Endometriosis in a pre-pubertal patient with 46,XY difference in sex development: a case report.

INTRODUCTION: Endometriosis typically presents in postmenarchal patients with cyclic and acyclic pelvic pain. However, there are reports of endometriosis in premenarchal patients. CASE: We report a ten-year-old individual with 46,XY DSD who was found to have endometriosis at the time of laparoscopic gonadectomy for gonadoblastoma. CONCLUSIONS: Although rare, endometriosis can occur in 46,XY individuals prior to puberty, highlighting the complex origin of the disease.

Feasibility of Enhanced Recovery After Surgery (ERAS) implementation in Pediatric Urology: Pilot-phase outcomes of a prospective, multi-center study.

INTRODUCTION/BACKGROUND: Enhanced Recovery After Surgery (ERAS) is a fundamental shift in perioperative care that has consistently demonstrated an improved outcome for a wide variety of surgeries in adults but has only limited evidence in the pediatric population. OBJECTIVE: We aimed to assess the success with and barriers to implementation of ERAS in a prospective, multi-center study on patients undergoing complex lower urinary tract reconstruction. STUDY DESIGN: Centers were directed to implement an ERAS protocol using a multidisciplinary team and quality improvement methodologies. Providers completed pre- and post-pilot surveys. An audit committee met after enrolling the first 5 patients at each center. Pilot-phase outcomes included enrollment of ≥2 patients in the first 6 months of enrollment, completion of 90 days of follow-up, identification of barriers to implementation, and protocol adherence. RESULTS: A total of 40 patients were enrolled across 8 centers. The median age at surgery was 10.3 years (IQR 6.4-12.5). Sixty five percent had a diagnosis of myelomeningocele, and 33 % had a ventriculoperitoneal shunt. A bladder augmentation was performed in 70 %, Mitrofanoff appendicovesicostomy in 52 %, Monti ileovesicostomy in 15 %, and antegrade continence enema channel in 38 %. The most commonly perceived barriers to implementation on the pre-pilot survey were "difficulty initiating and maintaining compliance with care pathway" in 51 % followed by a "lack of time, money, or clinical resources" in 36 %. The pre-pilot study experience, implementation, and pilot-phase outcomes are provided in the Table. All primary and secondary outcomes were achieved. DISCUSSION: The findings of the present study were similar to several small comparative studies with regard to the importance of a multidisciplinary team, strong leadership, and continuous audit for successful implementation of ERAS. Similar barriers were also encountered to other studies, which primarily related to a lack of administrative support, leadership, and buy-in from other services. The limitations of the present study included a relatively small heterogeneous cohort and absence of a comparative group, which will be addressed in the larger exploratory phase of the trial. The findings may also not be generaziable due to the need for sustainable processes that were unique to each center as well as an absence of adequate volume or resources at smaller centers. CONCLUSIONS: ERAS was successfully implemented for complex lower urinary tract reconstruction across 8 centers through a multidisciplinary team, structured approach based on the local context, and focus on a continuous audit.

Adult urological outcomes for patients with anorectal malformation.

Anorectal malformations (ARM) are rare congenital anomalies characterized by a spectrum of defects resulting in the absence of a normal anal opening with or without fistula. Urogenital involvement is common, and the fistulous tract may terminate in the genitourinary system in males or within gynecological structures in females. Surgical reconstruction occurs early in life and survival of these patients to adulthood is the norm. There has, therefore, been increased focus on their long-term outcomes to better anticipate and treat the sequelae that may impact their health and well-being as this population ages. For urologists, urinary health, sexual function, and fertility outcomes are of particular interest among this population. This article aims to provide a review of urological, sexual, and fertility outcomes for individuals born with ARM with a focus on key issues that may occur later in life to ensure adequate counseling, screening, and treatment.

Undescended testis: A roundtable discussion based on clinical scenarios - Part 1.

