Dana A. Weiss

New Insights on the Morphology of Adult Mouse Penis

ABSTRACT The adult mouse penis represents the end point of masculine sex differentiation of the embryonic genital tubercle and contains bone, cartilage, the urethra, erectile bodies, several types of epithelium, and many individual cell types arrayed into specific anatomical structures. Using contemporary high-resolution imaging techniques, we sought to provide new insights to the current description of adult mouse penile morphology to enable understanding of penile abnormalities, including hypospadias. Examination of serial transverse and longitudinal sections, scanning electron microscopy, and three-dimensional (3D) reconstruction provided a new appreciation of the individual structures in the adult mouse penis and their 3D interrelationships. In so doing, we discovered novel paired erectile bodies, the male urogenital mating protuberance (MUMP), and more accurately described the urethral meatus. These morphological observations were quantified by morphometric analysis and now provide accurate morphological end points of sex differentiation of mouse penis that will be the foundation of future studies to identify normal and abnormal penile development.

Specific morphogenetic events in mouse external genitalia sex differentiation are responsive/dependent upon androgens and/or estrogens

The objective of this study was to perform a comprehensive morphologic analysis of developing mouse external genitalia (ExG) and to determine specific sexual differentiation features that are responsive to androgens or estrogens. To eliminate sex steroid signaling postnatally, male and female mice were gonadectomized on the day of birth, and then injected intraperitoneally every other day with DES (200 ng/g), DHT (1 μg/g), or oil. On day-10 postnatal male and female ExG were dissected, fixed, embedded, serially sectioned and analyzed. We identified 10 sexually dimorphic anatomical features indicative of normal penile and clitoral differentiation in intact mice. Several (but not all) penile features were impaired or abolished as a result of neonatal castration. Those penile features remaining after neonatal castration were completely abolished with attendant clitoral development in androgen receptor (AR) mutant male mice (X(Tfm)/Y and X/Y AR-null) in which AR signaling is absent both pre- and postnatally. Administration of DHT to neonatally castrated males restored development of all 10 masculine features to almost normal levels. Neonatal ovariectomy of female mice had little effect on clitoral development, whereas treatment of ovariectomized female mice with DHT induced partial masculinization of the clitoris. Administration of DES to neonatally gonadectomized male and female mice elicited a spectrum of development abnormalities. These studies demonstrate that the presence or absence of androgen prenatally specifies penile versus clitoral identity. Differentiated penile features emerge postnatally and are sensitive to and dependent upon prenatal or pre- and postnatal androgen. Emergence of differentiated clitoral features occurs postnatally in either intact or ovariectomized females. It is likely that each penile and clitoral feature has a unique time-course of hormonal dependency/sensitivity.

Are sonographic characteristics associated with progression to surgery in men with Peyronie's disease?

PURPOSE Traditionally, diagnosis and treatment plans for Peyronies disease have been based on history and physical examination. Penile ultrasound provides rapid, anatomical information to establish disease severity, and to monitor progression and response to medical therapy. We determined the relationship between ultrasound characteristics and progression to surgical intervention in men with Peyronies disease. MATERIALS AND METHODS We conducted a retrospective cohort study of 518 patients with Peyronies disease. Patients completed a Peyronies disease specific questionnaire detailing medical history, health related behaviors and Peyronies disease characteristics, and underwent sonographic evaluation of the penis. Measurements of subtunical calcifications, septal fibrosis, tunical thickening (tunica thickness greater than 2 mm) and intracavernous fibrosis were made. Progression to surgery was determined from the medical record. RESULTS In this cohort (mean patient age 53.8 years, range 20 to 78) 31% of patients had calcifications, 50% had tunical thickening, 20% had septal fibrosis and 15% had intracavernous fibrosis. Overall 25% of the cohort progressed to surgical intervention after an average followup of 1.25 years (range 0 to 7.6). Patients who underwent surgery were more likely to have subtunical calcifications present at the first clinic visit (OR 1.75, 95% CI 1.16-2.62). No other sonographic characteristics were associated with progression to surgery. After adjustment for age, marital status, degree of curvature, additional penile deformity, difficulty with penetration, ability to have intercourse and prior treatment for Peyronies disease, calcifications were strongly associated with progression to surgery (OR 2.75, 95% CI 1.25-3.45). CONCLUSIONS In a large cohort of patients with Peyronies disease the presence of sonographically detected sub-tunical calcifications during the initial office evaluation was independently associated with subsequent surgical intervention.

