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Objective This study identifies trajectories of parent depressive symptoms after having a child born with genital atypia due to a disorder/difference of sex development (DSD) or congenital adrenal hyperplasia (CAH) and across the first year postgenitoplasty (for parents who opted for surgery) or postbaseline (for parents who elected against surgery for their child). Hypotheses for four trajectory classes were guided by parent distress patterns previously identified among other medical conditions. Methods Participants included 70 mothers and 50 fathers of 71 children diagnosed with a DSD or CAH with reported moderate to high genital atypia. Parents were recruited from 11 US DSD specialty clinics within 2 years of the child’s birth and prior to genitoplasty. A growth mixture model (GMM) was conducted to identify classes of parent depressive symptoms over time. Results The best fitting model was a five-class linear GMM with freely estimated intercept variance. The classes identified were termed “Resilient,” “Recovery,” “Chronic,” “Escalating,” and “Elevated Partial Recovery.” Four classes have previously been identified for other pediatric illnesses; however, a fifth class was also identified. The majority of parents were classified in the “Resilient” class (67.6%). Conclusions This study provides new knowledge about the trajectories of depressive symptoms for parents of children with DSD. Future studies are needed to identify developmental, medical, or familial predictors of these trajectories.

Parents of children with Disorders of Sex Development (DSD) report significant psychological distress, including posttraumatic stress symptoms (PTSS), with mothers consistently reporting higher rates of psychological distress than fathers. However, psychological factors contributing to PTSS in both parents are not well understood. The present study sought to fill this gap in knowledge by examining PTSS and illness uncertainty, a known predictor of psychological distress, in parents of children recently diagnosed with DSD. Participants were 52 mothers (M(age) = 32.55 years, SD = 5.08) and 41 fathers (M(age) = 35.53 years, SD = 6.78) of 53 infants (M(age) = 9.09 months, SD = 6.19) with DSD and associated atypical genital development. Participants were recruited as part of a larger, multisite study assessing parents’ psychosocial response to their child’s diagnosis of DSD. Parents completed measures of illness uncertainty and PTSS. Mothers reported significantly greater levels of PTSS, but not illness uncertainty, than fathers, and were more likely than fathers to report clinical levels of PTSS (21.2% compared to 7.3%). Hierarchical regression revealed that parent sex, undiagnosed or unclassified DSD status, and illness uncertainty were each associated with PTSS. The overall model accounted for 23.5% of the variance associated with PTSS. Interventions targeting illness uncertainty may be beneficial for parents of children with newly diagnosed DSD.

Summary Introduction Differences of sex development (DSD) are congenital conditions in which there is atypical chromosomal, gonadal and/or phenotypic sex. A phenotype of severe genital atypia in patients raised as male is a relatively rare occurrence and standards for management are lacking. Decision making for early surgical planning in these rare cases includes, but is not limited to, degree of atypia, location of testes, and presence of Mϋllerian remnants. In this study we describe surgical approaches and short-term outcomes for masculinizing genitoplasty in moderate to severe genital atypia in young patients raised male, for whom parents opted for early surgery. Methods This NIH-sponsored study is an ongoing, observational, multicenter investigation assessing medical, surgical and psychological outcomes in children and their parents affected by atypical genitalia due to DSD. Participants were prospectively enrolled from 12 children's hospitals across the United States that specialize in DSD care. Criteria for child enrollment were a Quigley score of 3–6 in those with a 46, XY or 45,X/46, XY chromosome complement, age Results Of the 31 participants, 30 underwent hypospadias repair and 1 patient did not undergo a genitoplasty procedure. The majority of participants (22) received a staged hypospadias repair. Seventeen complications were identified in 12 of the 31 children (41%) at 12 months of follow up. Glans dehiscence and urethrocutaneous fistula were the most common complications. Orchiopexy was performed in 14 (44%) and streak gonads were removed in 4 (13%) participants. Both parents and surgeons reported improved cosmesis after surgery when compared to baseline. Conclusion Genitoplasty was chosen by parents for the majority of children eligible for study. No single surgical approach for masculinizing moderate to severe genital ambiguity in young patients with 46, XY or 45,X/46, XY DSD was adopted by all surgeons. Complications occurred in 41% of those who underwent genitoplasty for severe hypospadias. Overall, appearance of the genitals, as determined by parents and surgeons, improved following genitoplasty. Outcomes of early genitoplasty are needed to guide families when making decisions about such procedures for their young children. Download : Download high-res image (286KB) Download : Download full-size image Summary Figure . River plot comparing Likert cosmesis score over time for mothers, fathers, and surgeons. Panel A includes all patients in the cohort.

Objective A subset of parents of children with disorders/differences of sex development (DSD) including ambiguous genitalia experience clinically elevated levels of anxious and depressive symptoms. Research indicates that uncertainty about their child’s DSD is associated with parent psychosocial distress; however, previous studies have been cross-sectional or correlational in nature. The current study is the first to examine the longitudinal trajectory of the relationship between caregiver-perceived uncertainty about their child’s DSD and caregiver anxious and depressive symptoms across the first 12 months following genital surgery in young children, or if surgery was not performed, the first 12 months following study entry. Methods One hundred and thirteen caregivers (Mage = 32.12; 57.5% mothers; 72.6% Caucasian) of children (N = 70; Mage = 9.81 months; 65.7% female) with DSD were recruited from 12 DSD specialty clinics in the United States. Caregivers completed psychosocial measures at baseline, 6 and 12 months following genitoplasty, or study entry if parents elected not to have surgery for their child. Results Caregiver illness uncertainty and both anxious and depressive symptoms were highest at baseline and decreased over time (ps < .05). Caregiver illness uncertainty predicted symptoms of anxious and depressive symptoms across all time points (ps < .05). Conclusions Caregivers’ perceptions of uncertainty about their child’s DSD are highest soon after diagnosis, and uncertainty continues to predict both anxious and depressive symptoms across time. Thus, the initial diagnostic period is a critical time for psychological assessment and intervention, with parent illness uncertainty being an important clinical target.

Purpose Little is known about the phenotypes, diagnoses, and sex of rearing of infants with atypical genital development in the United States. As part of a multicenter study of these infants, we have provided a baseline report from US difference/disorder of sex development clinics describing the diagnoses, anatomic features, and sex of rearing. We also determined whether consensus guidelines are followed for sex designation in the United States. Methods Eligible participants had moderate-to-severe genital atypia, were aged

Based on the hypothesis that bioscaffold permeability is a major factor in determining the outcome of histologically complete and functional bladder regeneration, we evaluated regeneration processes of four-layer porcine small intestinal submucosa (SIS) construct; and compared results between rat bladders augmented with single-layer SIS bioscaffolds. Sprague-Dawley female rats were subjected to hemi-cystectomy followed by anastomosis of a patch of either single- or four-layer porcine SIS. Permeability was analyzed in situ using magnetic resonance imaging (MRI) at post-operative days 7 and 14. Bladder sections excised at days 7, 14, 28, and 56 post-operation Samples were assessed by HE and Masson's trichrome stains. Urothelial differentiation was analyzed using cytokeratin AE1/AE3, and uroplakin III (UPIII). In addition, quantitative and qualitative evaluations of neutrophils, mast cells, eosinophils, and macrophages were performed using anti-myeloperoxidase, Alcian blue, Giemsa stain, and anti-CD68 staining methods, respectively. Four-layer SIS was consistently impermeable as evidenced by the absence of intravesical administered gadolinium with diethylenetriaminepentacetate (Gd-DTPA) contrast signal in peripheral regions of augmented bladders compared with single-layer SIS bioscaffold. Elevated and sustained eosinophil and neutrophil infiltrations were prominent in four-layered SIS-augmented bladders compared with single-layer SIS with comparable impermeability. Delayed but consistent urothelial regeneration and differentiation were observed in four-layer SIS-augmented bladders; and urothelial differentiation was observed at day 56 post-augmentation. In conclusion, four-layer SIS enacts an elevated inflammatory response along with extended urothelial regeneration. Four-layer SIS may activate a different but yet to be identified mechanism for inflammatory responses. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1960-1969, 2019.

