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This research concerns itself with increasing the accuracy of random projections used to quickly approximate the inner products of data vectors from a given dataset by adding additional information, namely, adding and storing more extra known vectors to the given dataset and associated information. We show how the variance of estimated inner products is reduced as more vectors are added, how variance reduction is related to the geometry of the dataset and moreover, the asymptotic behaviour of the variance as the number of extra vectors added goes to infinity. We provide the formulae governing the estimate of inner products for adding arbitrarily many extra vectors. Lastly, we demonstrate how to efficiently implement the computations of the estimates by showing we can use pre-computed and stored values for most of the computations. Numerical simulations are conducted to support the analytical results.

Multivariable calculus is one of the core subjects which engineering students study at university. Students may end up memorizing formulae in multivariable calculus due to the lack of ability in visualizing 3D surfaces, and hence not gain much intuition for the subject. We developed an in-house virtual reality (VR) application with the intention for students to visualize concepts in Multivariable Calculus. In order to evaluate the effectiveness of the VR application (which we term as the treatment), we performed a blinded randomized controlled trial with n = 312 students, where we divided them into a control group of nCO = 187 students and treatment group of nTR = 125 students. We gave both groups of students a test immediately after the treatment, as well as asking them to fill in anonymous survey questions using a Likert scale. Our findings show that students perform worse on some questions after using the VR application, and for some other questions students have similar performance to the treatment group. We hypothesize some reasons why this is so, opening the door for future research. We also give recommendations for future developers of VR applications.

Multivariable calculus is a subject undertaken by engineering students as a core module at the freshman level. One of the intended learning outcomes (ILOs) in multivariable calculus is to gain an intuition for visualizing three-dimensional surfaces and deducing their properties. For students to visualize more complex multivariable calculus concepts, a virtual reality (VR) application has been created. Tapping on existing infrastructures, we investigate the effectiveness of visualization through VR usage vis-à-vis a two-dimensional digital screen. We have conducted a controlled trial on a group of N=119 students across two groups. The first group (control group) comprises students who participated in an online quiz (as a baseline test). The second group (treatment group) is given two sets of tests, the first is the same baseline test that the control group participated in, before administering the test questions on the VR platform (termed the treatment test) to the same group of students. Our analysis reveals that students, in general, perform better on questions pertaining to the identification of the sign of partial derivatives in the treatment test, but for other intended learning outcomes linked to other questions, students have performance similar to the baseline test. Furthermore, low-progress students in the treatment group exhibited improvement after the treatment. Our work here has the potential to be developed into a future-ready smart classroom through VR usage.

Background: The costs associated with a contemporary active surveillance strategy compared with immediate treatment for prostate cancer are not well characterized. The purpose of this study is to elucidate the health care costs of an active surveillance paradigm for prostate cancer.Methods: A theoretical cohort of 120,000 men selecting active surveillance for prostate cancer was created. The number of men remaining on active surveillance and those exiting to each of 5 treatments over 5 years were simulated in a Markov model. Estimated total costs after 5 years of active surveillance with subsequent delayed treatment were compared with immediate treatment. Sensitivity analyses were performed to test the effect of various surveillance strategies and attrition rates. Additional analyses to include 10 years of follow-up were performed.Results: The average simulated cost of treatment for 120,000 men initiating active surveillance with 5 years of follow-up and subsequent delayed treatment resulted in per patient cost savings of $16,042 (95% confidence interval [CI], $16,039-$16,046) relative to initial curative treatment. This represents a $1.9 billion dollar savings to the cohort. The strict costs of active surveillance exceeded those of brachytherapy in the ninth year of follow-up. A yearly biopsy within the active surveillance cohort increased costs by 22%, compared with every other year biopsy. At 10 years of follow-up, active surveillance still resulted in a cost benefit; however, the savings were reduced by 38% to $9944 (95% CI, $9941-$9948) per patient relative to initial treatment.Conclusions: These data demonstrate that active surveillance represents a considerable cost savings over immediate treatment for prostate cancer in a theoretical cohort after 5 and 10 years of follow-up. [ABSTRACT FROM AUTHOR]

Cretostimogene grenadenorepvec is a serotype-5 oncolytic adenovirus designed to selectively replicate in cancer cells with retinoblastoma pathway alterations, previously tested as monotherapy in bacillus Calmette-Guérin (BCG)-experienced non-muscle-invasive bladder cancer. In this phase 2 study, we assessed the potential synergistic efficacy between intravesical cretostimogene and systemic pembrolizumab in patients with BCG-unresponsive non-muscle-invasive bladder cancer with carcinoma in situ (CIS). Thirty-five patients were treated with intravesical cretostimogene with systemic pembrolizumab. Induction cretostimogene was administered weekly for 6 weeks followed by three weekly maintenance infusions at months 3, 6, 9, 12 and 18 in patients maintaining complete response (CR). Patients with persistent CIS/high-grade Ta at the 3-month assessment were eligible for re-induction. Pembrolizumab was administered for up to 24 months. The primary endpoint was CR at 12 months as assessed by cystoscopy, urine cytology, cross-sectional imaging and mandatory bladder mapping biopsies. Secondary endpoints included CR at any time, duration of response, progression-free survival and safety. The CR rate in the intention-to-treat population at 12 months was 57.1% (20 out of 35, 95% confidence interval (CI) 40.7-73.5%), meeting the primary endpoint. A total of 29 out of 35 patients (82.9%, 95% CI 70.4-95.3%) derived a CR at 3 months. With a median follow-up of 26.5 months, the median duration of response has not been reached (95% CI 15.7 to not reached). The CR rate at 24 months was 51.4% (18 out of 35) (95% CI 34.9-68.0%). No patient progressed to muscle-invasive bladder cancer in this trial. Adverse events attributed to cretostimogene were low grade, self-limiting and predominantly limited to bladder-related symptoms. A total of 5 out of 35 patients (14.3%) developed grade 3 treatment-related adverse effects. There was no evidence of overlapping or synergistic toxicities. Combination intravesical cretostimogene and systemic pembrolizumab demonstrated enduring efficacy. With a toxicity profile similar to its monotherapy components, this combination may shift the benefit-to-risk ratio for patients with BCG-unresponsive CIS. ClinicalTrials.gov Identifier: NCT04387461 ., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background and Objective: Patients with intermediate-risk non-muscle-invasive bladder cancer (IR NMIBC) have a high risk of recurrence and need effective therapies to reduce the risk of disease recurrence or progression. This phase 1b study (NCT02720367) assessed the safety and tolerability of TAR-200, an intravesical drug delivery system, in participants with IR NMIBC., Methods: Participants with recurrent IR NMIBC were eligible. Participants received either two 7-d or two 21-d TAR-200 dosing cycles over a 4-6-wk period in a marker lesion/ablation design. TAR-200 was placed in the window between the cystoscopy showing recurrent papillary disease and the subsequent complete transurethral resection of the bladder tumour. The primary endpoint was TAR-200 safety. The secondary endpoints included TAR-200 tolerability, pharmacokinetics, and preliminary efficacy., Key Findings and Limitations: Twelve participants received TAR-200 treatment. No TAR-200-related serious or grade ≥ 3 treatment-emergent adverse events (TEAEs) occurred. Nine participants had grade ≤ 2 TAR-200-related TEAEs, with urgency, dysuria, and haematuria being most common. Two participants refused a second dosing cycle due to urinary urgency and frequency. Insertion and removal of TAR-200 was successful in all cases. Plasma gemcitabine concentrations remained below the lower limit of detection. Five participants (42%) had complete response (CR): four had pathological CR and one had CR based on visual assessment., Conclusions and Clinical Implications: TAR-200 appears to be safe and well tolerated, with encouraging preliminary efficacy in participants with IR NMIBC. This study lays the groundwork for the multiple phase 2 and 3 global studies that are currently on-going for TAR-200., Patient Summary: In this study, researchers evaluated the safety of the novel drug delivery system TAR-200 in participants with intermediate-risk non-muscle-invasive bladder cancer. They concluded that TAR-200 was safe and well tolerated with promising antitumour activity., (© 2024 The Authors.)

