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Hypospadias

Article  in  Current opinion in urology · September 2012

DOI: 10.1097/MOU.0b013e328357bc62 · Source: PubMed

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REVIEW

CURRENT
OPINION Hypospadias
Antonio Macedo Jr, Atila Rondon, and Valdemar Ortiz

Purpose of review
Hypospadias is one of the most common congenital anomalies in men. We searched the recent literature
(since 1 January 2011) using the following keywords in the title or abstract: hypospadia or hypospadias,
in order to provide the reader with an updated view of the subject.
Recent findings
Early repair is recommended; distal forms are mainly treated by the tubularized incised plate technique;
however, meatal stricture concerns are still noticed, limiting its use on proximal forms. The debate of
proximal primary repair in either one or two stages is still ongoing. Minor modifications for preparing the
distal bed for the urethroplasty in two stages are presented. One-stage repairs, either with reconstruction of
the urethral plate (three-in-one concept) or simply with the onlay to tunica albuginea (Rigamonti), is a viable
option with over 70% success in one surgery. The importance of barriers, such as tunica vaginalis and
dartos flap, was reassessed and flow rates may indicate obstructive voiding patterns after 1-year follow-up.
Summary
Further experience and comparative studies for distal and proximal hypospadias are required. Long-term
data may indicate the appropriate procedure selected for primary repair.
Keywords
hypospadias, urethra, surgery, penile reconstruction

INTRODUCTION CAUSE OF HYPOSPADIAS

Hypospadias is one of the most common congen-
ital anomalies in men. The incidence of hypo-
spadias in Western countries has been increasing
and is estimated in 150–300 of male births [1].
Numerous surgical techniques have been pre-
sented to treat hypospadias, including 200 differ-
ent subvariants of surgical repair. No consensus is
yet defined in this area. Despite numerous advan-
ces in tissue transfer and refinements in operative
techniques, there is seldom a consensus among
pediatric urologists when discussing their prefera-
ble approaches. Preferences may vary in topics
such as using grafts versus flaps, types of stents,
urinary diversion and the polemic issue of treating
in one or two steps.
We searched the recent literature (since 1
January 2011) that presented in the title or
abstract the keywords hypospadia or hypospadias
in order to provide the reader with an updated
view of the subject. We identified 159 articles from
which we selected 35, which were then classified
in topics and organized for discussion. We focused
our review on the clinical aspects of hypospadias
in humans.
The cause of hypospadias is probably a mix of mono-
genic and multifactorial forms, implicating both
genes and environmental factors. van der Zanden
et al. [2] performed a systematic review to define the
current knowledge about the cause of hypospadias.
The literature had been reviewed since 1995 and the
authors concluded that single mutations do not
cause the majority of isolated hypospadias cases.
Indeed, associations were found with polymor-
phisms. In addition, gene-expression studies ident-
ified CTGF, CYR61 and EGF as candidate genes.
Environmental factors consistently implicated in
hypospadias were low birth weight, maternal hyper-
tension and preeclampsia, suggesting that placental
insufficiency may play an important role in hypo-
spadias cause. Exogenous endocrine-disrupting
Department of Urology, Universidade Federal de São Paulo, São Paulo,
São Paulo, Brazil
Correspondence to Antonio Macedo Jr, Rua Maestro Cardim, 560 cj
215, 01323-000, São Paulo, São Paulo, Brazil. Tel: +55 11 32870639;
fax: +55 11 32873954; e-mail: macedo.dcir@epm.br
Curr Opin Urol 2012, 22:447–452
DOI:10.1097/MOU.0b013e328357bc62

