Vol.:(0123456789)1 3 Pediatric Surgery International (2018) 34:813–821 https://doi.org/10.1007/s00383-018-4271-z REVIEW ARTICLE Aphallia: a review to standardize management Tarryn Gabler1 · Robyn Charlton1 · Jerome Loveland1 · Ellen Mapunda2 Accepted: 17 April 2018 / Published online: 20 April 2018 © Springer-Verlag GmbH Germany, part of Springer Nature 2018 Abstract Congenital aphallia is a rare anomaly with little supporting literature and controversial management. The aim of this review is to assess the most recent literature with a focus on staged management of these cases. We performed a PubMed search of all English literature in the past 10 years using the term aphallia. Twenty-three articles were identified of which six were excluded. A further three papers meeting our criteria were found in the references to papers initially identified. We found that management can be staged in three phases: short, intermediate and long-term. We conclude that optimal short-term management centers on resuscitation and urinary diversion as necessary, intermediate-term management entails urethrorec- tal fistula division, urethrostomy and neophallus creation and long-term management results in successful neophalloplasty, urethroplasty, prosthetic implant and continued protection of the upper urinary tracts with a Mitrofanoff. All this within a multidisciplinary team ensuring shared decision-making with the patient and their family. Keywords Aphallia · Urethrorectal fistula · Neophalloplasty · Urethroplasty Introduction Aphallia is a rare disorder with only around 100 cases reported in the literature [1]. Because of its rarity (incidence estimated to be 1 in 10–30 million births) [2–4] and the dif- ficulties it presents to both patient and families, treatment of this condition has been controversial. We review the English literature over the last 10 years in an attempt to clarify and better understand aphallia and its management. Methods Ethics was obtained from the Human Research Ethics Com- mittee for the University of the Witwatersrand (R14/49). We performed a PubMed search of the English literature using the term ‘Aphallia’ with the following filters: Articles published in the last 10 years (2007–2017), Human subjects and children (birth–18 years). Because of the significant shift in attitude toward managing this subset of patients with feminizing genitoplasty to raising these children as male with phallus reconstructive procedures, we decided to limit our literature search to the last 10 years, thereby helping us strategize management based on recent literature more in line with current ‘standard of care’. Results The search rendered 23 articles. Six articles were excluded (one paper not in English, two papers on intra-vesical penises, one systematic review and two papers that did not report on interventions). A further three papers fitting our criteria were identified when assessing references to the arti- cles already included. Table 1 shows all applicable papers with their cases, asso- ciated abnormalities, site of the urethrorectal fistula and type of intervention. The above studies were case reports or case series report- ing 30 cases of aphallia with a maximum of four cases per publication. Patient age ranged from a gestational age of 35 weeks to 12 years old. Four cases did not comment on associated abnormalities and only 3 (10%) cases reported no * Tarryn Gabler tarryn.gabler@gmail.com 1 Paediatric surgery at Chris Hani Baragwanath Academic Hospital, University of the Witwatersrand, Parktown, Johannesburg, South Africa 2 Department of Paediatric Surgery at Charlotte Maxeke Johannesburg Academic Hospital, University of the Witwatersrand, Johannesburg, South Africa http://crossmark.crossref.org/dialog/?doi=10.1007/s00383-018-4271-z&domain=pdf 