The utilization of hyperbaric oxygenation therapy in hypospadias repair: a systematic review and meta-analysis.

INTRODUCTION: This study aimed to evaluate the efficacy and safety of Hyperbaric Oxygen Therapy (HBOT) use in hypospadias repair through systematic review and meta-analysis of comparative studies. METHODS: A systematic literature search was performed in May 2021. Comparative studies assessing the surgical outcome of hypospadias repair between control versus HBOT utilization were identified and evaluated according to Cochrane collaboration recommendations. The assessed outcome includes hypospadias repair failures and graft failure for staged repair using a buccal graft. Relative risk with corresponding 95% confidence intervals (CI) were extrapolated. A random-effect model was used to generate pooled effect estimates. Heterogeneity and inter-study variability were assessed using Chi-square and I-square. Subgroup analysis was performed according to primary repair versus redo-hypospadias with buccal graft. PROSPERO registration (CRD42021251423). RESULTS: Five comparative studies with 576 cases (301 HBOT versus 275 controls) were included. Overall pooled effect estimates showed that the HBOT group has significantly lesser hypospadias repair failure (RR 0.52, 95%CI 0.37, 0.72). Subgroup analysis on the use of HBOT for graft take showed lesser graft failure compared to the control group (RR 0.20, 95% CI 0.05, 0.75), while the use of HBOT for primary and redo single staged hypospadias repair showed lesser complication rate (RR 0.56, 95%CI 0.40, 0.78). Based on ROBINS-I assessment, all included comparative studies are determined to be of serious risk of bias mainly due to presence of confounding. CONCLUSION: The currently available low-quality of evidence suggests that compared to control groups, HBOT as an adjunctive intervention to complicated hypospadias repair was able to reduce surgical outcome failure and graft failure rates.

Analysis of the social and clinical factors affecting the age of children when receiving surgery for hypospadias: a retrospective study of 1611 cases in a single center.

We aimed to explore the associations between the age at which children undergo surgery for hypospadias and a range of social and clinical factors in a single center. Our aim was to promote the early surgical treatment of children with hypospadias. For a 6-year period, social and clinical data were collected from all children undergoing surgery to repair hypospadias in Children's Hospital of Chongqing Medical University (Chongqing, China), located in southwest of China. We analyzed the correlations between age at surgery and a range of social and clinical factors. A total of 1611 eligible cases were recruited, with a mean age of 54.3 months and a median age of 42 months: 234 cases (14.5%) were classified into a "timely operation" group, 419 (26.0%) cases into a "subtimely operation" group, and 958 (59.5%) cases into a "delayed operation" group. According to multivariate regression analyses, the higher the regional economic level, the closer the urethral opening to the perineum, and the higher the educational level of the guardians was, the younger the children were when they underwent the initial surgery for hypospadias; this was also the case for families without other children. Our subgroup analysis showed that the primary educational level of the guardians was a risk factor for subtimely surgery in their children (odds ratio [OR] = 1.52, 95% confidence interval [CI]: 1.08-2.15, P < 0.05). A lower regional economic level (OR = 1.87, 95% CI: 1.26-2.78, P < 0.01), a lower educational level of the guardians (OR = 3.84, 95% CI: 2.31-6.41, P < 0.01), and an anterior-segment urethral opening (OR1 [vs middle hypospadias] = 2.07, 95% CI: 1.42-3.03; OR2 [vs posterior hypospadias] = 2.63, 95% CI: 1.75-3.95; P < 0.01) were all risk factors for delayed surgery in children.

The current state of tissue engineering in the management of hypospadias.

Hypospadias is a congenital malformation resulting from the disruption of normal urethral formation with varying global prevalence. Hypospadias repair, especially that of proximal hypospadias (in which reconstruction of a long urethra is necessary), remains a surgical challenge despite more than two decades of surgical technique development and refinement. The lack of tissue substitutes with mechanical and biological properties similar to those of native urethra is a challenge for which the field of tissue engineering might offer promising solutions. However, the use of tissue-engineered constructs in preclinical studies is still hindered by complications such as strictures or fistulae, which have slowed progression to clinical application. Furthermore, the generation of uniform tubular constructs remains a challenge. Exciting advances in the application of nanotechnology and 3D bioprinting to urethral tissue engineering might present solutions to these issues.