Background/Aims: Parents of children born with disorders of sex development (DSD) often experience anxiety, but risk factors, including parental perception of the severity of their child’s DSD, have not been examined. We hypothesized that severity of illness (SOI) ratings would relate to parental anxiety, and would be higher for parents of children with a potentially life-threatening DSD (e.g., 21-hydroxylase deficiency). Methods: Eighty-nine parents (Mage = 33.0, 56.2% mothers) of 51 children (Mage in months = 8.7) with a DSD including ambiguous genitalia were recruited from 12 specialized DSD clinics. Parents completed questionnaires prior to genitoplasty, 6 months post-genitoplasty, and 12 months post-genitoplasty (if completed). Data were analyzed with linear mixed modeling. Results: Parental anxiety decreased over time, χ2(1) = 10.14, p < 0.01. A positive relationship between SOI and anxiety was found, with SOI being a strong predictor of anxiety (b = 0.53, p < 0.01; χ2[1] = 5.33, p < 0.05). An SOI by time interaction indicated SOI had an increasing effect on anxiety over time, b = 0.06, p < 0.05; χ2(1) = 6.30, p < 0.05. There was no diagnosis by SOI interaction. Conclusion: Parental anxiety decreased over time, but those with higher SOI ratings reported greater initial anxiety followed by slower resolution over time. Underlying etiology of DSD had no effect on the relationship between SOI and anxiety.

To assess the outcomes of "watering can" ureterocele puncture (WCP), a technique previously associated with decreased incidence of de novo vesicoureteral reflux (VUR), as a durable option for management of ureteroceles and to determine the need for subsequent surgery for VUR following watering can puncture.We retrospectively reviewed records of 55 consecutive endoscopic ureterocele procedures performed at our institution from 1999 to 2015. The WCP was performed using a holmium laser fiber to make 10-20 puncture holes through the ureterocele. Follow-up data were collected on infection, de novo VUR in the affected renal moiety and the need for further treatment and surgery.Of 55 patients who underwent endoscopic ureterocele management, 34 underwent WCP and 21 patients underwent either incision or puncture. Median follow-up was 3.4 and 2.8 years in the incision and puncture groups, respectively. Both groups had similar rates of ureterocele decompression (88% vs 90%; P .05) and improvement in hydronephrosis (82% vs 81%; P .05). The WCP group had a significantly decreased rate of de novo VUR (32% vs 67%; P .05) and of subsequent surgery due to de novo VUR (38% vs 71%; P .05). The average grade of de novo VUR was lower in the WCP group (1.4 vs 2.8; P .05).Our study shows that the endoscopic WCP successfully decompresses the obstructing ureterocele and results in a decreased incidence of de novo VUR and ultimately in fewer invasive procedures for the patient. This update demonstrates the durable outcomes of this novel technique.

Augmentation enterocystoplasty remains the gold standard surgical bladder reconstruction procedure to increase the capacity and compliance of dysfunctional bladders. Since the use of the patient's intestine has severe risks of complications, alternative biodegradable matrices have been explored. Porcine small intestinal submucosa (SIS) has gained immense interests in bladder reconstruction due to its favorable properties. However, trials have shown inconsistent regeneration with SIS, attributed to the heterogeneity in microstructures and mechanical properties. We hypothesize that uneven SIS permeability to urine is a factor responsible for the inconsistency. We measured permeability to urine in situ using a contrast enhanced-magnetic resonance imaging (MRI), and evaluated urothelium regeneration using immunohistochemical staining of urothelial cell markers in SIS-augmented rat bladders. Results showed significant differences in permeability among SIS-augmented rat bladders. Commercial SIS scaffolds were then categorized into nonleaky and leaky groups based on MRI results. Hematoxylin and eosin staining showed higher numbers of inflammatory cells in leaky SIS on day 14 relative to nonleaky SIS. In addition, trichrome staining showed major changes in the distribution of collagen on day 28 between SIS-augmented bladder groups. Furthermore, expressions of urothelium-associated markers (cytokeratins AE1/AE3, claudin 4, and uroplakin III) were completed in bladders augmented with nonleaky SIS, whereas limited urothelial differentiation was noticed in leaky SIS-augmented bladders at post-augmentative day 14. These results show that scaffold permeability to urine may be responsible for variations in regenerative capacity of porcine SIS. Applications of MRI technique will be helpful to understand a relationship between biomaterial property and regenerative capacity. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1778-1787, 2018.

Published cohorts of children with vesicoureteral reflux placed on antibiotic prophylaxis differ in baseline characteristics and methodology. These data have been combined in meta-analyses to derive treatment recommendations. We analyzed these cohorts in an attempt to understand the disparate outcomes reported.A total of 18 studies were identified from 1987 to 2013. These series retrospectively or prospectively evaluated children with vesicoureteral reflux who were on long-term antibiotic prophylaxis. Presenting demographic data, criteria and methods of evaluation were tabulated. Outcomes were compared, specifically recurrent urinary infections and renal scarring.Significant differences identified in baseline characteristics included gender, circumcision status and reflux grade, and differences in methodology included evaluation of bowel and bladder dysfunction, method of urine collection, definition of urinary infection, measurement of compliance and means of identifying renal scarring. Cohorts with larger numbers of uncircumcised boys had more breakthrough urinary infections. Infection and renal scarring rates were higher in series with higher grades of reflux. Bagged urine specimens were allowed in 6 series, rendering the data suspect. Children with bowel and bladder dysfunction were excluded from 3 cohorts, and bowel and bladder dysfunction was correlated with outcome in only 1 cohort. Compliance was monitored in only 6 studies.Subpopulations and methodologies vary significantly in published series of children with vesicoureteral reflux on antibiotic prophylaxis. It is inappropriate to combine outcomes data from these series in a meta-analysis, which would serve to blur distinctions between these subpopulations. Broad recommendations or guidelines based on meta-analyses should be viewed with caution.

Purpose: Interstitial cystitis/bladder pain syndrome is a bladder pain disorder associated with voiding symptomatology and other systemic chronic pain disorders. Currently diagnosing interstitial cystitis/bladder pain syndrome is complicated as patients present with a wide range of symptoms, physical examination findings and clinical test responses. One hypothesis is that interstitial cystitis symptoms arise from increased bladder permeability to urine solutes. This study establishes the feasibility of using contrast enhanced magnetic resonance imaging to quantify bladder permeability in patients with interstitial cystitis.Materials and Methods: Permeability alterations in bladder urothelium were assessed by intravesical administration of the magnetic resonance imaging contrast agent Gd-DTPA (Gd-diethylenetriaminepentaacetic acid) in a small cohort of patients. Magnetic resonance imaging signal intensity in patient and control bladders was compared regionally and for entire bladders.Results: Quantitative ...