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Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
 Urethral reconstruction
KEY POINTS
 Preoperative use of 1% testosterone propionate
ointment before hypospadias surgery produce
neovascularization in absolute numbers and in volume
density, but negative implications on wound healing
are still to be defined.
 Distal hypospadias repair is currently treated mostly by
the tubularized incised plate (TIP) technique and age at
surgery does not increase odds of urethroplasty
complication, being recommended at 4–6 months.
 Proximal hypospadias can be treated in two stages,
which is a more simple procedure, although data from
one-stage repair (three-in-one technique and onlay to
albuginea) show success in 70% of cases in one
setting.
 Bracka repair is considered the gold standard for
salvage hypospadias repair; however, complications
after second stage occur in approximately a third of
patients, mainly those with fibrotic and indurated grafts;
therefore, regrafting should be considered whenever
the aspect of the graft is not flat and mobile.
chemicals have the potential to induce hypospadias,
but it is unclear whether human exposure is high
enough to exert this effect.
Animal models of endocrine dysfunction have
associated male genital defects with reduced ano-
genital distance (AGD). Human studies have corre-
lated shorter AGD with exposure to putative
endocrine disruptors in the environment but have
not examined AGD in hypospadiac boys. Hsieh et al.
[3] from the University of California in San Francisco
group measured AGD in boys with hypospadias and
those with normal genitals, and concluded that
hypospadias may indeed be associated with reduced
AGD. The authors acknowledge, however, the lim-
ited size of their series and suggest that additional
studies are needed to corroborate these preliminary
findings and to determine their cause.
Penile size in hypospadias is subjectively
assumed by the parents to be inferior to normal
children because of ventral chordee. Fievet et al.
[4] measured penile length in two groups of children
aged up to 5 years. The first group comprised all boys
admitted for hypospadias (40 patients; 25 distal and
15 proximal hypospadias). The control group com-
prised 100 boys seen for other surgical procedures
excluding those with endocrine disorders. Mean
penile length in the control group was 4.07–
0.92 cm; mean penile length in the hypospadias
group was 4.36–0.9 cm (4.48–0.89 cm for distal
hypospadias and 4.21–0.79 cm for proximal hypo-
spadias). There was no difference in penile length
448 www.co-urology.com
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between the hypospadias group and the control
group regardless of degree of hypospadias. This
study provided useful information to educate
parents when discussing results and goals of surgical
treatment.
GENERAL ASPECTS
The clinical description of a patient with hypospa-
dias is currently based on the anatomical location
of the external meatus relative to either the penis
or to nonpenile structures such as the scrotum or
perineum. We are aware, however, that we can only
define the severity of hypospadias after penile
degloving and repair of chordee. Although the
position of the external meatus within the distal
penis (i.e. glanular, subcoronal or distal penile)
seems to be reliable and may be consistently
described, this measure is less reliable in patients
with penoscrotal, scrotal or perineal hypospadias, as
the scrotum may be translocated as far as the distal
penis in these patients. Orkiszewski [5] examined
the position of the corpus spongiosum division
relative to pelvic bone structures as an indicator
of the true level of hypospadias, basically consider-
ing a horizontal line at the upper pubis level and
categorizing hypospadias as penile (above) or proxi-
mal (below). As a critique comment, we believe that
this classification still does not consider curvature
and only after assessing this issue is it possible to
decide for a surgical procedure in proximal forms.
Two studies provided trends on hypospadias
repair either based on experts’ opinion or on a
&&
questionnaire survey [6 ,7]. In the survey study,
377 participants from 68 countries returned com-
pleted questionnaires. In distal hypospadias (sub-
coronal to midshaft), the tubularized incised plate
(TIP) repair was preferred by 52.9–71.0% of the
participants. In the repair of proximal hypospadias,
the two-stage repair was preferred by 43.3–76.6%.
TIP repair in proximal hypospadias was used by
0.9–16.7%. Onlay flaps and tubes were used by
11.3–29.5% of the study group. Simple plication
and Nesbit’s procedure were the techniques of
choice in curvature up to 308; urethral division
and ventral incision of the tunica albuginea with
grafting were performed by approximately 20% of
the participants in severe chordee. The frequency of
hypospadias repairs did not influence the choice
of technique [7].
The assessment and management of hypo-
spadias, considering questions, such as evaluation
of hypospadias severity, preoperative biological
assessment, preoperative hormonal stimulation
and choice of urethroplasty to the postoperative
evaluation were debated by Snodgrass, Macedo
Volume 22  Number 6  November 2012

