Hypospadias, epispadias and bladder exstrophy

Presentation covering hypospadias, epispadias and bladder exstrophy, basic embryology, developmental defects, management principles, surgical techniques and associated complications.

1. HYPOSPADIAS DR. SUDHIR KUMAR JAIN M.B.B.S, M.S, M.B.A, F.R.C.S, F.A.C.S, F.I.C.S DIRECTOR PROFESSOR DEPARTMENT OF SURGERY MAULANA AZAD MEDICAL COLLEGE

2. hypospadias Definition- urethral opening proximal (ventral) to the normal granular location Caused due to arrested penile development Characterised by: Ventral meatus Ventral curvature ( Chordee ) Dorsal hood of prepuce

3. Other defects: Downward glans tilt Deviation of the median penile raphe Ventral curvature Midline scrotal cleft Scrotal encroachment onto the penile shaft

4. Normal development Genital Tubercle elongation and enlargement + fusion of urethral folds Testosterone Penis

5. development Cloacal endoderm primitive urethral plate, ventrally Medial endoderm male urethra, ventrally Lateral ectoderm skin of penile shaft and prepuce Layers fuse posteriorly to anteriorly, forming median raphe Arrest in fusion HYPOSPADIAS Abnormal development of growth plate, disproportionate corpora and fibrosis leads to penile curvature

6. Main differential diagnosis is: Chordee without hypospadias aka Congenital Ventral Curvature Characterised by asymmetrical preputial development but normal granular meatus Another variant termed as

7. Incidence: 1: 300 males Risk is 13 fold in 1 st degree relatives 8% patients have father with hypospadias, 14% have male siblings with hypospadias Risk of hypospadias in next child, when one child is affected with hypospadias: 12% with negative family history 19% if cousin or uncle has hypospadias 26% if father or sibling has hypospadias 8.5 times more risk in monozygotic twins

8. Other risk factors: Placental dysfunction Low birth weight Preterm birth Pre-pregnancy maternal obesity Extremes of maternal age ( <24 and >40) Assistive Reproductive techniques

9. Associated ANomalies Undescended testes- 9% Inguinal hernias- 9% Upper urinary tract anomalies 1-3% Utriculus masculinus - Incomplete mullerian duct regression Cryptorchidism- intersexuality needs to be ruled out especially in cases of non palpable testis

10. timeline 100-200 AD Heliodorus and Antyllus Amputation distal to meatus 1838 Dieffenbach Pierced glans to meatus with stenting 1869 Thiersch Local tissue flaps Hook Multistage repairs One stage repair

11. syndromes 90% are isolated penile defects. Rest are syndromic namely: Smith Lemli Opitz syndrome WAGR syndrome Wolf Hirschhorn syndrome 13p deletion syndrome Hand foot Uterus syndrome

12. Anterior hypospadias is the most common: 50-70% Posterior: 10-15%

13. Types of hypospadias Coronal Hypospadias Peno -scrotal Hypospadias Perineal Hypospadias with Scrotal transposition

14. DIAGNOSIS AND TREATMENT Diagnosis is clinical Imaging not required in cases of isolated hypospadias, regardless of severity Surgery is the treatment of choice Performed at the age of 3 months or older

15. Algorithm for hypospadias urethroplasty PROXIMAL DISTAL RE-OPERATION TIP VC<30˚ 2 STAGE GRAFT Urethral plate maintained, no gross scar VC>30˚ 2 STAGE ORAL GRAFT BXO GROSS SCARRING VC>30˚ HAIR IN URETHRA INLAY ORAL GRAFT previously excised skin strip without scar PREPUCIAL FLAP Sufficient skin, no BXO

16. Tubularised incised plate (TIP) repair for distal hypospadias A: Circumscribing skin incision B: Incisions along the visible junction of the glans wings to the urethral plate C: Incision of the urethra plate extending to near the underlying corpora D: Tubularising the urethral plate from distally to proximally. Note that the first stitch is about 3 mm proximal to the end of the plate creating an oval opening E: The neourethra is covered with a dartos flap F: Glansplasty creating the neomeatus and continuing down to the corona G: Repair and circumcision completed

17. Alternative methods for distal hypospadias repair: MAGPI- Meatal Advancement and Granuloplasty Incorporation Mathieu or Flip Flap technique

