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Prune belly syndrome

Article  in  Pediatric Surgery International · December 2011

DOI: 10.1007/s00383-011-3046-6 · Source: PubMed

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Pediatr Surg Int (2012) 28:219–228
DOI 10.1007/s00383-011-3046-6
REVIEW ARTICLE
Prune belly syndrome
S. Hassett • G. H. H. Smith • A. J. A. Holland
Accepted: 14 December 2011 / Published online: 25 December 2011
Ó Springer-Verlag 2011
Abstract The majority of paediatric surgeons will
encounter a patient with prune belly syndrome (PBS) only
a few times in their clinical practice. There have been many
opposing views in the literature regarding the pathogenesis
and management of this complex condition. A detailed
review was conducted using PubMed to identify key pub-
lications involving PBS. This article discusses the evolu-
tion of our understanding of the pathogenesis and diagnosis
of PBS, including its typical characteristics. We describe
the management options available for bilateral intra-
abdominal testes, the deficient abdominal wall, the dilated
urinary system and examine the evidence base used to
support the current approaches employed.
Keywords Prune belly syndrome
Cryptorchidism

Abdominal wall
Hypotonia
Ectasia
Introduction
Prune belly syndrome (PBS) has been characterised by
deficient or absent abdominal wall musculature, hypotonia,
ectasia (that is pathophysiological dilatation or distension)
of the urinary system and bilateral intra-abdominal testes.
S. Hassett
A. J. A. Holland (&)
Douglas Cohen Department of Paediatric Surgery,
The Children’s Hospital at Westmead, Sydney Medical School,
The University of Sydney, Sydney, NSW, Australia
e-mail: andrew.holland@health.nsw.gov.au
G. H. H. Smith
Department of Urology, The Children’s Hospital at Westmead,
Sydney Medical School, The University of Sydney, Sydney,
NSW, Australia
It was initially reported by Frolich in 1839, although the
term ‘‘prune belly syndrome’’ was coined by Osler [1]. In
1950, nine cases were reported by Eagle and Barrett [2]
who described the condition as Eagle-Barrett Syndrome.
Other synonyms used in the literature include triad syn-
drome and abdominal musculature deficiency syndrome
[3]. Whilst PBS was originally described in male infants
with bilateral cryptorchidism as a diagnostic feature,
identical abdominal wall and urinary tract abnormalities
have been, albeit rarely, described in females [4].
While the triad of signs described remain a constant
feature in PBS, many other non genito-urinary associations
have been reported (Table 1). Recognition of these addi-
tional elements led Smolkin et al. [5] to suggest the term
prune belly association.
The purpose of this review article was to examine the
current evidence on the pathogenesis, diagnosis and man-
agement of PBS, together with the level and quality of the
evidence utilised to support the approach employed in the
treatment of patients.
Methods
A literature search was conducted using PubMed. The term
‘‘prune belly syndrome’’ was used and limited to humans.
A total of 642 publications were identified. Studies which
used a heterogeneous population of patients including PBS
were excluded. Case reports, apart from those describing
genetic associations, were also omitted. Seventy-two rele-
vant articles were identified where the study population
consisted solely of PBS patients. Levels of evidence were
assessed the Scottish Intercollegiate Guidelines Network
(SIGN) grading system for recommendations in evidence-
based guidelines [6].
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Table 1 Prune belly syndrome associations
Pulmonary (58%) Cardiovascular (25%)
Pulmonary hypoplasia PDA
Tetralogy of fallot
ASD
VSD
Valvular anomalies
Epidemiology
A recent review of the epidemiology of male infants with
PBS by Routh et al. [7] cited an incidence of 3.76 cases per
100,000 live births. An earlier study by Druschel et al. [8]
quoted an incidence in females of 1.1 per 100,000. Data
from the United States (US) indicates a significant increase
in incidence in the Afro-Caribbean population, with a
corresponding lower incidence in those of Hispanic origin
in comparison to the Caucasian population. There also
appears to be an increased incidence of PBS in children of
younger mothers [8].
There are reports of PBS occurring in association with
Trisomy 13, 18 and 21, but these cases are too few to
indicate a formal association with these genes [9–11].
There is some evidence to suggest a genetic influence in
PBS. There are 12 reported cases of familial PBS. Analysis
of these cases has implicated a sex hormone influenced
autosomal recessive mode of inheritance due to the male
predominance of the reported cases [12].
PBS is commoner in both monozygotic and dizygotic
twin pregnancies. Interestingly, in cases of monozygotic
twins, both discordance and concordance for PBS has been
reported, implying that inherited genetic mutations alone
cannot explain the pathogenesis of PBS [8, 13, 14].
An abnormality of hepatocyte nuclear factor 1b
(HNF1b) has been demonstrated in patients with sporadic
PBS. This transcription factor, expressed on chromosome
17, is found on numerous tissues in the body including
mesonephric duct derivatives, renal tubules of the meta-
nephros and the developing prostate [15, 16].
Pathogenesis
Pathogenic theories of PBS include urethral obstruction
and a mesodermal developmental defect.
The theory of urethral obstruction was based mainly on
observations of postmortem specimens and the anatomy of
infants with PBS [17]. Urethral obstruction causes bladder
distension and urinary tract dilatation in the developing
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Pediatr Surg Int (2012) 28:219–228
Gastrointestinal (24%) Musculoskeletal (23%)
Malrotation (40%) Scoliosis
Atresia of small bowel and colon Congenital hip dislocation
Splenic torsion Club feet
Imperforate anus Pectus carinatum
Gastroschisis Polydactylism
Omphalocele Arthrogryposis
Cloacal anomaly Hemivertebrae
Bilateral cervical ribs
foetus. This distension prevents normal abdominal mus-
culature development and testicular descent. Gonzalez
et al. [18] demonstrated PBS in sheep that had undergone
complete urethral obstruction between 43 and 45 days
gestation.
