What should be next in lifelong posterior hypospadias: Conclusions from the 2023 ERN eUROGEN and EJP-RD networking meeting.

BACKGROUND: A congenital disease is for life. Posterior hypospadias, the severe form of hypospadias with a penoscrotal, scrotal, or perineal meatus, is a challenging condition with a major impact on lifelong quality of life. AIM: Our network meeting is aimed to identify what is currently missing in the lifelong treatment of posterior hypospadias, to improve care, quality of life, and awareness for these patients. METHODS: The network meeting "Lifelong Posterior Hypospadias" in Utrecht, The Netherlands was granted by the European Joint Programme on Rare Diseases-Networking Support Scheme. There was a combination of interactive sessions (hackathons) and lectures. This paper can be regarded as the last phase of the hackathon. RESULTS: Surgery for hypospadias remains challenging and complications may occur until adulthood. Posterior hypospadias affects sexual function, fertility, and hormonal status. Transitional care from childhood into adulthood is currently insufficiently established. Patients should be more involved in defining desired treatment approach and outcome measures. For optimal outcome evaluation standardization of data collection and registration at European level is necessary. Tissue engineering may provide a solution to the shortage of healthy tissue in posterior hypospadias. For optimal results, cooperation between basic researchers from different centers, as well as involving clinicians and patients is necessary. CONCLUSIONS: To improve outcomes for patients with posterior hypospadias, patient voices should be included and lifelong care by dedicated healthcare professionals guaranteed. Other requirements are joining forces at European level in uniform registration of outcome data and cooperation in basic research.

Expression of mRNA vascular endothelial growth factor in hypospadias patients.

BACKGROUND: Hypospadias is a relatively common genital anomaly in humans, usually followed by inelastic dartos that causes penile chordee. Vascular endothelial growth factor (VEGF) is strongly linked to the viscoelasticity of tissues and their elastic phase. This study aimed to evaluate VEGF expressions in (1) fascia dartos between hypospadias and controls and (2) chordee severity. METHODS: This prospective cohort study involved 65 specimens from patients with hypospadias and ten specimens from controls. The samples were analyzed by quantitative real-time polymerase chain reaction (qPCR) for VEGF expression. RESULTS: The expressions of VEGF were not different between proximal and distal hypospadias patients and controls (fold change: distal - 0.25; fold change: proximal - 0.2; p = 0.664). The scaled expressions related to chordee severity were mild - 0.1; moderate 0.1; severe - 0.25 (p = 0.660). CONCLUSIONS: VEGF expressions might not affect the severity of hypospadias and chordee, implying the pathogenesis is complex involving many growth factors. Further study with a larger sample size is necessary to clarify and confirm our findings.

Disorders of sexual differentiation: Report of two rare cases.

Gonadal dysgenesis is a distinct variety of Disorders of Sexual Differentiation (DSD) characterised by incomplete or defective formation of the gonads due to either structural or numerical anomalies of the sex chromosomes or mutations in the genes involved in the development of the gland. Here we present two such rare cases that presented during childhood. Both patients presented with ambiguous genitalia with a 45XO/46XY mosaic chromosome pattern. First case, an infant underwent laparoscopic excision of streak gonad, and a single stage hypospadias repair later. Second case, an adolescent who underwent gonadectomy as a child, presented with a mass which was excised and found to contain uterine and ovarian tissue; second stage hypospadias repair is being planned. Mixed gonadal dysgenesis usually presents with a unilateral testis, a streak gonad on the contralateral side and persistent mullerian structures. The most common karyotype noted is 45XO/46XY. These cases are known to have ambiguous external genitalia. The streak gonads have an increased malignant potential and thus, these patients should be carefully screened and followed up for gonadoblastoma.

Short anogenital distance is associated with testicular germ cell tumour development.

