[Diagnosis and management of testicular torsion in children]. / Diagnostic et prise en charge de la torsion testiculaire chez l'enfant.

Testicular torsion is a true urologic emergency with a bimodal age presentation : the perinatal testicular torsion presenting with a hard, tender or non-tender scrotal mass usually with underlying dark discoloration of the skin and the peripubertal testicular torsion presenting with severe acute testicular pain, vomiting and frequently pain irradiation in the inguinal area, a high riding-horizontally positioned testis and absence of the cremasteric reflex. Obtaining a US Doppler must not add unnecessary delay to the urgent surgical treatment which entails detorsion and bilateral orchidopexy. We do not recommend manual detorsion as around 30 % of testis rotate externally. Up to 50 % of patients presenting with a testicular torsion suffered beforehand from intermittent testicular pain episodes.

La torsion testiculaire est une urgence urologique avec deux âges de présentation. La période périnatale, avec un « scrotum aigu ¼ (bourse bleuâtre ou rouge, tuméfiée, avec ou sans douleurs), présent à la naissance ou dans les jours qui suivent et les torsions plus tardives, se manifestant par des douleurs testiculaires aiguës avec irradiation abdominale, une perte du réflexe crémastérien, une position ascensionnée et horizontalisée du testicule et parfois des vomissements. Le diagnostic est clinique et l'examen radiologique ne doit pas retarder l'exploration chirurgicale urgente avec détorsion et fixation testiculaire bilatérale. La détorsion manuelle externe est déconseillée, le sens de rotation du testicule étant aléatoire. 50 % des torsions testiculaires sont précédées d'épisodes de douleurs testiculaires intermittentes.

[Patients with variations of sex development : an example of interdisciplinary care]. / Patients avec variation du développement sexuel : un exemple de prise en charge interdisciplinaire.

The medical, psychological and social aspects of disorders of sex development (DSD) represent a challenge for the management of these patients. However, advances in our understanding of the etiology and genetics of this condition, novel surgical approaches and the growing influence of patient groups as well as wider recognition of ethical issues have helped improve the care of patients with a DSD. Importantly, a multidisciplinary approach involving specialists is crucial for understanding and treating such rare and complex cases. According to the recommendations of the Swiss National Ethical Commission, we shall use the term « Variation of Sex Development ¼ rather than « Disorder of Sex Development ¼ in this publication. This article addresses the care of DSD patients throughout development from the point of view of specialists in complementary fields.

La prise en charge des personnes avec une variation du développement sexuel (VDS) (disorder of sex development, DSD) est un défi tant sur le plan médical, psychologique que social. L'amélioration des connaissances étiologiques et génétiques, les nouvelles approches chirurgicales et l'influence tant des groupes de patients que de la Commission d'éthique suisse ont considérablement modifié la vision de la prise en charge de ces personnes durant ces dernières décennies. Une approche pluridisciplinaire et spécialisée est cruciale pour appréhender ces situations rares et souvent complexes. Le point de vue des différents spécialistes impliqués au long de la vie dans la prise en charge d'une VDS est abordé dans cet article.

Evaluation and predictive factors of renal function progression using cystatin C and creatinine in neonates born with CAKUT.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) is a main cause leading to endstage renal disease (ESRD) during childhood occurring at a frequency of 1 in every 500 pregnancies. No early predictive markers of long-term renal function (RF) are validated in these neonates. The aim of this study was to compare CysC and creatinine (creat) as markers of RF from birth to 2 years and to identify factors of RF progression. METHODS: The 56 patients included in this study were followed for a median of 235 days (137 - 739). Repeated measures of CysC and creat during 2 years of RF evaluation were taken in 28 patients. Changes in RF with age were analyzed. Potential risk factors for RF progression were analyzed for: type of kidney disease (KD), bilateralism of KD, prenatal pelvic dilatation, reflux and initial relative RF (RRF) asymmetry obtained by scan. RESULTS: With age, a rapid decrease of CysC (16.3%, p < 0.001), and creat (68.6%, p < 0.001) was observed at 1 month. Between 1 month and 1 year, CysC decreased 4% per month (p < 0.001) and creatinine stabilized (+ 1.9%/m, p = 0.11). After 1 year, both CysC and creat stabilized. In the multivariate model, CysC significantly increased in patients with bilateralism (p = 0.004) or asymmetric RRF (p = 0.03). Creat was not significant. CONCLUSION: CysC was a better marker than creat to follow RF in neonates with CAKUT. Using CysC, bilateralism, and RRF asymmetry were significantly associated with RF progression.

