Should we correct hypospadias during childhood? Decision Regret And QUality of Life Assessment (DRAQULA) study.

AIM OF THE WORK: To evaluate patient's satisfaction, Decision Regret And QUality of Life Assessment (DRAQULA) among adolescents (older than 15 years) and adults after hypospadias surgery in childhood. PATIENTS AND METHODS: 234 Patients operated on hypospadias as children in our center and their parents were contacted after they reached the age of 15 years to complete a questionnaire survey to assess satisfaction with the operative result, the regret with the operative decision and the health related quality of life (HRQOL). The survey is based on the Decision Regret Scale available in the literature with a score of 100 meaning maximum dissatisfaction or regret, and on the Kidscreen10 index. Satisfaction was measured on a scale from 1 to 5 with 5 signifying full satisfaction. RESULTS: 81 of 234 patients from 15 to 43 years (mean age 19.7 years) completed the survey (34.6 %). 44 Patients had distal, and 17 proximal hypospadias and the remaining 20 patients could not remember the type of hypospadias they had. The patient's satisfaction with the operative result was 5 (full satisfaction) in 74.1 %, 4 in 18.5 %, 3 in 6.2 % and 2 in 1.2 % (mean satisfaction score 4.7 of 5). Regarding decision regret among patients, 64/81 patients (79.0 %) had no decision regret. Only 14.8 % reported mild and 6.2 % moderate decisional regret (mean decisional regret score 4.8). 71 of 234 parents answered the parents' questionnaire (30.0 %). Fifty-eight (81.7 %) had no decision regret. 13 parents (18.3 %) had decision regret; 10 parents (14.1 %) reported mild, 2 parents (2.8 %) moderate, and only one parent (1.4 %) reported strong decisional regret. The mean HRQOL T-score was 55.9 (SD 10, control Group of adolescent males from 12 to 18 years.) and thus corresponded to the average of the reference normal population. DISCUSSION: In this study, only 19.7 % had decision regret as compared to 50-65 % reported in literature. The decision regret scale of O'Connor needs to be revalidated as even candidates who approve of the decision of early surgery have a score less than 25 and considered to have decision regret. CONCLUSION: The results of the survey showed that 90 % of the patients were satisfied with early hypospadias surgery with average HRQOL and low level of decisional regret in patients as well as parents. The findings support the current practice of operating hypospadias in early childhood.

Hormone receptor expression in hypospadias.

INTRODUCTION: Sex hormone imbalance in utero is hypothesized to play an important role in the pathogenesis of hypospadias. Due to its easy accessibility, foreskin samples have been used to describe hormone receptor expression in rodents, and both adult and pediatric patients. In this study we conducted a systematic approach to assess hormone receptor expression in pediatric patients with hypospadias compared to healthy controls with a focus on age-matching and differences in severity and degree of hypospadias. METHODS: Foreskin samples were collected from 35 children during hypospadias operations (18 distal and 17 proximal hypospadias) and compared with ventral foreskin samples of a control group of 32 children during circumcision (15 age-matched and 17 older boys). The samples were stained with H/E, androgen (AR), estrogen (ER) and progesterone receptors (PR). The receptor stainings were blindly evaluated. An Allred score was used to evaluate receptor expression in both the epithelium as well as stroma. RESULTS: AR was detected in all cases. AR expression in the stroma was more evident than in the epithelium. AR expression in the hypospadias groups was significantly less than the age matched controls (p < 0.05). There was no significant difference between the two hypospadias groups nor between the two control groups. Older control group showed significantly elevated levels of AR expression compared to the hypospadias group (p < 0.05). ER was also detected in all cases. The stroma showed more ER than in epithelium. PR was minimal or negative in all samples. CONCLUSION: Boys with hypospadias showed significantly weaker expression of androgen receptors than age matched controls. The severity of hypospadias did not influence hormone receptor distribution. AR expression is better observed in the stroma than in the epithelium. There was no difference in ER expression between the hypospadias group (distal or proximal) and age matched normal controls. ER was expressed in larger numbers in normal older preputial tissue. The foreskin of prepubertal boys shows little to no expression of PR.

