History Of Hypospadias Research Articles

The Glanular-Frenular Collar (GFC) technique: Dual approach to hypospadias reconstruction

The Glanular-Frenular Collar (GFC) technique has evolved since it was first described in 2017. The technique involves reconstruction of the septum glandis, which has been overlooked in the history of hypospadias, and formation of the frenulum, creating the ventral wall of the glanular urethra without dissecting the glans, leaving room for the formation of the navicular fossa. We present a case of distal hypospadias corrected with the GFC technique and demonstrate the important steps of the surgical technique. The aesthetic result corresponded to the normal anatomy of the glans and frenular triangle, and the functional result showed a free and wavy shape of urine that resembled the normal flow from the urethra. In the normal anatomy of the penis, the wings of the glans are separated ventrally by the septum glandis and the frenulum. The navicular-shaped glanular urethra and its vertical, elliptical opening are covered by the fibroelastic septum glandis, unlike the penile urethra, which is surrounded by the corpus spongiosum. Reconstruction of hypospadias should include the formation of a septum glandis, frenulum, and navicular fossa. The GFC technique demonstrates the importance of a dual surgical approach for glanular and penile urethra reconstruction.

RF02 | PMON309 Two Siblings with p.Arg92Trp Variant in NR5A1 Presenting with Testicular Disorder of Sexual Differentiation

Abstract Introduction Disorders of sexual differentiation (DSD) are conditions of abnormal chromosomal development leading to atypical gonadal and anatomic sexual characteristics. We present the case of two siblings with 46, XX testicular DSD due to a mutation in the nuclear receptor subfamily 5 group A member 1 gene (NR5A1). While there is extensive literature about pathogenic variants of this gene, this is the first variant that has been shown to cause DSD in XX individuals, rather than XY. Case presentation This is the case of a sibling pair with male phenotype and history of hypospadias and hypogonadism in the setting of 46, XX karyotype. Sibling A presented with hypospadias at birth and hypergonadotropic hypogonadism in childhood, initially managed with testosterone. Testicular biopsy revealed bilateral germ cell aplasia with degeneration of seminiferous tubules. Sibling B presented at age 8 with precocious puberty. He had a history of hypospadias and cryptorchidism at birth. Gonadotropins and testosterone levels were prepubertal. Testicular biopsy showed only Sertoli cells. Their adrenal gland and thyroid function was normal, their bone age was advanced. FISH was negative for the SRY gene in both cases, no ovaries or mullerian structures found in pelvic imaging. DSD genetic panels were sent, resulting positive for the R92W variant in NR5A1. Neither of them have intellectual disability; however, sibling B has attention deficit and hyperactivity disorder (ADHD) and obsessive compulsive disorder (OCD). Family history is remarkable for two uncles that have been unable to conceive. Their mother had oligomenorrhea and difficulty conceiving, typical presentation of a female carrier of this mutation. Discussion and conclusions The majority of DSD in individuals with a 46, XX karyotype are due to congenital adrenal hyperplasia (CAH) secondary to 21-hydroxylase deficiency, however, mutations in NR5A1 have been among the most frequently identified genetic causes of gonadal development disorders and are associated with a wide phenotypic spectrum. NR5A1 is an essential transcription factor that regulates target genes crucial for normal reproductive physiology and endocrine function, controlling several steps of adrenal and gonadal development. While there is extensive literature about the phenotype caused by variants of NR5A1 in XY individuals, the recurrent heterozygous p.Arg92Trp NR5A1 variant R92W that our patients have, is the only one that has been shown to cause DSD in XX individuals, with variable degrees of testis development. It has previously been described, however, in women with primary ovarian insufficiency (POI). Morevariants of this gene will continue to arise, playing a pivotal role in reproductive endocrinology. Presentation: Saturday, June 11, 2022 1:00 p.m. - 1:05 p.m., Saturday, June 11, 2022 1:00 p.m. - 1:05 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Vascular dysfunction and increased cardiovascular risk in hypospadias.