Purpose: Half of patients with muscle-invasive bladder cancer worldwide may not receive curative-intent therapy. Elderly or frail patients are most affected by this unmet need. TAR-200 is a novel, intravesical drug delivery system that provides sustained, local release of gemcitabine into the bladder over a 21-day dosing cycle. The phase 1 TAR-200-103 study evaluated the safety, tolerability, and preliminary efficacy of TAR-200 in patients with muscle-invasive bladder cancer who either refused or were unfit for curative-intent therapy., Materials and Methods: Eligible patients had cT2-cT3bN0M0 urothelial carcinoma of the bladder. TAR-200 was inserted for 4 consecutive 21-day cycles over 84 days. The primary end points were safety and tolerability at 84 days. Secondary end points included rates of clinical complete response and partial response as determined by cystoscopy, biopsy, and imaging; duration of response; and overall survival., Results: Median age of the 35 enrolled patients was 84 years, and most were male (24/35, 68.6%). Treatment-emergent adverse events related to TAR-200 occurred in 15 patients. Two patients experienced treatment-emergent adverse events leading to removal of TAR-200. At 3 months, complete response and partial response rates were 31.4% (11/35) and 8.6% (3/35), respectively, yielding an overall response rate of 40.0% (14/35; 95% CI 23.9-57.9). Median overall survival and duration of response were 27.3 months (95% CI 10.1-not estimable) and 14 months (95% CI 10.6-22.7), respectively. Progression-free rate at 12 months was 70.5%., Conclusions: TAR-200 was generally safe, well tolerated, and had beneficial preliminary efficacy in this elderly and frail cohort with limited treatment options.

Objectives: Neoadjuvant chemotherapy and radical cystectomy (RC) are underutilized standards of care for the treatment of muscle-invasive bladder cancer (MIBC) due to high patient burden from systemic toxicities and postoperative complications, respectively. TAR-200 is a novel intravesical drug delivery system developed to release gemcitabine into the bladder urine continuously, resulting in distribution of drug into stromal layers of the bladder. The primary aim of the TAR-200-101 study was to evaluate the safety of TAR-200 in patients with MIBC prior to RC (NCT02722538)., Methods and Materials: This phase I, open-label study was conducted across 6 US and European sites. Eligible patients were aged ≥18 years with histologically confirmed T2a-T3b N0-N1 M0 urothelial cancer and had refusal or were ineligible to receive cisplatin-based combination chemotherapy. Two arms were enrolled serially. Patients in Arm 1 had residual tumor >3 cm after transurethral resection of bladder tumor (TURBT); those in Arm 2 had undergone maximal TURBT (residual tumor <3 cm). Patients received two 7-day cycles of intravesical gemcitabine delivery via TAR-200 before undergoing RC. Primary outcome was safety; secondary outcomes were tolerability, pharmacokinetics, and preliminary efficacy., Results: Of 23 patients in the intention-to-treat population (11 in Arm 1, 12 in Arm 2), 20 completed both dosing cycles of TAR-200. No patients were classified as intolerant to TAR-200. Ten patients (4 in Arm 1, 6 in Arm 2) experienced ≥1 treatment-emergent adverse events (TEAEs). The most common TAR-200-related TEAEs were pollakiuria (n = 3) and urinary incontinence (n = 2). All TEAEs prior to RC were grade ≤2; 1 patient in Arm 2 experienced a grade 3 non-treatment-related TEAE. Plasma gemcitabine levels were undetectable. In Arm 1, those with residual tumor, 4 of 10 patients exhibited pathologic downstaging; 1 experienced a complete response (CR) and 3 a partial response (PR). In Arm 2, those undergoing maximal TURBT, 6 of 10 patients exhibited downstaging; 3 experienced a CR and 3 a PR., Conclusion: Controlled intravesical gemcitabine release via TAR-200 was safe and well tolerated in patients with MIBC., Competing Interests: Conflict of interests M Aron, ISG Brummelhuis, KS Pohar, and JA Witjes have no financial or other conflict of interest related to this study. CJ Cutie and JC Maffeo are former employees of TARIS Biomedical and are employees of Janssen Pharmaceuticals. KA Keegan and B Raybold are employees of Janssen Pharmaceuticals. A Chau and D Reynolds were paid consultants for TARIS Biomedical. A Chau, S Daneshmand and D Reynolds are paid consultants for Janssen Pharmaceuticals. S Daneshmand has equity interest in TARIS Biomedical. GD Steinberg is a member of Clinical Trial Committees for Janssen Pharmaceuticals and has been a scientific adviser for TARIS Biomedical and Janssen Pharmaceuticals., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Earlier studies on the cost of muscle-invasive bladder cancer treatments are limited to short-term costs of care. We determined the 2- and 5-year costs associated with trimodal therapy (TMT) vs. radical cystectomy (RC)., Methods: We performed a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Total Medicare costs at 2 and 5 years following RC vs. TMT were compared using inverse probability of treatment-weighted propensity score models., Results: A total of 2,537 patients aged 66 to 85 years were diagnosed with clinical stage T2-4a muscle-invasive bladder cancer. Total median costs for patients that received no definitive treatment(s) were $73,780 and $88,275 at 2-and 5-years. Costs were significantly higher for TMT than RC at 2-years ($372,839 vs. $191,363, Median Difference $127,815, Hodges-Lehmann Estimate (H-L) 95% Confidence Interval (CI), $112,663-$142,966) and 5-years ($424,570 vs. $253,651, Median Difference $124,466, H-L 95% CI, $105,711-$143,221). TMT had higher outpatient costs than RC (2-years: $318,221 vs. $100,900; 5-years: $367,092 vs. $146,561) with significantly higher costs with radiology, medications, pathology/laboratory, and other professional services. RC had higher inpatient costs than TMT (2-years: $62,240 vs. $33,631, Median Difference $-29,174, H-L 95% CI, $-32,364-$-25,984; 5-years: $75,499 vs. $45,223, Median Difference $-29,843, H-L 95% CI, $-33,905-$-25,781)., Conclusions and Relevance: The excess spending associated with trimodal therapy vs. radical cystectomy was largely driven by outpatient expenditures. The relatively high long-term trimodal therapy costs are prime targets for cost containment strategies to optimize future value-based care., Competing Interests: Declaration of competing interest None, (Copyright © 2022 Elsevier Inc. All rights reserved.)