18. MAGPI Urethral plate is cut in dorsal midline, and meatus advanced distally Ventral lip of meatus is pulled distally and glans closed beneath it. Indications: Granular or coronal hypospadias Flat or convex glans Narrow meatus Skin and mucosa proximal to meatus thick and healthy No chordee or mild chordee

19. MATHieu repair Rectangular flap is outlined proximally on the ventral penile shaft, elevated and sutured distally to the urethral plate

20. Proximal hypospadias repair Choice of repair depends upon the extent of ventral curvature after degloving and excision of scrotal extensions onto the penile shaft VC<30- TIP, preputial flap VC>30- single stage tubularised preputial flaps, 2 stage preputial flaps or 2 stage preputial graft repair

21. Tip in proximal hypospadias A: Circumscribing incision preserves urethral plate in patient desiring circumcision. B: After degloving, glans wings are separated from the urethral plate. Corpus spongiosum is dissected from the cavernosal bodies and released distally from the glans wings for later spongioplasty . At this point artificial erection is performed and ventral curvature straightened as discussed in the text. C: Midline urethral plate incision. D: Two-layer urethral plate tubularization using interrupted subepithelial 7-0 polyglactin followed by running 7-0 polydioxanone. E: Spongioplasty approximates divergent corpus spongiosum over the neourethra, before a tunica vaginalis barrier flap is added.

22. 2 stage graft Indication- VC>30˚ Choice of flap depends whether patient undergoes circumcision or urethroplasty Urethral plate is transected as a part of straightening procedures followed by preputial or buccal mucosa graft If circumcision is preferred, then discarded prepuce is used for graft If urethroplasty is desired, then oral mucosa from lower lip is preferred

23. 1 st stage consists of transecting the urethral plate to correct the ventral curvature followed by substitution of urethral bed by using free preputial graft and creation of proximal urethrostomy . Defect to be grafted after the urethral plate has been excised, glans wings developed, and proximal urethrostomy created. Graft secured to glans, shaft skin, and scrotum at the perimeter of the defect and then quilted to the corpora first along the midline and then to either side at approximately 1-cm intervals. Detail showing the graft extending to either side of the urethrostomy before quilting. Tie-over dressing gently compresses the graft to reduce possibility for seroma or hematoma to accumulate beneath it. Healed graft.

24. 2 nd stage consists of creating a neomeatus by tubularising the artificially created urethral bed over a feeding tube and creating a distal meatus. 2 nd stage is usually carried out after 6 months of 1 st stage Tunica vaginalis flap is placed over the newly created urethra. Tunica vaginalis flap covering the neourethra

25. preputial flaps Onlay and tubularised flaps are single stage alternatived to TIP and 2 stage grafts.

26. Onlay preputial flap A. Lines of incision to create the preputial flap and preserve the urethral plate. B. Preputial flap mobilized on its vascular pedicle. C. Flap sewn to the urethral plate

27. Tubularised preputial flaps After degloving and release of ventral dartos , persisting ventral curvature greater than 30 degrees led to excision of the urethral plate. An inner preputial flap approximately 10 mm wide is dissected on its dartos vascular pedicle and transposed ventrally. This flap can be tubularized , with the proximal end anastomosed to the spatulated native urethra and the distal end to the glans wings. Alternatively, one edge of the flap can be fixed with interrupted sutures to the corpora cavernosa from the proximal meatus distally into the glans. Then the flap is trimmed and the opposite edge sutured along the first to create a tube with uniform caliber . Glansplasty and skin closure are similar to that described for onlay preputial flaps.

28. Salient features 90 % hypospadias are isolated, only 10% are syndromic Urinary tract imaging is not required for isolated cases. Surgery is the treatment of choice, performed at the age of 3 months or older Penile blocks are considered superior to caudal blocks for surgery owing togreater risk of penile engorgement Ventral curvature <30- corrected by dorsal plication, >30 by degloving and dissection Tubularised preputial flaps have better outcomes as compared to onlay flaps For distal repairs, follow up is desired at 2 months and 8 months post-operatively, while for proximal repairs, annual follow up is recommended till puberty.