This theory fits neatly with cases of PBS, which feature
urethral atresia but does not explain PBS when the urethra
is patent, or the failure to develop the PBS phenotype in
cases of posterior urethral valves. Delayed canalization of
the urethra during the 11th–16th weeks of gestation has
been proposed as a possible mechanism [19]. Transient
urethral obstruction at a critical time in the development of
the urinary tract may be responsible. One hypothesis is the
presence of a hypoplastic prostate, which occurs due to a
focal insult to the developing urogenital sinus mesoderm.
The resultant hypoplastic prostate may cause the unsup-
ported membranous urethra to twist, or to create a flap
valve mechanism resulting in transient urethral obstruction
[20]. This is supported by the presence of generalized
prostatic hypoplasia found in PBS patients [21].
The other main theory in PBS is a failure of mesodermal
development [22]. As the urinary tract, abdominal wall
musculature, kidneys and the prostate gland, all affected in
PBS, share a mesodermal origin, this appears attractive. An
insult to the mesodermal layer during the early stages of
gestation should impact on other organ systems, however,
which is not the case in PBS. Perhaps more importantly,
the cause of the insult to the mesodermal layer has not been
identified.
Diagnosis
Antenatal diagnosis in the second trimester is now the most
common presentation of PBS [23]. Cases of trans-abdom-
inal ultrasound diagnosis between 11 and 14 weeks of
gestation have been reported [23–25]. Key elements in the
sonographic diagnosis of PBS include bilateral hydroureter
and hydronephrosis, a distended, thin-walled bladder and
oligohydramnios [26]. Oligohydramnios implies reduced
urine output, poor renal function and subsequent lung
Pediatr Surg Int (2012) 28:219–228 221

hypoplasia. The presence of severe renal dysfunction and
pulmonary hypoplasia in PBS is a predictor of nearly 100%
mortality within the first few days of postnatal life [27].
The differential diagnosis includes posterior urethral
valves (PUV) and megacystis microcolon intestinal hypo-
peristalsis syndrome (MMIHS). In PUV, there is isolated
dilatation of the posterior urethra in association with a
thick-walled bladder leading to a keyhole sign. This can
also occur in PBS if there are associated urethral abnor-
malities making it difficult to differentiate between PBS and
isolated PUV on antenatal ultrasound [28]. In MMIHS, seen
much more frequently in females, a thin-walled bladder is
noted in association with normal liquor volume [29].
The issue of antenatal intervention in PBS is a part of
the wider question of the antenatal intervention in a foetus
showing signs of lower urinary tract obstruction (LUTO).
Decompression of the urinary system in utero can be
achieved via insertion of a vesico-amniotic shunt. Case
reports of vesico-amniotic shunting between 17 and
24 weeks gestation in PBS, in a foetus with a normal
karyotype and the absence of other severe congenital
abnormalities, have been reported [30–32]. In all cases
oligohydramnios improved with survival of the foetus
through the last trimester and into postnatal life, although it
remains difficult to ascertain whether this was a reflection
of the natural history of the condition or as a result of
antenatal intervention. A meta-analysis performed by
Clarke et al. [33] indicated that prenatal bladder drainage
may improve perinatal survival in fetal LUTO. An attempt
to definitively answer this question is currently being
undertaken by the percutaneous shunting of lower urinary
tract obstruction (PLUTO) trial, the first randomized con-
trol trial of intervention versus conservative management
in foetuses with evidence of lower urinary tract obstruction
[34]. The results of this trial will hopefully provide guid-
ance regarding antenatal intervention in the PBS patient.
Postnatal presentation
Classification of PBS, proposed by Woodard [35], was
based on antenatal and anatomical features (Table 2), with
20% of infants born with PBS classified as category 1. The
presence of severe renal dysfunction and pulmonary
hypoplasia resulted in near 100% mortality within the first
few days of postnatal life.
Category 2 patients have the classic features of PBS
with their prognosis dictated by the degree of renal dys-
plasia present. There appears wide variation in the degree
of renal dysplasia present in these patients with severe
forms requiring early dialysis. Routh et al. [7] reported an
incidence of 15% of newborns with PBS exhibiting some
degree of renal dysplasia with 4% presenting in acute renal
failure. Category 3 patients have normal renal function and
mild phenotypic features of PBS [36].
The initial postnatal course of PBS infants is dictated by
their co-morbidities: 75% of infants born with PBS have
co-existing morbidities [37, 38]. The most common is
prematurity with 43% of infants born preterm. Cardiovas-
cular and pulmonary problems are also common (Table 1)
[7, 39, 40].
Perinatal mortality rates for PBS are quoted between 10
and 25%. This is primarily related to the degree of pul-
monary hypoplasia, co-morbid conditions and prematurity.
Management issues in PBS
Urinary tract
The hallmark of PBS is a low-pressure dilated urinary
system, evident from the renal pelvis to the urethra.
