The ExstrophyEpispadias Complex Research Concepts and

Clinical Applications - 1st Edition

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DEDICATION

This book is dedicated to the following people: Madison Pryor, Ph.D. who taught me
that the study of biology is the basis of medicine; to Lonnie W. Howerton, M.D. who
taught me that urology is the pinnacle of surgical sub-specialities; to Hiram C. Polk, M.D.
who taught me to ask questions, and more importantly to find answers; to Roy Wither-
ington, M.D. who taught me the skills and science of urology; to Mr. J. Herbert Johnson,
MB, FRCS, who taught me the craft of pediatric urology; to Robert D. Jeffs, M.D. who
taught me the skills and science of reconstructive pediatric urology; and to Pat-
rick C. Walsh, M.D. for his mentorship and constant dedication to discovery and achieve-
ment.

v
PREFACE

The undertaking of the treatment of an infant born with bladder exstrophy is one of
the most weighty responsibilities that can fall upon the shoulders of the reconstructive sur-
geon. The modern treatment of a child born with bladder exstrophy began in the mid-
1970's with the widespread application of staged reconstruction. This approach has
consistently yielded very good results in several series. However, as in all serious congeni-
tal birth defects, there is certainly room for advancement.
Issues such as the routine use of osteotomy, timing and type of epispadias repair,
combining bladder closure with epispadias repair, the approach to the small bladder, and
the management of a failed exstrophy still remain. This National Institute of Health/Na-
tional Kidney Foundation/Johns Hopkins-sponsored seminar was an attempt to bring ex-
perts in the field of pediatric orthopedic surgery, pediatric urology, pediatric surgery, adult
urology, and basic science together to share their experiences in an attempt to foster new
clinical and basic science research communications between the participants. If these col-
laborations result, then this first international meeting will have been successful.
The editors would like to thank all of the contributors for their timely and complete
submissions.

John P. Gearhart, M.D.

Ranjiv Mathews, M.D.

vii
CONTENTS

1. The Embryology and Epidemiology of Bladder Exstrophy ................. .

Bruce Slaughenhoupt

2. Prenatal Diagnosis of Bladder and Cloacal Exstrophy and Related Conditions 5

Roger C. Sanders

3. Anatomy and Biomechanics of the Pelvis in Exstrophy . . . . . . . . . . . . . . . . . . . . 9

Mihir M. Jani, Paul D. Sponseller, John P. Gearhart, A. Valdevit, and
E.Y.-S. Chao

4. Detrusor Morphology and Innervation in Bladder Exstrophy: A Preliminary

Investigation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
J. A. Gosling, R. Mathews, and J.P. Gearhart

5. The Response of the Bladder Smooth Muscle to Increased Bladder Neck

Resistance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
Edward J. Macarak, Stephen Zderic, Howard M. C. Snyder,
Douglas Canning, and Pamela S. Howard

6. Muscarinic Cholinergic Receptors in Bladder Exstrophy: Pharmacological

Observations Supporting Functional Closure and Subsequent Bladder
Neck Reconstruction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
Ellen Shapiro, Robert D. Jeffs, John P. Gearhart, and Herbert Lepor

7. A Quantitative Histological Analysis of the Bladder in Classical Bladder

Exstrophy in Various Stages of Reconstruction Utilizing Color
Morphometry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
Dennis S. Peppas, Marie-Blanche Tchetgen, Benjamin R. Lee,
Robert D. Jeffs, and John P. Gearhart

8. Analysis of Smooth Muscle and Collagen Subtypes in the Normal Newborn and
Bladder Exstrophy Patient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
Benjamin R. Lee, Elizabeth J. Perlman, Alan W. Partin, Robert D. Jeffs, and
John P. Gearhart

ix
X Contents

9. A Large Animal Model of Bladder Exstrophy: Observations on Bladder Smooth

Muscle and Collagen Content and Function . . . . . . . . . . . . . . . . . . . . . . . . . 57
Bruce L. Slaughenhoupt and John P. Gearhart

10. Tissue Engineering Techniques For Closure of Bladder Exstrophy:

An Experimental Animal Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
Anthony Atala

11. Surgical Principles in the Primary Closure of Bladder Exstrophy . . . . . . . . . . . . . 65

John P. Gearhart and Ranjiv Mathews

12. Anterior and Posterior Innominate Osteotomy in Exstrophy Repair . . . . . . . . . . . 69

Paul D. Sponseller, John P. Gearhart, Mihir M. Jani, and Robert D. Jeffs

13. Bladder Exstrophy Closure without Osteotomy in Philadelphia . . . . . . . . . . . . . . 77

Douglas A. Canning, Thomas Lanchoney, Simone McKitty, Stephen Zderic,
Howard M. Snyder, III, and John W. Duckett, Jr.

