A Single-Center, Observational Study of 607 Children and Young People Presenting With Differences of Sex Development (DSD).

Context: Differences of sex development (DSD) represent a wide range of conditions presenting at different ages to various health professionals. Establishing a diagnosis, supporting the family, and developing a management plan are important. Objective: We aimed to better understand the presentation and prevalence of pediatric DSD. Methods: A retrospective, observational cohort study was undertaken in a single tertiary pediatric center of all children and young people (CYP) referred to a DSD multidisciplinary team over 25 years (1995-2019). In total, 607 CYP (520 regional referrals) were included. Data were analyzed for diagnosis, sex-assignment, age and mode of presentation, additional phenotypic features, mortality, and approximate point prevalence. Results: Among the 3 major DSD categories, sex chromosome DSD was diagnosed in 11.2% (68/607) (most commonly 45,X/46,XY mosaicism), 46,XY DSD in 61.1% (371/607) (multiple diagnoses often with associated features), while 46,XX DSD occurred in 27.7% (168/607) (often 21-hydroxylase deficiency). Most children (80.1%) presented as neonates, usually with atypical genitalia, adrenal insufficiency, undescended testes or hernias. Those presenting later had diverse features. Rarely, the diagnosis was made antenatally (3.8%, n = 23) or following incidental karyotyping/family history (n = 14). Mortality was surprisingly high in 46,XY children, usually due to complex associated features (46,XY girls, 8.3%; 46,XY boys, 2.7%). The approximate point prevalence of neonatal referrals for investigation of DSD was 1 in 6347 births, and 1 in 5101 overall throughout childhood. Conclusion: DSD represent a diverse range of conditions that can present at different ages. Pathways for expert diagnosis and management are important to optimize care.

Surgery in disorders of sex development (DSD) with a gender issue: If (why), when, and how?

Ten years after the consensus meeting on disorders of sex development (DSD), genital surgery continues to raise questions and criticisms concerning its indications, its technical aspects, timing and evaluation. This standpoint details each distinct situation and its possible management in 5 main groups of DSD patients with atypical genitalia: the 46,XX DSD group (congenital adrenal hyperplasia); the heterogeneous 46,XY DSD group (gonadal dysgenesis, disorders of steroidogenesis, target tissues impairments …); gonosomic mosaicisms (45,X/46,XY patients); ovo-testicular DSD; and "non-hormonal/non chromosomal" DSD. Questions are summarized for each DSD group with the support of literature and the feed-back of several world experts. Given the complexity and heterogeneity of presentation there is no consensus regarding the indications, the timing, the procedure nor the evaluation of outcome of DSD surgery. There are, however, some issues on which most experts would agree: 1) The need for identifying centres of expertise with a multidisciplinary approach; 2) A conservative management of the gonads in complete androgen insensitivity syndrome at least until puberty although some studies expressed concerns about the heightened tumour risk in this group; 3) To avoid vaginal dilatation in children after surgical reconstruction; 4) To keep asymptomatic mullerian remnants during childhood; 5) To remove confirmed streak gonads when Y material is present; 6) It is likely that 46,XY cloacal exstrophy, aphallia and severe micropenis would do best raised as male although this is based on limited outcome data. There is general acknowledgement among experts that timing, the choice of the individual and irreversibility of surgical procedures are sources of concerns. There is, however, little evidence provided regarding the impact of non-treated DSD during childhood for the individual development, the parents, society and the risk of stigmatization. The low level of evidence should lead to design collaborative prospective studies involving all parties and using consensual protocols of evaluation.

Timing and nature of reconstructive surgery for disorders of sex development - introduction.

The ideal timing and nature of surgical reconstruction in individuals with Disorders of Sex Development (DSD) is highly controversial. Despite the increasing number of publications on this topic, evidence-based recommendations still cannot be made. However it is generally accepted that optimal care for DSD requires an experienced multidisciplinary team. This means that surgical decisions are now made within the context of a multidisciplinary team and all members of the team - and not just specialist surgeons - may be called upon to discuss choices for surgery with patients and parents. To do this well, every clinician in the team should have an understanding of the range of techniques available for genital surgery, the risks and benefits of procedures and the controversies surrounding timing of surgery. The aim of this paper is to give an overview of the variety of surgical procedures in current use and in what situation a particular technique would be indicated. The short-term risks and benefits are described and where available long-term outcome data is discussed. To date, discussions surrounding genital surgery have been led primarily by surgeons. Some non-surgical clinicians have expressed unease about decision making in genital surgery but have felt ill equipped to comment on an area with which they are unfamiliar. This review gives a detailed explanation of current surgical practice offered in a specialized center for DSD and such information should facilitate a more balanced discussion.