AimsHypogonadism is associated with cardiovascular disease. However, the cardiovascular impact of hypogonadism during development is unknown. Using hypospadias as a surrogate of hypogonadism, we investigated whether hypospadias is associated with vascular dysfunction and is a risk factor for cardiovascular disease.Methods and resultsOur human study spanned molecular mechanistic to epidemiological investigations. Clinical vascular phenotyping was performed in adolescents with hypospadias and controls. Small subcutaneous arteries from penile skin from boys undergoing hypospadias repair and controls were isolated and functional studies were assessed by myography. Vascular smooth muscle cells were used to assess: Rho kinase, reactive oxygen species (ROS), nitric oxide synthase/nitric oxide, and DNA damage. Systemic oxidative stress was assessed in plasma and urine. Hospital episode data compared men with a history of hypospadias vs. controls. In adolescents with hypospadias, systolic blood pressure (P = 0.005), pulse pressure (P = 0.03), and carotid intima-media thickness standard deviation scores (P = 0.01) were increased. Arteries from boys with hypospadias demonstrated increased U46619-induced vasoconstriction (P = 0.009) and reduced acetylcholine-induced endothelium-dependent (P < 0.0001) and sodium nitroprusside-induced endothelium-independent vasorelaxation (P < 0.0001). Men born with hypospadias were at increased risk of arrhythmia [odds ratio (OR) 2.8, 95% confidence interval (CI) 1.4–5.6, P = 0.003]; hypertension (OR 4.2, 95% CI 1.5–11.9, P = 0.04); and heart failure (OR 1.9, 95% CI 1.7–114.3, P = 0.02).ConclusionHypospadias is associated with vascular dysfunction and predisposes to hypertension and cardiovascular disease in adulthood. Underlying mechanisms involve perturbed Rho kinase- and Nox5/ROS-dependent signalling. Our novel findings delineate molecular mechanisms of vascular injury in hypogonadism, and identify hypospadias as a cardiovascular risk factor in males.

Homozygosity for a novel INHA mutation in two male siblings with hypospadias, primary hypogonadism, and high-normal testicular volume.

BackgroundThe human INHA gene encodes the inhibin subunit alpha protein, which is common to both inhibin A and B. The functional importance of inhibins in male sex development, sexual function, and reproduction remain largely unknown.ObjectiveWe report for the first time two male siblings with homozygous INHAmutations.MethodsThe medical files were examined for clinical, biochemical, and imaging data. Genetic analysis was performed using next-generation and Sanger sequencing methods.ResultsTwo brothers complained of gynecomastia, testicular pain, and had a history of hypospadias. Biochemistry revealed low serum testosterone, high gonadotropin and anti-Mullerian hormone, and very low/undetectable inhibin concentrations, where available. Both patients had azoospermia in the spermiogram. We have identified a homozygous 2 bp deletion (c.208_209delAG, R70Gfs*3) variant, which leads to a truncated INHA protein in both patients, and confirmed heterozygosity in the parents. The external genital development, pubertal onset and progression, reproductive functions, serum gonadotropins, and sex hormones of mother and father, who were heterozygous carriers of the identified mutation, were normal.ConclusionHomozygosity for INHA mutations causes decreased prenatal and postnatal testosterone production and infertility in males, while the heterozygous female and male carriers of INHA mutations do not have any abnormality in sex development and reproduction.

Multi-institutional review of non-hypospadiac penile urethral stricture management and outcomes.

Penile urethral stricture disease not associated with hypospadias is rare, and there is a wide range of commonly used surgical repair techniques for this disease. We sought to compile a multi-institutional database of patients who had surgical correction of strictures in the penile urethra not limited to the meatus, and who had no history of hypospadias, for analysis using the Trauma and Urologic Reconstructive Network of Surgeons length, urethral segment and etiology classification system. A retrospective database from 13 institutions was compiled of patients who had undergone surgical correction of Trauma and Urologic Reconstructive Network of Surgeons length, urethral segment and etiology urethral stricture segments S2b/S2c and excluding E5, with a minimum follow-up time of 4 months. Failure was defined as cystoscopically confirmed recurrence of a stricture measuring less than 16-Fr. We analyzed 222 patients with a median age of 57 years and a follow-up of 49 months. The overall surgical success rate was 80.2%. On multivariate analysis, the two variables identified that were predictive of surgical success were stricture length ≤2 cm as well as use of a buccal mucosa graft as compared to use of a fasciocutaneous flap, which had success rates of 83% and 52%, respectively (P = 0.0004). No statistically significant differences were found based on incisional approach or surgical technique, nor were outcomes different based on etiology or preoperative patient demographics. Surgical repair of penile urethral strictures of non-hypospadiac origin have a favorable overall success rate, at 80.2%. Regardless of incisional approach or surgical technique, all operations appear to have similar outcomes other than repairs using fasciocutaneous flap, which were statistically less successful than those using buccal mucosa graft.

PD22-10 URINE miRNA BIOMARKERS THAT ARE DIFFERENTIALLY EXPRESSED IN LICHEN SCLEROSUS INDUCED AND NON-LICHEN SCLEROSUS INDUCED URETHRAL STRICTURE DISEASE