Gender trends of urology manuscript authors in the United States: a 35-year progression.

PURPOSE The presence of women in urology has gradually increased in the last 35 years with an accelerated rate in the last decade. We evaluated manuscript authorship trends by gender. Manuscript authorship is a metric that has been used as a marker of academic productivity. We hypothesized that the number of first and last author publications by women has increased proportionately to the number of women in the field during the last 35 years. MATERIALS AND METHODS We performed a bibliometric study to examine authorship gender in The Journal of Urology® and Urology®. We reviewed all original articles published from American institutions in 1974, 1979, 1984, 1989, 1994, 1999, 2004 and 2009. RESULTS Of the 8,313 articles reviewed 5,461 were from American institutions, including 97.5% for which we determined author gender. There were 767 articles with female authors, including 440 first and 327 last authors. First and last female authorship increased from 2.7% of all authors in 1979 to 26.5% in 2009 (test for trend p <0.001). This authorship rate surpasses the rate of growth of women in urology, which increased from 0.24% in 1975 to 6.2% in 2008. CONCLUSIONS Based on authorship gender analysis women urologists produce manuscripts at a rate that exceeds their number in the field. Findings show that women in urology are productive, active members of the academic community.

Mucinous Tubular and Spindle Cell Carcinoma of the Kidney

Mucinous tubular and spindle cell carcinoma (MTSC) was initially recognized as a distinctive subset of low grade collecting duct carcinomas in 1997,1 and it was incorporated in the 2004 WHO classification of renal neoplasms under its current name. Although MTSC was regarded as rare, more than 80 cases have been reported. The exact cell of origin is a matter of debate but accumulated evidence suggests that it originates from cells of the loop of Henle or from collecting duct epithelium, with more support for the latter site. MTSC occurs predominantly in females with a 1:4 male-to-female ratio and patient age is 13 to 82 years (mean 53).2 Although some tumors are symptomatic, the majority are discovered incidentally during abdominal imaging studies. Tumors are 2.2 to 12 cm (average 6 to 7) in diameter, sharply circumscribed and gray-white, tan or yellow, and sometimes have minimal hemorrhaging and/or necrosis. The cut surfaces are commonly bulging, shiny and mucoid due to the mucin content (fig. 1). Figure 1 MTSC exhibits bulging shiny mucoid cut surface. Microscopically MTSC is composed of round, ovoid or elongated tightly packed tubules separated by abundant basophilic extracellular mucin that sometimes has a bubbly myxoid consistency (fig. 2). Focally aggregates of spindled cells may be present, which may simulate sarcomatoid change but without necrosis, mitotic activity or significant nuclear pleomorphism (fig. 2, inset). The mucin stains strongly with Alcian blue at pH 2.5. Tubules are lined by uniform low cuboidal cells with scant cytoplasm, round nuclei of low nuclear grade and absent or inconspicuous nucleoli. Mitotic figures are rare.3 Figure 2 MTSC composed of tightly packed elongated tubules separated by abundant basophilic extracellular mucin with bubbly myxoid consistency. Aggregates of spindled cells may be present (inset). The histological spectrum of these tumors has been expanded to include cases in which the spindle cell component rivals or even exceeds the tubular component, as well as those with a relative paucity of mucinous matrix, aggregates of foamy macrophages, small components of well formed papillae, focal clear cell change in tubular cells, focal necrosis, oncocytic tubules, numerous small vacuoles, psammomatous calcification or heterotopic bone formation.3 Rarely neuroendocrine differentiation and true sarcomatoid components have been reported.4 Cytogenetic analyses and comparative genomic hybridization studies have revealed multiple genetic alterations, including losses of chromosomes 1, 4, 6, 8, 9, 13, 14, 15, 18 and 22.2 The prognosis for MTSC with classic morphology is generally favorable and complete surgical excision appears to be adequate treatment. These tumors are generally low pathological stage at excision and usually behave indolently. Few cases have demonstrated recurrence, regional lymph node metastases or distant metastases. However, 2 of 4 patients with MTSC exhibiting components of true sarcomatoid change died of the disease.4

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.

