Pierre Mouriquand, Daniela Gorduza, Pierre-Yves Mure

Department of Paediatric Urology. Hôpital Mère-Enfants – GHE – Claude-Bernard University             59, boulevard Pinel – 69500 Bron - France

  1. Definition and pathophysiology

Epispadias is a congenital anomaly of the urethra and the genital tubercle which belongs to the exstrophy/ epispadias complex (EEC). During the first 2 months of gestation, the embryo (germinal disc) is subjected to a complex process (delimitation) [1] of cranio-caudal tubularization resulting in the cavitation and connection of the pelvic organs to the pelvic floor. This leads to the creation of urinary, genital and intestinal cavities independently connected to the perineal surface by distinct conduits and their corresponding sphincter. If the delimitation process is interrupted early, the distal bowels, the bladder and the urethra are not individualized and appear as contiguous and often duplicated plates. This is a cloacal exstrophy which is rare (1:250 000 births) and often associated with other abnormalities. If the process halts a bit later in the gestation, the bowels are properly formed and connected but the bladder and urethra are both widely open. This results in a classical bladder exstrophy which is the most common presentation of the EEC although still quite rare (1:10-50 000 births). Finally, when the process stops late, only the urethra and the urethral sphincter are open and incompetent. This results in an epispadias which is much rarer than the classical bladder exstrophy (1:117 000 births) [2]. Depending on the timing of the cavitation failure, one may distinguish posterior epispadias involving the sphincteric mechanisms and various degrees of incontinence, from anterior epispadias where the continence mechanisms are completely or partially respected but the genital tubercle remains abnormal. Epispadias exists both in boys and girls with a clear predominance in the male gender.
Complex embryonic hypotheses have been described to explain these abnormalities. They involve the formation and positioning of the cloacal membrane with is situated at the caudal end of the germinal disc and occupies the infra-umbilical abdominal wall. Between the 2 layers (ectoderm and endoderm) initially forming the cloacal membrane comes a mesenchymal ingrowth [3] which will result in the formation of the lower abdominal muscles and the pelvic bones [4]. The surrounding mesoderm will be at the origin of the genital tubercle. The 3D development of the embryo progresses from the cephalic to the caudal extremity, and from the dorsum to the ventrum of the embryo. When the caudal delimitation is aborted, the mesenchymal ingrowth between the ectodermal and endodermal layers fails to progress and the overstretched cloacal membrane becomes fragile and subject to a premature rupture leading to exstrophy (or non-cavitation) of the pelvic organs [5]. This “zip down” process  [2] explains the progressive closure of the pelvis and the cavitation of the pelvic organs from the back to the front and from the top to the bottom of the embryo. It is possible that the middle period of the cloacal delimitation is more vulnerable than the early and late stages. This would explain why bladder exstrophy is mEpidemiological data confirmed that the incidence of bladder exstrophy is between 2.15 and 3.3 per 100 000 births [11, 12]) whereas epispadias was 2.4 per 100 000 with a sex ratio quite variable from almost even [11] to a marked male predominance of 5:1 [13]. White children, in vitro fertilization [14] and  socioeconomic status seem to be interacting factors. Significant genetic predisposition remains uncertain considering the small reported cohorts [15-17]. The recurrence risk varies from 0.3% [18] to 2.3% [16] [17] [15].ore frequent than cloacal exstrophy and epispadias [6]. Other embryonic hypotheses have been reported  [7] [8-10].


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  1. Anatomical and clinical presentation:

The description given hereunder is limited to the epispadiac penis itself. Associated urologic and non-urological pelvic anomalies often found with the exstrophy patient are detailed in another chapter.