Adenocarcinoma at the ureterosigmoidostomy site in a 16-year-old demonstrates the importance of screening in children.

We report the death of a 17-year-old male exstrophy patient from adenocarcinoma arising at the ureterosigmoidostomy. This was detected at reconstructive surgery at the age of 16 years, 13 years after ureterosigmoidostomy. This case highlights the importance of including children in endoscopic surveillance. We recommend annual sigmoid-colonoscopy commencing 10 years after ureterosigmoidostomy irrespective of age.

Long-term outcome of vaginal reconstruction: comparing techniques and timing.

OBJECTIVE: In a retrospective review, to analyse the long-term outcomes of vaginal reconstruction, comparing techniques and timing. PATIENTS AND METHODS: We identified 63 patients who underwent a total of 71 vaginoplasties in 1985-2000. The techniques used were posterior skin flap (42), intestinal replacement (21) and pull through (8). The majority of operations were performed before puberty (63%) and as primary procedures (79%). Presenting diagnoses were congenital adrenal hyperplasia (23), cloacal exstrophy (8), true persistent cloaca (12), androgen insensitivity (8), urogenital sinus anomaly (6), mixed gonadal dysgenesis (3), true hermaphroditism (2) and sacrococcygeal teratoma (1). RESULTS: The mean age at operation was 83.9 (2-235) and mean follow up was 116.8 (48-232) months. Strictures and discharge were the most common problems. Nine patients underwent revision surgery and a fistula repair was required in two patients. Mucosal prolapse was observed in one ileo- and one colovaginoplasty patient, and diversion colitis occurred after colovaginoplasty in one patient. More complications occurred in operations performed prior to than following puberty. CONCLUSION: If vaginoplasty is the only indicated operation, delaying until puberty may minimize complications. When other genital surgery is indicated or in the presence of symptoms pre-pubertal vaginoplasty should be performed, since the second procedure usually involves simple dilatations and is associated with good results.

Long-term followup of patients after redo bladder neck reconstruction for bladder exstrophy complex.

PURPOSE: The aim of this study was to determine whether redo bladder neck reconstruction is effective in achieving continence after a failed bladder neck reconstruction procedure. MATERIALS AND METHODS: We retrospectively reviewed the hospital records of patients with bladder exstrophy who had undergone redo bladder neck reconstruction. There were 30 patients in the study, including 20 boys and 10 girls. Mean patient age at redo bladder neck reconstruction was 9.3 years (range 3.2 to 15.5). The patients were divided into 3 groups on the basis of the preoperative pattern of incontinence--incomplete wetters, complete wetters and those on continuous suprapubic drainage. Of the patients 15 already had undergone bladder augmentation, 12 had undergone a Mitrofanoff procedure and 12 had been treated with bulking agents injected in the bladder neck in an attempt to achieve continence. Four patients had undergone more than 1 bladder neck procedure. The patients were investigated with a combination of noninvasive urodynamics, cystoscopy, cystogram and ultrasound. All patients underwent Mitchell's modification of Young-Dees-Leadbetter bladder neck reconstruction. Additional procedures performed included augmentation cystoplasty and Mitrofanoff formation. RESULTS: Mean followup was 6.9 years (range 1.2 to 15.5). Postoperatively 28 patients were using clean intermittent catheterization to empty the bladder (5 per urethra, 23 via Mitrofanoff). Two patients remained on continuous suprapubic catheter drainage. A total of 18 patients (60%) were dry postoperatively (80% of girls and 50% of boys). Among dry patients only 3 were performing clean intermittent catheterization per urethra and 15 via a Mitrofanoff channel. No patient was able to void per urethra without the need for clean intermittent catheterization. The 2 patients on continuous suprapubic catheter drainage continued to remain so. At night only 50% of the patients were dry (5 on free drainage, 4 on clean intermittent catheterization, 6 not on any drainage). Those patients who did not respond satisfactorily to redo bladder neck reconstruction underwent subsequent additional procedures, which included injection of bulking agents (3 patients), insertion of an artificial urinary sphincter (1), Mitrofanoff formation (2) and bladder augmentation plus Mitrofanoff channel (1). Postoperative complications included difficulty with clean intermittent catheterization (8 patients), perivesical leak (1), recurrent epididymo-orchitis (1), upper urinary tract dilatation (2) and incisional hernia (1). Bladder neck closure was being considered in 5 patients. CONCLUSIONS: In our experience redo bladder neck reconstruction cannot achieve continence with volitional voiding per urethra. Although redo bladder neck reconstruction can render a significant number of patients dry, it is only effective if performed in conjunction with augmentation. Failure of the initial bladder neck reconstruction may be a reflection of a bladder that is of inadequate capacity and/or compliance. Therefore, bladder augmentation should be considered in all patients requiring redo bladder neck reconstruction. Bladder neck closure may be a better alternative to redo bladder neck reconstruction.

