The prevalence of impostor phenomenon and its association with burnout amongst urologists.

OBJECTIVES: To characterise the prevalence of impostor phenomenon (IP; tendency for high-achieving individuals to perceive themselves as fraudulent in their successes) amongst attending staff in urology, to identify variables that predict more severe impostorism, and to study the association of IP with burnout. SUBJECTS AND METHODS: A survey composed of the Clance Impostor Phenomenon Scale (CIPS), demographic information, practice details, and burnout levels was e-mailed to urologists via urological subspecialty societies. Survey results were analysed to identify associations between IP severity, survey respondent characteristics, and symptoms of professional burnout. This study was conducted in the United States of America. RESULTS: A total of 614 survey responses were received (response rate 11.0%). In all, 40% (n = 213) of responders reported CIPS scores qualifying as either 'frequent' or 'intense' impostorism (i.e., scores of 61-100). On multivariable analysis, female gender, fewer years in practice (i.e., 0-2 years), and lower academic rank were all independently associated with higher CIPS scores (adjusted P < 0.05). Regarding burnout, 46% of responders reported burnout symptoms. On multivariable analysis, increase in CIPS score was independently associated with higher odds of burnout (odds ratio 1.06, 95% confidence interval 1.04-1.07; P < 0.001). CONCLUSION: Impostor phenomenon is prevalent in the urological community and is experienced more severely in younger and female urologists. IP is also independently associated with burnout. Increased female representation may improve IP amongst our female colleagues. More work is needed to determine strategies that are effective in mitigating feelings of IP and professional burnout amongst urologists, particularly those earlier in their careers.

Local treatment of rhabdomyosarcoma of the female genital tract: Expert consensus from the Children's Oncology Group, the European Soft-Tissue Sarcoma Group, and the Cooperative Weichteilsarkom Studiengruppe.

The International Soft-Tissue Sarcoma Consortium (INSTRuCT) was founded as an international collaboration between different pediatric soft-tissue sarcoma cooperative groups (Children's Oncology Group, European Pediatric Soft-Tissue Sarcoma Group, and Cooperative Weichteilsarkom Studiengruppe). Besides other tasks, a major goal of INSTRuCT is to develop consensus expert opinions for best clinical treatment. This consensus paper for patients with rhabdomyosarcoma of the female genital tract (FGU-RMS) provides treatment recommendations for local treatment, long-term follow-up, and fertility preservation. Therefore, a review of the current literature was combined with recommendations of the treatment protocols of the appropriate clinical trials. Additionally, opinions of international FGU-RMS experts were incorporated into recommendations. Results were that the prognosis of FGU-RMS is favorable with an excellent response to chemotherapy. Initial complete surgical resection is not indicated, but diagnosis should be established properly. In patients with tumors localized at the vagina or cervix demonstrating incomplete response after induction chemotherapy, local radiotherapy (brachytherapy) should be carried out. In patients with persistent tumors at the corpus uteri, hysterectomy should be performed. Fertility preservation should be considered in all patients. In conclusion, for the first time, an international consensus for the treatment of FGU-RMS patients could be achieved, which will help to harmonize the treatment of these patients in different study groups.

Vitrification versus slow freezing of human ovarian tissue: a systematic review and meta-analysis of histological outcomes.

A systematic review and meta-analysis of pertinent literature published from 2006 to January 2022 were conducted to study and compare vitrification and slow freezing, the two prominent methods of ovarian tissue cryopreservation. The primary outcome measures for this study were (1) proportion of intact primordial follicles, (2) proportion of intact stromal cells, (3) proportion of DNA fragmentation in primordial follicles, and (4) mean primordial follicle density. This meta-analysis of 19 studies revealed a significantly greater proportion of intact stromal cells in vitrified tissue versus slow-frozen tissue. No significant differences upon pooled analyses were observed between the two cryopreservation methods with respect to the proportion of intact primordial follicles, proportion of DNA fragmentation, or mean primordial follicle density. Due to differences seen in stromal cell viability, vitrification may be a preferred option to preserve histology of tissue. However, more work should be done to compare the two freezing techniques with less heterogeneity caused by patients, samples, and protocols.

