The potentiating effect of intravenous dexamethasone upon preemptive pudendal block analgesia for hypospadias surgery in children managed with Snodgrass technique: a randomized controlled study : Dexamethasone for pain management in children.

INTRODUCTION: Evidence regarding the potentiating effects of intravenous dexamethasone on peripheral regional anesthesia in children is sparse. The objective of the current study was to investigate the potentiating effect of intravenous dexamethasone upon pudendal block during surgical correction of hypospadias using Snodgrass technique. METHODS: The study consisted of a monocentric, randomized controlled, double-blinded study. Patients were randomized to receive either intravenous dexamethasone 0.15 mg.kg- 1 (D group) or a control solution (C group). Both groups received standardized anesthesia including a preemptive pudendal block performed after the induction of anesthesia. The primary outcome was the proportion of patients needing rescue analgesia. Secondary outcomes were other pain outcomes over the first 24 postoperative hours. RESULTS: Overall, 70 patients were included in the study. Age were 24 [24; 36] and 26 [24; 38] months in the D and C groups, respectively (p = 0.4). Durations of surgery were similar in both groups (60 [30; 60], p = 1). The proportion of patients requiring rescue analgesia was decreased in the D group (23% versus 49%, in D and C groups respectively, p = 0.02). The first administration of rescue analgesia was significantly delayed in the D group. Postoperative pain was improved in the D group between 6 and 24 h after surgery. Opioid requirements and the incidence of vomiting did not significantly differ between groups. CONCLUSION: Associating intravenous dexamethasone (0.15 mg.kg- 1) to pudendal block during hypospadias surgery improves pain control over the first postoperative day. Further studies are needed in order to confirm these results. GOV IDENTIFIER: NCT03902249. A. WHAT IS ALREADY KNOWN: dexamethasone has been found to potentiate analgesia obtained with regional anesthesia in children. B. WHAT THIS ARTICLE ADDS: intravenous dexamethasone was found to improve analgesia with a preemptive pudendal block during hypospadias surgery. C. IMPLICATIONS FOR TRANSLATION: results of this study indicate that intravenous dexamethasone could be used as an adjunct to pudendal block.

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

PURPOSE: Mid-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. METHODS: UP 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. RESULTS: Mean 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. CONCLUSIONS: UPC 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 EVIDENCE: Prognosis Study Level-Ⅱ.

Congenital Urethrocutaneous Fistula.

ABSTRACT: Male congenital urethrocutaneous fistula is an extremely rare anomaly that is commonly associated with chordee or anorectal malformations. It is characterised by an abnormal urethral opening on the ventral aspect of the penis with well-formed distal urethra and meatus at the tip of the glans. The treatment is individualised according to the site of the fistula, associated anomalies and condition of the distal urethra. The principles of hypospadias surgery should be strictly followed.

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

INTRODUCTION: 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. PATIENTS AND METHODS: 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. RESULTS: 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. DISCUSSION: 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. CONCLUSION: 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.

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OBJECTIVES: To investigate the clinical phenotypes, genetic characteristics, and pathological features of children with disorders of sex development (DSD). METHODS: A retrospective analysis was conducted on epidemiological, clinical phenotype, chromosomal karyotype, gonadal pathology, and genotype data of 165 hospitalized children with DSD at Children's Hospital of Hebei Province and Tangshan Maternal and Child Health Hospital from August 2008 to December 2022. RESULTS: Among the 165 children with DSD, common presenting symptoms were short stature (62/165, 37.6%), clitoromegaly (33/165, 20.0%), cryptorchidism (28/165, 17.0%), hypospadias (24/165, 14.5%), and skin pigmentation abnormalities/exteriorized pigmented labia majora (19/165, 11.5%). Chromosomal karyotype analysis was performed on 127 cases, revealing 36 cases (28.3%) of 46,XX DSD, 34 cases (26.8%) of 46,XY DSD, and 57 cases (44.9%) of sex chromosome abnormalities. Among the sex chromosome abnormal karyotypes, the 45,X karyotype (11/57, 19%) and 45,X/other karyotype mosaicism (36/57, 63%) were more common. Sixteen children underwent histopathological biopsy of gonadal tissues, resulting in retrieval of 25 gonadal tissues. The gonadal tissue biopsies revealed 3 cases of testes, 3 cases of dysplastic testes, 6 cases of ovaries, 11 cases of ovotestes, and 1 case each of streak gonad and agenesis of gonads. Genetic testing identified pathogenic/likely pathogenic variants in 23 cases (23/36, 64%), including 12 cases of 21-hydroxylase deficiency congenital adrenal hyperplasia caused by CYP21A2 pathogenic variants. CONCLUSIONS: Short stature, clitoromegaly, cryptorchidism, hypospadias, and skin pigmentation abnormalities are common phenotypes in children with DSD. 45,X/other karyotype mosaicism and CYP21A2 compound heterozygous variants are major etiological factors in children with DSD. The most commonly observed gonadal histopathology in children with DSD includes ovotestes, ovaries, and testes/dysgenetic testes.