814 Pediatric Surgery International (2018) 34:813–821 1 3 Ta bl e 1 S um m ar y of p ub lis he d ar tic le s o n ap ha lli a in cl ud in g th e as so ci at ed a bn or m al iti es a nd c ho se n in te rv en tio n A ut ho r Ty pe o f r ep or t N A ge A ss oc ia te d ab no rm al iti es Si te o f u re th ro re ct al fi stu la Ty pe o f i nt er ve nt io n G en ito ur in ar y N on -g en ito ur in ar y Jo sh i e t a l. [2 ] C as e re po rt 1 11  m on th s O lig oh yd ra m ni os N on ob str uc te d le ft m eg au re te r Sp in al c or d sy rin x Pr es ph in ct er ic Pl an ne d fo r s ta gg er ed p er in ea l ur et hr op la sty a nd p se ud o ph al lo pl as ty * A sl an ab ad i e t a l. [3 ] C as e re po rt 1 D ay 1 o f l ife R ig ht k id ne y hy po pl as ia Le ft ki dn ey d ys pl as ia – Pr es ph in ct er ic D ie d pr e- in te rv en tio n* G oy al e t a l. [5 ] C as e re po rt 1 N ot re po rte d Fu se d ki dn ey s i n le ft- to -r ig ht c ro ss ed ec to pi a co nfi gu ra tio n – Po sts ph in ct er ic St ag ed p ha llo pl as ty a nd u re - th ro pl as ty G ou ve a et  a l. [6 ] C as e re po rt 1 11  y ea rs N ot m en tio ne d N ot m en tio ne d N ot m en tio ne d Pr ev io us u re th ro sto m y, p ha l- lo pl as ty a nd M itr of an off La te r p en ile p ro st he si s M ac ed o et  a l. [7 ] C as e re po rt 1 6  m on th s N ot m en tio ne d N ot m en tio ne d Pr es ph in ct er ic Pr ev io us v es ic os to m y. P er in ea l ur et hr os to m y, M itr of an off , ph al lo pl as ty K an e et  a l. [1 ] C as e re po rt 1 D ay 1 o f l ife G ra de II I r ig ht V U R – Pr es ph in ct er ic In iti al c ys to sto m y La te r a nt er io r u re th ra l t ra ns - po si tio n Pl an ne d fo r p ha llo pl as ty a t pu be rty Fr ie dm an e t a l. [8 ] C as e se rie s 3 D ay 1 o f l ife R ig ht re na l a tro ph y an d pa rti al du pl ic at io n B ila te ra l h yd ro ne ph ro si s Le ft hy dr ou re te r B ila te ra l G ra de V V U R Pe riu re te ra l b la dd er d iv er tic ul um / di la te d ut ric le re ce iv in g ec to pi c le ft ur et er U re th ra l n ar ro w in g A nt er io rly d is pl ac ed a nu s Po sts ph in ct er ic U re th ra l d ila ta tio n B ila te ra l u re te ra l r ei m pl an ta tio n an d di ve rti cu le ct om y D ay 1 o f l ife R ig ht U V J o bs tru ct io n w ith h yd ro ur e- te ro ne ph ro si s a nd d up lic at io n Pa tu lo us b la dd er n ec k R ig ht -s id ed b la dd er d iv er tic ul um PU V – Po sts ph in ct er ic A bl at io n of P U V In tra ve si ca l e xc is io na l t ap er ed rig ht u re te ra l r ei m pl an ta tio n an d pa ra ur et er al d iv er tic ul ec - to m y La te r u re te ro ly si s a nd ri gh t-t o- le ft tra ns ur et er ou re te ro sto m y D ay 1 o f l ife St en ot ic u ro ge ni ta l s in us B ila te ra l r en al d ys pl as ia (r ig ht d ys - pl as tic k id ne y, le ft M C D K ) R ig ht u re te ra l e ct op ia le ft ur et er al at re si a bl ad de r a ge ne si s A nt er io r p at ul ou s a nu s K om m er el l d iv er tic ul um w ith o es op ha ge al ri ng Le ft in gu in al h er ni a U m bi lic al h er ni a M ild d ev el op m en ta l d el ay Po sts ph in ct er ic Re na l t ra ns pl an t Te m po ris in g ur et er os to m y Ile oc ae ca l n eo bl ad de r a nd M itr of an off w ith n on -r efl ux - in g im pl an ta tio n of tr an sp la nt ur et er 815Pediatric Surgery International (2018) 34:813–821 1 3 Ta bl e 1 (c on tin ue d) A ut ho r Ty pe o f r ep or t N A ge A ss oc ia te d ab no rm al iti es Si te o f u re th ro re ct al fi stu la Ty pe o f i nt er ve nt io n G en ito ur in ar y N on -g en ito ur in ar y G er ar d- B la nl ue t e t a l. [9 ] C as e re po rt 1 Po st- m or te m (3 5/ 40 ) U R SM S (c om pl et e ur og en ita l a pl as ia w ith im pe rfo ra te a