Pediatric Urology Evidence

Warren T.
Snodgrass
Editor
Pediatric Urology
Evidence for Optimal

Patient Management
123
Pediatric Urology
Warren T. Snodgrass
Editor
Pediatric Urology
Evidence for Optimal Patient
Management
Editor
Warren T. Snodgrass
Department of Pediatric Urology
University of Texas Southwestern Medical Center
and Children’s Medical Center Dallas
Dallas, TX, USA
ISBN 978-1-4614-6909-4 ISBN 978-1-4614-6910-0 (eBook)

DOI 10.1007/978-1-4614-6910-0
Springer New York Heidelberg Dordrecht London
Library of Congress Control Number: 2013934223
© Springer Science+Business Media New York 2013

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Preface
The primary aim of this book is to assemble data needed by clinicians in their
daily decision making.
The format differs from usual textbooks in that it assumes a basic knowl-
edge of pediatric urology and so is focused on pivotal clinical questions. Each
chapter begins with a statement of the primary and secondary aims for the
diagnosis and treatment of the condition, followed by a synopsis of the evi-
dence we found for those aims. Information from the primary sources is sum-
marized so that readers know how studies were done and reported.
To write the book an outline for each chapter was made including ques-
tions frequently encountered in diagnosis and management, and then broad-
based computer searches were done to identify articles potentially answering
them. We followed the general methodology of a guidelines panel to review
materials and results for pertinent information to extract.
We gave greater emphasis to meta-analyses, such as Cochrane Reviews,
RCTs, and prospective studies, as well as to well-done retrospective analyses
with clearly defined objectives and well-described results. In the absence of
these, useful information still could be obtained from primary sources that
otherwise would not rate high in current evidence-based standards.
Why do this?
Numerous studies report wide variations in practice among pediatric urol-
ogists, despite the obvious truth that recommendations a patient receives
should not be an accident of geography. One step towards greater consistency
is summarizing the expected findings and outcomes from diagnostic and
management options. Rather than base decisions on surgeon opinion and
preference, this book facilitates rapid review of published data to guide
treatment.
Study of the available evidence for most topics in this book also highlights
need for multicenter cooperation to enroll sufficient patients in trials to answer
important clinical questions. Most urologic conditions in children simply do
not affect sufficient numbers of patients for single centers to perform high-
quality studies. For example, no RCT proves benefit of antibiotic prophylaxis
in children with either prenatally detected hydronephrosis or VUR, and sev-
eral centers would need to pool their patients to power such a trial.
v
vi Preface
Management of various conditions by pediatric urologists has been chal-

lenged by outside specialties for focusing too much on surgical outcomes
rather than benefits to the child. We are experts in correcting reflux, or pre-
dicting when it will spontaneously resolve, but pediatricians are asking which
children need this expertise. A common theme throughout this book is that
there is less evidence on health benefits from therapy than on surgical success
rates. To that end, the book may also stimulate new avenues of research.
Writing this book has changed our own practice in many ways. When
questions arise, for example, in preoperative conferences, we no longer ask
each surgeon what he or she would do, but instead review available published
information to narrow the options. Although we each trained in different cen-
ters and bring different perspectives to discussions, this process has reduced
variations in our individual practice, with the additional benefits of simplify-
ing on-call coverage, instructions to nurses, and fellow training. Studying the
sometimes weak evidence on which clinical decision making is based has
stimulated us to design better prospective trials, some in collaboration with
other centers.
Here are three specific examples of changes made in our practices prompted
by this book. We operate much less often on an “undescended” testis in boys
older than 1 year, especially when records from the hospital and initial pri-
mary care provider indicate it was descended at birth, given the evidence
cited in Chap. 5 that even specialists are sometimes fooled by retractile testes
and most of those testes not in the scrotum after a normal newborn exam
return to the scrotum during puberty. We no longer consider baseline renal
function or diuretic washout times indications for pyeloplasty, since repair
most often does not improve differential function and “obstructive” drainage
curves do not predict future function loss. We now use results of semen analy-
sis at age 17 to recommend varicocelectomy, since testicular size discrepancy
does not appear to correlate with fertility potential.
Our work inevitably has similar shortcomings as textbooks. It is not pos-
sible to include every published study in a review, and while we tried to cast
a broad net to identify articles and then extract the best data from them, we
still could have overlooked a pertinent report. To minimize intrusion of our
own opinions we emphasized summaries from the original sources, but it is
difficult to be completely objective.
Nevertheless, we believe this book will be useful to pediatric urologists in
training and at all stages of practice, and hope it helps to improve care for the
children entrusted to us all.
The book is designed for use as a manual, and so studies are sometimes
mentioned in several sections within a chapter. It was written over a 1.5-year
period beginning in March 2011, with final editing completed in October
2012. An outline with specific clinical questions was used as a guide by
authors, who then performed computer searches to identify articles contain-
ing information to answer those questions. After drafts were completed and
edited, we met as a committee, repeating selected computer searches and
reviewing and critiquing each chapter to finalize the manuscript.
Preface vii
Two authors have advanced degrees of relevance, one a Master’s in Public

Health and Epidemiology and the other a Master’s in Clinical Studies.
Nevertheless, the Editor bears final responsibility for the reporting in this book.
Dallas, TX, USA Warren T. Snodgrass

Linda A. Baker
Nicol C. Bush
Patricio C. Gargollo
Micah A. Jacobs
Contents
1 Urinary Tract Infection ............................................................... 1

2 Vesicoureteral Reflux ................................................................... 19
3 Bladder and Bowel Dysfunction ................................................. 35
4 Nocturnal Enuresis ...................................................................... 53
5 Undescended Testes...................................................................... 67
6 Hernias and Hydroceles............................................................... 81
7 Testicular Torsion......................................................................... 89
8 Varicocele ...................................................................................... 103
9 Hypospadias.................................................................................. 117
10 Phimosis, Meatal Stenosis, and BXO ......................................... 153
11 Ureteropelvic Junction Obstruction ........................................... 165
12 Multicystic Dysplastic Kidney .................................................... 183
13 Ureteroceles and Ectopic Ureters ............................................... 191
14 Non-refluxing Megaureter ........................................................... 199
15 Posterior Urethral Valves and Ureterovesical
Junction Obstruction ................................................................... 205
16 Neurogenic Bladder ..................................................................... 223
17 Urolithiasis .................................................................................... 259
Index ...................................................................................................... 275
ix
Contributors
Linda A. Baker Department of Pediatric Urology, University of Texas

Southwestern Medical Center and Children’s Medical Center Dallas, Dallas,
TX, USA
Nicol C. Bush Department of Pediatric Urology, University of Texas
TX, USA
Patricio C. Gargollo Department of Pediatric Urology, University of Texas
TX, USA
Micah A. Jacobs Department of Pediatric Urology, University of Texas
TX, USA
Warren T. Snodgrass Department of Pediatric Urology, University of Texas
TX, USA
xi
Urinary Tract Infection
1
Warren T. Snodgrass and Nicol C. Bush
Primary goals in the diagnosis of urinary tract therapy for voiding dysfunction or consti-
infection (UTI) and the subsequent evaluation pation to reduce UTI.
of underlying factors predisposing to UTI: • Observations that renal scars occur in a
1. Reduce recurrent UTI. minority of patients after fUTI, and that
2. Prevent acquired renal damage. those without scarring on DMSA scan have
Summary of evidence for these goals: <5 % risk for developing scars with recur-
• After first febrile UTI (fUTI), less than one- rent UTI suggest there are two general pop-
third of patients will develop a second fUTI ulations of children—those with a greater
within 1–2 years. versus a lesser risk for scarring.
• Approximately 15 % of children will UTI occurs in approximately 8 % of children.
develop renal scarring after fUTI. While most have no discernible underlying etiol-
• Vesicoureteral reflux (VUR) increases risk ogy, and so their infections are presumed to
for renal scarring by approximately 2.5 times, reflect disturbed bacterial–host interaction, infec-
but no evidence demonstrates management tion can indicate structural anomalies of the uri-
reduces future acquired renal damage. nary tract, as well as functional bladder
• Patients with negative DMSA after UTI disturbances, or constipation. In the past, chil-
have £5 % risk for future abnormal DMSA dren with UTI, especially febrile infection, rou-
with recurrent UTI. tinely underwent radiologic investigations, and
• Potential interventions to reduce risk for those found to have anomalies, most often VUR,
recurrent UTI include circumcision and routinely had treatment. Several recent RCTs
therapy for voiding dysfunction and/or have called into question this paradigm, as
constipation. However, no RCT demon- reviewed below.
strates circumcision after infection is more
effective than the natural history of dimin-
ishing UTI occurrence in males. No RCTs Diagnosis
have been reported concerning efficacy of
The standard for diagnosis of UTI is greater
than 105 cfu/mL of a pure bacterial growth on
W.T. Snodgrass, M.D. (*) • N.C. Bush, M.D., M.S.C.S. urine culture from a symptomatic patient.
Department of Pediatric Urology, 2011 AAP guidelines recommend diagnosis
University of Texas Southwestern Medical Center based on ≥50,000 cfu/mL and a urinalysis that
and Children’s Medical Center Dallas,
demonstrates pyuria and/or bacilluria.
1935 Medical District Drive, MS F4.04,
Dallas, TX 75235, USA Suprapubic aspiration is considered the
e-mail: warren.snodgrass@childrens.com gold standard to obtain urine samples with the
W.T. Snodgrass (ed.), Pediatric Urology: Evidence for Optimal Patient Management, 1
DOI 10.1007/978-1-4614-6910-0_1, © Springer Science+Business Media New York 2013
2 W.T. Snodgrass and N.C. Bush
least risk for contamination in infants and non- (VCUG) after prior UTI (n = 71) or in evaluation
toilet-trained children, but is not often per- of prenatal HN (n = 27). There were 82 males, all
formed. One study found catheterized uncircumcised, and 16 females. All were receiv-
specimens more accurate than voided samples ing prophylactic antibiotics, and all obtained
in girls, but not in uncircumcised boys. specimens were negative for WBCs and nitrite.
One retrospective analysis reported likeli- Colony counts were greater in voided specimens
hood for true UTI was greatest in uncircum- in both boys and girls. However, if mixed bacte-
cised males with >105, and in females with >104 rial colonies were considered evidence of con-
growth on catheterized specimens, with inde- tamination, catheterized and clean catch specimens
terminate probability at lower colony counts. showed similar false-positive rates regardless of a
Urine gram stain, urine dipstick for leuko- threshold of 103, 104, or 105. There was moderate
cyte esterase (LE) and/or nitrite, and urine agreement between clean catch versus catheter-
microscopy may be useful to increase or ized specimens when comparing any bacterial
decrease suspicion for UTI during the 24- to growth to no growth in uncircumcised boys
48-h delay needed for urine culture results. (Kappa 0.42) but poor agreement in girls (Kappa
Gram stain showing any bacteria in uncen- 0.18). In other words, a catheterized specimen in
trifuged urine best predicts UTI. girls was more accurate than a voided specimen,
Nearly as reliable as gram stain is urine but the same was not true in boys, implying cath-
dipstick. UTI is very likely when both LE and eterized specimens in uncircumcised boys are
nitrite are positive and very unlikely when prone to contamination (Lau et al. 2007).
both are negative, with intermediate reliabil-
ity if only one of the tests is positive. Negative
dipstick results are less reliable to exclude UTI Colony Counts
in children <2 years of age.
Standard microscopy showing ≥5 WBCs A retrospective study compared results of urine
per high power field is less reliable than gram obtained by catheterization in children 1- to
stain or dipstick, except in children <2 years of 18-months old (median age 6 months). There were
age in which microscopy results are the same 952 samples, 492 (52 %) collected from uncir-
as dipstick. cumcised boys and the remainder from girls. Of
Microscopy showing both pyuria and bac- these, 435 (46 %) had bacterial growth that was
teria has similar accuracy to dipstick positive pure in 352 (81 %) and mixed in 83. Patients were
for LE and nitrite to rule in UTI. considered to have fUTI on the basis of positive
LE and nitrite and WBCs by microscopy, and
response to antibiotics. There were 212 patients
Catheterized Versus Voided Specimens diagnosed with fUTI, with 198 (93 %) having pure
colony growth and 14 (7 %) with mixed growth.
Pure growth of 103 colony-forming units has been Another 740 patients did not have UTI, with 223
considered diagnostic for catheterized specimens, (30 %) having positive growth that was pure in 154
versus 105 for voided urine specimens (AAP (69 %) and mixed in 69 (31 %). In uncircumcised
guidelines 1999). The 2011 AAP guidelines rec- boys, only colony counts >105 indicated high like-
ommend a minimum 50,000 cfu/mL in a speci- lihood for UTI (LR20.2 [95 % CI 12.01–34.02]).
men obtained by catheterization or suprapubic In females, 104 to 105 colony counts had a likeli-
aspiration. hood ratio (LR) 8.95 (95 % CI 3.08–25.98). Lesser
A prospective study compared clean catch ver- cfu/cc yielded indeterminate probability for true
sus catheterized urine specimens in 98 asymp- UTI, leading to the conclusion that catheter urine
tomatic children <2 years (mean 6 months, SD cultures have to be interpreted within the clinical
4.3) undergoing a voiding cystourethrogram context (Cheng and Wong 2005).
1 Urinary Tract Infection 3
Gram Stain, Dipstick, and Microscopy predict likelihood for UTI was reduced when
dipstick was only LE- or nitrite-positive.
Meta-analysis was done on 26 articles published • Dipstick was significantly less reliable in chil-
between 1966 and 1998 regarding rapid diagnos- dren <2 years versus older children
tic testing for UTI in children: • Dipstick was more reliable to make a rapid
• Gram stain demonstrating any bacteria in diagnosis of UTI than standard microscopy
uncentrifuged urine was most accurate to pre- (>5 WBC/hpf in centrifuged urine) in children
dict UTI, with a positive LR of 18.5 and nega- >2 years of age and the tests were nearly
tive LR of 0.07. equivalent in patients <2 years.
• Dipstick had a positive LR of 12.6 when both Given the small number of studies, the authors
LE and nitrites were positive, and a negative stated results should be interpreted with caution,
LR of 0.13 when both LE and nitrites were and it was not clear why tests had variable results
negative. by age (Mori et al. 2009).
• Microscopy (>5 WBC/hpf in centrifuged
urine) offered no advantage over dipstick with
lower sensitivity and specificity. Pyelonephritis Versus Febrile UTI
Most of the tests were found to have significant
heterogeneity among the included studies, Febrile UTI refers to urinary infection associ-
depending, for example, on how stringent was ated with fever ≥38 °C, whereas pyelonephri-
the diagnosis of UTI and what age patients were tis specifically refers to renal inflammation.
evaluated (Gorelick and Shaw 1999). Acute DMSA scintigraphy demonstrates
Another meta-analysis reviewed search data- that only approximately 50 % of fUTIs show
bases from their inception until 2004, finding 70 radiologic evidence of renal parenchymal
for inclusion concerning rapid testing to diagnose inflammation.
UTI in children under 5 years of age. Follow-up (late) DMSA scintigraphy indi-
• UTI was likely when dipstick was LE and cates renal scars do not develop in patients
nitrite positive (pooled LR 28.2 [95 % CI with negative acute scans, and are found in
17.3–46.0]) or microscopy was positive for 15–38 % of children with positive acute scans
both WBC and bacteria (pooled LR 37.0 in the region of prior inflammation.
[95 % CI 11.0–125.9]). The minimum time after acute infection
• UTI was ruled out when dipstick was negative needed for inflammation to resolve so that late
for both LE and nitrite (pooled LR 0.20 [95 % DMSA scintigraphy demonstrates permanent
CI 0.16–0.26]) renal damage is unknown.
• Microscopy was negative for both WBC and As part of a prospective trial, 309 children
bacteria (pooled LR 0.11 [95 % CI 0.05–0.23]). 1–24 months of age with first known fUTI had
Definition of pyuria and bacteriuria on micros- acute DMSA scintigraphy within 48 h of diagno-
copy was not stated (Whiting et al. 2005). sis. Of these, 190 (61 %) were positive, demon-
A third meta-analysis reviewed published arti- strating renal inflammation that involved a mean
cles from 1966 to 2009 for studies comparing of 31 % of renal parenchyma. Repeat DMSA
dipstick to microscopy in infants versus older scintigraphy was obtained in 275 (89 %) patients
children. A total of six met inclusion criteria, 6 months later. All those with negative acute scans
finding the following: had negative follow-up scans, while 26 (15 %) of
• Dipstick was useful to rule in bacteriuria when 173 whose initial scan was positive had apparent
both LE and nitrites were positive (LR 38.54 scar formation that involved a mean of 8 % of
[95 % CI 22.49–65.31]), and useful to rule out renal parenchyma (Hoberman et al. 2003).
bacteriuria when both were negative (LR 0.13 Another prospective study of first symptom-
[95 % CI 0.07–0.25]). Reliability of dipstick to atic UTI in term neonates £28 days of age also
performed acute DMSA scintigraphy (£72 h of females. After 1 year of age, most UTIs occur
diagnosis) and late DMSA scintigraphy at 6 in females.
months. Results in 72 patients were reported per Meta-analysis of articles published from 1950
renal unit: 27 (19 %) of 144 kidneys demonstrated to 2009 reporting prevalence data for UTI in
apparent parenchymal inflammation, of which 10 symptomatic children (fever and/or urinary tract
had presumed renal scar on the 6 months follow- symptoms) 0–19 years of age indicated the
up scan. No patient with an initially normal scan following:
had an abnormal late scan, while 10 (37 %) of • Prevalence of UTI in febrile infants <2 years
those with positive acute scans had presumed scar old was 7 % (CI 5.5–8.4). Most boys were less
on the 6-month scan (Siomou et al. 2009). than 3 months of age with declining likelihood
A third prospective study of DMSA scintigra- of UTI thereafter, while most UTIs in females
phy after first fUTI in 105 children a mean of occurred within the first year of life.
5.9 ± 4.7 years of age found 37 (35 %) patients • Prevalence in febrile circumcised boys less
had acute parenchyma lesions. Follow-up DMSA than 3 months was 2.4 % (95 % CI 1.4–3.5)
scans were then done at 6 and 12 months in those versus 20.1 % (95 % CI 16.8–23.4) in uncir-
with positive acute studies. Of the 37 children, 3 cumcised boys. Only one study reported prev-
were excluded for recurrent infection, leaving 34 alence of fUTI in circumcised versus
undergoing repeat DMSA at 6 months, of which uncircumcised boys 6–12 months, finding
13 (38 %) continued to show renal defects. These 0.3 % versus 7.3 %, respectively. No data
13 children then had a final DMSA scan at 12 regarding prevalence after 12 months were
months, with only 6 (18 %) still having a defect found.
(Agras et al. 2007). • Prevalence in children 2–19 years was 7.8 %
Fifty children with positive DMSA scintigraphy (95 % CI 6.6–8.9), which combined both
6 months after first fUTI responded to a letter 3 febrile and afebrile infections (Shaikh et al.
years later inviting study participation for a second 2010).
DMSA evaluation. There were 30 females, and A prospective study of first symptomatic infec-
patient age was 0–18 years, with 24 (48 %) less tions in 304 consecutive children (169 boys) less
than 2 years of age at time of first DMSA study. than 5 years of age presenting to the emergency
Comparison of the two DMSA scans was done by department of a pediatric hospital found 64 %
three blinded observers, reporting that of the 88 ini- were <1 year old, comprising 75 % of infections
tial defects, there was no change in lesion in 24 in males and 50 % in females (Craig et al. 1998).
(27 %), partial resolution in 56 (63 %), and com- Similarly, another prospective report of 209
plete resolution in 8 (9 %) (Parvex et al. 2008). consecutive children (77 boys) with first known
symptomatic UTI presenting to the emergency
department found 58 % occurred at age <1 year,
Incidence and 75 % by age 2 years (Ismaili et al. 2011).
Retrospective review was done of consecutive
Approximately 2 % of males and 8 % of infants born in 1996 in 12 facilities of the Kaiser
females will develop UTI. Permanente Medical Care Program of Northern
Most UTIs in males occur at £3 months of California, comprising 28,812 infants (52 %
age. Prevalence is 10 times less in circumcised males). Diagnosis of UTI over the following 12
versus uncircumcised males at this age, and months of life was determined from computer-
the likelihood for infection decreases rapidly ized databases using ICD-9 codes, reporting the
thereafter in both circumcised and uncircum- following:
cised infants. • 446 (1.5 %) had UTI; 2 % uncircumcised
First UTIs occur most often during infancy, males, 0.2 % in circumcised males, 2 % in
comprising 75 % of UTIs in males and 50 % in females.
• Mean age at hospitalization for UTI was 2.5 rate the authors noted was lower than in studies
months in uncircumcised males. including asymptomatic bacilluria detected by
• Mean age at hospitalization for UTI was 6.5 surveillance cultures, which were not done in
months in females (Schoen et al. 2000). these patients. Risk factors for recurrence
included white race (multivariable HR 1.97
[95 % CI 1.22–3.16]), age 2–6 years (HR 2.01
Recurrent UTI After Initial Infection [95 % CI 1.20–3.37]), and VUR grades 4–5 (HR
4.38 [95 % CI 1.26–15.29]), but not gender, no
Less than one-third of patients with or with- VCUG, or grades 1–3 reflux. VCUG was not
out VUR evaluated after a first fUTI will have performed in 400 (65.5 %) after initial UTI
a second fUTI within 1–2 years. (Conway et al. 2007).
Of those with recurrent infection, most will A study of 290 children less than 5 years of age
have a single recurrence with less than 10 % of presenting with first UTI included imaging with
patients with or without VUR having three or renal ultrasonography and VCUG, with antibiotic
more recurrences within 1–2 years. prophylaxis prescribed to the 29 % with VUR and
Recurrence rates are not significantly dif- the 1 % with obstructive uropathy. Recurrent UTI
ferent in males versus females. developed in 34 (12 %) children within 12 months.
Even though need and efficacy of antibiotic These recurrences were associated with age <6
prophylaxis relate to risk for recurrent infection, months at initial diagnosis (OR 2.9 [95 % CI 1.4–
likelihood for recurrent UTI after first known 6.2]) and VUR grades 3–5 (OR 3.6 [95 % CI 1.5–
infection has not been widely reported. 8.3]), but not with gender (OR 1.5 [95 % CI
A retrospective analysis of 262 children 1–2.2]) (Panaretto et al. 1999).
admitted to hospital for therapy of their first Data regarding recurrent UTI can also be
known UTI and then followed with monthly sur- extracted from several prospective RCTs compar-
veillance urine cultures for 2 years found a sub- ing antibiotic prophylaxis to no antibiotic therapy
sequent positive culture in 33 %, evenly in patients with and without reflux (Table 1.1). In
distributed by gender (all boys were uncircum- those studies in which all patients had VUR, at
cised). Of these, 71 % were symptomatic infec- least one recurrent fUTI occurred in from 16 to
tions, while the remainder were diagnosed by 37 % of patients followed for 18–24 months
scheduled urine culture in asymptomatic chil- (Pennesi et al. 2009; Roussey-Kesler et al. 2008;
dren; 61 % recurred within 3 months, and 92 % Brandstrom et al. 2010). Lower rates of recurrent
by 1 year, of the initial infection. During 3 years’ fUTI ranging from 2.5 to 13 % were noted in three
follow-up in the 88 children with recurrent UTI, other studies, in which approximately half the
48 (54 %) had only one recurrence, and another patients had reflux and there was shorter follow-up
25 (28 %) had only two. Patients with obstruc- of 1 year (Garin et al. 2006; Montini et al. 2009;
tive or neuropathic uropathies were excluded Craig et al., 2009). Most patients with recurrent
from the study. VCUG was performed in 121 UTI had only a single episode, with only 6 % hav-
(46 %) patients after first UTI, and analysis ing three or more recurrent fUTIs (Pennesi et al.
excluded the seven patients prescribed antibiotic 2009; Craig et al. 2009).
prophylaxis. VUR grades 3–5 were found a risk Data collected in 740 consecutive patients
factor for recurrence versus grades 1–2 and no with VUR between 1970 and 2008, who were
VUR (Nuutinen and Uhari 2001). all prescribed antibiotic prophylaxis with either
A review of electronic medical records from trimethroprim or nitrofurantoin, found recur-
27 primary care pediatricians within a common rent UTI during 58,856 person-months in 278
network also evaluated recurrent infection after (38 %) children. This equated to 8.4 episodes of
first known UTI. A cohort of 611 children was UTI per 1,000 person-months (95 % CI 7.7–
assembled, of which 83 (14 %) had subsequent 9.2). Of patients with recurrent UTI, 21 % had
infection (0.12 per person-year after first UTI), a a single recurrence, 10 % had two, and 7 %
6
Table 1.1 Recurrent UTI in patients on no antibiotic prophylaxis after UTI

Patients Age patients Recurrent fUTI
Author Study type VUR⊕ (grade) VUR– Source patients (mean or median) Duration f/u VUR ⊕ VUR–
Series of patients ± VUR
Garin 2006 RCT 58 60 fUTI, Excluded 3 month–18 year (2 year) 1 year 1 (1.7 %) 2 (3.3 %)
(1–3) VUR g 4,5
Montini 2009 RCT 46 81 First fUTI 2 month–7 year (15 month) 1 year 9 (19.6 %) 3 (3.7 %)
(1–3)
Craig 2009 RCT 121 115a ³1 UTI <18 year (15 month) 1 year 36 (13 %)
(1–5)
Series of patients all with VUR
Roussey-Kesler 2008 RCT 122 – First fUTI, g 1–3 VUR 1 month–3 year (11 month) 18 month 19 (15.5 %) –
Pennesi 2008 RCT 50 – First fUTI, g 2–4 VUR <30 month (8 month) 2 year 15 (30 %) –
Brandstrom 2010 RCT 68 – First fUTI, g 3–4 VUR 1–2 year (1.8) 2 year 25 (37 %) –
a
VUR status unknown in another 52 patients
W.T. Snodgrass and N.C. Bush
had three or more. The likelihood for recur- 22 %, and was noted equally in males and females.
rence diminished with time, from 16.8 episodes However, grades 4–5 reflux, which accounted for
per 1,000 person-months in the first 24 months, 25 % of detected VUR, was found only in boys.
to 7.8 between 24 and 48 months and was <5 The authors noted other studies with similar
episodes per 1,000 person-months thereafter to findings that together suggest VUR is less com-
10 years follow-up (Dias et al. 2010). monly found after UTI in neonates versus in older
children (Siomou et al. 2009).
Analysis of prospective data on 209 children
Associated Conditions presenting at median age 10 months (0.2–204)
with first known UTI reported on antenatal US
Anatomic Anomalies had been done in 198 (95 %), finding UPJO in
2.5 %, posterior urethral valve (PUV) in 0.5 %,
Obstructive uropathies and various renal and primary megaureter in 0.5 %. Renal US was
anomalies occur in <10 %. repeated in all patients, finding one new case each
VUR is diagnosed in £33 % of children of PUV and primary megaureter. VUR was diag-
imaged after fUTI. Most VUR is grades 1–3. nosed in 25 %, with grades 1–3 comprising 85 %
One prospective study using the 1999 AAP (Ismaili et al. 2011).
imaging guidelines (renal US and VCUG in chil- A retrospective study reviewed renal US
dren <24 months after fUTI) in 309 children (33 findings in 203 consecutive infants, 80 males, 5
boys) ages 1–24 months presenting with first days to 6 months of age with fUTI who had nor-
known fUTI reported renal US was normal in mal VCUG. Abnormalities were detected in 32
88 %, with another 5 % having findings likely to patients (16 %), but management was altered in
be insignificant (extrarenal pelvis, pelvic dila- only 9 (4 %) for UPJO (n = 1), ectopic ureter
tion, ureteral duplication); 4.5 % had “hydro- (n = 2), renal calculus (n = 1), UVJO (n = 3), mul-
nephrosis or pelvicaliectasis.” VCUG was normal ticystic dysplastic kidney (MCDK) (n = 1), and
in 61 % of patients, demonstrating reflux in the renal scar (n = 1) (Giorgi et al. 2005).
remaining 39 %. In these 115 children with reflux,
96 % had grades 1–3, 5 had grade 4, and none
had grade 5 (Hoberman et al. 2003) Bladder Dysfunction
Another prospective study of 297 consecutive
children under age 5 years with first symptomatic Lack of standardized means and criteria to diag-
UTI were imaged according to 1999 AAP recom- nose bladder dysfunction limits reliability of
mendations. Renal US demonstrated “obstructive reported studies to determine prevalence of these
uropathy” in three, a megaureter in seven, a disorders in children presenting with UTI.
horseshoe kidney in two, and duplex ureters in In one retrospective study of 109 consecutive
five. Accordingly, potentially significant findings children, 82 % female, referred for urologic eval-
(obstructive conditions and megaureters) were uation of UTI and/or voiding symptoms, children
noted in 3 %. VUR was diagnosed in 28 % (95 % were systematically queried for history of urinary
CI 23.3–33.6); grades were not reported (Craig frequency and urgency, with or without diurnal
et al. 1998). incontinence, considered indicative of urge syn-
A prospective study analyzed 72 term neo- drome. In females older than 3 years old with
nates 0–28 days of age with symptomatic UTI infection, 40 % had urge syndrome symptoms.
(fever, vomiting, poor feeding, failure to thrive). Of all females older than 3 years with urge syn-
Renal US findings were not reported, except to drome symptoms, 66 % had a history of UTI
note that one patient had ureteropelvic junction (Snodgrass 1991).
obstruction (UPJO) and another with VUR had During a 4-year period, 3,500 children were
congenital hypodysplasia of the ipsilateral kidney. evaluated for urinary incontinence, of which
VUR was reported by renal units, occurring in 1,000 underwent invasive urodynamic studies for
the following indications: history of UTI, small • Painful or hard bowel movements.
bladder capacity, repeated dysfunctional uroflow, • Presence of a large fecal mass in the rectum.
ultrasonographic abnormalities, and resistance to • Large-diameter stools that may obstruct the
therapy. Diagnostic categories assigned by UD toilet.
were urge syndrome (detrusor instability during Additional criteria include the following:
filling with normal voiding), dysfunctional void- • Without objective evidence of a pathological
ing (sphincteric activity during voiding diminish- condition.
ing or interrupting urine flow), and lazy bladder • Without fulfilling irritable bowel syndrome
(greater than predicted bladder capacity without criteria.
detrusor contraction during voiding). Mean Infants up to 4 years of age have to fulfill two
patient age was approximately 10 years, with 524 or more criteria for at least 1 month. Children >4
males and 476 females. UTI was reported in 5 % years should have two or more criteria from ³2
of males with urge syndrome and 7 % with dys- months (Tabbers et al. 2011).
functional voiding (no male was diagnosed with A prospective study reported an association
lazy bladder), versus 30 % of females with urge between constipation and UTI in patients >5 years
syndrome, 36 % with dysfunctional voiding, and old (176 boys) referred to an encopresis clinic for
53 % with lazy bladder (Hoebeke et al. 2001). soiling at least once a week for 6 months.
Another study defined dysfunctional elimina- Additional diagnostic criteria for functional con-
tion syndrome (DES) as “daytime wetting or stipation were not stated, except to note that all
soiling,” or the presence of at least three of the had fecal retention on rectal examination and
following: voiding <3 times daily, Vincent’s 45 % had a palpable abdominal mass from stool.
curtsy, thick-walled bladder by ultrasound, trabe- Diurnal urinary incontinence was reported by
culated or spinning top bladder on cystogram, or 29 % of patients without gender difference,
bladder capacity >30 % predicted value for age. whereas UTI occurred in 3 % of males versus
All 2,759 patients referred for these symptoms 33 % of females (p < 0.001). Of the 19 girls with
and/or UTI and reflux over a 14-year period were UTI, 8 reported only one infection. The remaining
identified from a database for multivariable logis- 11 had recurrent infections, 4 also having struc-
tic regression analysis. DES was diagnosed in tural urinary tract anomalies including reflux in 3
52 % of children having UTI and normal radio- and a “large” bladder diverticulum in 1. Successful
logic testing, versus 38.5 % of those with VUR. relief of constipation was said to prevent further
Girls were more likely than boys to have DES UTI. Infections were not categorized as febrile
(Chen et al. 2004). versus nonfebrile, and neither the number of
infections nor time interval during which they
occurred was stated for those with recurrent UTI.
Constipation Patients with recurrent UTI received antibiotic
prophylaxis for nonspecified intervals, with five
Constipation is considered a risk factor for continuing therapy at time of last follow-up. This
development of UTI, but the lack of standard- follow-up was performed at a mean of 15 months,
ized means and criteria to establish the diag- most often by a questionnaire mailed to families,
nosis hinders determination of its prevalence or by phone call (Loening-Baucke 1997).
in children with urinary infection. Other studies linking constipation to UTI,
Rome III criteria, currently recommended to mostly from the 1980s or earlier, suffer from
diagnose pediatric functional constipation, are small numbers of patients, lack of uniform
two or more of the following: definition of constipation, and poor study design
• Two or fewer defecations per week. without controls or multivariable statistical anal-
• At least one episode of fecal incontinence per yses. For example, one evaluation of 131 children
week. with UTI diagnosed constipation in 45 (34 %)
• Stool-retentive posturing. based on symptoms including hard stools,
infrequent stooling, fecal soiling, chronic laxative uncircumcised boys commonly quoted, and
use, or rectal fissures. Effective therapy for con- calculated that 195 circumcisions would be
stipation was reported to prevent UTI recurrence needed to prevent a single hospital admission for
at 1 year, although success was only defined as UTI (To et al. 1998).
“regular bowel movements of normal size” A retrospective review concerned recurrence
(Neumann et al. 1973). of UTI after initial infection in 128 uncircum-
cised boys within the first year of life in Finland.
Mean age for initial UTI was 0.33 years (SD
Circumcision Status 0.23), and in the following 3 years 35 % had a
second infection occurring at a mean of 85 days
Circumcision reduces the risk of UTI, with (SD 92 days) (Nuutinen and Uhari 2001).
relative risk (RR) 4.5 (95 % CI 2.4–8.4) in A meta-analysis of published data regarding
uncircumcised versus circumcised infants <1 effect of circumcision on UTI risk obtained infor-
month of age, and RR 3.7 (95 % CI 2.8–4.9) mation on 402,908 boys in 12 studies. From this,
during the first year of life. the number to treat to prevent one UTI was calcu-
One retrospective study reported first infec- lated to be 111. For boys with grades 3–5 VUR,
tion occurred at mean age 4 months in uncir- the number to treat to prevent one UTI is 4
cumcised boys, with recurrent UTI in 35 % a (Singh-Grewal et al. 2005).
mean of 3 months later.
Although circumcision reduces UTI risk,
more than 100 circumcisions are needed to Imaging After UTI
prevent one UTI. Calculated number needed
to treat to prevent one UTI in boys with grades Renal Ultrasound and VCUG
3–5 VUR is 4, which supports circumcision for
this higher-risk group. The 1999 AAP guidelines recommended renal
Meta-analysis of four articles concerning UTI US and VCUG after first known fUTI in chil-
and circumcision status reported prevalence of dren ages 1–24 months. 2011 AAP guidelines
febrile infection in 2.4 % (95 % CI 1.4–3.5) of only recommend renal US unless there is
circumcised boys <3 months of age versus 20.1 % “hydronephrosis, scarring, or other findings
(95 % CI 16.8–23.4) in those uncircumcised. For suggesting high-grade VUR.”
infants 6–12 months of age, prevalence for fUTI Findings reported by prospective studies in
in one study was 0.3 % in circumcised versus consecutive children undergoing these tests are
7.3 % in uncircumcised males. No data were summarized in the section “Anatomic Anomalies.”
found concerning febrile UTI after 1 year age
(Shaikh et al. 2008).
A prospective matched cohort study compared Diagnostic Accuracy of Cystography
29,217 circumcised to the same number of uncir-
cumcised Canadian newborns to determine rela- A single-fill (noncycled) cystogram fails to
tive risk for hospital admission for UTI. There detect VUR in approximately 20 % of cases.
were 1.88 infections per 1,000 person-years of Accuracy is increased with cycled cystography.
observation in circumcised boys versus 7.02 per Approximately 20 % of patients found to
1,000 person-years in uncircumcised boys. RR have unilateral VUR on initial (non-cycled)
for infection in uncircumcised boys was 4.5 VCUG will be found to have contralateral
(95 % CI 2.4–8.4) in the first month of life, and VUR on subsequent cystography.
3.7 (95 % CI 2.8–4.9) during the first year of life. Cycling during NC also increases diagnos-
The authors noted this reduction in risk was much tic yield; one study reported 15 % of VUR
less than the 10–20 times higher rate of UTI in found during the second cycle.
One study of consecutive children undergo- detect VUR in three patients, grade 1 in two and
ing both VCUG and NC found NC significantly grade 2 in one (Polito et al. 2000).
more accurate to detect both VUR overall and A retrospective study considered new contral-
high-grade VUR. ateral VUR after initial VCUG showed only uni-
A prospective study compared findings after lateral reflux. Therefore, all patients had ³2
the first cycle to findings after a second cycle of VCUGs, ranging to seven. Those found to have
VCUG in 275 children £2 years of age, 90 % fol- new contralateral VUR had a statistically
lowing UTI. Overall, VUR was detected in 68 significant greater number of cystograms
(25 %) patients. However, the first cycle only (3.5 ± 1.4 vs. 2.6 ± 1, p < 0.001). Overall, new
demonstrated reflux in 18 cases, whereas the sec- contralateral VUR was found in 33 (21 %) of 167
ond in another 50. Of the 257 children with a patients, comprising grade 1 in 4, grade 2 in 18,
negative initial cycle, the additional 50 found grade 3 in 9, and grade 4 in 1, with grade not
with VUR during the second cycle represented determined due to nuclear cystography in 1. The
another 19.5 % that otherwise would have been methods regarding VCUG cycling were not
missed. Grades found on the second cycle ranged clearly stated (cycled only if initial imaging was
from 1 to 5 (Papadopoulou et al. 2002). “unsatisfactory”); the interval between studies
Another prospective study analyzed first versus was not stated, and whether new reflux was seen
second cycle of cystrography in children after fUTI on a second versus later cystogram was not
(n = 124, all girls) and in follow up of known VUR reported (Barroso et al. 2008).
(n = 135, 127 girls). NC was done in 249 children
and VCUG in 10. Patient age ranged from 3 weeks
to 17 years. Of 124 studies after fUTI, VUR was “Top-Down” Imaging Using DMSA
found in the first cycle in 40/124 and the second in Scintigraphy
7/76, meaning 15 % of VUR was detected in the
second cycle. For follow-up patients, VUR was “Top-down” imaging limiting VCUG to
seen during the first cycle in 90/135 and the second patients with positive acute or delayed DMSA
in 8/34, indicating 8 % had VUR detected by a sec- scintigraphy reduces the number of VCUGs.
ond cycle (Gelfand et al. 1999). One study reported top-down imaging
To determine relative accuracy of VCUG ver- would have reduced VCUG by 50 % while not
sus NC, 124 consecutive children 1 month to 9 detecting VUR in 15 % of patients, all but one
years of age (mean 2 years) being imaged follow- of which had grades 1–2.
ing UTI, prenatal hydronephrosis, or multicystic Another study obtained DMSA later, at ≥3
dysplastic kidney underwent both studies. VCUG months after fTUI, and found VCUG would
was performed first, with NC then obtained have been done in 20 % of patients if limited to
immediately in 73, within 3 days in 21, and a those with abnormal findings.
mean of 17 days in 30 patients. VCUG was done A prospective study using DMSA scintigra-
twice in children less than 3 years of age. NC was phy at £7 days of onset of fever or urinary symp-
not cycled. Voiding occurred in all studies. toms combined with renal US and VCUG
Findings were concordant in 84 % of renal units, reported an 83 % positive predictive value and a
and 93 % for diagnosis of grades 4–5 VUR, cor- 92 % negative predictive value for “clinically
responding to “severe” VUR on NC. However, significant VUR” Significant VUR was defined
there were 4 refluxing units only detected by as including ³ grade 3 reflux, recurrent UTI, and
VCUG versus 36 seen only with NC (p = 0.0001), renal scarring. It is noteworthy that 73 % of the
of which VCUG did not exclusively detect severe 121 children (mean age 3.6 years, median 2.4,
VUR while NC did in 17/27 renal units (p = 0.004). range 2 months-11 years) had positive acute
Considering findings in patients, VCUG failed to DMSA scans, so the potential avoidance of
detect VUR found on NC in 23, 12 of which had VCUGs would be limited by their protocol to a
severe VUR on at least one side. NC failed to maximum 27 % of patients (Herz et al. 2010).
Another prospective observational study also into the affected kidney might be reduced and/
evaluated acute DMSA imaging (£2 weeks of or the risk of scarring increased.
onset of symptoms), in children <1 year old with A Cochrane Database review in 2010 included
first known symptomatic UTI. There were 290 23 studies with 3,407 children, finding the
children, with positive DMSA scans in 51 % and following:
VUR in 18 %. Abnormal DMSA occurred in • No difference in duration of fever or in renal
44 % of children without VUR, 72 % with grades damage as assessed 6 and 12 months after
1–2 VUR, and 96 % of those with ³ grade 3 fUTI based upon oral antibiotic therapy (ceft-
reflux. Reserving VCUG to those with positive ibuten, cefixime, or amoxicillin/clavulanic
acute DMSA studies would have reduced the acid) for 10–14 days versus initial intravenous
number of VCUGs by 50 %, missing VUR in therapy (cefotaxime or ceftriaxone) for 3 days
15 % which was grades 1–2 in all but one patient followed by 10 days of oral therapy.
with grade 3 (Preda et al. 2007). • No difference in renal scars between intrave-
A single “late” DMSA scan was done ³3 nous therapy for 3 days plus 10 days oral ther-
months after fUTI in another prospective study apy versus intravenous therapy for 7–10 days.
of 565 consecutive children referred for uro- Ten of the 23 studies excluded patients with
logic evaluation. Scintigraphy was obtained at known “severe urinary tract abnormalities”
a mean of 7 months (median 4 months) after (Hodson et al. 2010).
UTI. Focal cortical defects, whether resolving One RCT compared oral cefixime for 14 days to
renal inflammation or scars, were present in initial intravenous cefotaxime for 3 days followed
only 15.5 %. Another 4 % had presumed con- by oral cefixime for 11 days in children £2 years of
genital nephropathy (<44 % ipsilateral func- age with fUTI. Initial evaluation included urine
tion with no focal cortical defect). If VCUG gram stain, with gram-positive cocci an exclusion
was only obtained in patients with abnormal criteria. No significant differences were found in
DMSA ³3 months after fUTI, it would have duration of fever (oral: 25 h vs. IV plus oral: 24 h),
been done in only 19 % of patients (Snodgrass or renal scarring on DMSA performed at entry and
et al. 2012). at 6 months (oral:11 % vs. IV plus oral: 8 %).
Exclusion from the study included known genito-
urinary anomalies and severe clinical illness defined
Antibiotic Therapy as systolic blood pressure <60 mmHg or capillary
refill >3 min (Hoberman et al. 1999).
Intravenous Versus Oral Therapy
Children with fUTI can be treated with oral Longer Versus Shorter Duration
therapy using third-generation cephalosporins of Antibiotic Therapy
(following gram stain to exclude gram-positive
cocci). There is no difference in renal scarring based
Those judged too ill for initial oral therapy on 3 days initial intravenous antibiotic therapy
can receive initial intravenous antibiotics until plus 5 days oral therapy versus 8 days of intra-
clinical symptoms improve sufficiently to com- venous therapy in patients without uropathy.
plete therapy orally. There are no data regarding optimal dura-
There is no difference in duration of fever tion of therapy in those with known uropathies.
or renal scarring based on mode of antibiotic The Cochrane Database review mentioned
administration. above reported no significant difference in persis-
No data are available to guide optimal anti- tent renal damage between initial IV therapy for
biotic therapy in children with known uropa- 3–4 days followed by oral therapy versus IV ther-
thies, especially obstructive conditions or renal apy for 7–14 days (3 studies, 341 children: RR
hypodysplasia in which antibiotic penetration 1.13 [95 % CI 0.86–1.49]) (Hodson et al. 2010).
The shortest duration of therapy (8 days) day 4 of fever to determine effect of timing of
reported for fUTI was part of a RCT comparing antibiotic therapy on renal scarring. Second
outcomes in 383 children at median age 15 DMSA scans were obtained 5–26 months later
months (3 months-16 years) with first fUTI. All (median 6.5 months) in those with initially posi-
received 3 days intravenous antibiotics (netilm- tive findings. There was a significantly increased
icin for 48 h plus ceftriaxone for 72 h) followed number of renal defects observed during acute
by either 5 additional days of intravenous ceftri- DMSA scintigraphy with progressive delay in
axone or oral antibiotic based on sensitivities. therapy (41 % at <1 day, 59 % at day 2, 68 % at
Exclusion criteria were known uropathy, or day 3, and 75 % at ³ day 4 [p = 0.000]). Of 158
obstructive uropathy (pelvis dilation >10 mm) positive acute scans, follow-up scans were
or renal hypoplasia (length < 2 SD) on renal US. obtained in 76 without recurrent fUTI, with no
There was no difference in renal scarring deter- difference in persistently positive scan (overall
mined by DMSA at median 8 months later 51 %) in those treated at <1 day versus those later
(17 % longer intravenous therapy vs. 13 % (Doganis et al. 2007).
shorter intravenous therapy) (Bouissou et al.
2008).
Cranberry Supplements
Immediate Versus Delayed Therapy One study found no difference in the number
of children who developed UTIs in patients
Delay in starting antibiotic therapy was reported drinking cranberry juice versus placebo, but
to progressively and significantly increase posi- did report a decrease in the number of UTIs in
tive acute DMSA findings in one report. those with cranberry juice.
Three prospective studies found renal scar Two other trials reported a decrease in the
at DMSA 6–12 months after fUTI did not vary number of patients with UTI taking cranberry
according to antibiotic therapy started within 1 juice versus placebo.
day of fever onset versus a delay in treatment. In a multicenter Finnish trial, 263 children,
The prospective study by Bouissou et al. 88 % female, mean age 4 years (1–16) were
(2008) described in the preceding section ana- randomized to cranberry juice versus placebo for
lyzed risk for renal scar on DMSA a median of 8 6 months and monitored for UTI (fever and/or
months after first known fUTI for children start- symptoms) for a 1-year period; 20 (16 %) in the
ing intravenous antibiotic therapy <2 days versus cranberry group and 28 (22 %) in the placebo
³2 days after onset of fever, finding no difference group had at least one recurrent UTI, p = 0.21.
in renal scar (OR 1.34 [95 % CI 0.73–2.45]). While the intervention did not reduce the
Another prospective study included 287 chil- number of children with recurrent UTIs, it did
dren 1 month to 7 years of age with first known reduce the number of recurrences, with 27 and 47
fUTI and positive acute DMSA scan who had in the cranberry and placebo groups with a UTI
follow-up scintigraphy 12 months later. Risk incidence density per person-year at risk of 0.25
for renal scar was evaluated according to dura- versus 0.41 in the cranberry versus placebo group
tion of fever before antibiotic therapy of <1 day (p = 0.03, CI −0.31 to −0.01) as well as the total
to ³5 days. Overall prevalence of renal scar days on antibiotics (11.6 vs. 17.6 days, p < 0.001)
was 31 %, with no difference in renal damage (Salo et al. 2011).
based on delay in starting therapy (Hewitt Eighty-four girls mean age 7.5 years (3–14)
et al. 2008). with normal renal function and no genitourinary
A third prospective study evaluated 278 anomalies with more than one UTI due to E. coli
infants (153 boys) aged 6–12 months with first were randomized to cranberry juice (50 mL OD),
known fUTI started on antibiotics at <1 day to ³ lactobacillus (100 mL of 4 × 107 cfu lactobacillus
5 days/month), or control for 6 months. The Versus Age at UTI

results were that 34/80 (42.5 %) had at least one
UTI, with fewest in the cranberry treatment Despite common belief, renal scars are found
group; 5/17 (18.5 %) cranberry, 11/26 (42 %) less often, or at the same frequency, in infants
lactobacillus, and 18/27 (48 %) controls (p < 0.05) as in older children.
(Ferrara et al. 2009). A prospective study of first symptomatic UTI
Thirty-nine girls and one boy mean age 9.5 in term neonates £28 days of age obtained acute
years who had ³2 non-febrile UTIs in the year DMSA scintigraphy (at £72 h of diagnosis) and
prior to enrollment were randomly assigned to late DMSA scintigraphy at 6 months. Results in
receive daily cranberry juice versus placebo over 72 patients were reported per renal unit: 27 (19 %)
1 year. The incidence of non-febrile UTI was 0.4 of 144 kidneys demonstrated apparent parenchy-
in the cranberry versus 1.15 in the placebo arm mal inflammation, of which 10 (7 %) had renal
(p = 0.045), representing a RR reduction of 65 % scar on the follow-up scan (Siomou et al. 2009).
(Afshar et al. 2012). Another prospective analysis of 309 children
<2 years of age presenting with first known fUTI
included acute-phase (£48 h) DMSA scan, with
Renal Scar follow-up DMSA 6 months later obtained in 275
(89 %). Renal scarring was found on the second
Renal scars determined by DMSA scintigra- scan in 9.5 %, occurring with equal frequency in
phy occur in approximately 15 % of children those <1 year versus >1 year at initial infection
evaluated following first known fUTI. (Hoberman et al. 2003).
Renal scars were also found in 15 % of A third prospective study included 287 chil-
patients referred to urologic management dren 1 month to 7 years of age after first fUTI
after fUTI and/or VUR diagnosis. who all had acutely (<10 days) positive DMSA
The meta-analysis by Shaikh et al. described scans. This inflammation resulted in a renal scar
above included 33 studies to determine preva- on DMSA 1 year later in 55/184 (30 %) <1 year
lence of acute phase (£15 days) and follow-up of age versus 34/103 (33 %) at greater age during
(>5 months) DMSA scintigraphy in children after initial infection. Quartiles from age 1 to 24
first known UTI, finding the following: months and 2 to 7 years showed no differences in
• 57 % (95 % CI 50–64) had positive acute- renal scarring (Hewitt et al. 2008).
phase DMSA changes. A fourth prospective study enrolled 316 con-
• 15 % (95 % CI 11–18) had persistently posi- secutive children ages 1 month to 14 years with
tive follow-up DMSA scans. first fUTI. Acute-phase (<5 days) DMSA was
The authors found significant heterogeneity obtained in all, with late (>6 months) follow-up
between studies, but noted the rate of 15 % renal scan if the initial study was positive. There was
scar was stable in reports since 2002 (Shaikh no difference in renal scarring in those <1 year
et al. 2010). versus 1–4 years (OR 1.45 [95 % CI 0.62–3.37]),
Prospective evaluation of 565 consecutive but greater scarring in those 5–14 years (OR 3.35
children referred for urologic assessment after [95 % CI 1.04–10.78]) (Pecile et al. 2009).
fUTI and/or VUR diagnosis included DMSA The prospective study by Snodgrass et al. (2012)
scintigraphy ³3 months after infection, if present. described above, with 565 consecutive patients
Twenty-four (4 %) had congenital reflux neph- referred for urologic assessment after fUTI and/or
ropathy defined as £44 % ipsilateral function VUR, reported focal DMSA defects on scans done
without cortical defect, while 84/541 (15.5 %) a mean of 7 months (median 4 months) in 6 % of
had focal defects on scan done a mean of 7.4 patients <1 year of age versus 18 % of those >1 year,
months (median 4 months) after infection with each year of life increasing the odds of abnor-
(Snodgrass et al. 2012). mal DMSA by 20 % (OR 1.2 [95 % CI 1.1–1.3]).
Table 1.2 Renal scar versus VUR in 452 consecutive urology patients with fUTI and/or VUR
VUR grade Total patients No. abnormal DMSA OR estimate 95 % CI p
0 112 17 1.00 – –
1 23 4 3.94 1.05–14.85 0.04
2 133 15 3.12 1.35–7.21 0.008
3 130 19 3.93 1.68–9.22 0.002
4 44 21 28.91 10.73–77.88 <0.0001
5 10 6 77.37 16.62–360.20 <0.0001
Versus VUR versus no VUR, with similar odds for grades 1–3
and greatly increased odds for grades 4 and 5
VUR increases risk for renal scar by 2.5 times (Table 1.2).
in children following first fUTI. A retrospective study included 182 children
One study of patients referred for urology (32 boys) with VUR and UTI who had DMSA
assessment reported risk was greater in all scintigraphy to determine renal scarring 4–6
grades versus no VUR, with greatest risk in months after a positive acute-phase scan. Risk for
grades 4–5. scar for those with grades 1–3 VUR was 30/94
A retrospective study of children with VUR (32 %) versus 37/44 (84 %) with grades 4–5,
similarly reported increased scar in those with p = 0.000 (Soylu et al. 2008).
grades 4–5 versus 1–3.
The meta-analysis mentioned above by Shaikh
et al. (2010) was done specifically to assess risk Versus Number of fUTIs
for renal scarring in children with UTI. Published
articles were included if they reported acute- Few data are available regarding impact of
phase (£15 days) or follow-up (>5 months) recurrent UTI on renal scar risk.
DMSA results in patients 0–18 years of age, Most recent RCTs included patients with
resulting in 33 studies for review. As stated above, first known fUTI, or did not specify number of
57 % of children had positive acute-phase scans, fUTIs before enrollment.
of which 15 % demonstrated renal scar on fol- New DMSA defects after UTI in patients with
low-up scan. Those with VUR had increased risk prior negative DMSA occur in approximately
for scarring (RR 2.6 [95 % CI 1.7–3.9]), based on 5 % of patients, as discussed in the next section.
review of four articles. Risk by individual grade A study based on protocol assessment and man-
was not reported, but those with grades 3–5 were agement of children with symptomatic UTI from
2.1 times (95 % CI 1.4–3.2) more likely to have 1970 to 1979 included IVP-based diagnosis of renal
renal scar versus those with grades 1–2. However, scar (calyceal deformity with overlying parenchy-
in these four articles, one included only five mal defect). Prevalence of renal scar progressively
patients with grade 4 and none with grade 5 VUR, increased from 5 % in those without history of fUTI
and the other three lumped grades 3–5 together. to 9 % of those with one, 15 % with two, 35 % with
Renal scar risk was analyzed by individual three, and 58 % with four or more episodes of fUTI
reflux grades in a prospective series of 565 con- (Jodal 1987). Logistic regression analysis to control
secutive patients referred after fUTI and/or VUR influence of VUR grade was not done.
diagnosis described above (Snodgrass et al. Cross-sectional analysis of 565 consecutive
2012). Among consecutive patients referred for children with fUTI reported by Snodgrass et al.
urologic evaluation after UTI and/or VUR diag- (2012) as described above analyzed renal scar
nosis, multiple regression analysis showed all prevalence versus reported number of fUTIs in
grades of VUR increased risk for DMSA defects 529 patients (Table 1.3). A single fUTI did not
Table 1.3 Renal scar versus number of reported febrile UTIs in consecutive referred patients with UTI and/or VUR
No. febrile UTIs Total patients No. abnormal DMSA OR estimate 95 % CI p
0 81 9 1.00 – –
1 226 18 0.60 0.25–1.44 0.25
2 85 17 2.65 1.22–5.74 0.01
³3 137 36 3.97 2.06–7.63 <0.0001
increase renal scars over patients with no history progressive scarring after an earlier study with
of infection, although 9/81 (11 %) with no infec- scarring (Soylu et al. 2008).
tion history had DMSA defects, possibly indicat- The Swedish reflux trial included 203 patients
ing UTI attributed to other illnesses. Two or more with mean age 1.8 years (1–2) with grades 3–4
fUTI did increase scarring, although it could not VUR. Number of fUTI prior to entry was not
be determined if scarring occurred after the first stated, but baseline DMSA was positive in 124
or a subsequent infection. (61 %). New defects in those with negative
DMSA occurred in 9/79 (11 %). Timing of
DMSA and number of recurrent UTIs were not
Scar Risk After Recurrent UTI When stated (Brandstrom et al. 2010).
Initial DMSA Is Negative for Scar
Two studies report risk <5 %, and one study, References

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vention of recurrent urinary tract infection in children Soylu A, Demir BK, Turkmen M, Bekem O, Saygi M,
with low grade vesicoureteral reflux: results from a Cakmakci H, et al. Predictors of renal scar in children
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1084–91. 2005;5(1):4.
Vesicoureteral Reflux
2
Primary aims in the diagnosis and manage- • Antibiotic prophylaxis is no more effective
ment of vesicoureteral reflux (VUR): than placebo to prevent recurrent UTI in
1. Reduce recurrent febrile urinary tract children 1–24 months of age with grades
infection (fUTI). 1–4 VUR.
2. Prevent acquired renal damage. • There are no data regarding benefit of
Summary of evidence for these aims: antibiotic prophylaxis in children >2 years
Children with VUR have been assumed to of age with VUR, with VUR and no history
have high risk for renal scarring and recur- of UTI, with grade 5 VUR, or with recur-
rent fUTI, justifying therapy in most patients. rent UTI.
However: • Surgical correction of VUR (reimplanta-
• RCTs indicate only approximately one- tion or endoscopic injection) reduces recur-
third of patients with VUR will have recurrent fUTI.
rent UTI within 2 years of diagnosis • Identification and treatment of voiding dys-
• Acquired renal scarring occurs in approxi- function in children with VUR has not been
mately 15 % of children with VUR after clearly demonstrated to improve resolution
fUTI. or reduce fUTI.
• If DMSA scan for renal scar is negative, The two indications to diagnose and treat
risk subsequent fUTI will cause renal dam- VUR are to decrease likelihood for recurrent
age is £10 %. fUTI and renal scarring. The association of VUR
• No randomized controlled trial (RCT) has to fUTI and renal scarring has prompted investi-
been done to determine if VUR therapy gations not only to diagnose VUR after UTI, but
(medical or surgical) decreases additional also in siblings or offspring of patients with VUR,
acquired renal damage in children with and in newborns with prenatal hydronephrosis.
renal scar at presentation. However, recent prospective trials and observa-
tional studies indicate most children with VUR
will not have frequently recurrent infections after
W.T. Snodgrass, M.D. (*) • N.C. Bush, M.D., M.S.C.S. their initial one, and most will not develop renal
Department of Pediatric Urology, scarring. Furthermore, these studies also chal-
lenge the foundation of VUR management, ques-
1935 Medical District Drive, MS F4.04, tioning efficacy of continuous antibiotic
Dallas, TX 75235, USA prophylaxis to prevent recurrent UTI in children
e-mail: warren.snodgrass@childrens.com with VUR.
Most detected VUR is low grade, with

VUR Prevalence approximately 10 children per 100 screened
having grades 3–5.
After Febrile UTI Prevalence of VUR decreases with age.
Meta-analysis of 22 published articles by the
VUR is diagnosed in one-third or fewer of AUA Reflux Guidelines panel found data regard-
patients less than approximately 2 years of age ing VUR in siblings (n = 2,957) and offspring
following fUTI. Grades 1–3 account for over (n = 244), reporting the following:
75 % of cases, and are equally distributed • 100 % concordance in identical twins.
between genders, while grades 4 and 5 are • 35–50 % prevalence in fraternal twins.
more common in males. • Overall incidence was 27.4 (95 % CI 2.9–
Several prospective studies have reported VUR 51.9)/100 screened siblings.
incidence after first known symptomatic UTI: • Detected VUR grade was reported as “low grade”
• 302 children (33 boys) ages 1–24 months 1 and 2 vs. “high grade” 3–5. Most was low
underwent VCUG after first fUTI. VUR grade, with a mean prevalence of grades 3–5 in
occurred in 117 (39 %), grade 1 in 25, grade 2 9.8 (95 % CI 5.3–17.4)/100 siblings screened.
in 42, grade 3 in 45, grade 4 in 5, and grade 5 • Males and females were equally affected.
in 0 children. Therefore, 96 % of VUR cases • Incidence in offspring was 35.7 (95 % CI
were grades 1–3. Note the small percentage of 16.4–61)/100 screened.
males in the study, who are more likely than Likelihood for VUR in screened persons
females to have the higher VUR grades decreased with age at a rate of 4 % per year
(Hoberman et al. 2003). (Skoog et al. 2010).
• 297 consecutive children (169 boys) under
age 5 years with first symptomatic UTI (fUTI
in 242) reported reflux in 28 %, but did not Prenatal Hydronephrosis
state the grades (Craig et al. 1998).
• 209 children with first symptomatic UTI at VUR is found in 16 % of infants diagnosed
median age 10 months (0.2–204) had 53 (25 %) with prenatal hydronephrosis.
cases of VUR. Of these, 45 (85 %) were grades Prevalence is not influenced by extent of
1–3, while 8 (15 %) were grades 4 and 5 (gen- prenatal dilation, and it remains unchanged
der not stated) (Ismaili et al. 2011). even if postnatal ultrasound (US) is normal.
• 72 term neonates 0–28 days of age with symp- Two-thirds of detected VUR are grades 1–3.
tomatic UTI (fever, vomiting, poor feeding, There are no data to determine if antibiotic
failure to thrive) underwent VCUG, with VUR prophylaxis to prevent first UTI in neonates
reported by renal units occurring in 22 % with VUR is more effective than no treatment.
found equally in males and females. Of 144 Meta-analysis by the AUA Reflux Guidelines
renal units, there were grades 1 and 2 in 13 panel to determine prevalence of VUR in new-
(9 %), grade 3 in 10 (7 %), and grades 4 and 5 borns with prenatal HN included 34 studies in
in 8 (5.5 %). Grades 4 and 5, which accounted which the mean percentage of screened patients
for 25 % of detected VUR, were found only in was 78 % (11–100 %), reporting the following:
boys (Siomou et al. 2009). • VUR occurred in an average of 16 % (7–35 %)
with cystography.
• Grade distribution was approximately one-
Sibling and Offspring Screening third each for grades 1–2, 3, and 4–5.
• VUR occurred in the non-dilated kidney in
Siblings and offspring of affected patients 25 % of cases.
have similar prevalence of VUR, approxi- • Prevalence was 18 % even if postnatal US was
mately one-third of those screened. negative for HN.
2 Vesicoureteral Reflux 21
• Extent of prenatal dilation did not predict Presumed congenital reflux nephropathy
likelihood for postnatal VUR. was found in 4 % and focal scars in 19 % of
Relative risk for UTI posed by this VUR could referred patients with VUR in one study.
not be assessed from literature review, nor could Meta-analysis to determine risk for renal scarring
possible impact, if any, of antibiotic prophylaxis in children with UTI included 33 studies and
(Skoog et al. 2010). reported scar by follow-up DMSA scan in 15 %
(95 % CI 11–18). VUR had significantly increased
relative risk for scar (RR 2.6 [95 % CI 1.7–3.9]),
Likelihood for Recurrent fUTI based on four studies (Shaikh et al. 2010).
A prospective study of 565 consecutive children
Less than one-third of children diagnosed with referred for urologic assessment after fUTI and/or
VUR after first fUTI receiving no therapy will VUR diagnosis included DMSA scintigraphy ³3
have a second fUTI in the following 2 years. months after infection (mean 7.4 months; median 4
Of those with recurrent infection, most will months), if present. Presumed congenital reflux
have a single recurrence, with less than 10 % nephropathy (£44 % ipsilateral function and no
of patients having three or more recurrences cortical defects) was found in 24 (4 %), while focal
within 1–2 years. cortical defects likely representing scars were
The following is a summary of recurrent fUTI found in 84/541 (15.5 %) remaining study patients.
rates in patients with VUR from prospective Of 340 patients with VUR, excluding those with
studies: congenital nephropathy, 65 (19 %) had focal scar.
• 225 children (69 boys, “most” not circum- This comprised 12 % of patients with grades 1–2,
cised) ages 1 month to 3 years with first fUTI 15 % with grade 3, and 50 % for grades 4–5. The
found to have grades 1–3 VUR were followed OR for focal DMSA abnormalities by VUR grade
for 18 months. Recurrent fUTI developed in were grade 1, 3.94 (95 % CI 1.05–14.85); grade 2,
32 (14 %) (Roussey-Kesler et al. 2008). 3.12 (95 % CI 1.35–7.21); grade 3, 3.93 (95 % CI
• 100 children (48 boys) <30 months of age 1.68–9.22); grade 4, 28.91 (95 % CI 10.73–77.86);
with first fUTI and found to have VUR grades and grade 5, 77.37 (95 % CI 16.62–360.20) (see
2–4 were followed for 2 years. Recurrent fUTI Table 1.2) (Snodgrass et al. 2012).
occurred in 33 %, one episode in 11, two epi-
sodes in 3, and three or more episodes in 2
(Pennesi et al. 2008). New Renal Scars After Prior
• 87 children (22 boys) 3 months to 12 years of Negative DMSA
age with grades 1–3 VUR were enrolled after
fUTI (number of UTIs prior to enrollment was Our review found one RCT and one retrospec-
not stated). Recurrent fUTI occurred in 8 (9 %) tive review that reported 11 and 3 % of patients
during 1-year follow-up (Garin et al. 2006). with VUR and a prior negative DMSA scan
• 68 children (26 boys) ages 1–2 years with grades developed renal scar with recurrent UTI.
3 and 4 VUR were observed without treatment The IRS reported 15 % of patients and 4 %
for 2 years. Number of fUTIs before enrollment of kidneys with normal DMSA at entry devel-
was not stated. Recurrent fUTI developed in oped focal defects and/or renal function
25(37 %) (Brandstrom et al. 2010). decrease, but related events (fUTI, obstruction
after reimplantation) were not specifically
described for these children versus those with
Renal Scarring abnormal DMSA at entry.
The European branch of the IRS obtained DMSA
VUR increases likelihood of renal scar by at entry and again during follow-up at a duration of
approximately 2.5 times, with increasing risk 5 years (timing of second scan not clearly stated).
associated with increasing reflux grade, espe- There were 306 children, median age 3.5 years,
cially grades 4 and 5. with DMSA studies completed and/or of sufficient
quality for review in 287. All had UTI before entry, Reflux Guidelines panel. These 10 resolution
and initial DMSA was done afterwards at <2 curves for grades 1–4 were constructed using
months in 6 %, between 2 and 6 months in 40 %, data from three articles that comprised a total of
and at >6 months in 54 %. During follow-up, 95 % 587 patients, of which 250 (43 %) had grade 2
of DMSA were obtained >6 months after last UTI. (Elder et al. 1997). Subgroups with included
Entry DMSA was normal in 52 patients, and dur- patient numbers and percent chance for resolu-
ing follow-up 8 (15 %) showed deterioration; of tion in 1–5 years are found in Table 2.1.
246 normal kidneys at entry, 11 (4 %) showed Nomograms for VUR resolution were also
deterioration. There was no difference in changes constructed from a longitudinal database main-
based on randomization to medical versus surgical tained from 1998 and analyzed in 2006 contain-
therapy. Details regarding these patients with ini- ing 2,462 children. Annual cystography was done
tially normal scans who developed cortical defects following diagnosis, with resolution defined as
or renal function loss were not specifically one negative study. Spontaneous resolution
described. Overall DMSA changes occurred in 48 occurred in 51 % during mean follow-up
children, including 9 who developed obstruction 1.95 ± 1.37 years: 72 %, grade 1; 61 %, grade 2;
after reimplantation and 32 stated to not have UTI 49 %, grade 3; and 32 %, grades 4–5. Another
during management (Piepsz et al. 1998). 23 % had ongoing VUR at mean follow-up
The Swedish reflux trial included 203 patients 2.6 ± 1.6 years, and the remaining 26 % under-
with mean age 1.8 years (1–2) with grades 3 and 4 went surgery at 2.3 ± 1.6 years. Multivariable
VUR. Number of fUTI prior to entry was not stated, analysis showed increased spontaneous resolu-
but baseline DMSA was positive in 124 (61 %). New tion for the following:
defects in those with negative DMSA occurred in • Age <1 year (HR 1.31 [95 % CI 1.16–1.48])
9/79 (11 %). Timing of DMSA and number of recur- • Prenatal HN of sibling VUR (HR 1.24 [95 %
rent UTIs were not stated (Brandstrom et al. 2010). CI 1.08–1.42])
A retrospective analysis of 138 children (53 boys) • Single ureter (vs. duplication) (HR 1.55 [95 %
with VUR grades 1–5 included acute DMSA with CI 1.24–1.9])
subsequent DMSA 4–6 months later for abnormal • Male gender/unilateral female (HR 1.42 [95 %
findings, and another late DMSA 4–6 months after CI 1.26–1.59])
recurrent UTI. Recurrences developed in 118, but As a group, males and those females with uni-
only 26 were described as fUTI and only 16 involved lateral VUR resolved faster than females with
more than one recurrent episode. Of these, 2/71 bilateral VUR (Estrada et al. 2009)
(3 %) without scar during first evaluation were found Internet-based calculators have been developed
to have new scar formation (Soylu et al. 2008). to predict spontaneous resolution in individual
patients based on a variety of clinical data points.
Each was created using different methods based
Natural History upon retrospective data, including a logistic
regression model, a neural network, and literature
VUR may spontaneously resolve, with likeli- meta-analysis. A study inputting identical theo-
hood influenced by grade, laterality (unilateral retic patient characteristics into each reported
versus bilateral), and patient age at diagnosis. statistically significantly different predictions for
Initially diagnosed unilateral VUR is found spontaneous resolution (Routh et al. 2010).
in up to 20 % of cases to have contralateral
VUR on subsequent cystography.
New Contralateral VUR
Spontaneous Resolution A retrospective review was done in 167 children

(33 boys) diagnosed at mean age 55 months
Graphs summarizing VUR resolution during (2–169) with unilateral VUR from 1986 to 2004.
medical therapy were published by the first AUA Two-cycle VCUGs were performed. All patients
2
Vesicoureteral Reflux
Table 2.1 Percent chance of VUR resolutiona

Risk category (age in months)(number Percent chance (95 % confidence interval)
of patients on which estimates are based) 1 year 2 years 3 years 4 years 5 years
Grade Ib (n = 15) 39.3 (24.6–51.1) 63.1 (43.2–76.1) 77.6 (57.2–88.3) 86.4 (67.7–94.3) 91.8 (75.7–97.2)
Grade IIb (n = 250) 28 (24.1–31.7) 48.1 (42.3–53.4) 62.7 (56.2–68.1) 73.1 (66.8–78.2) 80.6 (74.8–85.1)
Grade III, unilateral, age 0–24 (n = 27) 21.4 (10.8–30.8) 38.2 (20.4–52.1) 51.5 (29–66.8) 61.9 (36.6–77.1) 70 (43.5–84.1)
Grade III, unilateral, age 25–60 (n = 27) 13.4 (4.6–21.4) 25 (8.9–38.3) 35.1 (13.1–51.5) 43.8 (17.1–61.9) 51.3 (20.9–70.1)
Grade III, unilateral, age 61–120 (n = 15) 10.8 (3.5–17.5) 20.5 (6.9–32) 29.1 (10.2–43.9) 36.7 (13.4–53.8) 43.6 (16.5–61.9)
Grade III, bilateral, age 0–24 (n = 62) 12.7 (7–18.1) 23.8 (13.5–32.9) 33.5 (19.5–45) 41.9 (25.1–55) 49.3 (30.3–63.1)
Grade III, bilateral, age 25–60 (n = 53) 7 (3.1–10.8) 13.5 (6.1–20.4) 19.6 (9–28.9) 25.2 (11.8–36.6) 30.5 (14.6–43.4)
Grade III, bilateral, age 61–120 (n = 14) 2.6 (0.7–4.5) 5.2 (1.4–8.8) 7.7 (2.1–13) 10.1 (2.8–16.9) 12.5 (3.5–20.7)
Grade IV, unilateralc (n = 28) 16.1 (8.5–23.1) 29.7 (16.4–40.8) 41 (23.5–54.5) 50.5 (30–65) 58.5 (36–73.1)
Grade IV, bilateralc (n = 96) 4.5 (1–7.9) 6.4 (2–15.1) 7.8 (3–21.8) 8.9 (4–28) 9.9 (4.9–33.7)
a
Reproduced with permission from Jack S. Elder, MD; Craig Andrew Peters, MD; Billy S. Arant, Jr., MD; David H. Ewalt, MD; Charles E. Hawtrey, MD; Richard S. Hurwitz,
MD; Thomas S. Parrott, MD; Howard M. Snyder, III, MD; Robert A. Weiss, MD. AUA Pediatric Vesicoureteral Reflux Clinical Guidelines Panel: The Management of Primary
Vesicoureteral Reflux in Children. American Urological Association Education and Research, Inc., © 1997. http://www.auanet.org/content/guidelines-and-quality-care/clinical-
guidelines/archived-guidelines/vesi_reflux07.pdf. The yearly rate of reflux resolution remains constant for each group
b
No difference shown by age or laterality (unilateral/bilateral); therefore, these categories were combined
c
Estimates only apply to the time of diagnosis and are not age-specific
23
had at least two cystograms, with 84 having three nonfebrile not stated). Those with symptoms of
to seven studies. Contralateral VUR not seen on frequency, urgency, holding maneuvers, and/or
the initial VCUG occurred in 33 (21 %) in patients diurnal incontinence for at least 6 months were
with a mean 3.5 ± 1.4 cystograms. This VUR was treated with timed voiding and oxybutynin 2.5–
grade 1 in 4, 2 in 18, 3 in 9, and 4 in 1 patient. 5.0 mg/dose 3 times daily at 6-month intervals
Variables analyzed included gender, side, age, until symptoms did not recur off medication. All
VUR grade, and voiding dysfunction. Of these, patients also received antibiotic prophylaxis. All
only higher VUR grade was predictive, with con- were considered to have a satisfactory response
tralateral VUR found in 12/91 (13 %) of grades to AC (not defined). Breakthrough UTI occurred
1–2 vs. 21/62 (34 %) with grades 3–5, p = 0.006 in a total of 23/86 (27 %) with follow-up of 1
(Barroso et al. 2008). year, 18 (78 %) with urge syndrome. Breakthrough
UTI was significantly more likely in females with
treated urge syndrome versus those without
Voiding Dysfunction symptoms, 18/42 (43 %) vs. 5/44 (11 %),
p = 0.001, despite similar age and VUR grades
Few studies report impact of treatment for (Snodgrass 1998).
voiding dysfunction on VUR outcomes. One-hundred one children, 67 % females,
Our review found only one retrospective mean age 5 years (6 week to 15 year) with recur-
analysis stating breakthrough UTI was rent UTI (febrile vs. nonfebrile; number of infec-
significantly more likely, despite AC in females tions not stated) underwent UD with fluoroscopy
with VUR and urge syndrome versus those that identified VUR. Grades were 1 (n = 1), 2
without voiding dysfunction. (n = 14), 3 (n = 13), 4 (n = 10), and 5 (n = 1). Of
One report found no difference in VUR these patients, detrusor instability was diagnosed
resolution at 3 years in patients with versus in 41 (41 %). Treatment comprised AC, and all
without detrusor instability. children had antibiotic prophylaxis. Reimplan-
Two others reported spontaneous resolu- tation was done as initial therapy in some patients
tion in approximately 60 % of ureters with and within 1 year in others (in £4 patients for
mostly grades 1 and 2 VUR in 6–12 months recurrent UTI), leaving 30 patients (39 ureters)
with biofeedback, but had no control groups. with detrusor instability with medical manage-
The 2010 AUA Reflux Guidelines reported ment and follow-up a mean of 3 years. Resolution
the following observations about VUR and occurred in 15/39 (38 %), vs. 27/57 (47 %) ure-
bladder/bowel dysfunction (BBD): ters in 42 patients with a stable bladder, p = 0.4.
• BBD increases risk for fUTI in children with UTI following treatment was not clearly described
VUR on antibiotic prophylaxis (44 % with (Scholtmeijer and Nijman 1994).
BBD vs. 13 % without) Twenty-five females, mean age 9 years (6–10),
• Spontaneous VUR resolution is less at 24 with VUR and dysfunctional voiding underwent
months in children with BBD (31 % with vs. a mean of seven biofeedback sessions (2–20)
61 % without) weekly–biweekly with repeat VCUG 1 year later.
• The rate of postoperative UTI after VUR sur- VUR grade was 1 (n = 10), 2 (n = 15), 3 (n = 5),
gery is greater with BBD (22 % vs. 5 %) and 4 (n = 1). Resolution occurred in 17/31(55 %)
Despite these observations, the panel stated there ureters. Correlation to dysfunctional voiding was
are few data regarding the impact of treatment for not described, except to state that all children
BBD on VUR outcomes (Peters et al. 2010). with resolved VUR had resolved or improved
A retrospective study of females ages 3–10 symptoms and decreased PVR from a mean
years old with VUR systematically obtained his- 40–10 % voided volume (Palmer et al. 2002).
tory for voiding dysfunction, found in 36/94 Seventy-eight children, 90 % females, mean age
(40 %) presenting after UTI (characterized as 1–2 9 years (5–14), were diagnosed with dysfunc-
or ³3 in the preceding 12 months; febrile vs. tional voiding (uroflow with pelvic floor EMG)
and VUR, which was grade 1 (n = 26), 2 (n = 32), with renal scarring had low birth weight
3 (n = 28), and 4 (n = 12). All received urotherapy (Hollowell 2008).
(“proper toilet posture,” hydration, timed void-
ing) and biofeedback for a median 6 (2–14) ses-
sions. At 6 months follow-up, subjective reduction Management
in symptoms of ³90 % was reported for diurnal
incontinence in 70 % and frequency in 76 %, and VUR management aims to reduce recurrent
normalization of uroflow patterns occurred in fUTI and renal scarring.
80 %. VUR resolved in 63 % of affected renal Historically, risk for fUTI and renal scar
units (96 and 81 % of grades 1 and 2, 36 % of have been assumed present in all children with
grade 3, and 8 % of grade 4). UTI was not dis- VUR, with management based on the general
cussed (Kibar et al. 2007). assumption that reflux should resolve or be
surgically corrected, especially in girls.
Few studies specifically address impact of
Impact of VUR on Pregnancy treatment on recurrent UTI and/or renal
scarring.
There are limited data regarding pregnancy
risks from uncorrected VUR.
One literature review reported the primary Continuous Antibiotic Prophylaxis
risk factor for pregnancy complications, includ-
ing UTI, gestational hypertension, preeclamp- Continuous antibiotic prophylaxis (CAP) has
sia, or fetal morbidity, was renal scarring. been routinely recommended in children with
The first AUA Reflux Guidelines panel VUR while awaiting spontaneous reflux
reviewed published literature on this subject and resolution.
concluded available data were insufficient to Meta-analysis of six RCTs by the 2011 AAP
determine actual risk of uncorrected VUR during UTI Guidelines panel concluded antibiotic
pregnancy. They reviewed five studies that dem- prophylaxis is no more effective than no ther-
onstrated renal insufficiency increased toxemia, apy to prevent recurrent fUTI in children 1–24
preterm labor, fetal growth retardation, and fetal months of age with grades 1–4 VUR.
demise (Elder et al. 1997). Overall fUTI recurrence was 19 % in 1–2
Literature review regarding impact of VUR on years, with increasing percentage recurrence
pregnancy identified 15 articles for inclusion, with increasing VUR grade.
reporting the following: There are no data regarding efficacy of
• fUTI in pregnancy (four studies) ranged from CAP to reduce recurrent fUTI in patients with
3 to 37 %; fUTI in patients with childhood grade 5 VUR.
ureteral reimplantation (two studies) occurred There are no data to determine if antibiotic
in 25/141 (18 %) and 5/77 (7 %). prophylaxis is effective to prevent initial fUTI
• Hypertension in pregnancy (three studies) was in children with VUR detected by sibling or
not increased by history of VUR with no renal prenatal hydronephrosis screening.
scarring; hypertension occurred in 31 and There are no data to determine efficacy of
42 % with renal scarring (extent of renal dam- antibiotic prophylaxis in patients presenting
age not described). with recurrent UTI.
• Preeclampsia (five studies) was increased by Meta-analysis was done on data provided by six
renal scarring; two studies reported no RCTs to determine efficacy of CAP to prevent
increased preeclampsia without renal scarring recurrent fUTI versus no treatment in infants 2–24
in a total of 23 women. months of age with VUR. Findings are shown in
• No study reported history of VUR impacted Table 2.2. There was no benefit of CAP versus no
fetal outcomes; one reported 8/39 pregnancies treatment for any grade of VUR, based on a sample
Table 2.2 Recurrence of febrile UTI/pyelonephritis in infants 2–24 months of age with and without antimicrobial
prophylaxis, according to grade of VURa
Prophylaxis No prophylaxis
Reflux grade No. of recurrences Total n No. of recurrences Total n p
None 7 210 11 163 0.15
I 2 37 2 35 1.00
II 11 133 10 124 0.95
III 31 140 40 145 0.29
IV 16 55 21 49 0.14
a
Reproduced with permission from Pediatrics, Vol.128, Page 604, Copyright 2011 by the AAP
size of 718 patients: 72, grade 1; 257, grade 2; 285, Surgical Correction of VUR: Primary
grade 3; and 104, grade 4. Recurrent fUTI occurred Outcomes
in 133 (19 %); percentage fUTI recurrences by
grade were 6 %, grade 1; 8 %. grade 2; 25 %, grade The two desired outcomes from surgical VUR
3; and 36 %, grade 4 (AAP 2011). correction are reduction in fUTI and renal
Compliance with drug therapy has been raised scarring.
as a potential confounder in these data, specifically One RCT demonstrated ureteral reimplan-
that patients assigned to antibiotic might not have tation in children with VUR grades 3 and 4
taken the medication, which likely would be repre- significantly decreased recurrent fUTI over
sentative of clinical practice. Of these six RCTs: antibiotic prophylaxis (8 % surgical vs. 22 %
• Craig et al. assessed adherence by counting medical therapy).
pills and direct questioning during visits. Three studies reported that recurrent fUTI
Sixteen percent of study patients discontinued after endoscopic injection occurs in £ approxi-
therapy by 3 months, and 31 % at 12 months, mately 10 % of patients. Odds for recurrence
with no difference in placebo versus drug were 8.5 times greater in patients having more
treatment groups. than three versus one febrile infection within 1
• Montini et al. tested antibiotic activity in rou- year before injection.
tine urine cultures, with 71 % positive in the Recurrent febrile UTI after initially suc-
drug treatment group. cessful Dx/HA injection is associated with
• Penesi et al. reported 6/50 (12 %) did not take recurrent VUR in approximately 50 % of
prophylaxis. cases. Cystography for febrile UTI after reim-
• Brandstrom et al. stated 2/67 (3 %) admitted plantation has not been reported.
to noncompliance. There are no RCTs demonstrating VUR
• Garin et al. excluded patients who self- correction reduces renal scarring.
admitted to noncompliance.
• Roussley-Kessler et al. did not assess
compliance. Ureteral Reimplantation
The AAP review limited analysis of antibiotic
prophylaxis to children <2 years of age with The International Reflux Study randomized chil-
grades 0–4 VUR after one febrile UTI. Our dren less than 11 years of age with grades 3 and 4
review found no reports concerning antibiotic VUR to either antibiotic prophylaxis or ureteral
prophylaxis in other scenarios: reimplantation (Politano-Leadbetter, Lich-
• Grade 5 VUR Grigoir, Cohen, based on surgeon preference).
• Children with VUR and no history of UTI The US arm comprised 62 patients, 24 with
• Children with recurrent UTI at diagnosis unilateral and 38 with bilateral VUR, while the
European arm had 151 patients, 33 with unilat- postoperative UTI occurrence in these patients.
eral and 118 with bilateral reflux. While overall UTIs were not characterized as febrile or not
UTI rates were similar between medical and sur- (Webster et al. 2000).
gical patients, fUTI occurred significantly less Another retrospective study found that preop-
often after reimplantation (22 % medical vs. erative and postoperative DMSA scans had been
8–10 % surgical, RR 0.43[95 % CI 0.27–0.70]) obtained in 74 children (45 boys) out of 223
(Wheeler et al. 2003). undergoing reimplantation from 1985 to 1997.
The European arm of the IRS obtained DMSA These scans had been done a median 2 months
at entry and during 5-year follow-up in 287 chil- (10 day to 58 months) before and a median 19
dren median age 3.5 years with grades 3 or 4 months (5–44) after surgery. fUTI occurred in
VUR. Of these, 52 (18 %) were initially normal. only two patients after operation. No new scars
Follow-up DMSA was considered to show dete- were diagnosed (Choi et al. 1999).
rioration (new or larger cortical defect and/or
renal function decrease >3 %) in 48 (17 %) chil-
dren, including 8 (15 %) initially normal. There Endoscopic Injection
was no difference in these changes between
those treated medically or surgically (Piepsz Meta-analysis of reported outcomes in 12 studies
et al. 1998). after endoscopic injection stated recurrent fUTI
One study reported preoperative and postop- occurred in 0.75 % (95 % CI 0.18–3.09) of
erative DMSA scan in 143 children (45 boys) patients. Incidence and frequency of pre-injection
with VUR undergoing ureteral reimplantation at fUTI were not described, nor was duration of
median age 2 years (2.5 month to 14 years). post-injection follow-up (Elder et al. 2006).
Maximum grade was 2–5 in 18, 59, 27, and 4 %. One study comprising 167 children with ini-
Preoperative scintigraphy was obtained less than tially successful Dx/HA injection involved chart
3 months after last UTI in 31 % of cases and not review and phone calls to both parents and PCP to
documented in 12 %, while 10 % had no history determine incidence of recurrent infection. At
of UTI. Interval from DMSA scan to surgery median follow-up of 32 months (7–53), 12 % had
was a mean 1.4 months (1 day to 1.5 years). recurrent fUTI, of which half had recurrent VUR
Preoperative DMSA findings included congeni- on subsequent cystography. Multivariable analysis
tal reflux nephropathy in 12 (8 %) and at least showed the number of preoperative fUTIs within 1
one kidney had abnormal findings in 94 (72 %) year of injection predicted UTI recurrence:
of the remainder. Postoperative DMSA was • Two to three preoperative infections, OR 3
obtained at median 3 years (1–9). Postoperative (95 % CI 1.1–8.2) for postoperative fUTI
UTI was known to have occurred in 12 %. One • Three preoperative infections, OR 8.5 (95 %
male developed a cortical defect, but he had UTI CI 3.3–22) for postoperative fUTI (Chi et al.
after his preoperative DMSA and before reim- 2008)
plantation, and another postoperatively 3 weeks Another retrospective study included 100
before the last DMSA, so designation as scar patients mean age 3.8 ± 0.3 years (24 % boys)
and timing of injury was uncertain. Two other after successful Dx/HA injection followed a
patients had new scars: one male with no pre- mean of 15 months. A fivefold reduction in UTIs/
operative UTI but “a scarred kidney” had one year (febrile vs. nonfebrile not stated) was noted,
UTI postoperatively, while one female with pre- from a mean 0.68 ± 0.09 pre-injection to
operative scarring had recurrent postoperative 0.12 ± 0.04 post-injection. Recurrent infection
UTI and a new scar. Timing of last DMSA in occurred in 13 %, of which half had recurrent
relation to last UTI was not stated. Overall mean VUR (Wadie et al. 2007).
change in ipsilateral renal function was 2.5 %, A third retrospective analysis reported Dx/HA
with nine kidneys in nine children having a injection in 311 children (41 boys) at mean age
13–48 % decrease. There was no mention of 5.7 years, of which 253 had negative cycled
VCUG post-injection. During mean follow-up of Glenn-Anderson in 10 % and “other modifications”

2.6 years, 7 (3 %) developed fUTI. VCUG was in 9 % (of patients). VUR persisted in five (6 %)
repeated in five, and each demonstrated recurrent patients, ultimately resolving spontaneously in
VUR (Traxel et al. 2009). all but one case at a mean of 20 months after sur-
gery. There were no obstructions from surgery
(Duckett et al. 1992).
Correction of VUR: Secondary The European arm operated on 150 patients
Outcomes (36 boys) and 237 ureters, using Politano-
Leadbetter in 55 %, Lich-Grigoir in 26 %, and
Reimplantation: Reflux Resolution Cohen in 18 % (of patients). Persistent VUR was
found at 6 months cystography in 15 % of bilat-
Published literature reviews indicate initial eral and 6 % of unilateral reimplanted children,
success for ureteral reimplantation to correct that resolved by 5-year cystography in 13/17
VUR in ≥95 % of ureters on cystography per- (76 %). Of 134 patients with negative 6-month
formed £6 months postoperatively. postoperative cystograms, recurrent VUR was
The International Reflux Study reported found during repeat cystography at 5 years in 4
VUR resolution 6 months after surgery in 94 and (3 %). Obstruction developed in 10 (7 %) chil-
89 % of US and European arms, respectively. dren, including 3 undergoing Politano-Leadbetter
The European arm reported recurrent VUR who had the ureter passed through the intestinal
in 3 % of patients at 5-year cystography. wall (Hjalmas et al. 1992).
There are few other data regarding recur-
rent VUR after reimplantation in either symp-
tomatic or asymptomatic children to verify Reimplantation: Intravesical Versus
common opinion that surgical success is dura- Extravesical
ble in the long term.
The first AUA Reflux Guidelines panel Extravesical reimplantation creates less gross
reviewed 86 articles providing reimplantation hematuria and subjective bladder spasm than
outcomes (published between 1965 and 1994) in intravesical repairs.
6,472 patients and 8,563 ureters. It reported over- Bilateral extravesical reimplantation can
all success was 95 % of patients, and >98 % of result in temporary postoperative urinary
ureters for VUR grades 1–4 and 81 % for grade 5. retention in £10 % of patients; this is not seen
Techniques reviewed and date of last cystography with intravesical techniques.
after surgery were not stated (Elder et al. 1997). One RCT randomized 44 children with
A review of published outcomes for case series unilateral VUR grades 2–4 to either extravesical
involving at least 100 reimplanted ureters analyzed Lich-Gregoir or intravesical Politano-Leadbetter
19 articles and the authors’ own data comprising reimplantation (method used to randomize was
3,346 patients and 5,008 ureters. Techniques used not stated). Mean age of patients in the two
included Cohen, Politano-Leadbetter, Glenn- groups was similar (69.7 months [18–110] vs.
Anderson, and Lich-Gregoir. Overall VUR resolu- 62.1 months [8–110]). Extravesical operations
tion occurred in 99 % of ureters. Five series were done through an ipsilateral inguinal inci-
reported failed reimplantation in a total of 40/1,116 sion, whereas intravesical procedures used a
(4 %) ureters on initial postoperative cystography, Pfannenstiel incision. All patients had postopera-
with spontaneous resolution in 1–5 years in 34 tive catheter drainage for 48 h, urethral for extra-
(85 %) (Bisignani and Decter 1997). vesical reimplants, and suprapubic for intravesical
The US arm of the International Reflux Study repairs. Postoperative pain was assessed using an
included surgery in 87 patients and 157 ureters objective scale, and episodes of bladder spasm
with grade 3–4 VUR done using the Cohen tech- quantified. The authors did not state who per-
nique in 52 %, Politano-Leadbetter in 28 %, formed these evaluations, and there is no mention
of blinding. They found that extravesical reim- Contralateral VUR After Unilateral
plantation had significantly less bladder spasm Reimplantation
and no gross hematuria. Objective pain scale
scores were significantly less after extravesical Meta-analysis reported approximately 10 %
surgery (potentially related in part to the smaller of patients undergoing unilateral reimplanta-
incision), but opioid use was not different. There tion will have contralateral VUR on postoper-
was no difference in mean postoperative post- ative cystography.
void residual urine volumes (time of assessment One review stated new contralateral VUR
not stated) (Schwentner et al. 2006). ranged from grades 1–5.
A prospective study involved 237 patients Potential risk factors, including one versus
undergoing extravesical reimplantation, of which more than one and cycled versus non-cycled
144 were bilateral. Mean age for the entire series preoperative cystography, grade of ipsilateral
was 5.5 years (2 months to 15 years), and all oper- VUR, and history of resolved contralateral
ations were done with a Pfannenstiel incision with VUR, have not been analyzed.
postoperative urethral catheter drainage for 12–36 Most this reflux resolves within 1 year of
h (reason for varying intervals not stated). Short- diagnosis.
term urinary retention developed in 8 % after bilat- The first AUA Reflux Guidelines panel
eral reimplantation that did not occur in unilateral reported its review of literature from 1965 to
cases. This retention resolved within 1 week in all 1994 and indicated that an average of 9 % of uni-
affected patients (Lapointe et al. 1998). lateral reimplantations demonstrated contralat-
A retrospective review evaluated 220 patients, eral VUR postoperatively. Repeat surgery was
mean age approximately 5.5 years, who under- not recommended for at least 1 year, because
went bilateral extravesical reimplantation with most reported new contralateral VUR resolved
postoperative urethral catheterization for 24–48 h during that time. Risk factors for contralateral
from 1991 to 1997. Complete inability to void VUR were not reported (Elder et al. 1997).
after catheter removal occurred in 23 (10 %), A retrospective review after either unilateral
treated with catheter replacement for another Cohen or Glenn-Anderson reimplantation found
7–10 days. Retention resolved in 22 during cath- 20 (19 %) of 120 patients had new contralateral
eterization, while one had clean intermittent cath- VUR. Seventy percent of patients had more than
eterization (CIC) for 4 months. Univariate one preoperative VCUG. The authors implied all
analysis reported grades 4–5 VUR, age £3 years subjects had only unilateral VUR diagnosed pre-
and male gender, but not treated preoperative operatively. New contralateral VUR was grade 1
voiding dysfunction (not defined) correlated with in nine, grade 2 in nine, grades 3 and 4 in two
urinary retention (Barrieras et al. 1999). each, and grade 5 in one patient. This reflux
Overnight Foley drainage was used in a retro- resolved in 12 (67 %) of 18 with grades 1–2, in 1
spective series of 50 consecutive toilet-trained with grade 3, and persisted in all with grades 4–5
children (13 boys), mean age 5 years (2–13 by 3 years follow-up. Reoperation to reimplant
years), undergoing bilateral extravesical reim- the contralateral ureter was done in 3 (15 %)
plantation for VUR grades 1–5. There was no (Hoenig et al. 1996).
case of postoperative urinary retention (McAchran Another retrospective study of 43 unilateral
and Palmer 2005). Lich-Gregoir reimplants found new contralateral
Another retrospective study included 41 chil- VUR in 5 (12 %) patients. Of these, four had
dren with mean age 38 months (16–81) who had known prior bilateral VUR with unilateral reso-
bilateral robotic extravesical reimplantation for lution. The number of preoperative cystograms
VUR grades 3–5. All had overnight catheteriza- for the entire group was not stated; nor was the
tion followed by post-void bladder scan that grade of new contralateral reflux. Spontaneous
found a mean residual of 13 mL. None developed resolution occurred in four of five cases within 1
urinary retention (Casale et al. 2008). year (Burno et al. 1998).
Endoscopic Injection: Reflux Resolution cystogram in 70 % of 168 patients and 78 % of