Outcome analysis of staged preputial graft technique for primary proximal hypospadias with and without post-operative vacuum physiotherapy.

PURPOSE: Management of proximal hypospadias remains challenging. We assessed the results of staged preputial graft repairs (SPG) for proximal hypospadias and hypothesize that post-operative vacuum physiotherapy (VP) improves graft suppleness and overall outcomes. MATERIALS AND METHODS: Retrospective analysis of n = 71 patients with proximal hypospadias and severe ventral penile curvature (PC) of ≥50° after degloving. PC was corrected using ventral transverse incisions of the tunica albuginea (VTITA) without applying a tourniquet, taking care to avoid injuring the underlying erectile tissue. The ventral raw area at the penile shaft, including VTITA, were covered with either divided and partially mobilized urethral plate, or with the inner preputial graft itself. During the second stage, a tunica vaginalis flap was often used to cover the tubularized neourethra. Outcomes and post-op complications were assessed after each stage, comparing patients who received vacuum physiotherapy (VP+, n = 49) with those who did not (VP-, n = 22). RESULTS: Mean PC was 66°, average follow-up duration was 13.01 months, and overall complication rate was 22.5%. Only 6 of 49 VP + patients experienced complications (12.24%; 4 fistulas; 2 urethral strictures) and no recurrence of PC after second stage was observed in this group. VP- patients displayed a significantly higher rate of complications, with 10 of 22 cases (45.45%) exhibiting fistula development (n = 5) and glans dehiscence (n = 5). Recurrence of mild PC after first-stage repair was comparable between patient groups (12% VP+, 18% VP-) and easily corrected by simple graft tubularization or dorsal plication during second-stage repair. CONCLUSIONS: Staged repair using VTITA is effective for correcting proximal hypospadias with severe chordee. VP appears to promote and expedite graft suppleness and significantly improves patient outcomes.

Hypospadias management in children with anorectal malformation: a multidisciplinary single center experience.

Anorectal malformation (ARM) is often associated to other congenital malformations, requiring a tailored management. Hypospadias' treatment in ARM is poorly described. Aim of study is to describe our experience in ARM-hypospadias patients especially in relation to occult spinal dysraphism (OSD). ARM patients treated from 1999 to 2022 were retrospectively reviewed, selecting male with hypospadias. Clinical data, hypospadias's severity, ARM sub-type (Group A: perineal fistula; Group B: urethral fistula, bladder fistula, no fistula), OSD, other associated malformations, NLUTD were evaluated. Exclusion criteria: uncomplete data. Among 395 ARMs, 222 were males, 22 (10%) had hypospadias. Two patients were excluded. Group A: 8 patients, Group-B: 12. Hypospadias: proximal 9 patients, distal 11. Neuro-urological evaluation was performed before hypospadias repair. Eleven patients (55%) had OSD. Four OSD patients presented NLUTD and underwent detethering and CIC (two via cystostomy button, two via appendicostomy); two of them had hypospadias repaired. All proximal hypospadias underwent two stages of surgery. Distal hypospadias was corrected in 4/11 cases. Hypospadias is quite common in ARM patients and its surgical management must be scheduled considering the possible OSD and NLUTD, with the possible need for intermittent catheterization. Complexity of ARM and hypospadias appears to be related to each other.

Preoperative hormone stimulation; does it increase hypospadias postoperative complications?