14. Bilateral Anterior Pubic Osteotomy in Bladder Exstrophy Closure 83

Peter Frey

15. The Failed Exstrophy Closure: Strategies for Management--the Johns Hopkins
Experience . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
John P. Gearhart and Ranjiv Mathews

16. Applications of Ureterosigmoidostomy in Bladder Exstrophy 97

Raimund Stein, Margit Fisch, and Rudolf Hohenfellner

17. Cystoplasty in Bladder Exstrophy: Indications and Techniques 105

Steven G. Docimo

18. Bladder Exstrophy: Therapeutic Alternatives Ill

Sami Arap and Amilcar M. Giron

19. Penile Length in Adulthood after Exstrophy Reconstruction . . . . . . . . . . . . . . . . 117

Richard I. Silver, Andrew Yang, Jacob Ben-Chaim, Robert D. Jeffs, and
John P. Gearhart

20. Complete Penile Disassembly for Epispadias Repair 127

Michael E. Mitchell

21. The Cantweii-Ransley Epispadias Repair in Exstrophy/Epispadias:

Lessons Learned . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
John P. Gearhart, Christopher Sciortino, Jacob Ben-Chaim, Dennis S. Peppas,
and Robert D. Jeffs

22. The Impact ofUrodynamics on Surgery for Incontinence in Children with

Exstrophy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
Stuart B. Bauer
Contents xi

23. The Use of Sub-Mucosal Collagen in the Small Bladder Associated with
Bladder Exstrophy............................................. 141
Paolo Caione and Alberto Lais

24. Review of Long-Term Results of Staged Functional Reconstruction and Bladder

Neck Plasty in Bladder Exstrophy Patients Followed from Birth at the
Johns Hopkins Hospital . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149
Yegappan Lakshmanan, John P. Gearhart, and Robert D. Jeffs

25. Psychological Aspects of Bladder Exstrophy: Vulnerabilities, Risks, and

Protective Factors from a Longitudinal Perspective . . . . . . . . . . . . . . . . . . 165
William G. Reiner

26. The Outcome of Patients with Classic Bladder Exstrophy in Adult Life . . . . . . . 169
Jacob Ben-Chaim, Robert D. Jeffs, William G. Reiner, and John P. Gearhart

27. Long Term Results of Bladder Exstrophy: The London Experience . . . . . . . . . . . 175
C. R. J. Woodhouse

28. Long Term Results of Bladder Exstrophy: The Mainz Experience 185
Raimund Stein, Margit Fisch, and Rudolf Hohenfellner

29. Semen Analysis and Transrectal Ultrasound Findings in Men with Bladder
Exstrophy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193
Terry W. Hensle, Erik T. Goluboff, and Harry Fisch

30. Anatomy of Cloacal Exstrophy: The Surgical Implications 199

Douglas A. Husmann and David R. Vandersteen

31. Current Urologic Management of Cloacal Exstrophy: Experience with 11

Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 207
Edwin A. Smith, John R. Woodard, Bruce H. Broecker, Rafael Gosalbez, Jr.,
and Richard R. Ricketts

32. Indications and Types of Bladder Augmentation in Cloacal Exstrophy 217

Michael E. Mitchell

33. Cloacal Exstrophy: Experience with 41 Cases from 1976--1997.............. 221

W. Hardy Hendren, Robert E. Gross, and Dennis P. Lund

Abstracts 237

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251
 1

THE EMBRYOLOGY AND EPIDEMIOLOGY OF

BLADDER EXSTROPHY

Bruce Slaughenhoupt

Division of Urology
University of Louisville School of Medicine
Louisville, Kentucky 40292

INCIDENCE
In 1987, the International Clearing House for Birth Defects estimated that classic
bladder exstrophy occurred at a rate of 1 in 30,000 live births. 1 In a more recent study pub-
lished in 1994, the University of Pittsburgh estimated classic bladder exstrophy to occur
once in 25,000 live births in the Pennsylvania, Virginia, Maryland, and Washington, D.C.
areas. 2 The University Hospital in Lund, Sweden recently cited an incidence of I in
33,500 live births. 3
The spectrum of bladder exstrophy and epispadias complex occurs much more com-
monly in males than in females. In 1973, Bennett reported a 2.3 to 1 ratio 4 and in 1980,
Ives reported a 6 to 1 male to female ratio. 5 Shapiro has also reported that a person with
exstrophy or epispadias has a 1 in 70 chance of having a child with bladder exstrophy.6
Most of the children reported in this study were children born to women with bladder ex-
strophy. Thus far, there have been very few reports of men with bladder exstrophy who
have fathered children. Most of these cases remain anecdotal.

