Giant omphalocele: A novel approach for primary repair in the neonatal period using botulinum toxin.

INTRODUCTION: Giant omphalocele (GO) is a complex condition for which many surgical treatments have been developed; however, no consensus on its treatment has been reached. The benefits and efficacy of botulinum toxin A (BTA) in the repair of large abdominal wall defects in adults has been proven, and its reported use in children has recently grown. The goal of this study is to describe a novel technique for primary repair of GO using BTA during the neonatal period and report our initial experience. METHODS: patients were followed from August 2020 to July 2022. BTA was applied to the lateral abdominal wall in the first days of life followed by surgical repair of the abdominal defect. RESULTS: while awaiting surgery, patients had minimal manipulation, without requiring mechanical ventilation, were on full enteral feeding, and in contact with their parents. The midline was approximated without tension and without the need for additional techniques or the use of a prosthesis. Patients were discharged with repaired defects. CONCLUSION: this approach represents a middle ground between staged and the nonoperative delayed repairs. It does not require aggressive interventions early in life, allowing maintenance of mother-child bonding and discharge of the patient with a repaired defect without the need for additional techniques or the use of a prosthesis. We believe that this technique should be considered as a new possible asset when managing this complex condition.

Predictors of surgical complications in boys with hypospadias: data from an internationa registry.

Background: Complications are frequently reported after hypospadias repair and there is a need to understand the factors that influence their occurrence. Methods: Data from boys with hypospadias born between 2000 and 2020 were obtained from the International Disorders of Sex Development (I-DSD) Registry. Logistic regressions, fisher's exact tests and spearman's correlation tests were performed on the data to assess associations between clinical factors and complication rates. Results: Of the 551 eligible boys, data were available on 160 (29%). Within the cohort, the median (range) External Masculinization Score (EMS) was 6 (2, 9). All presented with one or more additional genital malformation and 61 (38%) presented with additional extragenital malformations. Disorders of androgen action, androgen synthesis and gonadal development were diagnosed in 28 (18%), 22 (14%) and 9 (6%) boys, respectively. The remaining 101 (62%) patients were diagnosed as having non-specific 46,XY Disorders of Sex Development. Eighty (50%) boys had evidence of abnormal biochemistry, and gene variants were identified in 42 (26%). Median age at first hypospadias surgery was 2 years (0, 9), and median length of follow-up was 5 years (0, 17). Postsurgical complications were noted in 102 (64%) boys. There were no significant associations with postsurgical complications. Conclusions: Boys with proximal hypospadias in the I-DSD Registry have high rates of additional comorbidities and a high risk of postoperative complications. No clinical factors were significantly associated with complication rates. High complication rates with no observable cause suggest the involvement of other factors which need investigation.

Giant omphalocele: A novel approach for primary repair in the neonatal period using botulinum toxin / Onfalocele gigante: Uma nova abordagem para reparo primário no período neonatal utilizando toxina botulínica

ABSTRACT Introduction: Giant omphalocele (GO) is a complex condition for which many surgical treatments have been developed; however, no consensus on its treatment has been reached. The benefits and efficacy of botulinum toxin A (BTA) in the repair of large abdominal wall defects in adults has been proven, and its reported use in children has recently grown. The goal of this study is to describe a novel technique for primary repair of GO using BTA during the neonatal period and report our initial experience. Methods: patients were followed from August 2020 to July 2022. BTA was applied to the lateral abdominal wall in the first days of life followed by surgical repair of the abdominal defect. Results: while awaiting surgery, patients had minimal manipulation, without requiring mechanical ventilation, were on full enteral feeding, and in contact with their parents. The midline was approximated without tension and without the need for additional techniques or the use of a prosthesis. Patients were discharged with repaired defects. Conclusion: this approach represents a middle ground between staged and the nonoperative delayed repairs. It does not require aggressive interventions early in life, allowing maintenance of mother-child bonding and discharge of the patient with a repaired defect without the need for additional techniques or the use of a prosthesis. We believe that this technique should be considered as a new possible asset when managing this complex condition.