AIM OF THE STUDY: To assess the effect of Preoperative Hormone Stimulation (PHS) on glans size in proximal hypospadias with chordee and small glans, and to determine if PHS is associated with increased postoperative complications. PATIENTS & METHODS: Between 2014 and 2021, 101 cases of proximal hypospadias with small glans (12 mm or less) were operated upon in our hospital and are the basis of this cohort. All patients underwent a standard two-stage surgical repair, undergoing a correction of the chordee in the first operation and urethroplasty in the second operation. All patients included were operated by the same surgeon. They were classified into two groups; Group A: 50 children were operated upon between 2014 and 2017 and did not receive PHS and Group B: 51 children operated between 2018 and 2021 and received PHS. Glans dimensions including Dorsal Longitudinal Length (DLL) and Glans Width (GW) were measured during the first operation. PHS was given 1-2 months before the second operation in Group B. The glans dimensions were measured again during the second operation after PHS. Follow up period ranged from 2 to 9 years (mean 5 years). RESULTS: Following PHS a statistically significant increase in glans length (p = 0.042) and glans width (p = 0.011) was observed at the second operation, with 36 patients (70%) showing a mean glans width increase of 2.78 mm (range 2-8 mm) after receiving PHS. There was no statistically significant difference in the complication rates between the two groups (p = 0.556) with a fragility index of zero (FI = 0). DISCUSSION: The present study separates itself from most other studies in the literature, in the fact that it has included only a specific group of proximal and perineal hypospadias with severe chordee and glans width of 12 mm or less and that glans dimensions were always objectively and accurately measured under general anesthesia. The other major difference is that PHS in our study was given after and not before the first operation. Furthermore, the fact that all patients prior to 2018 did not receive PHS and all patients after 2018 received PHS, indicates that there was no selection bias. CONCLUSION: This study shows that PHS results in an increase the size of the glans in 70% of patients with hypospadias and a small glans without an increase in postoperative complications.

Does Preoperative Testosterone Administration Decrease Complications in Distal Hypospadias Repair With Urethroplasty?

PURPOSE: Testosterone administration prior to hypospadias repair is common practice among pediatric urologists; however, its impact on surgical outcomes remains controversial. We hypothesize that testosterone administration prior to distal hypospadias repair with urethroplasty significantly decreases postoperative complications. MATERIALS AND METHODS: We queried our hypospadias database for primary distal hypospadias repairs with urethroplasty from 2015 to 2021. Patients undergoing repair without urethroplasty were excluded. We collected information on patient age, procedure type, testosterone administration status, initial visit and intraoperative glans width, urethroplasty length, and postoperative complications. To determine the role of testosterone administration on incidence of complications, a logistic regression adjusting for initial visit glans width, urethroplasty length, and age was performed. RESULTS: A total of 368 patients underwent distal hypospadias repair with urethroplasty. One hundred thirty-three patients received testosterone and 235 did not. Initial visit glans width was significantly larger in the no-testosterone vs testosterone group (14.5 mm vs 13.1 mm, P = .001). Testosterone patients had significantly larger glans width at the time of surgery (17.1 mm vs 14.6 mm [no-testosterone group], P = .001). On multivariable logistic regression analysis after controlling for age at surgery, preoperative glans width, testosterone status, and urethroplasty length, testosterone administration did show significant association with reduced odds of postoperative complications (OR 0.4, P = .039). CONCLUSIONS: This retrospective review of patients shows that on multivariable analysis there is significant association between testosterone administration and decreased incidence of complications in patients undergoing distal hypospadias repair with urethroplasty. Future studies on testosterone administration should focus on specific cohorts of patients with hypospadias as benefits of testosterone may be more evident in some subgroups than others.

A newborn with ectrodactyly, tetralogy of Fallot, esophageal atresia, hypospadias and TP63 gene mutation: A new type of EEC Syndrome?

EEC syndrome is an autosomal dominant genetic disease with incomplete penetrance characterized by ectrodactyly, ectodermal dysplasia, and cleft lip/palate; these manifestations can differently occur in the affected subjects and can also be associated with other anomalies, such as in the urogenital tract.We reported the case of a newborn with prenatal diagnosis of EEC type 3 associated with severe cardiac abnormalities (Tetralogy of Fallot), high esophageal atresia with fistula and penoscrotal hypospadias.

'Waterproofing layers' for urethrocutaneous fistula repair after hypospadias surgery: evidence synthesis with systematic review and meta-analysis.

