Severe Hypospadias Research Articles

Letter to the editor regarding “Dissociated urethral plate Onlay and standard Onlay urethroplasty for mid-distal hypospadias: A comparative study” The main element responsible for the formation of penile curvature associated with severe hypospadias is not the fibrous tissue present under the urethral plate

Letter to the editor regarding “Dissociated urethral plate Onlay and standard Onlay urethroplasty for mid-distal hypospadias: A comparative study” The main element responsible for the formation of penile curvature associated with severe hypospadias is not the fibrous tissue present under the urethral plate

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.

Long term outcomes from uncorrected hypospadias: a scoping review

IntroductionThe goal of hypospadias repair is to optimize urinary and sexual function, improve cosmesis and minimise the psychosocial effects associated with a penile anomaly. However, a lack of clarity exists regarding the role of surgery in milder hypospadias where the anomaly is inconspicuous and there is no anticipated impact on function. The aim of this study was to review the long term functional, cosmetic and psychosocial outcomes in men with uncorrected hypospadias. This information may be helpful for parents who are burdened with deciding the correct treatment for their child's hypospadias. MethodsA scoping review of PubMed, EMBASE, and CINAHL + databases was performed in adherence with PRISMA guidelines. Eight studies were identified for inclusion in the review. ResultsMen with mild uncorrected hypospadias have similar functional outcomes to those without hypospadias, preferring to void standing and reporting similar IPSS scores. However, those with severe untreated hypospadias experience significant urinary difficulties, higher IPSS scores, and are more likely to sit when voiding. They reported worse SHIM scores, more ventral curvature, and greater difficulty with intercourse. Most men with incidentally identified hypospadias are unaware of their condition and are satisfied with their penile appearance. There was no difference in the attainment of psychosocial milestones between men with uncorrected hypospadias versus no hypospadias. ConclusionThere is a lack of research regarding the experiences of adult men with uncorrected hypospadias. However, there is some evidence to support the non-operative management of mild hypospadias. Therefore, the decision to defer surgery in infancy should balance parental wishes and physician guidance, particularly in cases where the risk of functional impairment is low.

Resultados a largo plazo de hipospadias no intervenidos: una revisión exploratoria

Introduction: The goal of hypospadias repair is to optimize urinary and sexual function, improve cosmesis and minimise the psychosocial effects associated with a penile anomaly. However, a lack of clarity exists regarding the role of surgery in milder hypospadias where the anomaly is inconspicuous and there is no anticipated impact on function. The aim of this study was to review the long term functional, cosmetic and psychosocial outcomes in men with uncorrected hypospadias. This information may be helpful for parents who are burdened with deciding the correct treatment for their child's hypospadias.Methods: A scoping review of PubMed, EMBASE, and CINAHL+ databases was performed in adherence with PRISMA guidelines. Eight studies were identified for inclusion in the review.Results: Men with mild uncorrected hypospadias have similar functional outcomes to those without hypospadias, preferring to void standing and reporting similar IPSS scores. However, those with severe untreated hypospadias experience significant urinary difficulties, higher IPSS scores, and are more likely to sit when voiding. They reported worse SHIM scores, more ventral curvature, and greater difficulty with intercourse. Most men with incidentally identified hypospadias are unaware of their condition and are satisfied with their penile appearance. There was no difference in the attainment of psychosocial milestones between men with uncorrected hypospadias versus no hypospadias.Conclusion: There is a lack of research regarding the experiences of adult men with uncorrected hypospadias. However, there is some evidence to support the non-operative management of mild hypospadias. Therefore, the decision to defer surgery in infancy should balance parental wishes and physician guidance, particularly in cases where the risk of functional impairment is low.

Short-Term Impact of Newly Imposed Legal Restriction on DSD Surgery in Children in Germany.

