Mixed Gonadal Dysgenesis: A Narrative Literature Review and Clinical Primer for the Urologist.

PURPOSE: Mixed gonadal dysgenesis is a difference of sex development that is often confused with other conditions. Individuals have a 45,X/46,XY karyotype. Gonads are characterized by a streak gonad and a dysgenetic testis at varying levels of descent. Persistent Müllerian structures are typical (eg, hemi-uterus). There is significant phenotypic heterogeneity of the internal and external genitalia that, together with different interpretations of the definition, have contributed to a poor understanding of the condition among pediatric urologists. Mixed gonadal dysgenesis is one manifestation of the 45,X/46,XY karyotype. 45,X/46,XY mosaicism can also be associated with typical female or male external genitalia. This review aims to clarify the mixed gonadal dysgenesis definition and to provide urologists with diagnostic and management considerations for affected individuals. MATERIALS AND METHODS: We searched 3 medical databases for articles related to mixed gonadal dysgenesis. Two hundred eighty-seven full-text abstracts and manuscripts were reviewed for content pertinent to: (1) clarifying the definition of mixed gonadal dysgenesis, and (2) describing the following related to the care of affected individuals: prenatal and neonatal evaluation and management, genital surgery, gonadal malignancy risk and management, fertility, gender dysphoria/incongruence, puberty and long-term outcomes, systemic comorbidities, and transitional care. RESULTS: Fifty articles were included. Key points and implications for each of the above topics were summarized. CONCLUSIONS: Mixed gonadal dysgenesis exists on a wide phenotypic spectrum and management considerations reflect this heterogeneity. Care for individuals with mixed gonadal dysgenesis is complex, and decisions should be made in a multidisciplinary setting with psychological support.

Intermittent catheterization and urinary tract infection in multiple sclerosis patients.

INTRODUCTION: We sought to investigate whether starting clean intermittent catheterization (CIC) for multiple sclerosis (MS) patients with lower urinary tract symptoms (LUTS) and elevated post-void residual (PVR) would improve urinary quality of life (QoL) and decrease risk of urinary tract infection (UTI). MATERIALS AND METHODS: We retrospectively reviewed an institutional data base for MS patients with PVR > 100 mL and obstructive LUTS. Patients were categorized by subsequent choice of treatment: CIC versus medical treatment. Outcomes compared over 1-year follow up included incidence of UTI, urinary QoL, emergency room visits, and adherence to therapy. RESULTS: Between 2014 and 2017, 37 patients met inclusion criteria. Nineteen patients started daily CIC, while 18 patients had pharmacologic therapy. At 1-year follow up, the CIC group had less improvement in urinary symptoms (26% improvement from baseline versus 72%, p = 0.02) and 7 times greater odds of having minimum one UTI within 1 year (OR 6.8, p = 0.01). The CIC group was also more likely to start an additional treatment for LUTS, and to visit the ED (all p < 0.05). CONCLUSIONS: In this group of MS patients with LUTS and elevated PVR, initiation of CIC was associated with increased incidence of UTI and less improvement in urinary symptoms over the subsequent year compared to pharmacologic treatment.

Use of other treatments before hysterectomy for benign conditions in a statewide hospital collaborative.

OBJECTIVE: We sought to analyze use of alternative treatments and pathology among women who underwent hysterectomy in the Michigan Surgical Quality Collaborative. STUDY DESIGN: Perioperative hysterectomy data including demographics, preoperative alternative treatments, and pathology results were analyzed from 52 hospitals participating in the Michigan Surgical Quality Collaborative from Jan. 1 through Nov. 8, 2013. Women who underwent hysterectomy for benign indications including uterine fibroids, abnormal uterine bleeding (AUB), endometriosis, or pelvic pain were eligible. Pathology was classified as "supportive" when fibroids, endometriosis, endometrial hyperplasia, adenomyosis, adnexal pathology, or unexpected cancer were reported and "unsupportive" if these conditions were not reported. Multivariable analysis was done to determine independent associations with use of alternative treatment and unsupportive pathology. RESULTS: Inclusion criteria were met by 56.2% (n = 3397) of those women who underwent hysterectomy (n = 6042). There was no documentation of alternative treatment prior to hysterectomy in 37.7% (n = 1281). Alternative treatment was more likely to be considered among women aged <40 years vs those aged 40-50 and >50 years (68% vs 62% vs 56%, P < .001) and among women with larger uteri. Unsupportive pathology was identified in 18.3% (n = 621). The rate of unsupportive pathology was higher among women age <40 years vs those aged 40-50 and >50 years (37.8% vs 12.0% vs 7.5%, P < .001), among women with an indication of endometriosis/pain vs uterine fibroids and/or AUB, and among women with smaller uteri. CONCLUSION: This study provides evidence that alternatives to hysterectomy are underutilized in women undergoing hysterectomy for AUB, uterine fibroids, endometriosis, or pelvic pain. The rate of unsupportive pathology when hysterectomies were done for these indications was 18%.

