Eila C. Skinner

All Publications

• Contemporary Use of Partial Nephrectomy: Are Older Patients With Impaired Kidney Function Being Left Behind? UROLOGY Leppert, J. T., Mittakanti, H. R., Thomas, I., Lamberts, R. W., Sonn, G. A., Chung, B. I., Skinner, E. C., Wagner, T. H., Chertow, G. M., Brooks, J. D. 2017; 100: 65-71

  View details for DOI 10.1016/j.urology.2016.08.044

  View details for Web of Science ID 000397168900017

• Prediction of Lymph Node Metastasis in Patients with Bladder Cancer Using Whole Transcriptome Gene Expression Signatures. journal of urology Seiler, R., Lam, L. L., Erho, N., Takhar, M., Mitra, A. P., Buerki, C., Davicioni, E., Skinner, E. C., Daneshmand, S., Black, P. C. 2016; 196 (4): 1036-1041

  Abstract

  Clinical staging in patients with muscle invasive bladder cancer misses up to 25% of lymph node metastasis. These patients are at high risk for disease recurrence and improved clinical staging is critical to guide management.Whole transcriptome expression profiles were generated in 199 patients who underwent radical cystectomy and extended pelvic lymph node dissection. The cohort was divided randomly into a discovery set of 133 patients and a validation set of 66. In the discovery set features were identified and modeled in a KNN51 (K-nearest neighbor classifier 51) to predict pathological lymph node metastases. Two previously described bladder cancer gene signatures, including RF15 (15-gene cancer recurrence signature) and LN20 (20-gene lymph node signature), were also modeled in the discovery set for comparison. The AUC and the OR were used to compare the performance of these signatures.In the validation set KNN51 achieved an AUC of 0.82 (range 0.71-0.93) to predict lymph node positive cases. It significantly outperformed RF15 and LN20, which had an AUC of 0.62 (range 0.47-0.76) and 0.46 (range 0.32-0.60), respectively. Only KNN51 showed significant odds of predicting LN metastasis with an OR of 2.65 (range 1.68-4.67) for every 10% increase in score (p <0.001). RF15 and LN20 had a nonsignificant OR of 1.21 (range 0.97-1.54) and 1.39 (range 0.52-3.77), respectively.The new KNN51 signature was superior to previously described gene signatures for predicting lymph node metastasis. If validated prospectively in transurethral resection of bladder tumor samples, KNN51 could be used to guide patients at high risk to early multimodal therapy.

  View details for DOI 10.1016/j.juro.2016.04.061

  View details for PubMedID 27105761

• Epidermal Growth Factor Receptor, Excision-Repair Cross-Complementation Group 1 Protein, and Thymidylate Synthase Expression in Penile Cancer. Clinical genitourinary cancer Dorff, T. B., Schuckman, A. K., Schwartz, R., Rashad, S., Bulbul, A., Cai, J., Pinski, J., Ma, Y., Danenberg, K., Skinner, E., Quinn, D. I. 2016; 14 (5): 450-456 e1

  Abstract

  To describe the expression of tissue epidermal growth factor receptor (EGFR), excision-repair cross-complementation group 1 protein (ERCC1), and thymidylate synthase (TS) in patients with penile cancer and explore their association with stage and outcome.A total of 52 patients with penile squamous cell cancer who were treated at the University of Southern California from 1995 to 2010 were identified. Paraffin-embedded tissue underwent mRNA quantitation and immunohistochemistry for expression of EGFR, ERCC1, and TS. KRAS mutations were evaluated using polymerase chain reaction-based sequencing.EGFR overexpression was common by mRNA (median, 5.09; range, 1.92-104.5) and immunohistochemistry. EGFR expression > 7 was associated with advanced stage and poor differentiation (P = .01 and .034 respectively) but not with survival in multivariate analysis. ERCC1 mRNA expression was a median of 0.65 (range, 0.21-1.87). TS expression was a median of 1.88 (range, 0.54-6.47). ERCC1 and TS expression were not associated with grade, stage, or survival. There were no KRAS mutations identified. A total of 17 men received chemotherapy; 8 (47%) had an objective response, including 1 with a pathologic complete response. There was a trend for lower expression of EGFR corresponding to a higher likelihood of response (response rate [RR]) to chemotherapy: 67% RR in EGFR mRNA < 7 versus 33% RR in EGFR > 7 (P = .31).High expression of EGFR mRNA in squamous cell carcinoma of the penis is associated with advanced stage and poor differentiation, but not survival. In our small heterogeneous subset, molecular marker expression did not show a correlation with the likelihood of chemotherapy response. A prospective evaluation of the role of the EGFR pathway and its regulatory environment in penile cancer is warranted. Given the rarity of this cancer, collaborative prospective cohort evaluations and trials need to be encouraged.

  View details for DOI 10.1016/j.clgc.2016.01.013

  View details for PubMedID 26935231

• Diagnosis and Treatment of Non-Muscle Invasive Bladder Cancer: AUA/SUO Guideline JOURNAL OF UROLOGY Chang, S. S., Boorjian, S. A., Chou, R., Clark, P. E., Daneshmand, S., Konety, B. R., Pruthi, R., Quale, D. Z., Ritch, C. R., Seigne, J. D., Skinner, E. C., Smith, N. D., McKiernan, J. M. 2016; 196 (4): 1021-1029

  Abstract

  Although associated with an overall favorable survival rate, the heterogeneity of non-muscle invasive bladder cancer (NMIBC) affects patients' rates of recurrence and progression. Risk stratification should influence evaluation, treatment and surveillance. This guideline attempts to provide a clinical framework for the management of NMIBC.A systematic review utilized research from the Agency for Healthcare Research and Quality (AHRQ) and additional supplementation by the authors and consultant methodologists. Evidence-based statements were based on body of evidence strength Grade A, B, or C and were designated as Strong, Moderate, and Conditional Recommendations with additional statements presented in the form of Clinical Principles or Expert Opinions.(1) RESULTS: A risk-stratified approach categorizes patients into broad groups of low-, intermediate-, and high-risk. Importantly, the evaluation and treatment algorithm takes into account tumor characteristics and uniquely considers a patient's response to therapy. The 38 statements vary in level of evidence, but none include Grade A evidence, and many were Grade C.The intensity and scope of care for NMIBC should focus on patient, disease, and treatment response characteristics. This guideline attempts to improve a clinician's ability to evaluate and treat each patient, but higher quality evidence in future trials will be essential to improve level of care for these patients.

  View details for DOI 10.1016/j.juro.2016.06.049

  View details for Web of Science ID 000382720500015

  View details for PubMedID 27317986

• Contemporary Use of Partial Nephrectomy: Are Older Patients With Impaired Kidney Function Being Left Behind? Urology Leppert, J. T., Mittakanti, H. R., Thomas, I., Lamberts, R. W., Sonn, G. A., Chung, B. I., Skinner, E. C., Wagner, T. H., Chertow, G. M., Brooks, J. D. 2016

  Abstract

  To assess whether patient factors, such as age and preoperative kidney function, were associated with receipt of partial nephrectomy in a national integrated healthcare system.We identified patients treated with a radical or partial nephrectomy from 2002 to 2014 in the Veterans Health Administration. We examined associations among patient age, sex, race or ethnicity, multimorbidity, baseline kidney function, tumor characteristics, and receipt of partial nephrectomy. We estimated the odds of receiving a partial nephrectomy and assessed interactions between covariates and the year of surgery to explore whether patient factors associated with partial nephrectomy changed over time.In our cohort of 14,186 patients, 4508 (31.2%) received a partial nephrectomy. Use of partial nephrectomy increased from 17% in 2002 to 32% in 2008 and to 38% in 2014. Patient race or ethnicity, age, tumor stage, and year of surgery were independently associated with receipt of partial nephrectomy. Black veterans had significantly increased odds of receipt of partial nephrectomy, whereas older patients had significantly reduced odds. Partial nephrectomy utilization increased for all groups over time, but older patients and patients with worse baseline kidney function showed the least increase in odds of partial nephrectomy.Although the utilization of partial nephrectomy increased for all groups, the greatest increase occurred in the youngest patients and those with the highest baseline kidney function. These trends warrant further investigation to ensure that patients at the highest risk of impaired kidney function are considered for partial nephrectomy whenever possible.

  View details for DOI 10.1016/j.urology.2016.08.044

  View details for PubMedID 27634733

• Radical cystectomy with super-extended lymphadenectomy: impact of separate vs en bloc lymph node submission on analysis and outcomes BJU INTERNATIONAL Zehnder, P., Moltzahn, F., Mitra, A. P., Cai, J., Miranda, G., Skinner, E. C., Gill, I. S., Daneshmand, S. 2016; 117 (2): 253-259

  View details for DOI 10.1111/bju.12956

  View details for Web of Science ID 000367717300013

• Continent cutaneous diversion CURRENT OPINION IN UROLOGY Skinner, E. C. 2015; 25 (6): 555-561

  Abstract

  This article updates the recently reported intermediate to long-term results with the most commonly used forms of continent cutaneous urinary diversion, and to discuss approaches to early and late complications.Many variations on construction of a continent cutaneous diversion have been described. Results with large series of patients demonstrate acceptable results with all of them, but with a significant revision rate. Long-term complication rates and adaptation to robotic approaches have recently been described.Continent cutaneous diversion is rarely offered in the USA to patients undergoing cystectomy except in a few centers. Most studies have found a high complication rate and need for revision surgery in 10-20% of patients. However, functional results are acceptable and many patients are willing to accept the complications in exchange for avoiding an external appliance.

  View details for DOI 10.1097/MOU.0000000000000225

  View details for Web of Science ID 000369252900012

  View details for PubMedID 26426413

• Randomized Trial of Studer Pouch versus T-Pouch Orthotopic Ileal Neobladder in Patients with Bladder Cancer JOURNAL OF UROLOGY Skinner, E. C., Fairey, A. S., Groshen, S., Daneshmand, S., Cai, J., Miranda, G., Skinner, D. G. 2015; 194 (2): 433-439

  Abstract

  The need to prevent reflux in the construction of an orthotopic ileal neobladder is controversial. We designed the USC-STAR trial to determine whether the T-pouch neobladder that included an antireflux mechanism was superior to the Studer pouch in patients with bladder cancer undergoing radical cystectomy.This single center, randomized, controlled trial recruited patients with clinically nonmetastatic bladder cancer scheduled to undergo radical cystectomy with neobladder. Eligible patients were randomly assigned to undergo T-pouch or Studer ileal orthotopic neobladder. Treatment assignment was not masked. The primary end point was change in renal function from baseline to 3 years. The CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation was used to calculate the estimated glomerular filtration rate.Between February 2002 and November 2009, 237 patients were randomly assigned to T-pouch ileal orthotopic neobladder and 247 to Studer ileal orthotopic neobladder. Baseline characteristics did not differ between the groups. Between baseline and 3 years the estimated glomerular filtration rate decreased by 6.4 ml/minute/1.73 m(2) in the Studer group and 6.6 ml/minute/1.73 m(2) in the T-pouch group (p=0.35). Multivariable analysis showed that type of ileal orthotopic neobladder was not independently associated with 3-year renal function (p=0.63). However, baseline estimated glomerular filtration rate, age and urinary tract obstruction were independently associated with 3-year decline in renal function. Cumulative risk of urinary tract infection and overall late complications were not different between the groups, but the T-pouch was associated with an increased risk of secondary diversion related surgeries.T-pouch ileal orthotopic neobladder with an antireflux mechanism did not prevent a moderate reduction in renal function observed at 3 years compared to the Studer pouch, but did result in an increase in diversion related secondary surgical procedures.

  View details for DOI 10.1016/j.juro.2015.03.101

  View details for Web of Science ID 000357742000050

  View details for PubMedID 25823791

• Best Practices in Robot-assisted Radical Cystectomy and Urinary Reconstruction: Recommendations of the Pasadena Consensus Panel EUROPEAN UROLOGY Wilson, T. G., Guru, K., Rosen, R. C., Wiklund, P., Annerstedt, M., Bochner, B. H., Chan, K. G., Montorsi, F., Mottrie, A., Murphy, D., Novara, G., Peabody, J. O., Palou Redorta, J., Skinner, E. C., Thalmann, G., Stenzl, A., Yuh, B., Catto, J. 2015; 67 (3): 363-375

  View details for DOI 10.1016/j.eururo.2014.12.009

  View details for Web of Science ID 000349374200011

• Best practices in robot-assisted radical cystectomy and urinary reconstruction: recommendations of the Pasadena Consensus Panel. European urology Wilson, T. G., Guru, K., Rosen, R. C., Wiklund, P., Annerstedt, M., Bochner, B. H., Chan, K. G., Montorsi, F., Mottrie, A., Murphy, D., Novara, G., Peabody, J. O., Palou Redorta, J., Skinner, E. C., Thalmann, G., Stenzl, A., Yuh, B., Catto, J. 2015; 67 (3): 363-375

  Abstract

  Robot-assisted surgery is increasingly used for radical cystectomy (RC) and urinary reconstruction. Sufficient data have accumulated to allow evidence-based consensus on key issues such as perioperative management, comparative effectiveness on surgical complications, and oncologic short- to midterm outcomes.A 2-d conference of experts on RC and urinary reconstruction was organized in Pasadena, California, and the City of Hope Cancer Center in Duarte, California, to systematically review existing peer-reviewed literature on robot-assisted RC (RARC), extended lymphadenectomy, and urinary reconstruction. No commercial support was obtained for the conference.A systematic review of the literature was performed in agreement with the PRISMA statement.Systematic literature reviews and individual presentations were discussed, and consensus on all key issues was obtained. Most operative, intermediate-term oncologic, functional, and complication outcomes are similar between open RC (ORC) and RARC. RARC consistently results in less blood loss and a reduced need for transfusion during surgery. RARC generally requires longer operative time than ORC, particularly with intracorporeal reconstruction. Robotic assistance provides ergonomic value for surgeons. Surgeon experience and institutional volume strongly predict favorable outcomes for either open or robotic techniques.RARC appears to be similar to ORC in terms of operative, pathologic, intermediate-term oncologic, complication, and most functional outcomes. RARC consistently results in less blood loss and a reduced need for transfusion during surgery. RARC can be more expensive than ORC, although high procedural volume may attenuate this difference.Robot-assisted radical cystectomy (RARC) is an alternative to open surgery for patients with bladder cancer who require removal of their bladder and reconstruction of their urinary tract. RARC appears to be similar to open surgery for most important outcomes such as the rate of complications and intermediate-term cancer-specific survival. Although RARC has some ergonomic advantages for surgeons and may result in less blood loss during surgery, it is more time consuming and may be more expensive than open surgery.

  View details for DOI 10.1016/j.eururo.2014.12.009

  View details for PubMedID 25582930

• Urinary Diversion: How Experts Divert UROLOGY Hautmann, R. E., Abol-Enein, H., Lee, C. T., Mansson, W., Mills, R. D., Penson, D. F., Skinner, E. C., Studer, U. E., Thueroff, J. W., Volkmer, B. G. 2015; 85 (1): 233-238

  Abstract

  To determine the rates of the available urinary diversion options for patients treated with radical cystectomy for bladder cancer in different settings (pioneering institutions, leading urologic oncology centers, and population based).Population-based data from the literature included all patients (n = 7608) treated in Sweden during the period 1964-2008, from Germany (n = 14,200) for the years 2008 and 2011, US patients (identified from National Inpatient Sample during 1998-2005, 35,370 patients and 2001-2008, 55,187 patients), and from Medicare (n = 22,600) for the years 1992, 1995, 1998, and 2001. After the International Consultation on Urologic Diseases-European Association of Urology International Consultation on Bladder Cancer 2012, the urinary diversion committee members disclosed data from their home institutions (n = 15,867), including the pioneering institutions and the leading urologic oncology centers. They are the coauthors of this report.The receipt of continent urinary diversion in Sweden and the United States is <15%, whereas in the German high-volume setting, 30% of patients receive a neobladder. At leading urologic oncology centers, this rate is also 30%. At pioneering institutions up to 75% of patients receive an orthotopic reconstruction. Anal diversion is <1%. Continent cutaneous diversion is the second choice.Enormous variations in urinary diversion exist for >2 decades. Increased attention in expanding the use of continent reconstruction may help to reduce these disparities for patients undergoing radical cystectomy for bladder cancer. Continent reconstruction should not be the exclusive domain of cystectomy centers. Efforts to increase rates of this complex reconstruction must concentrate on better definition of the quality-of-life impact, technique dissemination, and the centralization of radical cystectomy.

  View details for DOI 10.1016/j.urology.2014.06.075

  View details for Web of Science ID 000346648500054

  View details for PubMedID 25440985

• Outcomes After Urothelial Recurrence in Bladder Cancer Patients Undergoing Radical Cystectomy UROLOGY Mitra, A. P., Alemozaffar, M., Harris, B. N., Schuckman, A. K., Skinner, E. C., Daneshmand, S. 2014; 84 (6)

  View details for DOI 10.1016/j.urology.2014.05.080

  View details for Web of Science ID 000345580500054

• Discovery and Validation of Novel Expression Signature for Postcystectomy Recurrence in High-Risk Bladder Cancer JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE Mitra, A. P., Lam, L. L., Ghadessi, M., Erho, N., Vergara, I. A., Alshalalfa, M., Buerki, C., Haddad, Z., Sierocinski, T., Triche, T. J., Skinner, E. C., Davicioni, E., Daneshmand, S., Black, P. C. 2014; 106 (11)

  Abstract

  Nearly half of muscle-invasive bladder cancer patients succumb to their disease following cystectomy. Selecting candidates for adjuvant therapy is currently based on clinical parameters with limited predictive power. This study aimed to develop and validate genomic-based signatures that can better identify patients at risk for recurrence than clinical models alone.Transcriptome-wide expression profiles were generated using 1.4 million feature-arrays on archival tumors from 225 patients who underwent radical cystectomy and had muscle-invasive and/or node-positive bladder cancer. Genomic (GC) and clinical (CC) classifiers for predicting recurrence were developed on a discovery set (n = 133). Performances of GC, CC, an independent clinical nomogram (IBCNC), and genomic-clinicopathologic classifiers (G-CC, G-IBCNC) were assessed in the discovery and independent validation (n = 66) sets. GC was further validated on four external datasets (n = 341). Discrimination and prognostic abilities of classifiers were compared using area under receiver-operating characteristic curves (AUCs). All statistical tests were two-sided.A 15-feature GC was developed on the discovery set with area under curve (AUC) of 0.77 in the validation set. This was higher than individual clinical variables, IBCNC (AUC = 0.73), and comparable to CC (AUC = 0.78). Performance was improved upon combining GC with clinical nomograms (G-IBCNC, AUC = 0.82; G-CC, AUC = 0.86). G-CC high-risk patients had elevated recurrence probabilities (P < .001), with GC being the best predictor by multivariable analysis (P = .005). Genomic-clinicopathologic classifiers outperformed clinical nomograms by decision curve and reclassification analyses. GC performed the best in validation compared with seven prior signatures. GC markers remained prognostic across four independent datasets.The validated genomic-based classifiers outperform clinical models for predicting postcystectomy bladder cancer recurrence. This may be used to better identify patients who need more aggressive management.

  View details for DOI 10.1093/jnci/dju290

  View details for Web of Science ID 000345773500010

  View details for PubMedID 25344601

• Endoscopic molecular imaging of human bladder cancer using a CD47 antibody SCIENCE TRANSLATIONAL MEDICINE Pan, Y., Volkmer, J., Mach, K. E., Rouse, R. V., Liu, J., Sahoo, D., Chang, T. C., Metzner, T. J., Kang, L., van de Rijn, M., Skinner, E. C., Gambhir, S. S., Weissman, I. L., Liao, J. C. 2014; 6 (260)

  Abstract

  A combination of optical imaging technologies with cancer-specific molecular imaging agents is a potentially powerful strategy to improve cancer detection and enable image-guided surgery. Bladder cancer is primarily managed endoscopically by white light cystoscopy with suboptimal diagnostic accuracy. Emerging optical imaging technologies hold great potential for improved diagnostic accuracy but lack imaging agents for molecular specificity. Using fluorescently labeled CD47 antibody (anti-CD47) as molecular imaging agent, we demonstrated consistent identification of bladder cancer with clinical grade fluorescence imaging systems, confocal endomicroscopy, and blue light cystoscopy in fresh surgically removed human bladders. With blue light cystoscopy, the sensitivity and specificity for CD47-targeted imaging were 82.9 and 90.5%, respectively. We detected variants of bladder cancers, which are diagnostic challenges, including carcinoma in situ, residual carcinoma in tumor resection bed, recurrent carcinoma following prior intravesical immunotherapy with Bacillus Calmette-Guérin (BCG), and excluded cancer from benign but suspicious-appearing mucosa. CD47-targeted molecular imaging could improve diagnosis and resection thoroughness for bladder cancer.

  View details for DOI 10.1126/scitranslmed.3009457

  View details for Web of Science ID 000343920500006

• Endoscopic molecular imaging of human bladder cancer using a CD47 antibody. Science translational medicine Pan, Y., Volkmer, J., Mach, K. E., Rouse, R. V., Liu, J., Sahoo, D., Chang, T. C., Metzner, T. J., Kang, L., van de Rijn, M., Skinner, E. C., Gambhir, S. S., Weissman, I. L., Liao, J. C. 2014; 6 (260): 260ra148-?

  Abstract

  A combination of optical imaging technologies with cancer-specific molecular imaging agents is a potentially powerful strategy to improve cancer detection and enable image-guided surgery. Bladder cancer is primarily managed endoscopically by white light cystoscopy with suboptimal diagnostic accuracy. Emerging optical imaging technologies hold great potential for improved diagnostic accuracy but lack imaging agents for molecular specificity. Using fluorescently labeled CD47 antibody (anti-CD47) as molecular imaging agent, we demonstrated consistent identification of bladder cancer with clinical grade fluorescence imaging systems, confocal endomicroscopy, and blue light cystoscopy in fresh surgically removed human bladders. With blue light cystoscopy, the sensitivity and specificity for CD47-targeted imaging were 82.9 and 90.5%, respectively. We detected variants of bladder cancers, which are diagnostic challenges, including carcinoma in situ, residual carcinoma in tumor resection bed, recurrent carcinoma following prior intravesical immunotherapy with Bacillus Calmette-Guérin (BCG), and excluded cancer from benign but suspicious-appearing mucosa. CD47-targeted molecular imaging could improve diagnosis and resection thoroughness for bladder cancer.

  View details for DOI 10.1126/scitranslmed.3009457

  View details for PubMedID 25355698

• Level III-IV Inferior Vena Caval Thrombectomy Without Cardiopulmonary Bypass: Long-Term Experience with Intrapericardial Control JOURNAL OF UROLOGY Patil, M. B., Montez, J., Loh-Doyle, J., Cai, J., Skinner, E. C., Schuckman, A., Thangathurai, D., Skinner, D. G., Daneshmand, S. 2014; 192 (3): 682-688

  Abstract

  Inferior vena cava tumor thrombectomy requires experienced surgical teams due to complex hemodynamic considerations. The teams often use vascular bypass techniques that introduce additional risk. Inferior vena caval control in the pericardium obviates the need for cardiopulmonary bypass. We reviewed our experience with intrapericardial control during inferior vena caval tumor thrombectomy to evaluate perioperative outcomes and determine factors associated with overall survival.We retrospectively reviewed the records of 87 patients who underwent nephrectomy with inferior vena caval tumor thrombectomy using intrapericardial inferior vena caval control from 1978 to 2012. This technique was performed in all 43 and 35 cases of intrahepatic and supradiaphragmatic thrombi, respectively, and in 9 select cases of intra-atrial thrombi. Patient demographics, operative variables and postoperative outcomes were examined. Multivariate regression analysis was used to determine associations between clinical variables and overall survival.Mortality 30 days perioperatively was 9.2% and the incidence of high grade complications was 19.5%. Median survival was 3.1 and 2.5 years in patients with pT3bN0 and pT3cN0, respectively. Extended regional lymphadenectomy, which was performed in all cases, revealed nodal metastasis in 38%. On multivariate analysis ECOG greater than 2 and pT3c stage were associated with worse survival. Histological grade, perinephric fat invasion and lymph node involvement were not associated with worse survival.Intrapericardial control of the inferior vena cava enables a single surgical team to safely perform tumor thrombectomy for intrahepatic and supradiaphragmatic thrombi, eliminating the risk and morbidity related to cardiopulmonary bypass. Although supradiaphragmatic extent and ECOG greater than 2 are associated with worse survival, complete resection with lymphadenectomy can allow for long-term survival in patients with locally advanced disease.