259 ureters having grades 1–5 VUR. Patients
Endoscopic injection is less effective than failing the initial injection were offered a second,
reimplantation for VUR correction. with 61 % of those performed successful, achiev-
Results are best predicted by VUR grade, ing overall reflux resolution in the series in 82 %.
success diminishing with increasing grade. The initial 80 children had STING injection tech-
Creation of an elevated, coapted mound nique, whereas the remainder had intraorifice
correlates with VUR resolution, regardless of injection—in all cases with the intention to ele-
injection technique (STING vs. intraorifice vs. vate and coapt the orifice. Mean injected volume
HIT) or injected volume. was 0.54 cc (SD 0.27). Multivariable analysis of
Failures usually are found to have mound factors potentially impacting outcomes (gender,
loss or shift from under the orifice. unilateral vs. bilateral VUR, duplicated vs. single
Failure rates of 13–26 % have been reported system refluxing ureters, VUR grade, injection
at repeat cystographymore than 12 months technique, volume injected, satisfactory versus
after initially successful injection. One report unsatisfactory post-injection mound morphol-
found likelihood for recurrence increased ogy) found results independently predicted by
according to initial VUR grade. the following:
Meta-analysis of published results from 63 • VUR grade (OR 0.46 [95 % CI .29–72])
articles including 5,527 patients and 8,101 ure- • Injected volume <0.5 cc vs. >0.5 cc (OR 0.3
ters reported probability for resolving VUR [95 % CI 0.09–0.98])
(defined as negative cystography ³1 month post- • Desired mound morphology (OR 11.5 [95 %
injection) with one or more injections using pri- CI 5.3–25])
marily polytetrafluoroethylene, collagen, or Dx/ Increasing VUR grade predicted less success,
HA was 87 % of patients and 85 % of ureters, with a single injection resolving reflux in 100 %
with significantly less success in duplicated ver- grade 1, 83 % grade 2, 73 % grade 3, 53 % grade
sus single systems (50 % vs. 73 %). 4, and 29 % grade 5 ureters. “Satisfactory” mound
One injection success probability was as created in 196 of 243 ureters correlated with
follows: 89 % success, while an unsatisfactory mound in
• 67 % of patients (95 % CI 53.61–78.33) 47 ureters resolved reflux in only 36 % (Yucel
• 76 % of ureters (95 % CI 70.62–80.10) et al. 2007).
• Success by grade: 79 % for grades 1 and 2, A prospective study compared outcomes in
72 % grade 3, 63 % grade 4, 51 % grade 5. ureters after intraorifice or HIT in consecutive
Second injection success probability was as patients treated by a single surgeon. The first 96
follows: ureters had intraorifice injection, while the last 52
• 54 % of patients (95 % CI 39.97–68.10) had HIT, with single-injection VUR resolution in
• 68 % of ureters (95 % CI 61.04–74.29) 86.5 % vs. 79 %, p = 0.23. HIT resulted in
Third injection success probability was as significantly increased injection volumes versus
follows: intraorifice injection (0.68 cc vs. 0.51 cc,
• 34 % of ureters (95 % CI 20.24–50.89) (Elder p = 0.002) (Gupta and Snodgrass 2008).
et al. 2006). A retrospective review compared STING to
A systematic review of 47 articles and 7,303 HIT in 301 children and 453 ureters performed
ureters regarding Dx/HA injection found similar by five surgeons. Multivariable analysis found
outcomes, resolution in 77 % of ureters (95 % CI: only the surgeon and increasing VUR grade, but
76–78 %). The most predictive factor for outcome not injection technique or volume < or >1 cc, pre-
was VUR grade, with success in 81 % of grade 1 dicted results (Routh et al. 2007).
vs. 62 % of grade 5, p < 0.001 (Routh et al. 2010). A multicenter retrospective analysis reported
A prospective study reported a single Dx/HA 87 % of 97 ureters failing Dx/HA injection with a
injection resolved reflux on a 3-month post-injection mean 0.86 cc (0.3–2) were found to have mound
volume loss and/or shifting of the implant from Another retrospective report included 126
under the orifice (Higham-Kessler et al. 2007). children (30 boys) with unilateral Dx/HA injec-
There are limited data regarding recurrent tion, after excluding those with a history of
VUR after initial resolution by bulking agents, resolved contralateral VUR. New contralateral
but available reports indicate success diminishes VUR was found in 17 patients (13 %) during
with time: VCUG 12 weeks post-injection, grade 1 in 9,
• In a report of Dx/HA injection of 334 ureters, grade 2 in 6, and grade 3 in 2. There was no dif-
94 % with grades 3–4 VUR, 45 with VUR ference in mean patient age, mean number of pre-
resolution had subsequent cystography 2–5 injection VCUGs (1.9 vs. 1.8) or mean VUR
years later. Recurrent VUR was noted in six grade (2.5 vs. 2.7) in those with and without new
(13 %), four with grade 2 and one each with contralateral VUR (Elmore et al. 2006).
grades 3 and 4 (Lackgren et al. 2001). A third retrospective report analyzed cysto-
• Another retrospective review of 337 injected scopic assessment of the contralateral orifice to
ureters reported initial success in 246 (73 %) guide decision-making in unilateral VUR, per-
at 3-month cystography. Of these, 150 (61 %) forming bilateral injection when it had a stadium
underwent repeat cystography at 12 months or worse configuration and/or ³ grade 2 hydro-
and 39 (26 %) had recurrent VUR, found in distention. There were 146 patients with median
0 % of those originally with grade 1, 19 % of of 3 (1–6) pre-injection cystograms. Of these,
grade 2, 37 % of grade 3, 33 % of grade 4, and 101 (69 %) were judged to have an abnormal
60 % of grade 5 (Lee et al. 2009). orifice and received bilateral injection versus 45
who were not injected. New contralateral reflux
occurred in 8 and 13 %, which was not significantly
Contralateral VUR After Unilateral different (Routh et al. 2008).
Injection
Two studies reported approximately 10 % of References

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Infection, Steering Committee on Quality Improvement
Grade of new VUR ranged from 1 to 4.
and Management. Urinary tract infection: clinical
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One study reported a similar average of months. Pediatrics. 2011;128(3):595–610.
Barrieras D, Lapointe S, Reddy PP, Williot P, McLorie
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GA, Bagli D, et al. Urinary retention after bilateral
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Estrada Jr CR, Passerotti CC, Graham DA, Peters CA, scopic correction of unilateral reflux–is routine con-
Bauer SB, Diamond DA, et al. Nomograms for pre- tralateral injection indicated at initial treatment? J
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Gupta A, Snodgrass W. Intra-orifice versus hydrodisten- trolled trial. Pediatrics. 2008;121(6):e1489–94.
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acid injection for vesicoureteral reflux. J Urol. Hudson RG, et al. Summary of the AUA Guideline on
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2007;178(4 Pt 2):1702–5. discussion 5–6. Pediatr Nephrol (Berlin, Germany). 2008;23(12):
Routh JC, Inman BA, Reinberg Y. Dextranomer/hyaluronic 2227–32.
acid for pediatric vesicoureteral reflux: systematic Traxel E, DeFoor W, Reddy P, Sheldon C, Minevich E.
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Scholtmeijer RJ, Nijman RJ. Vesicoureteric reflux and mer/hyaluronic acid endoscopic injection. J Urol.
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study after three years of follow-up. Urology. 1994; Wadie GM, Tirabassi MV, Courtney RA, Moriarty KP.
43(5):714–8. The deflux procedure reduces the incidence of urinary
Schwentner C, Gozzi C, Lunacek A, Rehder P, Bartsch G, tract infections in patients with vesicoureteral reflux.
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Shaikh N, Ewing AL, Bhatnagar S, Hoberman A. Risk of Rosenberg AR, Kainer G. Low incidence of new renal
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Hudson RG, et al. Pediatric Vesicoureteral Reflux factors predicting success with dextranomer/hyaluronic
Guidelines Panel Summary Report: Clinical Practice acid injection for vesicoureteral reflux. J Urol.
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Bladder and Bowel Dysfunction
3
Nicol C. Bush
Primary goals in diagnosis and treatment of no added benefit to polyethylene glycol versus
functional bladder disorders: placebo, and another study reported improve-
1. Stop urinary incontinence. ment in diurnal incontinence in patients both
2. Reduce associated UTI. with and without improved stooling.
A secondary aim is to reduce behavior dys- • Our review found no evidence that the void-
function associated with incontinence. ing dysfunction treatment reduces UTI. Two
Summary of evidence for these goals: studies reported recurrent UTI within 1
• Several studies indicate placebo results in year in approximately 40 % of females
cure or improvement of symptoms in despite various treatments (urotherapy, bio-
approximately 40 % of children with void- feedback, AC).
ing dysfunction. • While children with voiding dysfunction
• There is little evidence that biofeedback, also have increased behavioral problems,
AC, or alpha-blockers are more effective our review found only one study that reports
than urotherapy or placebo to reduce diur- impact of therapy, finding decreased prob-
nal incontinence. One trial demonstrated an lems in those with dysfunctional voiding
alarm watch is better than timed voiding. but not urge syndrome. One case–control
• Several small series indicate botulinum A study found improved self-esteem in
injection in patients with refractory overac- patients after incontinence therapy.
tive bladder (OAB) stops incontinence in
approximately 50 %, with an average
response duration of 6 months. ICCS Definitions
• Two small series report transcutaneous
electrical nerve stimulation (TENS) or Subgroups listed below apply to children who have
Interstim devices improve symptoms in attained bladder control or are ³5 years of age. The
children refractory to other treatments. general phrase for voiding symptoms in children
• While urinary symptoms improve during is now similar to that in adults, “lower urinary
treatment for constipation, one RCT found tract symptoms” (LUTS), which replaces the
phrase “dysfunctional voiding.” The ICCS defines
N.C. Bush, M.D., M.S.C.S. (*) urinary frequency as ³8 voids/day and decreased
Department of Pediatric Urology, frequency as £3 voids/day (Neveus et al. 2006).
Overactive bladder (OAB). urinary urgency,
Dallas, TX 75235, USA defined as a sudden and unexpected need to
e-mail: nicol.bush@childrens.com void. Concomitant urinary frequency and/or
36 N.C. Bush
Table 3.1 Criteria for Diagnosis Commonly Referenced

Rome II (Rasquin-Weber PACCT (Benninga
et al. 1999) Rome III (Rasquin et al. 2006) et al. 2005)
Age Infant–16 years Developmental age ³4 years Not specified
Duration of symptoms Not specified ³2 months ³8 weeks
No. of symptom/exam At least 2 At least 2 At least 2
findings to meet criteria
Diagnostic criteria Majority of stools scybalous, £2 defecations per week <3 defecations per
pebble-like, hard week
Firm stools £2×/week ³1 episode of fecal >1 episode of fecal
incontinence/week incontinence/week
No metabolic, endocrine, Stool-retentive posturing Large fecal mass in
structural disease rectum or palpable in
abdomen
Hard or painful bowel Large-diameter stools
movements that could obstruct the
toilet
Large-diameter stools Stool-retentive
that could obstruct the toilet posturing
Large fecal mass in rectum Hard or painful bowel
movements
incontinence may be present but are not prerequi- Giggle incontinence. complete voiding occur-
sites. Children with OAB should not be diag- ring during or immediately after laughing in a
nosed with detrusor overactivity without child with normal bladder function when not
cystometric confirmation (Neveus et al. 2006). laughing.
Urge syndrome. frequent attacks of urinary Dysfunctional voiding. habitual contraction of

urgency with squatting or other holding maneu- the urethral sphincter during voiding verified
vers, voiding frequency >7×/day, and urge incon- with repeated uroflows demonstrating a staccato
tinence (Bael et al. 2008a). While the ICCS has pattern on UD.
adopted adult terminology in using “OAB” to
describe children with urgency, others continue Hinman’s syndrome. constellation of findings
to use “urge syndrome” to define children with a including diurnal urinary ± fecal incontinence,
characteristic pattern of urinary frequency and bladder trabeculation in the absence of outlet
urgency ± incontinence. obstruction or neurologic disease, and upper tract
changes including VUR and/or hydronephrosis.
Extraordinary daytime urinary frequency. The term was used by the editors of the Journal of
daytime voiding ³1×/h with small volumes Urology to replace “nonneurogenic neurogenic
£50 % estimated capacity for age, usually with- bladder” and was not included in 2006 ICCS ter-
out incontinence and with normal nocturnal blad- minology (Hinman 1986).
der behavior.
Constipation. the ICCS notes “there are no good
Underactive bladder. low voiding frequency definitions of constipation.” Table 3.1 lists crite-
and straining to initiate, maintain, or complete ria for diagnoses commonly referenced (Rome II,
voiding. Rome III and PACCT). The Bristol Stool Form
Scale has not been validated for the diagnosis of
Voiding postponement. daytime incontinence constipation in children. It was originally devel-
associated with low micturition frequency and oped as a measure of gastrointestinal transit time
holding maneuvers. in adults with various bowel pathologies.
3 Bladder and Bowel Dysfunction 37
Retrospective chart review of 336 children points; daytime wetting >2×/week was present
mean age 6 ± 3.5 years referred for defecation dis- in 1.9, 1.5, 1.0, 1.0, and 0.5 % at the above-
order compared Rome II and Rome III criteria; listed ages.
34 % versus 87 % (p < 0.001) met criteria for • At age 7.5 years, DUI frequency was <1 epi-
functional constipation using these diagnostic rec- sode per week in 9 %, 2–5 episodes per week
ommendations, respectively (Burgers et al. 2012). in 0.5 %, and nearly daily in 0.3 %.
A prospective longitudinal study of 128 con- • Voiding frequency was significantly less in
secutive children mean age 67 ± 46 months those without DUI, <5×/daily in 43 % and
referred to a tertiary constipation clinic compared 5–9×/daily in 56 % versus 36 % and 61.5 % in
Rome II to PACCT criteria. Functional defeca- incontinent children. Boys and those with
tion disorders (functional constipation, fecal DUI > 5 episodes/week had higher voiding
retention, or fecal soiling without retention) were frequency.
diagnosed in 48 % versus 89 %, p = 0.001. There • Both constipation and soiling were significantly
was poor agreement (Kappa = 0.173), implying more likely in those with DUI versus no incon-
these two sets of criteria identify different patient tinence (13 and 29 % vs. 10 and 5 %).
groups. Among those diagnosed with constipa- A validated questionnaire about bowel and blad-
tion, 80 % had straining and pebble-like stools, der habits was completed by the parents of 2,856
66 % had painful defecation, and 63 % had large- children (mean 7 ± 1 year) in a cross-sectional,
diameter stools (Boccia et al. 2007). population-based study. Daytime incontinence
Our review found no report concerning preva- (>1×/prior 6 months) was reported in 17 % of chil-
lence of the various categories of voiding dys- dren, constipation (Rome II criteria) in 6 %, and
function or constipation in unselected children encopresis in 10 % (Sureshkumar et al. 2009).
referred for urologic evaluation. A survey was done in 1,982 among 3,627 chil-
dren entering school at age 7 years, with school
nurses asking about voiding dysfunctions.
Prevalence Positive answers prompted an additional phone
call to parents from the study team. Incontinence
Population-based surveys found that reported was defined as one or more episodes of wetting in
LUTS and, specifically, OAB, decreases with 3 months. Daytime incontinence was reported by
age, with <20 % of children 7 years old having 5 %, which was less than 1×/week in 2 %, and
daytime incontinence, which occurred daily 3–7×/week in 0.7 % (Hellstrom et al. 1990).
in <1 %. OAB (urgency ± urge incontinence during the
Prevalence of the various clinical conditions past 3 months) was present in 2,740 (17 %)
that together comprise functional bladder dis- Korean children in a population-based, cross-
orders has not been reported in consecutive sectional parental survey of 16,516 children. Of
(unselected) patients. children with urgency, 739/2,740 (27 %) had urge
Constipation was reported in £20 % of chil- incontinence. Prevalence of urgency decreased
dren with LUTS. with age (23 % at age 5 decreasing to 12 % at age
The Avon Longitudinal Study of Parents and 13, p = 0.0001), and was evenly split between
Children, a prospective population-based study boys and girls (1,435 [52 %] boys and 1,305
with 14,000 children followed since birth, queried [48 %] girls) (Chung et al. 2010).
parents about daytime urinary incontinence Similar OAB prevalence of 18 % was reported
(DUI) in children at ages 4.5, 5.5, 6.5, 7.5, and in Japan despite older mean age of 9 ± 2 years.
9.5 years. Data were available for 10,819 chil- Among 5,282 children in this cross-sectional,
dren (Swithinbank et al. 2010): population-based survey, 19 % boys and 17 %
• DUI was present in 15.5 % at 4.5 years and girls experienced OAB, defined as increased
decreased to 4.5 % at 9.5 years, with girls daytime frequency (>1 SD beyond the average
exhibiting slightly higher rates at all time number voids/day for age) ± urge in the past
38 N.C. Bush
month (i.e., urge was not a prerequisite). Daytime voiding habits,” or UTI to 54 age-matched chil-
frequency decreased with increasing age. dren (1.3:1 female to male) without urologic
Constipation (<3×/week) was present in 971 complaints. Using receiver operating character-
(18.5 %) children, of which symptoms of OAB istics, the optimal cutoff score for “dysfunc-
were equally present in those with and without tional voiding” was 6 in females (93 %
constipation (20 % vs. 17.5 %, p > 0.05) (Kajiwara sensitivity, 87 % specificity) and 9 in males
et al. 2006). (81 % sensitivity, 91 % specificity) (Farhat et al.
2000). Among a subset of 48 patients who
underwent a bladder behavioral modification
Diagnostic Instruments program for “dysfunctional voiding,” follow-
up DVSS scores improved from 14.5 to >6.0
History among the 28 patients whose parents indicated
they were compliant with the program versus
The ICCS recommends that a detailed history no significant change (14.5 to >11.0) among the
be taken from the child when possible, but 20 patients who were reportedly not compliant
stated “literature on this topic is sparse” (Hoebeke (Farhat et al. 2001).
et al. 2010). The Incontinence Symptom Index-Pediatric is
a validated 11-item instrument with subdomains
for stress incontinence, urge incontinence, insen-
Questionnaires sate incontinence, enuresis, and pad use designed
for children 11–17 years of age to answer inde-
Four validated questionnaires have been pendently. Scores were significantly different in
developed—two answered by children, one by 19 patients (with incontinence) versus controls
their parents, one by either, depending on (well-child exams) for the full instrument and
patient age—that distinguish children with subdomains (Nelson et al. 2007).
voiding dysfunctions from normal children. Evaluation of these three instruments was
A scoring system was validated comparing done, with 37 children 4–10 years of age using
parent responses in 86 children (1.5:1 females to the DVSS (answered by patients) and Akbar
males, mean age 8 years, range 4–10) with “vari- questionnaire (scored by parents), and 35 chil-
ous wetting and daytime voiding problems” to dren 11–17 years old answering the Nelson
265 controls of similar age without urinary symp- survey. These scores were compared to blinded
toms. The questionnaire had 13 questions with physician rating using a scoring sheet.
potential scores ranging from 0 to 35. Median Physician rating correlated with all three instru-
scores in patients versus controls were 18.6 ver- ments, but was best with patient reporting
sus 2.9. Receiver operating characteristic plotting using either the DVSS or Nelson surveys
showed the optimal cutoff score of 8.5 distin- (Schneider et al. 2011).
guished children with “voiding abnormalities” A fourth instrument uses 14 questions to be
from normal children with 90 % sensitivity and answered by children ³9 years old, or by parents
specificity (Akbal et al. 2005). of younger patients, concerning bowel and blad-
The dysfunctional voiding symptom score der dysfunctions. A Likert scale scores each from
was adapted from the International Prostate 0 to 4, for a maximum score of 56. It was vali-
Symptom Score to include ten questions (poten- dated in 62 patients median age 8 years (4–16)
tial scores 0–30) relevant to children and and 50 healthy controls, with a median 14 in
designed to be answered by children. Validation patients and 6 in controls, p = 0.001. ROC curve
compared 104 consecutive patients (4:1 female indicated that a score of 11 was the optimum
to male) between ages 3 and 10 years with a threshold with AUC 0.9 (95 % CI 0.8–0.9)
history of diurnal incontinence, “abnormal (Afshar et al. 2009).
Voiding Diary/Pad Tests but did not consistently correlate with clinical
outcomes.
One study reported parent responses to the One study found uroflow pattern (bell-
questionnaire underestimated incontinence shaped vs. other) did not predict past history
and overestimated frequency when compared or future development of UTI.
to a 72-h voiding diary. The EBDS included 97 children with clini-
Two studies report pad tests did not record cally diagnosed urge syndrome and 105 with
wetting in approximately one-third of subjects clinically diagnosed dysfunctional voiding.
reporting incontinence. Uroflowometry was described by patterns as
Two hundred two children ages 6–12 enrolled “normal bell-shaped,” “steep tower-shaped,” or
in the EBDS had pretreatment questionnaires “staccato or fractionated.” Voided volumes were
regarding voiding frequency, volume, and diurnal not reported, nor was the minimum volume for an
incontinence completed by their parents. A 72-h acceptable test. Among 66 patients with urge syn-
voiding diary was then obtained, and a 12-h pad drome, 29 % had bell, 20 % had tower, and 51 %
test was used to measure urinary loss at home. had staccato or fractionated patterns. Patterns for
Parents were found to underestimate inconti- 78 patients with dysfunctional voiding were 18 %
nence and to overestimate frequency when bell, 6 % tower, and 76 % staccato or fractionated.
answering the questionnaire. The 12-h pad test Patterns for neither condition predicted clinical
provided quantitative data but had poor sensitiv- results of therapy (Bael et al. 2008b).
ity (64 %) in those with incontinence, because it A prospective trial included 86 children
missed wetting in 36 % of children. Specificity referred for dysfunctional voiding after failure of
for those without incontinence was 91 % (Bael timed voiding and constipation management for
et al. 2007). 3 months. Inclusion criteria were symptoms
Fifty children (39 females, mean age 9 years, (incontinence, straining, intermittent and/or weak
range 6–14) with urinary incontinence had pad stream) and three consecutive staccato and/or
testing done in a 2-h clinic setting and at home. interrupted uroflows with positive EMG activity
For clinic testing, an oral fluid load 13 mL/kg during voiding. Following therapy, urinary incon-
was given over 15 min and then various exercises tinence stopped in 22 and persisted in 20 who had
were done. The 12-h pad testing was used for post-treatment uroflowometry; 18/22 (82 %)
home, changing pads every hour, with or without cured had a bell-shaped curve versus 5/20 (25 %)
a similar fluid provocation. An increase in pad not cured, p < 0.001. Staccato/interrupted curve
weight of 0.5 g was considered “significant urine persisted in 3/22 (14 %) cured versus 7/20 (35 %)
leak.” Results were as folows: 35/50 (70 %) had a still incontinent, p = 0.15 (Vesna et al. 2010).
positive clinic test, 34 (68 %) a positive home A retrospective review was done in 81 consecu-
test, and 16/20 (80 %) a positive provocative fluid tive patients, 80 % female, mean age 8 years (4–17)
intake home test, with eight positive only in the treated with biofeedback for voiding dysfunction
clinic and eight positive only at home. The with incontinence and/or recurrent UTI. Baseline
authors concluded clinic testing was not needed uroflows were obtained, but timing for uroflow
(Hellstrom et al. 1986). during or after treatment was not stated. There was
significant improvement in Qmax, decrease in PVR,
and normalization of uroflow curves, but no
Uroflowometry significant differences when patients were stratified
as cured or unchanged (Nelson et al. 2004).
One prospective trial reported uroflow patterns A retrospective review of 23 children with
did not correlate with clinical diagnosis of either dysfunctional voiding treated with tamsulosin
urge syndrome or dysfunctional voiding. obtained baseline uroflowometry with two-thirds
Several studies report uroflow parameter bladder capacity and repeated the study at 1
(Qmax, curve shape) improved with treatment, month on therapy. Mean Qmax, mean voided
40 N.C. Bush
volume, and mean PVR all showed significant UD 1.3 ± 0.5 in 46 children; urge syndrome
improvement, while the proportion with a non- 2.0 ± 0.7 in 52 children; dysfunctional voiding
bell-shaped curve decreased from 100 to 50 %. 2.6 ± 0.5 in 33 children; and lazy bladder (bladder
Results were only presented as means for the underactivity) 0.9 ± 0.1 in 4 children, p < 0.05 for
study group, without dividing them according to all mean comparisons except normal versus
responders versus nonresponders (Vanderbrink underactive bladder. However, there was wide
et al. 2009). overlap in the bladder wall thickness between
A review of 148 consecutive toilet-trained groups such that a cutoff value was not possible
patients, 69 % female, mean age 9 years (4–18) (Cvitkovic-Kuzmic et al. 2002).
with voiding dysfunction analyzed uroflow pat- The retrospective review by Shaikh et al. (2005)
terns (bell-shaped vs. other) and recurrent UTI. mentioned above analyzed elevated PVR (>10 %
Of 78 baseline studies, 61 (78 %) were abnormal. bladder capacity for age) with number of UTIs.
No correlation was seen in abnormal pattern and Fifteen percent had elevated PVR, with 9/18 hav-
the number of prior or subsequent UTIs (Shaikh ing subsequent UTI during follow-up at a mean of
et al. 2005). 19 months (7–30). There was a positive correlation
between PVR and the number of subsequent UTIs
(r = 0.3, p < 0.002), even when controlling for
Bladder Wall Thickness/Post-void female gender, VUR, and UTIs prior to study.
Residual However, the risk for children to develop UTI could
not be predicted by elevated PVR, as 50 % of those
There is no consensus regarding the ultra- with PVR did not have recurrent infection.
sound (US) method to measure bladder wall
thickness, for example, with the bladder nearly
empty versus filled. Clinical usefulness was Urodynamics
limited in one study by overlap in normal and
abnormal patients. Cochrane review found no trial comparing
One study found that post-void residual clinical versus UD-based diagnosis or treat-
(PVR) >10 % bladder capacity for age (1998 ment in children with incontinence.
ICCS definition of abnormal) increased risk The EBDS reported 28 % of children with
for recurrent UTI, but was not strongly pre- clinical urge syndrome had either no or “slight”
dictive, as 50 % of patients with residuals did detrusor overactivity by UD, and 7 % of chil-
not have infection. dren with a clinical diagnosis of dysfunctional
Nomograms were developed from observa- voiding had normal UD patch EMG activity
tions in 3,376 consecutive children undergoing during voiding.
US for non-urologic indications, from which One study reported poor agreement
bladder volume wall thickness index values were between blinded versus unblinded UD inter-
calculated. Bladder wall thickness was measured pretation for detrusor overactivity.
in the transverse plane with the bladder nearly Two studies performing UD in selected
empty (after voiding), averaging anteriorlateral, referred patients with voiding dysfunctions
posteriorlateral, and lateral measurements. both reported detrusor overactivity in over
A trend of increasing thickness for increasing age 50 % of cases, followed by dysfunctional void-
was noted (Leung et al. 2007). ing in ≥25 %, “lazy bladder” in 4 %, and nor-
A retrospective study evaluated 139 children mal in 6–17 %. Neither correlated UD findings
(69 % girls, 7 months to 16 years) who under- to clinical diagnoses.
went UD for various indications and compared Cochrane Review was done to determine if
US measurements of bladder wall thickness at treatment for incontinence according to UD-based
maximum UD-determined capacity. Bladder wall diagnosis versus clinical diagnosis is more
thickness (mm) varied according to diagnostic effective. Seven trials were included, with the
category defined by 1998 ICCS criteria: normal following findings:
• No trial included children. dysfunction) in 25 %, normal in 17 %, and lazy

• There was no evidence that UD improved bladder in 4 % (despite exclusion of these). The
treatment of adult females; the proportion with authors did not correlate UD findings to clinical
persistent incontinence after 1 year, 70 %, was symptoms (Schulman et al. 1999).
with versus 62 % without UD, RR 1.23 (95 % A subsequent study performed UD in 1,000
CI 0.6–2.6). children, 48 % female, with “history of UTI,
• There was discordance regarding usefulness small bladder capacity despite urotherapy,
of UD in clinical management. Two studies repeated dysfunctional uroflow, US abnormali-
reported that a patient with UD was more ties, or resistance to therapy,” from a population
likely to receive drugs, but in three studies of 3,500 patients seen for incontinence. UD diag-
they were not more likely to have surgery nosis was urge syndrome (detrusor overactivity)
(Glazener and Lapitan 2012). in 58 %, dysfunctional voiding in 32 %, lazy
The EBDS described above also performed bladder (voiding postponement) in 4 %, and nor-
UD in patients clinically diagnosed with urge mal in 6 %, which also were not correlated to
syndrome and dysfunctional voiding. Detrusor clinical symptoms (Hoebeke et al. 2000).
overactivity expected in children with urge syn-
drome was absent or “slight” in 25/88 (28 %),
only occurred “before voiding” in 35 (40 %), and KUB
occurred throughout filling in 28 (32 %). Pelvic
floor relaxation determined by patch electrodes Systematic review did not support use of KUB
was considered normal in 6/91 (7 %) children to assist in the diagnosis of constipation.
with a clinical diagnosis of voiding dysfunction One study reported poor interrater reli-
and reported as incompletely relaxed in another ability using three fecal loading scoring sys-
22 (24 %). The remainder had increased pelvic tems (Barr, Blethyn, Leech).
floor activity during voiding. Inclusion in the trial Another trial found Blethyn and Leech
was based on clinical history rather than UD scores did not correlate to clinical symptoms
results (Bael et al. 2008b). before or after polyethylene glycol treatment.
The EBDS also reported agreement in UD Systematic review was done to determine the
interpretation between the unblinded reviewer association between KUB and signs and symp-
who performed the study versus a blinded com- toms of constipation, limited to controlled obser-
mittee of three other reviewers. All UD were per- vational studies in children 1–18 years old. Six
formed in the same manner following a consensus articles were included, of which only one was
3-day workshop before the study began, and a designed to determine whether clinical variables
standardized scoring sheet was used for interpre- identified patients with radiologically diagnosed
tations. Among 247 UD tracings, concordance constipation. Findings included the following:
for detrusor overactivity during filling was 37 %. • One study found a clinical diagnosis existed
Concordance for pelvic floor relaxation was 1.2× more often than the radiologic diagnosis,
greater at 81 %. The authors concluded investiga- LR 1.2 (95 % CI 1.0–1.4).
tor bias in UD interpretation could only be over- • Four studies examined whether KUB could
come with blinded reviews (Bael et al. 2009). discriminate children with versus without
UD was done in 366 of more than 500 referred clinical symptoms of constipation, with only
patients with dysfunctional voiding symptoms, one reporting significant discriminative value,
excluding those “too young, those who refused, LR 3.0 (95 % CI 1.6–4.3).
and those with infrequent voiding responding to • All but one study reported moderate to
behavioral modification.” Patients had diurnal excellent interobserver reliability (K 0.63–
incontinence ± enuresis and/or recurrent UTI. 0.95); intraobserver reliability reported by
UD diagnoses were detrusor overactivity in three studies was moderate to excellent
52 %, voiding dysfunction (bladder/sphincter (K 0.52–0.85).
42 N.C. Bush
• There was conflicting evidence for the corre- of constipated and 4–25 % of normal children
lation of radiologic versus clinical diagnosis would be misdiagnosed by this criteria.
of constipation, meaning there was no evi- One study compared rectal diameter behind
dence supporting use of KUB in the case of the bladder in 82 normal children (no history of
doubt for constipation in a child (Reuchlin- constipation), median age 5.5 years, and 95
Vroklage et al. 2005). patients, median age 6.5 years, with chronic con-
Another study had two pediatric urologists, a stipation for at least 6 months. Median rectal
pediatric radiologist, and three pediatric nurse diameter in controls was 2.4 cm (1.3–4.2) versus
practitioners score KUBs from children 4–12 years 3.4 cm (2.1–7) in patients, p < 0.001. Age was a
of age who had “lower urinary tract dysfunction significant confounder; the older the child, the
symptoms” and age-matched controls with radio- larger the rectal diameter, but no adjustment val-
graphs after foreign-body ingestion, using three ues were described. The authors recommended
methods: Barr, Blethyn, and Leech. Interrater reli- 3 cm as the threshold to diagnose rectal disten-
ability was poor to marginally good using all three tion, although use of that cutoff would result in
rating systems (kappa range Barr, 0.049–0.481; mis-classification of 25 % of both controls and
Blethyn, 0.045–0.451; Leech, 0.119–0.273; with patients (Singh et al. 2005).
kappa values of >0.75 indicating excellent, 0.4– A second study compared 120 children, mean
0.75 good, and <0.4 poor reliability). Similarly, age 6 years (1.5–18) with constipation by Rome II
intraclass correlations (which describe the repro- criteria to 105 controls, mean age 8 years, with “a
ducibility of measurements made by different normal defecation pattern.” Results were reported
observers rating the same image) were poor for all as the ratio between the diameter of the rectal
three rating systems (Barr, 0.026; Blethyn, 0.201; ampulla and pelvic width (distance between the
and Leech, 0.331). None of the scoring systems anterior superior iliac spines). There were
provided reliable results between observers in significantly greater ratios in patients than con-
grading constipation (Moylan et al. 2010). trols when analyzed by age groups <3, 3–6, 6–12,
One RCT used KUB scored using Leech and and >12 years. To compare to other publications,
Blethyn systems in 138 children mean age 7 the authors added that patients have a mean 4.3 cm
years, 62 % female, with OAB. Baseline urinary (3–8.2 cm) rectal diameter (Bijos et al. 2007).
and bowel symptom questionnaires were used, Another study included 51 children ages 4–12
with minimal bowel symptoms reported, yet years, 27 having constipation according to Rome
61(47 %) had KUB-defined constipation using III criteria and the other 24 considered normal.
either scale. There was no correlation of urinary US was done using a 7.5-MHz probe to measure
urge and bowel symptoms. Patients were then the rectal diameter. Constipated children had a
randomized to placebo versus polyethylene gly- larger diameter than controls, 4 ± 1 cm versus
col for 1 month. Complete response to urge 2 ± 0.6 cm, p < 0.001. When normal was consid-
symptoms occurred in 11/71(15 %) completers, ered the mean +2 SD of controls, a cutoff value
and overall 45 % had improvement (>20 % for constipation was 3 cm, the authors noting that
decrease in urge symptoms) in both cohorts, but this would misdiagnose 12/27 (44 %) patients
KUB scores did not change (Bush et al. 2012). and 1/24 (4 %) controls. Disimpaction and 4
weeks of polyethylene glycol significantly
reduced rectal diameter in patients to mean
Ultrasound-Determined Rectal 3 ± 0.5 cm, p < 0.001 (Joensson et al. 2008).
Diameter
Three studies reported constipated children Spinal Cord MRI

have a larger transverse rectal ampulla diam-
eter on pelvic US than normal controls. Less than 10 % of imaged patients with nor-
Two suggesting a 3 cm diameter as the mal neurologic examinations, no sacral skin
threshold for constipation stated that 25–44 % lesions, and persistent incontinence have
abnormal MRI findings (tethered cord, thick

filum, syrinx, lipoma). Associated Conditions
A prospective trial that enrolled 176 children
with functional urinary and bowel problems One study reported that a history of fUTI at
(enuresis, diurnal incontinence, urinary fre- age <2 years did not increase likelihood for
quency, UTI, VUR, chronic constipation, enco- dysfunctional elimination after toilet training,
presis) referred to a center after unsuccessful which occurred in 22 %. There was no differ-
management—88 with spina bifida occulta on ence in prevalence of dysfunctional elimina-
KUB and the other 88 age- and gender-matched tion in those with versus those without VUR.
controls. None had known neurologic conditions. One study using UD-based categorization of
MRI was abnormal in 12 (7 %) with tethered cord voiding dysfunction reported 34 % of all patients
(n = 5), syrinx (n = 4), club-shaped conus (n = 2), had a history of UTI and 14 % had VUR.
and thick filum (n = 1); there was no difference in
abnormal findings in those with versus those
without spina bifida occulta (Nejat et al. 2008). UTI/VUR (See Also Chap. 2)
Another prospective study included 114 chil-
dren, median age 9 years (5–14), with UTI and/or Dysfunctional elimination, variously defined,
voiding dysfunction symptoms. All had 6 months of was reported in from 14 to 51 % of children
therapy, mostly AC, with resolution of voiding with VUR and 34–43 % with UTI.
symptoms in 46 %, none of which had abnormal One study found no difference in preva-
sacral skin lesions. The other 61 who did not respond lence of dysfunctional voiding in patients
had MRI, and included 19 (31 %) with sacral skin with versus those without a prior history of
lesions, including “macula, lipoma, dimple, or hyer- UTI before age 2.
trichosis”; 7/19 (36 %) with skin lesions and 2/42 Children enrolled in the European branch of
(5 %) without skin lesions had abnormal MRI with the International Reflux Study in Children under-
tethered cord (n = 8), lipoma (n = 2), and diastemato- went a questionnaire of voiding symptoms.
myelia (n = 1) (Tarcan et al. 2012). Among these 310 children, all of whom had grade
A retrospective study included 23 children, III or IV VUR, 255 (82 %) were considered to
3–17 years of age, with persistent incontinence have normal bladder/sphincter function, with 26
despite treatment a mean of 29 months with timed (8 %) exhibiting symptoms of OAB, 4 (1 %) stac-
voiding, anticholinergics, and constipation man- cato voiding, 14 (5 %) incomplete voiding, 3
agement. Six also had intermittent back or leg (1 %) voiding postponement, and 8 (3 %)
pain, but all had normal neurologic examinations. “unclassifiable” voiding dysfunction by blinded
MRI was normal in 21 (91 %), showed a thoracic review of the questionnaires by two experienced
spine syrinx in one, and spinal cord tethering in pediatric nephrologists. However, exclusion cri-
one (Ritchey et al. 1994). teria for the study included “overt dysfunctional
A retrospective study of 456 patients with day voiding” (van Gool et al. 1992).
and night incontinence revealed spina bifida One study collected prospective data for 2,759
occulta in 48 children among the subset of 127 consecutive children who underwent VCUG.
(28 %) who underwent X-rays of the spine. The “Dysfunctional elimination syndrome” (DES)
outcomes of those with known spina bifida was defined as daytime wetting beyond 3.5
occulta were compared to the 79 children with years for girls/4.0 years for boys, or three of six
normal spine X-rays during mean follow-up of 3 criteria: thick-walled bladder on US, trabeculated
years in both groups. Most patients resolved the bladder on VCUG, >30 % bladder capacity for
incontinence with timed voiding ± AC, with simi- age on VCUG, spinning top deformity on VCUG,
lar results between groups. Of the 48 with spina Vincent’s curtsy, and/or voiding <3×/day. They
bifida occulta, MRI or US of the spine was per- reported the following:
formed in ten, and lipoma with tethered cord was • DES among 32 % of children with VUR, indi-
found in one (Ritchey et al. 1994). cating most VUR patients did not have DES.
44 N.C. Bush
• DES occurred in 43 % of children with UTI

(not further defined), also indicating most Therapy
UTI patients did not have DES (Chen et al.,
2004). Placebo/Timed Voiding/Urotherapy
The study of 1,000 UD by Hoebeke et al.
(2000) described the above reported history of One study reported that 45 % of children with
UTI (not defined) in 34 %, and VUR in 14 %. OAB given placebo had significant symptom
Among subgroups defined by ICCS criteria, reduction. Cochrane meta-analysis found
VUR was identified in 88/582 (15 %) patients approximately 40 % symptom improvement
with OAB, 46/316 (15 %) with dysfunctional among adults with OAB taking placebo.
voiding, and 4/40 (10 %) with underactive One RCT found children using a daytime
bladder. alarm watch to have significantly greater reso-
A prospective study evaluated 143 children, lution of diurnal incontinence than those with
73 % female, age not stated, who had VUR for timed voiding.
“dysfunctional elimination syndrome” (DES): Another trial reported no benefit (to reduce
bladder instability (urge ± incontinence), infre- recurrent UTI or incontinence) in urotherapy
quent voiding (<4×/day), and/or constipation plus uroflowmetry to produce bell-shaped
(£3×/week, encopresis, or stool on X-ray). Sixty- voiding patterns over urotherapy alone.
six (46 %) had DES, including OAB in 18, infre- Cochrane meta-analysis of adults assigned to
quent voiding in 15, and constipation in 33 (Koff placebo versus anticholinergics for symptoms of
et al. 1998). OAB found that 41 % of patients assigned pla-
A retrospective study evaluated 128 children, cebo reported cure or improvement in symptoms
84 % female, 3–10 years old, with VUR in whom (Nabi et al. 2006).
history for voiding dysfunction was systemati- One double-blinded RCT randomized chil-
cally obtained. Symptoms of frequency, urgency, dren with OAB to 1 month of placebo versus
holding maneuvers, and/or diurnal incontinence polyethylene glycol with no discussion of void-
for at least 6 months were diagnosed with voiding modification. Urinary symptom question-
ing dysfunction. Of females with a history of UTI naires modified from DVSS for OAB were
(characterized as 1–2 or ³3 in the preceding 12 administered at baseline and repeated at 1 month,
months; febrile vs. non-febrile not stated), 38/94 with improvement defined as ³20 % decrease in
(40 %) had voiding dysfunction. Of 128 children score. Symptom improvement occurred in 17/38
with VUR, 66 (51 %) had voiding dysfunction (45 %) given placebo, including complete symp-
(Snodgrass 1998). tom resolution in five (Bush et al. 2012).
The dysfunctional voiding symptom score Our review found no RCT comparing no treat-
questionnaire (described above) was adminis- ment to timed voiding.
tered to 123 children with a history of fUTI A RCT enrolled 60 children at mean age 7
before age 2 years and 125 controls without UTI, years with diurnal urge incontinence and OAB
with no difference in the two cohorts based on without constipation (Rome III criteria) to first
gender, age (mean 7 years), or ethnicity. undergo “standard urotherapy” for 1 month
Dysfunctional elimination was diagnosed by a (>1,200 mL fluid equally distributed through the
score >6 in females and >9 in males. Symptoms day, timed voiding every 2 h). Forty-eight hour
of dysfunctional voiding did not differ between voiding diaries confirmed frequency and inconti-
the two groups; they were present in 22 % with nence. Ninety-five percent of patients had previ-
and 21 % without UTI. Among patients with UTI ously failed urotherapy (not described). Two had
history, there was no difference in dysfunctional a complete response (no diurnal incontinence);
elimination in those with versus those without the remainder were randomized to continue stan-
VUR (18 % with vs. 25 %, p = 0.52) (Shaikh dard urotherapy versus standard urotherapy using
et al. 2003). an alarm watch for timed voiding for 12 additional
weeks. Using the alarm watch, 9/30 (30 %) had a The EBDS described above identified 97
complete response versus 0/28 using standard children with clinically diagnosed urge syndrome
time voiding, p = 0.002 (Hagstroem et al. 2010). and incontinence who all then received urother-
Another trial included 143 children at mean apy (education, adequate fluid intake, voiding
age 8 years with dysfunctional voiding who had diaries, proper voiding posture, and personal
“clear peaks and declines” in two uroflows with hygiene). In addition, patients were randomized
³100 cm3, PVR ³10 %, and recurrent UTI (not to biofeedback (12 sessions of uroflow/EMG)
defined). These were allocated to three treatment versus double blinded pharmacotherapy using
groups for 2 months: “standard treatment” (edu- placebo or oxybutynin (0.3 mg/kg/day). There
cation, “proper voiding pattern,” “good toilet were outcomes data at 6 months for 64 patients,
positioning”) standard treatment with video reported before medication cohorts were
instructions (reemphasizing voiding pattern and unblinded. Cure was defined as no incontinence,
toilet positioning, watched daily), and standard and did not significantly vary by therapy. Nine of
treatment with uroflowometry (and instructions 23 (39 %) with biofeedback, and 14/20 (70 %)
to produce a bell-shaped curve 4× daily). All and 9/21 (43 %) with either placebo or oxybu-
received antibiotic prophylaxis for 24 weeks. The tynin were cured, indicating a placebo effect (or
endpoint was no infections and no incontinence spontaneous resolution) of at least 43 % and no
at 52 weeks. There was no difference in results additional benefit to biofeedback (Misselwitz
between the groups; there were no further UTIs et al. 1999).
in 71/130 (55 %) and no incontinence in 66/95
(69 %) (Klijn et al. 2006).
Anticholinergics
Biofeedback One placebo-controlled trial in children with

urge syndrome reported cure in 43 % only
One RCT reported no benefit to biofeedback receiving urotherapy.
using pelvic floor EMG during voiding versus Cochrane review of OAB in adults also
pelvic floor contraction/relaxation exercises reported a 42 % placebo response for cure or
alone. improvement.
Another found no benefit to urotherapy plus One trial comparing urotherapy, placebo,
biofeedback over urotherapy plus placebo. and tolterodine found significant decrease in
A RCT recruited patients from a dysfunc- DVSS scores with both tolterodine and placebo.
tional voiding clinic with incontinence who The study by Misselwitz et al. (1999) described
failed prior treatment in their clinic with timed above had not unblinded placebo versus AC treat-
voiding, “hydration, proper hygiene and consti- ment groups at time of reporting (both receiving
pation management,” and, in some cases, AC. urotherapy). Fourteen of 20 (70 %) and 9/21
Fifty-six children, 66 % female, ages 6–15 years (43 %) with either placebo or oxybutynin were
(mean 10), were allocated to pelvic floor cured at 6-month follow-up.
contraction/relaxation exercises versus biofeed- Another trial included 71 children (49 %
back plus pelvic floor exercises (generating an females), ages 4–12 years (mean 8), with voiding
EMG tracing). Patients were evaluated at 1, 6, dysfunction defined as “incontinence, frequency,
and 12 months for reduction in incontinent epi- urgency or obstructive symptoms ± non-febrile
sodes, cure being defined as no incontinence UTI, with PVR < 20 mL” who scored >6 (females)
over 4 weeks. There was no difference in out- or >9 (males) on the DVSS (described above).
comes between the two groups, with cures noted All were trained in timed voiding, double void-
at 1 and 12 months in 43 % and 71 % with exer- ing, and pelvic floor relaxation during voiding.
cises alone versus 30 % and 75 % with additional Patients were then randomized to no additional
biofeedback (Vasconcelos et al. 2006). treatment, placebo, or tolterodine 1 mg 2× daily
46 N.C. Bush
with repeated DVSS scoring at 1 and 3 months. 3-h timed voiding and “bowel hygiene” who
Outcomes were determined using only 4 of the received tamsulosin (0.2–0.4 mg nightly). All
10 DVSS questions that the authors considered had a non-bell-shaped uroflow pattern and pelvic
relevant to OAB, and reported the decrease in floor EMG without “excessive” activity during
mean scores was significantly greater with tolt- voiding. Three-day voiding diaries were com-
erodine (9 vs. 3.5, p < 0.001) than placebo (9 vs. pleted before therapy and at £4 weeks follow-up
5, p < 0.05) or behavioral modification (8 vs. 7). while on medication. Mean number of voids and
There was no change from baseline in those with incontinent episodes decreased from baseline
urotherapy, but a significant reduction also 11.5 ± 7.6 and 5.6 ± 1.9 to 7 ± 1 and 0.8 ± 1,
occurred with placebo (Ayan et al. 2005). p < 0.05 (Vanderbrink et al. 2009).
Cochrane review of AC for OAB treatment in
adults analyzed 13 studies and 1,770 patients
typically treated for 3–12 weeks. Symptomatic Nerve Stimulation
improvement during treatment was greater with
AC versus bladder training (gradual increase in One RCT using TENS reported no cure and
intervals between voiding, voiding diaries), RR partial response in 60 % of children with
0.73 (95 % CI 0.59–0.90), and with AC + bladder refractory urge incontinence.
training versus bladder training alone, RR 0.55 One trial using Interstim reported complete
(95 % CI 0.32–0.93) (Alhasso et al. 2006). resolution of diurnal incontinence in 75 %, but
Another Cochrane review considered AC complete relief of all symptoms without medi-
versus placebo for OAB in adults, analyzing 61 cation in 25 %.
trials and 11,956 patients. Cure or improvement, A RCT enrolled 25 children, 60 % females,
difference in 24-h incontinent episodes and 5–14 years old (mean 9), with diurnal urge incon-
number of voids in 24 h all favored AC. However, tinence at least 2×/week refractory to urotherapy
placebo response was 42 % (cure or improve- (hydration and timed voiding), alarm timed
ment), with AC giving an additional 15 % voiding, and AC, and randomized them to sacral
response with number needed to treat of seven TENS versus sham for 4 weeks. All had pretreat-
(Nabi et al. 2006). ment UD demonstrating detrusor overactivity.
No child had complete cure of incontinence.
Partial response occurred in 61 % of TENS versus
Alpha-Adrenergic Blockers 17 % of sham TENS patients, p < 0.05 (Hagstroem
et al. 2009).
One retrospective study reported decreased A cohort of 20 patients, 75 % female, mean
frequency and incontinence with tamsulosin, age 11 years (8–17) had sacral nerve stimulation
while one RCT reported a nonsignificant (Interstim) after failure of prior medical thera-
reduction in incontinence versus placebo. pies. Of these, 16 had diurnal incontinence and at
A RCT evaluated doxazosin versus placebo follow-up at a median of 27 months, 12 (75 %)
for 1 month as primary therapy for voiding reported complete resolution. Urgency in 13 chil-
dysfunction (diurnal incontinence with fre- dren completely resolved in 9 (69 %). However,
quency and urgency) in 28 children 5–16 years complete resolution of all symptoms (day and
old. There was a nonsignificant decrease in night incontinence, urgency, frequency, constipa-
median incontinent episodes/week with dox- tion) only occurred in five patients (25 %), and
azosin (18–4 vs. 14 in placebo, p = 0.13) only six were able to stop all other medications.
(Kramer et al. 2005). Two patients had deactivation without recurrent
A retrospective study reviewed 23 children symptoms, while three others had prompt recur-
mean age 9 years (5–16), 52 % females, with rent symptoms and 18 continued with the device
dysfunctional voiding (not defined) refractory to (Roth et al. 2008).
Botulinum A Toxin Injection significant decrease in diurnal incontinence

with successful stool management (≥3 stools/
Complete resolution of OAB in three trials using week without soiling), but a significant reduc-
botulinum A injections occurred in approxi- tion in urinary symptoms also occurred in
mately 40–60 %, durable to at least 6 months. those with persistent constipation.
A prospective study identified 21 children, Prospective assessment was done for voiding
52 % females, mean age 11 years (8–14), with symptoms in 234 consecutive children, mean
OAB and UD-demonstrated detrusor overactivity age 9 years (5–18), 25 % female, with constipa-
refractory to AC and urotherapy. These were tion and encopresis referred to a university
injected with 100 m Botox (Allergan, Irvine, CA, encopresis clinic. Day incontinence was diag-
USA) at 15 sites sparing the trigone. There was nosed if occurring ³1 episode/week, and was
follow-up in 15 at 6 months, with 9 (60 %) hav- found in 46 %. Treatment included education,
ing a complete response (no incontinence or disimpaction, high-fiber diet, timed toilet sit-
urgency). Eight had continued complete response ting, daily laxatives (mostly milk of magnesia),
at 12 months. Side effects included urinary reten- and stooling diaries continued for “several
tion for 10 days in one, flank pain with voiding months” and then decreased to maintain daily
for 2 weeks in one, and UTI in two (Hoebeke stooling without soiling. Follow-up evaluation
et al. 2006). was at ³12 months (mean 15), mostly by a ques-
Another prospective trial included 13 children tionnaire mailed to families that included ques-
(8 females) at median age 11 years (7–19) with tions regarding urinary incontinence.
urge incontinence refractory to timed voiding and Constipation was rated successfully treated if a
AC. Twelve had detrusor overactivity on UD pre- patient had ³3 stools weekly without soiling.
treatment. Primary injections used 50–100 IU Daytime incontinence significantly decreased
botulinum A at 20–30 sites, sparing the trigone. in those with successful constipation treatment
Complete response was no incontinence reported from 28/121 (23 %) to 3/121 (2 %) and in those
at follow-up at a mean of 1.5 months later (0.3– without successful bowel management from
2.8), which occurred in five (38 %) and persisted 36/113 (32 %) to 14/113 (12 %) (Loening-
at 6 months in 30 % and 12 months in 33 % Baucke 1997).
(Lahdes-Vasama et al. 2011). A RCT assumed constipation diagnosis might
A retrospective review included 57 children, be inaccurate in children presenting with urge
39 % female, with OAB who failed AC or had syndrome, and so randomized all patients to ini-
side effects precluding further treatment. Injection tial therapy by polyethylene glycol versus pla-
was done using 12 IU/kg Dysport (Ipsen, Paris, cebo for 1 month. The endpoint was ³20 %
France) to maximum of 480 IU. Complete reduction in symptom score using a modified
response (no voiding symptoms and no inconti- DVSS (for urge syndrome). Among 71 com-
nence) was achieved in 38 (67 %) with mean pleters, improvement occurred in 45 % assigned
duration of 6 months (2–18). No side effects were to placebo and 48.5 % receiving medication,
reported (McDowell et al. 2012). demonstrating no added benefit to polyethylene
glycol in either intention to treat (p = 0.77) or per-
protocol (p = 0.84) analysis (Bush et al. 2012).
Constipation Management
One RCT reported 45 % of patients had Impact of Voiding Dysfunction

improvement in urge syndrome symptoms on Behavior
with placebo, and no added benefit to polyeth-
ylene glycol. Children with urge syndrome, dysfunctional
One study of patients referred to an enco- voiding, and voiding postponement have been
presis clinic, mostly males, reported a found to have increased behavioral problems.
48 N.C. Bush
Two studies found that severity of bladder controls had health-related quality-of-life and
or bowel dysfunction did not correlate with self-esteem assessments using standardized and
quality of life in one study. validated instruments. Thirty percent of children
One quality-of-life assessment reported with both conditions also had encopresis, versus
children do not report less self-esteem or qual- none in controls. Patients had significantly more
ity of life versus controls, but their parents behavioral problems, but there was no difference
score them lower. in quality of life or self-esteem versus controls.
One study reported that treatment for dys- However, parents rated quality of life lower in
functional voiding, but not urge syndrome, patients than controls, especially those with void-
resulted in improved behavior. Presence of ing postponement (Natale et al. 2009).
behavior problems did not reduce treatment A study of 138 children with incontinence of
efficacy. various etiologies who were referred to a tertiary
Another study found improved self-esteem clinic completed the PINQ (quality of life) and the
in children following treatment for day and/or Akbal (urinary symptom) questionnaire. Children
night urinary incontinence. with non-white race, older age, and female gender
A 2011 ICCS consensus statement recom- had lower quality of life scores on the PINQ;
mends screening all incontinent children for severity of urinary symptoms based on the Akbal
psychological symptoms with validated question- score (r = 0.15, p = 0.09) did not correlate with
naires such as the Child Behavior Checklist or worse quality of life (Deshpande et al. 2011).
the Short Screening Instrument for Psychological Another study in 103 children referred for
Problems in Enuresis (von Gontard et al. 2011). incontinence using a validated health-related
No data are available whether such widespread quality-of-life questionnaire showed type and
screening would improve either psychological or severity of urinary or fecal incontinence was not
urological outcomes. correlated with total scores, and that overall qual-
Prospective evaluation was done in 94 inconti- ity of life among children referred for inconti-
nent children clinically diagnosed with urge syn- nence were similar to reference samples of
drome (n = 42) and with voiding postponement children with other chronic conditions such as
(<5 voids/day, incontinence while watching tele- asthma, cystic fibrosis, and epilepsy (Bachmann
vision or playing) (n = 52) recruited at presenta- et al. 2009).
tion from pediatric and psychiatric clinics in The EBDS included the Achenbach’s Child
Germany. Parents answered the Achenback Child Behavioral Checklist (a validated checklist
Behavioral Checklist and a structured interview documenting social competence and problem
was done with the child regarding body image behavior) at enrollment and 12 months after treat-
and interpretation of wetting. There were ment, answered by parents. Of 202 patients, 188
significantly more females with urge syndrome completed forms at entry and 111 at 1 year.
(62 %) and more boys with voiding postpone- Overall, 19 % had abnormal behavioral scores,
ment (65 %), with mean age in both 7 years. which after treatment decreased to 11 %, the
Parents scored significantly more behavioral authors commenting that this approximates prev-
problems in those with voiding postponement alence in a normal population. However, this
(37 vs. 14 %). There were no differences in child improvement occurred in patients with dysfunc-
responses based on clinical diagnosis, with only tional voiding, whereas those with urge syndrome
11 % responding they had an illness, although did not change. Similarly, externalizing problems
70 % knew the reason for their evaluation. Thirty found in 12 % of children decreased significantly
percent did not know the origin of urine (von after treatment, but only in those with dysfunc-
Gontard et al. 1998). tional voiding. Internalizing problems occurred
In a subsequent study, consecutive children, in 16 % overall, with no significant change in
5–13 years old, with urge syndrome (n = 22) or either subgroup with therapy. The presence of
voiding postponement (n = 27) and 32 age-matched behavioral problems at entry did not influence
treatment success for either urge syndrome or Benninga M, Candy DC, Catto-Smith AG, Clayden G,
dysfunctional voiding (Bael et al. 2008a). Loening-Baucke V, Di Lorenzo C, et al. The Paris
consensus on childhood constipation terminology
Sixty-six children identified through school- (PACCT) group. J Pediatr Gastroenterol Nutr. 2005;
based questionnaire to have day and/or night 40(3):273–5.
wetting scored lower than age-matched controls Bijos A, Czerwionka-Szaflarska M, Mazur A, Romanczuk
on a Swedish validated self-esteem scale (12.5 W. The usefulness of ultrasound examination of the
bowel as a method of assessment of functional chronic
vs. 19.4, p < 0.001). Treatment of the inconti- constipation in children. Pediatr Radiol. 2007;37(12):
nence increased self-esteem levels to that of 1247–52.
controls at 6 months (19.5), with scores higher Boccia G, Manguso F, Coccorullo P, Masi P, Pensabene L,
in those who achieved dryness versus those Staiano A. Functional defecation disorders in children:
PACCT criteria versus Rome II criteria. J Pediatr.
still wetting (23.1 vs. 17.3, p < 0.001) (Hagglof 2007;151(4):394–8. 8 e1.
et al. 1998). Burgers R, Levin AD, Di Lorenzo C, Dijkgraaf MG,
Benninga MA. Functional defecation disorders in
children: comparing the Rome II with the Rome III
criteria. J Pediatr. 2012;161(4):615–20.e1.
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Nocturnal Enuresis
4
Nicol C. Bush
The primary reason to diagnose and treat noc- dren. Approximately two-thirds relapse
turnal enuresis is to achieve dryness. A second- when treatment stops after 3 months.
ary aim is to improve body image and/or low • There are few data regarding efficacy of
self-esteem associated with nocturnal enuresis. long-term medication use.
Primary outcome measures for therapy of • Our review found no reports regarding
nocturnal enuresis have been defined as follows: 6-month dryness in treated patients.
• Short-term success: dryness for 14 consecu- • Children with enuresis have greater behav-
tive nights ioral problems than non-bedwetters. However,
• Long-term success: dryness for 6 consecu- successful treatment of enuresis is reported to
tive months not impact behavior significantly.
• Adverse treatment events • One study reported improved self-concept
Secondary outcome measures include psy- with treatment.
chological and quality-of-life assessments.
Summary of evidence for these goals:
• Alarms achieve dryness for 14 consecutive Definitions
nights during use in 50–75 % of enuretic
children. Half of these maintain dryness Infrequent bedwetting: <2 nights per week.
when therapy stops.
• Desmopressin achieves dryness for 14 con- Enuresis: involuntary voiding during sleep ³2
secutive nights in approximately 20 % of nights per week for at least three consecutive
treated children. Nearly all resume wetting months and/or causing significant distress/impair-
when therapy stops. ment in a child >5 years old without CNS defects
• Desmopressin plus tolterodine was more effec- (DSM-IV).
tive than desmopressin plus placebo in one
trial enrolling children with mono-symptom- Mono-symptomatic nocturnal enuresis: wet-
atic enuresis who failed desmopressin alone. ting only when asleep.
• Imipramine achieves dryness for 14 con-
secutive nights in 20–33 % of treated chil- Non-mono-symptomatic (or poly-symptom-
atic) nocturnal enuresis: nighttime incontinence
N.C. Bush, M.D., M.S.C.S. (*) associated with daytime symptoms such as incon-
Department of Pediatric Urology, University of Texas tinence, urgency, and/or frequency.
Southwestern Medical Center and Children’s Medical
Center Dallas, 1935 Medical District Drive, MS F4.04,
Dallas, TX 75235, USA Secondary enuresis: previously dry for more
e-mail: nicol.bush@childrens.com than six consecutive months.
54 N.C. Bush
girls (4 vs. 2 % at age 7.5 years) (Butler and

Prevalence Heron 2008).
In the cross-sectional survey of 16,512 chil-
Infrequent Bedwetting dren aged 5–19 years in Hong Kong mentioned
above, enuresis ³3 nights/week occurred in 7 %
Bedwetting <2 nights/week occurs in £20 % at age 5 years, 3 % at age 7.5 years, and 2 % at
of 5-year-olds and diminishes to 2 % by 19 age 9.5 years. More frequent bedwetting (³3
years of age. nights/week) occurred in a higher proportion of
Infrequent bedwetting is more common in patients as age increased, such that 82 % of
boys than girls. patients with bedwetting aged >10 years had ³3
The Avon Longitudinal Study of Parents and wet nights/week versus 42 % of patients aged
Children (ALSPAC) is an ongoing, prospective, 5–10 years (p < 0.0001); 14.3 % of children aged
population-based cohort study in the UK that 5 years had enuresis 7 nights/week compared to
includes 13,973 children born in 1992–1993 and 48.3 % of 19-year-olds (p < 0.0001) (Yeung et al.
followed at regular intervals. Questionnaires that 2006). While bedwetting (infrequent plus fre-
included questions about enuresis were adminis- quent) was more common in boys than girls at all
tered at regular intervals between 54 and 115 ages, data were not gender-stratified for those
months of age. Infrequent bedwetting was present meeting DSM-IV criteria for enuresis.
in 22 % at 4.5 years; 16 % at 5.4 years; 13 % at 7.5 Data from 1,136 US children aged 8–11 years
years, and 8 % at 9.5 years. Boys had a greater in a cross-sectional, nationally representative
prevalence of infrequent bedwetting than girls at sample of children participating in the National
all ages up to 115 months (roughly two times), Health and Nutrition Examination Survey
with identical rates of decline for both males and (NHANES) demonstrated enuresis in 8 % of
females. At age 7.5 years, 15 % of boys versus children at 8 years, decreasing to 3 % at 11 years.
8 % of girls had infrequent bedwetting, which Enuresis was more prevalent in boys than girls
declined to 10 % of boys at age 9.5 years versus (6 vs. 2.5 %), with a 2.7-fold risk of enuresis
5 % of girls (Butler and Heron 2008). among 8- to 11-year-old boys (OR2.69 [95 % CI
In an epidemiologic cross-sectional survey of 1.37–5.2]) (Shreeram et al. 2009).
16,512 children aged 5–19 years in Hong Kong,
bedwetting more than once every 3 months was
present in 16 % at 5 years, 10 % at 7 years, and 2 % Poly-symptomatic Enuresis
at 19 years, with boys more likely to have bedwet-
ting than girls at all ages (Yeung et al. 2006). Prospective epidemiologic studies report day-
time symptoms occurred in approximately
20–40 % of children with enuresis.
Mono-symptomatic Nocturnal Enuresis Of consecutive children referred to an
enuresis clinic, daytime symptoms occurred in
Enuresis occurs in approximately 8 % of over 80 %.
children age 5 years, decreasing to 1–3 % by The ALSPAC prospective cohort study of
age 10 years. 13,973 children mentioned above described 1,260
Boys have ≥2 times greater risk for enuresis (15.5 %) children with bedwetting (infrequent
at all ages than girls. plus frequent), comprising mono-symptomatic
A higher proportion of older children have enuresis in 12 %, and day and nighttime wetting
bedwetting ≥3 nights/week. in 3 %. Only 0.2 % experienced frequent (>2×/
Prevalence estimates from 13,973 children in week) wetting episodes both during the day and
the UK prospective cohort study (ALSPAC) dem- night. Of children with nighttime wetting, 29 %
onstrated enuresis in 8 % of children at 4.5 years, had daytime urge symptoms, with increased like-
3 % at 7.5 years, and 1.5 % at 9.5 years. Boys lihood with increasing frequency of enuresis
were more likely to have enuresis at all ages than (Butler et al. 2005).
4 Nocturnal Enuresis 55
In the cross-sectional epidemiological study The prospective case–control study of 170

reported by Yeung et al. (2006) above, daytime referred patients to an enuresis clinic mentioned
incontinence was present in 106 (21 %) of the above (Robson et al. 2005) reported primary
512 patients with bedwetting (>1×/3 months), enuresis in 123 (72 %) and secondary enuresis in
including 38 (14 %) of 279 children aged 5–10 47 (28 %). Of the studied characteristics (demo-
years and 68 (29 %) of 233 adolescents >10 years graphic information, urologic history,
(Yeung et al. 2006). uroflowmetry, and post-void residual), the only
Another cross-sectional study of 5,282 difference in those with secondary enuresis was
Japanese school children mean age 9 years (7–12) the increased presence of constipation (diagnosed
found bedwetting (>1×/month) in 6 %. Daytime with palpable stool on abdominal exam and/or
symptoms, including frequency >8×/day and/or abdominal radiograph), in 75 % with primary
urge incontinence >1×/month, occurred in 41 % versus 56 % with secondary enuresis (OR 2.17
of these. The prevalence of poly-symptomatic [95 % CI 1.07–4.41]). Daytime symptoms,
enuresis was 3 % at age 7 years, and decreased to including incontinence, which was reported by
0.8 % at age 12 years (Kajiwara et al. 2006). 85 %, had similar frequency in both groups.
An Australian cross-sectional study involved A prospective birth cohort study of 1,265
a random sample of 2,856 children from ele- New Zealand children determined that the rate of
mentary schools with a mean age of 7.3 years nocturnal enuresis in 8-year-olds was 7 %, which
(SD 1.3), reporting enuresis in 6 %. Daytime the authors estimated represented secondary enure-
incontinence occurred in 17 %, associated with sis in one-third to one-half. Children exposed in any
mild, moderate, and severe enuresis (1–6×/ given year from ages 2–8 years to multiple life stres-
month; >7×/month but < nightly; 7×/week) in sors, defined as change of parents or residence and/
univariate analysis and multivariate logistic or other events from a 20-item Social Readjustment
regression (adjusted OR [95 % CI]: 3.0 [2.1– Rating Scale, were more likely to develop second-
4.2], 2.6 [1.3–5.2], and 4.8 [2.9–7.9]), respec- ary enuresis (OR 2.56 [95 % CI 1.18–5.50]). This
tively (Sureshkumar et al. 2009). likelihood for secondary enuresis also related to age
Among 170 patients with nocturnal enuresis at which nighttime dryness was first achieved, with
(quantity not specified) enrolled into a prospec- children not dry until age 5 years more susceptible
tive study of consecutive children aged ³3.5 years than those dry at age £3 years (OR 3.39 [95 % CI
presenting to a referral clinic for enuresis, 83 % 1.76–6.56]) (Fergusson et al. 1990).
experienced “urinary urgency” (not defined). A prospective study of 110 consecutive
Daytime wetting was present in 84 %, urinary children with primary (82, 75 %) versus secondary
frequency (>8×/day) in 39 %, and squatting (28, 25 %) enuresis that performed semi-struc-
maneuvers in 35 % of girls (Robson et al. 2005). tured child interviews and parental questionnaires
found a higher rate of behavioral disorders (pri-
marily internalizing) and/or life stressors (divorce,
Secondary Enuresis birth of sibling, school problems) in those with
secondary enuresis (von Gontard et al. 1996).
Approximately one-third of enuretics have
onset after a dry period, comprising secondary
enuresis. Family History
One study found no difference in daytime
symptoms in secondary versus primary One study of consecutive patients referred to a
enuretics. specialty enuresis clinic reported a positive
Two studies reported life stressors such as family history in first- or second-degree rela-
divorce, birth of siblings, and school problems tives in 62 %.
associated with secondary versus primary A prospective cohort study found approxi-
enuresis. mately 20 % of children with enuresis had a
56 N.C. Bush
parent with a history of bedwetting beyond age risk of enuresis. Rates of enuresis (>2 nights/week)
5 years, equally affecting mothers and fathers. at age 7.5 years were 3.63 and 1.85 times higher
Cross-sectional epidemiologic studies found among children with a family history of maternal
increased likelihood for a child having enuresis or paternal bedwetting, respectively (von Gontard
if either mother or father reported bedwetting. et al. 2011a).
One study found sibling enuresis an indepen- A prospective study in New Zealand followed
dent risk factor compared to parental history. children from birth to age 8 years, and obtained
Two twin studies report concordance in information regarding family history of enuresis
identical twins more than fraternal twins, sug- from mothers of the children at the 5-year visit,
gesting a strong genetic component. recorded as number of first-degree relatives with
A prospective study evaluated family history nocturnal enuresis. The mean age of attaining
among 167 consecutive children aged 5–10 years bladder control (“regularly remained dry through-
attending an outpatient enuresis clinic, of whom out the night”) in children with zero, one, and two
110 had mono-symptomatic enuresis. A positive first-degree relatives with nocturnal enuresis were
family history (parent, sibling, aunt, uncle, 3.7, 4.4, and 5.2 years, respectively (p < 0.0001).
cousin) was reported by 67 (62 %), including On multivariate analysis, the number of first-
21 % of mothers, 23 % of fathers, and 17.5 % sib- degree relatives was the strongest predictor of age
lings (von Gontard et al. 1996). to attain bladder control, which on average
A cross-sectional study of 3,206 Finnish 7-year- occurred 1.5 years later when two first-degree
olds, of whom 8 % experienced bedwetting, found relatives had nocturnal enuresis compared to those
a positive family history in 37 %, with the risk of without a family history (Fergusson et al. 1986).
enuresis in a child 7.1 times greater (95 % CI 5.1– Among 338 pairs of twins prospectively
9.8) when the father had bedwetting beyond 4 years enrolled in a study to evaluate “various behavior
of age, and 5.2 times greater (95 % CI 3.9–7.0) disorders,” including bedwetting, thumb-sucking,
when the mother did (Jarvelin et al. 1988). and nail-biting, 146/676 (22 %) had enuresis,
Enuresis occurred in 159 (10 %) of 1,694 defined as wetting repeatedly >4 years of age.
Turkish school children mean age 9 years (7–11 A positive history for a parent having had bed-
years) responding to a school-based cross- wetting was obtained in 85 %, equally involving
sectional survey. Univariate analysis found higher mothers and fathers (Bakwin 1971).
rates of parents and siblings with a history of Enuresis in the above-mentioned study
treatment for enuresis among children with reported that of the twins with enuresis, 68 %
enuresis compared to those without enuresis were monozygmatic versus 36 % dizygomatic,
(parental history: 68.5 vs. 4.6 %, p < 0.001; sib- further supporting a strong genetic component
ling history: 34.6 vs. 2.3 %, p < 0.001). Multiple (Bakwin 1971).
logistic regression demonstrated that parental Similarly, a nationwide Finnish Twin Cohort
and sibling history of enuresis were both inde- of over 11,000 patients demonstrated a higher
pendent risk factors for enuresis (parent: OR concordance rate of nocturnal enuresis in child-
12.17, 95 % CI 4.05–36.61; sibling: OR 3.79, hood among identical versus fraternal twins
95 % CI 1.23–11.68) (Inan et al. 2007). (43 vs. 19 %) (Hublin et al. 1998).
In the ALSPAC prospective birth cohort study
of 13,973 UK children mentioned above, detailed
family history was obtained during the pregnancy Associated Disorders
of the enrolled child. Parents were asked if they
experienced nighttime incontinence beyond the Constipation
age of 5 years; a positive history was reported by
9 % of both mothers and fathers. Parent/child pairs Three prospective studies reported that enco-
were constructed based on frequency of bedwet- presis, but not constipation, was a risk factor
ting, and odds ratios were calculated to determine for nocturnal enuresis.
Two stated that fecal incontinence was enuresis in 25 (83 %) (Hodges and Anthony
associated with enuresis; it was found in 11 % 2012). The number of wet nights/week before
of enuretics in one study. bowel therapy was not stated, and it was unclear
The Australian cross-sectional study of 2,856 if these patients had daytime incontinence. The
children described above categorized “severe” indications for radiography and the number of
(nightly the past 1 month), “moderate” (³7 epi- other patients with enuresis not undergoing x-rays
sodes in past month), and “mild” (1–6 episodes also were not stated.
the past month) enuresis. Constipation as defined
by ROME-II criteria was not associated with
mild, moderate, or severe enuresis (OR 0.7 [95 % Sleep-Disordered Breathing
CI 0.4–1.2], 1.5 [95 % CI 0.7–3.6], and 0.7 [95 %
CI 0.3–1.9], respectively). However, encopresis A systematic review reported that approxi-
was more likely with severe enuresis in multi- mately 33 % of children with sleep-disordered
variate logistic regression adjusting for age (OR breathing (snoring, obstructive sleep apnea)
2.7 [95 % CI 1.6–4.4]), and marginally associ- also had enuresis.
ated with mild and moderate enuresis (OR 1.6 Several population-based surveys report
[95 % CI 1.0–2.4] and 2.1 [95 % CI 1.1–4.3], enuresis in 7–22 % of children who report
respectively) (Sureshkumar et al. 2009). sleep-disordered breathing, which is
The survey of Turkish school children report- significantly greater than in children without
ing enuresis in 10 % mentioned above defined snoring or sleep apnea (2–16 %).
constipation as ³2 of the following: bowel move- Systematic review found tonsillectomy and
ment <3×/week, fecal incontinence >1×/week, adenoidectomy (T&A) reduced enuresis dur-
palpable stools, stopping up toilet, withholding ing median follow-up of 6 months.
maneuvers, and/or pain with defecation. A systematic review of 12 articles published
Univariable analysis reported both fecal inconti- from 1998 to 2010 included 3,550 children with
nence and constipation more likely in enuretic sleep-disordered breathing, of which 1,113
versus non-enuretic children, but multivariate (33 %) also had enuresis (not separated into pri-
analysis demonstrated that only fecal inconti- mary versus secondary). Patient age ranged from
nence, which occurred in 11 % with bedwetting, 2 to 19 years. The authors commented that their
was an independent risk factor for enuresis (OR finding that 33 % of patients age 6 years with
6.13 [95 % CI 1.46–43.83]) (Inan et al. 2007). sleep-disordered breathing also had enuresis sug-
The cross-sectional study of 5,282 Japanese gests a relationship, given the usual prevalence of
school children reported above defined constipa- <15 % enuresis reported for this age. Seven arti-
tion as <3 bowel movements/week. There was no cles with 1,360 patients (enuresis in 426, 31 %)
difference in rates of mono-symptomatic enure- had data regarding enuresis after T&A, finding
sis (6 %) in children with and without constipa- that postoperative prevalence with median fol-
tion, while poly-symptomatic urinary incontinence low-up of 6 months was reduced to 16 %
was more likely with constipation (3 % with vs. (p = 0.002) (Jeyakumar et al. 2012).
2 % without, p < 0.05) (Kajiwara et al. 2006). Among 17,646 children aged 5–7 years in
A retrospective review of 30 consecutive Kentucky completing a questionnaire about sleep
patients mean age 9 years (5–15) with a “chief habits, enuresis (defined as >2×/month) was
complaint of nocturnal enuresis” found 10 % present in 531/1976 (27 %) with habitual snor-
reported constipation (bowel movement < every ing (>3 nights/week and medium to loud on a
other day). Using a novel measurement of the loudness scale) versus 1,821/15,670 (12 %)
ratio of the widest point of rectal diameter to pel- without snoring (p < 0.00001, OR 2.79 [95 % CI
vic outlet diameter on abdominal radiograph, all 2.50–3.13]). A random sample of 378 children at
children had “fecal rectal distention” Therapy risk for sleep apnea based on these question-
with polyethylene glycol for ³2 weeks cured the naires underwent overnight polysomnography.
58 N.C. Bush
Of these, enuresis ³3×/week was present in A literature survey concerned the co-occur-
33/149 (22 %) with obstructive sleep apnea and rence of ADHD and enuresis in “recent studies”
36/229 (16 %) with habitual snoring but not characterized as epidemiological (n = 6) versus
obstructive sleep apnea. Severity of sleep distur- clinical (n = 12), reporting ADHD/behavioral
bance did not correlate with severity of enuresis problems occurred in approximately 16–29 % of
(Capdevila et al. 2008). enuretics. Four other studies reported that enure-
Two additional population-based cross- sis occurred in 21–32 % of children with ADHD
sectional studies also found increased rates of (Baeyens et al. 2005).
enuresis among children with snoring. Of 2,746 A population-based, nationally representative
5–13-year-old children in Istanbul, children with cross-sectional cohort of 1,136 US children found
occasional and habitual snoring had higher rates enuresis (defined by DSM-IV criteria and present
of nocturnal enuresis (quantity not specified) ver- within the past 12 months before the survey) in
sus non-snorers (10 and 15 % vs. 7.5 %, p = 0.005, 4 % children aged 8–11 years. Using a validated
OR 2.2 [95 % CI 1.2–3.5]) (Ersu et al. 2004). structured diagnostic interview that elicits
Among 1,821 children aged 5–14 years in DSM-IV criteria for both enuresis and ADHD,
Greece, children with habitual snoring (>3 nights/ nearly 10 % of children met DSM-IV criteria for
week) were more likely to have primary noctur- ADHD. Enuretic children were more likely than
nal enuresis (>1×/week) versus non-snorers (7.4 non-enuretics to have ADHD: 12.5 vs. 4 % with-
vs. 2 %, OR = 4.00 [95 % CI 1.93–8.32]) out, p = 0.001. There was a 2.9-fold risk for
(Alexopoulos et al. 2006). ADHD among children with enuresis, OR 2.88
A case–control study compared 149 children (95 % CI 1.26–6.57) (Shreeram et al. 2009).
in a sleep-disorders clinic to 139 controls from The ALSPAC prospective birth cohort men-
general pediatric practice, and found that chil- tioned above demonstrated higher rates of parent-
dren with obstructive sleep apnea had higher odds reported psychological problems, including
of having mono-symptomatic enuresis (quantity attention problems, in children with any bedwet-
not specified) (OR = 5.29 [95 % CI 2.25–12.45]) ting and combined day and night wetting versus
(Barone et al. 2009). in those without wetting at age 7.5 years, bedwet-
Another case–control study included 270 chil- ting OR 1.58 (95 % CI 1.32–1.90), and combined
dren referred to a sleep center for enuresis and wetting OR 2.23 (95 % CI 1.64–3.05) (Joinson
274 gender- and age-matched healthy children et al. 2007).
without enuresis as controls. Significant differ- Another cross-sectional study that controlled
ences in sleep patterns occurred in enuretic ver- for developmental delay among a cohort of 1,379
sus healthy controls, as measured by the validated children undergoing a mandatory school entry
sleep disturbance scale for children (Carotenuto medical examination in Germany demonstrated
et al. 2011). that nocturnal enuresis alone was not a significant
risk factor for symptoms of ADHD, whereas day-
time incontinence with or without nocturnal
Attention Deficit/Hyperactivity enuresis strongly increased the odds of ADHD
Disorder symptoms, OR 4.6 (95 % CI 1.6–13.0) (von
Gontard et al. 2011b).
One literature survey reported a co-occur- A cross-sectional study of 344 children
rence rate of attention deficit/hyperactivity enrolled in a genetic study of ADHD demon-
disorder (ADHD)/behavioral problems and strated a 17 % prevalence of enuresis (not
enuresis of 16–32 %. quantified), which localized to the inattentive
One population-based US study found ADHD ADHD phenotype, but genome-wide analysis of
increased in children with enuresis (12 %), while 51 of these children did not identify an associa-
a similar study of German children reported tion with chromosomal regions previously linked
enuresis was not related to ADHD. to enuresis (Elia et al. 2009).
and psychological risk factors (such as divorce,

Psychologic Impact of Enuresis sibling birth, entering kindergarten) (von Gontard
et al. 1996).
One study reported children age 9 years con-
sidered bedwetting a social problem that
ranked fourth of 21 difficult life events. Natural History
As noted earlier, behavioral problems are
increased in children with both primary and Spontaneous Resolution
secondary enuresis.
As part of the ALSPAC population-based Our review found no longitudinal study assess-
study concerning health and development of chil- ing spontaneous resolution rates of enuresis in
dren, questionnaires were sent to 10,985 children a population of untreated children.
age 9 years, with 8,209 returns (75 % response) Short-term dryness (within 2–22 weeks) in
equally distributed between genders. They were nine RCTs was achieved in only 4 % of
asked to rate perceived difficulty of life events untreated controls.
from a list of 21 items, as “not at all,” “a little No longitudinal study reports spontaneous
difficult,” “quite difficult,” and “really difficult.” resolution of bedwetting in untreated children.
The top four most difficult events were “don’t The 15 % annual spontaneous resolution
have friends,” “being teased,” “left out of things,” rate commonly quoted was derived from
and “wet the bed.” Those rated less severe patients failing at least two drug treatments
included “often ill,” “move to a new school,” and behavioral modifications.
“always in trouble,” and “don’t like how they A questionnaire-based study of 1,129 (of
look.” Enuretic children (³2 nights per week) 1,483) patients evaluated in an enuresis clinic
comprised 1 % of respondents, and reported bed- in Belfast between 1952 and 1959 reported
wetting a more difficult event than non-wetters. approximately 15 % “spontaneous” resolution
Nevertheless, 36 % of children dry at night rated per year in patients aged 5–19 years, with 33
bedwetting a “really difficult” problem. The fact (3 %) having continued enuresis after age 20
that children rated bedwetting a more difficult years (Forsythe and Redmond 1974). This study
problem than physical illness was interpreted by is frequently referenced in review articles of
the authors to indicate that they perceive this a enuresis for the often-quoted 15 % rate of
social, rather than medical, issue (Butler and “spontaneous resolution” in children not treated
Heron 2007). with a bedwetting alarm. However, all these
Another ALSPAC questionnaire study con- patients failed therapy with ³2 drugs and many
cerned parental attitudes regarding combined also failed various behavioral modifications,
bedwetting and daytime incontinence in children and so are not representative of untreated chil-
approximately 7.5 years old. Parents reported dren. Furthermore, the numbers of patients
more psychological problems in children with evaluated at different ages to calculate annual
combined wetting than those with only bedwet- resolution rates was not stated, and length of
ting or no wetting, as already mentioned in the time of follow-up was not taken into account.
section above (Joinson et al. 2007). Duration of time without wetting considered
One-hundred ten consecutive children present- “cure” was not stated.
ing to an enuresis clinic were diagnosed as having A Cochrane systematic review found no treat-
primary (n = 82) or secondary bedwetting. ment or placebo arms of RCTs demonstrate
Evaluation included a “full child psychiatric and <10 % of patients achieve 14 consecutive nights
psychological assessment,” and parent question- of dryness during the study periods (ranging from
naires for life events they considered to have caused 2 to 22 weeks), and only 1–2 % remain dry. This
enuresis. Patients with secondary enuresis had pooled analysis of nine trials reporting data for
significantly higher rates of behavioral disorders bedwetting alarm versus no treatment reported
60 N.C. Bush
failure (<14 consecutive dry nights) in 250 of 260

(96 %) controls (Glazener et al. 2009a). Treatment
Our review did not find any long-term longitu-
dinal cohort studies of enuretic patients reporting Behavioral Interventions (Random
spontaneous resolution without medical, behav- Awakening, Fluid Restrictions, Rewards)
ioral, and/or alarm therapy. Enuresis rates at vari-
ous ages in population-based, cross-sectional Cochrane review of RCTs reported wakening
studies such as those described provide preva- not triggered by a wetting episode was not
lence rates at various ages, but it is unknown or effective therapy for enuresis.
not specified how many of these children received Cochrane review of behavioral and educa-
therapy to alleviate enuresis at any given point in tional interventions for enuresis, including wak-
time, and so these studies cannot be used to esti- ening not triggered by a wetting episode, as well
mate true spontaneous resolution. as night-time fluid restriction and reward sys-
tems, analyzed 18 trials involving 1,174 chil-
dren. Behavioral interventions alone were not as
Evaluation effective as alarms alone or alarms plus behav-
ioral therapy, with RR for failure or relapse with
No laboratory, radiologic, or urodynamic test- behavioral intervention versus alarm plus inter-
ing is needed after history and physical exami- vention 2.81 (95 % CI 1.80–4.38) (Glazener
nation in children with mono-symptomatic et al. 2008).
enuresis.
The following is a summary of current guide-
lines for evaluation of enuresis. Alarm Conditioning
NICE guidelines (2010), derived from “best
available evidence” by a team selected by the Cochrane review reported alarm use for
National Clinical Guidelines Centre, recommend 2–22 weeks resulted in 14 consecutive dry
the following: nights in 50–75 % of children. Approximately
• Urinalysis when there is a suspicion of diabe- 50 % of children remained dry after active
tes or UTI, secondary enuresis, and/or daytime treatment.
symptoms A more rapid response may be achieved
• Voiding and fluid-intake diaries using medication, but overall effectiveness
• No radiographic studies during therapy was considered similar by
European Association of Urology guidelines, Cochrane review.
derived primarily from expert consensus, recom- Relapse rates were less after alarm therapy
mend the following: versus medication.
• Diagnosis is made by history alone without Cochrane review of 56 RCTs involved 3,257
further investigation for mono-symptomatic children, 2,412 of whom used an alarm. Duration
enuresis (Tekgul et al. 2009). of treatment varied but ranged from 2 to 8 weeks
ICCS guidelines, derived from “what evidence in 16 trials, up to more than 12 weeks in 22 trials.
there is” (described as weak) and expert consen- Only 29/56 (52 %) studies provided follow-up
sus, recommend the following: data to determine relapse rates. Here is a sum-
• Urinalysis to evaluate glycosuria and/or mary of key findings:
proteinuria • Alarm versus no treatment: About two-
• No renal ultrasound thirds of patients using alarms became dry
• A 2-day chart of urinary frequency/volume (RR for failure 0.38 [95 % CI 0.33–0.45]),
and fluid volume consumed and about half failed or relapsed after alarm
• A 1-week chart of enuresis, daytime incontinence, conditioning, while nearly all controls
and bowel movements (Neveus et al. 2010). remained wet.
• Alarm versus placebo: Alarms were better and were conducted for various lengths of time
than placebo for fewer wet nights during and at varying dosing regimens. Key summarized
after treatment. findings included the following:
• Alarm versus desmopressin: Desmopressin • Desmopressin versus placebo: At an intrana-
may achieve dryness faster than alarm, sal dose of 20 mg, pooled data demonstrated a
although there appear to be no differences mean of 1.34 fewer wet nights per week (95 %
during an entire treatment course, RR 0.85 CI 1.11–1.57). Doses of 40 mg and 60 mg
(95 % CI 0.53–1.37). In two small trials, decreased the number of wet nights per week
relapse was less after alarm therapy (26/57 by 1.33 and 1.50 nights/week, respectively
[46 %] vs. 40/62 [65 %]). (95 % CI 1.67–0.99 and 1.92–1.08). Nineteen
• Alarm versus tricyclics: There was no differ- percent of treated children became dry versus
ence in response during treatment, RR 0.59 2 % of controls. Four trials suggested results
(95 % CI 0.32–1.09), but alarms had lower were not sustained after treatment ended.
relapse rates after treatment, RR 0.58 (95 % • Desmopressin versus tricyclics: More children
CI 0.36–0.94). in two trials became dry with desmopressin
• Alarm plus desmopressin: there was no differ- during treatment, RR for failure to achieve 14
ence in treatment success in alarm versus consecutive dry nights 0.44 (95 % CI 0.27–
alarm plus desmopressin trials. 0.73), but there were no data regarding relapse
There were no clear-cut differences noted in after therapy.
types of alarms (body vs. pad), although two • Desmopressin versus alarms: See section
small trials demonstrated fewer wet nights among above.
alarms with immediate wakening versus time • Adverse Events: All reported events were
delay of 3 min (Glazener et al. 2009a). minor and did not result in stopping treatment.
There is a risk for water intoxication, which is
minimized by fluid restriction before bedtime
Desmopressin (Glazener and Evans 2009).
In one multicenter dose-escalation study, 148
Cochrane meta-analysis reported that desmo- children (ages 6–16 years, 73 % males, average
pressin achieved 14 consecutive dry nights in 10–11 wet nights per 2 weeks) were assigned to
approximately 20 % of children versus 2 % of placebo or desmopressin beginning at 0.2 mg at
controls. bedtime for 2 weeks, and then increased every 2
One trial increased desmopressin dosing at weeks at 0.2-mg increments until either dry or
2-week intervals, reporting progressively receiving a maximum 0.6 mg. There was a
decreased wet nights with increasing dose to significant linear decrease in wet nights from
0.6 mg, but only 8 % of treated children baseline a mean of 10, 27, 30, and 40 % for pla-
became dry. cebo, 0.2, 0.4, and 0.6 mg desmopressin. A 50 %
Relapse after therapy is similar in children reduction in wetting from baseline occurred in
treated with desmopressin and those receiving 28 % of patients at 0.2 mg, 16 % at 0.4 mg, and
no medication. 9 % at 0.6 mg. However, only 11/141 (8 %) des-
One RCT reported desmopressin plus tolt- mopressin patients became dry versus 0/47
erodine achieved >50 % reduction in wet receiving placebo (Schulman et al. 2001).
nights during 1 month of therapy in patients One RCT enrolled 34 nonresponders or partial
with enuresis failing desmopressin alone. responders to desmopressin with mono-symp-
Cochrane review included 47 RCTs involving tomatic enuresis (mean age 10.5 years, 70 %
3,448 children, with 2,210 receiving desmopres- males) to desmopressin plus 4 mg tolterodine
sin. All but 10 of these studies involved the intra- versus desmopressin plus placebo for 1 month.
nasal route (no longer available), with the Treatment outcomes were described as either
remaining using oral tablets. Sample sizes of these success (>50 % reduction in wet nights) or no
studies ranged from 10 to 182 patients (mean 73) success. Success was achieved significantly more
62 N.C. Bush
with desmopressin plus tolterodine, 8/18 (44 %) • Dose-related efficacy: Two trials compared
versus desmopressin plus placebo 5/16 (31 %) higher versus lower dose imipramine, with
(Austin et al. 2008). one reporting there was no difference (but not
providing data), while the other showed one
FDA Adverse Events Reporting fewer wet night per week at 25 mg compared
Desmopressin in combination with excessive to 10 mg.
fluid intake can result in hyponatremia, which • Tricyclics versus desmopressin: See section
can lead to brain swelling, seizure, and, rarely, above.
death. However, no RCTs involving its use • Tricyclics versus alarm: See above.
for bedwetting reported these events during the
study period. In 2007, the FDA indicated post- Adverse Events
marketing reports of 61 seizures among users of Twenty-nine trials provided some information
desmopressin nasal spray to treat various medical regarding side effects, but no major adverse
conditions. Thirty-one of these patients had other events, specifically arrhythmia or heart block,
concomitant medicines/diseases associated with occurred (Glazener et al. 2009b).
hyponatremia and/or seizures. Nevertheless, the
FDA recommended against intranasal adminis-
tration for the treatment of primary nocturnal Oxybutynin
enuresis in children.
Oxybutynin monotherapy is no more effective
than placebo for enuresis.
Imipramine NICE guidelines pooled results demonstrated
no difference in patients receiving oxybutynin
Cochrane review found that imipramine was versus placebo to achieve either >90 % (6/16
more effective than placebo for enuresis, with [37.5 %] vs. 5/23 [21.7 %], RR 1.73 [95 % CI
approximately 20–33 % achieving 14 consecu- 0.63–4.69]), or 50–90 % dry nights (6/15 [37.5 %]
tive dry nights during therapy. vs. 8/23 [4.8 %] RR 1.08 [5 % CI 0.46–2.51])
Relapse occurred in approximately 66 % of (NICE 2010).
patients when treatment stopped at 3 months. A crossover double-blinded RCT of 30 chil-
Cochrane review included 58 RCTs involving dren (mean age 10 years, 83 % boys, some previ-
3,721 children. Results were pooled for the various ously treated with imipramine) with primary
tricyclics, which was primarily imipramine but also nocturnal enuresis assigned to placebo versus
included desipramine, amitriptyline, nortriptyline, oxybutinin 5 mg nightly for 4 weeks demon-
viloxazine, trimipramine, mianserin, and clomip- strated no difference in the number of dry nights.
ramine. Study sample sizes were generally small. There was a mean decrease in wetting of 1.9
Various dosing regimens and lengths of treatment nights/week (Lovering et al. 1988).
were used. Key findings included the following:
• Tricyclics versus placebo: There were fewer
wet nights for patients receiving tricylics ver- Alternative Therapies: Acupuncture,
sus controls. Meta-analysis was possible using Hypnosis, Psychotherapy, Chiropractor
data from only three trials, finding an average Adjustment, Homeopathy
of one fewer wet night per week, −0.92 (95 %
CI −1.38 to −0.46). Eleven trials found 21 % No alternative therapy listed here has been
of treated children achieved 14 consecutive found effective for enuresis treatment.
dry nights, versus 5 % on placebo, RR for fail- A 2011 update regarding complementary and
ure 0.77 (95 % CI 0.72–0.83). After stopping miscellaneous interventions for enuresis was per-
therapy, only 4 % who took imipramine versus formed by the Cochrane Incontinence Group.
3 % who took placebo remained dry. Several small, poor-quality trials provide weak
evidence in support of hyponosis, psychotherapy, weeks” after treatment. Their teachers used a
acupuncture, chiropractic, and medicinal herbs different rating scale modified for the study and
(Huang et al. 2011). filled out just before treatment, 10 weeks later
(end of treatment), and another 3 months later.
The enuretic children and 30 of the controls were
Order of Therapy also tested by a psychologist using a novel “self-
image questionnaire” created for the study and a
Synthesizing outcomes data and cost analysis, “neurotic inventory” previously reported in
NICE guidelines recommended, in descending another study of enuretics. There was no differ-
order, the following: ence in patients versus controls on any pretreat-
• Alarm as first-line therapy ment test. Parent ratings after treatment were
• Alarm plus desmopressin or desmopressin significantly better in patients who stopped wet-
alone if alarm is ineffective ting. Teacher scores did not change regardless of
• Desmopressin plus anticholinergic response to therapy. Therapist ratings were
• Imipramine improved in patients who stopped wetting,
significantly different than the “improvement”
during the same time in controls. No children
Impact of Therapy on Self-Esteem who stopped wetting had worsening in adjust-
ment symptoms, but rather were reported to be
One study of enuretics versus matched con- happier and less anxious (Baker 1969).
trols using non-validated instruments to deter- A subsequent study used similar methods but
mine personality attributes and behavioral included more patients, used validated assessment
problems reported that parent and therapist instruments, and had longer follow-up to 1 year
assessment, but not that by teachers, improved after treatment. There were 83 enuretic children
with successful alarm therapy. (male to female ratio 3:1) who had been referred
Subsequent trials using validated instru- at median age 9 years to a child guidance center
ments found parent-rated behavior improved because of their bedwetting who were treated
in patients regardless of treatment outcomes. either with alarm (n = 64), psychotherapy/counsel-
Two trials concluded that successful treating (n = 10), or no treatment (n = 9), and of these
ment of enuresis did not impact psychological 51, 2, and 2, respectively, had success (13 con-
health of the child, although another reported secutive dry nights). Mothers completed a behav-
significant improvement in self-concept. One ioral questionnaire, the children a personality
trial using imipramine found improved behav- assessment, and their teachers a different behav-
ior that correlated with decreased wetting, but ioral rating before and 1, 6, and 12 months after
could not determine if the changes were sec- treatment. There was no difference in the three
ondary to therapeutic success versus euphoric groups in pretreatment or at 1 month posttreat-
effects of the medication. ment ratings. All three showed a decrease in
A study of 30 enuretic children and 60 gender- mother-reported behavioral problems at 1 month
and age-matched controls assessed personality post treatment, which the authors concluded rep-
characteristics and behavioral problems. Median resented either placebo effect (change in parental
age was 8 years (6–12), 20 boys, and enuresis perception because of clinic contacts) or the result
occurred nightly in “more than half.” Of the 30 of repeat testing, but was not due specifically to
with bedwetting, 10 were treated with alarms, 10 enuresis therapy. Similarly, 6- and 12-month data
with scheduled night wakening, and 10 were not showed patients successfully treated continued to
treated. Parents completed (non-validated) rating have decreased mother-reported ratings, but so did
scales to assess personality attributes (confidence, those not achieving “cure.” Consequently, there
anxiety) and behavioral problems (such as tan- was no evidence that enuresis treatment impacted
trums, thumb-sucking) before and “several psychological health (Sacks et al. 1974).
64 N.C. Bush
A RCT enrolled children with enuresis and

allocated them to alarm (n = 66) or no treatment
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Undescended Testes
5
Warren T. Snodgrass
Primary aims in diagnosis and treatment of • While cancer risk doubles if orchiopexy is
undescended testes (UDT): done after age 13 versus before, 69 patients
1. Improve fertility. have to be operated before that age to pre-
2. Preserve testosterone production. vent one tumor in males between ages 13
3. Reduce cancer risk. and 55 years.
Secondary aims: • Surgical reports on orchiopexy rarely state
1. Repositioning the testis into the dependent final testicular position or objectively assess
scrotum without atrophy testicular size. Based on “intra-scrotal”
2. Normal scrotal appearance position, a RCT reported 94 % success with
3. Distinction between UDT versus retractile both traditional inguinal and scrotal orchi-
testes opexy for palpable UDT.
Summary of evidence for these goals: • Meta-analysis found no difference between
• Limited available data suggest paternity open versus laparoscopic orchiopexy for
rates in men with former unilateral UDT nonpalpable testis.
are similar to those of normal men, whereas • A systematic review found a 5 % benefit to
paternity rates are diminished with for- two-stage versus single-stage Fowler-
merly bilateral UDT. Stephens orchiopexy, but cautioned data
• One RCT reported preoperative intranasal quality was poor.
GNRH improved the fertility index (adult • Our review found a single study using a
spermatogonia/tubule) over patients under- parent questionnaire that reported no dif-
going orchiopexy alone. ference in satisfaction between inguinal
• The overall risk that an operated UDT will versus scrotal orchiopexy.
develop cancer is <0.5 %; risk for nonoper- • Surgeons perform approximately two times
ated UDT is unknown. more orchiopexies than the rate of UDT,
suggesting confusion between UDT versus
retractile testes.
W.T. Snodgrass, M.D. (*) UDT is the most common congenital anomaly
Department of Pediatric Urology, University of Texas affecting boys. Three percent of newborns have
an undescended testis, but most subsequently
Dallas, TX 75235, USA descend within the first few months of life, result-
e-mail: warren.snodgrass@childrens.com ing in a prevalence of approximately 0.8 %.
68 W.T. Snodgrass
found descent to have occurred in 44 %, leaving

