Severity Of Hypospadias Research Articles

Retrospective studies and quantitative proteomics reveal that abnormal expression of blood pressure, blood lipids, and coagulation related proteins is associated with hypospadias.

Hypospadias refers to the abnormal position of the male urethral orifice, which not only leads to urination disorder but also causes sexual dysfunction in adulthood. However, the complex and diverse pathogenic factors of hypospadias are still unclear. To study the pathogenesis and prognosis of hypospadias, we counted the serological indexes of children with hypospadias, and found that sSBP, TC and LDL increased in children with mild, moderate and severe hypospadias. Subsequently, we used quantitative proteomics to find differential proteins in mild, moderate and severe hypospadias. After bioinformatics analysis and biochemical experiments on the screened DEPs, we found that the expression of proteins related to immune inflammation, coagulation, blood pressure and inflammation, and blood lipid were differential expressed in the prepuce tissue of children with hypospadias. We further confirmed that the proteins FGB, FGG, SERPINA1, and AGT involved in the angiotensin system, cholesterol metabolism, and coagulation were significantly up-regulated by biochemical experiments. In particular, the AGT protein of the angiotensin system involved in blood pressure regulation, we have shown that it increases with the severity of hypospadias. This study suggests that children with hypospadias are more likely to suffer from hyperlipidemia and cardiovascular disease (CVD). Our findings provide a theoretical basis for early monitoring of blood lipids and blood pressure to prevent CVD in children with hypospadias.

Correlation between anogenital distance and severity of hypospadias in male children

BackgroundPrevious studies have shown an association between anogenital distance (AGD) and types of hypospadias. This study aims to determine whether AGD can be used to predict the severity of hypospadias in male children.MethodsWe used a cross-sectional study design to evaluate (43) children with hypospadias. The severity of hypospadias based on the meatal position before surgery was classified using the meatal score of the glans-urethral meatal-shaft (GMS) classification into four groups of M1–M4. Three AGD parameters viz: ano-scrotal distance (ASD), the ano-penal distance 1 (APD1) and the ano-penal distance 2 (APD2) were measured using a digital calliper. The glanulomeatal distance 1 (GMD1) before and the glanulomeatal distance 2 (GMD2) after chordee correction were calculated for any change in the position of the meatus. Data were collected over 18 months and analysed using Statistical Package for Social Sciences (IBM SPSS) version 25 software. A P-value of < 0.05 was considered to be statistically significant.ResultsThe mean ano-scrotal distance (ASD), ano-penile distance 1 (APD1) and ano-penile distance 2 (APD2) were 35.0 ± 7.11 mm, 66.0 ± 13.0 mm and 82.05 ± 14.0 mm, respectively. The parameters of AGD and AGD index progressively decreased with increasing meatal score but these decreases were not statistically significant across the four categories of meatal score. Statistically significant, moderately negative correlations were observed between GMD2 and mean ASD (R = − 0.394, P ≤ 0.009), APD1 (R = − 0.308, P ≤ 0.045) and APD2 (R = − 0.391, P ≤ 0.010). There were also statistically significant predictive relationships between GMD2 (intra-operative meatal position) with ASD (R2 = 0.155, P ≤ 0.009), APD1 (R2 = 0.095, P ≤ 0.045) and APD2 (R2 = 0.153, P ≤ 0.010).ConclusionThe study demonstrated a significant relationship between the AGD and meatal position. Therefore, AGD may be used to predict the intra-operative meatal position and hence, the severity of hypospadias before surgery.

Novel evidence of CNV deletion in KCTD13 related to the severity of isolated hypospadias in Chinese population.

CNV in KCTD13 has been identified to influence androgen receptor function via its changes in gene dosage, which might contribute to hypospadias. However, there is lack of population-level evidence to assess the contribution of KCTD13 CNV to hypospadias. 349 isolated hypospadias patients were recruited and their genotyping was performed using real-time qPCR. We use Database of Genomic Variants (DGV) and CNV calls from SNP-array intensity data in 1,008 Chinese healthy men as reference. 11.17% of patients were identified to have KCTD13 CNV deletion, significantly higher than 0.05% in DGV (P < 0.001), but no cases found to have CNV duplication. Meanwhile, no CNV calls encompassing KCTD13 region were detected in Chinese healthy men. Incidence of KCTD13 CNV deletion was significantly increased with the severity of hypospadias, P _trend = 9.00 × 10-6. Compared to distal hypospadias, ORs for the proximal and midshaft were 10.07 (2.91-34.84) and 6.08 (1.69-21.84) respectively. In addition, the association between genital characteristics (stretched penile length and glans width) and KCTD13 CNV showed no significance in hypospadias children (P > 0.05). We demonstrate KCTD13 CNV deletion is strongly associated with hypospadias and its severity, but duplication is not, characterizing KCTD13 genetic variation in more detail than previously described.