EXTERNAL APPEARANCE
I would like to briefly describe the external anatomic appearance of a young child
born with classic bladder exstrophy for those who do not care for these patients in the
clinical setting. Classic bladder exstrophy is an infraumbilical defect in which the blad-
der's internal mucosal surface is exposed to the outside environment. The abdominal wall
fascial defect is limited inferiorly by the intersymphyseal band. The urethral plate is ex-
posed on its dorsal surface and is surrounded by dorsal chordee. This causes the phallus to
be drawn up against the abdominal wall and the exposed bladder. The penis is broad and
The Exstrophy-Epispadias Complex, edited by Gearhart and Mathews.
Kluwer Academic I Plenum Publishers, New York, 1999.
2 B. Slaughenhoupt

foreshortened. In the female, the vagina and urethra are short, the clitoris is bifid and the
labia are divergent. In both sexes, the symphysis pubis is widened and has an outward ro-
tation of the innominate bones at the sacroiliac joints. The anus is anteriorly displaced.
Gearhart and Peppas have shown that males born with classic bladder exstrophy have an
83% incidence of indirect inguinal herniae being present. 7

NORMAL EMBRYOLOGIC GENITAL DEVELOPMENT

I would like to briefly review normal embryonic development prior to discussing the
theories of the abnormal embryonic development which may lead to classic bladder ex-
strophy. At three weeks gestation, the bilaminar cloacal membrane normally undergoes
mesodermal ingrowth and caudal migration. That is, mesodermal tissue migrates from a
lateral to medial direction as well as from a cranial to caudal direction. The mesodermal
tissue then leads to formation of the abdominal wall and bony pelvic anatomy. At the con-
clusion of the mesenchymal infiltration of the cloaca, the distal most aspect of the me-
senchyme leads to labioscrotal swellings and formation of the genital tubercle.
At 4 weeks gestation, Tourneux's folds advance in a cranial-to-caudal direction and
Rathke's plicae grow toward each other in a lateral-to-medial direction. Therefore by 7
weeks gestation, the urorectal septum has migrated completely and merged with the cloa-
cal membrane to form the perineal body. 8 It is believed that the thin, bilaminar cloacal
membrane remnant ruptures due to the pressure of mesonephric urine. The cloacal mem-
brane ruptures anteriorly and leads to the opening of the urogenital sinus while the poste-
rior aspect opens into the rectum.

EMBRYOLOGY OF BLADDER EXSTROPHY

During the past century, there have been several theories proposed to explain the eti-
ology of bladder exstrophy. In 1869, Wood proposed that the defect was due to ulceration
of the anterior abdominal wall and symphysis pubis. This was then thought to lead to ne-
crosis and separation of the abdominal wall and pubis. It was actually suggested at the
time that syphilis infection might lead to bladder exstrophy. 9
In 1924, von Geldern summarized the views of several contemporaries who ascribed
bladder exstrophy as a developmental arrest in a normal embryologic phase through which
all fetuses pass. This has since been found to be at fault since fetuses that die of other
causes, do not also have findings consistent with bladder exstrophy. 10 ·

In 190 I, an article in JAMA supported the Berstung theory. This proposed that
11

bladder outlet obstruction led to rupture of the anterior bladder wall and abdominal wall.
It was also suggested that prior to its rupture, the distended bladder caused lack of fusion
of the bony pelvis and, therefore, separation of the pubic symphysis. It was proposed that
after rupturing, the bladder wall fused with the abdominal wall and healed together. It is
now felt that bladder outlet obstruction does not lead to classic bladder exstrophy. In fact,
many boys are born each year with bladder outlet obstruction from posterior urethral
valves. Their clinical picture is very different from those of children born with bladder ex-
strophy and often includes severe hydronephrosis, dilated ureters and an enlarged bladder.
In 1952, Patten and Barry theorized that bladder exstrophy and epispadias were due
to misplacement of the embryologic genital tubercles. 12 They felt that the genital tubercles
in these fetuses were in an abnormally low position. Therefore, midline abdominal wall
The Embryology and Epidemiology of Bladder Exstrophy 3

