Vascular dysfunction and increased cardiovascular risk in hypospadias.

AIMS: Hypogonadism is associated with cardiovascular disease. However, the cardiovascular impact of hypogonadism during development is unknown. Using hypospadias as a surrogate of hypogonadism, we investigated whether hypospadias is associated with vascular dysfunction and is a risk factor for cardiovascular disease. METHODS AND RESULTS: Our human study spanned molecular mechanistic to epidemiological investigations. Clinical vascular phenotyping was performed in adolescents with hypospadias and controls. Small subcutaneous arteries from penile skin from boys undergoing hypospadias repair and controls were isolated and functional studies were assessed by myography. Vascular smooth muscle cells were used to assess: Rho kinase, reactive oxygen species (ROS), nitric oxide synthase/nitric oxide, and DNA damage. Systemic oxidative stress was assessed in plasma and urine. Hospital episode data compared men with a history of hypospadias vs. controls. In adolescents with hypospadias, systolic blood pressure (P = 0.005), pulse pressure (P = 0.03), and carotid intima-media thickness standard deviation scores (P = 0.01) were increased. Arteries from boys with hypospadias demonstrated increased U46619-induced vasoconstriction (P = 0.009) and reduced acetylcholine-induced endothelium-dependent (P < 0.0001) and sodium nitroprusside-induced endothelium-independent vasorelaxation (P < 0.0001). Men born with hypospadias were at increased risk of arrhythmia [odds ratio (OR) 2.8, 95% confidence interval (CI) 1.4-5.6, P = 0.003]; hypertension (OR 4.2, 95% CI 1.5-11.9, P = 0.04); and heart failure (OR 1.9, 95% CI 1.7-114.3, P = 0.02). CONCLUSION: Hypospadias is associated with vascular dysfunction and predisposes to hypertension and cardiovascular disease in adulthood. Underlying mechanisms involve perturbed Rho kinase- and Nox5/ROS-dependent signalling. Our novel findings delineate molecular mechanisms of vascular injury in hypogonadism, and identify hypospadias as a cardiovascular risk factor in males.

Effects of Sex Hormones on Vascular Reactivity in Boys With Hypospadias.

BACKGROUND: Arteries from boys with hypospadias demonstrate hypercontractility and impaired vasorelaxation. The role of sex hormones in these responses in unclear. AIMS: We compared effects of sex steroids on vascular reactivity in healthy boys and boys with hypospadias. METHODS: Excess foreskin tissue was obtained from 11 boys undergoing hypospadias repair (cases) and 12 undergoing routine circumcision (controls) (median age [range], 1.5 [1.2-2.7] years) and small resistance arteries were isolated. Vessels were mounted on wire myographs and vascular reactivity was assessed in the absence/presence of 17ß-estradiol, dihydrotestosterone (DHT), and testosterone. RESULTS: In controls, testosterone and 17ß-estradiol increased contraction (percent of maximum contraction [Emax]: 83.74 basal vs 125.4 after testosterone, P < .0002; and 83.74 vs 110.2 after estradiol, P = .02). 17ß-estradiol reduced vasorelaxation in arteries from controls (Emax: 10.6 vs 15.6 to acetylcholine, P < .0001; and Emax: 14.6 vs 20.5 to sodium nitroprusside, P < .0001). In hypospadias, testosterone (Emax: 137.9 vs 107.2, P = .01) and 17ß-estradiol (Emax: 156.9 vs 23.6, P < .0001) reduced contraction. Androgens, but not 17ß-estradiol, increased endothelium-dependent and endothelium-independent vasorelaxation in cases (Emax: 77.3 vs 51.7 with testosterone, P = .02; and vs 48.2 with DHT to acetylcholine, P = .0001; Emax: 43.0 vs 39.5 with testosterone, P = .02; and 39.6 vs 37.5 with DHT to sodium nitroprusside, P = .04). CONCLUSION: In healthy boys, testosterone and 17ß-estradiol promote a vasoconstrictor phenotype, whereas in boys with hypospadias, these sex hormones reduce vasoconstriction, with androgens promoting vasorelaxation. Differences in baseline artery function may therefore be sex hormone-independent and the impact of early-life variations in androgen exposure on vascular function needs further study.

Gonadal Function in Boys with Bilateral Undescended Testes.

