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PURPOSE: The FLAME trial provides strong evidence that MR-guided external beam radiation therapy (EBRT) focal boost for localized prostate cancer increases biochemical disease-free survival (bDFS) without increasing toxicity. Yet, there are many barriers to implementation of focal boost. Our objectives are to systemically review clinical outcomes for MR-guided EBRT focal boost and to consider approaches to increase implementation of this technique. METHODS: We conducted literature searches in four databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guideline. We included prospective phase II/III trials of patients with localized prostate cancer underdoing definitive EBRT with MR-guided focal boost. The outcomes of interest were bDFS and acute/late gastrointestinal and genitourinary toxicity. RESULTS: Seven studies were included. All studies had a median follow-up of greater than 4 years. There were heterogeneities in fractionation, treatment planning, and delivery. Studies demonstrated effectiveness, feasibility, and tolerability of focal boost. Based on the Phoenix criteria for biochemical recurrence, the reported 5-year biochemical recurrence-free survival rates ranged 69.7-100% across included studies. All studies reported good safety profiles. The reported ranges of acute/late grade 3 + gastrointestinal toxicities were 0%/1-10%. The reported ranges of acute/late grade 3 + genitourinary toxicities were 0-13%/0-5.6%. CONCLUSIONS: There is strong evidence that it is possible to improve oncologic outcomes without substantially increasing toxicity through MR-guided focal boost, at least in the setting of a 35-fraction radiotherapy regimen. Barriers to clinical practice implementation are addressable through additional investigation and new technologies.

ObjectiveTo understand the effect of bicycle saddle shape and size on the pressure transmitted to the perineum, as prolonged perineal pressure and microtrauma amongst avid cyclists may increase the risk for complications following lower genitourinary surgery.MethodsWe tested five seats (Bontrager, Waterloo, WI) with varying levels of padding and morphology (comfort, fitness, fitness gel, race, and performance) for two different riders. The seats were installed on a Peloton stationary exercise bike (New York City, NY). Force measurements were performed using a 9833E-50 Large F-Socket Sensor (Tekscan, South Boston, MA). We measured total and perineal forces in three conditions at the same resistance: (a) at rest (not pedaling); (b) at 8mph; (c) at 15mph.ResultsSignificant differences across the bicycle seats were observed with fitness gel seats providing the lowest perineal pressure. In all measurements, perineal forces were significantly lower at 15mph compared to 8mph (P

PurposeTo investigate management trends for American Association for the Surgery of Trauma (AAST) grade V renal trauma with focus on non-operative management.MethodsWe used prospectively collected data as part of the Multi-institutional Genito-Urinary Trauma Study (MiGUTS). We included patients with grade V renal trauma according to the AAST Injury Scoring Scale 2018 update. All cases submitted by participating centers with radiology images available were independently reviewed to confirm renal trauma grade. Management was classified as expectant, conservative (minimally invasive, endoscopic or percutaneous procedures), or operative (renal-related surgery).ResultsEighty patients were included, 25 of whom had complete imaging and had independent confirmation of AAST grade V renal trauma. Median age was 35 years (Interquartile range (IQR) 25-50) and 23 (92%) had blunt trauma. Ten patients (40%) were managed operatively with nephrectomy. Conservative management was used in nine patients (36%) of which six received angioembolization and three had a stent or drainage tube placed. Expectant management was followed in six (24%) patients. Transfusion requirements were progressively higher with groups requiring more aggressive treatment, and injury characteristics differed significantly across management groups in terms of hematoma size and laceration size. Vascular contrast extravasation was more likely in operatively managed patients though a statistically significant association was not found.ConclusionSuccessful use of nonoperative management for grade V injuries is used for a substantial subset of patients. Lower transfusion requirement and less severe injury radiologic phenotype appear to be important characteristics delineating this group.

Background and purposeThe purpose of this study was to determine whether single nucleotide polymorphisms disrupting microRNA targets (mirSNPs) can serve as predictive biomarkers for toxicity after radiotherapy for prostate cancer and whether these may be differentially predictive depending on radiation fractionation.Materials and methodsWe identified 201 men treated with two forms of definitive radiotherapy for prostate cancer at two institutions: 108 men received conventionally-fractionated radiotherapy (CF-RT) and 93 received stereotactic body radiotherapy (SBRT). Germline DNA was evaluated for the presence of functional mirSNPs. Random forest, boosted trees and elastic net models were developed to predict late grade ≥2 GU toxicity by the RTOG scale.ResultsThe crude incidence of late grade ≥2 GU toxicity was 16% after CF-RT and 15% after SBRT. An elastic net model based on 22 mirSNPs differentiated CF-RT patients at high risk (71.5%) versus low risk (7.5%) for toxicity, with an area under the curve (AUC) values of 0.76-0.81. An elastic net model based on 32 mirSNPs differentiated SBRT patients at high risk (64.7%) versus low risk (3.9%) for toxicity, with an area under the curve (AUC) values of 0.81-0.87. These models were specific to treatment type delivered. Prospective studies are warranted to further validate these results.ConclusionPredictive models using germline mirSNPs have high accuracy for predicting late grade ≥2 GU toxicity after either CF-RT or SBRT, and are unique for each treatment, suggesting that germline predictors of late radiation sensitivity are fractionation-dependent. Prospective studies are warranted to further validate these results.

Mycoplasma genitalium (MG) infections are a growing concern within the field of sexually transmitted infections. However, diagnostic assays for M. genitalium have been limited in the United States. As most infections are asymptomatic, individuals can unknowingly pass the infection on, and the prevalence is likely to be underestimated. Diagnosis of M. genitalium infection is recommended using a nucleic acid test. This multicenter study assessed the performance of the cobas Trichomonas vaginalis (TV)/MG assay (cobas) for the detection of M. genitalium, using 22,150 urogenital specimens from both symptomatic and asymptomatic men and women collected at geographically diverse sites across the United States. The performance was compared to a reference standard of three laboratory-developed tests (LDTs). The specificity of the cobas assay for M. genitalium ranged from 96.0% to 99.8% across symptomatic and asymptomatic men and women. The sensitivities in female vaginal swabs and urine samples were 96.6% (95% confidence interval [CI], 88.5 to 99.1%) and 86.4% (95% CI, 75.5 to 93.0%), respectively. The sensitivities in male urine and meatal swab samples were 100% (95% CI, 94.0 to 100%) and 85.0% (95% CI, 73.9 to 91.9%), respectively. This study demonstrated that the cobas assay was highly sensitive and specific in all relevant clinical samples for the detection of M. genitalium.