INTRODUCTION: Individuals with bladder and cloacal exstrophy are at increased risk for kidney disease, renal failure, and bladder complications. Given the social implications and sensitive nature of the disease, these patients are also at risk for psychosocial problems. Lack of regular medical follow-up visits may pose serious risks to their long-term health status. The aim of this study is determine what factors place an affected individual at risk for limited long term follow up. MATERIALS AND METHODS: We identified all patients with bladder or cloacal exstrophy seen by the pediatric urology department at the Oklahoma University Health Sciences Center (OUHSC) between January 1996 and August 2016. Patient data included demographics, insurance coverage, distance from patient’s home to the clinic, medical and surgical history, and the date of their last clinic visit. Two groups for comparison were (1) those that had been seen within the last 2 years, and (2) those that were counted as failing to maintain follow-up because 2 or more years had passed since their last clinic visit. These groups were compared using the Student t-test, the chisquare test, or the Fisher exact test and p < 0.05 was treated as significant for the purposes of discussion. RESULTS AND DISCUSSION: Ninety-one patients with bladder or cloacal exstrophy were seen by the pediatric urology department between January 1996 and August 2016. Of the 91 patients, 24 left the clinic for known reasons thus leaving 67 patients that were considered for analyses: 51 had been seen within the last 2 years while 16 were counted as lost to follow-up. These two groups (active and lost to follow-up) did not differ significantly for age at last clinic visit, distance between family’s home and clinic, history of bladder reconstruction, sex, or insurance status. There was a significant difference between the two groups in the medical complexity of their condition. The group active in urological care had more patients with cloacal exstrophy and additional anomalies than the group lost to follow-up. CONCLUSIONS: Patients with bladder exstrophy and cloacal exstrophy are less likely to maintain annual follow-up visits with their urologist if they have a simpler diagnosis requiring fewer surgical interventions. For patients with exstrophy, regular clinic visits prioritizing education and psychosocial support may prevent hospitalizations, emergency interventions, and poor overall health outcomes. To maintain contact with the medical team and promote optimal health outcomes, a social worker or care coordinator/educator may play an integral part in addressing the unique needs of this population.

BACKGROUND: A substudy of the Management of Myelomeningocele Study evaluating urological outcomes was conducted. METHODS: Pregnant women diagnosed with fetal myelomeningocele were randomly assigned to either prenatal or standard postnatal surgical repair. The substudy included patients randomly assigned after April 18, 2005. The primary outcome was defined in their children as death or the need for clean intermittent catheterization (CIC) by 30 months of age characterized by prespecified criteria. Secondary outcomes included bladder and kidney abnormalities observed by urodynamics and renal/bladder ultrasound at 12 and 30 months, which were analyzed as repeated measures. RESULTS: Of the 115 women enrolled in the substudy, the primary outcome occurred in 52% of children in the prenatal surgery group and 66% in the postnatal surgery group (relative risk [RR]: 0.78; 95% confidence interval [CI]: 0.57–1.07). Actual rates of CIC use were 38% and 51% in the prenatal and postnatal surgery groups, respectively (RR: 0.74; 95% CI: 0.48–1.12). Prenatal surgery resulted in less trabeculation (RR: 0.39; 95% CI: 0.19–0.79) and fewer cases of open bladder neck on urodynamics (RR: 0.61; 95% CI: 0.40–0.92) after adjustment by child’s gender and lesion level. The difference in trabeculation was confirmed by ultrasound. CONCLUSIONS: Prenatal surgery did not significantly reduce the need for CIC by 30 months of age but was associated with less bladder trabeculation and open bladder neck. The implications of these findings are unclear now, but support the need for long-term urologic follow-up of patients with myelomeningocele regardless of type of surgical repair.

There is a demand for tissue engineering of the bladder needed by patients who experience a neurogenic bladder or idiopathic detrusor overactivity. To avoid complications from augmentation cystoplasty, the field of tissue engineering seeks optimal scaffolds for bladder reconstruction. Naturally derived biomaterials as well as synthetic and natural polymers have been explored as bladder substitutes. To improve regenerative properties, these biomaterials have been conjugated with functional molecules, combined with nanotechology, or seeded with exogenous cells. Although most studies reported complete and functional bladder regeneration in small-animal models, results from large-animal models and human clinical trials varied. For functional bladder regeneration, procedures for biomaterial fabrication, incorporation of biologically active agents, introduction of nanotechnology, and application of stem-cell technology need to be standardized. Advanced molecular and medical technologies such as next generation sequencing and magnetic resonance imaging can be introduced for mechanistic understanding and non-invasive monitoring of regeneration processes, respectively.

PURPOSE: Malone antegrade continence enema has been a successful and widely used procedure for achieving fecal continence in children. We present data on the previously uninvestigated issue of patient and caregiver regret following surgery for intractable constipation and fecal incontinence. MATERIALS AND METHODS: We reviewed all patients undergoing antegrade continence enema or cecostomy creation at a single institution between 2006 and 2016. Patients and caregivers were assessed for decisional regret using the Decisional Regret Scale. Results were correlated with demographics, surgical outcomes and complications. RESULTS: A total of 81 responses (49 caregivers and 32 patients) were obtained. Mean followup was 49 months. Decisional regret was noted in 43 subjects (53%), including mild regret in 38 (47%) and moderate to severe regret in 5 (6%). No statistical difference in regret was noted based on gender, complications or performance of concomitant procedures. On regression analysis incontinence was strongly associated with decisional regret (OR 4.4, 95% CI 1.1–18.1, p