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

AIM OF THE STUDY: To test the accuracy and reliability of the natural erection test (NET) as compared to the artificial erection test in assessing penile curvature in hypospadias. MATERIALS AND METHODS: 50 children underwent both natural and artificial erection tests intraoperatively between January 2020 and October 2021. These included 5 glandular, 26 distal, 9 proximal, and 10 perineal hypospadias patients with curvature. The mean follow up period was 20 months (range 16-37). Under anesthesia, the curvature was assessed before degloving, then after degloving using both the natural and the artificial erection test. The NET test was repeated after curvature correction (3 times per patient). The measurements were analyzed using paired t-test. TECHNIQUE OF NATURAL ERECTION TEST: Two fingers of the left hand press just below the symphysis pubis to stop blood drainage from the penis and two fingers of the right hand massage the blood from the perineum distally into the penis until it becomes hard without tourniquet. The standard artificial erection test was performed using saline injected through a butterfly needle into the corporeal bodies without tourniquet. Photos were taken of both tests using the exact angle and angle of curvature was measured using Angle Meter App. RESULTS: There was no statistically significant difference between both erection tests with a P value of 0.705. The Bland-Altman plot also showed that all studied children have a difference in their natural and artificial erection tests within the limits of agreements. DISCUSSION: Erection is commonly induced using the artificial saline injected erection test first described by Gittes and less commonly using pharmaceutical erection test first described by Perovic. The severity of chordee apparent during artificial erection test varies with the amount of pressure used during injection. Also, it is difficult to place the tourniquet proximal enough to detect chordee at the base of the penis. It may be associated with hematoma formation, oedema, postoperative pain and the need for multiple punctures to assess the curvature before and after repair. Disadvantages of the pharmacological-induced erections in hypospadias include increased blood loss during erection, additional cost, and the need for a reversal agent. The natural erection test mimic the normal erection mechanism and may avoid all these potential disadvantages. CONCLUSION: The study showed that the natural erection test is easy to perform, non-invasive, non-traumatic and can be repeated several times intraoperatively without the need of repeated puncturing of the corpora cavernosa and avoids the potential risks and complications of the artificial erection test.

The urethral plate and the underlying tissue; a histological and histochemical study.

OBJECTIVE: To examine the urethral plate and the underlying tissues in children with proximal hypospadias associated with severe chordee. MATERIALS AND METHODS: The urethral plate and the underlying tissue specimens were excised to correct severe chordee in 17 children with proximal and perineal hypospadias with severe chordee. The median age was 20 months (range 8-36). Sections samples were marked and examined from proximal to distal. Specimens were examined histologically using hematoxylin-eosin (H/E) and Elastic van Gieson (EvG) stain. Histochemical examination was also performed using smooth muscle actin (SMA) and factor 8 antibodies. For control, samples from four patients with hypoplastic urethra proximal to the meatus including the hypoplastic segments until the normal urethra were taken. In addition, the urethra of an adult patient with penile tumor was used as control. RESULTS: The average size of the 17 tissue samples was 0.5 cm × 0.5 cm x 0.3 cm in depth. There was a common pattern that was seen in all the 17 specimens with a variable degree of expression. H/E staining showed that the epithelial lining changed from pseudostratified epithelium at the proximal intact urethra to non-keratinized stratified squamous epithelium at the urethral meatus to keratinized stratified squamous epithelium distally at the urethral plate level. EvG staining showed overall very few elastic fibres that increased slightly in the distal urethral plate. SMA staining showed a circular pattern of smooth muscle cells in the proximal intact urethra that changed to a U-shaped pattern at the level of the meatus, to a triangle shaped pattern just distal to the meatus. The distal urethral plate showed an irregular, disorganized rather flat pattern of the smooth muscles. Factor 8 antibodies staining the blood spaces revealed dysplastic unorganized large blood sinusoids underneath the urethral plate that were different from normal capillaries surrounding the proximal urethra. CONCLUSION: The urethral plate and the underlying tissues in patients with severe chordee have different structure from normal urethra as compared to available literature and the adult control patient. The lack of elastic fibres may help to explain the rigidity of the ventral penis causing chordee. The disorganized irregular distribution of the smooth muscle fibres is suggestive of the hypoplastic corpus spongiosum. The abnormal large blood sinusoids may explain the poor healing quality of the ventral penis in patients with perineal and proximal patients associated with severe chordee. This may explain persistent/recurrent chordee observed later in those patients with severe chordee when dorsal plication is used. The study also supports the recent trend of 2 stage procedure as a plan of management for patients with proximal and perineal hypospadias with severe chordee and excision of all the dysplastic tissues during the first operation.

