompanies the robotic approach.

Shoulder arthroplasty options in young (<50 years old) patients: review of current concepts.

BACKGROUND: Prosthetic shoulder arthroplasty provides excellent pain relief and functional restoration for patients with glenohumeral arthritis, but concerns of survivorship have limited its use in younger patients. DISCUSSION: Despite general reports of high long-term survivorship, implant failure and functional deterioration after total shoulder arthroplasty are major concerns in the management of younger patients. In addition to having a longer life expectancy, younger patients also tend to be more active and can be expected to place greater demands on their shoulder arthroplasty. CONCLUSION: Alternative strategies have been developed and used for shoulder arthroplasty in younger patients. This manuscript reviews current concepts of shoulder arthroplasty in young patients.

Randomized controlled trial of oxybutynin extended release versus placebo for urinary symptoms during intravesical Bacillus Calmette-Guérin treatment.

PURPOSE: Intravesical bacillus Calmette-Guérin is used to decrease recurrence rates of nonmuscle invasive urothelial carcinoma. Irritative urinary symptoms are a common side effect of treatment and frequently limit treatment tolerance. While anticholinergic medications may be used for symptom prophylaxis, to our knowledge they have not been evaluated in a randomized controlled trial. MATERIALS AND METHODS: A total of 50 bacillus Calmette-Guérin naïve patients were randomized to 10 mg extended release oxybutynin daily or placebo starting the day before 6 weekly bacillus Calmette-Guérin treatments. A questionnaire assessing urinary symptoms (frequency, burning on urination, urgency, bladder pain, hematuria), systemic symptoms (flu-like symptoms, fever, arthralgia) and medication side effects (constipation, blurred vision, dry mouth) was recorded daily throughout the therapeutic course. A linear mixed repeated measures model tested the differences between each point and baseline score. RESULTS: The treatment group had a greater increase in urinary frequency and burning on urination compared to placebo (p = 0.004 and p = 0.04, respectively). There were no significant differences between groups for other urinary symptoms, which increased in severity after bacillus Calmette-Guérin but concomitantly returned to baseline in both groups. The treatment group experienced increases in fever, flu-like symptoms, dry mouth and constipation compared to placebo (p <0.0001, p = 0.0008, p = 0.045 and p = 0.001, respectively). There were otherwise no significant differences in nonurinary symptoms or medication adverse reactions. CONCLUSIONS: Oxybutynin increased urinary frequency and burning on urination compared to placebo in patients receiving intravesical bacillus Calmette-Guérin treatment. Our results do not support the routine use of oxybutynin as prophylaxis against urinary symptoms during bacillus Calmette-Guérin therapy.

Comparison of the learning curve and outcomes of robotic assisted pediatric pyeloplasty.

PURPOSE: We compared the learning curve and outcomes in children undergoing robotic assisted laparoscopic pyeloplasty during the initiation of a robotic surgery program compared to the benchmark of open pyeloplasty. MATERIALS AND METHODS: The records of our first consecutive 33 children undergoing robotic assisted laparoscopic pyeloplasty from 2006 to 2009 were retrospectively reviewed and compared to those of age and gender matched children who underwent open repair done by senior faculty surgeons before the initiation of our robotic surgery program. We compared operative time, complications, postoperative pain, length of stay and surgical success for 2 surgeons who adopted the robotic approach at an academic teaching institution. RESULTS: We found no significant differences in length of stay, pain score or surgical success at a median followup of 16 months. The number of complications was similar and they tended to be early and technical in the robotic assisted laparoscopic pyeloplasty group. Overall average operative time was 90 minutes longer (38%) for robotic assisted laparoscopic pyeloplasty (p <0.004). When evaluated chronologically, there was evidence of a learning curve. After 15 to 20 robotic cases overall operative times for robotic assisted laparoscopic cases was consistently within 1 SD of our average open pyeloplasty time with no significant difference in overall operative time (p = 0.23). Of the decrease in overall operative time 70% was due to decreased pyeloplasty time rather than peripheral time. CONCLUSIONS: There was similar safety and efficacy with robotic assisted laparoscopic pyeloplasty, although complications tended to be technical and early in our initial experience. Operative time decreased with experience and after 15 to 20 cases it was similar to that of open pyeloplasty with similar outcomes and surgical success.

Local and Regional Recurrences of Clinically Localized Renal Cell Carcinoma after Nephrectomy: A 15 Year Institutional Experience with Prognostic Features and Oncologic Outcomes.

OBJECTIVE: To evaluate outcomes for patients with local recurrence (LR) of clinically localized renal cell carcinoma (RCC) without concurrent systemic metastasis from our institution, an event that occurs rarely (1%-3%) after surgery. LR may be a harbinger of poor outcomes, and the best management of these patients is unclear. MATERIALS/METHODS: We retrospectively reviewed patients surgically treated for clinically localized RCC (cT1-2N0M0) with subsequent LR (in the partial or radical nephrectomy bed) and/or regional recurrence (RR; in the abdomen distant from the direct site of surgery) without concurrent metastasis from our institutional database (2004-2018). Comparative and survival analyses were performed. RESULTS: Out of 3038 total patients, 1895 had clinically localized RCC, with 30 patients (1.6%) having isolated LR/RR. Median time to recurrence was 26.5 months (IQR:16-35). Of 26 patients treated with local therapy, 14 (53.8%) recurred over a median follow-up time of 29.5 months (IQR:12-45). The 1-year and 2-year secondary recurrence-free survival rates are 60.7% and 49.7%, respectively. Two or more sites of locoregional recurrence significantly predicted secondary recurrence/metastasis after local therapy for local recurrence (hazard ratio: 2.22, P= .04). CONCLUSION: Our results suggest local therapy is appropriate for select patients with LR/RR, with almost 50% of patients undergoing a second local therapy remaining alive with "local cure" and no secondary recurrence. The number of sites of recurrence can be used to better select patients that will benefit from local therapy or systemic/combination therapy. This work provides a framework onto which further studies regarding local therapy and locoregional recurrence of RCC can be performed.