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.

Voiding school as a treatment for daytime incontinence or enuresis: Assessing the effectiveness of intervention by measuring changes in wetting episodes.

BACKGROUND: Most urotherapy interventions are planned for children with daytime incontinence or symptoms, and are based on individual education. This study conducted a voiding school (VS) program with groups of 4-6 children with daytime incontinence or enuresis with or without daytime symptoms. OBJECTIVE: The aim of this quasi-experimental study with a one-group pretest-posttest design was to assess the effectiveness of the VS intervention for treating children's daytime incontinence or enuresis. MATERIALS AND METHODS: Sixty-nine 6-12-year-old children with incontinence classified as treatment resistant participated in the VS at an outpatient clinic. Based on a power analysis, a sample of 52 participants was required. The VS involved two whole-day group visits 2 months apart. The educational content of the intervention was based on the International Children's Continence Society's standards for urotherapy, and was delivered with child-oriented teaching methods, including group discussions with peers. The primary outcome measure was the number of dry days and nights. The amount of wetting was also estimated, and the frequency of voiding measured. Data were collected with 1-week voiding diaries before and after each visit. Changes in dependent variables between four measurement points was measured by using repeated measures variance analysis. The long-term effectiveness was evaluated from patient records concerning 3-month follow-up phone calls or other contacts 8-18 months after the VS. RESULTS: Fifty-eight children, 34 girls and 24 boys, completed the study. Twelve children had daytime incontinence, 18 had enuresis, and 28 had both. The number of dry days increased from a mean of 3.5-5.3 (P < 0.001), and the number of dry nights increased from a mean of 2.4-3.9 (P < 0.001) (Summary table). Thirteen (22%) children became completely dry. Three of them had daytime incontinence, five enuresis, and five both. Twenty-four out of 40 (60%) children with daytime incontinence, and 23 out of 46 (50%) children with enuresis showed ≥50% decrease in wetting episodes. The amount of wetting reduced, but the voiding frequency remained unchanged based on the voiding diaries. Twenty-two (45%) of the children were completely dry (six had daytime incontinence, nine enuresis, and seven both), and 16 (39%) showed further improvement, but eight (16%) children remained unchanged 8-18 months after the VS. CONCLUSIONS: Voiding school (VS) was an effective intervention for treating both daytime incontinence and nocturnal enuresis in children who had not benefited from standard treatment and were classified as treatment resistant.

Voiding school as a treatment of daytime incontinence or enuresis: Children's experiences of the intervention.

BACKGROUND: Daytime incontinence and enuresis are common problems in otherwise healthy children, and negatively influence their social lives and self-esteem. Motivation for treatment is often a real clinical problem. Children's experiences of their incontinence treatments have not been previously described. OBJECTIVE: The aim of this study was to describe children's experiences of the Voiding School intervention as a treatment for their incontinence. STUDY DESIGN: A qualitative, descriptive focus-group study with a purposive sample was conducted at a Finish university hospital in 2014. Children aged 6-12 years participated in the Voiding School at an outpatient clinic. The intervention included two 1-day group visits 2 months apart. The educational content was based on the International Children Continence Society's standards for urotherapy. The education was delivered with child-oriented teaching methods. At the end of the second visit, 19 children were interviewed in five groups. Data were analysed with inductive content analysis. RESULTS: The children described incontinence as an embarrassing problem, which they had to hide at any cost. They had experienced bullying and social isolation because of it. Normal outpatient visits emphasized adult-to-adult communication, which made the children feel like outsiders. The children perceived the Voiding School as a nice and child-oriented experience. Making new friends was especially important to younger boys who felt that the Voiding School day was too long and issue-oriented. In the Voiding School, videos and 'learning by doing' helped the children to understand the basis of given advice, and they were able to learn new habits, which gave them control over the incontinence; this helped them to become 'the boss of the bladder'. Sharing experiences and improvements in their incontinence with their peers supported the children's self-esteem and encouraged them to do new things, such as staying overnight with friends. These experiences helped them to acquire control over the problem (Summary Figure). DISCUSSION: According to the children's experiences, normal outpatient visits were only appointments for adults, and not very useful for children. In the Voiding School, they were respected as being the main person, and their views were listened to. The results underlined the importance of a child-oriented approach to patient education with regard to children, and provided encouragement to further develop the intervention. CONCLUSION: Child orientation, peer support, learning by doing, and understanding the cause and effect helped children to gain control over their bladders. Based on the children's experiences, this could be achieved by a voiding school.

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.

Robust tests for one or more allometric lines.