fusion developed below the tubercles but not above them. When the genital tubercles arise
below the urogenital orifice, it is theorized that they cannot augment the abdominal wall
and urethral development.'' This concept has fallen out of favor in recent years because,
according to its theory, epispadias should be more likely to occur than classic bladder ex-
strophy. However statistically, simple epispadias is much rarer than classic bladder exstro-
phy. Therefore, this theory is subsequently felt to not be accurate.
In 1962, Marshall and Muecke published their paper proposing a very reasonable
theory concerning the etiology of bladder exstrophy. 13 They suggested that an abnormality
of the cloacal membrane prevented it from allowing mesodermal ingrowth, and sub-
sequent abdominal wall development. They felt the membrane remained bilaminar and
was thinner than it should be. It was then felt that the membrane ruptured under the force
of urine produced by primitive kidneys. They also proposed that the less mesodermal in-
growth which occurred at the time of rupture, the more severe the defect would be. That
is, if very little mesoderm was added to the cloacal membrane, the child would be born
with cloacal exstrophy. If more mesoderm migrated, the child would be born with classic
bladder exstrophy. And lastly, ifthere was a greater amount of tissue which augmented the
cloacal membrane, the child would simply be born with epispadias.
Muecke then published an article two years later and reported the use of an animal
model to demonstrate the effects of the non-regressing cloacal membrane. 14 He used fertil-
ized chick eggs which had been incubated for two of their 20-day incubation period. A
2 mm incision was made in the region of the chick cloacal membrane. A small wedge of
millipore plastic was then inserted into the incision. The eggshell was then resealed and
incubation continued. Muecke performed this procedure on 54-dozen chick eggs. None of
the chicks of the first 40 dozen survived. Thirteen percent of Muecke's chick embryos sur-
vived to hatching and the great majority of them had a caudal defect similar to cloacal or
bladder exstrophy. Muecke then concluded that the basic embryologic defect which leads
to classic bladder exstrophy occurs early in embryogenesis in the form of an overly devel-
oped, non-regressing cloacal membrane. He theorized that this acted as a mechanical bar-
rier to mesodermal migration and subsequent abdominal wall and bladder development.
In 1985, Mitchell, et a!, theorized that exstrophy was not due to a persistent cloacal
membrane, but rather due to its premature rupture and subsequent eventration of the clo-
aca.15 Like Muecke, they also used chicks in an animal model. However, rather than insert
a wedge of plastic to mimic a persistent cloacal membrane, they used a laser to incise the
membrane in the lower abdominal wall and created a hernia defect. The chicks then incu-
bated through gestation and were born with cloacal exstrophy. They, therefore, concluded
that the embryologic defect that most likely leads to exstrophy is not a persistent cloacal
membrane, but rather an untimely, premature rupture of the membrane. This is the theory
held by most at the present time to explain the etiology of classic bladder and cloacal ex-
strophy.

REFERENCES
1. Epidemiology of bladder exstrophy and epispadias: A communication from the International Clearinghouse
for Birth Defects Monitoring Systems. Teratology, 36:221, 1987.
2. Yang P, Khoury MJ, Stewart WF, et al: Comparative epidemiology of selected midline congenital abnor-
malities. Genetic Epidemiology, II: 141-54, 1994.
3. Kockum CC, Hansson E, and Stenberg A, et al.: Bladder exstrophy in Sweden, a longterm fol11ow-up
study, Eur J Ped Surg, 6:208-11, August 1996.
4 B. Slaughenhoupt

4. Bennett AH: Exstrophy of the bladder treated by ureterosigmoidostomies, long term evaluation. Urology,
2: 165, 1973.
5. lves E, Coffey R, Carter CO: A family study of bladder exstrophy, J Med Genetics, 17:139-41. 1980.
6. Shapiro E, Lepor H, and Jeffs RD: Inheritance of the exstrophy-epispadias complex. J Urol, 132:308,
1984.
7. Connolly JA, Peppas DS, Jeffs, RD, Gearhart JP: The prevalence and repair of inguinal hernias in children
with bladder exstrophy. J Urol, 154(5): 1900, 1995.
8. Stephens FD, Smith ED: Anorectal malformations in children. Chicago, Year Book Medical Publishers,
1971.
9. Wood J: On fission and extroversion of the bladder with epispadias. Tr Medico-Chir, 52:85, 1869.
10. von Geldern CE: The etiology of exstrophy of the bladder. Arch Surg, 8:61, 1924.
II. Connell FG: Exstrophy of the bladder: JAMA, 36:637, 1901.
12. Patten JF, Barry A: The genesis of exstrophy of the bladder and epispadias. Am J A nat, 90:35, 1952.
13. Marshall VF, Muecke EC: Variations in exstrophy of the bladder. J Urol, 88:766, 1962.
14. Muecke EC: The role of the cloacal membrane in exstrophy: the first successful experimental study. J
Urol, 92:659, 1964.
15. Thomalla JV, Rudolph RA, Rink RC, and Mitchell ME: Induction of cloacal exstrophy in the chick embryo
using the C0 2 laser. J Urol, 134:991-5, 1985.
 2