Prevalence at Birth and Natural unilateral UDT in 94 % and bilateral UDT in
History 6 %, p = 0.03; four considered to descend by 3
months were noted to be reascended at 12
Of term males, 1.5–3 % have UDT. months (Wagner-Mahler et al. 2011).
Presumably stimulated by the postnatal
testosterone surge 50 % or more will descend
by 3 months, with greater likelihood for UDT Prevalence
descent in bilateral versus unilateral cases.
Scorer reported observations in 3,222 term males, Unilateral Versus Bilateral
noting 90 (3 %) had UDT. Descent was specifically
defined as mid-testicular position greater than 4 cm Bilateral UDT occurs in <20 % of cases.
from the superior border of the pubic bone with The prospective study of 7,032 consecutive
downward traction on the testicle. Of these 90, 45 males described above (John Radcliffe Hospital
spontaneously descended during the first month of Cryptorchidism Study Group) reported 99 testes
life into the dependent scrotum 7–8 cm from the remained undescended at 3 months of age, of
pubic bone, and another 22 descended between 6 which 83 (84 %) were unilateral and 16 (16 %)
and 12 weeks of life to 5–6 cm from the pubic bone. were bilateral.
The others remained undescended (i.e., <4 cm below Similarly, the prospective trial of 6,246 males
the pubic bone), comprising 0.7 % of the total study reported 52 cases with persistent UDT at 3
group (Scorer 1964). months of age, unilateral in 94 % and bilateral in
A report from 10,000 consecutive army 6 % (Wagner-Mahler et al. 2011).
recruits in the 1940s stated 80 (0.8 %) either had Prospective evaluation of boys referred to sur-
prior surgery for UDT or had one on physical gical specialists for nonscrotal testis reported
examination (Baumrucker 1946). UDT were unilateral in 90 % and bilateral in
A prospective study of 7,032 consecutive 10 % (Snodgrass et al. 2011).
males examined at birth and again at 3 months
using the same measurements as Scorer reported
a total of 270 (3.8 %) had UDT, 179 unilateral Palpable Versus Nonpalpable
and 91 bilateral cases. At 3 months, 59 % of uni-
lateral and 72.5 % of bilateral UDT had descended Approximately 75 % of UDT are palpable. Of
into the dependent scrotum, p = 0.0004, leaving a the remaining nonpalpable testes, the condition
1.4 % prevalence of UDT. The authors were is unilateral in 90 % and bilateral in 10 %.
uncertain why their rates were higher than those Retrospective review of a clinical series of
of Scorer earlier, but believed they indicated a 1,866 patients operated for UDT reported 447
true increased prevalence of UDT (John Radcliffe (24 %) had a nonpalpable testis, unilateral in
Hospital Cryptorchidism Study Group 1992). 89 % and bilateral in 11 % (Kirsch et al. 1998).
However, another prospective study involving
6,360 term males also using Scorer examinations
did not find this apparent increased prevalence, but Location of the Undescended Testis
instead reported very similar results as had Scorer,
with 2.2 % of newborns and 0.9 % of 3-month-old Palpable
males having UDT (Berkowitz et al. 1993).
Finally, another prospective trial examined Most palpable testes are below the external
6,246 newborn males >34 weeks gestation ring, while a minority are between the internal
using Scorer methodology, reporting 95 (1.5 %) and external rings in the inguinal canal.
had UDT, unilateral in 83 (87 %) and bilateral A retrospective analysis reported surgical
in 12 (13 %). Repeat examination at 3 months location of 488 palpable UDT: 324 (66 %) were
5 Undescended Testes 69
distal to the external ring while 164 (34 %) were A prospective observational study included 75
canalicular (Cendron et al. 1993). patients with unilateral nonpalpable testes who
In a surgical series of 120 consecutive palpable underwent initial laparoscopy, with final diagno-
UDT, only 12 (10 %) were within the inguinal sis of testicular loss in 44 (59 %), intra-abdominal
canal, while all others were in various positions testis in 13 (17 %), and extra-abdominal testis in
below the external ring (Bianchi and Squire 1989). 18 (24 %) (Moore et al. 1994).
Differences in these two reports likely relate
to the surgical approach used to expose the testis.
Manipulation of the cord structures through an Bilateral Nonpalpable
inguinal incision may pull a testis proximally
through the external ring, whereas dissection Bilateral nonpalpable testes are most often both
from below in the scrotum could move a testis viable, with approximately half located intra-
distally through the external ring. abdominally and half extra-abdominally.
Anorchia is found in 5–25 % of patients.
The only prospective study regarding nonpal-
Unilateral Nonpalpable pable testes that distinguishes unilateral from
bilateral cases reported findings in 44 bilateral
Of unilateral nonpalpable testes (comprising nonpalpable testes in 22 patients. A viable testis
90 % of cases with nonpalpable testes), prenatal was found in 40/44 testes (91 %), equally likely
testicular loss has occurred in two-thirds. Nearly in the abdomen (20, 48 %) or inguinal canal (19,
all of these are represented by a scrotal nubbin. 45 %). The others sustained prenatal loss. The
Of the other third having a viable testis, difference in findings in unilateral (mentioned
approximately half are located in the abdo- above) versus bilateral cases was statistically
men and the other half are extra-abdominal significant (Moore et al. 1994).
within the inguinal canal. Reported findings from surgical series for non-
Although nonpalpable testes found to be nub- intersex patients with bilateral nonpalpable testes
bins traditionally have been included in series of are potentially influenced by preoperative hor-
UDT, the underlying pathophysiology is different monal assessment, which can obviate need for sur-
in these cases, as they are presumed to represent gical exploration. Anorchia was diagnosed in 5 and
intrauterine torsion or other vascular compromise 25 % of cases in two series of consecutive patients
of the testis before or during descent. (Moore et al. 1994; Tennenbaum et al. 1994).
Combining two prospective series of consecu-
tive boys with unilateral nonpalpable testes, a
total of 83 nonpalpable testes were evaluated. Of Diagnosis
these, 53 (64 %) had evidence of prenatal testicu-
lar loss, with scrotal nubbins (n = 48), canalicular History and Physical Examination
nubbins (n = 2), or intra-abdominal vanished tes-
tis without extra-abdominal nubbin (n = 3). The A positive birth history for UDT greatly increases
other 30 (36 %) had a viable testis that was extra- the likelihood that a boy referred for evaluation
abdominal (despite examination under anesthe- has UDT rather than a retractile testis.
sia) in 11 (13 %), and intra-abdominal in 19 Since most UDT are unilateral, visual
(23 %) (Snodgrass et al. 2004, 2007). inspection should precede palpation to detect
One-hundred four consecutive males with scrotal asymmetry.
nonpalpable testes, unilateral in 102 and bilateral Assessment of the prepubertal boy with uni-
in 2, underwent laparoscopy. Testicular loss was lateral nonpalpable testis should include mea-
diagnosed in 63/104 (60.5 %), an intra-abdominal surement of the contralateral descended testis
testis in 23 (22 %), and an inguinal testis in 18 for compensatory hypertrophy, which correlates
(17 %) (Diamond and Caldamone 1992). with prenatal testicular loss. Testis length
70 W.T. Snodgrass
≥1.8 cm measured with a ruler has a positive in school-age boys, when testicular retraction is
predictive value of 90 % that the nonpalpable most common (Brown et al. 2004).
testis is not viable. A review of a New York Department of Health
A prospective study of 118 consecutive refer- database for the years 1984–2002 considered
rals reported only 50 % had UDT. Boys younger orchiopexy rates determined by the number of
than 1 year of age and those older than 10 years operations versus live male births. While surgical
old in puberty were more likely to have a correct rates were stable throughout the study period, the
diagnosis by PCPs, versus those 1–10 years of average of 1.4 % operations consistently exceeded
age, who were more likely to have retractile tes- the expected 0.8 % prevalence of UDT (Capello
tes. UDT was predicted by the following: et al. 2006).
• A positive birth history for UDT, OR 21.4 The John Radcliffe Hospital Cryptorchidism
(95 % CI 3.8–120.8). Study Group calculated the orchiopexy rate from
• Scrotal asymmetry (visual inspection before the earlier Scorer report and noted surgery was
palpation), OR 121.3 (95 % CI 14.3 to >999). done twice as often as the UDT rate (1.9 % vs.
Only 6 % of referred boys with a negative 0.9 %). Their own evaluation of newborns and
birth history and visual scrotal symmetry had infants using Scorer’s technique found a higher
UDT (Snodgrass et al. 2011). rate of UDT of 1.4 %, but their orchiopexy rate
In patients 7 months to 11 years with unilat- was also higher, at 2.9 % (John Radcliffe Hospital
eral nonpalpable testis, a scrotal testis measur- Cryptorchidism Study Group 1960).
ing 1.8 cm or greater in length positively
predicts monorchidism in nearly 90 % of cases.
One study of 60 boys with unilateral nonpalpa- Ascending Testes
ble testis reported 14/15 1.8 to 2 cm and
14/16 > 2 cm had monorchidism (Hurwitz and Secondary ascent of a previously normally
Kaptein 2001). descended testis has been proposed to explain
Another prospective study of boys median age higher orchiopexy rates than UDT prevalence.
23 months found 26/30 (87 %) had monorchid- One prospective study using trained nurses
ism for scrotal testis ³1.8 cm, versus 8/10 (80 %) reported testicular ascent in 4 % at 12 months
having a viable testis when the scrotal testis was of age. Another prospective study with a single
<1.8 cm (Snodgrass et al. 2007). pediatrician performing all examinations
Both performed office measurements using reported no testicular ascent at 12 months.
rulers, which may differ from ultrasound mea- Two studies reported ascending testes were
surements of testicular length. There are no pub- bilateral in over 30 % of cases, versus UDT,
lished data regarding ultrasound-determined which is bilateral in <20 % (see above).
compensatory hypertrophy. Spontaneous re-descent of ascended testes
by mid-puberty was reported by two studies in
approximately 60 % of cases.
UDT Versus Retractile Testis A prospective study performed by five “trained
research nurses” within the Cambridge Baby
Orchiopexy rates are approximately two times Growth Study involved longitudinal examina-
the prevalence of UDT. tions in newborn males for testicular position.
A regional policy was adopted in a British UDT were noted in 6 % at birth, declining to 2 %
health trust stating that boys in whom there was at age 3 months, but rising to 6.7 % at 12 months
any doubt as to normal scrotal position of both from 4 % ascending. Continued exams showed
testes at 8 months of age were to be referred to additional new cases of ascending testes, which
surgical specialists for evaluation. When this pol- by 24 months reached 7 % (Acerini et al. 2009).
icy was implemented, the number of orchiopexies However, another prospective study involv-
decreased by 50 %, with most reduction occurring ing 6,246 newborns >34 weeks gestation, with
examinations by the same pediatrician at birth, nonpalpable testis to be 45 % (95 % CI 29–61) and
3, and 12 months using Scorer methodology, 78 % (95 % CI 43–94), respectively. US detected
assigned two controls to each case with UDT. 97 % of extra-abdominal and 38 % of intra-abdom-
None of 170 controls developed an ascended tes- inal viable testes (Tasian and Copp 2011).
tis at 12 months (Wagner-Mahler et al. 2011). Thirty of 118 (25 %) consecutive boys referred
Based on a policy of not operating on boys pre- in one prospective study had scrotal US ordered
senting with possible UDT if a normal newborn by their primary care physician; nonscrotal testes
examination was documented, two studies prospec- was reported in 29. Physical exam found 15
tively evaluated patients diagnosed with ascending patients had UDT, while 14 had descended testes
testes observed without surgery into puberty. (Snodgrass et al. 2011).
One reported findings in 557 consecutive
patients referred for possible UDT at mean age of
7.4 years (0.3–16.5). Of these, 415 (479 testes) MRI for Nonpalpable Testis
were considered from examination to have UDT,
congenital in 116 (129 testes) and acquired MRI was used preoperatively in the evaluation of
(ascending) in 299 (350 testes); 108/350 (31 %) 47 nonpalpable testes in boys ages 1–12 years, and
ascended testes were bilateral. There was com- found to be accurate in 39 (85 %), with a false-neg-
pleted follow-up in 139 patients (164 testes), with ative rate of 4/28 (14 %) and false-positive rate of
spontaneous descent in 98 (60 %) testes; 70 at 4/19 (21 %). All false positives were lymph nodes,
Tanner stage G2, 26 at Tanner G3-4, and 2 at and all false-negative testes were found in the ingui-
Tanner 5. Another 32 testes were confirmed to be nal canal at operation. The 24 MRI-identified testes
undescended at ³Tanner G3 and underwent sur- were found “in the inguinal canal or just proximal
gery, while 14 were lost to follow-up and 21 had to the internal ring” (n = 19), in the abdomen (n = 2),
surgery elsewhere (Sijstermans et al. 2006). or in the scrotum (n = 3) (Kanemoto et al. 2005).
A similar study followed 107 boys (133 tes- MRI and diffusion-weighted MRI were per-
tes) with ascended testes. Of these testes, bilat- formed in 36 boys and 38 testes, in which laparos-
eral involvement was diagnosed in 50 (38 %); 75 copy found 19 extra-abdominal, 11 low, and 4 high
(57 %) of the testes descended; 3 before puberty, intra-abdominal testes (<3 cm vs. >3 cm from
40 at G2, and 32 at G3-4 (Eijsbouts et al. 2007). internal ring), and 4 nubbins. Results were pre-
sented from two radiologists, with the combina-
tion of the two methods giving overall accuracy in
Imaging 92 and 86 %. Considering the observer with 92 %
accuracy, there were no false positives and 3 (8 %)
Genital US is sometimes used by PCPs to confirm false-negative assessments, which were not further
suspicions of UDT before referral to surgical explained except that one was an intra-abdominal
specialists, even though the test does not reliably “atrophic” testis (Kantarci et al. 2010).
distinguish between UDT and retractile testes. In a retrospective study in 26 boys with 29
Meta-analysis of US for nonpalpable testes nonpalpable testes, MRI correctly identified
reported detection in 97 % extra-abdominal 10/12 intra-abdominal testes, 4/6 canalicular
versus 38 % intra-abdominal testes. testes, 4/10 nubbins, and 0/1 scrotal testis, for an
MRI was reported by three studies as hav- overall accuracy of 62 % (Desireddi et al. 2008).
ing 60–85 % accuracy for nonpalpable UDT,
with false-negative rates of 8 and 14 %.
Diagnosis of Anorchia
Ultrasound Basal LH and FSH levels >3× normal are con-

sidered diagnostic for anorchia.
Meta-analysis of 12 studies involving 591 testes MIS was reported in one study to have
reported sensitivity/specificity for US to locate a 92 %/98 % sensitivity/specificity for anorchia.
72 W.T. Snodgrass
Twenty-eight prepubertal boys <11 years of • Intranasal LHRH versus placebo: Nine RCTs
age with bilateral nonpalpable testes had hCG with 1,049 boys reported complete testicular
therapy (3,000 u/m2 BSA injection daily for 5 descent in 19 % versus 5 %, OR 3.59 (95 % CI
days, then 2× weekly for 5 weeks); 21 had an 2.52–5.12).
“adequate” rise in testosterone, and all had viable Age of patients at treatment was not stated
testes at exploration, versus 7 with no rise in tes- (Henna et al. 2004).
tosterone, of which 6 had surgery, with none hav-
ing a viable testis. Six of seven with no testosterone
response had baseline LH and FSH >3× normal Adjunctive Hormonal Therapy
(Jarow et al. 1986).
Nine patients ranging from 10 months to >12 One RCT reported that preoperative intrana-
years with surgically confirmed anorchia had sal GNRH improved the fertility index over
endocrine evaluation preoperatively, including orchiopexy alone.
LHRH stimulation in five and hCG stimulation in A RCT randomized 42 boys (63 inguinal tes-
seven using varied protocols. There was no testes, 21 unilateral and 21 bilateral UDT) with mean
tosterone response to stimulation. FSH was ³3× age 33.5 months (11–100) to 1.2 mg/day intrana-
normal in 5/9 (56 %), with variation based on age sal GNRH for 4 weeks then orchiopexy versus
(Lustig et al. 1987). orchiopexy alone. Intraoperative testis biopsies
One series of 107 consecutive patients with non- were obtained from UDT, with fertility index cal-
palpable testes reported none of 12 with bilateral culated by counting the number of adult sperma-
nonpalpable testes met their criteria of elevated base- tagonia per tubule in at least 80 tubules. Treated
line gonadotrophin levels with negative hCG stimu- patients had a significantly higher mean fertility
lation testing, although 3 were confirmed surgically index of 1.05 ± 0.71 (0.27–3.33) spermatagonia/
to have anorchism (Tennenbaum et al. 1994). tubule versus nontreated with 0.51 ± 0.39 (0–1.17),
One report compared assays for testosterone p = 0.007. Considering only the 21 with bilateral
secretion versus MIS in 17 boys with anorchia. UDT, the 9 treated had a mean fertility index of
Diagnostic sensitivity and specificity for MIS 0.96 ± 0.47 versus 12 untreated with 0.56 ± 0.38
was 92 and 98 %, versus 69 and 83 % for tes- (0–1.12), p = 0.005 (Schwentner et al. 2005).
tosterone. Mean serum concentration of MIS The possibility that hormonal therapy may
was 0.8 ± 0.6 ng/mL in boys with anorchia, harm the testis has been proposed. One retrospec-
which was significantly less than the concen- tive study involved patients managed for UDT
tration of 48.2 ± 42.1 ng/mL in boys with testes over a 5-year period, 1985–1990, during which
(Lee et al. 1997). time 19 were given intranasal GHRH then orchi-
opexy; 8, IM hCG and orchiopexy; and 45, oper-
ated without preoperative hormones. Median
Management fertility indexes were 0.07 (0–0.31), 0.06
(0.0025–0.21) and 0.14 (0–0.86), reported as a
Hormonal Monotherapy significant difference between hormonally treated
versus only surgery groups. However, the num-
Hormone monotherapy results in complete bers of patients lacking any germ cells was the
testicular descent in £14 % of UDT. same in all groups (Cortes et al. 2000). Reasons
A meta-analysis was performed using for hormonal stimulation in some patients and
Cochrane Collaboration methodology to deter- not in others were not stated, nor was the time at
mine efficacy of hormonal therapy for UDT: which surgery was done after stimulation.
• Intramuscular hCG versus intranasal GnRH: An analysis of testis biopsies taken from the
Data from two RCTs comprising 201 patients UDT and the descended scrotal testis in 73 patients
reported complete testicular descent was 25 % compared apoptosis of spermatagonia in 43 with
versus 18 %, absolute risk reduction 7 % preoperative hCG (2 injections/week × 2 weeks,
(95 % CI 0.012–0.170). dose per injection: 250 IU if <12 months of age,
500 IU for 1–7 years of age, 1,000 IU if >7 years Observations that up to 90 % of palpable
of age) versus 30 without injection. Effects of testes have exited the external ring support
hCG were considered for three treated groups, single-incision orchiopexy through the scro-
those operated <1 month, at 1–3 months, and at tum as an alternative. Additional inguinal
3–14 months after last injection. Apoptosis was incision to obtain greater spermatic cord
increased in both the scrotal and UDT in treated length is reported in 0–4 % of cases.
patients at <1 months, but was similar to untreated Single upper scrotal incision was used in 104
patients by >1 month (Heiskanen et al. 1996). consecutive boys aged 2–12 years with 120 pal-
pable UDT. Scrotal orchiopexy resulted in a mid-
to lower scrotal position in 111 testes, and a testis
Orchiopexy Timing in the mid- to upper scrotum in 4. The other 5
required an additional inguinal incision to gain
Orchiopexy is recommended between ages 6 sufficient vascular length for orchiopexy. All testes
and 12 months. were described as viable, without specific mention
One RCT reported UDT had volume less of atrophy with follow-up at 6 months to 3 years
than 50 % of descended testes at 6 months of (mean not stated) (Bianchi and Squire 1989).
age, with subsequent growth in those operated A prospective study analyzed single scrotal
versus those not operated. incision orchiopexy in 114 consecutive patients
Current recommendations for surgery with 148 palpable UDT, accomplished in all cases
between 6 and 12 months are based on the obser- without need for additional inguinal incision. With
vation that spontaneous descent that occurs after mean follow-up of 10 months (3–22), all were
birth does so before 6 months, while decrease in described as palpable within the scrotum, without
germ cell counts can be diagnosed by 1 year of specific mention of either atrophy or low versus
age (AAP 1996). high scrotal position (Callewaert et al. 2010).
A RCT randomized boys with unilateral pal- A RCT assigned 292 children mean age 40
pable UDT to orchiopexy at age 9 months ver- ±10 months with 398 palpable UDT to either
sus 3 years, following them with periodic US scrotal or inguinal orchiopexy between 2007 and
performed at age <1, 6, 12, and 24 months. 2010. Surgical success at 12 months was defined
From birth to 6 months, scrotal testes increased as “intrascrotal testis.” With follow-up in 107
in volume by 89 % without further increase children (146 testes) after scrotal orchiopexy and
through age 2 years. UDT also grew from birth 105 children (141 testes) after inguinal orchio-
through 6 months, but by a significantly less pexy, there was no difference in overall success:
50 %. Initial and 6-month US demonstrated 135/146 (92 %) versus 136/141 (96 %). Nine of
significantly less volume in UDT versus scrotal 201 (4 %) scrotal orchiopexies additionally
testes (median volume at 6 months UDT required inguinal incision (Na et al. 2011).
0.36 mL vs. scrotal 0.53 mL, p < 0.001).
However, further significant growth of the oper-
ated UDT was observed by 2 years (0.36– Nonpalpable Testes
0.47 mL, p < 0.001); this was not seen in the
non-operated UDT (Kollin et al. 2007). Since exploration for nonpalpable testes can
find nubbins, extra-abdominal viable testes, or
intra-abdominal viable testes, several manage-
Palpable Testes ment options are available, and approach can
be tailored by likely findings in specific cases
Traditional orchiopexy includes an inguinal (Fig. 5.1):
incision to mobilize the testis and ligate an 1. Unilateral nonpalpable testes with a con-
associated patent processus vaginalis and a tralateral scrotal testis measuring ≥1.8 cm
separate scrotal incision for testis placement. have a 90 % probability of prenatal testis
74 W.T. Snodgrass
Fig. 5.1 Unilateral non-palpable testis. Findings if laparoscopy performed first. Created with data from (Moore et al.
1994; Diamond and Caldamone 1992)
Fig. 5.2 Unilateral non-palpable testis. Findings are based on the length of the descended testis. Data from (Hurwitz
and Kaptein 2001; Snodgrass et al. 2007)
loss, with a nubbin found in the scrotum in than those with a viable testis, whose contralat-
nearly all cases. Therefore, a scrotal inci- eral testicular length was 1.69 ± 0.09 cm (Hurwitz
sion can be made initially, reserving lap- and Kaptein 2001; Snodgrass et al. 2007).
aroscopy for the few without a nubbin (or A prospective observational study in
testis) in the scrotum or inguinal canal which consecutive patients with unilateral
(Fig. 5.2). nonpalpable UDT underwent scrotal explora-
As discussed above, testicular length tion first followed by laparoscopy reported
³1.8 cm in the contralateral descended testis has testicular absence in 23 boys having a scrotal
a 90 % predictive value that prenatal testicular nubbin in 22 and blind ending vas and vessels
loss has occurred. Patients with nubbins had at the internal ring without a nubbin in the
contralateral testicular length a mean of other. Of the 22 scrotal nubbins, six had blind
2.0 ± 0.56 cm, which was significantly longer ending vas and vessels at or above the inter-
nal ring at laparoscopy, indicating that this stated that “in most cases” those without a viable
finding more often represents the proximal extra-abdominal testis had “attenuated” vas and
extension of torsion after the testis reaches vessels (Moore et al. 1994).
the scrotum rather than an intra-abdominal Retrospective review was done for results of
event (Snodgrass et al. 2004). laparoscopy in 111 boys with 124 nonpalpable
2. Unilateral nonpalpable testes with a contral- testes, reporting that status of the internal ring
ateral scrotal testis measuring <1.8 cm most correlated with findings of viable testis versus
often have a viable testis with an equal likeli- nubbin in those without an intra-abdominal tes-
hood to be found extra- versus intra- tis. In this series, there were 38 intra-abdominal
abdominally. testes, 7 extra-abdominal testes, and 77 absent/
Preoperative ultrasound can detect the vanished testes. Six extra-abdominal testes had a
extra-abdominal testes, which are then widely patent processus vaginalis that allowed
approached either by inguinal or scrotal inci- them to be manipulated back into the abdomen
sion, as with palpable testes. Without preop- for laparoscopic orchiopexy, whereas in one, “no
erative imaging, scrotal or inguinal incision hernia was visualized” but at inguinal exploration
versus laparoscopy is an option. a viable testis with “a small patent processus vag-
Bilateral nonpalpable testes most often are inalis” was encountered (Elder 1994).
found to have two viable testes. Preoperative From these data, if neither an intra-abdominal
ultrasound can be used to detect those that are testis nor blind ending vas and vessels were found
extra-abdominal, or inguinal incision versus on laparoscopy, extra-abdominal exploration
laparoscopy can be done. would be mandated, since neither examination
Inguinal incision provides exposure to identify under anesthesia nor presence or absence of a pat-
scrotal nubbins and extra-abdominal testes, and ent processus vaginalis (open vs. closed internal
after opening the internal ring and peritoneum ring) predicted whether or not a testis would be
allows intra-abdominal inspection and orchiopexy. found. The possible exception would be those with
A retrospective series of 447 nonpalpable testes “attenuated” vessels who might not need further
reported 181 (40 %) were nubbins or vanished, 175 extra-abdominal exploration, but our review did
(40 %) were extra-abdominal, and only 91 (20 %) not find objective criteria for this determination.
intra-abdominal. All were managed inguinally, No RCT evaluates inguinal exploration versus
with 33 standard, 38 one-stage Fowler-Stephens, laparoscopy. The primary disadvantage of lap-
and 4 two-stage orchiopexies. Postoperative fol- aroscopy arises when neither a testis nor blind
low-up in 76 of the 91 intra-abdominal cases found ending structures are encountered, as extra-
55 (72 %) described as having a “good sized” testis abdominal exploration is still needed. Considering
in the mid- to low scrotum versus 9 (12 %) in the all patients undergoing initial laparoscopy in the
upper scrotum and another 12 (16 %) with atrophy, prospective trial by Moore et al., only 32.5 % had
including 26 % of those with Fowler-Stephens either an intra-abdominal testis or blind ending
orchiopexy (Kirsch et al. 1998). vas and vessels, meaning the remainder needed
A prospective analysis of initial laparoscopy in extra-abdominal assessment. Whether or not a
104 boys with 126 nonpalpable testes reported hernia sac extended through the internal ring did
only 33 (26 %) intra-abdominal testes and 8 (5 %) not predict whether an extra-abdominal viable
blind ending vas and vessels. Others had vas and testis or nubbin would be found, as 50 % of the
vessels exiting the internal ring associated with a testes had a closed internal ring, while 20 % of
patent processus vaginalis in 26 of 75 cases, com- the nubbins had an open sac (Moore et al. 1994).
prising 19/38 (50 %) with an extra-abdominal tes- Extra-abdominal exploration after laparos-
tis (meaning the others had a closed internal ring copy traditionally is done using an inguinal inci-
with an extra-abdominal testis) and 7/37 (19 %) sion, followed by a scrotal incision if a testis is
with an extra-abdominal nubbin. In 75 cases, there found. Alternatively, a scrotal incision can be
were vas and vessels exiting the internal ring, lead- used to remove a nubbin or to perform orchio-
ing to an extra-abdominal testis in 38. The authors pexy, without an inguinal incision.
76 W.T. Snodgrass
Intra-abdominal Orchiopexy 1,000/1,126 (89 %) extra-abdominal testes had

surgical success. Fowler-Stephens orchiopexy
Best management when there is insufficient had overall surgical success in 214/321(67 %),
vascular length to deliver the intra-abdominal with no difference reportedly found in staged
testis into the scrotum—staged ochiopexy pre- (43/56 [77 %]) versus single-stage (data not
serving the spermatic cord vessels versus one- or shown) procedures. Two-stage orchiopexy with-
two-stage Fowler-Stephens orchiopexy—cannot out vessel division had surgical success in 180/248
be determined from available data. (72.5 %) (Docimo 1995).
A summary of reported orchiopexies included The RCT by Na et al. described above com-
248 intra-abdominal testes treated with two-stage paring inguinal versus scrotal orchiopexy for pal-
orchiopexy preserving the spermatic cord ves- pable UDT reported success as an intrascrotal
sels, of which 73 % were considered by the vari- testis achieved in 271/287 (94 %) testes, with no
ous authors to be successful. Success for one-stage difference by technique used.
Fowler-Stephens orchiopexy was reported as Meta-analysis compared open versus laparo-
63 % versus success for two-stage Fowler- scopic abdominal orchiopexy using data obtained
Stephens of 77 %. This difference was not con- from two RCTs and five case series totaling 263
sidered statistically significant (Docimo 1995). and 176 cases, reporting no differences in:
To date no RCT compares one-stage versus two- • Testicular retraction, OR 0.6 (95 % CI
stage orchiopexy with spermatic cord division. 0.13–2.72).
No data were found regarding simultaneous • Viable testis, OR 1.61 (95 % CI 0.30–8.52).
bilateral one- or two-stage Fowler-Stephens • Testicular atrophy, OR 1.70 (95 % CI 0.49–
orchiopexy. 5.98) (Guo et al. 2011).
A systematic review was done comparing sin-
gle- versus two-stage Fowler-Stephens orchiopexy,
Outcomes with nine articles for single-stage, 36 for two-
stage, and 16 including both. Pooled estimated
Surgical Success success rates were 80 % (95 % CI 75–86) for sin-
gle-stage versus 85 % (95 % CI 81–90) for two-
Surgical success is usually defined as “scrotal stage orchiopexy, with no differences as to whether
position without atrophy,” with few articles orchiopexy was laparoscopic or open. Despite the
reporting actual scrotal position (high, mid, low) apparent increased success for two-stage orchio-
or objective measurement of testicular size. pexy, quality of the data from which the observa-
One review of series published before 1995 tions were made was low (Elyas et al. 2010).
reported surgical success of 89 % for extra-
abdominal and 74.5 % for intra-abdominal
testes. Fowler-Stephens orchiopexy success Cosmetic Results
was 67 %, while staged orchiopexy without
vessel division was 72.5 %. One study reported parents equally satisfied
No RCT compares intra-abdominal orchio- with cosmetic results of inguinal versus scrotal
pexy with versus without vessel division, or orchiopexy.
one-stage versus two-stage Fowler-Stephens The RCT by Na et al. described above compar-
procedures. ing inguinal versus scrotal orchiopexy included a
Review of published literature identified 64 parent questionnaire with response options of
articles with 8,425 UDT with data that could be “satisfied,” “not fully satisfied,” or “not satisfied”
evaluated to determine surgical success, defined (questionnaire not shown) regarding cosmetic
as “scrotal position and absence of atrophy.” Of results. No parent was “not satisfied,” and only
patients with postoperative evaluations ³6 months, 3 % were “not fully satisfied,” with no difference
420/564 (74.5 %) intra-abdominal testes and in response based on surgical procedure.
Reoperative Orchiopexy was attempted in the remaining 25 based on an

impalpable testis or need for additional vascular
Two retrospective studies reported outcomes of length. In two (8 %) of these cases, scarring was
reoperative orchiopexy via scrotal incision for present between the cord and the inguinal canal,
testicular retraction after prior orchiopexy or impeding the laparoscopy approach. After a mean
hernia repair. Only one (3 %) boy had second follow-up of 22 months (6–32), all 33 testicles
testicular retraction, and there was no atrophy. were within the scrotum. Atrophy (not defined)
A retrospective review of operated patients was reported in four (11 %) patients (two with
from 2005 to 2009 reported 17/687 (2.5 %) UDT laparoscopy, two after the inguinal procedure)
reascended after orchiopexy, of which eight (Tong et al. 2009).
found distal to the external ring were included
for study. In another two cases, a testis ascended
following inguinal hernia/hydrocele repairs. Cancer Risk
Three additional patients failed orchiopexy else-
where, and three had ascent of a testis after her- The overall risk that a previously operated UDT
nia surgery elsewhere, giving a total of 16 will develop a germ cell tumor is less than 0.5 %.
reoperative orchiopexies all for testes distal to Nonoperated UDT are more likely to develop
the external ring and approached by scrotal inci- seminoma, whereas tumors developing after
sion. One required additional inguinal incision orchiopexy are more likely nonseminomas.
and “wide preperitoneal” dissection to gain ade- It is unclear if orchiopexy performed
quate cord length. At mean follow-up of 12 before puberty is protective against cancer
months (3–36), all were reported to have normal development.
scrotal position and no atrophy on physical exam There is a theoretic risk for cancer to
(Karaman et al. 2010). develop in nubbins, since germ cells are found
Retrospective review reported 24 patients in £10 %, but no case has been reported.
mean age 6 years (1–16) undergoing 27 orchio- The overall risk for a germ cell tumor associ-
pexies after prior hernia (n = 13) or orchiopexy ated with UDT was characterized by a study of
(n = 6). Scrotal incision was used if it “could be 16,983 men surgically treated for UDT and then
manipulated near or over the testis,” comprising followed for a mean of 12 ± 7 years (209,984 man-
24/27 (89 %). At mean follow-up of 12 months in years), during which time only 56 (0.3 %) devel-
20 of the 21 patients with scrotal surgery, one tes- oped a germ cell tumor (Pettersson et al. 2007).
tis was high and none were atrophic (Dudley Meta-analysis of seven reported series found
et al. 2011). seminomas developed in 74 % of 121 nonoper-
One retrospective study reported outcomes in ated UDTs that developed germ cell tumors ver-
32 reoperations for UDT (15 high scrotum, eight sus 37 % of 247 previously UDTs repositioned
at external ring, and nine in the inguinal canal). into the scrotum that developed tumors; the oth-
Two inguinal testicles were only able to be ers were nonseminomas (Wood and Elder 2009).
brought down into the high scrotum, and one Two studies conclude orchiopexy performed
patient underwent orchidectomy. Overall, after a before puberty is protective against tumor
mean follow-up period of four (1–7) years fol- development:
lowing the second operation, 29 (93.5 %) testes • In 56 cases of testis cancer in former UDTs,
were scrotal without evidence of atrophy (Ziylan the relative risk was 2.23 (95 % CI: 1.58–3.06)
et al. 2004). when surgery was performed before age 13
Another retrospective study reported out- years, versus 5.40 (95 % CI: 3.20–8.53) when
comes in 35 patients with recurrent UDT after surgery was done after 13 years. Sixty-nine
failed inguinal orchiopexy. Ten inguinal testes patients had to undergo orchiopexy before age
were treated directly with open inguinal redo 13 to prevent one malignancy between ages 13
orchidopexy. Laparoscopy-assisted orchiopexy and 55 years (Pettersson et al. 2007).
78 W.T. Snodgrass
• The other report was a meta-analysis of five Several publications emphasize histological
studies with 80 germ cell malignancies associ- appearance of seminiferous tubules obtained by
ated with UDTs. Although the authors stated biopsy during orchiopexy. While a detailed dis-
prepubertal orchiopexy was protective, their cussion of potential fertility is beyond the scope
finding that surgery after approximately age of this review, it may be noteworthy that two
11 years was three times more likely to be recent reports concern sperm retrieval in men
associated with cancer than when surgery was previously undergoing orchiopexy, with success-
performed earlier was not statistically ful results in over 60 % of cases despite azoo-
significant (OR 3.4 95 % CI 0.7–17.7) (Walsh spermia on semen specimens (Wiser et al. 2009);
et al. 2007). (Haimov-Kochman et al. 2010). Prior orchiopexy
Nubbins are found to have germ cell elements at age <10 years versus later did not impact
in <10 % of cases. A single case found intratubu- results (Wiser et al. 2009). Success in men after
lar germ cell neoplasia (Rozanski et al. 1996), but orchiopexy was the same as in other men under-
no overt malignancies have been reported arising going sperm retrieval without a history of UDT
from a nubbin. (Haimov-Kochman et al. 2010).
Fertility References
Paternity rates for men with previously oper- AAP. Timing of elective surgery on the genitalia of male
children with particular reference to the risks, benefits,
ated unilateral UDT are considered similar to
and psychological effects of surgery and anesthesia.
those of men born with normal testes. Pediatrics. 1996;97(4):590–4.
Paternity rates in those with formerly bilat- Acerini CL, Miles HL, Dunger DB, Ong KK, Hughes IA.
eral UDTs are less than in normal men. The descriptive epidemiology of congenital and
acquired cryptorchidism in a UK infant cohort. Arch
Two articles report successful sperm
Dis Child. 2009;94(11):868–72.
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lar in one to infertile men without prior UDT. U S Army Med Dep. 1946;5:312–4.
Paternity data was obtained in 40 men who Berkowitz GS, Lapinski RH, Dolgin SE, Gazella JG,
Bodian CA, Holzman IR. Prevalence and natural his-
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C. Achieving early surgery for undescended testes:
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quality improvement through a multifaceted approach
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Cendron M, Keating MA, Huff DS, Koop CE, Snyder 3rd
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Duckett JW. Anatomical, morphological and volumet-
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Cortes D, Thorup J, Visfeldt J. Hormonal treatment may Kanemoto K, Hayashi Y, Kojima Y, Maruyama T, Ito M,
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John Radcliffe Hospital Cryptorchidism Study Group. testis. Int J Urol. 2005;12(7):668–72.
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Desireddi NV, Liu DB, Maizels M, Rigsby C, Casey JT, ble undescended testes: comparison with conventional
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80 W.T. Snodgrass
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Hernias and Hydroceles
6
Micah A. Jacobs
The primary reason to operate on hernias is to • Meta-analysis of laparoscopic versus open

prevent bowel incarceration. repair reported significant reduction in
Secondary aims of surgery: metachronous hernia with laparoscopic
1. Avoid recurrent hernia. surgery.
2. Decrease metachronous hernia. • Our review found no data regarding bother
3. Treat bother associated with the hernia. of untreated hydroceles or hernias in
Summary of evidence for these aims: children.
• Incarceration was reported by one case
series in 12 % of patients, decreasing with
age from 39 % in preterm neonates to 6 % Definitions
in teenagers.
• Bowel resection for necrosis is rare, occur- Hydrocele: Fluid distending the tunica vaginalis.
ring in <1 % of incarcerated hernias.
• One prospective longitudinal study reported Communicating hydrocele: A patent processus
84 % of newborn communicating hydroce- vaginalis allows fluid to intermittently distend the
les resolved by 18 months of age. tunica vaginalis.
• Two studies reported 0 and 5 % of commu-
nicating hydroceles observed in children <2 Hernia: Intestinal contents (bowel, omentum,
years of age developed hernias, none with bladder) enter a patent processus vaginalis.
incarceration.
• Recurrent hernia occurs in £4 %, with Incarcerated hernia: Intestinal contents become
meta-analysis finding no difference in open entrapped within the processus vaginalis.
versus laparoscopic repair.
• Meta-analysis of unilateral open repair
found metachronous hernia in 7 %, not pre- Prevalence
dicted by age <2 years versus older, or gen-
der, although left hernias had higher risk. One analysis of consecutive newborn males
undergoing circumcision reported hydrocele in
6 %, with approximately half communicating.
M.A. Jacobs, M.D., M.P.H. (*) Similar data were not found for prevalence
Department of Pediatric Urology, University of Texas of hernia in newborns; review articles cite £5 %
in full-term and £10 % in preterm newborns.
Dallas, TX 75235, USA No data were found for prevalence of
e-mail: micah.jacobs@childrens.com hydrocele/hernia in older children.
82 M.A. Jacobs
A prospective determination of the preva- A retrospective review of 110 infants presenting

lence of communicating hydrocele was made with communicating hydrocele at <18 months of
during 2002 and 2006 among 2,715 consecutive age and initially observed reported 69 (63 %)
neonates, mean age 8 ± 4 days, presenting to a uni- resolved spontaneously in a mean of 9 (2–55)
versity hospital in Nigeria for circumcision. Of months. Only six developed a hernia during obser-
these, 158 (6 %) had 190 hydroceles. Repair was vation, none with incarceration, and of those that
done in 25 patients and 27 hydroceles due to apparently resolved, only two recurred. The remain-
“parental anxiety”; the remaining 163 hydroceles der underwent surgery after mean observation of 9
were further characterized as communicating in months and at a mean age of 14 months for hernia,
75 (46 %) and non-communicating in 88 (54 %). persistent communicating hydrocele after age 1
These 163 hydroceles were bilateral in 69 %, right year and/or for increasing size of the hydrocele.
in 12 %, and left in 19 %. Of the patients, 28 % Age at presentation and history of prematurity <37
were preterm (Osifo and Osaigbovo 2008). weeks did not influence likelihood for resolution.
Our review found no cross-sectional analysis Based on findings, the authors changed their prac-
of consecutive premature and full- term newborns tice to include observation until ³2 years of age
to determine prevalence of hernia. Review articles before surgical intervention (Koski et al. 2010).
quote 3.5–5 % prevalence in full-term newborns Another retrospective review concerned 302
and 9–11 % in preterm infants (Grosfeld 1989). boys >1 year of age (mean 4, median 3, range 1–18)
No data were found for hydrocele/hernia presenting as outpatients with new-onset hydrocele
prevalence in older children. from 1994 to 2002. Of these, 35 % were non-com-
municating, 59 % communicating, and 6 % cord
hydroceles. Repair was done in all but five (3 %) of
Natural History the communicating hydroceles, and three of these
resolved; surgery was done in 35 % of non-com-
Hydroceles municating hydroceles either at diagnosis or after a
median of 8.5 months observation. Of the remain-
Most newborn hydroceles, communicating or ing 70 non-communicating hydroceles, 19 were
not, close spontaneously by 18–24 months, lost to follow-up and 51 were observed, with reso-
with 0 to <5 % developing a hernia (two lution reported by phone (n = 41) or follow-up exam
studies). (n = 8) in 39/49 (80 %) at a mean of 6 months. Of 17
There are no data regarding observation for cord hydroceles, 5 were observed and 3 resolved
communicating hydroceles in patients >2 years (interval not stated) (Christensen et al. 2006).
of age.
In the prospective study of newborn males under-
going circumcision mentioned above, one pediatric Hernias
urologist performed monthly examinations and
took photographs of those diagnosed with hydro- There are no long-term observational studies
cele for 2 years. Spontaneous resolution occurred in of hernias.
135 (83 %), with most resolving by 6 months and The overall incidence of incarceration in
none after 18 months. There was no difference in hernias is £12 %, and is greater in premies
resolution among preterm versus term boys, or and infants than in older children or teens.
communicating versus non-communicating hydro- Bowel resection in patients with incarcera-
celes (63/75 [84 %] communicating hydroceles tion was reported in two case series in £0.2 %.
resolved). Of the 27 persisting at 2 years (1 lost to The long-term clinical course of non-operated
follow-up) progressive enlargement was docu- hernias is unknown, since no longitudinal obser-
mented in 13, while the other 14 remained stable. vation studies have been reported.
No patient developed a clinical hernia, although two A retrospective analysis of 6,361 children with
“found to have a hernia” were excluded from analy- hernias operated by a single surgeon over a
sis (Osifo and Osaigbovo 2008). 35-year period ending in 2004 reported incarcer-
6 Hernias and Hydroceles 83
ation occurred overall in 12 %. Incidence was A prospective study used testicular ultrasound
39 % of 191 premies <36 weeks and 6 % in 143 preoperatively and then at <48 h and 6 months
teens aged 13–18 years. Of a total of 743 incar- following laparoscopic hernia repair to assess vol-
cerated hernias, only 8 % could not be reduced ume and blood flow (resistive index) in 100 boys
preoperatively, only 0.1 % presented with bowel mean age 4 years with 125 hernias. Of these, five
obstruction, and only two patients needed simul- presented with incarceration and were reduced
taneous bowel resection (Ein et al. 2006). with elective repair after 2 days. All testes showed
Another retrospective review specifically com- consistent blood flow, and there was no difference
prised premature infants (gestational age <37 in mean testicular volume between preoperative
weeks) undergoing hernia repair during a 2-year and last postoperative scan (Parelkar et al. 2011).
period from 2006 to 2008. There were 172 A retrospective review of hernias in children
patients, 81 % males, with mean gestational age <2 years of age during a 3-year period included
30.7 ± 3.9 weeks and birth weight 1,428 ± 713 g. 269 patients, of which 98 (37 %) were premature.
Of these, 80 (47 %) were diagnosed in the NICU; Of repairs, 39 (15 %) were emergent (defined as
45 were repaired before discharge and 35 elec- not electively scheduled), and all surgeries were
tively after discharge at the discretion of the sur- open repairs performed by five surgeons.
geon, while the remainder were diagnosed and Testicular atrophy occurred in one patient, while
operated after NICU discharge. Duration of injuries to the vas were documented in three; pre-
observation between diagnosis and surgery for term versus full-term birth, age at surgery, or
those discharged from NICU with a known hernia emergent versus elective repair did not predict
or diagnosed after discharge was not stated. In the these occurrences (Baird et al. 2011).
entire series, incarceration occurred in only eight The retrospective review by Ein et al. (2006)
(5 %), with all successfully reduced without seda- reported 0.3 % testicular atrophy and 0.06 %
tion and none progressing to bowel infarction. Of transection/avulsion of the vas. Of the 16 cases of
these eight, five occurred before discharge from testicular atrophy, 8 (1 %) were associated with
NICU and the other three had incarceration at ini- an incarcerated hernia.
tial presentation (Lee et al. 2011).
A retrospective study reviewed a Canadian
Institute of Health database to compare risk for Ventriculoperitoneal Shunt
incarceration based on waiting time from diagnosis
of hernia to elective surgery during the year 2002– A matched cohort study found that ventriculo-
2003. The overall rate of incarceration was 12 % peritoneal (VP) shunts in children 0–5 years of
in 1,065 patients during a median wait time of age increased risk for hernia development dur-
35 days (interquartile range 17–77 days). Those ing the initial 2 years after placement (HR 20
operated within a median 14 days had a signi- and 11 at years 1 and 2), but thereafter risk was
ficantly lower incarceration rate of 5 % versus equivalent to that of children without shunts.
10 % for median wait time of £35 days (p < 0.001). A nationwide database covering >99 % of the
Additionally, patients <1 year of age had RR 1.75 Taiwanese population was accessed to identify
(95 % CI 1.04–2.93) for incarceration versus those more than 1.5 million children born between 1996
1–2 years of age, as did girls versus boys, RR 2.07 and 2000, from which a study group of 675 less
(95 % CI 1.32–3.23) (Zamakhshary et al. 2008). than 5 years of age who underwent VP shunt were
compared over an 8-year follow-up period to a sex-
and age-matched cohort of 6,704 children without
Testicular Atrophy, Vasal Injury VP shunt. A total of 353 children underwent ingui-
nal hernia surgery, 12 % of those with a VP shunt
Testicular atrophy and/or vasal injury is at a mean time interval of 2 years versus 4 % of the
reported in <1 % of cases, without association to control group. The adjusted HR was 19.67 (95 %
preterm versus full-term birth, age at surgery, CI 9.89–39.12) during the first year after VP shunt
or incarceration. placement, and 11.36 (95 % CI 4.22–30.54) during
84 M.A. Jacobs
the second year, but subsequently was no different invasive repair (number of alternative repairs was
than controls (Chen et al. 2011). not mentioned), used a transperitoneal laparo-
scopic technique with two working trocars to
divide and ligate the sac just distal to the internal
Indirect Versus Direct Hernias ring. Follow-up in 146 patients >1 year after sur-
gery, mean 3 years, found four (2 %) recurrences
The retrospective study by Ein et al. (2006) described (Tsai et al. 2011).
above stated that 64/6,361 (0.1 %) were direct. A retrospective review using a similar laparo-
scopic technique in 315 patients, of whom 50 were
under 1 year of age at repair were analyzed. There
Surgical Management were no conversions to open surgery and with fol-
low-up greater than 1 year in all patients, recurrence
Open Versus Laparoscopic Repair was noted in one (2 %) (Esposito et al. 2010).
A single surgeon analyzed repair in 542 con-
Meta-analysis and two prospective studies com- secutive children, median age 1.6 years (4 days-
paring laparoscopic to open repair report no 14 years), ligating (without dividing) the sac (4–0
differences in hernia recurrence rates (£4 %). permanent monofilament) using two laparoscopic
Unilateral laparoscopic surgery (with sac transperitoneal needle holders. At median follow-
division and ligation) is associated with longer up of 39 months (1–84), recurrence occurred in
operative times, and there are variable results 20 (4 %) (Schier 2006).
regarding differences in postoperative pain Two randomized single-blinded trials com-
versus open repair. pared OHR to LHR with two working trocars.
Laparoscopic hernia repair can be done One performed LHR with sac ligation (n = 47)
using intracorporeal instruments or by percu- versus OHR (n = 42) in children with median age
taneous sac ligation, with no difference in of 6 years (0.65–16) and a unilateral hernia under-
recurrences. going day surgery. Follow-up was >6 months in
98 % and >2 years in 84 %. Recurrent hernia
Open repair (OHR): The retrospective review occurred in three—two LHR and one OHR. The
by Ein et al. (2006) mentioned earlier using high primary study outcome was time to resume nor-
sac division and ligation with mean follow-up of mal activity, which was 2.5 days in both cohorts.
6 months reported recurrent hernia in 84 (1 %), Secondary outcomes included operative time and
with 54 % detected within 1 year, 96 % by postoperative pain before and after discharge.
5 years, and 100 % by 10 years after surgery. Operative time in minutes (mean 33 [15–59]
LHR vs. mean 15 [8–35] OHR) and time
Laparoscopic repair (LHR): This technique can (minutes) in the day surgical unit before dis-
be done either transperitoneally or preperitone- charge (mean 300 [185–635] LHR vs. mean 230
ally with transperitoneal scope placement. The [145–432] OHR) were greater after LHR. LHR
technique has included division of the sac at the was associated with significantly greater
internal ring with suture closure, or suture clo- postoperative pain, which required rescue fenta-
sure of an intact sac. It can be accomplished using nyl analgesia before discharge and ibuprofen on
working ports or by percutaneous suture ligation postoperative day 2 (Koivusalo et al. 2009).
without additional ports. The other series used the same laparoscopic
technique and randomized consecutive patients to
outpatient LHR (n = 41) versus OHR (n = 42). The
Three-Instrument Laparoscopic Repair primary outcome was postoperative pain requiring
acetaminophen, which was less with LHR than
A prospective series of 161 patients, mean age 5.2 OHR. Operative time for unilateral repair was
years (1 month-16 years), undergoing a minimally significantly less with OHR (18 min ± 5.7) than
LHR (23 min ± 6.3), whereas time for bilateral in 2/67 (3 %) versus 7/146 (5 %), p = 0.49. SEAL
surgeries was the same (Chan et al. 2005). recurrences were greater with single purse-string
A meta-analysis of LHR versus OHR involv- ligation versus double ligation (5/35 vs. 2/77,
ing 10 studies (2 RCTs, 1 nonrandomized trial, 7 p = 0.02) (Bharathi et al. 2008).
observational comparative studies) with 2,699 Another retrospective study reported SEAL in
patients reported the following: 221 consecutive children (144 males) at mean
• No differences in hernia recurrences: OR 1.81 age 3 years (9 days–21 years) with mean body
(95 % CI 0.89–3.67). weight 14 kg (2–77). Nonabsorbable suture was
• Longer operative time for unilateral LR: used (size, type not stated). The technique could
WMD 10.23 (95 % CI 8.82–11.64). not be performed in two infants (13 and 80 days
• Reduction in metachronous hernias after LR: of age). Duration of follow-up was not stated;
OR 0.37 (95 % CI 0.20–0.67). two (1 %) developed recurrences at 43 and 161
There were insufficient data to analyze post- days (Chang et al. 2011).
operative pain differences (Alzahem 2011). Consecutive patients (1,107) with a pediatric
inguinal hernia underwent SEAL and were ana-
lyzed retrospectively. Contralateral patent proces-
One-Instrument Percutaneous Sac sus vaginalis (not defined) was found in 20 % of
Ligation with Laparoscopy patients and repaired. Mean follow-up was 36
months (range 9–74 months); six recurrences
Subcutaneous endoscopically assisted ligation were seen (0.54 %) within 2–6 months. All
(SEAL) used a single endoscope with percutane- occurred in boys with hernia ring defects larger
ous sac ligation with either Maxon absorbable or than 2.5 cm, and were reoperated using the same
Ticron nonabsorbable suture (size used not stated) laparoscopic technique successfully. Other com-
through a stab incision over the internal ring. plications were noted in seven cases—one punc-
A retrospective series reported 204 patients mean ture of the iliac artery (which stopped with external
age 2 years (3 days–16 years) with mean follow- pressure), four umbilical hernias, and two suture-
up of approximately 8 months. During the study site abscesses or granulomas) (Li et al. 2012).
period, another 68 patients underwent OHR for
incarcerated hernia that could not be reduced,
difficult laparoscopic visualization, hemody- Contralateral Exploration for Unilateral
namic instability during insufflation, an “extra- Hernia
ordinarily large” hernia, and parent or surgeon
preference (numbers for each indication not Meta-analysis reports approximately 7 % of
stated). Of the laparoscopic cases, eight were unilateral herniorraphies will have a metachro-
incarcerated. Complications occurred in 28/204 nous contralateral hernia.
(14 %), comprising 12 (6 %) hernia recurrences, Risk is not influenced by age at initial repair
10 suture abscesses or granulomas, 3 wound or gender.
infections, 2 umbilical hernias, and 1 femoral Left-sided hernias are more likely than right-
nerve injury. Recurrences were not associated sided ones to develop metachronous hernia.
with suture type (absorbable vs. nonabsorbable) One study found contralateral laparoscopic
(Ozgediz et al. 2007). appearance of the ring (open vs. closed)
A retrospective review compared laparoscopy through the ipsilateral sac did not predict
using two working ports and suture ligation with metachronous hernia.
3–0 silk to percutaneous (SEAL) laparoscopy One study reported that eight contralateral
with suture ligation using 1–0 polyglactin in repair explorations would be needed to avoid one
of 67 and 146 hernias, respectively. Median age hernia.
was 5 years (1–14). One percutaneous ligation Most metachronous hernias occur within 1
converted to open surgery. Recurrence was noted year after initial repair.
86 M.A. Jacobs
Metachronous hernia occurs significantly eral sac. With follow-up to 53 months (clinical
less often after laparoscopic versus open examination at 1 month, annual phone calls
surgery. thereafter) in 222 patients, metachronous hernia
A meta-analysis of unilateral hernia repairs developed in 15 (7 %). Of the 115 with an open
published from 1941 to 1996 that included 35 internal ring at laparoscopy, follow-up in 88
studies with 15,310 children reported 7 % (95 % found a metachronous hernia in 9 (10 %). Of the
CI 0.68–0.72) developed a metachronous con- 127 apparently closed internal rings, follow-up
tralateral hernia. Analysis of potential risk factors in 97 included a metachronous hernia in 4 (4 %),
found the following: p = 0.149 (Maddox and Smith 2008).
• Age <2 years did not increase risk: OR 1.34 Meta-analysis of eight articles reporting con-
(95 % CI 0.91–1.97). tralateral patent processus vaginalis and metachro-
• Male gender did not increase risk: OR 1.15 nous hernia found the contralateral processus was
(95 % CI 0.87–1.53). patent in 21–47 % at laparoscopy. There was a
• Left hernia increased risk: OR 1.49 (95 % CI significant reduction in metachronous hernia
1.23–1.81). associated with laparoscopy (14/1,571, 0.9 %)
Most new contralateral hernias occurred versus unilateral open surgery (72/1,144, 6 %),
within 5 years, with only 1 % presenting with OR 0.4 (95 % CI 0.2–0.7). Number needed to
incarceration (Miltenburg et al. 1997). treat is 19 LHR to prevent one metachronous her-
A subsequent prospective study limited con- nia by OHR (Alzahem 2011).
tralateral exploration to premature babies less
than post-conceptual age 56 weeks in a series of
264 infants and children undergoing unilateral Sutured Versus Skin Adhesive Wound
repair. During follow-up from 36 to 72 months, Closure
only 14 (5 %) developed a metachronous hernia.
These were statistically more likely to occur with Inguinal incisions can be closed using either
initially left-sided hernias, but there was no subcuticular sutures or skin adhesives, with
significant association by gender (although none equivalent functional and cosmetic outcomes.
occurred in females), age <2 years versus older, One RCT compared 70 subcuticular suture
or presentation with incarceration. If contralat- approximations (5–0 Monocryl) to 64 adhesive
eral exploration had been done to those with uni- skin (2-octylcyanoacrylate) closures in children
lateral left hernias, 84 procedures would have of mean age 3.7 years and mean weight 16 ± 0.8 kg.
been done to prevent 11 metachronous hernias. Outcomes were assessed at 6 weeks by the oper-
Eighty-five percent of metachronous hernias pre- ating surgeon using a validated visual analog
sented within 1 year of initial surgery. Overall, scale and an ordinate scale, and by an indepen-
unilateral exploration in this series avoided 153 dent surgeon using photographs. There were no
unneeded contralateral procedures (Manoharan cosmetic differences, and no clinical wound com-
et al. 2005). plications for either group (Brown et al. 2009).
Another prospective study evaluated the role
of laparoscopy (70° or 110° lens) through the
hernia sac in unilateral operations to assess the References
contralateral internal ring. Bilateral surgery was
Alzahem A. Laparoscopic versus open inguinal
only done if this visualization resulted in a bulge
herniotomy in infants and children: a meta-analysis.
and/or crepitance in the groin. There were 299 Pediatr Surg Int. 2011;27(6):605–12.
cases, with 13 (4 %) undergoing bilateral sur- Baird R, Gholoum S, Laberge JM, Puligandla P.
gery. Of the remaining 286, laparoscopy showed Prematurity, not age at operation or incarceration,
impacts complication rates of inguinal hernia repair.
a closed ring in 127 (44 %) and an open ring in
J Pediatr Surg. 2011;46(5):908–11.
115 (40 %), and was not technically feasible in Bharathi RS, Dabas AK, Arora M, Baskaran V.
the remaining 44 (15 %) due to a small ipsilat- Laparoscopic ligation of internal ring-three ports versus
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Testicular Torsion
7
Warren T. Snodgrass, Linda A. Baker,
and Nicol C. Bush
Two primary goals in diagnosis and manage- • Two retrospective studies that defined atro-
ment of testicular torsion: phy as ≥15 % or >50 % volume loss reported
1. Preserve the ipsilateral testis, when it 27 and 13 % occurrence.
remains viable. • We found one case of simultaneous bilateral
2. Prevent contralateral torsion. torsion, and none of asynchronous torsion,
Secondary goals include the following: after the neonatal period. Contralateral
1. Avoidance of risk factors for infertility. orchiopexy is done based on potential risks.
2. Maintain a normal scrotal appearance. • One retrospective review reported recurrent
Evidence for these aims—perinatal torsion: torsion in 4 % of patients after orchiopexy.
• Most case series report no ipsilateral testis • There are few data regarding fertility in men
salvage from neonatal surgery. One reported after torsion. Semen analyses most often are
2 of 30 explored testes had normal size at normal, with oligospermia in 0–35 %.
follow-up. Antisperm antibodies reported in three stud-
• Risk for contralateral postnatal torsion is ies were positive in only 2/80 patients.
not well defined, but case series report neo- • Our review found no article regarding psy-
natal ultrasound to be unreliable to exclude chologic impact of orchiectomy or testicu-
vascular compromise. lar atrophy after orchiopexy for torsion.
• Our review found no data regarding fertil-
ity or psychologic impact of asymmetric
scrotal appearance after perinatal torsion. Prenatal and Perinatal Torsion
Evidence for these aims—torsion in chil-
dren and teenagers: Most prenatal torsion presents as unilateral
• Few objective criteria are described to nonpalpable testis and is managed as a poten-
guide orchiopexy versus orchiectomy, and tial undescended testis (see Chap. 5). Our
there is no agreed-upon definition for atro- review found no report of contralateral post-
phy after orchiopexy. natal torsion in these patients.
Newborns with evidence of recent prenatal
torsion (firm, discolored testis), or neonates
W.T. Snodgrass, M.D. (*) • L.A. Baker, M.D.
N.C. Bush, M.D., M.S.C.S. who develop unilateral torsion postnatally, do
Department of Pediatric Urology, University of Texas have risk for contralateral torsion. Bilateral
Southwestern Medical Center and Children’s Medical torsion is either suspected on preoperative
assessment or encountered despite a lack of
Dallas, TX 75235, USA
e-mail: warren.snodgrass@childrens.com; preoperative findings in most cases.
linda.baker@childrens.com; nicol.bush@childrens.com Asynchronous torsion less commonly occurs.
90 W.T. Snodgrass et al.
Preoperative color Doppler ultrasound and resultant anorchia. Despite an obvious necrotic
erroneously reported blood flow to contral- appearance, six testes were maintained, and all six
ateral clinically normal testes in several atrophied. In eight (35 %) cases, contralateral
reported cases that were found, at explora- exploration/fixation was not done and none had
tion, to have ischemic necrosis. abnormal exams at follow-up (Brandt et al. 1992).
A systematic literature review reported sal- Another retrospective series reviewed 27 neo-
vage (not defined) in 9 % of published cases, nates and 30 testes operated between 2 h and 2
increasing to 22 % with “urgent exploration.” months of age, with orchiectomy performed in
Larger case series (16–27 patients) together 19 due to obvious necrosis. Orchiopexy was
comprising 108 cases report three testes with done in 11/30 testes, with follow-up physical
normal volume after orchiopexy and another examination in 10. Of these 10, 4 were atrophic,
two with partial atrophy. 2 were symmetric to the contralateral side, and 4
No study reported perioperative anesthesia- had partial atrophy. Therefore, salvage was
related morbidity from surgery in newborns. achieved in 6/30 (20 %) testes, of which 2/30
No study reported testis tumor mimicking (7 %) were considered on palpation to be normal
torsion. Scrotal incision is an option, especially (Pinto et al. 1997).
since extravaginal torsion can be identified A third retrospective review found 18 cases of
before the tunica vaginalis is opened, with neonatal torsion, with all having a normal con-
extravaginal dissection to the internal ring or tralateral testis on examination. Each underwent
conversion to an inguinal incision if torsion is urgent exploration (two delayed by transfer from
not found. another facility). No ipsilateral testis was sal-
A systematic review of published literature vaged; 4 (22 %) had asymptomatic contralateral
identified 18 case series reporting ³5 newborns torsion encountered during surgery, each of which
with perinatal torsion, comprising a total of 284 atrophied postoperatively. In two of these four
patients, of which 268 were operated. All but four cases, the contralateral testis was imaged preop-
patients were full-term. Testicular salvage was eratively by US (color Doppler vs. other methods
described in 24 (9 %). Three of these 24 were not stated) and reported to have “good flow”
diagnosed within 2 h of birth and considered to (Yerkes et al. 2005).
be prenatal events, while 10 were diagnosed A retrospective review included 24 neonates,
between 12 and 36 h and the remainder up to 72 h 2 with clinically bilateral torsion, of which 21
after birth. There were 19 cases with bilateral tor- had exploration. Time interval from diagnosis to
sion reported, 6 synchronous; in 7 cases, a preop- operation was not stated. No testis was salvaged.
erative diagnosis of unilateral torsion was found In one case described in detail, a unilateral abnor-
to have bilateral torsion. The authors concluded mal testis first noted on routine exam on “day 1”
from their review that only one case of asynchro- prompted US, which reported normal bilateral
nous torsion was clearly reported. One-hundred blood flow. At exploration on day 3, both testes
six cases were described as emergent operations, were necrotic (John et al. 2008).
with salvage (i.e., detorsion) reported in 23 Still another retrospective review reported 16
(22 %) (Nandi and Murphy 2011). Subsequent neonatal torsions, 13 (2 bilateral) considered to
outcomes from detorsion, specifically atrophy, have occurred prenatally and the other 3 postna-
were not discussed. tally. All prenatally torsed testes were necrotic,
A retrospective series found 23 cases, all ³37 and two that were preserved were atrophied at
weeks of gestational age and all stated to have 3-month assessment. One postnatally detected
abnormal testicular examination at birth. Nineteen testis was salvaged despite absent blood flow on
were operated urgently upon arrival (4 needed color Doppler US, and at 3-month follow-up
NICU stabilization), with 14 undergoing surgery at remained normal (method of postoperative assess-
age 6–12 h. No viable testis was found, and no tes- ment not stated). Timing of surgery after diagno-
ticular salvage occurred. Two had bilateral torsion sis was not mentioned (Kaye et al. 2008a).
7 Testicular Torsion 91
A case report described a newborn with bilat- observed, 2 with positive urinalyses and US diag-
eral hard testes within an enlarged, indurated nosis of epididymitis, 3 with clinical signs of a
scrotum. Color Doppler US showed no flow on torsed appendage, and 3 with normal US. Of the
the left, but central flow on the right. At explora- 113 operated cases, testis torsion was found in
tion, the left was necrotic and was removed; the 31 (27 %), 9 (29 %) of which were removed.
right was blue and was preserved, with follow-up A torsed appendage occurred in 64 (57 %) and
US at 5 months reporting a normal testis (Zinn epididymitis in 12 (11 %) (Murphy et al. 2006).
et al. 1998). Review of 135 patients 1–16 years of age pre-
senting with acute scrotal pain over a 5-year
period beginning in 2003 who all underwent
Torsion in Children and Adolescents exploration, found 89 (66 %) with torsed append-
age, 41 (30 %) with testicular torsion, and 2 (1 %)
Acute Scrotum: Incidence of Testicular with epididymitis (Soccorso et al. 2010).
Torsion Versus Torsed Appendage Another retrospective study used color
or Epididymitis Doppler US to assess the acute scrotum, but per-
formed surgical exploration in all cases with sus-
Several retrospective series report findings pected testicular torsion regardless of US findings.
from “universal” exploration for patients pre- In 298 males, mean age 11 ± 4 years, 62 (21 %)
senting with “acute scrotum.” Generally, had testicular torsion, 168 (56 %) had torsed
torsed appendage testis was the most common appendage, and 24 (8 %) epididymitis (Waldert
diagnosis, found in 32–57 %. Testicular tor- et al. 2010).
sion was found in 21–33 % and epididymitis in If all these five centers identified similar
8–18 %. patients with similar ages and categorized “acute
A retrospective review of universal explora- scrotum” the same, and if all those testes that
tion for “acute scrotum” (not defined) between were detorsed were subsequently healthy (all
1977 and 1995 included 388 consecutive boys unlikely suppositions), then universal surgery
<17 years of age. Findings included testicular would result in five scrotal explorations for each
torsion in 100 (26 %), torsed appendage in 174 testis salvaged.
(45 %), and epididymitis in 38 (10 %). Testicular
torsion occurred most often in the first year of life
and at ages 13–16 years, torsed appendages Clinical Parameters to Predict Testicular
between 9 and12 years, and epididymitis within Torsion
the first year of life. Urine cultures were positive
in 10/21 boys less than 1 year of age, and fever The main differential diagnosis for testicular
was present in 6, diagnosed with epididymitis torsion is a torsed appendage.
(Makela et al. 2007). Patients with torsion tend to be older than
Another retrospective review reported 100 those with a torsed appendage. Three studies
consecutive males, mean age 13.6 years (3 have reported mean ages >12 versus <12 years,
months to 37 years), with acute scrotal pain man- respectively.
aged by exploration without routine imaging. When present, nausea/vomiting increases
Testis torsion occurred in 33 at mean age 15.7 likelihood for testicular torsion.
years, torsed appendage in 32 at mean age 11.6 Two studies reported abdominal pain corre-
years, and epididymitis in 18 at mean age 14.8 lated with testis torsion, while another did not.
years (Hegarty et al. 2001). Studies found pain duration <24 h at pre-
A third unit with a policy for universal explo- sentation predicted testis torsion.
ration for acute scrotal pain or swelling did retro- Three studies report an elevated (“high-rid-
spective review of 121 boys mean age 11 years ing”) testicle most often indicates testicular
(1–14). Of these, 113 had surgery and 8 were torsion.
Five studies report that absent cremasteric 69 % of patients found to have testicular torsion,
reflex most often predicts testicular torsion. versus 8 and 0 % in those with a torsed appendage
Scrotal edema and scrotal erythema do not or epididymitis, OR 30.80 (95 % CI 6.8–139.5).
reliably distinguish between testicular torsion, The Waldert study (2010) found nausea or
torsed appendage, and epididymitis. vomiting in 32 % of torsion cases, versus 3 % for
torsed appendage and 12.5 % for epididymitis,
OR 22.98 (95 % CI 8.76–60.2).
Patient Age A retrospective review of 138 boys with a diag-
nosis of acute scrotum found nausea and vomiting
A retrospective study of 179 patients who under- in 47.4 % of torsion cases, 3.3 % of torsed append-
went scrotal exploration for suspected torsion at age, and none with epididymitis, OR 21.6 (95 %
median age 14 years (0–92), reported there was a CI 4.9–93.4) (Boettcher et al. 2012).
significant difference in the median age of those A prospective 5-month study of 79 boys with
with torsed appendage versus those with testicu- acute scrotum, 8 with torsion, performed multi-
lar torsion or epididymitis (11 vs. 15 vs. 21.5 years). variable analysis of predictive clinical factors and
A cutoff of 12 years of age gave a positive predic- reported nausea/vomiting was significantly associ-
tive value for torsed appendage of 52 % (95 % CI ated with testicular torsion versus all other diagno-
0.66–0.91), whereas patients >12 years were unlikely ses (data not shown) (Srinivasan et al. 2011).
to have this diagnosis (Molokwu et al. 2011). In contrast, the review by Makela et al. (2007)
Another retrospective study reviewed cases described above, which reviewed 388 boys with
undergoing exploration during a 10-year period an acute scrotum, found nausea/vomiting reported
beginning in 1986 (number of patients with acute in 5/100 with torsion versus 3/174 (2 %) and 1/38
scrotum not operated during this period was not (3 %) with torsed appendage or epididymitis.
stated). Of 115 patients, 83 had testicular torsion,
27 a torsed appendage, and 5 epididymitis. Mean
age of those with a torsed appendage was 9 years, Abdominal Pain
versus 14 years in those with testicular torsion or
epididymitis (Jefferson et al. 1997). The Beni-Israel et al. (2010) retrospective review
A study of 135 consecutive boys with acute of children with acute scrotum demonstrated an
scrotum who all underwent surgery reported that increased likelihood of torsion diagnosis when
the median age of those with torsed appendage abdominal pain was present, OR 3.19 (95 % CI
was 9 years (7–11) versus those with testicular 1.15–8.89).
torsion, whose median age was 14 years (3–16) Similarly, the Waldert et al. (2010) retrospec-
(Soccorso et al. 2010). tive review of boys with an acute scrotum who
also underwent scrotal US showed an increased
presence of abdominal pain in torsion cases, OR
Nausea and Vomiting 4.33 (95 % CI 2.13–8.84).
In contrast, the Makela et al. (2007) retrospec-
A review of records in a pediatric emergency tive review of acute scrotum cases did not show
department from 2005 to 2007 found 492 chil- this relationship, with only 7 % of torsion cases
dren with mean age 10.75 ± 5 years evaluated for with abdominal pain versus 7 % of appendiceal
an acute scrotum. In this series, the majority (169, torsion and 8 % of epididymitis, OR 1.01(95 %
32 %) had no diagnosis, with testis torsion in CI 0.39–2.51).
only 17 (3 %). Compared to all other etiologies,
nausea/vomiting increased the likelihood for tes-
ticular torsion (OR 8.87 [95 % CI 2.6–30.1]) Pain Duration >24 h
(Beni-Israel et al. 2010).
The study by Jefferson et al. (1997) mentioned The Beni-Israel et al. (2010) study demonstrated
above found that nausea/vomiting was present in that boys who presented with pain with duration
of less than 24 h were more likely to have testis Another retrospective review from 1997 to
torsion, OR 6.66 (95 % CI 1.54–33.33). 2002 identified 177 boys, mean 9 years (0–18),
Boettcher et al. (2012) similarly found shorter with an acute scrotum, of which testicular torsion
pain duration in the torsion group (mean 17.2 h) was diagnosed in 41 (23 %). Absent cremasteric
versus the non-torsion group (mean duration of reflex was noted in 28/31 (90 %) patients in
pain not reported), OR 4.2 (95 % CI 1.3–13.4). whom it was recorded, versus 30/122 (25 %) of
Soccorso et al. (2010) also reported that pain those with a torsed appendage or epididymitis,
duration less than 24 h was more frequent with p < 0.001 (Karmazyn et al. 2005).
testis torsion (69 %) versus non-torsion (37 %), The previously described study of emergency
OR 3.63 (95 % CI 1.66–7.92). department records by Beni-Israel et al. (2010)
calculated from 17 patients with testicular torsion
versus 475 with other or no diagnoses that abnor-
High Testicular Position mal (absent/ “reduced”) cremasteric reflex had OR
27.77 (95 % CI 7.5–100) for testicular torsion.
The analysis of 17 patients with testicular torsion
by Beni-Israel et al. (2010) discussed above cal-
culated OR 58.8 (95 % CI 19.2–166.6) for tor- Scrotal Reaction
sion versus other diagnoses when the testicle was
observed in a high position. A retrospective review of 90 patients <18 years
A retrospective review of 160 patients with diagnosed with testicular torsion, torsed append-
acute scrotum at mean age 12 years (8 months to age, or epididymitis reported that scrotal erythema/
15 years) between 1970 and 2000 reported an edema was present in 1/13 (8 %) with testicular
elevated testicular position had 83 % sensitivity torsion versus 45/77 (58 %) without testicular tor-
and 90 % specificity for testicular torsion (Ciftci sion, p < 0.007 (Kadish and Bolte 1998).
et al. 2004). The retrospective study by Karmazyn et al.
The report by Murphy et al. (2006) discussed (2005) previously mentioned reported scrotal
above with the policy of universal exploration erythema in 15/40 (37.5 %) boys with testicular
stated that a high testicular position was found in torsion versus 93/127 (73 %) with torsed append-
16/31 (52 %) patients with testicular torsion, ver- age or epididymitis, p < 0.001. However, scrotal
sus 7/64 (11 %) and 1/12 (8 %) with epididymi- swelling was similar between those with versus
tis, OR 9.07 (95 % CI 3.28–25.21). those without testicular torsion: 31/30 (77.5 %)
and 104/131 (79 %), p = 0.6.
Similarly, the review by Makela et al. (2007)
Cremasteric Reflex described above reported scrotal erythema in
16/100 (16 %) boys <17 years with testicular tor-
An absent cremasteric reflex was identified in the sion versus 69/211 (32 %), p < 0.002, with torsed
multivariable analysis by Srinivasan et al. men- appendage or epididymitis, but scrotal swelling
tioned above (2011) to predict testicular torsion did not vary between these etiologies and was
versus other causes for acute scrotum. recorded in <20 % of cases of each.
Absence of the cremasteric reflex was reported The retrospective review by Beni-Israel et al.
to have 92 % sensitivity and 98 % specificity for (2010) stated univariable analysis found scrotal
testicular torsion in the retrospective review by erythema did not distinguish between those with
Ciftci et al. (2004). testicular torsion versus other diagnoses [OR 1.37
The study by Waldert et al. (2010) described (95 % CI 0.47–3.95)] (Beni-Israel et al. 2010).
above that included exploration in all acute scrotum The retrospective study by Waldert et al.
cases reported absent cremasteric reflex in 43/62 described above, in which all patients with acute
(70 %) with testicular torsion versus 24/192 (12.5 %) scrotum underwent surgery, reported scrotal
with torsed appendage or epididymitis, p < 0.001. swelling in 47/62 (75 %) testicular torsions versus
81/192 (42 %) in those with torsed appendage or torsion (n = 8/79) and that absence of all three
epididymitis, p = 0.001. factors could rule out torsion. This was not vali-
Another retrospective review in which all dated in other samples.
patients had exploration found scrotal swelling in
40/41 (98 %) with testicular torsion versus 63/92
(68 %) with torsed appendage or epididymitis, Testicular Ultrasonography
p = 0.001, OR 58.4 (95 % CI 7.83–435). However, to Diagnose Torsion
erythema was present in 15/41(37 %) with tes-
ticular torsion versus 46/92 (50 %) with torsed A multi-institutional study reported high-reso-
appendage or epididymitis, p = 0.2, OR 0.58 lution US to detect spermatic cord twist cor-
(95 % CI 0.27–1.22) (Soccorso et al. 2010). rectly identified 96 % of testicular torsions,
Although scrotal edema and erythema poten- versus 76 % diagnosis by color Doppler of
tially indicate a subacute presentation, neither intra-parenchymal vascular loss.
duration of symptoms at presentation nor findings Several retrospective analyses of color
at surgery (viable versus necrotic testis) in tes- Doppler US report sensitivity/specificity for
ticular torsion with versus without scrotal reac- testicular torsion ranging from 89 to 100 %
tion were stated in any of these reports. and 98 to 100 %.
A multicenter European study compared color
Doppler to high-resolution US for the diagnosis of
Clinical Algorithms testicular torsion in 919 boys, mean age 9 years
(1 day to 18 years) with acute scrotum who under-
Three groups reported algorithms to predict tes- went both examinations. The final diagnosis was
ticular torsion versus other diagnoses based on testicular torsion in 208 (23 %). Of these, color
clinical parameters. The largest prospective study Doppler stated intra-parenchymal vascularization
was conducted in Brazil over a 2-year period iden- was absent in 158 (76 %), but was reported normal
tifying 282 patients with a mean age of 12.1 years to increased in the other 50 (24 %). Color Doppler
(41 with torsion). A 5 variable scoring system findings in the patients without testicular torsion
including scrotal swelling (2 points), hard testicu- were not stated. High-resolution scanning detected
lar mass (2 points), high-riding testis (1 point), and cord twisting in 199 (96 %), while in the remaining 9
absent cremasteric reflex (1 point) could stratify cases it was not seen due to high position in 5 and
patients into low (0–2 points), intermediate (3–4 confused with epididymitis in 4. In the other 711
points), and high risk of torsion (5–7). They vali- patients without testicular torsion, high-resolution
dated their system on a retrospective cohort of 116 US reported no cord twisting in 705 (99 %) and
patients and found that the high- and low-risk cat- was falsely positive in the other 6 with various
egories could predict the presence and absence of findings at surgery (Kalfa et al. 2007).
torsion in all cases (Barbosa et al. 2012). A retrospective study compared color Doppler
The study by Boettcher et al. (2012) identified US findings to surgical exploration in 298 boys,
four factors that were highly predictive of testicu- mean age 11 ± 4 years, with acute scrotum. All
lar torsion: pain <24 h, nausea or vomiting, high patients had US followed by surgery regardless
position of testis, and abnormal cremasteric of radiologic findings. Of these, 62 had surgically
reflex. They reported that presence of two or proven testicular torsion, with color Doppler US
more of those findings included 100 % of torsion correctly predicting the diagnosis in 60 (97 %)
cases at exploration (n = 19), but did not validate and falsely negative in 2 (3 %). Therefore, sensi-
this score on any other sample. tivity/specificity for US to detect testicular tor-
Similarly, Srinivasan et al. (2011) found that sion was 97 % and 98 % (Waldert et al. 2010).
the presence of three factors, namely, absence of A retrospective study considered the use of
cremasteric reflex, nausea/vomiting, and scrotal B-mode US, and color Doppler for those with low
skin changes, could predict all cases of testicular vascular flow, in patients with acute scrotum who
were not considered to have clinical findings of Retrospective reviews report that detorsion
testicular torsion sufficient to warrant immediate within a mean of 4–8 h of symptom onset is
exploration (number undergoing surgery without significantly more likely to result in testicular
imaging was not stated). Of 130 patients <23 years salvage than is later presentation.
of age, 17 had US evidence for torsion, prompting Our review found one article that reported
surgery, with 1 false-negative. Of 110 patients in scrotal erythema associated with a nonviable
which US reported no testicular torsion, 2/85 (2 %) testis.
with follow-up had atrophy indicating missed tor- Two retrospective studies report that nor-
sion. Sensitivity/specificity for color Doppler US mal parenchymal echogenecity by US predicts
was 89 and 99 % (Baker et al. 2000). a viable testis at surgery, versus hypoechoge-
Another retrospective study reviewed 61 boys, nicity and heterogenous parenchyma, which
mean age 8 years (1 day to 17 years), with acute predict a nonviable testis.
scrotum evaluated by color Doppler US. Fourteen
had decreased or absent intraparenchymal perfu-
sion leading to surgical exploration with torsion Duration of Symptoms
confirmed in all cases. Another 12 were operated
for pain, despite normal to increased perfusion, A retrospective review of 186 operations for
and none had testicular torsion. Thirty-three with testicular torsion in boys, median age 14 years (18
normal to increased perfusion were not operated, month to 20 years), reported median pain duration
and at follow-up in 32 “up to 2 years” none had of 5 h (0.5 h to 6 days) in those treated by orchio-
atrophy. In this series, sensitivity and specificity pexy, versus 2.2 days (2.5 h to 2 weeks) for those
of color Doppler US were both 100 % (Gunther with orchiectomy. Of 116 orchiopexies, there was
et al. 2006). follow-up in 90, with 34/116 (29 %) having median
follow-up at 8 months (1–39). Volume loss of
³15 % compared to the contralateral testis was
Investigational Tools to Diagnose seen in 11/90 (12 %) (Sessions et al. 2003).
Torsion Another retrospective study of 86 boys, mean
age 14 years, undergoing surgery for torsion found
Trans-scrotal near-infrared spectroscopy (NIRS) that mean pain duration in the 51 (61 %) with orchi-
was evaluated in 16 males, mean age 18 years, opexy was 4 h (40 min to 12 h) versus 58 h (20 h to
with acute scrotum; non-torsion cases (n = 5) had 5 days) in the 32 with orchiectomy. Of the 51 orchi-
mean testicular oxygen saturations of 61 % in opexies, there was follow-up in 37 at 1 month, with
both the affected and non-affected testis. Testis 2 (5 %) “mildly atrophic” (Jefferson et al. 1997).
torsion cases (n = 11) showed a significant differ- Review of 100 testicular torsions in boys <17
ence with the mean testicular oxygen saturation years of age reported that all 35 operated at £6 h
with the affected testis measuring 40 % compared from onset of pain had salvage, versus 8/16 oper-
to 64 % in the non-affected testis. A cutoff value ated between 6–12 h and 2/51 operated at >12 h
of −11.5 units difference between affected and (Makela et al. 2007).
non-affected testes could distinguish between A retrospective analysis of 97 boys with surgery
torsion and non-torsion cases (100 % sensitivity for testicular torsion found mean pain duration was
and 100 % specificity) (Baker 2011). 8 versus 56 h for those undergoing orchiopexy ver-
sus orchiectomy, and that all with pain for more
than 36 h had orchiectomy (Bayne et al. 2010).
Factors Predicting Testicular Viability Another review of 63 testis torsions in patients
mean age 18 years (11–45) reported no testicular loss
There is no emergency to operate on a dead tes- (either orchiectomy or atrophy >50 % at 3 months) in
ticle. Preoperative factors predicting testicular the 24 operated at <4 h, versus 8/27 (30 %) explored
viability include the duration of symptoms at at 4–24 h and 10/12 (83 %) at >24 h after symptom
presentation and the echogenic pattern on US. onset (Al-Hunayan et al. 2004).
Scrotal Reaction A retrospective review included 61 patients

with clinical diagnosis of testicular torsion, of
Although testicular salvage rates potentially are which 44 underwent immediate surgery, and 17,
different in patients with no scrotal reaction ver- with mean age of 15 years (13–28), had attempted
sus those with erythema and edema, our review manual detorsion, based on the preference of the
found only one report of viability correlated with attending urologist. Initial attempt was to derotate
these findings on physical examination: outwards, but if pain increased or there was resis-
One prospective study of 19 pubertal patients tance to lateral rotation, turning was done inwardly.
with testicular torsion (median 14 years, range The goal was immediate pain relief, which could
12–16) reported that 13/13 patients with non- not be achieved in three who then had surgery.
salvageable testes (necrotic appearance with no The other 14 had elective orchiopexy at mean
active bleeding with incision of tunica albuginea) 12 h (2 h to 3 months), and all testes were reported
had scrotal erythema versus 0/6 patients with sal- as normal without atrophy (not defined) at either
vageable testes. Median time to presentation in exploration or during follow-up at mean 22
the non-salvageable versus salvageable groups months (9–72) (Cornel and Karthaus 1999).
was 96 h (12–168) versus 6 (4–48) (Bush and Another retrospective review of 186 opera-
Bagrodia 2012). tions for testicular torsion reported information
on the direction and number of turns in 162 cases.
Inward twisting occurred in 67 %, and outward
Preoperative US twisting occurred in 33 %; turns ranged from
one-half to three. In 56 cases, manual detorsion
A retrospective analysis was done of color was done, followed by immediate surgery; 18/56
Doppler US done preoperatively in 55 of 79 boys, (32 %) had persistent twisting a mean of 360°
aged 1–17 years, with torsion. Parenchymal het- (180–720) (Sessions et al. 2003).
erogeneity was found in 37/55 (67 %), and all
had orchiectomy; homogeneity was found in 18,
of which 16 had orchiopexy without atrophy (not Intraoperative Tests to Determine
defined) 4 months later (Kaye et al. 2008b). Testis Viability
Another retrospective study reviewed findings
on color Doppler US before exploration for tes- Two prospective studies of young children with
ticular torsion in 16 patients aged 14–40 years. testicular torsion (mean ages <12 years) used a
Of these, seven had orchiectomy, and all were similar protocol of incision through the tunica
diffusely or focally hypoechoic or had parenchy- albuginea ± into parenchyma, followed by
mal heterogeneity. The other nine had normal observation for arterial bleeding within 10 min.
echogenicity and homogenous parenchyma and Orchiopexy was done in those with bleeding,
were salvaged, with none “who returned for fol- with subsequent atrophy in 17–22 %.
low-up” demonstrating subsequent atrophy (not A prospective study involved 19 children
defined) (Middleton et al. 1997). mean age 9 years (0–13) with testicular torsion in
which the tunica albuginea and testicular paren-
chyma were incised deeply for biopsy and warm
Manual Detorsion sponges applied. The surgeon observed for fresh
arterial bleeding for up to 10 min, pexing those
Manual untwisting can be performed to with flow (n = 12) and removing those without.
restore blood flow while awaiting surgery. Follow-up was done using color Doppler US at
Most torsion occurs inwardly, so initial dero- 15 days and 1 year in all undergoing orchiopexy.
tation is from medial to lateral. Atrophy (not defined) was diagnosed in 2/12
One retrospective series reported persistent (17 %) “after a month of follow-up” (Arda and
torsion in 32 %. Ozyaylali 2001).
Another prospective study reported 15 boys, Only three defined atrophy, as volume loss
median age 8 years (6–12), with testicular torsion ≥15 % or >50 % versus the contralateral testis.
who were operated, each having the tunica albug- Orchiopexy was done in 61–71 % of these
inea incised followed by observation for arterial cases, with atrophy reported in from 5 to 45 %.
bleeding for 10 min. Flow noted within 10 min A review of 186 operations for testicular
resulted in orchiopexy in nine; using color torsion found 116 (62 %) had orchiopexy at
Doppler US at follow-up a median of 2.6 years median 5 h (0.5 h to 6 days) after onset of pain.
(0.8–4), atrophy defined as volume loss of 50 % During follow-up (time not clearly stated) in
on the contralateral side occurred in two (22 %) 90 after orchiopexy, atrophy ³15 % contralat-
(Cimador et al. 2007). eral testis volume, which was determined using
A retrospective review was done in 59 boys, an orchidometer, occurred in 11 (27 %)
aged 1–17 years, who underwent surgical (Sessions et al. 2003).
detorsion after a minimum of 6 h of symptoms, Of 83 patients with testicular torsion
who had at least one postoperative follow-up. identified on retrospective review, orchiopexy
Following surgical detorsion, 31 (53 %) with was done in 51 (61 %). Thirty-seven of 51
mean symptom duration of 13 h had improved (73 %) had follow-up at 1 month, with 2 (5 %)
intraoperative “appearance and color” and demonstrating “mild atrophy” (not defined)
underwent orchiopexy. In the other 28 testes (Jefferson et al. 1997).
with a grossly ischemic appearance following In another review of 63 patients, mean age 18
detorsion, a tunica albugineal incision was years (11–45), with surgery for testis torsion,
made along the entire length of the testis; if orchiopexy was done in 52 (82.5 %), of which 7
blood flow to the parenchyma was observed (13 %) developed atrophy (volume <50 % non-
(n = 11, mean duration of symptoms 31 h), the torsed testis measured by US) by 3 months
defect was covered with a vascularized tunica (Al-Hunayan et al. 2004).
vaginalis flap and the testis preserved. Nineteen Thirty-one patients with torsion had mean
underwent orchiectomy for no parenchymal pain duration of 6 h (1 h to 7 day), with orchio-
blood flow (mean symptom duration 67.5 h). pexy done in 22 (71 %). At follow-up (not clearly
Salvage rates were defined as testicular volume stated for torsion patients) one (5 %) had atrophy
of 50 % or greater compared with the normal (not defined) (Murphy et al. 2006).
contralateral testis and presence of flow on In the study by Figueroa et al. (2012) described
Doppler ultrasound. The testicular viability in the section above, atrophy occurred in approxi-
rates were 62.5 % for the orchiopexy group and mately 40 % thought to have “good appearance
55 % of the tunica vaginalis flap group; there and color” after detorsion or parenchymal blood
was no difference in duration of symptoms in flow after tunica albuginea incision.
the salvaged versus atrophied patients (Figueroa A retrospective study identified 65 cases of
et al. 2012). torsion with varying durations of preoperative
symptoms: mean 13 h in those with detorsion
plus orchiopexy, 31 h for detorsion, tunica albug-
Testicular Salvage Rates inea incision plus tunica vaginalis flap, and 67 h
with Detorsion and Orchiopexy in those with detorsion and then orchiectomy.
Decision-making was not defined. Of those with
Our review found few reports with follow-up albuginea incision and grafting, “salvage” (not
to determine if detorsion and orchiopexy defined, postoperative US done “at least 4 weeks”
resulted in salvage or atrophy. postoperatively) occurred in 55 %. “Salvage”
All are retrospective, and criteria used to (determined without systematic postoperative
determine orchiopexy versus orchiectomy US) in those with detorsion plus orchiopexy was
were not stated by any. 62.5 % (Figueroa et al. 2012).
despite scrotal reaction in all patients (Bush and

