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Radical nephrectomy combined with contemporary chemotherapeutic and radiation therapy protocols has drastically improved outcomes for children with Wilms tumor. Patients with bilateral disease and a syndrome predisposing to tumor development have necessitated the use of nephron-sparing surgery in select cases. Success in managing these patients has increased the indication for partial nephrectomy, although current guidelines for unilateral Wilms tumor are limited. Given that children are being cured with increasing success, recent focus has shifted to long-term health outcomes in addition to tumor treatment. Specifically, renal function has an impact on long-term cardiovascular health and events. Adult outcomes with partial nephrectomy provide a guideline for a paradigm shift in the management of children with Wilms tumor, particularly with advances in imaging and adjuvant therapy. The data are limited for children undergoing partial nephrectomy for unilateral Wilms tumor and outcomes for larger tumors will need to be studied closely in future trials. Increased utilization of neoadjuvant chemotherapy could further expand the number of patients eligible for partial nephrectomy.

Telemedicine utilization rapidly expanded throughout the coronavirus disease 2019 (COVID-19) pandemic and yielded numerous patient benefits. However, its future remains uncertain, limiting further institutional investments in telemedicine. We aimed to evaluate trends in the volume of telemedicine visits throughout the pandemic and patient factors associated with telemedicine usage to inform the future role of telemedicine in pediatric urology. An Institutional Review Board (IRB)-approved registry of pediatric urology outpatient visits was queried from June 2019 to November 2021 at a single institution. Variables of interest included patient demographics, travel distance for care, insurance status, primary visit diagnosis, and visit type (in-person visits, IPVs; or video visits, VVs). IPVs and VVs were further categorized as new patient visits (NPVs), return patient visits (RPVs), and post-operative visits (post-ops). Monthly trends in descriptive variables were summarized. A total of 51,605 pediatric urology outpatient visits occurred during the study period. Patients had a median age of 5 years [interquartile range (IQR), 1–11] and were predominantly male (71.6%), white (61.6%), and held private insurance (69%). VVs increased substantially from 0% in February 2020 to 100% in April 2020 and then subsequently declined through November 2021, although total visit volumes were increasing throughout the period. As the pandemic progressed, compared to IPVs, VVs were more likely to have an RPV visit type (80% vs. 50%–60%) and longer median travel distance (30+ vs. 14 miles). VVs were less frequently covered by subsidized insurance (20%–30% vs. 50%–70%). In summary, this study found that telemedicine usage has declined since the peak of the COVID-19 pandemic, although its use remains higher than pre-pandemic levels and appears to be associated with RPVs, longer travel distance, and private insurance coverage. Utilization has stabilized as we have emerged from peak pandemic restrictions. Further work is required to elucidate the optimal role of telemedicine and its effects on access to care in pediatric urology.

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.

The medical terminology applied to differences/disorders of sex development has been viewed negatively by some affected individuals. A clinical population of patients with differences/disorders of sex development and their caregivers were surveyed regarding current nomenclature, hypothesizing that those unaffiliated with support groups would have more favorable attitudes.We recruited English and Spanish speaking patients 13 years old or older with differences/disorders of sex development and their caregivers at 5 national tertiary care clinics from July 2016 to December 2018. No diagnoses were excluded. Participants completed a survey rating terminology commonly applied to differences/disorders of sex development. Responses were compared between subgroups, including members vs nonmembers of a support group.Of 185 potential participants approached 133 completed the survey (72% response rate). Congenital adrenal hyperplasia (33%) was the most common diagnosis. "Variation of sex development" was the most liked term (37%) but was not liked more significantly than "disorders of sex development" (27%, p=0.16). No term was liked by a majority of respondents. "Disorders of sex development" (37%) and "intersex" (53%) were the only terms most frequently viewed unfavorably. Support group members were significantly more likely to dislike the term "intersex" (p=0.02) and to like "variation of sex development" (p=0.02).A clinical population of patients and their caregivers had generally neutral attitudes toward nomenclature applied to differences/disorders of sex development. Members of a support group had clearer terminology preferences. "Variation of sex development" was the most liked term, and "disorders of sex development" and "intersex" were the most disliked. No term was liked by most respondents, and no clear alternative to the present nomenclature was identified.

