Figure MCC of patients aged 6 monthse<5 years and 5e<18 years at baseline and week 24 (primary endpoint) and week 52 (secondary endpoint; full analysis set). Efficacy and safety of solifenacin in pediatric patients 180.e2

Aims: To evaluate the efficacy and safety of mirabegron in children and adolescents (aged 3 to <18 years) with neurogenic detrusor overactivity (NDO) using clean intermittent catheterization. Methods:In this open-label, multicenter, baseline-controlled, Phase III study (NCT02751931), participants received once-daily mirabegron at an adult dose equivalent of 25 mg. Dose was increased to 50 mg equivalent unless there were safety/tolerability concerns. The primary efficacy endpoint was change from baseline to Week 24 in maximum cystometric capacity (MCC). Secondary urodynamic assessments, Pediatric Incontinence Questionnaire (PIN-Q), Patient Global Impression of Severity (PGI-S), Clinician Global Impression of Change (CGI-C), and Acceptability questionnaires were included. Results: Overall, 86 participants (55 aged 3 to <12 years, 31 aged 12 to <18 years) received treatment; 68 were included in efficacy assessments. A statistically significant increase in MCC from baseline to Week 24 was observed (87.20 ml, 95% confidence interval: 66.07, 108.33; p < .001); this increase was apparent from Week 4. Significant increases in bladder compliance, bladder volume until first detrusor contraction, average volume per catheterization, maximum daytime catheterized volume and number of dry days per week.Significant decreases in detrusor pressure and number of leakage episodes per day were also observed. Significant improvement in PGI-S but not PIN-Q was observed. Most participants reported their condition had either much or very much improved using the CGI-C. Mirabegron was well tolerated in this population with a profile aligned with that in adults. Conclusions: Mirabegron was effective and well-tolerated in the treatment of pediatric patients with NDO.

Introduction. In patients with Y-chromosome in the karyotype, partial gonadal dysgenesis and disorders of male reproductive sex organs development are usually resected in childhood because of the high risk of germ cell tumours (GCT). In patients with Y-chromosome, complete gonadal dysgenesis and female genitalia gonadectomy is performed markedly later. However, due to the relatively low number of adult patients with preserved dysgenetic gonads, the true risk of neoplasm is unknown. The aim of the study was to evaluate the prevalence of neoplasia in dysgenetic gonads of children and adults with Y-chromosome in a retrospective study. Material and methods. A review of medical documentation of 94 patients with disorders of sex development (DSD), Y-chromosome and gonadal dysgenesis (GD), aged 1.2-32 years (47 prepubertal, 1.2-10 years; 47 pubertal/adult, 13-32 years), was conducted. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone were determined. Bilateral gonadectomy was performed in 73.4% of patients, and unilateral gonadectomy with biopsy of the contralateral gonad in 26.4%. All gonadal tissues were subjected to immunohistochemical evaluation with antibodies against PLAP and OCT3/4 (markers of malignant germ cells, but also foetal multipotent germ cells), while gonads of prepubertal patients were examined by c-KIT, as well. Results. Streak gonads were identified on both sides (complete GD) in 30.8%, a streak gonad on one side and an underdeveloped testis on the other (asymmetric GD) in 38.3%, and underdeveloped testicular structure on both sides (partial GD) in 30.8% of cases. Germ cell neoplasia was found in 53.2% of patients (51.1% in children, 55.3% in pubertal/adults). Invasive GCT were identified in 11.7% of cases, of which 90.9% were in pubertal/adult patients. Other neoplastic lesions included gonadoblastoma (16% prevalence) and testicular carcinoma in situ www.fhc.viamedica.pl (25.5%). In younger patients FSH serum levels were increased in 81% of cases (mean 2.82 ± 2.18 IU/L), while LH in 58% (mean 1.82 ± 1.69 IU/L). Hypergonadotropic hypogonadism was diagnosed in most of the pubertal/ /adult patients (mean FSH 54.2 ± 23.3 IU/L, mean LH 21.7 ± 12.1 IU/L, mean testosterone 5.5 ± 4.5 nmol/L). Conclusions. Dysgenetic gonads in patients with Y chromosome have a high risk of germ cell neoplasia (ca. 50%). If they are preserved until puberty/early adulthood, they may develop overt, invasive GCT. The gonads also have poor hormonal activity (hypergonadotropic hypogonadism) in most of the pubertal/adult patients. Each of these cases must be considered individually and a decision to remove the gonad or not should be based on the comprehensive analysis of the phenotype by a multidisciplinary team of specialists in consultation with the patient and the parents. If dysgenetic gonads are not resected in childhood, these patients need careful ongoing follow-up examination, including biopsy and histopathological evaluation.

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IntroductionBladder exstrophy is the most common form of the exstrophy – epispadias complex. It is observed in 1:30 000 life births, about four times more often in boys than in girls. Iliac osteotomy is used to facilitate bringing together pubic bones and to minimize the tension of fused elements. To analyze complications after primary bladder exstrophy closure with a special consideration of the role of pelvic osteotomy.Material and methodIt is a retrospective study evaluating 100 patients (chosen by chance out of 356) with bladder exstrophy (65 boys and 35 girls), treated in Pediatric Urology Department of the Children's Memorial Health Institute in Warsaw, Poland between 1982 and 2006. All children underwent primary bladder exstrophy closure, among them 32 elsewhere. Primary bladder exstrophy closure with contemporary iliac osteotomy was done in 36 children. In the rest 64 patients bladder was closed without osteotomy, regardless child's age.ResultsDehiscence after primary closure followed with bladder prolaps occurred in 31 patients, among them 13 out of 68 (19%) operated in our department and 18 out of 32 (56%) operated in another hospital. Primary bladder exstrophy closure with contemporary iliac osteotomy was done in 32 infants above 72 hours of life.ConclusionsOsteotomy performed at primary bladder exstrophy closure diminishes the risk of wound dehiscence independently of patient's age. Posterior iliac osteotomy is sufficient and safe and could be repeated if necessary.

Posterior urethral valve (PUV) is a condition that leads to characteristic changes in the bladder and upper urinary tract. Dysfunction of the bladder such as a hyperreflective, hypertonic, and small capacity bladder as well as sphincter incompetence and/or myogenic failure should be adequately treated. Poor compliance/small bladder could be treated with anticholinergics, but bladder augmentation will probably be indicated. Although bladder reconstruction with gastrointestinal segments can be associated with multiple complications, including metabolic disorders, calculus formation, mucus production, enteric fistulas, and malignancy formation, enterocystoplasty is still the gold standard. In contrast to a neuropathic or exstrophic bladder, augmentation of the valve bladder allows spontaneous voiding without significant residual urine in the majority of cases, but some require CIC (clean intermittent cathterization). Augmentation cystoplasty is also an efficient approach in those children who will require kidney transplantation in the future.

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Retrospective evaluation revealed previously unknown and established AR gene mutations being associated with a distinct long-term outcome. Identification of the molecular mechanisms causing DSD will likely improve timely diagnosis and therapy. Exact characterization of AR activation and function may offer a treatment modality in affected patients. These data may allow us to give prognostic estimations on the individual outcome adding objective criteria for gender assignment in 46 XY-DSD patients.