29. Salient features Risk factors for complications: Proximal meatus Re-operation Glans width <14mm Complications include: Fistula Glans dehiscence Meatal stenosis Neourethral stricture Diverticulum at the flap site BXO Graft contractures Obstructive urinary symtoms Sexual dysfunction

30. epispadias

31. Defect in the dorsal wall of urethra Normal urethra is replaced by a strip of mucosa Associated Defects: Dorsally placed meatus Dorsal chordee Sphincter incontinence Pubic bone diastasis Unilateral renal agenesis VUR in cases of complete epispadias Male: Female =3-5:1 Incidence is 1:1,00,000

32. treatment Treatment goals include: Cosmetically acceptable genitalia Preservation of urinary continence Prevention of reflux Urethroplasty and penile elongation procedures are carried out before bladder neck reconstruction Bladder capacity is the eventual indicator of continence and therefore is increased upto 95cc in 18 months post epispadias repair before carrying out bladder neck reconstruction procedures to have better functional outcomes Yound-dees-leadbetter and Marshall- Marchetti - Krantz suspension and ureteric reimplantation are performed usually between 4-5 years of age Meticulous repair of urethra, appropriate selection of patients and surgical expertise form the cornerstone for success

33. Female epispadias Rare anpomaly Incidence 1;480,000 Davis classification used for severity Mild: urethral orifice patulous Moderate: urethra dorsally split along most of the urethra Severe: cleft along entire urethra + incontinence Genital defect includes bifid clitoris, depressed mons with underdeveloped labia minora Vagina and internal genitalia usually normal

34. Deficient ureterovesical junction wity resultant reflux Small and thin bladder with limited capacity

35. A. Normal female anatomy. B. Vesicular epispadias —urethra mainly normal but relation to clitoris altered. C. Subsymphyseal epispadias —defect in anterior wall of urethra for about one half its length. D. Retrosymphyseal epispadias —defect in anterior wall of entire urethra. Sphincter is usually involved

36. treatment Objectives: Reconstruction of functionally and cosmetically acceptable genitalia Achievement of continence Preservation of upper urinary tract

37. A. Typical appearance of female epispadias with initial incisions outlined. Excision of the glabrous skin of the mons. Tapering of the urethra with a dorsal resection of a wedge of tissue. Reconstruction of the urethra over a catheter with running suture. and F, Medial aspect of the labia minora and clitoris. Initial layer of mons closure. Approximation of the labia minora over the urethral reconstruction. Second layer of mons closure. Creation of clitoral hood. Completion of mons closure.

38. Bladder exstrophy

39. Exstrophy-epispadias complex Bladder exstrophy generally occurs as a complex of meatal defects alongwith genitourinary malformations termed as exstrophy-epispadias complex Incidence 2.2 per 100,000 live births Risk is 500 times more in offsprings of affected parents Increased incidence in mothers who received large doses of progesterone in the early part of 1 st trimester Disruption in the 5’ region of CASPR3 gene on chromosome 9

40. SPECTRUM OF EXSTROPHY-EPISPADIAS COMPLEX: SUPERIOR VESICAL FISSURE CLASSICAL BLADDER EXSTROPHY MALE EPISPADIAS FEMALE EPISPADIAS

41. embryology Allantoic duct Midgut Cloacal membrane Tailgut Midgut Hindgut Cloacal membrane Incompletely divided cloaca Urorectal septum Genital tubercle Bladder anlage Cloacal membrane Genital tubercle Bladder Hindgut Urorectal septum Anal canal Peritoneum Peritoneum Hindgut Rectum Anal membrane Urogenital membrane Urogenital sinus Bladder Urachus The theory of embryonic maldevelopment in exstrophy held by Marshall and Muecke (1968) is that the basic defect is an abnormal overdevelopment of the cloacal membrane during the 4th week of gestation, which prevents medial migration of the mesenchymal tissue and proper lower abdominal wall development. 4 th Week 8 th Week

42. Classical exstrophy >50% of this complex Closure of lateral body wall folds results in exstrophy If failure of fusion in abdominal and pelvic regions both Cloacal exstrophy If failure of fusion in pelvis alone Bladder exstrophy Other theories: Abnormal development of genital hillocks Abnormal caudal insertion of body stalk with failure of mesenchyme interposition Maldevelopment of bony pelvis

43. Classical exstrophy Rotational Defects include: external rotation of the posterior pelvis/iliac wings; external rotation of the anterior pelvic segment Coronal rotation of the sacroiliac joint acetabular retroversion convergence of iliac wings femoral retroversion. Dimensional anomalies include: increased pubic diastasis shortened anterior pubic segment increased intertriradiate cartilage distance

44. These defects lead to short, pendular penis Bony defects also lead to bony deformities and waddling gait

45. Pelvic floor defects Pelvic floor muscles particularly levator ani group is positioned more posteriorly and outwards leading to a more flattened puborectal ling leading to exstrophy Pubococcygeus Puborectalis Pubococcygeus PAUCITY OF ANTERIOR PELVIC FLOOR MUSCULATURE