nu s, ur et hr al a tre - si a, b ila te ra l r en al c ys tic d ys pl as ia , pe rs ist en t u ro ge ni ta l h or ns ) R ig ht in gu in al te sti s O lig oh yd ra m ni os B ila te ra l c lu bf ee t Po tte r s eq ue nc e Si ng le u m bi lic al a rte ry U ni la te ra l l un g ag en es is Th or ac ic h em iv er te br ae 14 le ft rib s U re th ra l a tre si a Te rm in at io n of p re gn an cy a t 3 5 w ee ks g es ta tio n* B ah e et  a l. [1 0] C as e re po rt 1 6  da ys B ila te ra l h yd ro ne ph ro si s a nd h yd ro - ur et er – N ot m en tio ne d Ve si co sto m y at in iti al p re se nt a- tio n W ill ih ng an z- La w so n et  a l. [1 1] C as e re po rt 1 5  ye ar s H or se sh oe M C D K U re te ra l a nd b la dd er a tre si a – Po sts ph in ct er ic Pe rit on ea l d ia ly si s Pr ev io us c ad av er ic re na l tra ns pl an t w ith c ut an eo us ur et er os to m y La te r t ak ed ow n of u re te ro sto m y Ph al lo pl as ty R at ta n et  a l. [1 2] C as e se rie s 3 D ay 1 o f l ife U ni la te ra l r en al a ge ne si s Im pe rfo ra te a nu s Po sts ph in ct er ic U re th ra l d ila ta tio n Pl an ne d fo r l at er p ha llo pl as ty * N eo na te R ig ht e ct op ic p el vi c ki dn ey – Po sts ph in ct er ic Pl an ne d fo r p er in ea l ur et hr os to m y* 6  m on th s – – Pr es ph in ct er ic Pa re nt s r ef us ed tr ea tm en t Sh am sa e t a l. [1 3] C as e re po rt 1 18  m on th s – – Pr es ph in ct er ic Pr ev io us o pe n cy sto sto m y St on e re m ov al Pe rin ea l u re th ro sto m y C oq ue t-R ei ni er e t a l. [1 4] C as e re po rt 1 D ay 2 o f l ife B ila te ra l g ra de II V U R – Po sts ph in ct er ic Fe m in iz in g ge ni to pl as ty D es ca m ps e t a l. [1 5] C as e se rie s 2 D ay 1 o f l ife N ot m en tio ne d N ot m en tio ne d Po sts ph in ct er ic Fe m in iz in g ge ni to pl as ty La te r p ha llo pl as ty a nd st ag ed ur et hr al re co ns tru ct io n D ay 1 o f l ife B la dd er e xs tro ph y – N ot m en tio ne d Fe m in iz in g ge ni to pl as ty A ug m en ta tio n cy sto pl as ty a nd bl ad de r n ec k tig ht en in g U rin ar y di ve rs io n La te r p ha llo pl as ty a nd te sti cu la r im pl an ts N ak an o et  a l. [1 6] C as e re po rt 1 D ay 1 o f l ife U R SM S (im pe rfo ra te a nu s, co ve re d cl oa ca l e xs tro ph y, b ifi d sc ro tu m , ve si co in te sti na l fi stu la , d up lic at ed co lo n, c ae cu m a nd a pp en di x SS B S) Pa te nt u ra ch us M ild b ila te ra l r ad ia l d ys - pl as ia W id e pu bi c di as ta si s U re th ra l a tre si a C ys to sto m y 816 Pediatric Surgery International (2018) 34:813–821 1 3 Ta bl e 1 (c on tin ue d) A ut ho r Ty pe o f r ep or t N A ge A ss oc ia te d ab no rm al iti es Si te o f u re th ro re ct al fi stu la Ty pe o f i nt er ve nt io n G en ito ur in ar y N on -g en ito ur in ar y B ot hr a et  a l. [1 7] C as e re po rt 1 4  ye ar s B ila te ra l g ra de II I h yd ro ne ph ro si s Le ft V U R R ig ht h yd ro ur et er on ep hr os is – Pr es ph in ct er ic Pe rin ea l u re th ro sto m y Sh ar m a et  a l. [1 8] C as e re po rt 1 D ay 1 o f l ife O lig oh yd ra m ni os U R SM S (im pe rfo ra te a nu s, bi la te ra l re na l a ge ne si s) Si ng le u m bi lic al a rte ry D ep re ss ed n as al b rid ge En do ca rd ia l c us hi on d ef ec t Pr om in en t c er eb ra l v en tri - cl es w ith b ul ky c ho ro id pl ex us Pu lm on ar y hy po pl as ia N ot m en tio ne d N on -o pe ra tiv e (s up po rti ve ) c ar e M an e et  a l. [1 9] C as e re po rt 1 7  ye ar s Po or ly d ev el op ed sc ro tu m B ila te ra l U D Ts G ra de s I a nd II I V U R B ila te ra l h yd ro - ne ph ro si s U ni la te ra l m ed ia l r en al ro ta tio n U ra ch al fi stu la – Po sts ph in ct er ic Si ng le st ag e fe m in iz in g ge ni - to pl as ty A m iri e t a