Disorders Of Sex Differentiation: Evaluation And Management, A Dilemma.

The term intersex used in the past has been replaced by "Disorders of Sex Differentiation". In this condition the development of chromosomal, gonadal or anatomical sex is atypical. This problem creates anxiety to the parents and a challenge for attending doctor. The problems faced by the individual are sexual, reproductive, sex of raring, placement in the society and psychological impact. The optimal management of the patient should be individualized by multidisciplinary team. Three cases of Disorders of Sex Differentiation (DSD) are presented with different causes and presentations. Two cases carrying XY karyotype pattern, while one case was of XX. The diagnosis of swyers syndrome, 5 alpha reductase deficiency and congenital adrenal hyperplasia was made on the basis of genital tract development, hormonal analysis and karyotyping. The strange feature which was common in all these cases was the wish of patients as well as family members to adopt sex of raring as male.

An evaluation of the readability, quality, and accuracy of online health information regarding the treatment of hypospadias.

BACKGROUND: Hypospadias is one of the most common genital anomalies. Treatment of hypospadias requires surgical repair, usually in childhood. Patients are increasingly using the internet to learn more about their health or that of their children, which can often empower patients to make well-informed healthcare decisions. OBJECTIVE: The objective of this study was to evaluate not only the readability but also the quality and accuracy of available online health information for the treatment of hypospadias. STUDY DESIGN: Search terms for hypospadias treatment were queried on major search engines. Each website was classified into one of four categories: institutional, commercial, charitable organization, or personal website. Content on each website discussing treatment options was analyzed for readability using three readability formulas. A validated tool, the DISCERN instrument, was used to measure the quality of online health information regarding hypospadias treatment. Accuracy was independently assessed by two pediatric urologists on a 1-5 scale, in which 1 and 5 correspond to 0% and 100% of the information in the text being accurate, respectively. RESULTS: A total of 150 search engine results were acquired, of which 46 were analyzed for readability, quality, and accuracy. The mean readability scores across all websites were 14.89 (Gunning-Fog), 11.01 Simple Measure of Goddledygook (SMOG), and 8.44 (Dale-Chall), which correspond to an 11th- to 12th-grade reading level. Most websites (65.2%) were considered of 'good' quality. Readability and quality scores were not statistically different between website categories. Institutional and charitable websites had the highest mean accuracy scores (3.91 and 3.50, respectively), with institutional websites proving to have significantly more accurate information regarding hypospadias treatment than commercial websites (3.91 and 3.42, respectively; P = 0.001). DISCUSSION: Pediatric urologists should know what information about hypospadias and its treatment exists on the Internet and understand if it is accurate and of good quality and, more importantly, if the material is written at a reading level comprehensible by the majority of parents. Limitations included analysis of only English-written websites regarding hypospadias treatment specifically, using search engines alone rather than other online resources, not evaluating online videos or illustrations, and not using more than two pediatric urologists for determining content accuracy. CONCLUSION: This study demonstrates that online health materials regarding hypospadias and its treatment are written at a level far greater than the reading level of most adults. Most websites were considered of adequate quality, and websites from institutions or references had significantly more accurate information than those from commercial websites.

5-α-Reductase type 2 deficiency: is there a genotype-phenotype correlation? A review.

5-α-Reductase type 2 enzyme catalyzes the conversion of testosterone into dihydrotestosterone, a potent androgen responsible for male sexual development during the fetal period and later during puberty. Its deficiency causes an autosomal recessive disorder of sex development characterized by a wide range of under-virilization of external genitalia in patients with a 46,XY karyotype. Mutations in the SRD5A2 gene cause 5-α-Reductase deficiency; although it is an infrequent disorder, it has been reported worldwide, with mutational heterogeneity. Furthermore, it has been proposed that there is no genotype-phenotype correlation, even in patients carrying the same mutation. The aim of this review was to perform an extensive search in various databases and to select those articles with a comprehensive genotype and phenotype description of the patients, classifying their phenotypes using the external masculinization score (EMS). Thus, it was possible to objectively compare the eventual genotype-phenotype correlation between them. The analysis showed that for most of the studied mutations no correlation can be established, although the specific location of the mutation in the protein has an effect on the severity of the phenotype. Nevertheless, even in patients carrying the same homozygous mutation, a variable phenotype was observed, suggesting that additional genetic factors might be influencing it. Due to the clinical variability of the disorder, an accurate diagnosis and adequate medical management might be difficult to carry out, as is highlighted in the review.