      • In boys: The urethral plate is wide open along the dorsum of the penis on a variable length. The extent of exposed urethral mucosa can vary from the dorsum of the glans for anterior epispadias to the whole urethra and bladder neck for posterior epispadias. The penis may look short and is almost always bent dorsally due to the malrotation of the corpora cavernosa. In isolated epispadias, the pelvic bony cavity is usually normal although an interpubic gap may exist which shows that the EEC anomalies are in fact a continuum. When associated with a bladder exstrophy, the epispadiac penis appears foreshortened because of the wide separation of the corporal insertions [19, 20]. The displacement of each hemipelvis leads to a malrotation of each corpus, explaining the dorsal curvature of the erect penis; the flaccid epispadiac penis does not dangle. The corpora cavernosa are also shorter than in normal men especially in the exstrophy group [21]. The erection mechanisms are preserved but sexual intercourse is rendered impossible by the size and shape of the erect penis.  The hooded foreskin is only present on the ventral side of the penis although a complete foreskin may be seen in epispadiac penis. The corpus spongiosum is only present under the urethral plate which is itself often wide and healthy contrary to what is often found in hypospadiac penis where it can be hypoplastic [2]. Up to recently, it was thought that the nerves leading to the glans were essentially represented by 2 neurovascular bundles running along the dorso-lateral sides of the corpora cavernosa.  The work done by Baskin [22] demonstrated that the neurological fibres leading to the glans (and the clitoris) are spread around a large surface covering  the lateral aspects of the corpora and are probably less individualized than previously thought. In the epispadiac penis, the routes taken by the nerves are a bit more lateral due to the malrotation of the corpora. A better understanding of the anatomy of the nerves has significantly changed the way these nerves are separated from the corpora and the urethral plate. No vascular anastomosis exist between the epispadiac corpora which allows their full separation during repair. The veru montanum and the seminal tracts are normal [23], provided they are not injured iatrogenically. In posterior epispadias, retrograde ejaculation may occur as the sphincteric mechanisms are in essence defective. In epispadias following exstrophy closure, the prostate is only present posterior to the urethral plate. The testicles are normal although frequently located near the pubic tubercles, above the corresponding scrotum which usually appears wide and stretched.  Duplicated urethra and penis have been reported [24] with exstrophy.
          • In girls, the clitoris is bifid. The urethral plate is wide open up to the level of the bladder neck. The vagina is normal in isolated female epispadias as well as the bony pelvis. A hairless area separates the two hemimons pubis. The labia are divergent. The uterus, fallopian tubes and ovaries are normal except for occasional uterine duplication. In case of exstrophy where the vagina opening is anteriorly positioned, often stenotic, the vaginal conduit is horizontal.
          1. Surgery of epispadias


          Surgical repair of these genital anomalies are usually performed during the first two years of life.

            1. In boys: The aims of this surgery are 1) to correct the dorsal curvature of the penis by rotating the corpora cavernosa to obtain a dangling penis; 2) to relocate the reconstructed urethra on the ventral side of the penis; 3) to redistribute the skin around the penis to compensate the dorsal skin defect.  Although many procedures have been described over the years [25, 26] [27], the techniques of Ransley [28] ,Mitchell [29] and Kelly [30] are probably the most commonly used these days. Preoperative androgen stimulation of the genital tubercle makes surgery easier.
              1. In Ransley’s technique, the incision begins in the midline above the urethral opening and is extended far enough upwards to provide good access to the proximal corpora for mobilization.Figure 1 It continues down on each side of the urethral plate (backed by the corpus spongiosum) and sweeps ventrally around the coronal sulcus separating the prepuce and ventral skin from the corpora.  Once the ventral aspects of the corpora are fully exposed. The fascia covering each corpus  is vertically opened  all along the ventral aspect of each corpus. This maneuver allows exposure of the albuginea of each corpus. Dissection continues under the fascia around the albuginea of each corpus medially to separate the vascular tissues (spongiosum) leading to the urethral plate, and externally to separate the wide strip of neurological fibers innervating the glans. Each neurovascular bundle and the urethral plate with its spongiosal tissue are then separated from adjacent structures.  Figure 2.  The urethral plate is tubularized and a MAGPI type plasty (IPGAM) of its distal end allows ventralization of the future urethral meatus. The corpora are then rotated medially by approximately 90° and maintained in this new configuration by a proximal caverno-cavernostomy.  This new anastomosis between the corpora keeps the urethra in its ventral position and gives the penis a dangling position when flaccid. The skin shaft cover is performed with a transverse flap of ventral skin dissected with its pedicle and transfer to the dorsal side of the penis (reverse Duckett).Figure 3
              2. Mitchell’s technique [29, 31] is based on a complete disassembly of the penile structures which allows a tubularization and ventralization of the entire urethra, and a more complete release of the corporal rotation. The corpora cavernosa are completely separated from each other with their corresponding hemi glans. The urethral plate is dissected off of the corporeal bodies respecting  its blood supply coming from underneath. It is then tubularized and transferred ventrally. The corpora entirely separated and independent are rotated to correct the dorsal chordee and sutured together. The glans halves are subsequently brought together.
              3. The Kelly procedure or radical soft tissue mobilization is used by some [32, 33] for exstrophy closure. The technique is described elsewhere[30] and may be a valuable alternative for primary or secondary penile reconstruction in EEC patients. The periostium on the inner side of the ischium and pubis with the attachment of the sphincter muscles, the pudendal vessels and nerves are mobilized on both sides so that the outstretched muscles can help to reconstitute the membranous urethra without osteotomy. Others [34] have suggested a mobilization of the crura from the pubic rami to get more penile length without the complete Kelly mobilization