Background: Bilateral undescended testes (BUDT) may be a marker of an underlying condition that affects sex development or maturation. Aims: To describe the extent of gonadal dysfunction in cases of BUDT who had systematic endocrine and genetic evaluation at a single tertiary pediatric center. Methods: A retrospective review was conducted of all boys with BUDT who had endocrine evaluation between 2008 and 2021 at the Royal Hospital for Children, Glasgow (RHCG). Continuous variables were analyzed using Mann-Whitney U and non-continuous variables using Fisher's exact, via Graphpad Prism v 8.0. Multivariable logistic regression was used to identify any associations between groups. A P < .05 was considered statistically significant. Results: A total of 243 bilateral orchidopexies were performed at RHCG between 2008 and 2021. Of these 130 (53%) boys were seen by the endocrine team. The median (range) age at first orchidopexy was 1 year (0.2, 18.0) with 16 (12%) requiring re-do orchidopexy. The median External Masculinization Score of the group was 10 (2, 11) with 33 (25%) having additional genital features. Of the 130 boys, 71 (55%) had extragenital anomalies. Of the 70 who were tested, a genetic abnormality was detected in 38 (54%), most commonly a chromosomal variant in 16 (40%). Of the 100 who were tested, endocrine dysfunction was identified in 38 (38%). Conclusion: Genetic findings and evidence of gonadal dysfunction are common in boys who are investigated secondary to presentation with BUDT. Endocrine and genetic evaluation should be part of routine clinical management of all cases of BUDT.

Hypertrophic pyloric stenosis in premature infants: evaluation of sonographic criteria and short-term outcomes.

PURPOSE: To examine the sonographic measurements of pyloric muscle and pyloric thickness in premature infants with hypertrophic pyloric stenosis (HPS) and to correlate these measurements with patients variables. We aimed also to evaluate the clinical features and short-term outcome of HPS in premature compared to term infants. METHODS: The medical notes and the pyloric ultrasounds of all premature infants (<37 weeks) admitted to the Neonatal Surgical Unit with HPS over a 20-year period (1990-2010) were retrospectively reviewed. Sonographic measurements of the pyloric length, muscle thickness and the pyloric ratio (muscle thickness divided by pyloric diameter) were correlated to weight at presentation, duration of symptoms and corrected gestational age. Multiple regression and correlation analysis was carried out. RESULTS: Seventy-five preterm infants were identified (51M:24F). Median gestational age was 34 weeks. Median weight at presentation was 2.74 kg. Forty-two had an ultrasound (US) before surgery, 37 measurements were analysed. Pyloric length, muscle thickness and pyloric ratio were not affected by weight at presentation (p = 0.67, p = 0.122, p = 0.849), corrected gestational age (CGA) (p = 0.921, p = 0.678, p = 0.076), or duration of symptoms (p = 0.827, p = 0.268, p = 0.281). Mean length of stay was 6 days and overall complication rate was 27 %, both higher than reported in term infants (p < 0.001). CONCLUSIONS: Premature infants with HPS have a higher female preponderance than expected. Ultrasound measurements in premature infants with HPS are not affected by weight, corrected gestational age or duration of symptoms. In addition, they have a longer hospital stay and increased complication rate compared to term infants.

Laparoscopy versus ultrasonography for the evaluation of Mullerian structures in children with complex disorders of sex development.

PURPOSE: The diagnosis of children with disorders of sex development (DSD) requires a karyotype, different biochemical and radiological investigations in the context of a multidisciplinary team. The aim of this study was to compare the diagnostic accuracy of laparoscopy (L) versus ultrasonography (US) in the assessment of children with complex DSD. METHODS: We retrospectively examined the theatre database searching for children with DSD who underwent laparoscopic surgery from 1999 to 2011. The medical and radiological records were reviewed. RESULTS: Eighteen patients were identified. Age at diagnosis ranged from birth to 14 years (mean 2.5 years). There were seven patients with 46XY dysgenetic testicular DSD (4 mosaic Turner, 3 mixed gonadal dysgenesis), seven patients with 46XY non-dysgenetic testicular DSD (4 persistent Mullerian duct syndrome, 2 complete androgen insensitivity syndrome, one unknown), two patients with ovotesticular DSD, one patient with 46XX DSD (congenital adrenal hyperplasia) and one patient with 46XY DSD complete sex reversal. Fifteen underwent ultrasonography prior to laparoscopy. Both modalities identified Mullerian structures in seven (47 %) patients, in one (7 %) patient US and L confirmed the absence of Mullerian structures, while in six (40 %) patients there was discordance, with US failing to visualize pelvic Mullerian structures. In the last patient with 46XY non-dysgenetic testicular DSD, the rectum was thought to be a dilated uterus on ultrasonography. CONCLUSIONS: Pelvic ultrasonography failed to identify Mullerian structures in 40 % of patients with complex DSD. On the contrary, laparoscopy allowed excellent visualization of pelvic structures and gonads in children with complex DSD.

Contralateral inguinal exploration in premature neonates: is it necessary?