PRENATAL DIAGNOSIS OF BLADDER AND

CLOACAL EXSTROPHY AND RELATED
CONDITIONS

Roger C. Sanders

Department of Radiology
University of Maryland

Bladder exstrophy (Barth eta!., 1990; Bronshtein eta!., 1993; Gearhart eta!., 1995;
Jaffe et a!., 1990; Khandelwal et a!., 1996; Messelink et a!., 1994; Pinette et a!., 1996) and
its related cousin hypospadias (Sides et a!., 1996), are among the most challenging entities
that can be identified before birth with ultrasound. Hypospadias is the most common of
these lesions, but is most difficult to diagnose. A series of six cases and two case reports of
the prenatal diagnosis of hypospadias exist (Sides et a!., 1996). Typically, the penis is
short and it is often curved. The distal end of the phallus is widened forming a club shape.
Since, color flow Doppler records flow movement, whether of blood or urine, color flow
Doppler permits the visualization of urination, which is seen as an intermittent jet. Nor-
mally, jets of urine are seen coming from the tip of the penis but in hypospadias, the urine
originates from a more proximal and inferior site than the tip of the penis. The penis has to
be examined in a sagittal profile view for a decision as to the source if jet effect to be
made with confidence.
Hypospadias is associated with a number of syndromes, including Opitz BB syn-
drome, Opitz G syndrome and the Smith Lemli Opitz syndrome. It is also seen with some
chromosomal anomalies, such as triploidy, 4P syndrome and 13Q syndrome. Particular at-
tention to the configuration of the penis is often the result of finding of some other anom-
aly such as cleft lip or club feet, and therefore, the fetus as a whole is submitted to a very
detailed survey and hypospadias is then discovered. Isolated hypospadias detection is a
much greater challenge, but should be possible when there is an appropriate family his-
tory.
Bladder exstrophy is somewhat easier to diagnose because the bladder is a structure
that is routinely sought during a standard obstetrical sonogram performed for other rea-
sons. The absence of the bladder is a hallmark of bladder exstrophy. Eight individual case
reports, in which the diagnosis has been made antenatally, have been reported (Mirk et a!.,
1986; Barth et al, 1990; Jaffe et a!., 1990; Gearhart et a!., 1989) and a large retrospective
The Exstrophy-Epispadias Complex, edited by Gearhart and Mathews.
Kluwer Academic I Plenum Publishers, New York, 1999. 5
6 R. C. Sanders

series of 25 fetuses with bladder exstrophy has been reported (Gearhart et al., 1995). The
diagnosis of bladder exstrophy could be made retrospectively in 29 prenatal studies from
17 pregnancies. The time of the fetal ultrasound varied from 14-36 weeks gestation (mean
23). The diagnosis of bladder exstrophy, however, was made before delivery in only three
cases. Five abnormal ultrasonic features associated with bladder exstrophy were identi-
fied: 1) the bladder was not visualized on ultrasound in 12 of the 17 cases (71 percent); 2)
a lower abdominal bulge representing the exstrophied bladder was seen in 8 of the 17
cases (47 percent); 3) a small penis with anteriorly displaced scrotum was identified in 8
out of 14 males (57 percent); 4) the umbilical insertion was low-set in 5 of 17 cases (29
percent); and 5) abnormal widening ofthe iliac crest was seen in 3 ofthe 17 cases (18 per-
cent). An absent bladder is a consistent finding which is always seen, however the changes
in location of the genitalia and cord insertion are subtle and only visualized if the fetus is
examined in the sagittal alignment with the fetus supine. Mounding of the bladder rem-
nant is highly variable. In some instances, this is very obvious, and in others the exstro-
phied bladder has a flat surface. Secondary obstructive changes in the kidneys may
occasionally occur with bladder exstrophy.
The iliacs normally form a right angle to one another. In bladder exstrophy, this an-
gle is widened to about 110 degrees. This change in iliac crest angle is relatively easy to
recognize in utero because a view of the lumbosacral spine, obtained to rule out
myelomeningocele is routine. Recently, a large series of fetuses have had the iliac angle
analyzed in relation to Down's syndrome. A widened iliac angle is also a sign of Down's
syndrome (Kliewer et al., 1996). These normal standards for iliac angle can also be used
for the detection of bladder exstrophy.
The differential diagnosis of bladder exstrophy includes other abdominal wall mal-
formations such as omphalocele, which lies at a higher level since it is associated with the
cord insertion. In addition, the bladder is present with omphalocele. Gastroschisis, another
abdominal wall malformation, arises in the lower abdomen on the right. Gut occasionally,
including the bladder or stomach, lies outside the fetal abdomen with the gastroschisis, ex-
iting through a hole in the right iliac region. As a rule, the bladder is in its usual location,
so these conditions are not easily confused with exstrophy. Absence of the bladder may
occasionally be a normal finding in utero, although as a rule, the fetus does not completely
empty its bladder when it voids. Other causes of absent bladder that should be considered
include renal agenesis and any cause of absent urine output, such as bilateral multicystic
dysplastic kidney or severe infantile polycystic disease.
Although the absence of the bladder should make the diagnosis of bladder exstrophy
relatively easy to make, it is often missed. In the series by Gearhart et al., in 1995, only 3
out of 25 prenatally seen bladder exstrophy cases were recognized prenatally. In retro-
spect, 17 had features consistent with bladder exstrophy, such as absent bladder. Fourteen
of these cases were male and 3 female. It is easier to make this diagnosis in males because
of the genitalia changes. The fetal bladder is visible by 11-12 weeks. It becomes more ob-
vious as the pregnancy progresses. With modem equipment, the kidneys can be seen at
14-15 weeks.
Cloacal exstrophy (Bruch et al., 1996; Carr et al., 1994; Chitrit et al., 1993; Cilento et
al., 1994; Kutzner et al., 1988; Mandell et al., 1995; Meizner et al., 1995; Nishi et al., 1988;
O'Leary et al., 1995; Richards et al., 1992; Winderi et al., 1996; Zimmer et al., 1996) is a
syndrome with many obvious ultrasonic features. At least 17 single or double case reports
have been published of this entity discovered in utero. Although the many ultrasonic fea-
tures are obvious, it is sometimes difficult to combine them all to make the right diagnosis.
With the usual open type of cloacal exstrophy, there is absence of the fetal bladder. There is
Prenatal Diagnosis of Bladder and Cloacal Exstrophy and Related Conditions 7