and Mouriquand as a written dialogue following
their panel discussion at the World Congress of
Pediatric Urology. Piet Hoebeke was asked to referee
their comments to highlight the areas of agreement
and dispute. This study is quite different and pro-
vocative as the reader can observe different views to
the same questions and make his own conclusions
&&
[6 ].
The discussion of hypospadias repair is high-
lighted by the challenging need to reduce compli-
&
cation rate. Prat et al. [8 ] from Jerusalem revised
their date over the last three decades and provided a
frank reporting of a 58% immediate complication
rate in the proximal group and a 31% rate in the
second midshaft to distal group, which is refresh-
ingly honest. A way to improve these results could
be the use of tissue engineering techniques. During
the period of 2000–2002, six patients with severe
hypospadias were treated surgically with autologous
urothelial cells that had been isolated, expanded
and stored in vitro, according to Fossum et al. [9].
Patients have been followed for a median follow-up
time of 7.25 years and present good cosmetic
appearance. The authors acknowledge, however, a
limited series and lack of controls.
PREOPERATIVE TESTOSTERONE USE AND
HORMONAL IMPLICATIONS
Three studies were found on this subject. Estrogenic
endocrine disruptors acting via estrogen receptors
alpha and beta have been implicated in the cause of
hypospadias. Qiao et al. [10] from Larry Baskin’s
group in San Francisco searched for the expression
of estrogen receptor alpha and beta comparing fore-
skin in hypospadias patients and controls and
showed that expression is indeed decreased in hypo-
spadias. As the authors themselves state, their results
need to be interpreted with caution, as they did not
directly study normal or hypospadiac urethral tissue
in patients undergoing surgery. It is possible that
events occurring in the foreskin, whose epithelium
is ectodermal in origin, may not be occurring in the
urethra, whose epithelium is endodermal in origin.
Furthermore, they did not study the events at the
critical time of external genitalia development and
urethral malformation.
Androgen stimulation before hypospadias
surgery has resulted in increased penile size, fewer
complications and improved cosmesis, and suggests
increased neovascularization. Anyway, the real
effect on neovascularization remained to be proved.
&
Bastos et al. [11 ] studied a total of 26 boys with
hypospadias, who were randomly allocated to two
groups before surgical correction. Group 1 did not
receive any treatment and group 2 received 1%
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Hypospadias Macedo Jr et al.
testosterone propionate ointment twice daily for
30 days before surgery. The authors found that
the use of 1% testosterone propionate ointment
before hypospadias surgery produced neovasculari-
zation in absolute numbers and in volume density.
This finding suggests a beneficial role of preopera-
tive use of testosterone, although only a randomized
clinical trial could confirm it.
Gorduza et al. [12] from the Lyon’s group in
France designed a prospective study to compare
the outcomes of onlay urethroplasty with and with-
out preoperative androgen stimulation in patients
with severe hypospadias. The authors identified 126
patients and 30 of these received preoperative
androgen treatment (human chorionic gonado-
trophin and systemic testosterone) 1–24 months
before surgery. Thirty-five patients presented a com-
plication (27.7%) of whom 26 (20.6%) had a fistula
or dehiscence. Among patients on androgen stimu-
lation, there was a 30% healing complication rate (9
of 30), whereas those without androgen stimulation
presented a healing complication rate of 17.7% (17
of 96). The authors concluded that the numbers
were, however, too small to reach statistical signifi-
cance and further experience is still necessary for a
definitive conclusion.
TUBULARIZED INCISED PLATE REPAIR
Distal hypospadias repair today is mostly treated by
the TIP technique. Snodgrass presented three papers
on this theme. Reviewing his series of 669 consecu-
tive prepubertal patients aged 3–144 months (mean
17.1, standard deviation 22.5), he concluded that
age at surgery does not increase odds of urethro-
plasty complication and that surgery can be per-
formed any time after 3 months (in full-term
healthy boys) without raising the rate of compli-
cations [13]. In another study, the same group
showed that glans dehiscence occurred in 32 of
641 patients (5%). Age at surgery, preoperative tes-
tosterone use and glansplasty suture did not impact
the risk of glans dehiscence. Glans dehiscence
occurred in 20 of 520 distal (4%), 1 of 47 midshaft
(2%) and 11 of 74 proximal (15%) TIP repairs, with
the odds of glans dehiscence being 3.6 times higher
in patients with proximal versus distal meatal
location [14].
The use of the TIP concept for proximal hypo-
spadias is, however, controversial. The severity of
chordee and the need for urethral plate division
&
limits its use. Snodgrass and Bush [15 ] believe that
mobilizing the urethral plate to correct the curva-
ture may allow use of his principle also in proximal
forms. The authors reported 24 patients operated
