This study examines mental health status of patients with complex hypospadias, which include proximal (penoscrotal, scrotal or perineal) hypospadias or hypospadias of any degree with additional urogenital anomalies. Eligible patients of different ages (24% adults) were identified within three geographically and demographically diverse Kaiser Permanente health plans using an electronic health record screening algorithm, followed by a review of clinical notes. For each patient, we selected 10 male referents with no evidence of atypical sex genital development, matched on age, race/ethnicity, and study site, and all records were linked to mental health (neurodevelopmental or psychiatric) diagnoses. Poisson regression models, accounting for matching and controlling for enrollment duration, were used to calculate prevalence ratios (PR) and 95% confidence intervals (CI) for various mental health diagnoses. Over one-half (54%) of 335 patients with complex hypospadias and 38% of 3,346 male referents received at least one mental health (neurodevelopmental or psychiatric) diagnosis (PR = 1.47; 95% CI: 1.25, 1.71). The differences in mental health morbidity between patients with hypospadias and male referents were particularly pronounced for intellectual disabilities (PR = 10.26; 95% CI: (4.61, 22.86) and feeding and eating disorders (PR = 3.41; 95% CI; (1.45, 8.02). When the data were examined separately for proximal hypospadias and other hypospadias with additional urogenital anomalies, the PR estimates for most categories were either similar or with largely overlapping 95% CIs. Individuals with complex hypospadias carry a greater mental health burden than those without hypospadias. Management of mental health comorbidities is a healthcare priority in this population.

46,XY differences of sex development (DSD) comprise a heterogeneous group of congenital conditions affecting chromosomal, gonadal or anatomical sex differentiation. GATA4 is essential for cardiac and gonadal development, although its role in DSD is not fully understood. We report four 46,XY DSD cases with GATA4 variants from our center and performed a literature review. Case 1 presented with ambiguous genitalia, persistent Müllerian structures, and complex congenital heart disease; a GATA4 variant (p.Cys239Arg) was identified, and gonadectomy revealed atrophic testes. Case 2 had penoscrotal hypospadias and a ventricular septal defect, carrying a synonymous GATA4 variant (p.Cys275=) and showing normal hormonal evaluation and pubertal development. Case 3 presented with perineal hypospadias and a GATA4 variant (p.Val305Ile), along with a maternally inherited RET mutation; his twin brother, carrying the same variants, had no DSD. Both exhibited spontaneous puberty. Case 4 presented with isolated hypospadias and a GATA4 variant (p.Arg261GLn) without cardiac anomalies. GATA4 should be included in genetic panels for 46,XY DSD. Our work expand the clinical and molecular spectrum of GATA 4-associated 46,XY DSD and our review support the relevance of zinc finger domain variants ingonadal development. Phenotypic variability among carriers supports variable expressivity and incomplete penetrance.

First-stage procedure for proximal hypospadias with penile encasement/scrotal transposition (PEST) deformity.

The aim of this study was to evaluate the differences in physical examination and radiologic findings of patients with proximal hypospadias in terms of Disorders of Sex Development (DSD) groups. The ages, physical examination and radiological findings and diagnoses of the cases aged 0-18 years who were admitted to our hospital due to proximal hypospadias between 2005 and 2022 and whose male gender was determined because of their evaluation for DSD were evaluated. The study population included 43 patients with a median age of 4 months (1day-14 years): 19 presented with penoscrotal, 13 with scrotal, and 11 with perineal hypospadias. All cases exhibited severe ventral chordee, with micropenis observed in most patients. 46,XY DSD represented most cases, followed by sex chromosome DSD, 46,XX DSD, and other karyotype anomalies. Most patients in the DSD group had undescended testes and/or micropenis. Penoscrotal hypospadias was seen only in the 46,XY DSD group and no uterine remnants were seen in this group. Patients with proximal hypospadias accompanied by undescended testis and/or micropenis should be evaluated in detail before any surgical intervention. We believe that especially in cases with scrotal and perineal hypospadias should be investigated for possible uterine remnants.