Risk for Contralateral Torsion Bagrodia 2012).
In the study typically referenced to justify
Contralateral orchiopexy is done by most, delayed prosthesis placement, a survey study of
though not all, surgeons during operations for 488 urologists who were asked to recall the num-
testicular torsion. ber of complications they encountered after tes-
Only one study we reviewed reported syn- ticular prosthesis placement reported
chronous bilateral torsion in a single patient. complications in 87 (16 %) of 527 patients who
Our review found no report of asynchro- had prostheses secondary to testicular torsion.
nous torsion after the neonatal period. While the authors concluded this complication
With unknown risk for contralateral asyn- rate was greater in patients with torsion due to the
chronous testicular torsion, contralateral underlying inflammatory process, these data are
orchiopexy is based on concern for the conse- subject to recall bias (Marshall 1986).
quences of subsequent torsion, especially after
unilateral orchiectomy, the reported high
prevalence of contralateral bell clapper defor- Recurrent Torsion After Orchiopexy
mity, and the assumption that there is little
risk from the procedure to testicular Torsion despite orchiopexy has been reported
function. in both detorsed and contralateral testes, after
One of 41 boys aged 1–16 years was found to orchiopexy using either absorbable or nonab-
have synchronous, asymptomatic torsion of 180° sorbable sutures.
during routine contralateral exploration; it was A literature review reported 20 cases of recur-
treated by detorsion and orchiopexy (Soccorso rent torsion in patients with median age of 16
et al. 2010). years (10–24) that occurred at a median of 15
months (4–72) after initial orchiopexy. Twelve of
20 developed in the contralateral pexed testis.
Bell Clapper Deformity Suture material used was stated in 17 case reports;
15 were absorbable (catgut, polyglactin), and the
Surgical anatomy was described in 25 patients, others were polypropylene and silk. Suture place-
mean age 15 years (12–23), with unilateral tes- ment was only reported by five, ranging from a
ticular torsion and contralateral orchiopexy. Of single stitch to four stitches (Sells et al. 2002).
all 50 testes, 40 (80 %) had bell clapper defor- A retrospective review of testis torsion cases
mity, 8 (16 %) had a long mesorchium between operated between 1991 and 2003 identified 179
the epididymis and testis, and 2 (4 %) had normal patients, mean age 18 years (neonates-45 years),
anatomy, both on the contralateral side (Favorito of which 8 had recurrent torsion at mean age 18
et al. 2004). years (12–30) and 6 months to 23 years after initial
surgery. The method of orchiopexy changed dur-
ing this time: the first three cases had fixation of
Testicular Prosthesis tunica albuginea to dartos with two stitches medi-
ally and two stitches laterally using catgut; the
One study reported successful testicular pros- next four cases used the same method, but substi-
thesis placement at the time of orchiectomy for tuted polyglactin; the final case occurred after
torsion. three sutures of polypropylene (Mor et al. 2006).
One prospective study demonstrated no evi- A survey of pediatric surgeons in the UK elic-
dence of infection or extrusion in 12 consecutive ited response from 83 %; a total of 95 completed
adolescents who underwent placement of a the questionnaire. Fourteen (15 %) used suture-
saline-filled testicular prosthesis within the tunica less fixation in a dartos pouch. The remainder
vaginalis at the time of orchiectomy for torsion, used suture fixation alone (n = 51, 54 %) or in
combination with a dartos pouch or Jaboulay all controls. Of patients, nine had detorsion with
procedure (n = 30, 32 %). Of the 51 using suture bilateral orchiopexy (with testicular atrophy to
fixation alone, 30 used nonabsorbable and 21 length <1 cm in 2), and seven had orchiectomy;
absorbable suture. Four of 95 (4 %) did not pex mean age at surgery was 18 and 20 years for these
the contralateral testis (Bolln et al. 2006). two groups, and follow-up evaluation was done
approximately 3 years later. Mean duration of tor-
sion was 13 h in the detorsion group versus 69 h
Infertility After Torsion in the orchiectomy patients. Mean sperm density
was 132 million/mL in controls, 117 million/mL
Few studies report semen parameters in men in orchiopexy patients, and 29 million/mL follow-
after testicular torsion. Our review of four ing orchiectomy. One patient after orchiopexy
studies included 97 patients, with oligospermia had borderline density of 20 million/mL, versus
reported in 0–35 %. three orchiectomy patients with <20 million/mL.
Antisperm antibodies were tested in 80 There were no differences in motility or morphol-
patients in three studies, with only 2.5 % posi- ogy among the three groups, and antisperm anti-
tive results. body testing done in 12/16 patients was negative
One study with 16 patients reported ele- (Anderson et al. 1992).
vated baseline and stimulated LH and FSH Of 48 potentially eligible patients treated for
levels in torsion patients, whereas another torsion and now with age >16 years, 24 agreed to
with 28 patients found elevated FSH only in 9 further testing at age averaging 21–25 years, and
with torsion symptoms >24 h before surgery. were compared to a control group of 20 men for
Biopsy of the contralateral testis reported vasectomy (age not stated). One semen analysis
for 51 patients in two studies was reported as was done after 2–4 days of abstinence. Nine
abnormal in 47. patients had orchiopexy after mean 7 h ischemia,
and 15 had orchiectomy with mean ischemia time
of 48 h, p = 0.001. Mean sperm density was simi-
Semen Analysis/Sperm Antibodies lar in orchiopexy and orchiectomy patients and
controls, although 3/9 and 3/15 patients had oli-
Fifty-one cases of prepubertal testis torsion with gospermia. Mean motility was normal for patients
a “nonviable testis” replaced in the scrotum from and controls, while morphology was abnormal in
1960 to 1982 included 26 older than age 18 years both patients and controls. Antisperm antibodies
at the time of study. Of these 26, 18 operated at a were analyzed using Immunobead seminal assay
mean age 10 years (2–13) agreed to participate: 5 with no significant differences in patients and
had proven fertility (married with children) and controls (Arap et al. 2007).
the remaining 13 were unmarried without Fifty-five patients out of a total of 123 with
reported fertility. Testicular volume on the testicular torsion between 1971 and 1986 were
affected side was 0–1 mL in all 18. Semen analy- contacted and agreed to the study. Mean age at
sis (one sample following 3 days abstinence) torsion was 21.5 years (12–27), and management
found 3/13 (23 %) with oligospermia <20 million/ was detorsion in 44 and orchiectomy in 11.
mL, and no case with antisperm antibodies by Duration of symptoms before surgery was <2 h in
IgG and IgA specific mixed agglutination reac- 11 and 2–6 h in 29 who all had detorsion, >6 h in
tion testing (Puri et al. 1985). 9, 4 with detorsion, and >12 h in 6 who all had
Thirty-five patients with testicular torsion orchiectomy. All 55 had two semen analyses 2–8
between 1985 and 1990 were identified from chart years later, reported only by WHO criteria as nor-
review; 16 agreed to undergo fertility evaluation. mal in 7, OAT (oligospermia, asthenospermia,
Ten controls were randomly selected from a pool and teratospermia) in 19, and apparently isolated
of semen donors with known fertility. A single decreased motility in 10 and increased abnormal
semen analysis was obtained in 14/16 patients and forms in another 19. Serum from 36 patients was
tested at the time of torsion for sperm antibody found to be increased in all patients and espe-
testing; 2 had positive results, with titers >1:1,064. cially impacting spermatocytes, spermatids, and
Repeat testing 2–8 years later in these patients Sertoli cells, but not spermatogonia and, less
show no sperm antibodies in these two patients, often, Leydig cells (Hadziselimovic et al. 1998).
but new evidence for antibodies in another two
(Hagen et al. 1992).
Fifty-two men, mean age 23 years (17–46), Psychologic Impact of Unilateral
with past history of testis torsion agreed to further Orchiectomy
evaluation 4–10 years later, which included semen
analysis in 13 (selection for these not stated). Of Our review found no study concerning the psy-
these 13, the only 2 with abnormal results also had chological impact of orchiectomy in adolescents.
a history of surgery for undescended testis. Sperm
density in the other 11 ranged from 27 to
150 million/mL (Daehlin et al. 1996). Intermittent Torsion
Three retrospective studies were reviewed that

Hormonal Assays reported orchiopexy for acute, episodic testicu-
lar pain diagnosed as intermittent torsion. One
In the evaluation by Anderson et al. (1992) men- study reported that 10 % developed acute tor-
tioned above, mean baseline and stimulated FSH sion while waiting for surgery, but it did not state
levels were significantly different and highest in the interval.
orchiectomy and intermediate in orchiopexy Due to the retrospective nature of chart
patients versus controls. Mean baseline and stim- review identifying surgical patients, boys simi-
ulated LH levels were significantly elevated in larly diagnosed who did not undergo surgery
orchiectomy versus orchiopexy patients and con- were not included. Therefore, risk for torsion
trols. There was no difference in baseline or stim- and the natural history of non-operated inter-
ulated T levels between these three groups. mittent torsion are not known.
The report by Daehlin et al. (1996) above Two studies reported anatomy in at least
reported mean FSH levels significantly higher in some patients, with 85–100 % bell clapper
the 9 patients with symptom duration >24 h deformity affecting the ipsilateral testis and
(8.3 IU/l [5.9–10.4]) versus the 19 with symp- 80–90 % affecting the contralateral testes.
toms <8 h (3.1 IU/l [2.4–3.6]). There were no dif- Pain resolution was reported for nearly all
ferences in mean LH, T, or prolactin levels. patients with follow-up.
A retrospective review of 30 patients seen
from 1973 to 1982 with episodic pain thought to
Contralateral Testis Biopsy be due to intermittent testicular torsion noted that
3 (10 %) developed acute torsion while awaiting
Contralateral testis biopsy was obtained in 34 of elective orchiopexy (duration of waiting in these
the 55 patients in the study by Hagen et al. (1992) and the other 27 patients was not stated) (Creagh
mentioned above. Of these, 30/34 (88 %) were et al. 1988).
described as abnormal with “desquamated germi- A retrospective review searched for patients with
nal epithelium and Leydig cell atrophy.” history of acute, episodic pain who had orchiopexy.
Seventeen patients, mean age 20 years (14– During an 8-year period ending in 2003, there were
34), had contralateral testis biopsy during surgery 50 patients, mean age 12 years (4–17), with mean
for ipsilateral testis torsion after symptoms a four episodes (1–30) before pexy. Nausea/vomiting
mean of 4 ± 3 h (0.5–11). “Controls” comprised occurred in 12 (24 %), and a horizontal testicular lie
three men (age not stated) with biopsy for sus- in 21 (42 %). Anatomy was described in 28 cases—
pected infertility declared “in retrospect to be 24 with ipsilateral bell-clapper deformity that was
normal.” Specimens were studied for apoptosis, bilateral in 22. Follow-up in 38 patients at a mean of
9 months (1–60) found persistent pain in 1 (3 %) Baker LA, Sigman D, Mathews RI, Benson J, Docimo
(Eaton et al. 2005). SG. An analysis of clinical outcomes using color
Doppler testicular ultrasound for testicular torsion.
Another retrospective review of an 18-year Pediatrics. 2000;105(3 Pt 1):604–7.
period ending in 2006 found 17 patients, mean Baker L. Feasibility of transscrotal near-infrared spectros-
age 14 years, who were operated for acute tes- copy (NIRS) in the evaluation of acute scrotum: a pilot
ticular torsion and gave a history of a mean three human study. American Urological Association
Annual Meeting, Washington, DC, 2011.
prior pain episodes (51 with torsion but no prior Barbosa JA, Tiseo B, Barayan GA, Rosman BM, Torricelli
pain episodes excluded), and another 30, mean F, Passerotti CC, et al. Development and initial
age 12 years, with a mean of two pain episodes validation of a scoring system for diagnosing testicular
who had elective orchiopexy. Of the 30 with torsion in children. J Urol. 2012. http://dx.doi.org/
10.1016/j.juro.2012.10.056.
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none had an apparent transverse testicular lie, Gonzales Jr ET, Reavis KM, et al. Factors associated
while 6 of 12 pubertal adolescents were described with delayed treatment of acute testicular torsion-do
as having this finding. Bell clapper deformity was demographics or interhospital transfer matter? J Urol.
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At mean follow-up at 4 months, no patient with ment of testicular torsion: current practice within the
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graphic criteria of acute scrotum in children: a retro- nosis by house staff. J Pediatr Urol. 2011;7(4):470–4.
spective study of 172 boys. Pediatr Radiol. 2005; Waldert M, Klatte T, Schmidbauer J, Remzi M, Lackner J,
35(3):302–10. Marberger M. Color Doppler sonography reliably
Kaye JD, Levitt SB, Friedman SC, Franco I, Gitlin J, identifies testicular torsion in boys. Urology.
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proposed algorithm for management. J Urol. Yerkes EB, Robertson FM, Gitlin J, Kaefer M, Cain MP,
2008a;179(6):2377–83. Rink RC. Management of perinatal torsion: today,
Kaye JD, Shapiro EY, Levitt SB, Friedman SC, Gitlin J, tomorrow or never? J Urol. 2005;174(4 Pt 2):1579–82.
Freyle J, et al. Parenchymal echo texture predicts tes- discussion 82–3.
ticular salvage after torsion: potential impact on the Zinn HL, Cohen HL, Horowitz M. Testicular torsion in
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Suppl 4Suppl 4:1733–6. J Ultrasound Med. 1998;17(6):385–8.
Varicocele
8
Micah A. Jacobs
The primary reason to diagnose and treat varico- established in both adolescents and adults
celes in adolescents is to prevent future with varicoceles.
infertility. • Use of >10 % or >20 % volume discrepancy
Secondary reasons: as an indication for surgery is not based on
1. Relieve testicular pain. known infertility risks.
2. Correct the abnormal appearance of the • There are limited semen analysis data in
left scrotum with grade 3 varicoceles. adolescents with varicoceles, with two stud-
Evidence for these aims: ies reporting normal sperm densities but
• Evidence that treatment of varicoceles in decreased motility and normal morphology,
adolescents reduces or prevents adult infer- and one reporting decreased sperm density
tility is lacking. but normal motility and morphology.
• Treatment recommendations currently are • Our review found only a single study involv-
based on semen parameters and/or left tes- ing 33 adolescents with preoperative and
ticular volume loss, variously described as postoperative semen analysis that indicated
> 2 mL, >10 %, or >20 %. improved sperm density and motility.
• Most adolescents with varicoceles do not • Three retrospective studies reported pain
have decreased testicular volume compared relief from varicocelectomy in from 68 to
to controls. Up to 50 % of those with 97 %.
decreased left testicular volume on initial • One retrospective study stated that 87 % of
assessment have been reported to have teens had resolution of the scrotal mass
spontaneous improvement within 1–2 years with varicocelectomy.
of observation. Up to 33 % of those with
initial volume differences <20 % are
reported to develop volume discrepancy Prevalence
>20 % within 1–2 years.
• Relationship between any extent of volume Population based studies report varicocele
difference between the left and right testis occurs in <1 % of boys <10 years of age vs.
with impaired semen parameters is poorly 8–19 % of those aged 11–19 years.
Approximately 90 % are unilateral, and
M.A. Jacobs, M.D., M.P.H. (*) three studies found grade 3 to comprise £25 %
Department of Pediatric Urology, University of Texas of these.
A prospective, population based cross-sectional
Dallas, TX 75235, USA study on growth and development examined 6,200
e-mail: micah.jacobs@childrens.com white Bulgarian boys equally distributed into
104 M.A. Jacobs
20 age groups from <1 year to 19 years. All were orchidometer and US (Lambert’s formula). Mean
healthy and were examined by a single physician. right testicular volume was 18 ± 6 cc by orchi-
Diagnosis of varicocele was made by palpation, dometer vs. 18 ± 9 cc by US, p = 0.5; mean left
and Tanner stage was recorded. Prevalence of var- testicular volume was 17 ± 6 cc and 17 ± 8 cc,
icocele was 4 % overall, 0.2 % in boys <10 years, p = 0.8 (Schiff et al. 2004).
and 8 % in those >10 years. Prevalence significantly Testicular volume was also determined using
increased between Tanner stages until stage 3 and Prader orchidometers vs. US (5 and 7.5-MHz trans-
then remained constant. All were left-sided (grade ducers and Lambert’s formula) in 469 men with
not stated) (Kumanov et al. 2008). infertility. Orchidometry overestimated US vol-
Another prospective, population-based cross- umes by approximately 5 ± 3.7 cc, corresponding to
sectional study involved examination for varico- a mean percent difference of 46 % ± 40 % and
cele by two urologists in 1,938 Korean boys aged 54 % ± 45 % for the right and left testes. However,
13–16 years. A varicocele was diagnosed in 320 differences decreased as US-measured volume
(16.5 %), left-sided in 303 (95 %), and bilateral increased, such that there was a strong correlation
in 17. Unilateral left varicoceles were grade 1 in between orchidometry and US (r = 0.7 on right and
51 %, grade 2 in 27 %, and grade 3 in 25 %. The r = 0.746 on the left) (Sakamoto et al. 2007a).
right varicocele in boys with bilateral findings Another study compared the Prader and
was grade 1 or 2 in all cases (Baek et al. 2011). Rochester orchidometers and US to determine
In another prospective population-based study, volume discrepancies of 10, 15, 20, and 25 % in
4,052 Turkish boys aged 2–19 years were exam- 65 males aged 7–24 years old. Considering US
ined by two urologists who reported varicocele in volume to be most accurate, orchidometry over-
293 (7 %), <1 % in boys <10 years of age, and estimated volume a significant 6 cc. Still consid-
14 % in those ages 15–19. Of these, 1 was only ering US to be most accurate, neither
on the right, while 30 were bilateral. All varico- orchidometers correlated well to define volume
celes in boys <10 years were grades 1 and 2, as discrepancies (Diamond et al. 2000).
were all bilateral varicoceles; in 249 boys >10 Testicular volume was determined in nine dogs
years with unilateral varicocele, grades were 1 in using Prader and Rochester orchidometers and US
92 (35 %), grade 2 in 112 (45 %), and grade 3 in using two transducers (6–13 MHz and 5–10 MHz).
45 (18 %) (Akbay et al. 2000). Three formulas to calculate volume from US mea-
Examination in 3,186 Italian boys, mean age surements were compared (formula for an ellipsoid,
13 ± 1.6 years, a varicocele was diagnosed in 609 for a prolate spheroid, and Lambert’s formula).
(19 %), which were grade 1 in 332 (54.5 %), Bilateral orchiectomy was done, and the testes were
grade 2 in 143 (23 %), and grade 3 in 134 (22 %) weighed. In this study, true volume was considered
(Zampieri and Cervellione 2008). weight/density, with density approximately 1.04 g/
mL derived from prior studies in humans and dogs.
Regression analysis showed US had a stronger lin-
Assessing Testicular Size ear relationship to true volume than either orchi-
dometers, both of which overestimated volume.
Animal and human studies directly determin- Lambert’s formula (L × W × H × 0.71) best approxi-
ing testicular volume after orchiectomy indi- mated true volume with both US transducers,
cate that US using Lambert’s formula although there was no significant difference between
(L × W × H × 0.71) best correlates with true the three formulas tested (Paltiel et al. 2002).
volume. These methods were then used in a study of
One clinical study found no difference in human adult testes removed for androgen ablation
volume determined by orchidometry vs. US, with true volume determined by water displace-
while two others reported that orchidometry ment. Again, US volumes calculated by any of the
overestimates testicular volume. three formulas were more accurate than either of the
A prospective study evaluated 159 consecu- orchidometers, and Lambert’s formula best approx-
tive men presenting for infertility using both an imated true volume (Sakamoto et al. 2007b).
8 Varicocele 105
cele had testicular size discrepancy, whereas 24

Prevalence of Testicular Volume (10 %) of 249 boys >10 years of age with unilat-
Discrepancy eral varicocele did (Akbay et al. 2000).
Two population-based studies reported that

most adolescents with varicoceles do not have a Semen Analysis
left testicular volume discrepancy, defined as
> 2 mL and/or >10 % difference compared to There are few semen analysis data in adoles-
the right testis. cents with varicocele.
One reported volume difference by varico- One study found decreased sperm density
cele grade: 4 % without varicocele, 12 % with and motility, but mean values were still within
grade 1, 27.5 % with grade 2, and 37.5 % with WHO guidelines for fertility. Two studies
grade 3. reported no difference in sperm concentration,
Two population-based studies compared but decreased percent motility and normal
testicular volume in varicocele patients vs. morphology in varicocele patients vs. controls.
boys without varicoceles. One found no differ- One matched cohort study reported mean
ences for either mean left or right testis vol- left testicular volume significantly decreased
ume. The other reported that boys with vs. controls. Mean sperm density was similar,
varicoceles had normal mean right testicular while percent motility and normal morphol-
volume but decreased left mean volume begin- ogy were reduced in patients.
ning at age 14 and persisting through age 19 One retrospective review with 15 varicocele
years (end of study period). patients found decreased sperm density in half
The prospective cross-sectional examination the boys with <10 % left testicular volume dis-
of 6,200 Bulgarian boys aged 0–19 years men- crepancy and all those with volume discrepancy
tioned above measured testicular size using Prader >20 %, but normal motility and morphology.
orchidometers. All varicoceles were left-sided, Our review found no other studies that cor-
and mean left testicular volume was decreased related semen analysis with testicular volume.
compared to normal boys beginning at age 14 and As discussed below, correlation of infertility
remaining less through age 19 years (end of with testicular volume discrepancy of any
study). Mean right testicular volume was the same extent is poorly established in adult males with
in teens with varicocele vs. non-varicocele teens varicoceles.
(Kumanov et al. 2008). A prospective study included 360 adolescents,
The prospective cross-sectional examination mean age 15.7 ± 0.8 years, of which there were
of 1,938 Korean boys described above also used 100 with grade 2 (n = 72) or grade 3 (n = 28) vari-
Prader orchidometers but found no significant coceles. Tanner stage for the 360 was 5 in 66 %
differences in either mean left or right testicular and 4 in 31 %. Testicular volume was determined
volumes between 486 (which would be ³13 % in by orchidometers, and semen samples (number
their data), the left testicle was smaller in 4 % not stated) were obtained in 227. Findings on
without varicocele, 12 % with grade 1, 27.5 % semen analysis were as follows:
with grade 2, and 37.5 % with grade 3 varicoceles Mean sperm density was significantly less in
(OR 3, 7, and 9, respectively) (Baek et al. 2011). those with grades 2 and 3 varicoceles:
The prospective evaluation of 4,052 Turkish • No/grade 1: 88 ± 76 million/mL
boys referenced above found a total of 293 (7 %) • Grade 2: 50 ± 52 million/mL,
had a varicocele. Examination was performed by • Grade 3: 37 ± 41 million/mL, p = 0.003
two urologists, determined testicular volume Percent motility was also reduced in grades 2
using Prader orchidometers, with a volume dis- and 3 varicoceles, but values were still above
crepancy defined as >2 mL or >10 %. None of the WHO fertility standards.
14 boys less than 10 years of age with a varico- Normal morphology was not reduced.
106 M.A. Jacobs
Testicular volume discrepancy was defined as as without asymmetry vs. 30 % (20–61) in the five
>10 %, and diagnosed in 42 % with grade 2 and with asymmetry. A single semen specimen was
52 % with grade 3 varicoceles vs. 11 % in those obtained in all patients. Mean concentration in
without varicocele. Semen analysis in those with boys with testicular volume difference <20 % was
grades 2 and 3 varicoceles, with and without 26 million/mL vs. 3 million/mL in those with
10 % testicular volume difference, was not >20 %, p = 0.04, whereas mean percent forward
reported (Mori et al. 2008). motility and percent normal morphology were not
A cross-sectional study of 2,100 boys aged significantly different. Furthermore, 5/10 with
10–20 years old identified those with a varicocele <20 % volume difference had semen parameters
and selected 38 boys aged 17–19 years and Tanner (density and forward motility) below normal
stage 5 with grades 2 or 3 left varicocele, comparing WHO adult criteria, as did all those with >20 %
them to 36 similar boys without varicocele. Testicular testicular volume difference (Keene et al. 2012).
volume was determined by US, and all provided
two semen samples with the following results:
• Mean right testicular volume was similar Natural History of Testicular Growth
between controls and patients (18.7 ± 5 cc vs.
17.4 ± 4.6 cc). Testicular volume changes during pubertal
• Mean left testicular volume was significantly growth, and patients with varicoceles potentially
less in patients (18.3 ± 4.5 cc vs. 14.4 ± 4.3 cc, can spontaneously resolve left volume discrep-
p = 0.01). ancy observed at initial evaluation, or develop
• Sperm density was similar in controls vs. volume discrepancy not initially present.
patients (55.7 ± 36 million/mL vs. 52.9 ± 30.6 One prospective and two retrospective
million/mL). reviews reported 25–50 % of left testes with
• Percent motility and normal morphology were volume discrepancy >10–20 % had improve-
less in patients (Paduch and Niedzielski 1996). ment to <10–20 % within 12–24 months.
Another retrospective review compared semen Development of volume discrepancy >20 %
analyses in 31 adolescents, 14–20 years old, with occurred in 9 % of 559 boys at mean time of 29
left varicocele grade 1 in 8 (26 %), grade 2 in 15 months in one observational study. Several
(48 %), and grade 3 in 8 (26 %) to semen analy- retrospective studies reported 0–33 % of
ses in control men, mean age 34 years, who patients with volume discrepancy <20 % pro-
fathered a child within 1 year and had no varico- gressed to >20 % during 12–24 months.
cele, and to infertile men, mean age 32 years, One retrospective study reported outcomes
with left varicocele: in 19 adolescents with grade 1 varicoceles, of
• Sperm concentration was not significantly dif- which 8 developed >20 % volume discrepancy
ferent between groups; adolescents with vari- during 4 years follow-up despite stable varico-
coceles having mean 63 ± 60 million/mL. cele grade in 6.
• Both motility and normal morphology were
reduced in adolescents with varicocele com-
pared to controls. Spontaneous Resolution of Testicular
• There were no differences in semen parame- Size Discrepancy
ters between adolescents with varicocele and
adults with varicocele and infertility (Andrade- One prospective study allocated 27 adolescents,
Rocha 2007). median age 14.5 years (7–16), with left varico-
A retrospective review compared ten adoles- cele and US-measured testicular volume discrep-
cents with left varicocele and no testicular volume ancy >20 % to observation for 12 months. Eight
discrepancy by US to five with volume difference (30 %) resolved to <20 % (Spinelli et al. 2010).
>20 %. Mean age was similar at 15 years (12–17), One retrospective review of 543 varicocele
and all had grade 2 or 3 varicoceles. Differential patients managed between 1994 and 2008
testicular volume was 7 % (0–17) in those defined identified 181 at median age 14 years (range not
8 Varicocele 107
stated) who were observed after initial diagnosis originally and 20 (33 %) of 61 with initial asym-
and had at least one follow-up measurement of metry 10–20 %.
testicular volume (most the others apparently had A retrospective chart review identified 117
surgery). Measurements were performed by US patients with varicocele presenting at mean age
in 143 and orchidometer in 38. Median time 13 years (7–18). Testicular volume discrepancy
between initial and final examination was 12 was defined as ³15 % difference with measure-
months (interquartile range 8–21). ment using calipers, and was found initially in
At initial examination, 54 (30 %) had discrep- 10/33 (30 %) patients with grade 2 and 38/84
ancy <10 %, 61 (34 %) had asymmetry of (45 %) with grade 3. Of the remaining 69, vol-
10–20 %, and 66 (36 %) had >20 % volume dis- ume discrepancy developed in 12/50 (24 %)
crepancy. At final measurement, 59 (33 %) had with follow-up at a mean of 14 months (5–22),
less than 10 % volume difference, representing occurring in 3/16 (19 %) patients with grade 2
no change in 27, reduction from 10 to 20 % in 20, and 9/34 (26 %) with grade 3 (Thomas and
and improvement from >20 % in 12. Elder 2002).
Therefore, at a median follow-up of 12 months, Another retrospective review analyzed 89
decrease in volume discrepancy from >10 to adolescents, mean age 14 ± 2.7 years, with grades
<10 % occurred in 32/127 (25 %). Of the 66 with 1–3 left varicocele and <15 % testicular volume
initial volume discrepancy >20 %, 31 (47 %) had discrepancy by US or orchidometry, who were
<20 % at median 12 months reexamination (Poon observed for a median 27 months (range not
et al. 2010). stated). Fifty-two (58 %) remained with <15 %
Another retrospective study identified 33 patients volume difference, and 37 progressed—13 (15 %)
at median age 13 years (9–16) with a varicocele that to difference of 15–19 % and 24 (27 %) to >20 %
was grade 1 in 1, grade 2 in 11, and grade 3 in 21. (Korets et al. 2011).
Of these, 14 had volume discrepancy >20 % by US In another retrospective review, 11 of 33 patients
at diagnosis, of which 7 (50 %) had improvement to with varicocele diagnosed at median age 13 years
<20 % asymmetry during observation a median of (9–16) had initial testicular volume difference
2 years (0.5–5) (Preston et al. 2008). <20 %. During follow-up, a median of 2 years (0.5–
5), none progressed to >20 % (Preston et al. 2008).
A retrospective review identified 21 adoles-
Development of Size Discrepancy cents, mean age 12.5 ± 0.4 years, with grade 1 left
During Observation varicocele who were observed 4.8 ± 0.3 years.
Two of these had testicular volume discrepancy
A longitudinal observational study enrolled 609 >10 % determined by orchidometry. Of these
patients found during school screening with vari- varicoceles, 4 (19 %) resolved, 13 (62 %)
cocele, grade 1 in 332 (54.5 %), grade 2 in 143 remained stable, and 4 (19 %) progressed to grade
(23 %), and grade 3 in 134 (22 %). Of these, 40 2. Of the 19 initially symmetric testes, 8 (42 %)
(7 %) had >20 % volume discrepancy at initial developed volume difference >10 %, 2 of the 4
diagnosis and underwent surgery. Follow-up with progression to grade 2 and 6 with stable
occurred in 559 observed for <20 % testicular grade 1 varicocele (Shiraishi et al. 2009).
asymmetry on initial measurement, with 52 (9 %)
developing >20 % volume discrepancy at a mean
of 29 ± 3 months, occurring only in those with Varicoceles and Fertility in Adults
grades 2 and 3 (Zampieri and Cervellione 2008).
The retrospective review by Poon et al. (2010) According to the Centers for Disease Control,
mentioned above performed a follow-up exami- approximately one-third of men with male
nation at a median 12 months after the initial factor infertility have a varicocele.
assessment and found that progression to >20 % Infertile men with varicocele have been
size discrepancy occurred in 37/115 (32 %), com- reported to have decreased left testicular volume
prising 17 (31 %) of 54 with <10 % discrepancy in some retrospective reviews but not in others.
108 M.A. Jacobs
A WHO study reported that mean left tes- presented to 34 centers worldwide underwent
ticular volume was significantly less than mean standardized evaluation that included testicular
right volume in men with varicoceles, but still volume measurement using Prader orchidometers
one-third of men with varicoceles had normal and two semen analyses:
semen analysis. • 3,468 men had a normal semen analysis, of
A retrospective report of 611 infertile men which 396 (12 %) had a varicocele that was
with unilateral varicocele found 50 % had left grade 2 in 174 and grade 3 in 80.
testicular hypotrophy >3 mL, but mean motile • 3,626 men had an abnormal semen analysis,
sperm density was normal at 80 million/mL. of which 857 (24 %) had a varicocele that was
One report indicated total testicular vol- grade 2 in 374 and grade 3 in 191.
ume (right + left testicular volume) < 30 cc cor- • Men without varicocele had symmetric mean
related with diminished sperm density in right and left testicular volumes (18.8 mL left
infertile men. and 19.0 mL right).
One study found significant postoperative • Men with varicoceles had mean testicular vol-
increased left testicular volume in men at a ume significantly less than the right (18.5 mL
mean age 26 years, which would indicate that left vs. 19.5 mL right, p < 0.001).
“catch-up” growth may not be restricted to Total testicular volume was lower for each
adolescents. grade of varicocele, regardless of normal vs.
Cochrane review of eight RCTs involving abnormal semen analysis, and it was less in men
varicocele intervention for subfertility with abnormal vs. normal semen analysis.
reported no benefit. However, of 1,253 men with varicoceles identified
One subsequent RCT found infertile varic- because of an infertility assessment, 32 % had
ocelectomy patients had improved postopera- normal semen analyses despite palpable/visible
tive semen parameters and significantly greater varicocele and decreased left testicular volume
spontaneous pregnancy rates compared to (WHO 1992).
non-operated infertile men with varicocele. Another study involved 43 men, mean age 26
years (17–40), with left varicocele (fertility
status not stated) who had testicular measure-
Varicocele Prevalence in Infertile Men ments by US and semen analysis pre-and post-
varicocelectomy at 1 year. There were 6 grade 1,
The Division of Reproductive Health of the 16 grade 2, and 21 grade 3 varicoceles, of which
Centers for Disease Control and Prevention ana- 2 were bilateral. The authors stated that “more
lyzed data from the 2002 National Survey of than 60 %” had decreased left testicular volume
Family Growth, in which 4,109 sexually active compared to the right (data not shown), but there
men were questioned using structured interviews was a significant increase in mean left testicular
regarding infertility. A total of 308 (7.5 %) volume post-varicocelectomy (13.4 ± 4.4 ccm
reported at least one physician visit for infertility, [4–24] vs. 14 ± 4.5 ccm [4–25]). Similarly, sperm
of which 18 % (95 % CI 12.9–24.8) were diag- count significantly increased from 38 ± 33
nosed with a male factor problem. Of those with million/mL (2–80) to 48 ± 34 million/mL (5–60)
a diagnosis, 6 % (95 % CI 2.6–13) had a varico- (Zucchi et al. 2006).
cele (Anderson et al. 2009). A retrospective review considered 79 fertile
men with varicocele, 71 infertile men (>1 year
duration) with varicoceles, and 217 fertile men
Prevalence of Testicular Size without varicocele (unilateral vs. bilateral varico-
Discrepancy celes, and varicocele grade were not stated). Both
left and right mean testicular volumes were
Nine-thousand thirty-eight men reporting significantly less in infertile men with varicocele
infertility of at least 12 months’ duration who than in fertile men with or without varicocele (left
8 Varicocele 109
testis infertile men 17.6 ± 8.9 cc vs. fertile men tomy. Varicoceles were unilateral in 106 (73 %)
with varicocele 21.6 ± 7.8 cc and 23.4 ± 8.3 cc and bilateral in 39, comprising grade 1 in approxi-
without varicocele; right testis infertile men mately 40 %, grade 2 in 32 %, and grade 3 in
18.7 ± 8.3 cc vs. fertile men with varicocele 28 %. At follow-up of 12 months, spontaneous
25.2 ± 13 cc and 24.9 ± 10.7 cc without varico- pregnancy occurred in 14 % observed vs. 33 %
cele). There was no significant difference in left or treated patients, OR 3.04 (95 % CI 1.33-6.95) with
right testicular size in fertile men with vs. without number needed to treat five patients (95 % CI
a varicocele (Pasqualotto et al. 2005). 1.55–8.99). No changes in semen parameters from
Another study compared 143 men with a left baseline were noted in observed patients, whereas
varicocele—123 with infertility vs. 20 that were the mean of all parameters improved significantly
fertile (means to select fertile men with varico- in operated patients (Abdel-Meguid et al. 2011).
cele were not stated). There was no significant Prior to this study, Cochrane review included
difference in the prevalence of decreased left tes- eight RCTs, stating that one excluded men with
ticular volume at any reduction from 5 to 35 % sperm counts <5 million/mL and another at <2
(Sakamoto et al. 2008). million/mL, and three specifically concerned
A retrospective study included 611 men, mean subclinical varicoceles. Pregnancy rates was the
age 34 years (19–55), with infertility and unilat- outcome, with pooled analysis demonstrating OR
eral varicocele. Left testicular hypotrophy was 1.10 (95 % CI 0.73–1.68), indicating varicocele
defined as volume discrepancy >3 mL by orchi- treatment was no better than no treatment (Evers
dometer, and was diagnosed in 305 (50 %). et al. 2009).
Semen analyses were “performed in the standard
fashion” (number of studies per patient not
stated). Mean total motile sperm counts were Varicocelectomy in Patients <18 Years
significantly less in patients with vs. without of Age
hypotrophy, but both were within normal range
by WHO criteria, 80 ± 5 × 106 in those with Reported indications for varicocele therapy
hypotrophy (Sigman and Jarow 1997). include testicular volume discrepancy, abnor-
A study determined testicular volume in 486 mal semen parameters, pain, and cosmesis.
infertile Japanese males, median 33 years of age One cohort study allocated adolescents with
(23–51), using orchidometers and correlated varicocele and testicular volume discrepancy
global volume (right and left) with semen analy- >20 % to varicocelectomy vs. observation for 1
sis (two samples collected after 3–7 days absti- year, reporting left testicular growth to <20 %
nence). Total testicular volume was categorized asymmetry in significantly more operated
into ten groups ranging at 5-mL intervals from patients, 85 % vs. 30 %.
<10 mL to >50 mL. Median volume was 32 mL Retrograde sclerotherapy technically cannot
(5–60). Decreased sperm density occurred at vol- be performed in from 10 to 20 % of cases due to
umes <30 mL, and decreased motility occurred at the venous anatomy. Of those able to be sclero-
volumes < 45 mL (Arai et al. 1998). sed, varicocele resolution is reported in approxi-
mately 80–90 %. Scrotal pain, thought secondary
to phlebitis from the sclerosing agent traveling
Fertility After Varicocele Surgery distally to the pampiniform plexus, occurred in
7–15 % of treated patients. Recurrence was
A RCT randomized 145 married men with infer- reported by two studies in 8 and 21 %.
tility for >1 year with palpable varicoceles and at Antegrade sclerotherapy was described in
least one abnormal semen parameter (concentra- three studies in adolescents, with only one
tion <20 million/mL, progressive motility <50 %, patient in whom a vein could not be cannu-
normal morphology <30 %) to either observation lated. Persistent varicocele was reported in 2
(n = 72) or subinguinal microscopic varicocelec- and 7 %.
110 M.A. Jacobs
Open vs. laparoscopic varicocelectomy was was used, and mean procedure time was 50 min
reviewed by meta-analysis, finding a 5 % persis- (35–75). Pampiniform phlebitis occurred in 11/72
tent varicocele rate and 9.5 % development of (15 %) injected patients, attributed to the scleros-
hydrocele that was not different between the two ing agent reaching the scrotal aspect of the vari-
methods. Analysis reported that artery-sparing cocele and causing scrotal swelling and pain
varicocelectomy had a greater risk for varicocele 12–24 h post procedure that lasted “a few days.”
persistence than the Paloma technique, and that At mean follow-up of 31 months, 5/66 (8 %) ini-
lymph-sparing reduced risk for hydroceles. tially successful patients relapsed, 4 at 12 months
and 1 at 24 months. Three of these had recanali-
zation of the left internal spermatic vein and were
Varicocelectomy vs. Observation re-sclerosed (Granata et al. 2008).
A retrospective review comprised 319 teen and
Fifty-four adolescents, median 14.5 years (7–16), adult patients with grades 2 and 3 left varicocele,
with left varicocele and US-determined testicular treated for a variety of indications that included
volume discrepancy >20 % were divided into two infertility with abnormal semen analysis in 9 %,
cohorts with similar Tanner stage and age: varic- left scrotal pain in 25 %, cosmetic in 33 %, and
ocelectomy vs. observation for 12 months. volume discrepancy >15 % in 31 %. Of these
“Catch-up growth” to <20 % volume difference patients, retrograde sclerotherapy under local
occurred in 8/27 (30 %) observed patients vs. anesthesia was attempted in 126 (39 %) at median
23/27 (85 %) operated patients, p < 0.01 (Spinelli age 15.7 years (11–61), while others had laparo-
et al. 2010). scopic varicocelectomy or antegrade sclerotherapy
(selection for various therapies was not described).
The procedure could not be performed in 25
Retrograde Sclerotherapy (20 %) cases, due to venous spasm in 3, proximal
collateral veins in 6, distal collateral veins (iliac/
A retrospective review identified 367 patients lumbar) in 3, and difficulty with cannulating and/
with 396 varicoceles and testicular size discrep- or perforating the internal spermatic vein in 11.
ancy (not defined) at mean age 13 years (4–25) Median follow-up for the entire population was 69
who were all recommended for retrograde sclero- months (6–122), with success defined as “disap-
therapy. Vascular anomalies in 36 (10 %) and pearance” of the varicocele on physical examina-
“technical problems” in 11 precluded this treat- tion first done postoperatively at 3–6 months.
ment, whereas open surgery was performed for Outcomes for the 71 patients <19 years of age with
other reasons in 42, leaving 251 patients (277 retrograde sclerotherapy were separately reported:
varicoceles) that had sclerotherapy. A single pro- recurrence in 15 (21 %), hydrocele in 1, and
cedure was successful to resolve 220/277 (79 %) “epididymoorchitis” (probably scrotal phlebitis)
varicoceles. Painful scrotal swelling developed in in 5 (7 %) (Beutner et al. 2007).
17/251 (7 %) patients; there was no mention of
hydroceles (Mazzoni et al. 1999).
Another retrospective review identified 86 Antegrade Sclerotherapy
patients with left grades 2 or 3 varicoceles at
mean age 13.8 years (11–16) who underwent A prospective study evaluated antegrade sclero-
venography; it was possible to perform retrograde therapy in 45 consecutive adolescents, median
sclerotherapy in 72 (84 %) but not in the remain- age 15 years (13–17), with left varicocele that
ing 14 owing to “unfavorable anatomic variants was grade 1 in 4 (9 %), grade 2 in 18 (40 %), and
in the left spermatic vein.” Of these 72, the initial grade 3 in 23 (51 %). No immediate complica-
attempt was successful in 64, and a second tions from sclerotherapy were noted, and at fol-
attempt was successful in 2 of 5 patients, for a low-up at 6 and 12 months, 1 (2 %) had persistent
total success rate of 66/86 (77 %). No sedation varicocele (Ficarra et al. 2004).
8 Varicocele 111
A retrospective review involved 88 consecutive between 2000 and 2009 met inclusion criteria,
males, mean age 13 years (9–19), who underwent comprising 4 RCTs, 5 multicenter studies, and 2
scrotal antegrade sclerotherapy, 46 for grade 2 clinical studies. Together there were 1,443
and 42 for grade 3 varicocele. In one 10-year-old patients, mean age 14.6 years (6–17). Overall,
the procedure converted to Palomo varicocelec- recurrence rate was 5 %, and hydroceles occurred
tomy due to inability to isolate a suitable vein in 9.5 %, with no significant differences between
scrotally. Follow-up was available in 84 at mean surgical methods. Analysis comparing the
of 11 months (3–60), and included US. Persistent Ivanissevich procedure (artery sparing) vs.
varicocele was diagnosed in 6 (7 %), grade 2 in 4, Paloma (vein and artery ligation) showed OR 4
and grade 3 in 2. No hydroceles developed (Zaupa (95 % CI 1.6–10.3), less likely for recurrence
et al. 2006). using Paloma. Lymphatic sparing had OR 0.08
Another retrospective study involved 38 (95 % CI 0.67 to −2.32), less risk for hydrocele
adolescents at mean age 15 years (12–18) with (Borruto et al. 2010).
grade 1 (n = 3), grade 2 (n = 22), and grade 3
(n = 13) left varicoceles treated with antegrade
sclerotherapy followed by physical exam and Artery-Sparing vs. Non-sparing
Doppler US at 3-month intervals for a mean of 11 Laparoscopic Varicocelectomy
months (9–15). The procedure apparently was
not completed in one boy who was uncoopera- A RCT randomized patients with left grades 2 and
tive, and one developed postoperative “epididym- 3 varicoceles and testicular volume discrepancy
itis.” Two persistent grade 1 varicoceles were >20 % to laparoscopic varicocelectomy with
detected in two patients with initial grade 3 vari- artery ligation (n = 63) vs. artery sparing (n = 59)
coceles (Mottrie et al. 1995). at mean age 14.3 years (12–16). Semen analyses
were obtained at age 18 years, with the primary
outcome “normal” vs. “abnormal” spermiograms
Open vs. Laparoscopic Varicocelectomy (sperm concentration, motility, and morphology)
using WHO criteria, and the secondary outcome
One RCT enrolled 654 patients, 7 to 17 years of surgical complications. Semen analysis was
age, with grades 2 or 3 left varicoceles random- obtained in 110 and was normal in 76 (69 %),
ized to either laparoscopic (n = 434) or open with no difference between cohorts. There were
retroperitoneal varicocelectomy (n = 220) (ran- no persistent or recurrent varicoceles, whereas at
domization method and reason for disparate 6 months postoperatively, 7/63 (11 %) artery ligat-
groups was not stated). In all patients, 0.3 mL ing cases vs. 1/59 (2 %) artery sparing developed
methylene blue was injected under the tunica a hydrocele, p = 0.01 (Zampieri et al. 2007).
albuginea to delineate the lymphatic vessels for
sparing. Paloma procedure without artery sparing
was done. After the first 32 laparoscopic proce- Lymph Vessel Sparing vs. Non-sparing
dures done with vessel clipping had an 8 % recur- Laparoscopic Paloma Varicocelectomy
rence rate, the remaining cases had cord ligation
using two silk ties and coagulation of the inter- A RCT randomized 50 patients to laparoscopic
vening vessels. Duration of follow-up, postopera- Paloma varicocelectomy, 25 with mean age 16.5
tive assessment, and primary and secondary years (8–22) having lymph vessel sparing via
outcomes were not described. There were no dif- identification using isosulfan blue dye subdartos
ferences in recurrence rates (<2 %) or hydroceles injection (successful in 24 cases) vs. 25 with
(<2 %) (Podkamenev et al. 2002). mean age 17.9 years (11–25) who did not have
Meta-analysis was used to compare open vs. lymph sparing. The primary outcome was proce-
laparoscopic varicocelectomy in children and dure complications. At mean follow-up of 24
adolescents. From 37 publications, 11 published months (14–36), five (20 %) of the lymph vessel
112 M.A. Jacobs
non-sparing patients had hydroceles, with three Of retrospective studies that did report out-
undergoing surgery, vs. 0 in the lymph-sparing comes, pain was relieved in from 68 to 97 %.
cohort, p = 0.025. All hydroceles were identified Our review found no report concerning
on the 3-month postoperative examination. change in scrotal appearance after varico-
Persistence of varicocele was noted in one (4 %) celectomy, even though cosmetic concerns
patient in each cohort (Schwentner et al. 2006). were listed by several as an indication for
In a meta-analysis including six studies, 489 intervention. One study mentioned scrotal
lymphatic-sparing cases were compared to 307 mass resolution in 87 %.
non-sparing cases. The hydrocele rate was lower in
the lymphatic-sparing group (OR = 0.19 [95 % CI
0.10–0.36]), while no difference was found in recur- Change in Semen Parameters
rence rates or catch-up growth (Liang et al. 2011).
A retrospective study compared non-lymph Preoperative and postoperative semen analyses
sparing (first 59) to lymph-sparing (next 132) were obtained in 33 adolescents aged 15–19
laparoscopic Paloma varicocelectomy. No dye years. These patients were part of a series of 100
injection was done; lymph vessels were identified patients aged 7–19 undergoing varicocelectomy
visually during dissection within the spermatic for grades 2 or 3 varicoceles with hypotrophy
cord. The 191 patients were mean age 15 years (>2 mL or 10 % discrepancy), “soft testis,” pain,
(10–22), and varicoceles were considered bilat- or “large size.” Selection of these 33 for addi-
eral in 71 (37 %). At mean follow-up of 26 tional analysis was not discussed. Mean sperm
months, persistence/recurrence was 4/88 (4.5 %) concentration increased from 21.8 ± 3.6 million/
for non-sparing vs. 6/174 (3.4 %) for lymph spar- mL to 39.6 ± 5.7 million/mL, p = 0.007, and mean
ing sides, p = 0.7. Hydroceles developed in 10/88 percent motility from 33.6 ± 3.8 to 48.5 ± 3.9
(11 %) non-sparing vs. 6/174 (3.4 %) with lymph postoperatively, p = 0.001 (Cayan et al. 2005).
sparing, p = 0.025 (Glassberg et al. 2008). Neither Tanner stages nor time (“at least 1 year
postoperatively”) when semen analyses were
obtained was stated.
Surgical Outcomes
Our review found only one article describing Effect on Testicular Size Discrepancy
preoperative and postoperative semen analy-
sis in adolescents undergoing varicocelectomy, A meta-analysis concerning impact of surgery on
reporting a significant increase in sperm den- testicular hypotrophy included 14 studies (1,475
sity and motility. adolescents) that used orchidometers or US
One trial randomized patients with similar before and after treatment to determine volume,
testicular volume discrepancy to surgery vs. and reported either 10 % or 20 % size discrep-
observation, reporting that at 1 year surgical ancy preoperatively. All but one were retrospec-
patients had less volume discrepancy (3 %) tive. Findings reported included:
than those observed (9 %). • There was no difference in response between
Meta-analysis of studies reporting preop- those with 10 or 20 % discrepancies.
erative volume discrepancy >10 % or >20 % • Together, the number of patients with persistent
reported that after varicocelectomy, the num- 10 or 20 % size difference significantly decreased
ber of patients with persistent volume differ- with varicocelectomy, RR 4 (95 % CI 3–6).
ence significantly decreased. Catch-up growth • Catch-up growth was a mean of 76 % (53–
was a mean of 76 % the volume difference. 94 %) the volume difference (Li et al. 2012).
Several series that reported that pain was an A RCT identified boys aged 15–19 with grades
indication for varicocelectomy did not report 2 or 3 varicocele found during a school screening
results of intervention for relief of symptoms. program and randomized 88 to open Paloma
8 Varicocele 113
varicocelectomy vs. 36 to no therapy. Testicular follow-up of 19 months for the entire study group,
measurements were obtained by US, with follow- 20 (87 %) had resolution (Lee et al. 2011).
up studies in both cohorts done at 12 months.
There was no difference in mean percent volume
discrepancy preoperatively (surgery: 19 ± 17 %; Management of Persistent Varicocele
observation 15 ± 13 %), whereas at 12 months
there was significant growth in surgical patients Retrospective series report reoperative varico-
from a mean 12.6 % volume difference to only celectomy can be performed by a variety of
3.0 % difference but no significant change in con- methods with low risk for testicular atrophy.
trols (9.5–8.7 %) (Paduch and Niedzielski 1997). A retrospective review specifically concerned
reoperative varicoceles, occurring in 19 patients,
with known artery-sparing initially in 8. All had
Pain Resolution persistent grade 2 or 3 varicocele at a mean of 16
months after original surgery. Reoperative sur-
A retrospective review included 38 adolescents gery was done inguinally following prior laparo-
aged 14–16 with left grades 2 and 3 varicoceles scopic procedures (n = 13), open Paloma (n = 2),
and no testicular volume discrepancy who all had or microscopic inguinal (n = 1), while the others
pain. All failed “conservative management for at had embolization (n = 2) after prior inguinal sur-
least 2 months” (treatment not described) before gery or a laparoscopic procedure after a prior
varicocelectomy. Six months postoperatively, inguinal approach (n = 1). At mean follow-up of
pain resolved in 26 (68 %). No mention was made 23 months (6–53), one had persistent varicocele,
regarding persistent varicoceles, if any (Zampieri one had testicular atrophy, and three developed a
and Cervellione 2008); Zampieri et al. 2008. hydrocele. Eight of nine with volume discrep-
In another retrospective review of varicocelec- ancy >10 % had improved growth to a testicular
tomy with 230 males aged 8–40 years, 119 (52 %) volume <10 % (Glassberg et al. 2011).
had pain, of which postoperative follow-up was Another retrospective study concerned 106
available in 82 (69 %) at 3 months. While awaiting patients referred for embolization from 1992 to
surgery, all used scrotal support and nonsteroidal 2010, 46 for primary therapy and 60, with mean
anti-inflammatory medication for mean 4 weeks age 21 years (12–43), as salvage procedures.
(3–5), with pain resolution in 5/119. Of the 82 post- Eighty-nine percent of salvage cases had a patent
operative patients with follow-up, pain resolved in gonadal vein; 41 %, retroperitoneal collaterals;
72 (88 %), while others reported either decreased 28 %, inguinal collaterals; and 8.5 %, both retro-
pain or persistent pain that was unchanged. Two peritoneal and inguinal collateral branches.
with persistent pain were found by US to have per- Compared to primary embolizations, there were
sistent varicocele (Yaman et al. 2000). significantly more inguinal and combined inguinal/
A retrospective analysis involved 215 patients retroperitoneal collaterals in salvage cases (Rais-
mean age 20 ± 8.5 years undergoing varicocelec- Bahrami et al. 2012).
tomy for grades 2 and 3 varicoceles, of which left Twenty-eight males aged 13–55 years with
scrotal pain was the primary indication in 59 recurrent varicocele at a mean of 6.6 months
(27 %). At median follow-up of 59 months (5–130), (0–48) were all found to have venous drainage
2/59 (3 %) had persistent pain (May et al. 2006). from the pampiniform plexus to the left renal
vein treated with retrograde embolization. Initial
varicocelectomy was laparoscopic in 11, open
Cosmetic Improvement retroperitoneal in 7, inguinal in 7, and unknown
in 3. Persistent/recurrent varicocele was grade 1
One retrospective study reported varicocelectomy in 1, grade 2 in 3, and grade 3 in 24. In two cases,
was done in a subset of 23 adolescents for com- the procedure could be performed, and one had
plaints of a palpable scrotal mass. At median no follow-up. One had left scrotal pain due to
114 M.A. Jacobs
phlebitis from the sclerosing agent. In the remain- Diamond DA, Paltiel HJ, DiCanzio J, Zurakowski D,
ing 25, resolution was observed in 20 (80 %) at Bauer SB, Atala A, et al. Comparative assessment of
pediatric testicular volume: orchidometer versus ultra-
median follow-up 7 months (5 days-54 months) sound. J Urol. 2000;164(3 Pt 2):1111–4.
(Kim et al. 2012). Evers JH, Collins J, Clarke J. Surgery or embolisation for
Another retrospective review included men- varicoceles in subfertile men. Cochrane Database Syst
tion of 25 reoperative varicocelectomies in adults. Rev (Online). 2009;(1):CD000479.
Feneley MR, Pal MK, Nockler IB, Hendry WF. Retrograde
Of these, 22 followed prior ligations and were embolization and causes of failure in the primary treat-
recommended for retrograde embolization plus ment of varicocele. Br J Urol. 1997;80(4):642–6.
sclerotherapy, of which the procedure was tech- Ficarra V, Sarti A, Novara G, Dalpiaz O, Galfano A,
nically possible in 18 and reported successful in Cavalleri S, et al. Modified antegrade scrotal sclero-
therapy in adolescent patients with varicocele.
14. Three others had failure of initial emboliza- J Pediatr Surg. 2004;39(7):1034–6.
tion and underwent surgical ligation with results Glassberg KI, Poon SA, Gjertson CK, DeCastro GJ,
not stated (Feneley et al. 1997). Misseri R. Laparoscopic lymphatic sparing varico-
celectomy in adolescents. J Urol. 2008;180(1):326–30.
discussion 30–1.
Glassberg KI, Badalato GM, Poon SA, Mercado MA,
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Hypospadias
9
Primary goals in hypospadias repair: of proximal hypospadias. Short-term stud-

1. Restore normal penile function ies indicate that dorsal plication and ven-
2. Restore normal genital appearance tral lengthening used according to extent of
Normal function includes forceful, straight curvature reliably achieve straightening.
urination without spraying or dribbling, • Studies of dorsal plication done in adults
straight erection, and normal ejaculation. with congenital curvature report persis-
Normal genital appearance includes the tence in <10 %.
following: • The few surveys of adults operated as chil-
• A vertical slit urethral meatus correctly dren find similar prevalences of penile cur-
positioned within the glans. vature in patients and controls.
• Circumcision or foreskin reconstruction. • Ejaculation is more often reported by
• A symmetric scrotum without transposi- patients to have weak force with need to
tion, midline cleft, or encroachment onto milk semen than controls.
the penile shaft. • Objective assessment of postoperative
A secondary aim is to complete repair in as penile appearance indicates that tubular-
few stages with as few complications as ized incised plate (TIP) operation creates a
possible. more normal meatus and glans than flap
Summary of evidence for these goals: procedures (Mathieu and onlay preputial
• Uroflowometry consistently demonstrates flap). One study reported that parents of
decreased Qmax in patients after repair com- hypospadias patients scored outcomes after
pared to nomograms. No study reports distal and proximal TIP similarly to par-
uroflows comparing patients and controls. ents of normal boys after circumcision.
• Adults repaired as children more often • Questionnaires of adults operated in child-
complain of obstructive voiding, spraying, hood, sometimes by techniques no longer in
and/or deviated stream than controls. use, find patients have less satisfaction with
• Ventral penile curvature (VC) occurs in genital appearance than controls.
approximately 10 % of distal and over 50 % • Distal hypospadias repair has short-term
complication rates <10 %.
• A reduction in proximal TIP complications
W.T. Snodgrass, M.D. (*) • N.C. Bush, M.D., M.S.C.S. from 53 to 13 % was reported in one study
Department of Pediatric Urology, University of Texas after a series of technical modifications.
• Onlay and tubularized preputial flap proxi-
Dallas, TX 75235, USA mal hypospadias repairs have complica-
e-mail: warren.snodgrass@childrens.com tions of approximately 15–45 %.
• There are few reported data for complica- Another case–control study was performed in
tions after various staged repairs. northern Italy on boys born from 1978 to 1983.
• Multiple logistic regression analyses find There were 168 identified cases with hypospadias
proximal meatal location and reoperation to in 41,078 male births, a prevalence of 4.1/1000. Of
be independent risk factors for complica- these, 3/33 (9 %) brothers also had hypospadias, as
tions, whereas suture materials and methods did 5/166 (3 %) fathers (Calzolari et al. 1986).
(interrupted vs. continuous) and stent or not
(distal repair) did not impact outcomes.
• Age at surgery >4 years was an indepen- Isolated vs. Syndromic Hypospadias
dent risk factor in one study, but age was
not a factor in two other analyses. Case–control studies report additional nongenital
• Most urethroplasty complications are diag- anomalies in from 9 to 15 % of boys with
nosed within 1 year of repair. Two studies of hypospadias.
patients dismissed from childhood follow-up In the case–control study by Stoll et al. (1990)
reported that 8 and 17 % had a complication described above, 27/176 (15 %) newborns with
when evaluated again as teens or adults. hypospadias (4 distal, 17 penile, 6 perineal) had
two or more nongenital malformations. Ten of 27
had other urinary tract anomalies, including renal
Preoperative Assessment agenesis, vesicoureteral reflux (VUR), and horse-
and Management shoe kidney. Cardiac and intestinal malforma-
tions were the next most frequent.
Prevalence and Familial Risk The case–control study by Calzolari et al.
(1986) reported 15/168 (9 %) cases of newborn
Hypospadias occurs in £0.5 % of males. hypospadias were associated with additional
Relative risk for hypospadias recurrence in nongenital anomalies.
first-degree relatives is approximately 13×,
found in from 9 to 17 % of brothers and 1 to
3 % of fathers in case–control studies. Karyotyping
Risk ratios for relatives of a proband with
hypospadias were determined from analysis of No published series performed karyotyping in
all boys born in Denmark between 1973 and consecutive boys with hypospadias; conse-
2005, of which 5,380 (0.45 %) were diagnosed quently, selection bias likely overestimates prev-
with the condition. Of these patients, 228 (4.2 %) alence of abnormalities.
had another family member with a history of Sex chromosome abnormalities are reported
hypospadias. The relative recurrence risk for in <10 % of patients with isolated hypospadias.
first-degree relatives was the same: for a brother Several case series report patients with hypospa-
to have hypospadias it was 13.4 (95 % CI 11.0– dias and undescended testicle (UDT) have a 4–33 %
16.4), and for offspring of an affected male 10.4 likelihood for sex chromosome abnormalities.
(95 % CI 7.54–14.4), p = 0.16. Risk in same-sex Karyotyping was performed in 984 patients
twins was 50.8 (95 % CI 34.2–75.5) (Schnack 0–35 years of age that included 68 with hypospa-
et al. 2008). dias and 33 with both hypospadias plus UDT. Sex
A case–control study of all males born in chromosome abnormalities were found in 2/67
Alsace from 1979 to1987 found 176 hypospadias (3 %) and 5/33 (15 %). Of the seven patients, four
cases in 60,847 births, a prevalence of 2.9/1000. had dysmorphic features. Selection of patients
Hypospadias was described as glanular/coronal for study inclusion was not described (Moreno-
(n = 121, 69 %), penile (n = 44, 25 %) or perineal Garcia et al. 2002).
(n = 11, 6 %). Of the 176 cases, 2 (1 %) had Twenty-six males with hypospadias that was
fathers with hypospadias, as did 8/47 (17 %) glanular (n = 5), penile (n = 14), penoscrotal
brothers (Stoll et al. 1990). (n = 6), or scrotal (n = 1), and one with chordee
9 Hypospadias 119
without hypospadias had chromosome analysis. Imaging

Of these, hypospadias was isolated in 14, asso-
ciated with other congenital anomalies (not Renal abnormalities are reported in approxi-
described) in 4, and associated with UDT in 9, mately 20 % of hypospadias patients. Most are
of which 5 had additional anomalies. Sex chro- ureteral duplications, malrotations, or minor
mosome abnormalities were found in 1/14 hydronephrosis not requiring interventions.
(7 %) isolated hypospadias patients, 0/4 hypos- Voiding cystourethrogram (VCUG) in two
padias patients with other anomalies, and 2/9 studies reported VUR in approximately 10 %
(22 %) patients with hypospadias plus UDT of cases with cystography.
(1/4 without and 1/5 with other anomalies). A prospective study between 1972 and 1983
Selection for study inclusion was not stated; obtained intravenous pyelogram (IVP) and
cases of “male pseudohermaphroditism and VCUG in 153 boys <2 years of age with hypos-
gonadal intersex disorders” were not included padias (93 [61 %] glanular/coronal, 12 [8 %]
(Yamaguchi et al. 1991). penile shaft, 48 [31 %] penoscrotal/perineal). Of
Retrospective chart review was done in data- these, 36/153 (24 %) patients had abnormal imag-
bases for hypospadias (n = 1,057) and UDT ing: VUR in 18 patients, horseshoe kidney, soli-
(n = 2,105) registered between 1982 and 1996 to tary kidney, hydronephrosis, ureterovesical
identify 79 with both conditions. Karyotyping junction obstruction (UVJO), ureteral duplica-
was done in 54 (68 %) (reasons for selective test- tions in the others. Of these, 18/153 (12 %) were
ing not stated), of which 23 (43 %) were diag- judged to require surgery (Moore 1990).
nosed with sexual development disorders, Retrospective chart review was done to iden-
including mixed gonadal dysgenesis (n = 11), tify patients with hypospadias, finding 400 cases
ovatesticular DSD (n = 5), 5-alpha reductase of which 163 (41 %) had imaging. Selection cri-
deficiency (n = 2), Klinefelters (n = 2), and partial teria for upper tract imaging were not described,
androgen resistance (n = 3). Assuming normal but case distribution (26 % glanular, 22 % penile,
sex chromosomes in the two with 5-alpha 47 % penoscrotal) suggests it was weighted
reductase deficiency and three with partial andro- towards more severe forms. Upper tract imaging
gen resistance (and assuming that all with ovotes- was done by IVP (n = 65) or US (n = 98), with 31
ticular DSD (disorder of sex development) had (19 %) abnormal, mostly malrotations or posi-
abnormal sex chromosomes), karyotyping tional anomalies with “mild” hydronephrosis/
revealed abnormal sex chromosomes in 18 (33 %) hydroureter in 6 (4 %). Cystography was obtained
(Kaefer et al. 1991). in 68 patients, finding VUR in 6 and a bladder
Retrospective chart review of patients seen diverticulum in 2. No mention was made of pros-
between 1986 and 1999 was done, identifying tatic utricle (Friedman et al. 2008).
113 with hypospadias plus UDT. Of these, only Retrospective review of IVP was done in 87/121
48 (42 %) had karyotyping (selection not (72 %) patients undergoing hypospadias repair from
described), with 8 (17 %) demonstrating a chro- 1969 to 1974. Sixteen of 87 (18 %) were abnormal,
mosome abnormality that was autosomal in 6 and but of these only 1 with UPJO had upper tract sur-
involved sex chromosomes in 2 (mixed gonadal gery. These 16 abnormalities (ureteral duplications,
dysgenesis in 1 and ovatesticular DSD in 1) malrotation, horseshoe kidney, ureteral “ectasia,”
(McAleer and Kaplan 2001). UPJO) occurred in 21 % with glanular/coronal,
Another retrospective chart review was done 12 % with penile shaft, and 23 % with penoscrotal/
for patients between 1994 and 2006, finding 44 perineal hypospadias (Lutzker et al. 1977).
with hypospadias plus UDT. Karyotyping had
been done in 25 (57 %) (selection basis not dis-
cussed), of which 6 (24 %) had autosomal (n = 3) Adjuvant Hormonal Therapy
or sex chromosome (n = 3) abnormalities. The
latter all had mixed gonadal dysgenesis (Cox One cross-sectional study reported glans width
et al. 2008). in normal neonates at median age 1 month
was a mean of 14 mm (11–19), while mean padias to receive a mixture of testosterone

glans width in patients at median age 8 months propionate and enanthate, providing a dose of
with proximal hypospadias was significantly 2 mg/kg/week administered twice daily topi-
smaller, 13 mm (9–16). cally for 3 weeks or intramuscularly weekly 3×.
Several prospective studies demonstrate Meatal location was distal (n = 8), midshaft
androgens increase penile length and glans (n = 3), and proximal (n = 14). Mean pre-ther-
circumference. Two report that both IM apy/post-therapy length was 2/3 cm for topical
and topical androgens delivering 2 mg/kg vs. 1.85/3 cm for intramuscular treatment,
achieve similar effects. reported as nonsignificant differences. Non-
Objective endpoints for therapy have not responders were not clearly described, except
been described, so published regimens are to state that one patient with topical application
empiric. had no growth. Elevated serum levels >10 ng/mL
One study treated consecutive boys with were only noted after topical therapy, occurring
proximal hypospadias and glans width £14 mm in 2/13 patients, possibly from excessive appli-
with an escalating dose of IM testosterone to cation (Chalapathi et al. 2003).
achieve width ≥16 mm, reporting one injection Another prospective trial randomized 21 boys
of 2 mg/kg was sufficient in approximately with proximal hypospadias and “a significantly
50 %, while the others had additional monthly small penis” to either testosterone cream 2 mg/
injections increasing from 4 to 16 mg/kg. kg/week for 3 weeks or 2 mg/kg testosterone
One RCT reported decreased urethroplasty enanthate injections monthly for 3 months. Mean
complications in patients receiving preopera- pre-therapy/post-therapy length (cm) was 2.1/2.4
tive topical DHT vs. no therapy. vs. 2/2.4 cm for those receiving topical vs. IM
One prospective observational study found testosterone. Similar pre- and post-therapy glans
adjuvant testosterone therapy not only failed circumference measurements (cm) were 2.7/3.8
to decrease urethroplasty complications, but vs. 2.8/3.8, which would correspond to mean
was a risk factor predicting complications. glans diameter changes of approximately
There are few data concerning advanced 9–12 mm. The authors stated that there were no
bone age following androgen stimulation, but differences in the two groups and that the
no increased bone age has been reported. increased penile length and glans circumferences
One prospective study measured glans width observed were all statistically significant. Two
in 201 consecutive neonates undergoing circum- patients in each group did not respond (Nerli
cision, used to compare with older boys undergo- et al. 2009).
ing distal (n = 165) and proximal (n = 26) A study prospectively selected 40 patients,
hypospadias repair. Median ages were 1.3 months mean age 27 months (13–74), from a total of 170
(0.1–3.2), 8 months (3–117), and 8.5 months with primary hypospadias (selection methods not
(2.5–83), respectively, and median glans width for described; hypospadias severity not stated) to
each group was 14 mm (11–19), 15 mm (10–21), receive testosterone 2 mg/kg IM 5 and 2 weeks
and 13 mm (9–16), which were significantly dif- preoperatively. Mean pre-stimulation penile length
ferent. Although there was overlap in glans width was 3.5 ± 1.1 cm, which significantly increased to
between all groups, the cohort of boys with proxi- 5.9 ± 1.1 cm before partially regressing 12 months
mal hypospadias had a significantly smaller glans later to 4.9 ± 1.1 cm (Davits et al. 1993).
than did normal newborns (Dajusta et al. 2011). Thirty-six boys with hypospadias, 4 coronal, 7
distal shaft, 16 midshaft, 3 penoscrotal, and 6
with failed repair, received 2 mg/kg testosterone
Response to Androgens enanthate IM 5 and 2 weeks preoperatively. Mean
increased penile length was 4.7–7.4 cm, returning
A prospective study randomized 25 patients to 4.9 “postoperatively” (time not stated); mean
with microphallic (penile length <2 SD) hypos- increased glans circumference was 3.8–5.5 cm,
9 Hypospadias 121
then 4.0 cm postoperatively (12–17 mm, then 279 patients with distal (n = 231), midshaft
13 mm) (Gearhart and Jeffs 1987). (n = 10), and proximal (n = 29) hypospadias, of
An observational study involved 25 patients which 41 (15 %) received adjuvant therapy. Mean
9–12 months of age, 8 with penile, 14 with penos- glans diameter in those injected with testosterone
crotal, and 2 with perineal hypospadias who were was 12 mm, increasing to 16.5 mm, vs. 15.4 mm
considered to have a penis “significantly smaller in those not treated. Although glans size increased,
than usual” and so were scheduled to receive tes- urethroplasty complications remained significantly
tosterone enanthate 25 mg IM monthly for 3 greater in those with adjuvant therapy, 34 % vs.
months. Twenty-three out of 25 responded, with 11 %, p < 0.001. Multiple logistic regression anal-
mean increase in glans circumference (cm) from ysis showed that adjuvant therapy was an inde-
2.70 ± 0.01 to 3.74 ± 0.02 (9–12 mm) and penile pendent risk factor for complications when
length (cm) from 1.98 ± 0.02 to 2.38 ± 0.02, both controlling for meatal location, age, and primary
p < 0.001. Of the 23 responders, 4 were considered repair vs. reoperation (Bush et al. 2012).
to have sufficient increases after one injection and
another 6 after two injections (Luo et al. 2003).
Another study recommended preoperative tes- Side Effects
tosterone for glans width (at the widest point)
£14 mm, and used width ³16 mm as the endpoint Appearance of pubic hair was reported in 2/25
for treatment. Consecutive patients were given an (Chalapathi et al. 2003), 5/21 (Nerli et al.
escalating dose beginning at 2 mg/kg with remea- 2009), 2/40 (Davits et al. 1993), and 0/25 (Luo
surement 1 month later. There were 25 consecu- et al. 2003).
tive patients with proximal hypospadias; 13 Pre-and 12-month post-stimulation bone age
(52 %) needed only one injection of 2 mg/kg to was determined in all 40 patients in one study
achieve target growth, while the others needed (Davits et al. 1993), and only 12 month post-
4 mg/kg (n = 6), 8 mg/kg (n = 5), and 16 mg/kg stimulation in 20/36 patients in another (Gearhart
(n = 1) (Granberg et al. 2012). and Jeffs 1987), with neither reporting bone age
advancement.
Impact on Hypospadias Outcomes

Timing of Surgery
A RCT allocated 75 consecutive boys mean age
33 months (10–159) to preoperative topical DHT The commonly quoted ideal age of 6–18
(2.5 % transdermal gel to glans and shaft daily months was based on expert opinion.
for 3 months, ending 5 weeks preoperatively) vs. Several retrospective studies using logistic
no androgens. Treated vs. control patients had regression suggest that increasing patient age
coronal (70 % vs. 84 %), penile (24 % vs. 16 %), >6 months, >1.5 years, or >4 years predicts
and penoscrotal (5 % vs. 0 %) hypospadias. All increased risk for urethroplasty complica-
had TIP repair, with fewer urethroplasty compli- tions after TIP repair.
cations in those with preoperative stimulation One prospective study of consecutive pre-
(1/37 vs. 9/38, p = 0.01) (Kaya et al. 2008). pubertal patients undergoing TIP using mul-
A prospective observational trial measured tiple logistic regression reported that age was
glans width preoperatively at the widest point and not an independent risk factor for urethro-
then gave IM testosterone cyprionate for diameter plasty complications.
£14 mm with proximal and £12 mm with distal Surgery at ≥3 months of age in full-term
hypospadias. Injections began with 2 mg/kg with infants was not associated with anesthetic
remeasurement in 1 month and dose escalation to complications in one study.
4, 8 mg/kg, and so on, until a predetermined tar- Age guidelines for hypospadias repair were
get width of ³15 mm was achieved. There were derived from expert opinion. The 1996 commit-
tee for the American Academy of Pediatrics mean age 5 years (95 % CI 4.8–5.2). These repre-
Section on Urology reviewed psychological sented the first patients to undergo TIP by the two
factors, anesthetic considerations, and technical surgeons involved. Complications included fistula
aspects of repair before recommending surgery and/or “stenosis” (not defined) and/or foreskin
be performed between 6 and 12 months, assum- reconstruction problems (dehiscence, phimosis).
ing the surgeon, anesthesiologist, and facility Total complications were 4/57 (7 %) in those 1.5
were experienced in care of infants (AAP Section years old vs. 21/65 (32 %) in older boys, p = 0.0006.
on Urology, Pediatrics 1996). Year of surgery and surgeon did not predict out-
The 2012 EAU guidelines similarly state comes (Korvald and Stubberud 2008).
repair is usually between 6 and 18 months of age, Multivariable analysis was done on data from
based on evidence level 4 (case series), and noted retrospective chart review of 391 patients with
one report of surgery between 4 and 6 months. median age 2 years undergoing TIP over a 10-year
To test the hypothesis that the preferred age period ending 2007. Age was analyzed as a con-
for repair is <18 months for psychological adjust- tinuous variable and reported for those less than
ment and health-related quality of life, patients vs. greater than 4 years at repair. There was a
6–17 years of age were enrolled and divided into 3.25 relative risk (95 % CI 1.44–7.35) for com-
those having final surgery at age <18 vs. >18 plications in older boys (Eassa et al. 2011).
months. Of 102 eligible patients operated over a
14-year period, 77 consented to psychological
assessment using questionnaires and interviews. Intraoperative Assessment
No differences were found between the two and Management
cohorts regarding health-related quality of life,
psychological adjustment, gender-role behavior, Sutures
or penile self-perception (Weber et al. 2009).
Multivariable analysis of prospective data for Few studies compare suture material used in
669 consecutive boys aged 3–144 months under- hypospadias surgery. One RCT used polygly-
going TIP repair by a single surgeon reported that tone vs. polydioxanone to analyze relatively
age <6 months, >1 year, >5 years, log age, or age faster vs. slower suture absorption, finding no
quartiles did not predict risk for urethroplasty difference in fistulas.
complications. Furthermore, anesthetic risks Another RCT compared continuous vs.
were not increased in infants aged 3–5 months vs. interrupted sutures for distal to midshaft TIP
older patients (Bush et al. 2012). and reported no difference in overall compli-
A retrospective review of 316 distal hypospadias cations, but did not specifically report differ-
repairs by a single surgeon between 1999 and 2005 ences, if any, in fistula rates.
included 194 (60 %) TIP, 69 (21 %) meatal advance- A RCT allocated 100 patients to distal TIP
ment and glanuloplasty (MAGPI), and 53 (9 %) repair using either polyglytone (rapid absorp-
glans approximation procedure (GAP). Of these, tion) or polydioxanone (slow absorption) for
92 (29 %) were <6 months of age at surgery, and urethroplasty done in two layers, with running
urethroplasty complications were less than in older subepithelial stitches. All operations were done
patients (2/92 [2 %] vs. 23/224 [10 %], p = 0.006). by one surgeon. Follow-up assessment was
Considering only TIP repairs, complications in blinded. There was no difference in fistula rates
those <6 months (2/55 [4 %]) were significantly between the two cohorts to 2 years postopera-
less than those >6 months of age (19/139 [14 %], tively: 4/50 (8 %) polyglytone vs. 6/50 (12 %)
p = 0.027). Age was not related to outcomes after polydioxanone (Guarino et al. 2009).
MAGPI or GAP repairs (Perlmutter et al. 2006). A RCT studied 80 boys, mean age 4.5 years
Patients undergoing TIP between 2005 and (3–7), with primary distal (n = 64) and midshaft
2007 were analyzed, a younger cohort mean age (n = 16) hypospadias to TIP repair using subepi-
1.6 years (95 % CI 1.5–1.7) vs. older patients at thelial 6–0 or 7–0 polyglactin, randomized to
9 Hypospadias 123
continuous vs. interrupted sutures, finding no “very favorable” for incision and tubularization,
difference in overall complications (Sarhan et al. reporting poor to slight agreement regardless of
2009). All urethroplasty complications were meatal position (distal vs. midshaft vs. proxi-
considered, with a total of 8 fistulas, 2 glans mal) or years of surgical experience, Kappa = 0.06
dehiscences, and 3 meatal stenoses. (El-Hout et al. 2010).
Analysis of outcomes in 426 consecutive
boys, mean age 17 months (3–140), with distal
Perioperative Antibiotics hypospadias using prospectively collected data in
a database reported urethroplasty complications
Our review found no trials comparing preop- in 19 (4 %), comprising 9 fistulas, 9 glans dehis-
erative antibiotics to no antibiotics before cences, and 1 meatal stenosis during follow-up a
hypospadias surgery. mean of 8 months. All had TIP repair regardless
One RCT reported that febrile UTI was of UP appearance. Excluding 30 MIP variants,
less in patients receiving postoperative oral the UP was described in 337 as “flat” (n = 137,
antibiotics vs. no antibiotic. 41 %), “cleft” (n = 140, 42 %), or “deep”(n = 60,
One RCT comprising 101 patients undergoing 18 %), with no difference in outcomes. Calibration
TIP compared intraoperative intravenous cefo- was done in 263 (62 %) postoperatively, with all
nicid to intraoperative cefonicid plus postopera- ³8 Fr (Snodgrass et al. 2010).
tive oral cephalexin (TID) for 8 days (duration of Retrospective review was done in 48 patients,
catheterization). There were no differences in the median age 14 months (6–45), after distal TIP
two groups regarding surgical complications, but repair, with median follow-up 28 months (5–33).
both asymptomatic bacilluria (11/52 [21 %] vs. The UP was described as “shallow” (n = 15,
25/49 [51 %], p < 0.05) and febrile UTI (3/52 31 %), “moderate” (n = 20, 42 %) and “deep”
[6 %] vs. 12/49 [23 %], p < 0.05) were more com- (n = 13, 27 %), of which six (12.5 %) had fistulas
mon without postoperative oral antibiotics. Time with no difference between groups. The UP was
of febrile UTI postoperatively was not stated also analyzed by pre-incision width at its widest
(Meir and Livne 2004). point <8 mm (n = 11) or >8 mm. All fistulas and
meatal stenoses (n = 2) occurred in those <8 mm.
The final neourethra calibrated intra-operatively
Urethral Plate <6 Fr in 9/48 (19 %) (Holland and Smith 2000).
A RCT randomized 80 boys, mean age 4.5
One study asked pediatric urologists to judge years (3–7), with primary hypospadias (64 distal,
urethral plate (UP) suitability for incision and 16 midshaft) into two equal groups based on con-
tubularization from photographs, reporting tinuous vs. interrupted urethroplasty suture
poor agreement. method. Additionally, the UP was described as
Two studies report that UP characteristics “shallow” (n = 20, 25 %), “intermediate” (n = 34,
impact TIP outcomes. A “shallow” UP was 42.5 %), and “deep” (n = 26, 32.5 %), and was
associated with increased urethroplasty com- measured under stretch at its widest point before
plications in one study but not the other. Both incision and categorized as <8 mm (n = 39) or
stated that a pre-incision plate width <8 mm >8 mm (n = 41). There was no difference in out-
increased complications. comes for the primary endpoint (suture method),
One article analyzed TIP used in 426 consec- or based on UP description (shallow, intermedi-
utive patients with distal hypospadias and found ate, or deep). UP width <8 mm before incision
no difference in outcomes based on description had 9/39 (23 %) complications vs. >8 mm with
of the UP groove as “flat,” “cleft,” or “deep.” 2/41 (5 %), p = 0.048. However, plate width after
A study asked 21 pediatric urologists to rate incision <12 mm vs. >12 mm did not correlate
urethral plate quality based on photographs with complications (7/47 [15 %] vs. 4/33 [12 %],
using a Likert scale from “very unfavorable” to p = 0.49) (Sarhan et al. 2009). Severity of
hypospadias was not reported to be evenly dis- penis was shorter but 77 % stating they were
tributed between the groups with <8 mm vs. “modestly to very satisfied” with surgery.
>8 mm UP widths, adding a potential confounder Another study of adults including question-
to the result, since the same author earlier reported naires stated 95 % reported “good or excel-
meatal location a significant variable in TIP out- lent” results.
comes (Sarhan et al. 2009). Retrospective review was done in 43 patients
median age 25 months (6–163) for VC < 30°
(n = 20) or >30° (n = 23), associated with hypospa-
Ventral Curvature dias in 37 and congenital curvature in 6. Plication
was done in the dorsal midline using one or two
Distal Hypospadias (n = 2) 4–0 or 5–0 polypropylene sutures. At
Approximately 10 % of distal hypospadias median follow-up of 16 months (3–34), 3/43
patients have ventral curvature (VC) <30°, (7 %) had recurrent VC > 30°, including 2 with
with none >30° after degloving. initial VC > 30° (Bar-Yosef et al. 2004).
A series of 440 consecutive distal hypospadias Another retrospective review included 70
repairs that included artificial erection reported hypospadias patients and 13 with isolated VC
that 11 % had VC after degloving and ventral dar- median age 2 years who had dorsal plication
tos dissection that always was <30°. This extent using three 5–0 polypropylene sutures placed at
of curvature was corrected with a single dorsal 1, 12, and 11 o’clock. Extent of VC was not
midline plication of the tunica albuginea using stated. During mean follow-up 6 years (6
6–0 polypropylene (Snodgrass et al. 2009). months–10 years), repeat erection testing was
done in 28 (34 %%) during reoperations with 6
Proximal Hypospadias (7 % of the entire cohort) having repeated plica-
Prevalence tion. Parents reported that the other children all
One study reported VC in consecutive proxi- had straight erection (Chertin et al. 2004).
mal hypospadias cases, finding 50 % had Retrospective review was done in adult men,
either no or <30° curvature after degloving mean age 43 years (16–77), with VC > 30°, includ-
and ventral dartos dissection, while the other ing 25 with congenital curvature and 5 with curvature
50 % had >30° curvature. after prior hypospadias repair. Plication was done
In 70 consecutive boys with proximal shaft with 3–0 polypropylene sutures into the tunica
to perineal hypospadias, 13 (19 %) had no VC albuginea without corporal incision. At mean fol-
after degloving the penis and dissecting ventral low-up of 18 months, all these patients reported
dartos. Another 22 (31 %) had curvature <30° ability to have sexual intercourse and satisfaction
corrected by a single dorsal plication. The with penile appearance (Thiounn et al. 1998).
remaining 35 (50 %) had VC > 30° (Snodgrass Nineteen patients, mean age 19 years, with
and Prieto 2009). congenital curvature >30° underwent correction
using one to three pairs of 2–0 polypropylene for
plication, and then answered a (non-validated)
Dorsal Plication questionnaire a mean of 22 months later. Eighteen
of 19 reported “good or excellent” results and 1
Two retrospective reviews of dorsal plication (5 %) had recurrent curvature (extent not stated)
in children, one of which reported use for (Friedrich et al. 2000).
VC > 30°, found recurrent VC in 7 %. Fifty of 59 patients mean age 40 years (18–71)
Reports of adult patients undergoing plica- at time of surgery responded to a (non-validated)
tion for penile curvature indicate persistent/ questionnaire regarding outcomes of plication for
recurrent curvature in <10 %. curvature a mean of 55° (30–90°), including 22
One study reported (non-validated) ques- with congenital curvature. Straightening was
tionnaire responses by adults after plication done using six 3–0 polypropylene or Goretex
for VC a mean of 55°, with 74 % noting the sutures without tunica incision. At a mean of
9 Hypospadias 125
30 months after surgery, 2/22 (9 %) reported no A retrospective review was reported for 16
improvement in VC. Of the 50 respondents, 74 % patients, mean age 7 years (1–19), with cor-
noted the penis was shorter. Of the 22 with con- porotomy and dermal grafting who had follow-
genital curvature, 17 (77 %) were “moderately to up a mean of 10 years (6–15). At last review, all
very satisfied” with their outcome and 5 were were postpubertal, with 13 reporting straight
dissatisfied (van der Horst et al. 2003). erection, 1 having dorsal curvature from over-
correction, and 2 having persistent VC described
as “mild” and not requiring further surgery.
Ventral Lengthening vs. Dorsal Three had known sexual activity, with one hav-
Plication ing poor-quality erection requiring intracorpo-
real vasoactive drug injection (Badawy and
One retrospective study found reoperation for Morsi 2008).
recurrent VC was the same after dorsal plica- A two-institution retrospective review
tion vs. ventral lengthening in proximal hypos- identified 41 patients with VC > 15° after deglov-
padias patients. ing, dartos dissection, and UP transection who
A retrospective analysis identified 100 con- underwent ventral corporotomy and dermal graft-
secutive patients with proximal hypospadias ing at median age 13 months (5–70). None had
operated between 1994 and 2004. Decision- recurrent VC on artificial erection during a sec-
making for VC correction was not standardized, ond-stage procedure or reported during follow-
but done according to surgeon preference (number up a mean of 27 months (Pope et al. 1996).
of surgeons not stated). Of these 100 patients, 32 Retrospective chart review found 23 patients
had ventral lengthening by UP transection and with ventral corporotomy and dermal grafting in
corporotomy with graft or flap, and 68 had dorsal 6 primary repairs and 17 reoperations after
plication using one or two (numbers not reported) degloving, dorsal plication, and UP transection.
4–0 or 5–0 polypropylene sutures with UP At mean follow-up of 2 years, no patient had
transection also done in 16 (23 %). At mean recurrent VC (Caesar and Caldamone 2000).
follow-up of 2 years, recurrent curvature was
more likely after dorsal plications vs. ventral cor-
poral lengthening (19/68 vs. 3/32, p = 0.03). SIS Graft
Among patients with dorsal plication, recurrent
VC was more likely in those with UP preservation One- and four-ply SIS have been reported to
vs. UP transection (19/52 vs. 0/16, p = 0.002). Of be effective for grafting the ventral corporo-
the 22 patients described with recurrent VC, the tomy with <10 % recurrent VC. One review
extent of curvature was considered sufficient to stated that several patients developed palpable
warrant reoperation in 13, and if only these fibrosis after four-ply SIS grafting.
patients are analyzed, there was no difference in A retrospective review included 28 patients
corporal lengthening vs. dorsal plication (1/32 with ventral corporotomy and SIS grafting for
vs. 11/68, p = 0.09) (Braga et al. 2008). VC > 30° after degloving, dartos dissection, and
UP transection. Grafts were four-ply in 21 and
one-ply in 7. At follow-up a mean of 38 months
Dermal Graft (6–61) in 26 patients, there was no recurrent VC
(Elmore et al. 2007).
Three retrospective studies reported ventral Another retrospective review involved nine
corporotomy with dermal grafting corrected patients with proximal hypospadias and VC > 30°
VC with no or insignificant persistent bending. after degloving and UP transection. Ventral cor-
One adult with prior corporotomy and porotomy and single-ply SIS grafting was done,
grafting reported poor erections requiring and at follow-up at 16–21 months, no recurrent
medical therapy. VC occurred (Weiser et al. 2003).
Retrospective review of 12 patients with proxi- UP ± Urethral Elevation

mal hypospadias who underwent ventral corporo-
tomy and four-ply SIS grafting stated that two Dissection of the UP from the corpora cavern-
(17 %) had either a palpable fibrotic mass over the osa potentially reduces the extent of VC, and
graft site deemed necessary to excise, or recurrent can be continued proximally along the formed
VC. Another two also had palpable fibrosis that urethra to near the membranous segment to
was not treated (Soergel et al. 2003). gain additional straightening.
Twenty-five consecutive boys with proximal
hypospadias had VC > 30° after degloving and dar-
Tunica Vaginalis Graft tos dissection. UP elevation reduced VC to <30° in
four boys such that straightening was completed
Ventral corporotomy grafting using tunica by dorsal plication. UP elevation and continued
vaginalis has <10 % VC recurrence. dissection to mobilize the urethra proximally to
A retrospective review stated that 11 patients, near the membranous segment similarly reduced
mean age 3 years (16–62 months), with proximal curvature in another 4, leaving 17 with persistent
hypospadias had ventral corporotomy with tunica VC > 30°. Three ventral corporotomies were next
vaginalis grafting. At mean follow-up of 14 done without grafting, which achieved straighten-
months (maximum 37), one (9 %) had persistent ing while maintaining the UP in eight. The other
VC “of some degree” (Perlmutter et al. 1985). nine still had VC requiring UP transection. During
Retrospective review was done in 25 patients, follow-up a mean of 12 months (2–38), there was
median age 8 months (5 months–16 years), with no recurrent VC (Snodgrass and Bush 2011).
scrotal to perineal hypospadias who had VC after A retrospective study identified 34 patients
degloving, dartos dissection, and UP transection with proximal hypospadias (18 proximal shaft, 10
and underwent corporotomy with tunica vagina- penoscrotal, 6 scrotal), finding VC after deglov-
lis grafting. At follow-up of 1–5 years, one (4 %), ing was <30° in 6, 30°–60° in 12, and >60° in 16.
the 16-year-old, had recurrent VC requiring sur- The next step was dissection of the UP and proxi-
gery (Ritchey and Ribbeck 2003). mal urethra from the corpora cavernosa, which
Another retrospective study included 18 was reported to achieve straightening in 30 (88 %).
patients with proximal hypospadias: 13 had UP Another two also had dorsal plication, while two
elevation with ventral corporal incision and tunica others had UP transection (Bhat 2007).
vaginalis grafting, 5 had only UP transection. At
mean follow-up of 27 months (14–41), two
(11 %) had recurrent VC < 20°, one with UP ele- Single vs. Multiple Ventral
vation and one with UP transection (Kajbafzadeh Corporotomies
et al. 2007).
One study reported no recurrent VC with
either single ventral corporotomy with dermal
Tunica Vaginalis Flap grafting or three ventral corporotomies with-
out grafting.
Ventral corporotomy coverage was also One study reported prospectively collected
reported using tunica vaginalis flaps, rather data analyzing straightening maneuvers in 70
than the various grafts mentioned above. In one consecutive patients with primary proximal
analysis, recurrent VC developed in <10 %. hypospadias. Of these, 18 had persistent VC > 30°
A retrospective review reported ventral after degloving, dartos dissection, and either UP
corporotomy with tunica vaginalis flap in 23 transection or elevation, with 7 undergoing single
patients with proximal hypospadias and VC > 45°. corporotomy and dermal grafting vs. 11 straight-
At median follow-up of 5 years, recurrent VC > 30° ened by three corporotomies without grafting. No
occurred in 1 (4 %) (Braga et al. 2007a). recurrent curvature was apparent with follow-up
9 Hypospadias 127
of 27 months vs. 19 months, respectively complications ranged from 0 to 24 %, with 25