OBJECTIVE: To summarize the available evidence and to quantitatively evaluate the global results of different waterproofing layers in substantiating the UCF repair. MATERIAL AND METHODS: After defining the study protocol, the review was conducted according to the PRISMA guidelines by a team comprising experts in hypospadiology, systematic reviews and meta-analysis, epidemiology, biostatistics and data science. Studies published from 2000 onwards, reporting on the results of UCF closure after hypospadias repair were searched for on PUBMED, Embase and Google Scholar. Study quality was assessed using Joanna Briggs Checklist (JBI) critical appraisal tool. The results with different techniques were compared with the two samples independent proportions test with the help of Microsoft Excel, MedCalc software and an online calculator. RESULTS: Seventy-three studies were shortlisted for the synthesis; the final analysis included 2886 patients (71 studies) with UCF repair failure in 539. A summary of various dimensions involved with the UCF repair has been generated including time gap after last surgery, stent-vs-no stent, supra-pubic catheterization, suture material, suturing technique, associated anomalies, complications, etc. The success rates associated with different techniques were calculated and compared: simple catheterization (100%), simple primary closure (73.2%), dartos (78.8%), double dartos flaps (81%), scrotal flaps (94.6%), tunica vaginalis (94.3%), PATIO repair (93.5%), biomaterials or dermal substitutes (92%), biocompatible adhesives (56.5%) and skin-based flaps (54.5%). Several techniques were identified as solitary publications and discussed. CONCLUSIONS: Tunica vaginalis and scrotal flaps offer the best results after UCF closure in the synthesis. However, it is not possible to label any technique as ideal or perfect. Almost all popular waterproofing layers have depicted absolute (100%) success sometimes. There are a vast number of other factors (patient's local anatomy, surgeon's expertise and technical perspectives) which influence the final outcome.

Lateral incision 1-stage urethroplasty with oral mucosal graft for patients with penile urethral stricture after hypospadias repair-a preliminary report.

PURPOSE: To report our early experience of a novel surgical approach for penile urethral strictures after hypospadias repair, using a lateral incision to keep the ventral tissue and vasculature of the penis intact and to avoid the need for tissue interposition. PATIENTS AND METHODS: A total of 21 patients underwent lateral incision 1-stage urethroplasty with oral mucosal graft. The median age of the patients was 21 years old (range, 13-47). The median number of prior procedures for hypospadias repair was 3 (range, 1-9) with 18 of 21 patients (85.7%) undergoing greater than 1 prior reconstructive procedure. The mean length of the penile urethral strictures was 4.5 ± 1.7 cm, with a range of 1.0 to 8.0 cm. Selection criteria for lateral incision 1-stage urethroplasty include: non-obliterative stricture, no or mild penile curvature and no urethrocutaneous fistula. RESULTS: Median follow-up was 30 months (range, 6-73). Success was achieved in 17 of 21 patients (80.9%). The 4 (19.0%) patients with treatment failure developed recurrent urethral strictures. Of the 4 men with recurrent strictures, 3 were ultimately treated successfully by DVIU (2) or two-stage urethroplasty (1), and one patient chose repeated dilation. CONCLUSIONS: For patients with penile urethral stricture after hypospadias repair with non-obliterative stricture, no significant penile curvature and no urethrocutaneous fistula, a lateral approach with oral mucosal graft is a simple technique that avoids the need for tissue interposition and keeps the penile ventral tissue and vasculature intact, resulting in a low risk of complications.

Age-dependent early complications of hypospadias repair: a single institutional experience.

PURPOSE: To correlate age at hypospadias repair with early post-operative complications and highlight need for adaptation to post-operative care in older children. METHODS: Anecdotal evidence suggests boys with delayed surgery for hypospadias suffer increased rates of early post-operative complication. Hence, a retrospective analysis was conducted of all patients undergoing hypospadias repair between March 2019 and 2022. RESULTS: Ninety eight patients were divided into Group A (< 2years of age at first surgery) or Group B (> 2years). While patients in Group A encountered no early post-operative complications, seven in Group B (11%) suffered a range of complications including dislodged stents (3/7), significant spasmodic pain requiring prolonged hospital stay (2/7) and urinary retention (2/7). More than half of these children required emergency supra-pubic catheter insertion. CONCLUSION: Significantly more children undergoing hypospadias surgery after the age of 2 years suffered complications within the early post-operative period. This resulted in prolonged hospital stays and a number returning to theatre for insertion of a supra-pubic catheter. We recommend a tailored approach to the post-operative care of older children undergoing hypospadias repair, including strict parental education regarding dressing/stent care and medication compliance, as well as efforts to enhance robustness of dressings and stent anchorage in children likely to pull at stents.