Elongated, tortuous ureters occur as normal smooth muscle
is replaced by collagen and fibrous tissue. This does not
occur in a homogeneous fashion but rather in segments
along the ureter with the distal ureter most affected. Ves-
ico-ureteric reflux (VUR) is found in 75% of PBS children
(Fig. 1) [41]. Like the ureter, the bladder is enlarged and
distorted due to replacement of bladder muscle with col-
lagen and fibrous tissue. While the bladder may bulge in
different directions when intra-vesical pressure is
increased, trabeculations, and muscular hypertrophy are
uncommon. A urachal remnant appears common while
persistence of a patent urachus can be found in the presence

Table 2 Woodard classification of prune belly syndrome

Category 1 (20%) Category 2 (40%) Category 3 (40%)

Pulmonary hypoplasia and/or pneumothorax Typical external features External features mild or incomplete
Oligohydramnios Hydroureteronephrosis Normal renal function
Renal dysplasia Uropathy Mild degree of uropathy
Urethral obstruction patent urachus Renal dysplasia
Club feet Risk of urosepsis
Risk of azotemia

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Fig. 1 MCUG demonstrating irregular shaped floppy bladder with
gross VUR bilaterally
of urethral atresia, which allows decompression of the
urinary system in utero. Urodynamic profiles of PBS
bladders show that they are efficient at urine storage but
demonstrate significant residuals due to the high incidence
of VUR and poor detrusor contraction [42].
The prostatic urethra is wide and elongated and tapers as
it becomes the membranous urethra when it passes through
the urogenital diaphragm. This can give the impression of
mechanical obstruction, however, the tapering seen is
mainly due to redundant folds of urethral mucosa (Fig. 2).
Abnormalities of the anterior urethra have all been
reported in association with PBS. Both fusiform and sca-
phoid megalourethra have been found in association with
PBS but are rare. Conversely over 50% of cases of meg-
alourethra are associated with PBS [43]. A mildly dilated
anterior urethra is the most common abnormality present in
approximately 70% of PBS patients [44].
The primary aim in management of the urinary tract is
preservation of renal function and prevention of urinary
infection. Woodward and colleagues felt that this was best
achieved using an approach of early surgery. Proximal
urinary drainage with cutaneous ureterostomies followed
by later definitive reconstruction and remodelling of the
urinary tract was their procedure of choice in PBS patients.
They reported stable renal function and a reduced rate of
urinary tract infection in PBS patients treated using this
approach (Level 3) [45, 46]. The authors acknowledged
that the success of this approach relied on maintenance of
adequate bladder emptying which may or may not be
achieved with reduction cystoplasty (Level 3) [46].
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Pediatr Surg Int (2012) 28:219–228
Fig. 2 MCUG depicting large hypotonic bladder, wide open bladder
neck and dilated prostatic urethra
The rationale of ensuring adequate bladder emptying is
the basis of the conservative approach to the urinary tract in
PBS patients. Implementation of prophylactic antibiotics,
double voiding and timed voiding in toilet-trained children
coupled with regular functional renal assessments appears
as effective, with fewer complications, as early total uri-
nary reconstruction in the setting of stable renal function
(Level 3) [47–49]. If adequate bladder emptying cannot be
achieved by double voiding and timed voiding, regular
catheterisation can be implemented to aid urinary drainage.
If this proves problematic or painful, due to urethral
abnormalities, an appendicovesicostomy remains a useful
procedure to aid bladder emptying. Ectasia and drainage
patterns also improve over time making the conservative
approach a more attractive option in these complex
patients.
Long-term follow-up of PBS patients also provides
important insights into the early surgical versus conserva-
tive approach. Fallat et al. reported on 15 patients who had
undergone early urinary reconstruction, consisting of ure-
teric tapering, reimplantation and reduction cystoplasty. In
all patients, there were no changes in pre- and postopera-
tive serum creatinine levels (Level 3) [39]. Bukowski et al.
examined the reduction cystoplasty element of their urinary
reconstructions. In their cohort of 11 patients, there was
some improvement in voiding and reduction in number and
severity of urinary tract infections, but long-term review
Pediatr Surg Int (2012) 28:219–228 223

(mean 7.7 years) demonstrated no reduction in bladder

capacity or improvement in voiding dynamics (Level 3)
[50]. Kinahan et al. [42] also demonstrated no difference in
urodynamic profiles between reconstructed and non-
reconstructed PBS patients (Level 3).
There is a high complication rate associated with sur-
gery in PBS patients [39, 51]. This is likely due to the poor
peristalsis and inherent muscular deficiencies present in the
PBS ureter and bladder. Vesico-ureteric junction (VUJ)
obstruction requiring re-operation in 40% of patients and
failure of resolution of VUR post-reimplant in 30% of
patients was reported in one series [39].
It appears as if early aggressive surgery on the basis of
urinary tract dilatation alone without evidence of com-
promised renal function in PBS appears unwarranted given
the reported success of the conservative approach coupled
with the high complication rate of surgery associated with
PBS patients (Level 3) [39, 47–49, 51].
Anecdotal reports recommend circumcision in the set-
ting of recurrent urinary tract infection in PBS patients,
although no series exploring this question has been pub-
lished [52]. It is likely that the practice has evolved fol-
Fig. 3 Newborn male with PBS, demonstrating classic abdominal
lowing observations in the PUV and high-grade reflux wall appearance
populations of a reduction in urinary tract infections fol-
lowing circumcision [53]. the umbilicus where muscle may be entirely replaced by
One definite indication for early surgery is where fibrous tissue. In contrast, the peripheral abdominal wall
obstruction is present secondary to urethral atresia. These shows normal or nearly normal muscle and fascial layers
cases tend to have a patent urachus or bladder fistula that [55, 56].