(Snodgrass & Prieto 2009). series reporting £10 %. Nearly all of these were
fistulas or meatal stenoses (Snodgrass 2011).
A retrospective review included 324 distal TIP
Urethroplasty repairs done by seven surgeons from 1997 to
2002, during which time another 54 had MAGPI.
Distal Hypospadias At follow-up ranging from 6 months to 5 years,
A prospective case series by one surgeon using complications developed in 75 (23 %), compris-
only TIP to repair distal hypospadias in 426 ing 28 (9 %) with fistulas, 21 (7 %) with meatal
consecutive patients reported complications in stenosis, 11 (3 %) with both fistulas and meatal
4 %, fistulas and glans dehiscences. stenosis, 12 (4 %) with dehiscences, and 3 with
A systematic literature review reported a strictures (1 %) (Elicevik et al. 2004).
total of 1,872 TIP repairs, with fistulas in 4 %,
meatal stenosis in 3 %, and no urethral stric-
tures. Another review found complications TIP vs. Mathieu
ranged from 0 to 24 %, with most articles
reporting <10 %. A RCT allocated 30 patients, mean age 24
Two RCTs compared TIP to Mathieu, months, to TIP or Mathieu performed by one sur-
reporting no difference in urethroplasty com- geon. Mean follow-up was 15 months, with ure-
plications but improved meatal appearance throplasty complications in 1 (3 %) TIP and 3
with TIP. (10 %) Mathieu, p = 0.6. The meatus was
One systematic literature review reported described as slit in all TIP and round in “most”
fistulas more common after Mathieu and Mathieu (means to determine appearance was not
meatal stenosis more likely after TIP. stated) (Oswald et al. 2000).
Another prospective RCT resulted in 30
Mathieu and 37 TIP repairs in children at mean
TIP age 23 months, with follow-up scheduled to 6
months (mean not stated). Only fistulas and
Five-hundred fifty-one consecutive patients, meatal stenoses were reported, with 3/30 (10 %)
mean age 17 months (3–140), with distal hypos- Mathieu and 8/37 (22 %) TIP having complica-
padias all underwent TIP repair by a single sur- tions, p = 0.3. Meatal appearance was determined
geon. Meatal location was glanular/coronal/ by a urologist blinded to the repair type, who
subcoronal in 445 and distal shaft in 106; 83 rated all Mathieu rounded and all TIP slit
(15 %) were MIP variants. Follow-up in 426 was (Elganainy et al. 2010).
a mean of 8 months, and included calibration, A systematic review of published articles
uroflowometry, and/or urethroscopy in 279 from 1990 to 2009 reviewed a total of 23
(65 %). Complications occurred in 19 (4 %), papers, with 1,872 distal TIP and 1,496 Mathieu
comprising 9 fistulas, 9 glans dehiscences, and 1 repairs. Fistulas occurred in 4 % of TIP and
late presentation of meatal balanitis xerotica 5 % of Mathieu, p = 0.028; meatal stenosis was
obliterans (BXO). Otherwise, there were no stric- reported in 3 % of TIP and 0.7 % of Mathieu,
tures or meatal stenoses (Snodgrass et al. 2010). p < 0.001(Wilkinson et al. 2012).
A systematic review of outcomes for distal
TIP repair included 15 articles published before
December 2009, totaling 1,872 patients. Rates of Proximal Hypospadias
three complications were reported: fistulas (72,
4 %), meatal stenosis (57, 3 %), and urethral Urethroplasty options for proximal hypospa-
stricture (0) (Wilkinson et al. 2012). dias repair depend in part on whether or not
Review of 35 English publications between the UP is transected during penile straighten-
1994 and 2009 concerning distal TIP found overall ing, discussed above.
When the UP is preserved, both TIP and developed in six (12 %), including four fistulas,
onlay preputial flap are options. one meatal stenosis, and one glans dehiscence
When the UP is transected, urethroplasty (Ghanem and Nijman 2011).
options include one-stage tubularized prepu- A retrospective review compared 35 proximal
tial flaps or grafts, or two-stage preputial flaps TIP to 40 onlay preputial flap repairs done from
or grafts. 1998 to 2006 in children a mean age of 17 months
(9–91). The number of surgeons involved was not
TIP stated. At mean follow-up of approximately 3
One surgeon reported technical modifications years, there was no significant difference in ure-
(chromic to polyglactin/polydiaxone sutures, throplasty complications, 21/35 (60 %) TIP and
one-layer running epithelial to two-layer inter- 18/40 (45 %) onlay (Braga et al. 2007b).
rupted and running subepithelial tubulariza-
tion, and dartos barrier flap to tunica vaginalis Onlay Preputial Flap
flap) that reduced proximal TIP complications Several retrospective studies report urethro-
from 53 to 13 % in consecutive patients. plasty complications in 17–45 % after proxi-
One retrospective study similarly found mal onlay preputial flap repair (Table 9.1).
12 % complications with proximal TIP, while A retrospective review concerned patients
another compared proximal TIP to onlay with “proximal division of the corpus spongio-
preputial flap and found no difference in ure- sum after degloving and marked hypoplasia of
throplasty complications (60 % vs. 45 %). ventral tissues” operated by one surgeon from
Prospectively recorded data was used to evalu- 1997 to 2007. There were 126 primary onlay
ate 49 consecutive boys with TIP repair for proxi- repairs done at mean age 23 months (8–96), with
mal hypospadias by a single surgeon. Fifty-three follow-up a mean of 22 months (1–97). Of these,
percent of complications occurred in the first 15, only 13 (10 %) had VC corrected by dorsal pli-
25 % in the next 20, and 13 % in the final 24 cation. Urethroplasty complications developed
patients (p = 0.02), including fistulas (n = 7, 44 %), in 34 (27 %), including 18 fistulas, 13 dehis-
glans dehiscence (n = 5, 31 %), and meatal steno- cences, 2 strictures, and 1 diverticulum (de
sis or urethral stricture (1 each, 12.5 %). Technical Mattos e Silva et al. 2009).
modifications made to reduce fistulas included: The retrospective review by Braga et al.
• Change in urethroplasty sutures from chromic (2007b) described above included 40 onlay
to polyglactin/polydiaxone. repairs for children mean age 17 months with
• Change in urethroplasty suturing method from proximal hypospadias. Of these, 18 (45 %) had
one layer running epithelial to two-layer subepi- VC > 30° corrected by dorsal plication. With
thelial tubularization, the first interrupted polyg- follow-up a mean of 39 months, complications
lactin and the second running polydiaxone. occurred in 18 (45 %), including 8 fistulas, 2
• Addition of spongioplasty. dehiscences, 2 strictures, 1 meatal stenosis,
• Substitution of tunica vaginalis for dartos as a and 5 recurrent VC, of which 2 had subsequent
barrier flap over the neourethra. dorsal plication.
No fistulas occurred in the last 24 patients A retrospective chart review considered
(Snodgrass and Bush 2011). patients operated for proximal hypospadias from
A review was done in 49 patients, mean age 23 1981 to 1997, identifying 142 with follow-up of
months (16–72), undergoing proximal TIP repair which 20 had an onlay flap repair. Median age for
(dates of study period, number of surgeons, num- the entire series was 11 months, and follow-up
ber of alternative repairs not stated). Urethroplasty was a median of 9 months (1–79). Urethroplasty
was done using 6–0 polyglactin subepithelial complications after onlay flap occurred in six
continuous suture in one layer covered by a dorsal (30 %), including three fistulas, one stricture, one
dartos flap. During follow-up a mean of 3 years meatal stenosis, and one diverticulum (Powell
(14 months–6 years), urethroplasty complications et al. 2000).
9 Hypospadias 129
Table 9.1 One-stage proximal hypospadias repair using preputial flaps

No. patients Mean f/u (mos) Complications/Rate (%) F MS Stx GD D VC
Onlay preputial flap
Powell et al. 20 9 (median) 6/30 3 1 1 – 1 –
Braga et al. 40 39 18/45 8 1 2 2 – 5
de Mattos e Silva et al. 126 22 34/27 18 – 2 13 1 –
Hayashi et al. 52 NS 9/17 3 – – 9 – –
Tubularized preputial flap
Powell et al. 27 9 (median) 9/33 7 1 1 0
Shukla et al. 12 24.5 2/17 1 1 1
Chuang et al. 86 6 22/39 16a – – – – –
Aoki et al. 22 24 3/14 1 2 – – – –
F fistula, MS meatal stenosis, Stx stenosis, GD glans dehiscence, D diverticulum, VC ventral curvature
a
Other complications not described
Retrospective analysis was done in 52 patients 5 (19 %), for a total rate of 22 (39 %). These
after onlay preputial flap repair for proximal included mostly fistulas, as well as urethral stric-
hypospadias at median age of approximately 2 ture, meatal stenosis, glans dehiscence, and ure-
years (10–132 months). Duration of follow-up was thra diverticulum, but those specifically occurring
not stated. Urethroplasty complications occurred after proximal hypospadias repair were not stated
in a total of 9 (17 %) boys, including 9 glans dehis- (Chuang and Shieh 1995).
cences and 3 fistulas (Hayashi et al. 2007). The retrospective chart review by Powell et al.
(2000) described above with 142 patients oper-
Tubularized Preputial Flap ated for proximal hypospadias from 1981 to 1997
Four retrospective studies report urethro- reported outcomes for 27 tubularized preputial
plasty complications in from 14 to 39 % after flaps. Median age for the entire series was 11
tubularized preputial flap repairs for proxi- months, and follow-up was a median of 9 months
mal hypospadias (see Table 9.1). (1–79). Urethroplasty complications developed
One study reported that two-layer tubular- in nine (33 %)—seven fistulas, one stricture, one
ization of the flap had significantly fewer com- meatal stenosis, and 0 diverticulum.
plications that did one-layer repair. Another retrospective study of patients oper-
The two studies reporting the lowest com- ated with proximal hypospadias between 1997
plication rates both anchored one edge of the and 2001 by one surgeon found 12 corrected using
flap to the corpora cavernosa and then a tubularized preputial flap vs. 10 undergoing
stretched and fashioned it into a tube. two-stage repairs. All had UP transection while
A retrospective review analyzed 56 patients straightening VC. Rather than tubularizing the
with proximal hypospadias undergoing tubular- preputial flap over a catheter, the flap was anchored
ized preputial flap repair from1986 to 1993 within length-wise to the corpora cavernosa and then tai-
a cohort of 103 total patients mean age 4 years (5 lored into a tube. During follow-up at a mean of
months–14 years) who underwent that repair, the 24 months (20–33), two (17 %) with tubularized
others having distal hypospadias. Follow-up was preputial flap had complications—one fistula and
at least 6 months. Of the 56 cases, the flap was one meatal stenosis (Shukla et al. 2004).
tubularized in one layer in 29 and in two layers in Twenty-two boys, mean age 17 months (10–
27, the authors stating most the one-layer clo- 156), with proximal hypospadias had tubularized
sures were done earlier in the series and then preputial flap repair in 2005 and 2006. The flap
gradually phased out in favor of a two-layer tech- was first sutured to the corpora and then folded
nique. Complications occurred in 17 (59 %) and into a tube. At follow-up a mean of 24 months
Table 9.2 Proximal Byar’s flap outcomes

No. patients Mean f/u (mos) Complications/rate (%) F MS Stx GD D VC
Gershbaum et al.a 11 60–180 2/18 1 – – – 1 –
Cheng et al.b 14 6–36 2/14 1 – – – 2 –
Shukla et al. 10 43.5 7/70 7 3 – – 1 –
F fistula, MS meatal stenosis, Stx stenosis, GD glans dehiscence, D diverticulum, VC ventral curvature
a
Surgical technique not stated
b
Combined with distal TIP
(18–30), complications developed in three Two retrospective studies reported compli-

(14 %)—two meatal stenoses and one fistula cations after two-stage preputial graft repairs
(Aoki et al. 2008). in 6 and 26 %.
The retrospective study by Powell et al. (2000)
Two-Stage Preputial Flaps (Byar’s Flaps) discussed above included 61 one-stage tubular-
Our review found only three reports with infor- ized preputial skin grafts. At median follow-up of
mation regarding outcomes after two-stage 9 months for the entire study group, there were
preputial flap repairs, comprising 35 patients. 21 (34 %) complications after these grafts, includ-
Complications ranged from 14 to 70 % ing 11 fistulas, 8 strictures, 1 meatal stenosis, and
(Table 9.2). 1 diverticulum. However, glans dehiscence was
The study by Shukla et al. (2004) described also stated to occur in three patients not listed
above included ten patients who underwent two- among these complications.
stage preputial flap repair. During follow-up a Two-stage preputial grafts were the subject of
mean of 43 months (33–60), seven (70 %) had a retrospective review including 32 patients, of
urethroplasty complications that included fistulas which 8 (25 %) had midshaft hypospadias and
in all seven, meatal stenosis in three, and a ure- the remainder, proximal hypospadias. Initial sur-
thral diverticulum in one. gery was performed at median age 21 months
A retrospective study of patients operated (15–26), and follow-up after the second stage
between 1980 and 1995 reported 1,934 hypospa- was a median of 35 months (20–55) in 31 cases.
dias repairs, of which 51 (3 %) had scrotal/perineal The authors reported that one developed a fistula
defects. Of these, 11 had two- stage preputial flap and one had “mild residual” VC for a complica-
repair. Follow-up was only described as from 5 to tion rate of 2/31 (6 %), although the authors did
15 years. None had recurrent VC. Urethroplasty not specifically state there were no other prob-
complications occurred in two (18 %), a fistula lems such as glans dehiscence or diverticula
and a diverticulum, but only seven were described (Springer and Subramaniam 2012).
as voiding with a “normal stream”; four had Another retrospective study reported two-
“difficulty with terminal voiding and spraying” stage preputial grafts in 43 patients with proxi-
(Gershbaum et al. 2002). mal penile to perineal hypospadias and
Four surgeons reported results of two-stage “significant chordee” at median age 1 year (7
preputial flaps interposed between the glanular UP months–17 years). Of these, six were reopera-
and a more proximal urethral meatus in 14 patients. tions, and there was follow-up of 1 month to 4
At follow-up of between 6 months and 3 years, years (mean not stated) in 34 (number with pri-
complications developed in two (14 %)—two mary vs. reoperative repairs not stated). Penile
diverticula and a fistula (Cheng et al. 2003). straightening was not described, and 6/37 (16 %)
primary repairs had additional subsequent
One- and Two-Stage Preputial Grafts correction with dorsal plication. Complications
One study reported one-stage tubularized after the second stage occurred in nine cases
preputial grafts had 34 % complications, (26 %), including four glans dehiscences, two
including 13 % strictures. fistulas, one diverticulum, one “long urethral
9 Hypospadias 131
stenosis with BXO” and one “meatal retraction” ing mean follow-up of 9 ± 6 months (Almodhen
(Ferro et al. 2002). et al. 2008).
Postoperative Management Bandages

and Assessment
Two RCTs reported no differences in urethro-
Urinary Diversion plasty complications related to use or nonuse
of postoperative bandages.
One RCT reported no differences in urethro- One hundred consecutive patients undergo-
plasty outcomes following distal TIP repair ing distal to proximal primary and reoperative
with vs. without urinary diversion in toilet- hypospadias repair were eligible for random-
trained boys. However, there were significantly ization in a study comparing a transparent
more complications, including dysuria, uri- waterproof adhesive bandage around the penis
nary retention, and urinary extravasation for 2 days or no bandage (randomization pre- or
without stents, with 40 % of those not stented intra-operatively was not stated). Two were
having a catheter subsequently placed. excluded for bleeding at the end of the proce-
TIP urethroplasty without stent was dure. Parents of those with a bandage were told
reported in 32 consecutive non–toilet-trained to remove it on the second day “or sooner if it
boys with distal, midshaft, and proximal was soiled.” Mean follow-up was 1 year, with
hypospadias, with one developing extravasa- urethroplasty complications occurring in 4/49
tion with subsequent catheter placement. with vs. 3/49 without a bandage. Telephone
There are no data indicating optimal size or calls from patients were significantly greater in
duration of use of stents. No report compares those without bandages (0.3 vs. 0.8 calls/
urinary diversion by suprapubic vs. urethral patient, p = 0.02), but the authors did not state if
catheters in otherwise similar patients. these calls related specifically to bandages or
One RCT comprised 64 toilet-trained boys wound appearance vs. other questions (Van
(median age 6 years, range 2–17) undergoing dis- Savage et al. 2000).
tal TIP repair by a single surgeon, randomized at One-hundred twenty boys mean age 2 years
the end of the procedure to postoperative bladder with distal and proximal (n = 60) hypospadias
catheterization vs. no urinary diversion. There underwent repair by four surgeons and were ran-
were no differences in urethroplasty complica- domized at the end of the procedure to a transpar-
tions (3/35 vs. 6/29, p = 0.3); however, dysuria ent biomembrane adhesive film, compression
(14 % vs. 45 %, p < 0.01), urinary retention (0 % wrap, or no bandage (polymixin B and bacitracin
vs. 24 %, p < 0.05), and urinary extravasation zinc in a white petrolatum applied with diaper
(0 % vs. 17 %, p < 0.05) occurred significantly change or TID for 7 days). Three were withdrawn
more often in the unstented group. Of 29 unstented due to bleeding that resulted in a compressive
patients, 12 (41 %) had a catheter placed for uri- wrap. Bandages were removed at ³3 days when
nary retention or extravasation £3 days postop- bathing resumed and they soaked off, with subse-
eratively (El-Sherbiny 2003). quent white petrolatum applied until 7 days.
A prospective study involved 32 consecutive Urethroplasty complications developed in 16
non–toilet-trained boys (mean age 18 ± 6 months) (14 %) with no differences among the three
undergoing TIP by one surgeon for distal-midshaft groups (McLorie et al. 2001).
(n = 26) and proximal shaft (n = 6) hypospadias
with no urinary diversion. Urinary extravasation
developed in one patient (distal vs. proximal Preventing Erections
defect not stated) the second postoperative day,
resulting in catheter placement. There was 1 (3 %) One RCT found oral ketoconazole was no
urethroplasty complication, meatal stenosis, dur- more effective than placebo in preventing
postoperative erections, but did cause times present years after surgery with apparently
increased nausea and transient liver dysfunc- new onset of a fistula (Wood et al. 2008). The
tion in one patient. No medication therapy has total number of patients undergoing hypospadias
been reported effective to temporarily reduce repair that would need postoperative follow-up to
or prevent postoperative erections. as long as 8 years to detect these occasionally
One placebo-controlled double-blinded RCT late-appearing fistulas was not calculated.
enrolled 40 men at mean age 28 years undergoing
penile surgeries, such as circumcisions and ure-
throplasties, to either perioperative oral ketocon- Calibration
azole 400 mg TID or placebo for 1 week. There
was no reduction in either erections or painful Sounding the neomeatus and urethra provides
erections (both occurring in >80 %) using keto- objective evidence for the lack of anatomic
conazole, but three (16 %) treated patients with- obstruction.
drew due to nausea and another developed transient The minimum caliber of the urethra in nor-
liver dysfunction (DeCastro et al. 2008). mal boys varies in published reports. One
study found that 14 % of boys < 3 years of age
were <8 Fr, while two others performing cali-
Duration of Follow-up brations under general anesthesia stated mini-
mum size encountered was 10 Fr.
The minimum duration of follow-up needed to Meatal size was determined in 100 consecu-
encounter the majority of complications has tive full-term newborns using bougie a boules or
not been established for hypospadias repair. olive-tipped catheters on the second day of life.
Two studies report that >70 % are diagnosed The mean and median was 8 Fr. The meatus was
within 1 year of repair. less than 8 Fr in 51, the smallest reported as 4 Fr
No case series include continuous follow-up in 9 patients. The largest caliber was 12 Fr in a
into adulthood of patients after childhood single newborn (Allen et al. 1972).
hypospadias repair. Another study similarly used bougie a boules
One review concerning glans dehiscence to determine meatal size in 200 boys referred to
reported diagnosis in 32 patients a mean of 3.9 urology “with no voiding complaints.” Of 160 <1
months after surgery, with 88 % found at the first year of age, 22 (14 %) were <8 Fr, while the
postoperative visit (Snodgrass et al. 2011). remainder were 10 Fr. Results were the same for
Another analysis considered time to diagnosis boys 1–3 years of age. From ages 4–10 years, the
of urethroplasty complications after TIP repair meatus was “tight 8 Fr” in <10 % and 12 Fr in the
using prospectively maintained databases. There remainder (Litvak et al. 1976).
were 752 primary and 139 reoperations with Calibration using sounds under general anes-
complications in 78 and 37, respectively. These thesia was done in 88 uncircumcised boys aged
were diagnosed at the first postoperative visit in 0–14 years with non-urethral conditions. The
73 (64 %) and/or within the first year in 89 cohort included 10 patients <1 year, and 66 <4
(78 %), with median time 3 months. After 12 years of age. None had urethral caliber <10 Fr
months, 35 patients would need indefinite fol- (Yang et al. 2001).
low-up to detect an additional urethroplasty com- Sixty uncircumcised boys aged 5 months–16
plication (Villanueva et al. 2012). years undergoing hernia repairs or appendectomies
A retrospective review of 26 patients with were calibrated with Hegar dilators under general
fistulas reported that approximately 60 % were anesthesia. Considering those 5 months–12 years,
diagnosed within 1 month after surgery, and 70 % mean width was 4 mm (3.5–4.5), which corre-
within 1 year. However, time for follow-up to sponds to approximately 10–12 Fr. The number of
detect over 90 % of fistulas was 93 months after boys calibrated in various age groups was not stated
primary hypospadias repair, since patients some- (Orkiszewski and Madej 2010).
9 Hypospadias 133
Uroflowometry One study that reported that 49 % were

<2 SD stated that all had Qmax > 5 cc/s, and that
Most reported data compare patients to vari- had an alternative nomogram been used
ous nomograms rather than to controls. (Toguri rather than Miskolc), the percentage
Two studies reported uroflow in infants <2 SD would change to 11 %.
using ultrasound probes, one finding mean Seventeen (34 %) of the first 50 patients who
preoperative and postoperative Qmax no differ- had TIP repair and were toilet-trained during
ent than controls and the other reporting pre- follow-up had uroflowometry at a mean of 45
operative infants with distal hypospadias had months (6 months–7 years) postoperatively.
median Qmax less than controls. Fourteen had distal and three had proximal
Flow rates after hypospadias repair fre- repairs, and all Qmax were within 2 SD of normal
quently cluster below the fiftieth percentile for for “standard curves” (nomogram used was not
age compared to nomogram, regardless of ure- stated). All Qmax exceeded 5 cc/s. Curve patterns
throplasty technique, indicating that the neoure- were not reported (Snodgrass 1999).
thra is not a normal urethra. Significance of A retrospective study identified 48 patients who
diminished flow velocity in asymptomatic boys were toilet-trained and had uroflowometry >6
without anatomic obstruction is uncertain. months postoperatively after distal hypospadias
repair, from a cohort of 412 boys undergoing TIP
Preoperative from 1996 to 2000. Qmax were above 2 SD from nor-
A study compared preoperative uroflow data in 42 mal in 33 (78 %) using an institutional nomogram.
patients with distal hypospadias at mean age 16 ± 6 The curve was described as “flat” in 31 with normal
months to 51 controls with mean age 11 ± 11 peak flows, to distinguish it from either bell-shaped
months, obtained using an ultrasound flow probe or plateau patterns (Hammouda et al. 2003).
affixed around the penile base. There was no Another retrospective study reported uroflow
significant difference in mean Qmax in patients vs. data from 28 of a total of 70 patients who under-
controls (7.5 ± 2.5 cc/s vs. 6.8 ± 4.1 cc/s). Plateau went TIP for distal to midshaft hypospadias,
curves occurred in 6 % of patients and 3 % of con- excluding those not toilet trained or having fistula,
trols. Postoperative studies after 53 distal TIP and meatal stenosis, or urethral stricture. Follow-up
10 proximal TIP repairs were not significantly dif- was a mean of 18 months (10–40), and Qmax was
ferent than controls (7.3 ± 5.5 cc/s, 8.2 ± 4.6 cc/s compared to Toguri nomograms. Values <2 SD
vs. 10.9 ± 10.9 cc/s) (Wolffenbuttel et al. 2006). were found in two (7 %). Normal was defined as
Another study compared uroflow data in 21 greater than the twenty-fifth percentile and
unoperated infants with distal hypospadias at mean occurred in 22 (78.5 %). A bell-shaped curve was
age 14 months (13–22) to 19 normal infants at mean reported in 23 (82 %) (Kaya et al. 2007).
age 12 months (9–20) using an ultrasound flow Forty-eight patients with foreskin-preserving
probe fixed around the base of the penis. Median TIP repair, 38 distal and 10 proximal, who were
Qmax was significantly less in patients vs. controls toilet trained 1 year after surgery, had
(2.4 [0.9–10] vs. 4.4 [0.6–10], p < 0.01). Bell-shaped uroflowometry. Two to three determinations were
curves were noted in 43 % of patients and 63 % of made, the highest Qmax reported, and values then
controls, while plateau curves were found in 38 % compared to Miskolc nomograms. A urotherapist
of patients but in no controls. The hypospadias additionally questioned the patients for obstruc-
meatus calibrated to a median 10 Fr (6–12) and did tive voiding complaints. Eleven (23 %) had
not correlate with Qmax (Olsen et al. 2011). obstructive symptoms and were all diagnosed
with meatal stenosis. For the remaining 37, mean
Postoperative TIP Qmax was 14 cc/s (6–28). Eighteen (49 %) had
Qmax <2 SD from normal has been reported in Qmax below 2 SD, yet ³5 cc/s. Calibration was
0–22 % of toilet-trained patients having done in 6 of these 18 without evidence for ana-
uroflowometry after TIP. tomic obstruction. Curves were described in
26/37 (70 %), bell-shaped in 14 (54 %) and 18/40 (45 %) had urethroplasty complications.
plateau in 12. Repeated uroflows were obtained 6 An unspecified number had uroflowometry,
years later, with a significantly greater mean Qmax reporting mean Qmax 8 cc/s (4–17); 17/21(33 %)
19 cc/s (17–36), and 12 (32 %) with flows less with curve description had a plateau pattern.
than the fifth percentile. Curves were stated for Another study evaluated patients who underwent
24; bell-shaped in 11 (44 %) and plateau in the tubularized and onlay preputial flap repair by one
remainder. Considering all with flows less than surgeon for proximal hypospadias between 1981
the fifth percentile, all improved, with 28 % mov- and 1992. Of 125 patients, medical information
ing above the fifth percentile. Two others with could only be retrieved for 73, of which 49 could be
initial flow rates greater than the fifth percentile contacted for follow-up ³10 years postoperatively,
were later less than the fifth percentile, but were and 30 agreed to examination. These patients had
asymptomatic and not further evaluated. Boys been operated at mean age 17 months (8–74), and
having proximal repairs were more likely than late follow-up was a mean of 14 years later (12–21).
those with distal repairs to have Qmax less than the Uroflowometry was obtained in 25 of the 30, with
fifth percentile. The authors noted that the num- mean Qmax of 11 tubularized flaps, 17 cc/s (15–21),
ber of patients less than the fifth percentile 1 year and of 14 onlay flaps, 18 cc/s (7–36), p = 0.7. Post-
after surgery would have been less (4 vs. 18) had void residual by bladder scan ultrasound was a
they used Toguri rather than Miskolc nomograms mean of 5 cc (0–21) for tubularized and 17.5 cm3
(Andersson et al. 2011). (0–221) after onlay, p = 0.5 (Patel et al. 2004).
A retrospective study reported uroflowometry
after proximal TIP, in a series with urethroplasty
complications in 21/35 (60 %). “All toilet-trained” Cosmesis
patients had two uroflows, with the second used
for analysis, but the number of patients this com- One study using (non-validated) questionnaires
prised was not stated. Mean Qmax was 8 cc/s reported parents scored cosmetic outcomes after
(4–17), with 16/24 (67 %) having a plateau curve distal and proximal TIP repair similar to par-
pattern (Braga et al. 2007b). ents of normal boys undergoing circumcision.
No similar data comparing cosmetic hypos-
Postoperative Preputial Flaps padias outcomes to normal controls have been
One study reported no difference in results on published for flap-based repairs.
uroflowometry between onlay and tubularized Blinded photographic assessment in two
preputial flaps, with 27 % having Qmax < 2 SD. studies rated appearance after TIP superior
Most of the others had Qmax in the lower fiftieth than after Mathieu or preputial onlay flaps.
percentile. One study used photographs to judge post-
Retrospective review reported uroflow data operative appearance of the meatus after stan-
in patients undergoing tubularized or onlay dard proximal onlay preputial flap vs. a modified
preputial flap repairs between 1986 and 1992, version with ventral meatal slit to improve the
finding no significant differences between appearance of the neomeatus. While the
results obtained with these two methods. Of 51 modification increased likelihood for a slit-
boys without complications, 37 (73 %) had nor- meatal appearance (27 % vs. 55 %), the most
mal Qmax (>2 SD), while 14 (27 %) had reliable factor for optimal appearance of the
Qmax < 2 SD using an institutional nomogram. neomeatus was an already deeply grooved UP.
The authors reported that most normal Qmax were A study administered Likert-scale questionnaires
in the lower fiftieth percentile. Curves were not to parents of boys after 50 distal and 15 midshaft-to-
described (Jayanthi et al. 1995). proximal TIP, and 22 circumcisions (controls) in
The retrospective study by Braga et al. consecutive patients returning for 6-week follow-up.
(2007b) mentioned above included uroflow data There were no significant differences in scores rat-
on patients after proximal onlay repair, of which ing overall appearance or specific appearance of the
9 Hypospadias 135
meatus and penile skin by parents of patients vs. standard vs. modified technique for those with a
controls (Snodgrass et al. 2008). flat or intermediately clefted UP.
Another study used postoperative standardized
photographs obtained a median of 21 months
(1–120) after surgery to compare 16 TIP (10 distal Complications
and 6 proximal) done by one pediatric urologist to
10 Mathieu (distal) and 6 onlay (proximal) repairs General Risk Factors
done by a second pediatric urologist. A blinded
panel of three men and two women, comprising Logistic regression analysis of prospectively
another four surgeons and a nurse, scored the pho- collected data in over 600 consecutive patients
tographs assigning 1–4 points each for the appear- undergoing TIP by one surgeon found increased
ance of the meatus, glans, shaft, and overall urethroplasty complications predicted by
appearance. All mean scores were significantly meatal location (increasing with more proximal
higher for TIP (Ververidis et al. 2005). cases), and reoperation (vs. primary repair).
A study was done to determine if objective Similar analyses using retrospective data
scoring by photographs or subjective assessments after TIP also reported proximal repair
was superior. Twenty-seven patients with distal increased risk for complications.
hypospadias repaired by one surgeon using TIP Sutures (chromic, polyglactin, polydiaxone),
in 12 and Mathieu in 15 were assessed 6 months’ suturing methods (interrupted vs. continuous),
postoperatively. Objective scoring considered suture size (6–0,7–0), stents or not, and surgeon
five items assigned 0–2 points each: prepuce were not found to be independent risk factors.
(reconstructed in approximately 50 % of both The presence or absence of a barrier layer was
repairs), glans shape, meatal shape, meatal posi- significant in one report, while another found
tion, and shaft appearance. These photos were spongioplasty an independent factor, but not
reviewed by a surgeon blinded to the surgical when compared to a dartos flap.
technique. Then the same photos were rereviewed One report demonstrated a learning curve
by the same blinded surgeon, and the operating (first 100 cases), while another did not (first 50
surgeon was asked to give only an overall subjec- cases). One found age >4 years a risk factor,
tive score of 0–10. A parent also subjectively while two others did not find age at surgery a
scored an overall impression. The objective mean significant independent factor.
score was 7.4 ± 1.5, median 7 (5–10). Subjective Multiple logistic regression was used to deter-
scores by each observer were similar. Median mine odds for TIP urethroplasty complications
scores were significantly better for TIP vs. based upon potential risk factors, including age at
Mathieu (8 [5–10] vs. 7.25 [5–10], p = 0.02) surgery, meatal location, and primary vs. reoper-
(Scarpa et al. 2009). ative repair, in consecutive patients operated by
Retrospective analysis was done for two a single surgeon. All data were prospectively
groups of patients at median age approximately 2 collected in databases. From a total of 967 hypos-
years (10–132 months) with proximal hypospa- padias repairs done from 1999 to 2011, 156 TIP
dias undergoing the standard onlay procedure had no follow-up, 124 boys underwent inlay or
(n = 30) vs. a ventral slit modification (n = 22) staged graft operations, and 18 were postpuber-
designed to create a more slit-like neomeatus. tal, leaving the study cohort of 669 boys aged
Outpatient photographs were used to judge the 3–144 months with meatal location distal in 540
meatus, which was considered slit-like in 8/30 (81 %), midshaft in 50 (7.5 %), and proximal in
(27 %) standard onlays vs. 12/22 (55 %) modified 79 (12 %). Reoperations comprised 73 (11 %)
onlays, p = 0.04 (Hayashi et al. 2007). However, cases. Urethroplasty complications (fistula, glans
only those patients with a deeply grooved UP dehiscence, meatal stenosis, urethral stricture)
reliably had a slit-like neomeatus, while there occurred in 77 (11.5 %). Meatal location (dis-
was no significant difference in outcomes in the tal vs. midshaft vs. proximal) correlated with
complication risk (OR 1.79 [95 % CI 1.34–2.40]), Fistulas

as did reoperative TIP (OR 3.07 [95 % CI 1.54–
6.13]). Age, log age, age quartiles, age <6 months, Prevention
age >1 year, and age >5 years did not contribute One RCT indicated that one-layer subepithe-
to risk for urethroplasty complications, nor was lial distal-midshaft TIP urethroplasty had the
there a learning curve (first 50 cases) or differ- same outcomes whether suturing was inter-
ence in urethroplasty using chromic vs. polyglac- rupted or continuous.
tin sutures (Bush et al. 2012). One RCT found that a ventral dartos flap
A retrospective analysis was done to determine significantly reduced fistulas vs. no dartos flap
risk factors for urethroplasty complications after in distal TIP.
TIP in operations performed from 1997 to 2007 Technical modifications, including suture
by five surgeons. During this time, a total of 777 change (chromic to polyglactin and polydiax-
children had repairs, of which 391 were TIP at anone), change in suturing method (one-layer
median age 2 years (6 months–16 years). 347 running epithelial to two-layer subepithelial,
(89 %) were primary repairs, while another 44 the first interrupted and second running),
(11 %) were reoperations, and meatal location spongioplasty, and change in barrier flaps
was distal-midshaft in 334 (85 %) and proximal in (tunica vaginalis rather than dartos) resulted
57 (15 %). Urethroplasty complications occurred in a significant reduction in fistulas after prox-
in 48/391 (12 %). Logistic regression identified imal TIP in consecutive patient cohorts.
proximal hypospadias (RR 2.81 [95 % CI 1.42– Retrospective analyses report that one-
5.52]), age >4 years (RR 3.25 [95 % CI 1.44– layer subepithelial suturing had fewer fistulas
7.35]) and no neourethra barrier layer (RR 6.23 than one-layer epithelial closures in Mathieu
[95 % CI 1.87–20.77]) as risk factors for urethro- flap repairs, and two-layer epithelial suturing
plasty complications. Surgeon, polyglactin vs. resulted in fewer fistulas than one-layer tubu-
polydiaxone, continuous vs. interrupted suturing, larized preputial flap in proximal repairs.
6–0 or 7–0 suture, and stent were not found to be One RCT reported fibrin glue plus dartos
independent risk factors (Eassa et al. 2011). flap reduced fistulas and decreased size of
Another retrospective analysis also per- fistulas more than dartos flap alone in tubular-
formed multivariable logistic analysis to deter- ized preputial flap repair.
mine risk factors for complications after TIP. One RCT equally allocated a total of 80 boys at
There were 500 patients with mean age 6 years mean age 4.5 years (3–7) with primary distal shaft
(1–18), of which 439 (88 %) had primary repair (n = 64) or midshaft (n = 16) hypospadias to TIP
and 61 (12 %) a reoperation after one failed urethroplasty using interrupted vs. running subepi-
repair. The meatus was distal in 371 (74 %), thelial 6–0 or 7–0 polyglactin sutures (number of
midshaft in 78 (16 %), and proximal in 51 layers not stated). There were no differences in
(10 %). Operations were done by five surgeons fistulas, meatal stenosis, or wound dehiscence
(with results for each reported). Variables evalu- between patient groups (Sarhan et al. 2009).
ated included patient age, meatal location, pri- Another RCT allocated 130 patients with pri-
mary vs. reoperation, continuous vs. interrupted mary distal hypospadias to TIP with vs. without a
urethroplasty suture methods, use of a stent or ventral dartos flap barrier layer over the neoure-
not, spongioplasty or not, dartos barrier flap or thra. Operations were done by three surgeons;
not, surgeon, and learning curve. Multivariable urethroplasty was the same in all patients using
analysis found only proximal meatal location, 6–0 continuous polyglyconate (epithelial vs sub-
no spongioplasty, and learning curve (first 100 epithelial and number of layers was not stated),
cases) as independent risk factors for complica- and postoperative care was also uniform. Median
tions. However, the authors stated that spongio- follow-up was 24 months (6–60), with fistulas
plasty vs. a dartos flap was not significantly noted in 15/65 (23 %) without a dartos flap vs.
different (Sarhan et al. 2009). 5/65 (8 %), p = 0.03. Meatal stenosis and glans
9 Hypospadias 137
dehiscence occurred equally in both cohorts for Timing of randomization to receive fibrin glue vs.
overall rates of 4 % and 5 %, respectively none was not stated. Those treated had the glue
(Savanelli et al. 2007). coated directly onto the neourethra suture line, and
Statistically significant reduction in fistula then also over the dartos flap covering the neoure-
occurrence after proximal TIP was reported from thra. Fistulas were found in 6/60 (10 %) with fibrin
33 to10 to 0 % in 15, 20, and 24 consecutive glue vs. 19/60 (32 %) without glue, p = 0.027, and
patients in sequential series operated by a single were more likely to be <2 mm with glue than with-
surgeon after making several technical changes: out, 6/6 vs. 7/19, p = 0.015 (Gopal et al. 2008).
• Urethroplasty sutures from chromic to polyg-
lactin and polydioxanone. Treatment
• Suturing methods from one-layer running epi- Three retrospective case series found recur-
thelial to two-layer subepithelial interrupted rent fistulas in from 4 to 29 % despite barrier
(polyglactin) and then running (polydiaxone). layer coverage over the repair and either uni-
• Addition of corpus spongiosum coverage over versal or selective postoperative stenting.
the neourethra. There was no difference in recurrence for
• Replacement of dartos barrier flaps with tunica fistulas repaired after primary vs. reoperative
vaginalis flaps (Snodgrass and Bush 2011). hypospadias repair, or with first vs. subse-
A retrospective review of primary Mathieu dis- quent fistula closures.
tal hypospadias repairs done from 1993 to 1995 One study found recurrence greater in
found that 36 initial patients had one-layer urethro- fistulas >2 mm.
plasty using 6–0 polyglactin running epithelial One case series reported that one to seven
sutures, while 61 subsequent patients had one-layer topical applications of n-butylcyanoacrylate at
urethroplasty using 7–0 polydioxanone running diagnosis of fistula (as early as 3 days after
subepithelial sutures. All other aspects of surgery catheter removal) successfully closed approxi-
and postoperative care were said to be similar. mately 50 %.
During follow-up, described as between 6 and 12 One retrospective series reported outcomes
months, 6/36 (17 %) initial vs. 3/60 (5 %) later for 113 fistula closures. Interval between
patients had fistulas, p < 0.01, with no other compli- hypospadias and fistula repair was not stated.
cations noted in either group (Ulman et al. 1997). At surgery, eight had distal obstruction, result-
Another retrospective review analyzed prepu- ing in a simultaneous three meatal dilations,
tial flaps tubularized in one vs. two layers using two meatotomies, two direct visual internal
running epithelial 6–0 or 7–0 polyglactin. Single- urethrotomies (DVIU), and one reoperative
layer closures were more common initially and urethroplasty. All had subepithelial urethral
gradually replaced with two-layer repairs done closure and coverage with barrier tissues, and
from 1986 to 1993. Otherwise, surgical technique all were stented 1 week. Follow-up after the
and postoperative care were described as similar. last surgery was a median 7.5 years (2–17).
All patients were followed at least 6 months, but Thirty-three out of 113 (29 %) fistulas recurred
actual duration and timing of fistula diagnosis after initial closure, 10/33 (30 %) after a sec-
were not stated. There was no difference in fistula ond closure, and 5/10 (50 %) after a third clo-
rates in patients with distal hypospadias regardless sure, p = 0.4. Fistulas £2 mm were less likely
of methods, but there was a significant reduction than those >2 mm to recur (22/92 vs. 11/21,
of fistulas in proximal repairs with two-layer ure- p = 0.02 (Shankar et al. 2002).
throplasty (12/29 [41 %] one-layer vs. 4/27 [15 %] Another retrospective review reported out-
two-layer, p = 0.04) (Chuang and Shieh 1995). comes for closure of 99 fistulas, all >6 months
Reduction of fistula rate by using fibrin glue after hypospadias repair. Boys were divided
was reported in a prospective randomized trial of into those with simple closure (epithelial or
120 boys with proximal hypospadias undergoing subepithelial not stated) including coverage
tubularized preputial flaps by a single surgeon. with either a dartos flap or skin/dartos flap
(n = 69) or complex repairs that included reop- coronal, distal shaft, and midshaft locations
erative urethroplasty or meatotomy (n = 25). (Prestipino et al. 2011).
Stents were used “routinely” in complex but not
in simple cases. Duration of follow-up after
fistula closure was not stated. Recurrent fistula Glans Dehiscence
developed in 6/94 (4 %), including 3/69 simple
and 3/25 complex closures, p = 0.3 (Santangelo Glans dehiscence, defined as complete separa-
et al. 2003). tion of the glans wings, occurred in significantly
A third retrospective study identified 123 more patients after proximal or reoperative
patients with fistulas, 100 after initial hypospa- (15 %) than primary distal TIP (4 %).
dias repair and 23 failed fistula closures. Repair Recurrent glans dehiscence occurred in
was a median 13 months postoperatively (4 27 % of reoperative TIP glansplasties and over
months–12 years), and involved fistula closure 50 % of third glansplasties.
(epithelial vs. subepithelial not stated) and cov- A report comprising prospectively collected
erage with dartos. Duration of follow-up after data in 641 consecutive patients after primary
fistula closure was not stated. Successful closure distal and proximal and reoperative TIP reported
occurred in 36/54 (68 %) with postoperative glans dehiscence in 32 (3.8 %), 4 % after distal
catheter (used for “larger” fistulas and “more and 15 % after proximal and reoperative surger-
complex” repairs) vs. 35/46 (76 %) without cath- ies. Multivariable analysis found that primary
eters, p = 0.3. Successful repair was done at 4–6 proximal and reoperative TIP had greater odds
months in 11/16 (73 %) vs. 55/90 (61 %) at >6 for glans dehiscence than distal TIP (proximal
months, p = 0.4 (total repair number of 106 rather OR 4.38 [95 % CI 1.94–9.42]; reoperative TIP
than 123 was not explained). Success did not OR 3.95 [95 % CI 1.66–8.72]). Other potential
vary with initial vs. recurrent fistula repair: factors, including age and glansplasty suture
71/100 (71 %) vs. 46/61 (75 %), p = 0.6 (Waterman (chromic vs. polyglactin), did not predict this
et al. 2002). complication. Review of other published results
While a 6-month interval after urethroplasty indicated similar occurrence of glans dehiscence
before fistula repair is routine, one report indi- after glansplasty in either 1 or 2 layers, using 5–0,
cated topical application of n-butyl cyanoacry- 6–0, or 7–0 sutures of polyglecaprone, polydiox-
late (NBCA) was potentially successful when anone, or polyglactin (Snodgrass et al. 2011).
applied at first diagnosis of a fistula. There were Another report from the same institution
13 patients with single fistulas noted within 3 described outcomes for reoperations specifically
days of catheter removal or later after TIP repair. for repair of glans dehiscence. Most primary
In all cases, a urethral stent was placed, the fistula and secondary glansplasties used one-layer
site cleaned with 10 % iodopovidone, and then subepithelial 6–0 polyglactin suture, usually a
NBCA applied and the stent then removed. total of three stitches from the meatus to the
Patients with fistulas treated 6–24 months after corona. Of 618 primary distal and proximal TIP
surgery additionally had topical anesthesia to the repairs, 29 with glans dehiscence had reopera-
fistula site, which was then scarified using a 27-G tive glansplasty, of which recurrent dehiscence
needle before NBCA application. At follow-up developed in 7/26 (27 %) with follow-up.
2, 7 days, and apparently soon thereafter, if Another 100 patients had primary repair else-
needed, NBCA was again applied if the fistula where and presented with glans dehiscence,
persisted for a total of one to seven applications. with recurrent dehiscence occurring in 11/85
Success with >1.5 years follow-up was noted in (13 %) with follow-up, which was not
7/13 (54 %) and was similar for early vs. late significantly different, p = 0.13. A total of 11
treatment (4/6 vs. 3/7, p = 0.6), fistulas < vs. boys had a third glansplasty, with recurrent
>2 mm (5/7 vs. 2/6, p = 0.), after one vs. multiple dehiscence in 5/8 (63 %) with follow-up
applications (3/3 vs. 4/10, p = 0.2), and for sub- (Snodgrass et al. 2012).
9 Hypospadias 139
Meatal Stenosis achieve a long-term stable meatus. Meatotomy is

an option, but we found no articles describing its
There is no published, generally accepted use and outcomes after hypospadias repair.
definition for meatal stenosis. One report stated that four of the initial seven
The author considers meatal caliber <8 Fr distal TIP cases developed fistulas 2 weeks after
in an asymptomatic patient potential stenosis. surgery, attributed to meatal stenosis (which was
Systematic literature review found meatal not defined). Meatal dilations were done, a stent
stenosis reported in 3 % of patients after distal replaced for 5 days, and then daily dilation (size
TIP and 0.7 % following Mathieu. not stated) was done for 3 months. The fistulas all
A large series of consecutive patients under- closed. Follow-up was not described to determine
going distal TIP reported no meatal stenosis. if meatal stenosis recurred (Elbakry 1999).
We found no reports of outcomes following
treatment of meatal stenosis after hypospadias
repair. Strictures
A systematic literature review of primary distal
hypospadias repairs published from 1990 to 2009 Systematic literature review reported no case
included 23 papers, with 1,872 TIP patients in 15 of neourethra stricture after distal TIP.
case series and 1,496 Mathieu repairs in 10 series. Dissection of the UP and urethra from the
Reported meatal stenosis occurred in 3 % TIP and corpora cavernosa with proximal TIP repair
0.7 % Mathieu, p < 0.001, the authors noting that resulted in increased strictures, all symptomatic,
this diagnosis could vary from center to center over proximal TIP without these maneuvers
because it is subjective (Wilkinson et al. 2012). (17 % vs. 0 %) in one report, but not another.
A retrospective study reported that all post-
Prevention hypospadias repair strictures diagnosed in a
Analysis in 426 consecutive boys undergoing 6-year period presented with symptoms.
distal TIP hypospadias repair by one surgeon, The literature review by Wilkinson et al.
with 279/426 (65 %) having calibration, (2012) mentioned above also reported occurrence
uroflowometry, and/or urethroscopy postopera- of neourethral stricture after TIP and Mathieu
tively, reported no case of meatal stenosis (meatal repairs for primary distal hypospadias: 0/758 TIP
caliber <8 Fr). Technical details emphasized to and 2/302 Mathieu, p = 0.08.
avoid stenosis included: A report using prospectively collected data from
• UP incision to near the corpora cavernosa so consecutive proximal TIP operated by a single sur-
that the plate is sufficiently wide. geon analyzed 75 patients, of which 29 had the UP
• Tubularization of the UP not extending dis- and urethra mobilized from the corpora cavernosa
tally beyond the midglans (approximately to facilitate straightening the VC. Neourethra stric-
3 mm from the glans junction), leaving an tures ranging from 1 mm to 1 cm in length occurred
oval, not rounded, opening. in 5/29 (17 %) vs. 0/46, p = 0.02. The strictures
• Not suturing the neourethra to glans wings, were all symptomatic, with UTI and/or urinary
which allows UP tubularization to stop below retention, and were diagnosed at 6 weeks–1.5 years
the external neomeatus without leaving a postoperatively (Snodgrass et al. 2012).
glanular hypospadias (Snodgrass et al. 2010). In contrast, a retrospective review that included
32 patients with UP plus urethra mobilization/UP
Treatment tubularization with (n = 20) and without (n = 12)
Few reports discuss treatment for meatal stenosis dorsal incision reported no strictures during a
and subsequent outcomes. Early postoperative mean 24 months’ (6 months–3 years) follow-up
narrowing could represent transient edema and (Bhat 2007).
require no therapy. If stenosis occurs due to vas- A retrospective review identified stricture
cular insufficiency, it is unlikely dilations will repair in 38 patients during a 6-year period. All
patients presented with symptoms, predominantly tion reported that the indication for surgery was
“difficulty voiding/decreased stream” in 22 (58 %), stricture in 37. Mean length of the graft for the
with none detected by uroflowometry without com- entire cohort was 5 ± 2 cm (3–7.5), preferentially
plaints. Prior repairs included “Duplay or King harvested from lower lip. With follow-up a mean
tube” (n = 14), tubularized (n = 9) or onlay (n = 1) 23 ± 10 months (12–30), 3/37 (8 %) developed
preputial flaps, Mathieu (n = 3), and tubularized or recurrent stricture at the proximal junction to the
onlay grafts (n = 10), with 23 (61 %) originally hav- native urethra (Ye et al. 2008).
ing proximal hypospadias. Location and length of
the strictures was not stated (Duel et al. 1998).
Another retrospective study found 73 cases of Diverticula
urethral stricture after hypospadias repair over a
10-year period ending in 2007. Presenting com- Diverticula are more common following flap
plaints, if any, were not described, nor was stric- repairs than UP tubularizations, and can
ture length or location. Prior urethroplasties were occur in the absence of distal obstruction.
UP tubularizations with (n = 29) or without (n = 5) Retrospective review was done of a single sur-
incisions (47 %), meatal advancement (n = 5, geon experience with 130 proximal hypospadias
7 %), two-stage repairs (n = 21, 29 %), flap repairs repairs between 1991 and 2004. Operations used
(n = 10, 14 %), or tubularized grafts (n = 3, 4 %). included 72 (55 %) one-stage preputial flaps (36
Of these, 46 (63 %) were described as glanular to tubularized and 36 onlay), and 58 (45 %) staged
subcoronal, but means to distinguish meatal repairs (18 Belt-Fuque and 40 Bracka grafts).
stenosis from glanular stricture were not described Mean follow-up was 16 years (6–19), and mean
(Gargollo et al. 2011). age of patients at last evaluation was 15 years
(7–27). Assessments used during follow-up and
Treatment frequency of follow-up evaluations were not
A prospective study limited DIVU to strictures stated. A diverticulum (ventral ballooning and
<1 cm after hypospadias repair, reporting suc- post-void dribbling) was diagnosed in 5 cases, all
cess with 2-year follow-up in 56 %. Failure after preputial flaps, for an incidence of 5/72
was predicted by prior tubularized grafts or (7 %). None of these were diagnosed with simul-
flaps and prior DIVU. taneous distal stenosis, and all occurred before
A retrospective review of oral mucosal inlay puberty at a mean of 7 years (3–8) after surgery.
graft for hypospadias strictures reported There were no recurrences after diverticulum
success in 92 %, with the remainder forming repair with follow-up a mean of 9 years (5–15).
recurrent stricture at the proximal junction to “Proximal” hypospadias was not defined, nor
the native urethra. was original meatal location; it is noteworthy that
One prospective study of 72 patients with stric- only 20 (15 %) patients had VC, and all needed
tures <1 cm found technique in prior hypospadias only dorsal plication for correction, which implies
repair influenced response to DIVU, with urethro- less “severe” hypospadias (Vallasciani et al.
tomy successful at 2-year follow-up in 2/18 tubu- 2012), in press.
larized flaps and 0/32 tubularized grafts, vs. 8/11 A retrospective review of 58 onlay vs. 74
onlay flaps and 7/11 urethral plate tubularizations, tubularized preputial flaps by one surgeon found
p < 0.05. Of 32 recurrent strictures, 12 still <1 cm overall complications in approximately one-third
underwent repeat DIVU and all failed. This report of patients in both groups, but diverticula only
also found that adjunctive urethral dilation after after tubularized flaps [9/74 (12 %), p = 0.016]
DIVU did not improve outcomes over DIVU (Wiener et al. 1997). However, multivariable
alone. Failure of DIVU should not be treated with analysis was not done to take into account the
second DIVU, but should instead prompt open significant differences in severity of the hypospa-
urethroplasty (Husmann and Rathbun 2006). dias defect between these two cohorts.
A retrospective review of 53 patients, mean Another retrospective review concerning
age 12 ± 7 years (3–34), with inlay graft reopera- repair of hypospadias complications in 123
9 Hypospadias 141
patients included diverticula in 13, only 1 with tunica vaginalis flap was used, p = 0.008 (flap
associated neourethra obstruction. Prior repairs use was not recorded in two). Glans dehiscence
included seven onlay and five tubularized prepu- occurred in six patients, including one who
tial flaps and one bladder mucosa tubularized also had a fistula. Of 55 patients in whom the
graft (Snyder et al. 2005). prior surgical technique was known, complica-
Literature review did not find reports of diver- tions occurred in 7/35 with prior UP incision vs.
ticula after TIP (Snodgrass 2011). 5/20 without prior incision, p = 0.74 (Snodgrass
et al. 2009).
Treatment A retrospective analysis reported 30 reopera-
Recurrence or need for additional surgery tive TIP in boys at mean age 4 years following
after excision has been reported in two retro- a mean 1.6 failed repairs (1–3). The meatus was
spective series in 8 and 11 %. distal in 19, midshaft in 8, and proximal in 3.
Repair by Snyder et al. (2005) mentioned above Urethroplasty included subepithelial closure
included excision and “multilayered closure,” with using 5–0 or 6–0 polyglactin covered by a dar-
1/13 (8 %) recurring during follow-up a mean of tos flap. All were followed for 1 year, and then
24 months. Two other cases developed fistulas. recontacted for additional review at ³4 years.
Another retrospective review of hypospadias Complications occurred in nine (30 %) patients;
complications included 22 diverticula, of which there were six fistulas, with five also having
18 were repaired. Each was considered to have meatal stenosis, and three meatal stenoses.
distal obstruction and diverticula tissue was used Factors that appeared to increase likelihood for
in correction. Otherwise, surgical technique was complications included more than one prior
not described, and follow-up was not stated. Two operation and midshaft -proximal meatus, but
out of 18 (11 %) subsequently had additional sur- multivariable analysis was not done (Ziada
gery (Secrest et al. 1993). et al. 2006).
Another retrospective review included 40 TIP
reoperations for patients with fistulas (n = 14) or
Reoperations dehiscence (n = 26), using 7–0 polyglactin rapide
and either dartos or tunica vaginalis barrier cov-
TIP erage. The number of prior surgeries was not
stated. During follow-up a mean of 42 months
Reoperative TIP can be done when the UP is (for a larger series including primary repairs),
not grossly scarred, despite prior midline inci- complications developed in five (12.5 %)—three
sion, with complications reported in from 12 fistulas, one meatal stenosis, and one urethral
to 30 % of patients (Table 9.3). Use of a bar- stricture (Riccabona et al. 2003).
rier flap has been shown to reduce fistulas.
Analysis of prospectively collected data in
69 consecutive patients having a mean of 1.1 Buccal Inlay
(1–3) prior operations reported indications for
reoperation were repair dehiscence (n = 63), If the UP has been excised but an unscarred
coronal fistulas (n = 3), meatal stenosis (n = 2), skin strip remains as a neo-plate, dorsal inci-
and post-onlay diverticulum (n = 1). Of these, sion with buccal inlay grafting resembles TIP
62 originally had distal, 4 midshaft, and 3 repair.
proximal hypospadias. Complications occurred One prospective and two retrospective
in 12 (19 %) of 63 patients with follow-up a reviews reported 15 % complication rates in
mean of 6 months (1–53). Initially, a barrier patients with a mean of two to four prior oper-
flap was not created to cover the neourethra, ations (Table 9.4).
and 5 of these 10 patients developed fistulas vs. Prospective data were reported from 16 con-
2 in the next 51 in which either a dartos or secutive buccal inlay patients following a mean
142
Table 9.3 Reoperative TIP outcomes

Meatus Indications Complications
Mean
(range) Mean f/u No. pts.
Author No. pts. Surgeries D M P F MS Stx GD D VC No. pts. f/u (mos) complications F MS Stx GD D
(Riccabona 40 NS NS NS NS 14 – – 26 – – 40 42 5 (12.5 %) 3 1 1 0 0
et al. 2003)
(Ziada et al. 30 1.6 (1–3) 19 8 3 13 – – – – 0 30 NS (£60) 7 (23 %) 6 8 – – –
2006)
Snodgrass 2009 69 1.1 (1–3) 62 4 3 3 2 – 63 1 – 63 6.4 (1–53) 12 (19 %) 7 0 0 6 0
F fistula, MS meatal stenosis, Stx stenosis, GD glans dehiscence, D diverticulum, VC ventral curvature, NS not stated
W.T. Snodgrass and N.C. Bush
9
Hypospadias
Table 9.4 Inlay graft reoperations

Meatus Indications Complications
Mean (range) No. pts.
Author No. pts. prior surgeries D M P F MS Stx GD D No. pts. f/u Mean f/u (mos) complications F MS Stx GD D
(Schwentner 31 4(1–18) 13 – 18 – – – NS – 31 31 5 (16 %) 1 0 4 0 –
et al. 2006)
(Ye et al. 2008) 53 2(1–6) – – – – – 37 16 – 53 23 8 (15 %) 5 – 3 – 0
Snodgrass 2009 16 2(1–9) 10 3 3 – 1 – 15 1a 13 5 2 (15 %) 1 0 0 1 0
a
One patient had both meatal stenosis and a urethral diverticulum
143
of 1.9 (1–9) prior operations. The meatus was prior operations who underwent two-stage oral
distal in ten, midshaft in three, and proximal in mucosa graft reoperation. These included 9 dis-
three cases. Complications developed in 2/13 tal, 6 midshaft, and 33 proximal hypospadias
(15 %) with follow-up, comprising one glans cases, requiring reoperation for wound dehis-
dehiscence and one fistula despite a dartos flap cence (n = 27), VC (n = 13), stricture (n = 6),
(Snodgrass et al. 2009). meatal stenosis (n = 6) with BXO in two, fistula
The retrospective study by Ye et al. (2008) and dehiscence (n = 6), and hair in the urethra
mentioned above reviewed 53 patients, mean age (n = 1). Focal (n = 4) or complete (n = 1) graft
12 years (3–34), with inlay graft reoperation for complications (10 %) required patching in a sep-
stricture in 37 and dehiscence in 16. The mean arate stage before urethroplasty. Second-stage
number of prior repairs was two (1–6). Mean urethroplasty complications occurred in 17/45
length of the graft was 5 ± 2 cm (3–7.5), preferen- (38 %) with follow-up, mostly glans dehiscence
tially harvested from lower lip. With follow-up a when cheek rather than lip was used in the glans
mean 23 ± 10 months (12–30), complications (8/25 vs. 0/17, p = 0.01), fistulas (n = 7), and
developed in eight (15 %)—five fistulas and three meatal stenosis (n = 2), with no strictures or
recurrent strictures at the proximal junction to the diverticulum (Snodgrass et al. 2009).
urethra (Ye et al. 2008). A retrospective series of 100 patients failing
Another retrospective review included 31 an average of five (3–16) prior operations
patients, mean age 14 years (15 months–26 included 21 with distal, 40 with midshaft, and 37
years), who failed a mean of four prior repairs with proximal hypospadias. Graft donor sites
(1–18) and presented with a variety of complica- included prepuce (n = 39) (considered the optimal
tions, including fistulas, strictures, diverticula, source since prepuce is thinner than either skin
and dehiscence (numbers not stated). Grafts were from other sites or oral mucosa), oral mucosa
harvested from prepuce (n = 15), penile skin (n = 34), post-auricular (n = 22,) or from the upper
(n = 12), or groin skin (n = 4) with mean length of arm (n = 5). Partial graft loss occurred in seven,
4 cm (1–15). At mean follow-up of 30 months requiring regrafting before second-stage urethro-
(8–66), complications occurred in five plasty in two. Total number of patients with com-
(16 %)—four strictures at the proximal junction plications was not reported, but urethroplasty
and one fistula (Schwentner et al. 2006). complications included fistulas (n = 9), strictures
(n = 6), persistent hypospadias (n = 6), and persis-
tent curvature (n = 4) (Gill and Hameed 2011).
Two-Stage Buccal Grafting Another retrospective case series reported 30
patients undergoing two-stage oral mucosa graft-
Case series of patients having failed a mean of ing (mean number of failed prior repairs not stated),
four or five hypospadias repairs report first- of which there were 5 distal, 12 midshaft, and 13
stage complications needing an additional graft- proximal hypospadias cases. Indications for reop-
ing procedure before urethroplasty in £13 %. eration were not stated, although nine had BXO.
Second-stage urethroplasty complications Regrafting was required before second-stage
occurred in approximately 38 % of patients tubularization in four (13 %). Urethroplasty com-
(Table 9.5). plications occurred in 11 (37 %), comprising meatal
Lip grafts are thinner than cheek grafts stenosis (n = 5), fistulas (n = 3), and glans dehis-
and have a significantly smaller likelihood for cence (n = 3) (Leslie et al. 2011).
glans dehiscence. Donor site morbidity for buccal tissue harvest
Systematic literature review regarding donor (not specific to hypospadias surgery) was deter-
site morbidity (not limited to hypospadias sur- mined by systematic literature review to occur in
gery) reported complications in 4 % of adults. 4 % of adult patients, with no differences in over-
Prospective data were reported from 48 con- all complications between cheek vs. lip harvest
secutive patients with a mean of four (1–20) sites (Markiewicz et al. 2008).
9
Hypospadias
Table 9.5 Two-stage graft reoperations

Urethroplasty
Meatus Indications Graft complications
Mean No. pts.
(range) Other graft No. Meanf/u No. pts.
Author No. pts. surgeries D M P F MS Stx GD D VC BXO P O skin reop pts. f/u (mos) complications F MS Stx GD D VC
Snodgrass 48 4.3 9 6 33 6 6 7 27 – 13 2 0 48 0 5 45 8 17 (38 %) 7 2 0 8 0 –
2009 (1–20) (10 %)
(Gill & 100 5 (3–16) 21 40 37 82 – 33 98 – 88 – 39 34 27 2 (2 %) 100 NS (>1 year) NS 9 – 6 – – 4
Hameed
2011)
(Leslie 30 NS 5 12 13 – NS – – – – 9 0 30 0 4 30 25 11 (37 %) 3 5 3
et al. 2011) (13 %)
145
Table 9.6 Reoperative skin flaps

Complications
No. of Mean no. Mean follow-up Complication
Series patients prior repairs in months rate (%) F MS Stx GD D VC Failure
(Jayanthi 28a 1 in 30, 2–6 NS 8 (29) 2 1 1 – – – 4
et al. 1994) in 14
(Emir and 55a 1.4 (1–3) 3 16 (29) 14 – – 2 – – –
Erol 2003)
(Bar-Yosef 34a 1.6 (1–3) 29 9 (26) 5 2 – – – – 2
et al. 2005)
(Jayanthi 16b – NS 9 (56) 4 – 2 – – – 4
et al. 1994)
(Emir and 33c 1.5 (1–3) NS 16 (48) 14 – – 2 – – –
Erol 2003)
(Patel et al. 11c 2 (1–5) 24.5 6 (55) 5 – – – 1 1 –
2005)
a
Mathieu flip-flap
b
Tube or onlay flap
c
Onlay
Skin Flaps including fistulas and two meatal stenoses (Bar-

Yosef et al. 2005).
Several retrospective series report Mathieu Another retrospective review reported 11
reoperations after a mean of approximately reoperations after a mean of 2 (1–5) prior hypos-
1.5 prior repairs, with subsequent complica- padias repairs using onlay flap. During mean
tions in over 25 % (Table 9.6). follow-up of 24 months, complications occurred
Reoperative tubularized or onlay flaps were in six (55 %), including six fistulas, one divertic-
reported to have complications in over 50 % in ulum, and one flap contracture with persistent
two small case series. VC (Patel et al. 2005).
A retrospective review of cases from 1986 to
1992 found 39 reoperations, 25 after one failed
repair and 14 after two to six operations. Adult Outcomes After Prepubertal
Reoperation was done by Mathieu in 28 and Repair
skin flap in 16 (8 tubularized, 8 onlay).
Follow-up was a mean of 17 months (0.5–60), A systematic literature review pooled data
with complications developing in 8/28 Mathieu from 20 studies reporting outcomes in patients
(29 %) and 9/16 (56 %) island flaps (Jayanthi operated at <6 years of age using a variety of
et al. 1994). surgical techniques who had follow-up at >14
Another retrospective evaluation concerned years of age:
Mathieu reoperations performed in 55 patients • Urinary Function: Patients reported obstruc-
during a 20-year period for large fistulas or tive voiding symptoms, spraying, and devi-
glans dehiscence after a mean of 1.4 prior ated stream significantly more than controls,
operations (1–3). Mean follow-up was 3 and had decreased Qmax on uroflowometry.
months (1–8), with complications noted in 16 • Sexual Function: Erectile dysfunction,
(29 %), fistulas in 14, and dehiscence in 2 problems with ejaculation and overall
(Emir and Erol 2003). decreased sexual satisfaction were reported
A third retrospective study reported 34 reop- by significantly more patients than controls.
erative Mathieu procedures after a mean of 1.5 • Appearance: Patients, especially those with
(1–3) failures. With mean follow-up of 29 months proximal hypospadias, were less satisfied
(1–84), complications occurred in nine (26 %), with genital appearance than controls.
9 Hypospadias 147
Two studies reported long-term follow-up [3 %]). Patients with proximal hypospadias had
in men after childhood repair using various significantly lower Qmax (mean 21 cc/s) than did
preputial flaps, finding that 8 and 17 % had those with distal hypospadias.
complications occurring after last childhood
follow-up.
One study of men after Denis Browne repair Sexual Function
leaving the meatus a mean of 1 cm below the
glans tip found that 100 % who were not Erectile Dysfunction
satisfied with surgical outcomes desired addi- This complaint was not defined, but it was
tional surgery, and another 50 % who reported significantly more often in patients than
expressed greater satisfaction with their sur- age-matched controls (30/156 [19 %] vs. 3/249
gery but still wanted additional surgery. [1 %], p < 0.01).
A systematic literature review through 2010
concerned outcomes in men after childhood Ejaculation
hypospadias repair, and set inclusion criteria to Ejaculation problems, including milking semen
designate surgery before age 6 years and follow- and poor force, were significantly more common
up at >14 years of age. Twenty studies with a in patients than controls (99/385 [26 %] vs. 0/48,
total of 1,069 patients were analyzed. Mean p < 0.01).
number of operations was 2.7 (1–20); proximal
hypospadias outcomes were available for 180 Sexual Satisfaction
patients. Operative techniques included proce- Patients were less satisfied with sexual function
dures not commonly used today, such as than controls (153/188 [81 %] vs. 235/252
Ombredanne, Denis-Browne, van der Muelen, [93 %], p < 0.01). Mean frequency of intercourse
and Cecil-Culp, as well as the more recent per month did not vary (5.8 vs. 6.4).
MAGPI, Mathieu, onlay, and tubularized prepu-
tial flaps and Byar’s flaps. Assessments and
findings are presented here. Cosmesis
There was no difference in concern for abnormal

Urinary Function appearance in patients vs. controls (approxi-
mately 33 %), but patients were more likely
Symptoms dissatisfied with that appearance (143/493
Patients reported obstructive symptoms (77/217 [29 %] vs. 24/581 [4 %]). Patients with proximal
[35.5 %] vs. 30/196 [15 %], p < 0.01); spraying hypospadias were even more dissatisfied with
(245/818 [30 %] vs. 17/231 [7 %], p < 0.01); and penile appearance than those with distal hypos-
deviated stream (69/267 [26 %] vs. 9/81 [11 %], padias (25/46 [54 %] vs. 143/493 [29 %]).
p < 0.01) more often than controls. Post-void The authors commented that pooling data
dribbling and sitting to void did not significantly from studies with various methodological
vary, and were reported by 104/351 (30 %) and designs, heterogenous data, and small patient
15/174 (9 %) patients. Patients with proximal numbers is a weak method for comparisons
hypospadias reported spraying more often than (Rynja et al. 2011).
those with distal repairs (46/106 [43 %] vs. Sexual function was reported in a study of
245/818 [30 %]). men after Denis Browne repair by one surgeon
vs. age matched controls. Four hundred patients
Uroflowometry were eligible for inclusion after uncomplicated
Qmax was significantly less in patients than con- (i.e., no reoperations) midshaft or proximal
trols (mean 24 cc/s vs. 30 cc/s, p < 0.01), as was hypospadias surgery (mean age 4.5 years, range
Qmax less than 2 SD (36/265 [13.5 %] vs. 4/138 3–7) and current age ³21 years. Non-validated
questionnaires were mailed to all these and to milk the ejaculate vs. no reported problems by
another 150 age-matched controls (means for controls.
selection not stated). Of the patient question- • There was no difference in cohorts regarding
naires, 167 were returned with no address, and of either sexual inhibitions or relationships, and
the remaining 233, 104 (45 %) responded; of there was similar body image satisfaction
150 control questionnaires, 63 (42 %) responded. (approximately 85 % satisfied).
Mean age of patients and controls was 32 years. • Mean total sexual partners was lower in patients
The meatus was reported by patients to be a vs. controls (5 vs. 7, p = 0.02), and mean fre-
mean of 1 cm from the tip of the glans, and 79 % quency of intercourse during 1 month was also
stated that the urinary stream was deviated. less for patients (4 ± 4 vs. 7 ± 6, p = 0.04).
Sixty-three percent reported no VC, while 5 % • Fewer patients reported being “completely
had “major” curvature. Patients were significantly satisfied” with their sex life than controls (51 %
less satisfied with their genital appearance vs. vs. 77 %, p = −0.03) (Bubanj et al. 2004).
controls, yet reported significantly higher sexual Late complications were reported in another
satisfaction. Overall satisfaction with surgical study, mentioned above, that evaluated patients
results was 7 on a 10-point scale, but there were who underwent tubularized and onlay preputial
12 patients (12 %) who marked <5, with median flap repair by one surgeon for proximal hypospa-
score 3 (2–3) that was significantly less than dias between 1981 and 1992. Of 125 patients,
patients scoring ³5. This subgroup of patients medical information could only be retrieved for
also scored significantly lower than the others on 73, of which 49 could be contacted for follow-up
satisfaction with genital appearance, regular sex- ³10 years postoperatively and 30 agreed to exam-
ual activity, and sexual satisfaction. All these ination. These patients had been operated at mean
dissatisfied patients responded that they wished age 17 months (8–74) with tubularized repair in
to have additional surgery, vs. 50 % of those 14 and onlay in 16, and follow-up was a mean of
whose scoring satisfaction with surgery was 14 years later (12–21). New complications were
higher (Kiss et al. 2011). found in 5/30 (17 %)—two fistulas and three
Sexual function was compared in 57 patients meatal stenoses (Patel et al. 2004).
previously operated for hypospadias (34 distal, 9 Late complications were also reported by a
midshaft, 14 proximal, techniques used not stated) study that contacted all 44 patients who underwent
randomly selected from 130 cases repaired between second-stage preputial flap repair (Belt-Fuque) by
1985 and 1990 who were >18 years of age, and 60 one surgeon between 1985 and 1993, of which 25
age-matched controls (means of selection not could be restudied a mean of 13 years (11–17)
described). Questionnaires (non-validated) were later, and another 2 responded to questionnaires.
mailed, and 37 patients, mean age 28 ± 6 years, and Meatal location was midshaft in 14, penoscrotal
39 controls, mean age 26 ± 5 years, responded. in 9, and perineal in 4. Following initial repair,
These patients had been operated at mean age of complications developed in 13 (48 %) of these
11 ± 9 years of age, with a mean of 4 (1–17) opera- participants, but at late follow-up, none had addi-
tions. On a scale of 1–5, satisfaction with surgical tional problems. Another two (8 %) had new
outcomes was rated a mean of 3.9 ± 0.8. The fol- complications—one fistula and one stricture (Lam
lowing observations were reported: et al. 2005).
• Patients and controls similarly reported good-
quality erections.
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9 Hypospadias 151
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Merguerian P, et al. A prospective randomized clinical Rynja SP, de Jong TP, Bosch JL, de Kort LM. Functional,
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Split onlay skin flap for the salvage hypospadias repair. 6–7.
J Urol. 2005;173(5):1718–20. Secrest CL, Jordan GH, Winslow BH, Horton CE,
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Phimosis, Meatal Stenosis, and BXO
10
The primary aim in diagnosis and treatment • BXO involvement of glans and meatus clini-
of phimosis and meatal stenosis is relief of cally resolves in most patients within 2
symptoms. years of circumcision.
The primary aim in diagnosis and treatment
of balanitis xerotica obliterans (BXO) is to avoid
urethral stricture from progressive disease. Phimosis
A secondary aim for circumcision is to
reduce likelihood for sexually transmitted dis- Prevalence and Natural History
ease in adults.
Evidence for these aims: The foreskin normally does not fully retract at
• Our review found no study reporting the birth. Two studies by pediatricians reported
incidence of symptomatic phimosis. that phimosis persisted in <10 % of boys after
• The normal foreskin does not fully retract age 3 years. By age 16, the foreskin did not
at birth, but persistent failure to retract fully retract in 1 %.
occurs in <10 % of teens. Phimosis is normal at birth, with subsequent
• RCTs demonstrate betamethasone ointment retractability over time reported in several series:
is more effective than placebo to achieve • Observations were made by a pediatrician
partial or complete retraction, but placebo is in 100 newborns, 200 boys to age 5 years,
also effective in up to 45 % of cases. and 200 aged 5–13, noting the foreskin was
• Our review found no definition for meatal fully retractable in 4 % at birth, 20 % at 6
stenosis. months, 50 % at 1 year, and 90 % at ³3 years
• One study of boys with deflected urinary (Gairdner 1949).
stream undergoing meatotomy reported • Another pediatrician reported the state of the
that symptoms improved and mean Qmax foreskin in 9,545 boys 6–17 years of age,
increased. finding phimosis overall in 4 %, decreasing
• There is poor evidence that meatotomy is from 8 % at age 6 years to 1 % in those 16
indicated for a small-appearing meatus, years of age (Oster 1968).
dysuria, or incontinence. • Foreskin status was recorded in 10,421
Chinese boys presenting to a children’s hospi-
P.C. Gargollo, M.D. (*) tal, excluding urology clinic patients. All new-
Department of Pediatric Urology, University of Texas borns had non-retractable foreskin, vs. 7 % of
males 11–18 years of age (Yang et al. 2009).
Dallas, TX 75235, USA • Natural history of the prepuce was deduced
e-mail: patricio.gargollo@childrens.com from a sample of 600 Japanese boys 0–15
154 P.C. Gargollo
years of age presenting to pediatric surgical 137 boys, mean age 7 years (3–15), on a waiting
and urologic clinics (reasons for examination list for circumcision (indications, including
not stated) over a 1-year period. Status of the symptoms, not described). Retractability of the
prepuce was categorized into five types: prepuce was graded as follows:
• No retraction. 1. Full retraction
• Exposure of urethral meatus. 2. Full retraction but tight behind the glans
• Exposure of 50 % of glans. 3. Exposure of more than one-third of glans
• Exposure of glans to above the corona at site 4. Exposure of less than one-third of glans
of (inner) preputial adhesion. 5. Pinhole opening
• Exposure of entire glans. 6. No retraction
Before 6 months of age, no boy in this sample All patients had grades 4–6. Treatment was
had type 5 complete retraction, and after 11 years retraction to extent possible without causing pain
of age, no boy had type 1 no retraction (Kayaba or skin fissure with cream application twice daily
et al. 1996). for 4 weeks. The primary endpoint was grade 3 or
less, and all patients not improved to this extent
were treated with betamethasone for another 4
Medical Therapy weeks. Assessment was done by a different doc-
tor than the one that prescribed therapy; compli-
Because phimosis spontaneously corrects, ance was assessed by examining the tube of
therapy should be limited to boys with related cream at follow-up. It was not stated if phimosis
symptoms. grade was equivalent between groups. At 4
We found no population-based study weeks, 49/66 (74 %) betamethasone vs. 31/71
describing incidence of symptoms in uncir- (44 %) placebo patients were considered cured,
cumcised boys. p < 0.01. Of 57 not responding who completed
One study using uroflowometry and PVR four subsequent weeks of betamethasone, 43
reported no differences in boys with phimosis (75 %) were cured. Therefore, 118/137 (86 %)
and ballooning during voiding compared to had retractability to expose one-third of the glans
those without ballooning. or greater with steroid treatment. Retraction was
A study compared uroflow, PVR, and renal then recommended “several times a day,” with
US in 32 consecutive boys, mean age 7 years, follow-up at 18 months. Of the 118, 92 returned,
with phimosis, of which 18 had ballooning dur- with 13 (14 %) having recurrence of phimosis
ing voiding. Renal US was normal in all, there described as “minor.” Response by phimosis
was no difference in mean Qmax (15 cc/s), and no grade was not reported (Lund et al. 2005).
difference in mean PVR (3.5–6 cc) in those with Another double-blinded RCT used the five-
vs. without ballooning (Babu et al. 2004). point phimosis grading scale by Kayaba described
above:
Steroids for Primary Phimosis 1. No retraction (58 % patients)
Two RCTs reported that betamethasone 2. Exposure of urethral meatus (19 %)
significantly improved retraction vs. placebo: 3. Exposure of 50 % of glans (21 %)
• Neither described indications for therapy. 4. Exposure of glans to above the corona (2 %)
• Success defined as retraction exposing more 5. Exposure of entire glans
than one-third of the glans occurred in One hundred ninety-five boys, mean age 5 years
86 % steroid vs. 44 % placebo patients. (3–10), were randomized to four groups: (1) 0.2 %
• Success defined as full retraction occurred betamethasone plus hyaluronidase, (2) 0.2 %
in 55 % steroid vs. 30 % placebo. betamethasone, (3) 0.1 % betamethasone, and (4)
• Recurrent phimosis developed in £15 %. placebo. Indications for treatment were not stated.
A double-blinded RCT tested 0.1 % betame- There was no difference between groups based on
thasone cream vs. aqueous cream (placebo) in age or phimosis grade. Treatment was retraction
10 Phimosis, Meatal Stenosis, and BXO 155
with cream application twice daily for 60 days;

success was defined as grade 5, total retraction. Neonatal Circumcision
Success occurred in 57 %, 59 %, and 48 % of
groups 1 through 3 (no significant differences) vs. Anesthesia
29 % placebo, p < 0.001. Success by phimosis
grade was 54 % grades 1 and 2, and 33 % grade 3. Ring block was found to be significantly better
Follow-up was done at 240 days in successful than dorsal nerve block or EMLA for new-
cases (instructions for retraction, if any, not born circumcision.
stated). Recurrence (not defined) was reported in Cochrane review of RCTs comparing pain
2 % (Nascimento et al. 2011). interventions with no treatment or placebo during
A prospective study evaluated 260 boys, mean neonatal circumcision reported the following:
age 34 months (3–168), with “symptomatic phi- • Fourteen trials with 592 newborns compared
mosis” described as 42 % with ballooning and dorsal nerve block to no treatment/placebo,
16 % with balanoposthitis, but also 13 % UTI, finding significantly lower heart rate, decreased
and others with itching, “straining,” dysuria, and time crying, and increased O2 saturation with
smegma. Phimosis was graded as follows: nerve block.
1. Full retraction (including limitation by inner • Six trials with 200 newborns found that EMLA
preputial–glans adhesions) significantly reduced heart rate and time cry-
2. Full retraction, tight behind glans ing vs. placebo.
3. Meatus visible • Three trials with 139 newborns compared
4. Slight retraction, meatus and glans not visible nerve block to EMLA, reporting significantly
5. No retraction lower heart rate and pain scores with nerve
Treatment was done using 0.05 % betametha- block (Brady-Fryer et al. 2004).
sone 2×/daily until phimosis resolved, followed Fifty-four full-term newborns had Gomco
by “daily hygiene” (not described). Success was circumcision done in a double-blinded placebo
£ grade 2. Reassessment was done at 1, 2, and 4 controlled trial testing EMLA, dorsal nerve block,
weeks and 6 months. At 1 week, 72 %, and by 4 and ring block. Blocks used 1 % lidocaine.
weeks, 91 % had success, which was similar for Primary outcomes were heart rate and cry, which
grades 3–5 phimosis. At 6 months, 25 (9 %) had were significantly greater in the placebo group
recurrence (Reddy et al. 2012). than in all three treatment groups. The ring block
was more effective than EMLA or dorsal nerve
Steroids for Secondary Phimosis block, since the latter were not effective during
One study reported betamethasone for foreskin separation from the glans or dorsal slit
secondary phimosis after neonatal circumci- (Lander et al. 1997).
sion completely exposed the glans in 64 % of
patients.
One retrospective study concerned newborns Gomco and Plastibell
referred within 1 month of circumcision with a
“trapped penis” from secondary phimosis, identi- One review found wound separation more
fying 14 patients. Treatment was 0.05 % betame- common with Gomco circumcision and infec-
thasone 3×/daily for 3 weeks. Complete exposure tion more common after Plastibell
of the glans occurred in nine (64 %), complete circumcision.
exposure with a persistent cicatrix was noted in One retrospective review of Plastibell out-
another two who were also undergoing a vertical comes stated that malposition of the ring
relaxing incision, and the remaining three had no occurred in 0.5 %.
improvement, leading to reoperation. Follow-up One study reported greater complications
after medical therapy was 3–6 months without when Gomco was used in 6-month-old infants
secondary treatment (Palmer et al. 2005). than in newborns.
156 P.C. Gargollo
Review of 5,521 newborn circumcisions per- Circumcision with Bleeding Disorders

formed from 1963 to 1972 before nursery dis-
charge was done by medical students, residents, or Interventions to reduce bleeding from circum-
faculty physicians. Gomco was used in 48 %, and cision in hemophiliacs include preoperative
Plastibell in 52 %, with hemorrhage (requiring factor replacement and tranexamic acid,
“special efforts to stem blood flow”) in 59 (1 %), intraoperative fibrin glue, and postoperative
infection in 23 (0.4 %), wound separation in 9 factor replacement for up to 7 days.
(0.2 %), excess skin removal in 2 (0.04 %), and Bleeding despite these preventative mea-
Plastibell too tight in 7 (0.1 %): an overall inci- sures occurred in 4–24 % of patients.
dence of 100 (2 %) complications. There was no Bleeding was reported as late as 8 days
difference in hemorrhage, but wound separation after circumcision.
was significantly more common with Gomco; Literature review found six studies published
infection was more likely using the Plastibell from 1992 and 2004 with 163 hemophiliac patients
(Gee and Ansell 1976). undergoing circumcision. Factor replacement ther-
Plastibell neonatal circumcision was done in apy was used in five, antifibrinolytics alone were
3,000 boys from 2004 to 2008 by urologists or used in one, and postoperative replacement was
pediatricians. Complications occurred in 1 %, continued for 2–8 days. Bleeding complications
including hemorrhage in 8, “inappropriate penile were reported in up to 50 % (Hermans et al. 2009).
appearance” (apparently excessive residual skin As part of a prospective trial, 25 hemophiliac
or tags) in 12, and “malposition of the ring” in 14 boys, median age 20 months (7–34), who had
(Simforoosh et al. 2012). either no or “minimal” exposure to factor VIII,
Gomco circumcision was done in 98 neo- received factor VIII and tranexamic acid infusion
nates, mean age 17 days (4–30), and 32 infants, and then underwent circumcision. The wound
mean age 6.5 months (3–8.5), the latter using was dressed with a gelatin sponge absorbable
general anesthesia. During the initial 30 postop- hemostatic agent and Vaseline gauze removed at
erative days, there were no complications in £7 days. Patients were discharged home within
neonatal procedures, vs. 12 (30 %) infant cir- 6 h of circumcision. Bleeding occurred in one
cumcisions. All complications were bleeding, patient (4 %) on the eighth postoperative day
which required fulguration or suturing (Horowitz (Elalfy et al. 2012).
and Gershbein 2001). A retrospective review found 48 children with
bleeding disorders who had circumcision, includ-
ing 24 with hemophilia A, 5 with hemophilia B,
Mogen Clamp and 15 with von Willebrand disease. Overall,
bleeding complications occurred in 11 (23 %):
One report from Israel, where the Mogen • The bleeding disorder was known preopera-
clamp is commonly used by ritual circumcis- tively in 21 (44 %), with circumcision done at
ers, found one case of partial glans amputa- £6 weeks in 16. Of these 21, 12 had factor
tion from a presumed 19,478 procedures. replacement before surgery, but 3 still had bleed-
A review of complications after newborn cir- ing complications, including transfusion in 2.
cumcision in Israel, most done by certified ritual • The bleeding disorder was not known in 27, of
circumcisers who use the Mogen clamp, esti- which 25 were circumcised at £6 weeks.
mated a rate of 0.3 % based on assessment of 66 “Oozing” occurred in 8 (30 %), but none
cases from 19,478 male births. These included required transfusion.
hemorrhage in 16, wound infection in 2, and par- • Bleeding in the 11 patients occurred immedi-
tial glans amputation in 1. Late complications ately in 9, within hours in 1, and 2 weeks later
were excessive skin in 38 and shortage of skin in in 1 (with known disease and factor replace-
4 (Ben Chaim et al. 2005). ment) (Rodriguez et al. 2010).
Another retrospective review reported on the circumcision complication (bleeding, suture

Izmir protocol, which was done for 50 boys, mean laceration, wound-penis, etc.) were found in 287
age 9 years (1–16), with known hemophilia. These (0.2 %), or 1 of every 476 newborn circumcisions
children had oral tranexamic acid beginning 1 day (Christakis et al. 2000).
preoperatively and continuing for 7 days, factor
infusion to achieve ³90 % levels 1 h preopera-
tively, fibrin glue applied subepithelially and over Late Complications
the incision line, and postoperative factor infu-
sions every 12 h for 48 h. Postoperative bleeding Excess residual skin and meatal stenosis are
occurred in three (6 %) (Yilmaz et al. 2010). the most commonly reported late complica-
Comparison of the Izmir protocol was made to tions from circumcision.
patients treated earlier using factor replacement One report defining excess skin as covering
for up to 7 days without fibrin glue in a retrospec- ≥50 % of the glans with downward compres-
tive analysis. Bleeding complications developed sion of the penopubic junction reported occur-
in 6/20 circumcised with longer factor replace- rence in an estimated 0.2 %.
ment and no fibrin glue vs. 7/37 (19 %) following Meatal stenosis occurred in <1 % after
the Izmir plan, p = 0.5, indicating that the Izmir newborn circumcision in two studies, neither
protocol was as effective as traditional longer- of which defined criteria for the diagnosis.
duration factor replacement (Sasmaz et al. 2012). A cross-sectional study evaluated 3,125 cir-
cumcised boys aged 6–12 years in Iran, with most
(71 %) having the procedure after age 2 years and
Circumcision with Aspirin Therapy for only 3 % done as neonates. These operations had
Heart Disease been done by surgeons/urologists (32 %), primary
care physicians (19 %) or paramedical personnel
Our review found no report concerning cir- (6 %), and traditional circumcisers (44 %). Ninety-
cumcision in children with congenital heart three had a normal examination; the most com-
disease taking aspirin. mon complications diagnosed were excessive
residual skin (not defined) in 4 %, and excessive
removed skin, meatal stenosis (not defined), gran-
Early Complications uloma, penile rotation, and chordee in £1 % each.
Significantly fewer complications occurred after
Systematic review found early complications circumcisions performed by urologists/surgeons
after circumcision in 1.5 % of neonates and (4 %) than by primary physicians (10 %) or tradi-
6 % of children >1 year of age. tional circumcisers (8 %) (Yegane et al. 2006).
A systematic review was done regarding The prospective study by Simforoosh et al.
reported complications (excluding residual excess (2012) mentioned above reported meatal
skin) after circumcision, finding the following: stenosis (not defined) was diagnosed in 11
• Sixteen prospective studies of neonates and (0.4 %) at 15-month follow-up, with all under-
infants from 12 countries, median frequency going meatotomy.
of complications was 1.5 % (0–16 %) A review of newborn circumcisions in Israel
• Ten prospective studies of boys ³1 year of age defined excess residual skin as covering ³50 % of
from ten countries, median frequency of compli- the glans while pressure was applied at the peno-
cations was 6 % (2–14 %) (Weiss et al. 2010). pubic base to control for pre-pubic fat. By these
A review was done using the Comprehensive criteria, 38 cases were diagnosed at four medical
Hospital Abstract Reporting System to estimate centers, which had a total of 19,478 male births,
complications following 130,475 newborn cir- for a rate of 0.2 %, assuming all patients with this
cumcision over a 9-year period ending in 1996. complication returned for follow-up (Ben Chaim
Recorded diagnoses potentially indicating et al. 2005).
158 P.C. Gargollo
A retrospective review was done for patients outweigh the risks and that the procedure’s
referred to a pediatric surgical service for circum- benefits justify access to this procedure for
cision revision. Between 1995 and 1999, 56 boys, families that choose it. Specific benefits include
6 weeks to 11 years of age, had reoperation, all prevention of UTI, penile cancer, and transmis-
stated to have excessive residual skin (not sion of some sexually transmitted infections,
defined); 29 (52 %) also had penile adhesions including HIV.”
(not defined), and 8 (14 %) had phimosis. The
authors stated that “because dissatisfaction with UTI Reduction
the circumcision already had been expressed by See Chap. 1.
the parent or primary care physician, we revised
all referred children” (Brisson et al. 2002). Reduced Disease Transmission in Adults
HIV
Three RCTs conducted in young-adult African
Secondary Phimosis males reported a 50 % reduction in HIV infection
with circumcision during follow-up £2 years.
One study reported that secondary phimosis A RCT in South Africa included 3,274 men
developed in 3 % following newborn Gomco randomized to circumcision or control with fol-
circumcision. low-up to 21 months scheduled. The trial was
Treatment using either betamethasone or stopped at mean follow-up of 18 months after
mechanical stretching of the phimotic ring interim analysis found 20 HIV infections in cir-
was reported successful in 64–100 % of cases. cumcision men vs. 49 in controls, RR 0.4 (95 %
The study by Palmer et al. (2005) described CI 0.2–0.7). This represented a 60 % risk reduc-
above found that treatment using 0.05 % betame- tion (Auvert et al. 2005).
thasone applied 3×/daily for 3 weeks resolved A RCT was conducted in Kenya, mostly
secondary phimosis in 9/14 (64 %) infants referred within a tribal group with a circumcision preva-
within 1 month of circumcision. Follow-up after lence of approximately 10 % and an HIV preva-
medical therapy was 3–6 months without second- lence of 18 % males and 25 % females. Two
ary treatment (Palmer et al. 2005). thousand seven hundred eighty-four uncircum-
From a total of 521 infant (median age 2 cised HIV-negative males, mean age 20 years,
months, 2 weeks–4 months) Gomco circumci- were randomly assigned to circumcision or con-
sions, 15 (3 %) developed secondary phimosis. trol groups with follow-up HIV testing to 24
Another 13 with this complication were referred, months postoperatively. At 2 years, 2 % of cir-
and these 28 infants had nerve block performed cumcised and 4 % of uncircumcised males were
and dilation of the phimotic ring using a hemostat HIV-positive, p = 0.006; RR in circumcised men
to deliver the concealed glans. With follow-up of was 0.5 (95 % CI 0.3–0.8), corresponding to a
1 month, three (11 %) had recurrence treated with risk reduction of 53 %. The trial was stopped
repeat glans delivery from below the phimotic early, when interim analysis showed these results
ring. No circumcision revisions were done (Bailey et al. 2007).
(Blalock et al. 2003). A similar study was conducted in Uganda in
4,996 uncircumcised men aged 15–49 years,
which also showed circumcision efficacy of
Medical Benefits 51 % (95 % CI 16–72) for HIV avoidance (Gray
et al. 2007).
AAP Policy Statement, 2012
HPV
The AAP circumcision task force recently HPV prevalence is less in circumcised men.
updated 1999 recommendations stating that One meta-analysis found that circumcision
“the health benefits of newborn circumcision did not reduce risk for acquiring HPV.
Meta-analysis was done on 21 studies with was >5 cc/s in cases, and that mean Qmax was
8,046 circumcised and 6,336 uncircumcised greater after meatotomy.
males, with circumcision associated with A retrospective study of meatal stenosis
significantly reduced odds for genital HPV, OR identified 50 patients with the condition, 34
0.6 (95 % CI 0.4–0.8) (Albero et al. 2012). symptomatic and 16 without symptoms (criteria
A systematic literature review and meta-anal- for diagnosis not stated). All had newborn or neo-
ysis was done regarding impact of circumcision natal circumcision. Meatotomy in symptomatic
on human papillomavirus transmission, which cases was done at mean age 4 years for “poor
included 21 studies (two RCTs, both conducted stream” (36 %), dysuria (30 %), straining (14 %),
in Africa) with 8,046 circumcised and 6,336 retention (not defined) (8 %), dribbling (6 %),
uncircumcised men. Reported findings included and bedwetting (19 %) (all with other additional
the following: symptoms). All these complaints were said to be
• Circumcision reduced odds for genital HPV relieved at follow-up 1–3 months later.
prevalence (OR 0.57 [95 % CI 0.42–0.77]). Asymptomatic patients also had meatotomy
• Circumcision did not reduce risk for genital (Upadhyay et al. 1998).
HPV acquisition (summary effect 1.01 [95 % Another retrospective study found 120 males,
CI 0.66–1.53]) (Albero et al. 2012). mean age 2.5 years (3 months–6 years), diagnosed
with meatal stenosis based on a pinhole meatus
Other STDs and inability to pass a 6-Fr catheter. Twenty-seven
Circumcision did not reduce gonorrhea, chla- percent had no symptoms, while 33 % had a
mydia, or syphilis infections in the RCTs deflected and smaller urinary stream and 35 %
described above for HIV. There was reduced had dysuria. US done in all cases reported no
risk for herpes simplex virus type 2 infection. obstructive uropathy (Mahmoudi 2005).
The Kenyan RCT described above to determine Evaluation in 132 males aged 5–10 years old
circumcision impact on HIV seroconversion also with a history of neonatal circumcision referred
evaluated risk for Neisseria gonorrhea, Chlamydia to a surgical clinic without urinary complaints
trachomatis, or Trichomonas vaginalis infection in included meatal calibration with a 5-Fr catheter.
circumcised vs. control males. Circumcision did In 27 (20 %), the catheter would not pass, and 25
not reduce risk for these nonulcerative sexually of these had decreased-caliber stream and pro-
transmitted infections (Mehta et al. 2009). longed voiding (uroflowometry not reported).
The Ugandan RCT also studied circumcision Three had bilateral hydronephrosis and bladder
impact on prevention of herpes simplex virus thickening and UD showed “obstructed bladder
type 2 (HSV-2), human papillomavirus (HPV), outlet.” Results of meatotomy were not described
and syphilis, reporting no reduction for syphilis, except to state residual urine persisted in these
but reduced HSV-2 (8 % vs. 10 %, HR 0.7 [95 % three cases while others had improvement (means
CI 0.6–0.9], p = 0.008) and HPV (18 % vs. 28 %, to assess not stated) (Joudi et al. 2011).
RR 0.65 [95 % CI 0.5–0.9], p = 0.009) (Tobian A retrospective study was done in 22 boys,
et al. 2009). mean age 8 years (4–13), diagnosed with meatal
stenosis, for deflected urinary stream (n = 20,
91 %), frequency (n = 9, 41 %), dysuria (n = 6,
Meatal Stenosis 27 %), or after UTI (n = 2, 9 %). Uroflowometry
was done pre- and post-meatotomy (by 6 weeks);
Diagnosis the authors reported a significant increase in Qmax
from mean 10 cc/s to a mean of 16 cc/s, p = 0.001.
Our review found no definition for meatal Flow patterns were plateau in 16 pre-meatotomy,
stenosis. with persistence in 6 (37.5 %) after meatotomy.
One study in which 90 % of patients had a Mean PVR decreased from 19 to 14 cc, p = 0.01.
deflected urinary stream reported that Qmax It is noteworthy that Qmax was >5 cc/s in all
160 P.C. Gargollo
patients before meatotomy. All symptoms resolved years later in which 4 % stated that they had a
without recurrence in a mean of 12 months (6–28) “thin jet at voiding”(Stenram et al. 1986).
(VanderBrink et al. 2008). Eighteen hundred schoolboys aged 6–10 years
were examined by “spreading the meatus,” with
578 (32 %) considered to have meatal stenosis on
Prevalence the basis of a “pinpoint or just slightly larger”
opening. The authors admitted that these were
One study of consecutive males reported that “astounding” results (Allen and Summers 1974).
while meatal stenosis (meatal opening £2 mm
with symptoms) only occurred in circumcised
boys, there was no significant difference vs. Meatotomy
uncircumcised boys.
A study included 1,100 consecutive males £18 One study reported that office meatotomy
years of age undergoing physical examination by using EMLA was effective, with only 5 %
a single pediatrician from 1995 to 2001. Diagnosis experiencing discomfort.
of meatal stenosis was made on the basis of Fifty-eight boys, mean age 4 years (20
symptoms (“dysuria, voiding complaints, stream months–10 years), had office meatotomy using
abnormalities, abdominal discomfort”) and EMLA topical ointment applied 60 min before
meatal opening £2 mm. Ninety-one (8 %) were the procedure. Oral midazolam was used in two.
not circumcised. Meatal stenosis was diagnosed During meatotomy, three (5 %) were described as
only in circumcised boys, overall in 3 % (95 % having “some discomfort.” Follow-up in 57 was
CI 1.76–3.79 %), and with increased incidence in ³3 months, with one (2 %) partial recurrence
prepubertal boys >3 years of age (7 % [95 % CI (Cartwright et al. 1996).
4.48–10.10 %]). However, there was no significant
difference in circumcised vs. uncircumcised
males overall or in patients >3 years, OR with Balanitis Xerotica Obliterans
circumcision 3.5 (95 % CI 0.62–infinity). The
author commented that the study had sufficient Diagnosis
subjects to have an 80 % chance of detecting an
8 % difference in meatal stenosis rates (Van BXO is clinically suspected in secondary phi-
Howe 2006). mosis and/or from a white sclerotic ring at the
The prospective study by Simforoosh et al. tip of the prepuce.
(2012) mentioned above reported that meatal BXO is suspected when a previously retractile
stenosis (not defined) was diagnosed in 11 (0.4 %) prepuce becomes nonretractile, typically with a
at 15-month follow-up, with all undergoing white sclerotic ring at the tip of the foreskin.
meatotomy. Pathologic examination demonstrates atrophy of
A retrospective study was done in 117 patients the epidermis, loss of rete pegs, and inflammatory
undergoing circumcision at median age approxi- cell infiltration in the dermal-epidermal junction.
mately 5 years in a single clinic in 1976, for
recurrent balanitis in 45, preputial scarring in 25,
ballooning of the prepuce during voiding in 41, Incidence
and asymptomatic phimosis in 6. Follow-up
included determination of the width of the meatus Three studies reported BXO in from 10 to 40 %
at 3 months. Thirteen (11 %) were diagnosed as of consecutive boys undergoing circumcision.
having “stricture” of the meatus that required During a 10-year period ending 2001, 1,178
meatotomy, but criteria for that determination, consecutive boys, mean age 7 years (2–16), were
related symptoms, and results were not described. referred to a urology clinic in Hungary for phi-
A questionnaire was answered by 92 patients 5 mosis, excluding an unknown number wanting
circumcision for “cultural or social” reasons. Tacrolimus