Differential Insurance Plan Coverage and Surgeon Reimbursement of Pediatric Circumcision at an Urban, Midwestern Hospital.

OBJECTIVE: To explore private vs public pediatric circumcision insurance coverage and surgeon reimbursement. METHODS: A telephone survey about circumcision coverage (Current Procedural Terminology codes: 54150, 54161) was conducted in October 2021 with insurance plan representatives from the 12 plans that comprised ≥1% of institutional pediatric urology visits to compare plan characteristics and coverage details. Circumcision billing data were collected at one pediatric hospital to assess surgeon reimbursement (insurance+patient payment) by plan type using bivariate statistics. RESULTS: Ten plans (5 private and 5 public) responded (83.3% response rate). All except one public plan covered newborn circumcision. For non-newborn circumcisions, most public plans (80%) had unrestricted coverage, whereas all private plans required medical necessity. Median reimbursement for newborn circumcision (CPT: 54150) was $484 for private and $78 for public plans, P < .001 while median reimbursement for non-newborn circumcision (CPT: 54161) was $314 for private and $147 for public plans, P < .001. CONCLUSION: Private insurance plans reimburse significantly more than public plans for newborn circumcision. For non-newborn circumcision, private plans reimburse more than public but the coverage is more restricted, with a smaller differential between newborn and non-newborn circumcision. This coverage and reimbursement structure may indirectly encourage newborn circumcision for privately insured boys and non-newborn circumcision for publicly insured boys.

Retrograde incision from orifice (RIO) technique for endoscopic incision of ureterocele: 15 years of outcomes.

INTRODUCTION: Management of obstructing ureterocele often includes endoscopic transurethral incision (TUI) that can be challenging secondary to uncertainty in anatomic landmarks with risk of serious complications. To this end, we innovated a technique using predictable landmarks that begins endoscopic incision at the ureterocele orifice and extends retrograde proximal to the bladder neck (Figure). OBJECTIVE: With over 15 years of experience in performing this retrograde incision from orifice (RIO) technique, we aimed to examine post-operative outcomes and risk of surgical failure after RIO compared to traditional TUI techniques for ureteroceles. We hypothesized that clinical outcomes after RIO would be superior to traditional endoscopic approaches to decompression of obstructing ureterocele in infants. STUDY DESIGN: A retrospective study of patients ≤12 months old who underwent TUI ureterocele at our institution between 2007 and -2021 was conducted. Pre-, intra- and post-operative characteristics were compared between patients who underwent RIO vs non-RIO TUI. Primary outcome was post-incision febrile urinary tract infection (fUTI). Secondary outcome was a composite failure measure of fUTI, secondary surgery, de novo bladder outlet obstruction, or vesicoureteral reflux. Multivariable Cox proportional hazard models were fitted to compare the time-to-event risk of primary and secondary outcomes between groups. RESULTS: Ninety patients with 92 ureteroceles were included (49 RIO, 43 non-RIO). Median follow-up from TUI was 33 months. RIO had a shorter median operative duration (27 vs 35 min, p = 0.021). Primary and secondary outcomes were similar between groups (fUTI: 29% RIO vs 19% non-RIO, p = 0.27; composite failure 54% RIO vs 69% non-RIO, p = 0.15). In multivariable Cox proportional hazard models, there was no significant difference in risk of fUTI (RIO aHR 0.98, 95% CI 0.38-2.54, p = 0.97) or composite failure (RIO aHR 0.80, 95% CI 0.45-1.44, p = 0.46) between TUI techniques. DISCUSSION: RIO technique for TUI ureterocele is attractive in that it uses predictable anatomic landmarks making it simple to perform. In analyzing this 15-year institutional experience of TUI ureterocele, RIO showed similar success to non-RIO endoscopic incisions. This study is a retrospective, non-randomized, single-institutional study over 15 years and is therefore subject to change in surgeon practice over time and variable practices between providers. CONCLUSIONS: Given comparable success and durability over time to other TUI ureterocele techniques, and with the advantage of operator ease using consistent anatomic landmarks, RIO is a worthy option for endoscopic ureterocele decompression.