46. ABDOMINAL WALL DEFECTS Premature rupture of cloaca causes triangular defect being taken up by bladder and posterior urethra Associated indirect inguinal hernias can be seen owing to persistent processus vaginalis, large superficial and deep rings, and lack of obliquity of inguinal canal The perineum is short and broad and the anus is situated directly behind the urogenital diaphragm. Patient has varying degrees of anal incontinence and rectal prolapse due to deficient anterior pelvic musculature

47. Male Genital defects Male genital defects included: Corporeal bodies separated and triangular in shape Long convex ventral surface and short wedge shaped dorsal surface Varying length of neurovascular supply Prostate and accessory sex organs remain unaffected Autonomic innervation of corpora are displaced but maintained functionally Testis remain normal and descend normally without the need for orchiopexy

48. Female genital defects Female genital defects: Vagina is shorter in length, ≤6cm, but calibre normal Vaginal opening stenotic Clitoris bifid, and labia, mons and clitoris are divergent Cervix enters the vagina more superiorly, lying in the anterior vaginal wall near introitus

49. URINARY SYSTEM DEFECTS The most common malformation was a duplicated collecting system Others included: hypoplastic or absent kidney pelvic kidney ureteropelvic junction obstruction Multicystic dysplastic kidney. Reflux in the closed exstrophy bladder occurs in 100% of patients, and reimplantation surgery is required at bladder neck reconstruction. If excessive outlet resistance is gained at the time of either initial closure or combined epispadias and bladder exstrophy closure, and recurrent infections are a problem even with suppressive antibiotics, ureteral reimplantation or Deflux injections are required before bladder neck reconstruction.

50. diagnosis Clue to prenatal diagnosis can be provided by high resolution obstetric ultrasound. Features observed: Absence of bladder filling A low-set umbilicus Widening pubis ramus Diminutive genitalia A lower abdominal mass that increased in size as the pregnancy progressed and as the intra-abdominal viscera increased in size Fetal MRI is reserved for patients in whom 3D ultrasonography is not sufficient to differentiate satisfactorily between classic and cloacal exstrophy , or when other severe anomalies are suspected.

51. management Management is surgical with medical management playing a supportive role Previously exstrophy-epispadias complex was managed via surgery in a staged manner with B/L iliac osteotomies being oerformed 4-6 days prior to bladder closure and epispadais repair performed separately. In the current scenario, management include: bladder closure, abdominal wall closure, and posterior urethral closure well onto the penis in the newborn period bilateral innominate and vertical iliac osteotomy, if indicated epispadias repair at 6 months to 1 year of age bladder neck reconstruction along with antireflux procedure at age 4 to 5 years, when the child has achieved an adequate bladder capacity for bladder neck reconstruction and is motivated to participate in a postoperative voiding program

52. Osteotomy: Diastasis>4cm Malleability of the pelvis poor If the patient is younger than 72 hours and examination under anesthesia reveals that the pubic bones are malleable and able to be brought together easily in the midline by medial rotation of the greater trochanters, the patient can undergo closure without osteotomy. Complications of inadequate immobilization include: Failure of the closure bladder prolapse loss of suprapubic tubes, and ureteral stents. inadequate pain and movement control. Main role of osteotomy to be relaxation of tension on the bladder, posterior urethra, and abdominal wall repair during healing.

53. Bladder repair techniques Surgical treatment of choice is MSRE (Modern Staged Repair of Exstrophy ) Other repairs include: Warsaw Kelly Complete Mainz Erlangen The primary objective in functional closure is to convert the bladder exstrophy into a complete epispadias with the urethra well up onto the proximal shaft or midshaft of the penis

54. Initial incision around the bladder plate in the male. Initial incision around the bladder plate in the female. Incision follows the bladder template and includes the umbilicus. Dissection of the lateral aspect of the bladder from the abdominal wall.

55. E. Dissection of the crura from the symphysis pubis. F. Division of the urogenital (UG) diaphragm fibers . G. Initial layer of the bladder closure. Urethral meatus is calibrated to 14-Fr size. Stents are brought out of the bladder. H. Pubic approximation is performed with No. 2 nylon mattress suture (see inset). Abdominal wall closure is completed. Suprapubic tube and stents are brought out through the neoumbilicus .