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PDF file - 114K, Supplemental Figure 5 Cellular distribution of HIF-2alpha under normal oxygen conditions. (a) Representative confocal microscopy images (magnification 400x) showing HIF-2α or Nox4 immunofluorescense, DAPI nuclear staining, or merged images. b) Control (NS) or Nox4 shRNA (KD) cells were imaged following exposure to TEMPOL (0.25 mM), DTT (1mM). c) 786-0 NS cells imaged following transduction with Ad-GFP or Ad-MnSOD. d) 786-0 cells expressing pcDNA-Nox4 imaged with or without treatment with TEMPOL (0.25 mM).

PDF file - 376K, Supplemental Figure 2. Characterization of 786-0 cells stably transfected with the human, full-length Nox4 cDNA. (a) Morphology of 786-0 cells following exogenous expression of Nox4 reveals smaller, denser, more-rounded appearance relative to parental 786-0 cells. (b) Cell viability assay. Equal numbers of untransfected cells or 786-0 Nox4 cells were plated in 96-well plates. After attachment, assay reagent was added, incubated at 37{degree sign}C, and the fluorescent signal read at 590 nm.

PDF file - 224K, Supplemental Figure 1. Quantitative RT-PCR (a) and semi-quantitative RT-PCR (b) for detection of Nox1 in 786-0, RCC4 or LNCaP prostate cancer cells using two published primer pairs(14, 17),. Error bar represents +/- SE.

PDF file - 183K, Supplemental Figure 4. Cytotoxicity was measured by CellTiter-Blue (Promega, Madison, WI). 786-0 NS cells were plated at 1 x 104 cells per well in 96-well plates. After 24 hours, dithiothreitol was added as indicated in 5 replicate wells. 20 �l of the CellTiter-Blue reagent was added to each well and viability quantitated by spectrofluorometer (Spectra Max Plus384, Molecular Devices) and expressed as percentage of viability of media-only controls. Error bars indicate +/- S.E. mean.

Most sporadically occurring renal tumors include a functional loss of the tumor suppressor von Hippel Lindau (VHL). Development of VHL-deficient renal cell carcinoma (RCC) relies upon activation of the hypoxia-inducible factor-2α (HIF2α), a master transcriptional regulator of genes that drive diverse processes, including angiogenesis, proliferation, and anaerobic metabolism. In determining the critical functions for HIF2α expression in RCC cells, the NADPH oxidase NOX4 has been identified, but the pathogenic contributions of NOX4 to RCC have not been evaluated directly. Here, we report that NOX4 silencing in VHL-deficient RCC cells abrogates cell branching, invasion, colony formation, and growth in a murine xenograft model RCC. These alterations were phenocopied by treatment of the superoxide scavenger, TEMPOL, or by overexpression of manganese superoxide dismutase or catalase. Notably, NOX4 silencing or superoxide scavenging was sufficient to block nuclear accumulation of HIF2α in RCC cells. Our results offer direct evidence that NOX4 is critical for renal tumorigenesis and they show how NOX4 suppression and VHL re-expression in VHL-deficient RCC cells are genetically synonymous, supporting development of therapeutic regimens aimed at NOX4 blockade. Cancer Res; 74(13); 3501–11. ©2014 AACR.

PDF file - 98K, Supplemental Figure 3. Lucigenin chemiluminescence assay for superoxide detection performed as described in materials and methods on a) isolated membrane fractions from parental 786-0, RCC4 and Caki-1 cells or isolated cell fractions from 786-0 (b) or RCC4 (c) cells. RLU: relative light units.

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PDF file - 446K, Supplemental Figure 6 Immunohistochemistry for Nox4 and HIF-2alpha in 786-0 NS and KD xenograft explants confirms re-expression of Nox4 in KD tumors with corresponding elevated HIF-2alpha expression. Magnification 200X.

Background: Quantifying first ray mobility is crucial to understand aberrant foot biomechanics. A novel device (MAP1st) that can perform measurements of first ray mobility in different weightbearing conditions, foot alignments, and normalization was tested. The reliability of these measurement techniques was assessed in comparison to a handheld ruler considered representative of the common clinical examination. Methods: The study included 25 participants (50 feet). Two independent raters performed baseline, test-retest, and remove-replace measurements of first ray mobility with MAP1st and the handheld device. The effects of non-, partial, and full weightbearing in subtalar joint neutral and the resting calcaneal stance position were assessed. Measurement normalization relative to foot size was also investigated. Intra- and interclass correlation coefficients (ICCs) were calculated for each device between the 2 raters. In addition, Bland-Altman plots were constructed to determine if fixed biases or substantial outliers were present. Results: Similar intrarater ICC values were found for both devices (≥0.85). However, interrater ICC values were substantially improved by MAP1st compared with the handheld device (0.58 vs 0.06). Bland-Altman plots demonstrated biases of 1.27 mm for the handheld ruler, and 2.88 to 0.05 mm and −1.16 to 0.00 for linear and normalized MAP1st measurements, respectively. Improved reliability was achieved with MAP1st for normalized assessments of first ray mobility while the foot was placed in partial- and full-weightbearing resting calcaneal stance positions. Conclusion: MAP1st provided reliable assessments of partial- and full-weightbearing first ray mobility. It should help investigators to explore the potential relationships between first ray function and aberrant foot biomechanics in future research. Level of Evidence: Level II, prospective cohort study.

Subcapsular renal hematoma (SRH) is an infrequent complication of urologic interventions but can lead to serious consequences in patients with a solitary kidney. We present our experience with conservative management of a patient with a solitary kidney and multiple medical comorbidities who developed a SRH and subsequent renal failure after nephroureteral catheter placement. Literature on the management of this unique clinical scenario is limited. Herein, we share our experience with supportive care and temporary dialysis in a medically complex patient whose outcome is complete renal recovery.