            1. In girls, the open urethral plate extending from the bladder neck to the medial aspect of both hemi-clitoris anteriorly, and to the anterior vaginal edge posteriorly, is separated from the adjacent structures up into the perineal muscles and subsequently tubularized (Figure 4 ). The triangular hairless area separating both hemi-pubis is excised (Figure 5). The perineal muscles located in front of and between the neo-urethral conduit and the vaginal orifice are both sutured together which significantly increases the bladder outlet resistance and provides social continence in most cases(Figure 6). A secondary plasty of the mons venus may be needed at puberty if the cosmetic appearance of this area remains unsatisfactory. It is recommended not to dissect and suture together both medial aspects of the two hemi-clitoris to avoid any damage of the clitoral sensitivity [35].


          1. Incontinence surgery:

          As mentioned before, the degree of incontinence is quite variable in epispadiac patients. It is essentially in posterior epispadias where the sphincteric mechanisms are impaired that complementary treatments are discussed.  All procedures aim at increasing the bladder outlet resistance to achieve social dryness (> 3 hours) and allowing bladder emptying either via the reconstructed urethra or via a continent conduit (Mitrofanoff) [36]. Continence which implies complex, coordinated active neuromuscular mechanisms cannot be achieved by conventional surgery. Surgery can only create a sufficient static obstacle which, in the best cases, allows the child to hold urine for at least 3 hours without significant leakage. This is dryness which implies passive mechanisms not always easily controllable.

            1. The peri-cervical injection of biocompatible substance: It is the simplest option to increase the outlet resistance by injecting a bulking agent in the bladder neck region.  Although not very invasive this procedure provides disappointing results on a medium and long-term basis. The most optimistic results [37] report 30% to 40% of dryness with several years of follow-up. Although immediate results can be encouraging, continuous deterioration with increased leakage is common. It does not seem that the type of bulking agents used makes a significant difference.


            1. The cervico-cystoplasty / bladder neck reconstruction:
          This surgery is usually performed in incontinent epispadias after the age of 3 or 4 years when some collaboration between the child and the medical team can be established and when the bladder capacity is big enough (> 80 ml). It is the most hazardous part of this reconstruction as it aims at increasing the bladder outlet resistance to achieve intervals of dryness of at least 3 hours without compromising complete bladder emptying and upper tract drainage. Experience shows that this challenge is rarely achieved in the exstrophy group although results are better in the epispadiac group as the bladder behavior is probably more normal. A full description of the Young-Dees-Leadbetter cervicocystoplasty is done in the exstrophy chapter.  This technique often leads to “obstructive” micturitions i.e. high pressure emptying which represents a threat for the bladder and the whole upper tracts. Trigonal dissection can also damage the genital tracts. These patients often have poor or retrograde ejaculations related to the deficient sphincteric area.

            1. The artificial urinary sphincter: Insertion of an artificial sphincter cuff around the EEC bladder neck has had poor results although individual experience is always limited. There is a much higher risk of erosion in a reconstructed bladder neck and urethra. The artificial sphincter is therefore not a front line solution in the EEC group although silicone sheath placement has been reported to facilitate the insertion of the cuff in selected patients [38, 39] .
            1. The bladder neck closure:

          It is the ultimate solution when all others have failed. It is a difficult operation as these tissues have been previously dissected the separation of the trigone from the bladder neck region can be tricky. This procedure although quite successful in term of dryness is irreversible and obviously implies a concomitant Mitrofanoff diversion.