has enabled urinary tract decompression in utero. Forma- The basis of abdominal wall reconstruction is the
tion of a vesicostomy or short-term placement of an advancement of these well-innervated, well-vascularised
indwelling urachal catheter provides adequate decompres- peripheral muscle layers with or without excision of the
sion until more definitive surgery is performed in the future deficient central muscle and fascial portions. The rationale
(Level 3) [46, 54]. is that improved abdominal tone, due to the better quality
If there is a steady decline in renal function or consistent tissue, may lead to improved sensation of bladder disten-
failure to prevent or eradicate infection using conservative sion and an enhanced efficiency of the Valsalva manoeuvre
measures then surgery must be considered to provide more in bladder emptying (Level 4) [57].
effective drainage of the urinary system (Level 3) [39, 51]. A number of techniques have been described in abdomi-
Pyleoplasty, ureteric tapering and reimplantation and nal wall reconstruction in PBS. In 1981, Randolph [58]
cystoplasty may improve drainage and prevent infections reported his technique utilising a U-shaped incision between
in some cases, but carry complication rates of up to 40% the tips of the 12th ribs with full thickness excision of the
with revisional surgery often required (Level 3) [39, 51]. lower abdominal layers and advancement of the upper
The complexity of PBS patients means that each case must abdominal layers towards the groin and pubis (Fig. 4).
be approached on an individual basis with no general Erhlich [59] described advancing one fascial flap medially to
consensus as to which surgical procedure is most effective the opposite side via a midline vertical incision creating a
in aiding drainage and preventing infections. double-breasted fascial plate (Fig. 5). Whilst similar, the
Monfort technique, described in 1991, involves extensive
Abdominal wall dissection of both lateral fascial plates prior to a double-
breasted midline closure. This procedure was performed on
As with other anatomical manifestations of PBS, there is a nine patients (age range 1–10 years old) with reports of a
wide phenotypic variation in the abdominal wall of PBS. It satisfactory result in all cases (Fig. 6, Level 3) [60].
classically consists of poorly organized central abdominal The Firlit technique, reported in 1998, has the advantage
musculature interspersed with dense collagen (Fig. 3). All of an extra-peritoneal approach. Skin flaps are raised lat-
muscle layers are commonly affected particularly below erally to expose the fascial layer via a vertical midline

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Fig. 4 Randolph technique: this technique utilises a U-shaped
incision between the tips of the 12th ribs with full thickness excision
of the lower abdominal layers and advancement of the upper
abdominal layers towards the groin and pubis
Fig. 5 Erhlich technique: this technique advances one fascial flap
medially to the opposite side via a midline vertical incision creating a
double-breasted fascial plate
incision (Fig. 7). This lateral fascial layer is plicated in a
double-breasted fashion in the midline without lateral fas-
cial dissection or incision of the midline fascial plate. This
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Pediatr Surg Int (2012) 28:219–228
Fig. 6 Monfort technique: this technique involves extensive dissec-
tion of both lateral fascial plates prior to a double-breasted midline
closure
Fig. 7 Firlit technique: this technique plicates the lateral fascial
layers in a double-breasted fashion in the midline without lateral
fascial dissection or incision of the midline fascial plate
technique has been described in 13 boys (age range
9 months–11 years) with a follow-up period of
17–207 months. Three patients required further surgery at
14 months, 1 and 5 years post-initial surgery (Level 3)
[61]. A laparoscopic-assisted technique was described in
Pediatr Surg Int (2012) 28:219–228
2005 to visualise suture placement and prevent inadvertent
suturing of underlying bowel [62].
Smith et al. reported on improved bladder emptying in
their series of 12 patients following Monfort abdominal
reconstruction. Subjective improvements in continence,
sensation and urinary flow were noted in the majority of
patients. Improved postvoid residuals from 40% down to
13% were reported. Five out of 10 patients noticed a
reduced defecation time with increased quantities of stool
evacuated, while two out of 12 patients with poor bowel
control reported a reduced laxative requirement (Level 3)
[57]. The authors speculated that a contributory factor to
these improvements was as a result of the increased pres-
sure of the Valsalva manoeuvre in accordance with Pascals
principle (pressure = force/area), although no formal
measurements were performed.
Crompton et al. [63] demonstrated that air-trapping
secondary to poor respiratory effort from deficient
abdominal wall musculature was the main feature of spi-
rometry testing in patients with PBS (Level 4). No inves-
tigation of postoperative spirometry has been published in
PBS patients, but anecdotal evidence suggests an improved
clearance of respiratory secretions post-abdominal recon-
struction 64].
While these studies are informative, there is insufficient
evidence currently to justify abdominal wall reconstruction
as anything other than a measure to improve the appear-
ance of the abdominal wall. Advocates argue that the
improvement in a patient’s self-esteem post-reconstruction
warrants an aggressive approach at an early age although
this is based on anecdotal reports rather than any evidence
base. It is worth noting that good cosmetic outcomes have
also being achieved with improvement in abdominal wall
laxity over time using abdominal corsets for support,
although once again the evidence for corset use remains
weak [58, 65].
Cryptorchidism
Bilateral intra-abdominal testes remain one of the major
features of PBS. Mechanical obstruction secondary to the
enlarged bladder and urinary system, coupled with the
absence of central abdominal wall musculature likely
impedes normal descent of the testes. The gubernaculum,
important in testicular descent, has been noted to be atretic
or abnormally attached at the pubic tubercule [66]. The
presence of developmental abnormalities in the PBS testis
leading to failure of descent has also been suggested
although the evidence is contradictory.
Orvis et al. [67] studied the testes from fetal specimens
and noted reduced spermatogonia and Leydig cell hyper-
plasia. Conversely Nunn and Stephens [66] described
normal testicular histology for age in autopsy specimens
225
from newborns and prepubertal children. Massad et al. [68]
described atypical germ cells in testicular biopsy speci-
mens from three boys aged 5.5, 6 and 7 months old. Adult
males with PBS are azoospermic with little or no germ cell
maturation [69]. It is unclear whether this occurs due to
developmental arrest, failure of descent, late orchidopexy
or a combination of all three factors.