Undescended testis (UDT, cryptorchidism) is the most common congenital anomaly of the genital tract. Despite its high incidence, the management of UDT varies between specialties (urology, pediatric surgery, pediatric urology, pediatric endocrinology). Therefore, as the European Association of Urology - Young Academic Urologists Pediatric Urology Working Group, we requested experts around the world to express their own personal approaches against various case scenarios of UDT in order to explore their individual reasoning. We intended to broaden the perspectives of our colleagues who deal with the treatment of this frequent genital malformation.

Considerations and Outcomes for Adolescents and Young Adults With Cloacal Anomalies: A Scoping Review of Urologic, Colorectal, Gynecologic and Psychosocial Concerns.

The objective of this scoping review is to provide a summary of the current literature regarding adolescents and young adults with histories of cloacal anomalies. Preferred Reporting Items for Systematic Reviews and Meta-analysis Extension for Scoping Reviews were used. Data were categorized into four domains-urologic, colorectal, gynecologic/obstetric, and sexual/psychosocial. The current literature has poor study quality and mostly consists of retrospective studies of small cohorts with varying definitions of outcomes. Women with cloacal anomalies are at high risk for urologic dysfunction but can maintain kidney health and achieve social continence with medical and surgical management. Sexual function and adult healthcare transition are areas ripe for improved future research.

Anti-fibrotic effect of tocotrienols for bladder dysfunction due to partial bladder outlet obstruction.

PURPOSE: To investigate potential beneficial effects of tocotrienols which have been suggested to inhibit hypoxia-inducible factor (HIF) pathway, on partial bladder outlet obstruction (PBOO)-induced bladder pathology. MATERIALS AND METHODS: PBOO was surgically created in juvenile male mice. Sham-operated mice were used as controls. Animals received daily oral administration of either tocotrienols (T3) or soybean oil (SBO, vehicle) from day 0 to 13 post-surgery. Bladder function was examined in vivo by void spot assay. At 2 weeks post-surgery, the bladders were subjected to physiological evaluation of detrusor contractility in vitro using bladder strips, histology by H&E staining and collagen imaging, and gene expression analyses by quantitative PCR. RESULTS: A significant increase in the number of small voids was observed after 1 week of PBOO compared to the control groups. At 2 weeks post-surgery, PBOO+SBO mice showed a further increase in the number of small voids, which was not observed in PBOO+T3 group. PBOO-induced decrease in detrusor contractility was similar between two treatments. PBOO induced bladder hypertrophy to the same degree in both SBO and T3 treatment groups, however, fibrosis in the bladder was significantly less prominent in the T3 group than the SBO group following PBOO (1.8- vs. 3.0-fold increase in collagen content compared to the control). Enhanced levels of HIF target genes in the bladders were observed in PBOO+SBO group, but not in PBOO+T3 group compared to the control. CONCLUSIONS: Oral tocotrienol treatment reduced the progression of urinary frequency and bladder fibrosis by suppressing HIF pathways triggered by PBOO.

Management of the urological tract in children with anorectal malformations - a contemporary review.

Anorectal malformations (ARMs) consist of a broad spectrum of congenital anomalies that are associated with an equally wide variety of urological abnormalities, often with increasing incidence as the severity of the ARM increases. The importance of urologic involvement in the care of ARM patients has been noted for decades and is critical from birth to adulthood. Urology must be involved in the initial evaluation and operative care of the child as well as in monitoring and managing issues such as neurogenic bladder, renal disease, and eventually sexual function and fertility. Care of the ARM patient must be done through a multidisciplinary lens, with the urologist as a key player. This review will serve as an update on the management of the urologic tract in children with ARM.

Hypospadias: lessons learned. An overview of incidence, epidemiology, surgery, research, complications, and outcomes.

Hypospadias is a common condition and familiar, though sometimes challenging territory for the pediatric urologist. This review is a summary of hypospadias incidence, epidemiology, surgery, research, and complications intended for the non-specialist. It outlines the history, the principles of surgery for hypospadias, and the long-term outcomes.