Parental beliefs about nocturnal enuresis causes, treatments, and the need to seek professional medical care.

OBJECTIVE To better understand parental beliefs regarding the etiology and treatment of nocturnal enuresis (NE). METHODS A self-administered survey queried parental NE beliefs including perceived etiologies and home behavioral treatments. We assessed for associations between demographic characteristics and propensity to seek medical care for NE. RESULTS Of 216 respondents, 78% were female. The most common causes for NE reported were: deep sleeper (56%), unknown (39%), and laziness (26%). Popular home behavioral therapies included: void prior to sleep (77%) and limiting fluid intake at night (71%). Few reported they would use a bedwetting alarm (6%). Fifty-five percent reported they would seek medical care for NE and 28% reported awareness of effective treatments. On multivariable analysis, females (OR 2.3, 95% CI 1.04-5.0) and those with graduate level education (OR 4.8, 95% CI 1.5-15.7) were more likely to seek medical care for their child with NE. CONCLUSIONS General parental knowledge of the causes and effective treatments for NE is lacking. Only 55% reported they would seek medical care for their child with NE and only 28% reported awareness of effective treatments. Counseling should focus on dispelling common misconceptions about causes and treatments of NE and focus on proven effective treatments.

Intermediate-Term Followup of Proximal Hypospadias Repair Reveals High Complication Rate

Purpose: Results following distal hypospadias repair are favorable. Grouping proximal and distal hypospadias repair artificially increases the perceived success rate of proximal hypospadias. We identified our complication rate of proximal hypospadias repair and hypothesized a higher complication rate for 1‐stage repair. Materials and Methods: We retrospectively reviewed the records of consecutive boys who underwent proximal hypospadias from 2007 to 2014. Proximal hypospadias was defined as a urethral meatus location at or more proximal than the penoscrotal junction after penile degloving. We further stratified boys into those with planned 1‐stage vs 2‐stage repair. Univariate and Cox regression analyses were performed to assess associations with covariates and compare time to the first complication, respectively. Results: A total of 167 boys met study inclusion criteria. Median followup was 31.7 months for 1‐stage repair in 86 patients and staged repair in 81. The overall complication rate was 56%. Complications developed in 53 of 86 1‐stage (62%) vs 40 of 81 staged (49%) repairs (p = 0.11). The number of unplanned procedures per patient was higher in the 1‐stage than in the staged group (0.99 vs 0.69, p = 0.06), as was the number of patients who had at least 2 complications (29 of 86 or 33% vs 13 of 81 or 16%, p = 0.03). Cox regression showed no difference in time to the first complication for staged compared to 1‐stage repair (HR 0.77, 95% CI 0.43–1.39). Conclusions: Our 56% complication rate of proximal hypospadias warrants further long‐term patient followup. More patients in the 1‐stage group experienced at least 2 complications. However, when complications developed, they developed no differently in the 2 groups.

The robotic-assisted ureteral reimplantation: the evolution to a new standard.

The development of the robotic-assisted laparoscopic ureteral reimplantation has tracked a path searching for the optimal method of providing outcomes on par with the gold standard of open intravesical ureteral reimplantation combined with fewer complications and decreased discomfort for the patient. With this in mind, pioneers in pediatric urology minimally invasive surgery have put limits to the test with laparoscopic transvesicoscopic Cohen reimplants and laparoscopic extravesical Lich-Gregoir reimplants and then used the da Vinci platform to fine-tune and bring these skills into the 21st century.

The use of complementary and alternative fertility treatments.

Purpose of review Complementary and alternative medicine (CAM) is widely used for the treatment of infertility; however, few reviews have evaluated the quality of evidence underlying the use of CAM fertility treatments. This review summarizes and evaluates the evidence underlying the use of these therapies for male and female infertility. Recent findings A wide range of CAM treatments are used by subfertile couples. Their use depends upon the region studied and the type of fertility problems encountered. Acupuncture, the most commonly used CAM fertility treatment in the USA, has the most literature-based support. Few randomized trials have been performed to evaluate other CAM fertility treatments. Summary CAM is used commonly to treat infertility; however, additional high-quality studies need to be conducted to demonstrate the safety and effectiveness of these therapies before clear recommendations can be made by physicians about their safety and effectiveness.