RESUMO Introdução: onfalocele gigante (OG) é uma condição complexa para a qual muitas alternativas terapêuticas foram desenvolvidas; no entanto, não há consenso sobre qual o melhor tratamento. Os benefícios e eficácia da toxina botulínica A (TBA) no reparo de grandes defeitos da parede abdominal em adultos foram comprovados, e o relato de uso em crianças cresceu recentemente. O objetivo deste estudo é descrever uma nova técnica para reparo primário de OG utilizando TBA durante o período neonatal e relatar nossa experiência inicial. Métodos: os pacientes foram acompanhados de agosto de 2020 a julho de 2022. A TBA foi aplicada na parede abdominal lateral nos primeiros dias de vida, seguida de correção cirúrgica do defeito abdominal. Resultados: enquanto aguardavam a cirurgia, os pacientes tiveram mínima manipulação, sem ser exigida ventilação mecânica, permaneceram em alimentação enteral plena e mantiveram contato com os pais. A linha média foi aproximada sem tensão e sem necessidade de técnicas adicionais ou uso de prótese. Os pacientes receberam alta com o defeito reparado. Conclusão: essa abordagem representa um meio-termo entre o reparo estagiado e o tratamento não-operatório. Não requer intervenções agressivas no início da vida, permitindo a manutenção do vínculo materno-infantil e a alta do paciente com defeito reparado sem a necessidade de uso de técnicas adicionais ou prótese. Acreditamos que esta técnica deva ser considerada como um novo possível recurso no manejo desta complexa condição.

Anterior component separation technique for abdominal closure in bladder exstrophy repair: Primary results.

INTRODUCTION: Bladder exstrophy (BE) is a rare, complex malformation. There are three major approaches to closure. Despite this choice, abdominal wall closure in such patients is usually a challenging procedure specially in large defects and redo cases. OBJECTIVE: Our aim is to present our ten first cases' results, using Anterior Component Separation (ACS) to abdominal wall closure in BE patients. STUDY DESIGN: Ten male patients with BE (median age 7 months, range from 3 to 24 months) were operated from March 2020 to March 2021 by a multi-institutional Brazilian group using the Kelly technique. In addition to BE correction, anterior component separation was performed for abdominal closure. RESULTS: Postoperative suprapubic fistulae occurred in two of ten patients, but both closed spontaneously. No evisceration, abdominal wall dehiscence, or herniation was observed at a mean follow-up time of 14 months (range from 10 to 22 months). A 3 cm extent of advancement is achievable upon traction in each side (Fig. 3). CONCLUSION: We proposed the use of anterior component separation as an alternative for abdominal closure after BE correction using the Kelly procedure. This new technique avoids mesh usage, loosens the abdominal wall tension, and reduces complications. Even However, further studies are required.

Treatment of congenital adrenal hyperplasia in children aged 0-3 years: a retrospective multicenter analysis of salt supplementation, glucocorticoid and mineralocorticoid medication, growth and blood pressure.

Objectives: International guidelines recommend additional salt supplementation during infancy in classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. The influence of corticoid medication and growth has not been assessed. Aim: To investigate the current use of salt supplementation, fludrocortisone (FC) and hydrocortisone (HC) dosage as well as weight, height, BMI and blood pressure (BP) in CAH children aged 0-3 years. Methods: Retrospective multicentre analysis using data from the I-CAH registry. Salt-treated (ST) and non-salt-treated (NST) children were compared regarding FC and HC dosage, weight, height and BP at 0, 3, 6, 9, 12, 18, 24, 30, and 36 months. Results: We analysed 2483 visits of 331 patients born after year 2000 in 13 countries (male, n = 145) with 203 ST patients (61%). NST children had significantly higher FC dosages at 1.5-4.5 months and higher HC dosages until 1.5 months of age. No differences in weight, length and BP between subgroups were observed. Children of the whole cohort showed increased BMI-SDS during the study period and about half of the reported BP readings were >P95. Conclusion: In children treated with additional salt supplementation, FC and HC dosages are lower during the first months of life but without differences in weight, length and BP until 3 years of age compared to NST children. All children showed an increase in BMI-SDS and a high rate of BP readings >P95 until 3 years, indicating the start of weight gain and negative effects on blood pressure already in very early life.

Laparoscopy as a Facilitator in the Early Diagnosis of a Mullerian Aplasia During Ordinary Surgery.

Laparoscopy was introduced more than 100 years ago. However, in some fields its use still meets resistance. Technology such as laparoscopy may help to identify rare and complex disorders, even in very ordinary procedures, such as inguinal hernia repair. This report highlighted the importance of early diagnosis of a complex condition using commonly available technology. To the best of our knowledge, there has not been a similar reported case in such a young patient during laparoscopic inguinal hernia repair.

Surgical Practice in Girls with Congenital Adrenal Hyperplasia: An International Registry Study.