Purpose:Controversy remains within the pediatric urology community regarding adequate duration of followup after hypospadias repair. Some have suggested that minimal long-term followup is necessary...

Testosterone (T) administration prior to hypospadias surgery to increase glans size remains controversial. Understanding T's effect on glans width (GW) is essential to understanding its potential impact on surgical outcomes. We hypothesized that preoperative T in prepubertal boys significantly increases GW at the time of hypospadias surgery.Our single institutional database was queried to identify patients who underwent hypospadias surgery from 2016 to 2020, in which data for T administration and GW were available. Descriptive, nonparametric and categorical statistics were performed as indicated.A total of 579 patients were eligible for analysis. Median age at surgery was 0.9 years (IQR 0.6-1.6). A total of 247/579 patients (42.7%) received T. The median GW at surgery was 15 mm (IQR 13-17). When comparing patients who had T administered to those who did not, we found a significant difference in GW at surgery (16 mm vs 14 mm, p0.001). The median change in GW from the office to surgery was 4 mm for those receiving T vs 0 mm for those not receiving T (p0.001). We identified a greater change in GW from preoperative to intraoperative measurements in patients who received 2 doses of T vs 1 dose (4 mm vs 2 mm, p0.001). A histogram plot revealed the distribution of GW change at surgery.In our prospectively collected cohort of patients undergoing hypospadias surgery, we were able to quantitate the change in GW from preoperative T. Two doses of T resulted in a significant increase in GW vs 1 dose.

INTRODUCTION AND OBJECTIVE:The optimal management for ureteroceles has long been under debate, due to the anatomic variability and severity of this entity. Treatment strategies range from upper pol...

INTRODUCTION AND OBJECTIVE:In 2020, testis-sparing surgery was included in the Testis Cancer AUA Guidelines for adults with masses

IntroductionOsteopenia and osteoporosis have been reported in adults with Complete Androgen Insensitivity Syndrome (CAIS). Little is known about changes in bone mineral density (BMD) in adolescents with CAIS and whether it is affected by early gonadectomy. Body composition data have not been reported.MethodsSingle-center, retrospective study of CAIS adolescents who underwent dual-energy x-ray absorptiometry (DXA) (Hologic, Horizon A). Body composition is presented as lean and fat mass indices (LMI, FMI). Z-scores for lumbar spine areal BMD (LBMD), total body less head (TBLH), bone mineral content (BMC), LMI, and FMI were calculated using female normative data. Results are expressed as median and min, max.ResultsSix females with genetically confirmed CAIS were identified—one with intact gonads and five with history of gonadectomy at 2–11 months. In the subject with intact gonads, LBMD-Z and TBLH BMC-Z were −1.56 and −1.26, respectively, at age 16 years. Among those with gonadectomy, LBMD-Z was −1.8 (−3.59 to 0.49) at age 15.6 years (12–16.8) and decreased in all three subjects who had longitudinal follow-up despite hormone replacement therapy (HRT). Adherence to HRT was intermittent. LMI-Z and FMI-Z were 0.1 (−1.39 to 0.7) and 1.0 (0.22 to 1.49), respectively.ConclusionsThese limited data indicate that adolescents with CAIS have bone mass deficit. Further studies are needed to understand the extent of BMD abnormalities and the effect of gonadectomy, especially early in childhood, and to establish the optimal HRT regimen for bone accrual. Data on lean mass are reassuring.

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.