In allometry, the study of how size variables scale against each other, it is often of interest to fit lines to bivariate data and test hypotheses about slope and elevation about one or several lines. The nature of the problem suggests that bivariate techniques related to principal component analysis are more appropriate than linear regression. Inference methods have been developed for this problem and are in widespread use, however, we demonstrate that such methods are not robust to bivariate contamination, and propose alternative approaches which are. The new approaches use Huber's M-estimator via a plug-in approach, where robust test procedures have the same form as classical ones, but where we plug in robust estimators of parameters and standard errors in place of classical estimators. Simulations demonstrate that these new procedures are robust against bivariate contamination, and can make accurate inferences even from small samples.

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.

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.

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.

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.

Sexual development in patients treated for cryptorchidism.

An analysis of sexual development was carried out in adult patients treated in childhood for cryptorchidism. Forty-seven healthy men served as a control group. The cryptorchid patients had been treated between the ages of 10 months to 13 years and their ages ranged from 16 to 30 years at follow-up. The onset of puberty, and sexual development, were within normal limits in all patients, although spermarche occurred somewhat later in the patients than in the controls. In addition, the patients were on average slightly less sexually active than the controls. Neither age at the time of treatment nor the method of treatment correlated with current sexual activity. The patients with larger testes were, however, sexually more active. Both treatment age and the method of treatment, whether hormonal or surgical, should be selected on the basis of fertility prognosis.

Ultrasonography and colour Doppler flow in the testes of adult patients after treatment of cryptorchidism.

OBJECTIVE: To analyse the prevalence of post-operative structural, parenchymal and vascular testicular abnormalities and the incidence of epididymal abnormalities in adult men treated for undescended testes in childhood. PATIENTS AND METHODS: The testes and epididymi of 76 adult men treated for cryptorchidism in childhood were evaluated 16 to 27 years after treatment, using colour Doppler ultrasonography. RESULTS: The 61 spontaneously descended testes were significantly (P < 0.01) larger (mean [SD], 22 [8] mL) than the 90 undescended testes (13 [6] mL). The echo pattern in all the spontaneously descended testes was normal, whereas in 15 cases (17%) the testicular tissue was abnormal after cryptorchidism. In 12 of these 15 cases, the echo pattern was very irregular, and two other cases had microlithiasis of the testicular parenchyma, one of them bilaterally. No normal testicular artery was detected in two cases (3%) of normally descended testes, against 18 (20%) amongst those with undescended testes. Epididymal abnormalities were found in two (3%) of the group of normally descended testes against 32 (36%) in the undescended group. CONCLUSIONS: Infertility in patients with cryptorchidism may be a result not only of primary parenchymal degenerative changes of the testis directly due to the condition, but also of operative vascular trauma and epididymal anomalies. Operative trauma may be more common than has generally been believed. Ultrasonography is a suitable method to evaluate post-operatively the prevalence of the testicular abnormalities analysed in the present study.

Early treatment of cryptorchidism, semen quality and testicular endocrinology.

PURPOSE: We evaluated the effect of patient age at treatment of cryptorchidism in relation to subsequent semen quality. MATERIALS AND METHODS: Semen analyses and hormonal evaluations were performed in 51 men who were treated for cryptorchidism at ages 10 months to 12 years. RESULTS: Sperm concentration was normal in 90% of the patients with unilateral and 50% with bilateral cryptorchidism. No patient treated before age 4 years had severe sperm defects. Elevated follicle-stimulating hormone levels indicated severe testicular damage. CONCLUSIONS: Fertility is better in patients with bilateral cryptorchidism if treated before age 4 years. Age at treatment did not have a significant effect on semen quality in patients with unilateral cryptorchidism.

Measurement of testicular volume: comparison of 3 different methods.

PURPOSE: We compared 3 commonly used clinical methods to measure testicular volume. MATERIALS AND METHODS: The volumes of 151 testes in 76 adults treated for cryptorchidism during childhood were measured with an ordinary ruler, an orchidometer and ultrasonography. RESULTS: Mean testicular volume was 15 +/- 8 ml. (standard elevation) measured with a ruler, 16 +/- 7 ml. with an orchidometer and 17 +/- 8 ml. with ultrasonography. The correlation among methods was significant. CONCLUSIONS: To measure testicular size use of an ordinary ruler is recommended for clinical purposes because of its simplicity, availability and low cost.

Penile necrosis in a diabetic with renal disease and clean intermittent catheterization for recurrent urethral stricture. Case report.

In a patient with diabetic microangiopathy and renal disease, penile necrosis occurred in connection with clean intermittent catheterization. Microangiopathy of the urethral and penile arteries presumably lowered the local defences, so that the catheterization initiated penile necrotic changes by introducing bacteria and traumatizing the poorly vascularized urethral epithelium.

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.