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2.  p63 Expression Defines a Lethal Subset of Muscle-Invasive Bladder Cancers 
PLoS ONE  2012;7(1):e30206.
Background
p63 is a member of the p53 family that has been implicated in maintenance of epithelial stem cell compartments. Previous studies demonstrated that p63 is downregulated in muscle-invasive bladder cancers, but the relationship between p63 expression and survival is not clear.
Methodology/Principal Findings
We used real-time PCR to characterize p63 expression and several genes implicated in epithelial-to-mesenchymal transition (EMT) in human bladder cancer cell lines (n = 15) and primary tumors (n = 101). We correlated tumor marker expression with stage, disease-specific (DSS), and overall survival (OS). Expression of E-cadherin and p63 correlated directly with one another and inversely with expression of the mesenchymal markers Zeb-1, Zeb-2, and vimentin. Non-muscle-invasive (Ta and T1) bladder cancers uniformly expressed high levels of E-cadherin and p63 and low levels of the mesenchymal markers. Interestingly, a subset of muscle-invasive (T2–T4) tumors maintained high levels of E-cadherin and p63 expression. As expected, there was a strongly significant correlation between EMT marker expression and muscle invasion (p<0.0001). However, OS was shorter in patients with muscle-invasive tumors that retained p63 (p = 0.007).
Conclusions/Significance
Our data confirm that molecular markers of EMT are elevated in muscle-invasive bladder cancers, but interestingly, retention of the “epithelial” marker p63 in muscle-invasive tumors is associated with a worse outcome.
doi:10.1371/journal.pone.0030206
PMCID: PMC3254658  PMID: 22253920
3.  High Risk Patients with Hematuria Are Not Evaluated According to Guideline Recommendations 
Cancer  2010;116(12):2954-2959.
Purpose
To determine whether high risk patients with hematuria receive evaluation according to guideline recommendations.
Materials and Methods
We recently performed a screening study for bladder cancer using a urine-based tumor marker in 1502 subjects at high risk based on age over 50, ≥10-year smoking history, and/or a 15 year or more environmental exposure. We evaluated use of urinalysis (UA) within 3 years preceding the screening study. Chart review was performed to determine if this subset with microhematuria received any additional evaluation.
Results
Of 1502 study participants, routine urinalysis was performed in 73.2% and 164 (14.9%) subjects had documented hematuria (>3 RBCs/HPF) prior to inclusion. Of these, 42.1% had no further evaluation. Additional testing included repeat urinalysis (36%), urine culture (15.2%), cytology (10.4%), imaging (22.6% overall: 15.9% CT, 4.3% IVP; 2.4% MRI) and cystoscopy (12.8%).
Three subjects with microscopic hematuria (2%) were subsequently found to have bladder cancer during the screening study but were not referred for evaluation based on their hematuria. The source of hematuria was unknown in 65%, infection in 22%, benign prostatic enlargement in 10% and renal stone disease in 4% but these results are based on incomplete evaluation since only 12.8% underwent cystoscopy.
Conclusions
Subjects at high risk for bladder cancer based on ≥10 years of smoking or environmental exposure with microscopic hematuria are rarely evaluated thoroughly and only 12.8% were referred for urologic evaluation. Further studies are needed to evaluate both the utilization and effectiveness of guidelines for hematuria.
doi:10.1002/cncr.25048
PMCID: PMC2940122  PMID: 20564400
Hematuria; Guidelines Recommendations; bladder cancer
4.  Cardiac History and Risk of Post-Cystectomy Cardiac Complications 
Urology  2009;74(5):1085-1089.
Objectives
Patients undergoing cystectomy often have significant baseline cardiac disease. Despite pre-operative medical optimization, post-operative cardiac complications remain a significant source of morbidity. We sought to evaluate risk factors for post-cystectomy cardiac complications (POCC).
Methods
A retrospective review of all radical cystectomies for bladder cancer from 1/2004 through 9/2006 was performed. Twelve pre-operative risk factors were evaluated including age, Charleson Co-morbidity index, type of urinary diversion, and prior cardiac history. All complications were recorded for 90 days post-operatively including myocardial infarction (MI) and new onset arrhythmia (NOA). Univariate and multivariate analysis were performed.
Results
283 patients underwent cystectomy for bladder cancer from 1/2004 to 9/2006. The median age of the cohort was 70 (35–90). 64 pts (23%) had a significant pre-operative cardiac history, including 18 (6%) with prior coronary artery bypass and 30 (11%) with a history of MI’s. Thirty-one (11%) patients had either NOA (22, 8%) or MI (10, 4%); one had both. On univariate analysis, cardiac history, age, type of urinary diversion, and the Charleson co-morbidity index demonstrated significance. The risk of POCC was associated with ileal conduit urinary diversion (p=0.026, OR 5.58 [1.23–25.36]) and the Charleson Index score (p=0.030, OR 1.28 [1.024–1.60]) on multivariate analysis.
Conclusions
Multiple, inter-related factors may predict cardiac complications in the early post-operative period. Despite peri-operative optimization, patients with a prior cardiac history should be counseled regarding the increased risk of postoperative cardiac complications. The association between cardiac complications and ileal conduit diversion highlights the selection bias towards patients with pre-existing co-morbid disease.
doi:10.1016/j.urology.2009.04.103
PMCID: PMC2784244  PMID: 19758689
cystectomy; complications; cardiac; outcome
5.  Management of metastatic urothelial cancer: the role of surgery as an adjunct to chemotherapy 
Canadian Urological Association Journal  2009;3(6 Suppl 4):S228-S231.
Metastatic or unresectable disease is identified in approximately 20% of patients presenting with invasive urothelial cancer. In addition, up to 50% of patients will develop metastases following radical cystectomy for clinically localized disease. Multiagent cisplatin-based chemotherapy is considered standard first-line treatment for these patients. Although urothelial cancer is considered a chemosensitive tumour, metastatic disease is associated with poor prognosis and short-term survival. Here, we review the role of a multidisciplinary approach to treating patients with metastatic urothelial cancer.
PMCID: PMC2792450  PMID: 20019991

Results 1-5 (5)