Attitudes toward fertility-related care and education of adolescents and young adults with differences of sex development: Informing future care models.

INTRODUCTION: Adolescents and young adults (AYA) with differences of sex development (DSD) face many challenging healthcare decisions. Fertility preservation is an emerging but experimental option for AYA with DSD. Optimal counseling regarding future fertility options has not yet been defined for this population. OBJECTIVE: To examine the fertility-related attitudes and experiences of AYA with DSD to inform future care needs. STUDY DESIGN: Semi-structured interviews were conducted from 2015 to 2018 with AYA with a DSD diagnosis who were seen in our multidisciplinary clinic. Topics covered included attitudes toward fertility and family building, fertility-related communication, and perspectives on fertility-related education and decision-making. Qualitative content analysis was performed using an inductive and deductive approach. RESULTS: Eight AYA (median age 17 years, range 14-28) with various DSD diagnoses (Mayer-Rokitansky-Küster-Hauser syndrome, complete androgen insensitivity syndrome, congenital adrenal hyperplasia, and 46, XY DSD unspecified) participated. AYA were open to many options related to family building and fertility preservation, desired full disclosure of information, and recognized the importance of an age-related progression to autonomy in decision-making. Spanning all topics, the following were salient: 1) diversity of attitudes and care preferences amongst participants, 2) evolution of these attitudes and preferences over time, and 3) an emphasis on individualization of education and care (Fig. 1). DISCUSSION: This qualitative study provided information on the fertility-related experiences and attitudes of AYA with DSD. Prior studies have shown a diversity of patient and parent preferences in many aspects of DSD research as well as low rates of fertility-related education and satisfaction therefrom. The knowledge gained from this study can be used to guide individualized and compassionate education and care surrounding the complex and evolving topic of fertility. This study is limited by interviews being conducted prior to the implementation of our DSD-specific gonadal tissue cryopreservation protocol. Despite this, the fertility-related patient experiences and attitudes prior to protocol implementation are important to present. The results from the preliminary analysis of these data were used to inform a new, ongoing qualitative study to explore the patient experience with fertility preservation in a more targeted fashion. CONCLUSIONS: The perspectives on fertility and related healthcare experiences of AYA with DSD demonstrated openness to many family-building options, a desire for full disclosure of information, care needs that evolved over time, and a recognition of the importance of eventual autonomy in decision-making. A flexible and individualized approach by the provider can optimize fertility-related healthcare experiences for AYA with DSD.

COVID-19 Pandemic Adversely Affects the Provision of Desired Newborn Circumcision: Perinatal Physician Perspectives.

Over half of boys in the United States undergo circumcision, which has its greatest health benefits and lowest risks when performed during the newborn period under local anesthesia. The COVID-19 pandemic has affected delivery of patient care in many ways and likely also influenced the provision of newborn circumcisions. Prior to the pandemic, we planned to conduct a qualitative study to ascertain physician perspectives on providing newborn circumcision care. The interviews incidentally coincided with the onset of the pandemic and thus, pandemic-related changes emerged as a theme. We elected to analyze this theme in greater detail. Semi-structured interviews were conducted with perinatal physicians in a large urban city from 4/2020 to 7/2020. Physicians that perform or counsel regarding newborn circumcision and physicians with knowledge of or responsibility for hospital policies were eligible. Interviews were transcribed verbatim and qualitative coding was performed. Twenty-three physicians from 11 local hospitals participated. Despite no specific COVID-19 related questions in the interview guide, nearly half of physicians identified that the pandemic affected delivery of newborn circumcision care with 8 pandemic-related sub-themes. The commonest sub-themes included COVID-19 related changes in: (1) workflow processes, (2) staffing and availability of circumcision proceduralists, and (3) procedural settings. In summary, this qualitative study revealed unanticipated COVID-19 pandemic-related changes with primarily adverse effects on the provision of desired newborn circumcisions. Some of these changes may become permanent resulting in broad implications for policy makers that will likely need to adapt and redesign the processes and systems for the delivery of newborn circumcision care.