Cumulative re-operation rates during follow-up after hypospadias repair.

To assess the cumulative rates of re-operations after hypospadias repair and evaluate long-term surgical outcomes at a tertiary paediatric urology centre. Retrospective analysis of 293 boys born between 1991 and 2003 undergoing hypospadias surgery was conducted. The study included 274 patients: 165 with distal, 34 with midshaft, and 75 with proximal hypospadias. Kaplan-Meier methods were used to evaluate the re-operation data. The median age at primary surgery was 1.3 years, with a median follow-up of 14.4 years. The overall re-operation rate was 48.2%, with approximately half of the problems detected within the first 3 months after surgery. The risk of re-operation was correlated with hypospadias severity, with 5- and 15-year re-operation risks at 39.3% and 51.8%, respectively. Limitations of the study include its retrospective nature and variations in surgical techniques from current standards. There is a significant risk of unplanned re-operations following hypospadias repair, increasing with the severity of the original condition. This underscores the need for extended follow-up and effective communication with patients and their families about the likelihood of requiring multiple surgeries for optimal outcomes.

Correlation of Hand Digit Length Ratio, Anogenital Distance, and Severity of Hypospadias among Prepubertal Boys.

Antenatal androgen exposure has been suggested as a contributing factor in hypospadias etiology. This study aimed to investigate the correlation between anogenital distance (AGD), index finger-to-ring finger ratio (2D:4D ratio), and hypospadias severity in prepubertal boys, with the goal of exploring these parameters as potential markers of genital anomalies in utero. A cross-sectional observational study was conducted on boys under 8 years old presenting to our outpatient department (April 2020-December 2022). Those with hypospadias were included in the study group, whereas those without hypospadias formed the comparator group. Confounding factors (age, weight, and height) were accounted for using multivariate linear regression analysis. AGD, 2D:4D ratio, and hypospadias severity were measured during clinical visits, with still images taken for precise measurements. Statistical analysis was performed using the Mann-Whitney U and student's t-tests (software: STATA Version 14). Data were collected for 100 cases of hypospadias (26 proximal and 74 distal) and 50 controls. There was no significant difference in mean age between groups (P = 0.90). AGD was slightly lower in cases (3.44 ± 1.13 cm) compared to controls (3.70 ± 1.43) (P = 0.88). 2D:4D ratios were marginally higher in cases compared to controls (P = 0.12 for both hands). Although our study did not find significant associations between AGD and 2D:4D ratios with hypospadias severity, it offers insights into the role of prenatal androgen in genital development. The lack of significance underscores the need for region-specific research, suggesting AGD and 2D:4D ratio may not universally apply as hypospadias markers.

Time to complication after primary pediatric hypospadias repair with transverse preputial island flap urethroplasty.

Hypospadias is one of the most common congenital malformations in men. The transverse preputial island urethroplasty is widely used in China, especially for moderate and severe cases due to its convenient prepuce of the penis. This analysis aims to delineate the time to first complication following transverse preputial island urethroplasty. We analyzed the clinical data and follow-up results of children who underwent hypospadias repair by transverse preputial island urethroplasty in Beijing Children's Hospital, Capital Medical University from December 2018 to December 2019 retrospectively. Postoperative complications included urethral fistula, urethral diverticulum, urethral stricture, persistent chordee. Univariate analysis of clinical variables and time to complication was performed using Kaplan-Meier survival curve. One hundred and sixty-five patients were identified. During the follow-up period, complications occurred in 101 cases (61.2%). Ninety-four percent of complications occurred within 1 year. Among children who experienced complications, Kaplan-Meier survival analysis showed that age less than 18 months and the severity of hypospadias were statistically significant (P=0.005 and P=0.04, respectively). The time to urethral diverticulum was significantly longer than that of urethral fistula and urethral stricture. More than 90% of complications after the transverse preputial island urethroplasty of hypospadias occurred within 1 year, with those related to proximal hypospadias presenting earlier than those of midshaft/distal hypospadias. Surgeons may consider a more frequent follow-up within the first year after surgery to detect these complications as early as possible.

Use of Validated Questionnaires to Predict Cosmetic Outcomes of Hypospadias Repair.