Preoperative glans & penile dimensions in different hypospadias grades.

PURPOSE: To report glans and penile dimensions in 1023 consecutive boys with hypospadias. PATIENTS & METHODS: Boys admitted for hypospadias surgery between 2016 and 2018 were included in this study. Age ranged between 6 and 36 months. Boys who underwent previous surgery, received hormone therapy or older than 36 months were excluded. The hypospadias was classified according to ICD and WHO classification into glanular (Grade I), distal (Grade II), proximal (Grade III) and perineal (Grade IV). The flaccid penile length (PL), the dorsal glans length (DGL), the ventral glans length (VGL) and the glans width (GW) were measured in the operating room under anaesthesia just before operative correction. Small (GW) in this study was defined as less than 14 mm. RESULTS: 1023 boys were included. 273 had glandular, 468 distal, 194 proximal and 88 perineal hypospadias. The mean glans width was 14 mm with a range of 8 to 20 mm. The mean glans width for glanular hypospadias was 14.0 mm (range 9-19 mm), 14.0 mm (range 10-20 mm) for distal hypospadias (p > 0.05), 13.1 mm (range 9-19 mm) for proximal hypospadias (p < 0.0001) and 11.1 mm (range 8-16 mm) for perineal hypospadias (p < 0.0001). 460 (45.0%) of all patients presented with a small glans width. In glanular hypospadias it was 99 (36.3%), 167 (35.7%) in distal hypospadias, 111 (57.5%) in proximal hypospadias and 83 (94.3%) in perineal hypospadias. There was no significant difference in the glans size between the age of 6 and 24 months (p > 0.2), but there was a difference when compared to patients older than 25 months (p < 0.05). CONCLUSIONS: A small glans is found in about a third of distal, two thirds in proximal and more than 90% of perineal hypospadias.

Ano-Scrotal Distance (ASD) : Is it a marker for the severity of chordee?

OBJECTIVE: To evaluate the relation between ASD and the severity of chordee and hypospadias in a referral center. METHODS: The distance between the anal verge and proximal scrotal edge (ASD) was measured in hypospadias patients between 6 and 18 months between 2016 and 2020 in the operating room under anaesthesia. Patients older than 36 months and younger than 6 months were excluded. The patients were classified according to meatus into: Grade I (glandular or chordee without hypospadias), II (distal), III (proximal) and IV (perineal). Chordee was assessed by erection test and classified into 2 groups; Group I: no chordee or mild chordee <30 and Group II: with severe chordee >30. Short ASD was defined as ≤ 2.0 cm. RESULTS: 817 boys were included. The patients were classified according to the hypospadias grades I (180 pt), II (415 pt), III (120 pt) and IV (102 pt). The median ASD for group I was 3.07 cm (range 1.0-5.5), for group II 3.10 cm (range 1.5-5.0), for group III 2.40 cm (range 1.5-54.5) and for group IV 2.10 cm (range 1.0-3.5). The average ASD of the patients in Grade III and IV (2.26 cm) was significantly shorter than the average ASD of the patients in Grade I and II (3.09 cm) (p < 0.05). 184 patients had an ASD ≤2.0 cm. 38% of patients with glanular hypospadias (grade I) with ASD ≤ 2.0 cm had severe chordee. CONCLUSION: This study shows that short ASD is a helpful marker of the severity of chordee and hypospadias. Patients with glanular hypospadias and short ASD have 38% chance of having severe chordee.