  View details for DOI 10.1016/j.juro.2014.03.112

  View details for Web of Science ID 000342105600012

  View details for PubMedID 24704114

• The association of preoperative serum albumin level and American Society of Anesthesiologists (ASA) score on early complications and survival of patients undergoing radical cystectomy for urothelial bladder cancer. BJU international Djaladat, H., Bruins, H. M., Miranda, G., Cai, J., Skinner, E. C., Daneshmand, S. 2014; 113 (6): 887-893

  Abstract

  To evaluate the impact of the preoperative American Society of Anesthesiologists (ASA) score and serum albumin level on complications, recurrences and survival rates of patients who underwent radical cystectomy (RC) for urothelial bladder cancer (UBC).In all, 1964 patients underwent RC for UBC at our institution between 1971 and 2008. Preoperative serum albumin and ASA score were available in 1471 and 1140 patients, respectively. A complication was defined as any surgery related/unrelated event leading to lengthening hospital stay or re-admission. Endpoints were 90-day complication (90dC) rate, recurrence-free survival (RFS) and overall survival (OS).The median (range) follow-up was 12.4 (0.2-27.3) years. In all, 197 patients (13.4%) had a low albumin level (<3.5 g/dL) and 740 (64.8%) had a high ASA score (3 or 4). Low serum albumin and a high ASA score were associated with higher 90dC rate (42% vs 34%, P = 0.03 and 40% vs 28%, P < 0.001, respectively). On multiple logistic regression analysis, a high ASA score remained independently associated with increased 90dC rate (hazard ratio [HR] 1.52, P = 0.005) and decreased OS (HR 1.45, 95% confidence interval [CI] 1.13-1.86). A low serum albumin level was also independently associated with RFS (HR 1.68, 95% CI 1.16-2.43) and OS (HR 1.93, 95% CI 1.43-2.63).A low serum albumin level was independently associated with cancer recurrence and decreased OS after RC. A high ASA score was also independently associated with decreased OS. These parameters potentially could be used as prognosticators after RC.

  View details for DOI 10.1111/bju.12240

  View details for PubMedID 23906037

• Is extended lymphadenectomy of beneficial therapeutic value for T2 urothelial cancer? journal of urology Skinner, E. C., Sagalowsky, A. I. 2014; 191 (5): 1206-1208

  View details for DOI 10.1016/j.juro.2014.02.040

  View details for PubMedID 24560793

• Female gender is associated with a worse survival after radical cystectomy for urothelial carcinoma of the bladder: a competing risk analysis. Urology Messer, J. C., Shariat, S. F., Dinney, C. P., Novara, G., Fradet, Y., Kassouf, W., Karakiewicz, P. I., Fritsche, H., Izawa, J. I., Lotan, Y., Skinner, E. C., Tilki, D., Ficarra, V., Volkmer, B. G., Isbarn, H., Wei, C., Lerner, S. P., Curiel, T. J., Kamat, A. M., Svatek, R. S. 2014; 83 (4): 863-868

  Abstract

  To determine the association of gender with outcome after radical cystectomy for patients with bladder cancer.An observational cohort study was conducted using retrospectively collected data from 11 centers on patients with advanced bladder cancer treated with radical cystectomy. The association of gender with disease recurrence and cancer-specific mortality was examined using a competing risk analysis.The study comprised 4296 patients, including 890 women (21%). The median follow-up duration was 31.5 months for all patients. Disease recurred in 1430 patients (33.9%) (36.8% of women and 33.1% of men) at a median of 11 months after surgery. Death from any cause was observed in 46.0% of men and 50.1% of women. Cancer-specific death was observed in 33.0% of women and 27.2% of men. Multivariable regression with competing risk found that female gender was associated with an increased risk for disease recurrence and cancer-specific mortality (hazard ratio, 1.27; 95% confidence interval, 1.108-1.465; P = .007) compared with male gender. Important limitations include the inability to account for additional potential confounders, such as differences in environmental exposures, treatment selection, and histologic subtypes between men and women.Our analysis identified female gender as a poor-risk feature for patients undergoing radical cystectomy. This adverse prognostic factor was independent of standard clinical and pathologic features and competing risk from non-cancer-related death.

  View details for DOI 10.1016/j.urology.2013.10.060

  View details for PubMedID 24485993

• Reprogramming of the human intestinal epigenome by surgical tissue transposition GENOME RESEARCH Lay, F. D., Triche, T. J., Tsai, Y. C., Su, S., Martin, S. E., Daneshmand, S., Skinner, E. C., Liang, G., Chihara, Y., Jones, P. A. 2014; 24 (4): 545-553

  Abstract

  Extracellular cues play critical roles in the establishment of the epigenome during development and may also contribute to epigenetic perturbations found in disease states. The direct role of the local tissue environment on the post-development human epigenome, however, remains unclear due to limitations in studies of human subjects. Here, we use an isogenic human ileal neobladder surgical model and compare global DNA methylation levels of intestinal epithelial cells pre- and post-neobladder construction using the Infinium HumanMethylation450 BeadChip. Our study is the first to quantify the effect of environmental cues on the human epigenome and show that the local tissue environment directly modulates DNA methylation patterns in normal differentiated cells in vivo. In the neobladder, the intestinal epithelial cells lose their tissue-specific epigenetic landscape in a time-dependent manner following the tissue's exposure to a bladder environment. We find that de novo methylation of many intestine-specific enhancers occurs at the rate of 0.41% per month (P < 0.01, Pearson = 0.71), while demethylation of primarily non-intestine-specific transcribed regions occurs at the rate of -0.37% per month (P < 0.01, Pearson = -0.57). The dynamic resetting of the DNA methylome in the neobladder not only implicates local environmental cues in the shaping and maintenance of the epigenome but also illustrates an unexpected cross-talk between the epigenome and the cellular environment.

  View details for DOI 10.1101/gr.166439.113

  View details for Web of Science ID 000334055600002

  View details for PubMedID 24515120

  View details for PubMedCentralID PMC3975055

• A Panel of Three Markers Hyper- and Hypomethylated in Urine Sediments Accurately Predicts Bladder Cancer Recurrence CLINICAL CANCER RESEARCH Su, S., Abreu, A. L., Chihara, Y., Tsai, Y., Andreu-Vieyra, C., Daneshmand, S., Skinner, E. C., Jones, P. A., Siegmund, K. D., Liang, G. 2014; 20 (7): 1978-1989

  Abstract

  The high risk of recurrence after transurethral resection of bladder tumor of nonmuscle invasive disease requires lifelong treatment and surveillance. Changes in DNA methylation are chemically stable, occur early during tumorigenesis, and can be quantified in bladder tumors and in cells shed into the urine. Some urine markers have been used to help detect bladder tumors; however, their use in longitudinal tumor recurrence surveillance has yet to be established.We analyzed the DNA methylation levels of six markers in 368 urine sediment samples serially collected from 90 patients with noninvasive urothelial carcinoma (Tis, Ta, T1; grade low-high). The optimum marker combination was identified using logistic regression with 5-fold cross-validation, and validated in separate samples.A panel of three markers discriminated between patients with and without recurrence with the area under the curve of 0.90 [95% confidence interval (CI), 0.86-0.92] and 0.95 (95% CI, 0.90-1.00), sensitivity and specificity of 86%/89% (95% CI, 74%-99% and 81%-97%) and 80%/97% (95% CI, 60%-96% and 91%-100%) in the testing and validation sets, respectively. The three-marker DNA methylation test reliably predicted tumor recurrence in 80% of patients superior to cytology (35%) and cystoscopy (15%) while accurately forecasting no recurrence in 74% of patients that scored negative in the test.Given their superior sensitivity and specificity in urine sediments, a combination of hyper- and hypomethylated markers may help avoid unnecessary invasive exams and reveal the importance of DNA methylation in bladder tumorigenesis.

  View details for DOI 10.1158/1078-0432.CCR-13-2637

  View details for Web of Science ID 000333900000031

  View details for PubMedID 24691641

• Outcomes of radical cystectomy with extended lymphadenectomy alone in patients with lymph node-positive bladder cancer who are unfit for or who decline adjuvant chemotherapy BJU INTERNATIONAL Zehnder, P., Studer, U. E., Daneshmand, S., Birkhaeuser, F. D., Skinner, E. C., Roth, B., Miranda, G., Burkhard, F. C., Cai, J., Skinner, D. G., Thalmann, G. N., Gill, I. S. 2014; 113 (4): 554-560

  Abstract

  To analyse the long-term outcomes of patients with lymph node (LN)-positive bladder cancer, who did not receive any adjuvant therapy after radical cystectomy (RC) and extended pelvic lymph node dissection (ePLND).We conducted a retrospective, combined cohort analysis based on two prospectively maintained cystectomy databases from the University of Southern California and the University of Bern. Eligible patients underwent RC with ePLND for cN0M0 disease but were found to have LN-positive disease. No patient had neoadjuvant therapy, and all had negative surgical margins. Kaplan-Meier plots were used to estimate recurrence-free survival (RFS) and overall survival (OS). Subgroup comparisons were performed using log-rank tests, and multivariable analysis was based on Cox proportional hazard models.Of 521 patients with LN-positive disease, 251 (48%) never received adjuvant therapy. Although the pathological stage distribution was similar, the 251 patients who did not receive adjuvant therapy were older and had both fewer total and positive LNs than those who underwent adjuvant therapy. The median RFS for patients treated with RC alone was 1.6 years. Recurrences mainly occurred <2 years after RC, resulting in 5- and 10-year RFS rates of 32 and 26%, respectively. Pathological T stage, the total number of LNs and the number of positive LNs detected were independent predictors of RFS and OS.In this study, 25% of patients with documented LN metastases who did not receive adjuvant therapy were cured with RC and ePLND; however, a few relapses may occur later than 3 years. Predictors of survival were pathological T stage, the number of total LNs and the number of positive LNs identified.

  View details for DOI 10.1111/bju.12520

  View details for Web of Science ID 000332746900016

  View details for PubMedID 24131453

• Comprehensive molecular characterization of urothelial bladder carcinoma NATURE Weinstein, J. N., Akbani, R., Broom, B. M., Wang, W., Verhaak, R. G., McConkey, D., Lerner, S., Morgan, M., Creighton, C. J., Smith, C., Kwiatkowski, D. J., Cherniack, A. D., Kim, J., Pedamallu, C. S., Noble, M. S., Al-Ahmadie, H. A., Reuter, V. E., Rosenberg, J. E., Bajorin, D. F., Bochner, B. H., Solit, D. B., Koppie, T., Robinson, B., Gordenin, D. A., Fargo, D., Klimczak, L. J., Roberts, S. A., Au, J., Laird, P. W., Hinoue, T., Schultz, N., Ramirez, R., Hansel, D., Hoadley, K. A., Kim, W. Y., Damrauer, J. S., Baylin, S. B., Mungall, A. J., Robertson, A. G., Chu, A., Kwiatkowski, D. J., Sougnez, C., Cibulskis, K., Lichtenstein, L., Sivachenko, A., Stewart, C., Lawrence, M. S., Getz, G., Lander, E., Gabriel, S. B., Creighton, C. J., Donehower, L., Cherniack, A. D., Kim, J., Carter, S. L., Saksena, G., Schumacher, S. E., Sougnez, C., Freeman, S. S., Jung, J., Pedamallu, C. S., Bhatt, A. S., Pugh, T., Getz, G., Beroukhim, R., Gabriel, S. B., Meyerson, M., Mungall, A. J., Robertson, A. G., Chu, A., Ally, A., Balasundaram, M., Butterfield, Y. S., Dhalla, N., Hirst, C., Holt, R. A., Jones, S. J., Lee, D., Li, H. I., Marra, M. A., Mayo, M., Moore, R. A., Schein, J. E., Sipahimalani, P., Tam, A., Thiessen, N., Wong, T., Wye, N., Bowlby, R., Chuah, E., Guin, R., Jones, S. J., Marra, M. A., Hinoue, T., Shen, H., Bootwalla, M. S., Triche, T., Lai, P. H., Van den Berg, D. J., Weisenberger, D. J., Laird, P. W., Hansel, D., Hoadley, K. A., Balu, S., Bodenheimer, T., Damrauer, J. S., Hoyle, A. P., Jefferys, S. R., Meng, S., Mose, L. E., Simons, J. V., Soloway, M. G., Wu, J., Kim, W. Y., Parker, J. S., Hayes, D. N., Roach, J., Buda, E., Jones, C. D., Mieczkowski, P. A., Tan, D., Veluvolu, U., Waring, S., Auman, J. T., Perou, C. M., Wilkerson, M. D., Santoso, N., Parfenov, M., Ren, X., Pantazi, A., Hadjipanayis, A., Seidman, J., Kucherlapati, R., Lee, S., Yang, L., Park, P. J., Baylin, S. B., Xu, A. W., Protopopov, A., Zhang, J., Bristow, C., Mahadeshwar, H. S., Seth, S., Song, X., Tang, J., Zeng, D., Chin, L., Guo, C., Weinstein, J. N., Akbani, R., Broom, B. M., McConkey, D., Casasent, T. D., Liu, W., Ju, Z., Motter, T., Peng, B., Ryan, M., Wang, W., Verhaak, R. G., Su, X., Yang, J., Lorenzi, P. L., Yao, H., Zhang, N., Zhang, J., Mills, G. B., Kim, J., Noble, M. S., Cho, J., DiCara, D., Frazer, S., Gehlenborg, N., Heiman, D. I., Lin, P., Liu, Y., Stojanov, P., Voet, D., Zhang, H., Zou, L., Chin, L., Getz, G., Bernard, B., Kreisberg, D., Reynolds, S., Rovira, H., Shmulevich, I., Ramirez, R., Schultz, N., Gao, J., Jacobsen, A., Aksoy, B. A., Antipin, Y., Ciriello, G., Dresdner, G., Gross, B., Lee, W., Reva, B., Shen, R., Sinha, R., Sumer, S. O., Weinhold, N., Ladanyi, M., Sander, C., Benz, C., Carlin, D., Haussler, D., Ng, S., Paull, E. O., Stuart, J., Zhu, J., Liu, Y., Zhang, W., Taylor, B. S., Lichtenberg, T. M., Zmuda, E., Barr, T., Black, A. D., George, M., Hanf, B., Helsel, C., McAllister, C., Ramirez, N. C., Tabler, T. R., Weaver, S., Wise, L., Bowen, J., Gastier-Foster, J. M., Weinstein, J. N., Lerner, S., Jian, W., Tello, S., Ittman, M., Castro, P., McClenden, W. D., Morgan, M., Gibbs, R., Liu, Y., Saller, C., Tarvin, K., DiPiero, J. M., Owens, J., Bollag, R., Li, Q., Weinberger, P., Czerwinski, C., Huelsenbeck-Dill, L., Iacocca, M., Petrelli, N., Rabeno, B., Swanson, P., Shelton, T., Curley, E., Gardner, J., Mallery, D., Penny, R., Nguyen Van Bang, N. V., Phan Thi Hanh, P. T., Kohl, B., Xuan Van Le, X. V., Bui Duc Phu, B. D., Thorp, R., Nguyen Viet Tien, N. V., Le Quang Vinh, L. Q., Sandusky, G., Burks, E., Christ, K., Gee, J., Holway, A., Moinzadeh, A., Sorcini, A., Sullivan, T., Al-Ahmadie, H. A., Bajorin, D. F., Bochner, B. H., Garcia-Grossman, I. R., Regazzi, A. M., Solit, D. B., Rosenberg, J. E., Reuter, V. E., Koppie, T., Boice, L., Rathmell, W. K., Thorne, L., Bastacky, S., Davies, B., Dhir, R., Gingrich, J., Hrebinko, R., Maranchie, J., Nelson, J., Parwani, A., Bshara, W., Gaudioso, C., Morrison, C., Alexopoulou, V., Bartlett, J., Engel, J., Kodeeswaran, S., Antic, T., O'Donnell, P. H., Smith, N. D., Steinberg, G. D., Egea, S., Gomez-Fernandez, C., Herbert, L., Jorda, M., Soloway, M., Beaver, A., Carter, S., Kapur, P., Lewis, C., Lotan, Y., Robinson, B., Hansel, D., Guo, C., Bondaruk, J., Czerniak, B., Akbani, R., Broom, B. M., Liu, Y., Zhang, W., Weinstein, J. N., Lerner, S., Morgan, M., Kim, J., Cherniack, A. D., Freeman, S. S., Pedamallu, C. S., Noble, M. S., Kwiatkowski, D. J., Al-Ahmadie, H. A., Bajorin, D. F., Bochner, B. H., Solit, D. B., Rosenberg, J. E., Reuter, V. E., Koppie, T., Robinson, B., Skinner, E., Ramirez, R., Schultz, N., Hansel, D., Kim, W. Y., Guo, C., Bondaruk, J., Aldape, K., Czerniak, B., Jensen, M. A., Kahn, A. B., Pihl, T. D., Pot, D. A., Srinivasan, D., Wan, Y., Ferguson, M. L., Zenklusen, J. C., Davidsen, T., Demchok, J. A., Shaw, K. R., Sheth, M., Tarnuzzer, R., Wang, Z., Yang, L., Hutter, C., Ozenberger, B. A., Sofia, H. J., Eley, G. 2014; 507 (7492): 315-322

  View details for DOI 10.1038/nature12965

  View details for Web of Science ID 000333029000025

• Long-term cancer control after radical prostatectomy and bilateral pelvic lymph node dissection for pT3bN0M0 prostate cancer in the prostate-specific antigen era. Urologic oncology Fairey, A. S., Daneshmand, S., Skinner, E. C., Schuckman, A., Cai, J., Lieskovsky, G. 2014; 32 (2): 85-91

  Abstract

  We evaluated long-term cancer control outcomes of radical prostatectomy and bilateral pelvic lymph node dissection (RP) for pT3bN0M0 prostate cancer in the era of prostate-specific antigen (PSA) screening.A retrospective analysis of prospectively collected data from the University of Southern California Prostate Cancer Database was performed. Between 1987 and 2008, 229 men underwent open RP for pT3bN0M0 prostate cancer. The cohort was divided into early (1987-1997) and contemporary (1998-2008) PSA eras. The Kaplan-Meier method and Cox proportional regression models were used to analyze clinical recurrence (CR) and biochemical recurrence (BCR).The median follow-up duration was 14.5 years (range, 0.2-21.1y). The predicted 10-year freedom from CR and BCR rates for men treated in the early and contemporary PSA eras were 73% and 95% (Log-rank P = 0.001) and 65% and 73% (Log-rank P = 0.055), respectively. Multivariable analysis showed that pathologic Gleason grade 8-10 (CR: hazard ratio [HR] = 5.11; 95% confidence interval [CI] = 1.72-15.20; P = 0.003; BCR: HR = 3.47; 95% CI = 1.60-7.48; P = 0.002) and contemporary PSA era (CR: HR = 0.15; 95% CI = 0.06-0.41; P<0.001; BCR: HR = 0.49; 95% CI = 0.28-0.86; P = 0.013) were independently associated with cancer control. Adjuvant radiation therapy and positive surgical margins were not independently associated with outcomes.RP conferred long-term cancer control in men with pT3bN0M0 prostate cancer treated in the PSA era. Pathologic Gleason grade 8-10 and treatment in the early PSA era were independently associated with poorer cancer control outcomes.

  View details for DOI 10.1016/j.urolonc.2013.03.005

  View details for PubMedID 24183191

• Does presence of squamous and glandular differentiation in urothelial carcinoma of the bladder at cystectomy portend poor prognosis? An intensive case-control analysis UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS Mitra, A. P., Bartsch, C. C., Bartsch, G., Miranda, G., Skinner, E. C., Daneshmand, S. 2014; 32 (2): 117-127

  Abstract

  The prognostic significance of squamous and glandular elements, the most common histologic variants of urothelial carcinoma of the bladder (UCB), is unclear. This study aimed to examine the sole influence of squamous or glandular or both differentiation on UCB outcome following cystectomy and to identify factors that explain the relatively poor prognosis observed in UCB patients with these differentiation elements.A total of 2,444 patients who underwent radical cystectomy with extended lymph node dissection at a single referral center between 1976 and 2008 were considered. We identified 141, 97, and 21 patients with squamous, glandular, and squamous + glandular differentiation elements, respectively ("cases"). Pure UCB patients without differentiation were matched 1:1 to these cases for demographic, tumor, and treatment characteristics ("controls"). Cases were also compared with an independent cohort of 1,244 pure UCB controls. Recurrence-free and overall survivals were compared between cohorts using univariable and multivariable Cox proportional hazards analyses.Median follow-up for cases, controls, and independent control cohort was 15.2, 11.0, and 12.2 years, respectively. Cases were matched to controls for pathologic stage (chi-square P = 1.00) and administration of intravesical agents (P≥0.85), neoadjuvant (P≥0.31), and adjuvant (P≥0.96) chemotherapy. Cases were also balanced with controls for age, gender, and race (P≥0.30). Following this intensive matching, no differences in outcomes between cases and controls were observed (log-rank P≥0.12). Pathologic stage was predictive of outcome in cases with differentiation by multivariable analysis (P≤0.004). When compared to an independent control cohort, cases with differentiation were observed to present with higher pathologic stage at cystectomy (chi-square P≤0.005).Outcomes of UCB patients with squamous or glandular or both differentiation are similar to those of patients with pure UCB, given comparable demographic, clinicopathologic, and management characteristics. However, UCB with differentiation present with higher pathologic stage, thus explaining the aggressive clinical course in these patients.

  View details for DOI 10.1016/j.urolonc.2012.08.017

  View details for Web of Science ID 000330500300009

  View details for PubMedID 23477878

• Impact of micropapillary urothelial carcinoma variant histology on survival after radical cystectomy. Urologic oncology Fairey, A. S., Daneshmand, S., Wang, L., Schuckman, A., Lieskovsky, G., Djaladat, H., Cai, J., Miranda, G., Skinner, E. C. 2014; 32 (2): 110-116

  Abstract

  The role of micropapillary urothelial carcinoma (MUC) variant histology as an independent prognostic factor for survival after radical cystectomy has not been studied. Our aim was to examine the impact of MUC on survival.A retrospective analysis of prospectively collected data from the University of Southern California (USC) Bladder Cancer Database was performed. Between 1985 and 2008, 1,380 patients underwent radical cystectomy and superextended pelvic lymph node dissection for bladder cancer. All surgical specimens underwent central pathologic review by dedicated genitourinary pathologists. Histologic type was categorized as urothelial carcinoma (UC; n = 1,347) or MUC (n = 33). The outcomes were overall survival (OS) and recurrence-free survival (RFS). The Kaplan-Meier method and Cox proportional regression models were used to analyze survival data.The median follow-up duration was 10 years (range, 0-25 years). Baseline characteristics were similar between histologic types except MUC was associated with advanced clinical (cTanyN1-3: 2% vs. 9%, P = 0.03) and pathologic (pTanyN1-3: 22% vs. 46%, P = 0.01) TNM stage, multifocality (38% vs. 58%, P = 0.02), and high nuclear grade (83% vs. 97%, P = 0.03). The predicted 5-year OS (61% and 67%, Log rank P = 0.96) and RFS (69% and 58%, Log rank P = 0.33) rates did not differ between patients with UC and MUC. Multivariable analysis showed that histologic type was not independently associated with OS (HR 0.91, 95% CI 0.55-1.49, P = 0.70) or RFS (HR 0.97, 95% CI 0.55-1.73, P = 0.92).Outcomes of radical cystectomy for patients with MUC are similar to those with UC when controlling for other clinical and pathologic factors.

