Recommendations for 46,XY Disorders/Differences of Sex Development Across Two Decades: Insights from North American Pediatric Endocrinologists and Urologists.

Clinical decision-making for individuals with 46,XY disorders/differences of sex development (DSD) remains unsettled and controversial. The North American DSD Clinician Survey examines the recommendations of a large group of clinical specialists over the last two decades. Active members of the (Lawson Wilkins) Pediatric Endocrine Society and the Societies for Pediatric Urology were invited to respond to a web-based survey at three different timepoints: 2003-2004 (T1), 2010-2011 (T2), and 2019-2020 (T3). Data from 429 participants in T1, 435 in T2, and 264 in T3 were included in this study. The participants were presented with three XY newborn clinical case scenarios-micropenis, partial androgen insensitivity syndrome, and iatrogenic penile ablation-and asked for clinical management recommendations. The main outcomes assessed included the recommended gender of rearing, surgical decision-maker (parent or patient), timing of genital surgery, and age at which to disclose medical details and surgical history to the patient. For all scenarios, the overwhelming majority recommended rearing as male, including a significant increase across timepoints in those recommending a male gender of rearing for the infant with penile ablation. The proportions recommending female gender of rearing declined significantly across timepoints. In general, most recommended parents (in consultation with the physician) serve as surgical decision-makers, but these proportions declined significantly across timepoints. Recommendations on the timing of surgery varied based on the patient's gender and type of surgery. There has been a shift in recommendations away from the "optimal gender policy" regarding gender of rearing and surgical interventions for patients with XY DSD.

Recommendations for 46,XX Congenital Adrenal Hyperplasia Across Two Decades: Insights from the North American Differences of Sex Development Clinician Survey.

Several aspects of clinical management of 46,XX congenital adrenal hyperplasia (CAH) remain unsettled and controversial. The North American Disorders/Differences of Sex Development (DSD) Clinician Survey investigated changes, over the last two decades, in clinical recommendations by specialists involved in the management of newborns with DSD. Members of the (Lawson Wilkins) Pediatric Endocrine Society and the Societies for Pediatric Urology participated in a web-based survey at three timepoints: 2003-2004 (T1, n = 432), 2010-2011 (T2, n = 441), and 2020 (T3, n = 272). Participants were presented with two clinical case scenarios-newborns with 46,XX CAH and either mild-to-moderate or severe genital masculinization-and asked for clinical recommendations. Across timepoints, most participants recommended rearing the newborn as a girl, that parents (in consultation with physicians) should make surgical decisions, performing early genitoplasty, and disclosing surgical history at younger ages. Several trends were identified: a small, but significant shift toward recommending a gender other than girl; recommending that adolescent patients serve as the genital surgery decision maker; performing genital surgery at later ages; and disclosing surgical details at younger ages. This is the first study assessing physician recommendations across two decades. Despite variability in the recommendations, most experts followed CAH clinical practice guidelines. The observation that some of the emerging trends do not align with expert opinion or empirical evidence should serve as both a cautionary note and a call for prospective studies examining patient outcomes associated with these changes.

A Case of Ewing Sarcoma of the Bladder Presenting in Early Infancy.

A 6-week-old female presented with gross hematuria and was diagnosed with Ewing sarcoma of the bladder through ultrasound and cystoscopic biopsies, along with a negative metastatic workup. She was treated with transurethral resection, chemotherapy consisting of with vincristine, cycolphosphamide, doxorubicin, ifosfamide and etoposide, and partial cystectomy. After completing chemotherapy, the patient has been doing well with no evidence of disease. There have been 14 other cases, 4 pediatric, of Ewing sarcoma of the bladder reported. To our knowledge, our case is the youngest patient reported with this disease.

Development of Health-Related Quality of Life Instruments for Young Children With Disorders of Sex Development (DSD) and Their Parents.