Technological advances in three-dimensional (3D) reconstruction techniques have previously enabled paradigm shifts in our understanding of human embryonic and fetal development. Light sheet fluorescence microscopy (LSFM) is a recently-developed technique that uses thin planes of light to optically section whole-mount cleared and immunolabeled biologic specimens. The advent of commercially-available light sheet microscopes has facilitated a new generation of research into protein localization and tissue dynamics at extremely high resolution. Our group has applied LSFM to study developing human fetal external genitalia, internal genitalia and kidneys. This review describes LSFM and presents our group's technique for preparing, clearing, immunostaining and imaging human fetal urogenital specimens. We then present light sheet images and videos of each element of the developing human urogenital system. To the extent of our knowledge, the work conducted by our laboratory represents the first description of a method for performing LSFM on the full human urogenital system during the embryonic and fetal periods.

Technological advances in three-dimensional (3D) reconstruction techniques have previously enabled paradigm shifts in our understanding of human embryonic and fetal development. Light sheet fluorescence microscopy (LSFM) is a recently-developed technique that uses thin planes of light to optically section whole-mount cleared and immunolabeled biologic specimens. The advent of commercially-available light sheet microscopes has facilitated a new generation of research into protein localization and tissue dynamics at extremely high resolution. Our group has applied LSFM to study developing human fetal external genitalia, internal genitalia and kidneys. This review describes LSFM and presents our group's technique for preparing, clearing, immunostaining and imaging human fetal urogenital specimens. We then present light sheet images and videos of each element of the developing human urogenital system. To the extent of our knowledge, the work conducted by our laboratory represents the first description of a method for performing LSFM on the full human urogenital system during the embryonic and fetal periods.

Purpose/objectiveHypofractionated radiotherapy (HRT) regimens for prostate cancer are emerging, but tolerance doses for late adverse events are scarce. The purpose of this study is to define dose-volume predictors for late gastrointestinal and genitourinary (GI and GU) toxicities after HRT in the multi-center NRG Oncology/RTOG 0415 low-risk prostate cancer trial (N = 521).Material/methodsTreatment in the studied HRT arm was delivered as 70 Gy at 2.5 Gy/fraction with 3D-CRT/IMRT (N = 108/413). At a median follow-up of 5.9 years, the crude late ≥Grade 2 GI and GU toxicities were 19% and 29%, respectively. For modeling, the complete HRT cohort was randomly split into training and validation (70% and 30%; preserved toxicity rates). Within training, dose-response modeling was based on dose-volume cut-points (EQD2Gy; bladder/rectum: α/β = 6 Gy/3Gy), age, acute ≥Grade 2 toxicity, and treatment technique using univariate and multivariate logistic regression on bootstrapping (UVA and MVA). Candidate predictors were determined at p ≤ 0.05, and the selected MVA models were explored on validation where model generalizability was judged if the area under the receiver-operating curve in validation (AUCvalidation) was within AUCtraining ± SD with p ≤ 0.05, and with an Hosmer-Lemeshow p-value (pHL) > 0.05.ResultsThree candidate predictors were suggested for late GI toxicity: the minimum dose to the hottest 5% rectal volume (D5%[Gy]), the absolute rectal volume

The clinical performance of the Cobas CT/NG assay on the Cobas 6800/8800 systems (Cobas) for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae was established in a multisite, prospective collection study using male and female urogenital specimens; supportive data from archived specimens were also included. The results obtained with the Cobas assay were compared with the patient infected status derived from a combination of U.S. Food and Drug Administration-approved nucleic acid amplification tests to determine the sensitivity and specificity of detection from each sample type. The sensitivity of Cobas for the detection of C. trachomatis in female specimens was 95.6% (95% confidence interval [CI], 92.4% to 97.4%) for urine; 98.6% (95% CI, 95.2% to 99.6%) and 99.2% (95% CI, 95.4% to 99.9%) for clinician- and self-collected vaginal swab specimens, respectively; 93.3% (95% CI, 89.6% to 95.7%) for endocervical swabs; and 92.5% (95% CI, 88.7% to 95.1%) for cervical swab samples in PreservCyt. The specificity for the detection of C. trachomatis was ≥98.8% for all female sample types. Sensitivity and specificity estimates of Cobas for the detection of C. trachomatis in male urine samples were 100% (96.8% to 100.0%) and 99.7% (95% CI, 99.2% to 99.9%), respectively. The sensitivity of Cobas for the detection of N. gonorrhoeae in female specimens was 94.8% (95% CI, 89.6% to 97.4%) for urine; 100.0% (95% CI, 87.9% to 100.0%) and 100.0% (95% CI, 87.9% to 100.0%) for clinician- and self-collected vaginal swab specimens, respectively; 97.0% (95% CI, 91.5% to 99.0%) for endocervical swabs; and 96.6% (95% CI, 90.6% to 98.8%) for cervical samples in PreservCyt; the specificity for all female sample types was >99.0%. The sensitivity and specificity of Cobas for detecting N. gonorrhoeae in male urine were 100.0% (95% CI, 95.8% to 100.0%) and 99.5% (95% CI, 98.8% to 99.8%), respectively. Fully automated assays help fill the clinical need for a sensitive, high-throughput screening tool to aid public health efforts to control C. trachomatis and N. gonorrhoeae infections.

Recent studies in our lab have utilized three imaging techniques to visualize the developing human fetal urogenital tract in three dimensions: optical projection tomography, scanning electron microscopy and lightsheet fluorescence microscopy. We have applied these technologies to examine changes in morphology and differential gene expression in developing human external genital specimens from the ambisexual stage (13 weeks fetal age). This work outlines the history and function of each of these three imaging modalities, our methods to prepare specimens for each and the novel findings we have produced thus far. We believe the images in this paper of human fetal urogenital organs produced using lightsheet fluorescence microscopy are the first published to date.

This paper provides a detailed compilation of human prostatic development that includes human fetal prostatic gross anatomy, histology, and ontogeny of selected epithelial and mesenchymal differentiation markers and signaling molecules throughout the stages of human prostatic development: (a) pre-bud urogenital sinus (UGS), (b) emergence of solid prostatic epithelial buds from urogenital sinus epithelium (UGE), (c) bud elongation and branching, (d) canalization of the solid epithelial cords, (e) differentiation of luminal and basal epithelial cells, and (f) secretory cytodifferentiation. Additionally, we describe the use of xenografts to assess the actions of androgens and estrogens on human fetal prostatic development. In this regard, we report a new model of de novo DHT-induction of prostatic development from xenografts of human fetal female urethras, which emphasizes the utility of the xenograft approach for investigation of initiation of human prostatic development. These studies raise the possibility of molecular mechanistic studies on human prostatic development through the use of tissue recombinants composed of mutant mouse UGM combined with human fetal prostatic epithelium. Our compilation of human prostatic developmental processes is likely to advance our understanding of the pathogenesis of benign prostatic hyperplasia and prostate cancer as the neoformation of ductal-acinar architecture during normal development is shared during the pathogenesis of benign prostatic hyperplasia and prostate cancer.