A recent phase 3 trial of intravesical nadofaragene firadenovec reported a promising complete response rate for patients with bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer. This study examined the ability of antiadenovirus antibody levels to predict the durability of therapeutic response to nadofaragene firadenovec. A standardized and validated quantitative assay was used to prospectively assess baseline and post-treatment serum antibody levels among 91 patients from the phase 3 trial, of whom 47 (52%) were high-grade recurrence free at 12 mo (responders). While baseline titers did not predict treatment response, 3-mo titer >800 was associated with a higher likelihood of durable response (p = 0.026). Peak post-treatment titers >800 were noted in 42 (89%) responders versus 26 (59%) nonresponders (p = 0.001; assay sensitivity, 89%; negative predictive value, 78%). Moreover, 22 (47%) responders compared with eight (18%) nonresponders had a combination of peak post-treatment titers >800 and peak antibody fold change >8 (p = 0.004; assay specificity, 82%; positive predictive value, 73%). A majority of responders continued to have post-treatment antibody titers >800 after the first 6 mo of therapy. In conclusion, serum antiadenovirus antibody quantification may serve as a novel predictive marker for nadofaragene firadenovec response durability. Future studies will focus on large-scale validation and clinical utility of the assay. PATIENT SUMMARY: This study reports on a planned secondary analysis of a phase 3 multicenter clinical trial that established the benefit of nadofaragene firadenovec, a novel intravesical gene therapeutic, for the treatment of patients with bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer. Prospective assessment of serum anti-human adenovirus type-5 antibody levels of patients in this trial indicated that a combination of post-treatment titers and fold change from baseline can predict treatment efficacy. While this merits additional validation, our findings suggest that serum antiadenovirus antibody levels can serve as an important predictive marker for the durability of therapeutic response to nadofaragene firadenovec., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objectives: To investigate the relationship between gender, body mass index (BMI), and prognosis in renal cell carcinoma (RCC) patients., Materials and Methods: We retrospectively reviewed 1353 patients with RCC who underwent a partial or radical nephrectomy between 1988 and 2015. The association among sex, BMI, stage, grade, overall survival (OS), and recurrence-free survival (RFS) was analyzed., Results: The median age of the patients was 59.4 ± 11.9 years. Female patients had proportionally lower grade tumors than male patients (Grade I-II in 75.5% vs. 69.3% in women and men, respectively, P = 0.022). There was no relationship between Fuhrman grade and BMI when substratified by gender (p > 0.05). There was a nonsignificant trend toward more localized disease in female patients (p = 0.058). There was no relationship between T stage and BMI when stratified by gender (p > 0.05). Patients with higher BMI had significantly better OS (p = 0.0004 and P = 0.0003) and RFS (P = 0.0209 and P =0.0082) whether broken out by lower 33 rd or 25 th percentile. Male patients with higher BMI had significantly better OS and RFS rates. However, there was no relationship between BMI and OS or RFS for female patients (P > 0.05). Multivariate analysis of the entire cohort demonstrated that a BMI in the lower quartile independently predicts OS (hazard ratio 1.604 [95% confidence interval: 1.07-2.408], P = 0.022) but not RFS (P > 0.05). When stratified by gender, there was no relationship between BMI and either OS or RFS (P > 0.05)., Conclusions: Increasing BMI was associated with RCC prognosis. However, the clinical association between BMI and oncologic outcomes may be different between men and women., Competing Interests: None

Introduction: To assess and improve quality of care, the Commission on Cancer developed 3 evidence-based quality measures for the treatment of muscle invasive bladder cancer. We sought to assess performance of these measures prior to their implementation, whether compliance was associated with survival and whether patient factors influenced compliance., Methods: We assessed all patients 18 to 90 years old diagnosed with invasive, nonmetastatic bladder cancer between 2004 and 2015 using the National Cancer Database. Both univariable and multivariable analyses were utilized to determine the effect of compliance on survival and identify patient level predictors of compliance., Results: Of the 46,502 patients identified 22,218 underwent surgical management and 5,282 received trimodal therapy. All quality measures were achieved in 45.7% of the surgical cohort, which was associated with lower all cause mortality (HR 0.89, 95% CI 0.85-0.93, p <0.01). Time less than 90 days to trimodal therapy was achieved in 35.0% and was not associated with lower all cause mortality (HR 0.93, 95% CI 0.85-1.01, p=0.07). In the surgical cohort compliance was associated with higher income (OR 1.27, 95% CI 1.13-1.46, p <0.01), living in a higher educated zip code area (OR 1.15, 95% CI 1.02-1.30, p=0.02) and living 10 or more miles from the place of treatment (OR 1.38, 95% CI 1.29-1.47, p <0.01)., Conclusions: Quality measure compliance is associated with improved survival in patients undergoing surgical management of muscle invasive bladder cancer. Despite this benefit, achievement of all 3 metrics was observed in less than half of patients prior to quality measure implementation.