Opioid prescribing is excessive and variable after pediatric ambulatory urologic surgery.

BACKGROUND: Acute pain after surgery is one of the most frequent indications for opioid prescribing in children. Opioids are often not stored or disposed of safely after their use, placing children and others in the home at risk for accidental ingestion or intentional misuse. We currently lack evidence-based guidelines for post-operative pain management after common ambulatory pediatric urologic procedures. Thus, each surgeon must decide if and how much opioid to prescribe based on his/her own assumptions of perceived post-operative pain. OBJECTIVES: As part of an effort to establish opioid prescribing guidelines across two academic centers, the objectives of this study were to evaluate current variability in pediatric urologists' opioid prescribing factors and identify patients at greatest risk of being prescribed high doses of opioids after common ambulatory pediatric urologic procedures. METHODS: We retrospectively evaluated post-operative opioid prescribing patterns after common ambulatory pediatric urology procedures (circumcision, orchiopexy, and hernia/hydrocele) at two major children's hospitals. Specifically, we evaluated if and how much opioid was prescribed for all children (18 years or younger) between 2016 and 2017. Bivariate analysis was performed using Kruskal-Wallis Test and Wilcoxon Rank Sum. Multivariable logistic regression was performed to determine patient, surgeon, and procedural factors that predicted the prescription of a high dose of opioids (greater than the median number of doses prescribed for that procedure). RESULTS: Over the two-year period, 811 circumcisions and 883 inguinal surgeries (inguinal orchiopexy and hernia/hydrocele) were performed. 94% of patients undergoing circumcision and 97% of those undergoing inguinal surgery were prescribed opioid analgesia. The median number of doses prescribed for circumcision was 20; for inguinal surgeries, 23.75% of patients received 15 opioid doses or more. Patients ages 0-2 years, who represented the largest age group (41% of all patients), received significantly more opioid doses than all other age groups, followed by those >10 years (p < 0.01). There was significant variation in opioid prescribing patterns by provider (p < 0.01) (Figure 1) On multivariable logistic regression, younger age, pill form, and earlier year were all associated with a greater number of opioid doses prescribed for all surgeries. CONCLUSIONS: Across two institutions without a formal post-operative opioid prescribing policy for ambulatory pediatric urologic procedures, we observed considerable variability in provider prescribing patterns, with nearly all patients receiving an opioid, and those 0-2 years receiving the highest number of doses. This highlights the need for evidence-based guidelines for post-operative pain management after ambulatory pediatric urologic surgeries.

Rethinking the one-size-fits-most approach to venous thromboembolism prophylaxis after radical cystectomy.

OBJECTIVES: Empirically dosed enoxaparin is routinely given in the postoperative period for venous thromboembolism (VTE) prophylaxis after radical cystectomy (RC). Patient-specific factors may alter its pharmacokinetics, and it is unclear whether this leads to levels sufficient for antithrombosis. We sought to evaluate variability of anti-factor Xa levels in a cohort of RC patients receiving perioperative enoxaparin prophylaxis. MATERIAL AND METHODS: Patients undergoing RC at a single institution were placed on a postoperative pathway that included enoxaparin. An anti-factor Xa level was drawn 2 to 4 hours after the third dose. The target range for prophylaxis was 0.3 IU/ml to 0.5 IU/ml. RESULTS: The primary outcome was anti-factor Xa level. Demographics, operative time, hospital course, and 30-days post-operative VTE were compared by anti-factor Xa level group using univariate and multivariable analyses. Between January 2018 and 2019, 107 RC patients remained on pathway and were included in our analysis. Sixty-five (61%) were below target range for VTE prophylaxis.  A single VTE event (0.9%) occurred in a subprophylactic individual. The subprophylactic group had a significantly higher body mass index (P < 0.01) than those within target range. CONCLUSIONS: Higher body mass index was associated with subprophylactic enoxaparin dosing after RC. Nearly two-thirds of patients had below target anti-factor Xa levels. This suggests that dosing could be further individualized, but given the low incidence of VTE, implications of dose-adjusted prophylaxis on VTE prevention remain unknown.

Urodynamic and imaging findings in infants with myelomeningocele may predict need for future augmentation cystoplasty.

