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Objective: Guidelines for muscle-invasive bladder cancer (MIBC) recommend that patients receive neoadjuvant chemotherapy with radical cystectomy as treatment over radical cystectomy alone. Though trends and practice patterns of MIBC have been defined using the National Cancer Database, data using the Surveillance, Epidemiology, and End Results (SEER) program have been poorly described., Methods: Using the SEER database, we collected data of MIBC according to the American Joint Commission on Cancer. We considered differences in patient demographics and tumor characteristics based on three treatment groups: chemotherapy (both adjuvant and neoadjuvant) with radical cystectomy, radical cystectomy, and chemoradiotherapy. Multinomial logistic regression was performed to compare likelihood ratios. Temporal trends were included for each treatment group. Kaplan-Meier curves were performed to compare cause-specific survival. A Cox proportional-hazards model was utilized to describe predictors of survival., Results: Of 16 728 patients, 10 468 patients received radical cystectomy alone, 3236 received chemotherapy with radical cystectomy, and 3024 received chemoradiotherapy. Patients who received chemoradiotherapy over radical cystectomy were older and more likely to be African American; stage III patients tended to be divorced. Patients who received chemotherapy with radical cystectomy tended to be males; stage II patients were less likely to be Asian than Caucasian. Stage III patients were less likely to receive chemoradiotherapy as a treatment option than stage II. Chemotherapy with radical cystectomy and chemoradiotherapy are both underutilized treatment options, though increasingly utilized. Kaplan-Meier survival curves showed significant differences between stage II and III tumors at each interval. A Cox proportional-hazards model showed differences in gender, tumor stage, treatment modality, age, and marital status., Conclusion: Radical cystectomy alone is still the most commonly used treatment for muscle-invasive bladder cancer based on temporal trends. Significant disparities exist in those who receive radical cystectomy over chemoradiotherapy for treatment., Competing Interests: The authors declare no conflict of interest., (© 2021 Editorial Office of Asian Journal of Urology. Production and hosting by Elsevier B.V.)