Hypospadias is a syndrome of penile maldevelopment. The primary goal of hypospadias surgery is to create a penis with normal appearance and function. Historically, the outcome of hypospadias repair has been assessed based on the need for reoperation due to urethroplasty complications (UC), including fistula formation, dehiscence, meatal stenosis, or development of a urethral stricture. The Glans-Urethral Meatus-Shaft (GMS) score is a standardized tool to predict UC. Analysis of the cosmetic outcomes of hypospadias repair based on the appearance of the reconstructed penis has been validated, and standardized scores have been published. The Hypospadias Objective Penile Evaluation (HOPE) score is a validated questionnaire used to assess postoperative cosmetic outcomes. Although predictors of surgical outcomes and UC have been well documented, predictors of optimal cosmetic outcomes are lacking in the literature. Furthermore, reoperation due to cosmetic considerations has been poorly reported. To identify predictors of cosmetic outcomes after hypospadias repair and to assess the reoperation rate according to cosmetic considerations. This prospective cohort study included 126 boys who underwent primary hypospadias repair. The severity of hypospadias, degree of penile curvature, glans width, preoperative HOPE, and GMS scores were documented. The standard technique for single-stage repairs, the tubularized incised plate urethroplasty, was performed. The primary endpoint was cosmetic outcomes evaluated by the HOPE score questionnaire six months postoperatively. Optimal cosmetic results were defined by HOPE scores ≥ 57. The study population consisted of the following cases: 87 (69%) subcoronal, 32 (25%) shaft, and 7 (6%) proximal hypospadias. Among the study participants, 102 boys (81%) had optimal cosmetic results (HOPE ≥ 57), and 24 boys (19%) had surgeries with suboptimal cosmetic outcomes (HOPE < 57). Ancillary procedures were performed in 21 boys (16%), of which 14 (11%) were solely for cosmetic considerations, and 7 were secondary to UC. Using the Receiver Operating Characteristic analysis of potential predictors of optimal cosmetic outcomes, the preoperative HOPE score had the highest area under the curve (AUC = 0.79; 95% CI 0.69-0.89, p < 0.001). After multivariable analysis, the degree of penile chordee (p = 0.013), glans width (p = 0.003), GMS score (p = 0.007), and preoperative HOPE score (p = 0.002) were significant predictors of cosmetic outcomes. Although meatal location predicted suboptimal cosmetic results in univariate analysis, it was not a factor in multivariable analysis. Over 80% of boys undergoing hypospadias repair achieved optimal cosmetic outcomes. More than 10% of cases underwent ancillary procedures, secondary solely to cosmetic considerations. Predictors of optimal cosmetic outcomes after hypospadias surgery included degree of chordee, glans width, and preoperative HOPE and GMS scores, which were the best predictors of satisfactory cosmetic results. Although meatal location is the main predictor of UC, it was not a predictor for cosmetic outcomes. Factors affecting cosmetic outcomes should be clearly explained to parents during the preoperative consultation.

Insights into enlarged prostatic utricles and Müllerian duct system remnants associated with posterior hypospadias

The prostatic utricle (PU) consists of the caudal remnant of the Müllerian duct and the urogenital sinus. The term "vagina masculina" is used if other Müllerian structures are associated with the PU. This work aims to investigate the incidence, management, and follow up of enlarged PUs and Müllerian remnants in males with posterior hypospadias. This study presents a retrospective review of cases presented with posterior hypospadias over a 5-year period. Prior to hypospadias repair, retrograde urethrograms were used to investigate enlarged PU. Subsequently, they were classified according to the Ikoma score and further assessed by karyotyping and cystoscope. Surgical excision was indicated in cases with symptomatic utricles or vagina masculina. Thirty patients were included in the study in the period between 2015 and 2020 (Table). All cases were asymptomatic initially. Twelve patients were diagnosed with enlarged PU; three of them had vagina masculina. One case with perineal hypospadias had a separate perineal opening for PU. Following hypospadias repair, three of the eight cases treated conservatively turned symptomatic. The incidence of enlarged PU and Müllerian remnants varied among different studies. However, it increased as the severity of hypospadias increased. Preoperative urethrogram was helpful in the diagnosis and classification of PU, but it had its limitations. Cystoscope was more advantageous in diagnosing vagina masculina. Although most cases were asymptomatic, some turned symptomatic after hypospadias repair. Some cases with perineal hypospadias had PU with a separate perineal opening. The incidence of enlarged PUs or Müllerian remnants was 40%. Although cases were asymptomatic before hypospadias surgery, some cases turned into symptomatic after hypospadias repair. In some cases, the PU or Müllerian remnants had a separate perineal opening. They can be classified as a particular form of Ikoma grade III necessitating surgical intervention.