A 9-hour-old labrador and golden retriever cross puppy presented with an inability to urinate normally and a congenital malformation of the penis and urethra, and was euthanased on welfare grounds. On gross postmortem examination, running 3 mm caudal to the cranial prepuce and extending to the perineum was a 3.5 cm segmental incomplete fusion of the prepuce and absence of the penis, leaving a 3 mm wide gap. A focal urethral orifice of 1 mm diameter was located at the perineum (Figure 1). These findings are compatible with a diagnosis of perineal hypospadias with incomplete preputial fusion and penile agenesis. Hypospadias is a congenital malformation in which the urethra opens ventrally to its normal anatomical location, and can be further classified as glandular, coronal, penile, scrotal or perineal, depending on where the urethra is found in these cases. Often this is accompanied by incomplete fusion of the prepuce and the shortening or absence of the penis, as seen in this case. Genetic/breed and environmental aetiologies for hypospadias have been hypothesised in dogs, but have not yet been fully established.1 Catherine Ennett and Marta Pereira performed the postmortem examination. Catherine Ennett captured the images and drafted the manuscript. Marta Pereira co-drafted the manuscript. The authors declare they have no conflicts of interest. The postmortem examination was performed as a routine diagnostic case, and no further funding was received. This case was presented to the University of Nottingham Veterinary Pathology diagnostic service for postmortem examination after euthanasia on welfare grounds. The owner has consented in writing to the postmortem examination and to the use of the postmortem findings in this publication. This image (Figure 1) shows the external genitalia on gross postmortem examination of a newborn puppy after euthanasia on welfare grounds due to abnormal urination. What is the most likely diagnosis? 1) Urethrorectal fistula 2) Hypospadias 3) Anorchism 4) Paraphimosis 2) Hypospadias.

Two-Stage Repair for Primary Hypospadias: Functional and Cosmetic Outcomes in 145 Cases With a Follow-Up Period of Over Five Years.

46XY Partial gonadal dysgenesis(PGD) is a rare subset of disorders of sexual development (DSD).Diagnosing and managing such cases can be particularly challenging in resource-limited settingslike Pakistan. We present the case of a 17-year-old male with ambiguous genitalia andhypospadias. On presentation, he was diagnosed with perineal hypospadias, rudimentary blindending vagina, asymmetric testicular descent and a hypoplastic prostate. Hormonal testsrevealed high levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and lowtestosterone, and imaging studies showed a normal bladder shape but no prostate. Surgicaltreatment was performed in two steps. Stage one consisted of scrotoplasty, urethroplasty,chordea correction and grafting. The second operation involved tubular reconstruction of theurethra. Along with that, we also gave hormone replacement therapy for testosteronedeficiency and sent the patient for psychological counselling. To our knowledge, no previouslypublished cases of PGD have been reported from Pakistan. Nevertheless, a complete gonadaldysgenesis (Swyer Syndrome) case was described by Jawed et al in 2023. This case reportdescribes this patient’s unique presentation thereby exemplifying the wide spectrum of clinicalfindings and management difficulties of this case while adding to the scant literature on DSD inPakistan, in hopes of providing insight to improve patient outcomes.

Abstract 46XY Partial gonadal dysgenesis(PGD) is a rare subset of disorders of sexual development (DSD). Such challenges for diagnosis and management were particularly distressing in a developing country like Pakistan. In this case report, we present a case of a 17-years old male patient with ambiguous genitalia and hypospadias. On presentation he was diagnosed with perineal hypospadias, rudimentary blind ending vagina, asymmetric testicular descent and hypoplastic prostate. Hormonal tests revealed high levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and low testosterone, and imaging studies showed a normal bladder shape but no prostate. Surgical treatment was performed in two steps. Stage one consisted of scrotoplasty, urethroplasty, chordea correction and grafting. The second operation was for shaping the tube. We could not find anything on PGD in Pakistan via a detailed search. Nevertheless, a complete gonadal dysgenesis (Swyer Syndrome) case was described by Jawed et al in 2023. This case report describes this patient’s unique presentation thereby exemplifying the wide spectrum of clinical findings and management difficulties of this case while adding to the scant literature on DSD in Pakistan, in hopes of providing insight to improve patient outcomes.

To analyze the postoperative complications, reintervention rates, as well as long-term urinary and cosmetic outcomes in our patients who underwent two-stage re-do hypospadias repair. Files of 122 boys who underwent two-stage surgery for re-do hypospadias repair between June 2001 and October 2017 with > 5 years of follow-up were retrospectively reviewed. Demographics, preoperative clinical characteristics, postoperative complications, uroflowmetry findings, the Penile Perception Score (PPS), and the Hypospadias Objective Scoring Evaluation (HOSE) score at the last clinical visit were noted. Patients had undergone a median 2 (range 1-8) prior surgeries. Of these patients, 46.7% had mid penile hypospadias with a poor urethral plate/uncorrectable chordee, 44.3% had penoscrotal hypospadias, and 9% had scrotal or perineal hypospadias. Lower lip (78, 63.9%), a combination of cheek and lower lip (21, 17.2%), cheek (14, 11.5%), and upper lip (9, 7.4%) were the donor sites for the graft. After a median 121 (range 66-204) months of follow-up, the overall complication rate was 36.8%, and 23.8% required further intervention. Glans dehiscence (12.3%) was the most common complication, followed by urethrocutaneous fistula (10.7%), meatal stenosis (10.7%), residual chordee (6.6%), buried penis or skin deformities (6.6%), distal urethral dehiscence (4.9%), graft contracture after first stage (2.5%), urethral stricture (1.6%), complete urethral dehiscence (0.8%), and urethral diverticulum (0.8%). Median interval from second-stage repair to the repeat intervention for complications was 10 (range 4-30) months. According to the HOSE and PPS, almost 90% of the patients denoted functional and cosmetically acceptable outcomes. Two-stage repair is a viable alternative for the most challenging re-do hypospadias cases, with almost 90% satisfaction and a quarter requiring reintervention.