Background: BCG is the most effective therapy for high-risk non-muscle-invasive bladder cancer. Nadofaragene firadenovec (also known as rAd-IFNa/Syn3) is a replication-deficient recombinant adenovirus that delivers human interferon alfa-2b cDNA into the bladder epithelium, and a novel intravesical therapy for BCG-unresponsive non-muscle-invasive bladder cancer. We aimed to evaluate its efficacy in patients with BCG-unresponsive non-muscle-invasive bladder cancer., Methods: In this phase 3, multicentre, open-label, repeat-dose study done in 33 centres (hospitals and clinics) in the USA, we recruited patients aged 18 years or older, with BCG-unresponsive non-muscle-invasive bladder cancer and an Eastern Cooperative Oncology Group status of 2 or less. Patients were excluded if they had upper urinary tract disease, urothelial carcinoma within the prostatic urethra, lymphovascular invasion, micropapillary disease, or hydronephrosis. Eligible patients received a single intravesical 75 mL dose of nadofaragene firadenovec (3 × 10 11 viral particles per mL). Repeat dosing at months 3, 6, and 9 was done in the absence of high-grade recurrence. The primary endpoint was complete response at any time in patients with carcinoma in situ (with or without a high-grade Ta or T1 tumour). The null hypothesis specified a complete response rate of less than 27% in this cohort. Efficacy analyses were done on the per-protocol population, to include only patients strictly meeting the BCG-unresponsive definition. Safety analyses were done in all patients who received at least one dose of treatment. The study is ongoing, with a planned 4-year treatment and monitoring phase. This study is registered with ClinicalTrials.gov, NCT02773849., Findings: Between Sept 19, 2016, and May 24, 2019, 198 patients were assessed for eligibility. 41 patients were excluded, and 157 were enrolled and received at least one dose of the study drug. Six patients did not meet the definition of BCG-unresponsive non-muscle-invasive bladder cancer and were therefore excluded from efficacy analyses; the remaining 151 patients were included in the per-protocol efficacy analyses. 55 (53·4%) of 103 patients with carcinoma in situ (with or without a high-grade Ta or T1 tumour) had a complete response within 3 months of the first dose and this response was maintained in 25 (45·5%) of 55 patients at 12 months. Micturition urgency was the most common grade 3-4 study drug-related adverse event (two [1%] of 157 patients, both grade 3), and there were no treatment-related deaths., Interpretation: Intravesical nadofaragene firadenovec was efficacious, with a favourable benefit:risk ratio, in patients with BCG-unresponsive non-muscle-invasive bladder cancer. This represents a novel treatment option in a therapeutically challenging disease state., Funding: FKD Therapies Oy., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: Provide evidence- and expert-based recommendations for optimal use of imaging in advanced prostate cancer. Due to increases in research and utilization of novel imaging for advanced prostate cancer, this guideline is intended to outline techniques available and provide recommendations on appropriate use of imaging for specified patient subgroups., Methods: An Expert Panel was convened with members from ASCO and the Society of Abdominal Radiology, American College of Radiology, Society of Nuclear Medicine and Molecular Imaging, American Urological Association, American Society for Radiation Oncology, and Society of Urologic Oncology to conduct a systematic review of the literature and develop an evidence-based guideline on the optimal use of imaging for advanced prostate cancer. Representative index cases of various prostate cancer disease states are presented, including suspected high-risk disease, newly diagnosed treatment-naïve metastatic disease, suspected recurrent disease after local treatment, and progressive disease while undergoing systemic treatment. A systematic review of the literature from 2013 to August 2018 identified fully published English-language systematic reviews with or without meta-analyses, reports of rigorously conducted phase III randomized controlled trials that compared ≥ 2 imaging modalities, and noncomparative studies that reported on the efficacy of a single imaging modality., Results: A total of 35 studies met inclusion criteria and form the evidence base, including 17 systematic reviews with or without meta-analysis and 18 primary research articles., Recommendations: One or more of these imaging modalities should be used for patients with advanced prostate cancer: conventional imaging (defined as computed tomography [CT], bone scan, and/or prostate magnetic resonance imaging [MRI]) and/or next-generation imaging (NGI), positron emission tomography [PET], PET/CT, PET/MRI, or whole-body MRI) according to the clinical scenario.

Background: To evaluate the impact of salvage therapy (ST) on overall survival (OS) in recurrent primary urethral cancer (PUC)., Patients: A series of 139 patients (96 men, 43 women; median age = 66, interquartile range: 57-77) were diagnosed with PUC at 10 referral centers between 1993 and 2012. The modality of ST of recurrence (salvage surgery vs. radiotherapy) was recorded. Kaplan-Meier analysis with log-rank was used to estimate the impact of ST on OS (median follow-up = 21, interquartile range: 5-48)., Results: The 3-year OS for patients free of any recurrence (I), with solitary or concomitant urethral recurrence (II), and nonurethral recurrence (III) was 86.5%, 74.5%, and 48.2%, respectively (P = 0.002 for I vs. III and II vs. III; P = 0.55 for I vs. II). In the 80 patients with recurrences, the modality of primary treatment of recurrence was salvage surgery in 30 (37.5%), salvage radiotherapy (RT) in 8 (10.0%), and salvage surgery plus RT in 5 (6.3%) whereas 37 patients did not receive ST for recurrence (46.3%). In patients with recurrences, those who underwent salvage surgery or RT-based ST had similar 3-year OS (84.9%, 71.6%) compared to patients without recurrence (86.7%, P = 0.65), and exhibited superior 3-year OS compared to patients who did not undergo ST (38.0%, P<0.001 compared to surgery, P = 0.045 to RT-based ST, P = 0.29 for surgery vs. RT-based ST)., Conclusions: In this study, patients who underwent ST for recurrent PUC demonstrated improved OS compared to those who did not receive ST and exhibited similar survival to those who never developed recurrence after primary treatment., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Physician-led perioperative surgical home models are developing as a method for improving the American health care system. These models are novel, team-based approaches that help to provide continuity of care throughout the perioperative period. Another avenue for improving care for surgical patients is the use of enhanced recovery after surgery pathways. These are well-described methods that have shown to improve perioperative outcomes. An established perioperative surgical home model can help implementation, efficiency, and adherence to enhanced recovery after surgery pathways. For these reasons, the Tennessee Valley Healthcare System, Nashville Veterans Affairs Medical Center created an Anesthesiology Perioperative Care Service that provides comprehensive care to surgical patients from their preoperative period through the continuum of their hospital course and postdischarge follow-up. In this brief report, we describe the development, implementation, and preliminary outcomes of the service.

Introduction: The study aimed to investigate oncological outcomes of patients with concomitant bladder cancer (BC) and urethral carcinoma., Methods: This is a multicenter series of 110 patients (74 men, 36 women) diagnosed with urethral carcinoma at 10 referral centers between 1993 and 2012. Kaplan-Meier analysis was used to investigate the impact of BC on survival, and Cox regression multivariable analysis was performed to identify predictors of recurrence., Results: Synchronous BC was diagnosed in 13 (12%) patients, and the median follow-up was 21 months (interquartile range 4-48). Urethral cancers were of higher grade in patients with synchronous BC compared to patients with non-synchronous BC (p = 0.020). Patients with synchronous BC exhibited significantly inferior 3-year recurrence-free survival (RFS) compared to patients with non-synchronous BC (63.2 vs. 34.4%; p = 0.026). In multivariable analysis, inferior RFS was associated with clinically advanced nodal stage (p < 0.001), proximal tumor location (p < 0.001) and synchronous BC (p = 0.020)., Conclusion: The synchronous presence of BC in patients diagnosed with urethral carcinoma has a significant adverse impact on RFS and should be an impetus for a multimodal approach., (© 2016 S. Karger AG, Basel.)

The effect of radical cystectomy and extended pelvic lymph node dissection (RC/PLND) on the survival of patients with locally advanced and/or regionally metastatic bladder cancer is unknown. However, emerging evidence suggests that there may be survival benefit to a subset of select patients with this disease who demonstrate a response to chemotherapy. This article will review the current literature on the role of RC/PLND in the consolidative treatment of locally advanced and regionally metastatic bladder cancer., Competing Interests: Competing interests: The authors have declared that no competing interests exist.