There are three treatment options available to treat intra-
abdominal testes in PBS: single stage bilateral orchidopexy
with preservation of the vascular pedicle, single stage
bilateral Fowler-Stephens orchidopexy or a two stage
Fowler-Stephens bilateral orchidopexy. These can be per-
formed via either an open or a laparoscopic technique.
Success rates of 80 and 85% are reported for single stage
and two stage Fowler-Stephens orchidopexy, respectively
[70]. A standard single stage orchidopexy for intra-
abdominal testes has a reported success rate of [90% [71,
72]. The laparoscopic approach would seem the procedure
of choice for the management of intra-abdominal testes with
comparable rates of testicular survival reported [73, 74].
Literature relating specifically to orchidopexies in PBS
demonstrates higher rates of testicular loss. Denes et al.
[51] reported on single stage bilateral orchidopexy at the
time of urinary reconstruction. In 32 patients, an 8%
atrophy rate was noted and 8% of testes were positioned in
the inguinal region. The mean age of surgery was
23 months with a mean follow-up period of 60 months
(Level 3) [51]. Fallat et al. demonstrated that children
[2 years showed a higher atrophy rate (30%) compared
with only 4% of those \2 years following orchidopexy
performed at the time of urological reconstruction. Of
these, 82% were single stage orchidopexy, 14% the Fow-
ler-Stephens technique and 4% a staged Fowler-Stephens
technique [39]. The largest series was reported in 2004 by
Patil et al.: in the 31 boys who underwent a single stage
orchidopexy, at a mean age 8 years, there was a testicular
atrophy rate of 16% with 24% showing evidence of a
smaller testis. In the two stage orchidopexy group
(n = 30), where the mean age of surgery was 3.2 years, the
testicular atrophy rate was 3% with smaller testes noted in
13% of boys. Of those patients who had a single stage
bilateral orchidopexy, 10% required hormonal supple-
mentation at puberty while all children who had a two stage
orchidopexy underwent spontaneous puberty (Level 3)
[75].
There are only three reports in the literature of laparos-
copic orchidopexy in PBS and these primarily relate to
technical issues rather than testicular survival. Problems
with air leak were reported due to the absent abdominal
musculature. Recommendations from these reports suggest
careful port fixation, higher CO2 flow rates and the use of
longer instruments due to the lax abdominal wall (Level 4)
[76–78].
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The higher rates of testicular loss reported in PBS
patients might reflect older age at orchidopexy rather than
PBS as an independent risk factor for increased testicular
loss following orchidopexy. Orchidopexy was often timed
when urinary reconstruction and abdominal wall recons-
truction were performed which was beyond the first year
of life. Current guidelines recommend early orchidopexy
(\1 year) to maximise testicular function and reduce the
risk of malignancy [79]. These guidelines should also
apply to PBS patients. Where urinary or abdominal wall
reconstruction is considered in the first year of life, a
single stage abdominal orchidopexy should be performed
at the same time. At this early age, it has been noted that
it is easier to achieve mobilisation to allow for successful
scrotal placement of the testis (Level 4) [39]. If no
abdominal surgery is planned then a laparoscopic
approach should be utilised with a single stage procedure
used where possible to allow maximum potential for the
testes to survive and develop.
Renal transplantation
Nearly a third of PBS patients outside the postnatal period
will progress to renal failure requiring transplantation.
Early identifiable risk factors are renal cystic disease and
dysplasia reported in approximately 50% of infants with
PBS. The most accurate marker of significant renal dys-
plasia is nadir creatinine; that is the lowest consistent
creatinine level in the first 12 months of life. Canning et al.
reported that a creatinine level of [0.7 mg/dl was a strong
predictor of progression to renal failure in later life.
Interestingly, degree of dilatation of the urinary system was
not a significant prognostic factor for renal function,
lending credence to the non-obstructive nature of PBS
(Level 3) [80]. Renal failure may also occur from chronic
pyelonephritis related to urinary stasis and incomplete
bladder emptying with repeated infections and obstructive
nephropathy.
The commonest indications for a renal transplant in PBS
patients are renal failure secondary to chronic pyelone-
phritis and renal dysplasia [81–85]. While there remains no
specific data available on end stage renal failure (ESRF)
rates in PBS patients, the mean age at transplantation has
been reported to be between 7.5 and 13.5 years [82, 84,
85]. Early progression to ESRF is attributed to significant
renal dysplasia while later progression is thought to occur
due to renal damage from repeated infections and high
pressures generated from obstruction (Level 3) [81].
The literature has emphasized the importance of
achieving and maintaining adequate bladder emptying
prior to transplantation. Poor bladder emptying leads to
high detrusor pressures, stasis and infection, associated
with higher rates of graft deterioration post-transplant.
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Pediatr Surg Int (2012) 28:219–228
Improvement in bladder emptying may be achieved by
timed voiding and intermittent catheterisation. If low
postvoid residuals are not achieved using these conserva-
tive methods, then more aggressive treatment by internal
urethrotomy or vesicostomy has been reported (Level 4)
[83, 84]. Acute graft torsion secondary to the abdominal
wall laxity is a specific problem in PBS patients, with
abdominoplasty or transplant nephropexy advocated to
prevent occurrence (Level 4) [83, 84].
PBS patients have similar outcomes to age-matched
controls following renal transplantation. This is likely a
reflection of the preoperative preparation to ensure ade-
quate bladder emptying coupled with vigilant post-trans-
plant follow-up in these patients.