a large infraumbilical anterior midline defect with a massive protruding omphalocele. The
thorax is narrowed and the spine is kyphoscoliotic. There may well be caudal regression. A
sacral meningocele is often present with possible secondary changes in the cranium of the
Arnold Chiari Type I phenomenon. Bilateral club foot is usually seen. Ascitic fluid is often
present. Again, the iliac crest is widened. Recently, the anus has been recognized by ultra-
sound. Normally, there is a small echogenic spot surrounded by an echopenic area on a
transverse through view at the level of the external genitalia. This finding is absent in cloa-
cal exstrophy since imperforate anus is a typical feature of the syndrome. Obstruction of the
kidneys and ureters is also commonplace with perhaps, the development of multi cystic dys-
plastic kidney. The syndrome appears to be much more common in monochorionic twins
than expected. A sub variant is the OEIS complex (omphalocele, vesical exstrophy, imperfo-
rate anus and spinal abnormalities) and this is the form which occurs most often in twins
(Chitrit et al., 1993; Lee et al., 1997; Sherer et al., 1992).
Many of the milder cases are confused with omphalocele since caudal regression
and spinal changes are not easy to recognize. Severe examples of the entity are easily con-
fused with two other similar syndromes. The body stalk anomaly is a syndrome in which
the cord is exceptionally short. Cord tension is thought to be the reason why much of the
abdominal contents are exteriorized. There is myelomeningocele with secondary changes
of Arnold Chiari type 1 in the cranium. There is usually a markedly distorted spine which
may be shortened with caudal regression and is almost always curved and scoliotic. An-
other similar syndrome is the limb body wall complex, or cillosomia. In this entity, disrup-
tion of the amnion at approximately 6-8 weeks with subsequent amniotic band formation,
is thought to be responsible for many malformations. Almost always, one or more of the
limbs is absent. The spine is kyphoscoliotic and there is usually caudal regression. A spina
bifida is again a frequent feature with secondary cranial changes of the Arnold Chiari Type
I malformation. The abdominal wall is disrupted with most of the contents of the abdomen
lying anterior to the abdominal wall. Ectopia cordis is a common secondary malformation.
Both body stalk anomaly and limb body wall complex are lethal anomalies.
The key in distinguishing cloacal exstrophy, which is salvageable from lethal body
stalk anomaly or limb body wall complex, lies in close examination of the extent of the
caudal regression and seeing whether all limbs are present. As a rule, with limb body wall
complex, there is little or no amniotic fluid. In both conditions, the large myelomeningo-
cele can appear to be a sac containing amniotic fluid. Ascites surrounding the contents of
the large omphalocele can also be mistaken for amniotic fluid.
Hypospadias, bladder exstrophy and cloacal exstrophy represent rare entities which
are difficult to find with ultrasound. Experienced ultrasound practitioners should be able
to find all three problems when a 16-18 week standard obstetrical sonogram is performed.
Knowledge of the nature of the anomaly is very helpful to parents in deciding whether to
continue the pregnancy. It is standard practice to have a pediatric urologist talk to the pa-
tient about anomalies when they are discovered They counsel them on the type of surgery,
duration of time in hospital, delivery site and time of delivery. Patients with such anoma-
lies have a multitude of questions that only the pediatric urologist can properly answer.

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2. Bronshtein M, Bar-Hava 1., Blumenfeld Z.: Differential diagnosis of the nonvisualized fetal urinary blad-
der by transvaginal sonography in the early second trimester. Obstet Gynecol 1993; 82:490-493.
8 R. C. Sanders