Purpose: To evaluate risk factors for survival in a large international cohort of patients with primary urethral cancer (PUC)., Methods: A series of 154 patients (109 men, 45 women) were diagnosed with PUC in ten referral centers between 1993 and 2012. Kaplan-Meier analysis with log-rank test was used to investigate various potential prognostic factors for recurrence-free (RFS) and overall survival (OS). Multivariate models were constructed to evaluate independent risk factors for recurrence and death., Results: Median age at definitive treatment was 66 years (IQR 58-76). Histology was urothelial carcinoma in 72 (47 %), squamous cell carcinoma in 46 (30 %), adenocarcinoma in 17 (11 %), and mixed and other histology in 11 (7 %) and nine (6 %), respectively. A high degree of concordance between clinical and pathologic nodal staging (cN+/cN0 vs. pN+/pN0; p < 0.001) was noted. For clinical nodal staging, the corresponding sensitivity, specificity, and overall accuracy for predicting pathologic nodal stage were 92.8, 92.3, and 92.4 %, respectively. In multivariable Cox-regression analysis for patients staged cM0 at initial diagnosis, RFS was significantly associated with clinical nodal stage (p < 0.001), tumor location (p < 0.001), and age (p = 0.001), whereas clinical nodal stage was the only independent predictor for OS (p = 0.026)., Conclusions: These data suggest that clinical nodal stage is a critical parameter for outcomes in PUC.

Background and Purpose: Liposomal bupivacaine is a delayed-release preparation providing up to 72 hours of local analgesia. It costs much more than standard bupivacaine, however. A prospective, randomized, patient-blinded, controlled trial was performed to assess the efficacy of liposomal bupivacaine versus 0.25% bupivacaine when injected into surgical incisions during laparoscopic and robot-assisted urologic surgery., Methods: A total of 206 adults were randomized to receive liposomal bupivacaine or 0.25% bupivacaine. All surgical incisions were injected with liposomal bupivacaine or 0.25% bupivacaine with systematic dosing. The primary outcome was total opioid consumption during the postoperative hospital stay. All opioid doses were converted to morphine equivalents. Secondary end points included pain scores using visual analog pain scales, duration of hospital stay, and the time to first opioid use. A subgroup analysis was performed for renal surgery patients., Results: There was no significant difference in median total opioid use during the hospital stay between those who received liposomal bupivacaine (15 [interquartile range (IQR) 6.7-27] mg) and 0.25% bupivacaine (17.3 [IQR 8.3-30.5] mg) (P=0.39). Furthermore, pain scores, length of hospital stay, and time to first opioid use did not differ between groups. Subgroup analysis of laparoscopic renal surgery revealed no difference between liposomal bupivacaine and 0.25% bupivacaine., Conclusions: For laparoscopic and robot-assisted urologic surgery, there is no significant difference between liposomal bupivacaine and 0.25% bupivacaine for local analgesia at the incision sites.

Background: To investigate the impact of perioperative chemo(radio)therapy in advanced primary urethral carcinoma (PUC)., Patients and Methods: A series of 124 patients (86 men, 38 women) were diagnosed with and underwent surgery for PUC in 10 referral centers between 1993 and 2012. Kaplan-Meier analysis with log-rank testing was used to investigate the impact of perioperative chemo(radio)therapy on overall survival (OS). The median follow-up was 21 months (mean: 32 months; interquartile range: 5-48)., Results: Neoadjuvant chemotherapy (NAC), neoadjuvant chemoradiotherapy (N-CRT) plus adjuvant chemotherapy (ACH), and ACH was delivered in 12 (31%), 6 (15%) and 21 (54%) of these patients, respectively. Receipt of NAC/N-CRT was associated with clinically node-positive disease (cN+; P = 0.033) and lower utilization of cystectomy at surgery (P = 0.015). The objective response rate to NAC and N-CRT was 25% and 33%, respectively. The 3-year OS for patients with objective response to neoadjuvant treatment (complete/partial response) was 100% and 58.3% for those with stable or progressive disease (P = 0.30). Of the 26 patients staged ≥cT3 and/or cN+ disease, 16 (62%) received perioperative chemo(radio)therapy and 10 upfront surgery without perioperative chemotherapy (38%). The 3-year OS for this locally advanced subset of patients (≥cT3 and/or cN+) who received NAC (N = 5), N-CRT (N = 3), surgery-only (N = 10) and surgery plus ACH (N = 8) was 100%, 100%, 50% and 20%, respectively (P = 0.016). Among these 26 patients, receipt of neoadjuvant treatment was significantly associated with improved 3-year relapse-free survival (RFS) (P = 0.022) and OS (P = 0.022). Proximal tumor location correlated with inferior 3-year RFS and OS (P = 0.056/0.005)., Conclusion: In this series, patients who received NAC/N-CRT for cT3 and/or cN+ PUC appeared to demonstrate improved survival compared with those who underwent upfront surgery with or without ACH., (© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: There are growing concerns regarding the overtreatment of localized prostate cancer. It is also relatively unknown whether there has been increased uptake of observational strategies for disease management. We assessed the temporal trend in observation of clinically localized prostate cancer, particularly in men with low risk disease, who were young and healthy enough to undergo treatment., Materials and Methods: We performed a retrospective cohort study using the SEER-Medicare database in 66,499 men with localized prostate cancer between 2004 and 2009. The main study outcome was observation within 1 year after diagnosis. We performed multivariable analysis to develop a predictive model of observation adjusting for diagnosis year, age, risk and comorbidity., Results: Observation was performed in 12,007 men (18%) with a slight increase with time from 17% to 20%. However, there was marked increase in observation from 18% in 2004 to 29% in 2009 in men with low risk disease. Men 66 to 69 years old with low risk disease and no comorbidities had twice the odds of undergoing observation in 2009 vs 2004 (OR 2.12, 95% CI 1.73-2.59). Age, risk group, comorbidity and race were independent predictors of observation (each p <0.001), in addition to diagnosis year., Conclusions: We identified increasing use of observation for low risk prostate cancer between 2004 and 2009 even in men young and healthy enough for treatment. This suggests growing acceptance of surveillance in this group of patients., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Despite the documented survival benefit conferred by neoadjuvant (NAC) and adjuvant chemotherapy (AC), there has been a slow adoption of guideline recommendations for the use of perioperative chemotherapy (POC) in patients with muscle-invasive bladder cancer (MIBC)., Objective: To evaluate temporal trends in POC utilization and identify factors influencing POC delivery in a representative cohort of patients with MIBC., Design, Setting, and Participants: Retrospective cohort study identifying factors associated with receipt of POC and evaluating temporal changes in NAC and AC utilization. We included patients from the National Cancer Data Base (NCDB) with no prior malignancy who ultimately underwent radical cystectomy for ≥ cT2/cN0/cM0 MIBC between 2006 and 2010., Outcome Measurements and Statistical Analysis: Relationships between demographic and hospital factors and the likelihood of receiving POC were evaluated using Pearson chi-square and Wilcoxon rank-sum tests, and multivariable logistic regression. Temporal changes in NAC and AC use were detected using a linear test of trend., Results and Limitations: A total of 5692 patients met our inclusion criteria. POC use increased from 29.5% in 2006 to 39.8% in 2010 (p < 0.001). NAC use increased from 10.1% in 2006 to 20.8% in 2010 (p = 0.005); AC remained stable between 18.1% and 21.3% (p = 0.68). Multivariable modeling revealed advanced age, increasing comorbidity, lack of insurance, increased travel distance, geographic location outside the northeastern United States, and lower income as negatively associated with POC receipt (all p < 0.05). Limitations include retrospective design and potential sampling bias, excluding patients treated at non-NCDB facilities., Conclusions: POC use for MIBC increased from 2006 to 2010, with this increase disproportionately due to rising NAC utilization. Nonetheless, there is persistent variation in the likelihood of receiving POC secondary to nonclinical factors., Patient Summary: When retrospectively analyzing a representative cohort of patients undergoing radical cystectomy for muscle-invasive bladder cancer between 2006 and 2010, we noted that preoperative chemotherapy rates increased steadily while use of chemotherapy after surgery remained stable. Factors related to access to care significantly influenced receipt of chemotherapy., (Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate predictors of understaging in patients with presumed non-muscle-invasive bladder cancer (NMIBC) identified on transurethral resection of bladder tumour (TURBT) who underwent radical cystectomy (RC) with attention to the role of a restaging TURBT., Patients and Methods: We retrospectively evaluated 279 consecutive patients with clinically staged T1 (cT1) disease after TURBT who underwent RC at our institution from April 2000 to July 2011. In all, 60 of these cT1 patients had undergone a restaging TURBT before RC. The primary outcome measure was pathological staging of ≥T2 disease at the time of RC., Results: In all, 134 (48.0%) patients were understaged. Of the 60 patients who remained cT1 after a restaging TURBT, 28 (46.7%) were understaged. Solitary tumour (odds ratio [OR] 0.43, 95% confidence interval [CI] 0.25-0.76, P = 0.004) and fewer prior TURBTs (OR 0.84, 95% CI 0.71-1.00, P = 0.05) were independent risk factors for understaging., Conclusions: Despite the overall improvement in staging accuracy linked to restaging TURBTs, the risk of clinical understaging remains high in restaged patients found to have persistent T1 urothelial carcinoma who undergo RC. Solitary tumour and fewer prior TURBTs are independent risk factors for being understaged. Incorporating these predictors into preoperative risk stratification may allow for augmented identification of those patients with clinical NMIBC who stand to benefit most from RC., (© 2013 The Authors. BJU International © 2013 BJU International.)

