Peri-surgical imaging of intersex and gender diverse youths.

This publication provides an overview of current imaging indications and practices for patients undergoing gender-affirming surgery, with an emphasis on the importance of tailored, patient-specific care. Gender-affirming surgeries are performed with personalized approaches at various stages of life for those with intersex traits or differences in sex development (I/DSD) and transgender and gender diverse (TGD) individuals. For I/DSD patients, ultrasound, genitography, or MRI occurs during infancy and puberty to evaluate genital and gonadal anatomy. Facial harmonization involves bony and soft tissue modifications, guided by maxillofacial computerized tomography (CT) with three-dimensional reconstruction. Ultrasound is the main modality in assessing hormone-related and post-surgical changes in the chest. Imaging for genital reconstruction uses cross-sectional images and fluoroscopy to assess neoanatomy and complications.

Mendelian Disorders in an Interstitial Cystitis/Bladder Pain Syndrome Cohort.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pain disorder causing symptoms of urinary frequency, urgency, and bladder discomfort or pain. Although this condition affects a large population, little is known about its etiology. Genetic analyses of whole exome sequencing are performed on 109 individuals with IC/BPS. One family has a previously reported SIX5 variant (ENST00000317578.6:c.472G>A, p.Ala158Thr), consistent with Branchiootorenal syndrome 2 (BOR2). A likely pathogenic heterozygous variant in ATP2A2 (ENST00000539276.2:c.235G>A, p.Glu79Lys) is identified in two unrelated probands, indicating possible Darier-White disease. Two private heterozygous variants are identified in ATP2C1 (ENST00000393221.4:c.2358A>T, p.Glu786Asp (VUS/Likely Pathogenic) and ENST00000393221.4:c.989C>G, p.Thr330Ser (likely pathogenic)), indicative of Hailey-Hailey Disease. Sequence kernel association test analysis finds an increased burden of rare ATP2C1 variants in the IC/BPS cases versus a control cohort (p = 0.03, OR = 6.76), though does not survive Bonferroni correction. The data suggest that some individuals with IC/BPS may have unrecognized Mendelian syndromes. Comprehensive phenotyping and genotyping aid in understanding the range of diagnoses in the population-based IC/BPS cohort. Conversely, ATP2C1, ATP2A2, and SIX5 may be candidate genes for IC/BPS. Further evaluation with larger numbers is needed. Genetically screening individuals with IC/BPS may help diagnose and treat this painful disorder due to its heterogeneous nature.

The radiologist's role in assessing differences of sex development.

When infants are identified with a difference of sex development (DSD), a thoughtful approach to imaging is essential to appropriate clinical management. This review provides a comprehensive guide for radiologists who are tasked with performing this critical assignment. We review the embryologic basis of DSDs, with attention to the imaging findings that can indicate specific diagnoses. We also discuss techniques for optimal imaging, including strategies for identifying the gonads by US, tactics for performing genitograms with fluoroscopy and contrast-enhanced US, and the appropriate utilization of MRI. Finally, we review the clinical data and imaging findings that characterize some of the most common DSDs, including congenital adrenal hyperplasia, complete androgen insensitivity syndrome and gonadal dysgenesis.

Malignancy Yield of Testis Pathology in Older Boys and Adolescents with Cryptorchidism.

PURPOSE: We performed a retrospective, single-institution study to characterize the pathological findings of testis tissue specimens from older boys and adolescents with cryptorchidism. MATERIALS AND METHODS: With institutional review board approval, pathology reports were obtained for testicular specimens from patients age 10 years or older at a pediatric hospital from 1994 to 2016. Reports were excluded if they lacked clinical records, lacked testicular parenchyma, were from a descended testis or were from a patient with differences of sexual development. Variables of interest included age, testis location, procedure and pathological findings. Presence of malignancy among intra-abdominal versus extra-abdominal undescended testes was compared using Fisher's Exact Test. RESULTS: Seventy-one patients met inclusion criteria. The median age was 15.3 years (range 10.1-27.7). None had a history of testicular malignancy. Forty-five unilateral orchiectomies, 22 unilateral orchiopexies with biopsy and 4 bilateral procedures were performed. Seventeen testes (22.7%) were intra-abdominal, 42 (56.0%) were in the inguinal canal, 9 (12.0%) were at the external inguinal ring, 3 (4.0%) were in the superficial inguinal pouch and 4 (5.3%) were in the scrotum. Malignancy was detected in 2/71 patients (2.8%). By location, 2/16 patients (12.5%) with intra-abdominal testis and 0/55 patients (0%) with extra-abdominal testis demonstrated malignancy (p=0.048). CONCLUSIONS: Among males with cryptorchidism ages 10 years and older without differences of sexual development, 2/16 patients with intra-abdominal testis and 0/55 patients with extra-abdominal testis demonstrated malignancy. In older boys and adolescents, orchiectomy or biopsy is indicated for intra-abdominal testes but may not be necessary for extra-abdominal undescended testes.