Regionalization of complex surgical care results in increasing need for patients to travel for complex oncologic procedures such as cystectomy in bladder cancer. We examined the association between travel distance to a cystectomy center, readmission, and survival.Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we identified bladder cancer patients undergoing radical cystectomy during 2004-2011. Patients were grouped into quartiles of distance to cystectomy center in miles (6 [close], 6-16.9 [moderately close], 17-47.9 [moderately far], ≥ 48 [far]). Multivariable logistic regression, accounting for clustering within hospitals, was used to assess the association between travel distance and readmission. A secondary analysis examined the association between travel distance and survival using multivariable proportional hazard regression.Among 4556 patients who underwent cystectomy, 1857 (41%) were readmitted, and 1251 (67%) of readmissions were to the index hospital. With increasing travel distance there was no significant difference in the overall rate of 90-day readmission. However, the farther a patient traveled, the lower the odds of being readmitted to the index hospital (adjusted odds ratio [95% confidence interval] as follows: moderately close, 0.43 miles [0.29-0.63]; moderately far, 0.14 miles [0.10-0.19]; and far, 0.07 [0.05-0.11]). Increasing travel distance was associated with improved survival.With greater distance traveled to a cystectomy center, rates of readmission to nonindex centers increased. Survival differences may be explained by the impact of travel burden on processes of care and case mix. Future efforts should focus on improving care coordination between index and nonindex hospitals and ensuring equitable access to cystectomy and other critical cancer services.

OBJECTIVE: To characterize the use of multiparametric magnetic resonance imaging (mpMRI) in male Medicare beneficiaries electing active surveillance for prostate cancer. Multi-parametric resonance imaging (mpMRI) has emerged as a tool that may improve risk-stratification and decrease repeated biopsies in men electing active surveillance. However, the extent to which mpMRI has been implemented in active surveillance has not been established. METHODS: Using Surveillance, Epidemiology, and End Results (SEER) registry data linked to Medicare claims data, we identified men with localized prostate cancer diagnosed between 2008–2013 and managed with active surveillance. We classified men into two treatment groups: active surveillance without mpMRI and active surveillance with mpMRI. We then fit a multivariable logistic regression models to examine changing mpMRI utilization over time, and factors associated with the receipt of mpMRI. RESULTS: We identified 9,467 men on active surveillance. Of these, 8,178 (86%) did not receive mpMRI and 1,289 (14%) received mpMRI. The likelihood of receiving mpMRI over the entire study period increased by 3.7% (p=0.004). On multivariable logistic regression, patients who were younger, white, had lower comorbidity burden, lived in the northeast and west, had higher incomes and lived in more urban areas had greater odds of receiving mpMRI (all p

Objectives To describe the rate and determinants of palliative care use amongst Medicare beneficiaries with bladder cancer and encourage a national dialogue on improving coordinated urological, oncological, and palliative care in patients with genitourinary malignancies. Patients and methods Using Surveillance, Epidemiology, and End Results-Medicare data, we identified patients diagnosed with muscle-invasive bladder cancer (MIBC) between 2008 and 2013. Our primary outcome was receipt of palliative care, defined as the presence of a claim submitted by a Hospice and Palliative Medicine subspecialist. We examined determinants of palliative care use using logistic regression analysis. Results Over the study period, 7303 patients were diagnosed with MIBC and 262 (3.6%) received palliative care. Of 2185 patients with advanced bladder cancer, defined as either T4, N+ , or M+ disease, 90 (4.1%) received palliative care. Most patients that received palliative care (>80%, >210/262) did so within 24 months of diagnosis. On multivariable analysis, patients receiving palliative care were more likely to be younger, female, have greater comorbidity, live in the central USA, and have undergone radical cystectomy as opposed to a bladder-sparing approach. The adjusted probability of receiving palliative care did not significantly change over time. Conclusions Palliative care provides a host of benefits for patients with cancer, including improved spirituality, decrease in disease-specific symptoms, and better functional status. However, despite strong evidence for incorporating palliative care into standard oncological care, use in patients with bladder cancer is low at 4%. This study provides a conservative baseline estimate of current palliative care use and should serve as a foundation to further investigate physician-, patient-, and system-level barriers to this care.

Objective To determine the rate and determinants of neoadjuvant chemotherapy noncompletion in patients with muscle-invasive bladder cancer. Methods Using Surveillance, Epidemiology, and End Results-Medicare data, we identified all patients who underwent cystectomy between 2008-2013 and received chemotherapy within 6 months. Of these, 594 patients received neoadjuvant chemotherapy, defined as the presence of a claim for chemotherapy within the 180 days preceding cystectomy. Our primary outcome was noncompletion of neoadjuvant chemotherapy. We determined regimen-specific cut points for noncompletion based on clinical trials and national guidelines. Results Over the study period, 174 of 594 patients (29%) did not complete neoadjuvant chemotherapy. Noncompleters and completers received a median interquartile range of 4.4 (3.0-8.0) and 10.0 (7.7-11.2) weeks of chemotherapy, respectively. A total of 391 (66%) patients received a cisplatin-based regimen and 203 (34%) patients received an alternative regimen, with 27% and 33% not completing chemotherapy, respectively. After adjusting for covariates, age and geographic region were independently associated with failing to complete chemotherapy. Conclusion Nearly 30% of patients who received neoadjuvant chemotherapy did not complete their regimen. Advanced age and nonclinical factors, such as practice patterns in certain geographic regions, may influence a patient's likelihood of successfully completing chemotherapy.

