Disorders of sex development: timing of diagnosis and management in a single large tertiary center.

BACKGROUND: We describe the phenotypic spectrum and timing of diagnosis and management in a large series of patients with disorders of sexual development (DSD) treated in a single pediatric tertiary center. METHODS: DSD patients who had visited our tertiary center during the survey period (between 2004 and 2014) were identified based on an ICD-10 inquiry, and their phenotypic and molecular genetic findings were recorded from patient charts. RESULTS: Among the 550 DSD patients, 53.3% had 46,XY DSD; 37.1% had sex chromosome DSD and 9.6% had 46,XX DSD. The most common diagnoses were Turner syndrome (19.8%, diagnosed at the mean age of 4.7 ± 5.5 years), Klinefelter syndrome (14.5%, 6.8 ± 6.2 years) and bilateral cryptorchidism (23.1%). Very few patients with 46,XY DSD (7%) or 46,XX DSD (21%) had molecular genetic diagnosis. The yearly rate of DSD diagnoses remained stable over the survey period. After the release of the Nordic consensus on the management of undescended testes, the age at surgery for bilateral cryptorchidism declined significantly (P < 0.001). CONCLUSIONS: Our results show that (i) Turner syndrome and Klinefelter syndrome, the most frequent single DSD diagnoses, are still diagnosed relatively late; (ii) a temporal shift was observed in the management of bilateral cryptorchidism, which may favorably influence patients' adulthood semen quality and (iii) next-generation sequencing methods are not fully employed in the diagnostics of DSD patients.

Effect of onabotulinumtoxinA treatment on symptoms and urodynamic findings in pediatric neurogenic bladder.

OBJECTIVE: To evaluate clinical and urodynamic efficiency of onabotulinumtoxinA (Botox) treatment in pediatric patients with urinary incontinence due to neurogenic overactive bladder. PATIENTS AND METHODS: Seventeen patients aged from 6 to 17 years (median 11 years) were treated with Botox injections. Clinical response to incontinence, duration of the response, and urodynamic results before and 1-3 months after treatment were evaluated. RESULTS: Mean incontinence frequency decreased significantly (p = 0.036); six of 17 patients had >90% reduction, and a further three patients had a 50-90% reduction in incontinence episodes. Median duration of the response was 15 months (range 3-42 months). Mean bladder volume changed from 380 ± 148 ml to 453 ± 147 (p = 0.078), maximal detrusor pressure decreased from 45 ± 31 cmH2O to 32 ± 21 cmH2O (p = 0.030), and the number of patients with detrusor contractions during filling decreased from 12 to three (p = 0.005) after the treatment. The patients with poor bladder compliance had either no response or a short duration of response. At follow-up eight patients had undergone bladder augmentation because of persistent incontinence. CONCLUSIONS: About one third of pediatric patients with neurogenic bladder had a good response to Botox treatment. In many patients, the clinical response was longer than expected. The patients who initially had poor bladder compliance had a poor response to the treatment.

Urodynamic assessment of children treated with botulinum toxin A injections for urge incontinence: a pilot study.

OBJECTIVE: This study aimed to investigate changes in urodynamic findings and symptoms after detrusor injections of botulinum toxin A (BTX-A) in children with idiopathic detrusor overactivity (IDO) and urge incontinence. MATERIAL AND METHODS: Eight girls and five boys, aged 7-19 years, who had urge incontinence refractory to scheduled voiding and anticholinergics, were included this prospective study. Urodynamic studies showed postoperative IDO in 12 patients. A dose of 50-100 IU (1.3 -- 4.8 IU/kg) BTX-A was primarily administered at 15-20 detrusor sites. A control urodynamic study was performed within 3 months after the injections. Seven patients had a repeated procedure 16 (range 6-24) months on the average after the first one. RESULTS: Eleven of the 13 patients had daily incontinence and two had incontinence a couple of times a week in association with urge symptoms. Postoperatively, no patient had urinary retention, but one girl had a urinary tract infection 4 months after the therapy. Five patients had a full response, seven partial responses and one no response 1-3 months after the first treatment. After 1 year, three of nine patients still have full response. Maximum cystometric capacity increased after the first treatment from a median of 227 ml to 379 ml (p = 0.005) and the number of patients with uninhibited detrusor contractions more than 30 cmH2O during the filling phase decreased from eight to two out of 13 (p = 0.041). CONCLUSIONS: Intradetrusor BTX-A injections effectively reduce day-time wetting, significantly increase bladder volume and decrease detrusor overactivity in children with urge incontinence refractory to scheduled voidings and anticholinergics.