Neither symptoms nor clinical findings (white One study reported that tacrolimus applied to
sclerotic ring) were described. All patients had the glans and meatus effective to resolve BXO
circumcision with pathologic examination of the after circumcision, but without an untreated
specimen. BXO was diagnosed pathologically in control group.
471 (40 %) boys, mean age 9 years with youngest Tacrolimus ointment, 0.1 %, was applied to
2 years old. Ninety-three percent of these with the glans and meatus 2×/daily for 3 weeks
BXO had secondary phimosis, vs. 32 % of beginning 3 weeks after circumcision in 20
patients without BXO (Kiss et al. 2005). boys, mean age 10 years (5–16), with BXO. Of
Another study involved 100 consecutive boys, these, 11 only had the lesion apparent in the pre-
mean age 6 years (1–17), undergoing circumci- puce, while another 3 had visible glans, 4 had
sion in Switzerland (indications not described). visible meatal involvement, and 2 had both glans
BXO was diagnosed histologically in 10 (10 %) and meatal involvement. All visible signs disap-
after being suspected preoperatively in 12 (Meuli peared with 3 weeks treatment, with 1 (11 %)
et al. 1994). recurrence in 6 months on the glans successfully
After encountering a child with BXO, the next retreated with 6-month subsequent follow-up.
100 consecutive foreskins removed in an Of the 11 patients treated without known resid-
Australian hospital at parent’s request (n = 35), ual disease 1 (9 %) recurred at the meatus at 8
for phimosis (n = 38), or for balanitis or during months and responded to retreatment for 3 weeks
hypospadias repair and other “miscellaneous with subsequent 8-month follow-up. The authors
conditions” were histrologically examined. BXO admitted that circumcision alone can be effec-
was described in nine (9 %); age of these children tive for clearing visible glans and meatal lesions
and whether the condition was suspected clini- (Ebert et al. 2008).
cally was not stated (Bale et al. 1987).
Circumcision
BXO involving the glans and meatus was
Medical Treatment reported in two studies to resolve or improve
within 2 years after circumcision.
Topical Steroids In 231/471 (49 %) boys with BXO reported by
One trial reported that BXO phimosis Kiss et al. (2005) above, the glans also had whit-
improved with steroid ointment, but histologic ish discoloration that resolved spontaneously in
changes persisted. all cases within 2 years after circumcision. Seven
A double-blinded RCT compared 0.05 % (2 %) had meatal involvement treated with meato-
mometasone furoate vs. placebo in 40 boys, mean tomy at circumcision. Outcome in these was not
age 9 years (5–15), with phimosis due to BXO on specifically stated (Kiss et al. 2005).
the basis of “typical macroscopic findings” (not Of the ten confirmed cases of preputial BXO
described). Ointment was applied 1x daily for 5 in the series reported by Meuli et al. (1994) above,
weeks, then prepuce retraction was scored and seven had “characteristic glans lesions” (not
circumcision performed. Phimosis was graded defined) but none had meatal stenosis. These
1–4 (complete retraction vs. no retraction). Those resolved in five and improved in the other two at
with steroid had a significant improvement from 5-year follow-up after circumcision.
mean 3.4 ± 0.15 to 2.9 ± 0.2 (better in 7 and A retrospective review found 300 patients
unchanged in 10) vs. placebo, with decreased with BXO “limited to the foreskin or glans,” of
retraction from mean 3 ± 0.2 to 3.4 ± 0.2 (worse in which 287 (96 %) had circumcision as the sole
5 and unchanged in 11). The authors did not state therapy. In the others, meatotomy was done in
if any steroid-treated child had clinical resolution five, oral mucosa graft urethroplasty in four,
of phimosis, and apparently all had histologic and excision of BXO from the glans with skin
confirmation of BXO despite steroid treatment grafting in four. Of the 287 with only circumci-
(Kiss et al. 2001). sion, persistence of BXO was noted in 11 (4 %),
162 P.C. Gargollo
involving the glans in 5 or spreading to the treated severe hemophilia a children. Pediatr Hematol
urethra in 6. Treatment with topical clobetasol Oncol. 2012;29(5):485–93.
Gairdner D. The fate of the foreskin, a study of circumci-
was not effective for glans involvement (dura- sion. Br Med J. 1949;2(4642):1433–7. illust.
tion of use not stated). Length of follow-up Gee WF, Ansell JS. Neonatal circumcision: a ten-year
was not stated (Depasquale et al. 2000). overview: with comparison of the gomco clamp and
the plastibell device. Pediatrics. 1976;58(6):824–7.
Gray RH, Kigozi G, Serwadda D, Makumbi F, Watya S,
Nalugoda F, et al. Male circumcision for HIV preven-
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using Plastibell. J Pediatr Urol. 2012;8(3):320–3. cumcision in Iran. Pediatr Surg Int.
Stenram A, Malmfors G, Okmian L. Circumcision for 2006;22(5):442–5.
phimosis: a follow-up study. Scand J Urol Nephrol. Yilmaz D, Akin M, Ay Y, Balkan C, Celik A, Ergun O,
1986;20(2):89–92. et al. A single centre experience in circumcision of
Tobian AA, Serwadda D, Quinn TC, Kigozi G, Gravitt haemophilia patients: Izmir protocol. Haemophilia.
PE, Laeyendecker O, et al. Male circumcision for the 2010;16(6):888–91.
Ureteropelvic Junction Obstruction
11
Warren T. Snodgrass and Patricio C. Gargollo
The primary goal in diagnosing and treating • No RCT shows benefit for surgery over
ureteropelvic junction obstruction (UPJO) is observation to preserve ipsilateral renal
to prevent ipsilateral renal function loss. function.
Secondary goals are to minimize associated • Two studies reported resolution of renal
comorbidities, including the following: colic after surgery. No studies were found
1. fUTI. documenting impact of pyeloplasty on
2. Pain. recurrent UTI, hematuria, or renal stone
3. Hematuria. formation.
4. Urolithiasis.
Summary of evidence for these aims:
• Extent of hydronephrosis (HN) by either Threshold for Postnatal Evaluation
SFU grade or anterior-posterior (AP) diam- of Prenatal Hydronephrosis
eter does not correlate with renal function.
• To our knowledge, no study demonstrates There is no consensus on the threshold of ante-
that prolonged drainage determined by natal HN that should prompt postnatal imaging,
T1/2, appearance of the curve, or other no agreement on timing for postnatal imaging,
measurement correlates with renal func- and uncertainty as to the significance of some
tion or predicts future renal function loss. potentially pathologic findings, such as VUR.
• Most patients have <10 % change in ipsilat- Meta-analysis reports that likelihood for
eral renal function after pyeloplasty. pathologic findings increases with the extent
• Zero to 39 % of patients observed without of antenatal HN, based on AP diameter.
surgery have ipsilateral function loss vari- Increased risk for any pathology (UPJO, VUR,
ously described as >5 %, >10 %, or <40 %, PUV, ureteral obstruction, other), based on
but following pyeloplasty, final ipsilateral third-trimester AP diameter, was as follows:
renal function loss is 0–6 %. • £9 mm, 12 % (95 % CI 4.5–28).
• 10–15 mm, 45 % (95 % CI 25.3–66.6).
• 15 mm, 88 % (95 % CI 53.7–98.0).
Risk was greatest for UPJO, 5 % for AP
W.T. Snodgrass, M.D. (*) • P.C. Gargollo, M.D. £9 mm, 17 % for AP 10–15 mm, and 54 % for
Department of Pediatric Urology, University of Texas AP >15 mm.
Southwestern Medical Center and Children’s Medical One prospective study reported a third-tri-
mester antenatal AP diameter of 15 mm dis-
e-mail: warren.snodgrass@childrens.com; criminated obstruction in 80 % of fetuses with
patricio.gargollo@childrens.com 73 %/82 % sensitivity/specificity.
166 W.T. Snodgrass and P.C. Gargollo
VUR risk is approximately 16 %, regard- 16 % (7–35 %) of those with cystography. VUR

less of extent of antenatal HN or if postnatal in the non-dilated kidney comprised 25 % of
US is normal (see Chap. 2). detected cases. Extent of antenatal HN did not
A meta-analysis screened 1,645 articles on predict VUR likelihood. VUR grade was approx-
antenatal HN from 1966 to 2005 to determine if imately 1/3 each for grades I-II, grade III, and
the extent of dilation is associated with postnatal grades IV-V (Skoog et al. 2010).
outcome. Only 17 case series met criteria, from
which a dataset of 1,308 subjects was derived.
A summary (simplified here) defined classification Timing of Postnatal Imaging
of antenatal dilation based on AP diameter in the
third-trimester as “mild” £9 mm, “moderate” A single study reported that 38 % of renal
9–15 mm, and “severe” ³15 mm. Postnatal units in newborns with prenatal HN >8 mm
pathologies were defined as UPJ, VUR, PUV, had increased dilation on US done at ≥7 days
ureteral obstruction (ureterocele, ectopic ureter, compared to US done at £48 h after birth.
megaureter), and “other” (multicystic dysplastic One guideline recommended initial nuclear
kidney, PBS, hydrometrocolpos, bladder agene- renography at 1 month of age.
sis). Overall risk for any of these pathologies
increased by increasing extent of antenatal HN:
• £9 mm (n = 587), 12 % (95 % CI 4.5–28). Timing of Ultrasound
• 9–15 mm (n = 235), 45 % (95 % CI 25.3–66.6).
• ³15 mm (n = 94), 88 % (95 % CI 53.7–98.0). One prospective study of 21 newborns (37 kid-
Considering specific pathologic categories, neys) that defined prenatal HN as AP diameter
risks were highest for UPJ: mild, 5 % (95 % CI >8 mm at ³33 weeks obtained postnatal US within
2.0–11.9); moderate, 17 % (95 % CI 7.6–33.9); 48 h of birth and again at 7–10 days. Of the 37
and severe, 54 % (95 % CI 21.7–83.6). Only renal units, 5 showed no HN on either postnatal
VUR showed no significant trend for increasing US and in another 10 there was no change in HN
risk of occurrence with increasing degree of ante- observed between studies. An increase in HN was
natal HN (Lee et al. 2006). noted in 14/37 (38 %), of which 8 increased to
A prospective study defined antenatal HN by grade 3. The grade decreased in 8 (22 %), but only
third-trimester AP diameter ³7 mm, resulting in 1 of these had initial grade ³3 that decreased to
postnatal US at 3–4 weeks of age, “subsequent” grade 1 (Wiener and O’Hara 2002).
VCUG, and diuretic MAG-3 renography for
those with SFU grades 3–4 postnatal HN.
Pyeloplasty was indicated by differential renal Timing of Nuclear Renography
function loss >10 % and <40 % function and/or
progressive HN on serial US. Of 257 infants, Guidelines issued by the Pediatric Committee of
obstruction was diagnosed in 62 (24 %) with the European Association of Nuclear Medicine rec-
mean antenatal AP diameter 22.3 ± 12.1 mm. ommend 1 month of age for the initial renogram,
ROC analysis determined that an antenatal AP based on expert opinion (Gordon et al. 2011).
diameter threshold of 15 mm discriminated
obstruction in 80 % of fetuses with 73 % sensitiv-
ity and 82 % specificity (Coplen et al. 2006). Impact of Technical Factors in Nuclear
The meta-analysis performed by the 2010 Renography
AUA Reflux Guidelines Panel to determine risk
for VUR in newborns with antenatal HN consid- Renography provides information on individ-
ered 34 studies in which mean percentage of ual kidney percentage function and drainage,
newborns/infants screened by cystography was both of which are potentially impacted by
78 % (11–100 %). VUR occurred in a mean of various technical factors.
11 Ureteropelvic Junction Obstruction 167
One study reported a 5 % difference in two Drainage After Furosemide

common methods used to subtract background
nonrenal activity when determining differen- The Pediatric Committee of the European
tial renal function. Association of Nuclear Medicine reviewed expert
Another study of MAG-3 renograms found opinion regarding confounding factors in the
>5 % variation between the two common interpretation of radionuclide clearance. These
methods used to calculate renal function in include patient hydration, bladder fullness, supine
25 % of patients <1 year of age versus 10 % in positioning, reduced ipsilateral renal function
those >1 year of age. (which reduces tracer extraction from the circula-
Many factors potentially influence tion, slows filling of the dilated renal pelvis, and
observed drainage after furosemide, result- potentially reduces diuretic response), and vari-
ing in a recommendation by one guideline able renal pelvic size (despite similar SFU grades
panel that renogram drainage not be used as of HN). They concluded that qualitative assess-
an indication for pyeloplasty. ment of the renogram curve may be sufficient to
One retrospective study of hydronephrotic reduce concerns for obstruction when:
kidneys otherwise considered stable found • There is a short time to maximum tracer activ-
variation in drainage depending on technique ity and a rapidly descending curve with nearly
used and on serial diuretic renograms, also complete renal drainage.
concluding drainage should not be used as the • There is delayed time to maximum activity
indication for surgery. and delayed emptying followed by prompt
washout with furosemide.
• There is delayed uptake and delayed excretion
Estimates of Differential Renal Function despite furosemide, but rapid clearance on a
post-micturation view (if continuous bladder
Prospective analysis was performed in 8 kidneys drainage is not used).
with right HN, 17 with left HN, and 9 with bilat- Conversely, a continuously rising activity
eral HN as well as in 14 without HN using curve despite these maneuvers was said to increase
MAG-3 renography to determine effect of back- concern for obstructed emptying. The panel cau-
ground non-renal activity on differential function tioned T1/2 is an empiric determination, variable
measured by two methods: subrenal or perirenal. by the initial and final activity points chosen.
A significant mean difference in differential renal Because of several variables potentially
function of 4.8 % (−7 to +25, SD 5.3) was impacting drainage, the panel concluded that
observed, with the perirenal background correc- reduced drainage alone is not an indication for
tion method considered superior to accurately surgery (Gordon et al. 2011).
report renal function (Caglar et al. 2008). A retrospective review included 24 children
Three hundred ninety-four MAG-3 renograms with prenatally detected unilateral HN meeting
in children with unilateral HN were reprocessed the following criteria: AP renal pelvis diameter
to calculate differential renal function by two >15 and <45 mm at age 2–4 weeks, no increase in
methods—the “integral” versus the Rutland/ AP diameter >9 mm during minimum 2-year fol-
Patlak plot analysis. For the entire review, the low-up, and minimum of three diuretic renograms
mean difference was −0.8 % (range −21.0– without variation in renal function >5 % (all had
16.9 %, SD 3.9 %). There was a greater spread in function >40 %). Bladder catheters were not used,
differential renal function between these tech- and data acquisition was done supine, with post-
niques in children <1 year of age, with disparity void views after standing for 5 min. Drainage was
>5 % in 25 % versus 10 % in those >1 year analyzed using pelvic excretion efficiency and
(p < 0.0005). The greatest differences occurred half-time. Half-time was prolonged in 68 % of
in renograms performed at 0–3 months (Ozcan kidneys with HN, while it was delayed in 80 % by
et al. 2006). pelvic excretion efficiency before voiding and
44 % after voiding. Using pelvic excretion that supranormal function is infrequent and may
efficiency, 71 % showed variation in the pattern of indicate borderline contralateral hypofunction
drainage on serial studies despite other evidence (Maenhout et al. 2005).
that the HN was stable (Amarante et al. 2003). Another retrospective review included seven
patients with ipsilateral function ³55 % and nor-
mal contralateral kidney by ultrasound, reporting
Supranormal Renal Function that at 1 year after pyeloplasty, renal function
remained >55 % in four and decreased to 38, 44,
Supranormal function defined as >55 % was and 53 % in the other three (Song et al. 2007a).
found by one study to vary depending on the
means used to calculate renal function.
Three studies report supranormal function Etiologies of UPJO
in approximately 5 % of renograms.
Renography 1 year after pyeloplasty in Data from three retrospective reviews of pyelo-
seven kidneys with supranormal function plasty cases indicate that most prenatally
found four with persistent function >55 %, detected UPJO are due to intrinsic narrowing,
one with 53 %, and the other two to have and less commonly from either high ureteral
<45 % in one study. insertion or crossing vessels.
Prospective evaluation of 48 neonates with Older children presenting with symptoms
unilateral prenatal HN ³5 mm AP diameter that have a greater prevalence of crossing vessels.
included MAG-3 diuretic renography at 1 month A retrospective review of over 1,000 pyelo-
reported 4 (8 %) with ipsilateral renal function plasties reported fibroepithelial polyps in 0.5 %.
³55 % (Moon et al. 2003). Background subtrac- A retrospective review of 98 consecutive chil-
tion method was not stated, but it was described dren, median age 1 year (5 days–16 years), under-
similar to the integral technique. going pyeloplasty between 1986 and 1992
The study by Ozcan et al. (2006) mentioned reported the etiology was an intrinsic anomaly of
above analyzing MAG-3 renograms using two the UPJ in 78 %, high ureteral insertion in 11 %,
techniques for differential renal function (integral and crossing vessels in 11 % (Salem et al. 1995).
vs. Rutland/Patlak methods) reported that supra- A retrospective review of pyeloplasty for
normal function defined as >55 % was found less symptomatic UPJO between 1986 and 1999
often using the Rutland/Patlak plot analysis, and included 38 children, mean age 8 years, finding
that only 5 % of 394 renograms maintained supra- crossing vessels in 22 (58 %), intrinsic anomalies
normal function when both methods were used. of the UPJ in 10 (26 %), high ureteral insertion in
A retrospective database review identified 72 2 (5 %), and fibroepithelial polyps in 2 (5 %)
children with antenatal HN who underwent (Cain et al. 2001).
MAG-3 renography and Cr-EDTA glomerular Another retrospective review reported intrin-
clearance. Differential renal function by renog- sic narrowing versus crossing vessels in 54 pre-
raphy was determined using the integral method. natally detected and 30 symptomatic children
Absolute function for each kidney was expressed undergoing pyeloplasty at mean age 3.5 ± 7
in mL/min/1.72 m2/kidney, with values <40 mL/ months versus 6 ± 3 years. Crossing vessels were
min/1.72 m2 and values >70 mL/min/1.72 m2 encountered in 6/54 (11 %) and 12/30 (40 %),
considered abnormal. Abnormal differential p = 0.004 (Calisti et al. 2003).
function ³50 % was found in 4/72 patients over A retrospective review of 1,710 pyeloplasties
1 year of age, all involving the left kidney. All over a 35-year period identified 9 (0.5 %) cases
had absolute split renal function within the nor- with fibroepithelial polyp as the cause of UPJO.
mal range as defined, while in three patients the Patients ranged in age from 6 weeks to 9 years.
contralateral sonographically normal kidney had The diagnosis was made preoperatively in two,
£40 mL/min/1.72 m2, leading to the conclusion as a filling defect seen on IVP or antegrade
nephrostography. Follow-up after dismembered Risk for renal function decrease during
pyeloplasty was a mean 44 months (1–135) with observation is unclear, given that timing of ini-
no known recurrence or new polyp occurrence tial and follow-up renography, and definition
(Adey et al. 2003). of significant functional loss are not standard-
ized. Reported rates of renal function decrease
in observed units range from 1 to 25 %, with
Outcomes of Observational persistent differential renal function decrease
Management for Prenatally in 0–6 %.
Detected UPJO UTI has been reported in from 2 to 31 % of
infants with UPJO during observation in ret-
Kaplan-Meier curves showing time for resolu- rospective studies. Two studies had similar
tion of SFU grades 3 and 4 HN have not been infection rates, one using antibiotic prophy-
reported. laxis and the other not. No RCT has tested
Four series reported resolution (decrease to antibiotic prophylaxis in children with UPJO.
SFU grades 0–1 HN) occurring in from 0 to Renal colic has rarely been reported in
66 % SFU grade 3 and 0–14 % grade 4 kid- patients with prenatally detected UPJO dur-
neys during mean follow-up that ranged from ing observation.
15 to 142 months (Table 11.1).
Indications for pyeloplasty are not stan-
dardized. Reported reasons include progres- Spontaneous Resolution of SFU 1
sive HN, initial or acquired decreased and 2 HN
ipsilateral renal function and/or drainage,
failure to resolve HN, and symptoms (pain, A retrospective review reported outcomes in 56
UTI, stones). SFU grade 1 and 51 SFU grade 2 kidneys after
Pyeloplasty rates in four series for SFU prenatal detection. During follow-up at a mean of
grades 3 and 4 kidneys varied, in part by dif- 15 months (1.5–142, median 12), spontaneous
fering indications for surgery, but ranged from resolution occurred in 34 (61 %) and 33 (65 %),
11 to 70 % of grade 3 and 29–100 % of grade with none progressing to a higher grade or having
4 kidneys (Table 11.2). surgery (Karnak et al. 2009).
Another retrospective study of prenatally
Table 11.1 Spontaneous resolution (to SFU grades 0–1 detected HN reported follow-up a mean of 142
HN) in renal units with prenatally detected SFU grades 3 months with resolution in 250/273 (92 %) SFU
and 4 HN grade 1 and 25/165 (15 %) with SFU grade 2 HN,
Authors Mean f/u SFU grade 3 SFU grade 4 at mean of 13 months (2 weeks–6 years). All oth-
Bajpai 39 m 6/9 (66 %) 0/11 (0 %) ers were stable or improved, except for progres-
Onen 54 m 11/19 (58 %) 1/19 (5 %) sion to SFU grades 3 or 4 that occurred in 21
Karnak 15 m 17/50 (34 %) 3/21 (14 %) (13 %) with SFU grade 2 (time to progression not
Yang 142 m 0/122 (0 %) 0/69 (0 %) stated) (Yang et al. 2010).
Table 11.2 Pyeloplasty after initial observation for prenatally detected SFU grade 3 and 4 HN kidneys
Indications
Mean time Progressive Function Recovery of function
Authors to surgery SFU 3 SFU 4 HN loss Symptoms loss post-pyeloplasty
Onen 6.5 m 2/19 (11 %) 11/19 (58 %) 11 (29 %) 5 (14 %) – 5/5 (100 %)
Karnak 15 m 4/50 (8 %) 6/21 (29 %) NS 1 (1 %) NS NS
Hafez 7m 10/33 (30 %) 6/11 (55 %) 16 (36 %) 11 (25 %) – 5/11 (45 %)
Yang 6–20 m 85/122 (70 %) 69/69 (100 %) 85 (55 %) 60 (39 %) NS “all”
NS not stated
Spontaneous Resolution of SFU were all said to have no improvement, with 50 %

3 and 4 HN having surgery at a median 6 months and the oth-
ers at 20 months.
Initial observation was done in 15 infants with
prenatally detected HN evaluated at 4–12 weeks
of age with US and DTPA renography. SFU grade Pyeloplasty
3 HN occurred in 9 and grade 4 in 11 renal units
(bilateral in 5). Initial ipsilateral differential func- Twenty-four neonates with bilateral SFU grades
tion was ³35 % in all kidneys (mean 46.5, 35–65). 3 (n = 19) and 4 HN (n = 19) were initially
By mean follow-up of 39 months (8–60), 6/9 observed regardless of differential function, T1/2,
grade 3 kidneys resolved HN and 3 decreased to or HN grade, as discussed above (Onen et al.
grade 2. In contrast, of 11 grade 4 renal units, 2002). All had normal global renal function by
none improved to grades 0 to 1, 1 decreased to serum creatinine. Indications for pyeloplasty
grade 2, 6 showed no change, and 4 were oper- were decreased differential function >10 % and/
ated (Bajpai and Chandrasekharam 2002). or progressive HN. At mean age 6.5 months
Nineteen neonates with bilateral SFU grades 3 (2–22), pyeloplasty was done in 11/19 (58 %)
(n = 19) and 4 HN (n = 19) were initially observed SFU grade 4 and 2/19 (11 %) grade 3 kidneys for
regardless of differential function, T1/2 or HN progressive HN (n = 8), decreased function (n = 2),
grade. All had normal global renal function by or both (n = 3). Of these patients, 11 had SFU
serum creatinine. Indications for pyeloplasty were grade 4 HN and the changes on renal US that
decreased differential function >10 % and/or pro- defined progressive HN warranting pyeloplasty
gressive HN (means for determining progression were not described.
and number of US required for this diagnosis were The series by Karnak et al. (2009) described
not stated). During mean follow-up of 54 months above performed immediate pyeloplasty in
(14–187), resolution to SFU grades 0–1 HN infants with differential renal function <40 % or
occurred in 1/19 (5 %) grade 4 kidneys and 11/19 prolonged T1/2, which comprised no SFU grade
(58 %) grade 3 kidneys. Improvement to SFU 3 and 20/41(49 %) with grade 4 HN. With subse-
grade 2 occurred in 3/19 (16 %) grade 4 and 6/19 quent conservative management for 15 ± 14
(32 %) grade 3 kidneys. Pyeloplasty was done in months (1.5–142), 4/50 (8 %) SFU grade 3 and
11/19 (58 %) grade 4 and 2/19 (11 %) grade 3 kid- 6/21 (29 %) SFU grade 4 kidneys had pyeloplasty
neys, discussed below (Onen et al. 2002). for persistently prolonged T1/2, increased HN,
Another series utilizing a standardized proto- pain, or UTI (none of these indications were fur-
col reported outcomes in 71 SFU grades 3 and 4 ther described). Only one kidney had decreased
kidneys during observation for 15 ± 14 months. differential renal function, the extent and the
Renography was done at 1 month of age, and postoperative outcome of which were not stated.
those with ipsilateral differential renal function An observation protocol for unilateral prena-
<40 % underwent immediate pyeloplasty, leaving tally detected HN included 33 SFU grade 3 and
50 SFU grade 3 and 21 SFU grade 4 kidneys 11 grade 4 renal units, with differential renal
observed. HN resolution occurred in 20/71 (28 %), function <40 % in 18 (42 %) and T1/2 >20 min in
comprising 17/50 (34 %) grade 3 and 3/21 (14 %) 23 (53 %). Indications for surgery were increas-
grade 4 kidneys (Karnak et al. 2009). ing HN on two ultrasounds (the second within
The study by Yang et al. (2010) mentioned 2–4 weeks) or UTI. At mean follow-up of 38
above included 122 neonates with SFU grade 3 months (23–52), 16 (36 %) underwent pyelo-
and 69 with SFU grade 4 HN after prenatal detec- plasty (10/33 [30 %] grade 3; 6/11 [55 %] grade
tion. During follow-up a mean of 142 months, 4) at mean age of 7 months (3–12) (Hafez et al.
none resolved. Thirty percent with SFU 3 were 2002). Extent of increased AP diameter or paren-
stable or improved, while the other 70 % pro- chymal thinning used to define progression in
gressed to grade 4. Those with initial grade 4 grade 4 kidneys was not described.
Pyeloplasty was done in 70 and 100 % of SFU decreased renal function to <40 % during follow-up
grade 3 and 4 patients reported by Yang et al. a mean of 15 months.
(2010). Indications were progression of HN from Decreased renal function to <40 % (or >5 %
grade 3 to 4 or failure of grade 4 to improve on 2 for those with initial function <40 %) was
US (at 3 and 6 months) and “very poor” drainage. observed by Yang et al. (2010) in13/165 (8 %)
Together there were 154 pyeloplasties, with with SFU grade 2, 47/122 (39 %) with SFU grade
approximately half those with grade 3 and 4 hav- 3, and 35/67 (52 %) with SFU grade 4 HN.
ing surgery at a median of 6 months and the other Following pyeloplasty, the authors stated there
half at median 20 months. was “no persistent deterioration of renal func-
A study of patients with prenatally detected tion,” but rather demonstrated significant
HN, defined by AP diameter rather than SFU improvement.
grade, observed those with function >40 % on Hafez et al. (2002) obtained initial DTPA
DTPA renography obtained at 1 month of age renography at 4–6 weeks of age for 45 patients
regardless of washout times or curves or extent of with SFU grades 3 and 4 kidneys, repeated only
postnatal HN. There were 100 renal units (num- in the 16 with subsequent progressive HN lead-
ber of unilateral vs. bilateral cases was not stated) ing to pyeloplasty. In these 16, mean baseline
that were observed for at least 1 to ³6 years renal function was 32 % (8–54), and the decrease
(mean, median of observation were not stated). was to a mean 23 % (8–39), with 9/16 (56 %)
Of these, 23 (23 %) underwent pyeloplasty for having >5 % loss. DTPA 3 months after pyelo-
decreased function to <40 % (n = 14), UTI (n = 3), plasty was a mean of 30 % (10–48), with improve-
pain (n = 1), concentrating defect in a solitary ment in 14 and stable function in 2.
kidney creating polyuria (n = 1), and noncompli- A retrospective analysis of 272 patients (SFU
ance with follow-up (n = 4). Operations occurred grade not stated) was done, identifying 44
during the first year in 5, second in 7, third in 7, (16 %) patients (35 with SFU grades 3 and 4)
fifth in 2, and sixth in 2. AP diameter was <12 mm undergoing pyeloplasty for differential renal
in 34 and >12 mm in 66 during US at 1 month of functional loss. Patients were initially observed
age, and all 23 pyeloplasties derived from the after DTPA or MAG-3 renography at 6–8 weeks
cohort with >12 mm (23/66 [35 %]) (Ransley of age, and had pyeloplasty for decreased ipsi-
et al. 1990). The mean and range of AP diameters lateral function of >5 % (mean 8 ± 2 %), which
for those <12 and >12 mm were not stated. The occurred at a mean of 8 ± 1 months. Mean initial
extent of renal function loss resulting in pyelo- differential renal function in SFU grade 3 kid-
plasty was not described. Spontaneous resolution neys was 38 %, which decreased to a mean of
rates and time intervals were not reported. 30 % but then improved postoperatively to mean
of 39 %. For SFU grade 4 kidneys, initial renal
function was a mean of 34 %, decreasing to
Risk for Renal Function Loss 26 % and improving after surgery to 32 %
(Chertin et al. 2002).
As discussed above, Onen et al. (2002) reported Ransley et al. (1990) did not use SFU grading,
5/38 (14 %) bilateral SFU grades 3 and 4 kidneys but reported that 23/66 (35 %) kidneys with AP
had functional decrease of greater than 10 % dur- diameter >12 mm and initial DTPA differential
ing observation at follow-up a mean of 6.5 months renal function ³40 % at 1 month of age eventu-
(2–22). Recovery of function occurred in all five ally had pyeloplasty. Of these, 14/66 (21 %) had
after pyeloplasty. Actual function changes in preoperative decreased function to <40 % (actual
these renal units were not described. changes not reported). Five of 14 (36 %) had
Karnak et al. (2009) observed 71 kidneys with complete functional return after surgery, while 4
SFU grades 3 and 4 HN with differential renal improved, 3 remained unchanged, and 1 deterio-
function ³40 %, operating on only 1 (1 %) for rated further (data were not shown).
Risk for UTI for 1 to more than 6 years and stated that pain
occurred in one child, leading to pyeloplasty.
A retrospective study reviewed charts of 56 new- Coplen et al. (2006) performed pyeloplasty on 62
borns (45 males) having SFU grades 3 (n = 9) and 4 children for antenatally detected HN, with only 2
(n = 47) HN that was detected prenatally, with DTPA having colic at age 6 years.
renography demonstrating T1/2 >20 min. Exclusion Our review found no reports concerning hema-
included any grade of VUR. No antibiotic prophy- turia and stone incidence in prenatally detected
laxis was used. UTI was defined as “symptomatic HN. There are case reports of hypertension improv-
infection with a positive urine culture.” At mean ing after pyeloplasty or nephrectomy for UPJO.
follow-up of 26.7 months (1–122), UTI occurred in
one (2 %) patient (Roth et al. 2009).
Another retrospective review studied 64 males Postnatally Detected UPJO
and 11 females with SFU grades 3 (n = 37) and 4
(n = 38) HN from UPJO and “obstructive wash- UPJO not diagnosed antenatally presents with
out pattern” with T1/2 >20 min to determine UTI symptoms such as renal colic/abdominal pain,
occurrence during the first year of life. UTI was abdominal mass, hematuria, or UTI, or with-
only defined for those hospitalized (number not out symptoms as a coincidental finding.
stated) with febrile illness having “positive urine Two studies reported pain resolution in all
culture and bacteruria or pyuria ³5WBCs/HPF.” cases following pyeloplasty for renal colic.
No male was circumcised, and patients were not
given antibiotic prophylaxis. UTI occurred in
23/75 (31 %) patients, with no difference between Dietl’s Crisis
males and females or those with SFU grades 3
versus 4 HN. However, it was not clear if patients Prospective evaluation was performed in 18 con-
were all identified by HN or if some presented secutive children, mean age 7.5 years (4–15),
with fUTI and were then found to have HN (Song presenting during a 6-year period ending in 2004
et al. 2007b). with abdominal pain and found to have HN dur-
A retrospective analysis of fUTI risk in 192 ing the acute episode that resolved when asymp-
infants (125 males, none circumcised) with pre- tomatic. Symptoms were recurrent in 15/18
natal HN included patients with no uropathy, beginning a mean of 8 months (2–24) before
UPJO, VUR, and megaureters. Bagged urines diagnosis, and included flank pain in 14 and peri-
were used for specimens in infants. Antibiotic umbilical/epigastric or diffuse abdominal pain in
prophylaxis (cephalexin 2× months, then 8. Sixteen had vomiting. Symptoms resolved
trimethoprim) was used in all 53 with UPJO. within 2 days. Renal US during the acute episode
During median follow-up, for the entire series of reported SFU grades 3 and 4 HN, that decreased
24 months (IQ range 12–39), UTI occurred in to grades 1 and 2 in 16 when non-symptomatic.
13/53 (25 %) (Coelho et al. 2008). DTPA diuretic renography was obtained in 17
within 3 days of symptoms, finding ipsilateral
renal function a mean of 35 % (10–55), with
Other Symptoms “obstructive patterns and prolonged washout” in
15, and an “equivocal pattern” in the other 2. At
Symptoms are an uncommon cause for pyelo- pyeloplasty in 17 cases (1 lost to follow-up),
plasty in prenatally detected HN. Bajpai and intrinsic obstruction was found in 6, extrinsic fac-
Chandrasekharam (2002) reported that none of tors in 9 (“kinked ureter” in 6, high insertion in 2,
their 15 patients with SFU grades 3,4 HN were crossing vessels in 1), and a fibroepithelial
symptomatic at either presentation or follow-up polyp in 2. During follow-up a mean of 3.6 years
to a mean of 36 months (8–60). Ransley et al. (4 months–7 years), there was no recurrent flank/
(1990) followed 100 kidneys with antenatal HN abdominal pain (Tsai et al. 2006).
A retrospective review was done to identify renography, all initially treated with a percutaneous
children evaluated for UPJO over a 3-year period nephrostomy for 4 weeks with subsequent repeat
ending 2001, reporting 8/122 (7 %) had Dietl’s renography. Of these, 12 (71 %) had second reno-
crisis at mean age 12 years (5–19). All had recur- gram function >10 % (mean 29 ± 3 %) resulting
rent abdominal pain with nausea and vomiting in pyeloplasty, while the other 5 were unchanged
for ³1 year. Ipsilateral renal function ranged from and so had nephrectomy. At mean follow-up of
36 to 66 % (excluding one with a solitary kid- 2.3 ± 1.3 years, renal function was 31 ± 13 % after
ney). Surgery resolved symptoms in all patients pyeloplasty (Gupta et al. 2001).
at follow-up (time not stated) (Alagiri and Another retrospective review found 12
Polepalle 2006). patients among a group of 58 with UPJO pre-
senting at mean age 4.7 years (35 days–11 years)
with renal function less than 10 %. Nephrostomy
Other Presentations drainage was done preoperatively for 4–6 weeks
followed by pyeloplasty in all cases. Repeat pre-
A retrospective review of all unilateral pyelo- operative renography showed improvement to
plasties done between 1990 and 1997 identified 20–25 % function in all patients, and 6 months
21 children who presented at a mean age of 7 after surgery all had 30–35 % function (Aziz
years (9 months–18 years) with pain (n = 11), et al. 2002).
UTI (n = 8), or as an incidental finding in 2. All Nine kidneys with prenatally detected HN had
had SFU grades 3,4 HN with mean preoperative function <10 % by DTPA renography at 1 month
differential function of 39 % (10–58 %) and T1/2 of age. Nephrostomy tubes were placed for 3
>20 min (McAleer and Kaplan 1999). weeks with repeat renography and nephrectomy
Another retrospective review of 95 consecu- if function remained <10 %. Of the nine, six had
tive pyeloplasties done from 1986 to 1992 nephrectomy and three pyeloplasty, with postop-
reported presentation other than prenatal detec- erative function at 1 year of 10, 19, and 41 %
tion in 71 (75 %). UPJO was an incidental finding (Ransley et al. 1990).
in 21 (30 %). The remaining patients had symp-
toms, including abdominal pain (n = 17, 24 %),
UTI (n = 14, 20 %), mass (10, 14 %),and gross Management of Bilateral UPJO
hematuria (n = 9, 13 %) (Salem et al. 1995).
The prospective series by Onen et al. (2002) dis-
cussed above included 19 neonates with bilateral
Management of UPJO with Ipsilateral SFU grades 3 (n = 19) and 4 HN (n = 19) who
Differential Function <10 % were initially observed regardless of individual
kidney differential function, T1/2, or HN grade.
Two retrospective series reported symptom- All had normal global renal function by serum
atic UPJO with differential function <10 % creatinine. Indications for pyeloplasty were
initially managed by nephrostomy for 4–6 decreased differential function >10 % and/or pro-
weeks. Improved function to a mean ≥30 % gressive HN. At mean 6.5 months (2–22), pyelo-
occurred in 70 and 100 %. plasty was done in 13/48 (27 %) kidneys, 8 for
Only one series reported nephrostomy drain- increasing HN, 2 for decreased function, and 3
age for function <10 % in prenatally detected for both. These operations occurred in nine
(asymptomatic) UPJO in nine kidneys; only patients (37.5 %), and were bilateral in four and
two had improved function (19 and 41 %). unilateral in five. At follow-up of 54 months (14–
A series of symptomatic patients, mean age 5 187), resolution to SFU grades 0–1 HN occurred
years (2 months–11 years), included 17 (8 prena- in 12/48 (25 %). The five with renal functional
tally detected) with SFU grade 4 HN and differ- loss >10 % before surgery were stated to have
ential function less than 10 % with DTPA full recovery (data were not shown).
A retrospective study included 13 children • No difference in operative times, WMD

with prenatal HN and postnatal bilateral SFU −10 min (95 % CI −25–3).
grades 3 and 4 UPJO. All had initial surgery on • Significantly shorter hospitalization with
one kidney (with greatest HN or least renal func- robotic surgery, WMD −0.5 d (95 % CI −0.6–
tion) at mean 3 months (1–11). The other kidney 0.4) (Braga et al. 2009).
was scheduled for pyeloplasty in 2 months, but in A RCT compared open (performed by four
five (39 %) cases the HN improved sufficiently to surgeons) versus transperitoneal laparoscopic
not operate. At final follow-up at a mean 37 (one surgeon) pyeloplasty, excluding children
months (5–84), residual dilation ³SFU grade 3 less than 1 year of age. Enrollment was offered to
persisted in 4/21 (19 %) operated kidneys and 1/5 77 patients with 39 accepting. Mean age was
(20 %) not operated (Kim et al. 2010). similar at 7.5 years. All were stented postopera-
tively for 6 weeks, laparoscopic patients with a
double-J stent; open-stent type was not stated.
Laparoscopic Pyeloplasty (With Postoperative pain control was standardized for
or Without Robotic Assistance) all patients, using no regional blocks, bupivacaine
in all incisions, scheduled IV ketorolac, and nar-
Surgical Outcomes cotics as needed. There was no difference between
open and laparoscopic surgery regarding success
There was no difference in reported surgical 95 % versus 100 % (described as “no symptoms,
success rates or complications between open, normal T1/2, and improved HN”), mean opera-
laparoscopic, and robotic pyeloplasty. tive time 130 versus 151 min, mean hospitaliza-
Laparoscopic surgery was associated with tion 29 versus 36 h, or narcotic use 4 versus 5
greater double-J stent use. doses (Penn et al. 2010).
Meta-analysis found operative times less
with open surgery, and hospitalization less
with laparoscopic and robotic surgery. Cosmesis
A meta-analysis compared open to laparo-
scopic pyeloplasty, as reported by nine studies Two studies using patient questionnaires
with 7,334 open and 694 laparoscopic surgeries, reported increased satisfaction with incisions
finding: from robotic versus open renal surgery.
• No difference in reported success rates, OR A validated questionnaire used to determine
1.8 (95 % CI 0.7–4). patient satisfaction in children (Glasgow
• No difference in complications, OR 0.8 (95 % Children’s Benefit Inventory) was mailed to all
CI 0.5–1.3). undergoing open or robotic pyeloplasty over a
• Significantly shorter operative times for open 2-year period. Additional non-validated ques-
surgery, WMD 59 (95 % CI 41–77). tions were added to specifically distinguish
• Significantly shorter hospital stay with laparo- between the two surgical procedures. Of 69 open
scopic repair, WMD −0.4 (95 % CI −0.8–0.03). and 48 robotic cases, responses were obtained
In the articles reviewed there was also from 68 to 72 %. All reaching statistical
significantly greater use of double-J stents in lap- significance favored robotic surgery, including
aroscopic patients (Mei et al. 2011). speed of return to normal activities and the inci-
Meta-analysis compared robotic versus lap- sion scar (Freilich et al. 2010).
aroscopic pyeloplasty on the basis of eight arti- Twelve patients underwent HIdES (hidden
cles and 326 patients, reporting: incision endoscopic surgery) renal surgery, in
• No difference in reported success rates, OR which all port sites are hidden either in the
1.3 (95 % CI 0.5–3.5). umbilicus or below the bikini line, and their par-
• No difference in complications, OR 0.7 (95 % ents expressed their satisfaction with the cos-
CI 0.3–1.6). metic outcome 3 months postoperatively using
questions from the validated Patient Scar in observed patients with preoperative
Assessment Scale. They also compared patient decrease in renal function from baseline.
results to photos taken 3 months after flank inci- • Approximately half the kidneys with <20 %
sion and laparoscopy for renal surgery using tra- differential function preoperatively showed
ditional port placement using the validated improved function, varying from ≥+5 % to
Wound Evaluation Scale, Manchester Scar function >35 %.
Scale, and Patient Scar Assessment Scale. Mean Two retrospective studies described pre-
patient and parent scores were significantly bet- and post-pyeloplasty renogram drainage, one
ter for HIdES than either open or laparoscopic reporting 98 % had T1/2 <20 min after sur-
incisions (Gargollo 2011). gery, and the other finding improved clear-
ance from a mean 15 to 66 % 20 min after
furosemide.
Imaging Changes After Pyeloplasty
Pyeloplasty outcomes are determined by residual Ultrasonography

HN, renal function and drainage, and symptoms.
In one study of consecutive patients consid- A retrospective review included 47 kidneys, 21
ered to have surgical success, mean HN grade 3 and 26 grade 4 HN, that had pyeloplasty.
decreased a statistically insignificant 1 grade Initial postoperative US was done at 1 month in
(SFU 3–2), differential renal function remained 36, showing the same or increased HN in 33.
the same mean 46 %, and only drainage With mean follow-up at 4 years (2–9), resolution
significantly improved 1 year postoperatively. to SFU grades 0,1 was observed in only 9/47
Three retrospective studies described (19 %) kidneys. Improvement to SFU grade 2 or
changes in renal US after pyeloplasty, one less occurred in 12/26 (46 %) grade 4 kidneys,
reporting resolution to SFU grade 0 or 1 HN in and in 18/21 (86 %) grade 3 kidneys (Amling
20 % and to £SFU grade 2 in 64 %; the other et al. 1996).
two reported mean changes in HN that were Preoperative versus 12-month postoperative
unchanged in one and reduced in the other. renal ultrasounds were compared in 70 consecutive
A systematic review of published literature children undergoing laparoscopic pyeloplasty at
concerning renal function after pyeloplasty mean age 20.5 months (1–178). All were reported
reported studies that generally had poor to have decreased HN after surgery, although the
scientific quality, with heterogeneous indica- mean difference of SFU 2.9 ± 0.08 to 2 ± 0.1 was
tions for surgery and follow-up imaging. not significant (p = 0.6) (Szavay et al. 2010).
Conclusions regarding impact of pyeloplasty A retrospective study reported HN as AP pel-
on differential renal function were as follows: vic diameters in 54 consecutive patients with pre-
• No preoperative parameter, including SFU natally detected HN that underwent pyeloplasty.
grade or AP diameter, percent renal func- Postoperative US done between 6 and 12 months
tion, or drainage pattern predicted postop- showed significant improvement from mean
erative renal functional outcomes. 29 ± 10 mm to 14 ± 5 mm (p value not stated)
• Renal functional change with immediate (Calisti et al. 2003).
pyeloplasty in antenatally detected cases
was −1 to +14 %.
• Functional improvement after surgery was Differential Renal Function
a maximum average of 2.5 % (−1.6 to 9) in
antenatally detected HN and 5 % (−0.9 to A systematic literature review retrieved a total of
14) in postnatally detected HN. 704 articles, from which 36 were analyzed
• There was a mean loss of 3–7.5 % of renal regarding functional renal outcomes after unilat-
function on final postoperative renography eral pyeloplasty. Heterogeneity of isotope used,
surgical indications, follow-up protocols, and pyeloplasty mentioned above reported mean
means for data reporting precluded meta-analysis. differential renal function on MAG-3 renography
The 36 reports were characterized by the authors was 46 ± 12 % preoperatively, versus 46 ± 13 % 3
as low-quality RCT (n = 2), individual cohort months and 46 ± 15 % 1 year postoperatively,
studies (n = 8), or surgical case series (n = 26). p > 0.05 (Szavay et al. 2010). There was median
Results of their descriptive analysis were as follow-up at 24 months (1–48), with the number
follows: of patients undergoing postoperative renography
1. Six studies reported mean change in final renal not stated.
function in antenatally detected patients after Retrospective review of 137 consecutive
pyeloplasty between −1.6 and 9 %; six studies pyeloplasties done between 1994 and 2003
reported the mean change in postnatally identified 102 patients with preoperative and post-
detected cases was −0.9 to 14 %. operative renography. Median age at surgery was
2. Mean percent change in final renal functional 6 months (15 days–150 months) and postopera-
outcomes for antenatally detected HN under- tive follow-up was a median 36 months (6
going immediate pyeloplasty was −1 to 14 % months–10 years). Mean preoperative renal func-
in six studies. tion for the entire cohort was 35 % versus postop-
3. Six studies found neither AP diameter nor erative mean of 41 % (p < 0.001). Sixty-seven of
SFU grade nor parenchymal thickness pre- 109 (61.5 %) kidneys had ³5 % increased postop-
dicted postoperative renal functional outcome, erative function, 30 (27.5 %) were unchanged,
while two studies that reported drainage pat- and 12 (11 %) had >5 % decreased function,
tern did not predict post-pyeloplasty renal including 3 with failed repairs (Sheu et al. 2006).
functional outcomes. Another retrospective review found 27 kid-
4. Four studies with 60 patients reported mean neys with SFU grades 3 and 4 UPJO in children
final functional outcomes in antenatally <1 year of age who had pyeloplasty for differen-
detected HN who had a decrease from their tial function < 40 % and/or impaired drainage
initial renogram during observation. with flat or rising curve. Mean preoperative/
Initial/final preoperative differential renal postoperative renal function was 37 %/38 %.
function and postoperative renal function was Another 21 kidneys were initially observed and
45 % (40–50)/30.5 % (16–41) and 37.5 % had subsequent pyeloplasty for function loss
(25–47); 45 % (42–48)/33 % (28–41) and >5 % or “worsening drainage” (not defined) at
42 % (38–46); 49 % (45–50)/37 % (35–39) mean 1.4 years after initial presentation. Mean
and 45 % (41–50); 48 %/42 % and 44 %. preoperative/postoperative renal function was
Based on these data, mean final decrease in 46 % (19–60)/44 % (18–65) (Ross et al. 2011).
renal function ranged from −3 to −7.5 %.
5. Nine studies had data regarding renal units
with <20 % function, comprising a total of 88 Diuretic Renography Drainage
kidneys, of which 30/59 (51 %) had improve-
ment after pyeloplasty variously reported as A retrospective review defined surgical success
an increase in function of >5 % or differential as washout time <20 min on diuretic MAG-3
renal function >35 %. Two studies with a total renography in 127 patients with preoperative
of 29 patients reported mean data, with preop- T1/2 >20 min. All but two (2 %) had postopera-
erative function <20 % and postoperative tive T1/2 <20 min by 3–12 months. One of these
mean function 19 % (14–25) and 19.5 % (±8), with increasing T1/2 had reoperative pyeloplasty
respectively (Castagnetti et al. 2008). and subsequent improvement to <20 min (Pohl
Our review found three additional studies not et al. 2001).
included by Castagnetti et al. Drainage on MAG-3 diuretic renography was
The analysis of 70 consecutive children mean evaluated preoperatively and 1 year postopera-
age 20.5 months (1–178) undergoing laparoscopic tively in the 70 consecutive children, mean age
20.5 months (1–178), undergoing laparoscopic Incidence and Pathophysiology

pyeloplasty by Szavay et al. (2010) mentioned
above. Clearance was reported as decreased radi- Three series reported failure of £7 % dis-
onuclide activity 20 min after furosemide. All membered pyeloplasties, diagnosed in two at
patients had improved clearance, which was means of 13 and 26 months after primary
significant for the entire cohort from a mean repair.
14.7 ± 15.8 % to 66.9 ± 16.5 %, p < 0.0001. Diagnosis of recurrent UPJO was made by
various combinations of symptoms (pain, UTI)
and imaging (HN, “delayed drainage”).
Symptoms After Pyeloplasty Surgical findings at reoperation included
fibrosis of the UPJ, kinks due to redundant
Resolution of colic was reported in all patients renal pelvis or adhesions, high ureteral inser-
with post-pyeloplasty follow-up in two studies. tions, and crossing vessels.
Our review found no reports concerning post- A retrospective study included 105 dismem-
pyeloplasty UTI or hematuria. bered pyeloplasties in 103 children, mean age 60
A prospective study reported outcomes in 39 months (1–204), of which 7 (7 %) failed at mean
children, mean age 7 years (1–17), undergoing interval of 13 months (3–38). Patients presented
pyeloplasty, of which 29 (74 %) had renal colic. with pain (n = 6) or HN (n = 1), with recurrent
With mean postoperative follow-up approxi- UPJO diagnosed on the basis of appearance on
mately 8 months (1–32), none of 27 assessed IVP, CT, and/or US, and in five, renography with
reported colic (Penn et al. 2010). an “obstructive pattern.” Etiology was described
Another prospective study included 18 chil- as persistent high ureteral insertion in two, redun-
dren a mean age 7.5 years (4–15) diagnosed with dant pelvis with kinking in two, and crossing ves-
UPJO during Dietl’s crisis. Symptoms were recur- sels in two, with all said to have dense scarring
rent in 15/18 beginning a mean of 8 months (2–24) (Thomas et al. 2005).
before diagnosis, and included flank pain in 14 Another review of dismembered pyeloplasties
and periumbilical/epigastric or diffuse abdominal found a total of 524 children were operated over
pain in 8. Sixteen had vomiting. During follow-up an 11-year period ending in 2006, with 25 (5 %)
after pyeloplasty a mean of 3.6 years (4 months–7 failures presenting with increasing HN, pyelone-
years), there were no further episodes of renal phritis, or other symptoms (not described). Of
colic/abdominal pain (Tsai et al. 2006). patients undergoing reoperative pyeloplasty,
findings included adhesions causing ureteral
kinking in six, a redundant pelvis with kinking in
Failed Pyeloplasty one, high ureteral insertion in one, ureteral nar-
rowing in two, and fibrosis at the UPJ in six
Retrospective reviews of management for failed (Braga et al. 2007).
pyeloplasty generally have defined failure as Analysis of 590 dismembered pyeloplasties
symptoms and/or persistent or increasing HN in 562 patients at mean age 3.5 years reported
and/or impaired drainage. Success after re- 18 (3 %) had recurrent UPJO diagnosed a mean
intervention generally has been defined as of 26 months (7–48) postoperatively. Of these,
absence of symptoms, stable or decreased HN, 14 (78 %) had pain; all had persistent or
or improved drainage, usually without report- increased HN, and mean ipsilateral renal func-
ing actual findings. tion was 21 % (10–39) versus 30.5 % (20–48)
Reoperative pyeloplasty (open or robotic) before pyeloplasty. Findings at reoperation
had success reported as 90–100 %. included crossing vessels in one, redundant
Endopyelotomy was considered successful renal pelvis in three, and fibrosis of the UPJ in
in 40–95 %. all (Helmy et al. 2009).
Reoperative Pyeloplasty robotic vessel hitch (n = 1). Mean interval to

diagnosis of failure was 21 months (range not
Three series reported success in 90–100 % stated), and was determined due to SFU grades 3
with reoperative pyeloplasty. and 4 HN and T1/2 >20 min. Mean function was
Open reoperation was done in 12 patients age 39 % (8–61). Robotic pyeloplasty was done in 13
5 months to 22 years after failed pyeloplasty. and ureterocalicostomy in 3, with 1 open conver-
Procedures included a renal pelvic flap in three, sion (in the horseshoe kidney). Mean follow-up
dismembered pyeloplasty in seven, and nephrec- was 15 months. Decrease in HN ³1 grade occurred
tomy in two. With mean follow-up of 26 months, in 14 (88 %), from a mean 3.8 to 1.7. Only four
9 of 10 with repair were considered to have good had renography, with “improved T1/2 and stable
results, variously described as “improving or to improved function” (data not shown). All were
resolved HN and/or good washout,” while 1 had asymptomatic (Lindgren et al. 2012).
repeat obstruction and nephrectomy (Lim and
Walker 1996).
Sixteen patients had antegrade or retrograde Endopyelotomy
pyelography and open reoperative pyeloplasty in
another review: 2 with an “atretic ureter” had a Endopyelotomy was reported successful in
renal pelvic spiral flap, 3 had ureterocalicostomy, from approximately 80 to 95 % of cases.
and 11 had repeat dismembered pyeloplasty. All One retrospective comparison of reopera-
had postoperative nephrostomy and 14 of 16 also tive pyeloplasty versus endopyelotomy found
had a transanastomic stent. During follow-up at a reoperation significantly more successful,
mean of 46 months (3–90), 11 of 12 with 100 % versus 39 %.
decreased function improved (data not shown). Results of 11 percutaneous endopyelotomies
Gravity drip nephrostogram 2–3 weeks postop- for failed dismembered pyeloplasty in 10 chil-
eratively was said to show “good drainage” in all dren, median age 7 years (range not stated), were
cases. The authors reported 100 % success reviewed. Diagnosis of recurrent UPJO was done
(Rohrmann et al. 1997). based on Whitaker tests, diuretic renograms, or
Of the 18 patients undergoing reoperation nephrostograms (criteria not stated). Median
reported by Helmy et al. (2009) discussed above, interval from primary surgery to endopyelotomy
repeat dismembered pyeloplasty was done in 14, was 7.5 months (2–54). After endopyelotomy,
ureterocalicostomy in 2, and nephrectomy in 2 nephrostomy drainage was done for 48 h and a
(function <12 %). During follow-up a mean of 25 4.6- to 7-Fr double-J stent for 6 weeks. Success
months (8–41), the authors considered all out- was defined as “normalization or improvement of
comes a success, with no loss (or improvement) renogram washout time,” stable ipsilateral renal
of renal function, increased HN, or symptoms function, decreased HN, and no symptoms. One
(interval for postoperative assessments was not patient with an obliterated UPJ converted to open
stated; data were not shown) (Helmy et al. 2009). surgery, with endopyelotomy considered suc-
cessful in 7/9 (78 %) at mean follow-up 6 years
(2–10). One had repeat endopyelotomy at 4 years
Robotic Reoperative Pyeloplasty follow-up (Capolicchio et al. 1997).
Another retrospective series included nine
One report completed planned robotic repair percutaneous endopyelotomies for failed dis-
in 94 %, with radiologic improvement in 88 membered (n = 8) or flap (n = 1 with horseshoe
and 100 % relief of symptoms. kidney) pyeloplasty in 9 children, mean age 4
Sixteen children mean age 6 years (12 years (3 months–12 years). All were referrals
months–15 years) had failed open pyeloplasty with stents or nephrostomies, and all had a
(n = 12), robotic pyeloplasty (n = 2), ureterocali- stenotic segment <2 cm. Internal stents were
costomy in a horseshoe kidney (n = 1), and failed used postoperatively in all cases for 4–6 weeks.
There was mean follow-up of 59 months (16–110), term outcome in 47 renal units. J Urol. 1996;156(6):
with all having “improved drainage on US or 2020–4.
Aziz MA, Hossain AZ, Banu T, Karim MS, Islam N,
renography” (data not shown). One patient Sultana H, et al. In hydronephrosis less than 10 % kid-
remained symptomatic with intermittent flank ney function is not an indication for nephrectomy in
pain, for success in eight (89 %) by the author’s children. Eur J Pediatr Surg. 2002;12(5):304–7.
criteria (Figenshau et al. 1996). Bajpai M, Chandrasekharam VV. Nonoperative manage-
ment of neonatal moderate to severe bilateral hydro-
A third retrospective study had 31 endopyelo- nephrosis. J Urol. 2002;167(2 Pt 1):662–5.
tomies in children median age 6.5 years for failed Braga LH, Lorenzo AJ, Skeldon S, Dave S, Bagli DJ, Khoury
pyeloplasty diagnosed at median interval of 4 AE, et al. Failed pyeloplasty in children: comparative
months (1–186). Failure was defined by imaging analysis of retrograde endopyelotomy versus redo pyelo-
plasty. J Urol. 2007;178(6):2571–5. discussion 5.
(not further described) or recurrent flank pain. Braga LH, Pace K, DeMaria J, Lorenzo AJ. Systematic
Seventy-one percent were antegrade and the review and meta-analysis of robotic-assisted versus
remainder retrograde incisions. Success was conventional laparoscopic pyeloplasty for patients
defined as no symptoms and “improved features” with ureteropelvic junction obstruction: effect on
operative time, length of hospital stay, postoperative
on US, CT, renography, or IVP. By these criteria, complications, and success rate. Eur Urol. 2009;56(5):
the authors considered 29 (94 %) successful dur- 848–57.
ing median follow-up 61 months (1–204) (Kim Caglar M, Gedik GK, Karabulut E. Differential renal
et al. 2012). function estimation by dynamic renal scintigraphy:
influence of background definition and radiopharma-
Retrograde endopyelotomy (n = 18) was com- ceutical. Nucl Med Commun. 2008;29(11):1002–5.
pared to reoperative pyeloplasty (n = 12) or ure- Cain MP, Rink RC, Thomas AC, Austin PF, Kaefer M,
terocalicostomy (n = 2) in a retrospective study of Casale AJ. Symptomatic ureteropelvic junction
children median age 6.5 years with failed dis- obstruction in children in the era of prenatal sonogra-
phy—is there a higher incidence of crossing vessels?
membered UPJ repair. Mean follow-up was 47 Urology. 2001;57(2):338–41.
and 33 months, and outcomes were determined Calisti A, Perrotta ML, Oriolo L, Patti G, Marrocco G,
by US, with renography only done for persistent Miele V. Functional outcome after pyeloplasty in chil-
HN or recurrent symptoms. Using these criteria, dren: impact of the cause of obstruction and of the
mode of presentation. Eur Urol. 2003;43(6):706–10.
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pyeloplasties were considered successful, Stein L, Elhilali MM. Long-term results of percutane-
p = 0.002. The stenotic segment was 4–8 mm ous endopyelotomy in the treatment of children with
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Castagnetti M, Novara G, Beniamin F, Vezzu B, Rigamonti
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Urology. 2001;57(3):547–50. in children: preliminary report of a prospective ran-
Hafez AT, McLorie G, Bagli D, Khoury A. Analysis of domized trial. J Urol. 2010;184(2):690–5.
trends on serial ultrasound for high grade neonatal Pohl HG, Rushton HG, Park JS, Belman AB, Majd M.
hydronephrosis. J Urol. 2002;168(4 Pt 1):1518–21. Early diuresis renogram findings predict success fol-
Helmy TE, Sarhan OM, Hafez AT, Elsherbiny MT, lowing pyeloplasty. J Urol. 2001;165(6 Pt 2):2311–5.
Dawaba ME, Ghali AM. Surgical management of Ransley PG, Dhillon HK, Gordon I, Duffy PG, Dillon MJ,
failed pyeloplasty in children: single-center experi- Barratt TM. The postnatal management of hydroneph-
ence. J Pediatr Urol. 2009;5(2):87–9. rosis diagnosed by prenatal ultrasound. J Urol.
Karnak I, Woo LL, Shah SN, Sirajuddin A, Ross JH. 1990;144(2 Pt 2):584–7. discussion 93–4.
Results of a practical protocol for management of pre- Rohrmann D, Snyder 3rd HM, Duckett Jr JW, Canning
natally detected hydronephrosis due to ureteropelvic DA, Zderic SA. The operative management of recur-
junction obstruction. Pediatr Surg Int. 2009;25(1): rent ureteropelvic junction obstruction. J Urol. 1997;
61–7. 158(3 Pt 2):1257–9.
Kim J, Hong S, Park CH, Park H, Kim KS. Management Ross SS, Kardos S, Krill A, Bourland J, Sprague B, Majd
of severe bilateral ureteropelvic junction obstruction M, et al. Observation of infants with SFU grades 3–4
in neonates with prenatally diagnosed bilateral hydro- hydronephrosis: worsening drainage with serial diure-
nephrosis. Korean J Urol. 2010;51(9):653–6. sis renography indicates surgical intervention and
Kim EH, Tanagho YS, Traxel EJ, Austin PF, Figenshau helps prevent loss of renal function. J Pediatr Urol.
RS, Coplen DE. Endopyelotomy for pediatric uretero- 2011;7(3):266–71.
pelvic junction obstruction: a review of our 25-year Roth CC, Hubanks JM, Bright BC, Heinlen JE, Donovan
experience. J Urol. 2012;188(4):1628–33. BO, Kropp BP, et al. Occurrence of urinary tract infec-
Lee JH, Son CH, Lee MS, Park YS. Vesicoureteral reflux tion in children with significant upper urinary tract
increases the risk of renal scars: a study of unilateral reflux. obstruction. Urology. 2009;73(1):74–8.
Pediatr Nephrol (Berlin, Germany). 2006;21(9):1281–4. Salem YH, Majd M, Rushton HG, Belman AB. Outcome
Lim DJ, Walker 3rd RD. Management of the failed pyelo- analysis of pediatric pyeloplasty as a function of
plasty. J Urol. 1996;156(2 Pt 2):738–40. patient age, presentation and differential renal func-
Lindgren BW, Hagerty J, Meyer T, Cheng EY. Robot- tion. J Urol. 1995;154(5):1889–93.
assisted laparoscopic reoperative repair for failed Sheu JC, Koh CC, Chang PY, Wang NL, Tsai JD, Tsai
pyeloplasty in children: a safe and highly effective TC. Ureteropelvic junction obstruction in children: 10
treatment option. J Urol. 2012;188(3):932–7. years’ experience in one institution. Pediatr Surg Int.
Maenhout A, Ham H, Ismaili K, Hall M, Dierckx RA, Piepsz 2006;22(6):519–23.
A. Supranormal renal function in unilateral hydronephro- Skoog SJ, Peters CA, Arant Jr BS, Copp HL, Elder JS,
sis: does it represent true hyperfunction? Pediatr Nephrol Hudson RG, et al. Pediatric vesicoureteral reflux
(Berlin, Germany). 2005;20(12):1762–5. guidelines panel summary report: clinical practice
McAleer IM, Kaplan GW. Renal function before and after guidelines for screening siblings of children with vesi-
pyeloplasty: does it improve? J Urol. 1999;162(3 Pt coureteral reflux and neonates/infants with prenatal
2):1041–4. hydronephrosis. J Urol. 2010;184(3):1145–51.
Mei H, Pu J, Yang C, Zhang H, Zheng L, Tong Q. Song C, Park H, Park S, Moon KH, Kim KS. The change in
Laparoscopic versus open pyeloplasty for ureteropelvic renal function in the supranormal hydronephrotic kid-
junction obstruction in children: a systematic review ney after pyeloplasty. BJU Int. 2007a;99(6):1483–6.
and meta-analysis. J Endourol. 2011;25(5):727–36. Song SH, Lee SB, Park YS, Kim KS. Is antibiotic prophy-
Moon DH, Park YS, Jun NL, Lee SY, Kim KS, Kim JH, laxis necessary in infants with obstructive hydronephro-
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terns on 99mTc-mercaptoacetyltriglycine scintigraphy Szavay PO, Luithle T, Seitz G, Warmann SW, Haber P,
in relation to the extent of hydronephrosis for predicting Fuchs J. Functional outcome after laparoscopic
ureteropelvic junction obstruction in the newborn. dismembered pyeloplasty in children. J Pediatr Urol.
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Thomas JC, DeMarco RT, Donohoe JM, Adams MC, Wiener JS, O’Hara SM. Optimal timing of initial postnatal
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ureteropelvic junction obstruction: clinical and
imaging features. Pediatrics. 2006;117(1):139–46.
Multicystic Dysplastic Kidney
12
The primary aim in diagnosis and manage- tion, including UPJO in 5 %, ureterocele in
ment of multicystic dysplastic kidney (MCDK) 1 %, and PUV in 0.4 %.
is preservation of contralateral renal function. Contralateral VUR, mostly grades 1–3,
Secondary aims: occurs in 20 %.
1. Diagnosis and management of associated • One study found no difference in serum
HTN. creatinine for age in patients with versus
2. To prevent malignancy. without contralateral VUR.
Summary of evidence for these goals: • Twelve newborns with MCDK would need
Retrospective series variously define sub- VCUG to detect one ureter with grades 3–5
normal renal function as GFR <80 or 90 mL/ VUR.
min/1.73 m2, or <80 % normal for age and • Retrospective studies indicate that >50 %
gender. of contralateral VUR resolves by £2 years
• A prospective registry reported all 76 chil- of age.
dren followed for 5–10 years had GFR • No RCT shows benefit of antibiotic prophy-
>60 mL/min/1.73 m2, with 43 % between 60 laxis versus no therapy to prevent first fUTI
and 90 mL/min/1.73 m2. in patients with contralateral VUR.
• A retrospective series of 36 children with Our review found no evidence that the diagno-
similar follow-up and a normal contralat- sis of VUR significantly impacts renal functional
eral kidney by US reported 12 % had GFR outcomes in children with MCDK, suggesting
<80 mL/min/1.73 m2. that routine cystography is not necessary.
• Analysis of potential hyperfiltration injury Systematic literature review reports that
in patients with MCDK or unilateral renal the rate of HTN is 5 per 1,000, with insufficient
agenesis versus normal controls reported data to state duration of follow-up needed to
that patients had mean GFR less than con- detect most cases. Two studies with a total of
trols (93 ± 20 vs. 114 ± 14). 27 patients report BP normalization in 68 and
Meta-analysis reported contralateral 100 % after nephrectomy.
anomalies potentially impacting renal func- Malignancy, including Wilms’ tumor and
renal cell carcinoma, has only been published
P.C. Gargollo, M.D. (*) as case reports, with no cohort study reporting
Department of Pediatric Urology, tumor development during follow-up.
University of Texas Southwestern Medical Our review found no evidence that renogra-
Center and Children’s Medical Center Dallas,
phy demonstrating no uptake versus uptake
Dallas, TX 75235, USA alters prognosis or management of MCDK (i.e.,
e-mail: patricio.gargollo@childrens.com impacts risk for HTN or malignancy), so nuclear
184 P.C. Gargollo
renal scan should be considered an optional Renal US

investigation for children with this condition.
Sports-related renal injury was also Meta-analysis of 72 articles published between
reviewed to determine potential risk to a soli- 1964 and 2008 reported:
tary functioning kidney, finding the following: • 21/389 (5 %) prenatally detected MCDK were
• Injuries resulting in functional loss or neph- not visible on US postnatally (five studies).
rectomy are rare. • 5 % UPJO, 1 % ureterocele, 0.6 % horseshoe
• Most injuries are reported related to American kidney, and 0.4 % PUV (67 studies, 3,557
football, with an incidence of <0.7 %. patients) (Schreuder et al. 2009).
• Most injuries occur in children ≥12 years of A retrospective analysis reviewed US findings
age. correlated with VCUG results in 76 consecutive
• No evidence-basis to restrict sports partici- newborns with antenatally diagnosed MCDK
pation in children with a solitary kidney. evaluated with a systematic imaging protocol.
Two renal US were obtained, on day 3 and at 1
month, with abnormal findings defined as AP
Prevalence and Presentation diameter ³7 mm, calyceal or ureteral dilation,
“pelvic or ureteral wall thickening” (not further
MCDK occurs in approximately 1:4,300 described), absence of corticomedullary differen-
screened subjects, more often in males. tiation, or renal dysplasia:
Eighty percent are diagnosed prenatally. • Normal US (n = 61, 80 %); four (7 %) had
Systematic review of data from 19 studies VUR, grades 1 or 2.
published from 1986 to 2008 found a total of 371 • Abnormal US (n = 15, 20 %); 12 (80 %) had
patients with unilateral MCDK in 1,588,271 VUR, grades 1,2 in 5; grade 3 in 4; grades
screened subjects, an incidence of 1 per 4,281. 4,5 in 3.
Fifty-nine percent were males, and 53 % involved Sensitivity, specificity, positive predictive
the left kidney, both significantly increased over value, and negative predictive value of two US
the expected 51 and 50 %, respectively. within the first month of life to predict abnor-
Eighty-one percent of MCDK were diagnosed mal VCUG were 75, 95, 80, and 93 % (Ismaili
prenatally; the 19 % diagnosed postnatally were et al. 2005).
imaged for abdominal mass in 64 %, UTI in 7 %,
and various other reasons in the remainder
(Schreuder et al. 2009). Contralateral Renal Hypertrophy
Literature review by Schreuder et al. (2009)

Imaging and Associated Conditions found two reports of contralateral hypertrophy at
initial US soon after birth in 12/26 (46 %) and
Meta-analysis reported abnormalities of the 8/33 (24 %) patients.
contralateral kidney in approximately 5 % of Retrospective review of 66 children with
patients, mostly UPJO. MCDK with US at mean age 12 months (6–18)
Compensatory hypertrophy of the contral- found contralateral compensatory hypertrophy
ateral kidney has been reported on the initial (renal length >95 % standard values) in 53
US following birth, and occurs in >85 % with (80 %). Follow-up in 13 to ³10 years showed all
follow-up to 10 years. 13 had compensatory hypertrophy (Weinstein
Meta-analysis found contralateral VUR in et al. 2008).
20 % of patients, over 50 % grades 1,2. Twelve Ten-year follow-up was available in 43 patients
VCUGs are needed to detect one ureter with in a MCDK registry, with compensatory hyper-
grades 3–5 VUR. trophy (renal length >95 % standard values) in
Renographic activity ranging from 1 to 35/40 (87.5 %) with lengths recorded (Aslam and
18 % has been reported in MCDK. Watson 2006).
12 Multicystic Dysplastic Kidney 185
VCUG One study reported mean serum creatinine

for age was similar in those with and without
Meta-analysis by Schreuder et al. (2009) of 67 contralateral VUR.
articles and 3,557 patients found VUR preva- No cohort study has reported malignancy
lence was 20 % in patients with MCDK, grade arising from a MCDK.
1 in 16 %, grade 2 in 40 %, grade 3 in 24 %,
grade 4 in 17 %, and grade 5 in 5 %. From the
data, at least 12 newborns with MCDK would Involution
need VCUG to detect one ureter with grades
3–5 VUR. As mentioned above, meta-analysis by Schreuder
et al. (2009) included five studies reporting that
21/389 (5 %) prenatally detected MCDK were
Renography not visible on initial US postnatally.
Retrospective review of 323 children with pre-
Meta-analysis by Schreuder et al. (2009) reported natally detected MCDK managed by protocol
seven published cohorts (from a total of 72 from 1985 to 2009 reported that the MCDK was
included articles) and described a total of 27/347 not visible on the initial postnatal US within the
(8 %) patients who had ipsilateral activity rang- first weeks of life in 32 (10 %). Nonvisualization
ing from 1 to18% on renography. Since most additionally occurred in 35 % of 249 by 2 years,
cohorts did not report the number of positive and 47 % of 180 by 5 years, and 62 % of 94 by 10
negative renograms, the authors chose not to years. Likelihood for the lesion to become non-
present a percentage from these data. detectable by 10 years related to initial length;
21 % of those >5 cm versus 76 % <5 cm, p < 0.001
(Hayes and Watson 2012).
Outcomes of Observation A retrospective review of 31 children followed
a mean of 6 years (6 months–11 years) reported
Five percent of prenatally detected MCDK are that 17 (55 %) MCDK became undetectable on
not visible on initial postnatal US. two follow-up US studies, 7 (23 %) had partial
Disappearance on US occurs in approximately regression, and another 7 were unchanged. Mean
50 % of cases by age 5 years. Increased length time to become undetectable on US was 2.5 years
of MCDK has been reported during observa- (1–4) (Chiappinelli et al. 2011).
tion in 0–19 % of patients. Most contralateral Of 66 MCDK undergoing US at mean age 12
VUR is grades 1–3, with spontaneous resolu- months (6–18), 11 (17 %) were no longer visual-
tion in 50–80 % within 1–3 years. ized. Twenty-seven MCDK had follow-up ³6
Retrospective series reported routine use of years, with 15 (56 %) no longer seen on US; 13
antibiotic prophylaxis in patients with VUR. were followed to ³10 years, with 9 (68 %) not
One study found 8 % of MCDK patients devel- visualized (Weinstein et al. 2008).
oped fUTI during median follow-up of 53 Fourteen patients with unilateral MCDK and
months, with no difference in those with VUR complete cyst involution by US (mean age 13
versus without VUR (or antibiotic prophylaxis). months, 3–18) underwent laparoscopic nephrec-
Meta-analysis reported HTN develops in 5 tomy. Dysplastic renal tissue was encountered in
per 1,000 MCDK. each case in remnants measuring from 1 to 3.5 cm
Retrospective reviews concerning renal (Luque-Mialdea et al. 2007).
function are characterized by differing
definitions of insufficiency (<90 mL or <80 mL/
min/1.73 m2 or <80 % normal GFR for age), Increased Size
failure to analyze all patients, and varying
duration of follow-up. Percentage with renal A summary of nine articles on US changes in
insufficiency was ≥10 % at ≥5 years of age. observed MCDK published from 1992 to 2004,
186 P.C. Gargollo
noted that six reported an increase in size from occurred; non-febrile UTI was diagnosed in 13
1.5 to 19 % of a total of 496 patients (Rabelo children without VUR and 7 with VUR on antibi-
et al. 2004). The three reporting the largest otics, which was reported not significant. Repeat
percentages with increases are summarized here: VCUG was not done (Aslam and Watson 2006).
• Fifty-five patients were diagnosed with MCDK Retrospective review of 75 patients with
at mean age 15 weeks (0–48), all with no MCDK included 19 (25 %) with contralateral
uptake on renography. Two hundred thirty-six VUR (10 males) that was grade 1 (n = 1), grade 2
renal US (mean 4, range 2–6 per patient) were (n = 8), grade 3 (n = 8), and grade 4 (n = 2).
obtained during a mean follow-up of 32 months Antibiotic prophylaxis apparently was used in all
(2–69). Ten (18 %) had mean increase in length with VUR. Spontaneous resolution occurred in 13
of 2 cm (1.3–2.5) from an initial mean length (68 %) at median follow-up of 20 months, while
of 4.6 cm at diagnosis. Mean initial length of one child with grade 3 VUR and a “history of
those that reduced in size during follow-up breakthrough UTIs” had reimplantation. At median
was 4.5 cm (Rottenberg et al. 1997). follow-up for the entire group at 53 months, febrile
• Thirty-three patients with MCDK were diag- UTI occurred in six (8 %), four without and two
nosed prenatally (n = 30) or because of a pal- with contralateral VUR (Miller et al. 2004).
pable mass “afterwards.” Serial US was Another retrospective review of 65 children
obtained every 3 months for 2 years. During with MCDK diagnosed contralateral VUR in 10
this time the MCDK became non-visualized (15 %), 8 of which were boys. Grades were 1
in 7 (23 %), decreased in size (diameter) in 20 (n = 2), 2 (n = 2), 3 (n = 2), 4 (n = 1), and 5 (n = 3),
(67 %), and increased in 6 (20 %). There was and all were given antibiotic prophylaxis. During
no further description of these 6 patients to mean follow-up at 3 years (3 months–6 years),
state when increase occurred and to what five resolved and two with grade 5 had reimplan-
extent, whether it was a cystic or solid compo- tation. None developed UTI (it was unclear if this
nent that appeared to change, and what subse- statement applied only to those with VUR or to
quently occurred (Heymans et al. 1998). all patients) (Selzman and Elder 1995).
• A multicenter German study enrolled 204 chil- VCUG in the first month of life was obtained in
dren with MCDK, of which serial measure- all 76 newborns reported by Ismaili et al. (2005).
ments of the largest diameter were available in Grade 1 VUR occurred in two ipsilateral ureters,
74 cases. In 48 the diameter decreased, while both with bilateral reflux. VUR involving the con-
in 14 (19 %) it increased. Timing and extent of tralateral kidney was diagnosed in 16 (21 %),
increase were not further described, the authors comprising grade 1 (n = 2), grade 2 (n = 7), grade 3
only noting that neither increase nor decrease (n = 4), grade 4 (n = 1), and grade 5 (n = 2). Second
in diameter appeared to be clinically significant cystograms were obtained between ages 1 and 2
(Rudnik-Schoneborn et al. 1998). years, showing only three cases to persist, one with
unchanged grade 3 and both grade 5 decreased to
grade 2. There was no mention of UTI.
UTI/VUR
Data from a prospective registry of children with Hypertension

antenatally detected MCDK reported that 143
had VCUG, of which 27 (19 %) had VUR into A systematic review concerning MCDK managed
the contralateral kidney that was grades 1–2 in without nephrectomy identified 29 published stud-
74 %, grade 3 in 22 %, and grade 5 in 1 child. ies including 1,115 children with HTN reported in
Those with ³grade 2 were prescribed trimethop- 6, a rate of 5.4 per 1,000. Of these studies, 14 did
rim (2 mg/kg/day) for 2 years, while other infants not report follow-up duration, and mean follow-up
did not receive antibiotic therapy. During follow- in the others was an average 4 years (3–5), with
up at a mean of 8 years (0.1–20), no febrile UTIs maximum follow-up of 13 years (Narchi 2005a).
A summary of articles not included in this Retrospective review of 31 children (age not
review or subsequently published: stated) reported BP determinations biannually for
2 years and then annually, with two determina-
Series Reporting HTN tions at each visit and the results averaged. During
Retrospective review of 101 patients with MCDK follow-up a mean of 6 years (6 months–11 years),
with follow-up >1 year (mean 5.9 ± 4.4 [1–18]), no patient had BP >95 % for age and gender
reported HTN in 6/86 (7 %), presumably repre- (Chiappinelli et al. 2011).
senting those with BP measurements recorded.
All were described as having contralateral renal
abnormalities (Mansoor et al. 2011). Renal Function
A retrospective review of 43 children followed
for a mean time of 42 months (12–156) reported In 76 children with follow-up 5 (n = 7) to 10
2 (5 %) developed HTN, 1 diagnosed at age 4 (n = 69) years reported from a prospective regis-
months with spontaneous improvement at 12 try of 323 children with prenatally detected
months, and another diagnosed at age 5 years and MCDK mentioned above, median calculated
associated with obesity (Rabelo et al. 2004). GFR was 93 mL/min/1.73 m2 (47–181). Of these,
Retrospective review was done in 36 patients 40 (53 %) had normal calculated GFR >90
with MCDK at 2 and 10 years, 4 (11 %) with prior mL/min/1.73 m2, 33 (43 %) had GFR 60–90 mL/
nephrectomy. At 2 years 2 (6 %) and at 5 years, min/1.73 m2, and 2 had GFR >160 mL/min/
one (3 %) had systolic BP >95 % (Vu et al. 2008). 1.73 m2 (other not described) (Hayes and
Ninety newborns and children with MCDK Watson 2012).
diagnosed between 1990 and 2007 identified 16 Renal function was available during chart
(18 %) with HTN, defined as systolic and /or dia- review in 24/80 (30 %) children with MCDK at
stolic pressure >95 % for age and gender. BP was mean age 12 months (6–18), reporting calculated
measured monthly during the first 6 months of mean GFR of 84 mL/min/1.73 m2 , which was
life, and those with suspected HTN were admit- ³80 % normal for age and gender in all (Weinstein
ted to hospital for 3 days monitoring to confirm et al. 2008).
the diagnosis. Antihypertensives (nifedipine Retrospective review in 36 children with
alone in 14, and two-drug therapy with nifedipine MCDK and a normal contralateral renal US all
or propranolol plus captopril in 2) were pre- followed to 5 years and 16–10 years reported cal-
scribed pending nephrectomy. Mean age at diag- culated GFR was <80 mL/min/1.73 m2 in 2 (6 %)
nosis was 6 months (4 days–2 years) excluding at 2 years, 4 (11 %) at 5 years, and 2 (12.5 %) at
one discovered at age 13 years. Reported preop- 10 years (Vu et al. 2008).
erative systolic pressures ranged from 110 to 135, Retrospective review included data to calcu-
but records were lacking for review in six patients late GFR in 82/101 children with MCDK at
(Kiyak et al. 2009). 6.5 ± 4.7 years of age. Eight of 82 (10 %) had
GFR <90 mL/min/1.73 m2, of which 5 had con-
Series Without HTN tralateral renal abnormalities (HN, megaureter,
Analysis of a prospective registry of 323 children g3 VUR, hypoplasia) and another 2 had medical
with prenatally detected MCDK who had BP renal disease (UTI with renal failure, nephrotic
measurements at ages 3, 6, and 12 months, then syndrome). GFR ranged from 15 to 86 mL/
annually to age 5, then every other year to age 10, min/1.73 m2 in these patients (median 78)
reported no patient with HTN related to the (Mansoor et al. 2011).
MCDK. Six of 94 (6 %) who were followed to 10 Retrospective review was done concerning
years had BP exceeding 95 %; 4 were found to be hyperfiltration injury in 66 children at mean age
normal on 24-h ambulatory monitoring, 1 tran- 8 ± 5 years with either MCDK (n = 27) or unilateral
sient from balanitis, and 1 with mitral valve renal agenesis (n = 39) compared to 34 normal
anomaly (Hayes and Watson 2012). controls at mean age 9 ± 4 years (no difference).
188 P.C. Gargollo
Five other patients with abnormal contralateral renal mass that consisted of MCDK and
kidney by US and/or renography were excluded. Wilms’ tumor (Homsy et al. 1997).
Median serum creatinine and fractional sodium • A 19-year-old female with a history of absent
excretion were significantly higher in patients, as right kidney and left pyeloplasty at 6 months
was occurrence of microalbuminuria, which was presented with right flank pain and was
seen in 23 % versus none in controls. Mean calcu- thought to have pyelonephritis of a MCDK.
lated GFR (mL/min/1.73 m2) was significantly Subsequent nephrectomy found collecting
less in patients (93 ± 20 vs. 114 ± 14) (Schreuder duct carcinoma, a variant of renal cell carci-
et al. 2008). noma (Cuda et al. 2006).
One retrospective analysis of 75 patients diag- A listing of additional case reports of renal
nosed with MCDK at median age 0 months and cell tumors arising from MCDK in patients aged
followed a median 53 months compared mean 15–68 years was included in the report by Homsy
serum creatinine in 19 (25 %) with contralateral et al. (1997).
VUR (grades 1, 2 in 47 %, grade 3 in 42 %, and In a comment to an article, Beckwith stated that
grade 4 in 10.5 %) to 56 without VUR for the the National Wilms’ Tumor Study Pathology Center
same age categories. There was no difference by had 7,500 Wilms’ tumor specimens, of which 5
regression analysis (Miller et al. 2004). (0.07 %) arose from MCDK (Beckwith 1997).
Malignancy Nephrectomy for Hypertension
A systematic review of all published cohort stud- Nephrectomy for HTN has normalized BP in
ies for MCDK without nephrectomy included 26 63 and 100 % of patients in two studies with a
reports and 1,041 children, none of which devel- total of 27 patients.
oped Wilms’ tumor during mean follow-up A retrospective review of children undergoing
(reported by 18) ranging from 1 to 6.5 years and nephrectomy for HTN included 11 MCDK, of
a maximum of 23 years (Narchi 2005b). which 7 (63 %) had normalization of BP by the
The report from the MCDK registry by Hayes first postoperative visit at a median 1.7 months.
and Watson (2012) mentioned above included 323 Among the entire series of 21 nephrectomies for
children with prenatally detected MCDK, with 94 HTN reported, contralateral renal abnormalities
(29 %) undergoing US at 10 years. Nephrectomy were diagnosed in 5/14 (36 %) with BP normal-
was done in 12 patients, 11 initially before a uni- ization and in 3/7 (43 %) without normalization
versal observation protocol was adopted and 1 (Schlomer et al. 2011).
with suspected malignancy but benign pathology. All 16 patients diagnosed with HTN by Kiyak
Details of this case, including patient age, US et al. (2009) mentioned above underwent nephre-
findings, and pathology, were not discussed. ctomy within less than 40 days after diagnosis,
Several case reports detail malignancies devel- and all postoperative BP were <95 % percentile,
oping from a MCDK: systolic pressures ranging from 80 to 105.
• A 5-year-old girl with right MCDK diagnosed
at birth presented with a palpable mass that at
nephrectomy was found to include malignant Sports Participation with a Solitary
rhabdoid tumor (Cui et al. 2010). Kidney
• A 5-month-old female with antenatal diagno-
sis of MCDK presented with a palpable mass Three reports indicate that American football
with multifocal Wilms’ tumor and nephro- accounts for the majority of renal injuries in
genic rests (Homsy et al. 1997). children ≥12 years of age, at a rate £0.7 %.
• A 3-month-old female presented with HTN Risk for renal trauma from team or indi-
and during evaluation was found to have a vidual sports participation is very small; one
study calculating the risk for renal loss (46 %) described renal injuries were hematomas
showed one kidney per 2.67 million partici- without capsular disruption. Nephrectomy was
pating children per year. done in 21/519 (4 %) children with injury due to
Surgery for sports-related renal injuries is accidents or falls versus 4/177 (2 %) related to
rare. sports or bicycling (2 to sledding, 1 skiing and 1
A review of one trauma registry found simi- jet skiing), which was not significantly different,
lar nephrectomy rates for injuries due to p = 0.3 (Johnson et al. 2005).
motor vehicle accidents, pedestrians being A fourth study reviewed a regional trauma
struck, and falls versus bicycling and sports. registry of a single children’s hospital for 1993–
These data do not support restrictions on 2000. Sports examined included football, ice
sports participation in children with a solitary hockey, basketball, baseball, soccer, wrestling,
kidney. skiing, snowboarding, sledding, bicycling, and
Prospective data from the National Athletic playground play. Of 4,921 children with trauma,
Trainers’ Association High School Injury renal injuries occurred in 15 (0.3 %), 5 (33 %)
Surveillance Study collected from 1995 to 1997 associated with football. Renal injuries were
reported over 4.4 million athlete-exposures grade 1 (n = 2), grade 2 (n = 5), grade 3 (n = 4),
(one athlete participating in one game or prac- grade 4 (n = 3), and grade 5 (n = 1), and occurred
tice) with 18 (0.07 %) kidney injuries out of a at mean age 13.5 ± 2.4 years. Three (20 %) injured
total of 23,666 injuries. None required surgery. kidneys had UPJO, and one with grade 5 injury
Twelve (67 %) occurred playing football was removed. From these data and census data
(Grinsell et al. 2012). from the referring region, the authors calculated
A study queried the National Pediatric Trauma there is risk for one kidney being lost per 2.67
Registry from 1990 to 1999 for recorded sports- million participating children in sports per year
related renal trauma in three age groups: 5–11, (Wan et al. 2003b).
12–14, and 15–18 years. Sports searched for were All National Football League (NFL) renal
(team sports) American football, ice hockey, bas- injuries from 1986 to 2004 were reviewed. There
ketball, baseball, soccer, and (individual sports) were a total of 48 renal injuries, or 2.7 per season,
rollerblading, skateboarding, skiing, sledding, with 42 (81 %) contusions and 6 lacerations.
and wrestling. There were 5,439 sports-related None required surgery, and all athletes returned
injuries, with renal injuries in 42 (0.7 %), related to play (Brophy et al. 2008).
to football in 26 (62 %), ice hockey in 3, basket-
ball in 5, baseball in 6, soccer in 2, and none from
others searched. Most of these renal injuries References
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There were no resultant nephrectomies, nor inju- kidney: long term outcomes. Arch Dis Child.
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Wilms tumor. Cancer Invest. 1997;15(2):153–62.
Another study reviewed all renal injuries
Brophy RH, Gamradt SC, Barnes RP, Powell JW, DelPizzo
reported to the National Pediatric Trauma JJ, Rodeo SA, et al. Kidney injuries in professional
Registry from 1995 to 2001, finding 813 patients American football: implications for management of an
at average age 11 years. Of these, 293 (36 %) athlete with 1 functioning kidney. Am J Sports Med.
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Cuda SP, Brand TC, Thibault GP, Sutherland RS.
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Collecting duct carcinoma arising from multicystic
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Cui Y, Eom M, Jung SH, Kim KJ, Jung WH. Malignant Narchi H. Risk of Wilms’ tumour with multicystic kidney
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kidney: does initial size matter? Pediatr Nephrol tory of the multicystic dysplastic kidney in children.
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tory of the affected and the contralateral kidney. Eur J multicystic renal dysplasia in children. Eur J Pediatr.
Pediatr. 1998;157(8):673–5. 1998;157(8):666–72.
Homsy YL, Anderson JH, Oudjhane K, Russo P. Wilms Schlomer BJ, Smith PJ, Barber TD, Baker LA.
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discussion 9. tional studies on the incidence, associated urinary tract
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Miller DC, Rumohr JA, Dunn RL, Bloom DA, Park JM. dence of recreational genitourinary and abdominal
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90(9):921–4. 23(1):111–6.
Ureteroceles and Ectopic Ureters
13
Micah A. Jacobs and Warren T. Snodgrass
Primary aims in the diagnosis and treatment A prospective protocol was used to manage 13
of ureteroceles and ectopic ureters: patients with ureterocele that was duplex in 11
1. To prevent or reduce UTI. and single in 2 with MCDK who presented at
2. To prevent renal damage. median age 18 days. Ten were prenatally detected,
3. To prevent or correct urinary incontinence. and three presented with fUTI. Based on either
“good” or no function (MCDK) on MAG-3
renography, drainage from the upper pole
Postnatal Management of Prenatally <30 min, and no bladder outlet obstruction, these
Detected Ureteroceles and Ectopic patients were all observed with antibiotic pro-
Ureters phylaxis (medication not stated). During follow-
up at a median of 48 months (25–97), the
Selective Observation of Ureteroceles ureteroceles associated with MCDK were asymp-
tomatic. Upper pole hydronephrosis present in
Indications for surgical intervention in ure- six resolved (n = 3) or improved to SFU grade 2
terocele are febrile UTI (fUTI) and bladder (n = 3), and VUR grade 3 and 4 of the lower pole
outlet obstruction. present in five resolved. The other four had
One series managing patients by prospec- surgery at median 11 months, due to break-
tive protocol reported that 70 % had resolved through UTI in 3 and progressive obstruction in 1
or improved hydronephrosis (HN) and VUR, (Han et al. 2005).
while 23 % had breakthrough UTI and 8 % Retrospective analysis was done in 52 chil-
developed outlet obstruction. dren with prenatal duplex ureterocele, in which
Retrospective series with selective observa- surgical intervention was generally determined
tion based on various factors reported that by breakthrough UTI, upper pole function >10 %,
most patients had stable or improved HN and lower pole obstruction, grade 4 or 5 lower pole
resolved VUR, with <10 % developing break- reflux, or bladder outlet obstruction. Using these
through UTI and <5 % outlet obstruction. criteria, 14 were observed, eight with VUR, with
median follow-up of 8 years (1.6–13). Antibiotic
prophylaxis (medication not stated) was used
M.A. Jacobs, M.D., M.P.H. • W.T. Snodgrass, M.D. (*) “routinely until toilet training” or age 5, if there
Department of Pediatric Urology, University of Texas was VUR. No patient developed UTI, VUR
Southwestern Medical Center and Children’s Medical resolved in 3/4 cases with cystography, and
hydronephrosis was stable (n = 8) or improved/
e-mail: micah.jacobs@childrens.com; resolved with collapse of the ureterocele (n = 6)
warren.snodgrass@childrens.com (Shankar et al. 2001).
192 M.A. Jacobs and W.T. Snodgrass
A retrospective study found 10 newborns, six VUR in 10. Of these, 10 were evaluated within
females, with prenatally detected ureteroceles who the first week of life, 3 in the second, and 1 at 3
had “adequate drainage of the affected unit” with- and 6 weeks each. FUTI occurred in seven (47 %)
out lower pole obstruction, grade 4 or 5 VUR, or due to E. coli (n = 6) and S. aureus, in three despite
bladder outlet obstruction managed with antibiotic prophylactic antibiotics (medication not stated).
prophylaxis (medication not stated) and observa- There was no difference in UTI in those with ver-
tion. Six were duplex and 4 single-system uretero- sus without antibiotic (43 % vs. 62.5 %, p = 0.6)
celes, 1 with MCDK. During mean follow-up of 3 (Besson et al. 2000).
years, HN (initially SFU grade 3 in 2 and less in the Another retrospective study involved 72 neo-
others) resolved in six and was improved or stable nates with prenatally detected duplex system ure-
in 4. VUR grade 3 into the lower pole was initially teroceles all treated from birth with antibiotic
present in 4, which resolved in 2. No patient under- prophylaxis (medication not stated). Of these, 32
went repair (Direnna and Leonard 2006). had endoscopic puncture at a median age of 5
Another retrospective analysis included 40 neo- days, while the other 40 were initially observed
nates with prenatally detected ureterocele initially but had open surgery at £6 months of age (median
observed with antibiotic prophyaxis (medication 3 months, 2–6). UTI occurred after puncture and
not stated) with planned open surgery at 6 months before age 6 months in 3/32 (9 %) in 1 with blad-
(selection for observation vs. puncture was not der outlet obstruction from incomplete decom-
stated, but implied these had no lower pole VUR pression, and in 3/40 (8 %) with delayed
and no bladder outlet obstruction). During observa- intervention (Husmann et al. 2002).
tion, 3 (8 %) had UTI and 2 (5 %) had progressive The protocol used by Han et al. (2005)
ureterocele enlargement resulting in bladder outlet described above reported that 3/11 (27 %) neo-
obstruction (Husmann et al. 2002). nates with duplex ureteroceles selected for non-
surgical management in part because they were
considered to be at low risk for infection had
UTI in Newborns breakthrough UTI, despite antibiotic prophylaxis
at median time 11 months.
No trials compare antibiotic prophylaxis ver- The ten patients observed by Direnna and
sus no treatment for newborns with prenatally Leonard (2006) described above, with 6 duplex
diagnosed anomalies, including ureteroceles and 4 single-system ureteroceles, reported no
or ectopic ureters. breakthrough UTI during mean follow-up of 3
One small series of neonates with prenatal years. Antibiotic prophylaxis was used in all for a
ureterocele reported that 53 % had UTI with mean of 1.5 years.
no difference in those with versus without Retrospective review of consecutive neonates
antibiotic prophylaxis. treated with a systematic protocol included 12 pre-
A study in which newborns with ureteroce- natally detected with duplex ectopic ureter or ure-
les with VUR were punctured and those with- terocele without VUR and initially treated with
out VUR observed found breakthrough UTI antibiotic prophylaxis (medication not stated).
in 8 % of both groups by age 6 months. Five (42 %) developed breakthrough fUTI at
Another series that used antibiotic prophy- median age 3 months (2–8), three with ectopic
laxis in newborns with ureterocele or ectopic ureter and 2 with ureterocele (Prieto et al. 2009).
ureter without VUR reported that 42 % devel-
oped fUTI at median 3 months of age.
No trial has compared antibiotic prophylaxis Endoscopic Management
versus no treatment in neonates with prenatally of Ureterocele
detected ureterocele or ectopic ureter.
Retrospective review concerned 15 neonates, Secondary surgery after ureterocele puncture is
13 females, with prenatally detected ureterocele reported more likely with extravesical uretero-
that was duplex in 14 cases and associated with celes, duplex systems, and pre-puncture VUR.
13 Ureteroceles and Ectopic Ureters 193
One retrospective comparison of puncture Another retrospective series included 60 chil-