l. [2 0] C as e se rie s 3 D ay 1 o f l ife B ila te ra l h yd ro ne ph ro si s Le ft V U R Li m ite d hi p ab du ct io n Pr es ph in ct er ic Pl an ne d fo r p ha llo pl as ty * D ay 1 o f l ife M ul tic ys tic , a tro ph ic k id ne ys Pa te nt u ra ch us B ila te ra l V U R O lig oh yd ra m ni os Lo w -s et e ar s Sa dd le n os e H ep at om eg al y Su pe rio rly lo ca te d um bi lic us Sh or t s ac ru m B ila te ra l c lu bf oo t M ild T I a nd sm al l P D A U re th ra l a tre si a C ys to sto m y D ie d pr e- pe ni le in te rv en tio n* D ay 1 o f l ife B ifi d sc ro tu m M ild le ft V U R M ild T I Po sts ph in ct er ic Pa re nt al re fu sa l 817Pediatric Surgery International (2018) 34:813–821 1 3 associated abnormalities. Position of the urethrorectal fistula was pre-sphincteric in 12 patients (40%), post-sphincteric in 11 patients (36%) and complete urethral atresia with no com- munication was described in three patients (10%). There was no position reported in four patients (13%). Eight patients (27%) had planned interventions that were not carried out at the time of publication. Two patients (7%) refused treat- ment. Four patients underwent feminizing genitoplasties of which two patients later went on to gender identify as male with subsequent phalloplasties performed. Eighteen patients (60%) required multiple surgical procedures. Table 2 assessed only the papers that dealt with phallo- plasty with or without urethroplasty. Of the ten cases reported in Table 2, three patients (30%) had ‘interim’ phalloplasties necessitating future reconstruc- tive phalloplasty. Five patients (50%) underwent simultane- ous urethroplasty and phalloplasty although only one patient (10%) did not need further urethroplasty intervention and only one patient (10%) had a good cosmetic outcome. Seven patients (70%) underwent De Castro technique phalloplasty. Discussion Aphallia is defined as an absent phallus with an ectopic urethral opening, usually associated with a well-developed scrotum and bilaterally palpable testis. The absent phallus is characterized by absence of all three components of the phallus, namely the two corpora cavernosa and the corpus spongiosum [3, 8, 10, 14]. As the defining factor is absence of the corpora, aphallia may also occur in female patients although it is thought to be less common and more difficult to diagnose [8]. This is most likely attributable to a high association with bladder agenesis and higher in-utero mor- tality [8]. Aphallia may also be an association of the uro- rectal septum malformation sequence (URSMS) spectrum of disorders [9, 18]. As such, aphallia must be considered on a spectrum ranging from an isolated disorder where the rest of the genitourinary tract has a normal configuration, to a symptom of a broader spectrum of congenital malforma- tions, which is the case, in over 50% of patients [9, 18, 22]. These include anomalies of the genitourinary, gastrointesti- nal and musculoskeletal systems and sometimes with more severe anomalies incompatible with life [9, 18, 22]. The aetiology of aphallia is unknown but has been described as a sporadic malformation [11]. Genetic work based on murine models has shown association with abnor- malities in the Sonic Hedgehog (SHH) gene, which is criti- cal in bladder and bowel development, with impaired sign- aling of fibroblast growth factor [8]. Aberrant signaling of retinoic acid within the SHH pathway has also been found to be associated with impaired genital tubercle development via inhibited vasculogenesis [8].Ta bl e 1 (c on tin ue d) A ut ho r Ty pe o f r ep or t N A ge A ss oc ia te d ab no rm al iti es Si te o f u re th ro re ct al fi stu la Ty pe o f i nt er ve nt io n G en ito ur in ar y N on -g en ito ur in ar y D e C as tro e