Conclusion
This review highlights the complexities of patients with
PBS and the difficult management decisions that are faced.
The literature, while informative, has been predominately
retrospective reviews from single institutions reporting
treatment options and outcomes. A more collaborative
approach is now required in the form of multicentre pro-
spective randomized studies assessing specific treatment
outcomes. Without this, we will be none the wiser over the
coming decades into the correct management of these
complex set of patients.
References
1. Osler W (1901) Congenital absence of the abdominal muscle,
with distended and hypertrophied urinary bladder. Bull Johns
Hopkins Hosp 12:331–333
2. Eagle JF Jr, Barrett GS (1950) Congenital deficiency of abdom-
inal musculature with associated genitourinary abnormalities: a
syndrome. Report of 9 cases. Pediatrics 6:721–736
3. Welch KJ, Kraney GP (1974) Abdominal musculature deficiency
syndrome prune belly. J Urol 111:693–700
4. Rabinowitz R, Schillinger JF (1977) Prune belly syndrome in the
female subject. J Urol 118:454–456
5. Smolkin T, Soudack M, Goldstein I, Sujov P, Makhoul IR (2008)
Prune belly syndrome: expanding the phenotype. Clin Dysmor-
phol 17:133–135
6. Harbour R, Miller J (2001) A new system for grading recom-
mendations in evidence based guidelines. BMJ 323:334–336
7. Routh JC, Huang L, Retik AB, Nelson CP (2010) Contemporary
epidemiology and characterization of newborn males with prune
belly syndrome. Urology 76:44–48
8. Druschel CM (1995) A descriptive study of prune belly in New
York State, 1983 to 1989. Arch Pediatr Adolesc Med 149:70–76
9. Beckmann H, Rehder H, Rauskolb R (1984) Prune belly sequence
associated with trisomy 13. Am J Med Genet 19:603–604
10. Frydman M, Magenis RE, Mohandas TK, Kaback MM (1983)
Chromosome abnormalities in infants with prune belly anomaly:
association with trisomy 18. Am J Med Genet 15:145–148
Pediatr Surg Int (2012) 28:219–228
11. Baird PA, Sadovnick AD (1987) Prune belly anomaly in down
syndrome. Am J Med Genet 26:747–748
12. Ramasamy R, Haviland M, Woodard JR, Barone JG (2005)
Patterns of inheritance in familial prune belly syndrome. Urology
65:1227
13. Petersen DS, Fish L, Cass AS (1972) Twins with congenital
deficiency of abdominal musculature. J Urol 107:670–672
14. Balaji KC, Patil A, Townes PL, Primack W, Skare J, Hopkins T
(2000) Concordant prune belly syndrome in monozygotic twins.
Urology 55:949
15. Murray PJ, Thomas K, Mulgrew CJ, Ellard S, Edghill EL,
Bingham C (2008) Whole gene deletion of the hepatocyte nuclear
factor-1beta gene in a patient with the prune-belly syndrome.
Nephrol Dial Transplant 23:2412–2415
16. Haeri S, Devers PL, Kaiser-Rogers KA, Moylan VJ Jr, Torchia
BS, Horton AL, Wolfe HM, Aylsworth AS (2010) Deletion of
hepatocyte nuclear factor-1-beta in an infant with prune belly
syndrome. Am J Perinatol 27:559–563
17. Manivel JC, Pettinato G, Reinberg Y, Gonzalez R, Burke B,
Dehner LP (1989) Prune belly syndrome: clinicopathologic study
of 29 cases. Pediatr Pathol 9:691–711
18. Gonzalez R, Reinberg Y, Burke B, Wells T, Vernier RL (1990)
Early bladder outlet obstruction in fetal lambs induces renal
dysplasia and the prune-belly syndrome. J Pediatr Surg
25:342–345
19. Hutson JM, Beasley SW (1987) Aetiology of the prune belly
syndrome. Aust Paediatr J 23:309–310
20. Stephens FD, Gupta D (1994) Pathogenesis of the prune belly
syndrome. J Urol 152:2328–2331
21. Deklerk DP, Scott WW (1978) Prostatic maldevelopment in the
prune belly syndrome: a defect in prostatic stromal-epithelial
interaction. J Urol 120:341–344
22. Ives EJ (1974) The abdominal muscle deficiency triad
syndrome—experience with ten cases. Birth Defects Orig Artic
Ser 10:127–135
23. Papantoniou N, Papoutsis D, Daskalakis G, Chatzipapas I, Sindos
M, Papaspyrou I, Mesogitis S, Antsaklis A (2010) Prenatal
diagnosis of prune-belly syndrome at 13 weeks of gestation: case
report and review of literature. J Matern Fetal Neonatal Med
23:1263–1267
24. Yamamoto H, Nishikawa S, Hayashi T, Sagae S, Kudo R (2001)
Antenatal diagnosis of prune belly syndrome at 11 weeks of
gestation. J Obstet Gynaecol Res 27:37–40
25. Shigeta M, Nagata M, Shimoyamada H, Shibata S, Okuno S,
Hamada H, Watanabe T (1999) Prune-belly syndrome diagnosed
at 14 weeks’ gestation with severe urethral obstruction but
normal kidneys. Pediatr Nephrol 13:135–137
26. Chen L, Cai A, Wang X, Wang B, Li J (2010) Two- and three-
dimensional prenatal sonographic diagnosis of prune-belly
syndrome. J Clin Ultrasound 38:279–282
27. Sutherland RS, Mevorach RA, Kogan BA (1995) The prune-belly
syndrome: current insights. Pediatr Nephrol 9:770–778
28. KA Woodward PJ, Soahey R, Byrne JLB, Oh KY, Puchalski MD