3. Bruch SW, Adzick NS, Goldstein RB, Harrison MR. Challenging the embryogenesis of cloacal exstrophy. J
Pediatr Surg 1996; 31:768--770.
4. Carr MC, BenacerrafBR, Mandell J. Prenatal diagnosis of an XY fetus with aphallia and cloacal exstrophy
variant. J Ultrasound Med 1994;13:32~325.
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through antenatal ultrasound scanning. J Clin Ultrasound 1993; 21 :339-342.
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7. Gearhart JP, Ben-Chaim J, Jeffs RD, Sanders RC. Criteria for the prenatal diagnosis of classic bladder ex-
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8. Gearhart JP, Jeffs RD, State of the art reconstructive surgery for bladder exstrophy at the Johns Hopkins
Hospital. Am J Dis Child 1989; 143:1475-1479.
9. Jaffe R, Schoenfeld A, Ovadia J. Sonographic findings in the prenatal diagnosis of bladder exstrophy. Am J
Obstet Gynecol 1990; 162:675-678.
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Dysmorphologic features of the fetal pelvis in Down syndrome: Prenatal sonographic depiction and diag-
nostic implications of the iliac angle. Radiology 1996; 201 :681-{;84.
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trimester. Prenat Diagn 1988; 8:247-253.
13. Lee DH, Sanders RC, Meyers CM, Wulfsberg EA, Sun CCJ. The OEIS complex (omphalocele-exstrophy-
imperforate anus-spinal defects) in monozygotic twins. Proceedings: United States and Canadian Academy
ofPathology 1997; 10:6A.
14. Mandell J, Bromley B, Peters CA, BenacerrafBR. Prenatal sonographic detection of genital malformations
J Uroll995; 153:1994-1996.
15. Meizner I, Levy A, Barnhard Y. Cloacal exstrophy sequence: An exceptional ultrasound diagnosis. Obstet
Gynecol 1995: 86:446--450.
16. Messelink EJ, Aronson DC, Knuist M, Heij HA, Vos A. Four cases of bladder exstrophy in two families J
Med Genet 1994; 31 :490-492.
17. Mirk P, Calisti A, Fileni A. Prenatal sonographic diagnosis of bladder exstrophy. J Ultrasound Med 1986;
5:291-293.
18. Nishi T, Yamoto M, Nakano R. Prenatal diagnosis of exstrophy of the cloaca with ectopia cordis. Asia
Oceania J Obstet Gynecol 1988; 14:21~217.
19. O'Leary r, Davies P, Challis D, Bury G. Closed bladder exstrophy (pseudoexstrophy) associated with
mesodermal anomalies. J Ultrasound Med 1995; 14:311-314.
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cloacal exstrophy by ultrasound. A report of three cases. J Reprod Med 1996; 41:132-134.
21. Richards OS, Langham Jr MR, Mahaffey SM. The prenatal ultrasonographic diagnosis of cloacal exstro-
phy. J Ultrasound Med 1992; II :507-510.
22. Sherer DM, Abramowicz JS, Smith SA, Cusson CL, Metlay LA, Woods Jr JR, Normal lung structure and
pulmonary function in a twin with agenesis of the cloacal membrane and persistent severe oligohydram-
nios. J Maternal-Fetal Med 1992; I :24-28.
23. Sides D, Goldstein RB, Baskin L, Kleiner BC. Prenatal diagnosis ofhypospadias. J Ultrasound Med 1996:
15:741-746.
24. Winderi LM, Patel V. Hydrometrocolpos associated with uterovaginal duplication: The prenatal sonog-
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agn 1996; 16:65-69.
 3

ANATOMY AND BIOMECHANICS OF THE

PELVIS IN EXSTROPHY

Mihir M. Jani, Paul D. Sponseller, John P. Gearhart, A. Valdevit, and

E. Y.-S. Chao

Departments of Orthopedics and Urology

The Johns Hopkins School of Medicine
Baltimore, Maryland

I. ANATOMY OF THE PELVIS IN CLASSIC AND CLOACAL

EXSTROPHY

The Exstrophy Complex includes anomalies ranging from epispadias to classic to

cloacal exstrophy. Exstrophy of the bladder occurs due to abnormal anterior rupture of the
cloacal membrane early in the embryonic period. Mesenchymal ingrowth into the abdomi-
nal wall is inhibited. Since the pelvis is derived from sclerotomal components of the me-
senchyme, one may hypothesize that the development of the entire pelvis may be affected
by this altered migration of mesenchyme. It is important to understand the patho-anatomy
of the pelvis in exstrophy, for planning of appropriate soft-tissue and bony correction in
this disorder. However, there are very few specimen dissections reported, and no compre-
hensive analysis of pelvic shape in either classic or cloacal exstrophy. Therefore, analysis
of computed tomograms of patients with classic and cloacal exstrophy was carried out to
better define the differences in the shape of the pelvis between these patients and those
without congenital anomaly. We attempted to answer the question of where the pelvis in
exstrophy was rotated, to quantify the malrotation, and to determine whether there was an
actual deficiency of growth. An analysis of the rotation and the spacing of the hips was
also made. In addition, we wished to correlate these findings with the clinical picture of
patients' gait, which is commonly described as "out-toeing" or "waddling."