Primary Hyperoxaluria Type 3 Can Also Result in Kidney Failure: A Case Report.

Primary hyperoxaluria (PH) is a group of genetic disorders that result in an increased hepatic production of oxalate. PH type 3 (PH3) is the most recently identified subtype and results from mutations in the mitochondrial 4-hydroxy-2-oxoglutarate aldolase gene (HOGA1). To date, there have been 2 cases of kidney failure reported in PH3 patients. We present a case of a young man with a history of recurrent urinary tract infections and voiding dysfunction who developed kidney failure at 33 years of age. He developed a bladder stone and bilateral staghorn calculi at 12 years of age. Initial metabolic evaluation revealed hyperoxaluria with very low urinary citrate excretion on multiple measurements for which he was placed on oral citrate supplements. Further investigation of the hyperoxaluria was not completed as the patient was lost to follow-up observation until he presented at 29 years of age with chronic kidney disease stage 4 (estimated glomerular filtration rate 24mL/min/1.73m2). Hemodialysis 3 times a week was started at 33 years of age, and subsequent genetic testing revealed a homozygous HOGA1 mutation (C.973G>A p.Gly325Ser) diagnostic of PH3. The patient is currently being evaluated for all treatment options including possible liver/kidney transplantation. All cases of a childhood history of recurrent urinary stone disease with marked hyperoxaluria should prompt genetic testing for the 3 known PH types. Hyperhydration and crystallization inhibitors (citrate) are standard of care, but the role of RNA interference agents for all 3 forms of PH is also under active study.

Imaging of pre- and post-cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for pediatric intraperitoneal malignancy.

Although rare, pediatric peritoneal carcinomatosis does occur in primary abdominopelvic tumors. Additionally, peritoneal carcinomatosis has been described to occur as metastatic disease where the primary tumor is outside the abdominopelvic cavity. Where amenable, cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) can be beneficial in disease management. However, favorable outcomes are predicated on specific tumor histology as well as proper patient selection, which significantly relies on preoperative imaging. This review gives a comprehensive, up-to-date summary on pediatric peritoneal carcinomatosis pre-surgical evaluation; where imaging is beneficial and limited; pediatric radiologists' role in helping to quantify disease; and how we, as pediatric radiologists, can help the surgeons and oncologists in the selection of patients for cytoreductive surgery and HIPEC.

Benefit of delayed primary excision in rhabdomyosarcoma: A report from the Children's Oncology Group.

BACKGROUND: Most children with intermediate-risk rhabdomyosarcoma (RMS) have gross disease (group III) at the initiation of chemotherapy. Delayed primary excision (DPE) after induction chemotherapy allows for a reduction in adjuvant radiation dose, but with the risk of potential surgical morbidity. The objectives of this study were to compare outcomes in children with group III RMS who did and did not undergo DPE and to assess surgical morbidity. METHODS: The study included 369 patients who had clinical group III RMS at sites amenable to DPE from intermediate-risk Children's Oncology Group studies D9803 (encouraged DPE) and ARST0531 (discouraged DPE). RESULTS: The primary tumor site was bladder/prostate (136 patients; 37%), extremity (97 patients; 26%), trunk (24 patients; 7%), retroperitoneum (91 patients; 25%), or intrathoracic/perineum/perianal (21 patients; 6%). In total, 112 patients (53.9%) underwent DPE in D9803, and 26 patients (16.2%) underwent DPE in ARST0531 (P < .001), with loss of vital organ or function in 30 of 138 patients (22%). DPE allowed for a reduced radiation dose in 110 of 135 patients (81%; 51% were reduced to 36 Gy, and 30% were reduced to 42 Gy). Patients who underwent DPE had improved unadjusted overall survival (P = .013). In adjusted regression analysis, the risk of death (hazard ratio, 0.71; 95% CI 0.43-1.16) was similar for patients who did and did not undergo DPE and was improved for the subset of patients who had tumors of the trunk and retroperitoneum (hazard ratio, 0.44; 95% CI, 0.20-0.97). CONCLUSIONS: Children with group III RMS have equivalent or improved outcomes with DPE and can receive a decreased radiation dose for definitive local control. The choice of local control modality should weigh the potential morbidity of surgery versus that of higher dose irradiation.