To investigate the association of female sex with the selected treatment for patients with nonmetastatic muscle-invasive bladder cancer. Sex is a known independent predictor of death from bladder cancer. A potential explanation for this survival disparity is difference in treatment pattern and stage presentation among males and females.Using the surveillance, epidemiology, and end results-medicare data set, we identified 6809 patients initially diagnosed with nonmetastatic muscle-invasive bladder cancer between 2004 and 2014. We fit multivariable logistic regression and Cox models to assess the relationship of sex with treatment modality and survival adjusting for differences in patient characteristics.Of the 6809 patients with nonmetastatic muscle invasive bladder cancer, 2528 (37%) received a radical cystectomy while 4281 (63%) received an alternative bladder sparing intervention. Women were significantly more likely to receive a cystectomy (odds ratios [OR] 1.39; 95% confidence intervals [CI] 1.20-1.61), present at an older age with less comorbidities compared to men (P.001). Women were also found to have worse bladder cancer-specific survival (CSS) than men (hazard ratio [HR] 1.18; 95% CI 1.05-1.32), no difference in overall survival (OS) (female HR 0.93; 0.86-1.01) and lower mortality from other causes (HR 0.78; 95% CI 0.70-0.86). There were no differences in OS and CSS by sex in patients with stage pT4a.Female sex predicted more aggressive treatment with radical cystectomy yet worse cancer-specific survival than males. This sex disparity in CSS reduced the known OS advantage observed in women.

BACKGROUND Interactions between industry and prescribers have raised concerns regarding conflicts of interest. To the best of the authors' knowledge, quantitative data measuring these interactions have been limited until recently. In the current study, the authors sought to determine whether an association exists between industry payments and prescriber behavior with regard to abiraterone and enzalutamide. METHODS Two Centers for Medicare and Medicaid Services databases were combined to analyze oncologists and urologists who received industry payments and/or prescribed abiraterone and enzalutamide. Correlation analysis was constructed on prescription count and industry payments. Multivariable median regression examined predictors of change in prescription count per dollar of industry payment. Stratifying prescribers by quantile evaluated threshold effects on prescribers. RESULTS The number of prescriptions was similar between prescribers who did and those who did not receive industry payment for both drugs. The median industry payment amount to prescribers differed between prescribers and nonprescribers for abiraterone ($72 vs $56) and enzalutamide ($59 vs $31). Although no statistical association was found to exist between industry payment amount and prescription count for abiraterone prescribers, an association was found to exist for enzalutamide prescribers (rho = 0.31). A small change was found with regard to prescription count per dollar of industry payment for abiraterone (0.0007 prescriptions) and enzalutamide (0.0006 prescriptions). The amount of industry payment needed to predict one additional prescription was found to be lower in the fourth and fifth quantiles compared with the first through third quantiles. CONCLUSIONS No difference in prescription count was found to exist between prescribers who received industry payments and those who did not. A positive correlation was noted between industry payments and prescription count for enzalutamide. Ease of adoption may affect differences between the 2 drugs. Cancer 2017. © 2017 American Cancer Society.

To evaluate the association of biopsy perineural invasion (PNI) with adverse pathologic findings on radical prostatectomy in patients who would have been candidates for active surveillance (AS).Using a prospectively populated database of 3084 men who underwent open radical prostatectomy, candidates for AS by strict (Johns Hopkins) and expanded (University of Toronto) criteria were identified. The presence of adverse pathologic features at radical prostatectomy was compared between those men with and without biopsy PNI.Of 596 men who met strict criteria for AS, 16 (3%) had biopsy PNI. In the strict AS cohort, there were no differences in adverse pathologic features at radical prostatectomy between those with and without PNI. Of 1197 men who were candidates for AS by expanded criteria, 102 (9%) had biopsy PNI. Men with biopsy PNI in the expanded AS cohort were more likely to have extraprostatic extension (P .001) and pathologic upgrading (P = .01) at prostatectomy. In addition, those with PNI had larger dominant nodules (P .001), and cancer comprised a greater percentage of their prostate glands (P .001). There was no difference in the proportion with a positive margin between the 2 groups (P = .77).Biopsy PNI was rare in patients who met strict criteria for AS. Among those men who met expanded criteria, PNI was associated with adverse pathologic findings upon prostatectomy. The presence of biopsy PNI may have a role in further risk stratifying patients who meet expanded criteria for AS.

Background We use observational methods to compare impact of perioperative chemotherapy timing (ie, neoadjuvant and adjuvant) on overall survival (OS) in muscle-invasive bladder cancer because there is no head-to-head randomized trial, and patient factors may influence decision-making. Patients and Methods Using Surveillance, Epidemiology, and End Results-Medicare data, we identified patients receiving cystectomy for muscle-invasive bladder cancer diagnosed between 2004 and 2013. Patients were classified as receiving neoadjuvant or adjuvant chemotherapy. Propensity of receiving neoadjuvant chemotherapy was determined using gradient boosted models. Inverse probability of treatment weighted survival curves were adjusted for 13 demographic, socioeconomic, temporal, and oncologic covariates. Results We identified 1342 patients who received neoadjuvant (n = 676) or adjuvant chemotherapy (n = 666) with a median follow-up of 23 months (interquartile range, 9-55 months). Inverse probability of treatment weighted adjustment allows comparison of the groups head-to-head as well as counterfactual scenarios (eg, effect if those getting one treatment were to receive the other). The average treatment effect (ie, “head-to-head” comparison) of adjuvant compared with neoadjuvant on OS was not significant (hazard ratio, 1.14; 95% confidence interval, 0.99-1.31). However, the average treatment effect of the treated (ie, the effect if the neoadjuvant patients were to receive adjuvant instead) was associated with a 33% increase in risk of mortality if they were given adjuvant therapy instead (hazard ratio, 1.33; 95% confidence interval, 1.12-1.57). Conclusion Significant treatment selection bias was noted in peri-cystectomy timing, which limits the ability to discriminate differential efficacy of these 2 approaches with observational data. However, patients with higher propensity to receive neoadjuvant therapy were predicted to have increased OS with approach, in keeping with existing paradigms from trial data.