PURPOSE: The purpose of this study was to review our management of neonatal inguinal hernias in premature infants over a 5-year period to ascertain any change in practice. METHODS: Premature infants who underwent inguinal herniotomy between 2002 and 2006 were identified. Case notes were analyzed recording patient demographics, primary side, complications, recurrence and how many re-presented with a metachronous hernia. RESULTS: 172 preterm infants were identified: 162 males (94.2%) and 10 females (5.8%). Median gestation was 31 weeks (25-36.7). Eighteen (10.4%) were incarcerated. Median age at surgery was 66.5 days (0-284). Thirty-two (18.6%) had bilateral hernias. Of the 63 who underwent unilateral herniotomy, 9 (14.3%) re-presented with a metachronous hernia. Median time to returning was 24 days. The number of contralateral explorations decreased over the study period. The complication rate was 6.4%. Median follow-up was 2.83 years (0.33-5.4). CONCLUSIONS: This is one of the largest series showing the current practice in managing preterm infants with inguinal hernia. There are limitations to this study and the follow-up period is short. The value of contralateral groin exploration in premature neonates remains doubtful and we have shown that the overall practice has changed.

PUVs are more common in boys with hypospadias.

INTRODUCTION: The association between posterior urethral valves (PUVs) and hypospadias has previously been reported in case reports. After the identification of this twin pathology in a number of patients, a national retrospective review of all patients with this dual diagnosis was performed. PATIENTS AND METHODS: All patients were identified in each centre from surgical databases of prospectively collated information on all surgical procedures. The medical notes were reviewed to ascertain demographics, the type of hypospadias, the mode of presentation of the valves and the outcome. RESULTS: Twenty-eight patients who had the dual diagnosis of hypospadias and PUV between 2002 and 2017 in the four tertiary paediatric centres where specialist paediatric urology is undertaken in our country were identified. Most patients (n = 24) had the valves diagnosed after hypospadias surgery. The median age at the time of hypospadias surgery was 1.4 years (range 1-4 years). There were 12 proximal and 16 mid or distal hypospadias. The commonest presentation was with problems voiding after surgery in 14 cases with a further seven boys who had urinary tract infections. Four patients had a urethro-cutaneous fistula after repair that initiated further assessment. Two boys had distal dehiscence of their repair. There was one boy presented with new onset daytime incontinence. The median time of follow-up after valve incision surgery was 4.9 years (range 0.1-12.3 years). Twenty-two patients (three pre toilet training) had no ongoing urinary symptoms. Twenty-one boys have normal renal function with one patient in stage 3b chronic kidney disease. The incidence of this dual diagnosis in Scotland is estimated at one in 100 cases of hypospadias in the paediatric population. CONCLUSION: The incidence of PUV in boys with hypospadias is estimated at 1% patients.

Simple Purse String Laparoscopic Versus Open Hernia Repair.

AIMS: To compare surgical outcomes for a simple purse string method of laparoscopic hernia (LH) repair with a traditional open inguinal hernia (OH) repair in children in a single center. MATERIALS AND METHODS: Following ethical approval, a retrospective review of all children undergoing LH repair from January 2010 to December 2013 versus a historic cohort of all OH repairs between January 2010 and December 2011 was conducted. LH repair was performed by a simple purse string technique using nonabsorbable braided suture. Groups were compared using the independent t test or the Mann-Whitney test as appropriate. RESULTS: One hundred three patients (23 females, 80 males) underwent LH repair over the 4-year period compared with 151 (25 females, 126 males) OH procedures in the first 2 years. Median age in the LH group was 0.56 years (range, 0.04-14.7 years) compared with 0.52 years (range, 0.04-13.47 years) in the OH group (P = .81). In the LH group the intended operation was bilateral in 18 (17.4%); 85 were clinically unilateral, but at operation a contralateral patent processus vaginalis was repaired in 26 (30.5%). Median operative time was 50.5 minutes (range, 20-95 minutes) in the LH group and 20 minutes (range, 10-90 minutes) in the OH cohort (P < .0001). Recurrence rate was 2.9% in the LH group and 3.9% in the OH group, and overall complication rates were 7.8% and 9.9%, respectively. CONCLUSIONS: LH repair yields similar results to OH repair; however, the operation time is significantly longer. All complication rates were statistically similar on balance. Almost one-third of LH procedures resulted in concurrent detection and repair of a contralateral patent processus vaginalis at laparoscopy.

New tools in the treatment of motility disorders in children.