Objective: Research in disorders of sex development (DSD) is hindered by a lack of standardized measures sensitive to the experiences of affected children and families. We developed and evaluated parent proxy (children 2-6 years) and parent self-report (children ≤6 years) health-related quality of life (HRQoL) instruments for DSD. Methods: Items were derived from focus groups and open-ended interviews. Clarity and comprehensiveness were assessed with cognitive interviews. Psychometric properties were examined in a field survey of 94 families. Results: Measures demonstrated adequate to good psychometrics, including internal consistency, test-retest reliability, convergent validity, and ability to detect known-group differences. Parents reported greatest stress on Early Experiences , Surgery , and Future Concerns scales. Conclusions: These instruments identify patients' and families' needs, monitor health and quality of life status, and can evaluate clinical interventions. Findings highlight the need for improved psychosocial support during the diagnostic period, better parent-provider communication, and shared decision-making. HRQoL measures are needed for older youth.

Update on Multicystic Dysplastic Kidney.

Multicystic dysplastic kidney (MCDK) is the most common cause of cystic disease in children. It is characterized by multiple non-communicating cysts of varying sizes with no identifiable normal renal parenchyma. The incidence ranges from 1 in 1000 to 4300 live births, and it is one of the most commonly detected anomalies on prenatal ultrasound. MCDK has been shown to follow a benign course with relatively few sequelae and therefore should be managed conservatively. Currently, the key clinical questions revolve around the detection of anomalies in the contralateral kidney and follow-up imaging. The recent literature suggests that very limited radiographic evaluation of the MCDK is needed. The use of voiding cystourethrogram or nuclear medicine renal scans should be directed by any abnormalities on renal ultrasound or the development of urinary tract infections.

High recurrence rate at 5-year followup in children after upper urinary tract stone surgery.

PURPOSE: Pediatric urolithiasis has been treated with shock wave lithotripsy, ureteroscopy and percutaneous nephrolithotomy with high success rates during short-term followup. We studied our success rate and modifiable risk factors in patients with at least 5 years of followup postoperatively. MATERIALS AND METHODS: Retrospective chart review was performed for patients younger than 18 years who underwent upper tract stone surgery between 1999 and 2007, were stone-free afterward and had at least 5 years of followup. Recurrence rate, and anatomical and metabolic abnormalities were assessed. RESULTS: Of 60 eligible children 30 (33 kidneys) had at least 5 years of followup. Average patient age at surgery was 10 years, 17 patients were female and 20 kidneys had anatomical abnormalities. Overall recurrence rate at 5 years was 55% (95% CI 38%-70%). Ureteral stones had a lower recurrence rate than renal stones (5 of 19 and 13 of 14, respectively, p <0.001). Patients with abnormal anatomy had a 65% (95% CI 43%-82%) chance of recurrence within 5 years vs 38% (95% CI 18%-65%) in those with normal anatomy (p = 0.17). Of the 18 recurrences 10 required a second operation, 7 demonstrated abnormal anatomy and 14 involved calcium based stones. A 24-hour urine test in 13 children revealed 10 with hypercalciuria and 11 with hypocitraturia, with 9 patients exhibiting both conditions. CONCLUSIONS: We found a high recurrence rate in children with stones requiring surgical intervention, particularly those with abnormal anatomy. This finding should be confirmed in a larger multicenter study of recurrence rates. In the meantime our results suggest a need for aggressive diagnosis and treatment of metabolic abnormalities.

Bowel bladder dysfunction in control children in a pediatric urology office.