(2005) Diagnostic imaging obstetrics. Amirsys Inc, Salt Lake
City
29. Osborne NG, Bonilla-Musoles F, Machado LE, Raga F, Bonilla F
Jr, Ruiz F, Perez Guardia CM, Ahluwalia B (2011) Fetal mega-
cystis: differential diagnosis. J Ultrasound Med 30:833–841
30. Austin JC, Canning DA, Johnson MP, Flake AW, Carr MC
(2001) Vesicoamniotic shunt in a female fetus with the prune
belly syndrome. J Urol 166:2382
31. Galati V, Beeson JH, Confer SD, Frimberger D, Campbell JB,
Ramji FG, Kropp BP (2008) A favorable outcome following 32
vesicocentesis and amnioinfusion procedures in a fetus with
severe prune belly syndrome. J Pediatr Urol 4:170–172
227
32. Leeners B, Sauer I, Schefels J, Cotarelo CL, Funk A (2000) Prune-
belly syndrome: therapeutic options including in utero placement
of a vesicoamniotic shunt. J Clin Ultrasound 28:500–507
33. Clark TJ, Martin WL, Divakaran TG, Whittle MJ, Kilby MD,
Khan KS (2003) Prenatal bladder drainage in the management of
fetal lower urinary tract obstruction: a systematic review and
meta-analysis. Obstet Gynecol 102:367–382
34. Morris RK, Kilby MD (2009) An overview of the literature on
congenital lower urinary tract obstruction and introduction to the
PLUTO trial: percutaneous shunting in lower urinary tract
obstruction. Aust N Z J Obstet Gynaecol 49:6–10
35. Woodard JR (1978) The prune belly syndrome. Urol Clin North
Am 5:75–93
36. Smith EA (2002) Prune belly syndrome. In: Wein AJ (ed)
Campbells urology. WB Saunders, Philadelphia
37. Wright JR Jr, Barth RF, Neff JC, Poe ET, Sucheston ME,
Stempel LE (1986) Gastrointestinal malformations associated
with prune belly syndrome: three cases and a review of the
literature. Pediatr Pathol 5:421–448
38. Green NE, Lowery ER, Thomas R (1993) Orthopaedic aspects of
prune belly syndrome. J Pediatr Orthop 13:496–501
39. Fallat ME, Skoog SJ, Belman AB, Eng G, Randolph JG (1989)
The prune belly syndrome: a comprehensive approach to man-
agement. J Urol 142:802–805
40. Burbige KA, Amodio J, Berdon WE, Hensle TW, Blanc W,
Lattimer JK (1987) Prune belly syndrome: 35 years of experi-
ence. J Urol 137:86–90
41. Bellah RD, States LJ, Duckett JW (1996) Pseudoprune-belly
syndrome: imaging findings and clinical outcome. AJR Am J
Roentgenol 167:1389–1393
42. Kinahan TJ, Churchill BM, McLorie GA, Gilmour RF, Khoury
AE (1992) The efficiency of bladder emptying in the prune belly
syndrome. J Urol 148:600–603
43. Shrom SH, Cromie WJ, Duckett JW Jr (1981) Megalourethra.
Urology 17:152–156
44. Kroovand RL, Al-Ansari RM, Perlmutter AD (1982) Urethral and
genital malformations in prune belly syndrome. J Urol 127:94–96
45. Woodard JR, Parrott TS (1978) Reconstruction of the urinary
tract in prune belly uropathy. J Urol 119:824–828
46. Woodard JR, Zucker I (1990) Current management of the dilated
urinary tract in prune belly syndrome. Urol Clin North Am
17:407–418
47. Woodhouse CR, Kellett MJ, Williams DI (1979) Minimal sur-
gical interference in the prune belly syndrome. Br J Urol
51:475–480
48. Perlmutter AD (1976) Reduction cystoplasty in prune belly
syndrome. J Urol 116:356–362
49. McMullin N, Hutson J, Kelly J (1988) Minimal surgery in the
prune belly syndrome. Pediatr Surg Int 3:51–54
50. Bukowski TP, Perlmutter AD (1994) Reduction cystoplasty in the
prune belly syndrome: a long-term followup. J Urol
152:2113–2116
51. Denes FT, Arap MA, Giron AM, Silva FA, Arap S (2004)
Comprehensive surgical treatment of prune belly syndrome:
17 years’ experience with 32 patients. Urology 64:789–793 dis-
cussion 793–784
52. Caldamine A, Woodard JR (2011) Campbell-Walsh Urology,
10th edn, vol 4. Prune Belly Syndrome. Elsevier Saunders,
Philadelphia
53. Singh-Grewal D, Macdessi J, Craig J (2005) Circumcision for the
prevention of urinary tract infection in boys: a systematic review
of randomised trials and observational studies. Arch Dis Child
90:853–858
54. Chen IL, Huang HC, Lee SY, Liu CA, Tain YL, Ou-Yang MC,
Chao PH (2011) Urachal catheter provides new choice for
123
228
long-term urinary diversion in prune belly syndrome. Urology
77:466–468
55. Mininberg DT, Montoya F, Okada K, Galioto F, Presutti R (1973)
Subcellular muscle studies in the prune belly syndrome. J Urol
109:524–526
56. Afifi AK, Rebeiz J, Mire J, Andonian J, VMd Kaloustian (1972)
The myopathology of the Prune belly syndrome. J Neurol Sci
15:153–165
57. Smith CA, Smith EA, Parrott TS, Broecker BH, Woodard JR
(1998) Voiding function in patients with the prune-belly syn-
drome after Monfort abdominoplasty. J Urol 159:1675–1679
58. Randolph J, Cavett C, Eng G (1981) Surgical correction and
rehabilitation for children with ‘‘Prune-belly’’ syndrome. Ann
Surg 193:757–762
59. Ehrlich RM, Lesavoy MA (1993) Umbilicus preservation with
total abdominal wall reconstruction in prune-belly syndrome.