t a l. [2 1] C as e se rie s 4 6  m on th s – N ot m en tio ne d Pr es ph in ct er ic Ph al lo pl as ty + ur et hr op la sty . La te r r em ov al o f d ist al u re th ra an d sc ro ta l u re th ro sto m y (p la nn ed fo r s cr ot o- pl as ty + gl an ul op la sty / ne w di st al u re th ro pl as ty ) 17  m on th s R ig ht m ul tic ys tic d ys pl as tic k id ne y M eg ac ys tis a nd m eg au re th ra B ila te ra l u nd es ce nd ed te ste s H irs ch sp ru ng ’s D is ea se Pr es ph in ct er ic Ph al lo pl as ty + ur et hr op la sty Ve si co sto m y La te r r e- do g la nu lo pl as ty 3  ye ar s En la rg ed , i rr eg ul ar a nd h ar d rig ht te sti s N ot m en tio ne d Pr es ph in ct er ic Pr ev io us b ila te ra l l oo p ur et er - os to m ie s + at te m pt a t u re th ra l re lo ca tio n Ph al lo pl as ty + ur et hr op la sty 12  y ea rs N ot m en tio ne d N ot m en tio ne d Pr es ph in ct er ic Ph al lo pl as ty + ur et hr op la sty * Pl an ne d in te rv en tio ns th at h ad n ot y et ta ke n pl ac e at th e tim e of th e pu bl is he d re po rt N n um be r o f p at ie nt s i n pa pe r, VU R ve si co ur et er al re flu x, P U V po ste rio r u re th ra l v al ve s, U VJ u re te ro ve si ca l j un ct io n, U RS M S ur or ec ta l s ep tu m m al fo rm at io n se qu en ce , M C D K m ul tic ys tic d ys - pl as tic k id ne y, S SB S se ve re sh or t b ow el sy nd ro m e, U D T un de sc en de d te sti s, TI tr ic us pi d in su ffi ci en cy , P D A pa te nt d uc tu s a rte rio su s 818 Pediatric Surgery International (2018) 34:813–821 1 3 Ta bl e 2 P ha llo pl as tie s, ur et hr op la sti es a nd o ut co m e * P la nn ed in te rv en tio ns th at h ad n ot ta ke n pl ac e at ti m e of p ub lic at io n A ut ho r Ph al lo pl as ty –i nt er im /fi na l Te ch ni qu e U re th ro pl as ty O ut co m e of p ha llo pl as ty Jo sh i e t a l. [2 ] In te rim Fo r c re at io n of p ha lli c str uc tu re a t 18 m on th s a nd fu nc tio na l p ha llu s at p ub er ty (u si ng v as cu la ris ed fl ap ar ou nd p ro st he si s) Pl an ne d fo r p er in ea l u re th ro sto m y be fo re p ha llo pl as ty * G oy al e t a l. [5 ] In te rim Pa ra sc ro ta l fl ap p ha llo -u re th ro pl as ty St ag ed u re th ro pl as ty a t l at er st ag e G oo d sk in se ns at io n, p os iti on a nd ap pe ar an ce A de qu at e le ng th fo r a ge St an di ng m ic tu rit io n an d co nt in en ce G oo d ps yc ho so ci al fu nc tio ni ng G ou ve a et  a l. [6 ] Fi na l D e C as tro p ha llo pl as ty p er in ea l u re - th ro sto m y an d M itr of an off – Th in ne r p en ile sh af t Ex ce lle nt in iti al o ut co m e M ac ed o et  a l. [7 ] Fi na l D e C as tro p ha llo pl as ty Pe rin ea l u re th ro sto m y So m e de gr ee o f p en ile re tra ct io n in le ng th W ill ih ng an z- La w so n et  a l. [1 1] Fi na l b ut p os si bl e ne ed fo r fu tu re re co ns tru ct io n D e C as tro n eo ph al lo pl as ty Pr ev io us c at he te ris ab le st om a cr ea te d Re gr es si on o f d ist al n eo ph al lu s, So m e lo ss o f c on ic al g la nu la r s ha pe H ig h sa tis fa ct io n D es ca m ps e t a l. [1 5] Fi na l Pe di cl ed a nt er ol at er al th ig h fla p ph al - lo pl as ty St ag ed u re th ra l r ec on str uc tio n be gu n at tim e of p ha llo pl as ty W ou nd d eh is ce nc e at d ist al ti p of ne op ha llu s D e C as tro e t a l. [2 1] In te rim -fo r c os m et ic re op er at io n Q ua dr an gu la r a bd om in al sk in fl ap p ha l- lo pl as ty + bl ad de r/b uc ca l m uc os a fr ee gr af t u re th ro pl as ty In iti al u re th ro pl as ty a t t im e of p ha llo - pl as ty b ut la te r d ist al u re th ra re m ov ed an d sc ro ta l u re th ro sto m y pe rfo rm ed Pr og re ss iv e m ea ta l a nd u re th ra l s te no si s Fi na l Q ua dr an gu la r a bd om in al