In this article international trends in surgical practice in girls with congenital adrenal hyperplasia (CAH) are evaluated. All cases that had been classified in the I-CAH/I-DSD registry as 46,XX CAH and who were born prior to 2017 were identified. Centers were approached to obtain information on surgical decision making. Of the 330 included participants, 208 (63.0%) presented within the first month of life, and 326 (98.8%) cases were assigned female. Genital surgery had been performed in 250 (75.8%). A total of 64.3, 89.2, and 96.8% of cases residing in Europe, South America and Asia, respectively, had at least one surgery. In a logistic regression model for the probability of surgery before the second birthday (early surgery) over time an increase of probability for early vaginal surgery could be identified, but not for clitoral surgery or both surgeries combined. Genitoplasty in girls with CAH remains controversial. This large international study provides a snapshot of current practice and reveals geographical and temporal differences. Fewer surgeries were reported for Europe, and there seems to be a significant trend towards aiming for vaginal surgery within the first 2 years of life.

Spontaneous Pubertal Onset in a Male Patient With Mixed Gonadal Dysgenesis With Mosaicism 45,X/ 46, X, mar (Y)/ 47,X,mar(Y),+mar(Y) - Pediatric Case Report.

This report describes an adolescent with Mixed Gonadal Dysgenesis and unexpected mosaicism [karyotype 46,X,mar(Y)/ 47,X, mar(Y),+mar(Y)].). Diagnosis with 1 month of age due to atypical genitalia. He presented a right streak gonad, which was removed due to the risk for germ cell tumor, and a left testis with epididymis barely connected and without vas deferens. Left testis maintenance was sufficient for him to undergo spontaneous puberty. The patient was non-responsive to growth hormone. Webbed neck was the only dysmorphic feature. To the best of our knowledge, there were no similar cases reported with spontaneous pubertal progress reported in the literature.

Laparoscopic gonad-sparing procedure in Ovotesticular disorder of sex development - Case video technique.

INTRODUCTION: Ovotesticular disorder of sex development (OTD) is a rare condition. There's a lack of literature addressing gonad-sparing surgery for OTD. OBJECTIVE: Report the laparoscopic partial gonadectomy technique - gonad-sparing surgery - in an 11-year-old child, 46, XX karyotype with OTD with atypical genitalia. MATERIAL AND METHODS: After a complete diagnostic evaluation the patient underwent feminizing genitoplasty followed by laparoscopic partial gonadectomy (gonad-sparing surgery). The patient was positioned on supine position and Trendelenburg. One 5 mm port was placed on the umbilicus and two 3 mm ports in both flanks. A gonadal wedge biopsy was performed to achieve histopathological confirmation before resection. The testicular component of the ovotestis is clearly identified based on macroscopic aspects, and resected with laparoscopic scissors and limited use of electrocautery. DISCUSSION: This case was classified as bipolar or terminal ovotestis. At the 5-month follow-up, the patient attained menarche. No adverse outcomes have been recorded. Postoperative third year follow-up hormone evaluation revealed a= female pattern characteristic and ultrasound demonstraed uterine volume increase, as well as bilateral ovarian tissue development with follicles. CONCLUSIONS: Gonad-sparing procedure is feasible and desirable whenever possible, especially in 46, XX patients with female sex of rearing, since it preserves the fertility potential. The risk of malignancy must be monitored.

International practice of corticosteroid replacement therapy in congenital adrenal hyperplasia: data from the I-CAH registry.

OBJECTIVE: Despite published guidelines no unified approach to hormone replacement in congenital adrenal hyperplasia (CAH) exists. We aimed to explore geographical and temporal variations in the treatment with glucocorticoids and mineralocorticoids in CAH. DESIGN: This retrospective multi-center study, including 31 centers (16 countries), analyzed data from the International-CAH Registry. METHODS: Data were collected from 461 patients aged 0-18 years with classic 21-hydroxylase deficiency (54.9% females) under follow-up between 1982 and 2018. Type, dose and timing of glucocorticoid and mineralocorticoid replacement were analyzed from 4174 patient visits. RESULTS: The most frequently used glucocorticoid was hydrocortisone (87.6%). Overall, there were significant differences between age groups with regards to daily hydrocortisone-equivalent dose for body surface, with the lowest dose (median with interquartile range) of 12.0 (10.0-14.5) mg/m2/day at age 1-8 years and the highest dose of 14.0 (11.6-17.4) mg/m2/day at age 12-18 years. Glucocorticoid doses decreased after 2010 in patients 0-8 years (P < 0.001) and remained unchanged in patients aged 8-18 years. Fludrocortisone was used in 92% of patients, with relative doses decreasing with age. A wide variation was observed among countries with regards to all aspects of steroid hormone replacement. CONCLUSIONS: Data from the I-CAH Registry suggests international variations in hormone replacement therapy, with a tendency to treatment with high doses in children.