with a mean follow-up of 12 months. Complications
www.co-urology.com 449
 Urethral reconstruction
occurred in three (13%), glans dehiscence (2) and
neourethral stricture (1). Hafez and Helmy [16] also
believe that TIP is a valid procedure for repair of
penoscrotal hypospadias with chordee 308. The
overall success (86%) was satisfactory on 90 patients
treated, but they state that surgeon’s experience is
the pillar for better success.
One concern about TIP repair is that it often can
result in obstructed flow at uroflowmetry, owing to
meatal stenosis or as a result of a noncompliant
neourethra. Andersson et al. [17] designed a pro-
spective study to evaluate whether urinary flow
improves with time after TIP repair. The authors
found spontaneous improvement 7 years after TIP
repair, although 32% of the boys without symptoms
still had obstructive flows at this point. The authors
conclude that long-term follow-up is important as
there does not seem to be any way to predict which
boys will deteriorate and develop obstructions,
demanding intervention. They also believe that
the use of TIP repair in more severe cases of hypo-
spadias should be limited, considering that proxi-
mal hypospadias in this study presented worse
flows.
OTHER TECHNIQUES FOR DISTAL REPAIR
The Mathieu technique was revisited by two studies.
Elganainy et al. suggested that preputial preser-
vation during Mathieu repair is a timesaving pro-
cedure with similar complication rate to traditional
repair and Hadidi presented satisfactory results in
848 of 872 patients (97%) [18,19].
Elsayed et al. [20] presented the concept of dis-
tally folded onlay flap in the repair of distal penile
hypospadias, mainly for patients with a shallow
urethral plate, a small glans or those who had under-
gone a previous operation but still had available
preputial skin. This prospective study involved
36 patients with a mean age of 3.2 years. There were
no cases of meatal stenosis or requirement for ure-
thral dilatation. Two patients had an urethrocuta-
neous fistula: one closed spontaneously while the
other needed surgical repair 6 months later. Regard-
ing esthetic appearance, 32 were scored good and
four satisfactory.
PROXIMAL HYPOSPADIAS
The main discussion here is conceptual: treating in
&
two stages or one stage. Castellan et al. [21 ] reported
ventral corporal body grafting for correcting severe
penile curvature associated with small intestine sub-
stance. The authors obtained a straight phallus with
good cosmesis in 57 of 58 patients. As a result of
penile elongation with a graft, simultaneous island
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flap urethroplasty became difficult in many patients
and most surgeons agree that corporoplasty requires
two-stage hypospadias repair.
Also considering two-stage repair, Springer and
Subramaniam [22] described a modification of the
two-stage repair using a dorsal split dartos fascia
flap, as well as a vascularized bed for the graft in
the first stage with the advantage of providing excel-
lent blood supply for graft take. A comparison of
these data with regular uptake of the graft into the
corpora is still necessary. Different strategy for ante-
grade dissection of the preputial vascular pedicle
during hypospadias repair was reported and also a
variant of how to transpose tubularized flap into
ventral surface of the penis by a glandular incision in
the midline [23,24].
The three-in-one concept was reviewed with
long-term results. This one-stage strategy is based
on reconstruction of the urethral plate with buccal
mucosa graft and onlay transverse preputial flap
anastomosis protected by a tunica vaginalis flap.
&
Macedo et al. [25 ] reported 68.5% success in a single
operation, whereas 31.5% required a second repair
for a complex population of 35 patients that
required division of the urethral plate to correct
ventral curvature.
&
Rigamonti and Castagnetti [26 ] presented
results on the onlay on albuginea technique, which
follow the same principles of the three-in-one tech-
nique, except for the reconstruction of the urethral
plate after its division to get the penis straight. The
preputial flap was anastomosed onlay directly to the
tunica albuginea. The authors reported 14 patients
and 21% complications at a mean follow-up of
7 months. This procedure is indeed an advance
and can reduce time of surgery, although further
experience is awaited.
REDOS
A study and a video discussed the staged buccal
mucosa Bracka repair, the gold-standard procedure
today for salvage hypospadias repair [27]. Leslie
et al. [28] found complications after second stage
in approximately a third of patients, mainly those
with fibrotic and indurated grafts. A regrafting
should be considered whenever the aspect of the
graft is not flat and mobile, before considering
tubularization at the second stage. Mir et al. [29]
reviewed the medical records of six hypospadias
male patients who underwent tissue expansion
for phallic skin resurfacing, which may be a useful
approach for patients who have undergone
multiple attempted hypospadias repairs and lack
a sufficient amount of healthy, unscarred penile
skin for a successful outcome.
Volume 22  Number 6  November 2012