In recent years, changing paradigms, both culturally and scientifically, have fundamentally altered the approach to the treatment of children with Disorders of Sexual Development (DSD) prior to reaching the age of legal consent. In Germany, the situation changed with the introduction of legislation that includes a partial ban on DSD surgery in children in 2021. This study aims to analyze the impact of this legislation on clinical practice. From 2014 to 2024, all patients with DSD in our institution were included. The study group comprised all patients operated on after the legislation. All patients operated on before the legislation served as the control group. Karyotype, phenotype, resulting type of DSD, age at presentation and age at operation were recorded. A total of 35 patients were included in this study, with 15 in the study group and 20 in the control group. The operation was authorized by the family court for all patients in the study group. A total of 46,XY patients with severe hypospadias and clinical aspect of intersexual outer genitalia were the largest proportion (25 patients, 71.4%). Nine patients (25.7%) were 46,XX girls with classical congenital adrenal hyperplasia (CAH) type. One patient (2.9%) showed a mixed gonadal dysgenesis. The mean age of the patients at first presentation in our institution was 10.7 months in the control group and 11.0 months in the study group. The mean age at operation was significantly higher in the study group (20.1 months) compared to the control group (15.1 months; p = 0.032, unpaired t-test). The introduction of the legislation with a partial ban of genital surgery in DSD children in Germany has led to a significant delay in surgery. Since the majority of the patients comprise severe hypospadias and 46,XX CAH patients, further amendments of the law are proposed to minimize potential harm.

PRIMARY REPAIR OF PROXIMAL (GRADE IV) HYPOSPADIAS UTILIZING TUNICA VAGINALIS VASCULARISED FLAP

Background: Proximal (grade IV) hypospadias like scrotal and perineal are considered as severe challenging types for surgeons, problematic for the patients and their families, More than three hundreds surgical techniques were used to manage different type of hypospadias . Most of them associated with high incidence of complications. These complications are much more common in the proximal types as in our study. Post-operative fistula formation is expected complications. Utilising the tunica vaginalis as an additional layer during repair may prevent such complications. In this study we evaluated the benefits of using the tunica vaginalis flap as a supportive layer in the primary repair. Most related literatures about this subject used this technique after surgery to manage cases with post-operative fistulas. In the contrary we used this technique during the formal surgery to cover the new urethra to prevent fistula formation not after surgery. Aims of the study: A retrospective study, on fourteen patients with severe hypospadias (Proximal types), to evaluate the role of tunica vaginalis flap in the primary repair of the hypospadias. Patients and Methods: Between January 2016 and January 2024, fourteen children with Grade IV hypospadias were operated on. Only severe cases were treated with this method other simpler and more common cases were treated by different surgeries like Snodgrass technique. The age range was 2 to 16 years. All of them had 2 staged repair the first stage was correcting the chordae by incising the urethral plate excising the fibrous chordae tissues then covering the bare shaft with dorsal flaps. The tunica flap was used in the second stage which was done 6 to 12 months later. Folly's catheter was used for ten to fourteen days after surgery. And the patients were followed for a variable time 3months to 2 years period for the development of complications like fistula formation or stricture. Cosmetic considerations were also noted. Results: All the fourteen patients had proximal types (Grade IV) hypospadias. After surgery all patients had a good cosmetic outcome no fistula formation two had mild distal urethral stricture cured after few urethral dilatation. No post-operative penile torsion was noted. Two patients developed local infection treated conservatively. One patient had partial glanular dehiscence at the distal end which had no clinical significance. One patient complained from on and off penile cutaneous swelling lasted 3 weeks. Conclusions: Using tunica vaginalis vascularised flap to cover the new urethra in severe proximal hypospadias during the second stage seems to be a successful way in preventing fistula formation without increasing the patient's morbidity.

Effect of Pre-operative Parenteral Testosterone on Penile Dimensions and Vascularity in Proximal Hypospadias: A Prospective Observational Study.