Y-type urethral duplication in the male.

OBJECTIVE: To present a single series of Y-type duplication with an analysis of the presenting features, the management and outcome, as complete Y-type urethral duplication in the male is a rare congenital anomaly that presents many challenges. PATIENTS AND METHODS: We retrospectively reviewed patient charts, identifying those with urethral duplication, and then those with complete Y-type duplication. The age at presentation, investigations, management and outcomes were reviewed. RESULTS: Of 49 patients with a diagnosis of urethral duplication, 13 had the complete Y-type. Three were lost to follow-up and were therefore excluded from the study. The median (range) age at presentation was 2 months (birth to 10 years). All patients had other comorbidities, with anorectal malformations in seven, renal agenesis in four, sacral agenesis/partial agenesis in two, and unilateral/bilateral cryptorchidism in four. Presenting features included passage of urine perineally or rectally in seven, and dribbling from the orthotopic urethral meatus in one. The diagnosis was confirmed by micturating cysto-urethrography. A mean of 14 procedures was required to achieve a final complete repair, and included urethral reconstruction, repair of fistulae, urethral dilatation, and evaluative cystoscopy. Excluding cystoscopy and urethral dilatation, a mean (range) of 3 (1-5) reconstructive procedures was required in each patient. The median follow-up was 8 years. Five boys developed urethral strictures and one developed multiple fistulae. The best outcomes were in boys who had a staged urethral reconstruction. CONCLUSION: Due to the strong association with other congenital anomalies we recommend that all patients should be evaluated thoroughly, including a detailed physical examination, renal tract ultrasonography and spinal radiography. Surgical management remains a significant challenge, requiring many procedures with unpredictable outcomes, the goals of which should be to maintain continence and reconstruct the urethra with good cosmesis. The optimum management scheme must be individualized in this rare condition.

Urinary retention, erectile dysfunction and penile anaesthesia after circumcision: a mixed dissociative (conversion) disorder.

We report on the long-term followup of a mixed dissociative (conversion) disorder after circumcision in childhood.

Renal function and outcome following salvage surgery for bilateral Wilms' tumor.

PURPOSE: Maintaining adequate renal function without compromising cure in children with bilateral Wilms' tumor is surgically demanding and challenging. The aim of this study was to assess renal function and outcome in children treated in one institution for bilateral Wilms' disease by renal salvage procedures. METHODS: This study is a retrospective review of all patients with histologically proven bilateral nephroblastoma who underwent a renal salvage procedure between November 1973 and June 2002. The median follow-up time was 52 months (range, 8 to 326 months). RESULTS: Twenty-three patients were included in the study. The median age at diagnosis was 19 months (range, 5 to 65 months). Patients who presented before 1982 (n = 5) were treated surgically first followed by chemotherapy. The remainder (n = 18) received initial chemotherapy before the operation. Of the 46 kidneys, 18 had a nephrectomy. The remaining 28 underwent a renal salvage procedure. At follow-up, 19 patients had good renal function, 2 had satisfactory function, and 2 had renal failure. Seventeen of the 23 children are alive and tumor free at follow-up (74%). Four children died of distant metastases and 2 of renal failure. Local recurrence in the salvaged kidney was detected in 1 patient 12 years after surgery after the commencement of immunosuppression for renal transplantation. CONCLUSIONS: These results confirm that renal salvage procedures, in combination with chemotherapy, are a safe and effective way of treating children with bilateral Wilms' disease. In addition, renal salvage surgery can maintain satisfactory renal function in the majority of these patients without an increased risk of local recurrence. When transplantation is required, the remaining native kidney should be removed to prevent tumor recurrence.

Self-assessment of genital anatomy, sexual sensitivity and function in women: implications for genitoplasty.