[Aesthetic criteria in surgical treatment of hypospadias in children].

Aesthetically acceptable cosmetic results of surgical correction of external genital organ defects are important for treatment evaluation along with well-known criteria of good functional outcomes.The purpose of this study was to improve the results of treating children with hypospadias by improving the assessment of results and introducing multi-step correction modalities. MATERIALS AND METHODS: From 2013 to 2015, 476 patients with various forms of hypospadias were treated at the Department of Uroandrology of RCCH. The patients age ranged from 1 year to 17 years (mean age 3 years). All patients were divided into 3 groups depending on the form of hypospadias and type of treatment. They included patients with distal forms of hypospadias (group1, n=270), proximal forms (group 2, n=112) and patients with stem and penoscrotal hypospadias who underwent 3-6 operations before admission (group 3, n=94). RESULTS: The study evaluated both functional and cosmetic results. Cosmetic appearance was assessed using the HOPE scoring system [2]. Despite the difference in surgical methods used for all types of hypospadias, good cosmetic results have been achieved in the majority of patients (65%). Functional outcomes differed depending on the form of hypospadias. In primary patients with distal and proximal forms of hypospadias, good results were achieved in 96% and 77% of patients, respectively. At the same time, 72% of patients who underwent repeat interventions had good results, which is comparable to the group of primary patients with proximal forms. CONCLUSION: The results of treating patients after repeat/failed surgery confirm the high effectiveness of our surgical methods (the Bracka two-stage graft repair, buccal mucosa hypospadias repair, reconstruction with scrotal skin flaps, correction of scrotal transposition). Using the HOPE scoring system to assess cosmetic results helps motivate surgeons to achieve the best treatment results.

Use of Hormones, Tissue Factors and Bioengineering in the Management of Hypospadias.

Hypospadiology is a rapidly evolving field. Progress in the understanding of how hormonal therapy affects the growth of the phallus has allowed surgeons to optimize the tissues for surgery. But conflicting data from a number of studies and a lack of consensus on drugs, their dosing, mode of delivery and timing of use means that the creation of protocols is unlikely to happen in the near future. Nonetheless, there is a hope and the standardization of scientific reporting will make it easier to compare data at the global level. There are reports of the increasing incidence of hypospadias and the etiology is thought to be multifactorial. Although complex interactions between genetic polymorphisms and the environment make it difficult to identify the exact factors responsible for hypospadias, the advent of massively parallel gene sequencing, large scale epigenetic screens and CRISPR technology will definitely ease the process. The knowledge of culprit genes will not only broaden our understanding of embryology and growth but will also enable us to predict and/or modify tissue healing. Advances in tissue engineering are also expected to provide a plethora of biomaterials for urethral reconstruction. The development of this field is directly linked with the elucidation of the processes of proliferation and vascularization coupled with the cataloguing of the growth factors involved. One can safely conclude that the exciting new advances in the field will have far reaching consequences on patient care and counselling.

The Ideal Use of Catheters in Hypospadias Repair: An Experimental Study.