Purpose: Following surgery for nonmetastatic renal cell carcinoma with tumor thrombus the risk of recurrence is significant but variable among patients. The purpose of this study was to develop and validate a predictive nomogram for individual estimation of recurrence risk following surgery for renal cell carcinoma with venous tumor thrombus., Materials and Methods: Comprehensive data were collected on patients with nonmetastatic renal cell carcinoma and thrombus treated at a total of 5 institutions from 2000 to 2013. Independent predictors of recurrent renal cell carcinoma from a competing risks analysis were developed into a nomogram. Predictive accuracy was compared between the development and validation cohorts, and between the nomogram and the UISS (UCLA Integrated Staging System, SSIGN (Stage, Size, Grade and Necrosis) and Sorbellini models., Results: A total of 636 patients were analyzed, including the development cohort of 465 and the validation cohort of 171. Independent predictors, including tumor diameter, body mass index, preoperative hemoglobin less than the lower limit of normal, thrombus level, perinephric fat invasion and nonclear cell histology, were developed into a nomogram. Estimated 5-year recurrence-free survival was 49% overall. Five-year recurrence-free survival in patients with 0, 1, 2 and more than 2 risk factors was 77%, 53%, 47% and 20%, respectively. Predictive accuracy was similar in the development and validation cohorts (AUC 0.726 and 0.724, respectively). Predictive accuracy of the thrombus nomogram was higher than that of the UISS (AUC 0.726 vs 0.595, p = 0.001), SSIGN (AUC 0.713 vs 0.612, p = 0.04) and Sorbellini models (AUC 0.709 vs 0.638, p = 0.02)., Conclusions: We present a predictive nomogram for postoperative recurrence in patients with nonmetastatic renal cell carcinoma with venous thrombus. Improving individual postoperative risk assessment may allow for better design and analysis of future adjuvant clinical trials., (Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Loss of imprinting (LOI) is an epigenetic event that relaxes an allele-specific restriction on gene expression. One gene that experiences LOI is the paracrine insulin-like growth factor IGF2 , which occurs commonly in human prostate tissues during aging and tumorigenesis. However, the relationship between IGF2 LOI and prostate tumorigenesis has not been established functionally. In this study, we created a mouse model with CTCF-binding site mutations at the Igf2-H19 imprint control region that abolishes CTCF insulator activity, resulting in biallelic Igf2 expression that mimics increased levels seen with aging-induced LOI. We found that Igf2 LOI increased the prevalence and severity of prostatic intraepithelial neoplasia (PIN), a premalignant lesion. Engineering Nkx3.1 deficiency into our model increased the frequency of PIN lesions in an additive fashion. Prostates harboring LOI displayed increased MAPK signaling and epithelial proliferation. In human prostate tissue arrays, we documented a positive correlation in benign tissues of IGF2 levels with phospho-ERK and phospho-AKT levels. Overall, our results establish that Igf2 LOI is sufficient on its own to increase rates of neoplastic development in the prostate by upregulating critical cancer-associated signaling pathways. Cancer Res; 77(19); 5236-47. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Objective: To evaluate if moderate chronic kidney disease [CKD; estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m 2 ] is associated with high rates of non-muscle-invasive bladder cancer (NMIBC) recurrence or progression., Patients and Methods: A multi-institutional database identified patients with serum creatinine values prior to first transurethral resection of bladder tumour (TURBT). The CKD-epidemiology collaboration formula calculated patient eGFR. Cox proportional hazards models evaluated associations with recurrence-free (RFS) and progression-free survival (PFS)., Results: In all, 727 patients were identified with a median (interquartile range [IQR]) patient age of 69.8 (60.1-77.6) years. Data for eGFR were available for 632 patients. During a median (IQR) follow-up of 3.7 (1.5-6.5) years, 400 (55%) patients had recurrence and 145 (19.9%) patients had progression of tumour stage or grade. Moderate or severe CKD was identified in 183 patients according to eGFR. Multivariable analysis identified an eGFR of <60 mL/min/1.73 m 2 (hazard ratio [HR] 1.5, 95% confidence interval [CI]: 1.2-1.9; P = 0.002) as a predictor of tumour recurrence. The 5-year RFS rate was 46% for patients with an eGFR of ≥60 mL/min/1.73 m 2 and 27% for patients with an eGFR of <60 mL/min/1.73 m 2 (P < 0.001). Multivariable analysis showed that an eGFR of <60 mL/min/1.73 m 2 (HR 3.7, 95% CI: 1.75-7.94; P = 0.001) was associated with progression to muscle-invasive disease. The 5-year PFS rate was 83% for patients with an eGFR of ≥60 mL/min/1.73 m 2 and 71% for patients with an eGFR of <60 mL/min/1.73 m 2 (P = 0.01)., Conclusion: Moderate CKD at first TURBT is associated with reduced RFS and PFS. Patients with reduced renal function should be considered for increased surveillance., (© 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.)

Although surgical excision is the standard of therapy for small renal masses (SRMs), there is a growing recognition of active surveillance as an option in select patients who are poor surgical candidates or who have shorter life expectancy. A number of patients on expectant management, however, subsequently advance to definitive therapy. In this study, we systematically reviewed the literature and performed a pooled analysis of active surveillance series to evaluate the rate and indications for definitive treatment after initiating a period of active surveillance. Fourteen clinical series (1245 patients; 1364 lesions) met our selection criteria. Mean lesion size at presentation was 2.30 ± 0.40 cm with a mean follow-up of 33.6 ± 16.9 months. Collectively, 34.0% of patients underwent delayed intervention, which ranged in individual series from 3.6% to 70.3%. Of patients undergoing delayed intervention, the average time on active surveillance prior to definitive treatment was 27.8 ± 10.6 months. A pooled analysis revealed that 41.0% of patients underwent therapy secondary to tumor growth rate and 51.9% secondary to patient or physician preference in the absence of clinical progression. Overall, 1.1% of all patients progressed to metastatic disease during the average follow-up period. Thus, active surveillance may be an appropriate option for carefully selected patients with SRMs. However, delayed treatment is pursued in a significant percentage of patients within 3 years. Prospective registries and clinical trials with standardized indications for delayed intervention are needed to establish true rates of disease progressions and recommendations for delayed intervention.