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 Müllerian 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

An identifiable genetic malformation or predisposition syndrome is present in 18% of Wilms tumor cases. Given this, children with conditions associated with a greater than 1% risk of developing Wilms tumor are recommended to have regular surveillance imaging with renal ultrasound until age 7. Seven years is the recommended screening duration because 95% of cases will occur by this age. We present a case of a child with isolated hemihypertrophy, associated with 5% risk of Wilms tumor, who presented with a tumor after the recommended screening, at age 9, brining into question the age cutoffs currently used.

The risk factors for future infertility in adolescents with varicocele are controversial, and little is known about the association between hormone levels and semen parameters. Semen analysis is likely the closest marker of fertility but may be difficult to obtain in some boys secondary to personal, familial or religious reasons. Identifying other clinical surrogates for abnormal semen parameters may offer an alternative for assessing varicocele severity in these boys. We hypothesized that hormone levels and total testicular volume are predictive of abnormal total motile sperm count.We retrospectively reviewed Tanner 5 boys with palpable left varicoceles who underwent a semen analysis and had serum hormone levels tested (luteinizing hormone, follicle-stimulating hormone, inhibin B, anti-müllerian hormone and/or total testosterone) within a 6-month period. Total testicular volume was also calculated. Abnormal total motile sperm count was defined as9 million sperm per ejaculate.A total of 78 boys (median age 17.2 years, IQR 16.5-18.0) were included. Luteinizing hormone, anti-müllerian hormone and total testosterone were not correlated with any semen analysis parameter. There was a negative correlation between follicle-stimulating hormone and total motile sperm count (ρ -0.35, p=0.004) and positive correlation between inhibin B and total motile sperm count (ρ 0.50, p0.001). Total testicular volume was significantly positively correlated with total motile sperm count (ρ 0.35, p=0.01). ROC analyses revealed an optimal follicle-stimulating hormone cutoff of 2.9, an optimal inhibin B cutoff of 204 and an optimal total testicular volume cutoff of 34.4 cc to predict abnormal total motile sperm count.Total motile sperm count is inversely associated with follicle-stimulating hormone levels, and directly associated with inhibin B levels and total testicular volume. Optimized cutoffs for serum follicle-stimulating hormone, inhibin B and total testicular volume may prove to be reasonable surrogates for total motile sperm count in boys who defer semen analysis for personal or religious/cultural reasons.

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.

INTRODUCTION AND OBJECTIVE:There are ongoing efforts to adopt opioid-sparing analgesic regimens to control post-operative pain in all areas of Urology. Concerns regarding post-operative bleeding ha...

The 22q11.2 deletion syndrome (22q11.2DS) involves multiple organ systems with variable phenotypic expression. Genitourinary tract abnormalities have been noted to be present in up to 30-40% of patients. At our institution, an internationally recognized, comprehensive, and multidisciplinary 22q11.2DS care center has been providing care to these children. We sought to report on the incidence of genitourinary tract anomalies in this large cohort and, therefore, retrospectively reviewed all patients who underwent a complete evaluation from 1992 to March 2017. We identified all children with any genital or urinary tract anomaly. For all children with a diagnosis of hydronephrosis, the underlying etiology was determined, when possible. Overall, 1,073 of 1,267 children with 22q11.2DS underwent renal evaluations at our institution. Hundered Sixty-Two (15.1%) children had structural abnormalities of their kidneys/urinary tracts. The majority of children with hydronephrosis (63%) had isolated upper tract dilation without any additional diagnoses. Boys were significantly more likely to be diagnosed with a genital abnormality than girls (7.7 vs. 0.5%, p < 0.001). Of the 649 boys in the entire cohort, 24 (3.7%) had cryptorchidism and 24 (3.7%) had hypospadias, which was noted to be mild in all except one boy. Overall, findings of hydronephrosis, unilateral renal agenesis, and multicystic dysplastic kidney occur at higher rates than expected in the general population. Given these findings, in addition to routine physical examination, we believe that all patients with 22q11.2DS warrant screening RBUS at time of diagnosis.