PURPOSE: To find answers to some catheter-related questions in hypospadias repair such as which type of catheter should be used, with which catheter balloon inflation volume, and when should the catheter be removed from the urethra? As catheter use and post-op retention time varies among surgeons in hypospadias repair. MATERIAL AND METHODS: Fifty-four 10 French all-silicone- and 54 latex Foley catheters were prepared and assigned to groups as senary. The catheter's balloons were inflated with 2, 3 and 5 mL of sterile water. The catheters were submerged in artificial human urine and then removed from the solution at 24, 72, and 168 h after submersion. The catheter balloon volume losses, increases in the transverse diameter of the catheters, and angulation of the catheter tips were measured to determine catheter degradation. RESULTS: The minimum balloon volume loss was 0.4 mL in the group of all-silicone catheters that were inflated with 2mL and deflated after 24h (2mL 24h). According to balloon volume and deflation time, there were no increases in transverse diameter of the four groups of all-silicone catheters; 2mL 24h, 3mL 24h, 5mL 24h, and 2mL 72h. With 1 mm expansion, the lowest increase on transverse diameter of the latex catheters occurred in five groups; 2mL 24h, 3mL 24h, 5mL 24h, 2mL 72h, and 2mL 168h. CONCLUSION: An all-silicone catheter inflated with 2mL and removed from the urethra within 24-72 hours may be the ideal catheter use in hypospadias repair.   .

[Disorders of sex development and proximal hypospadias]. / Sexuelle Differenzierungsstörungen und proximale Hypospadie.

BACKGROUND: Children with ambiguous genitalia due to different chromosome or gonadal sex are a particular challenge concerning the diagnostic and therapeutic implications. Proximal hypospadias patients with normal gonadal development should be distinguished from children with DSD (disorders of sex development) to guarantee normal gender identity and the best possible surgical therapy. OBJECTIVES: This paper focuses on the terminology, embryology, and pathophysiology of the different manifestations of DSD. The state of knowledge about this disease pattern with particular emphasis on proximal hypospadias based on national and international scientific discussions is presented. MATERIALS AND METHODS: The different clinical pictures as well as therapeutic options of DSD with a special focus on recent literature and giving particular attention to patients with proximal hypospadias are presented. RESULTS: Because of the complexity of patients suffering from disorders of sex development an interdisciplinary DSD healthcare team including a paediatric endocrinologist as well as paediatric urologist should be provided. These specialists enable an accurate diagnosis in severe hypospadias patients without reference to DSD diseases patterns.

Three-week or one-week bladder catheterization for hypospadias repair? A retrospective-prospective observational study of 189 patients.

PURPOSE: While there is little scientific evidence over the optimal duration for transurethral bladder catheterization after hypospadias repair, most surgeons leave the catheter for 7-10 days. We herein describe our experience with bladder catheterization for three weeks after hypospadias repair, an approach not previously described in the literature. PATIENTS AND METHODS: We reviewed the charts of 189 patients who underwent hypospadias repair by a single pediatric urologist. The study population was divided as follows: group 1 consisted of children operated between March 2007 and September 2010 and whose catheters were left for one week (n=95); group 2 consisted of those operated between September 2010 and July 2013 and whose catheters were left for three weeks (n=94). The primary objective of the study was to compare complication rates between the two groups. Secondary outcomes were evaluation of the effect of age, surgical technique, curvature, and hypospadias degree as potential factors for postoperative complications. RESULTS: Median age at hypospadias repair was 18 months (range, 3-100 months) in group 1, and 16 months (range, 2-96 months) in group 2, P=.209. The complication rate was 22.1% (n=21) for group 1 and 7.4% (n=7) for group 2, P=.005. Complications observed in group 1 and 2 were meatal stenosis (n=4 and 2, respectively) and urethro-cutaneous fistulas (n=17 and 5, respectively). Coronal fistulas manifested more frequently in patients in group 1 compared to those in group 2 (13.7% vs. 3.2%, P=.01). Complications were observed in 20 patients out of 139 (11.5%) after Duplay, and in 8 patients out of 15 (53.3%) after Duckett (P<.001). In Duplay cases, complications were significantly associated with one-week bladder catheterization (OR: 5.00; 95% CI: 1.53-16.32; P=.008) and higher age group at operation (OR: 1.88; 95% CI 1.07-3.28; P=.026). In Duckett cases, number of surgeries, age, severity, curvature and catheter duration were not found to be associated with complications. CONCLUSION: In cases of Duplay, a three-week instead of one-week catheterization and age below 6 months at hypospadias repair are associated with a better outcome and fewer complications.

State of the art review in hypospadias: challenges in diagnosis and medical management.