Recent studies in our lab have utilized three imaging techniques to visualize the developing human fetal urogenital tract in three dimensions: optical projection tomography, scanning electron microscopy and lightsheet fluorescence microscopy. We have applied these technologies to examine changes in morphology and differential gene expression in developing human external genital specimens from the ambisexual stage (13 weeks fetal age). This work outlines the history and function of each of these three imaging modalities, our methods to prepare specimens for each and the novel findings we have produced thus far. We believe the images in this paper of human fetal urogenital organs produced using lightsheet fluorescence microscopy are the first published to date.

We present a detailed review of fetal development of the male and female human urogenital tract from 8 to 22 weeks gestation at the macroscopic and morphometric levels. Human fetal specimens were sexed based on macroscopic identification of fetal testes or ovaries, Wolffian or Müllerian structures and the presence of the SRY gene in the specimens at or near the indifferent stage (8-9 weeks). Specimens were photographed using a dissecting microscope with transmitted and reflected light. Morphometric measurements were taken of each urogenital organ. During this time period, development of the male and female urogenital tracts proceeded from the indifferent stage to differentiated organs. The kidneys, ureters, and bladder developed identically, irrespective of sex with the same physical dimensions and morphologic appearance. The penis, prostate and testis developed in males and the clitoris, uterus and ovary in females. Androgen-dependent growth certainly influenced size and morphology of the penile urethra and prostate, however, androgen-independent growth also accounted for substantial growth in the fetal urogenital tract including the clitoris.

We present a detailed review of fetal development of the male and female human urogenital tract from 8 to 22 weeks gestation at the macroscopic and morphometric levels. Human fetal specimens were sexed based on macroscopic identification of fetal testes or ovaries, Wolffian or Müllerian structures and the presence of the SRY gene in the specimens at or near the indifferent stage (8-9 weeks). Specimens were photographed using a dissecting microscope with transmitted and reflected light. Morphometric measurements were taken of each urogenital organ. During this time period, development of the male and female urogenital tracts proceeded from the indifferent stage to differentiated organs. The kidneys, ureters, and bladder developed identically, irrespective of sex with the same physical dimensions and morphologic appearance. The penis, prostate and testis developed in males and the clitoris, uterus and ovary in females. Androgen-dependent growth certainly influenced size and morphology of the penile urethra and prostate, however, androgen-independent growth also accounted for substantial growth in the fetal urogenital tract including the clitoris.

The urinary bladder collects urine from the kidneys and stores it until the appropriate moment for voiding. The trigone and ureterovesical junctions are key to bladder function, by allowing one-way passage of urine into the bladder without obstruction. Embryological development of these structures has been studied in multiple animal models as well as humans. In this report we review the existing literature on bladder development and cellular signalling with particular focus on bladder development in humans. The bladder and ureterovesical junction form primarily during the fourth to eighth weeks of gestation, and arise from the primitive urogenital sinus following subdivision of the cloaca. The bladder develops through mesenchymal-epithelial interactions between the endoderm of the urogenital sinus and mesodermal mesenchyme. Key signalling factors in bladder development include shh, TGF-β, Bmp4, and Fgfr2. A concentration gradient of shh is particularly important in development of bladder musculature, which is vital to bladder function. The ureterovesical junction forms from the interaction between the Wolffian duct and the bladder. The ureteric bud arises from the Wolffian duct and is incorporated into the developing bladder at the trigone. It was previously thought that the trigonal musculature developed primarily from the Wolffian duct, but it has been shown to develop primarily from bladder mesenchyme. Following emergence of the ureters from the Wolffian ducts, extensive epithelial remodelling brings the ureters to their final trigonal positions via vitamin A-induced apoptosis. Perturbation of this process is implicated in clinical obstruction or urine reflux. Congenital malformations include ureteric duplication and bladder exstrophy.

We have studied the ontogeny of the developing human male and female urogenital tracts from 9 weeks (indifferent stage) to 16 weeks (advanced sex differentiation) of gestation by immunohistochemistry on mid-sagittal sections. Sixteen human fetal pelvises were serial sectioned in the sagittal plane and stained with antibodies to epithelial, muscle, nerve, proliferation and hormone receptor markers. Key findings are: (1) The corpus cavernosum in males and females extends into the glans penis and clitoris, respectively, during the ambisexual stage (9 weeks) and thus appears to be an androgen-independent event. (2) The entire human male (and female) urethra is endodermal in origin based on the presence of FOXA1, KRT 7, uroplakin, and the absence of KRT10 staining. The endoderm of the urethra interfaces with ectodermal epidermis at the site of the urethral meatus. (3) The surface epithelium of the verumontanum is endodermal in origin (FOXA1-positive) with a possible contribution of Pax2-positive epithelial cells implying additional input from the Wolffian duct epithelium. (4) Prostatic ducts arise from the endodermal (FOXA1-positive) urogenital sinus epithelium near the verumontanum. (5) Immunohistochemical staining of mid-sagittal and para-sagittal sections revealed the external anal sphincter, levator ani, bulbospongiosus muscle and the anatomic relationships between these developing skeletal muscles and organs of the male and female reproductive tracts. Future studies of normal human developmental anatomy will lay the foundation for understanding congenital anomalies of the lower urogenital tract.

The urinary bladder collects urine from the kidneys and stores it until the appropriate moment for voiding. The trigone and ureterovesical junctions are key to bladder function, by allowing one-way passage of urine into the bladder without obstruction. Embryological development of these structures has been studied in multiple animal models as well as humans. In this report we review the existing literature on bladder development and cellular signalling with particular focus on bladder development in humans. The bladder and ureterovesical junction form primarily during the fourth to eighth weeks of gestation, and arise from the primitive urogenital sinus following subdivision of the cloaca. The bladder develops through mesenchymal-epithelial interactions between the endoderm of the urogenital sinus and mesodermal mesenchyme. Key signalling factors in bladder development include shh, TGF-β, Bmp4, and Fgfr2. A concentration gradient of shh is particularly important in development of bladder musculature, which is vital to bladder function. The ureterovesical junction forms from the interaction between the Wolffian duct and the bladder. The ureteric bud arises from the Wolffian duct and is incorporated into the developing bladder at the trigone. It was previously thought that the trigonal musculature developed primarily from the Wolffian duct, but it has been shown to develop primarily from bladder mesenchyme. Following emergence of the ureters from the Wolffian ducts, extensive epithelial remodelling brings the ureters to their final trigonal positions via vitamin A-induced apoptosis. Perturbation of this process is implicated in clinical obstruction or urine reflux. Congenital malformations include ureteric duplication and bladder exstrophy.