Introduction: A significant proportion of patients that fail active surveillance (AS) for prostate cancer management do so because of cancer upgrading. A previously validated upgrading nomogram generates a score that predicts risk of biopsy Gleason 6 upgrading following radical prostatectomy in lower-risk populations that are candidates for Active Surveillance (Cancer, 2013)., Objectives: We hypothesize that the upgrading risk (UR) score generated by this nomogram at diagnosis improves the ability to predict patients that will subsequently fail AS., Methods: To evaluate the nomogram, retrospective data from several institutional cohorts of patients who met AS criteria, group 1 (n = 75) and group 2 (n = 1230), were independently examined. A UR score was generated using the coefficients from the nomogram consisting of PSA density (PSAD), BMI, maximum % core involvement (MCI), and number of positive cores. AS failure was defined as Gleason score (GS) >6, >50 % maximum core involvement, or >2 positive cores on biopsy. Univariate and multivariate Cox proportional-hazards regression models, upgrading risk score, and other clinicopathologic features were each assessed for their ability to predict AS failure., Results: Clinicopathologic parameters were similar in both groups with the exception of mean PSAD (0.13 vs. 0.11, p < 0.01) and follow-up (2.1 vs. 3.2 years, p = 0.2). Most common cause of AS failure was GS > 6 (group 1) compared to >2 positive cores (group 2). On univariate analysis in both populations, features at diagnosis including PSAD and the UR score were significant in predicting AS failure by upgrading (Gleason > 6) and any failure. Multivariate analysis revealed the UR score predicts AS failure by GS upgrading (HR 1.8, 95 % CI 1.12-2.93; p = 0.01) and any failure criteria (HR 1.7, 95 % CI 1.06-2.65); p = 0.02) for group 1. Likewise, the UR score in group 2 predicts AS failure with GS upgrading (HR 1.3, 95 % CI 1.15-1.42; p < 0.0001) and any failure criteria (HR 1.18, 95 % CI 1.18-1.38; p < 0.0001). An ROC generated an AUC of 0.66. Decision curve analysis demonstrated a high net benefit for the UR score across a range of threshold probabilities. Based on these outcomes, at 3 years, patients in the lowest risk quartile have a 15 % risk of AS failure versus a 46 % risk in the highest quartile (p < 0.0001)., Conclusions: The UR score was predictive of pathologic AS failure on multivariate analysis in several AS cohorts. It outperformed single clinicopathologic criteria and may provide a useful adjunct using clinicopathologic data to stratify patients considering AS.

Because the majority of small renal masses (SRMs; <4 cm) demonstrate low metastatic potential and can be effectively treated with radical or partial nephrectomy, the role of lymph node dissection (LND) at the time of surgery is unclear. A randomized trial demonstrated no survival benefit of LND in clinically localized renal cell carcinoma. Thus, LND is not recommended routinely for SRMs. For patients with high-risk features or radiographic evidence of lymphadenopathy, however, LND may improve local staging and potentially provide a survival benefit. If performed, a LND template should be based on the known lymphatic drainage of the kidneys., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: Androgen deprivation therapy (ADT) commonly leads to incomplete cell death and the fate of persistent cells involves, in part, a senescent phenotype. Senescence is terminal growth arrest in response to cell stress that is characterized by increased lysosomal-β-galactosidase (GLB1) the origin of senescence associated-β-gal activity (SA-β-gal). In the current study senescence is examined in vivo after ADT use in a neoadjuvant trial., Methods and Materials: Tissue microarrays were generated from prostate cancer specimens (n = 126) from a multicenter neoadjuvant ADT trial. Arrays were subjected to multiplexed immunofluorescent staining for GLB1, Ki67, cleaved caspase 3 (CC3) and E-cadherin. Automated quantitative imaging was performed using Vectra™ and expression correlated with clinicopathologic features., Results: Tissue was analyzed from 59 patients treated with neoadjuvant ADT and 67 receiving no therapy preoperatively. Median follow-up was 85.3 mo and median ADT treatment was 5 mo. In PC treated with neoadjuvant ADT, GLB1 expression increased in intermediate Gleason score (GS 6-7; p = 0.001), but not high grade (GS 8-10) cancer. Significantly higher levels of GLB1 were seen in tissues undergoing neoadjuvant ADT longer than 5 months compared to untreated tissues (p = 0.002). In contrast, apoptosis significantly increased earlier (1-4 mo) after ADT treatment (p<0.5)., Conclusions: Increased GLB1 after neoadjuvant ADT occurs primarily among more clinically favorable intermediate grade cancers and enrichment of the phenotype occurs in a temporally prolonged fashion. Senescence may explain the persistence of PCa cells after ADT. Given concerns for the detrimental longer term presence of senescent cells, targeting these cells for removal may improve outcomes.