INTRODUCTION: Bowel bladder dysfunction (BBD) is common in children. Risk factors for BBD include age, gender, obesity, and behavioral issues such as ADHD. We investigated the modified Swedish Bowel-Bladder questionnaire as a sensitive indicator of BBD in healthy children. OBJECTIVES: We tested the usefulness of the Swedish Bowel-Bladder Questionnaire (BBQ) as an indicator of BBD in children not complaining of bowel/bladder dysfunction at the time of their visit to a pediatric urologist. Our secondary aim was to identify correlations between BBQ scores and risk factors such as gender, BMI, and ADHD. STUDY DESIGN: All families in our Pediatric Urology practice with patients >30 months old who were reportedly toilet trained were provided the Swedish BBQ. Total score as well as sub-scores for storage, emptying, and constipation were prospectively collected. Presenting diagnosis, gender, BMI, and ADHD history were collected. BBQ scores for patients with voiding dysfunction were compared to controls: a) those with genital problems (e.g. hydrocele/undescended testes), b) those with CAKUT (congenital anomalies of the kidneys and urinary tract). BBQ scores were analyzed as a continuous variable vs the potential risk factors (ADHD, obesity, age, and gender) using univariable/multivariable regression analysis. RESULTS: The median BBQ score for the 328 control patients (95 CAKUT and 233 genital) was 2.25 with an IQR: 1 to 6. In contrast, the median BBQ was higher for those with possible voiding dysfunction; n = 282; 9 with an IQR: 5 to 15). Total BBQ score exceeded 6 in 16% (52/328) of control patients. On multivariable analysis, age-adjusted total BBQ scores increased with ADHD in our controls (p = 0.03) but were unaffected by gender or BMI. On multivariable analysis of the voiding dysfunction group, total BBQ scores similarly decreased with age (p < 0.001) and increased with ADHD (p < 0.001) and were affected by gender (p = 0.024). BMI percentile had no significant effect in either cohort. DISCUSSION AND CONCLUSION: The Swedish BBQ was used in a U.S population and demonstrated trends towards increased voiding dysfunction associated with younger age, female gender, and ADHD. We learned that voiding dysfunction in children with ADHD is not associated with constipation and improves over time. Additionally, 16% of children with genital or urinary abnormalities and no voiding complaints have noticeable BBD uncovered by the BBQ. Hence, we conclude that the Swedish BBQ is a sensitive indicator of BBD even in children not complaining of those problems.

Revisiting Postoperative Pediatric Urology Opioid Prescriptions.

OBJECTIVE: To measure our opioid prescription rate, determine if our rate has decreased since 2019, and identify areas for future interventions to further decrease our opioid prescription rate. METHODS: We retrospectively reviewed all pediatric urology patients (age ..±18 years) who underwent a procedure between October 1, 2020 and October 22, 2021. We collected data on opioid prescribing, age, sex, surgeon, procedure, ethnicity, and race. We grouped procedures into 6 categories: circumcision, cystoscopy with the removal of foreign body/stone/stent, scrotal surgery, hypospadias repair/penile surgery, pyeloplasty/ureteral reimplant, and others. RESULTS: We analyzed 821 operative cases. Only 2.2% (18/821) of discharges included an opioid prescription. The prescription rate of 1 pediatric urologist was 4.6% (17/369), which was higher than the other 2 practitioners... (0.40%, 1/250%, and 0%, 0/202) (P.ß<.ß.001). The median age of patients who received an opioid prescription was older than patients without an opioid prescription (16.5 vs.ß5.0 years, P.ß<.ß.001). Surgery performed in an inpatient setting was more likely to result in an opioid prescription (9.7%, 3/31) than in the outpatient setting (1.9%, 15/790) (P.ß=.ß.03). No adverse effects of reduced opioid usage were noted. CONCLUSION: From October 2020 to October 2021, our institution had an opioid prescription rate of 2.2%. This represented a decrease from our previously reported rate of 8% in 2019. At the same time, we found no significant pain issues in our post-operative patients. Seventeen out of 18 prescriptions were written under 1 provider. Though heightened awareness has made a difference, targeted feedback is needed if we wish to reduce opioid usage further.

Urinary diversion results in marked decreases in proliferation and apoptosis in fetal bladder.