You have accessJournal of UrologyTrauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) II (PD22)1 Sep 2021PD22-10 URINE miRNA BIOMARKERS THAT ARE DIFFERENTIALLY EXPRESSED IN LICHEN SCLEROSUS INDUCED AND NON-LICHEN SCLEROSUS INDUCED URETHRAL STRICTURE DISEASE Karl Benz, Travis Sullivan, Thomas Kalantzakos, Amanda Sherman, Harjivan Kohli, Eric Burks, Kimberly Rieger-Christ, and Alex Vanni Karl BenzKarl Benz More articles by this author , Travis SullivanTravis Sullivan More articles by this author , Thomas KalantzakosThomas Kalantzakos More articles by this author , Amanda ShermanAmanda Sherman More articles by this author , Harjivan KohliHarjivan Kohli More articles by this author , Eric BurksEric Burks More articles by this author , Kimberly Rieger-ChristKimberly Rieger-Christ More articles by this author , and Alex VanniAlex Vanni More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002011.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Identifying non-invasive biomarkers that distinguish Lichen Sclerosus (LS) induced from non-LS induced urethral strictures would have broad implications for the diagnosis, counseling, and treatment of urethral stricture disease (USD). The objective of this study is to determine which miRNAs are differentially expressed in urine samples from patients with LS USD versus non-LS USD. METHODS: A prospectively maintained institutional USD database of patients who underwent urethroplasty was queried for patients with an available pre-operative voided urine sample obtained between July 2018 and February 2020. Urine miRNA were analyzed in patients with and without histologically confirmed LS USD. Total RNA was isolated and reverse transcribed from each urine supernatant sample. miRNA expression was then profiled using RT-qPCR arrays for 376 unique miRNAs. Urine samples were excluded if there was recent catheterization, if the urine was obtained from a suprapubic tube, or if the patient had a history of hypospadias. RESULTS: In total, 24 patients met inclusion criteria, 14 (58%) of which were post-operatively histologically classified as having LS. There were no significant differences between the LS and non-LS USD groups regarding patient age, body mass index, history of smoking, or history of diabetes mellitus. Of the 376 miRNAs tested, forty-five unique miRNAs were differentially expressed in LS urines (p<0.05), 4 of which had a p-value of <0.01. Of those four, miR-186-5p (p=0.002, AUC 0.736) and miR-185-5p (p=0.003, AUC 0.764) were upregulated in LS, while miR-153-3p (p=0.005, AUC 0.701) and miR-509-3p (p=0.006, AUC 0.688) were downregulated (Figure 1). CONCLUSIONS: This is the first study to demonstrate unique urine miRNA that distinguish LS from non-LS USD. This discovery could be used to create a non-invasive urine test to distinguish the LS vs non-LS USD, therefore obviating the need for biopsy. The two most promising candidates, miRNAs 185-5p and 186-5p, have been shown to mediate the androgen receptor, fibrosis pathways, and cell proliferation pathways. Further investigation is needed to validate these findings in a larger cohort. Source of Funding: Ellison Foundation and the R.E. Wise Research and Education Institute © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e383-e384 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Karl Benz More articles by this author Travis Sullivan More articles by this author Thomas Kalantzakos More articles by this author Amanda Sherman More articles by this author Harjivan Kohli More articles by this author Eric Burks More articles by this author Kimberly Rieger-Christ More articles by this author Alex Vanni More articles by this author Expand All Advertisement Loading ...

Orchidopexy for congenital and acquired undescended testes ‐ Long‐term follow up needed

AbstractIntroductionUndescended testis (UDT) is the most common urological anomaly in boys with orchidopexy as the standard of treatment. However, characteristics of UDT and long‐term outcomes after orchidopexy had not been reported in our locality. This study aimed to review the late surgical outcomes of these patients in our centre.MethodsA retrospective review was performed on patients under 16 years old with orchidopexy done for UDT from 2005 to 2010. Patient demographics, UDT characteristics, pre‐operative imaging, peri‐operative complications and any late testicular ascent or atrophy were documented. Only those with 1‐year follow up after operation were included for long‐term outcome analysis.ResultsA total of 331 testes in 290 boys were included; 244 (73.7%) testes were congenital while 43 (13%) were acquired UDT. Of the 43 acquired UDT, 28 (65.1%) had been followed up by us for retractile testis and had significantly earlier orchidopexy than those who had not (6 vs 9.6 years; P = .04). More patients with acquired UDT had hypospadias (20%) compared with 2.3% in those with congenital UDT (P &lt; .001). The median follow up time was 8 years (1‐13 years) and the overall success rate of orchidopexy was 93.8% (271/289). The median time to detect any late complication was 17.5 months (3‐46 months).ConclusionAcquired UDT accounted for at least 13% of orchidopexies in our centre. Patients after orchidopexy should have a minimum follow up time of 4 years in order to detect any late failures. Early referral of retractile testes to a specialised paediatric surgical centre for regular follow up is recommended for earlier detection of acquired UDT. Boys with a history of hypospadias and retractile testes had higher risk of acquired UDT.