Objective: To compare 1-dimensional (1D) and 3-dimensional (3D) volume measurements and determine whether primary tumor (PT) burden is predictive of overall survival (OS) following cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC)., Materials and Methods: Records and imaging studies of patients with mRCC treated with CN from 2006 to 2015 were included, with tumor volumes measured by a faculty radiologist blinded to clinical outcomes using Advantage Workstation Volume Share (Ver 4.6, GE, Waukesha, WI)., Results: Complete PT and metastatic tumor volumes were measured for 67 patients. For 15 (22.3%) patients, 1D volume was within ±10% of the measured 3D volume. In 40 (59.7%) patients, the 1D calculated PT volume was >10% of the actual 3D volume. Fractional percentage of tumor volume (FPTV) removed during CN was calculated using the formula PT volume/(PT + met volume). FPTV was not associated with OS when analyzed as a continuous variable. Patients were divided into 2 groups based on previously published cut point of 90% FPTV. No differences between cohorts in age, gender, grade, subtype, number of metastatic sites, performance status, Memorial Sloan Kettering Cancer Center risk group, or International Metastatic Renal Cell Carcinoma Database Consortium risk group were identified. OS was not different between cohorts (P = .38)., Conclusion: 1D measurements of PT diameter frequently overestimate mRCC PT volume. In patients with mRCC selected for CN, the ratio of primary to metastatic tumor does not predict OS., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To evaluate if body mass index (BMI) ≥ 40 is associated with risk of postoperative complications, receipt of perioperative blood transfusion (PBT), length of hospital stay (LOS), perioperative death, or hospital readmission rate following renal mass surgery., Materials and Methods: After Institutional Review Board approval, comprehensive information was collected for patients treated with surgery for renal mass from 2000 to 2015 at one institution. Univariable and multivariable analyses were used to evaluate the association of BMI ≥ 40 among other putative risk factors for perioperative outcomes., Results: A total of 1048 patients were treated surgically, including 115 (11%) with BMI > 40. Minimally invasive and open surgical approaches were used for 480 (45.8%) and 568 (54.2%) patients, respectively. Morbid obesity was not associated with risk of major complications, overall complications, receipt of PBT, LOS, hospital readmission rate, or perioperative death. Charlson comorbidity index was the only independent predictor of major complications following renal mass surgery, P = .0006, per point odds ratio 1.2 (95%C.I. 1.08-1.32). Surgical site infections (SSIs) were more common in patients with BMI ≥ 40 vs BMI < 40 (10.5% vs 4.8%, P = .01). Following multivariable analysis, BMI ≥ 40 was the only independent predictor of SSIs, odds ratio 2.6, 95% confidence interval 1.32-5.13; P = .006., Conclusion: Morbid obesity (BMI ≥ 40) is an independent predictor of developing SSIs following renal mass surgery. Morbid obesity is not predictive of risk for major complications, receipt of PBT, hospital readmission, perioperative death, or LOS., (Copyright © 2016. Published by Elsevier Inc.)

Objective: To assess whether extreme obesity (body mass index [BMI] ≥ 40 kg/m(2) ) is associated with peri-operative outcomes, overall survival (OS), cancer-specific survival (CSS), or recurrence-free survival (RFS) after surgical treatment for renal cell carcinoma (RCC)., Patients and Methods: After institutional review board approval, we used an institutional database to identify patients treated surgically between January 2000 and December 2014 with a pathological diagnosis of RCC. Comprehensive clinical and pathological data were reviewed. Kaplan-Meier analyses were used to estimate OS, RFS and CSS. Univariate and multivariate Cox proportional hazards analysis was used to evaluate associations with OS, CSS and RFS in patients with extreme obesity, among other known predictive variables., Results: In all, 100 patients (11.9%) with a BMI ≥ 40 kg/m(2) and 743 patients (88.1%) with a BMI < 40 kg/m(2) who were treated surgically for RCC were identified. Morbid obesity was not associated with an increased risk of blood transfusion (odds ratio [OR] 1, 95% confidence interval [CI] 0.587-1.70; P = 1.0). The median (interquartile range) length of hospital stay (LOS) was 4 (3-6) days. Morbid obesity was not associated with longer LOS (P = 0.26) or 30-day hospital readmission rates (P = 1.0). Major complications (Clavien ≥ 3a) were recorded in 67 patients (7.95%). BMI ≥ 40 kg/m(2) was not a predictor of major complications (OR 0.58, 95% CI 0.227-1.47; P = 0.251) or 90-day mortality (P = 0.4067). BMI ≥ 40 kg/m(2) was not associated with worse OS (P = 0.7), CSS (P = 0.2) or RFS (P = 0.5). BMI ≥ 35 kg/m(2) was also not associated with worse OS, CSS or RFS (P = 0.3, 0.1, 0.5, respectively). The 5-year OS rate was 68.9% for the entire cohort, including 69 and 70% for patients with BMI < 40 kg/m(2) and BMI ≥ 40 kg/m(2) , respectively (P = 0.69). The 5-year CSS was 79.5% for the entire cohort, including 78.4 and 87.9% (P = 0.16) for patients with BMI < 40 kg/m(2) and BMI ≥ 40 kg/m(2) , respectively. The 5-year RFS rates for BMI < 40 kg/m(2) and BMI ≥ 40 kg/m(2) were 84.1 and 90.6%, respectively (P = 0.48)., Conclusions: Extreme obesity is not associated with worse peri-operative or cancer outcomes after surgery for RCC. Surgery should remain a standard treatment option in well selected morbidly obese patients., (© 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.)