Retrospective analysis of bladder perforation risk in patients after augmentation cystoplasty using an extraperitoneal approach.

BACKGROUND: Initial management of pediatric patients with neurogenic bladder is focused on clean intermittent catheterization and medical therapies. Those with more hostile or small capacity bladders require surgical intervention including bladder augmentation that can result in significant clinical sequelae. This study examines a rarely described approach wherein the bladder reconstruction is extraperitonealized by bringing bowel segments through a peritoneal window and then closed. OBJECTIVE: The aim of this study was to determine if the rate of bladder rupture and subsequent morbidity differed between patients who have undergone an intraperitoneal versus extraperitoneal bladder augmentation. We hypothesized that an extraperitoneal approach reduced the risk of intraperitoneal bladder perforation, downstream Intensive Care Unit (ICU) admission, small bowel obstruction (SBO) requiring exploratory laparotomy, and ventriculoperitoneal (VP) shunt-related difficulties as compared to the standard intraperitoneal technique. METHODS: A retrospective chart review was conducted to assess surgical approach and outcomes in patients who underwent bladder augmentation performed between January 2009 and June 2021. Patients were identified through an existing database and manual chart review was conducted to extract data through imaging studies, operative notes, and clinical documentation. The primary outcome was bladder perforation. Secondary outcomes were ICU admission, exploratory laparotomy, and VP shunt externalization, infection, or revision for any cause. Nonparametric statistical analyses were performed. RESULTS: A total of 111 patients underwent bladder augmentation with 37 intraperitoneal and 74 extraperitoneal procedures. Median follow up was 5.8 years [IQR 3.0-8.6 years] and did not vary between groups (P = 0.67). Only one patient was found to have a bladder perforation in the intraperitoneal group (log-rank P = 0.154). There were no significant differences in time to post-augmentation ICU admission, exploratory laparotomy, or VP shunt events between the two groups (log-rank P = 0.294, log-rank P = 0.832, and log-rank P = 0.237, respectively). Furthermore, a Kaplan-Meier analysis assessing time to composite complication demonstrated no significant difference between the two techniques (log-rank P = 0.236). DISCUSSION: This study provides important data comparing the rate of bladder perforation and subsequent morbidity between intraperitoneal and extraperitoneal bladder augmentation. As expected, with a complex procedure, both groups suffered complications, but these data showed no difference between the two procedures. Rates of prior (abdominal) surgery may influence the decision to perform this procedure extraperitoneal. CONCLUSIONS: Outcomes related to bladder perforation and secondary consequences do not differ significantly between patients who had bladder augmentation performed with an intraperitoneal versus extraperitoneal approach. Given the low number of adverse events in this study, larger studies are warranted.

Reproductive and Family Building Considerations for Female Patients with Anorectal And Urogenital Malformations.

BACKGROUND: Little is known about fertility and pregnancy outcomes in patients with anorectal malformations (ARM), particularly those with long common channel cloaca and cloacal exstrophy who may have impaired fertility. The purpose of this study is to describe pregnancy and offspring data from a cohort of patients with ARM. METHODS: A retrospective review of female patients with ARM from our database, which includes patients operated on since 1980, was performed as well as a review of the literature. Demographic, operative, and self-reported fertility, obstetric, and offspring data were collected. RESULTS: There were 37 females identified in our database who reported any pregnancy or having children. There were 59 pregnancies, 48 (81.3%) of which resulted in live birth. The most common mode of delivery was cesarean delivery. There were five patients with long channel cloaca (>3 cm) and one with cloacal exstrophy that reported 11 total pregnancies, eight of which resulted in live birth. Four cloaca patients in which the native vagina was pulled through were able to conceive spontaneously. Three patients with cloacal anomalies required in vitro fertilization to conceive; one was unsuccessful. No patients who underwent bowel partial vaginal replacement became pregnant. Women with ARM face many unique challenges in assisted reproduction, pregnancy, and delivery owing to their anatomy and associated anomalies. CONCLUSIONS: Women with recto-perineal, recto-vestibular, and cloacas in which the native vagina was pulled through are capable of spontaneous pregnancy. Assisted reproduction, however, may be needed those with more complex anomalies and surgical repairs. LEVEL OF EVIDENCE: IV.