BACKGROUND: Testicular germ cell tumour is a multifactorial disease in which various genetic and environmental factors play a role. Testicular germ cell tumour is part of the testicular dysgenesis syndrome which includes also cryptorchidism, hypospadias, oligo/azoospermia and short anogenital distance. OBJECTIVES: The primary objective was to examine anogenital distance in testicular germ cell tumour cases and healthy fertile controls. The secondary objective was to assess the (CAG)n polymorphism of the Androgen Receptor gene in relationship with anogenital distances and testicular germ cell tumour development. MATERIAL AND METHODS: 156 testicular germ cell tumour patients and 110 tumour-free normozoospermic controls of Spanish origin. All subjects underwent full andrological workup (including semen and hormone analysis) and genetic analysis (Androgen Receptor (CAG)n). The main outcome measures were the anopenile distance (AGDap), the anoscrotal distance (AGDas) and AR(CAG)n. RESULT: We observed significantly shorter anogenital distances in the group of testicular germ cell tumour patients in respect to controls (P < .001) independently from sperm count and testis histology. Threshold values, applicable only to our cohort, were calculated for anogenital distances with the best sensitivity and specificity. Subjects with AGDap and AGDas below threshold showed a significantly increased risk for testicular germ cell tumour (OR = 4.97, 95% CI = 2.01-12.33, P = .001 and OR = 4.11, 95% CI = 1.89-8.92, P ≤ .001, respectively). No significant correlation was observed between AR(CAG)n polymorphism and anogenital distances. The median values of the AR(CAG)n were similar between cases and controls, excluding a major role for this polymorphism in the etiopathogenesis of these testicular dysgenesis syndrome components. CONCLUSIONS: Ours is the first study focusing on anogenital distances in testicular germ cell tumour patients. We identified short anogenital distances (which is a surrogate biomarker of androgen action during foetal life) as a significant risk factor for this disease. After further validation of our preliminary data, anogenital distance measurement could become part of testicular germ cell tumour screening in order to better define those individuals who would benefit from long-term active follow-up.

Genetic analysis of a Taiwanese family identifies a DMRT3-OAS3 interaction that is involved in human sexual differentiation through the regulation of ESR1 expression.

OBJECTIVE: To identify the genetic etiology of recurrent disorders of sex development (DSDs) in a Taiwanese family with 46,XY sex reversal and hypospadias. DESIGN: Genetic and functional studies. SETTING: Academic hospital. PATIENT(S): A three-generation family consisting of 22 members, with eight cases of 46,XY DSD, of whom four have 46,XY male-to-female sex reversal and four are 46,XY males with hypospadias. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Results of exome sequencing and in vitro protein and RNA analyses. RESULT(S): All patients with DSDs were found to carry heterozygous missense mutations in the doublesex and mab-3-related transcription factor 3 (DMRT3; rs187176004, c.A815C, p.K272T) and 2',5'-oligoadenylate synthetase 3 (OAS3; rs16942374, c.G2606A, p.R869H) genes. The DMRT3 mutation increased estrogen receptor 1 (ESR1) expression. Upon binding with the OAS3-RNase L complex, wild-type DMRT3 promoted degradation of ESR1 mRNA. However, the DMRT3A815C-OAS3G2606A complex interacted less strongly with ESR1 mRNA and RNase L, ultimately preventing ESR1 mRNA degradation. The interactions between DMRT3, OAS3, and RNase L were confirmed in the patients' testis. CONCLUSION(S): Our results indicate that DMRT3 and OAS3 are involved in human DSDs by controlling ESR1 expression.

Assessment of the effect of urethral plate width on outcome of hypospadias repair.

BACKGROUND: The paradigm for hypospadias repair is a straight penis with a vertical meatus at the tip of the glans that provides satisfactory urination and is cosmetically acceptable to the parents of the patient. OBJECTIVE: To determine the cosmetic and functional outcomes of hypospadias repair in relation to the width of the urethral plate. PATIENTS AND METHODS: This study was a prospective evaluation of patients operated for hypospadias. The urethral plate width (UPW) of the patients were measured preoperatively using vernier calipers. The patients were categorized into groups A and B. Group A patients have a UPW <8 mm, whereas group B patients have a UPW ≥8 mm. The width of the urethral plate was correlated to the cosmetic outcome (using hypospadias objective penile evaluation [HOPE]) and functional outcome (using the urinary stream) of hypospadias repair. RESULTS: Overall, 47 patients had their hypospadias repaired during the study period. But, only 42 patients who had their distal hypospadias repaired using tubularized incised plate urethroplasty were evaluated. There were 20 patients (47.6%) in group A and 22 patients (52.4%) in group B, with a mean urethral plate of 7.3 mm ± 0.50 SD. The mean UPW in group A was 5.6 mm ± 1.22 SD and the mean UPW in group B was 8.8 mm ± 0.88 SD. Overall, mean HOPE score was 40.0 ± 6.83 SD. Group A patients had a mean HOPE score of 38.7 ± 7.49 SD, whereas Group B patients had a mean HOPE score of 41.2 ± 6.08 SD. P-value was 0.725, which is not statistically significant. Relating good urinary stream (15 in group A and 20 in group B) with the width of the urethral plate statistically (using Spearman correlation technique) gave a P-value of 0.03 (P < 0.05), which is statistically significant. CONCLUSION: Our findings indicate that the cosmetic outcome of hypospadias repair may not be determined by UPW, but the functional outcome may be predicted by the width of the urethral plate.