Purpose: Prior reports suggest that renin-angiotensin system inhibition may decrease nonmuscle invasive bladder cancer recurrence. We evaluated whether angiotensin converting enzyme inhibitor or angiotensin receptor blocker treatment at initial surgery was associated with decreased recurrence or progression in patients with nonmuscle invasive bladder cancer., Materials and Methods: Using an institutional bladder cancer database we identified 340 patients with data available on initial transurethral resection of bladder tumor. Progression was defined as an increase to stage T2. Cox proportional hazards models were used to evaluate associations with recurrence-free and progression-free survival., Results: Median patient age was 69.6 years. During a median followup of 3 years (IQR 1.3-6.1) 200 patients (59%) had recurrence and 14 (4.1%) had stage progression. Of those patients 143 were receiving angiotensin converting enzyme inhibitor/angiotensin receptor blockers at the time of the first transurethral resection. On univariate analysis factors associated with improved recurrence-free survival included carcinoma in situ (p = 0.040), bacillus Calmette-Guérin therapy (p = 0.003) and angiotensin converting enzyme inhibitor/angiotensin receptor blocker therapy (p = 0.009). Multivariate analysis demonstrated that patients treated with bacillus Calmette-Guérin therapy (HR 0.68, 95% CI 0.47-0.87, p = 0.002) or angiotensin converting enzyme inhibitor/angiotensin receptor blocker therapy (HR 0.61, 95% CI 0.45-0.84, p = 0.005) were less likely to experience tumor recurrence. The 5-year recurrence-free survival rate was 45.6% for patients treated with angiotensin converting enzyme inhibitor/angiotensin receptor blockers and 28.1% in those not treated with angiotensin converting enzyme inhibitor/angiotensin receptor blockers (p = 0.009). Subgroup analysis was performed to evaluate nonmuscle invasive bladder cancer pathology (Ta, T1 and carcinoma in situ) in 85 patients on bacillus Calmette-Guérin therapy alone and in 52 in whom it was combined with angiotensin converting enzyme inhibitor/angiotensin receptor blocker. Multivariate analysis revealed that patients treated with bacillus Calmette-Guérin alone (HR 2.19, 95% CI 1.01-4.77, p = 0.04) showed worse recurrence-free survival compared to patients treated with bacillus Calmette-Guérin and angiotensin converting enzyme inhibitor/angiotensin receptor blocker (stage Ta HR 0.45, 95% CI 0.21-0.98, p = 0.04)., Conclusions: Pharmacological inhibition of the renin-angiotensin system is associated with improved outcomes in patients with bladder cancer. Renin-angiotensin system inhibitor administration in nonmuscle invasive bladder cancer cases should be studied in a prospective randomized trial., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

The increased use of abdominal imaging has led to identification of more patients with incidental renal masses, and renal mass biopsy (RMB) has become a popular method to evaluate unknown renal masses prior to definitive treatment. Pathologic data obtained from biopsy may be used to guide decisions for treatment and may include the presence or absence of malignant tumor, renal cell cancer subtype, tumor grade and the presence of other aggressive pathologic features. However, prior to using RMB for risk stratification, it is important to understand whether RMB findings are equivalent to pathologic analysis of surgical specimens and to identify any potential limitations of this approach. This review outlines the advantages and limitations of the current studies that evaluate RMB as a guide for treatment decision in patients with unknown renal masses. In multiple series, RMB has demonstrated low morbidity and a theoretical reduction in cost, if patients with benign tumors are identified from biopsy and can avoid subsequent treatment. However, when considering the routine use of RMB for risk stratification, it is important to note that biopsy may underestimate risk in some patients by undergrading, understaging or failing to identify aggressive tumor features. Future studies should focus on developing treatment algorithms that integrate RMB to identify the optimal use in risk stratification of patients with unknown renal masses.