We present a detailed review of fetal development of the male and female human urogenital tract from 8 to 22 weeks gestation at the macroscopic and morphometric levels. Human fetal specimens were sexed based on macroscopic identification of fetal testes or ovaries, Wolffian or Müllerian structures and the presence of the SRY gene in the specimens at or near the indifferent stage (8-9 weeks). Specimens were photographed using a dissecting microscope with transmitted and reflected light. Morphometric measurements were taken of each urogenital organ. During this time period, development of the male and female urogenital tracts proceeded from the indifferent stage to differentiated organs. The kidneys, ureters, and bladder developed identically, irrespective of sex with the same physical dimensions and morphologic appearance. The penis, prostate and testis developed in males and the clitoris, uterus and ovary in females. Androgen-dependent growth certainly influenced size and morphology of the penile urethra and prostate, however, androgen-independent growth also accounted for substantial growth in the fetal urogenital tract including the clitoris.

Recent studies in our lab have utilized three imaging techniques to visualize the developing human fetal urogenital tract in three dimensions: optical projection tomography, scanning electron microscopy and lightsheet fluorescence microscopy. We have applied these technologies to examine changes in morphology and differential gene expression in developing human external genital specimens from the ambisexual stage (13 weeks fetal age). This work outlines the history and function of each of these three imaging modalities, our methods to prepare specimens for each and the novel findings we have produced thus far. We believe the images in this paper of human fetal urogenital organs produced using lightsheet fluorescence microscopy are the first published to date.

This paper provides a detailed compilation of human prostatic development that includes human fetal prostatic gross anatomy, histology, and ontogeny of selected epithelial and mesenchymal differentiation markers and signaling molecules throughout the stages of human prostatic development: (a) pre-bud urogenital sinus (UGS), (b) emergence of solid prostatic epithelial buds from urogenital sinus epithelium (UGE), (c) bud elongation and branching, (d) canalization of the solid epithelial cords, (e) differentiation of luminal and basal epithelial cells, and (f) secretory cytodifferentiation. Additionally, we describe the use of xenografts to assess the actions of androgens and estrogens on human fetal prostatic development. In this regard, we report a new model of de novo DHT-induction of prostatic development from xenografts of human fetal female urethras, which emphasizes the utility of the xenograft approach for investigation of initiation of human prostatic development. These studies raise the possibility of molecular mechanistic studies on human prostatic development through the use of tissue recombinants composed of mutant mouse UGM combined with human fetal prostatic epithelium. Our compilation of human prostatic developmental processes is likely to advance our understanding of the pathogenesis of benign prostatic hyperplasia and prostate cancer as the neoformation of ductal-acinar architecture during normal development is shared during the pathogenesis of benign prostatic hyperplasia and prostate cancer.

BackgroundThe rarity of renal trauma limits its study and the strength of evidence-based guidelines. Although management of renal injuries has shifted toward a nonoperative approach, nephrectomy remains the most common intervention for high-grade renal trauma (HGRT). We aimed to describe the contemporary management of HGRT in the United States and also evaluate clinical factors associated with nephrectomy after HGRT.MethodsFrom 2014 to 2017, data on HGRT (American Association for the Surgery of Trauma grades III-V) were collected from 14 participating Level-1 trauma centers. Data were gathered on demographics, injury characteristics, management, and short-term outcomes. Management was classified into three groups-expectant, conservative/minimally invasive, and open operative. Descriptive statistics were used to report management of renal trauma. Univariate and multivariate logistic mixed effect models with clustering by facility were used to look at associations between proposed risk factors and nephrectomy.ResultsA total of 431 adult HGRT were recorded; 79% were male, and mechanism of injury was blunt in 71%. Injuries were graded as III, IV, and V in 236 (55%), 142 (33%), and 53 (12%), respectively. Laparotomy was performed in 169 (39%) patients. Overall, 300 (70%) patients were managed expectantly and 47 (11%) underwent conservative/minimally invasive management. Eighty-four (19%) underwent renal-related open operative management with 55 (67%) of them undergoing nephrectomy. Nephrectomy rates were 15% and 62% for grades IV and V, respectively. Penetrating injuries had significantly higher American Association for the Surgery of Trauma grades and higher rates of nephrectomy. In multivariable analysis, only renal injury grade and penetrating mechanism of injury were significantly associated with undergoing nephrectomy.ConclusionExpectant and conservative management is currently utilized in 80% of HGRT; however, the rate of nephrectomy remains high. Clinical factors, such as surrogates of hemodynamic instability and metabolic acidosis, are associated with nephrectomy for HGRT; however, higher renal injury grade and penetrating trauma remain the strongest associations.Level of evidencePrognostic/epidemiologic study, level III; Therapeutic study, level IV.

BACKGROUND:The rarity of renal trauma limits its study and the strength of evidence-based guidelines. Although management of renal injuries has shifted toward a nonoperative approach, nephrectomy remains the most common intervention for high-grade renal trauma (HGRT). We aimed to describe the contemporary management of HGRT in the United States and also evaluate clinical factors associated with nephrectomy after HGRT. METHODS:From 2014 to 2017, data on HGRT (American Association for the Surgery of Trauma grades III-V) were collected from 14 participating Level-1 trauma centers. Data were gathered on demographics, injury characteristics, management, and short-term outcomes. Management was classified into three groups-expectant, conservative/minimally invasive, and open operative. Descriptive statistics were used to report management of renal trauma. Univariate and multivariate logistic mixed effect models with clustering by facility were used to look at associations between proposed risk factors and nephrectomy. RESULTS:A total of 431 adult HGRT were recorded; 79% were male, and mechanism of injury was blunt in 71%. Injuries were graded as III, IV, and V in 236 (55%), 142 (33%), and 53 (12%), respectively. Laparotomy was performed in 169 (39%) patients. Overall, 300 (70%) patients were managed expectantly and 47 (11%) underwent conservative/minimally invasive management. Eighty-four (19%) underwent renal-related open operative management with 55 (67%) of them undergoing nephrectomy. Nephrectomy rates were 15% and 62% for grades IV and V, respectively. Penetrating injuries had significantly higher American Association for the Surgery of Trauma grades and higher rates of nephrectomy. In multivariable analysis, only renal injury grade and penetrating mechanism of injury were significantly associated with undergoing nephrectomy. CONCLUSION:Expectant and conservative management is currently utilized in 80% of HGRT; however, the rate of nephrectomy remains high. Clinical factors, such as surrogates of hemodynamic instability and metabolic acidosis, are associated with nephrectomy for HGRT; however, higher renal injury grade and penetrating trauma remain the strongest associations. LEVEL OF EVIDENCE:Prognostic/epidemiologic study, level III; Therapeutic study, level IV.