Feasibility Study of Vascularized Composite Urinary Bladder Allograft Transplantation in a Cadaver Model.

PURPOSE: The purpose of this study was to establish the feasibility of performing a urinary bladder vascularized composite allograft transplantation for either bladder augmentation or neobladder creation. MATERIALS AND METHODS: Six adult cadavers were studied. Cadavers were excluded for any previous pelvic surgery, radiation, vascular surgery or history of pelvic malignancy. An intravascular colored silicone and barium mixture was injected and both computerized tomography scans and gross dissections were performed. Contrast enhanced computerized tomography imaging was used to delineate urinary bladder vascular anatomy variability. Bladders were explanted en bloc from 2 cadavers with bilateral vascular pedicles based on the external iliac vessels and "transplanted" to replicate a bladder transplant. RESULTS: Contrast enhanced 3-D-computerized tomography reconstructions and cadaver dissections revealed distal vascular variability with proximal blood supply based primarily on the internal iliac artery. Urinary bladder vascularized composite allograft transplantation was successfully performed during 2 mock transplants with the vascular anastomosis done to the recipient external iliac artery and vein. CONCLUSIONS: Urinary bladder vascularized composite allograft transplantation is technically and anatomically feasible. This procedure may obviate the use of intestinal segments for bladder reconstruction in select patients. A phase 1 clinical trial is in progress.

Consult and procedure incidence outcomes following establishment of a fertility preservation program for children with cancer.

PURPOSE: Fertility is a quality of life outcome adversely affected by cancer therapy. Many childhood cancer patients, however, are not offered options to preserve their fertility. Providers acknowledge difficulty discussing impaired fertility to patients due to lack of knowledge of available options. Our objective was to review the impact of a pediatric multidisciplinary fertility preservation program on providers' fertility preservation counseling and discussion of options. METHODS: A retrospective medical chart review was conducted for pediatric cancer patients prior to and following program establishment. Fertility preservation discussions, consults, and incidence were noted. Following filtering and stratification, 198 and 237 patients were seen prior to and following program establishment, respectively. RESULTS: Following program establishment, provider-patient discussions of impaired fertility (p = 0.007), fertility preservation consults (p = 0.01), and incidence of fertility preservation procedures (p < 0.001) increased among patients. Furthermore, the number of patients who received fertility preservation consults after receiving gonadotoxic treatment decreased (p < 0.001). This trend was particularly noted in pre-pubertal and female patients, for whom fertility preservation options are limited without an established program. CONCLUSION: The establishment of a formal program greatly improved access to fertility preservation consults and procedures in children with cancer.

A Systematic Review of Complications of Minimally Invasive Surgery in the Pediatric Urological Literature.

PURPOSE: Minimally invasive surgery has been gaining momentum in pediatric urology and it is essential to analyze the unique complications pertinent to this approach. We conducted a systematic review to evaluate pediatric minimally invasive surgery complications in the published urological literature. MATERIALS AND METHODS: We searched PubMed®/MEDLINE® using relevant pediatric minimally invasive surgery terminology and applied specified eligibility criteria. The Clavien-Dindo classification scheme was used to categorize postoperative complications. For studies not using Clavien-Dindo, complications were recategorized into Clavien-Dindo grades. Primary outcome was frequency of grade III complications and conversions to open surgery. Covariates were surgery type (pyeloplasty, nephrectomy, partial nephrectomy, ureteral reimplantation and complex reconstruction) and surgical approach (laparoscopic, robotic assisted and/or laparoendoscopic single site). Proportions were compared using the chi-square test (α=0.05). RESULTS: Overall 123 studies met the inclusion criteria, reporting outcomes of 5,864 patients. About a third (35.8%) of studies used the Clavien-Dindo classification. Nephrectomy had a significantly lower frequency of grade III complications (1.18%) compared to pyeloplasty (3.64%), ureteral reimplantation (6.65%) and complex reconstruction (11.76%) (p <0.05). Complex reconstruction had a significantly higher frequency of grade III complications (11.39%) compared to all other analyzed surgeries (p <0.05). CONCLUSIONS: The rate of complications and open conversions varies by surgical procedure in pediatric urological minimally invasive surgery. Despite the existence of a standardized complication classification system, the majority of reviewed publications did not report complications in a standardized fashion. Our findings call for more robust studies in pediatric minimally invasive surgery and universal implementation of standardized complication reporting.