PURPOSE: We sought to determine if bladder cycling is required for remodeling during fetal development. MATERIALS AND METHODS: For this study 5 fetal sheep bladders were harvested after 2 weeks of urinary diversion, initiated at approximately 90 days of gestation. Six unoperated sheep bladders of approximately 105 days of gestational age were used as controls. Dividing cells and cells undergoing apoptosis were quantified by using Ki-67 antibody and TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling) assay, respectively. In addition, expression of the antiapoptosis gene, Bcl2, and cell division control protein 42 were quantified by real-time polymerase chain reaction. RESULTS: The thickness of bladder tissue layers is dramatically altered as a consequence of urinary diversion (defunctionalization). The percentage of Ki-67 and TUNEL positive cells in control bladders was 5.8% and 47.1%, respectively. However, in diverted bladders apoptosis and cell mitosis were significantly decreased with essentially 0% of Ki-67 and TUNEL positive cells per microscope field in the mucosa and detrusor muscle layers. In addition, relative mRNA expression of antiapoptotic gene Bcl2 was significantly lower in control than in diverted bladder tissue, while Cdc42 was significantly higher in the detrusor but not in the lamina propria. CONCLUSIONS: Cell mitotic activity and coordinated cell death appear to be involved in growth and remodeling, which are activated by the mechanical input that occurs during bladder cycling. Fetal urinary diversion results in a repression of mitotic and apoptotic activity, limiting normal bladder growth and remodeling.

Failure to Attend Urology Appointments: A Retrospective Analysis of a Single Urban Academic Practice.

INTRODUCTION: We sought to examine why patients miss appointments in a large academic urology practice. METHODS: We conducted a retrospective analysis of 83,983 patient appointments in our faculty urology group between May 1, 2017 and December 1, 2020. Appointment data from 17 providers were included. Data were collected on diagnosis, age, gender, insurance type, nonattendance history, lead time between scheduling and appointment, clinic location and outpatient procedures vs general office visit or telehealth visit. RESULTS: A total of 7,592 (9.0%) appointments were missed. Patients seen for oncologic diagnosis had the lowest missed appointment rate (4.5%), as compared with benign urology (9.6%) and pediatrics (13.0%). Previous nonattendance history within the last year was associated with nonattendance again (OR 2.47, 95% CI 2.29-2.66). Patients with Medicaid had the highest rate of missed appointments (17.2%; OR 2.16, 95% CI 2.02-2.32). Increased lead time between appointments increased the odds of nonattendance (OR 1.018/week, CI 1.016-1.020). Patients undergoing procedures had the lowest nonattendance rate (3.4%), compared with both new (11.4%) and followup (10.5%) visits, while both telephone (2.9%; OR 0.41, 95% CI 0.32-0.53) and video (2.8%; OR 0.37, 95% CI 0.20-0.71) visits had lower rates of nonattendance when compared to in-person visits. CONCLUSIONS: We found a nonattendance rate of 9% in our practice. Those patients with oncologic diagnoses and those having procedures or telemedicine visits had the lowest rates. Those who have missed an appointment in the past are at the highest risk nonattendance and should be targeted to improve patient health as well as practice efficiency.

Postoperative pediatric urology opioid prescriptions at a tertiary academic medical center.

INTRODUCTION: Opioid abuse is a public health crisis, and often this starts postoperatively. Limited data are available on pediatric urology practitioners. We examined the likelihood of postoperative opioid prescriptions in our practice. OBJECTIVE: To determine rates of post-operative opioid prescriptions following urologic surgery in a tertiary academic center, and to identify what factors are related to opioid prescriptions. STUDY DESIGN: We retrospectively reviewed opioid prescriptions for children who underwent a procedure in the operating room between 1/1/17 and 12/31/19. We collected data on gender, age, surgeon, procedure, length of stay, ethnicity, race, and whether opioids had been used pre-operatively. We grouped procedures into five categories: minor penile surgery, cystoscopic procedures, scrotal surgery, hypospadias repair/penoplasty, and pyeloplasty/ureteral reimplant. Multivariable logistic regression was used to determine odds ratios (OR) of opioid prescriptions. RESULTS: 1102 procedures had data available. 14.2% (n = 156) received opioid prescriptions. Using minor penile surgery as a baseline, scrotal surgery increased the odds of an opioid by 1.42; hypospadias, pyeloplasty, and other procedures reduced the odds by 0.53, 0.55, and 0.54, respectively (no patient received opioids for endoscopic procedures). Ambulatory procedures had a lower rate of opioids (0.40), and age was a major factor, with the odds of a prescription increasing by a factor of 1.45 per year of age. Since January of 2017, the opioid prescription rate has decreased from 18% in 2017 to 7.7% in 2019. DISCUSSION: We found a relatively low rate of opioid prescribing in our pediatric patients, mostly in older children undergoing penile and scrotal procedures. Our rate was comparable to several other institutions that have examined their prescription rates in surgical patients. Heightened awareness has resulted in decreased opioid usage over time (to 6.9%). Limitations included the retrospective nature of our study, which did not allow us to assess whether pain control was adequate or if the opioids prescribed were used by patients. Opioids are rarely needed in pediatric patients. CONCLUSIONS: 85.8% of post-operative pediatric urology patients at our institution were not provided with prescription opioids. Factors associated with a higher likelihood of receiving a prescription were increasing age and scrotal surgery.