  View details for DOI 10.1016/j.urolonc.2012.04.020

  View details for PubMedID 23499168

• Urinary functional outcomes in female neobladder patients. World journal of urology Bartsch, G., Daneshmand, S., Skinner, E. C., Syan, S., Skinner, D. G., Penson, D. F. 2014; 32 (1): 221-228

  Abstract

  The ratio between orthotopic and non-orthotopic diversions in women is far lower than in male patients. Data on urinary function in female patients with neobladders are therefore sparse.We investigated the urinary function of female neobladder patients utilizing the Bladder Cancer Index, a validated and reliable health-related quality-of-life (HRQOL) questionnaire. Furthermore, we tried to identify preoperative factors that may influence functional results. All living female patients with an orthotopic neobladder (N = 82) from the University of Southern California Bladder Cancer Database were sent a questionnaire including the University of Michigan Bladder Cancer Index. Univariate analyses were performed using the Kruskal-Wallis test followed by a multivariate stepwise regression model.Fifty-six patients (68.3 %) responded and were included in the analysis. Thirty-five (62.5 %) of these patients had to catheterize their neobladder to a certain amount, while 25 patients (44.6 %) depend on catheterization to empty their neobladder. Univariate analyses showed that patient age (>65 years) was the only variable associated with a statistically significant lower rate of neobladder catheterization. Better urinary bother scores were associated with organ-confined disease (p = 0.038) and education level (p = 0.01). However, these variables were not significant in a multivariate stepwise linear regression model.Considerably more women require urinary catheterization to void than previously reported. In this study, representing the largest investigated cohort in this topic, we were unable to identify any predictors of this outcome or any other urinary HRQOL in this cohort.

  View details for DOI 10.1007/s00345-013-1219-8

  View details for PubMedID 24317553

• Incidence and location of lymph node metastases in patients undergoing radical cystectomy for clinical non-muscle invasive bladder cancer: results from a prospective lymph node mapping study. Urologic oncology Bruins, H. M., Skinner, E. C., Dorin, R. P., Ahmadi, H., Djaladat, H., Miranda, G., Cai, J., Daneshmand, S. 2014; 32 (1): 24 e13-9

  Abstract

  The objective of this study is to investigate the incidence and location of lymph node metastases (LNMs) in patients undergoing radical cystectomy (RC) and lymph node dissection (LND) for clinical non-muscle invasive bladder cancer (NMIBC).Prospectively collected data of 637 patients who underwent RC and 'superextended' LND with intent-to-cure for urothelial carcinoma of the bladder between 2002 and 2008 were examined. Inclusion criteria were (a) clinical stage Ta, Tis-only, or T1, (b) muscle presence at diagnostic transurethral resection in clinical T1 patients, (c) no prior diagnosis of ≥ T2 disease, (d) no neoadjuvant therapy, and (e) lymphatic tissue sample submitted from all 13 predesignated locations. Lymph node mapping was performed in all patients to determine the location of metastatic lymph nodes. Median follow-up time was 4.7 years. Recurrence-free survival and overall survival were reported.A total of 114 patients were included of whom 9 patients (7.9%) had LNM. Stratified by clinical stage, LNM was present in 6/67 (9.0%) patients with cT1, 3/25 (12.0%) patients with cTis-only, and none of the 22 patients with cTa. Of the 9 node-positive patients (33.3%), 3 had LNM proximal to the aortic bifurcation. No skip metastases were found. After RC, 27 patients (23.7%) were upstaged to muscle invasive disease; of whom 16.7% had cT1, 2.6% had cTa, and 4.4% had cTis-only. Of the remaining 87 patients with pathologic NMIBC, 1 patient (1.1%) had LNM, limited to the true pelvis. Five-year RFS was 82.3%, 81.5%, and 62.0% in patients with pathologic NMIBC, clinical NMIBC, and pathologic muscle invasive bladder cancer, respectively.Routine LND is important in patients with cT1 and cTis-only bladder cancer, but may have limited value in patients with cTa. LNM beyond the boundaries of a standard LND occurred in up to one-third of node-positive patients. In the absence of skip metastases, however, performing a standard LND would correctly identify all node-positive patients. Whether removal of LNM proximal to the common iliac vessels provides a survival benefit remains to be evaluated in future prospective studies.

  View details for DOI 10.1016/j.urolonc.2012.08.015

  View details for PubMedID 23395238

• Outcome in patients with exclusive carcinoma in situ (CIS) after radical cystectomy. BJU international Zehnder, P., Moltzahn, F., Daneshmand, S., Leahy, M., Cai, J., Miranda, G., Bartsch, G., Mitra, A. P., Skinner, D. G., Skinner, E. C., Gill, I. S. 2014; 113 (1): 65-69

  Abstract

  To evaluate oncological outcomes of patients with carcinoma in situ (CIS) exclusively at radical cystectomy (RC) and no previous history of ≥T1 disease.Patients undergoing RC with curative intent for CIS between 1971 and 2008 at the University of Southern California were included if they met all the following criteria: (i) pathological CIS-only disease at RC, (ii) preoperative clinical stage cCIS and/or cCIS + cTa, and (iii) no previous history of lamina propria invasion (≥pT1). Kaplan-Meier plots were used to estimate the probabilities of recurrence-free survival (RFS) and overall survival (OS).Of the 1964 consented patients 52 met the inclusion criteria with a median (range) follow-up of 8.5 (0.008-34) years. A median (range) of 36 (10-95) lymph nodes were identified per patient but no metastases found. Estimated 5- and 10-year RFS rates were 94% and 90%, respectively and estimated 5- and 10-year OS rates were 85% and 66%, respectively. Different mechanisms of recurrence were found in four (8%) patients after a median (range) interval of 2.4 (0.6-7.1) years. While two patients had metachronous recurrence within the urinary tract, the first of the other two had early systemic recurrence and the second late local recurrence.We noticed excellent outcomes after RC for CIS-only disease. However, patients may have synchronous and/or develop metachronous tumours, as well as local and/or distant/systemic recurrence that can be cured but may also lead to fatal outcomes.

  View details for DOI 10.1111/bju.12250

  View details for PubMedID 23937628

• Effect of gender on outcomes following radical cystectomy for urothelial carcinoma of the bladder: a critical analysis of 1,994 patients. Urologic oncology Mitra, A. P., Skinner, E. C., Schuckman, A. K., Quinn, D. I., Dorff, T. B., Daneshmand, S. 2014; 32 (1): 52 e1-9

  Abstract

  The oncological basis behind the observation that females experience worse outcomes following radical cystectomy for urothelial carcinoma of the bladder (UCB) is unclear. This study was aimed at examining the sole effect of gender on postcystectomy UCB outcomes and identifying potential factors that may explain the poor prognosis in females using a balanced case-control approach.A review of 2,567 patients with UCB who underwent radical cystectomy identified 414 females ("cases") who were matched 1:1 for demographic, tumor, and treatment characteristics with 414 male counterparts ("controls"). Cases were also compared with an independent male UCB cohort (n = 1,166). Differences between females vs. matched control and independent male patients with UCB were analyzed. Recurrence-free survival, cancer-specific survival, and overall survival were compared by univariable and multivariable Cox regression models.Median follow-up for cases, controls, and independent control cohort was 12.2, 8.6, and 13.5 years, respectively. Females were matched to male controls for tumor and nodal stages (P = 1.00), lymphovascular invasion and surgical margin status, age, prior intravesical treatment, and neoadjuvant and adjuvant chemotherapy administration (P = 0.61-1.00). Cases were also balanced with controls for grade, p53 status, nodal yield, American Society of Anesthesiologists score, presence of hydronephrosis, and times to diagnosis and cystectomy (P ≥ 0.14). When thus matched, outcomes between females and males were not different (P ≥ 0.34). However, when compared with an independent unmatched male control cohort, females had significantly poorer outcomes (P ≤ 0.006). In this comparison, females presented with higher tumor (P<0.001) and nodal (P = 0.049) stages and a lesser proportion received precystectomy intravesical therapy (P = 0.032).Females have similar UCB outcomes to males when matched for demographic, clinicopathologic, and management characteristics. However, they present with more advanced tumors, thus explaining the observation of poor outcomes.

  View details for DOI 10.1016/j.urolonc.2013.08.007

  View details for PubMedID 24239476

• Radical cystectomy and orthotopic urinary diversion in male patients with pT4a urothelial bladder carcinoma: Oncological outcomes INTERNATIONAL JOURNAL OF UROLOGY Djaladat, H., Mitra, A. P., Miranda, G., Skinner, E. C., Daneshmand, S. 2013; 20 (12): 1229-1233

  Abstract

  The aim of the present study was to evaluate the oncological outcomes of radical cystectomy followed by orthotopic urinary diversion in male patients with urothelial bladder carcinoma involving prostatic stroma (pT4a). A total of 1964 patients with urothelial bladder carcinoma who underwent cystectomy between 1971 and 2008 were retrospectively analyzed. Among them, male patients with pT4aN0M0 disease at cystectomy and orthotopic urinary diversion were identified and included in the analysis. Exclusion criteria were perioperative mortality and primary urethrectomy. The outcomes were urethral recurrence, local recurrence, recurrence-free survival and overall survival. Univariate and log-rank statistics were used to examine associations between variables and outcome. A total of 33 patients (1.7%) entered the study with a median age of 71 years. Median follow up was 4.8 years (range 0.1-21 years). A total of two urethral recurrences (6%) occurred at a median of 2.4 years after cystectomy. No patient had local recurrence. The 5-year recurrence-free survival and overall survival was 56% ± 10% and 56% ± 9%, respectively. The probability of urethral and local recurrence after orthotopic diversion in pT4a urothelial bladder carcinoma patients is low. Thus, orthotopic urinary diversion appears to be oncologically safe in this patient population.

  View details for DOI 10.1111/iju.12133

  View details for Web of Science ID 000327533500021

  View details for PubMedID 23521752

• Incidental Prostate Cancer in Patients with Bladder Urothelial Carcinoma: Comprehensive Analysis of 1,476 Radical Cystoprostatectomy Specimens JOURNAL OF UROLOGY Bruins, H. M., Djaladat, H., Ahmadi, H., Sherrod, A., Cai, J., Miranda, G., Skinner, E. C., Daneshmand, S. 2013; 190 (5): 1704-1709

  Abstract

  We identified risk factors and determined the incidence and prognosis of incidental, clinically significant prostatic adenocarcinoma, prostatic urothelial carcinoma and HGPIN in patients treated with radical cystoprostatectomy for urothelial carcinoma of the bladder.We analyzed the records of 1,476 patients without a history of prostatic adenocarcinoma. We determined the incidence of clinically significant prostatic adenocarcinoma, prostatic urothelial carcinoma and HGPIN in the total cohort and in select patient subgroups. Prostatic urothelial carcinoma was stratified as prostatic stromal and prostatic urethral/duct involvement. Univariate and multivariate analyses were performed with multiple variables. Recurrence-free and overall survival rates were calculated. Median followup was 13.2 years.Of the 1,476 patients 753 (51.0%) had cancer involving the prostate. Prostatic adenocarcinoma, clinically significant prostatic adenocarcinoma, prostatic urothelial carcinoma and HGPIN were present in 37.9%, 8.3%, 21.1% and 51.2% of patients, respectively. Of the 312 patients (21.1%) with prostatic urothelial carcinoma 163 (11.0%) had prostatic urethral/duct involvement only and 149 (10.1%) had prostatic stromal involvement. We identified risk factors for clinically significant prostatic adenocarcinoma, prostatic urothelial carcinoma and HGPIN but the absence of these risk factors did not rule out their presence. Ten-year overall survival in patients with no prostatic urothelial carcinoma, and prostatic urethral/duct and prostatic stromal involvement was 47.1%, 43.3% and 21.7%, respectively (p<0.001). No patient with clinically significant prostatic adenocarcinoma died of prostatic cancer.More than half of the patients undergoing radical cystoprostatectomy had cancer involving the prostate. Prostatic urothelial carcinoma, particularly with prostatic stromal involvement, was associated with a worse prognosis, while clinically significant prostatic adenocarcinoma did not alter survival. Preoperative clinical and histopathological risk factors are not reliable enough to accurately predict clinically significant prostatic adenocarcinoma and/or prostatic urothelial carcinoma.

  View details for DOI 10.1016/j.juro.2013.05.034

  View details for Web of Science ID 000325471400021

  View details for PubMedID 23707451

• Neoadjuvant chemotherapy with gemcitabine/cisplatin vs. methotrexate/vinblastine/doxorubicin/cisplatin for muscle-invasive urothelial carcinoma of the bladder: A retrospective analysis from the University of Southern California UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS Fairey, A. S., Daneshmand, S., Quinn, D., Dorff, T., Dorin, R., Lieskovsky, G., Schuckman, A., Cai, J., Miranda, G., Skinner, E. C. 2013; 31 (8): 1737-1743

  Abstract

  We evaluated pathologic and survival outcomes of GC (gemcitabine/cisplatin) and methotrexate/vinblastine/doxorubicin/cisplatin (M-VAC) neoadjuvant chemotherapy (NAC) in patients with muscle-invasive bladder cancer (MIBC).A retrospective analysis of prospectively collected data on 116 patients who received NAC (GC: n = 58; M-VAC: n = 58) before radical cystectomy and superextended pelvic lymph node dissection for clinical stage T2-4N0M0 bladder cancer was performed. The outcomes were complete response rate (CRR; pT0N0), partial response rate (PRR; pT0N0, pTaN0, pT1N0, or pTisN0), overall mortality (OM), and recurrence. The Kaplan-Meier method and multivariable Cox regression analysis were used to analyze OM. The cumulative incidence method and Fine and Gray's competing risk regression analysis were used to analyze recurrence.The median follow-up duration was 2.1 years for the GC group and 7.4 years for the M-VAC group (P < 0.001). There were no statistically significant differences between the GC and M-VAC groups with regard to CRR (27.3% vs. 17.1%, P = 0.419) or PRR (45.5% vs. 37.1%, P = 0.498). The predicted 5-year freedom from OM rate (P = 0.634) and cumulative incidence of recurrence rate (P = 0.891) did not differ between the GC and M-VAC groups. Multivariable analysis showed that there was no independent association between type of NAC and OM (P = 0.721) or recurrence (P = 0.065).Pathologic and survival outcomes did not differ in patients who received GC and M-VAC NAC. These data support the use of the GC regimen in the neoadjuvant setting.

  View details for DOI 10.1016/j.urolonc.2012.07.005

  View details for Web of Science ID 000326556900049

  View details for PubMedID 23141776

• Null Association Between Histology of First and Second Primary Malignancies in Men With Bilateral Testicular Germ Cell Tumors AMERICAN JOURNAL OF EPIDEMIOLOGY Thomas, J. P., Davis-Dao, C., Lewinger, J. P., Siegmund, K. D., Hamilton, A. S., Daneshmand, S., Skinner, E. C., Thomas, D. C., Cortessis, V. K. 2013; 178 (8): 1240-1245

  Abstract

  Testicular germ cell tumors (TGCTs), the most common neoplasms of young men, are categorized histologically as either seminomas or nonseminomas/mixed germ cell tumors. These subtypes differ by age at diagnosis and clinical course, but little is known about etiological distinctions. To test the hypothesis that histological subtypes have distinct sets of unrecognized etiological factors, we used a recently described approach, estimating the association between histological types of first and second tumors of men with 2 primary TGCTs. The study population of 488 men each with 2 primary TGCTs was ascertained through population-based cancer registries in the United States between 1972 and 2006. Univariate logistic regression analysis revealed that the histology of second primary TGCTs was associated with the histology of first TGCTs (odds ratio = 1.70, 95% confidence interval: 1.14, 2.52); however, the association did not persist in analyses adjusted for age at diagnosis of first TGCT (odds ratio = 1.09, 95% confidence interval: 0.71, 1.70). These results would be expected if the subtypes share etiology but experience different rates of progression to diagnosis or if the histological fate of TGCTs is influenced by age-related processes. Men with 2 primary TGCTs provide novel opportunities to learn whether histological subtypes are likely to share etiology, so results may inform research designed to identify causes.

  View details for DOI 10.1093/aje/kwt100

  View details for Web of Science ID 000325759000009

  View details for PubMedID 23928263

  View details for PubMedCentralID PMC3792726

• SWOG S0353: Phase II Trial of Intravesical Gemcitabine in Patients with Nonmuscle Invasive Bladder Cancer and Recurrence after 2 Prior Courses of Intravesical Bacillus Calmette-Guerin JOURNAL OF UROLOGY Skinner, E. C., Goldman, B., Sakr, W. A., Petrylak, D. P., Lenz, H., Lee, C. T., Wilson, S. S., Benson, M., Lerner, S. P., Tangen, C. M., Thompson, I. M. 2013; 190 (4): 1200-1204

  Abstract

  Prior phase II studies of intravesical gemcitabine have shown it to be active and well tolerated, but durable responses in patients with nonmuscle invasive bladder cancer who have experienced recurrence after bacillus Calmette-Guérin treatment are uncommon. We performed a multi-institutional phase II study within the SWOG (Southwest Oncology Group) cooperative group to evaluate the potential role of gemcitabine induction plus maintenance therapy in this setting.Eligible patients had recurrent nonmuscle invasive bladder cancer, stage Tis (carcinoma in situ), T1, Ta high grade or multifocal Ta low grade after at least 2 prior courses of bacillus Calmette-Guérin. Patients were treated with 2 gm gemcitabine in 100 cc normal saline intravesically weekly × 6 and then monthly to 12 months. Cystoscopy and cytology were performed every 3 months, with biopsy at 3 months and then as clinically indicated. Initial complete response was defined as negative cystoscopy, cytology and biopsy at 3 months.A total of 58 patients were enrolled in the study and 47 were evaluable for response. Median patient age was 70 years (range 50 to 88). Of the evaluable patients 42 (89%) had high risk disease, including high grade Ta in 12 (26%), high grade T1 in 2 (4%) and carcinoma in situ in 28 (60%) with or without papillary lesions. At the initial 3-month evaluation 47% of patients were free of disease. At 1 year disease had not recurred in 28% of the 47 patients, all except 2 from the high risk group, and at 2 years disease had not recurred in 21%.Intravesical gemcitabine has activity in high risk nonmuscle invasive bladder cancer and offers an option for patients with recurrence after bacillus Calmette-Guérin who are not suitable for cystectomy. However, less than 30% of patients had a durable response at 12 months even with maintenance therapy.

  View details for DOI 10.1016/j.juro.2013.04.031

  View details for Web of Science ID 000325091700010

  View details for PubMedID 23597452

  View details for PubMedCentralID PMC4113593

• A novel precision-engineered microfiltration device for capture and characterisation of bladder cancer cells in urine EUROPEAN JOURNAL OF CANCER Birkhahn, M., Mitra, A. P., Williams, A. J., Barr, N. J., Skinner, E. C., Stein, J. P., Skinner, D. G., Tai, Y., Datar, R. H., Cote, R. J. 2013; 49 (15): 3159-3168

  Abstract

  Sensitivity of standard urine cytology for detecting urothelial carcinoma of the bladder (UCB) is low, attributable largely to its inability to process entire samples, paucicellularity and presence of background cells.Evaluate performance and practical applicability of a novel portable microfiltration device for capture, enumeration and characterisation of exfoliated tumour cells in urine, and compare it with standard urine cytology for UCB detection.A total of 54 urine and bladder wash samples from patients undergoing surveillance for UCB were prospectively evaluated by standard and microfilter-based urine cytology. Head-to-head comparison of quality and performance metrics, and cost effectiveness was conducted for both methodologies.Five samples were paucicellular by standard cytology; no samples processed by microfilter cytology were paucicellular. Standard cytology had 33.3% more samples with background cells that limited evaluation (p<0.001). Microfilter cytology was more concordant (κ=50.4%) than standard cytology (κ=33.5%) with true UCB diagnosis. Sensitivity, specificity and accuracy were higher for microfilter cytology compared to standard cytology (53.3%/100%/79.2% versus 40%/95.8%/69.9%, respectively). Microfilter-captured cells were amenable to downstream on-chip molecular analyses. A 40 ml sample was processed in under 4 min by microfilter cytology compared to 5.5 min by standard cytology. Median microfilter cytology processing and set-up costs were approximately 63% cheaper and 80 times lower than standard cytology, respectively.The microfiltration device represents a novel non-invasive UCB detection system that is economical, rapid, versatile and has potentially better quality and performance metrics than routine urine cytology, the current standard-of-care.

  View details for DOI 10.1016/j.ejca.2013.04.033

  View details for Web of Science ID 000325005200012

  View details for PubMedID 23849827

• Unaltered oncological outcomes of radical cystectomy with extended lymphadenectomy over three decades BJU INTERNATIONAL Zehnder, P., Studer, U. E., Skinner, E. C., Thalmann, G. N., Miranda, G., Roth, B., Cai, J., Birkhaeuser, F. D., Mitra, A. P., Burkhard, F. C., Dorin, R. P., Daneshmand, S., Skinner, D. G., Gill, I. S. 2013; 112 (2): E51-E58

  Abstract

  To evaluate oncological outcome trends over the last three decades in patients after radical cystectomy (RC) and extended pelvic lymph node (LN) dissection.Retrospective analysis of the University of Southern California (USC) RC cohort of patients (1488 patients) operated with intent to cure from 1980 to 2005 for biopsy confirmed muscle-invasive urothelial bladder cancer. To focus on outcomes of unexpected (cN0M0) LN-positive patients, the USC subset was extended with unexpected LN-positive patients from the University of Berne (UB) (combined subgroup 521 patients). Patients were grouped and compared according to decade of surgery (1980-1989/1990-1999/≥2000). Survival probabilities were calculated with Kaplan-Meier plots, log-rank tests compared outcomes according to decade of surgery, followed by multivariable verification.The 10-year recurrence-free survival was 78-80% in patients with organ-confined, LN-negative disease, 53-60% in patients with extravesical, yet LN-negative disease and ≈30% in LN-positive patients. Although the number of patients receiving systemic chemotherapy increased, no survival improvement was noted in either the entire USC cohort, or in the combined LN-positive USC-UB cohort. In contrast, patient age at surgery increased progressively, suggesting a relative survival benefit.Radical surgery remains the mainstay of therapy for muscle-invasive bladder cancer. Yet, our study reveals predictable outcomes but no survival improvement in patients undergoing RC over the last three decades. Any future survival improvements are likely to result from more effective systemic treatments and/or earlier detection of the disease.

  View details for DOI 10.1111/bju.12215

  View details for Web of Science ID 000320930200007

  View details for PubMedID 23795798

• Testicular germ cell tumor susceptibility associated with the UCK2 locus on chromosome 1q23 HUMAN MOLECULAR GENETICS Schumacher, F. R., Wang, Z., Skotheim, R. I., Koster, R., Chung, C. C., Hildebrandt, M. A., Kratz, C. P., Bakken, A. C., Bishop, D. T., Cook, M. B., Erickson, R. L., Fossa, S. D., Greene, M. H., Jacobs, K. B., Kanetsky, P. A., Kolonel, L. N., Loud, J. T., Korde, L. A., Le Marchand, L., Lewinger, J. P., Lothe, R. A., Pike, M. C., Rahman, N., Rubertone, M. V., Schwartz, S. M., Siegmund, K. D., Skinner, E. C., Turnbull, C., Van den Berg, D. J., Wu, X., Yeager, M., Nathanson, K. L., Chanock, S. J., Cortessis, V. K., McGlynn, K. A. 2013; 22 (13): 2748-2753

  Abstract

  Genome-wide association studies (GWASs) have identified multiple common genetic variants associated with an increased risk of testicular germ cell tumors (TGCTs). A previous GWAS reported a possible TGCT susceptibility locus on chromosome 1q23 in the UCK2 gene, but failed to reach genome-wide significance following replication. We interrogated this region by conducting a meta-analysis of two independent GWASs including a total of 940 TGCT cases and 1559 controls for 122 single-nucleotide polymorphisms (SNPs) on chromosome 1q23 and followed up the most significant SNPs in an additional 2202 TGCT cases and 2386 controls from four case-control studies. We observed genome-wide significant associations for several UCK2 markers, the most significant of which was for rs3790665 (PCombined = 6.0 × 10(-9)). Additional support is provided from an independent familial study of TGCT where a significant over-transmission for rs3790665 with TGCT risk was observed (PFBAT = 2.3 × 10(-3)). Here, we provide substantial evidence for the association between UCK2 genetic variation and TGCT risk.

  View details for DOI 10.1093/hmg/ddt109

  View details for Web of Science ID 000320125100017

  View details for PubMedID 23462292

  View details for PubMedCentralID PMC3674801

• Meta-analysis identifies four new loci associated with testicular germ cell tumor NATURE GENETICS Chung, C. C., Kanetsky, P. A., Wang, Z., Hildebrandt, M. A., Koster, R., Skotheim, R. I., Kratz, C. P., Turnbull, C., Cortessis, V. K., Bakken, A. C., Bishop, D. T., Cook, M. B., Erickson, R. L., Fossa, S. D., Jacobs, K. B., Korde, L. A., Kraggerud, S. M., Lothe, R. A., Loud, J. T., Rahman, N., Skinner, E. C., Thomas, D. C., Wu, X., Yeager, M., Schumacher, F. R., Greene, M. H., Schwartz, S. M., McGlynn, K. A., Chanock, S. J., Nathanson, K. L. 2013; 45 (6): 680-?