Establishing reproductive potential and advances in fertility preservation techniques for XY individuals with differences in sex development.

BACKGROUND: Discordance between gonadal type and gender identity has often led to an assumption of infertility in patients with differences in sex development (DSD). However, there is now greater recognition of fertility being an important issue for this group of patients. Currently, gonadal tissue that may have fertility potential is not being stored for individuals with DSD and, where gonadectomy forms part of management, is often discarded. The area of fertility preservation has been predominantly driven by oncofertility which is a field dedicated to preserving the fertility of patients undergoing gonadotoxic cancer treatment. The use of fertility preservation techniques could be expanded to include individuals with DSD where functioning gonads are present. METHODS: This is a systematic literature review evaluating original research articles and relevant reviews between 1974 and 2018 addressing DSD and fertility, in vitro maturation of sperm, and histological/ultrastructural assessment of gonadal tissue in complete and partial androgen insensitivity syndrome, 17ß-hydroxysteroid dehydrogenase type 3 and 5α-reductase deficiency. CONCLUSION: Successful clinical outcomes of ovarian tissue cryopreservation are paving the way for similar research being conducted using testicular tissue and sperm. There have been promising results from both animal and human studies leading to cryopreservation of testicular tissue now being offered to boys prior to cancer treatment. Although data are limited, there is evidence to suggest the presence of reproductive potential in the gonads of some individuals with DSD. Larger, more detailed studies are required, but if these continue to be encouraging, individuals with DSD should be given the same information, opportunities and access to fertility preservation as other patient groups.

Timing of pubertal development in boys born with cryptorchidism and hypospadias: a nationwide cohort study.

Pubertal development may be altered in boys with cryptorchidism and hypospadias, but existing knowledge is inconsistent. Therefore, we investigated the association between cryptorchidism and hypospadias and pubertal development in a large cohort study. Boys in the Puberty Cohort, a cohort nested within the Danish National Birth Cohort, were included in this study. Information on cryptorchidism and hypospadias was retrieved from the Danish National Patient Register. From 11 years until 18 years or full pubertal development, information on physical markers of pubertal development was provided biannually, including Tanner stages, axillary hair, acne, voice break, and first ejaculation. In multivariate regression models for interval censored data, the mean (95% confidence intervals [CIs]) differences in months in obtaining the pubertal markers between boys with and without the anomalies were estimated. Among 7698 boys, 196 (2.5%) had cryptorchidism and 60 (0.8%) had hypospadias. Boys with hypospadias experienced first ejaculation and voice break 7.7 (95% CI: 2.5-13.0) months and 4.5 (95% CI: 0.3-8.7) months later than boys without hypospadias. The age at attaining the Tanner stages for gonadal and pubic hair growth was also higher, though not statistically significant. Pubertal development seemed unaffected in boys with mild as well as severe cryptorchidism. In conclusion, hypospadias may be associated with delayed pubertal development, but pubertal development seems unaffected by cryptorchidism. The relation between hypospadias and later pubertal development may be due to the underlying shared in utero risk or genetic factors.

Cardiac disorders and structural brain abnormalities are commonly associated with hypospadias in children with neurodevelopmental disorders.

The objective of our study was to use an established cohort of boys to investigate common patterns of malformations in those with hypospadias. We performed a retrospective review of the phenotype of participants in the Deciphering Developmental Disorders Study with neurodevelopmental delay and an 'Abnormality of the genital system'. This group was divided into two subgroups: those with hypospadias and without hypospadias. Associated phenotypes of the two subgroups were compared and analysed. Of the 166 Deciphering Developmental Disorders participants with hypospadias and neurodevelopmental delay, 47 (28%) had cardiovascular and 40 (24%) had structural brain abnormalities. The rate of cardiovascular abnormalities in those with neurodevelopmental delay and genital abnormalities other than hypospadias (N = 645) was lower at 19% (P = 0.001). In addition, structural brain malformations were higher at 24% in the hypospadias group versus 15% in the group without hypospadias (P = 0.002). The constellation of these features occured at a higher rate in the hypospadias group versus the no hypospadias group (P = 0.038). In summary, this is the first study to indicate that cardiovascular and brain abnormalities are frequently encountered in association with hypospadias in children with neurodevelopmental disorders. Not only do these associations provide insight into the underlying aetiology but also they highlight the multisystem involvement in conditions with hypospadias.