Purpose: To describe the clinical characteristics, treatment patterns, and outcomes in patients with small cell bladder cancer at our institution, including those who received prophylactic cranial irradiation (PCI) for the prevention of intracranial recurrence. Materials and Methods: Patients with small cell bladder cancer treated at a single institution between January 1990 and August 2015 were identified and analyzed retrospectively for demographics, tumor stage, treatment, and overall survival. Results: Of 44 patients diagnosed with small cell bladder cancer, 11 (25%) had metastatic disease at the time of presentation. Treatment included systemic chemotherapy (70%), radical surgery (59%), and local radiation (39%). Six patients (14%) received PCI. Median overall survival was 10 months (IQR 4 – 41). Patients with extensive disease had worse overall survival than those with organ confined disease (8 months vs. 36 months, respectively, p = 0.04). Among those who received PCI, 33% achieved 5 - year survival. Conclusion: Outcomes for patients with small cell bladder cancer remain poor. Further research is indicated to determine if PCI increases overall survival in small call bladder cancer patients, especially those with extensive disease who respond to chemotherapy.

INTRODUCTION AND OBJECTIVES:In the United States, there is significant variation in the aggressiveness and quality of end-of-life care. Up to 50% of Medicare beneficiaries dying with cancer receive...

Introduction The influence of financial ties to pharmaceutical companies remains controversial. We assessed a potential relationship between pharmaceutical payments and prescription patterns for degarelix and denosumab. Methods We compared Medicare Provider Utilization and Payment Data: Physician and Other Supplier PUF (Public Use File) (Medicare B) data containing 2012 claims with data on Open Payments (Physician Payments Sunshine Act) for the second half of 2013. Urologists and medical oncologists who billed Medicare for degarelix or denosumab were cross referenced in both databases and payments were aggregated into a consolidated data set. Adjusted beneficiary count and total Medicare reimbursement were compared according to the receipt of Sunshine payment. An association between Sunshine payment amount and total Medicare reimbursement was also assessed. Results Of the 160 prescribers of degarelix and 1,507 prescribers of denosumab 91 (57%) and 854 (57%), respectively, received Sunshine payment. Degarelix prescribers who received Sunshine payment had higher median total Medicare reimbursement ($13,257 vs $9,554, p = 0.01). Denosumab prescribers who received Sunshine payment had higher median adjusted beneficiary count (55 vs 50, p Conclusions In the case of degarelix and denosumab there is a weak association between pharmaceutical company payments and prescriber prescription behavior patterns.

Objective To determine the association of statin use with oncological outcomes and risk of pathologic upgrading following radical prostatectomy. Materials and Methods Using a prospectively populated database of 3042 men who underwent open radical prostatectomy, patients were grouped according to reported statin use at the time of surgery. The primary outcome was time to biochemical recurrence. The secondary outcome was risk of pathologic upgrading among a subset of 1256 patients with Gleason pattern 3 + 3 = 6 on biopsy. A multivariable Cox model was used to assess risk of biochemical recurrence, and multivariable logistic regression was used to assess risk of pathologic upgrading. Results Eight hundred twenty-four men (27%) reported statin use at the time of radical prostatectomy. Statin users were older and had higher body mass index, higher Charlson Comorbidity Index, and lower pretreatment prostate-specific antigen values than statin nonusers. Over a median follow-up of 70 months (interquartile range: 36-107), a total of 455 men (15%) experienced biochemical recurrence. Statin use was not associated with biochemical recurrence (adjusted hazard ratio: 1.06, 95% confidence interval: 0.86-1.31). Of those men with biopsy Gleason 3 + 3 = 6 disease, 647 (52%) were upgraded to higher grade disease following radical prostatectomy; however, statin use was not associated with pathologic upgrading (adjusted odds ratio: 0.78, 95% confidence interval: 0.58-1.04). Conclusion Preoperative statin use at the time of radical prostatectomy was not associated with biochemical recurrence or risk of pathologic upgrading in this cohort. These data add to the existing body of literature suggesting that statin use is not associated with more favorable clinical outcomes following radical prostatectomy.

OBJECTIVE To quantify the use of downstream studies following staging bone scans in patients with muscle-invasive bladder cancer. Bone scans may be obtained in high-risk bladder cancer patients prior to radical cystectomy to exclude bone metastases. However, false-positive bone scans can occur, resulting in the need for additional studies. PATIENTS AND METHODS Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we identified 4404 patients diagnosed with muscle-invasive bladder cancer from 2004 to 2011. We further identified those who underwent a bone scan prior to treatment within 6 months of diagnosis and prior to any treatment with cystectomy, radiotherapy, or chemotherapy. We determined the proportion of patients who underwent a subsequent study (bone X-ray, bone CT, bone MRI, and/or bone biopsy) within 3 months of the bone scan and prior to treatment. RESULTS Among patients diagnosed with muscle-invasive bladder cancer, 1373 (31%) had a staging bone scan of whom 26% received a downstream study (n = 213). Overall, 61 patients (7%) received downstream bone-specific X-rays, more than 141 patients (>17%) received bone-specific CTs, and 28 patients (3%) received bone-specific MRIs. The use of bone biopsy was rare (n < 11