Hypospadias is a common congenital malformation in males, the cause of which may be genetic, hormonal, or environmental, although it usually is idiopathic or possibly multifactorial. Determining the optimal diagnostic testing and management remains a challenge. Hypospadias is corrected with surgery, and androgen therapy often is used preoperatively as an adjunctive therapy, although its use, timing, and effectiveness are unclear. No standardized approach has been established for the diagnostic testing for hypospadias or for preoperative androgen therapy. We reviewed current literature and used the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence and provide recommendations for a diagnostic testing algorithm from an endocrine and genetic perspective and for the optimal use of preoperative androgen therapy. These recommendations are an important step towards standardizing the use of diagnostic testing and the management of patients with hypospadias.

[Current and practice-relevant news from pediatric urology]. / Aktuelles und Praxisrelevantes aus der Kinderurologie.

Evidence-based medicine is established by conducting high-quality, well-structured, and ideally prospective randomized trials. The initiation and performance of such studies pose a challenge to pediatric urology. Several randomized studies on vesicoureteral reflux, stone treatment, and urinary incontinence in childhood have been published in recent years. In addition, relevant guidelines on the topic of vesicoureteral reflux and phimosis were issued. Comprehensive up-to-date data are also available on undescended testicles and correction of hypospadias from which a recommended course of action can be derived.

Tissue-engineered transplants for the treatment of severe hypospadias.

The surgical treatment of severe hypospadias can be very challenging. In selected cases with severe lack of tissue, cultured autologous urothelial cells can be used to create a transplanted neourethra. The algorithm for using tissue-engineering techniques for the surgical repair of the male urethra includes 3 main steps. First, the autologous urothelial cells are harvested from the patient, e.g. by bladder washing through a catheter with sterile saline. Second, the cells are propagated and expanded in the laboratory environment. Finally, the cells are transplanted back to the patient in the final surgical repair. We have used this technique in a clinical setting in severe hypospadias. Transplants for creation of the neourethra were used ventrally in an on-lay fashion with remaining skin dorsally in the urethra. Our follow-up shows a good clinical result including data concerning voiding position, urinary flow, artificial erection, cosmetic appearance, urethroscopy and biopsies. Tissue-engineering techniques can, however, benefit from further improvement and, thus, be developed for additional applications. We conclude that in hypospadias repair with cultured autologous urothelial cells is an option for the surgical treatment when there is a lack of local tissue for the repair.

A practical approach to intersex in the newborn period.

Sexual determination is a complex process that occurs in an organized sequential manner. When chromosomal, gonadal, or phenotypic sex determination goes awry,intersexuality develops. Advances in molecular biology have made it easier to understand the various phenotypes that are encountered. It is easy to be overwhelmed when reviewing the testosterone synthesis pathway and the intersex differential diagnosis. This article presents a useful approach to the evaluation of the newborn with ambiguous genitalia.

[Complications of surgical treatment of hypospadia]. / Oslozhneniia operativnogo lecheniia gipospadii.

127 new cases of hypospadia were treated in 1980-2002. A total of 348 operations including urethroplasty by Duplay and Cecil were made. 78 of the operations were followed by complications out of which 26 were corrected in the postoperative period and had no effect on the treatment results. The first stage of surgical correction of hypospadia (89 operations) brought complications in 13.48% cases. Recurrent distortion of the cavernous bodies was most typical complication at this stage. In most cases development of scarry deformation was due to inflammatory changes early after surgery. Derivatives of prednisolone proved effective in the treatment of hypertrophic scars. This complication correlated with skin plastic repair (longitudinal suturing or creation of oncoming triangular flaps) to correct the defect. The second stage of hypospadia surgery was urethroplasty made in 196 cases. It was accompanied with complications in 13.25 patients. Fistulas of newly-created urethra (11.73%) were the most typical and frequent complication. The number of postoperative complications varied greatly depending on the disease form and method of urethral reconstruction. Cecil urethroplasty brought complications in 7.94% cases. Efficacy of neurourethra creation by Duplay varied greatly depending on the length of the created neourethral portion and the number of local skin resources (8-33-83.33% complications).