No difference in cognitive performance or gender role behavior between men with and without hypospadias.

BACKGROUND: Hypospadias is a common malformation of the male external genitalia that results in urethral displacement with different levels of severity. Male genital development during the fetal period is dependent on androgen function, while the etiology of hypospadias differs and can be multifactorial. The psychosocial outcome is sometimes affected, but according to several studies acceptable. The question of whether hypospadias is associated with differences in psychosexual development has been investigated previously, with mixed results. There are no previous investigations of cognitive abilities in men with hypospadias. OBJECTIVE: The aim of this study was to investigate whether hypospadias is associated with differences in performance on cognitive tests and/or gender role behavior. PARTICIPANTS: Eighty-six men with hypospadias were compared to male and female controls from the general population. PROCEDURE: Cognitive tasks, previously shown to yield group level sex differences and questions regarding self-reported childhood gender role behavior, were administered either at an outpatient clinic visit or via online participation. RESULTS: The cognitive performance of men and women in the control groups differed significantly in the expected directions. Men and women also differed on self-reported childhood gender role behavior questions. There were no significant differences between men with and without hypospadias on any of the measures. Men with proximal hypospadias performed slightly lower on many of the cognitive tasks in comparison to men with distal hypospadias and controls. CONCLUSION: In general, hypospadias is not associated with differences in performance on cognitive tests that typically yield sex differences or with altered gender role behavior in childhood. Further studies on cognitive abilities in boys and men with proximal hypospadias are warranted.

The biomechanical properties of the urethra in boys with hypospadias: a preliminary study.

PURPOSE: The ventral aspect of the penis in boys with hypospadias is composed of dysplastic tissue of the skin and the urethra. The aim of this study was to assess the pre-operative size and biomechanical properties of urethrae in boys with and without hypospadias using a more objective catheter-based system. MATERIALS & METHODS: In this non-blinded clinical observation study, the study population consisted of 19 boys with hypospadias-the case group (median age 13.9 months [range: 12.2-21.3])-and seven boys without hypospadias-the control group (median age 8.5 months [range: 3.8-18.1]). Modified measurements of impedance were used to assess the size, compliance and viscoelasticity of the urethrae under stepwise increased pressures (between 0, 40 and 60 cmH2O) using a customised Endolumenal Functional Lumen Imaging probe (EndoFLIP®). RESULTS: The sizes of the urethrae in boys with hypospadias are variable but tend towards being narrower and less compliant than those of the control subjects i.e. median diameter for meatus urethra was 3.2 mm (range: 2.98-3.92) in the hypospadias group compared with 3.64 (range: 3.22-4.44) in the control group at 40 cmH2O, and the median change in diameter at meatus urethra was 0.08 mm (range: -0.02 to 0.52) in the hypospadias group compared with 0.23 mm (range: -0.02 to 0.34) when the pressure was increased from 40 to 60 cmH2O. This biomechanical analysis found that there was no significant viscoelasticity of the urethral meatus in both the groups, whereas the remainder of the urethral structure generally had viscoelastic properties in the control group, seen as a creep on the time/diameter curves (Figure). In the group of boys with hypospadias, evaluations of the urethrae revealed varying viscoelastic abilities, ranging from abilities that were comparable with those of the control subjects to no sign of viscoelasticity at all. CONCLUSIONS: This study is the first to measure the biomechanical properties of the urethra in children, which might help to provide an understanding as to the structural and functional changes associated with hypospadias. The urethrae in the subjects with hypospadias were variable in diameter but tended to be narrower overall, especially in the distal portion of the urethra. Furthermore, the urethrae in boys with hypospadias were frequently less viscoelastic than those of controls. CLINICAL RELEVANCE: The EndoFLIP® system may be a future way of objectively estimating the severity of a urethral obstruction and could potentially be included in the postoperative assessment of patients with signs of hampered voiding.

The genetic factors contributing to hypospadias and their clinical utility in its diagnosis.