OBJECTIVE: To assess the perceptions of healthy women of their genital anatomy and sexual sensitivity, and to provide suggestions for genitoplasty based on this information, as the success of genitoplasty has historically relied upon the surgeon's perception of the patient's anatomy and function, rather than the patient's perception of outcome in terms of appearance and erotic sensitivity. SUBJECTS AND METHODS: Fifty healthy, sexually active, adult women (aged 20-56 years) with no history of genital surgery completed the female version of the Self-Assessment of Genital Anatomy and Sexual Function. This self- report questionnaire comprises written text and images enabling women to rate the appearance, size and position of clitoris and vagina, as well as the intensity of orgasm and effort required for achieving orgasm in specified areas around the clitoris and within the vagina. Anatomical locations were compared for these ratings by repeated-measures analysis of variance. RESULTS: Anatomically, 46% of women described their clitoris as 'moderate-sized and raised', 42% as 'small and raised', and 78% reported that their vaginal opening was adequate for sexual penetration. The women reported the strongest orgasm and least effort to obtain an orgasm with stimulation of the area on and above the clitoris. For vaginal sensitivity, scores for orgasm intensity increased, and for orgasm effort decreased, with increasing vaginal depth, and they indicated less sexual sensitivity for the vagina than for the external genitalia. CONCLUSION: The skin above the clitoris, and the clitoris itself, appeared to be the most sexually sensitive. During genitoplasty, attention to preserving skin-flap integrity in this area seems appropriate.

A novel, inexpensive, double lumen suprapubic catheter for urodynamics.

PURPOSE: We describe a novel, double lumen, intravesical, suprapubic catheter designed to meet the requirements of pediatric urodynamics that is easy to use and has minimal complications. MATERIALS AND METHODS: A commercially available 10Fr pediatric suprapubic pigtail catheter forms the outer lumen for instilling filling media. A 16 gauge epidural catheter is inserted through the outer catheter providing an inner lumen for measuring intravesical pressures. The resultant double-lumen catheter is inserted suprapubically using a peel away needle supplied with the 10Fr catheter, with the patient under general anesthetic. RESULTS: The catheter has been used for 15 years in more than 700 patients with good reliability and few complications. The concentric construction of the double lumens and the rigidity of the inner intravesical pressure channel ensure there is no transmission of pressure from the filling channel to the inner lumen. The catheter has a circular cross section and a pigtail distal end which help to retain it within the bladder. There is low resistance to filling that allows adequate filling rates to be achieved by gravity rather than necessitating a pump. The catheter is easily made from readily available components and is less expensive than other double-lumen catheters suitable for suprapubic use. CONCLUSIONS: A reliable, double lumen catheter that fulfills criteria not found in commercially available alternatives can be inexpensively made for urodynamics.

The ultimate challenge of cloacal exstrophy.

PURPOSE: Our review addresses the various system abnormalities associated with cloacal exstrophy and revisits the question of gender assignment. Gender assignment decisions and psychological aspects of gender issues have become the "ultimate challenge." Exploration of gender identity, gender role behavior and sexual orientation has just begun. MATERIALS AND METHODS: A comprehensive literature review was performed with all world literature regarding the current management of cloacal exstrophy. Research focused on management principles, outcomes and documentation of concurrent anomalies. We also describe original research evaluating gender identity in our own series of patients raised as girls to illustrate the challenge of treatment and augment the available literature, which is scant. RESULTS: Abnormalities of the vertebral column ranged from hemivertebra to myelomeningocele. With magnetic resonance imaging, the incidence of spinal dysraphism approached 100% and cord tethering was also more frequently recognized. For children with the short bowel syndrome, advances in antibiotic usage, and parenteral and enteral nutrition have increased the survival rate and reduced morbidity. A neurological component has been recognized for bladder function, bladder neck continence, lower extremity function and erectile capacity. Mitrofanoff-type reconstruction with bladder neck closure and continent catheterizable stoma dramatically increased continence. Diminutive or absent penis has been documented in 30% of males, and no documentation of paternity exists. The majority of females have bicornuate uterus. However, ovaries and tubes were generally normal. No reports of proven fertility exist. CONCLUSIONS: The strategy and timing of surgery relating to gender assignment remain controversial. A desperate need exists for research focusing on gender development and quality of life. Until that time, a cautious watchful approach may be most appropriate as our patients with cloacal exstrophy mature into adulthood.