Gender differences in promotions and scholarly productivity in academic urology.

INTRODUCTION: The gender demographics within urology are changing as more women are entering the workforce. Since research productivity strongly influence career advancement, we aim to characterize gender differences in scholarly productivity and promotions in a cohort of graduated academic urologists. MATERIALS AND METHODS: Urologists who graduated between 2002 and 2008 from 34 residency programs affiliated with the top 50 urology hospitals as ranked in 2009 by U.S. News & World Report were followed longitudinally. Only urologists affiliated with an academic teaching hospital were included for analysis. RESULTS: A total of 543 residents graduated, 459 (84.5%) males and 84 (15.5%) females. Of these, 173 entered academia, 137 (79.2%) males and 36 (20.8%) females. Women had fewer publications compared to men (mean 19.3 versus 61.7, p = 0.001). Fewer women compared to men were promoted from assistant professor 11 (30.6%) versus 83 (60.6%), p = 0.005. Fewer women achieved associate professor 10 (27.8%) versus 67 (48.9%), p = 0.005 or professor ranks 1 (2.8%) versus 16 (11.7%), p = 0.005 respectively compared to men. In a multivariate logistic regression analysis, after controlling for the number of total publications and number of years since graduation, gender was not predictive of achieving promotion, OR = 0.81 (95% CI 0.31-2.13), p = 0.673. CONCLUSIONS: Women are underrepresented in senior faculty roles in urology. Scholarly productivity seems to play a major role in academic promotion within urology. With increasing women in academic urology, further studies are needed to explore predictors of promotion and how women can achieve higher leadership roles in the field.

Gender differences in academic productivity and academic career choice among urology residents.

PURPOSE: Gender disparities have long existed in medicine but they have not been well examined in urology. We analyzed a large cohort of graduating urology residents to investigate gender disparities in academic productivity, as measured by peer reviewed publications and academic career choice. MATERIALS AND METHODS: We assembled a list of urology residents who graduated from 2002 through 2008 who were affiliated with the top 50 urology hospitals, as ranked by 2009 U.S. News & World Report. PubMed® was queried to determine the publication output of each resident during the last 3 years of residency. We used an Internet search to determine the fellowship training, career choice and academic rank of each subject. Gender effects on each factor were evaluated. RESULTS: A total of 459 male (84.5%) and 84 female (15.5%) residents were included in analysis. During residency women produced fewer total publications (average 3.0 vs 4.8, p = 0.01) and fewer as first author (average 1.8 vs 2.5, p = 0.03) than men. A higher proportion of women than men underwent fellowship training (54.8% vs 48.5%, p = 0.29) and ultimately chose an academic career (40.5% vs 33.3%, p = 0.20), although these differences were not statistically significant. Of residents who chose an academic career a higher proportion of men than women (24.7% vs 2.9%, p = 0.01) obtained associate vs assistant professor rank. CONCLUSIONS: Women produced fewer peer reviewed publications than men during residency but they were equally likely to undergo fellowship training and choose an academic career. During the study period a higher proportion of men achieved associate professor rank.

Evolving practice patterns for the management of small renal masses in the USA.

UNLABELLED: What's known on the subject? and What does the study add? Treatment options for small renal masses include radical nephrectomy (RN), partial nephrectomy (PN), ablation, and surveillance. PN provides equivalent oncological as RN for small tumours, but long-term outcomes for ablation and surveillance are poorly defined. Due to changing techniques and technology, treatment patterns for small renal masses are rapidly developing. Prior studies had analysed utilisation trends for PN and RN to 2006, revealing a relative rise in the rate of PN. However, overall treatment trends including surveillance and ablation had not been studied using a population-based cohort. It has become increasingly clear that RN is associated with greater renal and cardiovascular deterioration than nephron-sparing treatments. Thus, it is important to understand current population-based practice patterns for the treatment of small renal masses to assess whether practitioners are adhering to ever-changing principles in this field. The present study provides up-to-date treatment trends in the USA using a large population-based cohort. OBJECTIVE: To describe the changing practice patterns in the management of small renal masses, including the use of surveillance and ablative techniques. PATIENTS AND METHODS: All patients in the Surveillance, Epidemiology and End Results (SEER) registry treated for renal masses of ≤7 cm in diameter, from 1998 to 2008, were included for analysis. Annual trends in the use of surveillance, ablation, partial nephrectomy (PN), and radical nephrectomy (RN) were calculated. Multinomial logistic regression was used to determine the association of demographic and clinical characteristics with treatment method. RESULTS: In all, 48 148 patients from 17 registry sites with a mean age of 63.4 years were included for analysis. Between 1998 and 2008, for masses of <2 cm and 2.1-4 cm, there was a dramatic increase in the proportion of patients undergoing PN (31% vs 50%, 16% vs 33%, respectively) and ablation (1% vs 11%, 2% vs 9%, respectively). In multivariable analysis, later year of diagnosis, male gender, being married, clinically localised disease, and smaller tumours were associated with increased use of PN vs RN. Later year of diagnosis, male gender, being unmarried, smaller tumour, and the presence of bilateral masses were associated with increased use of ablation and surveillance vs RN. CONCLUSIONS: PN is now used in half of all patients with the smallest renal masses, and its use continues to increase over time. Ablation and surveillance are less common overall, but there is increased usage over time in select populations.