BackgroundEpidemiological studies have shown that bicycle trauma is associated with genitourinary (GU) injuries. Our objective is to characterize GU-related bicycle trauma admitted to a level I trauma center.Materials and methodsWe queried a prospective trauma registry for bicycle injuries over a 20-year period. Patient demographics, triage data, operative interventions and hospital details were collected.ResultsIn total, 1659 patients were admitted with major bicycle trauma. Of these, 48 cases involved a GU organ, specifically the bladder (n=7), testis (n=6), urethra (n=3), adrenal (n=4) and/or kidneys (n=36). The median age of cyclists with GU injuries was 29 (range 5-70). More men were injured versus women (35 versus 13). GU-related bicycle trauma involved a motor vehicle in 52% (25/48) of injuries. The median injury severity score for GU-related bicycle trauma was 17 (range 1-50). The median number of concomitant organ injuries was 2 (range 0-6), the most common of which was the lungs (13/48, 27%) and ribs (13/48, 27%). The majority of GU injured cyclists were admitted to an ICU (15/48, 31%) or hospital floor (12/48, 25%). Operative intervention for a GU-related trauma was low (12/48, 25%). The most common GU organ injured was the kidney (36/48, 75%) however most were managed nonoperatively (33/36, 92%). Bladder injuries most often required operative intervention (6/7, 86%). Mortality following GU-related bicycle trauma was low (2/48, 4%).ConclusionsIn a large series of bicycle trauma, GU organs were injured in 3% of cases. The majority of cases were managed non-operatively and mortality was low.

BackgroundEpidemiological studies have shown that bicycle trauma is associated with genitourinary (GU) injuries. Our objective is to characterize GU-related bicycle trauma admitted to a level I trauma center.Materials and methodsWe queried a prospective trauma registry for bicycle injuries over a 20-year period. Patient demographics, triage data, operative interventions and hospital details were collected.ResultsIn total, 1659 patients were admitted with major bicycle trauma. Of these, 48 cases involved a GU organ, specifically the bladder (n=7), testis (n=6), urethra (n=3), adrenal (n=4) and/or kidneys (n=36). The median age of cyclists with GU injuries was 29 (range 5-70). More men were injured versus women (35 versus 13). GU-related bicycle trauma involved a motor vehicle in 52% (25/48) of injuries. The median injury severity score for GU-related bicycle trauma was 17 (range 1-50). The median number of concomitant organ injuries was 2 (range 0-6), the most common of which was the lungs (13/48, 27%) and ribs (13/48, 27%). The majority of GU injured cyclists were admitted to an ICU (15/48, 31%) or hospital floor (12/48, 25%). Operative intervention for a GU-related trauma was low (12/48, 25%). The most common GU organ injured was the kidney (36/48, 75%) however most were managed nonoperatively (33/36, 92%). Bladder injuries most often required operative intervention (6/7, 86%). Mortality following GU-related bicycle trauma was low (2/48, 4%).ConclusionsIn a large series of bicycle trauma, GU organs were injured in 3% of cases. The majority of cases were managed non-operatively and mortality was low.

PurposeHigh-dose-rate (HDR) brachytherapy alone is an effective treatment option for patients with early-stage prostate cancer. The purpose of this study was to quantify patient-reported short- and long-term toxicity and quality of life (QOL) after HDR monotherapy.Methods and materialsThirty-nine consecutive men between May 2001 and January 2012 were identified for this analysis. All patients underwent definitive HDR monotherapy for favorable prostate cancer to a total dose of 3150 cGy in three fractions, 3800 cGy in four fractions, or 3850 in five fractions. Patient-reported genitourinary function was assessed before HDR, during an acute period after treatment (within 90 days of HDR), and on long-term followup using the American Urological Association International Prostate Symptom Score, a urinary QOL Likert questionnaire, and the Sexual Health Inventory for Men questionnaire. Regression analyses were performed using the ordinary least squares method.ResultsWith median followup of 57 months, biochemical progression-free survival was 100%. There were no grade ≥3 toxicities. Dose to the urethra and bladder, as well as prostate size and intraprostatic urethra length were predictive for short-term changes in QOL. Advanced patient age was predictive for worse sexual function on both acute and long-term followup.ConclusionsToxicity after HDR monotherapy for prostate cancer is acceptable. Patients with larger prostates, longer intraprostatic urethras, and greater doses to the bladder and urethra may experience worse acute urinary QOL. Older patients may experience greater impairment in sexual function in the short and long terms.

PurposeHigh-dose-rate (HDR) brachytherapy alone is an effective treatment option for patients with early-stage prostate cancer. The purpose of this study was to quantify patient-reported short- and long-term toxicity and quality of life (QOL) after HDR monotherapy.Methods and materialsThirty-nine consecutive men between May 2001 and January 2012 were identified for this analysis. All patients underwent definitive HDR monotherapy for favorable prostate cancer to a total dose of 3150 cGy in three fractions, 3800 cGy in four fractions, or 3850 in five fractions. Patient-reported genitourinary function was assessed before HDR, during an acute period after treatment (within 90 days of HDR), and on long-term followup using the American Urological Association International Prostate Symptom Score, a urinary QOL Likert questionnaire, and the Sexual Health Inventory for Men questionnaire. Regression analyses were performed using the ordinary least squares method.ResultsWith median followup of 57 months, biochemical progression-free survival was 100%. There were no grade ≥3 toxicities. Dose to the urethra and bladder, as well as prostate size and intraprostatic urethra length were predictive for short-term changes in QOL. Advanced patient age was predictive for worse sexual function on both acute and long-term followup.ConclusionsToxicity after HDR monotherapy for prostate cancer is acceptable. Patients with larger prostates, longer intraprostatic urethras, and greater doses to the bladder and urethra may experience worse acute urinary QOL. Older patients may experience greater impairment in sexual function in the short and long terms.

PurposeTo report early clinical outcomes of high-dose-rate interstitial image-guided brachytherapy (BT) in the definitive management of locally advanced cervical cancer.MethodsWe retrospectively analyzed 31 locally advanced cervical cancer patients treated at our institution between January 2010 and April 2013. About 88% had advanced disease based on the International Federation of Gynecology and Obstetrics guidelines, and 87% received concurrent chemotherapy. All patients were treated with external beam radiation therapy to a median dose of 45 Gy (range, 39.6-58 Gy) before receiving BT. High-dose-rate BT was delivered in a single implant to a median dose of 6 Gy × five fractions to a CT-defined volume. Median total equivalent 2-Gy dose, dose covered by 90% of the high-risk clinical target volume (HR-CTV D90), and HR-CTV were 84, 87.4, and 49.9 cc, respectively. Kaplan-Meier method was used for actuarial survival analysis, and toxicity was graded using Common Terminology Criteria for Adverse Events, version 4.0.ResultsMedian followup was 19.3 months. Two-year actuarial local control, regional control, and distant metastasis (DM) were 90%, 93%, and 23.6%, respectively. Two-year disease-free survival was 55%. Genitourinary, gastrointestinal, or gynecologic Grade 3 toxicity was seen in 5 patients (3 T4a and 2 T3b) for crude rates of 13%, 7%, and 3%, respectively. Stratifying HR-CTV by 30 cc and then by HR-CTV D90 of 90 Gy showed that 100% of the local failures, regional failures, DM, and G3 toxicity occurred in >30 cc group. The rate of DM was also significantly higher in the >30 cc group (p = 0.036).ConclusionsAn interstitial approach can achieve excellent outcomes in cases where intracavitary and/or hybrid approaches are either not suitable or not available.