Clinical outcome of pediatric and young adult subclinical varicoceles: a single-institution experience.

Subclinical varicocele represents an abnormality of veins of the pampiniform plexus on scrotal ultrasound (US) without a clinically palpable varicocele. Its significance remains unclear. While guidelines do not recommend surgical intervention, clinical management is variable. As there is limited information on long-term outcome of subclinical varicoceles due to challenges in diagnosis and management, we performed a single-institution, retrospective review of patients from October 1999 to October 2014 with subclinical varicocele and with available US studies reviewed by a single radiologist. Subclinical varicocele was defined as dilation of the pampiniform venous plexus on US involving ≥2 vessels with diameter >2.5 mm, without clinical varicocele on physical examination or prior inguinal surgery. Thirty-six of 98 patients identified were confirmed as having a subclinical varicocele and analyzed. The mean age at initial visit was 15.5 years, with a mean follow-up of 26.5 months. The majority were right-sided (69.4%, n = 25), usually with a contralateral clinical varicocele. Testicular asymmetry (>20% volume difference of the affected side by testicular atrophy index formula) was assessed in 9 patients with unilateral subclinical varicocele without contralateral clinical or subclinical varicocele and observed in 1 patient. Of 17 patients with follow-up, 3 (17.6%) progressed to clinical varicocele without asymmetric testicular volume, as most remained subclinical or resolved without surgery. In our experience, subclinical varicoceles appeared unlikely to progress to clinical varicoceles, to affect testicular volume, or to lead to surgery. Although our study is limited in numbers and follow-up, this information may aid clinical management strategies and guide future prospective studies.

Fertility preservation in the pediatric cancer patient.

PURPOSE OF REVIEW: Long-term survival rates from childhood cancers approach 85% with many of these patients now reaching adulthood and facing the consequences of prior cancer treatment including infertility. This highlights the importance of discussing fertility risk and presenting fertility preservation options prior to initiation of cancer treatment. This article reviews the current literature on fertility preservation in adolescents, young adults, and prepubertal patients. RECENT FINDINGS: Sperm banking remains the gold standard for fertility preservation in adolescents and young adults. Testicular sperm extraction and electroejaculation may also be utilized in patients that are unable to produce a semen sample. Fertility preservation options for prepubertal patients remain experimental but recent data illustrate the potential to restore spermatogenesis using spermatogonial stem cells. SUMMARY: Fertility risk and fertility preservation options for pediatric patients should be routinely discussed at the time of cancer diagnosis. Sperm preservation should be routinely offered to adolescents and young adults at risk for infertility from cancer treatment. Preservation of prepubertal spermatogonial stem cells can be offered as an experimental option.

Improving Male Reproductive Health After Childhood, Adolescent, and Young Adult Cancer: Progress and Future Directions for Survivorship Research.