Summary Introduction Prior studies of outcomes following genitoplasty have reported high rates of surgical complications among children with atypical genitalia. Few studies have prospectively assessed outcomes after contemporary surgical approaches. Objective The current study reported the occurrence of early postoperative complications and of cosmetic outcomes (as rated by surgeons and parents) at 12 months following contemporary genitoplasty procedures in children born with atypical genitalia. Study design This 11-site, prospective study included children aged ≤2 years, with Prader 3–5 or Quigley 3–6 external genitalia, with no prior genitoplasty and non-urogenital malformations at the time of enrollment. Genital appearance was rated on a 4-point Likert scale. Paired t-tests evaluated differences in cosmesis ratings. Results Out of 27 children, 10 were 46,XY patients with the following diagnoses: gonadal dysgenesis, PAIS or testosterone biosynthetic defect, severe hypospadias and microphallus, who were reared male. Sixteen 46,XX congenital adrenal hyperplasia patients were reared female and one child with sex chromosome mosaicism was reared male. Eleven children had masculinizing genitoplasty for penoscrotal or perineal hypospadias (one-stage, three; two-stage, eight). Among one-stage surgeries, one child had meatal stenosis (minor) and one developed both urinary retention (minor) and urethrocutaneous fistula (major) ( Summary Figure ). Among two-stage surgeries, three children developed a major complication: penoscrotal fistula, glans dehiscence or urethral dehiscence. Among 16 children who had feminizing genitoplasty, vaginoplasty was performed in all, clitoroplasty in nine, external genitoplasty in 13, urethroplasty in four, perineoplasty in five, and total urogenital sinus mobilization in two. Two children had minor complications: one had a UTI, and one had both a mucosal skin tag and vaginal mucosal polyp. Two additional children developed a major complication: vaginal stenosis. Cosmesis scores revealed sustained improvements from 6 months post-genitoplasty, as previously reported, with all scores reported as good or satisfied. Discussion In these preliminary data from a multi-site, observational study, parents and surgeons were equally satisfied with the cosmetic outcomes 12 months after genitoplasty. A small number of patients had major complications in both feminizing and masculinizing surgeries; two-stage hypospadias repair had the most major complications. Long-term follow-up of patients at post-puberty will provide a better assessment of outcomes in this population. Conclusion In this cohort of children with moderate to severe atypical genitalia, preliminary data on both surgical and cosmetic outcomes were presented. Findings from this study, and from following these children in long-term studies, will help guide practitioners in their discussions with families about surgical management. Download : Download high-res image (236KB) Download : Download full-size image Summary Figure . Surgical complications at 12-month postoperative follow-up, n = 27. *Among the six complications in the masculinizing surgery group, one patient developed both urinary retention (minor) and urethrocutaneous fistula (major). ǂAmong the five complications in the feminizing surgery group, one patient had both a mucosal skin tag (minor) and vaginal mucosal polyp (minor).

PURPOSE: We examined the psychological adjustment of parents of children born with moderate to severe genital atypia 12 months after their child underwent genitoplasty. MATERIALS AND METHODS: Parents were recruited longitudinally from a multicenter collaboration of 10 pediatric hospitals with specialty care for children with disorders/differences of sex development and/or congenital adrenal hyperplasia. Parents completed measures of depressive and anxious symptoms, illness uncertainty, quality of life, posttraumatic stress and decisional regret. RESULTS: Compared to levels of distress at baseline (before genitoplasty) and 6 months after genitoplasty, data from 25 mothers and 20 fathers indicated significant improvements in all psychological distress variables. However, a subset of parents continued endorsing clinically relevant distress. Some level of decisional regret was endorsed by 28% of parents, although the specific decision that caused regret was not specified. CONCLUSIONS: Overall the majority of parents were coping well 1 year after their child underwent genitoplasty. Level of decisional regret was related to having a bachelor’s level of education, increased levels of illness uncertainty preoperatively and persistent illness uncertainty at 12 months after genitoplasty but was unrelated to postoperative complications.

Summary Background The birth of a child with a disorder of sex development (DSD) and atypical genitalia can be traumatizing and isolating for families. Parents of children with DSD are at risk for increased levels of psychological distress, including depression, anxiety, illness uncertainty (IU), post-traumatic stress symptoms (PTSS), and impairments in quality of life (QOL). Our previous report indicated that although the majority of parents of children with atypical genitalia were coping well prior to the child's genitoplasty, approximately 25% of them reported experiencing some type of psychological distress. Objective The current study sought to examine the trajectory of parental psychological distress prior to, and 6 months after their child underwent genitoplasty. Methods Parents were recruited as part of an ongoing, prospective, multi-site study involving 10 pediatric hospitals with specialized care for children with atypical genitalia. Results from 49 parents (27 mothers, 22 fathers) of 28 children (17 female sex of rearing, 11 male sex of rearing) born with atypical genitalia (Prader rating of 3–5 in 46,XX DSD or by a Quigley rating of 3–6 in 46,XY DSD or 45,XO/46,XY) were included in the study. Results There were no significant changes in level of depressive or anxious symptoms or quality of life between baseline and 6-month post-operative follow-up, although mothers continued to report significantly higher levels of depressive symptoms than fathers, and as a group, these parents reported lower QOL than published norms. The level of PTSS significantly decreased for all parents, suggesting that parents may have come through the acute stress phase associated with their child's diagnosis. Finally, while there were no significant changes in IU over the time period, the level of IU for parents of boys actually increased, while parents of girls reported no change (Figure). Conclusion Six months after their child has undergone genitoplasty, the majority of parents report minimal levels of psychological distress. However, a subset of these parents continue to experience significant distress related to their child's diagnosis. Specifically, parents of boys appear to be at increased risk for difficulties, which may be related to either the lack of clinical diagnosis for almost half of these children or the necessity of two-stage surgeries for the majority of them. We will continue collecting data on these families to better understand the trajectory of these adjustment variables. Download : Download high-res image (173KB) Download : Download full-size image Figure . Graphs of significant changes.

Augmentation enterocystoplasty remains the gold standard surgical bladder reconstruction procedure to increase the capacity and compliance of dysfunctional bladders. Since the use of the patient's intestine has severe risks of complications, alternative biodegradable matrices have been explored. Porcine small intestinal submucosa (SIS) has gained immense interests in bladder reconstruction due to its favorable properties. However, trials have shown inconsistent regeneration with SIS, attributed to the heterogeneity in microstructures and mechanical properties. We hypothesize that uneven SIS permeability to urine is a factor responsible for the inconsistency. We measured permeability to urine in situ using a contrast enhanced-magnetic resonance imaging (MRI), and evaluated urothelium regeneration using immunohistochemical staining of urothelial cell markers in SIS-augmented rat bladders. Results showed significant differences in permeability among SIS-augmented rat bladders. Commercial SIS scaffolds were then categorized into nonleaky and leaky groups based on MRI results. Hematoxylin and eosin staining showed higher numbers of inflammatory cells in leaky SIS on day 14 relative to nonleaky SIS. In addition, trichrome staining showed major changes in the distribution of collagen on day 28 between SIS-augmented bladder groups. Furthermore, expressions of urothelium-associated markers (cytokeratins AE1/AE3, claudin 4, and uroplakin III) were completed in bladders augmented with nonleaky SIS, whereas limited urothelial differentiation was noticed in leaky SIS-augmented bladders at post-augmentative day 14. These results show that scaffold permeability to urine may be responsible for variations in regenerative capacity of porcine SIS. Applications of MRI technique will be helpful to understand a relationship between biomaterial property and regenerative capacity. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1778-1787, 2018.