Discrepancies in Self-Reported and Actual Conflicts of Interest for Robotic Pediatric Urological Surgery.

PURPOSE: Transparency of conflicts of interest is essential when assessing publications that address the benefits of robotic surgery over traditional laparoscopic and open operations. We assessed discrepancies between self-reported and actual conflicts of interest as well as whether conflicts of interest are associated with favorable endorsement of robotic surgery. MATERIALS AND METHODS: We searched the Embase® and MEDLINE® databases for articles on robotic surgery within pediatric urology. We included English language articles published since 2013, when data in the Open Payments program (Centers for Medicare and Medicaid Services, Baltimore, Maryland) became available. For all United States based authors Open Payments was used to identify the total amount of financial payment received from Intuitive Surgical®. Chi-square test was used to assess the association between conflicts of interest and favorable endorsement of robotic surgery. RESULTS: A total of 191 articles were initially identified. After exclusion criteria were applied 107 articles remained (267 distinct authors). Of the articles 86 (80.4%) had at least 1 author with a history of payment from Intuitive Surgical, with 79 (91.9%) having at least 1 author who did not declare a conflict of interest despite history of payment. A total of 44 authors (16.5%) had a history of payment from Intuitive Surgical, with an average payment of $3,594.15. Articles with a first and/or last author with a history of payment were more likely to contain a favorable endorsement of robotic surgery compared to articles without a history of payment (85.1% vs 63.6%, p = 0.0124). CONCLUSIONS: Nondisclosure of conflict of interest with Intuitive Surgical is extremely common within pediatric urology. Steps to ensure accurate reporting of conflicts of interest are essential. There appears to be an association between a history of payment and favorable endorsement of robotic surgery.

Transscrotal Near Infrared Spectroscopy as a Diagnostic Test for Testis Torsion in Pediatric Acute Scrotum: A Prospective Comparison to Gold Standard Diagnostic Test Study.

PURPOSE: A rapid test for testicular torsion in children may obviate the delay for testicular ultrasound. In this study we assessed testicular tissue percent oxygen saturation (%StO2) measured by transscrotal near infrared spectroscopy as a diagnostic test for pediatric testicular torsion. MATERIALS AND METHODS: This was a prospective comparison to a gold standard diagnostic test study that evaluated near infrared spectroscopy %StO2 readings to diagnose testicular torsion. The gold standard for torsion diagnosis was standard clinical care. From 2013 to 2015 males with acute scrotum for more than 1 month and who were less than 18 years old were recruited. Near infrared spectroscopy %StO2 readings were obtained for affected and unaffected testes. Near infrared spectroscopy Δ%StO2 was calculated as unaffected minus affected reading. The utility of near infrared spectroscopy Δ%StO2 to diagnose testis torsion was described with ROC curves. RESULTS: Of 154 eligible patients 121 had near infrared spectroscopy readings. Median near infrared spectroscopy Δ%StO2 in the 36 patients with torsion was 2.0 (IQR -4.2 to 9.8) vs -1.7 (IQR -8.7 to 2.0) in the 85 without torsion (p=0.004). AUC for near infrared spectroscopy as a diagnostic test was 0.66 (95% CI 0.55-0.78). Near infrared spectroscopy Δ%StO2 of 20 or greater had a positive predictive value of 100% and a sensitivity of 22.2%. Tanner stage 3-5 cases without scrotal edema or with pain for 12 hours or less had an AUC of 0.91 (95% CI 0.86-1.0) and 0.80 (95% CI 0.62-0.99), respectively. CONCLUSIONS: In all children near infrared spectroscopy readings had limited utility in diagnosing torsion. However, in Tanner 3-5 cases without scrotal edema or with pain 12 hours or less, near infrared spectroscopy discriminated well between torsion and nontorsion.