Prostatic utricle cyst (PUC) is known to be associated with hypospadias. We aimed to investigate the prevalence of PUC in children with proximal hypospadias by cystoscopy, and risk of symptom development after hypospadias repair. We retrospectively reviewed the records of patients who underwent 2-stage repair for proximal hypospadias and had cystoscopy for PUC assessment over the period of January 2017-September 2022. A total of 34 patients with penoscrotal, scrotal or perineal hypospadias were included for review. First-stage repair was performed at a median age of 12 months. The median ventral curvature was 70 degrees (range 45-90). 4 patients had differences of sex development including 45,X/46,XY mosaicism (n = 2) and 46,XY partial gonadal dysgenesis (n = 2). PUC was detected by cystoscopy in 25/34(73.5%) patients, with longitudinal dimensions 10-35 mm (median = 15 mm). At a mean follow-up of 30 months after hypospadias repair, 3/25(12%) patients developed symptoms associated with PUC including recurrent epididymoorchitis (n = 1), post-void dribbling (n = 1) and pyuria (n = 1). 3/10 PUC ≥20 mm became symptomatic compared with none of PUC <20 mm (p = 0.024). The patient with recurrent epididymoorchitis eventually underwent definitive surgery of PUC excision by robot-assisted approach. PUC is highly prevalent in proximal hypospadias. The use of the smallest-sized cystoscope as a screening tool can increase the diagnostic yield. Integrating cystoscopy in hypospadias surgery for concurrent PUC assessment can be considered as an option for patients with proximal hypospadias. Although the vast majority of PUC remains asymptomatic, those ≥20 mm in longitudinal dimensions may be associated with an increased risk of subsequent symptom development.

Objective. It consists of developing a one-stage method for forming a neourethra with covering the skin defect with a non-free inguinal flap. Material and methods. The study included 11 patients with perineal and scrotal hypospadias admitted to the reconstructive surgery department of the Republican Scientific Center for Cardiovascular Surgery between 2012 and 2024. The average age of the patients was 13.8±6.4 years, ranging from 8 to 29 years. Of the patients in the study group, 3 had previously undergone at least one unsuccessful hypospadias surgery. Results. Satisfactory flap survival was observed in all cases. Both short- and long-term results demonstrated good urodynamic parameters in the operated patients. The inguinal flap technique is simple to perform, allows for the coverage of extended defects, and also provides an optimal aesthetic effect. It virtually eliminates tissue tension and, consequently, suture dehiscence in the immediate postoperative period. Conclusion. Thus, the proposed surgical technique allows for several stages of the procedure to be performed in a single operation. Penile length and girth are preserved, full erection is achieved, and urinary and ejaculatory functions are restored. Keywords: hypospadias, inguinal flap, urethral defect, uroflowmetry

Assessment of the CDC hypospadias atlas for epidemiological research - A survey of experts

Purpose of the study. It is to show the difficulty of making a diagnosis and choosing surgical treatment as a rare disease - duplication of the rectum in combination with other anomalies of the development of organs and systems.Material and research methods. Under our supervision there were 2 children diagnosed with congenital anomaly of the gastrointestinal tract. Isolated duplication of the rectum. Perineal hypospadias. Narrowing of the vesicoureteral segment on the right. Ureterohydronephrosis Ⅰ degree on the right.Results. A control study did not reveal any pathology in the internal organs of the children. Ultrasound of the urinary system: the pyelocaliceal system is not dilated, no symptoms of megaureter were detected. Children do not lag behind their peers in mental and physical development. Today, the children’s condition is satisfactory, there are no complaints, they are under the supervision of a pediatric surgeon.Conclusion. Duplication of the rectum is an isolated rare pathology in children in combination with malformations of the genitourinary system, with very diverse clinical manifestations, which poses a problem in making a diagnosis before surgery. Open surgery is safer and good results can be achieved.