No guidelines currently exist that address the need for rebiopsy in patients with a negative diagnosis of prostate cancer on initial biopsy sample analysis. Accurate diagnosis of prostate cancer in these patients is often complicated by continued elevation of serum PSA levels that are suggestive of prostate cancer, resulting in a distinct management challenge. Following negative initial findings of biopsy sample analysis, total serum PSA levels and serum PSA kinetics are ineffective indicators of a need for a repeat biopsy; therefore, patients suspected of having prostate cancer might undergo several unnecessary biopsy procedures. Several alternative strategies exist for identifying men who might be at risk of prostate cancer despite negative findings of biopsy sample analysis. Use of other serum PSA-related measurements enables more sensitive and specific diagnosis and can be combined with knowledge of clinicopathological features to improve outcomes. Other options include the FDA-approved Progensa(®) test and prostate imaging using MRI. Newer tissue-based assays that measure methylation changes in normal prostate tissue are currently being developed. A cost-effective strategy is proposed in order to address this challenging clinical scenario, and potential directions of future studies in this area are also described.

Purpose of Review: There is a major deficit in our ability to detect and predict the clinical behavior of prostate cancer (PCa). Epigenetic changes are associated with PCa development and progression. This review will focus on recent results in the clinical application of diagnostic and prognostic epigenetic markers., Recent Findings: The development of high throughput technology has seen an enormous increase in the discovery of new markers that encompass epigenetic changes including those in DNA methylation and histone modifications. Application of these findings to urine and other biofluids, but also cancer and noncancerous prostate tissue, has resulted in new biomarkers. There has been a recent commercial development of a DNA methylation-based assay for identifying PCa risk from normal biopsy tissue. Other biomarkers are currently in the validation phase and encompass combinations of multiple genes., Summary: Epigenetic changes improve the specificity and sensitivity of PCa diagnosis and have the potential to help determine clinical prognosis. Additional studies will not only provide new and better biomarker candidates, but also have the potential to inform new therapeutic strategies given the reversibility of these processes.