Contemporary guidelines recommend cystectomy with neoadjuvant or adjuvant cisplatin-based chemotherapy given with curative intent for patients with resectable muscle-invasive bladder cancer (MIBC). However, rates and appropriateness of perioperative chemotherapy utilization remain unclear. We therefore sought to characterize use of perioperative chemotherapy in older radical cystectomy MIBC patients and examine factors associated with use.Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we identified patients with MIBC diagnosed between 2004 and 2013 and treated with radical cystectomy. We classified patients into 3 treatment groups: cystectomy alone, neoadjuvant, or adjuvant chemotherapy. Chemotherapy was classified by regimen. We then fit a multinomial multivariable logistic regression model to assess association between patient factors with the receipt of each treatment.We identified 3,826 eligible patients. The majority (484; 65%) received cystectomy alone. Neoadjuvant (676; 18% overall, 69% cisplatin-based), and adjuvant chemotherapy (666, 17% overall, 55% cisplatin-based) were used in similar proportions of cystectomy patients. Over the study period, the odds of receiving adjuvant chemotherapy decreased by 7.5%, whereas neoadjuvant therapy increased by 27.5% (both P0.001). There was an increase in use of cisplatin-based regimens in the neoadjuvant setting (35 to 72%, P0.001), but not the adjuvant setting. Female gender, lower comorbidity, married status, and lower stage disease were associated with greater odds of receiving neoadjuvant chemotherapy (all P0.05).From 2004 to 2013 use of neoadjuvant chemotherapy for MIBC increased while use of adjuvant chemotherapy decreased. Future studies examining barriers to appropriate chemotherapy use, and the comparative effectiveness of neoadjuvant versus adjuvant chemotherapy are warranted.

Multimodal analgesia is an effective way to control pain and limit opioid use after surgery. The quadratus lumborum block and paravertebral block are two regional anesthesia techniques that leverage multimodal analgesia to improve postoperative pain control. We sought to compare the efficacy of these blocks for pain management following radical cystectomy.We performed a retrospective review of radical cystectomy patients who received bilateral continuous paravertebral blocks (n = 125) or bilateral single shot quadratus lumborum blocks (n = 50) between 2014-2016. The primary outcome was postoperative opiate consumption on day 0. Secondary outcomes included self-reported pain scores and hospital length of stay.Quadratus lumborum block patients had similar opioid use on postoperative day 0 compared with paravertebral block patients (29 mg versus 30 mg, p = 0.90). Pain scores on postoperative day 0 were similar between quadratus lumborum block and paravertebral block groups (4.0 versus 3.8, p = 0.72); however, the paravertebral block group had lower pain scores on days 1-3 compared with the quadratus lumborum block group (all p0.05). Hospital length of stay was similar between groups (6.6 days versus 6.2 days, p = 0.41).There were no differences in opioid consumption among patients receiving bilateral single shot quadratus lumborum blocks and bilateral continuous paravertebral blocks after radical cystectomy. These data suggest that the quadratus lumborum block is a viable alternative for delivering multimodal analgesia in cystectomy patients.

Background and Objectives To evaluate whether urologic procedures during cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) are associated with adverse postoperative outcomes. Methods We identified patients who underwent CRS-HIPEC at our institution from 2001 to 2012 and compared outcomes between operations that did and did not include a urologic procedure. Results A total of 938 CRS-HIPEC procedures were performed, 71 of which included a urologic intervention. Urologic interventions were associated with longer operative times (547 vs. 459 min, P

The obese patient undergoing radical cystectomy faces a unique set of challenges. We present the case of a 68-year-old gentleman who presented to our institution with Bacillus Calmette-Guerin refractory disease, a body mass index of 38.5, and a large pannus. The present paper describes our technique for performing radical cystectomy with ileal conduit urinary diversion and concomitant panniculectomy. We discuss the impact of obesity on patients undergoing radical cystectomy and how this may be mitigated by panniculectomy.

To determine whether transfusion using the Cell Saver system is associated with inferior outcomes in patients undergoing open partial nephrectomy.All patients who underwent open partial nephrectomy by a single surgeon (BJD) from August 2008 to April 2015 were retrospectively identified. Operations were grouped and compared according to whether they included a transfusion using the Cell Saver intraoperative cell salvage system.Sixty-nine open partial nephrectomies in 67 patients were identified. Thirty-three procedures (48%) included a Cell Saver transfusion. Most tumors were clear cell renal cell carcinoma (62%) and stage T1a (68%). There were no significant differences between groups for any measured clinical or pathologic characteristics. Operations including a Cell Saver transfusion were longer (141 vs 108 minutes, P .001), had significantly greater blood loss (600 vs 200 mL, P .001), and had longer median renal ischemia times (15 vs 10 minutes, P = .03). There were no significant differences in postoperative complication rate (21% vs 17%, P = .83) or median length of hospital stay (3 vs 3 days, P = .09). At a median follow-up of 23 months (interquartile range: 8-42 months), 1 patient in the non-Cell Saver transfusion group had cancer recurrence. There was no metastatic progression or cancer-specific mortality in either group.Cell Saver transfusion during open partial nephrectomy was not associated with inferior outcomes with short-term follow-up, and no patients developed metastatic disease.