PurposeTo report early clinical outcomes of high-dose-rate interstitial image-guided brachytherapy (BT) in the definitive management of locally advanced cervical cancer.MethodsWe retrospectively analyzed 31 locally advanced cervical cancer patients treated at our institution between January 2010 and April 2013. About 88% had advanced disease based on the International Federation of Gynecology and Obstetrics guidelines, and 87% received concurrent chemotherapy. All patients were treated with external beam radiation therapy to a median dose of 45 Gy (range, 39.6-58 Gy) before receiving BT. High-dose-rate BT was delivered in a single implant to a median dose of 6 Gy × five fractions to a CT-defined volume. Median total equivalent 2-Gy dose, dose covered by 90% of the high-risk clinical target volume (HR-CTV D90), and HR-CTV were 84, 87.4, and 49.9 cc, respectively. Kaplan-Meier method was used for actuarial survival analysis, and toxicity was graded using Common Terminology Criteria for Adverse Events, version 4.0.ResultsMedian followup was 19.3 months. Two-year actuarial local control, regional control, and distant metastasis (DM) were 90%, 93%, and 23.6%, respectively. Two-year disease-free survival was 55%. Genitourinary, gastrointestinal, or gynecologic Grade 3 toxicity was seen in 5 patients (3 T4a and 2 T3b) for crude rates of 13%, 7%, and 3%, respectively. Stratifying HR-CTV by 30 cc and then by HR-CTV D90 of 90 Gy showed that 100% of the local failures, regional failures, DM, and G3 toxicity occurred in >30 cc group. The rate of DM was also significantly higher in the >30 cc group (p = 0.036).ConclusionsAn interstitial approach can achieve excellent outcomes in cases where intracavitary and/or hybrid approaches are either not suitable or not available.

ObjectiveTo describe epidemiologic features of sports-related genitourinary (GU) injuries and determine patient cohorts and particular sporting activities associated with increased GU injury risk.Materials and methodsThe National Electronic Injury Surveillance System, a data set validated to provide a probability sample of injury-related US emergency department (ED) presentations, was analyzed to characterize GU injuries between 2002 and 2010. A total of 13,851 observations were analyzed to derive national estimates.ResultsBetween 2002 and 2010, an estimated 137,525 individuals (95% confidence interval, 104,490-170,620) presented to US EDs with GU injuries sustained during sporting activities. Nearly three-quarters of injuries occurred in the pediatric population. The most common product involved was a bicycle, representing approximately one-third of injuries in both adult and pediatric populations. Injuries related to team sports such as football, baseball or softball, basketball, and soccer were also common, particularly among boys where they represented a combined third of all injuries. Eighty-nine percent of all patients were evaluated and treated in the ED without inpatient admission. The large majority of injuries involved the external genitalia (60%), and significant injuries of paired GU organs (kidneys and testicles) requiring inpatient admission were rare (8.5%).ConclusionSports-related GU injuries are most commonly sustained during the use of a bicycle. However, there are other associated activities with identifiable high-risk cohorts, products, and situations. Consumers, practitioners, and injury-prevention experts can use our epidemiologic data to prioritize and develop strategies aimed at the prevention and limitation of such injuries, particularly when counseling at-risk cohorts, such as those with solitary kidneys or testicles.

ObjectiveTo describe epidemiologic features of sports-related genitourinary (GU) injuries and determine patient cohorts and particular sporting activities associated with increased GU injury risk.Materials and methodsThe National Electronic Injury Surveillance System, a data set validated to provide a probability sample of injury-related US emergency department (ED) presentations, was analyzed to characterize GU injuries between 2002 and 2010. A total of 13,851 observations were analyzed to derive national estimates.ResultsBetween 2002 and 2010, an estimated 137,525 individuals (95% confidence interval, 104,490-170,620) presented to US EDs with GU injuries sustained during sporting activities. Nearly three-quarters of injuries occurred in the pediatric population. The most common product involved was a bicycle, representing approximately one-third of injuries in both adult and pediatric populations. Injuries related to team sports such as football, baseball or softball, basketball, and soccer were also common, particularly among boys where they represented a combined third of all injuries. Eighty-nine percent of all patients were evaluated and treated in the ED without inpatient admission. The large majority of injuries involved the external genitalia (60%), and significant injuries of paired GU organs (kidneys and testicles) requiring inpatient admission were rare (8.5%).ConclusionSports-related GU injuries are most commonly sustained during the use of a bicycle. However, there are other associated activities with identifiable high-risk cohorts, products, and situations. Consumers, practitioners, and injury-prevention experts can use our epidemiologic data to prioritize and develop strategies aimed at the prevention and limitation of such injuries, particularly when counseling at-risk cohorts, such as those with solitary kidneys or testicles.

Among children, the incidence of bicycle-related genitourinary (GU) injuries was 448 per 100 000 (95% CI 383 to 514) and, among adults, was 53 per 100 000 (95% CI 36 to 71). Although children sustained more injuries, adults were more likely to being admitted to the hospital for the GU injury (OR 1.95, 95% CI 1.13 to 3.37). Children sustain nearly 10 times more GU injuries due to bicycles than adults, but adults have higher odds of sustaining injuries requiring admission.

Among children, the incidence of bicycle-related genitourinary (GU) injuries was 448 per 100 000 (95% CI 383 to 514) and, among adults, was 53 per 100 000 (95% CI 36 to 71). Although children sustained more injuries, adults were more likely to being admitted to the hospital for the GU injury (OR 1.95, 95% CI 1.13 to 3.37). Children sustain nearly 10 times more GU injuries due to bicycles than adults, but adults have higher odds of sustaining injuries requiring admission.

This article reviews recent publications evaluating the current epidemiology of urologic trauma. The authors briefly explain databases that have been recently used to study this patient population and then discuss each genitourinary organ individually, utilizing the most relevant and up-to-date information published for each one. The conclusion of the article briefly discusses possible future research and development areas pertaining to the topic.

This article reviews recent publications evaluating the current epidemiology of urologic trauma. The authors briefly explain databases that have been recently used to study this patient population and then discuss each genitourinary organ individually, utilizing the most relevant and up-to-date information published for each one. The conclusion of the article briefly discusses possible future research and development areas pertaining to the topic.