Hypospadias prevalence by severity and associated risk factors: A population-based active surveillance analysis

Hypospadias is one of the most common congenital anomalies. Trends of hypospadias prevalence by severity are not well reported. Most prevalence studies consist of pooled data from different countries or states suffer from low data quality due to inconsistent methodologies, limited variables, and lack of categorization of hypospadias severity. The objective of this study is to examine the prevalence of hypospadias by degrees of severity and associated risk factors using combined data sources from a stable and well-defined population. The study population includes infants born with hypospadias to mothers residing in Arkansas from 1997 to 2016. Cases were identified from an active population-based surveillance program of birth defects. Identified hypospadias cases from surveillance data were linked to birth certificate and to a clinical database. These two data sources provide more details on the location of the defect and maternal and infant characteristics. The prevalence and 95% confidence intervals were calculated using total male live births as denominator. Chi-square test was used to assess the association of nominal variables. Logistic regression was used to calculate adjusted odds ratio. A total 3230 hypospadias cases were identified from 1997 to 2016. The overall prevalence is 83.0 per 10,000 male births. A majority of cases (56.7%) were classified as first degree with the others having second degree (22.8%), third degree (4.7%) or not otherwise specified (15.6%). The highest prevalence of hypospadias was observed among Non-Hispanic whites. Higher prevalence also was observed among mothers in the older age group with no prenatal care in the first trimester and with gestational hypertension or diabetes. Premature or small for gestational age infants tend to have higher prevalence across all levels of severity. The number of hypospadias cases increased over time. After maternal age, race and education were adjusted, higher risk persisted for infants of restricted fetal growth, mothers with gestational hypertension or diabetes and the cohort of 2013-2016. There is an increase of hypospadias cases in Arkansas. Several maternal and infant characteristics associated with higher prevalence for all levels of severity are worth further investigation.

Hormone receptor expression in hypospadias

Sex hormone imbalance in utero is hypothesized to play an important role in the pathogenesis of hypospadias. Due to its easy accessibility, foreskin samples have been used to describe hormone receptor expression in rodents, and both adult and pediatric patients. In this study we conducted a systematic approach to assess hormone receptor expression in pediatric patients with hypospadias compared to healthy controls with a focus on age-matching and differences in severity and degree of hypospadias. Foreskin samples were collected from 35 children during hypospadias operations (18 distal and 17 proximal hypospadias) and compared with ventral foreskin samples of a control group of 32 children during circumcision (15 age-matched and 17 older boys). The samples were stained with H/E, androgen (AR), estrogen (ER) and progesterone receptors (PR). The receptor stainings were blindly evaluated. An Allred score was used to evaluate receptor expression in both the epithelium as well as stroma. AR was detected in all cases. AR expression in the stroma was more evident than in the epithelium. AR expression in the hypospadias groups was significantly less than the age matched controls (p<0.05). There was no significant difference between the two hypospadias groups nor between the two control groups. Older control group showed significantly elevated levels of AR expression compared to the hypospadias group (p<0.05). ER was also detected in all cases. The stroma showed more ER than in epithelium. PR was minimal or negative in all samples. Boys with hypospadias showed significantly weaker expression of androgen receptors than age matched controls. The severity of hypospadias did not influence hormone receptor distribution. AR expression is better observed in the stroma than in the epithelium. There was no difference in ER expression between the hypospadias group (distal or proximal) and age matched normal controls. ER was expressed in larger numbers in normal older preputial tissue. The foreskin of prepubertal boys shows little to no expression of PR.