Urology 41:231–232
60. Monfort G, Guys JM, Bocciardi A, Coquet M, Chevallier D
(1991) A novel technique for reconstruction of the abdominal
wall in the prune belly syndrome. J Urol 146:639–640
61. Furness PD III, Cheng EY, Franco I, Firlit CF (1998) The prune-
belly syndrome: a new and simplified technique of abdominal
wall reconstruction. J Urol 160:1195–1197 discussion 1216
62. Franco I (2005) Laparoscopic assisted modification of the firlit
abdominal wall plication. J Urol 174:280–283
63. Crompton CH, MacLusky IB, Geary DF (1993) Respiratory
function in the prune-belly syndrome. Arch Dis Child
68:505–506
64. Woodard JR (2003) Prune-belly syndrome: a personal learning
experience. BJU Int 92(Suppl 1):10–11
65. Woodhouse CR, Ransley PG, Innes-Williams D (1982) Prune
belly syndrome–report of 47 cases. Arch Dis Child 57:856–859
66. Nunn IN, Stephens FD (1961) The triad syndrome: a composite
anomaly of the abdominal wall, urinary system and testes. J Urol
86:782–794
67. Orvis BR, Bottles K, Kogan BA (1988) Testicular histology in
fetuses with the prune belly syndrome and posterior urethral
valves. J Urol 139:335–337
68. Massad CA, Cohen MB, Kogan BA, Beckstead JH (1991) Mor-
phology and histochemistry of infant testes in the prune belly
syndrome. J Urol 146:1598–1600
69. Woodhouse CR, Snyder HM III (1985) Testicular and sexual
function in adults with prune belly syndrome. J Urol 133:607–609
70. Elyas R, Guerra LA, Pike J, DeCarli C, Betolli M, Bass J, Chou
S, Sweeney B, Rubin S, Barrowman N, Moher D, Leonard M
(2010) Is staging beneficial for Fowler-Stephens orchiopexy? A
systematic review. The Journal of urology 183:2012–2018
71. Baker LA, Docimo SG, Surer I, Peters C, Cisek L, Diamond DA,
Caldamone A, Koyle M, Strand W, Moore R, Mevorach R, Brady
123
View publication stats
Pediatr Surg Int (2012) 28:219–228
J, Jordan G, Erhard M, Franco I (2001) A multi-institutional
analysis of laparoscopic orchidopexy. BJU Int 87:484–489
72. Kirsch AJ, Escala J, Duckett JW, Smith GH, Zderic SA, Canning
DA, Snyder HM 3rd (1998) Surgical management of the non-
palpable testis: the Children’s Hospital of Philadelphia experi-
ence. J Urol 159:1340–1343
73. Abolyosr A (2006) Laparoscopic versus open orchiopexy in the
management of abdominal testis: a descriptive study. Int J Urol
13:1421–1424
74. Lindgren BW, Franco I, Blick S, Levitt SB, Brock WA, Palmer
LS, Friedman SC, Reda EF (1999) Laparoscopic Fowler-Ste-
phens orchiopexy for the high abdominal testis. The Journal of
urology 162:990–993 discussion 994
75. Patil KK, Duffy PG, Woodhouse CR, Ransley PG (2004) Long-
term outcome of Fowler-Stephens orchiopexy in boys with prune-
belly syndrome. J Urol 171:1666–1669
76. Saxena AK, Brinkmann OA (2007) Unique features of prune
belly syndrome in laparoscopic surgery. J Am Coll Surg
205:217–221
77. Philip J, Mullassery D, Craigie RJ, Manikandan R, Kenny SE
(2011) Laparoscopic orchidopexy in boys with prune belly syn-
drome-outcome and technical considerations. J Endourol
25:1115–1117
78. Docimo SG, Moore RG, Kavoussi LR (1995) Laparoscopic
orchidopexy in the prune belly syndrome: a case report and
review of the literature. Urology 45:679–681
79. Hutson JM, Balic A, Nation T, Southwell B (2010) Cryptorchi-
dism. Semin Pediatr Surg 19:215–224
80. Noh PH, Cooper CS, Winkler AC, Zderic SA, Snyder HM 3rd,
Canning DA (1999) Prognostic factors for long-term renal
function in boys with the prune-belly syndrome. J Urol
162:1399–1401
81. Reinberg Y, Manivel JC, Pettinato G, Gonzalez R (1991)
Development of renal failure in children with the prune belly
syndrome. J Urol 145:1017–1019
82. Reinberg Y, Manivel JC, Fryd D, Najarian JS, Gonzalez R (1989)
The outcome of renal transplantation in children with the prune
belly syndrome. J Urol 142:1541–1542
83. Fusaro F, Zanon GF, Ferreli AM, Giuliani S, Zacchello G,
Passerini-Glazel G, Rigamonti W (2004) Renal transplantation in
prune-belly syndrome. Transpl Int 17:549–552
84. Kamel MH, Thomas AA, Al-Mufarrej FM, O’Kelly P, Hickey DP
(2007) Deceased-donor kidney transplantation in prune belly
syndrome. Urology 69:666–669
85. Fontaine E, Salomon L, Gagnadoux MF, Niaudet P, Broyer M,
Beurton D (1997) Long-term results of renal transplantation in
children with the prune-belly syndrome. J Urol 158:892–894