Little data exist about the surgical interventions taking place for children with disorders of sex development (DSD). Most studies that have evaluated cosmetic outcomes after genitoplasty have included retrospective ratings by a physician at a single center.The present study aimed to: 1) describe frequency of sex assignment, and types of surgery performed in a cohort of patients with moderate-to-severe genital ambiguity; and 2) prospectively determine cosmesis ratings by parents and surgeons before and after genital surgery.This prospective, observational study included children aged2 years of age, with no prior genitoplasty at the time of enrollment, moderate-to-severe genital atypia, and being treated at one of 11 children's hospitals in the United States of America (USA). Clinical information was collected, including type of surgery performed. Parents and the local pediatric urologist rated the cosmetic appearance of the child's genitalia prior to and 6 months after genitoplasty.Of the 37 children meeting eligibility criteria, 20 (54%) had a 46,XX karyotype, 15 (40%) had a 46,XY karyotype, and two (5%) had sex chromosome mosaicism. The most common diagnosis overall was congenital adrenal hyperplasia (54%). Thirty-five children had surgery; 21 received feminizing genitoplasty, and 14 had masculinizing genitoplasty. Two families decided against surgery. At baseline, 22 mothers (63%), 14 fathers (48%), and 35 surgeons (100%) stated that they were dissatisfied or very dissatisfied with the appearance of the child's genitalia. Surgeons rated the appearance of the genitalia significantly worse than mothers (P 0.001) and fathers (P ≤ 0.001) at baseline. At the 6-month postoperative visit, cosmesis ratings improved significantly for all groups (P 0.001 for all groups). Thirty-two mothers (94%), 26 fathers (92%), and 31 surgeons (88%) reported either a good outcome, or they were satisfied (see Summary Figure); there were no significant between-group differences in ratings.This multicenter, observational study showed surgical interventions being performed at DSD centers in the USA. While parent and surgeon ratings were discordant pre-operatively, they were generally concordant postoperatively. Satisfaction with postoperative cosmesis does not necessarily equate with satisfaction with the functional outcome later in life.In this cohort of children with genital atypia, the majority had surgery. Parents and surgeons all rated the appearance of the genitalia unfavorably before surgery, with surgeons giving worse ratings than parents. Cosmesis ratings improved significantly after surgery, with no between-group differences.

Before surgery is considered, conservative protocols have to be maximized because twothirds of patients can become continent by clean intermittent catheterization and medication alone. Fecal continence and bowel management is an integral part of spina bifida treatment. Reconstructive lower tract surgery remains the best-studied, most successful, permanent, and long-term satisfactory surgery to deal with urinary and stool incontinence. The urological care of patients with spina bifida consists of 2 components: the medical management with preservation of renal function and the quality-of-life issues with achieving dryness and independence of bladder and bowel management. Both components are equally important for patients to live a healthy and fulfilled life. Continuouseducationandcareofthefamiliesandpatientsarenecessarytomotivatethem for participation in treatment plans and to avoid frustration and unrealistic expectations. Achieving continence is a long road that requires understanding and compliance that is best delivered by a team of specialists.

Total and partial urogenital mobilization procedures are the most common contemporary vaginoplasty surgeries for patients with congenital adrenal hyperplasia, urogenital sinus and cloacal anomalies. There is controversy regarding the urinary continence outcomes of these procedures. We reviewed the urinary continence outcomes of children who underwent total or partial urogenital mobilization at our institution and reviewed the literature to determine the continence rates of these procedures.We retrospectively reviewed 25 patients who underwent total or partial urogenital mobilization with a focus on postoperative continence status. Continence was defined as parental report of full toilet training with no accidents during the day and rare accidents (fewer than 2 per month) at night after age 3 years.A total of 14 congenital adrenal hyperplasia, 5 urogenital sinus and 6 cloacal anomaly cases were managed by total (18) or partial (7) urogenital mobilization procedures with a mean followup of 4.41 years (range 0.21 to 12.1). In our cohort 21 of 22 patients (95.5%) were continent by age 3 years and there were no urinary complications. A total of 111 patients were identified in the literature with congenital adrenal hyperplasia or urogenital sinus, with 107 in 7 studies being continent (96.4%) by age 3 to 4 years. In 4 studies 32 patients were identified with cloacal anomalies who underwent total or partial urogenital mobilization, of whom 28 (87.5%) were continent by age 3 to 4 years.There was no significant difference between total and partial urogenital mobilization procedures regarding postoperative urinary continence in our cohort and the literature. The urinary continence rate was 96% in the congenital adrenal hyperplasia/urogenital sinus group and 89.5% in the cloacal group.

What's known on the subject? and What does the study add? Re-epithelialization demucosa stomach patch is important to prevent the patch being exposed to urine that might cause patch shrinkage and fibrosis formation due to urine-derived chemical irritation. Additionally, Botox A acts by blocking the transmission of nerve impulses to smooth muscles and so paralysing the muscles, which is commonly used to relax muscle for treatment of oesophageal achalasia due to overactive smooth muscle and sphincters of gastrointestinal tract. We fabricated in vitro tissue engineered urothelial mucosa with multi-layers of urothelium and smooth muscle layers seeded on SIS scaffold and then used this cell-scaffold construct to cover nuke gastro patch combining with Botox A for gastrocystoplasty in a canine model. OBJECTIVE • To evaluate the demucosalized stomach patch covered with tissue-engineered urothelium for gastrocystoplasty and to determine whether or not injections of Botox A into the re-epithelialized stomach patch can protect the graft from contraction in a canine bladder reconstruction model. MATERIALS AND METHODS • Gastrocystoplasty was performed in 10 adult beagles after hemi-cystectomy using five types of stomach patch (n= 2 per group): entire stomach patches (group I); demucosalized patches (group II); demucosalized patches covered with cell-free small intestinal submucosa (SIS) (group III); demucosalized patches with urothelial and smooth muscle cell-seeded SIS (group IV); and demucosalized patches with the cell-seeded SIS combined with injections of Botox A (group V). • The bladder volume/pressure and the graft sizes were measured before surgery and again 10 weeks after bladder augmentation. • The graft tissues were examined both histologically and using immunohistochemistry. RESULTS • All dogs survived and their gastric grafts were all vital with a good blood supply. • Gastric metaplasia of urothelium appeared on the top of stomach mucosa patches in two animals in group I. There was calcification formation at the centre of the graft in one animal in group II. • As compared with urothelium that was partially covered over with stomach patches in groups II and III, stratified urothelium completely covered the demucosalized gastric patches in groups IV and V. • There was less shrinkage of the stomach grafts in groups I and V, which shrank to half of their original size, than of the stomach grafts in groups II, III, and IV, which shrank significantly to one-quarter of their original sizes. CONCLUSIONS • Botox A injections appear to protect the graft contraction in the re-epithelialized stomach flaps. • The gastrocystoplasty using demucosalized patches covered with tissue-engineered urothelial mucosa combined with an injection of Botox A could have clinical potential for use in bladder reconstruction.

Objective Our goals were to assess long-term outcome for patients with posterior urethral valves (PUV) and determine the impact of the timing of diagnosis. Patients and methods We reviewed the hospital records for patients with PUV treated in 1994–2008. Only those patients diagnosed, treated surgically, and followed clinically at our center were included. Results There were 52 patients with PUV. Thirty-nine were diagnosed by 1 year of age (early diagnosis cohort), while 13 were diagnosed after 1 year (late diagnosis cohort). Mean follow up after valve operation was 7.2 years (range 15 months–14 years). Chronic renal failure rates were not statistically different between the early and late diagnosis groups after surgical intervention: 48% (14/29) vs 25% (3/12), P = 0.30. Among the early diagnosis cases, 10% (3/29) eventually required renal transplant, while no child in the late diagnosis group has developed end-stage renal disease to date ( P = 0.55). Conclusions Gestational age at diagnosis is an important predictor of postnatal renal outcome. Our results suggest that diagnosis after 1 year of age is associated with a lower risk of developing renal insufficiency on long-term follow up.