  Abstract

  We conducted a meta-analysis to identify new susceptibility loci for testicular germ cell tumor (TGCT). In the discovery phase, we analyzed 931 affected individuals and 1,975 controls from 3 genome-wide association studies (GWAS). We conducted replication in 6 independent sample sets comprising 3,211 affected individuals and 7,591 controls. In the combined analysis, risk of TGCT was significantly associated with markers at four previously unreported loci: 4q22.2 in HPGDS (per-allele odds ratio (OR) = 1.19, 95% confidence interval (CI) = 1.12-1.26; P = 1.11 × 10(-8)), 7p22.3 in MAD1L1 (OR = 1.21, 95% CI = 1.14-1.29; P = 5.59 × 10(-9)), 16q22.3 in RFWD3 (OR = 1.26, 95% CI = 1.18-1.34; P = 5.15 × 10(-12)) and 17q22 (rs9905704: OR = 1.27, 95% CI = 1.18-1.33; P = 4.32 × 10(-13) and rs7221274: OR = 1.20, 95% CI = 1.12-1.28; P = 4.04 × 10(-9)), a locus that includes TEX14, RAD51C and PPM1E. These new TGCT susceptibility loci contain biologically plausible genes encoding proteins important for male germ cell development, chromosomal segregation and the DNA damage response.

  View details for DOI 10.1038/ng.2634

  View details for Web of Science ID 000319563900017

  View details for PubMedID 23666239

  View details for PubMedCentralID PMC3723930

• Critical analysis and validation of lymph node density as prognostic variable in urothelial carcinoma of bladder. Urologic oncology Kassouf, W., Svatek, R. S., Shariat, S. F., Novara, G., Lerner, S. P., Fradet, Y., Bastian, P. J., Aprikian, A., Karakiewicz, P. I., Fritsche, H. M., Dinney, C. P., Tilki, D., Kamat, A. M., Izawa, J. I., Ficarra, V., Lotan, Y., Sagalowsky, A. I., Schoenberg, M. P., Skinner, E. C. 2013; 31 (4): 480-486

  Abstract

  To validate the prognostic relevance of lymph node density (LND) and identify its optimal cut-points in a large international multicenter series of patients treated with radical cystectomy (RC) for invasive bladder cancer.From 1993 to 2005, 4,430 bladder cancer patients who underwent RC without neoadjuvant chemotherapy were reviewed; of these, 1,038 were pN+M0 disease and form the basis of this report.Median age of patients was 67 years with median follow-up in survivors of 33 months. Overall, 5-year DSS estimate was 36%. Median number of lymph nodes removed was 18 (IQR, 11-32), median number of positive lymph nodes was 2 (IQR, 1-5), and median LND was 14.3% (IQR, 6.67-33.3%). LND as continuous variable was a stronger prognostic factor for DSS in patients that underwent a more extensive PLND (P < 0.001). HR for inverse association of LND with DSS increased incrementally with increasing LND cut-points. Categorizing LND into quintiles revealed strong tertiary distribution of risk based on LND <6%, 6%-41%, or >41% with cumulative 5-year DSS of 47%, 36%, and 21%, respectively (P < 0.001). When patients were stratified by adjuvant chemotherapy, LND remains independently prognostic in patients who received adjuvant chemotherapy as well as those who did not.Lymph node density is prognostic in bladder cancer patients who undergo a more extensive PLND and remains prognostic even when adjuvant chemotherapy is used. Prognostic value of LND is best represented as a continuum of risk and LND <6% represents the best possible outcome in patients with nodal disease.

  View details for DOI 10.1016/j.urolonc.2011.02.011

  View details for PubMedID 21478035

• Urinary Functional Outcome Following Radical Cystoprostatectomy and Ileal Neobladder Reconstruction in Male Patients JOURNAL OF UROLOGY Ahmadi, H., Skinner, E. C., Simma-Chiang, V., Miranda, G., Cai, J., Penson, D. F., Daneshmand, S. 2013; 189 (5): 1782-1788

  Abstract

  Orthotopic neobladder reconstruction is the preferred method of urinary diversion after radical cystoprostatectomy. We evaluated urinary functional outcomes in male patients after orthotopic neobladder using a patient questionnaire.Between 2002 and 2009 patients with bladder cancer were enrolled in a clinical trial, randomly assigned to undergo T pouch or Studer pouch diversion after radical cystoprostatectomy. Male patients were mailed a questionnaire 12 or more months after surgery including items on urinary function, intermittent catheterization, number/size/wetness of pads and mucus leakage.The questionnaire response rate was 68%. Mean followup was 4.5 years (range 1 to 8). Only 22.3% of patients did not use pads. In the daytime 47% of patients used at least 1 pad, 32.2% used small/mini pads and 22.6% used diapers. At night 72% used pads, 14.7% used small/mini pads and 38.9% used diapers. During the day and night 47% said their pads were dry/barely wet. Overall 62.5% of patients reported mucus leakage. Only 9.5% of patients performed clean intermittent self-catheterization, of whom 70.6% started clean intermittent self-catheterization within the first year after surgery. Increasing age and diabetes mellitus were predictors of urinary function (p = 0.005 and 0.03, respectively) but did not affect pad use.Ileal orthotopic neobladder offers good functional results but most patients wear at least 1 pad and many require diapers at night. Increasing age and diabetes mellitus predict worse urinary function but are not associated with pad use. Emptying failure is uncommon and occurs early in the postoperative period. Pad size/wetness and mucus leakage should be considered when evaluating urinary incontinence.

  View details for DOI 10.1016/j.juro.2012.11.078

  View details for Web of Science ID 000319262900053

  View details for PubMedID 23159582

• Long-term outcomes of salvage radical cystectomy for recurrent urothelial carcinoma of the bladder following partial cystectomy BJU INTERNATIONAL Bruins, H. M., Wopat, R., Mitra, A. P., Cai, J., Miranda, G., Skinner, E. C., Daneshmand, S. 2013; 111 (3B): E37-E42

  View details for DOI 10.1111/j.1464-410X.2012.11438.x

  View details for Web of Science ID 000315642700003

• Long-term outcomes of salvage radical cystectomy for recurrent urothelial carcinoma of the bladder following partial cystectomy. BJU international Bruins, H. M., Wopat, R., Mitra, A. P., Cai, J., Miranda, G., Skinner, E. C., Daneshmand, S. 2013; 111 (3): E37-42

  Abstract

  Study Type - Therapy (outcomes) Level of Evidence 2b What's known on the subject? and What does the study add? Data on the oncological outcomes in patients undergoing salvage cystectomy for recurrent disease following bladder-sparing treatment is limited and mostly based on case reports. We present the clinical outcomes and prognostic factors in patients undergoing radical cystectomy for recurrent disease following partial cystectomy with long-term follow-up.To report the clinical outcomes and prognostic factors in patients undergoing salvage radical cystectomy (sRC) for recurrent urothelial carcinoma (UC) of the bladder following partial cystectomy (PC).Between 1971 and 2011, a total of 2290 patients underwent radical cystectomy for UC of the bladder, including 72 patients (3.1%) who underwent sRC following PC. Clinical and pathological data at the time of both PC and sRC were collected. Median follow-up time after sRC was 10.9 years. Overall survival and recurrence-free survival were the primary outcomes of interest. Univariate and multivariate analyses were performed to identify prognostic factors after sRC.The median time from PC to sRC was 1.6 years. Median age at sRC was 64 years. Peri-operative mortality was 2.8%. After sRC, 44 patients (61.2%) had pathologically organ-confined disease, 14 patients (19.4%) extravesical disease and 14 patients (19.4%) lymph node positive disease. Five-year recurrence-free survival and overall survival following sRC were 56% and 41%, respectively. On multivariate analysis, the presence of pathological tumor stage ≥pT3a (hazard ratio 6.86, P < 0.001) and the presence of lymph node metastases (hazard ratio 8.78, P < 0.001) were associated with increased risk of recurrence after sRC.sRC can provide prolonged survival following failure of PC. Prognosis, however, is highly dependent on pathological tumour stage and nodal status at sRC. Only 15% of patients with locally advanced recurrent disease were salvaged by sRC.

  View details for DOI 10.1111/j.1464-410X.2012.11438.x

  View details for PubMedID 22974410

• Combination of Molecular Alterations and Smoking Intensity Predicts Bladder Cancer Outcome A Report From the Los Angeles Cancer Surveillance Program CANCER Mitra, A. P., Castelao, J. E., Hawes, D., Tsao-Wei, D. D., Jiang, X., Shi, S., Datar, R. H., Skinner, E. C., Stein, J. P., Groshen, S., Yu, M. C., Ross, R. K., Skinner, D. G., Cortessis, V. K., Cote, R. J. 2013; 119 (4): 756-765

  Abstract

  Traditional single-marker and multimarker molecular profiling approaches in bladder cancer do not account for major risk factors and their influence on clinical outcome. This study examined the prognostic value of molecular alterations across all disease stages after accounting for clinicopathological factors and smoking, the most common risk factor for bladder cancer in the developed world, in a population-based cohort.Primary bladder tumors from 212 cancer registry patients (median follow-up, 13.2 years) were immunohistochemically profiled for Bax, caspase-3, apoptotic protease-activating factor 1 (Apaf-1), Bcl-2, p53, p21, cyclooxygenase-2, vascular endothelial growth factor, and E-cadherin alterations. "Smoking intensity" quantified the impact of duration and daily frequency of smoking.Age, pathological stage, surgical modality, and adjuvant therapy administration were significantly associated with survival. Increasing smoking intensity was independently associated with worse outcome (P < .001). Apaf-1, E-cadherin, and p53 were prognostic for outcome (P = .005, .014, and .032, respectively); E-cadherin remained prognostic following multivariable analysis (P = .040). Combined alterations in all 9 biomarkers were prognostic by univariable (P < .001) and multivariable (P = .006) analysis. A multivariable model that included all 9 biomarkers and smoking intensity had greater accuracy in predicting prognosis than models composed of standard clinicopathological covariates without or with smoking intensity (P < .001 and P = .018, respectively).Apaf-1, E-cadherin, and p53 alterations individually predicted survival in bladder cancer patients. Increasing number of biomarker alterations was significantly associated with worsening survival, although markers comprising the panel were not necessarily prognostic individually. Predictive value of the 9-biomarker panel with smoking intensity was significantly higher than that of routine clinicopathological parameters alone.

  View details for DOI 10.1002/cncr.27763

  View details for Web of Science ID 000314657000010

  View details for PubMedID 23319010

• A precystectomy decision model to predict pathological upstaging and oncological outcomes in clinical stage T2 bladder cancer BJU INTERNATIONAL Mitra, A. P., Skinner, E. C., Miranda, G., Daneshmand, S. 2013; 111 (2): 240-248

  Abstract

  To categorize patients with clinical stage T2 bladder cancer into risk groups based on their potential for pathological upstaging and eventual oncological outcomes at cystectomy. To pre-emptively identify such patients who will be upstaged and have poor outcomes after cystectomy, aiming to better determine the ideal candidates for neoadjuvant chemotherapy.A retrospective review was conducted of 1964 patients who underwent radical cystectomy for bladder cancer with intent to cure at the University of Southern California between 1971 and 2008. Neoadjuvant chemotherapy-naïve patients with clinically organ-confined urothelial carcinoma invading bladder muscle (cT2N0M0) were included. Univariate analysis and multivariable decision tree modelling with cross-validation were employed to identify precystectomy variables that could predict pathological upstaging and poor oncological outcomes.A total of 948 patients met the inclusion criteria, of whom 512 (54%) patients were upstaged at cystectomy; upstaging was associated with a worse recurrence-free and overall survival (both P < 0.001). Age, presence of hydronephrosis, evidence of deep muscularis propria invasion and lymphovascular invasion on transurethral resection specimen, as well as tumour growth pattern and count, were significantly associated with upstaging. When these factors were included in a decision tree model, 70.6% of patients with hydronephrosis experienced upstaging and had the worst outcome (P < 0.001). In patients without hydronephrosis, tumour growth pattern was a second-tier discriminator (P < 0.001); in patients with non-papillary tumours, 71.7% of cases with evidence of deep muscularis propria involvement experienced upstaging compared to 53.8% of cases with no deep muscle involvement (P = 0.012), whereas, among patients with combined papillary and non-papillary features, 33% of cases aged ≤65 years were upstaged compared to 47% of cases aged >65 years (P = 0.036). The cross-validated decision tree resulted in three risk groups with significantly varying probabilities of recurrence-free and overall survival (both with overall P < 0.001).Hydronephrosis, tumour growth pattern, deep muscle involvement and age can collectively identify patients with cT2N0M0 bladder cancer who have varying risks of pathological upstaging. Such categorization using a visually intuitive model can facilitate clinical decision-making with respect to neoadjuvant therapy in these patients.

  View details for DOI 10.1111/j.1464-410X.2012.11424.x

  View details for Web of Science ID 000315030200012

  View details for PubMedID 22928881

• ICUD-EAU International Consultation on Bladder Cancer 2012: Urinary Diversion EUROPEAN UROLOGY Hautmann, R. E., Abol-Enein, H., Davidsson, T., Gudjonsson, S., Hautmann, S. H., Holm, H. V., Lee, C. T., Liedberg, F., Madersbacher, S., Manoharan, M., Mansson, W., Mills, R. D., Penson, D. F., Skinner, E. C., Stein, R., Studer, U. E., Thueroff, J. W., Turner, W. H., Volkmer, B. G., Xu, A. 2013; 63 (1): 67-80

  Abstract

  A summary of the 2nd International Consultation on Bladder Cancer recommendations on the reconstructive options after radical cystectomy (RC), their outcomes, and their complications.To review the literature regarding indications, surgical details, postoperative care, complications, functional outcomes, as well as quality-of-life measures of patients with different forms of urinary diversion (UD).An English-language literature review of data published between 1970 and 2012 on patients with UD following RC for bladder cancer was undertaken. No randomized controlled studies comparing conduit diversion with neobladder or continent cutaneous diversion have been performed. Consequently, almost all studies used in this report are of level 3 evidence. Therefore, the recommendations given here are grade C only, meaning expert opinion delivered without a formal analysis.Indications and patient selection criteria have significantly changed over the past 2 decades. Renal function impairment is primarily caused by obstruction. Complications such as stone formation, urine outflow, and obstruction at any level must be recognized early and treated. In patients with orthotopic bladder substitution, daytime and nocturnal continence is achieved in 85-90% and 60-80%, respectively. Continence is inferior in elderly patients with orthotopic reconstruction. Urinary retention remains significant in female patients, ranging from 7% to 50%.RC and subsequent UD have been assessed as the most difficult surgical procedure in urology. Significant disparity on how the surgical complications were reported makes it impossible to compare postoperative morbidity results. Complications rates overall following RC and UD are significant, and when strict reporting criteria are incorporated, they are much higher than previously published. Fortunately, most complications are minor (Clavien grade 1 or 2). Complications can occur up to 20 yr after surgery, emphasizing the need for lifelong monitoring. Evidence suggests an association between surgical volume and outcome in RC; the challenge of optimum care for elderly patients with comorbidities is best mastered at high-volume hospitals by high-volume surgeons. Preoperative patient information, patient selection, surgical techniques, and careful postoperative follow-up are the cornerstones to achieve good long-term results.

  View details for DOI 10.1016/j.eururo.2012.08.050

  View details for Web of Science ID 000312004100013

  View details for PubMedID 22995974

• Radical cystectomy with orthotopic neobladder reconstruction following prior radical prostatectomy WORLD JOURNAL OF UROLOGY Huang, E. Y., Skinner, E. C., Boyd, S. D., Cai, J., Miranda, G., Daneshmand, S. 2012; 30 (6): 741-745

  Abstract

  To review the perioperative and follow-up outcomes of patients undergoing radical cystectomy with orthotopic neobladder reconstruction for bladder cancer after prior radical prostatectomy (RP) for prostate cancer.A retrospective review of more than 1,900 patients treated with radical cystectomy at USC between 1990 and 2011 was conducted. Fifty-six patients were identified who were previously treated with RP for prostate cancer. Twenty-four of these patients (43 %) underwent orthotopic neobladder reconstruction. Perioperative data and follow-up including postoperative continence were analyzed.The median age at cystectomy for these 24 patients was 68 years (range 55-89). The types of neobladder reconstruction were Kock neobladder in 3, Sigmoid reservoir in 1, Studer neobladder in 12, and T-pouch ileal neobladder in 8 patients. There were no major intraoperative complications. Of 19 patients eligible for evaluation of post-cystectomy urinary control, 11 patients (57.9 %) with good continence (0-1 pad/day) after RP regained preoperative level of urinary control after cystectomy within 1 year. The continence rate of 13 post-RP patients with good continence was 84.6 %. Among the 4 patients who received adjuvant radiotherapy after RP, 1 regained good continence. One with poor continence after prostatectomy had an artificial urethral sphincter (AUS) placed 2 months after cystectomy, and 2 with fair and poor continence after prostatectomy had an AUS placed at the time of cystectomy.Patients undergoing radical cystectomy after prior RP pose a challenge to urologists. Those who are continent post-RP have a fair chance of regaining good urinary control with neobladder reconstruction. Adjuvant radiotherapy for prostate cancer may have a negative impact on continence with neobladder reconstruction.

  View details for DOI 10.1007/s00345-012-0861-x

  View details for Web of Science ID 000311793500003

  View details for PubMedID 22457033

• Multicenter validation of the prognostic value of patient age in patients treated with radical cystectomy WORLD JOURNAL OF UROLOGY Chromecki, T. F., Mauermann, J., Cha, E. K., Svatek, R. S., Fajkovic, H., Karakiewicz, P. I., Lotan, Y., Tilki, D., Bastian, P. J., Volkmer, B. G., Montorsi, F., Kassouf, W., Novara, G., Fritsche, H., Ficarra, V., Stief, C. G., Dinney, C. P., Skinner, E., Pummer, K., Fradet, Y., Shariat, S. F. 2012; 30 (6): 753-759

  Abstract

  Small studies have suggested that older patients have worse outcomes following radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB). We evaluated the association of patient age with clinical outcomes in a large multi-institutional RC series.Data were collected from 4,429 patients treated with RC and lymphadenectomy for UCB without neoadjuvant chemotherapy. Age at RC was analyzed both as a continuous and categorical variable.Higher age at RC, analyzed as a continuous or categorical variable, was associated with advanced pathologic stage (P < 0.001), higher tumor grade (P = 0.045), presence of lymphovascular invasion (P = 0.018), and positive soft-tissue surgical margin status (P = 0.004). Elderly patients were less likely to receive postoperative chemotherapy (P < 0.001). In multivariable analyses, higher age was associated with disease recurrence, cancer-specific, and overall mortality (P < 0.001). Patients ≥ 80 years had a significantly greater risk of cancer-specific mortality than patients <50 years (HR 1.763, P < 0.001). Age minimally improved the accuracy of a base model that included standard pathologic features for prediction of disease recurrence (+0.2-0.3%) and cancer-specific survival (+0.3%). Conversely, age improved the predictive accuracy for overall survival by a sizeable margin (+4.2-4.5%).This large external validation study confirms that advanced patient age is minimally but significantly associated with worse prognosis after RC. Nevertheless, a large proportion of elderly patients benefitted from RC with curative intent. We need to improve our understanding of the reasons for the worse UCB outcomes in this growing segment of the population and to develop strategies to improve cancer care in the elderly.

  View details for DOI 10.1007/s00345-011-0772-2

  View details for Web of Science ID 000311793500005

  View details for PubMedID 22009117

• Reproductive Organ Involvement in Female Patients Undergoing Radical Cystectomy for Urothelial Bladder Cancer JOURNAL OF UROLOGY Djaladat, H., Bruins, H. M., Miranda, G., Cai, J., Skinner, E. C., Daneshmand, S. 2012; 188 (6): 2134-2138

  Abstract

  We evaluated pathological involvement of the reproductive organs in a cohort of female patients treated with anterior pelvic exenteration for invasive urothelial carcinoma of the bladder.A total of 2,098 patients with bladder cancer underwent cystectomy at our institution between 1971 and 2008, including 458 females, of whom 411 had urothelial carcinoma of the bladder. Median followup was 12.2 years (range 0.1 to 35.5). We reviewed the clinicopathological features of female patients treated with cystectomy who had pathological reproductive organ involvement. Recurrence-free and overall survival is reported using Kaplan-Meier survival curves.Of 411 patients with urothelial carcinoma of the bladder 267 underwent reproductive organ removal with cystectomy. A total of 20 patients (7.5%) had reproductive organ involvement, including 10 (3.8%) with vaginal, 2 (0.7%) with cervical and 1 (0.3%) with uterine involvement only, while the remaining 7 (2.6%) had multiple reproductive organs involved. Median age was 71 years. Clinical stage T4a was diagnosed in 25% of cases. A palpable mass, hydronephrosis (each p <0.001) and positive lymph nodes at anterior pelvic exenteration (p = 0.001) were associated with reproductive organ involvement. Recurrence developed in 14 patients (70%) at a median of 7 months (range 1 to 22). Five-year recurrence-free and overall survival rates were 14.9% and 8.8%, respectively.The risk of reproductive organ involvement in female patients who undergo anterior pelvic exenteration for urothelial carcinoma of the bladder was about 7.5% with the vagina the most commonly involved organ. A palpable mass and hydronephrosis were among the preoperative clinical factors associated with reproductive organ involvement. The prognosis is poor in patients with reproductive organ involvement.

  View details for DOI 10.1016/j.juro.2012.08.024

  View details for Web of Science ID 000311581400024

  View details for PubMedID 23083874

• Critical Evaluation of the American Joint Committee on Cancer TNM Nodal Staging System in Patients with Lymph Node-Positive Disease after Radical Cystectomy EUROPEAN UROLOGY Bruins, H. M., Dorin, R. P., Rubino, B., Miranda, G., Cai, J., Daneshmand, S., Skinner, E. C. 2012; 62 (4): 671-676

  Abstract

  The current 7th edition of the American Joint Committee on Cancer TNM staging system for bladder cancer stages lymph node (LN)-positive disease based on LN location rather than LN size. In addition, common iliac LNs are now considered regional LNs. Whether these changes improve prognostication for node-positive patients, however, remains unclear.To investigate whether the 7th edition of the TNM nodal staging system provides superior prognostication compared with the 6th edition.Patients between 2002 and 2008 with LN metastases after radical cystectomy combined with extended or superextended LN dissection were included. Patients were staged using both TNM staging systems. Median follow-up was 54 mo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Kaplan-Meier curves were used to estimate overall survival (OS) and recurrence-free survival (RFS). Log-rank tests and Cox proportional hazard regression models were used to test associations of pathologic variables with OS and RFS.Included were 146 patients with LN metastases of whom 131 patients underwent superextended LN dissection and 15 patients underwent extended LN dissection. Although in the 7th TNM edition many patients moved from the N2 category to the N3 category, RFS did not significantly differ within the nodal subgroups in either editions. LN metastases at or above the aortic bifurcation were not associated with decreased RFS (p=0.67). On multivariable analysis, the presence of extravesical disease (hazard ratio [HR]: 2.84; p=0.002), absence of adjuvant chemotherapy (HR: 0.32; p<0.0001), and more than six positive LNs (HR: 2.72; p=0.007) were associated with decreased RFS. This was a retrospective study with inherent limitations.LNs at or above the aortic bifurcation should be considered regional LNs. Neither the 6th nor the 7th TNM staging system performed well as a prognostic tool. A better staging system for LN-positive bladder cancer needs to be developed.