Background Recent studies suggest that anesthetic technique during radical prostatectomy for prostate cancer may affect recurrence or progression. This association has previously been investigated in series that employ epidural analgesia. The objective of this study is to determine the association between the use of a multimodal analgesic approach incorporating paravertebral blocks and risk of biochemical recurrence following open radical prostatectomy. Patients and methods Using a prospective database of 3,029 men undergoing open radical prostatectomy by a single surgeon, we identified 2,909 men who received no neoadjuvant androgen deprivation and had at least 1 year of follow up. We retrospectively compared patients who received general analgesia with opioid analgesia (1999–2003, n = 662) to those who received general analgesia with multimodal analgesia incorporating paravertebral blocks (2003–2014, n = 2,247). The primary outcome was time to biochemical recurrence. Biochemical recurrence-free interval was assessed using the Kaplan-Meier technique and compared using a multivariate Cox-proportional hazards regression model. Results In total, 395 patients (14%) experienced biochemical recurrence following radical prostatectomy, including 265 (12%) who received multimodal analgesia and 130 (20%) who did not (adjusted P = 0.27). After adjusting for age, race, body mass index, preoperative prostate specific antigen, grade, stage, perineural invasion, margin status, percent of tumor in the gland, and diameter of the dominant nodule, there was no difference in recurrence-free interval between groups (HR = 0.92, 95% CI: 0.73–1.17). Conclusion Use of a multimodal analgesic approach incorporating paravertebral blocks is not associated with a reduced risk of biochemical recurrence following radical prostatectomy.

To investigate the use of a high-arginine immunonutrient supplement prior to radical cystectomy for bladder cancer.We recruited 40 patients to consume a total of four high-arginine immunonutrient shakes per day for 5 days prior to radical cystectomy. The primary outcome measures were safety, tolerability and adherence to the supplementation regimen. Ninety-day postoperative outcomes were also compared between supplemented patients and a cohort of 104 prospectively identified non-supplemented radical cystectomy patients. Multivariable logistic regression models were used to compare overall complications, infectious complications, and readmission rates between groups.There were no serious adverse events during supplementation. Four patients (10%) stopped supplementation due to nausea (n = 2) and bloating (n = 2). Thirty-three patients (83%) consumed all prescribed shakes. Immunonutrient supplementation was not significantly associated with overall complications (adjusted odds ratio [OR] 1.08; 95% confidence interval [CI] 0.50-2.33), infectious complications (OR 1.23; 95% CI 0.49-3.07), or readmissions (OR 1.48; 95% CI 0.62-3.51) on multivariable analyses.Preoperative supplementation with a high-arginine immunonutrient shake was safe and well tolerated prior to radical cystectomy. Contrary to prior reports, immunonutrient supplementation was not associated with lower postoperative infectious complications in this cohort, perhaps owing to the 5 day supplementation period. Further study is needed to identify the optimal immunonutrient supplement regimen for radical cystectomy patients.

The incidence of kidney cancer has steadily increased over recent decades, with the majority of new cases now found when lesions are asymptomatic and small. This downward stage migration, in part, relates to the increasing use of abdominal imaging. Three public health epidemics—smoking, hypertension, and obesity—also play a role in the increasing incidence of the disease. Treatment of kidney cancer has mirrored the rise in incidence, with increasing interest in nephron-sparing therapies. Despite earlier detection and increasing treatment, the mortality rate of kidney cancer has not decreased. This treatment disconnect phenomenon highlights the need to decrease unnecessary treatment of indolent tumors and address modifiable risk factors, which may ultimately reduce kidney cancer incidence and mortality.

Interactions between industry and prescribers have raised concerns regarding conflicts of interest. To the best of the authors' knowledge, quantitative data measuring these interactions have been limited until recently. In the current study, the authors sought to determine whether an association exists between industry payments and prescriber behavior with regard to abiraterone and enzalutamide.Two Centers for Medicare and Medicaid Services databases were combined to analyze oncologists and urologists who received industry payments and/or prescribed abiraterone and enzalutamide. Correlation analysis was constructed on prescription count and industry payments. Multivariable median regression examined predictors of change in prescription count per dollar of industry payment. Stratifying prescribers by quantile evaluated threshold effects on prescribers.The number of prescriptions was similar between prescribers who did and those who did not receive industry payment for both drugs. The median industry payment amount to prescribers differed between prescribers and nonprescribers for abiraterone ($72 vs $56) and enzalutamide ($59 vs $31). Although no statistical association was found to exist between industry payment amount and prescription count for abiraterone prescribers, an association was found to exist for enzalutamide prescribers (rho = 0.31). A small change was found with regard to prescription count per dollar of industry payment for abiraterone (0.0007 prescriptions) and enzalutamide (0.0006 prescriptions). The amount of industry payment needed to predict one additional prescription was found to be lower in the fourth and fifth quantiles compared with the first through third quantiles.No difference in prescription count was found to exist between prescribers who received industry payments and those who did not. A positive correlation was noted between industry payments and prescription count for enzalutamide. Ease of adoption may affect differences between the 2 drugs. Cancer 2017;123:4356-62. © 2017 American Cancer Society.

To examine factors associated with bone scan use in patients undergoing radical cystectomy and to assess trends in use over time.Using Surveillance, Epidemiology, and End Results-Medicare data, we identified 5573 patients who underwent radical cystectomy from 2004 to 2011. The primary outcome was completion of a bone scan within 6 months prior to surgery. Demographic, regional, and clinicopathologic predictors of bone scan use were examined using a mixed logit model with health service area as a random effect.Among radical cystectomy patients, 1754 (31%) completed a preoperative bone scan. Urologists ordered most of these studies (69%). The adjusted probability of a patient undergoing a bone scan decreased from 0.40 in 2004 to 0.29 in 2011 (P = .01). Compared with patients in the northeast region, those in the south, central, and west regions were less likely to have a bone scan (P .001). Compared with those with stage ≤T1, patients with higher stage disease were more likely to have a bone scan (P .001). Among the highest volume surgeons, there was significant variation in the proportion of patients who completed preoperative bone scans (P .001).Despite a recent decline, bone scans are used frequently in the preoperative staging of bladder cancer. Although some clinical factors are associated with bone scan use, significant regional and provider variation suggest areas to improve standardization of practice.