What's known on the subject? and What does the study add? Urinary bladder tissue can be produced by several regenerative techniques although consistent regeneration remains elusive and no single protocol is superior to the others. Small intestinal submucosa has been used as substrate for regeneration in several models and allows for full-thickness bladder regeneration. Nanotechnology has been applied to impart specific physical and biological properties onto biological substrates. Nanoparticles composed of PLGA can be modified by the addition of hyaluronic acid and can be added to SIS. This modified SIS demonstrates a potential improvement in biological activity as suggested by more consistent smooth muscle regeneration in a canine model of bladder regeneration. This study demonstrates both the feasibilty and potential of synthetically-modified natural biomaterials. OBJECTIVE • To determine if hyaluronic acid (HA) can be incorporated into porcine small intestinal submucosa (SIS) through poly (lactide-co-glycolide-acid) (PLGA) nanoparticles to improve the consistency of the naturally derived biomaterial and promote bladder tissue regeneration. METHODS • Beagle dogs were subjected to 40% partial cystectomy followed by bladder augmentation with commercial SIS or HA-PLGA-modified SIS. • Urodynamic testing was performed before and after augmentation to assess bladder volume. • A scoring system was created to evaluate gross and histological presentations of regenerative bladders. RESULTS • All dogs showed full-thickness bladder regeneration. • Histological assessment showed improved smooth muscle regeneration in the HA-PLGA-modified SIS group. • For both groups of dogs, urodynamics and graft measurements showed an approximate 40% reduction in bladder capacity and graft size from pre-augmentation to post-regeneration measurements. • Application of the scoring system and statistical analysis failed to show a significant difference between the groups. CONCLUSIONS • SIS can be modified through the addition of HA-PLGA nanoparticles. The modified grafts showed evidence of improved smooth muscle regeneration on histological assessment, although this difference was not evident on a novel grading scale. • The volume loss and graft shrinkage experienced are consistent with previous models of SIS bladder regeneration at the 10-week time point. • Additional research into the delivery of HA and the long-term benefits of HA on bladder regeneration is needed to determine the full benefit of HA-PLGA-modified SIS. In addition, a more objective biochemical characterization will be needed to evaluate the quality of regeneration.

Fetal megacystis, an abnormally enlarged bladder identified at any gestational age, may be transient and resolve spontaneously or may be an early manifestation of bladder outlet obstruction. Anterior urethral valves are the most common cause of the rare condition of congenital obstruction of the anterior urethra. Herein is reported the prenatal observation and postnatal management of a case of megacystis with anterior urethral valves. The etiology is reviewed and strategies recommended for patients with these rare entities.

OBJECTIVE To examine the histological differences in the inflammatory response and regenerative outcomes of distal vs proximal porcine small intestinal submucosa (SIS) grafts in the rat bladder, as SIS from distal small intestine yields reliable and reproducible bladder regeneration, while SIS from proximal portions of small intestine does not provide similar results. MATERIALS AND METHODS In all, 30 Sprague-Dawley rats underwent hemi-cystectomy followed by anastomosis of a bladder patch of SIS prepared from either distal or proximal small intestine. After bladder harvest, immunohistochemistry was used to quantify mast cells, eosinophils, macrophages, and neutrophils (PMNs). Total cell count per unit area was compared across the time course in univariate and logistic regression modelling. RESULTS There were more eosinophils and mast cells in proximal SIS grafts, while there were more macrophages and PMNs in distal SIS grafts (all P

Objective To assess parental satisfaction with e-mail consultations and fetal outcomes after consultation for offspring with 45,X/46,XY mosaicism. Patients and methods A chart review was performed of prenatal and postnatal e-mail consultations concerning 45,X/46,XY mosaicism at our institution. Prenatally, mosaicism was detected by amniocentesis; postnatally by phenotype and subsequent genotyping. Parents e-mailed us for a second opinion after internet searches. Follow-up parental satisfaction was evaluated by e-mail. Results E-mail consultation occurred in six prenatal and eight postnatal cases. One of the eight postnatal cases had a prenatal diagnosis but without our second opinion. In 7/8 postnatal cases, abnormal neonatal phenotype was evaluated by genotyping. Termination of pregnancy was a consideration in all six prenatal consultations, although not discussed by us. One fetus was stillborn. Postnatal karyotype was mosaic in 11/13 surviving neonates. Phenotypes in surviving fetuses were normal male (2/13), hypospadias and an undescended testis or streak gonad (9/13), female with mild clitoral hypertrophy (1/13), and normal female (1/13). The stillborn fetus was noted only to have a penis. Conclusion All parents reported in follow up that e-mail consultations provided them with enhanced clinical information, allowing them to make better informed clinical decisions.

We reviewed our initial results with complete primary repair of exstrophy in regard to continence status and the need for subsequent continence procedures.We performed a retrospective review of our surgical records from 1996 to 2008 to identify all patients with bladder exstrophy managed at our center.Sixteen children were closed successfully. Six patients (37.5%) experienced complications: umbilical hernias in two, transient penopubic fistula in three, and subcoronal fistula due to meatal stenosis in one. Of the 12 males, seven (58.3%) were left with a hypospadias at the time of primary closure. Two (22.2%) children required a formal bladder neck reconstruction to achieve continence. Bladder augmentation and continent catheterizable stoma was performed in four cases (44.4%), and bladder neck injection in one case (11.1%). Bladder neck closure was also performed in another child following primary closure. Three of these children are continent and void spontaneously (33.3%). The remaining six require clean intermittent catheterization four to six times a day, resulting in four (44.4%) being continent. The number of continence procedures and mean number per patient were 15 and 1.66, respectively.Our early experience with this technique has been encouraging, with few major complications, a highly successful closure rate and a cosmetically normal result.

BACKGROUND Human prostate cancer LNCaP and PC-3 cell lines have been extensively used to study prostate cancer progression and to develop therapeutic agents. Although LNCaP and PC-3 cells are generally assumed to represent early and late stages of prostate cancer, respectively, there is limited information regarding gene expression patterns between these two cell lines and its relationship to prostate cancer.

Objectives To present our long-term results with complete penile disassembly for epispadias repair. Methods We performed a retrospective review of our surgical records from 1996 to 2008. Group 1 included 12 patients who had undergone complete penile disassembly as a part of complete primary repair of bladder exstrophy, and group 2 included 9 patients with isolated epispadias. Results The mean follow-up after epispadias repair was 58.2 and 58.6 months for groups 1 and 2, respectively. At the last follow-up visit, 83.3% of group 1 and 100% of group 2 were completely dry or had dry intervals >4 hours. Of the 21 children, 7 (33.3%) experienced minor complications, 4 in group 1 and 3 in group 2. No ischemic changes of the glans penis or corporal bodies were observed in either group. Erectile function was preserved in all patients. Conclusions Complete penile disassembly technique can achieve total or near complete urinary continence, decreasing the morbidity of multiple procedures and potentially allowing children to achieve continence at an earlier age. Our experience, with a mean follow-up of nearly 5 years and an overall complication rate of 33.3%, is comparable to that of other published series.

Tissue engineering provides exciting therapeutic potential in urology. Urinary bladder regeneration is the most heavily researched aspect of tissue engineering in urology. Recent clinical research demonstrated the feasibility of bladder regeneration in children with neurogenic bladders. Despite this success, the ideal materials and methods for tissue engineering in urology have not been identified. We review the advances that have been made in tissue engineering in urology over the past 3 years. We particularly emphasize advances in our understanding of the raw materials and the methodology currently employed in urologic tissue engineering protocols.