Urethral strictures. Diagnosis and treatment

Urethral strictures represent the intrinsic and permanent narrowing of the urethral lumen with urodynamic effects and genitourinary complications resulting from obstruction in the path of urine and seminal fluid elimination. In men, urethral stricture refers to a narrowed segment of the anterior urethra caused by a process of fibrosis and scarring of the urethral mucosa and surrounding spongiosum tissue ("spongiofibrosis"). In the male posterior urethra, there is no spongiosum tissue, and the term stenosis is preferred in this location. The definition of meatal stenosis is accepted as a distal narrowing at the level of the meatus, without involving the navicular fossa. There is no universal definition of female urethral stricture. Female urethral stricture is defined by most authors as "a fixed anatomical narrowing" that leads to a reduction in urethral caliber. This reduced urethral caliber is defined as being between &lt;10 Fr and &lt;20 Fr, with most studies defining it as &lt;14 Fr, compared to the normal urethral caliber of 18-30 Fr. In transgender patients, the term stricture is used to define narrowing of the reconstructed urethra despite the absence of spongiosum tissue around it.[1] In men, a marked increase in incidence is observed after the age of 55, with a median age of 45.1 years. The estimated incidence is generally 229-627 cases per 100,000 men [2]. The anterior urethra is most commonly affected (92.2%), especially the bulbar urethra (46.9%) [3]. In women, 2-29% of patients with refractory lower urinary tract symptoms have obstructive flow at the level of the bladder, of which 4-20% will have urethral strictures [4]. There is a significantly increased incidence in women over 64 years of age. In children, most strictures are traumatic: iatrogenic causes account for 27.8-48% and external trauma for 34-72% of cases [1]. Congenital (13%), inflammatory (4%), or postinfectious (1%) strictures are less commonly observed. The bulbar urethra is the most frequently affected part of the urethra [1]. After hypospadias repair, meatal stenosis and urethral strictures are reported in 1.3-20% of cases, depending on the severity of hypospadias and the technique used [5]. There is a significantly higher incidence of this type of stricture in resource-rich countries due to a higher rate of surgical interventions. It has been reported that up to 18% of urethral strictures involving the meatus or navicular fossa are caused by surgical repair of hypospadias, lichen sclerosus, instrumental/traumatic causes, or idiopathic causes. Post-circumcision meatal stenosis has been reported in less than 0.2% of infants undergoing circumcision. In transgender patients ("trans men"), approximately 51% will suffer from a urethral stricture, while in "trans women" (male to female), the incidence is 14.4% [6].

PD06-07 HOW DURABLE IS THE CHILDHOOD HYPOSPADIAS REPAIR? A DATA-LINKAGE STUDY OF PENILE REOPERATIONS OVER 30 YEARS

You have accessJournal of UrologyCME1 Apr 2023PD06-07 HOW DURABLE IS THE CHILDHOOD HYPOSPADIAS REPAIR? A DATA-LINKAGE STUDY OF PENILE REOPERATIONS OVER 30 YEARS Sergey Vavilov, Erin Nolan, Grahame H. Smith, Peter Pockney, Malcolm Starkey, and Aniruddh V. Deshpande Sergey VavilovSergey Vavilov More articles by this author , Erin NolanErin Nolan More articles by this author , Grahame H. SmithGrahame H. Smith More articles by this author , Peter PockneyPeter Pockney More articles by this author , Malcolm StarkeyMalcolm Starkey More articles by this author , and Aniruddh V. DeshpandeAniruddh V. Deshpande More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003230.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The aim of this study is to estimate the overall risk of penile reoperations after a childhood hypospadias repair, especially in the second and third decades of life, and explore the risk factors of reoperations. METHODS: All children operated on for hypospadias in three children’s hospitals in NSW Australia between April 1991 and December 2006 were identified and their health records linked (July 2001 to December 2020) using the Centre of Health Record Linkage NSW. The details regarding penile reoperations (procedure codes and dates) were captured. Patients were then grouped in three age categories for the analysis: 1 - 0-10, 2 - 10-20, and 3 - 20-30 years old. Primary reconstructive operations performed over 15 years (between 1991 and 2006) were classified into six categories: Distal – Hemicircumcision, Distal – MAGPI, Distal – TIP, Distal – Other, Proximal, Multi-Stage Repair. The reoperations were collapsed into four patient relevant categories: 1) Urethroplasty related, 2) Chordee related 3) Cystoscopies, and 4) Others. The cumulative incidence rate was measured by calculating the sum of reoperations divided by 100 person years at risk. The differences in the incidence of reoperations by hypospadias severity, urethral plate division and persistent chordee after degloving were calculated using chi-square tests with the Yates continuity correction to account for smaller cell sizes. RESULTS: 1105 patients (group 1=617, group 2=1099, group 3=473) were identified with a median follow-up of 18.4 years. The cumulative incidence rate of a penile reoperation in group 1 was 7.3, in group 2 was 1.7, and in group 3 was 0.6 per 100-patient years at risk. The cumulative incidence (risk) of a penile reoperation over 20 years was 37%. Over the entire follow-up period, the highest incidence rate of penile reoperations was after multi-stage (9.9) and single-stage proximal hypospadias repair (5.7) and TIP repair (3.6). There was a higher penile reoperation risk after proximal hypospadias repair, if at primary repair the native urethral plate was divided (p<0.0001), and if there was a persistent chordee after degloving (p=0.04). No reoperations for chordee were identified. CONCLUSIONS: This study is the first of its kind that identifies the quantum and the risk factors for reoperations over 30 years of follow-up and will inform not only better counselling but also further research into technical and non-technical aspects of hypospadias care. Source of Funding: 1. School of Medicine and Public Health, University of Newcastle, Small Project Grant. 2. Hunter New England Research and Translation Centre Research Grant 3. Priority Research Centre GrowUpWell Seed Funding 2020 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e158 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sergey Vavilov More articles by this author Erin Nolan More articles by this author Grahame H. Smith More articles by this author Peter Pockney More articles by this author Malcolm Starkey More articles by this author Aniruddh V. Deshpande More articles by this author Expand All Advertisement PDF downloadLoading ...