History of hypospadias: Lost in translation.

The evolution of hypospadias surgery can be classified under 3 periods that were closely related to advances in surgical instruments, introduction of anesthesia, and newer suture materials. Stretching dominated the early period, tunneling during the Middle Ages, and flaps during the modern period. Suture materials have included at various time silver wires, horsehair, and stainless steel. Examination and translation of the original manuscripts showed that Galen recommended stretching and suturing of glanular hypospadias and not amputation or partial penectomy as has been currently reported. The term chordee was first introduced in the 18th century in relation to gonorrhea and was defined as "painful imperfect erection of the penis during gonorrhea, with downward incurvation." This was a common complication of gonorrhea before the introduction of antibiotics. Mettauer, Duplay, Mayo, and others used the terms incurvation, ventral deformity, ventral curvature, and others. Clinton Smith in 1938 was the first surgeon to use the term congenital chordee in direct relation to hypospadias. The use of prepuce for urethroplasty, popular now, was first reported by Liston in 1838, Rochet in 1899, Russell in 1900, and Mayo in 1901. The two stage repair performed in the early 20th century differed from that in the early 21st century in that urethroplasty was performed in the first stage and only anastomosis to the original meatus was performed in the second stage. The two-stage repair, currently known as Bracka's two-stage repair, was first described in 1962 by Cloutier. The use of the urethral plate in epispadias was first described by Liston in 1838, Thiersch in 1869 and by Anger & Duplay in hypospadias in 1874. Partially epithelialized urethroplasty using the urethral plate was described by Duplay in 1880, Russell 1915, Denis Browne 1940, Reddy 1975, Orkiszewski 1987, Rich 1989, and Snodgrass in 1994. LEVEL OF EVIDENCE: V.

Development of the human male urethra: a histochemical study on human embryos.

PURPOSE: Controversy persists regarding the formation of human penile urethra. The classic fusion theory for the development of the spongy urethra and ectodermal ingrowth or endodermal transformation theories for the development of the glanular urethra do not explain the wide spectrum of anomalies seen in patients with hypospadias. This histological study was made to clarify the mechanism of urethral development. MATERIALS & METHODS: 15 human male embryos ranging from 6 to 14 weeks were studied. The phalluses were examined microscopically and photographed. Tissues were prepared as serial histological sections and stained with haematoxylin and eosin and with special immuno-histochemical stains. RESULTS: 1) The penile urethra: At 6 weeks of gestation, the urethral plate which is solid distally and partially grooved proximally becomes grooved distally and has fused proximally by 8 weeks. At 14 weeks of gestation; the urethral opening migrates only to the middle of the shaft. 2) The glanular urethra: At the 6th week of gestation, a solid epithelial plate reached the tip of the genital tubercle, and a glans cannot be identified. At the 7th week, a central vacuolation appears and the penile urethral groove does not reach the tip of the phallus. At the 8th week; coronal sulcus starts to appear, and a well defined blind central canal was evident in the 13th week. During the 14th week, the floor of the glanular canal degenerated to form a glanular groove. CONCLUSIONS: Our observations suggest that the spongy urethra passes through 3 stages of development: a solid epithelial plate, deep urethral groove, and fused urethra. The glanular urethra passes through 4 developmental stages: a solid epithelial plate, a blind central canal, a deep glanular groove, and the floor from the preputial lamella. There was no evidence of ectodermal ingrowth. These observations raise serious questions to the current theories for human urethra development. Further studies on fresh human embryos are needed.