Urology resident publication output and its relationship to future academic achievement.

PURPOSE: Scholarly research is considered by many to be an important component of residency training but little is known about the quantity and types of publications produced by urology residents. To our knowledge whether publication efforts during residency predict future academic publication performance is also unknown. We evaluated resident productivity, as measured by peer reviewed publication output, and determined its relation to future publication output as junior faculty. MATERIALS AND METHODS: We assembled a list of graduating residents from 2002 to 2004 who were affiliated with the top 50 urology hospitals, as ranked in 2009 by U.S. News&World Report. PubMed® was queried to determine the publication total in the last 3 years of residency of each individual and during years 2 to 4 after residency graduation. Resident publication output was stratified by research time and fellowship training. The relationship between resident productivity and future achievement was assessed. RESULTS: We assessed the publication output of 251 urologists from a total of 34 training programs affiliated with the top 50 urology hospitals. Subjects published a mean total of 3.5 and a mean of 2.0 first author papers during training. Greater research time during residency was associated with increased productivity during and after residency. Publication during training correlated with publication during the early academic career. CONCLUSIONS: Publication output correlated with increasing dedicated research time and was associated with the pursuit of fellowship training and an academic career. Publication during residency predicted future academic achievement.

Squamous cell carcinoma at the site of a Prince Albert's piercing.

INTRODUCTION: Medical practitioners should be aware of genital piercing and its potential complications. General piercings are associate with complications common to all piercings as well as some unique to urethral piercings. Specifically, the association between carcinoma and genital piercing is not well recognized. AIM: The present study is a report of two cases describing squamous cell carcinoma associated with genital piercing. METHODS: Case reports of two men admitted to an academic medical center. RESULTS: A 60-year-old man with a history of HIV and hepatitis C as well as a Prince Albert piercing presented for treatment of a urethrocutaneous fistula. A biopsy of indurated granulation tissue surrounding the fistula revealed invasive, moderately-differentiated squamous cell carcinoma. A 56-year-old man with a history of HIV, hepatitis C, and a Prince Albert piercing presented following a single episode of gross hematuria. He also reported splitting of his urinary stream. On physical examination, areas of necrosis were noted on the glans penis; biopsy revealed invasive, poorly-differentiated squamous cell carcinoma. CONCLUSIONS: The present study is the first to suggest a possible association between squamous cell carcinoma of the penis/urethra and genital piercing. Patients with genital piercings, especially those with concurrent risk factors such as HIV and HCV, should be counselled about this rare complication.

The incidence of erectile dysfunction after pelvic fracture urethral injury: A systematic review and meta-analysis.

BACKGROUND: Pelvic fracture urethral injury (PFUI) is associated with a high risk of erectile dysfunction (ED). The effect of the type of posterior urethral disruption repair on erectile function has not been clearly established. We systematically reviewed and conducted a meta-analysis of the proportion of patients with ED at (i) baseline after pelvic fracture with PFUI, (ii) after immediate primary realignment, and (iii) after delayed urethroplasty. METHODS: Using search terms for primary realignment or urethroplasty and urethral disruption, we systematically reviewed PubMed and EMBASE. A meta-analysis of the proportion of patients with ED was conducted assuming a random-effects model. RESULTS: Of 734 articles found, 24 met the inclusion criteria. The estimate of the proportion (95% confidence interval) of patients with ED after (i) PFUI was 34 (25-45)%, after (ii) immediate primary realignment was 16 (8-26)%, and after (iii) delayed urethroplasty was an additional 3 (2-5)% more than the 34% after pelvic fracture in this cohort. CONCLUSIONS: After pelvic fracture, 34% of patients had ED. After primary endoscopic alignment, patients had a lower reported rate of ED (16%). Delayed urethroplasty conferred an additional 3% risk above the 34% associated with PFUI alone, with 37% of patients having de novo ED. The difference in de novo ED after primary endoscopic alignment vs. delayed urethroplasty is probably due to reporting differences in ED and/or patients with less severe injury undergoing primary realignment.