Surgical treatment of undescended testes.

UNLABELLED: The mainstay of therapy for undescended testes is operative treatment within the first years of life in order to avoid ongoing testicular degenerative changes. The surgical therapy for the palpable undescended testis is orchiopexy and when the testis is non-palpable, a supplementary laparoscopic approach. Success of orchiopexy for inguinal testes has been >95% and for abdominal testes >85-90% in most series. CONCLUSION: Operation within the first year of life is a safe therapy for undescended testes.

Nordic consensus on treatment of undescended testes.

AIM: To reach consensus among specialists from the Nordic countries on the present state-of-the-art in treatment of undescended testicles. METHODS: A group of specialists in testicular physiology, paediatric surgery/urology, endocrinology, andrology, pathology and anaesthesiology from all the Nordic countries met for two days. Before the meeting, reviews of the literature had been prepared by the participants. RECOMMENDATIONS: The group came to the following unanimous conclusions: (1) In general, hormonal treatment is not recommended, considering the poor immediate results and the possible long term adverse effects on spermatogenesis. Thus, surgery is to be preferred. (2) Orchiopexy should be done between 6 and 12 months of age, or upon diagnosis, if that occurs later. (3) Orchiopexy before age one year should only be done at centres with both paediatric surgeons/urologists and paediatric anaesthesiologists. (4) If a testis is found to be undescended at any age after 6 months, the patient should be referred for surgery--to paediatric rather than general surgeons/urologists if the boy is less than one year old or if he has bilateral or non-palpable testes, or if he has got relapse of cryptorchidism.

Growth patterns in young men treated for undescended testes in childhood.

Testicular maldescent may be caused by endocrinological deficiency in some cases, and, on the other hand, cryptorchidism itself may have an injurious effect on testicular development and function. The purpose was to examine whether testicular maldescent is associated with abnormal growth in various body dimensions in otherwise healthy males treated for the malformation during childhood. A total of 76 young men, 16-30 years of age, who were treated for undescended testes at an age ranging from 10 months to 13 years, were examined by measuring various body dimensions. Previously cryptorchid men were slightly taller than age-matched controls, except for those with bilateral cryptorchidism treated preoperatively with hCG. The most prominent finding was a high bihumeral to bicristal ratio. In addition, testicular volume was positively correlated to both the bicristal and bihumeral width, as well as to the sitting and total height.

Cryptorchidism in boys with congenital abdominal wall defects.

Cryptorchidism (CPT) has been suggested to be common in boys with congenital abdominal wall defects (CAWD). It has been hypothesized that the low intra-abdominal pressure in both omphalocele (OMP) and gastroschisis (GS) and brain malformations in patients with OMP contribute to the high incidence of CPT. To determine the incidence of CPT in boys with OMP and GS and to assess the relationship of CPT to the size of the AWD, prematurity, and concomitant anomalies, the hospital records and autopsy reports of 113 boys with CAWD (OMP n = 75; GS n = 38) were reviewed. Twelve (16.0%) boys with OMP had undescended testes; 5 (41.0%) of those had bilateral and 4 (23.5%) intraabdominal undescended testes. The occurrence of CPT in OMP patients did not correlate with the size of the AWD, birth weight, or gestational age. However, congenital cardiac anomalies and cleft lip and palate were significantly more common (P < 0.05) among those with CPT. Two (5.0%) boys with GS, both of whom were born prematurely, had unilateral CPT. In patients with OMP, the incidence of CPT was significantly higher than that of healthy children. There was a correlation between CPT and congenital midline defects such as cardiac anomalies and cleft lip and palate. In patients with GS, the incidence of CPT only slightly exceeded that of normal children and may have been related to prematurity.

Germ cell apoptosis after treatment of cryptorchidism with human chorionic gonadotropin is associated with impaired reproductive function in the adult.