Real-World Estimates of Adrenal Insufficiency-Related Adverse Events in Children With Congenital Adrenal Hyperplasia.

BACKGROUND: Although congenital adrenal hyperplasia (CAH) is known to be associated with adrenal crises (AC), its association with patient- or clinician-reported sick day episodes (SDE) is less clear. METHODS: Data on children with classic 21-hydroxylase deficiency CAH from 34 centers in 18 countries, of which 7 were Low or Middle Income Countries (LMIC) and 11 were High Income (HIC), were collected from the International CAH Registry and analyzed to examine the clinical factors associated with SDE and AC. RESULTS: A total of 518 children-with a median of 11 children (range 1, 53) per center-had 5388 visits evaluated over a total of 2300 patient-years. The median number of AC and SDE per patient-year per center was 0 (0, 3) and 0.4 (0.0, 13.3), respectively. Of the 1544 SDE, an AC was reported in 62 (4%), with no fatalities. Infectious illness was the most frequent precipitating event, reported in 1105 (72%) and 29 (47%) of SDE and AC, respectively. On comparing cases from LMIC and HIC, the median SDE per patient-year was 0.75 (0, 13.3) vs 0.11 (0, 12.0) (P < 0.001), respectively, and the median AC per patient-year was 0 (0, 2.2) vs 0 (0, 3.0) (P = 0.43), respectively. CONCLUSIONS: The real-world data that are collected within the I-CAH Registry show wide variability in the reported occurrence of adrenal insufficiency-related adverse events. As these data become increasingly used as a clinical benchmark in CAH care, there is a need for further research to improve and standardize the definition of SDE.

Genetic Evidence of the Association of DEAH-Box Helicase 37 Defects With 46,XY Gonadal Dysgenesis Spectrum.

CONTEXT: 46,XY Gonadal dysgenesis (GD) is a heterogeneous group of disorders with a wide phenotypic spectrum, including embryonic testicular regression syndrome (ETRS). OBJECTIVE: To report a gene for 46,XY GD etiology, especially for ETRS. DESIGN: Screening of familial cases of 46,XY GD using whole-exome sequencing and sporadic cases by target gene-panel sequencing. SETTING: Tertiary Referral Center for differences/disorders of sex development (DSD). PATIENTS AND INTERVENTIONS: We selected 87 patients with 46,XY DSD (17 familial cases from 8 unrelated families and 70 sporadic cases); 55 patients had GD (among them, 10 patients from 5 families and 8 sporadic cases had ETRS), and 32 patients had 46,XY DSD of unknown etiology. RESULTS: We identified four heterozygous missense rare variants, classified as pathogenic or likely pathogenic in the Asp-Glu-Ala-His-box (DHX) helicase 37 (DHX37) gene in five families (n = 11 patients) and in six sporadic cases. Two variants were recurrent: p.Arg308Gln (in two families and in three sporadic cases) and p.Arg674Trp (in two families and in two sporadic cases). The variants were specifically associated with ETRS (7/14 index cases; 50%). The frequency of rare, predicted-to-be-deleterious DHX37 variants in this cohort (14%) is significantly higher than that observed in the Genome Aggregation Database (0.4%; P < 0.001). Immunohistochemistry analysis in human testis showed that DHX37 is mainly expressed in germ cells at different stages of testis maturation, in Leydig cells, and rarely in Sertoli cells. CONCLUSION: This strong genetic evidence identifies DHX37 as a player in the complex cascade of male gonadal differentiation and maintenance.

Gender dysphoria and XX congenital adrenal hyperplasia: how frequent is it? Is male-sex rearing a good idea?