We determined the rate of stone clearance in children following percutaneous nephrolithotomy, endoscopic assessment of residual stone and the judicious use of second look nephroscopy.We retrospectively reviewed the charts of all children undergoing percutaneous nephrolithotomy from 1996 to 2007. Cases were reviewed for pertinent details including preoperative and postoperative imaging, specifics of the procedure and followup. On completion of percutaneous nephrolithotomy the collecting system was assessed via combined nephrostogram and direct nephroscopy. If the collecting system could not be completely visualized or all stone fragments could not be cleared, the patient was referred for second look nephroscopy. Any residual stone present on initial followup imaging constituted a treatment failure.A total of 24 patients underwent percutaneous nephrolithotomy for 30 separate renal calculi. Mean patient age was 9.6 years, and mean stone burden was 2.53 cm. The success rate for percutaneous nephrolithotomy (inclusive of second look nephroscopy) was 87%. Of 30 cases 16 were managed by second look nephroscopy, with findings of residual fragments in all 16. Treatment failure was noted in 1 patient without second look nephroscopy and in 3 patients with second look nephroscopy. Of the 4 patients with treatment failure all were eventually rendered stone-free.Second look nephroscopy based on endoscopic findings during initial percutaneous nephrolithotomy is a reliable method of detecting and clearing residual stone fragments. Using such a protocol we achieved a high success rate of stone clearance in a population of patients with a significant stone burden.

Generally, it is recommended that all urachal remnants be excised to avoid recurrent disease and possible malignant transformation later in life. However, spontaneous resolution with no need for further intervention has been reported. We reviewed the experience with urachal remnants at a single institution and evaluated which patients could be treated nonoperatively and which required surgical intervention.We reviewed the medical records and radiographic studies of all patients with urachal remnants from January 1999 to January 2007. Patients were analyzed according to initial presentation, imaging findings and treatment. Serial clinical examinations and radiographic imaging were used to follow patients.An external urachal sinus was found in 9 patients (39.1%) and 1 was surgically excised. Of the 12 urachal cysts (52.2%) 9 ultimately required surgical excision, of which 6 were infected initially. A patent urachus was found in 2 patients, which resolved during an observation period. Radiographic imaging and/or physical examination diagnosed all remnants initially and confirmed complete resolution during followup. Eight of the 10 urachal remnants (80.0%) that resolved developed in patients younger than 6 months. Various accompanying urogenital anomalies were found in 8 patients (34.8%).A small urachal remnant, especially at birth, may be viewed as physiological. Urachal remnants in patients younger than 6 months are likely to resolve with nonoperative management. However, if symptoms persist or the urachal remnant fails to resolve after 6 months of age, it should be excised to prevent recurrent infections.

The definition of interstitial cystitis (IC) has evolved over the years from being a well-defined entity characterized by diagnostic lesion (Hunner’s ulcer) in the urothelium to a clinical diagnosis by exclusion [painful bladder syndrome (PBS)]. Although the etiology is unknown, a central theme has been an association with increased permeability of the bladder. This article reviews the evidence for increased permeability being important to the symptoms of interstitial cystitis/painful bladder syndrome (IC/PBS) and in treating the disorder. Recent work showing cross-communication among visceral organs is also reviewed to provide a basis for understanding IC/PBS as a systemic disorder of a complex, interconnected system consisting of the bladder, bowel and other organs, nerves, cytokine-responding cells and the nervous system.

The angiogenic potential of a biomaterial is a critical factor for successful graft intake in tissue engineering. We developed a modified, rapid and reproducible chicken embryo chorioallantoic membrane (CAM) assay to evaluate the ability of biomaterials in inducing blood vessel density. Five biomaterials including one-layer porcine small intestinal submucosa (SIS), two-layer SIS, four-layer vacuum pressed (VP) SIS, polyglycolic acid (PGA) and PGA modified with poly(lactic-co-glycolic acid) (PLGA) were analyzed. A circular section (1.2 mm diameter) of each biomaterial was placed near a group of blood vessels in the CAM. Blood vessels around the biomaterials were captured with black and white images at 96 h post implantation; and the images were subjected to densitometry evaluation. One-layer SIS induced a significant increase in blood vessel density as compared to the cellulose nitrate negative control, and had the greatest increase in blood vessel density as compared to four-layer VP SIS, PGA, or PLGA modified PGA. Although two-layer SIS has enhanced physical structure for surgical manipulation, its induction in blood vessel density was significantly lower than the one-layer SIS. Stripping the SIS proteins or incubating one-layer SIS with neutralizing antibodies against basic fibroblast growth factor (bFGF) or vascular endothelial growth factor (VEGF) resulted in decreased angiogenesis. Consistent with results obtained from bladder augmentation animal models, these results confirmed that angiogenic growth factors were present in SIS and affected the angiogenic potential of biomaterials. These data also demonstrated that the CAM assay can be used to ascertain methodically the angiogenic potential of biomaterials.

Continent urinary diversion has gained increasing popularity in the pediatric population during the last few decades. In adults, continent diversions are usually needed to replace a bladder after cystectomy for invasive carcinoma. Subsequently, the creation of functional and cosmetically hidden urinary and cecal abdominal stomas has become an integral part of many urinary reconstructive procedures. These techniques, originally developed for pediatric urinary reconstruction have gained increasing popularity for adult patients in need of a continence procedure. In the current manuscript, we review the technical aspects of site selection, mucocutaneous anastomosis, cosmetic appearance, and management of associated complications.

Neuropathic bladder dysfunction results from abnormal development of the spine, spinal cord injuries, or diseases such as diabetics. Patients with neuropathic bladders often require surgical intervention such as bladder reconstruction to improve incontinence and prevent renal damage. Tissue engineering with ex-vivo cultured bladder cells has been suggested as one means for improving bladder function. However, we previously demonstrated that cultured bladder smooth muscle cells (SMCs) derived from neuropathic bladder exhibit and maintain altered pathologic phenotypes in culture. To identify genes that are responsible for the abnormal neuropathic phenotypes specifically elevated cell proliferation, the expression levels of 1,185 genes were compared between cultured SMCs derived from normal and neuropathic bladders using a cDNA array consisting of well-annotated genes. The expression data were analyzed using several methods to identify differentially expressed genes. The resulting sets of differentially expressed genes were examined by pathway analysis to identify the networks that remain abnormal in the culture-stable phenotype of neuropathic SMCs. A total of 18 genes that are differentially expressed between cultured normal and neuropathic bladder SMCs were identified. Of these 17 were up-regulated greater than 2-fold in neuropathic bladder SMCs, six of them along with one gene that was not up-regulated greater than 2-fold in cultured neuropathic bladder SMCs were confirmed and identified by more stringent analysis methods including significance analysis of microarrays, class comparison, and class prediction analyses. The major dysregulated pathways include fibroblast growth factor signaling, PTEN signaling, and integrin signaling. Our results further suggest that altered neuropathic bladder SMC phenotypes is stable in the culture environments and that SMCs derived from diseased bladders may not be appropriate for tissue engineering purpose without modification of pathologically altered genes expression.