The treatment and management of advanced urothelial carcinoma of the bladder is a considerable therapeutic challenge. Prospective, randomized clinical trial data demonstrate a survival advantage for those patients who receive chemotherapy prior to radical cystectomy. Despite the overall survival benefits, results from both institutional and administrative datasets suggest that historical use of a neoadjuvant chemotherapy paradigm is remarkably low. This review will evaluate the recent trends in pre-operative chemotherapy utilization that suggest small, but progressively increased use-currently on the order of 20 % of radical cystectomy patients. Additionally, this analysis will explore the various processes and structural barriers that preclude its receipt such as patient age and comorbidity, as well as physician preference, delay to potentially curable surgery, geographic region, distance to treatment facility, and socioeconomic status.

Objectives: Radical cystectomy (RC) is associated with significant blood loss and transfusion requirement. We performed a prospective, randomized trial to compare blood loss, operative time, and cost using 2 different and commonly employed approaches to tissue ligation and division during RC: mechanical (stapler device) and electrosurgical (heat-sealing device)., Methods and Materials: Eighty patients undergoing RC for urothelial bladder carcinoma were randomized to use of either an Endo GIA Stapler or Impact LigaSure device for tissue ligation and division. Primary outcomes were blood loss, operative time, and device costs. Data were analyzed with Wilcoxon rank sum test and Welch 2-sample t test., Results: There were no significant demographic or preoperative differences between the cohorts. Mean estimated blood loss was similar between the electrosurgical (687 ml) and stapler (708 ml) arms (P = 0.850). There were no significant differences between cohorts when comparing operative times or transfusion requirement. There was a significant increase in the mean number of adjunctive suture ligatures used in the stapling device arm (3.0 vs. 1.5, P = 0.047). Total device costs were significantly lower with the LigaSure compared with the GIA Stapler ($625.00 vs. $1490.10, P<0.001). There were no complications attributable to either device., Conclusions: This prospective, randomized study demonstrates no significant difference in blood loss, transfusion requirement, or safety between mechanical vs. electrosurgical control of the vascular pedicles. The LigaSure device, however, is significantly less costly than the GIA Stapler and required fewer additional measures for hemostasis., (Copyright © 2014 Elsevier Inc. All rights reserved.)

In March 2010, the Patient Protection and Affordable Care Act as well as its amendments were signed into law. This sweeping legislation was aimed at controlling spiraling healthcare costs and redressing significant disparities in healthcare access and quality. Cancer diagnoses and their treatments constitute a large component of rising healthcare expenditures and, not surprisingly, the legislation will have a significant influence on cancer care in the USA. Because genitourinary malignancies represent an impressive 25% of all cancer diagnoses per year, this legislation could have a profound impact on urologic oncology. To this end, we will present key components of this landmark legislation, including the proposed expansion to Medicaid coverage, the projected role of Accountable Care Organizations, the expected creation of quality reporting systems, the formation of an independent Patient-Centered Outcomes Research Institute, and enhanced regulation on physician-owned practices. We will specifically address the anticipated effect of these changes on urologic cancer care. Briefly, the legal ramifications and current barriers to the statutes will be examined., (Published by Elsevier Inc.)