Hypospadias is among the most common congenital malformations in male neonates. It results from abnormal penile and urethral development, but is a multifactorial disorder that is highly heterogeneous, with several genetic and environmental determinants. Monogenic and chromosomal abnormalities are present in approximately 30% of cases, although the genetic factors contributing to hypospadias remain unknown in 70% of cases. While defects in androgen synthesis can lead to this malformation, mutational analyses have shown several genes, such as sonic hedgehog, fibroblast growth factors, bone morphogenetic proteins, homeobox genes, and the Wnt family, are involved in the normal development of male external genitalia. Mutations in the genes of penile development (e.g., HOX, FGF, Shh) and testicular determination (e.g., WT1, SRY), luteinizing hormone receptor, and androgen receptor have also been proposed to be implicated in hypospadias. Here we review the recent advances in this field and discuss the potential genes that could determine the risk of hypospadias.

Involvement of Activation of Mitogen-Activated Protein Kinase (MAPK)/Extracellular Signal-Regulated Kinase (ERK) Signaling Pathway in Proliferation of Urethral Plate Fibroblasts in Finasteride-Induced Rat Hypospadias.

BACKGROUND We investigated the role of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway in finasteride-induced hypospadias rats and explored the mechanisms involved. MATERIAL AND METHODS The hypospadias model was established by intragastric administration of finasteride and confirmed by hematoxylin and eosin (HE) staining. The urethral plate fibroblasts (UPF) were obtained from normal and modeled rats and identified based upon vimentin expression. Thereafter, UPF were divided into a normal control group, a model group, a model + MAPK inhibitor group, and a model + ERK inhibitor group. Cell proliferation, apoptosis, and cell cycling of UPF were assessed. Quantitative real-time PCR and Western blot analysis were used to evaluate expression of the MAPK signaling pathway and apoptosis-related genes. RESULTS HE staining confirmed that 10 mg/kg finasteride caused severe hypospadias in rats. UPFs obtained from the 10 mg/kg finasteride group showed higher proliferation and cell cycling and lower apoptosis compared with those obtained from the normal control group (P<0.05). Interestingly, a MAPK inhibitor or an ERK inhibitor could attenuate the abnormalities of cell proliferation, cycling, and apoptosis of UPF induced by finasteride. Compared with controls, the relative expression of p-MEK1/MEK1, caspase 3, and P53 in the UPF of the model group were reduced, while the relative expression of p-MAPK14/MAPK14 was increased in the cells of the model group. By contrast, a MAPK inhibitor or an ERK inhibitor could alleviate the abnormalities of MAPK/ERK signaling pathway and apoptosis-related gene expression induced by finasteride. CONCLUSIONS Our study reveals that the MAPK/ERK signaling pathway is involved in the regulation of proliferation, apoptosis, and cell cycling of UPFs in finasteride-induced hypospadias.

Childhood Sex-Typed Behavior and Gender Change in Individuals with 46,XY and 46,XX Disorders of Sex Development: An Iranian Multicenter Study.

Disorders of sex development (DSD) are congenital conditions in which the typical genetic and hormonal profiles are affected and thereby the usual process of sexual differentiation. Most of these studies, however, have been conducted in Western countries. In the present study, preschool sex-typed activities of Iranian individuals with DSD and their age-matched non-affected male and female relatives were assessed using the Pre-School Activities Inventory (PSAI) modified for retrospective self-report. A total of 192 individuals participated in our study, including 33 46,XX individuals with congenital adrenal hyperplasia (CAH; M age = 10.36, SD = 5.52), 15 46,XY individuals with complete androgen insensitivity syndrome (CAIS; M age = 19.8, SD = 7.14), and 16 46,XY individuals with 5-alpha reductase deficiency type-2 (5α-RD-2; M age = 17.31, SD = 7.28), as well as one age-matched non-affected male and female relative for each patient. With regard to PSAI scores, male-identifying participants with 5α-RD-2 and male controls reported similar levels of male-typical childhood play. Female-identifying participants with 5α-RD-2 and CAH showed comparable scores: significantly less masculine and more feminine than male controls, but significantly more masculine and less feminine than females with CAIS and female controls. These findings support the role of androgens in the development of sex-typical childhood play behavior, with those being exposed to higher levels of fetal functional androgens expressing more masculine behavior at preschool ages.

Psychosocial and Sexual Outcomes in Adolescents following Surgery for Proximal Hypospadias in Childhood.