Variation in Urinary Stone Parameters Throughout the Day and the Effect of Increased Fluid and Citrate Supplementation.

Background: Because 24-hour urine collections are cumbersome, many studies have evaluated the use of spot urine samples as a substitute, mostly finding poor concordance between the two. Daily variation in stone parameters probably contributes to the lack of concordance, but specific variation in various stone parameters is not well delineated. The variations likely lead to peaks and troughs, which can increase the risk of stone formation. Methods: We prospectively recruited 20 nonstone-forming patients, recording their total fluid intake over 24 hours and collecting voids at first morning, 9 to 10 A.M., 1 to 2 P.M., and 4 to 5 P.M. for evaluation of pH, specific gravity, calcium, citrate, and creatinine. Participants were then asked to double their fluid intake and take a daily True Lemon supplement over the course of the next 3 days. Urine was recollected postintervention. Results: Baseline [citrate]/[creatinine] increased throughout the day such that the 5 P.M. level was significantly higher compared with first void (0.58 vs 0.42, p = 0.027); [calcium]/[creatinine] daily variation was not statistically significant, but showed a distinct pattern that was present in both sets of collections. Daily [calcium]/[citrate] variation was significantly (p = 0.004) and consistently highest in the early morning on both day 1 (0.43) and day 4 (0.45). There was no significant variation in specific gravity and pH. Increasing fluid intake and citrate supplementation increase the daily variation in pH and [citrate]/[creatinine], but did not increase the values compared with their respective preintervention void times. There was also no detectable postintervention effect on [Ca]/[creatinine] or specific gravity. Conclusions: Urinary citrate concentration follows a circadian pattern, while urinary calcium has a diurnal excretion pattern. [Calcium]:[citrate] is highest in the early morning, indicating a high-risk time of day for stone formation. Spot urine samples identify a key time of day, which 24-hour urine collections may miss, for clinical monitoring.

Individualized care for patients with intersex (differences of sex development): part 4/5.Considering the Ifs, Whens, and Whats regarding sexual-reproductive system surgery.

Issues and concerns regarding surgery of the sexual-reproductive anatomy during infancy and early childhood are discussed using four actual examples. A case of a 46, XX infant with 21 hydroxylase deficiency congenital adrenal hyperplasia (CAH) with atypical (ambiguous) genitalia is discussed regarding timing and potential harms and benefits of surgery. We present the perspective of balancing the child's rights to bodily autonomy and right to an open future versus parents' decision making authority regarding what they perceive as their child's future best interests. The second case is a newborn with complete androgen insensitivity syndrome and we discuss the harms, benefits and timing of gonadectomy. The third case examines the physical and psychological impact of penile shaft hypospadias, raising the question of whether surgery is justified to prevent what may or may not be considered a permanent disability. The fourth case involves an adult woman with classic CAH, born with a urogenital sinus and clitoromegaly, who never had genital surgery and is now requesting vaginoplasty, but not clitoral reduction. The primary message of this article, as the previous articles in this series, is to encourage patient-family centered care that individualizes treatment guided by shared decision making.