Reproductive health is a common concern and often a source of distress for male childhood, adolescent, and young adult cancer survivors. Clinical and epidemiologic research in survivor populations has identified alkylating agent chemotherapy, testicular radiation, and surgery or radiation to the genitourinary organs, lower spine, or the hypothalamic-pituitary region as risk factors for adverse reproductive outcomes, including impaired spermatogenesis, testosterone insufficiency, and sexual dysfunction. Much of the research on male survivors has focused on the outcome of fertility, using spermatogenesis, serum gonadotropins, and paternity as the measures. However, these studies often fail to account for the clinically relevant but difficult-to-quantify aspects of fertility such as sexual function, cancer-related delayed psychosocial development, medical comorbidities, and socioeconomic concerns. Clinical and basic science research has made significant contributions to improving reproductive outcomes for survivors, with recent advancements in the areas of fertility preservation, clinical assessment of reproductive function, and treatment of adverse reproductive outcomes. Furthermore, there is an emerging qualitative literature addressing the psychosexual aspects of male reproductive health, the clinical application of which will improve quality of life for survivors. This review summarizes the current survivorship literature on reproductive health outcomes for male survivors, including the epidemiology of impaired spermatogenesis, testosterone insufficiency, and sexual dysfunction; clinical and laboratory assessment of reproductive function; and established and investigational interventions to preserve reproductive function for patients newly diagnosed and survivors. Although survivorship research has made significant contributions to improving reproductive outcomes, additional scientific progress is needed in the areas of fertility preservation, risk assessment, and psychosexual support with the aim of optimizing reproductive health for current and future survivors.

Common genitourinary catheters: a systematic approach for the radiologist.

Catheters are commonly used to treat and diagnose urinary tract abnormalities in the pediatric population. This pictorial essay reviews commonly placed genitourinary catheters imaged by radiography, fluoroscopy, computed tomography (CT) and ultrasonography (US). The purpose of the catheter, how the catheter is placed, and the imaging findings associated with appropriately positioned catheters as well as misplaced and displaced catheters are described. It is important for radiologists to recognize common genitourinary catheters, and be familiar with their normal and abnormal positions as displacement is often first recognized by diagnostic imaging.

Robotic Assistance Confers Ambidexterity to Laparoscopic Surgeons.

STUDY OBJECTIVE: To examine whether a robotic surgical platform can complement the fine motor skills of the nondominant hand, compensating for the innate difference in dexterity between surgeon's hands, thereby conferring virtual ambidexterity. DESIGN: Crossover intervention study (Canadian Task Force classification II-1). SETTING: Centers for medical simulation in 2 tertiary care hospitals of Harvard Medical School. PARTICIPANTS: Three groups of subjects were included: (1) surgical novices (medical graduates with no robotic/laparoscopic experience); (2) surgeons in training (postgraduate year 3-4 residents and fellows with intermediate robotic and laparoscopic experience); and (3) advanced surgeons (attending surgeons with extensive robotic and laparoscopic experience). INTERVENTIONS: Each study group completed 3 dry laboratory exercises based on exercises included in the Fundamentals of Laparoscopic Surgery (FLS) curriculum. Each exercise was completed 4 times: using the dominant and nondominant hands, on a standard laparoscopic FLS box trainer, and in a robotic dry laboratory setup. Participants were randomized to the handedness and setting order in which they tackled the tasks. MEASUREMENTS AND MAIN RESULTS: Performance was primarily measured as time to completion, with adjustments based on errors. Means of performance for the dominant versus nondominant hand for each task were calculated and compared using repeated-measures analysis of variance. A total of 36 subjects were enrolled (12 per group). In the laparoscopic setting, the mean overall time to completion of all 3 tasks with the dominant hand differed significantly from that with the nondominant hand (439.4 seconds vs 568.4 seconds; p = .0008). The between-hand performance difference was nullified with the robotic system (374.4 seconds vs 399.7 seconds; p = .48). The evaluation of performance for each individual task also revealed a statistically significant disparate performance between hands for all 3 tasks when the laparoscopic approach was used (p = .003, .02, and .01, respectively); however, no between-hand difference was observed when the tasks were performed robotically. On analysis across the 3 surgeon experience groups, the performance advantage of robotic technology remained significant for the surgical novice and intermediate-level experience groups. CONCLUSION: Robot-assisted laparoscopy may eliminate the operative handedness observed in conventional laparoscopy, allowing for virtual ambidexterity. This ergonomic advantage is particularly evident in surgical trainees. Virtual ambidexterity may represent an additional aspect of surgical robotics that facilitates mastery of minimally invasive skills.

Minor procedure, major impact: Patient-reported outcomes following urethral meatotomy.