The role of sonic hedgehog homologue signal pathway in hypospadias aetiology

Hypospadias is one of the most common congenital anomalies of the male genitalia. Sonic hedgehog homologue (SHH) signalling pathway is believed to be involved in the development of the male genital system. In this clinical prospective study, the role of the SHH pathway in hypospadias aetiology was investigated. In this study, 200 healthy children (boys without hypospadias, control group), 118 patients (boys with distal hypospadias) and 82 patients (boys with proximal hypospadias) of age 0-16 years were included. The expression of the genes suppressor of fused protein (SUFU), SHH, protein patched homologue (PTCH; PTCH1 and PTCH2), glioma-associated oncogene homologue (GLI; GLI1, GLI2, GLI3 and GLI4), smoothened, frizzled-class receptor (SMO) and serine/threonine-protein kinase 36 (STK36) that are involved in SHH pathway were investigated. Furthermore, polymorphism analyses of GLI2, SHH and PTCH1 genes were performed. The history of hypospadias in the first and second-degree relatives of the patients in boys with distal hypospadias and boys with proximal hypospadias was inquired. Ten patients in the boys with distal hypospadias and twenty patients in the boys with proximal hypospadias had a history of hypospadias in first or second-degree relatives (p<0.05). There was a significant decrease in mRNA expressions of SHH and PTCH1 genes in boys with proximal hypospadias compared to boys without hypospadias (p<0.05). Besides, a significant decrease in mRNA fold-change of GLI2 gene was detected in boys with both distal hypospadias and proximal hypospadias compared to boys without hypospadias (p<0.05). In contrast, there was no significant difference in the mRNA fold-changes of PTCH2, SUFU, GLI1, GLI3, GLI4, SMO and STK36 genes among the groups. Moreover, there were no significant differences in the frequencies of variant genotypes and alleles rs735557, rs12711538 and rs4848632 (GLI2 gene), rs104894049 (SHH gene) and rs41313327 (PTCH1 gene) (p>0.05). SHH expression is required for the growth and differentiation of the genital bulge. Developmental defects in the external genital organs were demonstrated in mice with SHH deletion. It has been demonstrated that SHH mainly plays a role in the formation of sinusoid morphology of the penis. In the present study, although SHH and PTCH gene expressions were found to be decreased only in the penile tissues of proximal hypospadias, GLI2 gene expression was decreased in penile tissues of boys with both distal hypospadias and boys with proximal hypospadias. Genes involved in the SHH pathway might play a role in the aetiology of hypospadias. Furthermore, there is a correlation between molecular defects in this pathway and severity of hypospadias.

Management of the Transitional Urology Patient: the Role of the Adult Reconstructive Urologist.

Patients with congenital urologic conditions present unique challenges as adults. Herein, we review the literature relevant to the adult reconstructive urologist confronted with complex surgical concerns affecting their patients with a history of hypospadias, spina bifida, and other syndromes affecting the genitourinary tract. Urethral stricture disease related to hypospadias is complex, but successful urethroplasty and penile curvature correction can be achieved with an anatomically minded approach. Multiple urinary diversion techniques can be considered in a patient-centered approach to bladder management in the adult spina bifida patient, but complications are common and revision surgeries are frequently required. Strong evidence is lacking for most surgical techniques in this population, but experiences reported by pediatric and adult urologists with genitourinary reconstruction training can help foster consensus in decision-making. Urologists trained in genitourinary reconstruction may be uniquely positioned to care for the transitional urology patient as they enter adolescence and adulthood.

Hipospadiaslı Çocuklarda Risk Faktörlerinin Değerlendirilmesi

Objective: Hypospadias is one of the most common congenital defects in boys. Multifactorial factors such as genetic predisposition and environmental factors play a role in the etiology of hypospadias. In this study, we investigated the risk factors of patients diagnosed with hypospadias. Materials and Methods: Thirty-six patients who applied to the pediatric endocrinology and urology outpatient clinics with the diagnosis of hypospadias were evaluated retrospectively. Risk factors were evaluated by recording the parental ages, exposure to environmental factors, the maternal BMI, history of pregnancy, drug use, and the father’s fertility status. Results: The mean age of the patients was 3.5 ± 2 years. The patients had anterior (n:27 : 75%), middle (midshaft) (n:8 ; 22.2%), and posterior (n:1 ; 2.8%) hypospadias. The mean body mass index (BMI) of the mothers was 24 ± 4.1 kg/m2. Eight (22.2%) mothers were overweight and six (16.6%) mothers were obese. There was a history of hypospadias in the family of 4 (11%) patients. Conclusion: Although combinations of environmental and genetic factors play a role in the etiology of hypospadias, many unexplained factors are responsible for this disease.

