A PAX-8-Positive Female Urethral Adenocarcinoma, Intestinal-Type: A Case Report with Diagnostic Challenges and a Review of the Literature.

Female urethral adenocarcinoma (FUA) is extremely rare. It is an aggressive malignancy, and clear cell and columnar/mucinous ("intestinal") represent the two primary histologic subtypes. Diagnosis is often delayed in patients because of their vague symptomatology; hence, they present with an advanced disease and a poor prognosis. The rarity of FUA brings challenges when determining treatment and management, and treatment guidelines for various stages are lacking. We report an intestinal-type FUA that developed from inflammation-related metaplasia in urethral diverticulum with positive paired box 8 (PAX-8) staining. In addition to intestinal-type FUA being extremely rare, this particular entity exhibiting PAX-8 positivity has not been previously described, to the author's best knowledge. The present report highlights the importance of clinical and radiological assessment as well as histomorphologic and immunophenotypic features for an accurate diagnosis of this rare and aggressive malignancy.

Scholarly Activity and Research Training in Urology Residency Programs: Assessment of Current Practice and Barriers.

OBJECTIVE: To identify factors associated with effective scholarly activity and identify barriers to research during urology residency. METHODS: An online survey was sent to 134 urology residency program directors in the United States. The survey assessed program characteristics, available support, and barriers for scholarly activity. Logistic regression analysis was used to identify characteristics of programs in the top quintile for success in scholarly activity. RESULTS: There was a 40% response rate (n = 40). The majority of programs (86%) were university affiliated. Nearly all programs (98%) require participation in scholarly activity as a requirement for graduation. There were 3 primary outcomes evaluated: participation in original research, published scholarly activity and presentation of scholarly activity. Factors significantly associated with participation in original research were required research time (P = 0.06), lack of experienced faculty (P = 0.006), statistical and IRB support (P = 0.03, P = 0.01), funding (P = 0.02), and research curriculum (P = 0.006). Factors significantly associated with publication in peer reviewed journals were lack of funding and experienced faculty (P = 0.07, P = 0.01). Factors significantly associated with presentation of scholarly activity included research director (P = 0.05), chairman support (P = 0.02), research training (P = 0.03), protected time for faculty (P = 0.07), and faculty /resident attitudes toward conducting scholarly activity (P = 0.08, P = 0.02) and resident promotion linked to scholarly activity (P = 0.01). CONCLUSION: Training urology residents in research is essential. Current methods and available resources are variable. Programs should identify resources and barriers that have the greatest impact on resident success in scholarly activity, and may implement changes to improve productivity within their program.

Predictors and Barriers to Faculty Scholarly Activity in United States Urology Residency Programs.

OBJECTIVE: To determine factors and barriers associated with scholarly activity among faculty members at urology residency programs in the United States. METHODS: An online survey was sent to all 134 urology residency program directors. The survey assessed program characteristics including size, location and definition of scholarly activity. It assessed available support for and barriers to resident scholarly activity, faculty participation in scholarly activity and mentorship of residents. Linear regression analysis was used. RESULTS: We had a 40% response rate (N = 40). Faculty attitudes toward conducting scholarly activity (P < .001) and lack of a research curriculum (P = .05) were barriers to the outcome 'participation in scholarly activity'. Faculty attitudes toward conducting scholarly activity was also a barrier to the outcomes 'mentorship of residents' (P = .004) and 'publication of at least 1 paper' (P = .004). Available statistician was positively associated with the outcomes 'publications' (P = .062) and 'presentations' (P = .032). A minimum requirement of a local presentation (P=0.04) and chairman support (P = .015) were positively associated with the outcome 'presentation at a conference.' CONCLUSION: Training residents in research matters for the resident, the institution and future generations of surgeon scientists. Higher levels of faculty scholarly activity were associated with a minimum requirement for residents to submit a manuscript for publication, strong chairman support for resident research, and the availability of a statistician. A common barrier to faculty scholarly activity, publications, and resident mentorship was faculty attitudes toward resident scholarly activity. Urology residency programs seeking to prioritize scholarly activity among faculty should consider these factors.

Tips and Tricks for Performing a Retrograde Pyelogram.

OBJECTIVE: To demonstrate indications, review tools and techniques, as well as abnormal findings when performing a retrograde pyelogram. METHODS: Retrograde pyelogram is a procedure which consists of introducing water-soluble contrast in a retrograde fashion into the ureter and collecting system of the kidney under fluoroscopic guidance. Conditions in which a retrograde pyelogram are indicated include iatrogenic ureteral injuries, ureteral obstruction, identification of stones or tumors, assistance for stent placement or ureteroscopy, and trauma evaluation. This video will explain surgical technique to perform a retrograde pyelogram in an operative setting. Normal and commonly encountered abnormal findings when performing a retrograde pyelogram will be reviewed. RESULTS: This video will review a series of 8 cases and will demonstrate normal and abnormal findings and complications identified when performing a retrograde pyelogram. In some cases, anterograde nephrostogram was also performed to further delineate the ureteral injury or obstructions. CONCLUSION: The tips and tricks reviewed can facilitate surgical techniques to perform a successful retrograde pyelogram and identify abnormal findings; especially in situations in which a urologist is not readily available. A retrograde pyelogram can be performed intraoperatively to identify iatrogenic ureteral injuries, ureteral obstruction, identification of stones or tumors, assistance of stent placement and ureteroscopy, and evaluation of trauma.