INTRODUCTION: Urethral meatotomy as treatment for meatal stenosis is a common pediatric urology procedure; however, little is known about the patient experience following this procedure. OBJECTIVE: We aim to evaluate clinical factors associated with patient-reported symptom improvement after urethral meatotomy. STUDY DESIGN: The families of boys undergoing urethral meatotomy between 2/2013 and 8/2016 received a survey by mail 6 weeks after surgery. Families were queried on changes in symptoms using a Likert-type scale (5 = much improved, 4 = somewhat improved, 3 = no change, 2 = somewhat worse, and 1 = much worse). Patient and procedure characteristics of the respondents were obtained via chart review. These included surgical indication(s) (abnormal stream, dysuria, or storage symptoms), postoperative complications, reoperation, and unplanned postoperative communications. Patients who had procedures other than simple urethral meatotomy were excluded. Descriptive statistics were compiled, and generalized estimating equations used to determine the associations of patient and procedure characteristics with symptom improvement. RESULTS: We sent 629 surveys and received 194 responses (30.4%). Twelve respondents were excluded for complex procedures or miscoding. The majority of respondents were privately insured (74%) and were between 5 and 12 years old (45%) or 1 and 4 years old (42%). The most frequent surgical indication was abnormal stream (72%) followed by pain (21%) and storage symptoms (15.5%). Nine respondents had minor complications (4.9%). Four patients had restenosis requiring repeat urethral meatotomy. After surgery, a majority (79%) were "much improved," 16% were "somewhat improved," 3% had "no change," and 1% were "somewhat worse." No family reported "much worse." Those patients who had "abnormal stream" as a surgical indication were significantly more likely to report "much improved" (OR 1.83, p = 0.014) than those without. Patient-reported improvement was not associated with suture use, patient age, insurance, surgeon, or location of the procedure (Table). DISCUSSION: Little has been written about patient-reported outcomes following urethral meatotomy. Our study affirms that the majority of boys improve following this procedure. However, improvement is significantly more likely if the child has a preoperative indication of an abnormal stream, such as deflection or spraying. Boys with symptoms of dysuria, frequency, or incontinence may be experiencing sequelae of meatal stenosis that simply take longer to improve. Alternatively, the meatal stenosis may be incidental to the primary symptoms. CONCLUSIONS: A majority of families report substantial symptomatic improvement after urethral meatotomy. However, boys undergoing urethral meatotomy for reasons other than a urinary stream abnormality are less likely to experience improvement.

The Decline of the Open Ureteral Reimplant in the United States: National Data From 2003 to 2013.

OBJECTIVE: To examine trends in the number of cases of primary vesicoureteral reflux managed by ureteral reimplantation nationally over the last decade. Substantial changes have occurred in management of vesicoureteral reflux (VUR) over time, but trends in use of ureteral reimplantation have yet to be investigated on a national scale with annualized data. MATERIALS AND METHODS: Using the Premier Healthcare Database, we extracted hospital discharge data for pediatric patients (age ≤ 18 years) with a procedure code for ureteroneocystostomy (International Classification of Diseases, Ninth Revision, 56.74) between January 1, 2003 and December 31, 2013. We excluded patients with secondary VUR. The presence of a temporal trend in reimplantation was examined via regression using generalized estimating equations. RESULTS: In 4301 cases of primary VUR (23,602 weighted), there was a substantial decrease in the number of reimplantations performed, with an estimated decline in the rate of 0.239 cases per attending per year (P = .006). Average patient age declined 1.2 months in each year (P < .0001) due largely to a decline in reimplantation in those over age 2, which fell by 0.15 reimplantations per attending per year (P = .026). There was no difference between rates of decline in reimplantation for children with and without reflux nephropathy (P = .21) CONCLUSION: Nationally there has been a marked decrease in the incidence of ureteral reimplantation among children with primary VUR. The potential factors contributing to this are broad, including changes in diagnostic patterns, treatment recommendations, and the rise of endoscopic intervention.

Fertility and sexual function: a gap in training in pediatric endocrinology.