Severe or proximal hypospadias is associated with inadequate local tissue and small phallus size. Pre-operative androgens have been used to increase phallus size, but there are very few studies on its role in proximal hypospadias. This study aimed to assess the effects of pre-operative intramuscular (IM) testosterone on proximal penile hypospadias in terms of penile morphology and tissue characteristics of penile skin. This prospective observational study was conducted on 27 patients of proximal hypospadias over a period from June 2017 to July 2018. The patients were sequentially enrolled into two groups: Group A and Group B. Group A patients received IM testosterone before surgery, whereas Group B patients were operated without pre-operative testosterone. Outcomes were analysed in terms of change in penile dimensions and effect on vascularity of penile skin. Pre-operative IM testosterone in Group A caused a significant increase in stretched penile length from a mean of 3.058 cm (±0.691) to 3.9 cm (±0.875) ( P = 0.002), penile circumference from a mean of 4.142 cm (±0.772) to 4.667 cm (±1.174) ( P = 0.029) and glans width from a mean of 1.225 cm (±0.245) to 1.750 cm (±0.571) ( P = 0.002). There was higher microvessel density in the preputial skin of Group A (mean: 12.212 [±4.745] blood vessels/high-power field [HPF]) compared to Group B (8.867 [±3.258] blood vessels/HPF) ( P = 0.043). Pre-operative testosterone in proximal hypospadias causes significant changes in penile dimensions and tissue characteristics. Improvement in penile dimensions leads to ease in operability and better tissue handling. However, more studies with large sample size are required to establish the beneficial effects of pre-operative hormone stimulation on urethroplasty.

Advantages of Urethroplasty Terminating at the Corona for Severe Hypospadias: Complications, Uroflowmetry, and Esthetics

PurposeMid-shaft/proximal (msp) and penoscrotal/scrotal/perineal (pssp) hypospadias treated by urethroplasty (UP) terminating at the corona (UPC) or UP terminating at the tip of the glans (UPG) were compared. MethodsUP performed at a single institute (n = 234) between 2003 and 2020 were grouped as: msp-UPC (n = 23), msp-UPG (n = 75), pssp-UPC (n = 81), and pssp-UPG (n = 55) to compare data obtained from medical records for post-UP complications (PUC; urethral stenosis, urethrocutaneous fistula, diverticulum formation, and bleeding; n = 234), post-UP uroflowmetry (PUF; average flow rate (Qave), maximum flow rate (Qmax), voiding time (VT), voided volume (VV) and urine flow curves) in 57 UP patients [msp-UPC (n = 5), msp-UPG (n = 12), pssp-UPC (n = 32), pssp-UPG (n = 8)] and 9 controls, and post-UPC esthetics (EST; n = 104). P < 0.05 was considered significant. ResultsMean ages at UP (years) were: msp-UPC (3.1 ± 3.0), msp-UPG (3.3 ± 1.4), pssp-UPC (4.6 ± 2.4), and pssp-UPG (3.4 ± 1.4); p < 0.0001 by ANOVA test. Overall, there were significantly more PUC in pssp-UPG compared with pssp-UPC except for bleeding.Ages at PUF assessment were similar. Mean Qave (mL/s) for pssp-UPG (4.0 ± 1.0) was significantly less than pssp-UPC (5.9 ± 2.5; p < 0.05) and both were significantly less than controls (6.9 ± 1.8; p < 0.05, p < 0.01, respectively). Mean Qmax (mL/s) for pssp-UPC (11.4 ± 4.8) was significantly better than pssp-UPG (7.8 ± 2.3; p < 0.05) and for controls (14.9 ± 4.4) was significantly better than pssp-UPG (7.8 ± 2.3; p < 0.01). All VT (seconds) were similar to controls; all urine flow curves were normal. For EST in UPC (n = 104), 3 cases requested meatal advancement. ConclusionsUPC may be a valid option for treating pssp hypospadias because of significant differences in PUC/PUF and minimal EST issues compared with UPG. Level of evidencePrognosis Study Level-Ⅱ

Establishing diagnoses in a cohort of boys from East London with 46XY DSD and severe hypospadias

Establishing diagnoses in a cohort of boys from East London with 46XY DSD and severe hypospadias

Is cystourethroscopy a crucial preoperative step in severe and complex types of hypospadias?