FINAL COMMENTS
Three studies discussed the importance of barriers
and sealants in hypospadias surgery. Dhua et al. did
not find a difference comparing dartos flap and
tunica vaginalis to cover the neourethra, Bertozzi
et al. recommended the double dartos flap and
Kajbafzadeh et al. evaluated the efficacy of fibrin
sealant for repair of urethrocutaneous fistula after
multiple failed hypospadias and epispadias surgeries
[30–32]. The study population comprised 11 boys
(mean age 12.18 years) with a history of hypospadias
or epispadias and at least two failed fistula repair
operations leading to recurrent urethrocutaneous
fistula. The authors concluded that single-donor
fibrin glue could be a useful adjunct to surgical
management of patients after multiple failed
surgical attempts.
The early age at surgery between 6 and 9 months
is strongly recommended, two studies presented
higher complications rate by older patients [33,34].
González and Ludwikowski [35] reviewed the
literature in regard to flow studies after hypospadia
repair and suggested that, as early abnormal flows
improve spontaneously, children operated on after
toilet training that are asymptomatic should
undergo their first uroflow measurement 1 year after
surgery. Olsen et al. [36] showed that infants with
hypospadias in the preoperative setting void with a
lower Qmax and a lesser degree of dyscoordination
as compared to normal infant boys. The authors
speculated that decreased urethral compliance
may contribute to the lower Qmax. The exact mean-
ing of this finding is however to be defined.
CONCLUSION
The current knowledge on hypospadias repair is still
evolving. Early repair is recommended, distal forms
are mainly treated by the TIP technique, but meatal
stricture concerns are still observed, limiting its use
on proximal forms. The debate of proximal primary
repair either in one stage or two stages is still run-
ning. Minor modifications for preparing the distal
bed for the urethroplasty in two stages were pre-
sented. One-stage repair, either with reconstruction
of the urethral plate (three-in-one concept) or
simply the onlay to tunica albuginea (Rigamonti),
is a viable option with over 70% success in one
surgery. The importance of barriers like tunica
vaginalis and dartos flap was reassessed, and flow
rates may indicate obstructive voiding patterns after
1-year follow-up.
Acknowledgements
No funding was received.
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Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Hypospadias Macedo Jr et al.
Conflicts of interest
There are no conflicts of interest.
REFERENCES AND RECOMMENDED
READING
Papers of particular interest, published within the annual period of review, have
been highlighted as:
& of special interest
&& of outstanding interest
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&&
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 Urethral reconstruction
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Volume 22  Number 6  November 2012