  View details for DOI 10.1016/j.eururo.2012.04.050

  View details for Web of Science ID 000308563100025

  View details for PubMedID 22575915

• Factors influencing post-recurrence survival in bladder cancer following radical cystectomy BJU INTERNATIONAL Mitra, A. P., Quinn, D. I., Dorff, T. B., Skinner, E. C., Schuckman, A. K., Miranda, G., Gill, I. S., Daneshmand, S. 2012; 109 (6): 846-854

  Abstract

  To identify prognostic indicators that influence post-recurrence survival following radical cystectomy for bladder cancer.In all, 2029 patients with bladder cancer underwent radical cystectomy with intent to cure between 1971 and 2005 at our institution. Of these, 447 patients (22%) developed non-urinary tract recurrence and were chosen for further analysis. Clinicopathological characteristics were analysed by univariate and multivariate analysis to identify factors prognostic for post-recurrence survival.Median time to recurrence was 13.21 months and median post-recurrence overall survival was 5.59 months. Pathological stage (P < 0.001), intravesical therapy (P= 0.035), tumour upstaging (P < 0.001), lymph node density (P < 0.001) and recurrence site (P= 0.017) were associated with time to recurrence. Age (P= 0.042), type of urinary diversion (P < 0.014), surgical margin status (P= 0.049), pathological stage (P < 0.001), lymph node density (P < 0.001), time to recurrence (P < 0.001), recurrence site (P < 0.001) and post-recurrence chemotherapy administration (P < 0.001) were univariately prognostic for post-recurrence overall survival. Multivariate analysis confirmed the associations of pathological stage, type of urinary diversion, lymph node density, time to recurrence after cystectomy, site of recurrence and post-recurrence chemotherapy administration with outcome following bladder cancer recurrence. Median post-recurrence survival with either local or distant recurrence was 7.95 months and 5.95 months, respectively, whereas patients with both local and distant recurrences had median post-recurrence survival of 3.98 months.Bladder cancer recurrence forebodes poor prognosis, with 6 months' median survival following recurrence. Advanced pathological stage, positive surgical margins, high lymph node density and early recurrence portends poorer outcome. Although patients with local recurrence have a slightly better prognosis, those with disease recurrence at local and distant sites perform very poorly; nearly 97% of all patients with recurrence eventually succumb to the disease. Chemotherapy administration following recurrence may improve survival, although further studies are needed to exclude selection bias.

  View details for DOI 10.1111/j.1464-410X.2011.10455.x

  View details for Web of Science ID 000300703400009

  View details for PubMedID 21812902

• Robotic and Laparoscopic High Extended Pelvic Lymph Node Dissection During Radical Cystectomy: Technique and Outcomes EUROPEAN UROLOGY Desai, M. M., Berger, A. K., Brandina, R. R., Zehnder, P., Simmons, M., Aron, M., Skinner, E. C., Gill, I. S. 2012; 61 (2): 350-355

  Abstract

  With the increasing use of laparoscopic and robotic radical cystectomy (RC), there are perceived concerns about the adequacy of lymph node dissection (LND).Describe the robotic and laparoscopic technique and the short-term outcomes of high extended pelvic LND (PLND) up to the inferior mesenteric artery (IMA) during RC.From January 2007 through September 2009, we performed high extended PLND with proximal extent up to the IMA (n=10) or aortic bifurcation (n=5) in 15 patients undergoing robotic RC (n=4) or laparoscopic RC (n=11) at two institutions.We performed robotic extended PLND with the proximal extent up to the IMA or aortic bifurcation. The LND was performed starting from the right external iliac, obturator, internal iliac, common iliac, preaortic and para-aortic, precaval, and presacral and then proceeding to the left side. The accompanying video highlights our detailed technique.Median age was 69 yr, body mass index was 26, and American Society of Anesthesiologists class ≥ 3 was present in 40% of patients. All urinary diversions, including orthotopic neobladder (n=5) and ileal conduit (n=10), were performed extracorporeally.All 15 procedures were technically successful without need for conversion to open surgery. Median operative time was 6.7h, estimated blood loss was 500 ml, and three patients (21%) required blood transfusion. Median nodal yield in the entire cohort was 31 (range: 15-78). The IMA group had more nodes retrieved (median: 42.5) compared with the aortic bifurcation group (median: 20.5). Histopathology confirmed nodal metastases in four patients (27%), including three patients in the IMA group and one patient in the aortic bifurcation group. Perioperative complications were recorded in six cases (40%). During a median follow-up of 13 mo, no patient developed local or systemic recurrence. Limitations of the study include its retrospective design and small cohort of patients.High extended PLND during laparoscopic or robotic RC is technically feasible. Longer survival data in a larger cohort of patients are necessary to determine the proper place for robotic and laparoscopic surgery in patients undergoing RC for high-risk bladder cancer.

  View details for DOI 10.1016/j.eururo.2011.09.011

  View details for Web of Science ID 000298248700025

  View details for PubMedID 22036642

• Super Extended Versus Extended Pelvic Lymph Node Dissection in Patients Undergoing Radical Cystectomy for Bladder Cancer: A Comparative Study JOURNAL OF UROLOGY Zehnder, P., Studer, U. E., Skinner, E. C., Dorin, R. P., Cai, J., Roth, B., Miranda, G., Birkhaeuser, F., Stein, J., Burkhard, F. C., Daneshmand, S., Thalmann, G. N., Gill, I. S., Skinner, D. G. 2011; 186 (4): 1261-1268

  Abstract

  There is evidence from retrospective studies that radical cystectomy with extended pelvic lymph node dissection provides better staging and outcomes than limited lymph node dissection. However, the optimal limits of extended lymph node dissection remain unclear. We compared oncological outcomes at 2 cystectomy centers where 2 different extended lymph node dissection templates are practiced to determine whether removing lymphatic tissue up to the inferior mesenteric artery confers an additional survival advantage.Patients undergoing radical cystectomy and extended lymph node dissection with curative intent from 1985 to 2005 were included in analysis if they met certain criteria, including clinically organ confined urothelial bladder carcinoma (cN0M0), pathological stage pT2-pT3, negative surgical margins and no neoadjuvant therapy. Survival and recurrence data were analyzed.Demographic data and pathological subgroup distribution (pT2 and pT3) were similar in the 554 University of Southern California and 405 University of Bern patients. University of Southern California patients had higher median number of lymph nodes removed than University of Bern patients (38 vs 22, p <0.0001) and a higher incidence of lymph node metastasis (35% vs 28%, p = 0.02). However, the University of Southern California and University of Bern groups had similar 5-year recurrence-free survival for pT2pN0-2 (57% vs 67%) and pT3pN0-2 (32% vs 34%) disease (p = 0.55 and 0.44, respectively). The overall recurrence rate was equal at the 2 institutions (38%).Meticulous extended lymph node dissection up to the mid-upper third of the common iliac vessels appears to provide survival and recurrence outcomes similar to those of a super extended template up to the inferior mesenteric artery. Complete skeletonization in the extended lymph node dissection template is more important than nodal yield. This does not exclude the possibility that certain patient subgroups with suspicious nodes or after neoadjuvant chemotherapy may benefit from more extensive lymph node dissection.

  View details for DOI 10.1016/j.juro.2011.06.004

  View details for Web of Science ID 000295399500018

  View details for PubMedID 21849183

• Choosing the right urinary diversion: Patient's choice or surgeon's inclination? UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS Skinner, E. C. 2011; 29 (5): 473-475

  View details for DOI 10.1016/j.urolonc.2010.09.002

  View details for Web of Science ID 000295609000001

  View details for PubMedID 21396838

• Prognostic risk stratification of pathological stage T2N0 bladder cancer after radical cystectomy BJU INTERNATIONAL Sonpavde, G., Khan, M. M., Svatek, R. S., Lee, R., Novara, G., Tilki, D., Lerner, S. P., Amiel, G. E., Skinner, E., Karakiewicz, P. I., Bastian, P. J., Kassouf, W., Fritsche, H., Izawa, J. I., Ficarra, V., Dinney, C. P., Lotan, Y., Fradet, Y., Shariat, S. F. 2011; 108 (5): 687-692

  Abstract

  • To stratify risk of pathological (p) T2N0 urothelial carcinoma of the bladder after radical cystectomy (RC) based on pathological factors to facilitate the development of adjuvant therapy trials for high-risk patients.• The study comprised 707 patients from a database of patients with pT2N0 urothelial carcinoma of the bladder who had undergone RC and not received perioperative chemotherapy. • The effect of residual pT-stage at RC, age, grade, lymphovascular invasion and number of lymph nodes removed on recurrence-free survival was evaluated using Cox regression analyses. A weighted prognostic model was devised with significant variables.• The median follow up was 60.9 months. In multivariable analyses, residual disease at RC (pT2a: hazard ratio (HR) 1.740, P = 0.03; for pT2b: HR 3.075, P < 0.001; both compared with

  View details for DOI 10.1111/j.1464-410X.2010.09902.x

  View details for Web of Science ID 000294112000012

  View details for PubMedID 21087453

• Heterogenous effect of androgen receptor CAG tract length on testicular germ cell tumor risk: shorter repeats associated with seminoma but not other histologic types CARCINOGENESIS Davis-Dao, C. A., Siegmund, K. D., Vandenberg, D. J., Skinner, E. C., Coetzee, G. A., Thomas, D. C., Pike, M. C., Cortessis, V. K. 2011; 32 (8): 1238-1243

  Abstract

  Increasing rates of testicular germ cells tumors (TGCTs) overtime suggest that environmental factors are involved in disease etiology, but familial risk and genome-wide association studies implicate genetic factors as well. We investigated whether variation in the functional CAG(n) polymorphism in the androgen receptor (AR) gene is associated with TGCT risk, using data from a population-based family study. We estimated odds ratios (OR) and 95% confidence intervals (CI) for the association of CAG repeat length and TGCT risk using matched pairs logistic regression. Analyses of 273 TGCT case-mother pairs revealed no association between AR CAG repeat length and overall TGCT risk. However, risk of seminoma was significantly associated with shorter CAG repeat length [CAG 20-21 versus CAG ≤ 19: OR = 0.82 (95% CI: 0.43-1.58), CAG 22-23 versus CAG ≤ 19: OR = 0.39 (95% CI: 0.19-0.83) and CAG ≥ 24 versus CAG ≤ 19: OR = 0.42 (95% CI: 0.20-0.86)], with a highly significant trend over these four categories of decreasing CAG repeat length (P(trend) = 0.0030). This is the first report of a statistically significant association between AR CAG repeat length and seminoma risk, suggesting that increased AR transactivation may be involved in development of seminoma and/or progression of carcinoma in situ/intratubular germ cell neoplasia unclassified to seminoma. This result provides a rationale whereby androgenic environmental compounds could contribute to increases in TGCT incidence, and identifies for the first time a potential biological pathway influencing whether TGCTs achieve seminomatous versus nonseminomatous histology, a clinically and biologically important distinction.

  View details for DOI 10.1093/carcin/bgr104

  View details for Web of Science ID 000293636700017

  View details for PubMedID 21642359

  View details for PubMedCentralID PMC3202310

• Prognostic Risk Stratification of Pathological Stage T3N0 Bladder Cancer After Radical Cystectomy JOURNAL OF UROLOGY Sonpavde, G., Khan, M. M., Svatek, R. S., Lee, R., Novara, G., Tilki, D., Lerner, S. P., Amiel, G. E., Skinner, E., Karakiewicz, P. I., Bastian, P. J., Kassouf, W., Fritsche, H., Izawa, J. I., Scherr, D. S., Ficarra, V., Dinney, C. P., Lotan, Y., Fradet, Y., Shariat, S. F. 2011; 185 (4): 1216-1221

  Abstract

  Patients with pathological T3N0 stage urothelial carcinoma of the bladder show a range of outcomes after radical cystectomy. Given that nomograms have included heterogeneous groups of patients, we focused on and stratified patients with pT3N0 urothelial carcinoma of the bladder after radical cystectomy into prognostically different risk groups to facilitate the development of adjuvant therapy trials for those at high risk.The study comprised a total of 578 patients from 9 centers worldwide with pT3N0 urothelial carcinoma of the bladder who underwent radical cystectomy without perioperative chemotherapy. We evaluated the effect of pT3 substage at radical cystectomy, age, grade, lymphovascular invasion, margin status and number of lymph nodes removed on recurrence-free survival using Cox regression analysis. A weighted prognostic model was devised.Median followup was 39.4 months (IQR 64). On multivariate analysis pT3 substage at radical cystectomy (pT3b vs pT3a HR 2.056, p <0.0001), lymphovascular invasion (positive vs negative HR 2.004, p <0.0001) and margin status (positive vs negative HR 2.503, p = 0.002) were associated with recurrence-free survival (concordance index 0.66) in the context of generally adequate lymph node dissection, that is with a median of 17 removed. Three risk groups were devised based on weighted variables with a 5-year recurrence-free survival rate of 79% (95% CI 70-84), 57% (95% CI 50-64) and 37% (95% CI 26-48) in the low, intermediate and high risk groups, respectively.We constructed a user friendly prognostic risk model for patients with pT3N0 urothelial carcinoma of the bladder treated with radical cystectomy based on pT3 substage at radical cystectomy, lymphovascular invasion and margin status. These data warrant validation and may enable tailored monitoring and selection of appropriate patients for adjuvant therapy trials.

  View details for DOI 10.1016/j.juro.2010.11.082

  View details for Web of Science ID 000288430200012

  View details for PubMedID 21334687

• A Prospective, Randomised EORTC Intergroup Phase 3 Study Comparing the Oncologic Outcome of Elective Nephron-Sparing Surgery and Radical Nephrectomy for Low-Stage Renal Cell Carcinoma EUROPEAN UROLOGY Van Poppel, H., Da Pozzo, L., Albrecht, W., Matveev, V., Bono, A., Borkowski, A., Colombel, M., Klotz, L., Skinner, E., Keane, T., Marreaud, S., Collette, S., Sylvester, R. 2011; 59 (4): 543-552

  Abstract

  Nephron-sparing surgery (NSS) can safely be performed with slightly higher complication rates than radical nephrectomy (RN), but proof of oncologic effectiveness is lacking.To compare overall survival (OS) and time to progression.From March 1992 to January 2003, when the study was prematurely closed because of poor accrual, 541 patients with small (≤5 cm), solitary, T1-T2 N0 M0 (Union Internationale Contre le Cancer [UICC] 1978) tumours suspicious for renal cell carcinoma (RCC) and a normal contralateral kidney were randomised to NSS or RN in European Organisation for Research and Treatment of Cancer Genito-Urinary Group (EORTC-GU) noninferiority phase 3 trial 30904.Patients were randomised to NSS (n=268) or RN (n=273) together with limited lymph node dissection (LND).Time to event end points was compared with log-rank test results.Median follow-up was 9.3 yr. The intention-to-treat (ITT) analysis showed 10-yr OS rates of 81.1% for RN and 75.7% for NSS. With a hazard ratio (HR) of 1.50 (95% confidence interval [CI], 1.03-2.16), the test for noninferiority is not significant (p=0.77), and test for superiority is significant (p=0.03). In RCC patients and clinically and pathologically eligible patients, the difference is less pronounced (HR=1.43 and HR=1.34, respectively), and the superiority test is no longer significant (p=0.07 and p=0.17, respectively). Only 12 of 117 deaths were the result of renal cancer (four RN and eight NSS). Twenty-one patients progressed (9 after RN and 12 after NSS). Quality of life and renal function outcomes have not been addressed.Both methods provide excellent oncologic results. In the ITT population, NSS seems to be significantly less effective than RN in terms of OS. However, in the targeted population of RCC patients, the trend in favour of RN is no longer significant. The small number of progressions and deaths from renal cancer cannot explain any possible OS differences between treatment types.

  View details for DOI 10.1016/j.eururo.2010.12.013

  View details for Web of Science ID 000288013700020

  View details for PubMedID 21186077

• Discrepancy between clinical and pathological stage: external validation of the impact on prognosis in an international radical cystectomy cohort BJU INTERNATIONAL Svatek, R. S., Shariat, S. F., Novara, G., Skinner, E. C., Fradet, Y., Bastian, P. J., Kamat, A. M., Kassouf, W., Karakiewicz, P. I., Fritsche, H., Izawa, J. I., Tilki, D., Ficarra, V., Volkmer, B. G., Isbarn, H., Dinney, C. P. 2011; 107 (6): 898-904

  Abstract

  • To compare the clinical and pathologic stage among a large, multi-institutional series of patients undergoing radical and to determine the effect of stage discrepancy on outcomes.• Data was collected from nine centers and 3,393 patients with urothelial carcinoma of the bladder (UCB) treated with radical cystectomy and pelvic lymphadenectomy without neo-adjuvant chemotherapy. • A retrospective cohort design was used to assess the percentage of patients experiencing stage discrepancy and the impact of stage discrepancy on time to disease relapse and time to death from UCB.• Clinical under staging occurred in 50% of patients and pathologic down staging occurred in 18% of patients. • Up staging to muscle invasive disease occurred in 45.9% (n = 592) of 1,291 patients with clinical ≤T1, including 30.6% of patients with Tis only at transurethral resection. • Of the 3,166 patients with clinically organ confined (OC) tumor stage, 1,357 (42.9%) were up staged to non-organ confined pathologic tumor stage. • Within each clinical stage stratum, patients who were clinically under staged had a higher probability of disease relapse or death from UCB compared to those who were same staged or down staged on pathologic examination (P < 0.05).• We identified clinical under staging in half of the patients undergoing radical cystectomy for UCB. • Up staging resulted in a higher likelihood of disease progression and eventual death from UCB. • These findings should be considered when utilizing pre-operative risk-adapted strategies for selecting candidates for neoadjuvant chemotherapy.

  View details for DOI 10.1111/j.1464-410X.2010.09628.x

  View details for Web of Science ID 000288212700008

  View details for PubMedID 21244604

• Disease-Free Survival at 2 or 3 Years Correlates With 5-Year Overall Survival of Patients Undergoing Radical Cystectomy for Muscle Invasive Bladder Cancer JOURNAL OF UROLOGY Sonpavde, G., Khan, M. M., Lerner, S. P., Svatek, R. S., Novara, G., Karakiewicz, P. I., Skinner, E., Tilki, D., Kassouf, W., Fradet, Y., Dinney, C. P., Fritsche, H., Izawa, J. I., Bastian, P. J., Ficarra, V., Schoenberg, M., Sagalowsky, A. I., Lotan, Y., Shariat, S. F. 2011; 185 (2): 456-461

  Abstract

  The conventional primary end point in trials of perioperative systemic therapy for muscle invasive bladder cancer is 5-year overall survival. We identified an association between disease-free survival at 2 to 3 years and 5-year overall survival.We retrospectively analyzed a multicenter database containing records of 2,724 patients treated with radical cystectomy for muscle invasive bladder cancer with negative margins. Of these patients 844 had received adjuvant chemotherapy. We evaluated the association of disease-free survival at 2 and 3 years with overall survival at 5 years using Cox proportional hazards modeling and the kappa statistic.Overall 2-year/3-year disease-free survival was 0.63/0.57 and 5-year overall survival was 0.47. The overall agreement between 2-year disease-free survival and 5-year overall survival was 79%, and between 3-year disease-free survival and 5-year overall survival was 81%. Agreements were similar when analyzed within pathological substages, radical cystectomy decades and adjuvant chemotherapy subgroups. The kappa statistic was 0.57 (95% CI 0.53-0.60) for 2-year disease-free survival/5-year overall survival and 0.61 (95% CI 0.58-0.64) for 3-year disease-free survival/5-year overall survival, indicating moderate agreement. The hazard ratio for disease-free survival as a time dependent variable was 12.7 (95% CI 11.60-13.90), indicating a strong relationship between disease-free and overall survival.Disease-free survival rates at 2 and 3 years correlate with and are potential intermediate surrogates for 5-year overall survival in patients treated with radical cystectomy for muscle invasive bladder cancer regardless of adjuvant chemotherapy. These data warrant external validation and may expedite the development of adjuvant systemic therapy. In addition, they may be applicable to the neoadjuvant setting.

  View details for DOI 10.1016/j.juro.2010.09.110

  View details for Web of Science ID 000286047500021

  View details for PubMedID 21167527

• Lymph node dissection technique is more important than lymph node count in identifying nodal metastases in radical cystectomy patients: a comparative mapping study European Urology Dorin, R., Daneshmand S, Eisenberg MS, Chandrasoma S, Cai J, Miranda G, Nichols PW, Skinner DG, Skinner EC 2011; 60: 946
• Concomitant Carcinoma in situ in Cystectomy Specimens Is Not Associated with Clinical Outcomes after Surgery UROLOGIA INTERNATIONALIS Nuhn, P., Bastian, P. J., Novara, G., Svatek, R. S., Karakiewicz, P. I., Skinner, E., Fradet, Y., Izawa, J. I., Kassouf, W., Montorsi, F., Mueller, S. C., Fritsche, H., Sonpavde, G., Tilki, D., Isbarn, H., Ficarra, V., Dinney, C. P., Shariat, S. F. 2011; 87 (1): 42-48

  Abstract

  The aim of this study was to externally validate the prognostic value of concomitant urothelial carcinoma in situ (CIS) in radical cystectomy (RC) specimens using a large international cohort of bladder cancer patients.The records of 3,973 patients treated with RC and bilateral lymphadenectomy for urothelial carcinoma of the bladder (UCB) at nine centers worldwide were reviewed. Surgical specimens were evaluated by a genitourinary pathologist at each center. Uni- and multivariable Cox regression models addressed time to recurrence and cancer-specific mortality after RC.1,741 (43.8%) patients had concomitant CIS in their RC specimens. Concomitant CIS was more common in organ-confined UCB and was associated with lymphovascular invasion (p < 0.001). Concomitant CIS was not associated with either disease recurrence or cancer-specific death regardless of pathologic stage. The presence of concomitant CIS did not improve the predictive accuracy of standard predictors for either disease recurrence or cancer-specific death in any of the subgroups.We could not confirm the prognostic value of concomitant CIS in RC specimens. This, together with the discrepancy between pathologists in determining the presence of concomitant CIS at the morphologic level, limits the clinical utility of concomitant CIS in RC specimens for clinical decision-making.

  View details for DOI 10.1159/000325463

  View details for Web of Science ID 000293591400007

  View details for PubMedID 21659717

• Early Complications of Cystectomy After High Dose Pelvic Radiation JOURNAL OF UROLOGY Eisenberg, M. S., Dorin, R. P., Bartsch, G., Cai, J., Miranda, G., Skinner, E. C. 2010; 184 (6): 2264-2269

  Abstract

  Radical cystectomy in patients with a history of pelvic radiation therapy is often a challenging and morbid procedure. We report early complication rates in patients undergoing cystectomy and urinary diversion after high dose pelvic radiation.From 1983 to 2008, 2,629 patients underwent cystectomy with urinary diversion at a single institution. Of these patients 148 received 60 Gy or greater pelvic radiation therapy before surgery. Patient medical records were retrospectively reviewed and any complication within 90 days of surgery was graded using the Clavien-Dindo system.Median patient age was 74 years with a median American Society of Anesthesiologists score of 3. Patients received a median of 70 Gy pelvic radiation therapy a median of 2.3 years before surgery. Urinary diversions performed were ileal conduit in 65 patients (43.9%), continent cutaneous pouch in 35 (23.6%) and orthotopic neobladder in 48 (32.4%). A total of 335 early complications were identified. The highest grade complication was 0 in 23% of the patients, grade 1 in 12.2%, grade 2 in 32.4%, grade 3 in 18.9%, grade 4 in 7.4% and grade 5 in 6.1%. Age older than 65 years and American Society of Anesthesiologists score were statistically significant predictors of postoperative complications (p=0.0264 and p=0.0252, respectively). The type of urinary diversion did not significantly affect the grade distribution or number of early complications per patient (p=0.7444 and p=0.1807, respectively).The early complication rate using a standardized reporting system in patients undergoing radical cystectomy after radiation therapy is higher than previously published in nonirradiated subjects. Age and American Society of Anesthesiologists score but not urinary diversion type were associated with early complications in this population.

  View details for DOI 10.1016/j.juro.2010.08.007

  View details for Web of Science ID 000284037900012

  View details for PubMedID 20952024

• Extended lymphadenectomy in bladder cancer CURRENT OPINION IN UROLOGY Dorin, R. P., Skinner, E. C. 2010; 20 (5): 414-420

  Abstract

  Radical cystectomy with pelvic lymph node dissection (PLND) is the preferred treatment for invasive bladder cancer. It not only results in the best disease-free term survival rates, but also provides the most accurate disease staging and most effective local symptom control. Recent investigations have demonstrated a clinical benefit to performance of an extended PLND, including all lymphatic tissue to the level of the aortic bifurcation. This review will summarize recent findings regarding the clinical benefits of radical cystectomy with extended lymphadenectomy, and will also examine the latest surgical techniques for optimizing the performance of this technically demanding procedure.Recent studies have demonstrated increased recurrence-free survival and overall survival rates in patients undergoing radical cystectomy with extended PLND, even in cases of pathologically lymph node negative disease. The growing use of minimally invasive techniques has prompted interest in robotic radical cystectomy and extended PLND, and recent reports have demonstrated the feasibility of this technique. The standardization of extended PLND templates has also been a focus of contemporary research.Contemporary research strongly suggests that all patients undergoing radical cystectomy for bladder cancer should undergo concomitant extended PLND. Randomized trials are still needed to confirm the benefits of extended over 'standard' PLND, and to clarify which patients may receive the greatest benefit from this procedure.