Proximal hypospadias is considered the most severe subtype of the hypospadias spectrum and represents approximately one-fifth of the total cases. It is well-evidenced by many studies that the rate of postoperative complications following the repair of this complex subtype is significantly higher when compared to the distal variants. Few reports described the proximal hypospadias from the other perspective which is the preoperative one. Most pediatric surgeons notice an unexplained incidence of lower urinary tract infection and occasional difficulty of urinary catheterization in those children. This sometimes requires the use of additional measures such as the use of urethral sounds, filiforms and followers, and even catheterization under anesthesia. The aim of the work is to evaluate the role of preoperative cystourethroscopy in detecting associated anomalies in cases of proximal and severe hypospadias. This prospective study was conducted in the pediatric surgery unit at Alexandria Faculty of Medicine between July 2020 and December 2021 and included all children with severe grades of hypospadias. After thorough evaluation, all children underwent cystourethroscopy just before the procedure. Any abnormalities in the urethra, urinary bladder, or ureteric openings were recorded if present. Finally, the definitive operation was performed as per schedule. Fifty-two patients (41 fresh and 11 redo patients) with a median (range) age at presentation of 5 (1-16) years were enrolled in this study. The intraoperative cystourethroscopy was done in all of the patients. Significant abnormal findings were recorded in 32 patients (61.5%), while the other 20 patients (38.5%) were revealed to be normal. The most common abnormal findings were dilated prostatic utricle opening and hypertrophied verumontanum (in 23 and 16 cases, respectively). Although most of the associated anomalies with proximal hypospadias are asymptomatic, cystourethroscopy is better used owing to a high incidence of these anomalies. This can facilitate an early diagnosis as well as early detection and intervention at the time of repair.

Genotype-phenotype correlations, surgical selections, and postoperative complications of 5a-reductase 2 deficiency in 69 children with hypospadias.

5α-reductase 2 deficiency prevents testosterone from being converted to dihydrotestosterone, which causes abnormal urogenital sinus development. The aim of this study was to analyze the relationship between genotype-phenotype, surgical selections, and postoperative complications of 5α-reductase 2-deficient patients with hypospadias. We retrospectively evaluated the medical records of patients who were diagnosed with 5α-reductase 2 deficiency after genetic testing in the Department of Endocrinology and underwent initial hypospadias surgery in the Department of Urology in Beijing Children's Hospital, Capital Medical University (Beijing, China), from April 2007 to December 2021. A total of 69 patients were included in this study; the mean age at surgery was 34.1 months, and the average follow-up time was 54.1 months. Sixty children were treated with preoperative hormone stimulation (PHS) to promote penile growth. The average penis length and glans width were increased by 1.46 cm and 0.62 cm, respectively. The most frequent mutations were p.R227Q (39.1%, 54/138), p.Q6* (15.2%, 21/138), p.G203S (12.3%, 17/138), and p.R246Q (11.6%, 16/138). In 64 patients who were followed up, 43 had a one-stage operation and 21 had a staged operation, and there were significant differences in external masculinization score (EMS) (P = 0.008) and the average number of operation required to cure (P < 0.001) between one-stage and staged operations. PHS had a positive effect (P < 0.001) on penile development. The p.R227Q mutation was associated with higher EMS and less severe hypospadias. One-stage surgery can be selected if conditions permit. The growth and development of children are acceptable in the long term, but penis growth remains unsatisfactory. Long-term complications of hypospadias should be considered during puberty.

Whole-exome sequencing study of hypospadias

Hypospadias results from the impaired urethral development, which is influenced by androgens, but its genetic etiology is still unknown. Through whole exome sequencing analysis, we identified NR5A1, SRD5A2, and AR as mutational hotspots in the etiology of severe hypospadias, as these genes are related to androgen signaling. Additionally, rare damaging variants in cilia-related outer dynein arm heavy chain (ODNAH) genes (DNAH5, DNAH8, DNAH9, DNAH11, and DNAH17) (p= 8.5×10-47) were significantly enriched in hypospadias cases. The Dnah8 KO mice exhibited significantly decreased testosterone levels, which had an impact on urethral development and disrupted steroid biosynthesis. Combined with trios data, transcriptomic, and phenotypical and proteomic characterization of a mouse model, our work links ciliary genes with hypospadias. Overall, a panel of ODNAH genes with rare damaging variants was identified in 24% of hypospadias patients, providing significant insights into the underlying pathogenesis of hypospadias as well as genetic counseling.