INTRODUCTION: Urologic issues are persistent and important causes of morbidity and mortality in patients with myelomeningocele. Classically, patients with elevated bladder pressures despite adherence to clean intermittent catheterization (CIC) and pharmacotherapy undergo augmentation cystoplasty (AC). Currently, there is little understanding of which infants are more likely to require AC later. OBJECTIVE: In this context, the authors studied whether unfavorable urodynamic or imaging findings in patients with myelomeningocele during infancy could predict future AC. The authors hypothesized that infants born with elevated bladder pressures, vesicoureteral reflux (VUR), and/or hydronephrosis would be more likely to undergo AC. STUDY DESIGN: The authors retrospectively identified patients with myelomeningocele at their institution who were followed-up since infancy (<1 year of age), with a minimum of eight continuous years of follow-up. Standard care protocol included cystometrogram, voiding cystourethrogram (VCUG), and renal ultrasound during infancy. The primary outcome was AC for elevated bladder pressures despite attempts at more conservative management with medical therapy and CIC. Specifically, the authors evaluated for differences in augmentation rates based on gender, level of lesion, presence of detrusor leak point pressure (DLPP) or end-fill pressure (EFP) greater than 40 cm H2O, presence of hydronephrosis, VUR, initiation of CIC, and initiation of antimuscarinics in infancy. The authors excluded patients who underwent surgical intervention for urinary incontinence. RESULTS: A total of 97 patients met the inclusion criteria. The median follow-up time was 13.8 years. Augmentation cystoplasty was performed for 17 patients (17.5%) at a median age of 114 months (9.5 years). Detrusor leak point pressure/EFP was greater than 40 cm H2O in 34.0% (33/97) of infant cystometrogram studies, while 30.9% (30/97) had VUR on infant VCUG and 20.6% (20/97) had hydronephrosis on infant renal ultrasound. Patients with DLPP/EFP greater than 40 cm H2O or VUR during infancy were more likely to undergo AC (P = 0.02 and P = 0.03, respectively). Binomial logistic regression revealed that DLPP/EFP greater than 40 cm H2O (odds ratio [OR]: 4.28, 95% confidence interval [CI]: 1.34-13.62) and VUR (OR: 3.73, 95% CI: 1.18-11.77) were independent risk factors for future AC. DISCUSSION: Infants with myelomeningocele and elevated bladder pressures and VUR should be closely monitored by urodynamic testing and imaging studies. Parents can be counseled regarding the potentially higher risk for future AC in these patients. Nonetheless, the majority of high-risk infants will safely avoid AC with conservative management.

Urethral Pressure Measurement as a Tool for the Urodynamic Diagnosis of Detrusor Sphincter Dyssynergia.

PURPOSE: To describe a technique for urodynamic diagnosis of detrusor sphincter dyssynergia (DSD) using urethral pressure measurements and examine potential associations between urethral pressure and bladder physiology among patients with DSD. METHODS: Multiple sclerosis (MS) and spinal cord injured (SCI) patients with known DSD diagnosed on videourodynamics (via electromyography or voiding cystourethrography) were retrospectively identified. Data from SCI and MS patients with detrusor overactivity (DO) without DSD were abstracted as control group. Urodynamics tracings were reviewed and urethral pressure DSD was defined based on comparison of DSD and control groups. RESULTS: Seventy-two patients with DSD were identified. Sixty-two (86%) had >20 cm H2O urethral pressure amplitude during detrusor contraction. By comparison, 5 of 23 (22%) of control group had amplitude of >20 cm H2O during episode of DO. Mean duration of urethral pressure DSD episode was 66 seconds (range, 10-500 seconds) and mean urethral pressure amplitude was 73 cm H2O (range, 1-256 cm H2O). Longer (>30 seconds) DSD episodes were significantly associated with male sex (81% vs. 50%, P=0.013) and higher bladder capacity (389 mL vs. 219 mL, P=0.0004). Urethral pressure amplitude measurements during DSD were not associated with significant urodynamic variables or neurologic pathology. CONCLUSION: Urethral pressure amplitude of >20 cm H2O during detrusor contraction occurred in 86% of patients with known DSD. Longer DSD episodes were associated with larger bladder capacity. Further studies exploring the relationship between urethral pressure measurements and bladder physiology could phenotype DSD as a measurable variable rather than a categorical observation.