Caroli disease, bilateral diffuse cystic renal dysplasia, situs inversus, postaxial polydactyly, and preauricular fistulas: a ciliopathy caused by a homozygous NPHP3 mutation.

UNLABELLED: We report the rare association of Caroli disease (intrahepatic bile duct ectasia associated with congenital hepatic fibrosis), bilateral cystic renal dysplasia, situs inversus, postaxial polydactyly, and preauricular fistulas in a female child. She presented with end-stage renal disease at the age of 1 month, followed by a rapidly progressing hepatic fibrosis and dilatation of the intrahepatic bile ducts, leading to secondary biliary cirrhosis and portal hypertension. Combined liver-kidney transplantation was performed at the age of 4 years, with excellent outcome. DNA analysis showed a NPHP3 (coding nephrocystin-3) homozygote mutation, confirming that this malformation complex is a ciliopathy. CONCLUSION: This rare association required an exceptional therapeutic approach: combined simultaneous orthotopic liver and kidney transplantation in a situs inversus recipient. The long-term follow-up was excellent with a very good evolution of the renal and hepatic grafts and normalization of growth and weight. This malformation complex has an autosomal recessive inheritance with a 25% recurrence risk in each pregnancy.

Trans-scrotal treatment of giant bilateral abdominoscrotal hydroceles in a 7-month-old boy.

Abdominoscrotal hydrocele (ASH) is a rare condition characterized by a large scrotal and abdominal fluid-filled sac. An inguinal surgical approach is generally described in literature. We report the case of a 7-month-old child who underwent surgical repair of bilateral ASH through bilateral transverse scrotal incisions. The scrotal approach enabled optimal visibility and access to the hydrocele sacs. Separation of the sac from the testicular pedicle was possible with excellent control. Complete excision of the sac was performed. The postoperative course was uneventful. Follow-up after three years shows an excellent result. We recommend ASH repair through a transverse scrotal incision.

How useful is a complete urinary tract ultrasound in orchiepididymitis?

Orchiepididymitis (OE) is a frequent cause of pediatric emergency department attendance in boys presenting with acute scrotum. The etiology of most episodes of OE remains unclear and there is no consensus regarding the correlation between OE and underlying genitourinary malformations. Whether imaging evaluation should comprise complete urinary tract ultrasonography (US) or voiding cystography is a subject of debate. The aim of this retrospective, single-center study was to analyze i) the number/type of urinary tract malformations detected by US following a first episode of OE in boys with no previously known malformation and ii) the frequency of associated urinary tract infection (UTI). We reviewed the records of 495 boys <16 years presenting to our pediatric emergency department with acute scrotum between January 2012 and December 2017. Patients with incomplete radiological data were excluded. Of 119 boys with a radiologically-confirmed first episode of OE, 99 had a complete urinary tract US and were included in the study. No genitourinary malformation was detected (0%). Urinary cultures showed UTI in 3/98 (3.1%) patients. Mean age at presentation was 9.7 years (standard deviation, 3.9) with a three-peak incidence of OE at 10-13 years, 4-5 years, and during infancy. Conclusion: Complete urinary tract US does not appear to be useful during a first episode of OE in countries with an antenatal US screening rate similar to Switzerland. The very low UTI rate suggests that a urinalysis is sufficient to investigate a first episode of OE and antibiotics should be reserved for positive urinalysis only.

How the First Year of COVID-19 Affected Elective Pediatric Urology Patients: A Longitudinal Study Based on Waiting Lists and Surveys From 10 European Centers.

Introduction: COVID-19 impacted healthcare systems worldwide, and elective surgical activity was brought to a minimum. Although children were not primarily affected by the disease, pediatric urology was halted by clinical closedown and staff allocation. We aimed to document how these prioritizations affected waiting lists, and to investigate how European centers dealt with the challenge of these logistical and financial prioritizations. Materials and Methods: This was a 1-year prospective study, starting March 2020. Participants were surveyed at 3-month intervals about waiting lists for several common procedures as well as OR capacity and funding. Further, centers retrospectively reported on surgical and outpatient activity rates during 2019-2021. Waiting list tendencies were evaluated in relation to study baseline. Results: A marked decrease in surgical and outpatient activity was seen in the spring of 2020. Some included pediatric urology centers were able to increase their budget (15%) and staff working hours (20%) during part of the study period. Still, at the end of the study, the centers had increased the total number of patients on waiting lists with 11%, whereas the average days on waiting lists had accumulated with 73%, yielding a total of 6,102 accumulated waiting days in the study population. Centers with decreased resources had markedly negative effects on waiting lists. Conclusions: Correlations between COVID-19 derived burdening of healthcare systems and the availability of pediatric urology greatly depends on the prioritizations made at individual centers. Ongoing monitoring of these correlations is warranted to safely avoid unnecessary negative impact on the pediatric population.