Dorsal shortening vs. ventral lengthening for congenital ventral curvature in patients with/without severe hypospadias A meta-analysis of comparative studies.

Herein, we compared surgical outcome of dorsal shortening (DS) vs. ventral lengthening (VL) for correcting congenital ventral curvatures. A systematic literature search was performed in September 2021 using the PubMed, EMBASE, Scopus, CENTRAL, ProQuest, and Clinicaltrials.gov databases. Comparative studies were identified and evaluated according to Cochrane Collaboration recommendations. Assessed outcomes included success and complication rates, which were extrapolated for the respective odds ratios (OR) with 95% confidence intervals (CIs). Subgroup analyses were performed according to congenital curvature, with or without severe hypospadias or recurrent curvatures (PROSPERO: CRD42021276193). Based on pooled effect estimates from 12 studies with 430 (DS 253, VL 177) cases of ventral curvature repair, VL rendered a better success rate for curvature correction (OR 4.20, 95% CI 2.11, 8.33) than DS, with comparable composite surgical complication rates (OR 0.77, 95% CI 0.27, 2.18). Subgroup analysis showed that the success rate remained significantly better for VL among patients with associated severe hypospadias (OR 3.59, 95% CI 1.25, 10.26) and recurrent penile curvatures (OR 5.70, 95% CI 1.69, 19.21) but not among those with congenital curvature without hypospadias or those with mild hypospadias (OR 2.99, 95% CI 0.32, 27.57). For congenital curvature associated with severe hypospadias and recurrent curvatures, VL renders a modestly better success rate; however, careful selection of patients is key for best outcome.

Sexual well-being and penile appearance in adolescents operated for distal hypospadias in childhood

The importance of patient-reported outcomes (PRO) in hypospadias is increasing. However, more knowledge is needed concerning genital self-perception on appearance and function in adolescents. The complication rates for distal hypospadias is different from that for severe hypospadias, and expected outcomes related to sexual well-being and cosmetics may also differ. To investigate 16-year-olds' self-reported outcomes on penile appearance, sexual well-being, and voiding function in distal hypospadias, and compare with that of healthy male adolescents and a surgeon's view. Sixteen-year-old patients operated for distal hypospadias were included in this cross-sectional study and compared to a group of healthy adolescents. The assessment tools included the adolescents' self-perception on genital appearance and function measured by Pediatric Penile Perception Score (PPPS) and their responses to a structured interview. We also included information on clinical data from the electronic medical records, together with a physical examination and an uroflowmetry. Seventy patients and 61 healthy adolescents participated. Patients and the comparison group reported no differences on sexual well-being. The patients were satisfied with penile appearance, however their overall PPPS was significantly lower (8.9), compared to the comparison group (9.6, p=0.03). Thirty-nine percent of patients had complications leading to re-interventions and reported lower scores on genital self-perception on appearance and function compared to those who had not re-interventions. Voiding function was normal. The surgeon's score on appearance was comparable to the patients' score. A key finding in our study is the patients' high satisfaction on sexual well-being, which was similar to healthy adolescents. The patients were also satisfied with penile appearance but scored significantly lower than the comparison group. Surgeons and patients had comparable scores on appearance; however, they seemed to emphasize different aspects of appearance. Our results on penile appearance and sexual well-being are comparable to those of other studies on distal hypospadias. In our study, re-interventions were associated with more negative genital self-perception on appearance and function, similar to findings in other studies. Our results show overall positive satisfaction on sexual well-being, voiding function and penile appearance despite less satisfaction on penile appearance when compared with the comparison group. Satisfaction was reported to be good also in patients experiencing re-interventions.