sk in fl ap p ha l- lo pl as ty + bl ad de r/b uc ca l m uc os a fr ee gr af t u re th ro pl as ty La te r r e- do g la nu lo pl as ty Si m ul ta ne ou s u re th ro pl as ty G oo d co sm et ic o ut co m e Fi na l Q ua dr an gu la r a bd om in al sk in fl ap p ha l- lo pl as ty + bl ad de r/b uc ca l m uc os a fr ee gr af t u re th ro pl as ty Si m ul ta ne ou s u re th ro pl as ty Ep is pa di c ur et hr al m ea tu s d ue to p ar tia l de hi sc en ce o f d or sa l u re th ra l s ut ur es Fi na l Q ua dr an gu la r a bd om in al sk in fl ap p ha l- lo pl as ty + bl ad de r/b uc ca l m uc os a fr ee gr af t u re th ro pl as ty Si m ul ta ne ou s u re th ro pl as ty Ep is pa di c ur et hr al m ea tu s d ue to p ar tia l de hi sc en ce o f d or sa l u re th ra l s ut ur es 819Pediatric Surgery International (2018) 34:813–821 1 3 During the fourth week of gestation, a mesenchymal prominence within the cloacal membrane proliferates to form the genital tubercle [8]. Aphallia is likely due to failed development, hence absence of the genital tuber- cle, related in part to inadequate development of caudal mesenchyme or an early insult in cloacal maturation [8]. In the more severe aphallia associated malformations, the problem may originate with a defect in the induction of cloacal differentiation [9] occurring in early embryo- genesis as a defect in blastogenesis [18]. This occurs at the same time as organogenesis of other systems, which explains the wide range of associated malformations seen, principally in URSMS, which may be partial or full [9, 18]. Partial URSMS is characterized by a single perineal opening draining a common cloaca with any number of associated systemic malformations (GU, GIT, MSK), whereas full URSMS is characterized by absence of both perineal and anal openings, usually associated with severe pulmonary hypoplasia and oligohydramnios secondary to severe associated renal anomalies, and is not compatible with postnatal life [9, 18]. Diagnosis is made clinically with the absence of the phallus in a child with normal karyotype on genetic test- ing. The absence of the phallus should not be mistaken for a concealed or rudimentary penis, micropenis, male pseudohermaphroditism or intra-uterine amputation of the penis [10]. Aphallia may be classified in three ways: 1) As a disorder of sex development of the non-hormonal/ non-chromosomal type [23]. 2) Skoog’s anatomical classification related to the position of the ectopic urethra in relation to the anus, and the number of associated anomalies [2, 9, 12, 24]. a. Post-sphincteric (fistula below the dentate line or anywhere on the perineum). This is the most com- mon subtype (60%) and is commonly associated with a skin tag. It has the highest survival rate (87%) and the lowest incidence of associated anomalies (1.2 per patient) [9, 24]. b. Pre-sphincteric (fistula above the dentate line, i.e., a urethrorectal fistula). This group makes up 28% of the aphallia population and has 36% mortality in the neonatal period related to associated life-threatening malformations [9, 24]. c. Urethral atresia. This occurs least commonly (12%) and is uniformly fatal. It also has the highest number of associated malformations (4 per patient) [9, 21]. 