24-Hour urine collection for first time pediatric stone formers: Is it worth it?

INTRODUCTION/OBJECTIVE: 24-h urine collections are recommended for motivated first-time stone formers. Given that children have a lifetime potential for recurrences, metabolic work-up has been recommended. 24-hour urine collections can be problematic, especially in children. We sought to study the benefits of 24-h urine collections in children with stones. STUDY DESIGN: We performed a single center, retrospective chart review of the most recent pediatric nephrolithiasis patients under age 18 at our center who supplied their first 24-h urine collection. We assessed whether 24-h urine results led to a change in management and if those patients were adherent to the recommendations. RESULTS: Seventy pediatric nephrolithiasis patients who had 24-h urine collection were reviewed. Recommendations other than standard dietary and fluid intake changes were made in 8/70 (11%). A low citrate/calcium ratio (327 vs. 525, p < 0.03) and whether the test was ordered by nephrology vs. urology (26% vs. 2%, p < 0.003) were predictive of an additional recommendation. Of the 8 patients who had changes recommended only 1/8 completed a repeat 24-h urine collection, 3/8 never returned for followed up and 2/8 stopped the medicines prior to follow up. There was no difference in early stone recurrence rates, 55% of the studies were incorrectly collected, and total costs are estimated at $9800. DISCUSSION: Our study aimed to evaluate the impact and value of 24-h urine collection in first time pediatric stone formers. We found that 24-h urine collections altered management from standard dietary recommendations in only 11% of cases. These collections were fraught with challenges - 55% of our samples appeared to be incorrectly collected, there was at least one abnormality noted in 100% of collections, these tests are expensive, and patients were poorly compliant with recommendations based on test results. Additionally, changes made based on the 24-h urine results seemed to vary depending on who evaluated the test results. Among cases in which changes were made, nephrologists made alterations at a far greater rate than urologists did. We do acknowledge there are several limitations to our study. First, this is a retrospective chart review. Second, for the urology patients, we were only able to review patient records that were available due to a transition from one electronic medical record to another, resulting in a loss of some earlier patient records. We highly doubt that those records we could not review were significantly different than those we did review. Third, this is a single center design and includes the practice patterns of the providers here. We acknowledge that our local practice patterns may or may not be reflective of national practice patterns, however, most clinicians are likely faced with similar interpretation issues and poor rates of compliance and could benefit from guidelines. CONCLUSION: 24-h urine collection for first time pediatric stone formers is expensive, difficult to accomplish and infrequently leads to treatment changes. Our data suggest it adds little for most children with stones and may be better reserved for those children with recurrent stone disease.

Cost-benefit analysis of scrotal ultrasound in treatment of adolescents with varicocele.

PURPOSE: Varicoceles are a major cause of male factor infertility, although management of adolescent varicoceles is controversial. Most clinicians advocate repair if there is a persistent testicular size discrepancy of greater than 20%. Using previously published data, we performed a cost-benefit analysis of testicular ultrasound vs orchidometry to evaluate for this size difference. MATERIALS AND METHODS: We performed a PubMed search using the terms "adolescent varicocele," "ultrasound and varicocele," and "testis size and varicocele." Using the data from the relevant studies and Medicare reimbursement data from our region, we determined the cost of missing a persistent testicular size difference of greater than 20%. RESULTS: Approximately 25% of adolescents with varicocele have a persistent size discrepancy of greater than 20%. Approximately 40% of this group would be identified as having a size discrepancy with conventional orchidometry. The annual cost of ultrasound for every adolescent male with a varicocele would be $364 million if the imaging were done in an office based setting. If the testing were done at a hospital, the annual cost would be $795 million. The cost per case of missed persistent size discrepancy spanning 3 years is approximately $5,597 for office ultrasound and $12,226 for hospital ultrasound. CONCLUSIONS: There is limited evidence that adolescent varicocele repair improves paternity in adulthood. In an era of increasing health care costs the expense of ultrasound to evaluate for size discrepancy is significant and should be thoughtfully evaluated.