Diagnosing Testicular Torsion before Urological Consultation and Imaging: Validation of the TWIST Score.

PURPOSE: The TWIST (Testicular Workup for Ischemia and Suspected Torsion) score uses urological history and physical examination to assess risk of testis torsion. Parameters include testis swelling (2 points), hard testis (2), absent cremasteric reflex (1), nausea/vomiting (1) and high riding testis (1). While TWIST has been validated when scored by urologists, its diagnostic accuracy among nonurological providers is unknown. We assessed the usefulness of the TWIST score when determined by nonurological nonphysician providers, mirroring emergency room evaluation of acute scrotal pain. MATERIALS AND METHODS: Children with unilateral acute scrotum were prospectively enrolled in a National Institutes of Health clinical trial. After undergoing basic history and physical examination training, emergency medical technicians calculated TWIST score and determined Tanner stage per pictorial diagram. Clinical torsion was confirmed by surgical exploration. All data were captured into REDCap™ and ROC curves were used to evaluate the diagnostic usefulness of TWIST. RESULTS: Of 128 patients (mean age 11.3 years) 44 (13.0 years) had torsion. TWIST score cutoff values of 0 and 6 derived from ROC analysis identified 31 high, 57 intermediate and 40 low risk cases (positive predictive value 93.5%, negative predictive value 100%). CONCLUSIONS: TWIST score assessed by nonurologists, such as emergency medical technicians, is accurate. Low risk patients do not require ultrasound to rule out torsion. High risk patients can proceed directly to surgery, with more than 50% avoiding ultrasound. In the future emergency medical technicians and/or emergency room triage personnel may be able to calculate TWIST score to guide radiological evaluation and immediate surgical intervention at initial assessment long before urological consultation.

DNA copy number variations in patients with 46,XY disorders of sex development.

PURPOSE: Less than 50% of cases of 46,XY disorders of sex development are genetically defined after karyotyping and/or sequencing of known causal genes. Since copy number variations are often missed by karyotyping and sequencing, we assessed patients with unexplained 46,XY disorders of sex development using array comparative genomic hybridization for possible disease causing genomic variants. MATERIALS AND METHODS: DNA from unexplained cases of 46,XY disorders of sex development were tested by whole genome array comparative genomic hybridization. In cases where novel copy number variations were detected parental testing was performed to identify whether copy number variations were de novo or inherited. RESULTS: Of the 12 patients who underwent array comparative genomic hybridization testing 2 had possible copy number variations causing disorders of sex development, both maternally inherited microdeletions. One case, with a maternal history of premature ovarian failure, had a cosegregating microdeletion on 9q33.3 involving NR5A1. The other case, with a maternal family history of congenital heart disease, had a cosegregating microdeletion on 8p23.1 upstream of GATA4. CONCLUSIONS: In this cohort copy number variations involving or adjacent to known causal genes led to 46,XY disorders of sex development in 2 of 12 previously unexplained cases (17%). Copy number variation testing is clinically indicated for unexplained cases of 46,XY disorders of sex development to aid in genetic counseling for family planning.

Tamsulosin and spontaneous passage of ureteral stones in children: a multi-institutional cohort study.

PURPOSE: Tamsulosin is associated with increased passage of ureteral stones in adults but its effectiveness in children is uncertain. We determined the association between tamsulosin and the spontaneous passage of ureteral stones in children. MATERIALS AND METHODS: We performed a multi-institutional retrospective cohort study of patients 18 years or younger who presented between 2007 and 2012 with ureteral stones up to 10 mm and who were treated with tamsulosin or oral analgesics alone. The outcome was spontaneous stone passage, defined as radiographic clearance and/or patient report of passage. Subjects prescribed tamsulosin were matched with subjects prescribed analgesics alone, using nearest neighbor propensity score matching to adjust for treatment selection. Conditional logistic regression models were used to estimate the association between tamsulosin and spontaneous passage of ureteral stones, adjusting for stone size and location. RESULTS: Of 449 children with ureteral stones 334 were eligible for inclusion, and complete data were available for 274 patients from 4 institutions (99 receiving tamsulosin, 175 receiving analgesics alone). Following case matching, there were no differences in age, gender, weight, height, stone size or stone location between the 99 subjects prescribed tamsulosin and the 99 propensity score matched subjects prescribed analgesics alone. In the tamsulosin cohort 55% of ureteral stones passed, compared to 44% in the analgesics alone cohort (p=0.03). In multivariate analysis adjusting for stone size and location tamsulosin was associated with spontaneous passage of ureteral stones (OR 3.31, 95% CI 1.49-7.34). CONCLUSIONS: The odds of spontaneous passage of ureteral stones were greater in children prescribed tamsulosin vs analgesics alone.