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

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.

Summary Introduction Widespread utilization of telemedicine in our practice to date has been limited to the evaluation of certain post-surgical patients. The COVID-19 pandemic acutely stressed our established system and required us to enhance our utilization of telemedicine. We hypothesized that expansion of telemedicine to new and follow up patient visits for pediatric urology could be done effectively in a way that satisfied patient and parental expectations. Materials and methods Using a pre-COVID-19 established telemedicine program based in our electronic medical record (EMR), patients and providers transitioned to primarily virtual visits when clinically appropriate. Guidelines were formulated to direct patient scheduling, provider and staff education was provided, including a process map designed for multiple providers to complete video visits (VV), and the EMR was redesigned to incorporate telehealth terminology. The number of VV per provider was recorded using the electronic medical record, and patient reported outcomes (PRO) were measured using a standardized questionnaire. Results A total of 631 VV met inclusion criteria during the period of May 2018–April 2020. This included 334 follow up, 172 new, and 125 postoperative visits. The median age of patients at time of visit was 7 years (IQR 2–12 years), median visit time was 20 min (IQR 15–30 min), and the median travel distance saved by performing a VV was 12.2 miles (IQR 6.3–26.8 miles). Diagnoses were varied and included the entire breadth of a standard pediatric urology practice. The PRO questionnaire was completed for 325 of those patient visits. Families reported a high overall satisfaction with the video visits (median score of 10 out of 10) and felt that the visit met their child's medical needs. 90% stated that they would strongly recommend a telehealth visit to other families. Patients and parents reported benefits of VV including decreased travel costs and less time taken off from work and school. Conclusion The EMR enabled nimble redirection of clinical care in the setting of a global pandemic. The enhanced use of telemedicine has proved to be an alternative method to provide care for pediatric urology patients. Families indicate a high degree of satisfaction with this technology in addition to significant time and cost savings. Telemedicine should remain a key aspect of medical care and expanded from post-operative visits to new patient and follow up visits, even as we return to our normal practices as the pandemic restrictions soften. Download : Download high-res image (855KB) Download : Download full-size image Summary figure . Program map depicting the sequence of a video visit (VV). The process begins with our scheduling team which provides the necessary information to the family and ensures that they can be scheduled properly. The family is encouraged to conduct the visit in a quiet place with at least one parent and the child present. Relevant records, imaging, and laboratory studies should be uploaded prior to the visit. In addition, pictures and/or videos uploaded by the family prior to the visit can facilitate the examination portion of the visit. VV = video visit; AVS = after visit summary.

Purpose Gonadal damage is a common consequence of treatment for pediatric malignancies. Nononcologic conditions may also utilize treatments with potential impact on fertility. Models for oncology fertility preservation programs have emerged and demonstrate that a multidisciplinary team approach can have a positive impact on referral patterns, appropriate risk counseling, and access to fertility preservation options. Expansion of programmatic breadth is needed, providing improved care to nonmalignant conditions where the disease itself may impact reproductive health or treatment modalities. Methods With support from the Department of Pediatrics Chair's Initiative, a multidisciplinary, hospital-wide Fertility Preservation Service was created at the Children's Hospital of Philadelphia. A centralized team provides fertility consults across the institution, allowing for risk-based counseling and facilitation of fertility preservation options (both standard care and experimental). Results Team structure, consult process, and available fertility options for prepubertal and pubertal males and females are described. Preinitiative and postinitiative referral patterns were analyzed. Postinitiative referrals from divisions outside oncology more than doubled (34% vs. 15% at baseline). Conclusions A comprehensive model for fertility counseling provides accessible, high-value fertility preservation care to pediatric and young adult patients with a wide variety of diagnoses. A centralized point of contact ensures timely referrals and risk-based counseling and streamlines access to fertility preservation procedures.

