Association between extra-genital congenital anomalies and hypospadias outcome

Extra-genital congenital anomalies are often present in cases of hypospadias, but it is unclear whether they have an association with the outcome of hypospadias surgery. The aim of this study was to review all hypospadias cases that had surgery between 2009 and 2015 at a single centre and identify clinical determinants of the surgical outcome. An extra-genital congenital anomaly was reported in 139 (22%) boys and 62 (10%) had more than 1 anomaly. Of the 626 boys, 54 (9%), including 44 with proximal hypospadias, had endocrine as well as limited genetic evaluation. Of these, 10 (19%) had a biochemical evidence of hypogonadism and 5 (9%) had a molecular genetic abnormality. At least 1 complication was reported in 167 (27%) patients, with 20% of complications (most frequently fistula) occurring after 2 years of surgery. The severity of hypospadias and the existence of other anomalies were clinical factors that were independently associated with an increased risk of complications (p < 0.001). In conclusion, complications following surgery are more likely in those cases that are proximal or who have additional extra-genital anomalies. To understand the biological basis of these complications, there is a greater need to understand the aetiology of such cases

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 17β-estradiol, dihydrotestosterone (DHT), and testosterone. Results: In controls, testosterone and 17β-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). 17β-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 17β-estradiol (Emax: 156.9 vs 23.6, P < .0001) reduced contraction. Androgens, but not 17β-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 17β-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

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. Key question Is hypospadias associated with vascular dysfunction? Key finding Boys with hypospadias have evidence of hypercontractility and impaired vasodilation secondary to increased Rho kinase activation and oxidative stress. This leads to raised systolic blood pressure in adolescence and increased risk of admission to hospital for cardiovascular diseases in adulthood. Take-home message Hypospadias is a risk factor for cardiovascular dysfunction in males

Parental decisional satisfaction after hypospadias repair in the United Kingdom

Background: in hypospadias, the aim of surgical treatment is to achieve both desirable functional and cosmetic outcomes; however, complications following surgery are common and 18% of boys require re-operation. In mild degrees of hypospadias, repair may be offered entirely to improve cosmesis, meaning parents should be fully informed of this and the potential for complications, during the consent process. Parents’ decision-making may be aided by making them aware of how others in a similar position have felt about the decision that they made for their child. One method of measuring parental satisfaction is decisional regret (DR). Objectives: to assess parental satisfaction following hypospadias surgery in the United Kingdom by assessing DR and to determine the feasibility of obtaining meaningful data via a mobile phone survey. Study design: the National Outcomes Audit in Hypospadias database was commissioned by the British Association of Paediatric Surgeons to capture clinical information from hypospadias repairs. Following ethical approval (16/NW/0819), a text message was sent to mobile numbers in the database inviting participation in a questionnaire incorporating the validated DR scale (DRS). The primary outcome measure was mean DRS score, which was correlated with clinical information, a score of zero indicated no regret and 100 indicated maximum regret. Results: there were 340 (37%) responses. The median age at the primary procedure was 16 (interquartile range 13–20) months. No DR (score = 0) was detected in 186 (55% [95%CI 49–60]) respondents; however, moderate-to-severe DR (score = 26–100) was seen in 21 (6.2% [95%CI 3.6–8.7]) respondents. On multivariate analysis, a distal meatus, a small glans and developing complications requiring repeat surgery were all associated with increased levels of regret (Table). There was no association between DR and cases performed per surgeon. Discussion: around half of respondents demonstrated no DR and postoperative complications requiring surgery were associated with the highest levels of DR, which is similar to a Canadian study. Lorenzo et al. however found that DR was associated with circumcision, which was undertaken in all boys; however, in this UK study, around a third of boys were circumcised and regret levels between those circumcised and those not circumcised were similar. The limitations of this work include the following: surgeons submitting their own data on complications and there is potential of selection bias between respondents and non-respondents as with any survey. Conclusions: data from this study can be used to improve pre-operative counselling during the consent process. Smart mobile phone technology can be used successfully to distribute and collect parent-reported outcomes. [Table presented]</p