Prospective Assessment of Genital Pain in Patients With Urethral Stricture: Incidence, Associations, and Impact of Urethroplasty.

OBJECTIVE: To assess the incidence of genital pain in patients with urethral stricture and examine the impact of urethroplasty. Genital pain is a common and challenging urological condition and potentially associated with urethral stricture. METHODS: From 2011-2019, patients were offered enrollment in a prospective single-center study assessing patient-reported genital pain pre- and 6-months posturethroplasty. Genital pain was assessed with the question, "Do you experience genital (scrotum or penis) pain?" answered on a five-point scale ["Never" (1), "Occasionally" (2), "Sometimes" (3), "Most of the Time" (4) or "All of the Time" (5)]. Responses of 3, 4, or 5 were considered clinically significant. Wilcoxon signed-rank test was used to compare pre- and postoperative states and logistic regression was used to evaluate the association between genital pain and clinical variables. RESULTS: Of the 387 patients completing enrollment, 36.4% (141/387) reported genital pain preoperatively. Patients with panurethral stricture reported higher rates (57.1%) of pain (Odds Ratio 2.93, 95%CI 1.32-6.50; P = .008). Posturethroplasty, pain scores improved with an incidence of 14.2% (P < .0001). In patients reporting preoperative pain, 88.7% (125/141) experienced improvement, 8.5% were unchanged and 2.8% reported worsening pain. On logistic regression, patients with penile strictures (O.R. 0.24, 95%CI 0.06-0.91; P = .04), hypospadias (O.R. 0.14, 95%CI 0.02-0.88; P = .04), and staged reconstruction (O.R. 0.22, 95%CI 0.05-0.90; P = .04) were less likely to report improvement. CONCLUSION: Genital pain is common in patients with urethral stricture and improves in the majority of patients undergoing urethroplasty but less so in patients with penile strictures, hypospadias and staged reconstruction.

Hypospadias: lessons learned. An overview of incidence, epidemiology, surgery, research, complications, and outcomes.

Hypospadias is a common condition and familiar, though sometimes challenging territory for the pediatric urologist. This review is a summary of hypospadias incidence, epidemiology, surgery, research, and complications intended for the non-specialist. It outlines the history, the principles of surgery for hypospadias, and the long-term outcomes.

Distal hypospadias repair: Comparative study between snodgrass and transverse preputial onlay flap.

INTRODUCTION: Distal hypospadias repair has several operative strategies such as tubularized incised plate (TIP); Transverse preputial onlay flap (TPOF) and Modified Mathieu Procedure. The aim of our work is to compare between TIP and TPOF techniques in the outcome. MATERIAL AND METHOD: We conducted this comparative study on 66 patients with different types of distal hypospadias divided in two groups A and B for TIP and TPOF respectively. We reported outcome and complications for both TIP and TPOF repair. Our results revealed mean operative time was significantly higher in group B (123.1 ± 6.8 min) than in group A (93.73 ± 3.9 min, P value < 0.001). Postoperative urinary fistula was reported in group A (15.2%) while no fistula in group B (p value = 0.05). The vertical slit appearance of meatus was better in group A (54.5%) than in group B (24.2%, P value 0.023). As regard to hypospadias objective scoring evaluation (HOSE) (Summary Figure) the meatal shape score was higher in group A (1.55 ± 0.51) than in group B (1.24 ± 0.44, p value = 0.0 l), the urinary stream score was significantly higher in group A (1.82 ± 0.39) than in group B (1.97 ± 0.17, p value = 0.04) and the urinary fistula score was significantly higher in group A (3.79 ± 0.60) than in group B (4 ± 0, p value = 0.04). DISCUSSION: Complications are more common after TIP than in TPOF. As regard the meatus shape, the naturally looking vertical slit like meatus was achieved more in the TIP than in TPOF. We advocate further studies with a large number of patients with a long follow up period. CONCLUSION: TPOF is a great option to consider in cases of distal hypospadias because it is an effective technique for primary distal hypospadias repair with a good cosmetic outcome and a low associated complication.

Emerging phenotypes linked to variants in SAMD9 and MIRAGE syndrome.