We present 2 patients found to have ovotesticular disorder of sexual development (otDSD) in late adolescence. Two 15-year-old phenotypically male patients presented to a large pediatric hospital with different complaints: 1 with concern for testicular rupture after a straddle injury; 1 with gynecomastia. Further workup, including imaging and laboratory tests, was performed before surgical exploration. The first patient had unilateral ovotestis, contralateral testis, and SRY-negative 46,XX karyotype. The second patient with gynecomastia had unilateral ovotestis with hemi-uterus and fallopian tube, contralateral ovarian tissue, and 46,XX/47,XXY Klinefelter mosaic karyotype. Although rare, phenotypically normal male patients may present later with ovotesticular disorder of sexual development.

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

Numerous medications can predispose patients to stone formation. Some induce metabolic changes that alter urine chemistries, such as topiramate, which can cause a mixed renal tubular acidosis. Others or their breakdown products form stones composed of the drugs themselves, like those that are renally excreted and become supersaturated in the urine in a favorable environment.1,2 Like all stones, they can cause obstruction and infection. Here we present a case of ampicillin stone formation in an 11-year-old girl during a pelvic reconstructive procedure, which required ureteral stenting to prevent obstruction from an institutional guideline's perioperative antimicrobial dosing. While there are many reports of amoxicillin and ampicillin crystalluria, there is only one account in the literature of an adult with resultant ureteral obstruction requiring intervention.3, 4, 5 Our case is the first report, to our knowledge, in a child, and highlights the potential for significant crystal formation and if unrecognized, complete urinary obstruction. Since ampicillin is a commonly administered perioperatively, awareness of ampicillin stone formation during surgery is important.

OBJECTIVE: To assess the prevalence of therapy-related kidney outcomes in survivors of Wilms tumor (WT). STUDY DESIGN: This prospective cohort study included survivors of WT who were ≥5 years old and ≥1 year from completing therapy, excluding those with pre-existing hypertension or prior dialysis or kidney transplant. Participants completed 24-hour ambulatory blood pressure monitoring (ABPM). Abnormal blood pressure (BP) was defined as ≥90(th) percentile. Masked hypertension was defined as having normal office BP and abnormal ABPM findings. Urine was analyzed for KIM-1, IL-18, EGF, albumin, and creatinine. Estimated glomerular filtration rate (eGFR) was calculated using the bedside CKiD equation. Recent kidney ultrasounds and echocardiograms were reviewed for contralateral kidney size and left ventricular hypertrophy (LVH), respectively. Clinical follow-up data was collected for approximately 2 years following study enrollment. RESULTS: Thirty-two participants (median age 13.6 [IQR: 10.5-16.3] years; 75% ≥Stage 3 WT) were evaluated at a median of 8.7 years (IQR: 6.5-10.8) post-therapy. Twenty-nine participants underwent unilateral radical nephrectomy, 2 bilateral partial nephrectomy, and 1 radical and contralateral partial nephrectomy. 72% received kidney radiotherapy and 75% received doxorubicin. Recent median eGFR was 95.6 ml/min/1.73m(2) (IQR: 84.6-114.0; 11 (34%) had an eGFR