Fibrinogen/poly(l-lactide-co-caprolactone) copolymer scaffold: A potent adhesive material for urethral tissue regeneration in urethral injury treatment.

Since a scarcity of sufficient grafting materials, several complications can arise after urothelial defect reconstruction surgery, including severe hypospadias. Accordingly, developing alternative therapies, such as urethral restoration via tissue engineering are needed. In the present study, we developed a potent adhesive and repairing material using fibrinogen-poly(l-lactide-co-caprolactone) copolymer (Fib-PLCL) nanofiber scaffold to achieve effective urethral tissue regeneration after seeding with epithelial cells on the surface. The invitro result found the Fib-PLCL scaffold promoted the attachment and viability of epithelial cells on their surface. The increased expression levels of cytokeratin and actin filaments were observed in Fib-PLCL scaffold than PLCL scaffold. The invivo urethral injury repairing potential of Fib-PLCL scaffold was evaluated using a rabbit urethral replacement model. In this study, a urethral defect was surgically excised and replaced with the Fib-PLCL and PLCL scaffolds or autograft. As expected, the animals healed well after surgery in the Fib-PLCL scaffold group, and no significant strictures were identified. As expected, the cellularized Fib/PLCL grafts have induced the luminal epithelialization, urethral smooth muscle cell remodelling, and capillary development all at the same time. Histological analysis revealed that the urothelial integrity in the Fib-PLCL group had progressed to that of a normal urothelium, with enhanced urethral tissue development. Based on the results, the present study suggests that the prepared fibrinogen-PLCL scaffold is more appropriate for urethral defect reconstruction.

Glans dehiscence after severe hypospadias repair. Is it a real complication? Clues from a study in post-pubertal patients

IntroductionGlans dehiscence (GD) is reportedly a common complication after proximal hypospadias repairs. However, the need for surgical correction is controversial. The aim of this study was to assess awareness, risk factors, and outcome of GD in post-pubertal patients. The agreement with surgeon assessment was also evaluated.MethodsThe design was retrospective. All consecutive patients treated for proximal hypospadias between 2000 and 2011 were included. The presence of GD was self-reported, and the participants could optionally upload a photograph for surgeon assessment. Cosmetic and functional outcomes were assessed by validated questionnaires (HOSE, PPPS, KINDL®, IIEF-5). Results were compared between patients with and without GD.ResultsOf 219 patients, 34 (16%) participated. Fourteen of them (41%) self-reported GD. Eighteen patients (8%) also uploaded a photograph and, in ten of them (56%), the surgeon noted the presence of GD with poor agreement [k = − 0.444 (95 CI − 0.856 to − 0.033)] with patient report. Patients self-reporting GD had had more frequently a penile curvature at diagnosis (12/14 = 86%, p = 0.01), and had undergone a single-staged repair (100% vs. 65%, p = 0.03). No difference was found in cosmetic and functional outcomes. Results were similar also comparing groups with and without GD as assessed by the surgeon.ConclusionGD was a common finding after severe hypospadias repair. It was more common in case of surgeon assessment with poor agreement between patients and surgeons. GD did not prove to have clear clinical implications. Therefore, in our opinion, surgical repair of GD should be recommended only on patients request.

Dorsal shortening versus ventral lengthening procedure for correction of congenital ventral curvature in patients with and without severe hypospadias: A meta-analysis of comparative studies

Dorsal shortening versus ventral lengthening procedure for correction of congenital ventral curvature in patients with and without severe hypospadias: A meta-analysis of comparative studies

Role of epigenetics in the etiology of hypospadias through penile foreskin DNA methylation alterations