OR17-05 Hypospadias Is a Predictor of Adverse Cardiometabolic Risk in Adulthood - a Case-Control Study

Introduction: Abnormal development of the genital tract during the first trimester can lead to hypospadias. This stage coincides with the programming window during which androgens are required for normal masculinisation of the genital tract. Since fetal development may also be associated with long-term effects on cardiometabolic outcome and testosterone is itself an important vascular hormone, we questioned whether adults with a history of hypospadias are at increased risk of long-term cardiovascular and metabolic disease. Aim: This retrospective study determined if hypospadias is associated with increased risk of cardiometabolic disease later in life. Methods: Cardiovascular and diabetes admissions data were extracted through record linkage for all males with a history of hypospadias (ICD10 Q54) from 1981 to 2019 through the NHS Scotland Information Services Division after ethics approval. Controls were matched for age, birthweight, gestation and deprivation index. Incident admissions for angina, arrhythmia, diabetes, heart failure, ischaemic heart disease, myocardial infarction, peripheral arterial disease, renal failure and stroke were obtained for each individual. Case control analysis was performed using Chi square test using R. Results: Admission data on 13,481 men with hypospadias and 9,615 matched controls were reviewed. Men with hypospadias had a 10- fold higher risk of diabetes (9.7 [8.4-11.2], p<0.0001); 9- fold higher risk of ischaemic heart disease (OR [95% CI] 9.1[8.1-10.2], p<0.0001); 8- fold higher risk of renal failure (7.9 [6.9-9.1], p<0.0001); 6- fold higher risk of stroke (6.2 [5.2-7.2], p<0.0001); 6- fold higher risk of myocardial infarction (6.4 [5.6-7.3], p<0.0001); 6-fold higher risk of angina (5.9 [5.3;6.8], p<0.0001); 5-fold higher risk of arrhythmia (4.8 [4.2-5.4], p<0.0001) 5- fold higher risk of peripheral arterial disease (4.8 [3.7-6.1], p<0.0001) and 4- fold higher risk of heart failure (3.6 [3.1-4.1], p<0.0001). Conclusions: Men with a history of hypospadias are at significantly increased risk of admission for treatment for cardiovascular and metabolic conditions, especially ischaemic heart disease, diabetes and renal failure. The mechanisms underlying this observed increase are unclear and merit further evaluation.

MP35-19 DECREASED SUCCESS OF GERIATRIC BULBAR URETHROPLASTY

You have accessJournal of UrologyTrauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) I (MP35)1 Apr 2020MP35-19 DECREASED SUCCESS OF GERIATRIC BULBAR URETHROPLASTY Jeffrey Wooliscroft*, Nicolas Ortiz, Adam Baumgarten, Ellen Ward, Steven Hudak, and Allen Morey Jeffrey Wooliscroft*Jeffrey Wooliscroft* More articles by this author , Nicolas OrtizNicolas Ortiz More articles by this author , Adam BaumgartenAdam Baumgarten More articles by this author , Ellen WardEllen Ward More articles by this author , Steven HudakSteven Hudak More articles by this author , and Allen MoreyAllen Morey More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000879.019AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Recent studies suggest that older men may have decreased success rates after urethroplasty. We hypothesize that older men have lower success rates after bulbar stricture repair. We aimed to compare stricture characteristics, method of repair, and outcome in patients undergoing bulbar urethroplasty in young, middle, and older aged patient groups. METHODS: We retrospectively reviewed our single–surgeon urethral stricture database between 2007 and 2019. Men were age-stratified into cohorts based on age at the time of surgery. These criteria were chosen to represent the wide range at which bulbar stricture patients present including young (≤30), middle (31-60), and older age (>60) patient cohorts. Surgical success rate, mean stricture length, and stricture method of repair were analyzed. We included only selected patients with isolated bulbar urethral strictures; for this reason, individuals with history of hypospadias, penile strictures, posterior urethral strictures, perineal urethrostomy, and pelvic radiotherapy were excluded as they represent pathologic processes outside the focus of this study. RESULTS: We identified 654 patients with isolated bulbar urethral strictures. Of these, 130 (19.87%) were younger than 30 years old, 340 (51.99%) were 31-60, and 184 (28.13%) were older than 60. Over a median follow-up of 35.2 months, overall success rates decreased as patients advanced in age between cohorts (97.7% vs. 91.4% vs. 88.8%, p=0.01). Mean stricture length was significantly longer in patients aged 31-60 and over 60 compared to patients under 30 (2.81 cm and 2.80 cm vs. 2.26 cm respectively, p=0.005). Urethroplasty with buccal mucosal graft (BMG) had decreased success rates among men greater than 60 (90.9% vs. 90.9% vs. 70%, p=0.01) while the success rate of excision and primary anastomosis (EPA) remained constant in all age cohorts (98.7% vs. 93.5% vs. 95%, p>0.05). Both older patient cohorts were less frequently managed with excision and primary anastomosis than younger men (71.2% and 60.8% vs. 82.3% respectively, p=0.0002). CONCLUSIONS: Among patients who underwent bulbar urethroplasty, older men had the lowest overall success rate. Patients treated with EPA urethroplasty appeared to have better success than those treated with BMG urethroplasty. Regardless of technique, urethral reconstruction remains a safe and effective treatment for aging males with bulbar urethral strictures. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e520-e520 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jeffrey Wooliscroft* More articles by this author Nicolas Ortiz More articles by this author Adam Baumgarten More articles by this author Ellen Ward More articles by this author Steven Hudak More articles by this author Allen Morey More articles by this author Expand All Advertisement PDF downloadLoading ...

