Pierre Mouriquand, Daniela Gorduza, Pierre-Yves Mure
Department of Paediatric Urology. Hôpital Mère-Enfants – GHE – Claude-Bernard University 59, boulevard Pinel – 69500 Bron - France
Pierre Mouriquand, Daniela Gorduza, Pierre-Yves Mure
Department of Paediatric Urology. Hôpital Mère-Enfants – GHE – Claude-Bernard University 59, boulevard Pinel – 69500 Bron - France
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)  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) . 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  which will result in the formation of the lower abdominal muscles and the pelvic bones . 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 . This “zip down” process  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  to a marked male predominance of 5:1 . White children, in vitro fertilization  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%  to 2.3%   .ore frequent than cloacal exstrophy and epispadias . Other embryonic hypotheses have been reported  [8-10].
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.
Surgical repair of these genital anomalies are usually performed during the first two years of life.
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) . 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.
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.
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 
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 .
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 , social dryness was achieved in approximately 75% of their exstrophy females compared to a 87.5% of dry patients 15 years earlier . Our long-term results , and those of others  and  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 . Simplification of the technique of bladder neck plasty has been reported . 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 . 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  using bladder neck wraparound.
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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