The SRD5A2 V89L polymorphism is associated with severity of disease in men with early onset prostate cancer.

BACKGROUND: Emerging evidence indicates that testosterone (T), and not dihydrotestosterone (DHT), is the most relevant androgen that promotes carcinogenesis in the prostate. Steroid 5-alpha reductase type II (SRD5A2) catalyzes the irreversible conversion of T to DHT in male reproductive organs. Because the SRD5A2 gene is highly polymorphic at codon 89, two SRD5A2 isoforms are expressed that differ in K(m) and V(max) values. The more common and rapid catalytic isoform contains a valine residue at position 89; the slower-catalytic variant contains leucine at this position. METHODS: Thirty-three men with early onset prostate cancer (PCa) were genotyped for the SRD5A2 V89L substitution and other polymorphisms in genes encoding receptors or enzymes that play important roles in pathways of steroid metabolism to ascertain if they were associated with standard clinical measures of disease progression at the time of diagnosis. RESULTS: The expression of at least one SRD5A2 leucine allele in young men with PCa was associated with more significant disease at the time of presentation, as was defined by pretreatment PSA level, clinical staging and Gleason score when compared with affected subjects harboring the more common SRD5A2 valine variant. A dosage effect of a single leucine allele was evident in heterozygotes, as values of their clinical and pathological variables were consistently situated between the extremes of the homozygous V or L phenotypes. CONCLUSION: The SRD5A2 leucine isoform appears to be acting in a dose-dependent manner as a significant disease-modifying factor in young men diagnosed with PCa.

Pelvic Organ Prolapse Stage and the Relationship to Genital Hiatus and Perineal Body Measurements.

OBJECTIVES: This study aimed to describe the relationship between genital hiatus (GH) and perineal body (PB) measurements with increasing pelvic organ prolapse (POP) stage in a large cohort of women referred to Urogynecology clinic for pelvic floor disorders. METHODS: Retrospective chart review of all new patients seen in an academic Urogynecology clinic between January 2007 and September 2011 was performed. Data were extracted from a standardized intake form. All patients underwent a Pelvic Organ Prolapse Quantification (POPQ) examination. Descriptive statistics compared the study population. Analysis of variance was used to compare GH and PB measurements by prolapse stage. Fisher least significant differences were used for post hoc comparisons of means between prolapse stages. Pearson correlations were used to evaluate the associations between GH and PB measurements and patient characteristics. RESULTS: A total of 1595 women with POPQ examinations comprised the study population. The mean age was 55.3 ± 14.8 years with a body mass index of 30.3 ± 7.6 kg/m, most women were parous (90%), 40% were Hispanic, and 33% had undergone prior hysterectomy for indications exclusive of POP. Women with any prior prolapse repair were excluded, 6.5% had a prior incontinence procedure. Perineal body measurements were slightly larger for stage 2 POP, but overall did not vary across other prolapse stages (all P > 0.05). In contrast, GH measurements increased through stage 3 POP, GH measurements decreased for stage 4 POP. CONCLUSIONS: Mean PB measurements did not demonstrate large changes over prolapse stage, whereas GH measurements increased through stage 3 POP. Genital hiatus serves as an important marker for underlying pelvic muscle damage.

Basal and parathyroid hormone induced expression of the human 25-hydroxyvitamin D 1alpha-hydroxylase gene promoter in kidney AOK-B50 cells: role of Sp1, Ets and CCAAT box protein binding sites.

The regulation of the gene for renal 25-hydroxyvitamin D 1alpha- hydroxylase (1alpha(OH)ase; CYP27B1) by parathyroid hormone (PTH) under hypocalcemic conditions is fundamentally important for the maintenance of calcium and phosphate homeostasis. The molecular mechanism that underlies this hormonal response is of current interest and has been investigated in the present study by transfection analysis of the human 1alpha(OH)ase promoter in kidney AOK-B50 cells. We have shown that the first 305 bp of promoter can be induced by hormone in transient transfection assays and also within a chromatin environment when stably integrated. Mutagenesis of possible transcription factor binding sites within this promoter length has shown that three sites clustered within the region from -66 to -135 contribute to basal expression. A likely Sp1 and a CCAAT box site are particularly important for basal expression although these sites are not likely to functionally cooperate in a major way. Mutagenesis of the CCAAT box site consistently reduced PTH induction although mutagenesis of the Sp1, Ets and other possible binding sites in the 305 bp of promoter has no significant effect on the level of PTH induction. Other experiments showed that PTH induction but not basal expression was sensitive to the protein kinase inhibitor H89. We have therefore identified for the first time the sites in the 1alpha(OH)ase promoter responsible for basal expression and provide evidence for the role of a CCAAT box binding protein in a PTH mechanism of induction that involves an H89 sensitive step.