versus upper pole heminephrectomy for dren, 68 % female, with ureteroceles treated with
duplex ureterocele with no VUR reported sec- puncture: duplex in 51 that was intravesical in 22
ondary surgery more likely after puncture, and extravesical in 29, and single system in nine
mostly for new VUR. with intravesical ureterocele. Thirty-two (52 %)
Indications for secondary surgery often are presented before 3 months of age, and 31 (52 %)
not reported. were prenatally detected, while 29 (48 %) had
Systematic literature review was done to deter- fUTI. With follow-up a mean of 20 months
mine secondary operation rates after ureterocele (4–62), 19 (32 %) had additional surgery.
puncture, reporting additional surgery was more • None of the nine single-system ureteroceles
likely with: had additional surgery, and of four of nine
• Extravesical ureterocele, RR 2.8 (95 % CI with new VUR after puncture, three resolved.
2.06–3.74). • Of 51 duplex ureteroceles, 19 had secondary
• Duplex system, RR 3.9 (95 % CI 1.14–10.93). surgery, including seven (14 %) with “persis-
• Pre-puncture VUR, RR 1.56 (95 % CI tent VUR and infection.”
1.24–1.96). Otherwise, indications for secondary surgery
The authors used secondary surgery as the end- were not described (Hagg et al. 2000).
point, but indications for both initial puncture and A third retrospective series of 28 patients with
subsequent surgery were not always reported in duplex ureterocele and no VUR that underwent
reviewed articles (Byun and Merguerian 2006). puncture reported new VUR in 16 (57 %) and
Retrospective review was done in 52 children, persistent obstruction in 2 (7 %). During follow-
42 % female, undergoing ureterocele puncture up a median of 2 years (3 months–6 years), reim-
done at median age 3 months (1 month–12 years). plantation was done in 12 for breakthrough UTI
This series dated from 1984 to 2001, and only 12 or persistent reflux. Compared to partial nephrec-
(23 %) had prenatal diagnosis, while the others tomy in patients with similar preoperative findings
presented after UTI. Ninety-two percent had ure- (duplex ectopic ureterocele and no VUR), punc-
teral duplication, and the 52 cases were classified ture was significantly more likely to result in fur-
as intravesical in 73 % and extravesical in 27 %. ther surgery or persisting VUR, 64 % versus
Antibiotic prophylaxis (not described) was used 15 % (see below) (Husmann et al. 1999).
for all with VUR until resolution. Preoperative
and postoperative nuclear renography was done
(postoperative time interval not stated). Upper Tract Surgery for Ureterocele
Nonfunctioning upper poles (n = 10) or kidneys and Ectopic Ureter
(n = 9) were removed. Median follow-up was 9
years (6 months–18 years): Retrospective series report secondary surgery
• Poor function in the upper pole (n = 25) did not in <20 % for VUR or symptomatic remnant
improve, and normal to moderately impaired upper pole stumps (see below).
function did not decrease after puncture and In a retrospective review, 26 patients with duplex
during follow-up (“moderate” and “poor” ureterocele and no VUR had partial nephrectomy
were not defined; actual data not shown). as initial therapy. New lower pole VUR occurred in
• No patient with poor function had eight (30 %), which then resolved in 4 and led to
pyelonephritis. reimplantation in 4 (15 %) due to breakthrough
• VUR spontaneously resolved in 59 % of UTI during median follow-up of 2 years (1–4).
affected renal units; others mostly had endo- These outcomes were compared to puncture in
scopic correction. Indication for VUR treat- similar patients, and it was concluded that hemi-
ment was not stated. nephrectomy results in fewer secondary operations
• No patient had incontinence. (see section above) (Husmann et al. 1999).
• No patient had infection after puncture Another review included 29 patients with 30
(Chertin et al. 2003). ureteroceles, six with VUR, who underwent
upper pole heminephrectomy (n = 29) or pyelopy- Postoperative fUTI was reported in 0–10 %.
elostomy and then had follow-up for a mean of Complications from retained upper pole
25 months (9–30). New VUR occurred in 4 and segments did not occur.
then resolved in 3, and 4 (14 %) others developed Fifty-seven patients, 94 % female, at mean age
breakthrough UTI leading to lower tract surgery approximately 28 months, underwent ureterocele
(Gomes et al. 2002). surgery at three institutions by four surgeons
An upper tract approach was used in 31 duplex based on their preference. Thirty-nine (68 %) had
systems with ectopic ureters in 30 females and one prior puncture, and operations comprised ure-
male as newborns to age 17 years. Of these, 23 terocele excision or unroofing and ureteral reim-
systems were considered on various imaging stud- plantation. During mean follow-up of 55 months
ies (IVP, CT, nuclear renography) to have poor or (6–234), new VUR occurred in seven (12 %) and
no function and had heminephrectomy, while the fUTI in six (11 %), of which two had reflux.
other eight had “sufficient function to warrant sal- Outcomes for the new VUR were not described
vage” (not defined) and so had high ureteroureter- (Lewis et al. 2008).
stomy or ureteroplyelostomy. The orifice of the A review was done in 16 children, 15 females,
ectopic ureter was identified in 19 (58 %), at the with duplex ureteroceles and nonfunctioning
bladder neck or urethra in 15, and vagina or vesti- upper poles who had lower tract reconstruction
bule in 4. During follow-up a mean of 4.5 years (8 without upper pole excision at two institutions.
months–10 years), 3 (10 %) had fUTI leading to Thirteen had prior puncture, and all had uretero-
remnant stump removal (subsequent clinical cele excision, bladder neck reconstruction, and
course not described), and 1 had pain with void- reimplantation. Follow-up was a mean of 62
ing, resulting in stump removal (see below). months (33–127). VUR was found in 2 (12.5 %),
Preoperative VUR occurred in nine (29 %), into 1 observed and the other not further described,
the ipsilateral lower pole in 5 and contralateral in and there were no fUTIs. The retained nonfunc-
4. One of these had reimplantation for “persistent tioning upper pole moiety did not cause hyper-
reflux,” while outcomes of VUR in the others were tension or other recognized complication (Gran
not stated (Plaire et al. 1997). et al. 2005).
Laparoscopic heminephrectomy was done in Another review included 31 children, 28
17 consecutive patients with 19 affected units females, mean age 30 months (19 days–10 years)
having ectopic ureter (n = 8) or ureterocele (n = 7), with duplex ectopic ureters. Twelve with func-
of which three had lower pole VUR. Follow-up tioning upper poles (visualization in IVP) had
was a mean of 57 months (8–115), during which ureteral reimplantation of the ectopic ureter,
time lower pole VUR resolved in 3/4 units. The while 18 with non-visualization had upper pole
only infections involved the stump and occurred heminephrectomy; one kidney had no function.
in three patients (18 %) leading to removal. One During follow-up a mean of 66 months
patient had loss of function to the remaining (6 months–20 years), one patient in each treat-
lower pole. Two of seven with ureteroceles had ment group had recurrent UTI (not otherwise
persistent, but smaller, ureteroceles that were described). None had incontinence, and none
asymptomatic (Denes et al. 2007). with reimplantation had further surgery (El
Ghoneimi et al. 1996).
Lower Tract Surgery for Ureterocele

Simultaneous Upper and Lower Tract
Ureterocele excision or unroofing with reim- Reconstruction for Ureterocele
plantation, sometimes following prior punc-
ture, resulted in new or persistent VUR in One study reported secondary surgery after
12 %, reported by two series. “complete” reconstruction in 6 % of patients.
Retrospective review was done in 18 patients 4 in 13 (50 %); postoperative ultrasound at 12

with 20 ureteroceles who all had VUR and under- weeks showed resolution (n = 17) or reduction to
went upper heminephrectomy (n = 11) or upper grade 2 or less in all ureters. One patient had fUTI
pole ureteral tailoring (n = 9) and ureterocele and was found to have new grade 1 ipsilateral
excision, bladder neck reconstruction, and cross- VUR treated with endoscopic injection, for sec-
trigonal reimplantation. Duration of follow-up ondary surgery rate of 4 % (Prieto et al. 2009).
was not stated (mean 33 months for all patients in
the series); new contralateral VUR occurred in 1,
and two patients had postoperative complica- Renal Function
tions, including bilateral obstruction after bilat-
eral reimplantation and one requiring intermittent Our review found only two studies mentioning
catheterization. There was no mention of postop- renal functional outcomes. One stated that
erative UTI; 1 (6 %) patient had reoperation (not 8 % of patients had a decrease >10 % in reno-
further described) (Gomes et al. 2002). graphic differential renal function after
heminephrectomy.
From a retrospective review of 101 patients
Ureteroureterostomy with heminephrectomy renal function, data were
available in 60, of which 42 had upper pole (ure-
Two series using different inclusion criteria terocele in 20) and 18 lower pole excision. Mean
reported secondary surgery in <10 % of chil- age at operation was 44 months, and follow-up
dren after ureteroureterstomy (UU). was a mean of 25 months (3–64). Preoperative
Of 142 children undergoing surgery for duplex and postoperative MAG-3 or DMSA scans were
ureters, 39 (17 %), 86 % females, underwent 41 obtained (date of postoperative study not stated).
UUs. There were five with ectopic ureter and four Mean preoperative differential function was 40 %
with ureterocele who only had UU. Nine others (22–61 %), and 33 % (13–60 %) postoperatively
with ectopic ureters with lower pole reflux had (statistical analysis not reported). Five (8 %) had
UU and reimplantation, as did another 12 with a decrease >10 %—one who had recurrent post-
prior ureterocele puncture. The remaining patients operative UTI and without known reason in oth-
had lower pole reflux without ectopic ureter or ers (Gundeti et al. 2005).
ureterocele. Mean follow-up was 12 months The retrospective study by Gran et al. (2005)
(3–34). Two cases of new contralateral VUR described above, in which bladder but not renal
were corrected with endoscopic injection, as was level surgery was done, reported that no patient
one of two cases with ipsilateral persistent VUR, had loss of renal function by nuclear renography,
comprising secondary interventions in 8 %. There but timing of studies and resultant data were not
was no mention of postoperative UTI and “all stated or shown.
showed improvement of dilation” on ultrasound
(Chacko et al. 2007).
Another review included 23 consecutive chil- Histology of Nonfunctioning Renal
dren, (74 %) female, and 26 duplex systems with Segments
ectopic ureter (n = 18) or ureterocele (n = 8) and
no lower pole reflux, who represented 37 % of Histology of resected upper pole segments was
patients with these conditions operated during a reported in two studies to most often demon-
4-year study period. Median patient age was 10 strate inflammatory changes or dysplasia.
months (2–56), and two of seven patients with Retrospective review of the upper pole was
ureteroceles had prior puncture with resultant done in 50 consecutive heminephrectomy speci-
upper pole reflux. Mean follow-up was 26 months mens related to ureterocele (n = 30) or ectopic
(2–48). Preoperative upper pole hydronephrosis ureter. Twenty-five demonstrated nonspecific
occurred in 22 ureters and was SFU grades 3 and inflammatory findings in the interstitial tissues,
chronic inflammatory changes with collecting

system involvement in 15, microabscesses in 3, Bladder Dysfunction
xanthogranulomatous pyelonephritis in 2, and
dysplasia (parenchymal disorganization with There are no reliable data to determine if
cysts, primitive ducts, cartilage) in 30 with children with ureteroceles and ectopic ureters
nephroblastomatosis in 1. Only one was inter- have increased bladder dysfunction compared
preted as normal. There were no apparent dif- to normal children.
ferences in patients with antenatal versus A retrospective series analyzed 34 children,
postnatal diagnosis, but age at surgery and pre- 79 % females, after ureterocele management.
surgical morbidities, including fUTI, were not Eighteen (53 %) had extravesical ureteroceles.
described. The implication of these findings, Median age at surgery was 10 months (3–101)
however, was that there was little expectation and involved heminephrectomy for ten, uretero-
that earlier diagnosis and treatment would cele excision and reimplantation in six, both
significantly improve upper pole findings (Abel upper and lower tract surgery in 15, and no inci-
et al. 1997). sion or no treatment in 3. Of these, 32 had blad-
The 16 upper pole specimens with ectopic der function assessment at median 5 years of
ureters removed for non-visualization on IVP by age (1–12). Infrequent voiding <4×/daily was
El Ghoneimi et al. (1996) as described above diagnosed in 19 (59 %). Another three (9 %) had
demonstrated “lesions of chronic pyelonephritis” incontinence, none with prior bladder surgery,
in 13 and “focal lesions of dysplasia” in 4. including one with a persistent ureterocele. Two
The practice of routinely removing upper (6 %) used CIC because of “high” PVR. UD
poles based on such histologic findings was chal- was done in 27 children, with 55 % having mea-
lenged by a review article that addressed associa- sured capacity >150 % predicted for age and
tion of renal dysplasia to UTI, hypertension, and 11 % detrusor instability; all had normal com-
tumor potential and concluded that occurrence of pliance and mean PVR was 12 cc. Uroflow pat-
these is so rare that it does not support extirpation tern was stated to be normal in all cases. The
(Husmann 1998). authors considered only eight (25 %) to have
normal bladder function defined as normal
capacity and PVR <5 cc, but they did not corre-
Continence late factors they considered abnormal to clinical
symptoms or complications, such as UTI
One study reported no postoperative inconti- (Abrahamsson et al. 1998).
nence after surgery for ectopic ureter. The four-surgeon series with ureterocele exci-
Of the 28 females with duplex ectopic ureters sion and reimplantation by Lewis et al. (2008)
reported by El Ghoneimi et al. (1996) above, the described above reported voiding dysfunction
upper pole ureter entered the bladder neck in six, (infrequent voiding, holding maneuvers, urgency)
posterior urethra in 5, vagina in seven, vestibule postoperatively in 11 (20 %). One other child had
in six, and was unclear in 4. Preoperative inconti- incontinence, possibly due to bladder neck
nence occurred in 13 (46 %), corrected in all dysfunction.
cases by either upper pole reimplantation or
heminephrectomy.
Of 31 duplex systems with ectopic ureters in Symptomatic Stumps
30 females and one male reported by Plaire et al.
(Plaire et al. 1997) above, the orifice of the ecto- Three retrospective series report removal of the
pic ureter was identified in 19 (58 %), at the blad- remnant “stump” after partial upper pole ure-
der neck or urethra in 15, and vagina or vestibule terectomy in from 7 to 18 %, mostly due to UTI.
in 4. The authors did not mention postoperative None reported postoperative UTI occur-
incontinence. rence after stump excision.
Stump removal was done in 4 (7 %) of 55 Denes FT, Danilovic A, Srougi M. Outcome of laparo-
patients with duplex ureters with ureterocele, scopic upper-pole nephrectomy in children with
duplex systems. J Endourol. 2007;21(2):162–8.
ectopia, and/or VUR who underwent upper pole Direnna T, Leonard MP. Watchful waiting for prenatally
heminephrectomy as described by Ade-Ajayi detected ureteroceles. J Urol. 2006;175(4):1493–5.
et al. (2001) above. All had recurrent UTI (not discussion 5.
described), but follow-up after removal and UTI el Ghoneimi A, Miranda J, Truong T, Monfort G. Ectopic
ureter with complete ureteric duplication: conservative
occurrence, if any, in other patients with stumps surgical management. J Pediatr Surg. 1996;31(4):
was not stated. 467–72.
Of the 32 patients described by Plaire et al. Gomes J, Mendes M, Castro R, Reis A. Current role of
( 1997) with duplex ectopic ureters who all simplified upper tract approach in the surgical treat-
ment of ectopic ureteroceles: a single centre’s experi-
had upper tract surgery (heminephrectomy in ence. Eur Urol. 2002;41(3):323–7.
23 and reconstruction in eight), 4 (12 %) had Gran CD, Kropp BP, Cheng EY, Kropp KA. Primary
secondary surgery to remove the remnant lower urinary tract reconstruction for nonfunctioning
stump, 1 during a reimplantation for persistent renal moieties associated with obstructing ureteroce-
les. J Urol. 2005;173(1):198–201.
lower pole reflux, 1 for pain during voiding, Gundeti MS, Ransley PG, Duffy PG, Cuckow PM, Wilcox
and two for fUTI. DT. Renal outcome following heminephrectomy for
Laparoscopic heminephrectomy was done in duplex kidney. J Urol. 2005;173(5):1743–4.
17 consecutive patients with 19 affected units Hagg MJ, Mourachov PV, Snyder HM, Canning DA,
Kennedy WA, Zderic SA, et al. The modern endoscopic
having ectopic ureter (n = 8) or ureterocele (n = 7). approach to ureterocele. J Urol. 2000;163(3):940–3.
Follow-up was a mean of 57 months (8–115), Han MY, Gibbons MD, Belman AB, Pohl HG, Majd M,
during which time infections involved the stump Rushton HG. Indications for nonoperative manage-
in three patients (18 %) and were removed (Denes ment of ureteroceles. J Urol. 2005;174(4 Pt 2):1652–5.
discussion 5–6.
et al. 2007). Husmann DA. Renal dysplasia: the risks and conse-
quences of leaving dysplastic tissue in situ. Urology.
1998;52(4):533–6.
References Husmann D, Strand B, Ewalt D, Clement M, Kramer S,
Allen T. Management of ectopic ureterocele associ-
ated with renal duplication: a comparison of partial
Abel C, Lendon M, Gough DC. Histology of the upper nephrectomy and endoscopic decompression. J Urol.
pole in complete urinary duplication–does it affect 1999;162(4):1406–9.
surgical management? Br J Urol. 1997;80(4):663–5. Husmann DA, Strand WR, Ewalt DH, Kramer SA. Is
Abrahamsson K, Hansson E, Sillen U, Hermansson G, endoscopic decompression of the neonatal extravesi-
Hjalmas K. Bladder dysfunction: an integral part of cal upper pole ureterocele necessary for prevention of
the ectopic ureterocele complex. J Urol. urinary tract infections or bladder neck obstruction? J
1998;160(4):1468–70. Urol. 2002;167(3):1440–2.
Ade-Ajayi N, Wilcox DT, Duffy PG, Ransley PG. Upper Lewis JM, Cheng EY, Campbell JB, Kropp BP, Liu DB,
pole heminephrectomy: is complete ureterectomy nec- Kropp K, et al. Complete excision or marsupialization
essary? BJU Int. 2001;88(1):77–9. of ureteroceles: does choice of surgical approach affect
Besson R, Ngoc BT, Laboure S, Debeugny P. Incidence of outcome? J Urol. 2008;180 Suppl 4Suppl 4:1819–22.
urinary tract infection in neonates with antenatally discussion 22–3.
diagnosed ureteroceles. Eur J Pediatr Surg. Plaire JC, Pope JC, Kropp BP, Adams MC, Keating MA,
2000;10(2):111–3. Rink RC, et al. Management of ectopic ureters: experi-
Byun E, Merguerian PA. A meta-analysis of surgical prac- ence with the upper tract approach. J Urol. 1997;158(3
tice patterns in the endoscopic management of uretero- Pt 2):1245–7.
celes. J Urol. 2006;176(4 Pt 2):1871–7. discussion 7. Prieto J, Ziada A, Baker L, Snodgrass W.
Chacko JK, Koyle MA, Mingin GC, Furness 3rd PD. Ureteroureterostomy via inguinal incision for ectopic
Ipsilateral ureteroureterostomy in the surgical man- ureters and ureteroceles without ipsilateral lower pole
agement of the severely dilated ureter in ureteral dupli- reflux. J Urol. 2009;181(4):1844–8. discussion 8–50.
cation. J Urol. 2007;178(4 Pt 2):1689–92. Shankar KR, Vishwanath N, Rickwood AM. Outcome of
Chertin B, de Caluwe D, Puri P. Is primary endoscopic patients with prenatally detected duplex system ure-
puncture of ureterocele a long-term effective procedure? terocele; natural history of those managed expectantly.
J Pediatr Surg. 2003;38(1):116–9. discussion 116−9. J Urol. 2001;165(4):1226–8.
Non-refluxing Megaureter
14
Patricio C. Gargollo and Warren T. Snodgrass
The primary goal in diagnosing and treating • The review reporting the highest occurrence
non-refluxing megaureters is to prevent ipsi- of UTI during observation, with 57 % of
lateral renal function loss. patients initially diagnosed following UTI,
Secondary goals are to minimize associated reported that prophylaxis reduced infections.
comorbidities, including febrile UTI (fUTI) • Surgical series did not systematically report
and pain. UTI occurrence postoperatively.
A summary of evidence for these aims is One review found abdominal and/or flank
presented: pain as the presenting complaint in 16 % of
Loss of ipsilateral renal function during diagnosed megaureters in children at a mean
observation was reported in £10 % of age of 6 years. Pain did not recur after sur-
megaureters. gery, or in those selected for observation.
Recurrent obstruction occurs in <10 %
after surgical repair.
Reported UTIs were generally not charac- Observation
terized as febrile versus nonfebrile:
• Although most patients were males, no Spontaneous resolution of non-refluxing
study reported circumcision status. megaureters was reported in between 34 and
• All reviews of observation patients reported 72 % at a mean time ranging from 1.5 to
antibiotic prophylaxis in most or all patients 4 years in four retrospective studies.
during the first year of life. Generally, initial distal ureteral diameter
• UTI incidence during observation varied <1 cm predicted greater likelihood for resolution.
from 6 to 71 %. Two studies reported that no ureter with initial
• No study randomized patients to prophy- diameter >15 mm resolved spontaneously.
laxis or no treatment; no study related UTI One study reported 9 % of observed mega-
occurrence to circumcision status, initial ureters had renal functional loss from a mean
presentation with UTI or not, extent of 45–33 %, all within 6 months.
hydronephrosis (HN), or renography drain- All reported antibiotic prophylaxis in some
age patterns. or all patients, especially in the first year of
life. Reported UTI (not characterized as febrile
P.C. Gargollo, M.D. • W.T. Snodgrass, M.D. (*) vs. nonfebrile) widely ranged from 6 to 71 %.
Department of Pediatric Urology, University of Texas None reported pain or other symptoms.
Surgical rates for various indications,
Dallas, TX 75235, USA including UTI, decreased function, increased
e-mail: warren.snodgrass@childrens.com HN, and solitary kidney, were 16–23 %.
200 P.C. Gargollo and W.T. Snodgrass
A retrospective study included 60 neonates, excluding VUR or PUV, and DTPA renography
80 % males, diagnosed with 72 non-refluxing at age 1 month. All were prescribed antibiotic
megaureters defined as dilation of the distal ure- prophylaxis with trimethoprim for the first year
ter >6 mm by initial US and negative VCUG. of life. Mean follow-up was 3 years:
Cases were detected by prenatal US (80 %) or by • Twenty three (34 %) megaureters resolved at a
neonatal US done for other reasons. These mean 1.6 years.
patients received antibiotic prophylaxis for • Eleven (16 %) had surgical correction for UTI
12 months, and follow-up renal US at 3-month in 3, poor function (10 %) or solitary kidney in
intervals for 1 year and then every 6 months. 2, and for decreased renal function in 6 fol-
DTPA renography was done two times the first lowed £12 months, with initial mean function
year and then annually. Resolution was defined 45 % (39–56 %) decreasing to mean 33 % (26–
as a distal ureter <6 mm. Surgical indications 39 %). Renal function was regained in half.
were “symptomatic” UTI despite prophylaxis, • Of 53 ureters with diameter <1 cm, 23 (43 %)
decrease renal function to <40 % or >10 % initial resolved; of 14 ureters with diameter >1 cm, 0
value, and solitary kidney. Mean follow-up for resolved.
conservatively managed patients was 5 years • Of 52 ureters with T1/2 £10 min, 22 (42 %)
(6 months–15 years): resolved; of 15 with T1/2 >10 min, 1 (7 %)
• Mean presenting HN grade was 4 ± 1 (based resolved (Liu et al. 1994).
on possible five grades modified from SFU Another retrospective review identified 54
scale); mean initial ureteral diameter was newborns, 67 % males, with abnormal prenatal
13 ± 5 mm (6–22). US found to have 69 non-refluxing megaureter
• Initial renogram diuretic drainage (reported as T between 1993 and 1998. Antibiotic prophylaxis
75, time for 75 % clearance) was <5 min in was given during the first year of life. Median
58 %, 5–10 min in 28 %, and >10 min in 14 %. follow-up was 26 months (2–72):
• Resolution occurred in 38 ureters (53 %) at • Thirty nine patients (72 %) resolved.
mean time 2 years (6 months–8 years). • Ten patients (19 %) had surgical repair at
• Megaureter persisted in 18 (25 %), including mean age 10 months (4–25) for increasing HN
10 not changed from initial assessment and 8 in 3, “obstructive appearance on IVP” in 2,
with decreased ureteral diameter still >6 mm. decreased renal function (31–22 %) in 1, high-
• Surgery was done in 16 (22 %) at mean age grade HN in 2, solitary kidney in 1, and acute
17 months (6–48); specific indications were renal failure in 1.
not stated. • Median distal ureteral diameter on first US
Time to resolution significantly increased with was 0.8 cm in those that resolved versus
increasing initial HN grade; initial mean ureteral 1.1 cm in those with surgery, p = 0.04
diameter of 9.5 ± 2 mm in the group that resolved (McLellan et al. 2002).
was significantly less than the 15.6 ± 4.5 mm in the A fourth retrospective study described out-
persisting group and the 16.7 ± 3 mm in the surgi- comes in 49 children, 71 % males, with 56 non-
cal group. No case with diameter >15 mm resolved. refluxing megaureters. Of these, 20 were
Surgery was not done for any ureter with T75 diagnosed prenatally while the others presented
<5 min, and for 30 % and 80 % of those with 5–10 at a mean of 10 months (all but 1 with UTI).
and >10 min. No observed patient had renal func- There were 35 (71 %) males. HN was SFU grade
tion loss as defined (Arena et al. 2012). 1 in 10, grade 2 in 39, grade 3 in 5, and grade 4 in
Retrospective analysis was also done in 53 1. Mean follow-up was 47 months (12–78):
patients (66 % males) with prenatal US abnor- • Fifty percent of megaureters resolved during
malities found postnatally to have 67 dilated ure- observation; including all with ureteral diam-
ters due to presumed UVJO. Mean cross-sectional eter <8.5 mm versus 0 with >15 mm.
diameter of the ureter adjacent to the bladder on • Resolution was not predicted by initial HN
the first US was 8 ± 4 mm. All had VCUG grade or renogram washout.
14 Non-refluxing Megaureter 201
• Thirteen (23 %) had surgery, four as initial

therapy and nine for “later deterioration” (not Surgery
defined).
• Six (11 %) had renal function <40 % at last Three studies reported minimally invasive
follow-up, all with impaired function on techniques, including double-J stenting alone,
initial scan (data not shown). balloon dilation with stenting, and
• Thirty-five (71 %) patients had UTI, with endoureterotomy, successfully resolved or
36 % having more than two episodes (sub- decreased HN in from 50 to 70 % of ureters
jects were German, and males likely were not with mean follow-up of 3 years. None reported
circumcised). systematic posttreatment cystography.
• Antibiotic prophylaxis reduced UTI incidence In retrospective studies of ureteral plica-
by 55 % (7 UTIs/199 patient months with vs. tion, folding, or excisional tapering with reim-
19 UTIs/244 patient months without prophy- plantation, all report reduction in HN with
laxis, or 0.4 vs. 0.9 UTIs/year, p < 0.05). risk <10 % for postoperative obstruction.
Prophylaxis seemed most beneficial in the first Occurrence of postoperative UTI, if any,
6 months of life. Neither UTI occurrence nor was not routinely stated, and those reported
prophylaxis use was described in those were not characterized as febrile or not.
detected prenatally versus the 57 % who were
diagnosed after UTI (Gimpel et al. 2010).
Double-J Stenting
Dietl’s Crisis Stenting ≥6 months was reported successful in

nearly 50 % of ureters in one study.
One review found that 16 % of diagnosed A retrospective review was done for 31 non-
megaureters presented with pain. refluxing megaureters that had double-J stent
A review was done of all patients diagnosed (3–4.7 Fr) placed as curative therapy without
with megaureter from 1993 to 2009, from which surgery. Median age at stent placement was
103 with primary megaureter (including patients 37 months (2 months–15 years); indications were
with refluxing megaureter) were identified. Of progressive HN on serial US (not further
these, 17 children (16 %) with 20 megaureters described) in 20, decrease in renal function to
presented with acute pain at median age of <40 % in 7, and pyonephrosis or other symptoms
77 months (40–208). The authors then focused in 4. Degree of HN and distal ureteral diameter
on the 10 who specifically had ipsilateral flank were not reported. Duration of stenting was
pain. Renography in eight showed function ³6 months. Median follow-up subsequently was
>40 % in all cases and variable drainage patterns: 39 months (24–110):
five with T1/2 >20 min, one “indeterminate,” and • Complications during stenting occurred in six
two with “no obstruction.” Cystography demon- (19 %)—two with UTIs and four with gross
strated no VUR. Repair was done in six patients hematuria treated with tranexamic acid.
with resolution or improvement in HN (not • Fifteen (48 %) units resolved HN.
described) who then had follow-up a median of • Fifteen had recurrent HN. Seven were treated
54 months (33–99) without recurrent pain. Four with repeated stenting, of which five were
children (two diagnosed with obstructed and two successful.
with non-obstructed megaureters) were initially • Eleven (35 %) had reimplant.
observed for a median of 9 months (6–28), with Stenting was accomplished in 36/38 attempts
one lost to follow-up, one demonstrating increas- (95 %), with one resulting in perforation and
ing HN (not described) leading to surgery, and reimplantation. Duration of time for recurrent
two with stable or decreased HN and no pain HN to develop after initial stenting was not stated
continuing observation (Anderson et al. 2012). (Carroll et al. 2010).
Balloon Dilation perform the procedure (n = 3), postoperative

obstruction (n = 1), or recurrent UTI (n = 1). Renal
Balloon dilation with 8 weeks stenting for functional data were not reported, nor were distal
distal narrowed ureteral segments <2 cm, or ureteral diameters (Kajbafzadeh et al. 2007).
combined with ureterotomy for segments
2–3 cm, was reported successful in 71 %.
Balloon dilation ± laser endoureterotomy was End Cutaneous Ureterostomy
done in 17 non-refluxing megaureters at mean
age 7 years (3–12). Retrograde pyelography One study of end cutaneous ureterostomy as
defined the length of the distal narrowed segment, initial therapy in non-refluxing megaureter did
with those <2 cm undergoing balloon dilation not report preoperative extent of ureteral dila-
(n = 12, 71 %), those 2–3 cm having dilation plus tion. At reimplantation, 31 % were tapered.
laser ureterotomy at 12 O’clock (n = 5), and those fUTI occurred in 40 %.
>3 cm reimplanted. All endoscopic cases were A retrospective review was done to identify
stented using two 4.7-Fr pigtail stents for 8 weeks. patients who had end cutaneous ureterostomy, 15
There were no perioperative or stent complica- with primary megaureter (refluxing vs. non-
tions. Preoperative extent of HN and distal ure- refluxing not stated; 2 had duplicated systems
teral diameters were not reported; postoperatively, with lower pole VUR and upper pole obstruc-
12 (71 %) had “significant improvement” on US tion). Age at diversion was not stated for this
(not defined). Five had magnetic resonance urog- cohort. During diversion, six (40 %) had fUTI
raphy when HN persisted, and were considered with positive cultures from the ureterostomy
non-obstructed. Posttreatment cystography was (time interval after diversion to UTI or recurrent
not done. Follow-up was a mean of 3 years (2–6) UTI was not stated). None showed increasing
(Christman et al. 2012). HN. At take down of the ureterostomy done in 13
cases, 4 (31 %) were tapered. Size of distal ureter
before end cutaneous ureteroscopy was not stated
Endoureterotomy (Kitchens et al. 2007).
One study found endoureterotomy to be suc-

cessful in 71 % of cases with distal narrowed Plication
segment <1.5 cm.
Fifty two non-refluxing megaureters with a Two studies reported no obstructive complica-
distal narrowed segment <1.5 cm had endouretero- tions, and one noted 6 % VUR after plication
tomy at 6 O’clock extending through the ureteral and reimplantation.
wall to detrusor muscle and double-J stent for Over 50 % of renal units still demonstrated
1 week. Success was defined as resolution of HN HN, in one including those with SFU grades ≥2.
(or “mild pelvis fullness ± minor lower-ureteral One reported return of renal function loss in
dilation”) and stable or improved renal function. 50 % of those affected, while the other stated
Mean follow-up was 39 months (14–62), with 37 that mean function was unchanged by surgery.
(71 %) considered successful and 10 (19 %) Renogram drainage was reported improved or
improved. There was no VUR postoperatively, normal after surgery, but data were not shown.
but also any mention of postoperative cystogra- Eleven of 67 megaureters managed by Liu
phy in the follow-up protocol. A second et al. (1994) described above had surgical correc-
endoureterotomy was done in 6, and was suc- tion for breakthrough UTI in 3 at mean age
cessful in 5 (apparently counted among the 47 9 months, for poor function (10 %) or solitary
resolved or improved cases), while the other had kidney in 2, and for decreased renal function in
reimplantation. Five (10 %) ureters needed open 6 at mean age 6 months, with initial mean function
surgery for inability to place a ureteral stent to 45 % (39–56 %) decreasing to mean 33 %
14 Non-refluxing Megaureter 203
(26–39 %). Repair included excision of the distal Ureteral Folding

aperistaltic segment, Starr plication, and cross-
trigonal reimplantation. Postoperative UTIs were One report stated that ureteral folding with reim-
not described; decreased renal function in eight plantation significantly reduced distal ureteral
was regained in four and stable in four. There was diameter, with only one (4 %) obstruction. Mean
persistent HN in 55 % (not described), but preoperative ureteral diameter was 19 mm.
improved renogram drainage (not described). Technical results of distal segment excision and
The authors stated that there were no postopera- Kalicinski ureteral folding with Leadbetter–
tive complications. Indirect nuclear cystography Politano reimplantation were reported in 26 non-
was done postoperatively to evaluate for VUR, refluxing megaureters. All were stented with a 6- to
but results were not stated. 8-Fr catheter for 1 week. One (4 %) developed
Retrospective analysis was done in 17 non- postoperative stenosis leading to reoperation.
refluxing megaureters operated by distal segment Preoperative distal ureteral diameter was a
excision and cross-trigonal reimplantation with or significantly greater mean 19 mm versus 5 mm
without Starr plication. Indications were impaired postoperatively (Perdzynski and Kalicinski 1996).
renogram drainage (not defined) in 11, fUTI in 4,
failure to thrive in 1, and increasing HN in 1 (not
described). The postoperative assessments Excisional Tapering
described below were done at 3 months:
• Preoperative HN was SFU grade 1 in 2, grade A study of excisional tapering did not report
2 in 7, grade 3 in 7, and grade 4 in 1. After preoperative ureteral diameter. Resolved or
surgery, HN was SFU grade 0–1 in 6, grade 2 reduced HN without VUR was achieved in
in 9, and grade 3 in 2; there was a reduction in 87 %.
13, and 4 were unchanged. A retrospective study considered 31 patients
• Preoperative median ureteral diameter by US undergoing excisional tapering of the distally
was 11 mm (6–24); postoperatively, the distal dilated ureter followed by intra- (n = 15) or extra-
ureter was not detected in 14 and was “greatly vesical reimplantation (n = 16) based on surgeon
reduced” in 3. preference. Preoperative ureteral diameter was
• Preoperative renal function was normal not stated. “Indwelling stents” were used for
(median 50 %, range 43–54 %) in 15 kidneys 4–6 weeks. Follow-up was mean 3.5 years
and 40 % in two kidneys; postoperative func- (8 months–12 years). Surgical success was defined
tion was not described except to state that as resolved or improved HN and no VUR (time
there was no significant change in mean renal for these evaluations was not stated), achieved in
function. 13 (87 %) and 15 (94 %), p = 0.6. Changes in HN
• Preoperative renogram drainage was were not described, nor were problems classified
“impaired” in 11 (65 %), described as T1/2 as “failure” in three patients (Defoor et al. 2004).
>15 min in 7 or “retention of >30 % isotope”
30 min after furosamide in 8 (disparity
between 11 impaired kidneys vs. these 15 References
with delayed drainage was not explained);
postoperative renograms were all stated to Aksnes G, Imaji R, Dewan PA. Primary megaureter:
results of surgical treatment. ANZ J Surg.
be normal.
2002;72(12):877–80.
• Postoperative UTIs occurred in two patients; Anderson CB, Tanaka ST, Pope JC, Adams MC, Brock
the infant with poor feeding improved. 3rd JW, Thomas JC. Acute pain crisis as a presentation
• No ureter developed obstruction after surgery, of primary megaureter in children. J Pediatr Urol.
2012;8(3):254–7.
and one (6 %) had VUR (assessment done by
Arena S, Magno C, Montalto AS, Russo T, Mami C,
either direct or indirect cystography; numbers Baldari S, et al. Long-term follow-up of neonatally
of each not stated) (Aksnes et al. 2002). diagnosed primary megaureter: rate and predictors of
spontaneous resolution. Scand J Urol Nephrol. Kajbafzadeh AM, Payabvash S, Salmasi AH, Arshadi H,
2012;46(3):201–7. Hashemi SM, Arabian S, et al. Endoureterotomy for
Carroll D, Chandran H, Joshi A, McCarthy LS, Parashar treatment of primary obstructive megaureter in chil-
K. Endoscopic placement of double-J ureteric stents in dren. J Endourol. 2007;21(7):743–9.
children as a treatment for primary obstructive megau- Kitchens DM, DeFoor W, Minevich E, Reddy P, Polsky E,
reter. Urol Ann. 2010;2(3):114–8. McGregor A, et al. End cutaneous ureterostomy for
Christman MS, Kasturi S, Lambert SM, Kovell RC, the management of severe hydronephrosis. J Urol.
Casale P. Endoscopic management and the role of 2007;177(4):1501–4.
double stenting for primary obstructive megaureters. Liu HY, Dhillon HK, Yeung CK, Diamond DA, Duffy PG,
J Urol. 2012;187(3):1018–22. Ransley PG. Clinical outcome and management of
DeFoor W, Minevich E, Reddy P, Polsky E, McGregor A, prenatally diagnosed primary megaureters. J Urol.
Wacksman J, et al. Results of tapered ureteral reim- 1994;152(2 Pt 2):614–7.
plantation for primary megaureter: extravesical versus McLellan DL, Retik AB, Bauer SB, Diamond DA, Atala
intravesical approach. J Urol. 2004;172(4 Pt 2):1640– A, Mandell J, et al. Rate and predictors of spontaneous
3. discussion 3. resolution of prenatally diagnosed primary
Gimpel C, Masioniene L, Djakovic N, Schenk JP, nonrefluxing megaureter. J Urol. 2002;168(5):2177–
Haberkorn U, Tonshoff B, et al. Complications and 80. discussion 80.
long-term outcome of primary obstructive megau- Perdzynski W, Kalicinski ZH. Long-term results after
reter in childhood. Pediatr Nephrol. 2010;25(9): megaureter folding in children. J Pediatr Surg.
1679–86. 1996;31(9):1211–7.
Posterior Urethral Valves
and Ureterovesical Junction 15
Obstruction
Warren T. Snodgrass
Primary aims in the diagnosis and manage- with hyperechogenicity, volume loss, and/or
ment of posterior urethral valves (PUV): loss of corticomedullary differentiation.
1. To prevent acquired renal damage. There are no reports of longitudinal objective
2. To improve bladder function. analysis of bladder function after valve ablation:
A secondary aim is to facilitate achievement • One study compared UD in infants after
of urinary continence. ablation to control males with UTI, report-
Summary of evidence for these goals: ing no difference in median maximum void-
Case series report end-stage renal disease ing pressures.
(ESRD) in from 3 to 42 % of patients during • Three retrospective studies found increased
mean follow-up ranging from 4 to 12 years: bladder capacity and decreased end filling
• No prenatal finding (oligohydramnios, ana- pressures in bladders after valve ablation
mnios, renal hyperechogenicity, loss of cor- versus urinary diversion, but did not
ticomedullary differentiation) or fetal urine account for selection bias.
test accurately predicts postnatal renal • Continence is reported by age 5 in approxi-
function. mately 20–60 %.
• Prenatal bladder drainage improves sur- • There are few data regarding indications
vival but not renal function. and outcomes for medical bladder therapy
• Neither prenatal versus postnatal diagnosis in valve patients using anticholinergics,
nor age at postnatal diagnosis predicts like- alpha-blockers, and/or CIC.
lihood for ESRD. One matched cohort study using validated
• There are conflicting results from retrospec- questionnaires reported adult men mean age
tive analyses regarding potential risk for 37 years with prior valves had 2× greater
CRF/ESRD by vesicoureteral reflux (VUR), LUTS than controls.
recurrent febrile UTI (fUTI), bladder dys-
function, and/or pop-off mechanisms.
Factors predicting poor renal functional Prenatal Diagnosis
outcomes are nadir creatinine >1 mg/dL and
abnormal initial postnatal renal ultrasound Despite advances in ultrasound technology, one
retrospective study reported high sensitivity to
W.T. Snodgrass, M.D. (*) diagnose PUV but low specificity to distinguish
Department of Pediatric Urology, University of Texas valves from bilateral VUR and PBS in male
fetuses with bilateral HN. The best indicators
Dallas, TX 75235, USA were increased bladder thickness and dilation,
e-mail: warren.snodgrass@childrens.com whereas the keyhole sign was not diagnostic.
206 W.T. Snodgrass
Table 15.1 Prevalence of prenatal ultrasound signs in those fetuses that were postnatally diagnosed with posterior
urethral valves (PUV Group, n = 31) and those that were diagnosed with other pathologies (non-PUV group, n = 23)a
Sign PUV group (n [%]) Non-PUV group (n [%]) Pb
Keyhole sign 16 (51.6) 8 (34.8) 0.27
Bladder dilatation 30 (96.8) 11 (47.8) <0.0001c
Thickened bladder wall 29 (93.5) 9 (39.1) <0.0001c
Oligohydramnios 19 (61.3) 7 (30.4) 0.024c
Dilated and thick-walled bladder 28 (90.3) 9 (39.1) 0.0001c
Dilated and thick-walled bladder 14 (45.2) 6 (26.1) 0.18
with the keyhole sign
a
Reproduced from Bernardes LS, Aksnes G, Saada J, Masse V, Elie C, Dumez Y, et al. Keyhole sign: how specific is it
for the diagnosis of posterior urethral valves? Ultrasound Obstet Gynecol. 2009;34(4):419–23, with permission from
John Wiley and Sons
b
For difference between PUV-diagnosed and non-PUV diagnosed groups
c
Statistically significant
A second retrospective series found prena- Prenatal Assessment of Renal

tal ultrasound to have low sensitivity to detect Function
PUV antenatally.
A retrospective study reviewed prenatal There currently is no prenatal test able to
findings in 54 males with bilateral HN between accurately predict postnatal renal function.
2000 and 2006 to determine ability to diagnose A systematic literature review found that
PUV versus bilateral VUR and PBS. Median no fetal urine test is sufficiently accurate in
gestational age at first diagnosis of HN was predicting poor postnatal renal function to be
similar in those with PUV versus other etiolo- clinically useful.
gies (25 weeks [19–36] vs. 23 weeks [12–33]). Three retrospective studies found neither
Forty eight (89 %) had more than one prenatal oligohydramnios/anamnios nor abnormal
ultrasound, with a mean of five (1–7). PUV fetal renal appearance (hyperechogenicity,
was suspected prenatally in 42, confirmed post- loss of corticomedullary differentiation) cor-
natally in 29 (69 %); PUV was not suspected related with postnatal renal function.
prenatally in 12, but found postnatally in 2
(17 %). Overall sensitivity and specificity of
prenatal evaluation were 94 % (95 % CI Fetal Urine Analysis
87–99 %) and 43 % (95 % CI 30–57 %). The
keyhole sign was found in 52 % of those with A systematic review of publications concerning
PUV versus 35 % without PUV, p = 0.27. accuracy of prenatal urine chemistries to predict
Combinations of ultrasonographic findings are poor postnatal renal function in fetuses with con-
summarized in Table 15.1. genital bladder outlet obstruction included 23
These findings indicate prenatal diagnosis articles involving 572 women. The two most
continues to have poor specificity (Bernardes accurate tests were calcium >95th percentile for
et al. 2009). gestation (LR + 6.65 [0.23–190.96]; LR − 0.19
Another retrospective review evaluated 34 [0.05–0.74]) and sodium >95th percentile for
boys with PUV diagnosed between 1992 and gestation (LR + 4.46 [1.71–11.6]; LR − 0.39
2004, reporting16 (47 %) had normal prenatal [0.17–0.88]). Beta (2)-microglobulin was less
ultrasound. PUV was diagnosed in the other 18 at accurate (LR + 2.92 [1.28–6.69]; LR − 0.53 [0.24–
<24 weeks in 12 and >24 weeks in 6, whereas 6 1.17]). Since fetal urine anlaytes vary through
of 16 not detected had an ultrasound at >24 weeks gestation, becoming more hypotonic, results
(Harvie et al. 2009). using the 95th percentile were more accurate than
15 Posterior Urethral Valves and Ureterovesical Junction Obstruction 207
absolute thresholds. Nevertheless, the authors costomy with subsequent valve ablation was done
conclude that there currently is no accurate uri- postnatally shortly after birth or at diagnosis.
nary analyte to predict poor postnatal renal func- There were 34 patients, 18 (53 %) with prenatal
tion (Morris et al. 2007). diagnosis and 16 with a normal antenatal evalua-
tion. Of those with prenatal detection, no ultra-
sound parameter (oligohydramnios, HN, renal
Fetal Ultrasound echogenicity) predicted renal functional out-
comes (Harvie et al. 2009).
A retrospective analysis was performed in 31
fetuses with proven PUV. Pregnancy was termi-
nated at a median gestational age of 30 weeks Prenatal Intervention Versus
(21–36) in six for oligohydramnios plus adverse Observation
biochemical markers. Shunting was not attempted.
Of the other 25 delivered, 4 previously had uri- One systematic review of published inter-
nary ascites (three undergoing prenatal shunt and ventions found prenatal bladder drainage
the fourth delivered at 33 weeks). All patients improved postnatal survival but not renal
underwent valve resection. Outcomes for these function. Results from a RCT of prenatal
25 with median follow-up of 40 months (12–79) shunting are pending.
included 1 death at day 16 from renal failure, and To date no published RCT compares prenatal
4 (17 %) others with renal impairment (abnormal shunting versus observation in fetuses diagnosed
serum creatinine) at last assessment. Prenatal with bladder outlet obstruction. The multicenter
oligohydramnios/anamnios and timing of its PLUTO (Percutaneous Shunting in Lower Tract
onset did not predict postnatal renal function. Obstruction) trial was initiated with the primary
Similarly, prenatal renal ultrasonographic features objective to determine if prenatal shunting
(hyperechogenicity, lack of corticomedullary improves postnatal mortality and renal function
differentiation) did not predict postnatal serum (Morris and Kilby 2009). Recruitment has closed,
creatinine. Creatinine was normal in three of the but results are pending.
four with prenatal ascites. It was also normal in Systematic review of published antenatal
10 of 13 with oligohydramnios, including 4 with intervention for bladder outlet obstruction
anamnios. Ten of 11 with bilateral hyperechoge- identified 20 articles with 369 fetuses, of which a
nicity had a normal creatinine, as did 7 of 8 with total of 261 had antenatal intervention. Most were
bilateral hyperechogenicity, loss of corticomed- percutaneous vesico-amniotic shunts, but 9 were
ullary differentiation, and oligohydramnios open fetal surgeries and 26 were fetal cystosco-
(Bernardes et al. 2011). pies with 14 valve ablations. Prenatal bladder
A retrospective review of 30 patients with PUV drainage improved perinatal survival (likely due
diagnosed in utero with postnatal valve ablation to fewer deaths from pulmonary complications)
and follow-up a mean of 4 years (1–8) reported 6 versus no treatment (OR 3.86 [95 % CI 2.00–
(20 %) had CRF (serum creatinine >2 SD for age)/ 7.45]), primarily in a subgroup with predicted
ESRD. No prenatal factor predicted poor renal poor prognosis on the basis of fetal urinalysis
outcomes: diagnosis at gestational age <24 weeks (OR 12.85 [95 % CI 1.25–153.03]). However,
(OR 0.15 [95 % CI 0.88–2.26]), oligohydramnios improvement in postnatal renal function was not
(OR 0.81 [95 % CI 0.11–5.63]), or hyperechogenic found (OR 0.50 [95 % CI 0.13–1.90])
renal cortex (OR 0.25 [95 % CI 0.62–10.14]) Complications included shunt dislodgement or
(El-Ghoneimi et al. 1999). occlusion in 34 % with vesico-amniotic shunting,
Another retrospective review included all live- two premature rupture of membranes, four cases
born males with PUV and at least one docu- of chorioamnionitis, three hernias, and one blad-
mented prenatal sonogram. There was no mention der rupture from shunting, and three patient
of prenatal intervention. Valve ablation or vesi- deaths (Morris et al. 2010).
208 W.T. Snodgrass
nosis of CRF varies (<90 mL/min/1.73 m2 vs.

Prognosis Based on Prenatal Versus <60–64 mL/min/m2), and definitions of factors
Postnatal Diagnosis were not always stated.
Factors not predicting poor renal functional
The likelihood that boys with PUV will develop outcomes include age at diagnosis and VURD.
CRF/ESRD does not vary by prenatal versus Factors correlating with poor renal func-
postnatal diagnosis. tional outcomes are nadir creatinine >1 mg/dL
Analysis was performed in 46 boys diagnosed and abnormal initial renal ultrasound (hyper-
with PUV between 1983 and 1997, with mean echogenicity, loss of volume, loss of corticome-
follow-up 12.5 years (5.5–20) using a prospective dullary differentiation).
protocol. Antenatal diagnosis was made in 23/40 Abnormal bladder function is also associ-
(57.5 %) at median gestational age 28 weeks ated with poor renal function, but usefulness
(16–38). In the other 23, the diagnosis was made of this observation is limited by lack of a con-
postnatally at median 31 days of age (1 day–1 year) sistent definition for diagnosis.
for uremia/acidosis, UTI, respiratory symptoms, There are mixed findings concerning the
and/or weak urinary stream. Treatment was nearly relationships between urinomas, VUR, and UTI
identical in both cohorts, comprising valve ablation and CRF/ESRD. Although results of analyses of
in 23 (50 %) or vesicostomy or supravesical diver- VUR and CRF/ESRD varied, no study reviewed
sion in 23 (50 %). CRF (GFR £ 59 mL/m/1.73 m2) found VUR grade to predict renal outcomes.
developed in 6 (13 %) and ESRD in 8 (17 %), with
no difference in antenatal versus postnatal detection
(Ylinen et al. 2004). Age at Diagnosis
A retrospective review of 34 boys with PUV
compared prenatal versus postnatal diagnosis for A retrospective review of 227 males with PUV
risk of CRF (serum creatinine >2 SD for age)/ undergoing primary valve ablation analyzed factors
ESRD. Sixteen of 34 had normal prenatal ultra- leading to ESRD. Mean age at diagnosis was
sound with postnatal diagnosis made at a median 30 months (10 days–16 years), with only 2 diag-
3.5 months (2 day–5 year). Follow-up after valve nosed prenatally and 107 (47 %) during infancy.
ablation was a mean of 8 years. There was no dif- Mean follow-up was 7 years (0.5–16), during
ference in poor outcomes based on antenatal ver- which time ESRD occurred in 27 (12 %), and
sus postnatal diagnosis (5/13 vs. 2/14, p = 0.4) was not influenced by presentation before versus
(Harvie et al. 2009). after infancy (Ansari et al. 2010).
Another retrospective review compared 30 A similar retrospective analysis of 120 males
boys with prenatally detected PUV and 10 with undergoing primary valve ablation between 1987
postnatal diagnosis at mean of 21 days (1–60). At and 2004 considered factors potentially associ-
mean follow-up of 4 years, 2/30 (7 %) and 1/10 ated with ESRD. Age at diagnosis was a mean of
(10 %) had ESRD. If another five with prenatal 2 years (1 day–15 years), presenting with urinary
diagnosis leading to termination were included, retention, UTI, stranguria/dysuria, and inconti-
poor outcomes remained similar (El-Ghoneimi nence. With follow-up a median of 3.6 years,
et al. 1999). ESRD occurred in 18 (15 %). Age at presentation
did not correlate with renal function (although
statistical means to evaluate age, i.e., <1–2 years
Prognosis Based on Postnatal vs. >2 years mentioned in discussion, or as a con-
Parameters tinuous variable, were not described) (Sarhan
et al. 2011).
Several reports analyzed factors potentially Another retrospective evaluation also found
correlating with CRF/ESRD. All are retro- age at presentation not predictive of renal func-
spective, many involve few patients, the diag- tional outcomes. This study included 52 males
with PUV divided into two groups, those diagnosed renal function versus 19 with GFR (using
and treated before (n = 39, mean age 30 days at Schwartz formula) <90 mL/min/1.73 m2 through-
surgery) versus after 1 year of age (n = 13, mean out mean follow-up of 5.2 years. Serum creati-
age 3.8 years at surgery). Those with late diagno- nine levels at age 1 year were available in 19/23
sis presented with UTI, voiding dysfunction, or and 14/19 patients in the two groups, with median
failure to thrive. Follow-up was a mean of 7 years calculated GFR 112 mL/min/1.73 m2 (IQR 96.0–
after valve ablation, but specific times for the two 134.0) in those with preserved normal renal func-
groups were not stated. ESRD did not vary tion versus 24.5 mL/min/1.73 m2 (IQR 14.0–62.3)
significantly between the two groups (8 % vs. in those with renal insufficiency, p < 0.001 (Pohl
0 %, p = 0.55) (Kibar et al. 2011). et al. 2012).
Nadir Serum Creatinine Renal Ultrasound Parameters
Retrospective analysis was performed in 227 Retrospective analysis reported by Pohl et al.
males with PUV undergoing valve ablation (2012) mentioned above evaluated renal ultra-
between 1992 and 2008, at mean age 30 months sound parameters from the first postnatal study in
(10 days–16 years) and mean follow-up 7 years 42 PUV patients diagnosed at median age
(0.5–16). ESRD developed in 27 (12 %). <3 months and compared them to functional out-
Multivariable logistic regression analysis found comes of normal calculated GFR versus CRF
nadir serum creatinine >1 mg/dL correlated with (<90 mL/min/1.73 m2). Total renal volume less
renal failure (OR 23.79 [95 % CI 8.20–69.05]). than the third percentile was significantly more
Twenty two of 27 patients with ESRD had nadir common in those with CRF (OR 17.42 [95 % CI
creatinine >1 mg/dL, although a creatinine 3.28–92.61]), with 79 % of those with CRF hav-
>1 mg/dL was also found in 18/200 without renal ing hypoplastic kidneys. Similarly, hyperechoge-
failure (Ansari et al. 2010). nicity greater than the liver or spleen (OR 21.33
A retrospective analysis of renal functional [95 % CI 2.37–192.03]) and loss of corticomed-
outcomes evaluated presenting and nadir serum ullary differentiation (OR 28 [95 % CI 3.11–
creatinine in a series of 120 males with primary 252.48]) correlated with CRF.
valve ablation. Mean age at treatment was 2 years The retrospective review by Sarhan et al.
(1 day–15 years), with follow-up a mean (2011) referenced above including 120 males
4.4 years. CRF was defined as GFR (determined with PUV diagnosed at mean age 2 years (1 day–
by Schwartz formula) £59 mL/min/1.73 m2. 15 years) with follow-up a median 3.6 years also
Patients with CRF (n = 44) were compared to considered first renal ultrasound appearance ver-
those with normal or less severe renal insufficiency sus calculated GFR. However, in this study, CRF
(n = 76). Mean initial serum creatinine (1.7 mg/dL was defined as £59 mL/min/1.73 m2. Univariable
vs. 0.8 mg/dL), mean nadir serum creatinine analysis found significant differences in hyper-
(1 mg/dL vs. 0.55 mg/dL) and mean initial calcu- echogenicity occurring in 12/76 (16 %) with nor-
lated GFR (34 mL/min vs. 117 mL/min) were all mal GFR versus 16/44 (36 %) with CRF,
significantly different between the two groups. p = 0.014.
Nevertheless, 24 % of patients with a nadir crea-
tinine <1 mg/dL still developed CRF, while 16 %
with nadir creatinine >1 mg/dL did not (Sarhan VUR
et al. 2010).
Retrospective analysis was done in 42 males, VUR was not predictive for CRF (<90 mL/
median age 0.97 months (interquartile range min/1.73 m2) in the retrospective analysis
0.03–58.49) with PUV treated between 1983 and reported by Pohl et al. (2012) mentioned earlier.
2009 that segregated patients into 23 with normal VUR was initially diagnosed in 21/40 (52.5 %)
210 W.T. Snodgrass
(no information was available in 2), which was VUR, there was no difference in renal outcomes
unilateral in 12 and bilateral in 9 patients for a for grades 1–2 versus 3–5.
total of 30 renal units. VUR was grades 1–2 in 9
and 3–5 in 21 renal units. No difference in VUR
was noted in patients with normal versus reduced UTI
renal function (OR 2.89 [95 % CI 0.79–10.57]).
Similarly, the retrospective analysis by Sarhan Recurrent fUTI was another risk factor for ESRD
et al. (2011) discussed above that defined CRF as considered by DeFoor et al. (2008), occurring in
calculated GFR £59 mL/min/1.73 m2 found that 58/119 (49 %) patients despite antibiotic prophy-
VUR was not a predictive factor on univariable laxis for VUR, bladder dysfunction requiring
analysis that compared no, unilateral, and bilateral CIC, and/or “severe” HN. These infections were
VUR but did not report grade differences, if any. equally likely in patients with preserved renal
Another retrospective review identified 142 function versus those with ESRD.
patients with PUV treated between 1975 and The analysis by Ansari et al. (2010) discussed
2005, of which 119 had sufficient data for analy- above also reported that recurrent fUTI (not fur-
sis at mean follow-up of 7 years (3–24). Fifteen ther defined) did not correlate with progression to
(13 %) progressed to ESRD. Although VUR ESRD in 227 males presenting at mean age of
grades III–V occurred in 93 % with ESRD versus 30 months. Seventy seven (34 %) had fUTI dur-
48 % in patients without ESRD, multivariable ing mean follow-up of 7 years, with no difference
logistic regression analysis found differences in those with versus without ESRD.
were not significant (OR 2.0 [95 % CI 0.2–24]) One study that specifically defined fUTI simi-
(DeFoor et al. 2008). larly found it was not a significant risk factor for
In contrast, one retrospective analysis did find renal function > than or <90 mL/min/1.73 m2 cal-
bilateral VUR a risk factor for ESRD in multi- culated GFR, occurring in a total of 33/42 (79 %)
variable logistic regression. There were 116 patients (OR 3.72 [95 % CI 0.67–20.63]). However,
males with PUV presenting at mean age of >3 fUTIs (occurring in 50 %) did correlate with
13 months (0–120) who underwent primary valve reduced renal function (OR 6.40 [95 % CI 1.65–
ablation, followed by diversion in 32 (28 %) by 24.77]) (Pohl et al. 2012).
Sober ureterostomies (31) or vesicostomy (1) for However, Ylinen et al. (2004) reported that
“severe VUR and HN” (22) or poor renal func- UTIs occurred in 30/46 (65 %) boys with PUV,
tion (9). Subsequent follow-up was a mean of with a mean of 1.9 episodes of fUTI in 22 of
10 years (18 months–22 years), during which them, and that these patients were more likely to
time 49 (42 %) developed ESRD. VUR was have CRF (<64 mL/min/1.73 m2)/ESRD than
found in a total of 52/116 (45 %) patients, includ- those without UTI.
ing 18/49 (37 %) with ESRD, unilateral in 10 and
bilateral in 8. Bilateral VUR, found in 16 % of
those with ESRD, was reported a significant risk Bladder Dysfunction “Valve Bladder”
factor in multivariable logistic regression, but the
OR was not stated. However, neither high-grade Ansari et al. (2010) defined bladder dysfunction
VUR (3–5) nor unilateral VUR was found to be a for their retrospective multivariable analysis as
risk factor (Ghanem et al. 2004). the presence of one or more factors: end filling
The retrospective analysis by Ylinen et al. pressure >40 cm H2O, post-void residual urine
(2004) of 46 boys reported VUR initially in 32 >30 % of the maximum cystometric bladder
(70 %), unilateral in 17 and bilateral in 15 (grades capacity, myogenic failure, and/or need for CIC.
not stated). Both unilateral and bilateral VUR By these criteria, 21/27 (78 %) with ESRD had
increased risk for CRF (<60 mL/min/1.73 m2)/ bladder dysfunction versus 38/200 (19 %) patients
ESRD versus no VUR. Among patients with without ESRD (OR 5.67 [95 % CI 1.90–16.93]).
A retrospective analysis included urodynamic a nonfunctioning kidney, which was found in

findings in 116 boys with PUV presenting at nine patients, with three developing ESRD.
mean age 13 months (0–120) and then undergo- Urinary extravasation was noted in four patients,
ing primary valve ablation, with 31 also having one progressing subsequently to ESRD. Neither
Sober ureterostomies and 1 a vesicostomy. “pop-off” mechanism was found protective of
A total of 52 (45 %) developed ESRD. Age and renal function.
number of UDs (assuming some had more than “Pop-off” mechanisms, including VURD,
one study) were not stated. Studies were done large bladder diverticulum, urinoma, and/or
transurethrally with a 7-Fr catheter at a filling ascites, were considered a single factor in the ret-
rate of 5–10 cc/min. Expected bladder capacity rospective analysis of 120 PUV cases by Sarhan
was determined by formula (age + 2) × 30 cc; “loss” et al. (2011). Presence of these did not predict
of bladder compliance was not defined, although future renal function.
used as a factor in logistic regression. Eighty per- Another retrospective study involved 73 con-
cent of all patients had abnormal bladder parame- secutive patients with PUV presenting at mean
ters. Univariable analysis found bladder compliance age of 1.6 years (0–11). Of these 35 had VUR,
and/or detrusor overactivity to be significant with VURD (unilateral VUR with renal dyspla-
predictive factors for ESRD, specific results of sia) in 21. Follow-up was a mean of 5.6 years
multivariable analysis for these factors were not (1–17). Logistic regression analysis was not
stated (Ghanem et al. 2004). done, but chi square analysis found no differ-
Bladder dysfunction leading to CIC was found ences in patients with versus without VUR, or in
on retrospective chart review in 37/119 (31 %) those with VURD versus others having VUR
patients with PUV, generally due to low capacity without VURD (Hassan et al. 2003).
and filling pressures >40 cm H2O in younger A retrospective review divided 89 consecutive
patients or myogenic failure with retention in patients with PUV diagnosed as neonates and
older patients (“low capacity, younger, older, treated between 1989 and 2009 into the 9 (10 %)
retention” were not defined). These patients were with urinomas versus those without to determine
found on multivariable logistic regression to have impact, if any, on renal function. These urinomas
increased risk for ESRD (OR 8.9 [95 % CI 1.1– were bilateral in one and unilateral in the remain-
73]) (DeFoor et al. 2008). der, ranging in size from 4 × 3 × 4 to 9 × 9 cm.
In contrast, Sarhan et al. (2011) reported that Median initial nadir creatinine after valve abla-
bladder dysfunction occurring in 35 % of toilet- tion or vesicostomy was significantly lower in
trained boys did not correlate with ESRD. those with urinomas (0.35 mg/dL [0.2–0.5] vs.
However, definition of “bladder dysfunction,” 0.5 mg/dL [0.2–6.5], p < 0.01). Ipsilateral renal
means to diagnose it, and time to diagnosis after function was not reported. Initial management of
valve ablation that was done at mean age 2 years, the urinomas was conservative, although four
were not stated. underwent percutaneous drainage due to respira-
Ylinen et al. (2004) simply defined bladder tory or feeding impairment; neither the time of
function as total urinary continence (day and drainage nor the time for resolution of those
night) and compared achieving this threshold at observed was stated (Wells et al. 2010).
age <5 years versus >5 years. By this definition,
bladder function did not correlate with CRF/
ESRD (OR 0.45 [95 % CI 0.13–1.65]). Diagnosis by VCUG
Our review found no report on the sensitivity

VURD/Urinary Extravasation and specificity of VCUG in diagnosis of PUV.
Two studies agreed that the catheter in the
The analysis by Ylinen (2004) of 46 PUV boys urethra during voiding imaging does not
included VURD, defined as unilateral VUR into impair diagnosis of PUV.
212 W.T. Snodgrass
Three radiologists reviewed preoperative but not defined by others. Two studies using
VCUGs in 48 patients with cystoscopically objective urethral ratios to diagnose persistent
confirmed PUV to determine if the urethral cath- posterior urethral dilation reported residual
eter used in the test impacted visualization of the valves in those with ratios above the medians
valve. Studies were done leaving the catheter in of controls (1.73, 2.6) during follow-up VCUG
the urethra in 28, without in 17, and both in 3. 6–12 weeks later. Re-ablation resulted in nor-
Valves were diagnosed in 25/28 (89 %) with the malization of ratios.
catheter versus 15/17 (88 %) without (Ditchfield Urethral strictures occurring in up to 50 % of
et al. 1995). newborns and infants when 10-Fr or larger
In another study, 123 males had VCUG using resectoscopes were used prompted vesicostomy
a 6- or 8-Fr catheter at median age 2.6 months or ablation using either hooked electrodes with-
during investigations of prenatal HN or UTI. For out direct visualization or bugbee electrodes
inclusion, four voiding phase images were introduced through smaller cystoscopes. Today
required, two with and two without the catheter; 9-Fr resectoscopes potentially allow more pri-
only 80 studies met this criteria. Of these, three mary ablations under direct vision in newborns
showed PUV, seen in views with and without the with less concern for urethral trauma. Our
catheter (Chaumoitre et al. 2004). review found only one contemporary study
reporting inability to use a 9-Fr resectoscope in
newborns, occurring in 47 %, and none concern-
Initial Management ing stricture presence or absence after ablation.
No RCT compares outcomes for treatment in

newborns by primary valve ablation versus diver- Ablation Technique
sion by vesicostomy or supravesical diversion.
Our review found only one study comparing Thirteen neonates at mean age 9 days underwent
primary valve ablation versus vesicostomy for transurethral YAG laser valve ablation at maxi-
newborn management of PUV, with selection mum power of 25 W via an 8-Fr cystoscope.
determined by whether or not the urethra admit- Vaporization began centrally and moved peripher-
ted a 9-Fr resectoscope. Preoperative mean serum ally, leaving a small rim circumferentially. VCUG
creatinine and mean serum creatinine at 1 year was repeated at 4 weeks, with subsequent follow-
were reported as similar in the two groups. up to a mean of 2.3 years (6 month–5 years). No
Another review of patients <1 year at sur- strictures occurred, and no delayed repeat abla-
gery found no difference in renal insufficiency tions were reported. Four infants who had ureteral
or ESRD based on initial valve ablation versus reimplantation, apparently within 6 months of
supravesical diversion, although reasons for ablation, also had cystoscopy stated to demonstrate
different interventions were not stated. no residual valves (Biewald and Schier 1992).
Within the limitations of retrospective chart
reviews and the potential for selection bias in
deciding valve ablation versus diversion, our Adequacy of Valve Ablation
review found no report indicating diversion
superior to ablation. The retrospective report from Sarhan et al. (2011)
Valve ablation can be done by a variety of with 120 PUV patients treated at mean age 2 years
methods, including fulguration, laser, or cold stated that all underwent primary valve ablation,
knife incision. Our review found few descrip- done in 65 (54 %) with a cold knife versus fulgu-
tions of technique and outcomes. ration using a hot loop or bugbee hook electrode
“Residual valves” have been reported by (43 [36 %] and 12 [10 %]). Repeat VCUG was
several authors, described by one as leaflets obtained 1–3 months later, with “adequate valve
that could be engaged with a cold knife hook ablation” in 85 %. The remaining 18 (15 %)
underwent a second ablation. Specific findings to ondary ablation and resultant decrease in urethral
determine adequate ablation on VCUG were not ratio to 3.1 (2.9–6.4) (Bani Hani et al. 2006).
defined, nor were findings at residual fulguration VCUG and repeat cystoscopy was done in 30
described or correlated with initial surgical patients 8–12 weeks after valve ablation at a
methods. median age of 13 months (1 day–11 years).
Retrospective analysis was done in 31 consecu- Ablation was performed using either a 7- or
tive patients with post-ablation cystoscopy during 10-Fr cystoscope with bugbee electrode, but oth-
a 2-year period from 2006 to 2008. Ablation was erwise technical details (location and number of
done using an 11-FR cold knife (n = 21) or 3-Fr fulgurations) were not described. There were 30
point electrocautery (n = 9) and was unknown in controls for urethral ratio undergoing VCUG for
one. Further details (location and number of inci- “suspected urinary tract pathology.” Mean ure-
sions) were not stated. Follow-up cystoscopy and thral ratio in controls was 1.73 ± 0.57, versus
VCUG were done in all at median 5 months pre-ablation mean in patients of 4.94 ± 2.97,
(3–12). VCUG reported resolution in 10, improve- p < 0.001 (21/30 had ratios >2.3). Mean post-
ment in 8, and persistence of posterior urethral ablation ratio was 2.13 ± 1.19, which was not dif-
dilation in 12 (39 %). Cystoscopy found valves ferent from controls. However, two patients had
sufficient for further ablation in 16 (52 %). Cold persistently abnormal post-ablation ratios (6.5)
knife ablation was done in all but one, and these and both had residual valves not seen in others
incisions were described: at 5, 7, 12 O’clock (Gupta et al. 2010).
(n = 5); at 5, 7 O’clock (n = 8); at 7 or 12 O’clock
only in one each. Potential clinical relevance for
these valve remnants was assumed by ability to Urethral Stricture After Ablation
engage them with the hook of the cold knife. Based
on secondary ablation, the positive/negative pre- A review of 28 patients with transurethral valve
dictive value of visualized valves plus persistent ablation noted that strictures, diagnosed by
posterior urethral dilation on VCUG was VCUG, all occurred in newborns and infants.
83 %/75 %, but either valve or posterior urethral Ablation was done using a loop electrode via a
dilation alone was only 40 %/50 %. (Smeulders 10-Fr (n = 2) or 12-Fr (n = 12) resectoscope, and
et al. 2011). strictures developed in 7/14 (50 %), located in the
In another retrospective analysis, 20 patients membranous (n = 2), bulbar (n = 4) or anterior
underwent valve ablation at median age (n = 1) urethra (Myers and Walker 1981).
1.5 months (1–12) and then had urethral ratios Urethral stricture at the site of prior ablation
(transverse midpoint diameter of posterior ure- occurred in 3/82 (4 %) patients in one retrospec-
thra/transverse diameter at widest point of bulbar tive series in which all newborns and infants
urethra during voiding without catheter) deter- underwent vesicostomy with subsequent closure
mined by repeat VCUG 6–8 weeks later. Ablation and valve ablation at age 9–12 months. Fulguration
was performed using an 11-Fr resectoscope with was done using a 9-Fr resectoscope with a loop
Collins knife and cutting diathermy current or a electrode applied at 5, 7, and 12 O’clock. VCUG
9-Fr cystoscope with 2.4-Fr electrode, with loca- was done 6 months after ablation. Of the three
tion and number of incisions not stated. Controls strictures, one occurred following urethral trauma
were similarly aged boys undergoing VCUG “for with a false passage and “profuse bleeding” done
suspected urinary tract pathology.” Median ure- elsewhere, with re-fulguration subsequently done
thral ratio in 13 patients with available studies for residual valves. The other two had prelimi-
before valve ablation was 8.6 (4–14.7) versus nary diversion. Means of diagnosis, time after
post-ablation median in 20 patients of 3.4 (1.9– ablation to stricture, and any associated symp-
15) and controls of 2.6 (1.3–5.5). Repeat cystos- toms were not stated, nor were treatment and
copy was selective, in five patients with persistent results for the strictures described (Lal et al.
dilation a mean of 8 (5–15.5), who all had sec- 1998). Considering the subgroup of patients
214 W.T. Snodgrass
<12 months old at presentation (comprising those primary valve ablation versus urinary diversion
with diversion before ablation) strictures occurred was not described, nor was analysis presented to
in 2/38 (5 %). demonstrate if patient groups had similar initial
renal function.
Another retrospective review included 67
TUR Valves Versus Urinary Diversion patients treated between 1985 and 2000, 38
undergoing primary valve ablation, 25 vesicos-
A review of 45 newborns with PUV managed tomy for a small urethra, and 4 ureterostomy for
between 1997 and 2002 found that 24 underwent “gross pyuria and sepsis with dilated and tortuous
primary valve ablation, while 21 had vesicostomy ureters, or failure of serum creatinine to diminish
because the urethra would not admit a 9-Fr scope. with catheter drainage.” Patients undergoing
Mean preoperative serum creatinine was similar in vesicostomy were significantly younger at a mean
the two groups (1.6 ± 1.5 mg/dL vs. 1.7 ± 1.5). Nine of 16.3 ± 29.1 months versus 37.2 ± 36.1 and
were lost to follow-up, and six died before 40.5 ± 17.9 months for valve ablation or ureteros-
12 months (four valve ablation, two vesicostomy). tomy. Initial renal function for each of the three
Apparently, diverted patients still had vesicostomy groups was not stated or compared, nor was tim-
at 12 months. Mean postoperative serum creati- ing for post-surgical analysis of renal function
nine at 1 year was 0.7 ± 0.2 mg/dL in 12 patients described—the authors only stating that improve-
after ablation versus 0.9 ± 0.7 mg/dL in 9 with ment in serum creatinine levels was not
vesicostomy, which was said to be similar by chi significantly different in diverted patients versus
square analysis (Narasimhan et al. 2004). those with valve ablation (Puri et al. 2002).
Another review included 46 patients, 23 pre-
natally detected and 23 diagnosed within 1 year
of life. In each group approximately 50 % under- Bladder Function
went primary valve ablation or supravesical
diversion, but decision making was not described. Although bladder dysfunction is a potential
During a mean observation period of approxi- risk factor for ESRD in boys with PUV, we
mately 12 years, six (13 %) developed renal found no published systematic protocol to diag-
insufficiency (<59 mL/min/1.73 m2) and eight nose and manage patients. While functional
(17 %) ESRD, with no differences in outcomes characteristics of the bladder may evolve over
based on initial surgical management (Ylinen time after valve ablation, our review found no
et al. 2004). studies describing longitudinal UD evaluations.
A retrospective review included 100 consecu- Two studies reported bladder capacity and
tive patients with PUV born before 1985 and compliance better after primary valve ablation
reported in 1996. Forty-two presented at less versus diversion by vesicostomy or supravesi-
than 1 month of age, and 56 at less than 1 year cal diversion, although selection bias for diver-
(mean, median, range not reported). Initial man- sion could account for this observation.
agement included valve ablation (74), vesicos- One study with UD performed in infants
tomy (13), or supravesical diversion (9); after within 2 weeks of valve ablation found no dif-
valve ablation, three also had supravesical diver- ference in median maximum detrusor pres-
sion without further improvement in serum crea- sures during voiding compared to age-matched
tinine, and four others had vesicostomies, with controls evaluated after UTI.
one then having decreased creatinine. Median Bladder dysfunction is also suspected from
follow-up was 11 years, but follow-up for each urinary incontinence in boys after the usual age
group was not stated. Data were presented as of toilet training, reported in 42–80 %, but few
Kaplan Meier curves, showing no statistical dif- reviews described ages at which continence was
ferences in risk for ESRD based on initial ther- achieved, and none was found that used objec-
apy (Smith et al. 1996). Selection of patients for tive assessments to define normal versus altered
bladder function. Potential contributing factors, The retrospective analysis of 67 patients