Age ≤40 is an independent predictor of anastomotic urethroplasty and successful repair of bulbar urethral strictures.

Among men with bulbar strictures, we aimed to analyze stricture characteristics, repair type, and treatment success in younger versus older patient cohorts. We retrospectively reviewed our single surgeon database with patients undergoing bulbar urethroplasty from 2007 to 2017. This population was then age-stratified into ≤40 and >40-year-old cohorts. Exclusion criteria included patients with penile strictures and those with history of hypospadias. Patient characteristics, surgical approach, and outcome were compiled by medical record and database review. Criterion for success included functional emptying and lack of repeat surgical intervention. Parameters associated with failure were included in multivariate logistic regression models. Eight hundred and fifty-three patients with bulbar strictures were identified, 231 patients (27.1%) ≤40 years old and 622 patients (72.9%) >40 years old. Mean stricture length was significantly longer in older men (2.3 vs. 2.7 cm, P=0.005). Excision and primary anastomosis (EPA) were more commonly utilized when managing younger compared to older patient groups (87% in ≤40 group, 77% in >40, P=0.0009). Younger men underwent significantly fewer endoscopic stricture treatments than older men (2.1 vs. 4.9, P=0.001). Traumatic etiology was more commonly attributable in the younger group (48% vs.17%, P<0.0001). Younger men presented less frequently with diabetes (1.7% vs. 21.7%, P<0.0001), coronary artery disease (0.4% vs. 19.1%, P<0.0001), and erectile dysfunction (11.5% vs. 29.2%, P<0.0001) relative to older men. Over a median follow-up of 52.4 months, success rates were higher in the ≤40 cohort (97.4%) than the >40 cohort (87.3%, P<0.0001). On multivariate logistic regression, independent predictors of urethroplasty success include younger age), utilization of EPA, and lack of pelvic radiation. Although men ≤40 years old have a higher incidence of traumatic etiology, bulbar urethroplasty has a higher success rate when compared to patients >40 years old. Bulbar strictures are more amenable to EPA in the younger population, likely due to fewer endoscopic treatments and favorable tissue characteristics.

Endocrine and Cytogenetic Profile of Variations in Genital Development: Series of 9 Cases at the Mali Hospital

We carried out a retrospective and descriptive study in the Medicine and Endocrinology service of the Mali Hospital from January 2015 to December 2018. Nine cases of anomalies in sexual differentiation were referred for pubertal delay, growth retardation, gynecomastia, micropenis or infertility. Outcomes: The average age was 14 years; 5 patients were declared female at birth; 2 were married without children; 7 patients came from the region of Kayes; 8 patients consulted for pubertal delay; 1 patient presented with association of a blind vagina and 2 bilateral inguinal gonads. 3 of 4 patients declared male at birth had a micropenis; 2 patients had gynecomastia with a history of hypospadias. Ultrasound and biological data showed a clinical-hormonal picture of hypergonadotropic hypogonadism in 6 patients, 1 case of hypogonadotropic hypogonadism with hypercorticism and 2 cases with normal gonadotropic axis; two cases of azoospermia. Karyotypic analysis showed: 3 cases of SK, 2 cases of Klinefelter Syndrome, 2 cases of Androgen Insensitivity Syndrome and 2 cases of male 46 XX syndrome including one with sry negative. Conclusion: The precise diagnosis of anomalies in sexual differentiation remains complicated in Mali, due to the inadequacy of the technical platform. Diagnosis must be made at an early stage to allow normal growth, puberty and satisfactory fertility. Taking charge of the medical treatment possibly associated with plastic surgery could give good results.

SAT-285 Role of Chromosome Microarray in Identifying a Genetic Cause of Undervirilized External Genitalia and Growth Delay in an Infant: 6p Duplication Associated with Short Stature and Micropenis