Background: Heterozygous de novo variants in SAMD9 cause MIRAGE syndrome, a complex multisystem disorder involving Myelodysplasia, Infection, Restriction of growth, Adrenal hypoplasia, Genital phenotypes, and Enteropathy. The range of additional clinical associations is expanding and includes disrupted placental development, poor post-natal growth and endocrine features. Increasingly, milder phenotypic features such as hypospadias in small for gestational age (SGA) boys and normal adrenal function are reported. Some children present with isolated myelodysplastic syndrome (MDS/monosomy 7) without MIRAGE features. Objective: We aimed to investigate: 1) the range of reported SAMD9 variants, clinical features, and possible genotype-phenotype correlations; 2) whether SAMD9 disruption affects placental function and leads to pregnancy loss/recurrent miscarriage (RM); 3) and if pathogenic variants are associated with isolated fetal growth restriction (FGR). Methods: Published data were analyzed, particularly reviewing position/type of variant, pregnancy, growth data, and associated endocrine features. Genetic analysis of SAMD9 was performed in products of conception (POC, n=26), RM couples, (couples n=48; individuals n=96), children with FGR (n=44), SGA (n=20), and clinical Silver-Russell Syndrome (SRS, n=8), (total n=194). Results: To date, SAMD9 variants are reported in 116 individuals [MDS/monosomy 7, 64 (55.2%); MIRAGE, 52 (44.8%)]. Children with MIRAGE features are increasingly reported without an adrenal phenotype (11/52, 21.2%). Infants without adrenal dysfunction were heavier at birth (median 1515 g versus 1020 g; P < 0.05) and born later (median 34.5 weeks versus 31.0; P < 0.05) compared to those with adrenal insufficiency. In MIRAGE patients, hypospadias is a common feature. Additional endocrinopathies include hypothyroidism, hypo- and hyper-glycemia, short stature and panhypopituitarism. Despite this increasing range of phenotypes, genetic analysis did not reveal any likely pathogenic variants/enrichment of specific variants in SAMD9 in the pregnancy loss/growth restriction cohorts studied. Conclusion: MIRAGE syndrome is more phenotypically diverse than originally reported and includes growth restriction and multisystem features, but without adrenal insufficiency. Endocrinopathies might be overlooked or develop gradually, and may be underreported. As clinical features including FGR, severe infections, anemia and lung problems can be non-specific and are often seen in neonatal medicine, SAMD9-associated conditions may be underdiagnosed. Reaching a specific diagnosis of MIRAGE syndrome is critical for personalized management.

Biologic adjuvant urethral coverings for single-stage primary hypospadias repairs: A systematic review and pooled proportional meta-analysis of postoperative urethrocutaneous fistulas.

BACKGROUND: The use of barrier layers between the neourethra and skin is associated with lower rates of post-operative urethrocutaneous fistula (UCF) following hypospadias surgery. Recent studies have evaluated the ability of biologic adjuvant urethral coverings (BAUCs) - namely acellular matrix (AM), tissue adhesives (TAs), and autologous platelet-rich plasma or fibrin (PRP/PRF) - to prevent wound complications following hypospadias surgery. In general, however, these studies are small and conducted at single institutions. OBJECTIVE: To assess the effect of BAUCs on the rate of UCF following single-stage primary hypospadias repair. METHODS: We conducted a systematic review of studies reporting the rate of postoperative UCF in pediatric patients undergoing single-stage, primary hypospadias repairs using either AM, TA, or PRP/PRF as a layer interposed between the neourethra and skin. We then performed a pooled proportional meta-analysis of post-operative UCF. Patients within each study who underwent comparable surgery but did not receive a BAUC were used as controls. RESULTS: 10 studies were included in our review. The meta-analysis included 280 patients from 7 studies who underwent hypospadias repairs with BAUCs. The pooled incidence of UCF was 10% (95% CI 6-14%). Mean follow-up ranged 5-23.5 months in the 5/7 studies reporting specific durations, and ≥6 month and 14-30 months, respectively, in the other two studies. Patients in whom a BAUC was used had significantly lower odds of UCF than control patients (OR 0.39, 95% CI 0.24-0.64, p = 0.0002). In subgroup analyses, significant superiority held for AM and TA; proximal or penoscrotal cases; transverse preputial island flap (TPIF) technique; when both cases and controls had local flaps; and when neither cases nor controls had flaps. DISCUSSION: The use of BAUCs was associated with decreased rates of post-operative UCF in single-stage primary hypospadias repairs and may be most beneficial in more severe cases and when used in addition to local flaps or when using a flap is not possible. In 2/3 studies of PRP/PRF and 2/4 studies of tubularized incised plate (TIP) technique, dartos flaps were used in controls but not BAUC patients, which may explain the lack of benefit demonstrated for these subgroups. This meta-analysis is limited by the quality of evidence in the included studies, which are not uniformly randomized. Furthermore, the follow-up durations and methods for assessing complications are not standardized between included studies. CONCLUSION: The meta-analysis herein suggests that using BAUCs may reduce UCF rates following hypospadias surgery. Rigorous prospective evaluation is needed to validate this benefit.