  View details for DOI 10.1097/MOU.0b013e32833c9194

  View details for Web of Science ID 000280552100013

  View details for PubMedID 20657290

• Stage pT0 at Radical Cystectomy Confers Improved Survival: An International Study of 4,430 Patients JOURNAL OF UROLOGY Tilki, D., Svatek, R. S., Novara, G., Seitz, M., Godoy, G., Karakiewicz, P. I., Kassouf, W., Fradet, Y., Fritsche, H., Sonpavde, G., Izawa, J. I., Ficarra, V., Lerner, S. P., Schoenberg, M., Stief, C. G., Dinney, C. P., Skinner, E., Lotan, Y., Sagalowsky, A. I., Reich, O., Shariat, S. F. 2010; 184 (3): 888-894

  Abstract

  We describe the cancer related outcome in patients with pT0 bladder urothelial carcinoma at radical cystectomy who did not receive preoperative chemotherapy in a large multicenter series. We also compared outcomes in patients with pT0 bladder urothelial carcinoma to those in patients with other stages and assessed the effect of clinical stage on outcome.We reviewed the records of 4,430 patients treated with radical cystectomy for bladder urothelial carcinoma without neoadjuvant chemotherapy at 12 centers in the United States, Canada and Europe.Of the patients 228 (5.1%) had pT0 disease at radical cystectomy. Clinical stage was cTa or cTis in 13.6% and cT1 in 29.8% of these patients, and disease was muscle invasive (cT2-4a) in 56.2%. Metastasis developed to regional lymph nodes in 17 cases (7.5%). At a median 48.2-month followup 15 patients (6.6%) had died of bladder cancer. Five-year recurrence-free and cancer specific survival estimates were 89.7% (95% CI 85.3-93.1) and 93.1% (95% CI 88.9-95.6), respectively. Disease-free and cancer specific survival in pT0 cases was similar to that in pTa/pTis cases but significantly better than in pT1 or pT2 cases. On multivariate analysis increased disease recurrence and cancer specific mortality risks were significantly associated with lymph node metastasis (each p <0.001) and female gender (p <0.001 and 0.013, respectively).Although stage pT0 at radical cystectomy confers a benefit in survival, some patients experience disease recurrence and eventual death. Identifying these patients may help tailor postoperative decision making in patients with pT0.

  View details for DOI 10.1016/j.juro.2010.04.081

  View details for Web of Science ID 000280725600015

  View details for PubMedID 20643448

• pT3 Substaging is a Prognostic Indicator for Lymph Node Negative Urothelial Carcinoma of the Bladder JOURNAL OF UROLOGY Tilki, D., Svatek, R. S., Karakiewicz, P. I., Novara, G., Seitz, M., Sonpavde, G., Gupta, A., Kassouf, W., Fradet, Y., Ficarra, V., Skinner, E., Lotan, Y., Sagalowsky, A. I., Stief, C. G., Reich, O., Shariat, S. F. 2010; 184 (2): 470-474

  Abstract

  We assessed the prognostic value of pT3 bladder urothelial carcinoma substaging.We reviewed the records of 2,605 patients treated with radical cystectomy for bladder urothelial carcinoma at 6 international centers, of whom 808 (31.0%) had pT3 disease. No patient received systemic chemotherapy or radiotherapy preoperatively. Median followup was 45 months in survivors at last followup.Median patient age was 68 years. Stage was pT3a in 310 patients (38.4%) and pT3b in 498 (61.6%). Of the patients 352 (43.6%) had metastasis to regional lymph nodes. Five-year recurrence-free (43.8% and 41.4%) and cancer specific (48.6% and 46.8%) survival estimates were similar in pT3a and pT3b cases (p = 0.277 and 0.625, respectively). Conversely in patients with pathologically negative lymph nodes pT3b substaging was associated with worse 5-year recurrence-free (60.7% vs 47.9%) and cancer specific (64.4% vs 55.0%) survival (p = 0.020 vs 0.048).Macroscopic perivesical fat extension (pT3b) is associated with a worse outcome than pT3a disease in lymph node negative cases of bladder urothelial carcinoma. Together with other features pT3 substaging may help identify patients with pT3 who could benefit from adjuvant chemotherapy.

  View details for DOI 10.1016/j.juro.2010.04.007

  View details for Web of Science ID 000279707700014

  View details for PubMedID 20620401

• Validation of the AJCC TNM Substaging of pT2 Bladder Cancer: Deep Muscle Invasion Is Associated with Significantly Worse Outcome EUROPEAN UROLOGY Tilki, D., Reich, O., Karakiewicz, P. I., Novara, G., Kassouf, W., Erguen, S., Fradet, Y., Ficarra, V., Sonpavde, G., Stief, C. G., Skinner, E., Svatek, R. S., Lotan, Y., Sagalowsky, A. I., Shariat, S. F. 2010; 58 (1): 112-117

  Abstract

  The current TNM bladder cancer staging system stratifies bladder muscle invasion into superficial (pT2a) and deep (pT2b). Controversy exists regarding the significance of the extent of muscle invasion on clinical outcome.Our aim was to compare the cancer-specific outcomes of patients with pT2 urothelial carcinoma of the bladder (UCB) at radical cystectomy (RC) in a large international cohort of patients.The records of patients treated with RC for UCB at six centers were reviewed. Of the 2605 reviewed patients, 565 (21.7%) had pT2 disease. None of the patients received preoperative systemic chemotherapy or radiotherapy.Patients' characteristics and outcome were evaluated.The median patient age in the entire group was 66.2 yr. Of the 565 patients with pT2 UCB, 249 patients (44.1%) had substage pT2a; 316 patients (55.9%) had pT2b. One hundred and eleven patients (19.6%) had metastases to regional lymph nodes. Median follow-up was 50.5 mo. Recurrence-free survival (73.2% vs 58.7%) and cancer-specific survival (78.0% vs 65.1%) estimates were significantly better for pT2a patients compared with those with pT2b (p=0.002 and p=0.001, respectively). Pathologic T2 substaging was associated with worse recurrence-free and cancer-specific survival after adjusting for the effects of standard pathologic features (p=0.011 and p=0.006, respectively). The statistical significance of these associations was reconfirmed in subgroup analysis limited to those patients with pathologically negative lymph nodes.In this large international cohort, pathologic substaging helped to stratify patients with lymph node-negative pT2 UCB into statistically significantly different risk groups. These data support the value of the current American Joint Committee on Cancer TNM staging.

  View details for DOI 10.1016/j.eururo.2010.01.015

  View details for Web of Science ID 000278414100017

  View details for PubMedID 20097469

• Soft Tissue Surgical Margin Status is a Powerful Predictor of Outcomes After Radical Cystectomy: A Multicenter Study of More Than 4,400 Patients JOURNAL OF UROLOGY Novara, G., Svatek, R. S., Karakiewicz, P. I., Skinner, E., Ficarra, V., Fradet, Y., Lotan, Y., Isbarn, H., Capitanio, U., Bastian, P. J., Kassouf, W., Fritsche, H., Izawa, J. I., Tilki, D., Dinney, C. P., Lerner, S. P., Schoenberg, M., Volkmer, B. G., Sagalowsky, A. I., Shariat, S. F. 2010; 183 (6): 2165-2170

  Abstract

  We evaluated the association of soft tissue surgical margins with characteristics and outcomes of patients treated with radical cystectomy for urothelial carcinoma of the bladder.We retrospectively collected the data of 4,410 patients treated with radical cystectomy and pelvic lymphadenectomy without neoadjuvant chemotherapy at 12 academic centers in the United States, Canada and Europe. A positive soft tissue surgical margin was defined as presence of tumor at inked areas of soft tissue on the radical cystectomy specimen.Positive soft tissue surgical margins were identified in 278 patients (6.3%). On univariate analysis positive soft tissue surgical margin was significantly associated with advanced pT stage, higher tumor grade, lymphovascular invasion and lymph node metastasis (p <0.001). Actuarial 5-year recurrence-free and cancer specific survival probabilities were 62.8% +/- 0.8% and 69% +/- 0.8% for patients without soft tissue surgical margins vs 21.6% +/- 3.1% and 26.4% +/- 3.3% for those with positive soft tissue surgical margins (p <0.001). On multivariable analyses adjusting for the effect of standard clinicopathological features and adjuvant chemotherapy positive soft tissue surgical margin was an independent predictor of disease recurrence and cancer specific mortality (HR 1.52 and HR 1.51, p <0.001, respectively). Soft tissue surgical margin retained independent predictive value in subgroups with advanced disease such as pT3Nany, pT4Nany or Npositive.Positive soft tissue surgical margin is a strong predictor of recurrence and eventual death from urothelial carcinoma of the bladder. Soft tissue surgical margin status should always be reported in the pathological reports after radical cystectomy. Due to uniformly poor outcomes patients with positive soft tissue surgical margins should be considered for studies on adjuvant local and/or systemic therapy.

  View details for DOI 10.1016/j.juro.2010.02.021

  View details for Web of Science ID 000277628700013

  View details for PubMedID 20399473

• Characteristics and Outcomes of Patients With Clinical Carcinoma In Situ Only Treated With Radical Cystectomy: An International Study of 243 Patients JOURNAL OF UROLOGY Tilki, D., Reich, O., Svatek, R. S., Karakiewicz, P. I., Kassouf, W., Novara, G., Ficarra, V., Chade, D. C., Fritsche, H., Gerwens, N., Izawa, J. I., Lerner, S. P., Schoenberg, M., Stief, C. G., Skinner, E., Lotan, Y., Sagalowsky, A. I., Shariat, S. F. 2010; 183 (5): 1757-1763

  Abstract

  We describe the rate of up staging and the cancer specific outcomes of patients with carcinoma in situ refractory to transurethral resection with intravesical therapy treated with radical cystectomy.The records of 3,207 patients treated with radical cystectomy for urothelial carcinoma of the bladder at 8 centers in the United States, Canada and Europe were reviewed.Of the 3,207 patients who underwent radical cystectomy 243 (7.6%) had clinical carcinoma in situ only disease before radical cystectomy. At radical cystectomy 117 patients (48.1%) had carcinoma in situ only, 20 (8.2%) had pT0 urothelial carcinoma of the bladder, 19 (7.8%) had pTa urothelial carcinoma of the bladder and 36% had disease up staged (32 [13.2%] pT1, 29 [11.9%] pT2, 12 [4.9%] pT3 and 14 [5.8%] pT4). A total of 22 patients (9.1%) had lymphovascular invasion in the radical cystectomy specimen and 14 (5.8%) had metastasis to regional lymph nodes. Overall 5-year recurrence-free and cancer specific survival estimates were 74% (95% CI 68-79) and 85% (95% CI 80-89), respectively. On multivariable analysis adjusting for the effects of standard predictors, lymph node metastasis and lymphovascular invasion were associated with an increased risk of disease recurrence (p = 0.017 and p = 0.043, respectively) and cancer specific mortality (p = 0.019 and p = 0.001, respectively). Female gender was an independent risk factor for cancer specific mortality (p = 0.029) but not for disease recurrence (p = 0.173).Approximately a fourth of patients treated with radical cystectomy for clinical carcinoma in situ only had muscle invasive disease and 5.8% had metastasis to regional lymph nodes. Identification of those patients with a potentially aggressive natural history of carcinoma in situ is of the utmost importance as they are likely to benefit from early radical cystectomy.

  View details for DOI 10.1016/j.juro.2010.01.025

  View details for Web of Science ID 000276747600026

  View details for PubMedID 20299059

• International validation of the prognostic value of lymphovascular invasion in patients treated with radical cystectomy BJU INTERNATIONAL Shariat, S. F., Svatek, R. S., Tilki, D., Skinner, E., Karakiewicz, P. I., Capitanio, U., Bastian, P. J., Volkmer, B. G., Kassouf, W., Novara, G., Fritsche, H., Izawa, J. I., Ficarra, V., Lerner, S. P., Sagalowsky, A. I., Schoenberg, M. P., Kamat, A. M., Dinney, C. P., Lotan, Y., Marberger, M. J., Fradet, Y. 2010; 105 (10): 1402-1412

  Abstract

  To externally validate the prognostic value of lymphovascular invasion (LVI) in a large international cohort of patients treated with radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB).We collected data from 4257 patients treated with RC and pelvic lymphadenectomy for UCB, without neoadjuvant chemotherapy, at 12 centres. LVI was defined as presence of nests of tumour cells within an endothelium-lined space.LVI was detected in 1407 patients (33.1%); the proportion of LVI increased with advancing stage, higher grade, soft-tissue surgical margin involvement, and lymph node metastasis (P < 0.001 for all). In standard multivariate models, LVI was associated with both disease recurrence (hazard ratio 1.43, P < 0.001) and cancer-specific mortality (1.45, P < 0.001). In the entire cohort, adding LVI to a base model that included standard features improved only minimally its predictive accuracy for both recurrence and cancer-specific mortality (by 1.1% and 1.2%, respectively). In 3122 patients with negative lymph nodes, LVI remained independently associated with and improved the predictive accuracy of the standard predictors for recurrence (hazard ratio 1.68, P < 0.001; +2.3%) and cancer-specific mortality (1.70, P < 0.001; +2.4%). By contrast, in 1071 node-positive patients, LVI only marginally improved the prediction of cancer-specific recurrence (hazard ratio 1.20, P < 0.001; +0.2%) and survival (1.23, P < 0.001; +0.5%).LVI is strongly associated with clinical outcome in node-negative patients treated with RC. The assessment of LVI might help to identify patients who could benefit from adjuvant therapy after RC. After confirmation in different populations, LVI should be included in the staging of UCB.

  View details for DOI 10.1111/j.1464-410X.2010.09217.x

  View details for Web of Science ID 000277122900013

  View details for PubMedID 20132195

• Characteristics and Outcomes of Patients with Clinical T1 Grade 3 Urothelial Carcinoma Treated with Radical Cystectomy: Results from an International Cohort EUROPEAN UROLOGY Fritsche, H., Burger, M., Svatek, R. S., Jeldres, C., Karakiewicz, P. I., Novara, G., Skinner, E., Denzinger, S., Fradet, Y., Isbarn, H., Bastian, P. J., Volkmer, B. G., Montorsi, F., Kassouf, W., Tilki, D., Otto, W., Capitanio, U., Izawa, J. I., Ficarra, V., Lerner, S., Sagalowsky, A. I., Schoenberg, M., Kamat, A., Dinney, C. P., Lotan, Y., Shariat, S. F. 2010; 57 (2): 300-309

  Abstract

  Management of T1 grade 3 (T1G3) urothelial carcinoma of the bladder (UCB), with its variable behaviour, represents one of the most difficult challenges for urologists and patients alike.To evaluate the characteristics and long-term outcome of patients with clinical T1G3 UCB treated with radical cystectomy (RC).Data from 1136 patients treated with RC for clinical T1G3 UCB without neoadjuvant chemotherapy were collected at 12 centres located in Europe, the United States, and Canada. Median age was 67 yr (range: 29-94), with a male-to-female ratio of 4:1.Patients' characteristics and outcome are evaluated.Of the 1136 patients, 33.4% had non-organ-confined stage at cystectomy, and 16.2% had lymph node (LN) metastasis; 49.7% were upstaged after RC to muscle-invasive disease, while 21.4% were downstaged to lower than T1G3. Within a median follow-up of 48 mo, 35.5% of patients died of metastatic UCB.Approximately half of the patients treated with RC without neoadjuvant chemotherapy for clinical T1G3 UCB are upstaged to muscle-invasive UCB. These rates support the inadequacy of clinical decision making based on current treatment paradigms and staging tools. Therefore, identification of patients with clinical T1G3 disease at high risk of disease progression is of the utmost importance, as these patients are likely to benefit from early RC.

  View details for DOI 10.1016/j.eururo.2009.09.024

  View details for Web of Science ID 000273106400030

  View details for PubMedID 19766384

• Does reflux in orthotopic diversion matter? A randomized prospective comparison of the Studer and T-pouch ileal neobladders WORLD JOURNAL OF UROLOGY Skinner, E. C., Skinner, D. G. 2009; 27 (1): 51-55

  Abstract

  Orthotopic neobladder reconstruction has become a standard form of urinary diversion in many centers for patients undergoing radical cystectomy for bladder cancer. There is still controversy about the best technique for construction of the neobladder, and especially whether it is necessary to include an antireflux mechanism.We designed a prospective randomized clinical trial comparing two forms of ileal neobladder: the Studer pouch and the T-pouch. The latter includes an extraserosal tunneled afferent limb which prevents reflux from the pouch to the kidneys. The primary endpoint of the study is renal function and anatomy at 3 years following surgery, with secondary endpoints including early and late postoperative complications, renal infections and need for secondary procedures.To date we have randomized 462 patients over approximately 6 years, with a planned full enrollment of 550 patients. Ten percent of patients have been withdrawn because they did not undergo the planned orthotopic diversion due to a positive urethral margin on frozen section. We expect approximately 70% of patients to be alive and available for follow-up at 3 years, which will give us ample power to detect clinically meaningful differences in the outcome of these two diversions.This trial has been feasible and randomization has been acceptable to most patients. Long-term follow-up of the patients on this trial should be able to definitively answer the question of the importance of an antireflux mechanism in the orthotopic neobladders construction.

  View details for DOI 10.1007/s00345-008-0341-5

  View details for Web of Science ID 000262704200009

  View details for PubMedID 19002689

• Guideline for the management of nonmuscle invasive bladder cancer (Stages Ta, T1, and Tis): 2007 update JOURNAL OF UROLOGY Hall, M. C., Chang, S. S., Dalbagni, G., Pruthi, R. S., Seigne, J. D., Skinner, E. C., Wolf, J. S., Schellhammer, P. F. 2007; 178 (6): 2314-2330

  View details for DOI 10.1016/j.juro.2007.09.003

  View details for Web of Science ID 000250847900020

  View details for PubMedID 17993339

• The best treatment for high-grade T1 bladder cancer is cystectomy UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS Skinner, E. C. 2007; 25 (6): 523-525

  Abstract

  To evaluate the role of initial cystectomy in the management of high-grade T1 bladder cancer.A selected review of the literature was performed to evaluate outcomes with intravesical therapy vs. initial cystectomy in this patient population, with a focus on identifying risk factors for failure of conservative therapy.Many studies in the literature fail to include central pathologic review and re-TUR clinical staging, and there are no randomized studies comparing outcomes with these two initial approaches. Retrospective studies of patients with high-grade T1 tumors treated with initial intravesical therapy suggest that approximately 30% of patients will ultimately require cystectomy, and 30% will die of their disease with or without cystectomy. The risk of progression continues for the life of the patient, and late recurrence and progression is common. Initial clinical and pathologic factors can be identified that predict a high risk of progression and are reasonable indicators for initial cystectomy.Radical cystectomy can provide a very high cure rate for these patients and should be considered early in the treatment plan.

  View details for DOI 10.1016/j.urolonc.2007.05.023

  View details for Web of Science ID 000251482600015

  View details for PubMedID 18047965

• A prospective randomized EORTC intergroup phase 3 study comparing the complications of elective nephron-sparing surgery and radical nephrectomy for low-stage renal cell carcinoma EUROPEAN UROLOGY Van Poppel, H., Da Pozzo, L., Albrecht, W., Matveev, V., Bono, A., Borkowski, A., Marechal, J., Klotz, L., Skinner, E., Keane, T., Claessens, I., Sylvester, R. 2007; 51 (6): 1606-1615

  Abstract

  This study compared the complications and the cancer control of elective nephron-sparing surgery (NSS) and radical nephrectomy (RN) in patients with a small (

  View details for DOI 10.1016/j.eururo.2006.11.013

  View details for Web of Science ID 000246912300024

  View details for PubMedID 17140723

• Functional heterogeneity of prostatic intraepithelial neoplasia: the duration of hormonal therapy influences the response BJU INTERNATIONAL Kang, T. Y., Nichols, P., Skinner, E., Groshen, S., Valin, G., Ye, W., Raghavan, D. 2007; 99 (5): 1024-1027

  Abstract

  To use a clinical model of androgen-deprivation therapy (ADT) followed by radical prostatectomy (RP) to test the hypothesis that prostatic intraepithelial neoplasia (PIN, a premalignant lesion of the prostate causally linked to prostate cancer) is heterogeneous for hormone responsiveness, which might explain aspects of the heterogeneity of the natural history of prostate cancer, for although ADT has been used to reduce prostate cancer, there are controversial data on the effect of ADT on PIN.We assessed retrospectively patients with biopsy-confirmed prostate cancer who had RP; some patients had received >or=3 months of ADT at the discretion of their surgeons, and patients from the same cohort who did not have ADT were used as controls. Patients were sequentially selected from the database and their pathology slides were reviewed by a pathologist unaware of the initial presence of PIN (assessed by an independent observer). Fisher's exact test was used to compare the proportions of patients who had residual PIN in the study and control groups. Exact logistic regression was used to evaluate the duration of ADT on PIN regression.Eighteen patients initially diagnosed with PIN who had no ADT were identified, and 28 with PIN who had ADT were also assessed. All patients who had had no ADT had residual PIN, whereas seven of 28 receiving ADT had no residual PIN (P=0.043). The evaluation of ADT between responders and nonresponders showed a statistically significant association between PIN regression and the duration of ADT (P<0.001). However, the response of PIN to ADT was not uniform, as 16% of patients on ADT for >6 months had residual PIN, suggesting variable sensitivity of PIN to ADT.These results show that ADT causes PIN to regress, and that there is heterogeneity in this effect with the duration of ADT. We propose future prospective, multicentre, randomized trials in which the effect of ADT on PIN is characterized further.

  View details for DOI 10.1111/j.1464-410X.2006.06738.x

  View details for Web of Science ID 000245603200017

  View details for PubMedID 17244277

• Radical cystectomy with extended lymphadenectomy: Evaluating separate package versus en bloc submission for node positive bladder cancer JOURNAL OF UROLOGY Stein, J. P., Penson, D. F., Cai, J., Miranda, G., Skinner, E. C., Dunn, M. A., Groshen, S., Lieskovsky, G., Skinner, D. G. 2007; 177 (3): 876-881

  Abstract

  To provide future mapping analysis of lymph node positive disease we modified our lymphadenectomy at radical cystectomy for bladder cancer from an en bloc packet to 13 separate nodal packets. We evaluated the clinical and pathological findings resulting from this modification.A total of 1,359 patients underwent en bloc radical cystectomy and extended lymphadenectomy for bladder cancer. They were compared to 262 patients who underwent radical cystectomy and extended lymphadenectomy with lymph nodes submitted in 13 distinct nodal packets. Overall 317 patients (23%) of the en bloc group (group 1) and 66 of the 262 (25%) in the separately packaged group (group 2) had node positive disease. Clinical and pathological findings were analyzed to compare these 2 groups of patients.Although the incidence of lymph node positivity was not different, the median number of total lymph nodes removed in group 2 was significantly higher than that in group 1 (68, range 14 to 132 vs 31, range 1 to 96, p<0.001). A trend toward more lymph nodes involved was observed in group 2 compared to group 1 (3, range 1 to 91 vs 2, range 1 to 63, p=0.062). These findings significantly lowered median lymph node density in group 2 compared to that in group 1 (6% vs 9%, p=0.006).Although the overall incidence of lymph node positive disease was not different, the submission of 13 separate nodal packets at radical cystectomy significantly increased the total number of lymph nodes removed/analyzed and identified a slightly higher number of positive lymph nodes compared to en bloc submission.