Disorders of sex development (DSD) represent a spectrum of conditions in which chromosomal, gonadal, or anatomic sex are atypical and affect 1 in 4,500-5,000 live births. The diagnosis of DSD raises concerns of tumor risk and treatment as well as future fertility preservation. We review the current understanding of the types of gonadal tumors that arise in DSD patients as well as possible markers and treatment. The goal is to inform the members of the DSD team (urologist, endocrinologist, geneticist, psychologist) of the latest findings regarding malignancy in DSD. PubMed® and Google ScholarTM literature searches were performed of current and past peer-reviewed literature on DSD (intersex) regarding gonadal development and tumor formation/treatment. Relevant reviews and original research articles were examined, including cited references, and a synopsis of the data was generated. DSD patients are at increased risk for the development of testicular carcinoma in-situ (CIS) and germ cell tumors (GCT), including seminoma, non-seminoma, juvenile granulosa cell, gonadoblastoma, and dysgerminoma. Cancer risk factors include Y-chromosomal material and gonadal position, especially for streak gonads. The 46 XX DSD patients [congenital adrenal hyperplasia (CAH)] with no genetic Y-chromosomal material are not at higher risk of cancer. Post-pubertal complete androgen insensitivity syndrome (AIS) patients remain prone to tumor development if the testes remain in the abdomen. Estimates of the risk of GCT in partial AIS for untreated undescended testes may be as high as 50%. The cancer risk of scrotal testes in partial AIS is unknown. CIS occurs almost exclusively in patients with hypovirilization, most notably in AIS. Persistent Mullerian Duct Syndrome (PMDS) confers the usual cancer risk associated with cryptorchidism, but also a possible tumor risk of the Mullerian remnant. Several markers are under investigation for tumor evaluation in the DSD population beyond hCG and AFP (Oct3/4, TSPY, WT-1). The management of patients with DSD is complex and evaluation of tumor risk is aided by advances in genotyping for Y-chromosomal material not evident in traditional karyotyping. More complete genetic screening for DSD patients should increasingly become the standard of care. Developments in pathologic diagnosis will further challenge our traditional understanding of the oncologic management and surveillance of these patients. Future studies utilizing more advanced histologic examination of gonads will improve our understanding of the true incidences of malignancy in this diverse population.

BACKGROUND: 22q11.2 deletion syndrome (22q11.2DS) is caused by recurrent, chromosome specific, low copy repeat mediated copy number losses of chromosome 22q11. The Children’s Hospital of Philadelphia has been involved in the clinical care of individuals with what is now known as 22q11.2DS since our initial report of the association with DiGeorge syndrome in 1982. METHODS: We reviewed the medical records on our continuously growing longitudinal cohort of 1,421 patients with molecularly confirmed 22q11.2DS from 1992 to 2018. RESULTS: Most individuals are Caucasian and older than eight years old. The median age at diagnosis was 360 days. The majority of patients (85%) had typical LCR22A-LCR22D deletions, and only 7% of these typical deletions were inherited from a parent harboring the deletion constitutionally. However, 6% of individuals harbored other nested deletions that would not be identified by traditional 22q11.2 FISH, thus requiring an orthogonal technology to diagnose. Major medical problems included immune dysfunction or allergies (77%), palatal abnormalities (67%), congenital heart disease (64%), gastrointestinal difficulties (65%), endocrine dysfunction (>50%), scoliosis (50%), renal anomalies (16%), and airway abnormalities. Median full-scale IQ was 76, with no significant difference between individuals with and without congenital heart disease or hypocalcemia. Characteristic dysmorphic facial features were present in most, but dermatoglyphic patterns of our cohort are similar to normal controls. CONCLUSIONS: This is the largest longitudinal study of patients with 22q11.2DS, helping to further describe the condition and aid in diagnosis and management. Further surveillance will likely elucidate additional clinically relevant findings as they age.

Maintenance of adult tissues depends on stem cell self-renewal in local niches. Spermatogonial stem cells (SSC) are germline adult stem cells necessary for spermatogenesis and fertility. We show that testicular endothelial cells (TECs) are part of the SSC niche producing glial cell line-derived neurotrophic factor (GDNF) and other factors to support human and mouse SSCs in long-term culture. We demonstrate that FGF-2 binding to FGFR1 on TECs activates the calcineurin pathway to produce GDNF. Comparison of the TEC secretome to lung and liver endothelial cells identified 5 factors sufficient for long-term maintenance of human and mouse SSC colonies in feeder-free cultures. Male cancer survivors after chemotherapy are often infertile since SSCs are highly susceptible to cytotoxic injury. Transplantation of TECs alone restores spermatogenesis in mice after chemotherapy-induced depletion of SSCs. Identifying TECs as a niche population necessary for SSC self-renewal may facilitate fertility preservation for prepubertal boys diagnosed with cancer., Self-renewal of spermatogonial stem cells (SSC) is necessary for spermatogenesis and male fertility. Here the authors identify testicular endothelial cells (TECs) as a source of 5 key growth factors for self-renewal and expansion of human and mouse SSCs.