PURPOSE: We evaluated psychosocial outcomes, psychosexual development and sexual function in adolescents who had undergone surgery for proximal hypospadias. We hypothesized that these outcomes would be impaired compared to peers. MATERIALS AND METHODS: We identified 55 males age 14 years or older who underwent surgery for penoscrotal to perineal (intraoperatively defined) hypospadias between 1996 and 2005. A total of 33 patients with a median age of 17.5 years (range 14 to 25) answered a Web based questionnaire with self-constructed questions, completed the validated Psychological General Well-Being Index, Body-Esteem Scale for Adolescents and Adults and Penile Perception Score, and underwent clinical evaluation. A total of 31 patients with distal hypospadias (median age 19 years, range 14 to 35) and 25 age matched healthy men (17.5 years, range 14 to 25) served as controls. RESULTS: Interest in sex, age at sexarche and satisfaction with sexual experiences were comparable between patients and controls. Three patients with proximal hypospadias (10%) and 1 control (4%) reported occasional erectile problems. Three patients with proximal hypospadias (11%), 1 patient with distal hypospadias (3%) and 1 control (4%) affirmed anejaculation. There were no differences in results between validated questionnaires. Patients with proximal hypospadias were more dissatisfied with penile length (39%) compared to controls (12%, p = 0.049). Concerning physical contact, 10 patients (38%) expressed uncertainty. Extra support in school was more frequent among patients with proximal hypospadias (p = 0.024 vs distal hypospadias, p = 0.068 vs control group). CONCLUSIONS: Despite concerns regarding penile length, sexual experiences were comparable to those of other adolescents, although more than a third of patients with proximal hypospadias demonstrated uncertainty on questions relating to desire for physical contact. Specialized tutoring in school was more common in patients with proximal hypospadias. Continuous followup throughout childhood allowing extra time for age adequate information and support is warranted.

Contemporary outcomes of hypospadias retrieval surgery in adults.

OBJECTIVE: To describe the surgical approach and outcomes in the treatment of adult patients with complications of childhood hypospadias surgery, as such patients present a significant reconstructive challenge due to the combination of anatomical and cosmetic deformity, which often results in major functional and psychosexual sequelae. PATIENTS AND METHODS: We analysed prospectively collected data on 79 adults with complications of childhood hypospadias surgery, who were operated on between 2004 and 2016. Of the 79 patients, 48 underwent a two-stage urethroplasty using a buccal mucosa graft, and 31 underwent a one-stage distal urethroplasty. RESULTS: Patients were followed up using flexible cystoscopy (every 6-9 months). The mean (range) follow-up was 48 (12-96) months. Of the 48 patients who underwent a two-stage repair, eight (16%) needed a revision of the first-stage graft. In total, nine of the 48 patients (16%) developed fistula requiring closure after the second stage; all but one was closed successfully on the first attempt, whilst one required two attempts before closure. Only two of the 48 patients that underwent a two-stage procedure required a re-do urethroplasty within 3 years. Of the 31 patients who underwent a one-stage repair, six (19%) needed fistula closure, all of which were successful. No patient required a further urethroplasty during follow-up. CONCLUSIONS: Despite the significant surgical challenges found in this patient group, excellent long-term functional outcomes can be achieved. As expected there is a need for additional intervention, either for revision of the first stage or to close fistulae and less commonly for further reconstruction for stricture recurrence.

Age-related changes in urinary flow following dorsal inlay graft urethroplasty for hypospadias in early childhood: Potential improvement over 11 years of age.