THE CASE 4 mo M born at term 7lbs 7.5oz, 19.5 inches via C-section, referred for micropenis found during evaluation for circumcision. No history of hypoglycemia. Of note, dad is s/p hypospadias repair and is short at 5th %ile. PE showed short stature, length at 3rd %ile (-1.91 SDS), wt 53rd %ile, HC 76th %ile. Stretched penile length 1.5 cm (-2.5 SDS = 1.9cm), testes 1.5 cm each, normal. Periorbital hemangioma noted. Otherwise normal exam. Chromosome microarray showed a 6.1 Mb duplication of the terminal region of 6p, pathogenic; and a 222 kb deletion of terminal 17p (felt to have no clinical significance). Patient referred to Genetics. Parental testing showed balanced translocation in dad's chromosome 46,XY,t(6;17)(p25.1;p13.1)]. GH, TSH, FT4, LH, FSH, AMH levels normal. Total Testosterone 68 ng/dL. CAH-6 panel within expected limits. Testosterone therapy 50mg/mo x 3mos initiated to improve penile length. DISCUSSION Workup of underlying cause of male undervirilization is challenging. More often than not, a definitive diagnosis remains elusive. The current case underlines the invaluable contribution of chromosomal microarray in this endeavor. Duplication of distal fragment of chromosome 6p is extremely rare, with <50 cases reported thus far. There are several genes located in this region, and as expected, case reports thus far have a wide phenotypic variability. Common features include pre-/postnatal growth delay, developmental disability, congenital malformations of the heart, kidneys, eyes. However to our knowledge, this is the first report of a patient with 6p25pter with micropenis. Of note, a patient with 6p25pter + 22q11.2pter trisomies was reported to have penile chordee and cryptorchidism (Scarborough, et al, 1986). Patienit's dad has history of hypospadias as well, suggesting a correlation between this specific mutation and undervirilized male external genitalia. Review of 26 OMIM genes contained in the reported abnormal region showed scant known data about these genes. However, gene transcripts from 5 of these OMIM genes (DUSP22, FAM50B, HUS1B, FOXQ1, SERPINB9) were shown to be highly expressed in the testis +/- brain in humans/animals, suggesting a possible role that these genes play in male genital development. CONCLUSION A genetic cause of micropenis is often hard to establish. We report a case associated with a pathogenic duplication of the terminal region of 6p chromosome. To our knowledge, no such case has been previously reported. This rare chromosome abnormality does have other associated medical complications for which he needs to be monitored. The crucial role of chromosome microarray in picking up such abnormalities in workup of undevirilization is emphasized. More research is needed to elucidate the mechanism by which the affected genes influence male genital development.

092 Age ≤40 Is An Independent Predictor Of Anastomotic Urethroplasty And Successful Repair Of Bulbar Urethral Strictures

Our impression is that younger men tend to have straightforward bulbar urethral strictures compared to middle-aged and older patients, with more robust tissue characteristics and fewer attempts at endoscopic manipulation We sought to compare stricture characteristics, repair type, and treatment success in younger versus older patient groups. A single surgeon retrospective review of patients undergoing bulbar urethroplasty between 2008 and 2017 was performed, age-stratified into ≤40 and >40 yo. Penile strictures and those with history of hypospadias were excluded. Patient characteristics, surgical approach and outcomes were collected by review of a large, tertiary urethroplasty database. Success was defined by functional emptying and lack of repeat surgical intervention. Parameters associated with failure were included in multivariate logistic regression models. A total of 750 patients with bulbar strictures were identified, with 204 patients (27.2%) ≤40 years old, and 546 patients (72.8%) >40 years old. Mean stricture length was similar between the younger and older groups (2.4 vs. 2.7 cm, respectively, p=0.10). Percentage of patients managed with excision and primary anastomosis (EPA) declined with age (89% in ≤40 group, 77% in >40, p=0.002). Younger men had undergone significantly fewer endoscopic stricture treatments than the older group (1.8 vs. 5.4, p<0.001). Traumatic etiology was more commonly identified in the younger cohort (48% vs. 24%, p<0.001). The ≤40 group less frequently presented with diabetes (2% vs. 22%, p<0.0001), coronary artery disease (0.5% vs. 20%, p<0.0001), and erectile dysfunction (11% vs. 27%, p<0.0001) compared to older men. Over a median follow-up of 52.4 months, success rates were higher in the ≤40 cohort (96.9%) than the >40 cohort (85.8%, p=0.001). On multivariate logistic regression analysis, independent predictors of urethroplasty success include younger age (OR 0.51, CI 0.28-0.95, p=0.02), utilization of EPA (OR 2.49, CI 1.27-4.90, p=0.01), and lack of pelvic radiation (OR 2.40, CI 1.09-5.28, p=0.03).

Clinical significance of cystoscopic urethral stricture recurrence after anterior urethroplasty: a multi-institution analysis from Trauma and Urologic Reconstructive Network of Surgeons (TURNS).

To assess the functional Queryoutcome of patients with cystoscopic recurrence of stricture post-urethroplasty and to evaluate the role of cystoscopy as initial screening tool to predict future failure. Cases with cystoscopy data after anterior urethroplasty in a multi-institutional database were retrospectively studied. Based on cystoscopic evaluation, performed within 3-months post-urethroplasty, patients were categorized as small-caliber (SC) stricture recurrence: stricture unable to be passed by standard cystoscope, large-caliber (LC) stricture accommodating a cystoscope, and no recurrence. We assessed the cumulative probability of intervention and the quality of life scores in association with cystoscopic recurrence 1-year post-urethroplasty. Patients with history of hypospadias, perineal urethrostomy, urethral fistula, and meatal pathology were excluded. From a total of 2630 men in our cohort, 1054 patients met the inclusion criteria: normal (n = 740), LC recurrence (n = 178), and SC recurrence (n = 136) based on the first cystoscopic evaluation performed at median 111days postoperatively. Median follow-up was 350days (IQR 121-617) after urethroplasty. Cystoscopic recurrence was significantly associated with secondary interventions (2.7%, 6.2%, 33.8% in normal, LC, and SC groups, respectively). Quality of life variables were not statistically significantly different among the three study groups. Many patients with cystoscopic recurrence do not need an intervention after initial urethroplasty. Despite good negative predictive value, cystoscopy alone may be a poor screening test for stricture recurrence defined by patient symptoms and need for secondary interventions.