Method of Analysis

The bony pelvis is comprised of three bones in addition to the sacrum: the ilium, is-
chium and pubis, which are joined at the triradiate cartilage of the acetabulum. The ilium is
posterior, while the ischium and pubis are anterior to it. For the purpose of this analysis, the
pelvis was conceptualized as being composed of an anterior (ischio-pubic) segment and a
The Exstrophy-Epispadias Complex, edited by Gearhart and Mathews.
Kluwer Academic I Plenum Publishers, New York, 1999. 9
10 M. M. Jani et al.

posterior (iliac) segment, joined at the triradiate cartilage. Computed tomographic (CT)
scans were obtained of twenty-five patients who had not had an osteotomy for exstrophy: 19
had classic exstrophy and 9, cloacal exstrophy. Clinical exams were performed on each pa-
tient, assessing the gait , strength and rotation. Controls were obtained from 36 age-matched
patients who underwent pelvic CT for other reasons and had no congenital anomaly. Most
were done for trauma, and those with pelvic fractures or dislocation were excluded.
On the CT images, parameters measure included the length and angulation of the an-
terior and posterior segments, as well as the diastasis (spread) of the pubis. The transverse
orientation (version) of the acetabulum was also measured, as well as the increased dis-
tance between the two hips, which has special biomechanical significance. The antever-
sion of the femur, or the orientation of the proximal and distal joints in the transverse
plane, was also measured in order to determine if any compensatory growth occurred in
response to the primary, acetabular change in orientation.
Clinical exams were performed on each patient. In order to study all of the compo-
nents of the limb which determine the final rotation of the knees and the feet during gait,
we measured the internal and external rotation of the hips in extension, as well as the
thigh-foot angle (for tibial torsion) and the foot progression angle, or the angle of the foot
during gait. The Trendelenburg test was used as a measure of gluteal muscle strength.
Patients with simple epispadias were not examined by CT scan, since the use of ra-
diation could not be justified for a condition which does not require osteotomy. Plain ra-
diographs of the pelvis were routinely available, usually as part of an intravenous
pyelogram. These were analyzed for diastasis of the symphysis.

Findings
Rotational Abnormalities. On analysis of the CT data, it was shown that the not only
was the anterior portion of the pelvis abnormal, but also the posterior segment was af-
fected as well, with a mean external rotation in classic exstrophy patients of 12 degrees on
each side (Figure 1). This was greater in the patients with cloacal exstrophy. The degree of
external rotation tended to decrease with time, however. The anterior segment was further
externally rotated 6 degrees beyond the posterior segment in the classic exstrophy pa-
tients, and showed little tendency to correct with time (Figure 1). The acetabulum was

18"

ANTERIOR SEGMENT

'"
POSTERIOR SEGMENT

r - r - - - - - INTER-TRIRADIIttE
DISTANCE ii!H")

Figure 1. Diagram of the pelvis showing the changes in the anatomy of the pelvis in classical exstrophy.
Anatomy and Biomechanics of the Pelvis in Exstrophy l1

retroverted, or rotated externally, on each side, but there was no measurable change in the
femur in response to this

Size and Shape of Segments. The size of the posterior segment, that is, of the iliac
bone, was equal to that of age-matched controls. The anterior segment, however, showed a
very interesting and significant decrease in length. In classic exstrophy, this length was
30% less than controls (Figure l) . Not only were the bones malrotated, but there was also
a deficiency of their length anteriorly. In cloacal patients, the anterior deficiency was often
much more pronounced.
The diastasis of the pubic symphysis increased linearly in patients with classic ex-
strophy, from a mean of 4 centimeters at birth to 8 centimeters at age ten, to 14 centime-
ters at skeletal maturity. The patients with epispadias also had a diastasis of the symphysis
pubis, a fact which is not commonly appreciated. By contrast, the normal width of the
symphysis in persons without exstrophy or epispadias is essentially constant throughout
life, at 0. 7 to 1 em.
Many other malformations were seen in the group with cloacal exstrophy. There was
a 25% incidence of hip dislocation. Many patients had malformation of the sacroiliac
joint, in which it was underdeveloped and functioned as a hinge joint instead of a strong
junction with almost no detectable motion, as in the normal state.

Clinical Exams. The patients with classic exstrophy walked with an external place-
ment of the feet up until approximately school age, after which time the angle began to
correct. There were no significant abnormalities in the femur or the tibia. There was no
evidence of hip muscle weakness, and all patients were able to participate in sports and
physical activities normally.

Summary. The event which occurs early in embryonic life in exstrophy affects not
only the genitourinary system but also the migration and formation of the bony pelvis.
Specifically, the following have been shown9 :
• The posterior (iliac) segments are externally rotated a mean of 12 degrees but cor-
rect partially with time.
• The anterior (ischiopubic) segments are further externally rotated.
• The anterior segment is shortened by 30%.
• The pubic diastasis increases linearly with age.
• The acetabulum is retroverted.
• The patients with cloacal exstrophy have more severe degrees of all of the above
findings. They also may have malformations such as dislocated hips and abnor-
mal sacroiliac joints.
Changes in the pelvis in exstrophy are summarized in Figure I. They are important
to understand in designing an osteotomy to correct the pelvis in order to help with geni-
tourinary reconstruction. They also have implications for the forces about the hip, which
may determine its long-term fate.

II. BIOMECHANICAL ANALYSIS OF HIPS IN ADULTS WITH

BLADDER EXSTROPHY

Several types of pelvic osteotomies have been developed to decrease the stress on
the initial exstrophy closure. Indications for pelvic osteotomy so far have been to lower