Preoperative hormone stimulation (PHS) is used to increase the glans size and may improve the cosmetic appearance after hypospadias surgery. The exact effect of PHS on different penile tissues remains unclear and controversial. Previous studies showed that PHS increased vessel density in the foreskin. However, the effect of PHS on the urethral has never been studied before. In this study we examine the PHS effects on the urethral plate. Specimens of the urethral plate and the underlying tissue were excised to correct severe chordee in 16 children with proximal and perineal hypospadias with severe chordee in 2 groups. Group A consisted of 8 children received PHS prior to surgery. Group B included 8 children with proximal and perineal hypospadias with severe chordee who did not receive PHS and served as a control group. Specimens were examined blindly using hematoxylin-eosin and elastic van-Gieson stain as well as factor 8 and SMA antibodies. The median age of Group A was 13 (range 10-20) months. The median age of Group B (without prior PHS) was 17 (range 14-29) months (p=0,03). The median vessel-density in group A (82 vessels per mm2) was significantly higher than in Group B (65 per mm2), (p<0.05). The median vessel diameter was also significantly higher in Group A (13μm) than in Group B (11μm), (p<0.05). The median epithelial layer thickness in Group A was 110μm and in Group B 98μm, but showed no statistical significance (p=0,16). There was no significant change in dartos fascia layer thickness or androgen receptor expression. There was no visual change in the organization of elastic fibers. This study is the first study to document the effect of PHS on the urethral plate in hypospadias with severe chordee. PHS significantly increased the median vessel-density as well as median vessel diameter as compared to a matching control group. The findings of the study may justify PHS administration before the first operation to improve the vascularity and may reduce the severity of chordee.

Hypospadias (HS) is a congenital defect that occurs due to defective androgenization. It is characterized by the aberrant location of the urinary meatus on the ventral aspect of the penis with various degrees of severity. The molecular mechanisms and genetic associations underlying the condition remain largely unknown. Existing literature revolves around surgical and medical management of the condition. Human chorionic gonadotropin pretreatment in HS is proposed to decrease the severity of the anomaly and improve the clinical outcome of surgery. The underlying mechanisms that drive these outcomes have not been explored. Few studies have explored the endocrine signaling and pathways which lead to the development of the condition. Hence, a prospective study was conducted to understand the same. Eighteen children with mid or proximal penile HS were included as cases, and nine children undergoing circumcision for phimosis (nonpathological) were included as controls. Serum samples from all these children and preputial skin samples taken during surgery were used in the analysis. The hormonal milieu was normal in all children in our cohort. A comparison of previously reported genes with our cohort sequencing revealed changes in several major pathways involved in cell proliferation and differentiation, cell signaling, angiogenesis, and immune response pathways. Compared with healthy controls, HS subjects had 152 differentially expressed genes. Of these, 93 genes were up-regulated, and 59 genes were found to be significantly down-regulated. The gene expression evaluation also showed changes in expression patterns in inflammatory genes and link RNAs, unlike previously reported genes.

Surgical treatment of perineal hypospadias with complete penoscrotal transposition in DSD patients: Our experience with a “three-staged” reconstructive procedure

This study objective is to examine the intracavernosal pressure (ICP) in hypospadias boys with and without previous corporotomies. Retrospectively, the ICPs that were measured routinely as part of the artificial erection test in boys who underwent hypospadias repair were collected. The measurement (mmHg) included a slow manual saline instillation and a 21-gauge needle in the corpora cavernosa, which was connected to a pressure monitor. The full and rigid erections were defined according to the Erection Hardness Score by agreement between the two surgeons operating on the patient. Included were 61 boys with a median age of 15 months (IQR 8-27). Group A included 32 boys with coronal, subcoronal, or penile hypospadias. Group B included 29 boys with penoscrotal, scrotal, and perineal hypospadias. The median pressures at full erection for Groups A and B were 71.5 (IQR 59-79) and 62.5 (IQR 48-71) (p = 0.036), respectively, and at rigid erection were 283 (IQR 219-310) and 237 (IQR 182-278) (p = 0.032), respectively. In group B, median pressures at full erection for boys with and without previous corporotomies were 53.5 (IQR 45-65) and 69 (IQR 57-82), respectively (p = 0.001), and at rigid erection were 189.5 (IQR 113-263) and 264.5 (IQR 226-298), respectively (p = 0.003). In a comparison between group A boys to 18 boys in group B who did not have corporotomies, the median pressures at full erection were 71.5 (IQR 59-79) and 69 (IQR 57-82), respectively (p = 0.9), and at rigid erection were 283 (IQR 219-310) and 264 (IQR 226-298), respectively (p = 0.86). In conclusion, ICPs of artificial erections are lower in proximal hypospadias and in boys with previous corporotomies. The durability and the implications of these pressures require further research.

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

Outpatient surgery for penile hypospadias in pediatric urology: A monocentric experience with a mean follow-up of 3years

The Natural (non-invasive) Erection Test: Is it a reliable alternative to the artificial erection test?