Purpose: Salvage robotic assisted laparoscopic prostatectomy is a treatment option for certain patients with recurrent prostate cancer after primary therapy. Data regarding patient selection, complication rates and cancer outcomes are scarce. We report the largest, single institution series to date, to our knowledge, of salvage robotic assisted laparoscopic prostatectomy., Materials and Methods: We reviewed our database of 4,234 patients treated with robotic assisted laparoscopic prostatectomy at Vanderbilt University and identified 34 men who had surgery after the failure of prior definitive ablative therapy. Each patient had biopsy proven recurrent prostate cancer and no evidence of metastases. The primary outcome measure was biochemical failure., Results: Median time from primary therapy to salvage robotic assisted laparoscopic prostatectomy was 48.5 months with a median preoperative prostate specific antigen of 3.86 ng/ml. Most patients had Gleason scores of 7 or greater on preoperative biopsy, although 12 (35%) had Gleason 8 or greater disease. After a median followup of 16 months 18% of patients had biochemical failure. The positive margin rate was 26%, of which 33% had biochemical failure after surgery. On univariable analysis there was a significant association between prostate specific antigen doubling time and biochemical failure (HR 0.77, 95% CI 0.60-0.99, p = 0.049) as well as between Gleason score at original diagnosis and biochemical failure (HR 3.49, 95% CI 1.18-10.3, p = 0.023). There were 2 Clavien II-III complications, namely a pulmonary embolism and a rectal laceration. Postoperatively 39% of patients had excellent continence., Conclusions: Salvage robotic assisted laparoscopic prostatectomy is safe, with many favorable outcomes compared to open salvage radical prostatectomy series. Advantages include superior visualization of the posterior prostatic plane, modest blood loss, low complication rates and short length of stay., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Context: New guidelines of the International Consultation on Urological Diseases for the treatment of muscle-invasive bladder cancer (MIBC) have recently been published., Objective: To provide a comprehensive overview of the current role of radical cystectomy (RC) in MIBC., Evidence Acquisition: A detailed Medline analysis was performed for original articles addressing the role of RC with regard to indication, timing, surgical extent, perioperative morbidity, oncologic outcome, and follow-up. The analysis also included radiation-based bladder-preserving strategies., Evidence Synthesis: The major findings are presented in an evidence-based fashion and are based on large retrospective unicenter and multicenter series with some prospective data., Conclusions: Open RC is the standard treatment for locoregional control of MIBC. Delay of RC is associated with reduced cancer-specific survival. In males, standard RC includes the removal of the bladder, prostate, seminal vesicles, and distal ureters; in females, RC includes an anterior pelvic exenteration including the bladder, entire urethra and adjacent vagina, uterus, and distal ureters. A procedure sparing the urethra and the urethra-supplying autonomous nerves can be performed in case of a planned orthotopic neobladder. Further technical variations (ie, seminal-sparing or vaginal-sparing techniques) aimed at improving functional outcomes must be weighed against the risk of a positive margin. Laparoscopic surgery is promising, but long-term data are required prior to accepting it as an option equivalent to the open procedure. Lymphadenectomy should remove all lymphatic tissue around the common iliac, external iliac, internal iliac, and obturator region bilaterally. Complications after RC should be reported according to the modified Clavien grading system. In selected patients with MIBC, bladder-preserving therapy with cystectomy reserved for tumor recurrence represents a safe and effective alternative to immediate RC., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: Hospital volume and surgeon volume are each associated with outcomes after complex oncological surgery. However, the interplay between hospital and surgeon volume, and their impact on these outcomes has not been well characterized. We studied the relationship between surgeon and hospital volume, and overall mortality after radical cystectomy., Materials and Methods: The SEER (Surveillance, Epidemiology and End Results)-Medicare linked database was used to identify 7,127 patients with urothelial carcinoma of the bladder who underwent radical cystectomy from 1992 to 2006. Hospital volume and surgeon volume were expressed by tertile. The primary outcome measure was overall survival. Covariates included age, Charlson comorbidity index, stage, grade, node count, node density, number of positive nodes, urinary diversion and year of surgery. Multivariate analyses using generalized linear multilevel models were used to determine the independent association between hospital and surgeon volume and survival., Results: When hospital volume or surgeon volume was included in the multivariate model, a significant volume-survival relationship was observed for each. However, when both were in the model, hospital volume attenuated the impact of surgeon volume on mortality while the significant hospital volume-mortality relationship persisted (HR 1.18, 95% CI 1.08-1.30, p <0.01). In addition, the adjusted 3-year probability of survival was significantly correlated with hospital volume in each distinct surgeon volume stratum while survival was not correlated with surgeon volume in each hospital volume stratum., Conclusions: After adjustment for patient and disease characteristics, the relationship between surgeon volume and survival after radical cystectomy is accounted for by hospital volume. In contrast, hospital volume remained an independent predictor of survival, suggesting that structure and process characteristics of high volume hospitals drive long-term outcomes after radical cystectomy., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Previous studies of the impact of renal cell carcinoma histopathology on survival are conflicting and generally limited to institutional analyses. Thus, we determined the role of renal cell carcinoma histopathology on the stage specific survival rate in a large population based cohort., Materials and Methods: We used the 2000 to 2005 National Cancer Institute SEER (Surveillance, Epidemiology and End Results) database to identify 17,605 patients who underwent surgery for renal cell carcinoma and met study inclusion criteria. Patients were stratified by histological subtype (clear cell, papillary, chromophobe, collecting duct and sarcomatoid differentiation) and pathological stage. We performed Cox proportional hazard modeling and Kaplan-Meier survival analysis to determine overall and cancer specific survival., Results: Patients with papillary and chromophobe pathology were less likely to present with T3 or greater disease (17.6% and 16.9%, respectively) while patients with collecting duct and sarcomatoid variants were more likely to present with T3 or greater disease (55.7% and 82.8%, respectively) compared to those with clear cell histology (p <0.001). On multivariate analysis histology was significantly associated with overall and cancer specific survival. Patients with chromophobe pathology had improved survival (HR 0.56, 95% CI 0.40-0.78) while those with collecting duct and sarcomatoid variants had worse survival (HR 2.07, 95% CI 1.44-2.97 and 2.26, 95% CI 1.93-2.64, respectively)., Conclusions: Renal cell carcinoma histological subtype predicts overall and cancer specific survival. Patients with collecting duct and sarcomatoid variants of renal cell carcinoma have poor survival, even those who present with low stage disease. These data suggest inherent differences in renal cell carcinoma biology and may ultimately form the basis of future histologically targeted therapies., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Despite the increased morbidity and mortality of radical cystectomy in elderly individuals with bladder cancer numerous studies show that surgery can provide a survival benefit. We sought to better identify patients at substantial risk for postoperative mortality., Materials and Methods: We evaluated 220 consecutive patients 75 years old or older treated with radical cystectomy for bladder cancer at a single institution from 2000 to 2008. The analytical cohort comprised 169 patients with complete preoperative data available. A Cox proportional hazards model was used to determine the value of precystectomy clinical information to predict 90-day survival after radical cystectomy. Results were used to create a nomogram predicting the probability of 90-day survival after radical cystectomy. The model was then subjected to 200 bootstrap resamples for internal validation., Results: Of the 220 patients 28 (12.7%) died within 90 days of surgery. Older age (HR 2.30, 95% CI 1.22-4.32) and lower preoperative albumin (HR 2.50, 95% CI 1.40-4.45) were significant predictors of 90-day mortality. We developed a nomogram based on patient age, clinical stage, Charlson comorbidity index and albumin to predict the likelihood of 90-day mortality with 75% accuracy. Internal validation showed a bootstrap adjusted concordance index of 71%., Conclusions: We developed a nomogram that provides individualized risk estimations to predict the probability of 90-day mortality, potentially enhancing preoperative counseling and providing clinicians with an added tool to individualize treatment decisions in this challenging patient population. These data suggest that albumin is a strong predictor of postoperative mortality and show the importance of assessing this variable before surgery., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Pelvic lymph node dissection (PLND) represents the standard for detection of occult pelvic nodal metastases from prostate cancer, and may be performed separately from or at the time of radical prostatectomy. In addition to its potential for diagnostic staging, a PLND may be therapeutic in some patients. However, considerable debate centers on the appropriate candidates for the procedure, the extent and proper boundaries of dissection, optimal surgical approach, and absolute oncologic benefit. Several series suggest that there likely is limited benefit of PLND in low-risk patients and that PLND can be safely omitted in a high percentage of men undergoing contemporary radical prostatectomy. Furthermore, the value of PLND in patients with intermediate- and high-risk disease must be balanced against the potential morbidity of the procedure. In the setting of this debate, concern over morbidity directly attributable to this procedure is of paramount importance. This review focuses on the complications associated with PLND, including lymphocele, thromboembolic events, ureteral injury, nerve injury, vascular injury, and lymphedema.