Puberty Blocker and Aging Impact on Testicular Cell States and Function.

Spermatogonial stem cell (SSC) acquisition of meiotogenetic state during puberty to produce genetically diverse gametes is blocked by drugs collectively referred as 'puberty blocker' (PB). Investigating the impact of PB on juvenile SSC state and function is challenging due to limited tissue access and clinical data. Herein, we report largest clinically annotated juvenile testicular biorepository with all children with gender dysphoria on chronic PB treatment highlighting shift in pediatric patient demography in US. At the tissue level, we report mild-to-severe sex gland atrophy in PB treated children. We developed most extensive integrated single-cell RNA dataset to date (>100K single cells; 25 patients), merging both public and novel (52 month PB-treated) datasets, alongside innovative computational approach tailed for germ cells and evaluated the impact of PB and aging on SSC. We report novel constitutional ranges for each testicular cell type across the entire age spectrum, distinct effects of treatments on prepubertal vs adult SSC, presence of spermatogenic epithelial cells exhibiting post-meiotic-state, irrespective of age, puberty status, or PB treatment. Further, we defined distinct effects of PB and aging on testicular cell lineage composition, and SSC meiotogenetic state and function. Using single cell data from prepubertal and young adult, we were able to accurately predict sexual maturity based both on overall cell type proportions, as well as on gene expression patterns within each major cell type. Applying these models to a PB-treated patient that they appeared pre-pubertal across the entire tissue. This combined with the noted gland atrophy and abnormalities from the histology data raise a potential concern regarding the complete 'reversibility' and reproductive fitness of SSC. The biorepository, data, and research approach presented in this study provide unique opportunity to explore the impact of PB on testicular reproductive health.

Screening and familial characterization of copy-number variations in NR5A1 in 46,XY disorders of sex development and premature ovarian failure.

The NR5A1 gene encodes for steroidogenic factor 1, a nuclear receptor that regulates proper adrenal and gonadal development and function. Mutations identified by NR5A1 sequencing have been associated with disorders of sex development (DSD), ranging from sex reversal to severe hypospadias in 46,XY patients and premature ovarian failure (POF) in 46,XX patients. Previous reports have identified four families with a history of both 46,XY DSD and 46,XX POF carrying segregating NR5A1 sequence mutations. Recently, three 46,XY DSD sporadic cases with NR5A1 microdeletions have been reported. Here, we identify the first NR5A1 microdeletion transmitted in a pedigree with both 46,XY DSD and 46,XX POF. A 46,XY individual with DSD due to gonadal dysgenesis was born to a young mother who developed POF. Array CGH analysis revealed a maternally inherited 0.23 Mb microdeletion of chromosome 9q33.3, including the NR5A1 gene. Based on this finding, we screened patients with unexplained 46,XY DSD (n = 11), proximal hypospadias (n = 21) and 46,XX POF (n = 36) for possible NR5A1 copy-number variations (CNVs) via multiplex ligation-dependent probe amplification (MLPA), but did not identify any additional CNVs involving NR5A1. These data suggest that NR5A1 CNVs are an infrequent cause of these disorders but that array CGH and MLPA are useful genomic screening tools to uncover the genetic basis of such unexplained cases. This case is the first report of a familial NR5A1 CNV transmitting in a pedigree, causing both the male and female phenotypes associated with NR5A1 mutations, and the first report of a NR5A1 CNV associated with POF.