Cryptorchidism results in impaired fertility. Reduced numbers of testicular germ cells can be shown histologically during the first years of life. The process causing germ cell loss in cryptorchid prepubertal boys is unknown, but it could be the result of a form of programmed cell death known as apoptosis. 25 adult men with a history of surgically treated cryptorchidism were studied, 15 of whom had received an unsuccessful human chorionic gonadotropin (hCG) therapy before orchidopexy. Apoptotic DNA fragmentation was assayed in testis biopsies taken during orchidopexy by end-labeling, both in extracted DNA and histochemically in situ. Only a few scattered apoptotic spermatogonias were seen by end-labeling of biopsies from patients not treated with hCG, whereas more extensive labeling of spermatogonia was seen after hCG treatment. As estimated by gel electrophoresis, the amount of low molecular weight DNA was 4.3-fold higher in the hCG-treated group when compared with the level in scrotal testis of non-hCG-treated patients (P < 0.001). About 20 yr after the biopsy, the low molecular weight DNA fragmentation correlated negatively with the testis volume (r = -0.84; P < 0.001) and positively with serum FSH levels (r = 0.73; P < 0.001). Findings in the semen analysis were similar between the groups. Apoptotic loss of spermatogonia after hCG treatment of cryptorchidism warrants reevaluation of the safety of this treatment.

Effect of age at operation, location of testis and preoperative hormonal treatment on testicular growth after cryptorchidism.

PURPOSE: We evaluated the effect of patient age, primary location of the gonad and preoperative human chorionic gonadotropin administration on future testicular growth in patients treated for cryptorchidism. MATERIALS AND METHODS: Testicular volume was measured in 75 adults treated for cryptorchidism when they were 10 months to 13 years old. RESULTS: The mean volume of the cryptorchid testes plus or minus standard deviation, whether unilateral or bilateral, was 11 +/- 6 ml. compared to 20 +/- 7 ml. for the spontaneously descended testes in patients with unilateral cryptorchidism. The results showed no significant correlation between patient age at treatment or original testicular location and final testicular volume, although the 22 testes of 18 patients undergoing surgery after age 5 years were somewhat smaller (9 +/- 5 ml.) than the 66 testes of 55 younger patients (12 +/- 6 ml.). However, 26 patients who had received human chorionic gonadotropin treatment had a significantly smaller testis (9 +/- 5 ml.) than did 57 treated with surgery alone (12 +/- 6 ml., p < 0.05). CONCLUSIONS: Early orchiopexy at age younger than 2 years is not necessarily essential. Adult testicular volume is slightly greater in patients with cryptorchidism if treated at ages up to 5 years. Preoperative location of the testis in otherwise healthy boys exerts no definite effect on final testicular volume. Preoperative human chorionic gonadotropin administration may have an adverse effect on future testicular growth.

Tracheobronchial rupture due to blunt chest trauma: a follow-up study.

From 1970 to 1988, 9 patients were treated for tracheobronchial rupture arising from nonpenetrating thoracic trauma. All patients had dyspnea and pneumothorax. Four patients had rupture of the right main bronchus, 3 had rupture of the left main bronchus, 1 had rupture of the right intermediate bronchus, and 1 had rupture of the trachea. Four patients were operated on within 24 hours. Three of them had a massive air leak into the suction drainage and underwent thoracotomy. The fourth patient presented difficulties with endotracheal intubation and required a collar incision. Primary reconstruction was performed in all 4 patients. Five patients had a delay of nine to 89 days before operation. All of them had good primary healing but later developed dyspnea. Bronchoscopy revealed scar obstruction in all 5. The stenosed segment was resected in 4 patients at thoracotomy. The fifth patient, who had an intermediate bronchus rupture, underwent lobectomy. Seven patients were followed from 6 months to 18 years. One of them, who had a nine-day delay in treatment, needed further operation 6 months after the accident because of scar obstruction. The other 6 patients were interviewed, examined, and studied with spirometry, body plethysmography, bronchoscopy, and bronchography. In these 6 patients no stricture was seen, and there was no reduced pulmonary function due to the rupture even when operation was delayed.