PurposeWe describe the epidemiological features of adult genitourinary injuries related to consumer products and determined the patient cohorts, products and situations associated with increased genitourinary injury risk.Materials and methodsThe National Electronic Injury Surveillance System, a data set validated to provide a probability sample of injury related emergency department presentations in the United States, was analyzed to characterize genitourinary injuries from 2002 to 2010. We analyzed 3,545 observations to derive national estimates.ResultsAn estimated 142,144 adults (95% CI 115,324-168,964) presented to American emergency departments with genitourinary injuries from 2002 to 2010. Of the injuries 69% occurred in men. A large majority of injuries involved the external genitalia. The most common categories of products involved were sporting items in 30.2% of cases, clothing articles in 9.4% and furniture in 9.2%. The highest prevalence of injury was at ages 18 to 28 years (37.5%), which was most often related to sports equipment, such as bicycles. Older cohorts (age greater than 65 years) more commonly sustained injuries during falls and often in the bathroom during use of a shower or tub. Of all patients 88% were evaluated and treated in the emergency department without inpatient admission, although the admission rate increased with increasing patient age.ConclusionsAcute genitourinary injury is often associated with common consumer items and with identifiable high risk cohorts, products and situations. Consumers, practitioners and safety champions can use our epidemiological data to prioritize and develop strategies aimed at the prevention, limitation and informed treatment of such injuries.

PurposeWe describe the epidemiological features of adult genitourinary injuries related to consumer products and determined the patient cohorts, products and situations associated with increased genitourinary injury risk.Materials and methodsThe National Electronic Injury Surveillance System, a data set validated to provide a probability sample of injury related emergency department presentations in the United States, was analyzed to characterize genitourinary injuries from 2002 to 2010. We analyzed 3,545 observations to derive national estimates.ResultsAn estimated 142,144 adults (95% CI 115,324-168,964) presented to American emergency departments with genitourinary injuries from 2002 to 2010. Of the injuries 69% occurred in men. A large majority of injuries involved the external genitalia. The most common categories of products involved were sporting items in 30.2% of cases, clothing articles in 9.4% and furniture in 9.2%. The highest prevalence of injury was at ages 18 to 28 years (37.5%), which was most often related to sports equipment, such as bicycles. Older cohorts (age greater than 65 years) more commonly sustained injuries during falls and often in the bathroom during use of a shower or tub. Of all patients 88% were evaluated and treated in the emergency department without inpatient admission, although the admission rate increased with increasing patient age.ConclusionsAcute genitourinary injury is often associated with common consumer items and with identifiable high risk cohorts, products and situations. Consumers, practitioners and safety champions can use our epidemiological data to prioritize and develop strategies aimed at the prevention, limitation and informed treatment of such injuries.

PurposeWe describe the epidemiological features of pediatric genitourinary injuries, and determine the products and events that may predict an increased risk of genitourinary injury during childhood.Materials and methodsThe National Electronic Injury Surveillance System was queried to identify children 18 years or younger who sustained genitourinary injuries and presented to emergency departments in the United States between 2002 and 2010. Demographics and injury characteristics of these children were analyzed. Analyses were performed with adjustments for sample weighting and the stratified survey design. All data are reported as national estimates along with 95% confidence intervals.ResultsBased on 10,286 actual cases, an estimated 252,392 children (95% CI 205,579-299,194) sustained genitourinary injuries during the 9-year study period. Children 4 to 7 years old were most frequently injured (36.8% of all injuries), followed by those 8 to 11 years old (20.6%). Girls comprised 55% of the injured children. The yearly incidence of genitourinary injuries was stable across the period studied. The most commonly injured organs were female external genitalia (37.7%), penises (21.6%) and testicles (12%). Genitourinary injuries were most commonly associated with sporting and exercise equipment (35.7%), furniture (15.5%) and clothing items (11.9%). Of the patients 91% were treated at the emergency department and discharged home.ConclusionsGenitourinary injuries in children result in approximately 28,000 emergency department visits yearly. Efforts should be made to decrease the risk of genitourinary injuries in children by promoting the use of protective gear and safer product selection for those at greatest risk for injury.

PurposeWe describe the epidemiological features of pediatric genitourinary injuries, and determine the products and events that may predict an increased risk of genitourinary injury during childhood.Materials and methodsThe National Electronic Injury Surveillance System was queried to identify children 18 years or younger who sustained genitourinary injuries and presented to emergency departments in the United States between 2002 and 2010. Demographics and injury characteristics of these children were analyzed. Analyses were performed with adjustments for sample weighting and the stratified survey design. All data are reported as national estimates along with 95% confidence intervals.ResultsBased on 10,286 actual cases, an estimated 252,392 children (95% CI 205,579-299,194) sustained genitourinary injuries during the 9-year study period. Children 4 to 7 years old were most frequently injured (36.8% of all injuries), followed by those 8 to 11 years old (20.6%). Girls comprised 55% of the injured children. The yearly incidence of genitourinary injuries was stable across the period studied. The most commonly injured organs were female external genitalia (37.7%), penises (21.6%) and testicles (12%). Genitourinary injuries were most commonly associated with sporting and exercise equipment (35.7%), furniture (15.5%) and clothing items (11.9%). Of the patients 91% were treated at the emergency department and discharged home.ConclusionsGenitourinary injuries in children result in approximately 28,000 emergency department visits yearly. Efforts should be made to decrease the risk of genitourinary injuries in children by promoting the use of protective gear and safer product selection for those at greatest risk for injury.

Schistosoma haematobium is the etiologic agent for urogenital schistosomiasis, a major source of morbidity and mortality for more than 112 million people worldwide. Infection with S. haematobium results in a variety of immunopathologic sequelae caused by parasite oviposition within the urinary tract, which drives inflammation, hematuria, fibrosis, bladder dysfunction, and increased susceptibility to urothelial carcinoma. While humans readily develop urogenital schistosomiasis, the lack of an experimentally-tractable model has greatly impaired our understanding of the mechanisms that underlie this important disease. We have developed an improved mouse model of S. haematobium urinary tract infection that recapitulates several aspects of human urogenital schistosomiasis. Following microinjection of purified S. haematobium eggs into the bladder wall, mice consistently develop macrophage-rich granulomata that persist for at least 3 months and pass eggs in their urine. Importantly, egg-injected mice also develop urinary tract fibrosis, bladder dysfunction, and various urothelial changes morphologically reminiscent of human urogenital schistosomiasis. As expected, S. haematobium egg-induced immune responses in the immediate microenvironment, draining lymph nodes, and systemic circulation are associated with a Type 2-dominant inflammatory response, characterized by high levels of interleukin-4, eosinophils, and IgE. Taken together, our novel mouse model may help facilitate a better understanding of the unique pathophysiological mechanisms of epithelial dysfunction, tissue fibrosis, and oncogenesis associated with urogenital schistosomiasis.