INTRODUCTION: One of the goals of hypospadias repair is to create a neourethra with normal urinary stream and normal growth. Several studies have reported that dorsal inlay graft urethroplasty (DIG) has wide indications for various clinical phenotypes of hypospadias, with good short-term outcomes and few complications. However, there have been no reports that evaluated both short-term and long-term functional outcomes using uroflowmetry in patients with DIG. OBJECTIVE: The aim was to investigate whether uroflowmetry parameters change with time following DIG for hypospadias in early childhood. MATERIALS AND METHODS: Uroflowmetry parameters after DIG for hypospadias in childhood were retrospectively evaluated and compared between two defined ages at follow-up: 4-6 years and 11-13 years. Maximum urinary flow (Qmax) under the 25th percentile on the Miskolc nomogram was defined as obstruction. To evaluate the shapes of uroflow quantitatively, the flow index (FI) was used. The FI cut-offs for the flow shapes were defined as tower >1.253, plateaus <0.659; bells were between these two values. RESULTS: Thirty-four patients met the inclusion criteria. The median operative age was 1.8 years (range 1.0-4.9 years). The median follow-up time was 10.3 years (range 7.2-12.3 years). The mean ± SD Qmax at the two follow-up times increased with time, from 9.2 ± 3.7 to 18.8 ± 7.8. The mean ± SD FI changed from 0.53 ± 0.19 to 0.85 ± 0.31. Both Qmax and the FI were significantly improved (p < 0.001, p < 0.001, respectively). There were significantly fewer patients with obstruction evaluated by the Miskolc nomogram at 11-13 years of age (n = 11, 32.4%) than at 4-6 years (n = 31, 91.2%) (p < 0.001). Plateau shapes assessed by the FI were seen in 24 (70.6%) patients at 4-6 years and 10 (29.4%) patients at 11-13 years (Table). The number of patients with plateau shapes was significantly decreased (p = 0.001). DISCUSSION: Only one report noted long-term outcomes and spontaneous uroflowmetry resolution after tubularized incised plate urethroplasty. The current report is the first to present the short-term and long-term uroflowmetry outcomes after DIG. In addition, the FI was used for the first time to evaluate uroflowmetry after hypospadias repair. It was found that the uroflowmetry parameters improved spontaneously over 11 years of age following DIG for hypospadias in early childhood. CONCLUSION: Uroflowmetry parameters improved spontaneously over 11 years of age following DIG for hypospadias in early childhood.

Comparison between two inhibin B ELISA assays in 46,XY testicular disorders of sex development (DSD) with normal testosterone secretion.

BACKGROUND: Inhibin B is a hormone produced by the Sertoli cells that can provide important information for the investigation of disorders of sex development (DSD) with 46,XY karyotype. The aim of this study is to compare two enzyme-linked immunosorbent assay (ELISA) assays for dosage of serum inhibin B in patients with 46,XY DSD with normal testosterone secretion. METHODS: Twenty-nine patients with 46,XY DSD and normal testosterone secretion (partial androgen insensitivity syndrome [PAIS] [n=8]; 5α-reductase deficiency [n=7] and idiopathic 46,XY DSD [n=14]) were included. Molecular analysis of the AR and SRD5A2 genes were performed in all patients and the NR5A1 gene analysis in the idiopathic group. Measurements of inhibin B were performed by two second-generation ELISA assays (Beckman-Coulter and AnshLabs). Assays were compared using the interclass correlation coefficient (ICC) and the Bland-Altman method. RESULTS: ICC was 0.915 [95% confidence interval (CI): 0.828-0.959], however, a discrepancy was observed between trials, which is more evident among higher values when analyzed by the Bland-Altman method. CONCLUSIONS: It is recommended to perform the inhibin B measurement always using the same ELISA kit when several evaluations are required for a specific patient.

A 1-year randomized controlled trial to compare the outcome of primary repair of hypospadias with vascular cover using tunica vaginalis flap with those using preputial dartos fascia.

BACKGROUND: : Tubularized incised plate (TIP) urethroplasty is the most common technique noted to correct hypospadias. However, urethrocutaneous fistula (UCF) is still one of the most common complications of this technique. Several techniques of providing vascularized flaps to the neourethra have been recommended to decrease this complication rate. The aim of the study was to assess the outcome of primary repair of hypospadias using tunica vaginalis (TV) flap with those using preputial dartos (PD) fascia. PATIENTS AND METHODS: : Children diagnosed with hypospadias between the age group of 9 months to 18 years, who fulfilled the criteria were randomly divided into two groups by computerized randomization technique. Initially, TIP urethroplasty was done. Children with PD vascular cover were included in Group A and those with TV vascular cover were included in Group B. All the patients were followed up for a minimum of 6 months after surgery. RESULTS: : Two (10%) patients in Group A developed UCF and one (5%) patient developed stricture urethra in the follow-up period. None of the patients developed UCF in the Group B. One (5%) patient had stricture urethra in Group B. Two (10%) patient developed meatal stenosis in Group A. Two (10%) patient in Group B developed meatal stenosis. CONCLUSIONS: TV flap could be an alternative to PD flap as a vascular cover of neourethra in patients undergoing primary hypospadias repair by TIP urethroplasty.