  View details for DOI 10.1016/j.juro.2006.10.043

  View details for Web of Science ID 000244211600017

  View details for PubMedID 17296365

• Surgical benchmarks for the treatment of invasive bladder cancer UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS Skinner, E. C., Stein, J. P., Skinner, D. G. 2007; 25 (1): 66-71

  Abstract

  Radical cystectomy is the gold standard for treatment of localized invasive bladder cancer in the United States. In recent years, there has been increasing focus on the importance of surgical technique as a factor that may influence the clinical and oncologic outcome of the operation, beyond the classically recognized patient and tumor-related factors. There is still insufficient high-quality evidence to support the absolute standardization of the surgical technique or the establishment of firm benchmarks by which the individual surgeon can measure performance. However, there is considerable evidence suggesting that 3 aspects of surgical technique have an impact on outcome: (1) Positive surgical margins nearly always result in ultimate cancer death. The rate of positive margins varies with surgeon experience as well as with cancer-specific variables. (2) The extent of lymphadenectomy has a significant impact on recurrence rates of the cancer, regardless of whether the lymph nodes are pathologically positive or not. (3) Higher volume surgeons have lower operative mortality and fewer positive surgical margins than low-volume surgeons. Higher volume hospitals also have lower operative mortalities and shorter hospital stays for patients who have undergone radical cystectomy. In this review, the authors evaluate the evidence supporting each of these statements and suggest potential areas of standardization of surgical technique that could translate into improved patient outcomes.

  View details for DOI 10.1016/j.urolonc.2006.05.010

  View details for Web of Science ID 000243702000011

  View details for PubMedID 17208142

• A critical analysis of perioperative mortality from radical cystectomy JOURNAL OF UROLOGY Quek, M. L., Stein, J. P., Daneshmand, S., Miranda, G., Thangathurai, D., Roffey, P., Skinner, E. C., Lieskovsky, G., Skinner, D. G. 2006; 175 (3): 886-889

  Abstract

  Operative mortality from radical cystectomy has decreased as a result of improvements in surgical and anesthetic care. We reviewed the perioperative deaths from a large group of patients treated with radical cystectomy for primary bladder cancer.All perioperative mortalities from radical cystectomy were identified from a single high volume institution. The medical records were reviewed to assess the cause of death as well as possible contributing factors.From August 1971 to December 2001, 1,359 patients with primary bladder cancer were treated with radical cystectomy and pelvic iliac lymphadenectomy at our institution. Of these patients, 27 (2%) died within 30 days of surgery or before discharge from hospital. Median patient age at surgery was 67 years (range 47 to 78) and males accounted for 81% of the patients. The median time to death was 28 days from cystectomy (range 0 to 80). Most deaths were cardiovascular related (including acute myocardial infarction, cerebrovascular accident, arterial thrombosis) or due to septic complications with resulting multi-organ system failure, followed by pulmonary embolism, hepatic failure and hemorrhage. Septic related mortality was most often associated with postoperative urine or bowel leak. While most deaths occurred before hospital discharge, 2 patients died at home due to a late pulmonary embolus. No association was seen between pathological stage or type of urinary diversion and mortality.Perioperative mortality from radical cystectomy is low in this group of patients. Most deaths are due to cardiovascular or septic complications. Careful patient selection and meticulous surgical technique may help decrease the incidence of perioperative mortality.

  View details for DOI 10.1016/S0022-5347(05)00421-0

  View details for Web of Science ID 000235289400019

  View details for PubMedID 16469572

• Quality of life after cystectomy and urinary diversion: An evidence based analysis JOURNAL OF UROLOGY Gerharz, E. W., Mansson, A., Hunt, S., Skinner, E. C., Mansson, W. 2005; 174 (5): 1729-1736

  Abstract

  We critically examined the evidence supporting the widely accepted notion that patients undergoing continent urinary tract reconstruction after cystectomy experience superior quality of life outcomes than patients receiving a conduit.Based on a comprehensive MEDLINE literature search we retrieved and evaluated all full-length articles published in the English, French, German, Italian and Spanish languages comparing conduit diversion with continent cutaneous diversion and/or orthotopic bladder substitution with respect to quality of life or similar concepts. All studies were rated according to the International Consultation on Urological Diseases modification of Oxford Center for Evidence-Based Medicine levels of evidence.The literature on quality of life after radical cystectomy for bladder cancer was rather extensive but generally of questionable quality. The main problems were flaws in the patient materials and methodologies used. To our knowledge not a single randomized, controlled study exists in the field. Because only few articles achieved a level of evidence better than III, the International Consultation on Urological Diseases rating system does not allow further differentiation among studies. Most studies showed that overall quality of life after cystectomy remained good in most patients irrespective of urinary diversion type.Existing studies are unable to prove that continent reconstruction after radical cystectomy is superior to conduit diversion. This review emphasizes the importance of performing well designed studies in the future.

  View details for DOI 10.1097/01.ju.000176463.40530.05

  View details for Web of Science ID 000232619700005

  View details for PubMedID 16217273

• Prognostic significance of lymphovascular invasion of bladder cancer treated with radical cystectomy JOURNAL OF UROLOGY Quek, M. L., Stein, J. P., Nichols, P. W., Cai, J., Miranda, G., Groshen, S., Daneshmand, S., Skinner, E. C., Skinner, D. G. 2005; 174 (1): 103-106

  Abstract

  We determined the prognostic significance of lymphovascular invasion (LVI) in patients treated for invasive transitional cell carcinoma of the bladder with radical cystectomy.From August 1971 to June 2004, 2,005 patients underwent radical cystectomy for primary bladder cancer with intent to cure. All patients with nontransitional cell carcinoma histology, palliative procedures, unknown lymphovascular status, less than pT1 pathological stage, or any neoadjuvant or adjuvant chemotherapy/radiation therapy were excluded, leaving 702 comprising the study cohort. Of the 702 patients 249 (36%) had LVI.Median followup was 11.0 years (range 8 days to 23.2 years). Overall 5 and 10-year survival was 51% and 34%, while 5 and 10-year recurrence-free survival was 66% and 64%, respectively. Ten-year recurrence-free survival in patients without LVI was 74% compared with 42% in those with LVI (p <0.0001). Similarly 10-year overall survival was 43% in patients without LVI compared with 18% in those with LVI (p <0.0001). In the organ confined/lymph node negative and lymph node positive pathological subgroups survival outcomes were significantly worse if LVI was present. Although a trend was observed, LVI status was not statistically significant in patients with extravesical node negative disease. Stepwise Cox regression analysis revealed that pathological subgroup (organ confined, extravesical and lymph node positive) (p <0.0001) and LVI status (p = 0.0004) were independent prognostic variables for recurrence-free and overall survival.Lymphovascular invasion appears to be an important and independent prognostic variable in patients with invasive bladder cancer treated with radical cystectomy. LVI status should be determined in cystectomy specimens, which may provide further risk stratification in patients following radical cystectomy.

  View details for DOI 10.1097/01.ju.0000163267.93769.d8

  View details for Web of Science ID 000229946400028

  View details for PubMedID 15947587

• Prognosis of patients with lymph node positive prostate cancer following radical prostatectomy: Long-term results JOURNAL OF UROLOGY Daneshmand, S., Quek, M. L., Stein, J. P., Lieskovsky, G., Cai, J., Pinski, J., Skinner, E. C., Skinner, D. G. 2004; 172 (6): 2252-2255

  Abstract

  We determined the prognostic factors that affect recurrence and survival in patients with lymph node positive prostate cancer.Between 1972 and 1999, 1,936 patients underwent radical retropubic prostatectomy and pelvic lymph node dissection for clinically organ confined prostate cancer. A total of 235 patients (12.1%) were found to have disease metastatic to the lymph nodes (stage D1). Of the patients 69% received no adjuvant treatment. We reviewed the tumor stage (TNM), Gleason score, number and percent of involved lymph nodes (lymph node density), preoperative prostate specific antigen when available and adjuvant treatment. Overall survival and recurrence-free survival were estimated using Kaplan-Meier plots.Followup was 1 to 24 years (median 11.4). Overall median survival was 15 years. Overall clinical recurrence-free survival at 5, 10 and 15 years was 80%, 65% and 58%, respectively. Patients who had 1 or 2 positive lymph nodes had a clinical recurrence-free survival of 70% and 73% at 10 years, respectively, vs 49% in those who had 5 or more involved lymph nodes (p = 0.0031). When stratified by lymph node density, patients with a lymph node density of 20% or greater were at higher risk for clinical recurrence compared to those with a density of less than 20% (relative risk = 2.32, p <0.0001). On stratified log rank test only prostate cancer T stage, and the number and percent of positive lymph nodes correlated with recurrence-free and overall survival.Local tumor bulk and the number/percent of involved lymph nodes significantly affect disease progression and the survival rate. Radical prostatectomy may offer long-term survival in patients who have limited tumor bulk and nodal involvement.

  View details for DOI 10.1097/01.ju.0000143448.04161.cc

  View details for Web of Science ID 000225194900029

  View details for PubMedID 15538242

• Prognosis of seminal vesicle involvement by transitional cell carcinoma of the bladder JOURNAL OF UROLOGY Daneshmand, S., Stein, J. P., Lesser, T., Quek, M. L., Nichols, P. W., Miranda, G., Cai, M., Groshen, S., Skinner, E. C., Skinner, D. G. 2004; 172 (1): 81-84

  Abstract

  Transitional cell carcinoma (TCC) of the bladder that extends directly into contiguous organs (pT4) portends a poor prognosis. The 2002 American Joint Committee on Cancer staging system does not include seminal vesicle involvement by primary TCC of the bladder. In this analysis we evaluated the clinical outcomes and prognostic significance of seminal vesicle involvement with TCC of the bladder after radical cystectomy.From 1971 to 2001, 1,682 patients underwent radical cystectomy and pelvic lymphadenectomy for bladder cancer. Only those tumors that involved adjacent organs through the bladder wall (pT4) were included. Overall 132 male patients with a median age of 68 years (range 36 to 98) qualified for analysis. Patients were stratified into 4 subgroups of 1) direct extravesical prostatic stromal involvement only in 37 patients (28%), 2) prostatic stroma and seminal vesicle involvement in 37 patients (28%), 3) seminal vesicle involvement only in 10 patients (8%) and 4) other contiguous pelvic organ involvement (stage pT4b) in 48 patients (36%). Overall 88 patients (67%) received some form of adjuvant therapy. At a median followup of 12.5 years (range 0 to 15.2) clinical outcomes were analyzed including overall and recurrence-free survival using Kaplan-Meier plots.There was no significant difference in clinical outcomes or prognosis for groups 2 and 3, thus they were combined for analysis. Five-year overall survival for any seminal vesicle involvement (10%) was significantly worse than prostatic stromal involvement only (38%) but was similar to pT4b tumors (7%, p <0.0001). The 5-year recurrence-free survival for seminal vesicle involvement (14%) was also significantly worse than prostatic stromal involvement alone (68%) but similar to that pT4b disease (25%, p = 0.01). Results were controlled for lymph node status.Patients with extravesical tumor extension into seminal vesicles and contiguous pelvic organs are at high risk for recurrence and progression. Involvement of the seminal vesicles by direct extension of bladder TCC portends a prognosis similar to that of pT4b disease and should, therefore, be classified as such.

  View details for DOI 10.1097/01.ju.0000132131.64727.ff

  View details for Web of Science ID 000222115700017

  View details for PubMedID 15201742

• Pubovaginal slings for stress urinary incontinence following radical cystectomy and orthotopic neobladder reconstruction in women JOURNAL OF UROLOGY Quek, M. L., Ginsberg, D. A., Wilson, S., Skinner, E. C., Stein, J. P., Skinner, D. G. 2004; 172 (1): 219-221

  Abstract

  We evaluated the clinical efficacy of pubovaginal slings for new onset stress urinary incontinence following radical cystectomy and orthotopic lower urinary tract reconstruction in women.Between June 1990 and July 2002, 101 female patients with primary transitional cell carcinoma of the bladder were treated with radical cystectomy and orthotopic ileal neobladder reconstruction. Four patients 61 to 73 years old underwent pubovaginal slings (autologous rectus fascia in 2 and dermal graft in 2) for stress urinary incontinence persisting 9 to 20 months following reconstruction with a Studer (2) or T pouch (2) ileal neobladder. Pre-cystectomy continence was excellent in 3 patients, while 1 had mild stress incontinence. All patients had high grade, muscle invasive transitional cell carcinoma and/or carcinoma in situ with negative urethral margins and 3 of the 4 had lymph node negative disease on pathological examination. Two patients were treated with transurethral bulking material 4 to 5 months prior to the sling procedure without noticeable improvement.Two patients who underwent autologous pubovaginal slings had significant complications arising from dissection in the retropubic space, including 1 entero-pouch fistula and 1 enterotomy resulting in an enterocutaneous fistula, sepsis and subsequent death. These 2 patients had persistent stress incontinence despite the sling procedures and they ultimately underwent conversion to continent cutaneous urinary diversions. Two patients were treated with a dermal graft sling using infrapubic bone anchors through a transvaginal approach, obviating the need to enter the pelvis. These patients had uneventful postoperative courses and they are currently hypercontinent, performing intermittent catheterization with complete daytime continence and only occasional nighttime leakage 3 and 9 months following sling surgery.Pubovaginal sling procedures for incontinence following orthotopic neobladder reconstruction in women may be complicated due to extensive pelvic surgery. Dissection in the retropubic space should be avoided because potentially fatal complications may occur. Slings using infrapubic bone anchors may provide the best option in such patients in whom conservative management has failed because the pelvis need not be violated.

  View details for DOI 10.1097/01.ju.0000132149.63834.33

  View details for Web of Science ID 000222115700053

  View details for PubMedID 15201778

• Genitourinary cancer in the elderly SEMINARS IN ONCOLOGY Raghavan, D., Skinner, E. 2004; 31 (2): 249-263

  Abstract

  Genitourinary malignancy comprises nearly half of the cancers diagnosed in men, and the incidence of this group of cancers increases with age. The key to successful management is to define appropriate goals (cure v palliation) based on the natural history and extent of disease, physiology and life expectancy of the patients, and cost-benefit ratio of treatment options. Of particular importance, the chance for cure should not be sacrificed because of age-based considerations in early-stage cancers of the prostate or kidney nor in the early stage of locally advanced urothelial malignancy.

  View details for DOI 10.1053/j.seminoncol.2003.12.034

  View details for Web of Science ID 000220886600012

  View details for PubMedID 15112154

• Prevention of prostate cancer with finasteride. New England journal of medicine Ross, R. K., Skinner, E., Cote, R. J. 2003; 349 (16): 1569-1572

  View details for PubMedID 14562807

• High-risk localized prostate cancer: primary surgery and adjuvant therapy UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS Skinner, E. C., Glode, L. M. 2003; 21 (3): 219-227

  Abstract

  High risk localized prostate cancer includes patients with palpable disease outside the capsule (clinical stage T3) as well as those with apparently localized disease but with adverse prognostic factors such as Gleason 8-10 tumors or very extensive disease on biopsy. The goals of therapy for these patients are to achieve both long-term local control and to remain free of metastatic disease. The ideal treatment to achieve these goals is unknown. We present a review of the outcome of contemporary reported series of such patients treated with primary radical prostatectomy, with or without neoadjuvant or adjuvant therapies. Over 80% of the patients overall achieved a 5-year disease-specific survival, though well under 50% have undetectable prostate specific antigen at that time point. We also review what is known about the choice and timing of adjuvant therapies, and describe current cooperative group studies underway to answer some of these questions.

  View details for DOI 10.1016/S1078-1439(03)00018-8

  View details for Web of Science ID 000183857300009

  View details for PubMedID 12810210

• Sexuality and intimacy following radical prostatectomy: Patient and partner perspectives HEALTH PSYCHOLOGY Perez, M. A., Skinner, E. C., Meyerowitz, B. E. 2002; 21 (3): 288-293

  Abstract

  Most research on adjustment following radical prostatectomy has focused on limited assessments of urinary and erectile functioning. In this study, the authors provided a more comprehensive assessment of sexuality from 134 radical prostatectomy patients and their partners and determined the extent to which various components of sexuality are associated with psychosocial adjustment. Measures of sexuality and intimacy modestly predicted patients' emotional distress and quality of life (QoL), with body image and dyadic adjustment playing the most important roles after controlling for medical variables, general physical functioning, and optimistic outlook. Urinary incontinence and other sexuality variables were not unique predictors. In contrast, partner ratings of sexual satisfaction played a more important role in predicting their QoL.

  View details for DOI 10.1037//0278-6133.21.3.288

  View details for Web of Science ID 000175237400009

  View details for PubMedID 12027035

• Radical cystectomy in the treatment of invasive bladder cancer: Long-term results in 1,054 patients JOURNAL OF CLINICAL ONCOLOGY Stein, J. P., Lieskovsky, G., Cote, R., Groshen, S., Feng, A. C., Boyd, S., Skinner, E., Bochner, B., Thangathurai, D., Mikhail, M., Raghavan, D., Skinner, D. G. 2001; 19 (3): 666-675

  Abstract

  To evaluate our long-term experience with patients treated uniformly with radical cystectomy and pelvic lymph node dissection for invasive bladder cancer and to describe the association of the primary bladder tumor stage and regional lymph node status with clinical outcomes.All patients undergoing radical cystectomy with bilateral pelvic iliac lymphadenectomy, with the intent to cure, for transitional-cell carcinoma of the bladder between July 1971 and December 1997, with or without adjuvant radiation or chemotherapy, were evaluated. The clinical course, pathologic characteristics, and long-term clinical outcomes were evaluated in this group of patients.A total of 1,054 patients (843 men [80%] and 211 women) with a median age of 66 years (range, 22 to 93 years) were uniformly treated. Median follow-up was 10.2 years (range, 0 to 28 years). There were 27 (2.5%) perioperative deaths, with a total of 292 (28%) early complications. Overall recurrence-free survival at 5 and 10 years for the entire cohort was 68% and 66%, respectively. The 5- and 10-year recurrence-free survival for patients with organ-confined, lymph node-negative tumors was 92% and 86% for P0 disease, 91% and 89% for Pis, 79% and 74% for Pa, and 83% and 78% for P1 tumors, respectively. Patients with muscle invasive (P2 and P3a), lymph node-negative tumors had 89% and 87% and 78% and 76% 5- and 10-year recurrence-free survival, respectively. Patients with nonorgan-confined (P3b, P4), lymph node-negative tumors demonstrated a significantly higher probability of recurrence compared with those with organ-confined bladder cancers (P <.001). The 5- and 10-year recurrence-free survival for P3b tumors was 62% and 61%, and for P4 tumors was 50% and 45%, respectively. A total of 246 patients (24%) had lymph node tumor involvement. The 5- and 10-year recurrence-free survival for these patients was 35%, and 34%, respectively, which was significantly lower than for patients without lymph node involvement (P <.001). Patients could also be stratified by the number of lymph nodes involved and by the extent of the primary bladder tumor (p stage). Patients with fewer than five positive lymph nodes, and whose p stage was organ-confined had significantly improved survival rates. Bladder cancer recurred in 311 patients (30%). The median time to recurrence among those patients in whom the cancer recurred was 12 months (range, 0.04 to 11.1 years). In 234 patients (22%) there was a distant recurrence, and in 77 patients (7%) there was a local (pelvic) recurrence.These data from a large group of patients support the aggressive surgical management of invasive bladder cancer. Excellent long-term survival can be achieved with a low incidence of pelvic recurrence.

  View details for Web of Science ID 000166803100009

  View details for PubMedID 11157016

• Quality of life with reconstruction. Seminars in urologic oncology Skinner, E. C. 2001; 19 (1): 56-58

  Abstract

  Quality-of-life considerations were one of the main driving forces behind the development of continent urinary diversion. However, the field of formal quality-of-life study that allows us to document these aspects of treatment is still relatively young. In the past decade, a number of quality-of-life studies of cystectomy patients have been undertaken, with somewhat mixed results. Many of these studies have been limited by small patient numbers, and the differences in the various treatment groups, for example, in age and comorbidities. Most have shown that overall quality of life after cystectomy remains good for most patients, with the expected problems with urinary diversion and sexual dysfunction. However, few differences between the diversion groups have been demonstrated, suggesting that patients adapt to whatever is required of them. One large study from Germany did find significant improvement in several aspects of quality of life in patients with continent diversion. Patient education, exploration of the pros and cons of the various alternatives, and active patient participation in the treatment decisions seem to be key to postoperative satisfaction.

  View details for PubMedID 11246735

• Quality of life after radical cystectomy for bladder cancer in patients with an ileal conduit, or cutaneous or urethral Kock pouch JOURNAL OF UROLOGY Hart, S., Skinner, E. C., Meyerowitz, B. E., Boyd, S., Lieskovsky, G., Skinner, D. G. 1999; 162 (1): 77-81

  Abstract

  Radical cystectomy for bladder cancer is associated with many changes in bodily function with sexual and urinary dysfunction most prevalent. However, little research has been done on how efforts to improve erectile function relate to quality of life. Also, the psychological benefits associated with continent urinary diversion have not been fully explored. We compared long-term quality of life outcomes among 3 urinary diversion groups, and between patients who had and had not received an inflatable penile prosthesis.The 224 participating patients completed 4 self-reporting questionnaires, including the profile of mood states, and adapted versions of the sexual history form, body image dissatisfaction scale and quality of life questionnaire. We compared self-reports of emotional distress, global quality of life, sexuality, body image dissatisfaction, urinary diversion problems, and problems with social, physical and functional activities in patients with advanced bladder cancer who underwent urinary diversion, including an ileal conduit in 25, cutaneous Kock pouch in 93 and urethral Kock pouch in 103. Patients who had or had not received an inflatable penile prosthesis after cystectomy were also compared in regard to quality of life variables.Regardless of type of urinary diversion the majority of patients reported good overall quality of life, little emotional distress and few problems with social, physical or functional activities. Problems with urinary diversion and sexual functioning were identified as most common. After controlling for age analysis of variance showed no significant differences among urinary diversion subgroups in any quality of life area. However, t tests controlling for age indicated that penile prosthesis placement was significantly associated with better sexual function and satisfaction.Quality of life appears good in these long-term survivors of advanced bladder cancer. The type of urinary diversion does not appear to be associated with differential quality of life. Findings suggest that physicians may wish to discuss urinary diversion problems and sexual dysfunction as long-term correlates of radical cystectomy for bladder cancer. Furthermore, they may also wish to discuss the option of erectile aids in men with erectile dysfunction after cystectomy.

  View details for Web of Science ID 000080753700018

  View details for PubMedID 10379744

• Hydronephrosis as a prognostic indicator in bladder cancer patients JOURNAL OF UROLOGY Haleblian, G. E., Skinner, E. C., Dickinson, M. G., Lieskovsky, G., Boyd, S. D., Skinner, D. G. 1998; 160 (6): 2011-2014

  Abstract

  Pathological stage is the standard measure of prognosis in patients who have undergone radical cystectomy for bladder cancer. Despite the development of new imaging techniques, clinical staging for bladder cancer continues to be inaccurate. We investigated whether the presence of unilateral or bilateral upper tract obstruction could accurately predict advanced cancer stage (extravesical extension, stage greater than p3b or N+).A retrospective study of 415 patients diagnosed with transitional cell carcinoma of the bladder who were treated with radical cystectomy between 1983 and 1993 was conducted. All patients were followed for survival. The criteria for analysis included hydronephrosis status (no obstruction, unilateral, bilateral) as well as pathological stage of the tumor.Of 415 patients 72% presented with no, 22.7% unilateral and 5.3% bilateral obstruction. Our results showed a significant correlation between hydronephrosis and advanced cancer stage (p <0.0001), and decreased patient survival (p <0.0001). More than 90% of patients with bilateral obstruction had disease with extravesical extension. Of the patients with unilateral obstruction a third had disease confined to the bladder with a significant proportion confined to the bladder mucosa.The presence of unilateral or bilateral hydronephrosis is a clinical datum that is already available to help accurately stage bladder tumors. The presence of bilateral obstruction is an ominous sign, while a significant proportion of patients presenting with unilateral obstruction have disease confined to the bladder.