Hydronephrosis caused by kidney malrotation.

Hydronephrosis associated with kidney malrotation can be a surgical challenge. We present the case of a 3.5 y.o.-boy presenting with left pyelo-ureteric obstruction caused by kidney hyperrotation (270°) resulting in recurring urinary tract infection. After complete radiological work-up, we opted for a primary laparoscopic ureterocalicostomy, which allowed for complete resolution of the pelvic dilatation. Kidney malrotation can present with a wide variation in anatomic features. Radiological work-up is the cornerstone of surgical strategy planning. Laparoscopic ureterocalicostomy is a useful primary option in unusual anatomical situations.

Diagnosis and Therapy of Female Genital Malformations (Part 1). Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry Number 015/052, May 2019).

Objectives Female genital malformations may take the form of individual entities, they may involve neighboring organs or they may occur in the context of complex syndromes. Given the anatomical structures of the vulva, vagina, uterus and adnexa, the clinical picture of malformations may vary greatly. Depending on the extent of the malformation, organs of the urinary system or associated malformations may also be involved. Methods This S2k-guideline was developed by representative members from different medical specialties and professions as part of the guidelines program of the DGGG, SGGG and OEGGG. The recommendations and statements were developed using a structured consensus process with neutral moderation and voted on. Recommendations The guideline is the first comprehensive presentation of the symptoms, diagnosis and treatment options for female genital malformations. Additional chapters on classifications and transition were included.

Diagnosis and Therapy of Female Genital Malformations (Part 2). Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry Number 015/052, May 2019).

Objectives Female genital malformations may be present in the form of individual entities, they may involve neighboring organs or they may occur in the context of complex syndromes. Given the anatomical structures of the vulva, vagina, uterus and uterine appendages, the clinical picture of malformations varies greatly. Methods This S2k-guideline was developed by representative members from different medical specialties and professions as part of the guidelines program of the DGGG, SGGG and OEGGG. The recommendations and statements were developed and voted on using a structured consensus process with neutral moderation. Recommendations This guideline is the first comprehensive summary of female genital malformations from infancy to adulthood which covers clinical examinations, diagnostic workups and treatment options. Additional chapters have been included on complex urogenital malformations, vascular malformations, psychosomatic care, and tumor risk.

Biosafety in ex vivo gene therapy and conditional ablation of lentivirally transduced hepatocytes in nonhuman primates.

Ex vivo gene therapy is an interesting alternative to orthotopic liver transplantation (OLT) for treating metabolic liver diseases. In this study, we investigated its efficacy and biosafety in nonhuman primates. Hepatocytes isolated from liver lobectomy were transduced in suspension with a bicistronic liver-specific lentiviral vector and immediately autotransplanted (SLIT) into three cynomolgus monkeys. The vector encoded cynomolgus erythropoietin (EPO) and the conditional suicide gene herpes simplex virus-thymidine kinase (HSV-TK). Survival of transduced hepatocytes and vector dissemination were evaluated by detecting transgene expression and vector DNA. SLIT was safely performed within a day in all three subjects. Serum EPO and hematocrit rapidly increased post-SLIT and their values returned to baseline within about 1 month. Isoforms of EPO detected in monkeys' sera differed from the physiological renal EPO. In liver biopsies at months 8 and 15, we detected EPO protein, vector mRNA and DNA, demonstrating long-term survival and functionality of transplanted lentivirally transduced hepatocytes. Valganciclovir administration resulted in complete ablation of the transduced hepatocytes. We demonstrated the feasibility and biosafety of SLIT, and the long term (>1 year) functionality of lentivirally transduced hepatocytes in nonhuman primates. The HSV-TK/valganciclovir suicide strategy can increase the biosafety of liver gene therapy protocols by safely and completely ablating transduced hepatocytes on demand.

The surgical challenges of disorders of sex development (DSD).