Most sporadically occurring renal tumors include a functional loss of the tumor suppressor von Hippel Lindau (VHL). Development of VHL-deficient renal cell carcinoma (RCC) relies upon activation of the hypoxia-inducible factor-2α (HIF2α), a master transcriptional regulator of genes that drive diverse processes, including angiogenesis, proliferation, and anaerobic metabolism. In determining the critical functions for HIF2α expression in RCC cells, the NADPH oxidase NOX4 has been identified, but the pathogenic contributions of NOX4 to RCC have not been evaluated directly. Here, we report that NOX4 silencing in VHL-deficient RCC cells abrogates cell branching, invasion, colony formation, and growth in a murine xenograft model RCC. These alterations were phenocopied by treatment of the superoxide scavenger, TEMPOL, or by overexpression of manganese superoxide dismutase or catalase. Notably, NOX4 silencing or superoxide scavenging was sufficient to block nuclear accumulation of HIF2α in RCC cells. Our results offer direct evidence that NOX4 is critical for renal tumorigenesis and they show how NOX4 suppression and VHL re-expression in VHL-deficient RCC cells are genetically synonymous, supporting development of therapeutic regimens aimed at NOX4 blockade. Cancer Res; 74(13); 3501–11. ©2014 AACR.

Cowper's gland syringoceles are rare cystic dilations of the Cowper's gland duct. They are typically diagnosed in childhood but occasionally occur in adults. We report the case of a 28-year-old man who presented with a painful perineal and inferior scrotal mass and was found to have a large Cowper's gland syringocele extending into the scrotum associated with a scrotal abscess. Treatment consisted of surgical excision. The magnetic resonance imaging findings of this case are described.

Laparoscopic pyeloplasty and open pyeloplasty have comparable efficacy for ureteropelvic junction obstruction in pediatric patients. The role of laparoscopic pyeloplasty in infants is less well defined. We present our updated experience with laparoscopic pyeloplasty in children younger than 1 year.We retrospectively reviewed the records of all 29 infants treated with transperitoneal laparoscopic pyeloplasty for symptomatic and/or radiographic ureteropelvic junction obstruction from May 2005 to February 2012. Patients were followed with renal ultrasound at regular intervals. Treatment failure was defined as the inability to complete the intended procedure, persistent radiographic evidence of obstruction and/or the need for definitive adjunctive procedures.Transperitoneal laparoscopic pyeloplasty was performed in 29 infants 2 to 11 months old (mean age 6.0 months) weighing 4.1 to 10.9 kg (mean ± SD 7.9 ± 1.6). Followup was available in all except 5 patients (median 13.9 months, IQR 7.7-23.8). Mean operative time was 245 ± 44 minutes. All cases were completed laparoscopically. Three postoperative complications were reported, including ileus, superficial wound infection and pyelonephritis. Two patients had persistent symptomatic and/or radiographic evidence of obstruction, and required reoperative pyeloplasty. The overall success rate was 92%.Laparoscopic pyeloplasty in infants remains a technically challenging procedure limited to select centers. Our early experience revealed a success rate comparable to that of other treatment modalities with minimal morbidity.

Up to 25% of men with prostate cancer who undergo radical prostatectomy will recur. In this setting, salvage radiotherapy may cure patients with local recurrence, but is unable to cure those with occult metastatic disease. The objective of this study is to examine how prostate-specific antigen (PSA) response to radiotherapy predicts subsequent disease progression and survival.Using a prospectively populated database of 3089 men who underwent open radical prostatectomy, 212 patients (7%) were identified who received early salvage radiotherapy for biochemical recurrence. The main outcome was time to disease progression after salvage radiotherapy. Patients were stratified by PSA response after radiotherapy: 1) PSA0.1 ng/mL, 2) persistently detectable PSA, and 3) rising PSA.Patients received salvage radiotherapy at a median PSA of 0.20 ng/mL (IQR 0.10-0.30 ng/mL). At a median follow up of 47.3 months, a total of 52 (25%) patients experienced disease progression. On multivariable analysis, both persistent PSA (HR 5.12; 95% CI 1.98-13.23) and rising PSA (HR 16.55; 95% CI 6.61-41.48) were associated with increased risk of disease progression compared to those with PSA0.1 ng/mL after adjusting for pre-radiotherapy PSA, Gleason score, margin status, stage, and time to radiotherapy. Only rising PSA was associated with an increased risk of cancer-specific and all-cause mortality.PSA response is associated with the risk of disease progression following salvage radiotherapy. This information can be used to counsel patients on the potential need for additional therapy and identify those at greatest risk for progression and cancer-related mortality.

Introduction Payments to practitioners from drug and device manufacturers or group purchasing organizations are reported in the Centers for Medicare and Medicaid Services (CMS) databases as a part of the Sunshine Act. Characterizing these payments is a necessary step in identifying conflicts of interest and the influence of payments on practice patterns, if any. Payments have never been analyzed in detail among urologists. Methods We reviewed the most recent CMS Open Payments database for the full year 2014, released on June 30, 2015. Urology practitioners were extracted and the database was analyzed for number of total payments, total dollar value of payments, mean, median and number of physicians, number of manufacturers, and number of drugs/biologicals. Data were further categorized according to provider specialty, form of payment, nature of payment, practitioner ownership and dispute status. Results Payments totaled $32,450,382. Practitioner payments were unevenly distributed, with a median payment of $15. The majority of payments were in the form of food and beverage. Female pelvic medicine practitioners received the highest payments out of the provider specialties. The largest categorical difference from the median was in the form of stock, options and other ownership interests ($24,050). Ownership status and disputed payments were associated with payment values above median values ($400 and $61, respectively). Conclusions There are major disparities in industry payments to urology practitioners. Whether this influences practice patterns remains to be seen, although identifying categorical differences in payments is an important first step in the process.