Simultaneous penile prosthesis and male sling/artificial urinary sphincter.

Erectile dysfunction (ED) and stress urinary incontinence (SUI) from urethral sphincteric deficiency is not an uncommon problem. The commonest etiology is intervention for localized prostate cancer and/or radical cystoprostatectomy for muscle invasive bladder cancer. Despite advances in surgical technology with robotic assisted laparoscopic prostatectomy and nerve sparing techniques, the rates of ED and SUI remain relatively unchanged. They both impact greatly on quality of life domains and have been associated with poor performance outcomes. Both the artificial urinary sphincter and penile prosthesis are gold standard treatments with proven efficacy, satisfaction and durability for end-stage SUI and ED respectively. Simultaneous prosthesis implantation for concurrent conditions has been well described, mostly in small retrospective series. The uptake of combination surgery has been slow due in part to technical demands of the surgery and to an extent, a heightened anxiety over potential complications. This paper aims to discuss the technical aspect of concurrent surgery for both disease entity and the current published outcomes of the various surgical techniques with this approach.

Illness uncertainty and quality of life of patients with small renal tumors undergoing watchful waiting: a 2-year prospective study.

BACKGROUND: Few studies have examined factors associated with the quality of life (QOL) of patients with renal tumors. Illness uncertainty may influence QOL. OBJECTIVE: To prospectively examine the influence of uncertainty on general and cancer-specific QOL and distress in patients undergoing watchful waiting (WW) for a renal mass. DESIGN, SETTING, AND PARTICIPANTS: In 2006-2010, 264 patients were enrolled in a prospective WW registry. The decision for WW was based on patient, tumor, and renal function characteristics at the discretion of the urologist and medical oncologist in the context of the physician-patient interaction. Participants had suspected clinical stage T1-T2 disease, were aged ≥ 18 yr, and spoke and read English. The first 100 patients enrolled in the registry participated in this study. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients completed questionnaires on demographics, illness uncertainty (Mishel Uncertainty in Illness Scale), general QOL (Medical Outcomes Study 36-item short-form survey), cancer-specific QOL (Cancer Rehabilitation Evaluation System-Short Form), and distress (Impact of Events Scale) at enrollment and at 6, 12, and 24 mo. Age, gender, ethnicity, tumor size, estimated glomerular filtration rate, comorbidities, and assessment time point were controlled for in the models. RESULTS AND LIMITATIONS: Among the sample, 27 patients had biopsies, and 17 patients had proven renal cell carcinoma. Growth rate was an average of 0.17 cm/yr (standard deviation: 0.35). Mean age was 72.5 yr, 55% of the patients were male, and 84% of the patients were Caucasian. Greater illness uncertainty was associated with poorer general QOL scores in the physical domain (p=0.008); worse cancer-related QOL in physical (p=0.001), psychosocial (p<0.001), and medical (p=0.034) domains; and higher distress (p<0.001). CONCLUSIONS: This study is among the first to prospectively examine the QOL of patients with renal tumors undergoing WW and the psychosocial factors that influence QOL. Illness uncertainty predicted general QOL, cancer-specific QOL, and distress. These factors could be targeted in psychosocial interventions to improve the QOL of patients on WW.

Estrogen receptors alpha (ESR1) and beta (ESR2) are expressed in circulating human lymphocytes.

Bone marrow thymocytes in part mediate the bone-preserving effects of estrogen by decreasing their production of osteoclast growth factors such as interleukin-1 and -6 and tumor necrosis factor alpha in the presence of physiological amounts of estradiol. Although several in vitro studies implicate the T-lymphocyte as a candidate mediator of estrogen signaling in the skeleton, whether these cells or any lymphocytes ordinarily express one or both nuclear estrogen receptors was previously unresolved. The purpose of our investigation was therefore to ascertain, by using real-time PCR, immmunoblotting, and cytometric techniques, if any of the nuclear estrogen receptors could be detected in normal peripheral blood mononuclear cells (PBMNC) collected from healthy volunteers. The results of immunoblotting experiments revealed that both estrogen receptor alpha (ESR1) and beta (ESR2) proteins are expressed in nuclei, but not in the cytoplasm of PBMNC harvested from all of the 15 healthy male and female volunteers (aged 23-50 years) we tested. PBMNCs contained mRNA coding for the two major full-length isoforms of ESR2 and the expression of ESR2 protein was localized within a lymphocyte subpopulation by cytometric analysis. Our data provide further evidence that lymphocytes and monocytes are responsive to estrogen and underscore its importance in modulating the immune response, as well as the vascular and skeletal health of men and women.