Disorders of Sex Development (DSD) remain a fascinating challenge for the paediatricians, endocrinologists, biologists, psychiatrists, geneticists, radiologists, surgeons and for the whole society. This article aims at highlighting the current controversies and questions met with genital reconstruction in children born with abnormal genitalia. The main current techniques of masculinization and feminization are reviewed with their progress and their problems. The tools of decision used to assign a gender in some newborns with complex DSD are discussed showing that at the dawn of the third millenium, one still does not know why a boy is a boy, and a girl is a girl.

[Perinatal asphyxia and neonatal hydronephrosis]. / Pédiatrie.

Perinatal asphyxia. Perinatal asphyxia remains one of the most important causes for high mortality and morbidity in the neonatal population. Despite intensive animal and clinical research in this field, no pharmocological strategy has been shown neuroprotective in humans. Moderate hypothermia for severely and moderately asphyctic babies has been aknowledged since a few years as therapeutical approach to improve the outcome of these infants, specifically the long-term follow up (18 months). Neonatal hydronephrosis. Neonatal hydronephrosis is a pathology that requires regular and efficient follow up by a multidisciplinary team. One of the causes of neonatal hydronephrosis is obstructive pathologies which may endanger the kidney. We have developed a strategy that allows a rapid diagnosis of obstructive pathologies with minimal radiological exams. Moreover, this strategy assures the coordination between obstetricians, neonatologists, pediatric urologists, and pediatric nephrologists.

Ex vivo lentivirus transduction and immediate transplantation of uncultured hepatocytes for treating hyperbilirubinemic Gunn rat.

BACKGROUND: Ex vivo liver gene therapy provides an attractive alternative to orthotopic liver transplantation for the treatment of liver diseases. We previously reported a protocol in which human primary hepatocytes are highly transduced in Suspension with Lentiviral vectors and Immediately Transplanted (SLIT). Here, we evaluated the SLIT approach in Gunn rats, the animal model for Crigler-Najjar syndrome type 1, a defect in bilirubin UDP-glucuronosyltransferase (BUGT). METHODS: We constructed lentiviral vectors coding for BUGT under control of an ubiquitous promoter. Control vectors contained Green Fluorescent Protein (GFP) under control of the same promoter. Hepatocytes were isolated from jaundiced Gunn rats and transduced in suspension for four hr. After washing, 2x10 hepatocytes were immediately transplanted into syngeneic rats. Bilirubinemia and bile pigments were regularly assessed after cell transplantation. The percentage and presence of transduced hepatocytes was analyzed by immunohistochemistry in GFP-transplanted animals. RESULTS: In rats receiving BUGT-transduced hepatocytes, bilirubinemia decreased by about 30%. The level of correction remained stable for up to 240 days. Bilirubin glucuronides were present in the bile of treated animals, indicating the metabolic activity of engrafted hepatocytes. In contrast, bilirubinemia in GFP-transplanted rats did not decline but rather increased. GFP-positive hepatocytes amounted to 0.5-1% of the liver, which is in agreement with the number of transplanted and genetically-modified hepatocytes (6x10). CONCLUSIONS: This work reports the first demonstration of long-term metabolic benefit after rapid transplantation of ex vivo lentivirally tranduced hepatocytes. Therefore, this study demonstrates the therapeutic proof-of-principle and potential of the SLIT approach for treating inherited metabolic liver diseases.

Laparoscopic-assisted vaginal pull-through: A new approach for congenital adrenal hyperplasia patients with high urogenital sinus.

BACKGROUND: To open vaginal cavity to the pelvic floor is part of surgical treatment for urogenital sinus (UGS) in girls with congenital adrenal hyperplasia (CAH). For high UGS, this operative procedure can be challenging and may jeopardise urinary continence. Combined perineal and laparoscopic approaches could be useful to minimise perineal dissection and to facilitate the vaginal lowering. PATIENTS AND METHODS: We report the procedure of a laparoscopic-assisted vaginal pull-through for supra-sphincteric UGS in a 5-year-old girl with CAH. Laparoscopic dissection of the vagina from the posterior wall of the bladder and urethra, division of the confluence and vaginal pull-through to the perineum are described. DISCUSSION: The technique is derived from laparoscopic-assisted treatment for high ano-rectal malformations. Compared with current procedures for treatment for high UGS, laparoscopic-assisted approach allows mobilising vagina with minimal dissection of perineum and complete preservation of urethra. Another major advantage is to provide a direct vision for dissection of the space between rectum and urethra prior to vaginal pull-through. CONCLUSION: Laparoscopic-assisted vaginal pull-through appears to be an interesting approach for high UGS in CAH patients, reducing dissection and risk of urinary incontinence. This new approach needs to be strengthened by other cases.