Effect of Preoperative Androgen Stimulation on Penile Size and Postoperative Complication Rate in Patients with Hypospadias: A Systematic Review and Meta-Analysis.

To systematically review and evaluate the beneficial effects of preoperative androgen stimulation (PAS) on penile length, glans width, and postoperative complications in patients with hypospadias using meta-analysis. A comprehensive search of the published literature between 1980 and 2022 was done on PubMed, Embase, Google Scholar, Scopus, Web of Science, and Proquest. Studies of patients with 5-alpha reductase deficiency, differentiation sex disorder, or micro-penis without hypospadias were excluded. The full-text screening, quality assessment, and data acquisition were done independently by two reviewers. Meta-analysis was done to quantify the penile growth and postoperative complications. The initial literature search yielded 2,389 records, wherein 32 studies were eligible for the systematic review and meta-analysis. Preoperative testosterone stimulation increased the penile length and glans width by 9.34 mm (95% CI: 6.71-11.97) and 3.26 mm (95% CI: 2.50-4.02), respectively. A longer penis at the baseline led to greater length gain following treatment (1 mm longer at the baseline was likely to gain 0.5 mm more). However, the increase in penile length was not associated with the severity of hypospadias. While the treatment did not affect the overall complication rate, the postoperative fistula risk was lower in those receiving PAS (RR=0.52, 95% CI: 0.30-0.91, p=0.02). The beneficial effects of PAS on increasing the penile length and glans width were again confirmed. More gain of penile length was expected in the larger penis at baseline. There are no reported increased postoperative complications in association with PAS.

Hypospadias and anorectal malformation: A difficult combination

IntroductionAnorectal malformation (ARM) and hypospadias are both multifactorial and complex diseases, and they present in a spectrum of varieties. However, these pathologies have not been studied jointly in literature. The objective of this study was to look for the association between subtypes of ARM and types of hypospadias. Material and MethodsWe conducted a retrospective review of the male patients with ARM, who had been treated at our center. We retrieved information regarding demographic details, ARM sub-type, hypospadias type, and urological problems after the chart review. All data were analyzed using SPSS version 26. ResultsA total of 408 patients were included, and 87 patients (20%) had hypospadias and ARM. There was no significant association between the severity of ARM and the severity of hypospadias. Most of the patients having proximal hypospadias belonged to the “simple” ARM group (15/22). The frequency of Vesicoureteric reflux (VUR), hydronephrosis, atrophic kidney, and at least one urological abnormality was significantly higher in patients having hypospadias and showed the strongest relationships with hypospadias. Holding the presence of hypospadias constant, ARM severity was noticeably correlated with all outcomes except solitary kidney. ConclusionWe conclude that hypospadias is a common entity among patients with ARM. These patients, having dual pathologies, are at significantly higher risk to develop other urological problems. And they should be considered a special group of patients and need close surveillance for urological issues. Level of EvidenceIII

Preliminary Reference Interval for 5-Alpha Reductase in Normal Male Children and Its Association with Hypospadias.

5-alpha reductase (5-AR) enzyme is responsible for conversion of testosterone to dihydrotestosterone (DHT) in humans, which subserves various functions. The aim of the study was to establish a normal reference interval (RI) for blood levels of the enzyme 5-AR. We conducted a prospective study on 150 boys, 75 of whom underwent circumcision for various benign conditions or for religious reasons (Group A/controls) and 75 suffering from hypospadias of variable severity (Group B/cases). The plasma levels of 5-AR were measured by enzyme-linked immunosorbent assay (ELISA) in all 150 boys and correlated with the severity of hypospadias. The 5-AR levels in Group A ranged from 14.6 to 17.3 ng/mL. The enzyme levels decreased in value with increasing severity of hypospadias in Group B (P-value &lt;0.01 - statistically significant). The levels of the enzyme in this group ranged from 0.6 ng/mL (in the most severe variety of hypospadias) to 11.5 ng/mL (mild variety of hypospadias). There is no record of RI values of 5-AR in the literature. The RI of 5-AR needs to be determined by conducting more studies globally. Its levels falls considerably with clinical severity of hypospadias, reinforcing the importance of the enzyme in the development of male external genitalia.