Abnormal expression and function of chromatin regulators results in the altered chromatin structure seen in cancer. The chromatin regulator CTCF, its cofactor CHD8, and antagonistic paralogue BORIS have wide-ranging effects on gene regulation. Their concurrent expression and regulation was examined in benign, localized, and metastatic prostate cancer (PCa) arrays with extended follow-up using an automated quantitative imaging system, VECTRA. Epithelial staining was quantified and compared against a range of clinicopathologic variables. CHD8 expression was decreased in HGPIN, localized, and metastatic PCa compared to benign (P < .001). CHD8 promoter hypermethylation, assessed by Quantitative Pyrosequencing, occurred in over 45% of primary cancers in this population as well as the TGCA database. Treatment of cell lines with the demethylating agent 5-Aza-2'-deoxycytidine reinduced expression. An interesting dichotomy for CHD8 was observed within primary cancers, with higher nuclear protein expression associated with adverse clinical outcomes including extracapsular extension (P = .007), presence of metastases (P = .025) and worse PSA-recurrence free survival (P = .048). CHD8 outperformed Gleason score and predicted biochemical failure within intermediate grade prostate cancers. The BORIS/CTCF expression ratio increased in localized (P = .03) and metastatic PCa (P = .006) and was associated with higher Gleason score (P = .02), increased tumor volume (P = .02) and positive margins (P = .04). Per cell heterogeneity of expression revealed all protein expression to be more heterogeneous in cancerous tissue (both P < .001), especially high grade (P < .01). In the first detailed analysis in cancer, a marked loss of CHD8 expression and increased BORIS/CTCF ratio indicate frequent disruption of CTCF and its effector genes in PCa., (Copyright © 2014 Neoplasia Press, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the value of the R.E.N.A.L nephrometry scoring system in predicting treatment success for image-guided percutaneous cryoablation (PCA)., Patients and Methods: The study included 139 patients with renal masses treated with PCA. Preoperative computed tomography or magnetic resonance images were reviewed by a urology resident. The primary endpoint variable was incomplete treatment or tumour recurrence. R.E.N.A.L. scores were categorized into low (4-6), moderate (7-9), and high (10-12). Logistic regression analysis was conducted to predict tumour recurrence. Additional variables collected included age at surgery, American Society of Anesthesiologists score, lesion size, skin-to-tumour distance, skin-to-hilum distance, and number of treatment cryoprobes., Results: At a median follow-up of 24 months, there were 10 tumour recurrences (six moderate and four high R.E.N.A.L. score categories). Nephrometry score and number of probes used were not associated with recurrence (odds ratio [OR] 1.02, P = 0.9 and P = 0.53, respectively). The tumour distances for patients with recurrence and no recurrence were 10.8 cm and 8.5 cm, respectively (P ≤ 0.05), the skin-to-tumour distance was associated with treatment failure (OR 1.24, P = 0.015); for each unit increase in the mean value, patients were 1.5 times more likely to have a tumour recurrence (95% confidence interval [CI] 1.04-1.72). The model that best predicted complications included the number of probes used (P = 0.002) and R.E.N.A.L. score (OR 1.35, P = 0.027). For each additional probe used, patients were twice as likely to have complications (OR 1.98, 95% CI 1.28-3.05). With each unit increase in R.E.N.A.L. score, patients were 1.5 times more likely to experience a complication (OR 1.49, 95% CI 1.05-2.11)., Conclusions: An increased skin-to-tumour distance is associated with a higher risk of treatment failure after PCA. Furthermore, an increase in both R.E.N.A.L nephrometry score and number of probes used was associated with an increased risk of complications after PCA. The R.E.N.A.L. nephrometry score as a measure of tumour complexity was not associated with tumour recurrence., (© 2012 THE AUTHORS. BJU INTERNATIONAL © 2012 BJU INTERNATIONAL.)

Introduction: To assess the variability of pre-prostate biopsy prophylaxis among American urologists., Materials and Methods: A survey was electronically mailed to 3355 urologists around the country. Urologists were surveyed on their antibiotic prophylaxis choice, the route and duration of antimicrobial prophylaxis. Additionally they were questioned about their knowledge of local antimicrobial resistance and if rectal enemas were routinely used., Results: There were 679 (21%) responses to the survey. The survey revealed differences in pre-prostate biopsy prophylaxis among urologists. Ten different classes of antibiotics were used orally, 4 classes intramuscular, 5 classes intravenous, and there was also 14 different duration regimens., Conclusion: Despite the initiation of the 2008 American Urological Association Guidelines on this topic, there still is a lack of uniformity in prostate biopsy prophylaxis.

Objective: To determine the pressure-flow characteristics of neobladders created in various configurations that may be constructed intra-abdominally. Complete intracorporeal neobladder construction has been previously described but is limited due to excessive operative time and the need for an advanced laparoscopic skill set., Materials and Methods: Four neobladder configurations were constructed, each using 20 cm of human cadaveric small intestine. The standard hand sewn Studer pouch was compared with a circular loop, W-pouch, and U-pouch with stapled anastamoses. Pressure flow studies were completed using the Aquarius TT UDS system (Laborie Medical Technologies, Toronto, Ontario) and each neobladder was filled to a pressure of 50 cm H2O. Neobladder change in pressure, capacity, and overall compliance were determined., Results: The cystometric capacities of the stapled U-pouch, W-pouch, Circle pouch, and Studer pouch were 167.3 mL, 177.5 mL, 114 mL, and 145.2 mL respectively. The first increase in intravesical pressure was at 90.3 mL, 103 mL, 50 mL, and 85 mL. The greatest compliance of 3.81 mL/cmH2O was demonstrated in the U-pouch, with the W-pouch revealing a compliance of 3.44 mL/cmH2O. The least compliant neobladder was the circle pouch (2.24 mL/cmH20) followed by the standard Studer pouch (2.94 mL/cmH2O)., Conclusion: The construction of an orthotopic neobladder must not only be technically feasible but maintain adequate capacity and compliance for optimal functioning. Pressure-flow studies demonstrated equivalent results in alternate neobladder configurations. Additional data is needed to determine feasibility in vivo., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)