Abnormal penile foreskin development in hypospadias is the most frequent genital malformation in male children, which has increased dramatically in recent decades. A number of environmental factors have been shown to be associated with hypospadias development. The current study investigated the role of epigenetics in the etiology of hypospadias and compared mild (distal), moderate (mid shaft), and severe (proximal) hypospadias. Penile foreskin samples were collected from hypospadias and non-hypospadias individuals to identify alterations in DNA methylation associated with hypospadias. Dramatic numbers of differential DNA methylation regions (DMRs) were observed in the mild hypospadias, with reduced numbers in moderate and low numbers in severe hypospadias. Atresia (cell loss) of the principal foreskin fibroblast is suspected to be a component of the disease etiology. A genome-wide (> 95%) epigenetic analysis was used and the genomic features of the DMRs identified. The DMR associated genes identified a number of novel hypospadias associated genes and pathways, as well as genes and networks known to be involved in hypospadias etiology. Observations demonstrate altered DNA methylation sites in penile foreskin is a component of hypospadias etiology. In addition, a potential role of environmental epigenetics and epigenetic inheritance in hypospadias disease etiology is suggested.

Reoperation frequency after transverse preputial Island flap urethroplasty "Duckett's technique" in treatment of severe hypospadias: A single center study.

Transverse Preputial Island Flap Urethroplasty (TPIFU) is one of the most common techniques for treating severe hypospadias. Studies on the reoperation frequency after TPIFU is lacking. In the present study, we reported our clinical outcomes of severe hypospadias treated with one-staged TPIFU and analyzed the operation frequency. We retrospectively analyzed the clinical data of severe hypospadias patients who underwent one-stage TPIFU from December 2018 to December 2019 in the department of Urology at Beijing Children's Hospital. A stepwise approach was used to manage the curvature. Severe hypospadias was defined as those residual curvature was higher than 30° after degloving. Urethroplasty complications included fistula, urethral stricture, and diverticulum. The short-term cure was identified as no complications occurring for 12 months after the date of last-time surgery. The reoperation rate and operation frequency of TPIFU were analyzed. A total of 136 patients who underwent one-stage TPIFU were included in the study. The follow-up after primary urethroplasty ranged from 22 to 50 months. The median age at primary surgery was 22.5 months (range from 13 to 132 months). After primary TPIFU surgery, 53 (39%) patients underwent additional surgical interventions to treat postoperative complications. Among them, 24 patients (17.6%) developed fistula, 17 patients (12.5%) developed urethral stricture and 11 patients (8.1%) developed diverticulum. After the second surgery, five patients remained fistula, five patients remained urethral stricture, and seven patients remained diverticulum. Overall, 61% (85 patients) met the cured standard after the primary operation, and the two operations cure rate was 87.5% (119 patients). 91.2% (124 patients) were cured in three operations. Although the complication rates after primary TPIFU were relatively high, more than half of patients achieved short-term cured through a single operation, and the cure rate after two or three operations was acceptable.

Application of a free preputial tube graft coupled with urethral plate urethroplasty combined with a Buck's fascia integral covering for the single-stage repair of severe hypospadias.

To assess the outcome of a free preputial tube graft coupled with urethral plate urethroplasty combined with a Buck's fascia integral covering (BFIC) for the single-stage repair of severe hypospadias in children. A retrospective study was performed on 40 children with hypospadias who were treated in our hospital from December 2017 to February 2022. The inclusion criteria were as follows: (1) the patient had proximal hypospadias, or penile curvature over 30° after degloving the penis; and (2) the patient underwent surgery for hypospadias for the first time. A free preputial tube graft coupled with urethral plate urethroplasty combined with a Buck's fascia integral covering was performed, and all patients were followed up for more than 6 months. After degloving the foreskin, the urethral orifice was retracted to the perineum and scrotum in 20 cases, penoscrotal in 8 cases, and penile in 12 cases. Single-stage repair was achieved without complications in 34 (85%) patients. The remaining six patients experienced postoperative complications: urethrocutaneous fistula occurred in five cases and glans dehiscence with urethrocutaneous fistula in one case. No urethral diverticulum occurred in any case. A neomeatus with a vertically oriented slit-like appearance was achieved at the tip of the glans in all cases, with one exception. The single-stage operation with a free preputial tube graft coupled with urethral plate urethroplasty combined with a Buck's fascia integral covering in the treatment of severe hypospadias achieves favorable functional and cosmetic outcomes.