Sexual function and fertility of adult males with anorectal malformations or Hirschsprung disease.

PURPOSE: The long-term impact of anorectal malformations (ARM) and Hirschsprung disease (HD) on sexual function is well recognized but understudied. This study evaluated self-reported sexual and fertility outcomes in adult males with ARM and HD. METHODS: This was an IRB approved, prospective study of males in the Adult Colorectal Research Registry who completed surveys between October 2019 and March 2022. Electronic surveys were administered after consenting to being contacted for research. Patients completed the International Index of Erectile Function (IIEF) questionnaire and provided information on fertility outcomes. RESULTS: Sixty-five patients completed outcome questionnaires: 11 (16.9%) had HD and 54 (83.1%) had an ARM. Nineteen patients reported some degree of erectile dysfunction per IIEF criteria, a greater proportion of whom have ARM (p = 0.046). Twenty (30.7%) have reported having children; there were no differences in rates between HD and ARM patients. Most patients had not attempted to conceive, but eight patients, all of whom have ARM, have pursued fertility investigation or treatments. CONCLUSION: More patients with ARM reported some degree of erectile dysfunction compared to those with HD. Additionally, some have required fertility treatments. Further investigation is warranted to ensure true low rates of sexual and fertility dysfunction in patients with HD.

Patient-reported urinary outcomes in adult males with congenital colorectal conditions.

PURPOSE: Long-term urinary outcomes for patients born with Hirschsprung disease (HD) and anorectal malformations (ARM) may impact their health and wellbeing into adulthood. This study describes self-reported long-term urinary outcomes in males with HD and ARM. METHODS: This was a prospective study of male patients in the Adult Colorectal Research Registry who completed surveys on urinary function between October 2019 and March 2022. Self-reported health and functional outcomes were summarized, and differences based on type of condition were compared. RESULTS: Sixty-seven patients completed the questionnaire (response rate: 59.1%), of which 17.9% (12) had HD and 82.1% (55) had an ARM. Rates of urinary incontinence and stress urinary incontinence were 16.4% (11) and 4.5% (3), respectively. On sub-analysis of patients with ARM, patients with sacral ratio (SR) of 0.4-0.69 reported higher UTI rates compared to those with SR ≥ 0.7 (57.9 vs 25.8%, p = 0.023). Renal failure rates were highest among patients with recto-bladder neck fistulas (66.0%, p = 0.012). CONCLUSION: Patients with HD and ARM report a variety of urological sequelae in adulthood. Outcomes appear to be more common in patients with ARM and may be impacted by both anatomy and sacral ratios. Transitional care to monitor and manage renal and urological function is imperative.

Sexual dimorphic impacts of systemic vincristine on lower urinary tract function.

Vincristine (VCR) is one of the most common chemotherapy agents used in pediatric oncology. Despite the well-known VCR-induced peripheral neuropathy, potential impacts of VCR on lower urinary tract (LUT) function remain poorly defined. We investigated the effects of systemic VCR exposure in childhood on LUT function by using juvenile mice treated with VCR (4 mg/kg) or saline and evaluated at 5 weeks later. VCR induced a decreased urinary frequency with increased functional bladder capacity and non-void contractions. There were no changes in detrusor contractility between the groups. VCR exposure caused sexual dimorphic changes; in females, increased intravesical pressure at micturition and downregulations of a major player in bladder afferent firing, Htr3b, in the bladders, and Cav1.2 in the lumbosacral dorsal root ganglia (Ls-DRG), while male mice displayed increases in bladder compliance and detrusor activity, upregulations of IL-2, Trpa1 and Itga1 in the bladders and neuroinflammation-related genes, P2×4, P2×7, IL-2 and CD68 in the Ls-DRG. These results suggest that that systemic VCR exposure caused sensory neuropathy via sex-dimorphic mechanisms, leading to altered LUT function. These changes might clinically present as gender-specific signs or symptoms of LUT dysfunction, and follow-up urological assessment may be of benefit for pediatric cancer patients treated with VCR.