BACKGROUND: Infertility and sexual dysfunction result from many different pediatric conditions and treatments and can profoundly impact quality of life. The American Academy of Pediatrics (AAP) has recommended consulting "fertility specialists" for counseling, but it remains unclear who these specialists are. Our objective was to assess whether pediatric subspecialists who manage hypogonadism and/or genitourinary conditions feel adequately trained to provide fertility and sexual function counseling. METHODS: An online survey was distributed to members of Pediatric Endocrine Society (PES), Society for Pediatric Urology (SPU), and North American Society for Pediatric and Adolescent Gynecology (NASPAG). Providers' comfort in counseling various age groups about fertility and sexual function was assessed via a five-point Likert scale. Providers reported whether they felt adequately trained in these areas. RESULTS: Two hundred and eighty-four surveys were completed by endocrinologists, 124 surveys by urologists, and 41 surveys by gynecologists. Respondents (44% male, 86% Caucasian) represented 39 states and Canada. Seventy-nine percent were at academic centers. Thirty-four percent of providers had been practicing for >20 years. Comfort level was variable and lowest in young males. Ninety-one percent of pediatric endocrinologists reported routinely seeing patients at risk for infertility, but only 36% felt adequately trained in fertility, and 25% felt adequately trained in sexual function. CONCLUSIONS: Infertility and sexual dysfunction are often overlooked in pediatric care. Our results suggest that pediatric endocrinologists, who frequently manage male and female hypogonadism, should also receive formal training in these areas. Optimizing counseling would help prevent missed opportunities for fertility preservation and alleviate distress among patients and families.

Robot-assisted laparoscopic lower pole partial nephrectomy in the pediatric patient.

INTRODUCTION: In pediatric urology, partial nephrectomy is used primarily to remove a non-functioning renal moiety in a duplicated system. There are few data on infants undergoing this procedure. As such, we present a robot-assisted laparoscopic lower pole partial nephrectomy in an infant. METHODS: Our patient was an 11-month-old (10.7 kg) male with a history of prenatal hydronephrosis, who was diagnosed postnatally with a duplicated right collecting system and severe hydroureteronephrosis of the right lower collecting system. A DMSA scan demonstrated no radiotracer uptake in the right lower pole. A robot-assisted laparoscopic lower pole partial nephrectomy was performed. RESULTS: A lower pole partial nephrectomy was accomplished. At 1 month postoperatively, an ultrasound demonstrated no hydronephrosis or perinephric fluid collection. CONCLUSIONS: Robotic partial nephrectomy is safe and feasible in pediatrics including both older children and infants. It is successful for both upper and lower pole partial nephrectomies.

Robotic versus open pediatric ureteral reimplantation: Costs and complications from a nationwide sample.

INTRODUCTION: We sought to compare complications and direct costs for open ureteral reimplantation (OUR) versus robot-assisted laparoscopic ureteral reimplantation (RALUR) in a sample of hospitals performing both procedures. Anecdotal reports suggest that use of RALUR is increasing, but little is known of the outcomes and costs nationwide. OBJECTIVE: The aim was to determine the costs and 90-day complications (of any Clavien grade) in a nationwide cohort of pediatric patients undergoing OUR or RALUR. METHODS: Using the Premier Hospital Database we identified pediatric patients (age < 21 years) who underwent ureteral reimplantation from 2003 to 2013. We compared 90-day complication rates and cost data for RALUR versus OUR using descriptive statistics and hierarchical models. RESULTS: We identified 17 hospitals in which both RALUR and OURs were performed, resulting in a cohort of 1494 OUR and 108 RALUR cases. The median operative time was 232 min for RALUR vs. 180 min for OUR (p = 0.0041). Incidence of any 90-day complications was higher in the RALUR group: 13.0% of RALUR vs. 4.5% of OUR (OR = 3.17, 95% CI: 1.46-6.91, p = 0.0037). The difference remained significant in a multivariate model accounting for clustering among hospitals and surgeons (OR, 3.14; 95% CI, 1.46-6.75; p = 0.0033) (Figure). The median hospital cost for OUR was $7273 versus $9128 for RALUR (p = 0.0499), and the difference persisted in multivariate analysis (p = 0.0043). Fifty-one percent (55/108) of the RALUR cases occurred in 2012-2013. DISCUSSION: We present the first nationwide sample comparing RALUR and OUR in the pediatric population. There is currently wide variation in the probability of complication reported in the literature. Some variability may be due to differential uptake and experience among centers as they integrate a new procedure into their practice, while some may be due to reporting bias. A strength of the current study is that cost and 90-day postoperative complication data are collected at participating hospitals irrespective of outcomes, providing some immunity from the reporting bias to which individual center surgical series' may be susceptible. CONCLUSIONS: Compared with OUR, RALUR was associated with a significantly higher rate of complications as well as higher direct costs even when adjusted for demographic and regional factors. These findings suggest that RALUR should be implemented with caution, particularly at sites with limited robotic experience, and that outcomes for these procedures should be carefully and systematically tracked.