PurposeWe examined the psychosocial characteristics of parents of children with disorders of sex development at early presentation to a disorders of sex development clinic. Parental anxiety, depression, quality of life, illness uncertainty and posttraumatic stress symptoms were assessed. Additionally we evaluated the relationship of assigned child gender to parental outcomes.Materials and methodsA total of 51 parents of children with ambiguous or atypical genitalia were recruited from 7 centers specializing in treatment of disorders of sex development. At initial assessment no child had undergone genitoplasty. Parents completed the Cosmetic Appearance Rating Scale, Beck Anxiety Inventory, Beck Depression Inventory, SF-36, Parent Perception of Uncertainty Scale and Impact of Event Scale-Revised.ResultsA large percentage of parents (54.5%) were dissatisfied with the genital appearance of their child, and a small but significant percentage reported symptoms of anxiety, depression, diminished quality of life, uncertainty and posttraumatic stress. Few gender differences emerged.ConclusionsAlthough many parents function well, a subset experience significant psychological distress around the time of diagnosis of a disorder of sex development in their child. Early screening to assess the need for psychosocial interventions is warranted.

During wound healing and fibrocontractive diseases fibroblasts acquire a smooth muscle cell-like phenotype by differentiating into contractile force generating myofibroblasts. We examined whether regulation of myofibroblast contraction in granulation tissue is dominated by Ca2+-induced phosphorylation of myosin light chain kinase or by Rho/Rho kinase (ROCK)-mediated inhibition of myosin light chain phosphatase, similar to that of cultured myofibroblasts. Strips of granulation tissue obtained from rat granuloma pouches were stimulated with endothelin-1 (ET-1), serotonin, and angiotensin-II and isometric force generation was measured. We here investigated ET-1 in depth, because it was the only agonist that produced a long-lasting and strong response. The ROCK inhibitor Y27632 completely inhibited ET-1-promoted contraction and the phosphatase inhibitor calyculin elicited contraction in the absence of any other agonists, suggesting that activation of the Rho/ROCK/myosn light chain phosphatase pathway is critical in regulating in vivo myofibroblast contraction. Membrane depolarization with K+ also stimulated a long-lasting contraction of granulation tissue; however, the amount of force generated was significantly less compared to ET-1. Moreover, K+-induced contraction was inhibited by Y27632. These results are consistent with inhibition of myosin light chain phosphatase by the Rho/ROCK signaling pathway, which would account for the long-duration contraction of myofibroblasts necessary for wound closure.

Type 2 3α-hydroxysteroid dehydrogenase (3α-HSD) is a multi-functional enzyme that possesses 3α-, 17β- and 20α-HSD, as well as prostaglandin (PG) F synthase activities and catalyzes androgen, estrogen, progestin and PG metabolism. Type 2 3α-HSD was cloned from human prostate, is a member of the aldo-keto reductase (AKR) superfamily and was named AKR1C3. In androgen target tissues such as the prostate, AKR1C3 catalyzes the conversion of Δ4-androstene-3,17-dione to testosterone, 5α-dihydrotestosterone to 5α-androstane-3α,17β-diol (3α-diol), and 3α-diol to androsterone. Thus AKR1C3 may regulate the balance of androgens and hence trans-activation of the androgen receptor in these tissues. Tissue distribution studies indicate that AKR1C3 transcripts are highly expressed in human prostate. To measure AKR1C3 protein expression and its distribution in the prostate, we raised a monoclonal antibody specifically recognizing AKR1C3. This antibody allowed us to distinguish AKR1C3 from other AKR1C family members in human tissues. Immunoblot analysis showed that this monoclonal antibody binds to one species of protein in primary cultures of prostate epithelial cells and in LNCaP prostate cancer cells. Immunohistochemistry with this antibody on human prostate detected strong nuclear immunoreactivity in normal stromal and smooth muscle cells, perineurial cells, urothelial (transitional) cells, and endothelial cells. Normal prostate epithelial cells were only faintly immunoreactive or negative. Positive immunoreactivity was demonstrated in primary prostatic adenocarcinoma in 9 of 11 cases. Variable increases in immunoreactivity for AKR1C3 was also demonstrated in non-neoplastic changes in the prostate including chronic inflammation, atrophy and urothelial (transitional) cell metaplasia. We conclude that elevated expression of AKR1C3 is highly associated with prostate carcinoma. Although the biological significance of elevated AKR1C3 in prostatic carcinoma is uncertain, AKR1C3 may be responsible for the trophic effects of androgens and/or PGs on prostatic epithelial cells.

We examine the hypotheses underlying the clinical decision to assign female gender at birth in male neonates with severe phallic inadequacy.A total of 18 genetic males with severe phallic inadequacy were assessed longitudinally for physical, social, psychological and sexual identity development. Diagnoses included cloacal (11) and classic (1) exstrophy, partial androgen resistance (3), mixed gonadal dysgenesis (2) and penile agenesis (1). Neonatal sex assignment was female in 15 and male in 3 patients.All patients demonstrated marked male typical behaviors and interests. Of the 15 female assigned patients 1 died, 1 refused to declare sexual identity or orientation, 1 converted to male before initial evaluation, 1 was reassigned male by the parents and 5 others declared male sexual identity. Thus, of 17 living patients 10 live as males and 6 as females. Of patients 17 years or older only those living as male lived independently. The 4 oldest patients living as male but only 1 patient living as female would discuss sexual orientation-all 5 declared orientation toward females, and 3 of these 4 males had girlfriends or were married. The sexually undeclared patient lived in a residential treatment center because of major behavioral difficulties since age 15. Only patients living as male had dated.This longitudinal study implies that males with severe phallic inadequacy reared male and those reared female but converting to male can have functional psychosocial developmental trajectories. Those reared female have a realistic likelihood of recognizing male sexual identity and converting to male. Those not converting to male appear to have less successful psychosocial developmental trajectories.

Clinically bladder cells used in tissue engineering techniques will come from neuropathic bladders and not normal bladders. We determined if neuropathic bladder smooth muscle (SM) cells (SMCs) retain functional differences when cultured in vitro.Primary cultures of SMCs were established from patients with a neuropathic bladder (5) and a normal bladder (5). Expression of alpha-SM actin and SM myosin heavy chain was determined using immunocytochemical staining and Western blot analysis. Baseline cell proliferation and the mitogenic response to angiotensin II was assessed by cell counting and cell viability assays. Cell contractility was determined for normal and neuropathic SMCs using an in vitro collagen lattice assay. Cell adherence was measured assessed using partial and complete trypsinization assays.Normal and neuropathic SMCs showed similar morphology in culture, and similar patterns of alpha-SM actin and SM myosin expression. Following 10 days of plating under optimal growth conditions the number of neuropathic SMCs was 170% more than normal SMCs. In response to angiotensin II neuropathic SMCs reached 54% of maximal growth capacity as opposed to 30% for normal SMCs (p0.01). Neuropathic SMCs contracted significantly less in 10% serum and calcium ionophore (p0.05), as determined by in vitro contractility assays. Neuropathic SMCs had 19% and 30% less adherent cells than normal SMCs (p0.01) following isotonic solution washes and trypsinization, respectively.These results demonstrate that cultured neuropathic bladder SMCs possess and maintain different characteristics than normal SMCs in vitro. The potential clinical implications of using these cells in conjunction with tissue engineering techniques for the promotion of bladder regeneration requires further investigation.