Four Cousins with Hypospadias, Is It Familial or Environmental? (Case Report)

Hypospadias is one of the most common birth defects. However, its etiology remains largely unknown. Genetic and also intrauterine environmental factors have a principal role in causing familial hypospadias. Hypospadias repair is done through several techniques, one of which is Snodgrass technique which has many advantages. The 4 cousins underwent repair with no complications during 6 months follow up period. Methods: Urethroplasty using Snodgrass hypospadias repair of 4 cousins with positive parental consanguinity and absent family history of hypospadias. Results: 4 cousins underwent Snodgrass (Tubularized incised plate urethroplasty) with no complications after 6 months follow up. Conclusion: Although there is high heritability of hypospadias that also aggregates within second- and third-degree relatives, environmental factors may play a principal role in causing familial hypospadias. Hypospadias repair has a long learning curve. The continuous auditing should be done to improve the results.

Excision and Primary Anastomosis Reconstruction for Traumatic Strictures of the Pendulous Urethra

ObjectivesTo present a multi-institutional experience with functional and patient-reported outcomes among men undergoing excision and primary anastomosis (EPA) urethroplasty for pendulous urethral strictures. MethodsWe describe the technique and present our experience with EPA for focal penile strictures. Patients undergoing urethroplasty (2004-2017) at 2 tertiary referral centers were reviewed, of whom 14 (0.7%) underwent EPA of radiographically confirmed pendulous urethral strictures. Validated questionnaires were utilized to evaluate overall improvement (Patient Global Impression of Improvement), urinary bother (International Prostate Symptom Score), and sexual function (International Index of Erectile Function-5). Treatment success was defined as urethral patency without need for subsequent reconstruction. ResultsAmong 14 men undergoing penile EPA, 13/14 (93%) had durable treatment success over a median follow-up of 43 months. No patient reported penile curvature postoperatively. Stricture etiology in most cases was posttraumatic (12/14), of which 4 had a history of urethral disruption secondary to penile fracture and 8 iatrogenic trauma. Median age was 51 years (IQR 30-60) and stricture length 1.0 cm (IQR 1.0-1.4). Erectile function was normal in 8/14 patients preoperatively, and postoperative median International Index of Erectile Function was 21. Most men reported significant global improvement in condition (median Patient Global Impression of Improvement 2, IQR 1-3) and most had only mild urinary bother (median International Prostate Symptom Score 4, quality of life 1). The single treatment failure had a history of hypospadias with multiple prior urethral procedures. ConclusionFor men with short strictures of the pendulous urethra, EPA has a high success rate, without adverse sequelae such as erectile function or penile curvature.

Urethral Reconstruction in Aging Male Patients

To report stricture characteristics, complications, and treatment outcomes among elderly men undergoing urethral reconstruction. A retrospective review of urethroplasty cases and outcomes by a single surgeon from 2007 to 2014 was performed. Men were stratified by decade of life at time of surgery (<50, 50-59, 60-69, ≥70 years). Individuals with a history of hypospadias were excluded. Among 514 urethroplasty procedures, 184 (36%) were evaluated in men ≥60 years. When stratified by decade of life, elderly men were more likely to have a history of radiation therapy (0% vs 5% vs 19% vs 50%; P <.0001) and experience treatment failure (6% vs 16% vs 20% vs 26%; P <.0001) during follow-up (median 63 months). The estimated 60-month stricture recurrence-free survival decreased with increasing age at time of urethroplasty (94% vs 89% vs 78% vs 74%; P <.0001). In patients ≥60 years, success rates of anastomotic, substitution, and urethrostomy techniques were 80%, 65%, and 88%; anastomotic urethroplasty success improved after excluding those patients with prior radiation. After surgery, elderly were more likely to have voiding dysfunction and <90-day Clavien ≥3 complications requiring endoscopic intervention. On multivariable analysis, advancing age per decade beyond 50 years was independently associated with risk of urethroplasty failure-50-59 (hazard ratio [HR] 2.39; P = .02), 60-69 (HR 2.80; P = .009), and ≥70 (HR 3.43; P = .003). Urethroplasty is safe and effective in the majority of elderly men. Early reconstructive intervention with anastomotic urethroplasty or urethrostomy techniques may optimize outcomes. Voiding dysfunction and prostatic obstruction are common in this population and should be pursued as clinically indicated.