Institutional Policy Changes to Prevent Cardiac Toxicity Associated With Bupivacaine Penile Blockade in Infants.

Dorsal penile nerve block is a widely used method of analgesia for infants undergoing penile surgery. Because of its potency, extended duration of action, and lack of vasoconstriction, bupivacaine remains the most commonly used local anesthetic. Rapid systemic absorption of bupivacaine, however, has been associated with profound central nervous system and cardiovascular side effects, including cardiac arrest. As determined by retrospective medical record analysis, the incidence of complications associated with dorsal penile blockade in our institution was 0.075%. This was significantly higher than previously reported prompting a change in institutional policy that has eliminated penile block complications.

Sperm Retrieval in Adolescents and Young Adults with Klinefelter Syndrome: A Prospective, Pilot Study.

OBJECTIVE: To assess sperm retrieval rates in adolescents and young adults with Klinefelter syndrome, with the ultimate goal of improving fertility in this population. Secondary aims were to evaluate other clinical characteristics of the cohort and identify predictors of sperm retrieval. STUDY DESIGN: Patients 12-25 years of age with Klinefelter syndrome (47,XXY) were recruited at the Boston Children's Hospital. Physical examination, biochemical evaluation, scrotal ultrasonography, and semen analysis were performed. Neurocognitive data were collected. Microdissection sperm extraction (unilateral micro-testicular sperm extraction) was offered to individuals with no sperm in their ejaculates. Given the small sample size, analysis was primarily descriptive. RESULTS: Fifteen patients were enrolled. None had sperm in their ejaculates. Ten patients underwent unilateral micro-testicular sperm extraction. Sperm retrieval rate was 50%. From a neurocognitive standpoint, subjects reported problems with peers, conduct, and overall difficulties. Incidentally, one-third of the patients were found to have testicular microlithiasis and 17% of subjects with renal ultrasound imaging had bilateral renal medullary nephrocalcinosis. CONCLUSIONS: This pilot study suggests that sperm retrieval rates in adolescents and young adults with Klinefelter syndrome are comparable with those reported in older men. However, larger studies are needed to confirm our findings. The clinical significance of the scrotal and renal ultrasound findings merits further investigation. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01817296.

Management of testosterone therapy in adolescents and young men with hypogonadism: are we following adult clinical practice guidelines?

OBJECTIVE: Male hypogonadism is a common disorder that is associated with low bone density, poor muscle mass, anemia, and sexual dysfunction. The Endocrine Society recently published a Clinical Practice Guideline for testosterone therapy in androgen-deficient men. Because treatment is frequently initiated in adolescence, the goal of this quality improvement initiative was to assess whether pediatric endocrinologists at a large tertiary care center follow these guidelines and to identify opportunities for improvement. DESIGN: We performed a retrospective chart review at Boston Children's Hospital. Inclusion criteria were as follows: current age ≥16 years, diagnosis of hypogonadism, and testosterone replacement therapy. Data were collected about current age, age at treatment initiation, diagnoses, pre- and on-treatment testosterone levels, route of testosterone administration and dose, bone density, hematocrit levels, and adherence with therapy. RESULTS: Fifty-nine patients were included. Fourteen (24%) were prescribed lower testosterone doses than those recommended in the Clinical Practice Guideline. Seven (12%) had no pre-treatment testosterone levels, and 10 (17%) had no on-treatment levels. In 49 patients with on-treatment testosterone levels, 36 had at least one value that was lower than the adult reference range. Ten (28%) of the 36 men with low testosterone levels had no dose adjustments. Thirty-seven (63%) of the 59 patients had no dual-energy X-ray absorptiometry scans, and 18 (31%) did not have hematocrit levels. CONCLUSIONS: Pediatric endocrinologists in this review did not consistently follow the Clinical Practice Guideline for testosterone therapy in hypogonadal adult males. Strategies that improve adherence to guidelines could help maximize the benefits of therapy and minimize treatment-associated risks.