A prospective survey study of lower urinary tract dysfunction in childhood cancer survivors after vincristine and/or doxorubicin chemotherapy.

BACKGROUND: Two chemotherapeutic agents used widely in pediatric oncology are vincristine (VCR) and doxorubicin (DOX), which may cause neuropathy and myopathy, respectively. The study hypothesis is that neurotoxic effects of VCR and/or myotoxic effects of DOX affect bladder physiology and manifest clinically as lower urinary tract dysfunction (LUTD). PROCEDURE: Based on a priori power analysis, 161 children divided evenly by gender were recruited. Children aged 5-10 years completed the dysfunctional voiding scoring system (DVSS) survey. The study cohort comprised cancer survivors treated with VCR and/or DOX. Healthy controls were recruited from well-child clinic visits. Exclusion criteria included pelvic-based malignancy, pelvic irradiation, pre-existing LUTD, neurologic abnormalities, and treatment with cyclophosphamide/ifosfamide. DVSS scores and presence of LUTD, defined as DVSS scores above gender-specific thresholds (males ≥9, females ≥6), were compared across cohorts. RESULTS: Median DVSS scores were higher in the study cohort (6 vs. 4, p = .003). Moreover, children in the study cohort were more likely to exceed threshold scores for LUTD (38.8% vs. 21%, p = .014; OR 1.8). Subanalysis by gender revealed female cancer survivors are more likely to report LUTD than controls (57.5% vs. 30%, p = .013, OR 1.9). This did not hold true for males (20% vs. 12.2%, p = .339). CONCLUSIONS: Childhood cancer survivors who received VCR and/or DOX reported higher rates of LUTD than controls. Female cancer survivors appear more likely to suffer from LUTD than males. Further study with a positive control cohort of cancer survivors who received non-VCR, non-DOX chemotherapy is underway to elucidate the contribution of a cancer diagnosis to LUTD.

Functional constipation induces bladder overactivity associated with upregulations of Htr2 and Trpv2 pathways.

Bladder and bowel dysfunction (BBD) is a common yet underdiagnosed paediatric entity that describes lower urinary tract symptoms (LUTS) accompanied by abnormal bowel patterns manifested as constipation and/or encopresis. LUTS usually manifest as urgency, urinary frequency, incontinence, and urinary tract infections (UTI). Despite increasing recognition of BBD as a risk factor for long-term urinary tract problems including recurrent UTI, vesicoureteral reflux, and renal scarring, the mechanisms underlying BBD have been unclear, and treatment remains empirical. We investigated how constipation affects the lower urinary tract function using a juvenile murine model of functional constipation. Following four days of functional constipation, animals developed LUTS including urinary frequency and detrusor overactivity evaluated by awake cystometry. Physiological examination of detrusor function in vitro using isolated bladder strips, demonstrated a significant increase in spontaneous contractions without affecting contractile force in response to electrical field stimulation, carbachol, and KCl. A significant upregulation of serotonin receptors, Htr2a and Htr2c, was observed in the bladders from mice with constipation, paralleled with augmented spontaneous contractions after pre-incubation of the bladder strips with 0.5 µM of serotonin. These results suggest that constipation induced detrusor overactivity and increased excitatory serotonin receptor activation in the urinary bladder, which contributes to the development of BBD.

Neovagina stricture complicated by high-grade dysplasia in a patient with history of cloaca and ulcerative colitis: a case report and review of the literature.

Vaginoplasty with colon is a common technique for vaginal replacement in patients with cloaca. Malignancy in the neovagina is a rare outcome and typically presents decades after reconstruction. We present a case of an adolescent female with history of cloaca, ulcerative colitis, and high-grade dysplasia of the sigmoid neovagina.