Targeted p21WAF1/CIP1 activation by RNAa inhibits hepatocellular carcinoma cells.

RNA activation (RNAa) is a mechanism of gene activation triggered by promoter-targeted small double-stranded RNA (dsRNA), also known as small activating RNA (saRNA). p21(WAF1/CIP1) (p21) is a putative tumor suppressor gene due to its role as a key negative regulator of the cell cycle and cell proliferation. It is frequently downregulated in cancer including hepatocellular carcinoma (HCC), but is rarely mutated or deleted, making it an ideal target for RNAa-based overexpression to restore its tumor suppressor function. In the present study, we investigated the antigrowth effects of p21 RNAa in HCC cells. Transfection of a p21 saRNA (dsP21-322) into HepG2 and Hep3B cells significantly induced the expression of p21 at both the mRNA and protein levels, and inhibited cell proliferation and survival. Further analysis of dsP21-322 transfected cells revealed that dsP21-322 arrested the cell cycle at the G(0)/G(1) phase in HepG2 cells but at G(2)/M phase in Hep3B cells which lack functional p53 and Rb genes, and induced both early and late stage apoptosis by activating caspase 3 in both cell lines. These results demonstrated that RNAa of p21 has in vitro antigrowth effects on HCC cells via impeding cell cycle progression and inducing apoptotic cell death. This study suggests that targeted activation of p21 by RNAa may be explored as a novel therapy for the treatment of HCC.

An orthotopic bladder tumor model and the evaluation of intravesical saRNA treatment.

We present a novel method for treating bladder cancer with intravesically delivered small activating RNA (saRNA) in an orthotopic xenograft mouse bladder tumor model. The mouse model is established by urethral catheterization under inhaled general anesthetic. Chemical burn is then introduced to the bladder mucosa using intravesical silver nitrate solution to disrupt the bladder glycosaminoglycan layer and allows cells to attach. Following several washes with sterile water, human bladder cancer KU-7-luc2-GFP cells are instilled through the catheter into the bladder to dwell for 2 hours. Subsequent growth of bladder tumors is confirmed and monitored by in vivo bladder ultrasound and bioluminescent imaging. The tumors are then treated intravesically with saRNA formulated in lipid nanoparticles (LNPs). Tumor growth is monitored with ultrasound and bioluminescence. All steps of this procedure are demonstrated in the accompanying video.

Intravesical delivery of small activating RNA formulated into lipid nanoparticles inhibits orthotopic bladder tumor growth.

Practical methods for enhancing protein production in vivo remain a challenge. RNA activation (RNAa) is emerging as one potential solution by using double-stranded RNA (dsRNA) to increase endogenous gene expression. This approach, although related to RNA interference (RNAi), facilitates a response opposite to gene silencing. Duplex dsP21-322 and its chemically modified variants are examples of RNAa-based drugs that inhibit cancer cell growth by inducing expression of tumor suppressor p21(WAF1/CIP1) (p21). In this study, we investigate the therapeutic potential of dsP21-322 in an orthotopic model of bladder cancer by formulating a 2'-fluoro-modified derivative (dsP21-322-2'F) into lipid nanoparticles (LNP) for intravesical delivery. LNP composition is based upon clinically relevant formulations used in RNAi-based therapies consisting of PEG-stabilized unilamellar liposomes built with lipid DLin-KC2-DMA. We confirm p21 induction, cell-cycle arrest, and apoptosis in vitro following treatment with LNP-formulated dsP21-322-2'F (LNP-dsP21-322-2'F) or one of its nonformulated variants. Both 2'-fluoro modification and LNP formulation also improve duplex stability in urine. Intravesical delivery of LNP-dsP21-322-2'F into mouse bladder results in urothelium uptake and extends survival of mice with established orthotopic human bladder cancer. LNP-dsP21-322-2'F treatment also facilitates p21 activation in vivo leading to regression/disappearance of tumors in 40% of the treated mice. Our results provide preclinical proof-of-concept for a novel method to treat bladder cancer by intravesical administration of LNP-formulated RNA duplexes.

Oncological and functional outcomes of radical cystectomy and orthotopic bladder replacement in women.