Missed urethral duplication associated with hypospadias, post-hypospadias repair urethral stenosis, and recurrent urinary tract infections in an adult: a case report.

BACKGROUND: Duplication of urethra is a very rare congenital disorder. Several types of this anomaly have been reported around the world, and are also discussed in this report. However, the mechanism of this anomaly is still unclear. CASE: A 45-year-old Persian man with a complaint of recurrent urinary tract infection was referred to our clinic. He had a history of repairing penoscrotal hypospadias in childhood along with obstructive and irritating symptoms in adolescence. On his last voiding cystourethrogram and retrograde urethrogram, stenosis was observed in the proximal bulbar urethra along with a double urethra in the dorsal region of the main urethra. The double urethra was removed with operation, and he was followed for 1 month after surgery. He had no complaints of recurrence or urinary incontinence. CONCLUSIONS: This report shows the different classification systems, types of double urethra, and approach and management, which mainly involves surgery; however, surgical management should be done according to the anatomical findings of the abnormality.

Clinical characteristics, socioeconomic factors and COVID-19 were associated with delayed surgery in children with hypospadias: a retrospective study of 4439 cases in a single center.

BACKGROUND: Hypospadias is one of the most common congenital diseases of the genitourinary system in children. The European Association of Urology (EAU) Guidelines recommend that children undergoing hypospadias surgery should be between 6 and 18 months. In China, where many children have hypospadias, it remains unknown whether clinical characteristics, socioeconomic factors and COVID-19 were associated with delayed surgery in children with hypospadias. METHODS: We retrospectively analyzed children with hypospadias who underwent primary surgery at the Department of Pediatric Urology in Guangzhou Women and Children's Medical Center between January 2010 and October 2021. Patients who had two-stage surgery or a second round of surgery due to complications were excluded to eliminate data duplication. The clinical characteristics and demographic information were collected. We defined delayed surgery as primary surgery performed after 18 months following the EAU Guidelines. RESULTS: A total of 4439 children diagnosed with hypospadias were included in the study. The median age (29.1 ± 16.7 months) of surgery for hypospadias in our study was much higher than the recommended age reported in the EAU guidelines, and 76.6% of the children underwent surgery after the age of 18 months. Children without comorbidities including cryptorchidism (odds ratio [OR] = 1.562; 95% confidence interval [CI] 1.199-2.034; p = 0.001), prostatic cyst (OR = 2.613; 95% CI 1.579-4.324; p < 0.001), penile hypoplasia (OR = 1.778; 95% CI 1.225-2.580; p = 0.002), inguinal hernia (OR = 2.070; 95% CI 1.394-3.075; p < 0.001), and penoscrotal transposition (OR = 4.125; 95% CI 1.250-13.619; p = 0.020) were more likely to receive delayed surgery. Living in a low economic area (OR = 1.731; 95% CI 1.068-2.806; p = 0.026) or not close to a main medical center (OR = 1.580; 95% CI 1.370-1.824; p < 0.001) was highly associated with delayed surgery. The proportion of children undergoing delayed surgery and the median age of surgery during the COVID-19 pandemic were significantly higher than those before the COVID-19 pandemic (p = 0.004 and < 0.001, respectively). CONCLUSIONS: Most children with hypospadias received delayed surgery (surgical age > 18 months). Comorbidities, living in a low economic area, too far from a main medical center and the COVID-19 pandemic were highly associated with delayed surgery. It is vital to improve the public awareness of hypospadias and strengthen the re-education of primary community doctors to reduce delayed surgery.