[show abstract][hide abstract] ABSTRACT: Estrogen reprogramming of the prostate gland as a function of developmental exposures (aka developmental estrogenization) results in permanent alterations in structure and gene expression that lead to an increased incidence of prostatic lesions with aging. Endocrine disrupting chemicals (EDCs) with estrogenic activity have been similarly linked to an increased prostate cancer risk. Since it has been suggested that stem cells and cancer stem cells are potential targets of cancer initiation and disease management, it is highly possible that estrogens and EDCs influence the development and progression of prostate cancer through reprogramming and transforming the prostate stem and early stage progenitor cells. In this article, we review recent literature highlighting the effects of estrogens and EDCs on prostate cancer risk and discuss recent advances in prostate stem/progenitor cell research. Our laboratory has recently developed a novel prostasphere model using normal human prostate stem/progenitor cells and established that these cells express estrogen receptors (ERs) and are direct targets of estrogen action. Further, using a chimeric in vivo prostate model derived from these normal human prostate progenitor cells, we demonstrated for the first time that estrogens initiate and promote prostatic carcinogenesis in an androgen-supported environment. We herein discuss these findings and highlight new evidence using our in vitro human prostasphere assay for perturbations in human prostate stem cell self-renewal and differentiation by natural steroids as well as EDCs. These findings support the hypothesis that tissue stem cells may be direct EDC targets which may underlie life-long reprogramming as a consequence of developmental and/or transient adult exposures.
Molecular and Cellular Endocrinology 09/2011; 354(1-2):63-73. · 4.04 Impact Factor
[show abstract][hide abstract] ABSTRACT: Early work on the hormonal basis of prostate cancer focused on the role of androgens, but more recently estrogens have been implicated as potential agents in the development and progression of prostate cancer. In this article, we review the epidemiological, laboratory and clinical evidence that estrogen may play a causative role in human prostate cancer, as well as rodent and grafted in vivo models. We then review recent literature highlighting potential mechanisms by which estrogen may contribute to prostate cancer, including estrogenic imprinting and epigenetic modifications, direct genotoxicity, hyperprolactinemia, inflammation and immunologic changes, and receptor-mediated actions. We discuss the work performed so far separating the actions of the different known estrogen receptors (ERs), ERα and ERβ, as well as G-protein-coupled receptor 30 and their specific roles in prostate disease. Finally, we predict that future work in this field will involve more investigations into epigenetic changes, experiments using new models of hormonal dysregulation in developing human prostate tissue, and continued delineation of the roles of the different ER subtypes, as well as their downstream signaling pathways that may serve as therapeutic targets.
Expert Review of Endocrinology & Metabolism 05/2011; 6(3):437-451.
[show abstract][hide abstract] ABSTRACT: The benefit of urethrectomy in patients with bladder cancer who are undergoing cystectomy is controversial. We describe the frequency of urethrectomy by bladder cancer stage and identify clinical characteristics that predict urethrectomy. We also investigated whether urethrectomy offers any additional independent survival benefit.
A total of 2,401 men who underwent radical cystoprostatectomy between 1991 and 2002 were identified in the Surveillance, Epidemiology and End Results-Medicare database. A multivariate logistic regression model was used to analyze factors driving urethrectomy. We then analyzed the records of 195 men who underwent urethrectomy to find predictors of that procedure as salvage for urethral recurrence vs concurrently with cystoprostatectomy or as a staged procedure. Using multivariate Cox regression analysis we analyzed whether urethrectomy had an independent effect on disease specific survival.
The only significant predictor of urethrectomy was stage. Patients at a teaching hospital were more likely to undergo salvage urethrectomy for recurrence vs immediate urethrectomy compared to those at urban nonteaching hospitals. Patient age, race, number of comorbidities and tumor stage were significant independent predictors of survival. Survival in men who underwent urethrectomy concurrently with cystoprostatectomy was higher than in those who did not undergo urethrectomy but not statistically significant (HR = 0.775, 95% CI 0.592-1.014, p = 0.0632).
Disease stage is related to urethrectomy performance. Age, race, stage and comorbidities were independent predictors of overall survival in patients with bladder cancer undergoing cystectomy. Urethrectomy did not confer a significant independent survival benefit.
The Journal of urology 10/2008; 180(5):1933-6; discussion 1936-7. · 4.02 Impact Factor
[show abstract][hide abstract] ABSTRACT: Marital status has been found to influence survival in a number of malignancies. We examined data from the Surveillance, Epidemiology, and End Results (SEER) cancer survival database to see if married patients with bladder cancer had a survival advantage vs. nonmarried patients.
The SEER database contains data on 127,015 patients diagnosed with bladder cancer between 1973 and 2002. Using multivariate Cox proportional hazard regression analyses, we examined the impact of marital status (single, married, separated, divorced, or widowed) on survival after diagnosis with bladder cancer. Age, race, AJCC stage, radiation and chemotherapy, and cystectomy were other variables analyzed.
Marital status did not appear to have a significant survival effect for women. However, men who were widowed had a risk of death of 1.74 relative to married men (95% CI 1.15, 2.26, P = 0.008). For widowed men over 70, this effect was even more pronounced, with a risk of death of 2.1 (95% CI 1.33, 3.31, P = 0.001).
While we did not see any definite survival advantage to being married vs. not being married for patients who are diagnosed with bladder cancer, there is a significant risk to widowed men, particularly older widowed men. This risk is independent of age, race, stage, and may reflect the patient's willingness to seek medical treatment in addition to psychoneuroimmune factors.
[show abstract][hide abstract] ABSTRACT: Published single institutional case series are often performed by one or more surgeons with considerable expertise in specific procedures. The reported incidence of complications in these series may not accurately reflect community-based practice. We sought to compare complication and mortality rates following urologic procedures derived from population-based data to those of published single-institutional case series.
In-hospital mortality and complications of common urologic procedures (percutaneous nephrostomy, ureteropelvic junction obstruction repair, ureteroneocystostomy, urethral repair, artificial urethral sphincter implantation, urethral suspension, transurethral resection of the prostate, and penile prosthesis implantation) reported in the U.S.'s National Inpatient Sample of the Healthcare Cost and Utilization Project were identified. Rates were then compared to those of published single-institution series using statistical analysis.
For 7 of the 8 procedures examined, there was no significant difference in rates of complication or mortality between published studies and our population-based data. However, for percutaneous nephrostomy, two published single-center series had significantly lower mortality rates (p < 0.001). The overall rate of complications in the population-based data was higher than published single or select multi-institutional data for percutaneous nephrostomy performed for urinary obstruction (p < 0.001).
If one assumes that administrative data does not suffer from under reporting of complications then for some common urological procedures, complication rates between population-based data and published case series seem comparable. Endorsement of mandatory collection of clinical outcomes is likely the best way to appropriately counsel patients about the risks of these common urologic procedures.
International braz j urol: official journal of the Brazilian Society of Urology 36(5):548-56.