3) Evans’ prognostic classification based on the presence or absence of major associated anomalies [2, 12, 25] a. First group—This occurs in 16% of cases and is associated with renal aplasia, renal dysplasia and other caudal abnormalities and has a high mortality [2, 25]. b. Second group—72% of cases. This group has fewer associated malformations and has a lower mortality rate [2, 25]. c. Third group—the remaining 12% of cases are not associated with any specific pattern of anomalies [2, 25]. Aphallia should, thus, be considered a developmental field defect. Although it does occur in an isolated form (with a good prognosis), it can be associated with multiple other anomalies with high mortality [25]. Overall, more than half aphallia patients will have an associated anomaly [2, 13], which can be broadly divided into genitourinary and non- genitourinary [13] (Table 1). Management of this rare disorder has been controversial. As recently as 1997, the recommended surgery and only available reconstructive option for these children was femin- izing genitoplasty. This was based on the belief that ‘raising these patients as male can be disastrous’, and that ‘it is better to be incompletely female than inadequately male’ [26]. This management strategy comprised a bilateral orchidectomy within the first few days of life, to prevent early post-natal androgen imprinting, followed by vaginal interposition and hormonal therapy at puberty [11, 26]. These patients expe- rienced a high rate of gender dysphoria [2, 11] due, in part, to prenatal androgen imprinting that had already taken place. Prenatal and early neonatal androgen imprinting has been studied in animal models, pregnant females on hormone therapy and in children with congenital adrenal hyperplasia proving that exposure of the fetus to testosterone affects sex- typed interests in childhood (including toy, playmate and activity preferences) as well as sexual orientation in later life tending toward male typical behavior and gynephilia (erotic interest in females) [27]. Extrapolating from surgical management of patients with disorders of sex development, sexual designation should be based on the gender that pro- vides the best prognosis in terms of reproductive function, capability of sexual function, appearance of the external genitalia and self-identity of the patient with a specific gen- der [4]. Therefore, although feminizing genitoplasty has still been recommended for infants and newborns in case reports as recent as 2015 [10], it is now generally accepted, and the opinion of these authors, that a normally genetic male with aphallia should be supported surgically as a male until the patient is old enough to gender identify. As such, management can be divided into short, inter- mediate and long-term treatment phases [2]. From the most recent literature (Tables 1, 2), management can be divided as follows: 820 Pediatric Surgery International (2018) 34:813–821 1 3 1) Short term—supportive care of life-threatening compli- cations and associations of aphallia usually presenting in the neonatal period (resuscitation of compromised air- way, breathing and circulation according to protocolled algorithms). Most pertinent is relief of urinary obstruc- tion if present, this with the creation of a vesicostomy. Urinary obstruction may not always be present (as in cases of a urethro-perineal fistula) and would therefore, not need urinary diversion at this stage. 2) Intermediate term—division of the urethrorectal fistula with perineal urethrostomy with or without temporary phallus formation. This is preferably fashioned from scrotal skin to allow use of other sites for neophallus creation at puberty, allowing the imprinted male to out- wardly identify as male from an early age (usually before toilet training). 