  View details for Web of Science ID 000076875500017

  View details for PubMedID 9817312

• The effect of finasteride on the prostate gland in men with elevated serum prostate-specific antigen levels BRITISH JOURNAL OF CANCER Cote, R. J., Skinner, E. C., Salem, C. E., Mertes, S. J., Stanczyk, F. Z., Henderson, B. E., Pike, M. C., Ross, R. K. 1998; 78 (3): 413-418

  Abstract

  Prostate cancer is a disease associated with androgens. It has been hypothesized that reducing the conversion of testosterone (T) to dihydrotestosterone (DHT) in the prostate by the use of the drug finasteride, a 5alpha-reductase inhibitor, will reduce the incidence of prostate cancer. We investigated the chemopreventive potential of finasteride by evaluating its effect on the prostate gland of men with elevated serum prostate-specific antigen (PSA). Fifty-two men with elevated PSA and prostate sextant biopsies negative for cancer were randomized to receive finasteride 5 mg day(-1) (27 patients) or no medication (25 patients) for 12 months and were rebiopsied at 12 months. The biopsies were evaluated for the presence of cancer, the proportion of glandular and hyperplastic tissue, and the presence of high-grade prostatic intraepithelial neoplasia (PIN). Epithelial proliferation was assessed in the prestudy and 12-month biopsies by immunohistochemistry using antibody to proliferating cell nuclear antigen (PCNA). Serum blood samples were drawn at baseline and after 1, 3, 6 and 12 months of study. In the control group, serum levels of PSA and T were unchanged throughout the 12 months. In the finasteride group, PSA decreased 48% (P < 0.001), DHT decreased 67% (P < 0.001) and T increased 21% (P < 0.001). Histological evaluation of prestudy and 12-month biopsy specimens revealed that the finasteride group had a 30% reduction in the percentage of hyperplastic epithelial tissue (P = 0.002), although this decrease was not statistically significantly different between the finasteride and control groups (P = 0.11). In patients with PIN on prestudy biopsy, no change occurred in the PIN lesions with finasteride treatment. Finasteride also had no effect on the proliferation index of prostatic epithelial cells. Of the 27 patients treated with finasteride, eight (30%) had adenocarcinoma of the prostate detected on the 12-month biopsy, compared with one (4%) of the control patients (P = 0.025). In the treatment group, six cancers occurred in the eight patients with PIN on the prestudy biopsy; in the observation group no cancers were detected in the five patients with PIN on the prestudy biopsy (P = 0.021). Two cancers occurred in the 19 men in the treatment group with no evidence of PIN on the prestudy biopsy, compared with one cancer in the 20 men in the observation group with no evidence of PIN on the prestudy biopsy (P = 0.60). This study, using a novel model for evaluating short-term efficacy of chemopreventive or therapeutic agents in men at high risk of prostate cancer, provides little evidence that finasteride is an effective chemopreventive agent for prostate cancer in men with elevated PSA.

  View details for Web of Science ID 000075150400024

  View details for PubMedID 9703292

• Radical cystectomy for elderly patients with bladder carcinoma - An updated experience with 404 patients CANCER Figueroa, A. J., Stein, J. P., Dickinson, M., Skinner, E. C., Thangathurai, D., Mikhail, M. S., Boyd, S. D., Lieskovsky, G., Skinner, D. G. 1998; 83 (1): 141-147

  Abstract

  The authors evaluated the experiences at their institution with radical cystectomy and urinary diversion performed on elderly bladder carcinoma patients to determine whether age had an impact on the clinical or functional results for this group of patients.Between August 1971 and December 1996, 404 patients age 70 years or older (median age, 74 years) underwent radical cystectomy and urinary diversion for invasive bladder carcinoma: 352 (87%) were ages 70-79 years and 52 (13%) were age 80 years or older. Data analyzed included the following: perioperative mortality; early (within 90 days after surgery) and late (more than 90 days after surgery) postoperative complications, related and unrelated to the urinary diversion; length of hospital stay; pathologic staging; and clinical outcome. These data were then compared with those for 762 patients younger than 70 years (median age, 61 years) who underwent the same procedure during the same time period.The overall mortality rate for patients age 70 years or older was 2.8% (3.2% for those ages 70-79 years, 0% for those age 80 years or older), compared with 2% for patients younger than 70 years. The early complication rate for patients age 70 years or older was 32%, compared with 25% for patients younger than 70 years. Patients age 80 years or older had a similar early complication rate of 29%. Late postoperative complications occurred in 12.4% of patients age 70 years or older, compared with 22.8% of patients younger than 70 years. There was no significant difference between the two groups with regard to pathologic stage or length of hospital stay. The 3-year and 5-year overall survival rates for patients age 70 years or older were 60% and 53%, respectively, compared with 68% and 63%, respectively, for patients younger than 70 years (P=0.001). There was no statistical difference between the groups when rates of disease recurrence were compared (P=0.3627). The 5-year recurrence rate for patients age 70 years or older was 35%, compared with a 5-year recurrence rate of 31% for patients younger than 70 years.These data suggest that an aggressive, curative, radical surgical approach and urinary diversion may be a viable treatment strategy for properly selected elderly patients who are in generally good health and require definitive therapy for invasive bladder carcinoma.

  View details for Web of Science ID 000074360600019

  View details for PubMedID 9655304

• 25-year experience in the management of invasive bladder cancer by radical cystectomy 6th Heinrich Warner Symposium on Invasive Bladder Carcinoma - Progress in Basic Research, Surgical and Medical Therapy Skinner, D. G., Stein, J. P., Lieskovsky, G., Skinner, E. C., Boyd, S. D., Figueroa, A., Jones, P., Cote, R., Groshen, S. ELSEVIER SCIENCE BV. 1998: 25–26

  View details for Web of Science ID 000073857600013

  View details for PubMedID 9615206

• Quality of life and sexuality following radical prostatectomy in patients with prostate cancer who use or do not use erectile AIDS UROLOGY Perez, M. A., Meyerowitz, B. E., Lieskovsky, G., Skinner, D. G., Reynolds, B., Skinner, E. C. 1997; 50 (5): 740-746

  Abstract

  It is well established that prostate cancer patients undergoing radical prostatectomy may experience disruptive side effects, most notably urinary incontinence and erectile dysfunction. The purpose of this study is to compare relevant outcomes between patients awaiting radical prostatectomy for prostate cancer and patients who already underwent the surgery, taking into account type of prostatectomy and use of erectile aids.We compared self-reports of global quality of life, sexuality, urinary continence, and physical capabilities in 86 nerve-sparing patients, 89 standard-prostatectomy patients, 74 prostatectomy patients who used erectile aids, and a comparison group of 45 patients awaiting radical prostatectomy.Regardless of type of surgery, use of erectile aid, or preoperative status, most patients reported good quality of life. The best outcomes in sexuality were reported by patients who used erectile aids, who appeared similar in sexuality to patients awaiting surgery. When differences were detected, standard prostatectomy patients who did not use erectile aids scored worse in most areas of sexuality than nerve-sparing patients who did not use erectile aids. There were no differences in frequency of urinary leakage among the three surgery subgroups.Although most patients reported problems in sexual and urinary function, global quality of life does not appear to be compromised following radical prostatectomy. Findings suggest that postsurgical sexuality differs depending on type of prostatectomy and use of erectile aids, while urinary function is similar across surgery groups. We conclude that erectile aids should be offered routinely to patients who are ineligible for nerve-sparing surgery or experience erectile difficulties following the nerve-sparing procedure.

  View details for Web of Science ID A1997YG34600017

  View details for PubMedID 9372885

• Orthotopic lower urinary tract reconstruction in women using the kock ileal neobladder: Updated experience in 34 patients JOURNAL OF UROLOGY Stein, J. P., Grossfeld, G. D., Freeman, J. A., Esrig, D., Ginsberg, D. A., Cote, R. J., Skinner, E. C., Boyd, S. D., Lieskovsky, G., Skinner, D. G. 1997; 158 (2): 400-405

  Abstract

  Orthotopic lower urinary tract reconstruction has revolutionized urinary diversion following cystectomy. Initially performed solely in male patients, orthotopic diversion has now become a viable option in women. Currently, the orthotopic neobladder is the diversion of choice for women requiring lower urinary tract reconstruction at our institution. We evaluate and update our clinical and functional experience with orthotopic reconstruction in female patients.Since June 1990, 34 women 31 to 86 years old (median age 67) have undergone orthotopic lower urinary tract reconstruction following cystectomy. Indications for cystectomy included transitional cell carcinoma in 29 patients, urachal adenocarcinoma in 1, mesenchymal tumor of endometrial origin in 1, cervical carcinoma in 1 and a fibrotic radiated bladder in 1. In addition, 1 woman underwent undiversion to the native urethra following a previous simple cystectomy and cutaneous diversion for eosinophilic cystitis. Data were analyzed according to postoperative early and late complications, survival, tumor recurrence, pathological evaluation of the cystectomy specimen, continence status, voiding pattern and patient satisfaction. The median followup in this group of patients was 30 months (range 17 to 70).There were no perioperative deaths, and 4 early (11%) and 3 (9%) late complications. Four patients died, none with a urethral recurrence, including 3 of metastatic bladder cancer and 1 of unrelated causes. In another patient with an extensive mesenchymal tumor of the uterus a sigmoid tumor recurred requiring conversion of the orthotopic reservoir to a cutaneous diversion. All of the remaining 29 patients are alive without evidence of disease. Intraoperative frozen section of the distal surgical margin (proximal urethra) accurately evaluated (confirmed by permanent section) the proximal urethra prospectively for tumor in all 29 specimens removed for transitional cell carcinoma, including 28 specimens (97%) without evidence of tumor and 1 specimen with carcinoma in situ. Complete daytime and nighttime continence was reported by 29 (88%) and 27 (82%) of 33 evaluable patients, respectively. A total of 28 patients (85%) void to completion, while 5 (15%) require some form of intermittent catheterization to empty the neobladder. Patient satisfaction is overwhelming.The excellent clinical and functional results demonstrated with further followup confirm our initial experience with orthotopic diversion in women. Careful selection of appropriate female candidates for orthotopic diversion is critical, and includes preoperative evaluation of the bladder neck and intraoperative frozen section analysis of the distal cystectomy margin. Furthermore, close monitoring of the retained urethra is mandatory in all women undergoing orthotopic diversion. We believe that the orthotopic neobladder is the urinary diversion of choice in women following cystectomy.

  View details for Web of Science ID A1997XL14300019

  View details for PubMedID 9224311

• Transitional cell carcinoma involving the prostate with a proposed staging classification for stromal invasion JOURNAL OF UROLOGY Esrig, D., Freeman, C. A., Elmajian, D. A., Stein, J. P., Chen, S. C., Groshen, S., Simoneau, A., Skinner, E. C., Lieskovsky, G., Boyd, S. D., Cote, R. J., Skinner, D. G. 1996; 156 (3): 1071-1076

  Abstract

  We investigated the effect on survival of transitional cell carcinoma of the prostatic urethra, ducts and stroma, and determined the difference between prostatic stromal involvement occurring via direct extension through the bladder wall versus stromal invasion arising intraurethrally.Between August 1971 and December 1989, 489 men underwent radical cystoprostatectomy for transitional cell carcinoma, including 143 (29.2%) identified with prostate involvement by transitional cell carcinoma, in the cystectomy specimen. Patients were separated into 2 groups: 1-19 in whom the primary bladder tumor extended full thickness through the bladder wall to invade the prostate (classified as P4a) and 2-124 in whom prostate involvement arose from within the prostatic urethra.Five-year recurrence-free and overall survival rates were 25 and 21%, respectively, in group 1 versus 64 and 55%, respectively, in group 2. In the 124 patients in group 2 survival rates were similar for those with prostatic urethral tumors or carcinoma in situ and ductal tumors (no stromal invasion). Five-year overall survival rates without and with stromal invasion were 71 and 36%, respectively (p < 0.0001). Transitional cell carcinoma of the prostatic urethra or ducts does not alter survival predicted by primary bladder stage alone. Prostatic stromal invasion arising intraurethrally significantly decreases survival, which varies based on primary bladder stage (64.6% in stage P1, 30.8% in stages P2/P3a and 13.6% in stage P3b, p = 0.0001). P1 bladder tumors with prostatic stromal invasion arising intraurethrally had a significantly higher survival rate than P4a tumors (64.6 versus 21%, p = 0.0001). P3b bladder tumors with stromal invasion had a survival rate similar to that of P4a tumors (p = 0.78).Prostatic urethral or ductal transitional cell carcinoma does not alter survival determined by primary bladder stage alone and it should not be classified as P4a. Prostatic stromal involvement arising intraurethrally significantly decreases survival predicted by primary bladder stage alone. P1 bladder tumors with prostatic stromal invasion arising intraurethrally have a significantly higher survival rate than P4a tumors and they should be separately classified as P1str. Muscle invasive (P2/P3a) bladder tumors with stromal invasion have a higher survival rate than P4a tumors (no statistical significance) and they should be designated separately (that is P2str). P3b bladder tumors with prostatic stromal invasion arising intraurethrally are indistinguishable from P4a tumors.

  View details for Web of Science ID A1996VB45300063

  View details for PubMedID 8709310

• Management of complex urologic injuries SURGICAL CLINICS OF NORTH AMERICA Skinner, E. C., Parisky, Y. R., Skinner, D. G. 1996; 76 (4): 861-?

  Abstract

  The management of complex urologic trauma requires considerable experience and familiarity with reconstructive techniques. The goal should always be maximum preservation of normal function, with the fewest serious complications. Ideally these cases are treated by a multidisciplinary team rather than the trauma surgeon alone.

  View details for Web of Science ID A1996VC95500015

  View details for PubMedID 8782478

• Complications of the afferent antireflux valve mechanism in the kock ileal reservoir JOURNAL OF UROLOGY Stein, J. P., Freeman, J. A., Esrig, D., Elmajian, D. A., Tarter, T. H., Skinner, E. C., Boyd, S. D., Huffman, J. L., Lieskovsky, G., Skinner, D. G. 1996; 155 (5): 1579-1583

  Abstract

  Since 1982 the Kock ileal reservoir has been the primary form of urinary diversion in patients requiring lower urinary tract reconstruction at our institution. The intussuscepted afferent nipple valve of the Kock ileal reservoir is designed to prevent reflux and protect the upper urinary tract. Problems associated specifically with the afferent antireflux valve have been few. We defined and characterized all complications associated with the Kock pouch antireflux nipple valve.From November 1984 through July 1992, 802 patients underwent construction of a continent Kock ileal reservoir. All complications associated with the afferent antireflux valve in this group and their management were identified.Overall, 79 of 802 patients (9.8%) had a total of 84 complications of the afferent antireflux valve (10.4%), including formation of stones on staples securing the afferent nipple valve in 42 cases (5.2%), stenosis of the afferent valve in 35 (4.3%) and prolapse of the valve in 7 (0.9%). A total of 81 patients required surgical intervention to correct the afferent valve complication: 56 (7.0%) were treated endoscopically and 25 (3.1%) required open surgical revision.We report an overall complication rate of 10.4% associated with the afferent antireflux nipple valve in the Kock ileal reservoir. Most complications can be treated endoscopically without difficulty on an outpatient basis with the use of local sedation. With these results, and only a 3% incidence of open surgical correction of all afferent nipple problems, we encourage the continued use of the intussuscepted afferent nipple valve whenever continent urinary diversion is performed.

  View details for Web of Science ID A1996UF00800009

  View details for PubMedID 8627827

• Alterations in circulating levels of androgens and PSA during treatment with finasteride in men at high risk for prostate cancer 2nd International Hormonal Carcinogenesis Symposium Stanczyk, F. Z., Skinner, E. C., Mertes, S., Spahn, M. F., Lobo, R. A., Ross, R. K. SPRINGER-VERLAG. 1996: 404–407

  View details for Web of Science ID A1996BF44F00054

• INDICATIONS FOR LOWER URINARY-TRACT RECONSTRUCTION IN WOMEN AFTER CYSTECTOMY FOR BLADDER-CANCER - A PATHOLOGICAL REVIEW OF FEMALE CYSTECTOMY SPECIMENS JOURNAL OF UROLOGY Stein, J. P., Cote, R. J., Freeman, J. A., Esrig, D., Elmajian, D. A., Groshen, S., Skinner, E. C., Boyd, S. D., Lieskovsky, G., Skinner, D. G. 1995; 154 (4): 1329-1333

  Abstract

  In an attempt to identify women who may be appropriate candidates for orthotopic lower urinary tract reconstruction, archival cystectomy specimens from female patients undergoing cystectomy for primary bladder cancer were reviewed. These pathological findings should provide a better understanding of tumor involvement at the bladder neck (vesicourethral junction) and urethra in women with transitional cell carcinoma of the bladder.Cystectomy specimens of 67 consecutive women undergoing surgery for biopsy proved transitional cell carcinoma of the bladder between July 1982 and July 1990 were pathologically reviewed.Histological evidence of tumor (carcinoma in situ or gross carcinoma) involving the urethra was present in 9 patients (13%). Tumor was confined to the proximal and mid urethra, and the distal urethra was not involved. All patients with carcinoma involving the urethra had concomitant evidence of carcinoma involving the bladder neck. A total of 17 patients (25%) had tumor involvement of the bladder neck and those with an uninvolved bladder neck also had an uninvolved urethra. The association between the presence of tumor in the bladder neck and urethra was highly significant (p < or = 0.00012). Tumor involving the bladder neck and urethra tended to be more commonly associated with high grade and stage tumors, and node-positive disease.Although the fate of the retained urethra following cystectomy for bladder cancer in women is unknown, these results show that women with transitional cell carcinoma of the bladder without evidence of tumor involving the bladder neck are at low risk for urethral malignancy. These patients may be offered lower urinary tract reconstruction that includes preservation of and diversion through the urethra (orthotopic diversion). Urethral surveillance will be necessary, as it is in men after orthotopic urinary diversion.

  View details for Web of Science ID A1995RU47200013

  View details for PubMedID 7658531

• DOES THE RACIAL-ETHNIC VARIATION IN PROSTATE-CANCER RISK HAVE A HORMONAL BASIS National Conference on Prostate Cancer Ross, R. K., Coetzee, G. A., Reichardt, J., Skinner, E., Henderson, B. E. WILEY-LISS. 1995: 1778–82

  View details for Web of Science ID A1995QP39300003

• Continent and orthotopic urinary diversion following radical cystectomy. Should these reconstructive procedures now be considered standard of care? Surgical oncology clinics of North America Boyd, S. D., Skinner, E., Lieskovsky, G., Skinner, D. G. 1995; 4 (2): 277-286

  Abstract

  Our extensive operative experience with various forms of the continent ileal reservoir in more than 1000 patients over the past 12 years has demonstrated clearly the extreme reliability and durability of this diversion system. Reflux reliably can be prevented and the upper urinary tracts protected. Patients can void or catheterize with confidence. Orthotopic diversions should now be available to most patients, both male and female. Patients should be able to live a more normal life style with a positive self image. We believe that because our modifications of the ileal reservoir systems have decreased the need for reoperation, these forms of continent urinary diversion have emerged as optimal operations and even as the standard of care in cystectomy patients. Ileal conduits should be reserved for poor-risk candidates with short-term life expectancy or for those patients not motivated for continent diversion. The most vocal advocates of the procedures remain those continent diversion patients who have had urinary diversion by another method. Patients still must be aware that complications can occur. Appropriate patient motivation and a thorough understanding of the continent diversion technique and its potential problems continue to be essential prerequisites of the operation. Although minor refinements to these systems will continue to be made, we feel that continent diversion, most often in the form of orthotopic reconstruction, can be offered safely and wisely most to patients.

  View details for PubMedID 7796286

• XANTHOGRANULOMATOUS PYELONEPHRITIS - CLINICAL FINDINGS AND SURGICAL CONSIDERATIONS UROLOGY Eastham, J., Ahlering, T., Skinner, E. 1994; 43 (3): 295-299

  Abstract

  Xanthogranulomatous pyelonephritis (XGP) is an uncommon but well-characterized inflammatory process of the kidney. Few reports, however, have correlated preoperative radiographic features with findings at surgical exploration. We report our experience in the surgical management of XGP with emphasis on the use of computed tomography (CT) in the preoperative evaluation.We retrospectively reviewed all medical records including radiographic materials of 27 patients with a pathologic diagnosis of XGP. In particular, preoperative CT features were analyzed to see if they correlated with surgical findings.A CT scan was performed in 23 of the 27 patients. Of these 23 patients 20 (87%) were diagnosed with XGP based on the CT findings. CT accurately defined the extent of the perinephric inflammatory reaction, identifying 8 patients with muscular extension, 3 with splenic involvement, 1 with extension into the colon, and 5 with encasement of the great vessels. In no case did CT underestimate the involvement of adjacent tissues.Although XGP is a rare disease, a careful preoperative evaluation can suggest its diagnosis. CT is particularly valuable in that it not only demonstrates characteristic renal findings, but also shows the extent of inflammation and extent into adjacent tissues. This will aid in surgical planning in choosing an approach that will provide adequate exposure and facilitate patient care.

  View details for Web of Science ID A1994NC22100003

  View details for PubMedID 8134982

• THE RATIONALE FOR EN-BLOC PELVIC LYMPH-NODE DISSECTION FOR BLADDER-CANCER PATIENTS WITH NODAL METASTASES - LONG-TERM RESULTS JOURNAL OF UROLOGY Lerner, S. P., Skinner, D. G., Lieskovsky, G., Boyd, S. D., Groshen, S. L., Ziogas, A., Skinner, E., Nichols, P., Hopwood, B. 1993; 149 (4): 758-765

  Abstract

  From August 1971 through June 1989, 591 consecutive patients underwent curative pelvic lymphadenectomy with en bloc radical cystectomy for bladder cancer. Of these patients 132 (22%) had pathologically proved nodal metastases. The incidence of positive nodes increased with increasing pathological stage of the primary tumor: stage PIS (0.75%), stage P1 (13%), stage P2 (20%), stage P3a (24%), stage P3b (42%) and stage P4 (45%). The median followup for the 31 patients still alive was 5.5 years (range 2.6 to 18.8). Recurrent bladder cancer was documented in 89 patients (67%) with a median interval to progression of 1.5 years. Pelvic recurrence as the first site of progression was uncommon, occurring in 15 patients (11%). The actuarial 2, 3, 5 and 10-year survival rates were 55%, 38%, 29% and 20%, respectively. Increased risk of progression and death was associated with advanced pathological tumor stage (stage P3b or greater, p < 0.001 and p < 0.001, respectively) and 6 or more positive nodes (p < 0.001 and p = 0.012, respectively). There was no significant difference in survival and interval to progression among patients who received preoperative irradiation or adjuvant chemotherapy compared to those treated with surgery alone. This retrospective analysis further substantiates the philosophy that single stage pelvic lymphadenectomy with en bloc radical cystectomy can provide long-term progression-free survival, particularly for patients with localized primary tumors and minimal metastatic nodal disease.

  View details for Web of Science ID A1993KV97800016

  View details for PubMedID 8455238

• RADICAL CYSTECTOMY IN REGIONALLY ADVANCED BLADDER-CANCER UROLOGIC CLINICS OF NORTH AMERICA Lerner, S. P., Skinner, E., Skinner, D. G. 1992; 19 (4): 713-723

  Abstract

  The distinction pathologically of invasive tumors confined to the muscularis propria from those that penetrate the bladder wall and invade the perivesical fat or adjacent organs is a critical prognostic determinant. Nodal metastases are evident in approximately one half of patients with tumors pathologically staged as P3b or greater. Five-year survival rates after radical cystectomy with or without preoperative irradiation for stage P3b tumors range from 17% to 46%. Long-term survival is the exception when bladder cancer invades the pelvic sidewall or adjacent structures, yet cystectomy can provide palliation and accurate staging and can be considered in the context of combination therapy. Supravesical diversion can provide palliation when there is nodal disease above the bifurcation or pelvic fixation. The optimal role of adjuvant chemotherapy in the treatment of regionally advanced bladder cancer is yet to be defined. Tannock has delineated the many serious pitfalls inherent in interpreting nonrandomized trials of new therapies (see also his article elsewhere in this issue). Randomized trials are currently under way to determine if survival can be improved with adjuvant or neoadjuvant chemotherapy and the most efficacious timing of chemotherapy administration. Clinicians should generally resist the tendency to treat all patients with these regimens until it is clear that we are truly improving the outcome of therapy and the quality of life for our patients.

  View details for Web of Science ID A1992LA25700010

  View details for PubMedID 1279876

• RADICAL CYSTECTOMY AKTUELLE UROLOGIE Skinner, E. C., Lieskovsky, G., Skinner, D. G. 1991; 22 (5): AR1-AR14

  View details for Web of Science ID A1991HL46200015

• URINARY-DIVERSION CURRENT PROBLEMS IN SURGERY Skinner, D. G., Skinner, E. C., Lieskovsky, G., Boyd, S. D. 1987; 24 (7): 401-471

  View details for Web of Science ID A1987J467400001