Uterocervicoplasty with a bladder mucosa layer for the treatment of complete cervical agenesis.

OBJECTIVE: To create an endocervical canal in a patient with a complete cervical agenesis. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 12-year-old girl presented with lower abdominal pain. On examination, complete vaginal agenesis was noted, with a 2-cm vaginal dimple. A pelvic magnetic resonance imaging scan disclosed an hematometra and absence of the cervix and vagina. INTERVENTION(S): Initial surgical therapy consisted of a vaginoplasty with a sigmoid bowel segment and opening of the uterus by puncture and stenting. The cervical permeation failed, with immediate complete stenosis. A new attempt was made through a low sagittal hysterotomy by removing a central muscular cylinder and lining the channel with a free tubularized bladder mucosa graft. A stent was left in place. MAIN OUTCOME MEASURE(S): Hysteroscopy, hysterography, and clinical follow-up evaluation. RESULT(S): The cervical stent was removed after 5 months. A hysterography and hysteroscopy confirmed the permeability of the cervix, which was lined by a well-vascularized longitudinally folded mucosa. Regular menses had been noted for more than 3 years as of this report. CONCLUSION(S): Cervicoplasty with mucosal lining permits the creation of a patent cervical canal, even in the reputedly unfavorable forms of congenital cervical agenesis.

Adenovirus-induced obstructive uropathy with acute renal failure in an immunodeficient child.

Viral infections represent severe complications in immunodeficient patients, associated with significant morbidity and mortality. We report a case of a bone marrow-transplanted adolescent with hemorrhagic cystitis 4 weeks after transplant, associated with renal failure because of obstructive pyelonephritis. Diagnostic workup finally revealed adenovirus infection. A double-J stent was inserted with spontaneous favorable evolution thereafter. Adenovirus infection in an immunocompromised patient can cause hemorrhagic cystitis without specific symptoms and might evolve toward obstructive pyelonephritis because of tubular necrosis. Diagnosis is made by urine culture and/or blood polymerase chain reaction. In case of fatal dissemination, diagnosis might only be revealed on autopsy.

A novel SRY mutation leads to asymmetric SOX9 activation and is responsible for mixed 46,XY gonadal dysgenesis.

BACKGROUND: SRY, located on the Y chromosome, is one of the key genes involved in human sex determination. SRY mutations are responsible for 10-15% of all cases of 46,XY gonadal dysgenesis (GD) but are rarely implicated in the pathogenesis of mixed GD. METHODS: SRY was analyzed by sequence analysis of DNA extracted from blood leukocytes. SRY activity was evaluated by SOX9 immunostaining, one of the targets of SRY. RESULTS: We report a case of mixed GD due to a novel SRY point mutation in a patient with a 46,XY karyotype, without mosaicism or submicroscopic genomic imbalances. Hormonal studies showed low anti-müllerian hormone and histological examination of the gonads showed a streak gonad on the right side and a left dysgenetic testis, thus permitting the diagnosis of mixed GD. Immunostaining for SOX9, a target of SRY, was positive in nuclei of Sertoli and epididymal cells in the left gonad and negative on the right, thus indicating asymmetric activation of SRY. CONCLUSION: Mixed GD can result from SRY mutations without mosaicism, neither in peripheral blood, nor within the gonads. The asymmetric effect of the point mutation implies the presence of local factors modulating SRY expression or action.

Are abdominal wall defects and external genitalia anomalies randomly expressed in some families?

Familial cases of isolated abdominal wall defects with variable expressivity in more than one generation have rarely been observed. We report four affected individuals within a small three-generation family with either variable non-syndromic abdominal wall defects or external genital anomalies. We discuss the possible transmission of non-syndromic abdominal wall defects. It could be hypothesized that similar developmental defects may result in anomalies like hypospadias in males or developmental anomalies of the labia minora or labia majora in females.

Urethral duplication in a 12-year-old child.

Urethral duplication is a rare congenital malformation affecting mainly boys. The authors report a case in a Cameroonian child who was diagnosed and managed at the Gynaeco-Obstetric and Paediatric Hospital, Yaounde. The malformation was characterized by the presence of an incontinent epispadic urethra and a normal apical urethra. We describe the difficulties faced in the management of this disorder in a developing country.