The impact of sociodemographic factors and PSA screening among low-income Black and White men: data from the Southern Community Cohort Study.

BACKGROUND: Variation in PSA screening is a potential source of disparity in prostate cancer survival, particularly among underserved populations. We sought to examine the impact of race and socioeconomic status (SES) on receipt of PSA testing among low-income men. METHODS: Black (n=22 167) and White (n=9588) men aged ⩾40 years completed a baseline questionnaire from 2002 to 2009 as part of the Southern Community Cohort Study. Men reported whether they had ever received PSA testing and had testing within the prior 12 months. To evaluate the associations between SES, race and receipt of PSA testing, odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from the multivariable logistic models where age, household income, insurance status, marital status, body mass index and educational level were adjusted. RESULTS: Black men were younger, had a lower income, less attained education and were more likely to be unmarried and uninsured (all P<0.001). Percentages of men having ever received PSA testing rose from <40% under the age of 45 years to ~90% above the age of 65 years, with Whites >50 more likely than Blacks to have received testing. Lower SES was significantly associated with less receipt of PSA testing in both groups. After adjustment for SES, White men had significantly lower odds of PSA testing (OR 0.81; 95% CI: 0.76-0.87). CONCLUSIONS: Greater PSA testing among White than Black men over the age of 50 years in this low-income population appears to be mainly a consequence of SES. Strategies for PSA screening may benefit from tailoring to the social circumstances of the men being screened.

Emerging association between androgen deprivation therapy and male meningioma: significant expression of luteinizing hormone-releasing hormone receptor in male meningioma.

BACKGROUND: There is emerging data suggesting a potential risk for meningioma growth stimulation in patients on luteinizing hormone-releasing hormone (LHRH) analogs for prostate cancer. We examined the expression of LHRH receptor (LHRH-R), progesterone receptor (PR) and Ki67 labeling index (LI) in specimens from male meningioma (MM) and female meningioma (FM) patients. METHODS: A total of 24 MM and 24 FM paraffin blocks were retrieved from our institution between 1991 and 2008. Sections from the paraffin blocks were stained with mouse monoclonal antibodies against LHRH-R, PR and Ki67. All male patients had no previous history of prostate cancer (PCa) or previous history of hormone therapy. RESULTS: LHRH-R positivity was extensive in 92% of MM and 88% of FM samples, with both showing strong intensity (67% and 79%, respectively). PR was positive in 20 of 24 (83%) MM and 23 of 24 (96%) FM samples. MM is less likely to exhibit Ki67 LI >4% compared with FM. CONCLUSIONS: The majority of MM and FM samples were strongly positive for LHRH-R expression and PR expression. The emerging association of androgen deprivation therapy and meningioma growth should be recognized in urological practice. Caution should be taken when considering LHRH agonist administration for patients with PCa and concurrent meningioma or previous history of meningioma.

High level of dioxin-TEQ in tissue is associated with Agent Orange exposure but not with biochemical recurrence after radical prostatectomy.

BACKGROUND: Agent Orange (AO) was previously identified as a significant risk factor for biochemical recurrence (BCR) after radical prostatectomy (RP) in prostate cancer patients. In this study, we determined the levels of dioxin biological toxicity using toxic equivalency (TEQ) values and examined the impact of dioxin-TEQ level on BCR. METHODS: A total of 93 men who underwent RP, with a median of 5.3 years of postoperative follow-up, were included in the study. The dioxin-TEQ level of each patient was measured using intraoperatively harvested abdominal subcutaneous fat. The dichotomous categorization of dioxin-TEQ by the 50th percentile (low<50% vs high 50%) was also used to regroup the patient cohort, regardless of the previous history of AO exposure. Comparisons between the dioxin-TEQ levels, clinicopathological characteristics and BCR in AO-exposed and -unexposed men were made to allocate possible risk factors. The multivariable logistic regression model was used to identify significant risk factors associated with BCR, adjusting for other confounding factors. RESULTS: The median dioxin-TEQ level in 37 AO-exposed patients was significantly higher than that in 56 unexposed patients (22.3 vs 15.0 pg g(-1) fat, respectively, P<0.001). The men with AO exposure were more likely to have a high dioxin-TEQ level (P<0.001). Neither AO exposure nor the level of dioxin-TEQ was associated with BCR. Tumor stage (T3/T4 vs T2) and Gleason grade (Gleason 3+4) were independent risk factors for BCR after RP. CONCLUSIONS: Exposure to AO significantly increases the adipose level of dioxin-TEQ in patients treated with RP. However, exposure to AO or a high dioxin-TEQ level was not associated with an increased risk of BCR after RP. This lack of association supports the current conclusion that the evidence of carcinogenicity of AO in prostate cancer patients is not sufficient and remains 'limited'.

Radical cystectomy and orthotopic urinary reconstruction in patients with bladder cancer after renal transplantation: clinical outcomes and description of technique.