Gastrointestinal motility disorders can develop in neurologically impaired children and those with congenital malformations of the gut. It is characterized by moderate to severe abdominal pain, vomiting, and failure to thrive. Antral dysmotility after fundoplication and increased sympathetic over activity are 2 factors associated with this condition that make it difficult to treat. This paper proposes a management strategy using metoclopramide, celiac plexus blockade, and thoracic splanchnectomy. It reviews our experience with 11 patients.

A mesothelial-lined cyst: an unusual presentation.

A 12-year-old girl presented with a "threadlike fiber" in her underwear associated with lower abdominal pain. She denied insertion of any foreign body, and at examination under anesthetic, a threadlike substance was seen exiting her external cervical os. Her only medical history was of an open appendicectomy for perforated appendicitis. Subsequent pathologic examination showed a collapsed mesothelial cyst, and laparoscopy showed a cyst and inflammatory changes consistent with previous appendicectomy surrounding her right ovary. We review the possible causes for this most unusual presentation.

Sign on the dotted line: parental consent.

The issue of informed consent in paediatric surgery has always been contentious. Despite the fact that taking consent is one of the most frequently performed tasks of a surgeon, it is rarely audited. Indeed, there are few studies looking at the consent process in adult practice and fewer in the paediatric setting. The aim of this study was, therefore, to determine parental understanding, recall, attitudes and opinion of the consent process in a busy paediatric day surgery unit. A prospective study was conducted using a questionnaire consisting of 20 questions. These were handed out to the parents of all children undergoing one of four procedures: circumcision, prepuceplasty, orchidopexy and herniotomy over a 3-month-period. Completed questionnaires were collected and analysed. One hundred and sixty-one parents were asked to complete the questionnaire. Ninety-three were collected, a response rate of 58%, 87% believed consent was taken by the performing surgeon, 15% felt the consent process was rushed, but 91% thought the right amount of detail was given. Ninety-seven percent of parents believed that the consent form was a legal necessity and 72% believed that a child in Scotland had to be aged 16 or over to sign the consent form. Interestingly, 23% of parents were unsure if signing the consent form meant that they could not claim compensation if anything went wrong. Ninety-one percent recalled the procedure being explained in the outpatient clinic, but 22% did not remember potential complications being discussed. The amount parents recalled of potential complications varied. Seventy percent felt that a leaflet about the procedure prior to attending the unit would be helpful. In conclusion consent is an extremely important part of our practice. This study highlights some of the common parental misconceptions and limitations of the process. Parents appear satisfied and consenting for procedures is overall performed well. Some areas could be improved and more research is required in this area.

Haemangiomas and vascular malformations of the limb in children.

Haemangiomas and vascular malformations of the limb in children are often difficult to manage. The role of surgery and intervention in current management is still not clear. The aim of this study was to review our experience of such patients. Patients were identified using the health board database of inpatient admissions between 1999 and 2003. Clinical notes were reviewed and data collected looking at patient demographics, site of lesion, clinical findings, investigative procedures, intervention and follow-up. A total of 288 patients were identified with a diagnosis of "Haemangioma" or "vascular malformation". Thirty-eight of these patients were found to have limb haemangiomas or vascular malformations (20 boys and 18 girls). The median age at referral was 1.9 years (0-13.2). The clinical presentation included gigantism, swelling, bruising, bleeding and cosmetic concern. Cosmetic concerns and bleeding being the most frequent. Investigative modalities were used in 19 patients. These included ultrasound, CT, MRI and angiography. Many patients had more then one imaging modality employed. Treatment options included observation, steroids, laser, embolisation and surgical excision. Twenty-five patients (66%) required surgical intervention. Most patients were required one or two procedures, mainly laser or simple excision. However two patients required multiple procedures while one patient with Kasabach-Merritt syndrome required a limb amputation. Patients were followed-up for a median of 3.75 years (0.08-14). Two patients were lost to follow-up. Two patients were noted to have related psychological problems. Haemangiomas and vascular malformations of the limb can be associated with significant functional impairment, especially if they are extending to deeper tissue planes. Such patients are likely to require surgical intervention. For many patients referred to tertiary care, surgery is still the mainstay of treatment and the only curative option. Serious complications were more common in patients with arterio-venous malformations and Kasabach-Merritt syndrome. Two of 38 patients (5.3%) were referred for formal psychological assessment. Given the potential for psychological morbidity we fear this is an aspect of care that may be under-recognised and require further specialist input.

Esophageal adenocarcinoma: a long-term complication of congenital diaphragmatic hernia?

A 22-year-old man presented with a lower esophageal adenocarcinoma having been treated for a left-sided congenital diaphragmatic hernia (CDH) as a neonate. There is no known association or similar case reported in the literature. We review the known long-term sequelae of CDH, possible theories for the occurrence of adenocarcinoma, and its implications for follow-up of patients with CDH.