Urinary tract interventions can lead to multiple complications in the renal collecting system, includingretained foreign bodies from endourologic or percutaneous procedures, such as stents, nephrostomytubes, and others. We report a case of very delayed erosion of embolization coils migrating into therenal pelvis, acting as a nidus for stone formation, causing mild obstruction and finally leading to grosshematuria roughly 18 years post transarterial embolization. History is significant for a remoteunsuccessful endopyelotomy attempt that required an urgent embolization. [West J Emerg Med.2012;13(1):127–130.]

Schistosoma haematobium is the etiologic agent for urogenital schistosomiasis, a major source of morbidity and mortality for more than 112 million people worldwide. Infection with S. haematobium results in a variety of immunopathologic sequelae caused by parasite oviposition within the urinary tract, which drives inflammation, hematuria, fibrosis, bladder dysfunction, and increased susceptibility to urothelial carcinoma. While humans readily develop urogenital schistosomiasis, the lack of an experimentally-tractable model has greatly impaired our understanding of the mechanisms that underlie this important disease. We have developed an improved mouse model of S. haematobium urinary tract infection that recapitulates several aspects of human urogenital schistosomiasis. Following microinjection of purified S. haematobium eggs into the bladder wall, mice consistently develop macrophage-rich granulomata that persist for at least 3 months and pass eggs in their urine. Importantly, egg-injected mice also develop urinary tract fibrosis, bladder dysfunction, and various urothelial changes morphologically reminiscent of human urogenital schistosomiasis. As expected, S. haematobium egg-induced immune responses in the immediate microenvironment, draining lymph nodes, and systemic circulation are associated with a Type 2-dominant inflammatory response, characterized by high levels of interleukin-4, eosinophils, and IgE. Taken together, our novel mouse model may help facilitate a better understanding of the unique pathophysiological mechanisms of epithelial dysfunction, tissue fibrosis, and oncogenesis associated with urogenital schistosomiasis.

Hypospadias is one of the most common congenital anomalies in the United States, occurring in approximately 1 in 250 newborns or roughly 1 in 125 live male births. It is the result of arrested development of the urethra, foreskin, and ventral surface of the penis where the urethral opening may be anywhere along the shaft, within the scrotum, or in the perineum. The only treatment is surgery. Thus, prevention is imperative. To accomplish this, it is necessary to determine the etiology of hypospadias, the majority of which have been classified as idiopathic. In this paper we briefly describe the normal development of the male external genitalia and review the prevalence, etiology, risk factors, and epidemiology of hypospadias. The majority of hypospadias are believed to have a multifactorial etiology, although a small percentage do result from single gene mutations. Recent findings suggest that some hypospadias could be the result of disrupted gene expression. Discoveries about the antiandrogenic mechanisms of action of some contemporary-use chemicals have provided new knowledge about the organization and development of the urogenital system and may provide additional insight into the etiology of hypospadias and direction for prevention.

Hypospadias is one of the most common congenital anomalies in the United States, occurring in approximately 1 in 250 newborns or roughly 1 in 125 live male births. It is the result of arrested development of the urethra, foreskin, and ventral surface of the penis where the urethral opening may be anywhere along the shaft, within the scrotum, or in the perineum. The only treatment is surgery. Thus, prevention is imperative. To accomplish this, it is necessary to determine the etiology of hypospadias, the majority of which have been classified as idiopathic. In this paper we briefly describe the normal development of the male external genitalia and review the prevalence, etiology, risk factors, and epidemiology of hypospadias. The majority of hypospadias are believed to have a multifactorial etiology, although a small percentage do result from single gene mutations. Recent findings suggest that some hypospadias could be the result of disrupted gene expression. Discoveries about the antiandrogenic mechanisms of action of some contemporary-use chemicals have provided new knowledge about the organization and development of the urogenital system and may provide additional insight into the etiology of hypospadias and direction for prevention.

A population-based case-control study was conducted in men aged 60 or less to assess the risk of prostate cancer associated with vasectomy and other factors. Data were obtained from 216 case-control pairs by telephone interviews; this number represented 55% of all eligible cases. The matched pairs relative risk (RR) for vasectomy in ever married men was 1.4 with a 95% confidence interval (CI) of 0.9-2.3. There was a positive association between the number of years since vasectomy and prostate cancer risk (1-sided P = 0.01). Early age at first sexual intercourse was associated with increased prostate cancer risk (age less than 17 vs. 21+, RR = 2.3, 95% CI = 1.3, 4.0) but there were no consistent associations with number of sexual partners or frequency of sexual intercourse. Cigarette smoking was also associated with increased risk of prostate cancer (RR = 1.9, 95% CI = 1.2, 3.0) and there was a positive dose-response relationship with years of smoking (1-sided P = 0.001). We discuss the possible implication of the low response rate on each of these findings. To determine whether the association with vasectomy might have a hormonal basis, we compared levels of testosterone (T) and testosterone binding globulin-binding capacity (TeBG-bc) in 33 of the vasectomized control men with levels in 33 non-vasectomized controls of the same age, weight and height. T levels were higher in vasectomized than in non-vasectomized controls (1-sided P = 0.06). The ratio of T to TeBG-bc (an index of bioavailable T) was 13.5% higher in vasectomized men (1-sided P = 0.03).

A population-based case-control study was conducted in men aged 60 or less to assess the risk of prostate cancer associated with vasectomy and other factors. Data were obtained from 216 case-control pairs by telephone interviews; this number represented 55% of all eligible cases. The matched pairs relative risk (RR) for vasectomy in ever married men was 1.4 with a 95% confidence interval (CI) of 0.9-2.3. There was a positive association between the number of years since vasectomy and prostate cancer risk (1-sided P = 0.01). Early age at first sexual intercourse was associated with increased prostate cancer risk (age less than 17 vs. 21+, RR = 2.3, 95% CI = 1.3, 4.0) but there were no consistent associations with number of sexual partners or frequency of sexual intercourse. Cigarette smoking was also associated with increased risk of prostate cancer (RR = 1.9, 95% CI = 1.2, 3.0) and there was a positive dose-response relationship with years of smoking (1-sided P = 0.001). We discuss the possible implication of the low response rate on each of these findings. To determine whether the association with vasectomy might have a hormonal basis, we compared levels of testosterone (T) and testosterone binding globulin-binding capacity (TeBG-bc) in 33 of the vasectomized control men with levels in 33 non-vasectomized controls of the same age, weight and height. T levels were higher in vasectomized than in non-vasectomized controls (1-sided P = 0.06). The ratio of T to TeBG-bc (an index of bioavailable T) was 13.5% higher in vasectomized men (1-sided P = 0.03).