              • Complementary procedures: The unpredictible results of cervico-cystoplasty often lead to a combined Mitrofanoff continent diversion which allows complete, regular and low pressure bladder emptying [36]. If the bladder capacity does not increase after urethroplasty, it is sometime necessary to augment the bladder capacity with a bowel segment. Finally, most EEC bladders are associated with reflux which is usually corrected at the time of the cervicocystoplasty. We will not describe here diversions of urine towards the distal colon [40] and their variants (Mainz Pouch II) which have the advantage of reducing the number of operations and achieving a reasonable level of continence although expose patients to a high risk of severe retrograde urinary infection and bowel cancer [41].
              1. Results
                1. The cosmetic results


              Reported results are usually better in the epispadiac group compared to the exstrophy group and better in girls than in boys. Cosmetically, the outcome is satisfactory in girls [42]
              although complementary surgery of the mons pubis may be requested at puberty. The repaired epispadiac penis is often short and broad with better result in isolated epispadias compared to the exstrophy group.  Undoubtedly the Cantwell-Ransley penile repair has been a major step forward not only in the surgical outcome but also in the understanding of this condition [43-47]. The Mitchell penile disassembly [29, 31, 48-50] provides equivalent results with possibly a higher risk of glans or hemi-glans necrosis. The Kelly procedure has strong supporters who have a solid experience of this difficult dissection associated with a significant risk of penile loss [33, 51]. Skin coverage of the reconstructed epispadiac penis aims at transferring ventral skin to the dorsum. The post-operative cosmetic appearance may often be disappointing with a penis which often looks small and buried. Attempts to improve this have been reported [52].

                1. Dryness


              Functionally the primary reconstruction of the urethra in both sexes is an essential first step which allows the bladder to grow. In the Baltimore group [53], social dryness was achieved in approximately 75% of their exstrophy females compared to a 87.5% of dry patients 15 years earlier [54]. Our long-term results [55], and those of others [56] and [57] clearly showed a long-term deterioration of dryness as well as serious complications related to “obstructive” micturitions (infections, stones, bladder perforation, upper tract dilatation) mostly in the exstrophy group. In our own series of 25 incontinent epispadias dryness was achieved day and night in 28%, day only > 3 hours in 24%, between 1 and 3 hours in 16% and less than 1 hour in 8%. These results were better in this group than in the exstrophy group (80 patients) where only 45% presented with a dry interval of > 3 hours with transurethral voiding. Complications related to “obstructive micturition” and other complications were also significant with 48% of recurrent urinary tract infections (vs.65% in the exstrophy group), 8% of stone (vs. 24%), 20% of upper urinary tract dilatation (vs. 26%), 4% of bladder perforation (vs. 16%), 1 patient with adenocarcinoma in both groups [55]. Simplification of the technique of bladder neck plasty has been reported [58]. The key issue is the growth of the bladder after increasing the outlet resistance. The epispadiac bladder has a much safer behavior and therefore a better dryness outcome than the exstrophy bladder which is essentially abnormal [59]. The role of endoscopic injection remains uncertain as published series are short, retrospective and often mix neurological bladder and EEC. It might be helpful to treat partial urinary incontinence and to help bladder growth. Redo bladder neck is an even greater challenge with little success in our series [43, 55] leading to other technical adjustments [60] using bladder neck wraparound.

                  • Sexual and psychological dysfunctions are significantly high in the EEC patients with a lesser degree in the pure epispadiac group. Female patients probably have a better adjustment to this handicap than males whose repaired penis is often short and broad with preserved erections but poor ejaculations [61-64].

                  1. Conclusion

                  Epispadias is a complex and rare malformation of the genital tubercle which requires a very challenging surgical reconstruction to achieve acceptable cosmetic and functional results. Its rarity has led to the suggestion that these patients should be referred to a limited number of expert centers for management. Current management of epispadias usually starts with a urethral reconstruction to increase the outlet resistance and to let the bladder grow. In some cases (mainly in girls) this sole procedure may be sufficient to achieve social dryness. If not, an attempt to use injections of bulking agents around the bladder neck might be temporarily helpful.  On a long-term basis, bladder neck reconstruction associated with anti-reflux surgery is the classical approach knowing that the outcome of this surgery is unpredictable with a significant morbidity. Bladder neck closure is the ultimate solution especially in boys despite long-term complications. Outcomes in adolescents and adults and large series are lacking which should encourage prospective multicentric studies.

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