Quantification of the Androgen and Estrogen Receptors in the Penile Tissues of Hypospadias in Comparison with Normal Children

Introduction Hypospadias is a common congenital abnormality typified by a proximally placed ectopic urethral meatus along the ventral surface of the penis. Androgen receptor (AR) and estrogen receptor (ER) expression in the hypospadias tissues may be altered in hypospadias. Methodology We evaluated by immunohistochemistry the AR and ER expression in 75 tissues from hypospadias repair, and compared this expression to that of tissue from 75 patients undergoing circumcision. We also compared the intensity of AR and ER expression between different severities of hypospadias. Results AR quantitative grading score decreased with severity of hypospadias, while the ER score increased as the hypospadias worsened, which was statistically significant (p-value <0.05). Conclusion The penile tissue AR expression is decreased and ER expression is increased with increasing severity of hypospadias.

Prevalence and Clustering of Congenital Heart Defects Among Boys With Hypospadias

Hypospadias is a common birth defect of the male urinary tract that may be isolated or may co-occur with other structural malformations, including congenital heart defects (CHDs). The risk for co-occurring CHDs among boys with hypospadias remains unknown, which limits screening and genetic testing strategies. To characterize the risk of major CHDs among boys born with hypospadias. This retrospective cohort study used data from population-based birth defect surveillance programs on all male infants born in 11 US states from January 1, 1995, to December 31, 2014. Statistical analysis was performed from September 2, 2020, to March 25, 2022. Hypospadias. Demographic and diagnostic data were obtained from 2 active state-based birth defect surveillance programs for primary analyses, the Texas Birth Defects Registry and the Arkansas Reproductive Health Monitoring System, with validation among 9 additional states in the National Birth Defects Prevention Network (NBDPN). Birth defect diagnoses were identified using the British Pediatric Association coding for hypospadias (exposure) and major CHDs (primary outcomes). Maternal covariates and birth year were also abstracted from the vital records. Poisson regression was used to estimate adjusted prevalence ratios and 95% CIs for major CHDs within Texas and Arkansas and combined using inverse variance-weighted meta-analysis. Findings were validated using the NBDPN. Among 3.7 million pregnancies in Texas and Arkansas, 1485 boys had hypospadias and a co-occurring CHD. Boys with hypospadias were 5.8 times (95% CI, 5.5-6.1) more likely to have a co-occurring CHD compared with boys without hypospadias. Associations were observed for every specific CHD analyzed among boys with hypospadias, occurred outside of chromosomal anomalies, and were validated in the NBDPN. An estimated 7.024% (95% CI, 7.020%-7.028%) of boys with hypospadias in Texas and 5.503% (95% CI, 5.495%-5.511%) of boys with hypospadias in Arkansas have a co-occurring CHD. In addition, hypospadias severity and maternal race and ethnicity were independently associated with the likelihood for hypospadias to co-occur with a CHD; boys in Texas with third-degree (ie, more severe) hypospadias were 2.7 times (95% CI, 2.2-3.4) more likely than boys with first-degree hypospadias to have a co-occurring CHD, with consistent estimates in Arkansas (odds ratio, 2.7; 95% CI, 1.4-5.3), and boys with hypospadias born to Hispanic mothers in Texas were 1.5 times (95% CI, 1.3-1.8) more likely to have a co-occurring CHD than boys with hypospadias born to non-Hispanic White mothers. In this cohort study, boys with hypospadias had a higher prevalence of CHDs than boys without hypospadias. These findings support the need for consideration of additional CHD screening programs for boys born with hypospadias.

An experimental evaluation of the efficacy of perinatal sulforaphane supplementation to decrease the incidence and severity of vinclozolin-induced hypospadias in the mouse model