3) Long-term—definitive phalloplasty and urethroplasty, with or without creation of a Mitrofanoff. Successful creation of a neophallus should allow the patient to appear outwardly male, urinate standing up and perform adequately from a sexual perspective, usually with the help of a prosthesis. When specifically considering the phalloplasty, the reconstructive techniques can be divided into microsur- gical and non-microsurgical procedures [4]. Non-micro- surgical procedures essentially constitute flap surgery, with techniques that are technically easier and simpler to perform but are generally performed as temporizing procedures, necessitating more definitive reconstructions during puberty. These more definitive procedures usually utilize microsurgical free flap techniques in combination with implantation of prostheses. This staged approach is necessary as rotational flap procedures performed in early life may not grow appropriately in relation to the patient and may not accommodate prosthesis implantation [4, 6]. The reason that these flap phalloplasties are used preferen- tially in infants is that construction of a permanent adult- sized neophallus in a paediatric patient is undesirable and this technique spares tissues used for microsurgical free flap phalloplasty for use at a later stage. Non-microsurgical options for phalloplasty include groin, abdominal and scrotal flaps [4]. Although the De Castro flap (abdominal wall flap based on vascular supply from the superficial epigastric arteries) has been reported as a tempo- rary reconstructive or pseudophallus option [11], it has been reported to grow adequately with the patient and has allowed prosthetic implantation allowing ‘erectile’ function [6]. Microsurgical procedures are complex with a much longer intra-operative time and necessitate multidisciplinary team management [4]. They are designed as a single-stage pro- cedure to be performed in adulthood with the concomitant insertion of a penile prosthesis. Microsurgical procedures used in the past include osteocutaneous fibular flap, myocu- taneous latissimus dorsi flap and the radial forearm flap [4]. Although many options exist for phalloplasty, the greatest reconstructive challenge in aphallia patients is the urethro- plasty. Again, many options exist but the most commonly used option is the combined use of groin skin to create the posterior urethra and a buccal mucosal graft to fashion the anterior urethra. However, the majority of patients ultimately require a Mitrofanoff channel to adequately decompress the bladder and protect the upper tracts [4]. It is vitally impor- tant to understand which aspect of the reconstructive surgery is most important to the patient and their family to properly manage expectations. Long-term follow-up is essential but there is a distinct lack of information regarding the long- term outcomes of these patients. This is a major limitation to this review. Conclusion Because of the rarity of aphallia and its reconstructive complexity, management of this condition remains a chal- lenge. Its management should be approached as a multidis- ciplinary team consisting of paediatric surgeons, paediatric urologists and plastic surgeons as well as nephrologists and psychologists. One conclusive statement that can be made is that feminizing genitoplasty should be avoided at all costs. When appraising the small number of cases reported it seems that the De Castro technique for non-microsurgical flap phalloplasty is the most commonly used technique with the best outcome. This flap is reported to grow with the patient, allows simultaneous urethroplasty with acceptable outcomes, and the potential for penile prosthesis implant at a later stage remains. It has the advantage of using skin and tissue in the surrounding area and so spares any area that may need to be used at a later stage for microsurgical free flap phalloplasty. All interventions should be undertaken with the end goal of meeting and managing patient expecta- tions and protecting upper urinary tracts. Funding No funding was received for this study. Compliance with ethical standards Conflict of interest The authors declare no conflicts of interest. References 1. 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