OBJECTIVE: To report oncological and functional results in women undergoing radical cystectomy and orthotopic bladder replacement. MATERIALS AND METHODS: The charts of all women undergoing bladder replacement after radical cystectomy at UCSF through April 2008 were reviewed. Pathologic characteristics, survival (overall and disease-specific), and urinary functional outcomes are reported. Survival was estimated using Kaplan-Meier methods, and Cox proportional hazards regression analyses were performed to determine factors associated with incontinence, retention, and mortality. RESULTS: Fifty-six women with a mean follow-up of 35 months were analyzed. The cancer recurrence rate was 32%. Kaplan-Meier estimated 5-year recurrence-free, cancer-specific, and overall survival were 54%, 57%, and 47%, respectively. Pathologic lymph node status (HR 14.2, P <.001) and age at diagnosis (HR 1.7, P = .04) were the only clinical or pathologic characteristics significantly associated with survival. The overall continence rate (no pads) was 57%. Hypercontinence occurred in 24% of patients. CONCLUSIONS: With careful patient selection and usage of urethral frozen section, rates of local recurrence are low. Overall rates of incontinence (43%) and hypercontinence (24%) are similar to those previously reported. When pathologically organ-confined, women have an excellent disease-specific survival. Orthotopic bladder replacement is a safe and effective form of urinary diversion after radical cystectomy in women.

Condyloma overgrowth caused by immune reconstitution inflammatory syndrome.

A 46-year-old man with human immunodeficiency virus presented with a condyloma that formed during 6 months and encased his penis, scrotum, and perineum. Visible condyloma growth began when this immunocompromised patient started highly active antiretroviral therapy, and it grew rapidly as his viral load plummeted. The patient underwent resection and reconstruction with skin grafting. Pathology findings revealed benign condyloma acuminatum. This rapid progression of condyloma growth is a cutaneous manifestation of immune reconstitution inflammatory syndrome.

Assessment of teacher interruptions on learners during oral case presentations.

BACKGROUND: Studies have only recently begun to investigate the effects of interruptions on physicians in the emergency department (ED). OBJECTIVES: To determine the frequency and nature of interruptions by the training physician that occur when medical trainees do oral case presentations (OCPs) in the ED. METHODS: This was an observational study. Learner OCPs to attending emergency physicians were observed in the ED of an urban Level 1 trauma center at a major teaching hospital. A single investigator followed attending physicians blinded to the study objective in a nonrandomized convenience sampling of all ED shifts, recording information regarding teacher interruptions during new patient presentations. Learners completed a brief questionnaire after each OCP. RESULTS: A total of 196 OCPs were observed. The mean (+/-SD) duration of OCPs was 3.30 (+/-1.85) minutes, and the mean (+/-SD) number of interruptions was 0.75 (+/-0.60) per minute and 2.49 (+/-1.95) per OCP. The number of interruptions (per OCP) and duration of OCP varied by learner level of training, with more experienced learners giving shorter presentations and being interrupted less often. Frequency (per minute) of interruptions did not vary by learner level. In 40.3% of OCPs, attending physicians interrupted to give an assessment and/or a plan before the learner had done so, but 8.3% of interrupted learners believed that teacher interruptions were "disruptive" to their OCP. CONCLUSIONS: Attending emergency physicians frequently interrupt learners during new patient OCPs, with the number of interruptions varying by learner level of training. Teacher interruptions appear to have minimal, if any, detrimental effect on the perceived effectiveness of OCPs as a learning experience.

The kinetics of the return of motile sperm to the ejaculate after vasectomy reversal.

PURPOSE: In prior analyses we observed that the achievable patency rate after vasectomy reversal is a key factor in whether reversal surgery is more cost-effective than in vitro fertilization-intracytoplasmic sperm injection for fertility after vasectomy. Because pregnancies will occur sooner with an earlier time to patency, this clinical parameter becomes important with advanced maternal age. We hypothesize that there are predictors of time to patency after reversal that are valuable for patient counseling and intraoperative decision making in cases of advanced maternal age. MATERIALS AND METHODS: We retrospectively reviewed a cohort of consecutive men who underwent vasectomy reversal. Data obtained included patient demographics, semen analyses, intraoperative findings, patency rates and time to achieve patency. RESULTS: A total of 150 patients met the inclusion criteria. Mean patient age was 42.9 years (range 27 to 61) and mean followup was 12.5 months (range 1 to 90). The presence of motile sperm in vasa predicted faster patency rates postoperatively. Of patients with motile sperm 95% achieved patency by 6 months whereas 76% of patients without motile sperm achieved patency within 6 months (p = 0.04). An obstructive interval of 8 years or less and undergoing vasovasostomy instead of epididymovasostomy predicted faster time to patency within the first 3 months after reversal. Patient age was not associated with time to patency after bilateral vasovasostomy. CONCLUSIONS: Motile sperm found intraoperatively at the testicular vas, undergoing vasovasostomy and an obstructive interval of 8 years or less predict shorter time to patency after vasectomy reversal. Patient age does not appear to affect patency kinetics after reversal. Patient counseling regarding fertility after vasectomy may benefit from this information especially in the setting of advanced maternal age.