Determining the mechanisms of toxicity induced by pollutants has long been a research priority in lieu of considering the mechanisms of resilience that prevent deleterious impacts. Protective mechanisms in many taxa can be therapeutically targeted to enhance resilience to synthetic toxicants. For example, the environmental sensor, Nuclear factor (erythroid-derived 2)-like 2 (Nfe2l2 or Nrf2), a transcription factor, facilitates transcription of many protective genes. Hypospadias is a common malformation of the penis. The risk of being born with hypospadias increases with pollutant exposure. We use vinclozolin-induced hypospadias in the mouse as a model to test the hypothesis that pollutant-induced birth defects can be prevented and reduced in severity by augmenting natural mechanisms of resilience. Pregnant mice were exposed to the demasculinizing toxicant, vinclozolin, in combination with increasing doses of the NRF2 activator, sulforaphane. The sulforaphane dose that most effectively increased masculinization (anogenital distance) was identified and used to test the hypothesis that sulforaphane reduces the hypospadias-inducing potency of vinclozolin. Finally, a Nrf2 knockout study was conducted to test whether NRF2 was required for the sulforaphane-induced rescue effects. Sulforaphane supplementation to vinclozolin exposed embryos increased anogenital distance in a nonlinear fashion typical of Nrf2 activators. The most effective dose of sulforaphane (45 mg/kg) reduced the occurrence and severity of vinclozolin-induced hypospadias and corrected penis morphogenesis. The sulforaphane-induced rescue effect was dependent on the presence of Nrf2. Nrf2 plays a critical role in protecting the fetus from vinclozolin and reduces the incidence and severity of hypospadias, the most common birth defect in boys in many countries. This work lays a foundation for developing prenatal supplements that will protect the fetus from pollutant-induced hypospadias. Studying the protective mechanisms that drive resilience to toxicants will facilitate innovation of protective therapies.

An objective hypospadias classification system

Current approaches to classifying hypospadias severity are based on meatus position. These classification tools lack precise reflection on the degree of urethral hypoplasia and extent of urethral underdevelopment hence are not good representative of hypospadias severity. Here, an alternative classification system is introduced that objectively reflects the developmental pathology underlying this condition. The study goal was to appraise location of bifurcation in the corpus spongiosum (BCS) relative to the penile shaft as an indicator of hypospadias severity. Patients aged <18 years with primary hypospadias were included in the study. Urethral defect ratio (UDR) was calculated by dividing the extent of urethral defect (distance between the glandular knobs and BCS) relative to stretched penile length (SPL). Hypospadias severity was then categorized into three distinct grades (UDR <0.5, 0.5-0.99, ≥1.0). The Inter-Class Correlation (ICC) was evaluated to assess the intra- and inter-rater agreement between the reviewers of UDC ratio. Linear regression analysis was performed to estimate the correlation between UDC ratios and either plate objective scoring tool (POST) and Curvature degrees. A total of 67 patients aged 12.3±3.7 months with primary hypospadias were enrolled. UDR ranged between 0.2 and 1.3. A significant difference in hypospadias level was observed between UDR grades, which further correlated degree of curvature (P<0.0001), urethral plate quality (P<0.0001), and associated anomalies (P<0.05). The Inter-Class Correlation (ICC) value to examine the intra- and inter-rater agreement between the two reviewers in UDC ratio was 0.998 (95% CI 0.998, 0.999). Regression analysis revealed that UDR and both POST and Curvature degree were significantly associated (P<0.001). A hypospadias severity scoring system based on embryological etiology and urethral hypoplasia and assessed relative to the penile shaft represents an objective, feasible, and consistent tool. These results clearly indicate that the reviewers have had excellent consistency/reliability across their consecutive readings. This new system can facilitate objective description of hypospadias-spectrum anomalies and thus support precise communication between individual surgeons and centers.

Clinical Profiles and Surgical Outcome of Hypospadias Repair at a Teaching Hospital in Ethiopia.

Hypospadias repair is one of the commonest and challenging surgery done in pediatric age groups. This study was conducted to assess clinical profiles and surgical outcomes of hypospadias repair. A retrospective analysis of pediatric hypospadias repairs at St. Paul's hospital millennium medical college from September 2015 to August 2019 was conducted. A total of 277 patients with hypospadias repair were investigated. The mean age was 3.7+/- 3.5 years (Range, 0.5-14 years) and only one-third (98,35.4%%) of patients were operated on in the recommended age group (6-18 months). Anterior/distal hypospadias was the commonest (123,44.4%) variant identified. The majority (176,63.5%) had chordee and 105(37.9%) were severe forms. Tubularized incised plate repair was the major (164,59.2%) surgical technique employed followed by staged urethroplasty (61,22%). Post-operative complications occurred in 135(48.7%) patients and the commonest was urethrocutanous fistula (95,34.3%). No significant correlation was found between the occurrence of these complications and factors such as age at repair, the severity of hypospadias, presence of concomitant urogenital anomaly, type of procedure and duration of urinary diversion. However, the presence of severe chordee (AOR=3.09; 95%CI 1.21-7.54; p=0.013) was an independent factor found to be associated with postoperative complications on multivariate analysis. Higher rate of complications following hypospadias repair was observed in our study. Our study also demonstrated no significant advantage of any repair technique in reducing operative complications. Extensive preoperative evaluation, proper operative plan and regular follow-up of such patients is paramount for a better outcome.