Purpose of Review: To review the epidemiology, diagnosis, and management of all stages of bladder cancer with an emphasis on studies published within the last year., Recent Findings: Smoking continues to be the most important risk factor for the development of bladder cancer, and this risk has increased over time. Although a number of urinary markers for bladder cancer are now approved by the Food and Drug Administration, there is not enough evidence that any marker can replace surveillance cystoscopy. Management of high-risk patients with nonmuscle-invasive cancer remains a challenge, with continued controversy over which patients may safely be treated with bladder-sparing regimens. Efforts toward developing agents for bacillus Calmette-Guerin-refractory superficial bladder cancer continue, however, none to date have shown high rates of long-term success. In patients undergoing cystectomy, reports using more standardized measures of complications have demonstrated high rates of postoperative morbidity and mortality, particularly in elderly individuals. Robot-assisted radical cystectomy is being more widely studied as a potential approach to decrease operative blood loss and shorten recovery. Although more expensive, increasing evidence suggests that it is well tolerated, does not increase the risk of positive surgical margins, and can achieve similar lymph node counts as open cystectomy in experienced hands and with careful patient selection. Despite level I evidence supporting the use of neoadjuvant chemotherapy, there remains disagreement regarding its use vs. selective adjuvant therapy, given the modest benefits seen with current regimens., Summary: Progress continues in bladder cancer diagnosis and management, and we anticipate that future work will further advance the care of patients with this disease.

Background: Rodent studies show that neurogenesis is necessary for mediating the salutary effects of antidepressants. Nonhuman primate (NHP) studies may bridge important rodent findings to the clinical realm since NHP-depression shares significant homology with human depression and kinetics of primate neurogenesis differ from those in rodents. After demonstrating that antidepressants can stimulate neurogenesis in NHPs, our present study examines whether neurogenesis is required for antidepressant efficacy in NHPs. MATERIALS/METHODOLOGY: Adult female bonnets were randomized to three social pens (N = 6 each). Pen-1 subjects were exposed to control-conditions for 15 weeks with half receiving the antidepressant fluoxetine and the rest receiving saline-placebo. Pen-2 subjects were exposed to 15 weeks of separation-stress with half receiving fluoxetine and half receiving placebo. Pen-3 subjects 2 weeks of irradiation (N = 4) or sham-irradiation (N = 2) and then exposed to 15 weeks of stress and fluoxetine. Dependent measures were weekly behavioral observations and postmortem neurogenesis levels., Results: Exposing NHPs to repeated separation stress resulted in depression-like behaviors (anhedonia and subordinance) accompanied by reduced hippocampal neurogenesis. Treatment with fluoxetine stimulated neurogenesis and prevented the emergence of depression-like behaviors. Ablation of neurogenesis with irradiation abolished the therapeutic effects of fluoxetine. Non-stressed controls had normative behaviors although the fluoxetine-treated controls had higher neurogenesis rates. Across all groups, depression-like behaviors were associated with decreased rates of neurogenesis but this inverse correlation was only significant for new neurons in the anterior dentate gyrus that were at the threshold of completing maturation., Conclusion: We provide evidence that induction of neurogenesis is integral to the therapeutic effects of fluoxetine in NHPs. Given the similarity between monkeys and humans, hippocampal neurogenesis likely plays a similar role in the treatment of clinical depression. Future studies will examine several outstanding questions such as whether neuro-suppression is sufficient for producing depression and whether therapeutic neuroplastic effects of fluoxetine are specific to antidepressants.

Purpose: The recent literature places significant emphasis on decreased pain and length of stay after endoscopic treatment of vesicoureteral reflux compared to historical open ureteroneocystostomy. We documented postoperative pain and outcomes of a contemporary series of minimally invasive ureteral reimplantation., Materials and Methods: For 100 consecutive patients who underwent ureteroneocystostomy we examined the association of the variables patient age, weight, gender, reflux grade, year of surgery, extravesical or intravesical approach and operative time with the outcomes length of hospital stay and pain score (0 to 10), with univariate linear and multivariate regression analyses., Results: Mean patient age was 5.5 years and median followup was 16 months. All patients received ketorolac and acetaminophen with codeine for pain, and early in the series 7 patients received morphine. Average pain scores were mean 1.2, median 0.9 and maximum 3.4. Mean length of stay was 24.4 hours. Multiple regression analyses demonstrated that date of surgery, lower weight, intravesical approach and operative time were independently associated with greater length of stay. A total of 26 patients underwent voiding cystourethrography postoperatively. There was 1 case of recurrent (from bilateral grade V to unilateral grade I) and 1 case of de novo (contralateral grade I) reflux., Conclusions: Open ureteroneocystostomy can be performed in a minimally invasive manner. A small incision combined with administration of ketorolac is associated with a short length of stay and low pain scores. When comparing endoscopic and open treatment of reflux investigators should consider the high success rate and low morbidity of contemporary, minimally invasive open series.

Chronic fatigue syndrome (CFS) is a controversial diagnosis because of the lack of biomarkers for the illness and its symptom overlap with neuropsychiatric, infectious, and rheumatological disorders. We compared lateral ventricular volumes derived from tissue-segmented T(1)-weighted volumetric MRI data and cerebrospinal fluid (CSF) lactate concentrations measured by proton MRS imaging ((1)H MRSI) in 16 subjects with CFS (modified US Centers for Disease Control and Prevention criteria) with those in 14 patients with generalized anxiety disorder (GAD) and in 15 healthy volunteers, matched group-wise for age, sex, body mass index, handedness, and IQ. Mean lateral ventricular lactate concentrations measured by (1)H MRSI in CFS were increased by 297% compared with those in GAD (P < 0.001) and by 348% compared with those in healthy volunteers (P < 0.001), even after controlling for ventricular volume, which did not differ significantly between the groups. Regression analysis revealed that diagnosis accounted for 43% of the variance in ventricular lactate. CFS is associated with significantly raised concentrations of ventricular lactate, potentially consistent with recent evidence of decreased cortical blood flow, secondary mitochondrial dysfunction, and/or oxidative stress abnormalities in the disorder.

Female urethral stricture disease is a rare entity. The most common etiologies are traumatic injury, iatrogenic injury, and inflammatory disease resulting in periurethral fibrosis. Hallmark symptoms are frequency and urgency, and may also be dysuria, hesitancy, slow stream, incontinence, and recurrent urinary tract infections. Female bladder outlet obstruction is a difficult entity to define, and the subset representing stricture disease may also be elusive. The diagnosis of female urethral stricture disease is usually based on symptoms, meatal appearance, and difficult instrumentation of the patient. Other testing, such as urodynamics, voiding urography, or cystoscopy, may be helpful. Treatment options are conservative management with dilatation, endoscopic treatment, or open repair with various tissue flaps or grafts. Considerable controversy surrounds the efficacy of urethral dilatation in women with voiding dysfunction.

Objects placed in the bladder often become encrusted with stone. Using a technique combining endoscopic visualization and a small open cystotomy, a large encrusted foreign body was successfully and safely removed. The combination of endoscopy and cystotomy is rapid, safe, and potentially applicable for the removal of large vesical calculi.