A longitudinal vaginal septum can be obstructive or nonobstructive. We report on an adult woman who presented with involuntary fluid loss per vagina and had a partially obstructive longitudinal vaginal septum. A 36-year-old nulliparous female presented with malodorous, clear, leakage per vagina that she described as “urinary incontinence.” Examination revealed a fluid-filled fluctuant anterior vaginal wall with a draining sinus. Imaging revealed a solitary right kidney with duplicated ectopic fluid-filled ureters inserting into a partially obstructed left hemivagina with a longitudinal vaginal septum. A longitudinal vaginal septum may present in adulthood with the complaint of urinary incontinence.

Upper pole nephrectomy has been the traditional surgical management of children with poorly functioning upper pole moieties in duplex renal collecting systems having ureteral ectopia and ureterocele. However, ablative surgery confers a risk of functional loss to the remnant moiety due to vasospasm or vascular injury. It was hypothesized that ipsilateral ureteroureterostomy (IUU) is a safe and feasible approach for the management of these patients and that residual function in the obstructed upper pole does not affect surgical outcomes.All patients with duplex systems who underwent IUU between 2010 and 2016 were retrospectively reviewed. Patients were sorted into two groups based on pre-operative imaging: those having10% upper pole moiety function (UPMF) and those having ≥ 10% UPMF. Outcomes assessed were postoperative complications (Clavien-Dindo classification), need for secondary surgery, and radiological outcomes.The study cohort comprised 53 children with ectopia or ureterocele affecting the upper pole in a duplex system, 21 with UPMF10% (median function 0% and median age 1.49 years) and 32 with UPMF ≥ 10% (median function 15% and median age 0.91 years). Median follow-up was 27.4 months and 27.6 months. In both the groups, prenatal hydronephrosis was the most common presentation (57% and 56%, respectively; p = 0.18) followed by urinary tract infection. Mann-Whitney U test comparing the two groups revealed no significant differences in any of the outcomes assessed. No patient required secondary surgery.Ipsilateral ureteroureterostomy is a safe, definitive surgical intervention that preserves the renal architecture in children with duplex collecting systems regardless of upper pole function.

Cryopreservation of testicular tissue with subsequent reimplantation after therapy has the potential to preserve fertility for prepubertal boys with cancer. We present the histology and feasibility of testicular tissue procurement for this novel approach.We performed a prospective cohort study of boys at significant risk for treatment associated gonadotoxicity who were eligible for an experimental research protocol between 2008 and 2011. Open testicular biopsy was performed while the patients were anesthetized for another treatment related procedure. Half of the specimen was reserved for cryopreservation, while the other half was used for research purposes. Semithin sections of the biopsy specimens were evaluated for histological features and compared to age adjusted reference values.A total of 34 boys underwent biopsy between March 2008 and October 2011. Of the patients 29 had solid tumors and 5 underwent hematopoietic stem cell transplantation for benign disease. A total of 27 patients had adequate tissue for histological analysis. Median patient age was 8.7 years (IQR 2.2 to 11.5). All children had either normal (81.5% of patients) or increased (18.5%) numbers of germ cells per tubule for their age. However, 5 of 26 patients (19%) older than 6 months had no evidence of adult dark spermatogonia and 9 of 16 (56%) older than 6 years had no evidence of primary spermatocytes on biopsy, which would be expected based on age norms. These findings are suggestive of abnormal germ cell maturation.The preliminary histological findings of abnormal spermatogenesis maturation in the testes of prepubertal boys with cancer warrants further investigation.