Percutaneous renal biopsy (PRB) is a safe and effective modality for sampling kidney tissue. In limited circumstances, alternative methods for kidney biopsy may be indicated. Historical contraindications for PRB such as bleeding diathesis, morbid obesity and solitary kidney have been called into question in the literature. We present a review of the literature on PRB and the risks and benefits associated with alternatives.A review of the literature was performed through MEDLINE and PubMed. A total of 726 articles exist under the query, "percutaneous renal biopsy." Large series describing indications, contraindications, procedural methods, and complications were extracted. To further investigate the risks of percutaneous renal biopsy on solitary kidneys, the literature on percutaneous nephrolithotomy (PCNL) and biopsy of transplant kidneys were queried. Summaries of the data were compiled and synthesized in the body of the text.Percutaneous renal biopsy is safe and effective in the majority of kidney units for the evaluation of medical renal disease. Rates of bleeding range from 0.3%-7.4%, and nephrectomy rates are exceedingly low (0.1%-0.5%). Bleeding rates in open and laparoscopic approaches are comparable and range from 0%-7.0%, with major complications ranging from 0%-6.1%.The successes of percutaneous methods have called into question traditional contraindications such as solitary kidney, bleeding diathesis, and morbid obesity. In limited cases, alternative methods may be appropriate. We present a review of the literature for the various approaches and their associated complication rates.

Horseshoe kidney is the most common congenital renal fusion anomaly, with an estimated incidence of 1.7 to 2.5 cases per 1000 live births. In these patients, nephron-sparing surgical management of renal tumors may be complicated by abnormal renal location, aberrant vasculature, and the presence of a renal isthmus. We present the largest known series of patients with renal malignancy in horseshoe kidneys managed by partial or hemi-nephrectomy with associated outcomes.A retrospective review of our institution's electronic medical record was conducted to identify consecutive cases over an 11 year period. Pediatric patients and those who underwent surgery for benign indications were excluded from analysis.Eight patients with horseshoe kidney who underwent partial or hemi-nephrectomy for renal malignancy were identified. Median tumor size was 6.0 cm (IQR 3.7 cm-9.5 cm). Six patients had clear cell renal cell carcinoma (RCC), 1 patient had papillary RCC, and 1 patient had a renal carcinoid tumor with concurrent adenocarcinoma. Median length of stay was 4 days (IQR 2-.5.5 days). Median perioperative change in eGFR was -6 mL/min/1.73² (IQR -2.6-8.6 mL/min/1.73m²). One patient developed postoperative urine leak requiring percutaneous drainage and ureteral stent placement. Median follow up was 38.5 months, with a cancer-specific survival of 87.5% and an overall survival of 62.5%.Partial and hemi-nephrectomy for renal malignancy can safely be performed in patients with horseshoe kidney with acceptable operative and oncologic outcomes.

The term sustainability covers a broad set of issues. As a result, each organization has to identify specific issues that it can effectively address and that are relevant to its industries, markets, geographic locations, and stakeholders. But if an organization fails to focus on a reasonable number of organization-wide commitments, resources will be scattered and fail to yield significant value to the company. This article provides advice on how to deploy sustainability using change management techniques and examples from industry. © 2012 Wiley Periodicals, Inc.

Dancers frequently present with hip pain. The etiology of this pathology has not been clearly identified from an anatomical perspective. Structural variations including hip dysplasia and dynamic variables from the foot to the pelvis will be discussed. Understanding the etiology as a structural entity, neuromuscular entity or a combination of the two, allows for a successful rehabilitative process and a successful return to dance. This article describes the possible correlation between hip dysplasia and hip pain in the dancer, the relationship of dance postures to the kinematic chain and outlines possible treatment strategies for management.

The translational diffusion constant, D , has been measured for each of the 1-alkenes 1-C 6 H 12 , 1-C 8 H 16 , 1-C 12 H 24 , and 1-C 14 H 28 in each of the even n -alkanes n -C 6 H 14 – n -C 14 H 30 ; the D values have also been measured for 1-C 10 H 20 in each of the even n -alkanes n -C 8 H 18 – n -C 14 H 30 . Cyclohexene has been studied in each of the even n -alkanes n -C 8 H 18 – n -C 14 H 30 and cyclohexane. Deviations from the Stokes–Einstein (SE) relation ( D = k B T /6 πηr ) were found. For a given solute, the hydrodynamic radius r decreased as the viscosity η increased. Analyses of literature data for n -alkane solutes in n -alkane solvents, including self-diffusion, also gave values of r that decreased as η increased. These solvent-dependent r values are discussed in terms of the relative sizes of the solutes and solvents. The data also were analyzed using D / T = A / η p ( p = 1 for the SE relation). The p values for the 1-alkenes and the n -alkane solutes with six or more carbon atoms were all p values for the analogous n -alkane solutes were roughly the same and indicated that the similar shapes and polarities of the two types of hydrocarbon play key roles in determining their diffusion. In the n -alkane solvents, the p value of the more globular cyclohexene is somewhat larger than those of both 1-hexene and n -hexane.

Pure Gleason 3 + 3 = 6 prostate cancer lacks many of the established hallmarks of malignancy at the molecular level. In patients undergoing radical prostatectomy with Gleason 6 disease on final pathology, the likelihood of synchronous metastatic disease is extremely low as is the risk of recurrence. While contemporary active surveillance series emphasize an indolent disease course for patients with Gleason 6 disease, they also highlight the undersampling and undergrading associated with current biopsy techniques. Calling Gleason 3 + 3 = 6 something other than cancer may decrease anxiety and overtreatment of clinically insignificant disease; however, diagnostic shortcomings have limited widespread enthusiasm for a shift in nomenclature.