INTRODUCTION: The frequency of gender dysphoria (GD) among 46,XX congenital adrenal hyperplasia (CAH) patients is unknown. These data are needed to put into perspective the debate about the timing of reconstructive surgery and possible male-raising of the most severely virilized children. OBJECTIVE: To analyze the frequency of female to male GD between 46,XX individuals raised as females; to identify subgroups with higher chances of showing GD; to describe the results of male-raising among 46,XX CAH patients. MATERIALS AND METHODS: Analytic/descriptive literature review (January 1988 to April 2018). RESULTS: Female-raised patients frequently report the desire to be male, adopt male-typical behavior and are frequently homosexual/bisexual as adults, but this does not correspond to GD. Declared GD among 46,XX CAH patients attained 9% of the reported cohorts, generally in late adolescence/adulthood. We could not prove a relationship between inadequate treatment, null-genotype, late diagnoses, a higher degree of virilization, type of CAH or higher levels of androgens and female to male GD, but this may be due to statistical limitations. Male gender raised patients (MGR) were 10.1% of CAH cohorts included in this review, mostly from underdeveloped countries, with a high proportion of late diagnoses (76.3%) and familial choices. GD was more common in this group than among female-raised patients. Opting for male gender relates to a short final height, the need for multiple surgeries, surgical castration before puberty and infertility. CONCLUSION: Both male to female and female to male GD may present in 46,XX CAH patients in a contemporaneous cohort. The proportion of GD is higher among patients raised as males. DSD patients sexual maladjustments are complex and not comparable to the transgender population. Many 46,XX CAH patients with GD define themselves as gender-fluid and do not seek for legal/formal transition. Male-raising Prader 4/5 46,XX CAH patients imply infertility and multiple surgeries. There is no proof that any subgroup of CAH is more prone to GD, despite null genotypes, salt wasting phenotypes and Prader 4/5 cases being related to male-typical behavior and female homosexuality. TYPE OF STUDY: Descriptive/analytic non-systematic REVIEW. LEVEL OF EVIDENCE: 3.

Controversies on Timing of Sex Assignment and Surgery in Individuals With Disorders of Sex Development: A Perspective.

Appropriate management of disorders of sex development (DSD) has been a matter of discussion since the first guidelines were published in the 1950s. In the last decade, with the advent of the 2006 consensus, the classical methods, especially regarding timing of surgery and sex of rearing, are being questioned. In our culture, parents of DSD newborns usually want their children to undergo genital surgery as soon as possible after sexual assignment, as surgery helps them to confirm the assigned sex. Developmental psychology theories back this hypothesis. They state that anatomic differences between sexes initiate the very important process of identification with the parent of the same sex. Sex-related endocrinological issues also demand early care. For example, using dihydrotestosterone cream to increase penile length or growth hormone treatment to improve final height require intervention at young ages to obtain better results. Although the timing of surgery remains controversial, recent evidence suggests that male reconstruction should be performed between 6 and 18 months of age. Feminizing surgery is still somewhat controversial. Most guidelines agree that severe virilization requires surgical intervention, while no consensus exists regarding mild cases. Our perspective is that precocious binary sex assignment and early surgery is a better management method. There is no strong evidence for delays and the consequences can be catastrophic in adulthood.

Vaginal ectopic ureter diagnosed by magnetic resonance imaging in a child with complete transverse vaginal septum and hydrocolpos

Ectopic ureter draining into the vagina is a rare cause of urinary incontinence. Some cases have been reported in association with malformations of the genitourinary tract, but very few published cases are associated with vaginal septum. Our article describes the case of a girl who presented with hydrocolpos shortly after birth and was found to have a complete transverse vaginal septum. Despite successful correction of this genital anomaly, the patient developed persistent dribbling of clear fluid from the genital area. Extensive testing revealed unilateral kidney dysplasia and probable genital ectopia of the corresponding ureter. Magnetic resonance imaging (MRI) showed insertion of the ureter into the upper third of the vagina. The patient underwent nephroureterectomy of the dysplastic kidney with subsequent improvement in urinary incontinence. Ureteral ectopia is difficult to diagnose with conventional imaging methods (plain radiography, ultrasound, and CT). MRI has proved to be an excellent method for assessment of genitourinary tract conditions, particularly when other diagnostic modalities have failed or are limited, due to the high resolution of MRI scans and the possibility of native image acquisition on all three orthogonal planes. MRI is the best diagnostic modality for visualization of the course and insertion of ectopic ureters, and enables precise surgical correction.

Diagnosis and management of congenital rectourethral fistula in a child with long tubular duplication of the colon and Klippel-Feil syndrome.

We describe a unique association of congenital rectourethral fistula with long tubular duplication of the colon in a boy with Klippel-Feil syndrome and Sprengel deformity. He presented with a rectourethral fistula after surgical repair of a tubular duplication of the terminal ileum, colon, and proximal rectum. Preoperative identification of the fistula was challenging and was only achieved after cystoscopy with injection of methylene blue under pressure through Foley catheters placed into the anus and distal stoma of a colostomy. Surgical repair was performed through the posterior sagittal approach. The patient is doing well after 4 years of follow-up.