OBJECTIVES: Radical cystectomy (RC) with pelvic lymph node dissection and urinary diversion is the standard treatment for muscle-invasive bladder cancer. In the setting of prior renal transplantation, surgical treatment remains the mainstay but is technically challenging. We report our patient outcomes in this unique population with a description of the technique. METHODS: We identified five patients with a history of renal transplantation who underwent RC and orthotopic urinary diversion. Preoperative clinical and demographic features were compiled and disease-specific and functional outcomes were assessed. Intraoperative technical challenges and maneuvers for avoiding complications are highlighted. RESULTS: Four patients were male and one was female, with a median age of 64 years. Gross hematuria was the most common sign at presentation. Clinical staging was T2, T2 with carcinoma in situ (CIS), high-grade (HG) Ta with CIS, T2 with squamous differentiation, and HG T1, and pathologic tumor stage was pTisN1, pT3N0, pTisN0, pT3N0, and pT0N0, respectively. One patient received a Studer-type diversion and four underwent Hautmann diversion. Median follow-up after cystectomy was 12.9 months. Graft ureteral identification was aided by the use of intravenous dye in all patients. Ipsilateral pelvic lymph node dissection was not possible in any patient. All patients are alive at follow-up, with two experiencing recurrence at 7.2 months and 66.8 months. No patient experienced a significant decrease in estimated creatinine clearance postoperatively. Postoperative daytime control was reported by all patients whereas two noted complete nighttime control. CONCLUSIONS: RC with orthotopic diversion is a technically demanding procedure in patients with a history renal transplantation. Meticulous technique and careful attention to the altered anatomy are required for successful outcomes.

The association of diabetes and positive prostate biopsy in a US veteran population.

BACKGROUND: Several studies have shown a protective effect of diabetes mellitus (DM) on incidence of prostate cancer; however, the data are not consistent. Moreover, whether or not DM is associated with a positive result among patients referred for prostate biopsy due to abnormal PSA and/or abnormal digital rectal examination is not clear. METHODS: A retrospective review of 3162 consecutive men who underwent prostate biopsy between January 2000 and July 2009 at the Atlanta Veterans Affairs Medical Center was performed. Men with positive and negative biopsies were compared for various demographic and clinical factors. The data were analyzed using logistic regression models with results expressed as adjusted odds ratios (ORs) with corresponding 95% confidence intervals (CI). RESULTS: DM was associated with increased odds of positive biopsy in the overall cohort (OR 1.26, 95% CI: 1.01-1.55; P = 0.04). Subjects with DM had higher odds of more aggressive disease (Gleason ≥ 7) than those without the condition (OR 1.31, 95% CI: 0.98-1.74; P = 0.07). Race had no significant impact on these results. CONCLUSIONS: In this large series of prostate biopsies, diabetes is associated with higher odds of positive biopsy and higher Gleason grade. More studies investigating the role of DM and its associated comorbidities in prostate carcinogenesis are needed.

Expression of an Nkx3.1-CRE gene using ROSA26 reporter mice.

The genetic locus of Nkx3.1, an early murine marker of sclerotome and prostate development, was disrupted by a knock in of CRE recombinase via homologous recombination in embryonic stem cells. Cell fate mapping revealed previously unidentified cell lineages expanded from Nkx3.1-expressing cell populations and recapitulated reported Nkx3.1 expression patterns. In lineage trace experiments of E18.5 Nkx3.1-CRE; R26R embryos novel staining was observed in areas of the lungs, portions of the duodenum, and vertebral elements of the skeleton. beta-galactosidase activity measured in Nkx3.1-CRE; R26R and Nkx3.2-CRE; R26R embryos was observed in overlapping regions of the sclerotome but no apparent change in Nkx3.1 expression was seen in the Nkx3.2 mutants by in situ hybridization.

Regulation of organ development by the NKX-homeodomain factors: an NKX code.

Mammalian development is a highly coordinated process that involves sequential and time-dependent gene regulation. Deregulation of this process can have functional or morphological consequences, possibly causing lethality or organ dysfunction. Homeotic genes are considered the master regulators of early developmental processes. Of the many homeodomain genes, the NK2 class represents a family of phylogenetically ancient proteins. NK2 homeobox family members are tissue-specific transcription factors distinguished by a common DNA binding structure unique among the homeodomain genes. Increasing evidence indicates that individual Nkx factors are critical regulators of whole organ development. In the sections below, we review the structure, regulation, and expression of the NK2 gene family beginning with their discovery in Drosophila and relating the known features of vertebrate counterparts to the Drosophilaproteins. In particular, we note that each of the vertebrate NK2 proteins are associated with particular genetic anomalies leading to a variety of described disease states. Further, based upon our examination we propose a new paradigm of development based upon the regulatory capacity of the NK2 homeodomain proteins termed the "Nkx Code"

Embryonic expression of an Nkx2-5/Cre gene using ROSA26 reporter mice.

Nkx2-5, one of the earliest cardiac-specific markers in vertebrate embryos, was used as a genetic locus to knock in the Cre recombinase gene by homologous recombination. Offspring resulting from heterozygous Nkx2-5/Cre mice mated to ROSA26 (R26R) reporter mice provided a model system for following Nkx2-5 gene activity by beta-galactosidase (beta-gal) activity. beta-gal activity was initially observed in the early cardiac crescent, cardiomyocytes of the looping heart tube, and in the epithelium of the first pharyngeal arch. In later stage embryos (10.5-13.5 days postcoitum, dpc), beta-gal activity was observed in the stomach and spleen, the dorsum of the tongue, and in the condensing primordium of the tooth. The Nkx2-5/Cre mouse model should provide a useful genetic resource to elucidate the role of loxP manipulated genetic targets in cardiogenesis and other developmental processes.