such as detrusor overactivity, poor compliance, treated initially by primary valve ablation (n = 38)
and/or polyuria, have not been systematically versus vesicostomy (n = 25) or supravesical diver-
assessed when continence is delayed. sion (n = 4) mentioned above (Puri et al. 2002)
Few studies report medical therapy with included UD testing in all patients. Studies were
anticholinergics, alpha-blockers, and/or CIC in performed using an 8-Fr transurethral catheter at
patients after valve ablation. Indications, age at a filling rate of 10 % expected bladder capacity
initiation of therapy, duration of treatment, and for age. A significant difference was found in
results have not been systematically reported. maximum bladder capacity between ablated ver-
One study found imipramine abolished detru- sus vesicostomy patients (mean % 96 ± 33 vs.
sor overactivity in nearly 90 % and improved 62 ± 28). Compliance of <10, 10–20, and >20 cc/
compliance in 43 % of patients treated, with cm H2O was also significantly better in ablated
symptomatic improvement reported in 59 %. versus vesicostomy patients. Age at which UD
Two studies reported alpha-blocker therapy was performed, time interval from valve treat-
using terazosin for PVR >10 % predicted blad- ment, and number of UDs performed per patient
der capacity reduced post-void residuals from a were not described.
mean of approximately 15 cc to a mean of 2 cc. UD was obtained in 116 patients who under-
One matched cohort study of adult men went valve ablation at mean age 14 months
using a validated questionnaire found symp- (6 days–164 months), followed by supravesical
toms of voiding dysfunction reported by 32 % diversion in 32 (28 %) for “severe VUR and HN”
of former valve patients, who also had in 22 and “poor renal function” in 9 for an unre-
significantly greater urge and/or stress incon- ported duration. Time after ablation for UD test-
tinence compared to age-matched controls. ing, the number of tests obtained per patient or, if
more than one study was done, which was selected
for analysis, were not stated. Filling was done via
Urodynamics a 7-Fr transurethral catheter at 5–10 mL/min.
Abnormal bladder parameters were found in 93
A retrospective study created two groups: 11 (80 %). Cystometric capacity was greater than
patients treated from 1970 to 1983 who under- expected by formula for age in 34 (29 %) and less
went supravesical diversion versus 8 undergoing in 33. Compliance loss was reported for 30 (26 %)
primary valve ablation from 1980 to 1983. and detrusor overactivity in 44 (38 %). Patch
Indications for diversion were small urethra, EMG electrodes indicated impaired pelvic floor
“severe urinary tract infections and failure to sta- relaxation in 31 (27 %), while retention >10 %
bilize renal function or improve a poor clinical voided volume was noted in 47 (41 %). Although
condition despite bladder drainage via a urethral 80 % of patients were considered to have abnor-
catheter and medical treatment.” Mean patient mal bladder function, when the authors catego-
age at surgery was 10.2 ± 8.1 months (diversion) rized them further, 86 (74 %) had normal
versus 11.8 ± 11.2 months (valve ablation), and compliance (61 without and 25 with detrusor
mean duration of diversion was 57 ± 39 months. overactivity), while 30 (26 %) had decreased
All had “rapid fill” UD testing at mean ages of compliance (13 without and 17 with detrusor
13.6 ± 2.2 years (diversion) versus 11 ± 4.1 years. overactivity). Definitions of increases/decreases
Mean maximum bladder capacity adjusted for in capacity, decreased compliance, or abnormal
age by the formula age + 2 × 30 was significantly pelvic EMG were not stated. Differences, if any,
greater in those ablated (1.37 ± 0.19 %) versus between those with ablation versus ablation plus
diverted (0.9 ± 0.3 %), and end filling pressure at diversion were not discussed. Multivariable
this capacity was significantly less in ablated regression analysis found only bilateral VUR,
(8 ± 2.6 cm H2O) versus diverted (19.3 ± 4 cm and not bladder dysfunction, to independently
H2O) bladders (Podesta et al. 2002). predict ESRD (Ghanem et al. 2004).
216 W.T. Snodgrass
Another retrospective analysis identified 25 alpha-blockers, 3 were dry on CIC, 3 had noctur-
males evaluated from 1994 to 2007 at a median nal enuresis (presumably dry during the day), and
age of 0.5 month (0–10.2). UD was performed in 10 were wet day and night (Sarhan et al. 2008).
six boys 2–6 days before valve ablation, and in Of 70 boys presenting at mean age 7.5 years
the other 19 at median 2 days (0–15) after abla- (2–14), 33 (47 %) had diurnal incontinence.
tion. Detrusor pressures were monitored using Following valve ablation, incontinence resolved
4-Fr catheters, presumably transurethrally, with in 24 at an unspecified interval and persisted in
infusion done at 2–5 cc/min using a second 4-Fr 9 (27 %). In four of nine, symptoms were
tube placed suprapubically in 8. A control group controlled with medication (desmopressin, anti-
of males without PUV was created from infants cholinergics), but use in others was not stated.
having UD after UTI at median age 3.3 months Incontinence resolved in six of nine patients
(1.5–9.6). Median maximum detrusor pressure during a mean of 11 months (4–18) and persisted
during voiding was similar in PUV patients in two receiving medical therapy; one was lost to
(112 cm H2O, 40–331) and controls (91 cm H2O, follow-up (Schober et al. 2004).
48–191, p = 0.39). Repeat UD was obtained at Bother from bladder dysfunction can extend
12 months after valve ablation in 17 patients, into adulthood. A study from Finland identified
finding a significant increase in median bladder 106 patients with PUV treated after 1953, and
capacity and decrease in median maximal void- received a response from 68 (64 %) to a vali-
ing pressures to 100 cm H2O, 60–193, p = 0.01 dated LTUS questionnaire. These data were
(Taskinen et al. 2009). compared to age-matched controls at a 4:1 ratio
(272 controls: 68 PUV patients) at median age
of 37.5 years (18–57). Of PUV patients, 32 %
Urinary Continence reported at least one moderate or severe symp-
tom, versus 16 % of controls (p = 0.002). Overall,
Continence was assessed in 100 boys with PUV, patients had 2× increase in LTUS (hesitancy,
excluding an unspecified number who died or weak stream, incomplete emptying, straining)
had ESRD before age 5 years. Total continence over controls. Urge incontinence was reported
(dry day and night) occurred in 19 % of boys by by 15 % PUV patients versus 5 % of controls
age 5, 46 % by age 10, and in 99 % by age 20, (p = 0.014), while stress incontinence occurred
with no significant differences based on initial in 12 % versus 3 % (p = 0.005) (Tikkinen et al.
therapy by valve ablation versus urinary diver- 2011).
sion (Smith et al. 1996). Additional therapies
(anticholinergics, CIC), if any, were not
described. Medical Bladder Therapy
In another study of 46 patients diagnosed (Anticholinergics, Alpha-Blockers, CIC)
either prenatally or within the first year of life
and then undergoing either valve ablation or A longitudinal study involved 30 PUV patients,
supravesical diversion, total urinary continence all ³5 years of age (5–20, mean or median not
was achieved in 17 (37 %) by age 5 years, and in stated), who had UD testing and were treated
22/27 (81 %) with follow-up to 10 years. with imipramine. Indications for investigation
Differences, if any, based on initial surgery were of these patients versus others of similar age, if
not described (Ylinen et al. 2004). any, were not described. Although all were con-
In another retrospective series, 63/65 cases of sidered toilet-trained, 27/30 had symptomatic
PUV diagnosed prenatally underwent primary voiding dysfunction described as diurnal incon-
valve ablation. During follow-up a median of tinence in 22 and only nocturnal enuresis in 5.
6.8 years, 55 patients were toilet-trained, of which UD used an 8-Fr transurethral catheter with
32 (58 %) were dry at mean age 3 years. Of the filling rates at 10 % expected capacity for age by
remaining 23, 7 were dry using anticholinergics ± formula, and needle electrodes for sphincter
EMG. All were considered to have abnormal age 1.5 months (1 day–13 years), post-void resid-
UD, with detrusor overactivity in 18 (60 %) and uals were measured by ultrasound during outpa-
compliance <10 mL/cm H2O in 21 (70 %). tient follow-up, with those having PVR >10 %
Imipramine was used at 1.5–2 mg/kg/24 h in a expected bladder capacity started on terazosin
single or divided doses. “Significant” symptom- 0.04–0.4 mg/kg/day. Patient age, interval after
atic improvement occurred in 16/27 (59 %). ablation before alpha-blocker treatment, duration
Repeat UD was reported at 1 and 2 years. of therapy, and number of patients treated were
Detrusor overactivity resolved on medication in not stated. Mean PVR pretreatment was 15 and
16/18 (89 %), while compliance improved in 2.5 cc with terazosin (Sudarsanan et al. 2009).
9/21 (43 %) (Puri et al. 2005).
As mentioned above, of 23 toilet-trained boys
with prenatally diagnosed PUV and primary Radiologic Changes After Valve
valve ablation, 7 (30 %) were dry using anticho- Ablation
linergics ± alpha-blockers, 3 were dry on CIC, 3
had nocturnal enuresis (presumably dry during Posterior urethral dilation decreases within
the day), and 10 were wet day and night. Specific 12 weeks, with persistent dilation suggesting
indications for these therapies were not described inadequate valve ablation (reviewed above).
(Sarhan et al. 2008). VUR occurs in approximately 50 % of patients
Another retrospective analysis of 119 patients with PUV and is reported to resolve in 25 % to
undergoing valve ablation reported 37 (31 %) 80 % of renal units, often within a year of valve
were started on CIC for “hostile bladder dynam- ablation. Resolution is more likely and occurs
ics” (DeFoor et al. 2008). The authors generally more rapidly in grades 1–3 versus 4–5 VUR.
described these patients in two categories: Two studies reported decreased HN in 70 %
“younger” ones who had low capacity and high- of renal units within 6–12 months of valve
end fill pressures that also received anticholin- ablation.
ergics, and “older” ones with myogenic failure
and retention who did not need anticholinergics.
The number of older versus younger patients, age Posterior Urethral Dilation
at initiation of medical therapy, and response to
treatment were not described. Thirty patients underwent repeat VCUG 12 weeks
Forty two patients were diagnosed with post- following valve ablation, with urethral ratio (trans-
void residual volumes by ultrasound >10 % of verse midpoint posterior urethral diameter/trans-
expected bladder capacity for age 1 week after verse widest anterior urethral diameter) measured
valve ablation. Age ranged from neonates to and compared to controls without PUV undergoing
>5 years, with 69 % less than 1 year. Terazosin, VUCG after UTI. Median age of patients at abla-
0.02–0.4 mg/kg, was given daily, with 25 % tion was 13 months (1 day–11 years) and 12 months
increases in dose every 2 weeks until residual vol- (2 days–16 years) in controls. Mean pre-ablation
umes were <10 % capacity. After 6 months of suc- urethral ratio was 4.94 ± 2.97, mean post-ablation
cessful therapy, medication was weaned. Mean was 2.13 ± 1.19 (p < 0.001), and was 1.73 ± 0.58 in
pretreatment residual volume was 16 cc (34 % controls (p < 0.001 vs. pre-ablation and p = 0.1 vs.
expected capacity) versus mean residual 2 cc post-ablation). Two patients with persistent dila-
(1.5 % expected capacity) on therapy. Symptomatic tion (ratios 5,6) after ablation were both found to
hypotension occurred in one, and another two boys have residual valves (Gupta et al. 2010).
did not respond. Four had therapy successfully
ended after 14 months, while others apparently
continued medication at mean follow-up 17 months VUR
(2 months–6 years) (Abraham et al. 2009).
In another retrospective series of 65 consecu- A prospective observational study included 20
tive patients undergoing valve ablation at median patients undergoing valve ablation at median
218 W.T. Snodgrass
15 months (12 days–5.5 years), of which 12 had HN resolved in one patient, but diminished
VUR into19 renal units (grade 1 in 2, grade 3 in significantly in the remainder; of 17 renal units
4, grade 4 in 6, and grade 5 in 7). Follow-up with moderate to severe dilation, 5 (29 %) had
VUCG was obtained at 3 and 6 months. By persistent moderate to severe HN at 6 months
6 months VUR had resolved in 15 (79 %) renal after ablation.
units, leaving one case each with grade 1–4 and Fifty consecutive patients, mean, median age
no grade 5 (Priti et al. 2004). 2 years (1–12), undergoing valve ablation during
A retrospective review concerned VUR in 127 a 3-year period from 2004 to 2007 had follow-up
patients and 200 renal units treated from 1953 to a mean of 30 months and minimum of 1 year.
2003. Data were available for 141 refluxing ure- Pre-ablation HN was described as 0 in 8 (16 %),
ters after valve ablation. Resolution occurred at grade 1 in 10 (20 %), grade 2 in 12 (24 %), grade
median 1.28 years (0.04-15.16) in 88 (62 %) renal 3 in 14 (28 %), and grade 4 in 6 (12 %) (grading
units, while another 24 (17 %) were removed for system not defined). At 1 year after ablation, 31
poor function, and 29 (21 %) were reimplanted. (62 %) had grade 0, 4 (8 %) had grade 3, and
Resolution was significantly faster for unilateral none had grade 4 HN (Gupta et al. 2009).
VUR (median 0.7 vs. 1.36 years), and for grades
1–3 (median 0.68 years) versus grades 4 and 5
(median 1.47 years), and was not influenced by Ureteral Reimplantation
ipsilateral renal function (<10 %, found in 22/73 or Endoscopic Injection
with scintigraphy). Likelihood for specific grades
to resolve was not stated (Heikkila et al. 2009). As discussed above, VUR often resolves within
Of 73 consecutive patients with PUV, 35 a year of valve ablation, and it is unclear if
(48 %) had VUR, unilateral in 18. There was VUR represents a modifiable factor for renal
mean follow-up of 5.6 years (1–17) in this retro- function.
spective analysis, during which resolution One study found less postoperative VUR
occurred in 11/44 (25 %) units at a mean of after excisional tapering with versus without
12 months. There was no difference in unilateral psoas hitch reimplantation.
versus bilateral reflux resolution, nor in resolu- VUR was present in 38/54 (70 %) boys in a ret-
tion according to ipsilateral function <20 % ver- rospective study. Spontaneous resolution occurred
sus greater, but grades 1–3 were more likely than in 9/38 (24 %) after ablation, and nephrectomy
grades 4–5 to resolve (6/9 [67 %] versus 5/35 was done in 7 patients for nonfunction. Twenty
[14 %], p = 0.0038) (Hassan et al. 2003). patients had surgical reflux resolution, by reim-
Another retrospective series included 65 con- plant in 5 and by injection with polytetrafluoro-
secutive boys with PUV treated from 2001 to 2007 ethylene in 15 patients and 24 ureters (grade 4 in 6,
with primary valve ablation at median age grade 5 in 18). Indications for intervention were
1.5 months (1 day–13 years). VUR occurred in 26 not described. Age at injection was a mean of
(40 %), unilateral in 18. During median follow-up 2.2 years (8 months–6 years), and all but one (with
of 24 months (6–75), 11/32 (34 %) ureters resolved UTI) had injection ³12 months after valve abla-
(grades not stated). (Sudarsanan et al. 2009). tion. A single injection resolved VUR in 17/24
(71 %) ureters, and with up to three injections all
were reported successful. The number and results
Hydronephrosis of any subsequent VCUGs, if done, were not dis-
cussed (Puri and Kumar 1996).
The prospective study by Priti et al. (2004) also A retrospective review of 106 boys with PUV
reported renal ultrasonography findings at abla- found 20 patients undergoing ureteral surgery, by
tion and repeated 3 and 6 months following abla- reimplantation in 25 renal units and transureter-
tion, reported as grades 0–3. All initially had HN, oureterostomy in 7 renal units. Of these, 5 patients
which was bilateral in 90 %. During follow-up and 12 ureters had VUR, while the remaining 15
patients and 20 ureters had UVJ obstruction (dis- before transplant. The indication was polyuria,
cussed below). Mean interval from valve ablation defined as sustained urine output >2.5 cc/kg/h, in
to reimplant was 1.8 years (6 months–4.5 years) 22 children, of which 10 had congenital urinary
for the entire group, and grade of VUR was not tract anomalies that were not further described.
clearly stated, but was grade 4 or 5 “in most.” Of these 22 children, 15 had unilateral surgery
Excisional tapering to 10–12-Fr was done in all (sometimes the first of staged removal) and
25 reimplanted ureters, with a psoas hitch in 18 median urine output decreased from 3.9 cc/kg/h
and not in the other 7, whose technique was not to 2.4 cc/kg/h, a change of −40 % from 2.1 to
further described. Four out of five refluxing 1.4 L per day (Ghane Sharbaf et al. 2012).
patients had persistent VUR; grades were not
stated. Of the entire group undergoing surgery for
either obstruction or VUR, psoas hitch reimplan- Renal Transplantation
tation had significantly less postoperative VUR
than did repairs without hitch (2/18 ureters with Several cohort studies indicate that graft sur-
hitch vs. 7/7 ureters without hitch, p < 0.004) vival is similar in patients with renal failure
(El-Sherbiny et al. 2002). due to PUV versus those with medical renal
disease.
A retrospective cohort study compared graft
Ureterovesical Junction Obstruction survival after living unrelated donor transplanta-
tion in 15 PUV patients, mean age 12.5 ± 2.8 years,
Impaired ureteral drainage across the ure- to 45 matched controls of similar age also receiv-
terovesical junction generally has been attrib- ing living unrelated grafts and all managed with a
uted to valve bladder and/or intrinsic ureteral similar immunosuppressive protocol. Preoperative
dysfunction rather than UVJ obstruction. Our urologic assessment included VCUG, cystoscopy,
review found only one article specifically report- and UD; of these 15 patients, 4 took anticholin-
ing UVJ obstruction in 12 % of PUV patients. ergics, 2 used CIC, and 9 had prior ileocystoplasty.
El-Sherbiny et al. (2002) diagnosed UVJ There were no differences in acute or chronic
obstruction in13/106 (12 %) boys and 20 renal rejection episodes between patients and controls,
units following valve ablation at a mean of and mean graft survival was 7 years in patients
1.8 years (6 months–4.5 years). All had bilateral and 6.2 in controls, p = 0.9 (Otukesh et al. 2008).
“grade 3 or 4” HN (grading scale not defined). Another retrospective study compared renal
Diuretic renography demonstrated T1/2 >20 min graft outcomes in 18 PUV patients transplanted
in 7 patients and 11 renal units, while Whitaker at mean age 9.1 years (1–18) 1:1 with a selected
test found renal pressures >22 cm H2O over blad- control group with medical renal disease of
der pressures in 6 patients and 9 renal units with similar age, donor type, and immunosuppres-
supravesical diversion before repair. sive therapies. No pre-transplant UD or bladder
reconstruction was done in any patient, but no
mention was made of other medical therapies
Nephrectomy to Reduce Urine Output for bladder management, if any, and the authors
admitted there were neither UD data nor void-
One study reported that unilateral nephrec- ing histories for any PUV patients before or
tomy reduced polyuria by 40 % before renal during 10 years of post-transplant follow-up.
transplant. Nevertheless, 10-year graft survival was not
A retrospective study evaluated consecutive significantly different between patients and
patients undergoing unilateral or bilateral native controls, 54 % versus 41 % p = 0.35 (Indudhara
nephrectomy from a total of 126 consecutive et al. 1998).
pediatric kidney transplants. These nephrecto- A third retrospective matched cohort study
mies were done a median of 1.9 months (0–41) compared cadaveric transplantation in 19 PUV
220 W.T. Snodgrass
patients at mean age of 10 years (1.3–17) to 62 alter the evaluation of the urethra? J Urol.
controls with glomerulonephropathies and 42 con- 2004;171(3):1280–1.
DeFoor W, Clark C, Jackson E, Reddy P, Minevich E,
trols with renal dysplasia—neither control group Sheldon C. Risk factors for end stage renal disease in
including patients with known bladder dysfunc- children with posterior urethral valves. J Urol.
tion. There were no differences in PUV patients 2008;180(4 Suppl):1705–8. discussion 8.
versus controls for graft survival at 1, 5, or 10 years. Ditchfield MR, Grattan-Smith JD, de Campo JF, Hutson
JM. Voiding cystourethrography in boys: does the
In this series, all PUV patients underwent pre- presence of the catheter obscure the diagnosis of pos-
transplant UD, which diagnosed “severe” bladder terior urethral valves? AJR Am J Roentgenol.
dysfunction in 8 (42 %) described as detrusor 1995;164(5):1233–5.
overactivity, poor compliance, reduced bladder El-Ghoneimi A, Desgrippes A, Luton D, Macher MA,
Guibourdenche J, Garel C, et al. Outcome of posterior
capacity, and bladder sphincter “incoordination” urethral valves: to what extent is it improved by prena-
(none specifically defined). Pre-transplant aug- tal diagnosis? J Urol. 1999;162(3 Pt 1):849–53.
mentation was performed in five of these. All El-Sherbiny MT, Hafez AT, Ghoneim MA, Greenfield SP.
transplant reimplantations were antirefluxing Ureteroneocystostomy in children with posterior ure-
thral valves: indications and outcome. J Urol.
done into the native bladder. No patient had pre- 2002;168(4 Pt 2):1836–9. discussion 9–40.
transplant bilateral nephrectomies, but eight had Ghane Sharbaf F, Bitzan M, Szymanski KM, Bell LE,
unilateral nephrectomy before or during the trans- Gupta I, Tchervenkov J, et al. Native nephrectomy
plant, and six had unilateral nephrectomy after- prior to pediatric kidney transplantation: biological
and clinical aspects. Pediatr Nephrol. 2012;27(7):
wards, resulting in three with bilateral removal 1179–88.
of native kidneys. Another patient had bilateral Ghanem MA, Wolffenbuttel KP, De Vylder A, Nijman RJ.
nephrectomy after transplant, so that altogether Long-term bladder dysfunction and renal function in
4/19 (21 %) received bilateral nephrectomies. boys with posterior urethral valves based on urody-
namic findings. J Urol. 2004;171(6 Pt 1):2409–12.
Indications for nephrectomy were not clearly Gupta SD, Khatun AA, Islam AI, Shameem IA. Outcome
stated (Mendizabal et al. 2006). of endoscopic fulguration of posterior urethral valves
in children. Mymensingh Med J. 2009;18(2):239–44.
Gupta RK, Shah HS, Jadhav V, Gupta A, Prakash A,
Sanghvi B, et al. Urethral ratio on voiding cystoure-
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2006;21(4):566–71. Pediatr Surg. 2005;15(5):347–53.
Morris RK, Kilby MD. An overview of the literature on Sarhan O, Zaccaria I, Macher MA, Muller F, Vuillard E,
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Gynaecol. 2009;49(1):6–10. 2008;179(1):307–12. discussion 12–3.
Morris RK, Quinlan-Jones E, Kilby MD, Khan KS. Sarhan O, El-Dahshan K, Sarhan M. Prognostic value of
Systematic review of accuracy of fetal urine analysis serum creatinine levels in children with posterior ure-
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congenital urinary tract obstruction. Prenat Diagn. Urol. 2010;6(1):11–4.
2007;27(10):900–11. Sarhan OM, El-Ghoneimi AA, Helmy TE, Dawaba MS,
Morris RK, Malin GL, Khan KS, Kilby MD. Systematic Ghali AM, Ibrahiem el HI. Posterior urethral valves:
review of the effectiveness of antenatal intervention multivariate analysis of factors affecting the final renal
for the treatment of congenital lower urinary tract outcome. J Urol. 2011;185(6 Suppl):2491–5.
obstruction. BJOG. 2010;117(4):382–90. Schober JM, Dulabon LM, Woodhouse CR. Outcome of
Myers DA, Walker 3rd RD. Prevention of urethral stric- valve ablation in late-presenting posterior urethral
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Urol. 1981;126(5):655–7. Smeulders N, Makin E, Desai D, Duffy PG, Healy C,
Narasimhan KL, Kaur B, Chowdhary SK, Bhalla AK. Cuckow PM, et al. The predictive value of a repeat
Does mode of treatment affect the outcome of neona- micturating cystourethrogram for remnant leaflets
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Int. 2002;18(5–6):438–43. 874–9.
Neurogenic Bladder
16
Warren T. Snodgrass, Micah A. Jacobs,
and Patricio C. Gargollo
Primary reasons to diagnose and manage Of newborns with initial UD end filling pres-
neurogenic bladder: sures <40 cm H2O, 10 % had loss of compli-
1. Prevent acquired renal injury. ance at median age 9 months, with reduction
2. Prevent acquired loss of bladder compliance. again to <40 cm H2O with CIC plusAC.
Secondary aims: No prospective study reports impact of
1. Achieve urinary (and bowel) continence. detrusor leak-point pressure (DLPP) on future
2. Improve self-care and/or facilitate manage- bladder compliance.
ment by other caregivers. No prospective series reports overall rates of
Summary of evidence for these goals: spontaneous voiding, urinary continence with
Renal scar has been diagnosed by DMSA in medical management, or evidence of sphincter
25–32 % of patients with spina bifida in retro- incompetency leading to surgery in a cohort of
spective series. No longitudinal data relates consecutive children with spina bifida.
UD findings or management of neurogenic Optimal medical management (frequency
bladder to renal scarring. of CIC, overnight catheter drainage, AC regi-
Although UD findings are the cornerstone mens and doses) for detrusor overactivity or
for therapeutic decision-making, technical decreased compliance before augmentation is
aspects of the test (catheter size, filling rates, not standardized.
temperature of infused fluids, seated versus Many retrospective, and a few prospective,
supine positioning, number of cycles) are not series report outcomes from bladder neck sur-
standardized, and no study reports inter- and gery ± augmentation, with dryness in 50–90 %.
intra-observer agreement in their interpreta- Generally, LMS, AUS, and bladder neck clo-
tion for neurogenic bladder. sure more reliably achieve dryness than slings
One prospective study showed 20 % of or bladder neck injections.
newborns had end filling pressures >40 cm One-third or fewer of patients undergoing
H2O, with medical management (CIC plus bladder outlet surgery without augmentation
AC) decreasing pressures to <40 cm H2O in all. will manifest decreased compliance on postop-
erative UD. Most respond to medical therapy.
Health-related quality-of-life surveys found
W.T. Snodgrass, M.D. (*) • M.A. Jacobs, M.D., M.P.H.
P.C. Gargollo, M.D. no differences reported by patients before ver-
Department of Pediatric Urology, sus after surgery for incontinence, but reported
University of Texas Southwestern Medical improved independence and self-esteem fol-
Center and Children’s Medical Center Dallas,
lowing ACE.
Dallas, TX 75235, USA ACE procedures can improve self-esteem
e-mail: warren.snodgrass@childrens.com and independence with bowel care.
Few series comparing ACE to retrograde UD in 29 consecutive patients with lipomy-

enemas report no additional benefit of ACE to elomeningocele evaluated at a mean age 1.9 years
achieve fecal continence. (1 month to 13 years) were considered abnormal
LACE uses less irrigation volume and in 11 (38 %) (Dushi et al. 2011).
requires less toilet time than ACE. A retrospective analysis of 502 children with
Complications after ACE occur in 15 % to spinal dysraphism referred to a multi-specialty
more than 50 % in published series, most com- center at median age 12 years reported neuro-
monly stoma stenosis or leakage. Pain with genic bladder occurred in 33/98 (34 %) with spi-
irrigation is also reported in some series with nal lipoma. Neurogenic bladder was diagnosed in
phosphate, saline, or tap water enemas. significantly more with lipomyelomeningocele
Series reporting >5-year follow-up indicate (18/31, 58 %) versus lipomyeloschisis and phy-
that 10–45 % of patients no longer use the ACE. lum lipomas (33/98, 34 %) (Torre et al. 2011).
Definition Sacral Agenesis/Caudal Regression
There is no consensus definition for “neurogenic Fifty to seventy-five percent of children

bladder” in children, which generally refers to referred with sacral agenesis have a neuro-
bladder dysfunction diagnosed by a combination genic bladder, with one study reporting the
of symptoms, imaging, and/or UD findings in likelihood increasing with increasing extent of
patients with neurologic conditions. the sacral deformity.
A retrospective analysis of 502 children with
spinal dysraphism referred to a multi-specialty
Prevalence of Neurogenic Bladder center at median age 12 years reported neuro-
with Spinal Cord Anomalies genic bladder occurred in 54/90 (60 %) with cau-
dal regression syndrome (Torre et al. 2011).
Myelodysplasia Another retrospective analysis reported that
11/15 (73 %) children with sacral agenesis had a
UDs appear normal in 25–33 % of newborns neurogenic bladder confirmed by UD at mean
with spina bifida. Spontaneous continence rates age 40 months (for the entire series of 28 patients
in these, and in newborns observed despite that included others with anorectal malforma-
abnormal UDs, have not been reported. tions). Those with normal bladder function were
Three studies with UD assessments in con- described as having minor sacral defects in only
secutive newborns with myelomeningocele parts of S4 and S5 pedicles versus those with
reported abnormal findings in ³75 % (Sidi et al. neurogenic bladders having total S5 and partial
1986; Sillen et al. 1996; Granberg et al. 2011). S4 absence (Boemers et al. 1994).
A retrospective analysis of 502 children with A 20-year retrospective review of all patients
myelomeningocele referred to a multi-specialty evaluated in a neurourology clinic with sacral
center reported that neurogenic bladder occurred agenesis found 22 cases initially evaluated at
in 275/283 (97 %) patients evaluated at median median 10.5 (2–24) years of age. UD was per-
age 12 years (2 months to 42 years) (Torre et al. formed in each, and all were abnormal, with
2011). detrusor overactivity in 19 (86 %) and DSD in 14
(64 %) (Wilmshurst et al. 1999).
Lipomeningocele
Primary Tethered Cord
Two studies reported neurogenic bladder in
approximately one-third of patients with Primary tethered cord is diagnosed during eval-
spinal cord lipoma. uation for orthopedic deformities or cutaneous
16 Neurogenic Bladder 225
lesions (generally in patients before toilet train- alone did not. In contrast, Guerra et al. and
ing) and for urinary incontinence in older chil- Macejko et al. reported a variety of lesions,
dren. Retrospective series report abnormal UD including thickened filum, lipoma, syearinx,
in 20–87 % of patients with orthopedic and/or diastematomyelia, and spina bifida occulta.
cutaneous lesions, mostly detrusor overactivity.
A retrospective review analyzed all cases of
tethered cord releases during a 7-year period to Other Etiologies for Neurogenic
identify infants and children <3 years of age with Bladder
a primary tethered cord. Underlying diagnoses
included spinal cord lipoma, fatty filum, and Cerebral Palsy
diastematomyelia presenting due to cutaneous
manifestations or musculoskeletal disorders. UD Three retrospective studies reported that the
was obtained in 66/79 patients before neurosur- most common abnormal UD findings in chil-
gery done at mean age 10 months, and was con- dren with cerebral palsy referred for urologic
sidered abnormal in 30 (45 %), with varying evaluation were detrusor overactivity in
findings of overactivity, “hypotonia,” DSD, poor approximately 50 % and DSD in £10 %.
compliance, and high voiding pressures. The A retrospective report comprised 57 children
authors did not consider isolated uninhibited con- with cerebral palsy referred from ages 2 to 20
tractions abnormal (Macejko et al. 2007). years with voiding complaints, including inconti-
Another retrospective review of cases under- nence in 49 (86 %), isolated urgency and frequency
going tethered cord release identified 48 non- in 3, and retention in 1. UD was performed (with
syndromic children that were subdivided into needle electrode EMG for external sphincter func-
three groups based on clinical presentation: tion). Findings included detrusor overactivity in 34
• Group 1—orthopedic deformities/scoliosis: (60 %), DSD with retention in 3, reduced capacity
19 patients, mean age 8 years (8 months to 14 in 2, and “hypertonia” in 2. The authors consid-
years); 4 had daytime urinary incontinence; ered findings consistent with an upper motor neu-
UD showed detrusor overactivity in 3 (16 %). ron injury in 49 (86 %) patients, while 6 (11 %)
• Group 2—cutaneous lesions: 16 patients, mean had EMG evidence of an incomplete lower motor
age 1 year (1 month to 11 years), with only 1 neuron injury (Decter et al. 1987).
patient beyond the age of toilet training; UD Another retrospective review of 31 consecu-
diagnosed detrusor overactivity in 4 (25 %), tive children with cerebral palsy at median age 10
while the remainder were considered normal. years (4.5–17) reported 7 (23 %) were voiding
• Group 3—diurnal incontinence: 13 patients, and continent, 3 (10 %) used CIC plus AC, and
mean age 9 years (4.5–14). Preoperative UD the remainder wore diapers. UD demonstrated
indicated detrusor overactivity in 11 and areflexia detrusor overactivity in 16 (52 %) (Richardson
in 2 (DLPP not stated) (Nogueira et al. 2004). and Palmer 2009).
A third retrospective review considered 24 A third retrospective study included 36 chil-
patients diagnosed with a tethered cord, present- dren with cerebral palsy evaluated at mean age 8
ing at median age 6 years (1 month to 12 years). years (4–18), of which 24 (67 %) had voiding
Nineteen (79 %) had cutaneous lesions, 15 (62 %) symptoms. UD was abnormal in 21 (58 %), with
had orthopedic deformities/scoliosis, and 7 (of 14 detrusor overactivity in 17 (47 %) and DSD in 4
toilet trained) had incontinence. Preoperative UD (11 %) (diagnosed using patch EMG electrodes)
was abnormal in 21 (87.5 %): 17 with detrusor (Karaman et al. 2005).
overactivity and 4 with decreased compliance
(Guerra et al. 2006).
MRI spinal cord findings varied in these stud- Anorectal Malformations
ies: Nogueira et al. stated that a conus positioned
at the midpoint or below the second vertebra Prevalence of neurogenic bladder in children
diagnosed tethered cord, but a thickened filum with anorectal malformation is 12–35 %, with
two studies reporting most, but not all, associ- lished reports cannot be certain the authors
ated with spinal/sacral anomalies. categorized patients as they would have.
Ninety consecutive children, mean age 17
months (1–128), with anorectal malformations
(29 % high, 51 % low) had a mean of two UD Urodynamics: Technical Considerations
evaluations. Neurogenic bladder was diagnosed
in 22 (24 %), all but 1 of which also had partial DLPP is potentially increased by larger transure-
sacral agenesis. UD in 52 patients with a normal thral catheters (7, 10 Fr versus 5 Fr) and faster
sacrum found uninhibited detrusor contractions infusion rates (25 cc/min versus 2.5 cc/min).
in 5 that were considered possibly normal for Uninhibited contractions are reported more
patient age and so were not considered evidence likely seen with UD performed in the seated
of neurogenic bladder (Boemers et al. 1996). than supine position, in the first versus second
Another study included 89 patients with ano- cycle, and with room temperature versus body
rectal malformation classified as low in 39 temperature infusions.
(44 %), high in 45 (51 %), and as cloaca in 5 There are no published standards for tech-
(6 %). Sixty had UD at mean age 5 years, done in nical aspects of the examinations.
54 because of spine abnormalities, with neuro- One study performed UD in 23 children 5
genic bladder diagnosed in 31/89 (35 %) with weeks to 21 years of age with neurogenic bladder
detrusor overactivity in 21 and areflexia in 10. (20 myelomeningocele, 1 lipomeningocele, 1
These occurred in both low (40 %) and high spinal cord injury, and 1 sacral agenesis). Infusion
(51 %) malformations. Of the 31 patients, spinal/ was done by gravity at a rate of 15–22 cc/min.
sacral anomalies were found in 28 (90 %) Studies were performed using first a 7-Fr and
(Mosiello et al. 2003). then 10-Fr triple-lumen catheter, and finally with
A German registry of patients with anorectal two 5-Fr feeding tubes transurethrally. DLPP
malformation was used to identify 267 individu- increased in 75 % of cases with larger catheter
als who then were visited at home by physicians size. Extent of change was not described, except
using standardized forms to collect data. Thirty- to state that in 8 (35 %) there was no leakage
two (12 %) had neurogenic bladder dysfunction despite bladder distention when a 7- or 10-Fr
(not defined) (Maerzheuser et al. 2011). catheter was used, and that in seven patients
DLPP was <40 cm H2O using 5-Fr and >40 cm
H2O using larger catheters. These differences
Urodynamics occurred in patients up to age 14 years (Decter
and Harpster 1992).
Even though urodynamic assessment is a cor- Although transurethral catheters can create
nerstone in the diagnosis and treatment of partial obstruction, no study has compared supra-
neurogenic bladder, best practices in its per- pubic to transurethral pressure measurements in
formance and terminology to describe its children.
results remain ill-defined. Infusion rates may also impact DLPP. One
Since technical factors described below study compared filling at approximately 25 cc/min
potentially impact UD findings, caution is to 2.5 cc/min via a 7-Fr catheter in 38 children
needed in clinical decision-making based on ranging in age from 16 days to 18 years (mean 3
urodynamic assessment. years) with myelodysplasia. In 26 cases there was
Furthermore, no study shows inter- and no variation in detrusor pressure based on infusion
intra-observer agreement in UD interpretation rate, while in the other 12 (32 %) there was a
in children with neurogenic bladder. significant increase of >15 cm H2O with more
Consequently, urologists analyzing the same rapid than slower infusion. In 14 (37 %) DLPP
patient might draw different conclusions regard- exceeded 40 cm H2O with rapid infusion but not
ing bladder function, and readers studying pub- with slower inflow (Joseph 1992).
A prospective randomized trial compared with myelomeningocele. Filling was done at a

both room temperature versus body tempera- rate of 3–5 % of expected capacity per minute
ture (heated) saline infusion in 58 children using a 6- or 7-Fr dual-channel urethral catheter
mean age 9 years (for larger cohort of 101 in 506 children at mean age 5 years. Patients
patients) with spinal dysraphism and reported received no anticholinergic or sympathomimetic
room temperature studies had significantly medications, and prior bladder surgery and VUR
greater (16 %) bladder capacity, pressure dur- were exclusions. Capacity was defined as the vol-
ing filling, and uninhibited detrusor contrac- ume when there was leakage or voiding, or dis-
tions (Chin-Peuckert et al. 2004). comfort, or infusion spontaneously stopped.
A nonrandomized study sequentially allocated Capacity was found to be related to age through 9
patients to undergo urodynamic evaluation supine years, and approximately 25 % less in patients
versus sitting. The study population was not with myelodysplasia versus neurologically nor-
defined, except for mean age 10 years with spinal mal children (Palmer et al. 1997).
dysraphism in 19/48 patients. No differences
were noted for bladder capacity or DLPP, but
detrusor overactivity (60 % versus 53 %) and ICCS Recommendations
observed incontinent episodes (42 % versus
35 %) were significantly more common in Based on expert opinion, the ICCS recommends
patients sitting (Lorenzo et al. 2007). UD be performed using “as small a catheter as
Concordance of findings in two consecutive possible” at a rate in cc/min calculated from body
studies performed during one session was weight (kg)/4, or 5–10 % expected bladder capac-
reported in a retrospective study of 66 children a ity for age (Neveus et al. 2006).
mean age of 7.4 years with varying diagnoses,
including spinal dysraphism in 43 (65 %), but
also non-neurogenic conditions (posterior ure- Leak Point Pressure >40 cm H2O
thral valves, voiding dysfunction). These patients
were selected from a larger cohort of 112 chil- DLPP >40 cm H2O has been widely accepted
dren to include those who underwent two trials as an indicator of bladder pressure posing a
during a single session using the same inflow rate high risk for development of hydronephrosis,
and patient position. Why these patients had two VUR, and loss of detrusor compliance, based
tests while others did not was not stated. on a single retrospective study.
Maximum bladder capacity, end filling pressure, Technical factors in UD studies discussed
and DLPP were not significantly different above potentially impact DLPP and so could
between the two studies, although detrusor over- result in an error in diagnosis of high risk.
activity was more often observed during the first In addition, storage time at pressure >40 cm
than second trial (Chin-Peuckert et al. 2003). H2O before leakage occurs varies between
patients, potentially creating different expo-
sures to high pressures even in children with
Bladder Capacity identical DLPP.
DLPP is defined as the lowest detrusor pres-
One study reported capacity in myelodysplas- sure at which urine leakage occurs in the absence
tic children to age 9 years is 25 % less than of either a detrusor contraction or increased
predicted using the common age-based for- abdominal pressure (Abrams et al. ICS 2002).
mula [capacity cc = (age + 2) × 30]. A retrospective analysis was reported in 42
UD results from patients studied between patients with myelodysplasia followed a mean of 7
1983 and 1994 were reviewed to determine if years (3–15), without further description of age,
age-based formulas [capacity cc = (age + 2) × 30] number of UD, or other inclusion/exclusion crite-
accurately predict bladder capacity in children ria. UD findings were compared to IVP and
VCUG. UD was done using a transurethral triple- Risk Factors for Renal Scar
lumen catheter (size not stated), or two 8-Fr cath-
eters, with “slow filling” (infusion rate not stated). Three retrospective studies reported that
In five patients, a Foley balloon was used to DMSA scintigraphy found renal scar in
occlude the bladder neck because of leakage at 15–32 % of myelodysplastic patients.
low bladder volume. Seven of 42 (17 %) were VUR and febrile UTI were significant risk
described as having “a reflex detrusor response” to factors, but two studies reported urodynamic
filling that was considered normal in 4 and DSD in parameters (DLPP, compliance) were not.
3. The other 35 had areflexia, with 30 having No longitudinal study reports initial and
decreased compliance and 5 having no increase in follow-up DMSA to determine baseline
pressure during filling. Of the entire cohort, intra- findings and risk for subsequent acquired
vesical pressure at urine leakage was less than renal damage.
40 cm H2O in 20, none of whom had VUR and 2 A retrospective analysis included DMSA and
had ureteral dilation. DLPP was greater than 40 cm UD obtained in 113 sequential patients from
H2O in 22, with VUR in 15 (68 %) and ureteral 2005 to 2007, from which a study cohort of 64
dilation in 18 (81 %), p < 0.001. Actual DLPP were patients over 10 years of age (mean 16, 10–23)
not provided, and the number of patients with was selected. All had a history of CIC. Function
DLPP >40 cm H2O having neither VUR nor dila- <40 % or focal scar were considered abnormal,
tion was not stated (McGuire et al. 1981). and were found in 16 (25 %). Risk factors for
abnormal DMSA included VUR (OR 2.06 [95 %
CI 1.43–2.97]) and febrile UTI (OR 9.53 [95 %
DMSA-Based Acquired Renal Damage CI 2.674–34.34]) but not DLPP (44 ± 20 versus
46 ± 28 cm H2O) or detrusor compliance (8.8 ± 5.9
One endpoint in patient management is avoid- versus 12 ± 11) (Shiroyanagi et al. 2009).
ance of acquired renal damage, but our review Another retrospective study also obtained UD
found only one study describing DMSA results and DMSA scintigraphy in all referred children
in newborns, and two retrospective studies and adolescents for incontinence and/or recurrent
reporting DMSA findings in children, with UTI from 1996 to 2004. Renal scar was defined
myelomeningocele. as focal cortical defects, while children with
No longitudinal study analyzes risk factors “shrunken kidney or renal atrophy and diffuse
for renal scarring in patients with neurogenic scarring” were excluded as possibly having con-
bladder. genital nephropathy. In patients with mean age
7 ± 4 years, renal scarring was found in 30/95
(32 %) with neurogenic bladder due to myelo-
Baseline DMSA dysplasia (79 %), sacral agenesis (6 %) and spi-
nal cord tumors, myelitis, etc. (14.6 %). At
DMSA scintigraphy in newborns with myelo- presentation, 40 % were on AC and 33 % used
dysplasia has only been reported in one pro- CIC, the authors commenting that treatments
spective observational study, finding 8 % to were started “late in life.” Univariable analysis
have abnormalities considered congenital. found febrile UTI and VUR as risk factors for
One prospective study obtained DMSA as a renal scar, but not neurogenic versus non-neuro-
baseline evaluation in 38 consecutive newborns genic incontinence (evaluated in another 15 chil-
at approximately age 6 weeks. Of these, 35 dren). Multivariable analysis reported only VUR
(92 %) were normal, while 1 showed a focal cor- correlated with scarring, OR 8.12 (95 % CI 2.92–
tical defect and another 2 had differential func- 23.14). Of the entire cohort of 120 patients, mean
tion <45 % (1 with ipsilateral grade 5 VUR)—all pressure at maximum bladder capacity was
considered by clinical history to represent con- 25 ± 23 cm H2O, with 14 having pressures >40 cm
genital abnormalities (Granberg et al. 2011). H2O. No urodynamic parameter, including end
pressure at capacity, decreased compliance of six, and was SFU grade 2 (n = 3), 3 (n = 2), and
with end pressure >40 cm H2O, detrusor over- 4 (n = 1). VUR was bilateral in four, and grade 1
activity, or DSD, predicted renal scarring (n = 2), 2 (n = 4), 3 (n = 1), 4 (n = 1), and 5 (n = 3)
(Leonardo et al. 2007). (Granberg et al. 2011).
A third retrospective study reviewed DMSA UD in these three series are summarized in
and VCUG results in 180 children with myelom- Table 16.2. Differences in methodologies and ter-
eningocele evaluated between 1970 and 1988, minologies limit direct comparisons of results
with DMSA introduced in 1983 but then between these.
obtained in all patients. Mean age at DMSA UD studies by Sidi et al. (1986) used a 7-Fr
evaluation was not stated. UD was done selec- transurethral double-lumen catheter infusing CO2
tively in an unspecified number of patients, with at 10–15 cc/min, and a monopolar 27-gauge
neither results nor treatments for neurogenic needle electrode in the external urethral or anal
bladder described. VUR was found in 72 (40 %) sphincter in 30 consecutive newborns. Nine of 30
patients, and renal scar (focal cortical defects) (30 %) were considered to have normal, coordi-
in 28 (15.5 %) patients. Of these 28 patients nated detrusor and sphincter activity. Three of 30
with scar, 21 (75 %) had VUR grades 2–5 (10 %) had DSD, 3 (10 %) had no detrusor con-
(Cohen et al. 1990). traction with no pressure rise from baseline, and
15 (50 %) had no detrusor contraction associated
with rising pressures, of which 6 (20 %) exceeded
Newborn Assessment 40 cm H2O. No patient was diagnosed with detru-
sor overactivity.
Initial Imaging and Urodynamics Sillen et al. (1996) reported that 34 consecu-
tive infants underwent UD at 1 month of age
Three prospective studies reported that using a 6-Fr transurethral catheter with inflow
21–32 % of newborns had UD that was consid- between 1.6 and 8 cc/min and patch EMG elec-
ered normal. In these three studies, detrusor trodes. Areflexia was defined as including con-
pressures >40 cm H2O were found in 15–25 % tractions <20 cm H2O, and poor compliance as
of newborns. pressures >20 cm H2O. Patch EMG tracings
Initial US and VCUG were described in obtained were unsatisfactory to diagnosis DSD.
two of these studies, with 21 % of newborns Eleven of 34 (32 %) studies were considered
reported to have hydronephrosis (8 %) and/or normal, 8 (23 %) had areflexia, and 15 (44 %)
VUR (15 %). had detrusor overactivity. Pressures >20 cm H2O
Three prospective, consecutive patient series was only seen in those with detrusor overactiv-
describe newborn imaging (Table 16.1). ity, occurring in 14/15, of which 8 exceeded
Thirty newborns with myelodysplasia under- 40 cm H2O.
went renal ultrasound and VCUG between 1981 The prospective observational study by
and 1984. Reported imaging results combined Granberg et al. (2011) evaluated 71 consecutive
HN, VUR, and bladder trabeculation (without newborns and infants <6 months of age, using a
definition) and stated that 11/30 (36 %) had 5-Fr transurethral urodynamic catheter, inflow at
abnormal findings. Grades of HN and VUR were 10 cc/min and patch EMG electrodes. No attempt
not stated (Sidi et al. 1986). was made to diagnose DSD. Sixteen of 71 (23 %)
Thirty-four consecutive newborns with myel- were considered normal. Eleven (15 %) had no
odysplasia underwent imaging, with 7 (21 %) detrusor contraction and all had end filling pres-
having HN (n = 2, 6 %) or VUR (n = 5, 15 %), sures <25 cm H2O. The remaining 45 (63 %) had
without describing grades (Sillen et al. 1996). detrusor overactivity with filling pressures (base-
Imaging in 71 consecutive patients <6 months line from which contractions occurred) <25 cm
of age reported 14 (20 %) to have HN (n = 6, 8 %) H2O in 15, between 25 and 40 cm H2O in 17 and
or VUR (n = 11, 15 %). HN was bilateral in five >40 cm H2O in 11.
Table 16.1 Upper tract imaging in newborns with spina bifida

Authors No. patients Age at imaging Total abnormal Hydronephrosis (SFU grades) VUR (grades)
Sidi et al. (1986) 30 <1 month 11 (36 %)a NS NS
Sillen et al. (1996) 34 1 month 7 (21 %) 2 (6 %) (NS) 5 (15 %) (NS)
Granberg et al. (2011) 71 <6 months 14 (20 %) 6 (8 %) 11 (15 %)
SFU 2:3 G 1:2
3:2 2:4
4:1 3:1
4:1
5:3
NS not stated
a
Included hydronephrosis, VUR, and/or bladder trabeculation
Table 16.2 UD findings in consecutive newborns with myelomeningocele

“Normal” (%) DSD (%) No contraction (%) Overactivity (%)
Sidi et al. (1986) 30 10a 60 0
n = 30
Sillen et al. (1996) 32 0b 23 44
n = 32
Granberg et al. (2011) 23 0b 31 46
n = 71
a
Used needle electrodes
b
Used patch electrodes; findings considered inconclusive for DSD
Changes in Imaging and Urodynamics UD study without prior deterioration, and all
were described as voiding “voluntarily with com-
One retrospective study reported 50 % of new- plete, or nearly complete, continence and bowel
borns considered to have a normal UD voided elimination” (Tarcan et al. 2001).
spontaneously after age 3. Another 33 % The 30 newborns reported by Sidi et al.
developed abnormal UD patterns, all consid- described above were divided into two groups
ered due to tethered cord. based on initial UD-based risk assessment and
Two prospective studies reported 5 and followed a mean of 18 months (4–42) with peri-
15 % of newborns considered by UD to be low odic imaging (Fig. 16.1):
risk (normal findings, or pressures <40 cm • Nine were considered at high risk, including
H2O) developed pressures 40 cm H2O and/or three with DSD and six with no contractions
new hydronephrosis or VUR within 2 years. and end pressures >40 cm H2O. Of these, five
A retrospective review found 25 newborns with abnormal radiologic findings underwent
considered to have normal UD from among 204 therapy (CIC plus anticholinergics or vesicos-
studied between 1979 and 1998. Follow-up tomy), while four with initial normal radiol-
included imaging and annual UD. Eight of 25 ogy were observed. At a mean of 13 months
(32 %) had adverse urodynamic changes, six (6–22), all four had radiologic changes (not
without clinical symptoms, UTI in one, and urge defined) leading to CIC plus anticholinergics.
incontinence in the other. All eight were diag- • Twenty-one newborns with normal urody-
nosed with tethered cord and underwent release namic tests or no detrusor contraction with
that was restored initial UD patterns in two. None end pressures <40 cm H2O were considered
developed hydronephrosis or VUR. Twelve chil- low risk. Initially, six had abnormal radiology,
dren were over age 3 years who retained a normal and all were observed with only antibiotic
Fig. 16.1 UD-based selective therapy. Created with data from Sidi et al. (1986)
Fig. 16.2 UD-based selective therapy. Created with data from Granberg et al. (2011)
prophylaxis, with four becoming normal in imaging that prompted repeat UD, which other-
one to more than 2 years, one remaining sta- wise were not done in stable or improved patients.
ble, and one progressing VUR from grade I to Adverse changes specifically in those thought to
IV, with repeat UD showing decreased com- be at low risk occurred in only 1/21 (5 %).
pliance, resulting in treatment by reimplanta- The prospective trial described by Granberg
tion, CIC, and anticholinergics. The remaining et al. (2011) followed a similar protocol for 71
15 with normal imaging had no adverse newborns (Fig. 16.2): therapy for those with
changes on subsequent imaging. high-risk UD and abnormal imaging versus
During follow-up in both groups, adverse observation in those with low-risk UD regardless
changes were initially diagnosed on the basis of of imaging results:
• Seventeen (24 %) considered high risk had All have a limited evidence basis for the
detrusor overactivity with end filling pressures goals of avoiding acquired renal damage or
>40 cm H2O, of which 12 started CIC and adverse changes in bladder compliance.
anticholinergics, while 5 with normal imaging CIC in newborns and infants, started in
were observed. Of the five that were observed, those with HN and/or VUR with end filling
one developed new SFU grade 2 hydronephro- pressures >40 cm H2O was associated with
sis, while four others remained stable a mean greater fUTI rates than was observed in one
of 9 months later. prospective study.
• Fifty-four (76 %) were considered low risk A Cochrane review of RCTs found no dif-
with normal UD, or having either no detrusor ference in rate or time for onset of symptom-
contraction or detrusor overactivity with end atic UTI based on sterile versus clean
filling pressures <40 cm H2O, observed with catheterization, single versus multiple catheter
renal US every 6 months and repeated UD at use, or coated versus uncoated catheters,
12 and 36 months. Of these, 6 (11 %) con- although participants reported coated cathe-
verted to DLPP over 40 cm H2O at mean of 9 ters were easier to insert and remove.
months later (4–12), with new bilateral SFU 3 Available data for each of three management
HN and bilateral VUR grade 4 in one, and new options are summarized below, but most reports
unilateral VUR grade 4 in another. Two others are retrospective, with long study periods during
who did not have conversion on UD to which treatments might have changed, and end-
increased DLPP >40 cm H2O still had a change points to assess management, specifically avoid-
in imaging, one having new bilateral SFU 2 ance of renal damage and loss of bladder
and 3 HN at 15 months and the other new compliance, are poorly defined and were not sys-
grade 5 VUR at 24 months. tematically determined. As already mentioned,
DMSA scintigraphy to monitor renal function and
scarring has not been routinely obtained. Some
Management from Birth protocols have not included cystography, yet a cor-
to Toilet-Training Age relation between VUR and renal scarring has been
reported similar to the relationship seen in patients
As noted above, “normal” UD have been without neurogenic bladder. Several reports note
reported in up to 33 % of newborns with myel- augmentation rates related to therapy, although
odysplasia. Only one retrospective study indications were not described and there are no
reported likelihood for spontaneous voiding clearly defined UD or clinical parameters for
after toilet training, which occurred in half the enterocystoplasty. Therefore, the level of evidence
children with an initially normal UD. to support any treatment protocol is poor.
Twenty-five percent or less of newborns
with myelodysplasia have UD findings of blad-
der pressures >40 cm H2O. Up to 15 % of those Imaging-Based Observation
thought to be low risk and observed convert to
high risk within 2 years. A retrospective review of new patients with
Therefore, ≥60 % of newborns and infants myelomeningocele evaluated between 1975 and
are not at high risk for renal damage or loss of 2000 identified 184 patients, 83 of which were £6
bladder compliance in the first 3 years of life, months of age and comprised the study group.
based on UD findings of detrusor pressures Initial assessment was renal US and physical
<40 cm H2O. examination to detect urinary retention. Eighteen
Three newborn assessment and manage- (22 %) patients were defined as high risk because
ment options have been proposed: of HN (n = 6 [7 %]) or retention (n = 12 [14 %]).
• Initial evaluation and follow-up with imaging Sixteen of 18 high-risk patients had various inter-
• Universal CIC and anticholinergics ventions (CIC, AC, vesicostomy). Twenty-nine of
• Selective UD-based assessment and treatment 65 (45 %) initial low-risk patients were later con-
sidered high-risk at mean age of 3 years (2 months Urodynamic-Based Selective Therapy

to 12 years), on the basis of f UTI (n = 13), new HN
(n = 5), finding of VUR during assessment for con- The prospective observational study by Sidi et al.
tinence (n = 5) or urinary retention (n = 5). However, (1986) described earlier divided newborns
some of these patients had been started on CIC, with myelodysplasia into high- versus low-risk
presumably for continence, as 4/13 with f UTI categories based on UD (see Fig. 16.1). The end-
were being catheterized. Based on new HN alone, point in this evaluation was imaging deterioration,
5/65 (8 %) initially observed had adverse upper but the authors did not separately describe VUR
tract changes. Renal deterioration defined as failure versus HN. There were no data regarding acquired
of renal growth or renal scar on ultrasound was renal functional loss or scarring, and no follow-up
noted in 2/83 patients, but DMSA imaging was not UD data after the initial newborn assessment.
routinely obtained. The number of children with The prospective trial described above by
UD testing was not stated, and since VCUG was Granberg et al. (2011) followed a similar
not systematically done the prevalence of VUR UD-based risk assessment for 71 consecutive
was not reported (Hopps and Kropp 2003). newborns (see Fig. 16.2). Imaging and UD
changes from initial high- and low-risk designa-
tions are described earlier. Baseline DMSA data
Universal CIC and Anticholinergics were available in 38, also reported above, but
follow-up DMSA results were pending.
A retrospective review reported patients treated Two retrospective studies reported early therapy
on a protocol from 1988 to 2001 that placed all reduced later need for augmentation specifically in
newborns on CIC, AC, and antibiotic prophylaxis patients considered at high risk on UD.
(frequency of CIC and type/dosing of medica- In the first, a chart review identified and com-
tions not stated). Renal US and serum creatinine pared two patient groups thought to have high risk
were obtained at initial assessment, with baseline for renal damage based on initial UD, those with
UD performed at approximately 3 months of age, CIC and AC begun at <1 year of age versus those
and then annually (technique only described as presenting later with similar therapy starting after
“standard 5 channel”). DMSA was obtained for age 4 years. High risk was defined as “positive
suspected renal abnormality on US (number perineal patch EMG activity and narrowing of
obtained not stated). There were 144 total membranous urethra on VCUG (presumably
patients, of which 35 (24 %) had spina bifida representing DSD), detrusor contractions to
occulta. Follow-up was a mean of 81.6 months >30 cm H2O, and/or poor compliance at volumes
(5.4–162.2). Initial renal US was normal in less than expected capacity.” Treatment was CIC
271/288 (94 %) renal units, and showed “mild” every 3 h plus oxybutynin 0.1 mg/kg 3× daily.
or “gross” dilation in 5 and 4. During follow-up, The 46 beginning treatment at age <1 year
repeat renal ultrasonography remained normal in were considered comparable to the 52 with initia-
262 (91 %) renal units, while (new) mild and tion of therapy at age >47 months, with HN in 14
gross dilation were found in 7 and 1, and 10 were (30 %) versus 13 (27 %), bladder trabeculation in
thought to have new renal scarring confirmed 10 (22 %) versus 12 (23 %), VUR in 9 (20 %)
with DMSA in 6 (4 %). Continence outcomes versus 12 (23 %), and “high pressure on cystom-
were reported for 82 children >6 years of age. etry” in 45 (98 %) versus 47 (90 %):
Twenty-two were voiding, indicating universal • There was no difference in response to medi-
CIC was discontinued at some point, 34 (41 %) cal therapy determined by changes in renal US
had undergone augmentation, and presumably (“improvement” in 8/14 [57 %] versus 6/13
the other 26 continued on CIC and AC (Dik et al. [47 %]; persistence in 6 [43 %] versus 7
2006). There was no comparison group without [54 %]).
treatment, and the number of patients not compli- • There was no difference in persistent VUR
ant with therapy was not stated. (2/9 [22 %] versus 5/12 [42 %]).
• Continence, defined as no pads, was similarly 9/17 (53 %) considered high risk on initial UD
achieved in 18/ 46 (39 %) versus 20/54 (38 %). (end filling pressures >40 cm H2O plus HN and/
• The only significant difference was in rate of or VUR) versus 9/54 (17 %) with low-risk UD.
enterocystoplasty, 5/45 (11 %) versus 14/52 These fUTIs were more likely in children on CIC,
(27 %) p < 0.05, which was performed for 10/18 (56 %) CIC versus 8/53 (15 %) being
“recurrent symptomatic UTI, worsening HN, observed, p = 0.001 (Granberg et al. 2011).
or nontolerance to therapy”—none of which Development of symptomatic UTI (positive
was found to be different between groups. urine culture and symptoms) was the primary
Mean age was significantly greater during endpoint of a Cochrane review of RCTs com-
follow-up in the late presenting group (143 ver- paring catheterization techniques (three trials
sus 85 months) (Wu et al. 1997). Since initial and of sterile versus clean, six trials for single ver-
subsequent assessments were similar for all sus multiple use, one comparing standard lubri-
parameters between the two groups, the differ- cant to antibiotic gel) and catheter types (four
ence in augmentation rate may only have indi- trials of coated versus uncoated, two compar-
cated follow-up to an older age in those presenting ing coated versus multiuse uncoated catheters)
after age 4 years versus those beginning therapy in both adults and children. No trials were
as infants. found comparing self versus caregiver cathe-
The second also retrospectively identified terization or comparing catheter cleaning tech-
and assessed two cohorts, but these were all niques. A total of 565 participants were
infants less than 1 year of age considered to be enrolled, with 74 % completing. Key findings
at high risk for bladder deterioration based on included:
initial UD showing DSD and/or high filling
pressures (>30 cm H2O at 75 % predicted capac- Sterile Versus Clean CIC
ity) or high voiding pressures (>80 cm H2O in • No difference in symptomatic UTI.
males and >65 cm H2O in females). Forty-seven • No difference in time to onset of symptomatic
infants observed after testing between 1978 and UTI, with mean times ranging from 1 to 4
1984 did not begin medical therapy until a mean weeks in the three studies.
of 4 years (1–14) were compared to 18 similar
patients after 1985 who had CIC and AC (oxy- Single-Use (Sterile) Versus Multiple-Use
butynin 0.2 mg/kg given 2–4× daily) instituted (Clean)
at less than 1 year of age. Deterioration was • No difference in symptomatic UTI.
defined as incontinence and/or HN ± VUR. • No difference in time to onset of symptomatic
During follow-up, 6/47 (13 %) versus 3/18 UTI.
(17 %) had incontinence; 5/47 (11 %) had HN
and/or VUR versus 0/18; and augmentation was Coated Versus Uncoated Catheters
eventually done in 11/47 (23 %) versus 3/18 • One of four trials reported marginally
(15 %), p = 0.74 (Kaefer et al. 1999). significant fewer UTIs with coated catheters;
Consequently, neither retrospective study three studies found no difference.
demonstrated a difference in objective outcome • Two trials reported participants scored coated
variables based on early versus delayed medical catheters better for insertion, extraction, and
therapy in patients considered to have high- comfort (Moore et al. 2007).
risk UD.
Medical Management
Febrile UTI
Few management studies describe AC dose or
Febrile UTI occurred in 25 % of newborns and interval, clinical or UD efficacy, or discontinu-
infants in one prospective observational study, ation due to side effects.
Initial therapy in infants and children is H2O and resolution or decrease in HN in two with
oxybutynin 0.2 mg/kg/dose given 2–4× daily, resolution or decrease grade VUR in two. Side
with one study reporting reduction in end effects were not described.
filling pressures to <40 cm H2O in all infants Another series of 502 patients with neurogenic
treated. bladder treated at median age 12 years (2 months
One trial reported patients intolerant or to 42 years) prescribed oxybutynin 0.3 mg/kg/
having insufficient response to oxybutynin day in two or three divided doses that was
XL had dose adjustment to a tolerable level increased to a maximum of 0.5 mg/kg/day.
plus either tolterodine LA or solifenacin for Neither response nor side effects were described
two-drug AC therapy. Incontinent episodes (Torre et al. 2011).
decreased and mean bladder capacity Twenty-six consecutive patients, mean age 8
increased, with no patient having side effects years (3–17), had bladder neck sling without aug-
to discontinue treatment. mentation and were managed with oral oxybu-
Systematic review of intravesical oxybutynin tynin 0.2 mg/kg given 3–4× daily, or
reported therapy decreased end filling pres- extended-release 2× daily. Intravesical oxybu-
sures a pooled mean of −16 cm H2O. Intravesical tynin 5 or 10 mg given 2× daily for children and
and oral therapy can also be combined. teens was added to those with side effects or
Systematic review of botox injection in chil- insufficient UD improvement. Eight patients with
dren with neurogenic bladder reported ther- postoperative increased detrusor pressures and/or
apy decreased incontinent episodes and uninhibited contractions had increased AC ther-
detrusor end filling pressures, with effects sus- apy, comprising an increase from 3 to 4× daily in
tained to £6 months. five and addition of intravesical instillation in
three. One patient did not comply, and another
resumed prior dosing due to side effects, with
Oral Anticholinergics subsequent UD showing no change, while the
other six had decreased end filling pressures to
One report described treatment in newborns using <40 cm H2O (Snodgrass et al. 2010).
oral oxybutynin 0.2 mg/kg/dose given 2–4× daily,
with conversion to intravesical oxybutynin (regi-
men not described) for side effects. The number Double Oral Anticholinergic Therapy
of infants treated 2× versus 4× daily, the number
changed to intravesical AC, and the impact of A prospective open label protocol added a second
treatment on UD parameters were not described oral anticholinergic when a first single agent
(Kaefer et al. 1999). failed. The study included 19 children, mean age
The prospective series by Granberg et al. 13.5 ± 3 years, with neurogenic bladder initially
(2011) reported medical management in 71 new- treated with oxybutynin XL (maximum 30 mg).
borns and infants. AC was started in those with Non-responders and those with intolerable side
both end filling pressures >40 cm H2O and HN effects had the oxybutynin reduced to the greatest
and/or VUR using oxybutynin 0.2 mg/kg given dose tolerated and then tolterodine LA (4 mg) or
2–4× daily. Twelve met criteria for therapy after solifenacin (5–10 mg) was added. Mean number
their initial UD and radiologic assessment and of incontinence episodes daily diminished from
another eight initially observed began medical 4.5 ± 2.1 to 0.09 ± 0.5, and mean UD bladder
therapy for increased end filling pressure to capacity increased from 210 ± 98 to 428 ± 159 mL.
>40 cm H2O (two with new unilateral or bilateral Side effects included dry mouth, blurred vision,
grade 4 VUR) or adverse imaging changes with- constipation, and headache in 10/19 (53 %),
out increased pressures (new unilateral grade 5 although the authors stated no patient discontin-
VUR, new bilateral HN grades 2, 3). Subsequent ued therapy during median duration 18 months
UD and imaging demonstrated pressures <40 cm (3–42) (Bolduc et al. 2009).
Intravesical Anticholinergics continence with medical therapy versus

require surgery.
A systematic review found eight studies (two pro- Therapy to achieve social continence begins
spective and six retrospective) concerning intra- around ages 3–4 years in children not already
vesical oxybutynin in children with neurogenic on medical therapy. CIC ± AC are used initially.
bladder. These encompassed 297 children who Patients with persistent incontinence due to
started therapy, of which 66 (27 %) discontinued sphincteric incompetency require outlet sur-
it due to side effects in 28 (9 %) or other causes, gery to achieve continence.
including the inconvenience of crushing pills to Enterocystoplasty increases bladder capac-
create the solution. Mean change in bladder com- ity and compliance, but specific indications
pliance was only reported in two studies, both have not been defined.
+7 cc/cm H2O, while pooled mean change in pres- One prospective analysis of health-related
sure at capacity was −16.4 cm H2O (95 % CI quality of life before and after surgical recon-
−22.8 to −10). Dosing is not standardized, with structions for spina bifida in 31 children and
the eight studies reviewed using a maximum of adolescents reported no significant overall
0.2 mg/kg/day or 20 mg/day (Guerra et al. 2008). changes despite improved continence.
Botox Injections Medical Therapy
One systematic literature review identified six See above.

studies concerning botox injection in children
with neurogenic detrusor overactivity; all were
small open-label trials involving fewer than 26 Surgery for Sphincteric Incompetency
patients with follow-up 12–26 weeks (1–52
weeks). Together these trials enrolled a total of Urine leakage in the absence of a detrusor
108 patients at mean age 9.8 years, with 93 % contraction defines an incompetent urethral
having myelodysplasia. Dose injected varied closure mechanism.
from 5 to12 U/kg, maximum 300 U, injected Surgical options to achieve continence
throughout the dome and base sparing the trig- include implantation of the artificial urinary
one. All reported decreased incontinence, with sphincter, bladder neck revision and/or sling,
>65 % patients dry. Maximum detrusor pressures and bladder neck closure.
also decreased in all studies, while mean bladder The role of enterocystoplasty in these
compliance increased. However, not all these patients is ill-defined.
observations in all studies were statistically
significant. Improvement was noted generally
within 2 weeks of injection, lasting from 2 weeks Definition of Sphincteric Incompetency
to 6 months. Neuromuscular side effects were not
reported. There are no data regarding possible The ICCS (2002) defines an incompetent ure-
injury to the detrusor musculature from repeated thral closure mechanism as one allowing leak-
injections over time (Game et al. 2009). age of urine in the absence of a detrusor
contraction.
Clinical reports of children undergoing
Management for Continence bladder outlet surgery have further charac-
terized sphincter incompetency in children
No longitudinal study has reported how many with neurogenic bladder as having stress
infants with myelodysplasia will be able to incontinence, or incontinence despite CIC and
void voluntarily with continence versus achieve AC with areflexia, a smooth bladder contour,
and open bladder neck on cystography. LMS reduces the bladder outlet diameter by
Reported mean DLPP was £45 cm H2O. 50 % to improve coaptation by sling.
A retrospective series described 36 consecu- A prospective study compared initial and
tive patients with neurogenic bladder, 2 with long-term continence in 37 consecutive patients
exstrophy/epispadias and 1 with cecoureterocele with neurogenic bladder undergoing LMS to 34
as having stress incontinence secondary to prior consecutive patients undergoing sling alone.
intrinsic sphincteric deficiency that was treated Of the entire series, 39/71 (55 %) were male, 44
by bladder neck sling. Mean DLPP was £38 cm (62 %) were ambulatory, and mean age was 8
H2O (range not stated) (Perez et al. 1996). years (3–18), with no differences between the
Another retrospective review concerned 16 two cohorts. Preoperative UD found mean blad-
patients with myelodysplasia and 2 with spinal der capacity of 85 % (28–200 %) predicted capac-
cord injury with incontinence despite CIC, AC, ity by formula age +2 × 30, and mean DLPP
and sympathomimetics. Twelve had SUI, and 15 21 cm H2O (3–50), also similar between the two
demonstrated “reflex incontinence” (not stated if groups. No prior or simultaneous augmentations
this was before or despite AC therapy) with UD were done, and all had a Mitrofanoff procedure.
findings of mean DLPP 23 ± 10 cm H2O and mean There were no differences in outcomes based on
stress leak point pressure 42 ± 19 cm H2O. All gender, age at surgery, or ambulatory versus
had an “incompetent bladder outlet” on cystogra- wheelchair status. Initial continence (dry, no
phy (Austin et al. 2001). pads) determined at 6 months after surgery was
Criteria for sling was defined in a retrospec- significantly different: 29/37 (78 %) LMS versus
tive review of 63 patients with neurogenic blad- 18/34 (53 %) sling, p = 0.04. Kaplan Meier curves
der as DLPP <45 cm H2O, open bladder neck on initially showed dry sling patients to have recur-
cystography, and SUI (Castellan et al. 2005). rent incontinence during follow-up to nearly 100
Sphincter incompetency was diagnosed in two months, leaving fewer than 25 % still dry, versus
additional retrospective series with 89 and 17 no loss of continence in LMS patients after 18
patients as DLPP £30 cm H2O in patients incon- months, with 60 % still dry at maximum follow-
tinent despite CIC and AC (Chrzan et al. 2009; up of 55 months. Postoperative compliance
Salle et al. 1997). changes in these patients are discussed below
A prospective series of 30 children with neu- (Granberg et al. 2011).
rogenic incontinence reported bladder outlet pro-
cedures were done for SUI and/or leakage despite
CIC and AC to achieve areflexia. There were four Sling
with SUI, and DLPP or end filling pressure (in
those without UD leakage) ranged from 8 to Reported dryness after slings ranges from 37
53 cm H2O (mean 22). Cystography in 28 showed to 88 % of children, with similar results in
a smooth bladder; the bladder outlet was not males and females, and augmented versus
described (Snodgrass et al. 2007). non-augmented patients.
Prior or simultaneous augmentation has
been done in less than 10–100 % of patients in
Leadbetter/Mitchell Bladder Neck reported series.
Revision Plus Sling Persistent incontinence after sling was due
to persistent sphincteric incompetency in all
One prospective study found Leadbetter/ series reviewed below.
Mitchell bladder neck revision plus sling A prospective study performed tight 360° rec-
(LMS) had better initial and long-term conti- tus fascial sling with Mitrofanoff and no prior or
nence than did sling alone in both males and simultaneous augmentation in a consecutive
females undergoing bladder outlet surgery series of 30 children (18 males) with neurogenic
without augmentation. bladder at a mean age of 8.6 years (3–17), com-
prising all patients operated during the study mean follow-up of 17 months (8–31). Results did
period for neurogenic outlet insufficiency. With not vary by gender. Nine wet patients were all
mean follow-up 22 months (6–60), 17/30 (57 %) stated to have no change in postoperative DLPP,
were dry, with no differences in outcomes by implying continued sphincteric incompetency
gender, age, or ambulatory status. Postoperative (Perez et al. 1996).
UD found DLPP increased a mean of 12 cm H2O A retrospective series reported outcomes of
(−5 to 42). Five (17 %) without improvement all slings and augmentation in 58 children (15 males)
had persistent outlet incompetency on postopera- with neurogenic bladder operated at a median
tive UD (Snodgrass et al. 2007). Bladder response age of 11.4 years (4–40) and followed postopera-
to outlet surgery without augmentation is dis- tively for a mean of 4 years (1–10). “Complete
cussed below. passive continence” was achieved in 51 (88 %)
Subsequent longer follow-up in these patients (the time point at which this observation was
found new incontinence over time due to recur- made was not stated, nor was loss of continence
rent outlet insufficiency (sling failure), resulting in those previously dry described). Postoperative
in 25 % dryness at 100 months, as mentioned in UD performed in 28 patients found DLPP
the section above (Granberg et al. 2011). increased a mean of 9 cm H2O (0–20). Persistent
Bladder outlet suspension versus 360° tight incontinence was due to persistent outlet incom-
wrap using rectus fascia was reported in a retro- petency in all cases (Castellan et al. 2005).
spective review of 27 children with neurogenic
incontinence. Nineteen (70 %) had simultaneous
augmentation (indications not described). With Artificial Urinary Sphincter
follow-up ranging from a mean of 2–3.5 years, 10
(37 %) were dry, with no difference based on sur- Artificial urinary sphincter (AUS) implanta-
gical technique or augmentation versus no aug- tion achieves continence in approximately
ment. Fourteen that remained completely wet had 60–90 % of patients.
persistent outlet incompetency, including four A stated advantage to AUS is potential to
without augmentation (Barthold et al. 1999). empty without CIC, reported in 20–45 % after
A retrospective study was done in 89 children surgery.
(46 male) undergoing rectus fascial sling at mean Ten-year device survival varies from less
age 10 years (2–14). During follow-up at a mean than 10–80 %, with mechanical revisions
of 6 years (2–14), 42 (47 %) were dry. needed in 25–50 % of patients.
Detrusorraphy was done simultaneously in 59 Reported prior or simultaneous augmenta-
(66 %) and augmentation in 11 (12 %) for capac- tion rates vary from a total of 5–43 %.
ity less than 80 % predicted for age and/or com- AMS 800 was implanted in 35 children with
pliance with filling pressures >20 cm at 70 % neurogenic bladder at mean age 14.4 years (11–
predicted capacity. There were no differences in 18); the indication “sphincteric incompetence”
continence outcomes between those undergoing was not defined. During follow-up a mean of 5.5
only sling versus sling with detrusorraphy or aug- years (5 months to 11 years), dryness was
mentation, or in males versus females (Chrzan achieved in 32 (91 %), with 28 (80 %) using CIC.
et al. 2009). The device was placed at the bladder neck with
Another retrospective study described 39 chil- cuff pressure 61–70 cm H2O. Implantation with-
dren (24 female) with mixed etiology inconti- out augmentation was done for filling pressure
nence (34 myelodysplasia) who underwent rectus <15 cm H2O at 50 % of predicted bladder capac-
fascial sling at mean age 9 years (4–17). Sling ity for age (formula used not stated).
alone was performed in four, with all others hav- Enterocystoplasty was done simultaneously in 13
ing either prior or simultaneous augmentation (37 %). Nine mechanical failures occurred in
(criteria for augmentation not stated). Twenty- seven (20 %) patients, and device removal for
three of 39 (59 %) were dry after surgery with erosion in three (at 2–48 months). In total, 36
devices were implanted into these 35 children, tion (indications not defined) was done in 38
with 32 functioning at the study’s end (Lopez and 19, for a total of 57 (43 %). Dryness for all
Pereira et al. 2006). patients was realized in 115 (86 %) with series
A retrospective study reported outcomes in 30 follow-up at 7 years. One advantage attributed
males with myelodysplasia undergoing AMS 800 to AUS use was postoperative ability to empty
device placement at the bladder neck. Indications without CIC, which was reported in 72 % of
were only defined as incontinence with mean those with neurogenic bladders preoperatively
DLPP 38 mmHg (0–70). Mean age at implanta- and 33 % postoperatively. In contrast to Hafez
tion was 12.6 years (9–19), and with mean fol- et al., mechanical malfunction was reported
low-up 4.7 years, 19 (63 %) were dry, with 22 more often with AMS 742/792 devices versus
(73 %) using CIC. Prior or simultaneous aug- AMS 800 (38/59 [64 %] versus 33/109 [30 %],
mentation was done in four (13 %) for “small p < 0.0001; occurring every 7.6 versus 16
capacity, low compliance or unstable bladders.” patient-years, p = 0.0001). Ten-year device
Mean device survival was 4.7 years (3 months to survival was 62.5 % for AMS 800 (Herndon
15 years), with only four (8 % of originally and et al. 2003).
subsequently implanted devices) functioning
after 8 years. Thirty-two revisions in 17 patients
were done for mechanical failure/malfunction Salle Bladder Neck Repair
(9), reservoir leak (13), erosion (5), infection (6)
or too large a cuff (4) (Spiess et al. 2002). Two retrospective studies reviewed the Salle
A retrospective analysis of results at a postop- bladder neck procedure, including simultane-
erative mean of 12.5 years (5–22) in 79 patients ous augmentation in 50 and 76 %, reporting
(75 myelodysplasia, 5 bladder exstrophy) reported that 61 and 69 % of patients were dry.
that 57 (72 %) were dry for 4 h and 36/63 (57 %) Fistulas shortening the continence mecha-
with an intact device used CIC. The indication nism were reported in one study as occurring
for implantation was incontinence with no detru- in 12 %.
sor overactivity in bladders with “near normal” Difficulty with urethral CIC occurred in 17
capacity and compliance. Simultaneous augmen- and 29 %.
tation was done in four (5 %) patients to achieve The Salle repair creates a midline anterior
these criteria. Age at surgery was a mean of 11.7 bladder wall flap extending cephalad from the
years (5–18). The study period included use of bladder neck, which is sewn to a mucosal strip on
three different AUS models (AMS 742 [3], 792 the floor of the bladder between the ureteral
[41], 800 [35]) but found no outcome differences orifices to lengthen the sphincteric mechanism.
among them. Varying cuff pressures were also A retrospective report of 17 children (7 males)
used (61–70 [36], 71–80 [36], 81–90 [9]) with no with mean age 9 years having mixed-etiology
outcome differences, but reasons for selecting incontinence (13 neurogenic bladder) reported
these were not stated. A functioning device Salle repair with follow-up at a mean of 26
remained in 63/79 (80 %). Device failure required months (9–49) with 9/13 (69 %) dry. Thirteen of
revisions in 18 (23 %) patients, and erosion in 16, 17 (76 %) had simultaneous augmentation. The
including 4/5 with exstrophy, led to device postoperative follow-up protocol was not
removal at a mean of 5.6 years (1–11) (Hafez described, nor was new HN or VUR mentioned.
et al. 2002). UD results and anticholinergic use were not dis-
Another retrospective analysis included 134 cussed. Urethrovesical fistula shortening the con-
patients, of which 107 had neurogenic bladder. tinence mechanism occurred in two, and three
Indications for AUS were not specifically patients had difficulties catheterizing though the
described, except as an option to increase out- repair (Salle et al. 1997).
let resistance. Mean age at implantation was 10 Another retrospective review involved 18 chil-
years (3–39). Prior or simultaneous augmenta- dren (11 males) with neurogenic incontinence
despite CIC and “pharmacologic treatment” oper- bladder neck, with additional injections lateral
ated with Salle repair at median age 7 years and distal to the verumontanum in males. Mean
(3–14), including simultaneous augmentation in injected volume was 3.5 cc per session and 5.7 cc
9 (50 %) and Mitrofanoff procedure in 4. At per patient. One injection was done in 23, with
median follow-up of 2 years (7 months to 3 two or more injections in the remainder, the
years), 11 (61 %) were dry, and 12 (67 %) needed authors noting that three to four injections were
anticholinergics. Four of 14 (29 %) performing only successful in one of four patients. For 20
transurethral CIC had difficulty (Jawaheer and children, treatments were primary, while 24 had
Rangecroft 1999). prior Young-Dees bladder neck repair or a sus-
pension, and 17 (39 %) had prior augmentation.
Postoperative CIC continued per urethra without
Bladder Neck Injection suprapubic drainage. There was no significant
difference in results based on gender, primary
Injection has been done as primary therapy or versus secondary therapy, or augmented versus
for persistent incontinence after sling or blad- non-augmented patients (Guys et al. 2001).
der neck revisions, with prior or simultaneous A retrospective evaluation was reported for
augmentation in 0–39 %. 27 patients with persistent outlet incompetency
Less than 33 % of reported patients became after fascial sling without augmentation at
dry, regardless of gender, primary versus sec- median age 8.5 years who then underwent
ondary treatment, injected volume, injection injection with either Dx/HA (3) or polydimeth-
antegrade versus retrograde, or bladder aug- ylsiloxane (24), performed transurethrally in 16,
mentation or not. antegrade in 8 and both in 3. A single injection
Two studies found second injections suc- was done in 15, with two to three in the remain-
cessful in <10 % of patients undergoing ther- der, using 4–8 cc per injection (mean not stated).
apy after failed sling. At mean follow-up of 8 years (2.4–14), 2 (7 %)
A prospective trial injected Dx/HA in 27 chil- were dry. Repeat injections were not effective
dren with neurogenic bladder (4 after failed (de Vocht et al. 2010).
sling). Augmentation was only described for Twenty-six consecutive children (16 males)
other patients with exstrophy/epispadias. With with neurogenic bladder and persistent outlet
follow-up a mean of 26 months (6–84), 8 (30 %) incompetency after bladder neck sling (n = 17) or
were dry. A maximum of three injection sessions LMS (n = 9) underwent one to two Dx/HA injec-
were used, with mean volume per session of 4 cc tions done antegrade (8), transurethrally (1), or
(1.6–12). All injections were done transurethrally, both (5). None were augmented. Six of 24 (23 %)
in males at the bladder neck and the external with follow-up were dry (Fig. 16.3). Median age
sphincter, whereas in females Dx/HA was was 8.9 years (4.6–17.8). Mean injected volume
injected all along the urethra. A suprapubic cath- was 2.2 cc (1.5–3). Of nine dry after one injec-
eter was used for continuous drainage for 5 days tion, five remained dry at mean 27 months (6–52);
post-injection. The time at which continence was of 14 with a second injection, one remained dry
determined, the number of injections needed and at 39 months. Injected volume, injection method,
duration of continence were not described. Male initial bladder neck surgical technique, and
versus female outcomes were similar for the patient gender did not correlate with outcomes
entire group, which included patients with exstro- (DaJusta et al. 2012, in press).
phy/epispadias (Lottmann et al. 2006).
A study using polydimethylsiloxane in 44
patients (19 males) with neurogenic bladder at Bladder Neck Closure
mean age 13 years (7–17) reported 15 (34 %)
became dry at median follow-up of 28 months Primary bladder neck closure was reported in
(6–53). All were injected transurethrally at the two studies, achieving dryness in 77 and 88 %.
Fig. 16.3 Results of bladder neck injection for incontinence after sling
Closure after failed outlet surgery was reported urgent intervention, while overall stomal com-
in one study with 100 % dryness. plications developed in 17 (33 %), including
Prior or simultaneous augmentation was stenosis in 12 and urinary leakage in 5.
done in 9–81 %, with 9 % developing bladder Re-canalization of the bladder neck was found
perforation in one report. in one (2 %). Bladder stones developed in 7/51
Bladder neck re-canalization was described (14 %) and bladder perforation in 4/44 (9 %)
by two reports occurring in 2 and 23 %. (assuming all occurred following augmenta-
A retrospective review included 52 patients tion) (Bergman et al. 2006).
(23 male) with mixed-etiology incontinence Twenty-one patients with myelodysplasia (15
(36 with myelodysplasia, 3 with sacral agene- males) underwent bladder neck closure as pri-
sis) undergoing bladder neck closure as primary surgical therapy at mean age 8 years (3–16)
mary surgery after failed medical therapy. and had mean follow-up at 20 years (15–23),
Indications were persistent incontinence reporting that 17 (80 %) were dry. Simultaneous
despite CIC and AC in non-ambulatory patients augmentation was done in two (9 %).
with BMI ³ 30 and “low” DLPP (not defined). Re-canalization of the bladder neck occurred in 5
Mean age was 13.9 years (1.5–58). Simultaneous (23 %); stomal complications developed in 15
augmentation was done in 41 (81 %) appar- (68 %), including stenosis in 9 and leakage in 5
ently for “inadequate bladder capacity” (not (Liard et al. 2001).
defined). At mean follow-up 20 months (2–68), Another retrospective review included 17 chil-
44/50 (88 %) were dry with CIC every 3 h. Six dren, mean age 13.5 years, with mixed-etiology
(12 %) developed stomal stenosis requiring incontinence (10 with myelodysplasia); prior
outlet surgery had been done in 12 (71 %). Prior Bladder capacity (and therefore compli-
or simultaneous augmentation was done in 13 ance) can also increase after bladder outlet
(76 %).With mean follow-up of 35 months, all procedures:
patients were dry; difficulty with catheterization • One study with consecutive patients under-
occurred in eight (47 %) (Hoebeke et al. 2000). going sling without augmentation reported
increased bladder capacity ranging from 12
to 437 % (mean 90 %) over preoperative
Bladder Compliance Changes After volume in 65 % of patients. This included
Bladder Neck Surgery 4/5 patients with preoperative capacity
<50 % predicted by age-based formula.
Decreased bladder compliance after the outlet • Mean increase in capacity and compliance
procedures described above could indicate a was also reported in patients undergoing
change in detrusor dynamics in response to AUS without augmentation.
increased outlet resistance, or only represent Therefore, UD bladder capacity cannot be
the true preoperative bladder status previ- used as an indicator for enterocystoplasty, as
ously concealed by leakage. leakage may underestimate true capacity and
No series report findings in studies per- small-capacity bladders may increase in vol-
formed with and without bladder neck occlu- ume following bladder outlet procedures.
sion in patients with outlet incompetency.
Analysis of a prospective cohort of con-
secutive patients undergoing sling or LMS Bladder Compliance Changes After LMS
without augmentation found approximately or Sling Without Augmentation
25 % had postoperative decreased compli-
ance, with all changes diagnosed within the A prospective study analyzed 26 consecutive
first postoperative year and successfully patients undergoing 360° tight sling and having two
treated with increased AC and overnight postoperative UD within 18 months of operation,
continuous catheter drainage. the first a mean of 7 months (3–12) and the last at a
Need for secondary augmentation is unclear mean of 39 months (19–94). Preoperative bladder
given that retrospective reports often do not capacity at pressures <40 cm H2O ranged from 70
state when adverse changes first occurred or to 500 cc, corresponding to 26–120 % predicted
what changes in medical management pre- [based on formula of capacity = (age +2) × 30], with
ceded augmentation: 5 (19 %) having <50 % predicted volume. DLPP
• Two retrospective series of sling without aug- was <40 cm H2O in 24 (92 %). Eight of 26 (31 %)
mentation reported 0 and 5 % of patients. patients had decreased compliance and/or uninhib-
• One report of AUS without augmentation ited contractions on the first postoperative UD man-
having follow-up at 18–48 months stated aged with an increase in anticholinergics. Volumes
that no delayed enterocystoplasties were at last UD versus preoperative UD ranged from −45
done. Other series had secondary augmen- to +437 %, and were decreased in 5, stable in 4, and
tation rates of 3, 32, and 44 %. increased in 17 (65 %). Increased volume ranged
• One report of Dx/HA bladder neck injec- from 12 to 437 %, averaging 90 %, and occurred in
tion noted that 19 % of patients mani- 4/5 with preoperative capacity <50 % predicted by
fested decreased compliance leading to formula. All adverse findings were found on the
augmentation. initial postoperative UD, with no trend towards pro-
As there is no agreed indication for augmen- gressive compliance loss. No patient developed
tation, selection bias is inevitable, both for those new HN, VUR, or bladder trabeculation (Snodgrass
undergoing simultaneous enterocystoplasty et al. 2010).
during bladder outlet procedures and those A subsequent publication from the same institu-
thought to need subsequent augmentation. tion concerned a total of 71 patients (including the
26 described above) after sling versus LMS. “severe detrusor instability and low compliance”
Postoperative compliance changes leading to excluded from study. During follow-up a mini-
increased medical therapy occurred in 16/71 (23 %) mum of 18 months, dryness was achieved in 28
that were all detected less than a year after surgery (64 %). Eight (18 %) used CIC. Preoperative and
on initial UD and that responded to increased postoperative UDs were compared with maxi-
oral anticholinergics (oxybutynin 5 mg 4× daily ± mum follow-up of 48 months (mean and range
intravesical oxybutynin 5−10 mg 2× daily) not stated), finding mean capacity and compli-
and overnight catheter drainage. New HN grades ance for the entire group studied increased. The
2–4 was found on postoperative imaging at any actual numbers of patients with increases versus
time during follow-up in 4/71 (6 %), and new decreases was not stated. HN developed in 2 %
VUR in 10/71 (14 %), grade 1 in 2, grade 2 in 6, and resolved with CIC; new VUR, if any, was not
grade 3 in 1, and grade 4 in 1 patient. Augmentation reported. No patient had augmentation (Churchill
was done in three (4 %), one for loss of compli- et al. 1987).
ance and two others after second opinions for Of 35 patients with neurogenic incontinence
persistent incontinence or pubic pain. There were undergoing AUS described by Lopez Pereira
no differences in these outcomes between sling et al. (2006), 22 (63 %) with detrusor filling pres-
versus LMS, but initial and durable continence sures <15 cm H2O at 50 % of predicted capacity
was significantly greater for LMS (Granberg for age [capacity = (age +2) × 30] did not have
et al. 2011). augmentation. During mean follow-up of 5.5
The review by Chrzan et al. (2009) mentioned years (3 months to 11 years), 7 (32 %) underwent
above included 89 patients undergoing sling, of enterocystoplasty. All were using CIC. The deci-
which 11 had augmentation and 59 detrusorec- sion for augmentation was reached a mean of 3
tomy for preoperative filling pressures >20 cm years postoperatively (1–6) based on poor com-
H2O at <70 % predicted capacity (formula not pliance in patients only described as having
stated). At mean follow-up at 6 years (2–14), incontinence (2) or VUR (5) without clinical
15/19 (79 %) who had sling alone were dry or symptoms. Postoperative medical therapy before
improved (sporadic incontinence, no diapers). augmentation and preoperative and postoperative
Apparently one (5 %) had subsequent augmenta- UD findings were not described.
tion, but indications and attempted medical thera- Similarly, Spiess et al. (2002) reported AUS
pies were not described. Postoperative UD and without augmentation in 27 males with neuro-
imaging findings also were not described. genic continence and bladder capacity “corre-
Austin et al. (2001) also described the above sponding to age,” of which 12 (44 %) underwent
reported sling in 18 patients with neurogenic postoperative augmentation for decreased com-
incontinence, of which 12 (66 %) did not have pliance. Time for this occurrence and use of alter-
augmentation, while 2 had prior and 4 simultane- native treatments (CIC, AC) before proceeding to
ous enterocystoplasty (indications not stated). At augmentation were not described.
mean follow-up of 21 months (6–57), mean com- In contrast, only 3 % of patients in the retro-
pliance (27 ± 10 mL/cm H2O) was unchanged in spective review by Hafez et al. (2002) had post-
the 12 non-augmented children. Imaging changes, AUS augmentation. Of 79 patients (74 with
if any, were not reported. neurogenic incontinence), the bladder preopera-
tively was described as having “near normal com-
pliance and age-adjusted capacity” except for 4
Bladder Compliance Changes After AUS with “poor compliance” who had simultaneous
Without Augmentation augmentation. With follow-up a mean of 12.5
years (5–22), postoperative detrusor overactivity
A retrospective series involved 44 children (35 developed in 13/75 (17 %) not augmented, which
with neurogenic bladder) with AUS and no aug- was managed by AC in 8, spinal cord detethering
mentation, an unknown additional number with in 3, and enterocystoplasty in only 2 (3 %).
Bladder Compliance Changes After with conditions that included myelomeningocele

Bladder Neck Injection (n = 272, 54 %) or other causes of neurogenic
bladder (n = 87, 17 %), and bladder exstrophy
Lottmann et al. (2006) described Deflux bladder (n = 42, 8 %) or other nonneurogenic etiologies
neck injection without augmentation in 27 chil- (n = 99, 20 %). Augmentation used ileum
dren with neurogenic bladder (four after failed (297, 59 %), sigmoid (85, 17 %), cecum/ileoce-
sling). With follow-up a mean of 26 months cum (46, 9 %), ileo-sigmoid (8, 2 %), stomach
(6–84), six (22 %) manifested diminished com- (38, 8 %), stomach/bowel (7, 1 %), ureter (8, 2 %),
pliance following injection, with five undergoing and ureter/ileum (3, 0.6 %) With mean and median
augmentation (interval to change in bladder follow-up of 13 years, 169 (34 %) had complica-
parameters, extent of pressure changes, upper tions specifically related to augmentation, result-
tract changes, or changes in medical therapy used ing in 254 additional operations: 3 (0.6 %)
were not stated) (Lottmann et al. 2006). malignancy with death, 43 (9 %) perforations with
1 death, 16 (3 %) bowel obstructions, 47 (9 %)
repeat augmentation, 75 (15 %) bladder calculi.
Enterocystoplasty Multivariable analysis was not reported to deter-
mine potential contributions of underlying diag-
Bladder augmentation using ileum or colon nosis, segment used for augmentation, Mitrofanoff
segments increases bladder capacity and channel, or bladder neck surgery to likelihood for
compliance. complications (Metcalfe et al. 2006a).
No randomized trial compares ileum versus
colon regarding improvement in compliance
versus complications. Inadequate Bladder Compliance
Potential complications after enterocysto- or Bowel Contractions
plasty include metabolic acidosis, B12 deficiency,
bladder calculi, persistent decreased compli- Systematic postoperative UD assessment has
ance, bladder rupture, and malignancy. not been reported to determine rate or timing
One prospective study reported that colon of changes in neobladder dynamics, including
had greater complication rates than ileum, bowel segment contractions.
and one retrospective study found sigmoid Phasic contractions were found in a retrospec-
augments more likely than other enterocysto- tive review of postoperative UD in 13/29 (45 %)
plasties to rupture. children 1 year after ileo- (n = 22) or colo- (n = 7)
One study reported data obtained on a prospec- cystoplasty. Mean pressure was 35 ± 13 cm H2O.
tive protocol in 86 children undergoing augmenta- Subsequent UD 10–14 years later found
tion for various reasons, including neurogenic these contractions in 11 patients, new in 4 and
bladder in 52 (60 %). Augmentation was done using resolved in 6, occurring in 6/22 (27 %) ileal ver-
ileum (32), colon (30), or stomach (18), and bladder sus 5/7 (71 %) colon augments, p = 0.07. Medical
replacement was done using colon (6) at mean age therapy, if any, was not stated (Lopez Pereira
of 12.5 years (4–21) with follow-up a mean of 8.6 et al. 2009).
years (1–20). Fifty-six of 86 (65 %) had 105 com- In the report by Kispal et al. (2011) described
plications that included 39 (10 %) bladder calculi, 5 above, 3/86 (3 %) bladders were found to have
(6 %) ruptures, 3 (3 %) inadequate bladder compli- decreased capacity, compliance and/or “deterio-
ance, 3 (3 %) premalignant histological changes, rating renal morphology” 3–8 years after colocys-
and 4 (5 %) epididymoorchitis. Overall complica- toplasty (2) or gastrocystoplasty (1), leading to
tions and bladder calculi were more frequent after re-augmentation. Additional clinical information
colocystoplasty (Kispal et al. 2011). regarding symptoms, length of the original bowel
A retrospective review identified 500 augmen- segment, or therapy before re-augmentation was
tations done at mean age 11.8 years for patients not described (Kispal et al. 2011).
Re-augmentation was done in 47/500 (9.4 %) normal values with greater duration of follow-up,
patients reported by Metcalfe et al. (2006a) for especially after 7 years. The study population
decreased compliance with upper tract changes comprised 86 patients with B12 data from >300
or incontinence at a mean time of 7.5 years ileal augments performed. Of these, only 25
(3 months to 23 years) postoperatively. This patients had two levels obtained. In 29 patients
occurred less often after ileal augmentation than tested ³7 years postoperatively, 5 (17 %) had
sigmoid (OR 0.22, 95 % CI 0.089–0.52), gastric low values (defined as £200 pg/mL), without
(OR 0.23, 95 % CI 0.075–0.72), or cecal/ileoce- megaloblastic anemia in any case. Neurologic
cal (OR 0.11, 95 % CI 0.044–0.28) augments examinations were not done, and there were no
(Metcalfe et al. 2006a). control patients or testing for serum homo-
cysteine or methylmalonic acid to determine if
observed low B12 levels were clinically significant
Metabolic Acidosis (Rosenbaum et al. 2008).
Another series of 105 children who had annual
No metabolic acidosis was found in children B12 levels a mean of 50 ± 30 months (2–183) after
with both preoperative and postoperative iliocystoplasty were retrospectively reviewed,
electrolytes and venous blood gases following finding two had decreased values (< 150 pg/mL)
enterocystoplasty. at more than 7 years after surgery. This occurred
Follow-up in the series reported by Lopez in 15 children (13 %) having follow-up ³80
Pereira et al. (2009) included serum electrolytes months. Neither had megaloblastic anemia;
and venous blood gases “at regular intervals.” potential neurologic changes were not sought
With mean postoperative assessment to 11 years, (Blackburn et al. 2010).
only 1/29 (3 %) had metabolic acidosis requiring Oral B12 replacement (250 mg daily) was
alkali therapy, and this patient had metabolic aci- prescribed to 36 asymptomatic children with
dosis before enterocystoplasty. low (<200 pg/dL) or low normal (200–300 pg/
One study retrospectively analyzed preopera- dL) levels. With three monthly levels obtained,
tive and postoperative electrolytes and venous values increased to >300 pg/dL in all patients
blood gases collected by protocol in 71 children with mean follow-up of 4 months (Vanderbrink
with spina bifida after ileal or colonic augmenta- et al. 2010).
tion, reporting no changes to suggest new meta-
bolic acidosis or respiratory compensation during
follow-up a mean of 46.8 months (1–138) (Adams Bladder Calculi
et al. 2010).
Bladder stones develop in approximately
10–25 % of children after augmentation at a
B12 Vitamin Deficiency mean time of ≥4 years.
These calculi occur significantly more often
Two retrospective studies report asymptom- after enterocystoplasty versus gastrocysto-
atic B12 deficiency, without megaloblastic ane- plasty, and during CIC via Mitrofanoff versus
mia, found ≥7 years post-iliocystoplasty in 17 transurethrally.
and 13 % of tested patients. Most are struvite or calcium apatite.
One short-term study found oral B12 Recurrence after treatment is reported in
replacement effective to restore normal levels approximately 33 %, with no difference in
within a mean of 4 months. intact stone removal versus lithotripsy.
One study reported postoperative B12 levels Two reports suggest neither daily nor weekly
in children after iliocystoplasty that used bladder irrigation reduced stone development.
15–20 cm of ileum taken 15 cm from the ileoce- No RCT evaluates impact of irrigation on blad-
cal valve, finding increased likelihood of sub- der stone formation or recurrence.
A retrospective review of 403 children using Another retrospective study involved 105
CIC created four cohorts: transurethral CIC, no patients (myelodysplasia in 41) after augmenta-
augment (227); Mitrofanoff, no augment (18); tion using ileum (37), colon (18), and stomach
transurethral CIC and augment (100); Mitrofanoff (50) with subsequent follow-up a minimum of 1
and augment (58). All augments used sigmoid or year and a median of 8.4 years (2–15) follow-up.
ileum. A total of 28 (7 %) developed stones, but Twelve (11 %) formed bladder calculi, 10/37
mean follow-up intervals were not stated. There (27 %) with ileum, 1/18 (6 %) with colon, and
was no difference in prevalence among the four 1/50 (2 %) with stomach, at a mean time of
groups. Stones formed in augmented patients at 5.2 years (1.4–14). Stones developed in 12/68
a mean of 43 months (3–132), and in non- catheterizing per Mitrofanoff versus 0/37 per
augmented children a mean of 103 months urethra, p = 0.007. Stone analysis reported cal-
(36–204). Recurrence after treatment occurred in cium apatite/struvite (7), ammonium acid urate
9/28 (32 %) at a mean of 23 months. New calculi (4), and calcium phosphate/oxalate (1). Recurrent
formed in 4/6 with lithotripsy versus 6/22 with calculi occurred in 4/12 (33 %) despite recom-
intact removal, p = 0.15. Analysis reported apatite mendations for “high volume” saline irrigation
(11), struvite (10), urate (2), and oxalate (2), with after the first episode (DeFoor et al. 2004).
a foreign-body nidus, hair, or suture in 2 (Barroso Three patient cohorts followed a prospective
et al. 2000). management protocol. Thirty patients without
Bladder stones occurred in 20/86 (23 %) aug- augmentation underwent CIC alone, while
mented children, and recurred after treatment in another 30 patients with augmentation and “con-
ten followed after surgery on a protocol that tinent diversion” (presumably Mitrofanoff pro-
included ultrasonography annually for 4 years cedure) and 30 patients with augmentation alone
and every other year thereafter. Underlying eti- all performed weekly bladder irrigations with
ologies were mixed, with myelodysplasia (43) sterile water (volume not stated). If urine demon-
and exstrophy/epispadias (24) predominating. strated debris, irrigation was done more fre-
Mean time to the first episode was 4 years (5 quently during the week until clear. Etiologies of
months to 13 years). These developed significantly bladder dysfunction were diverse, but neurogenic
more often after colocystoplasty than after ilio- bladder accounted for 38/60 (63 %) augmented
cystoplasty or gastrocystoplasty (29/30, 3/32, children, while need for CIC in the medically
1/18, p = 0.000), and in those catheterizing via a treated group was not defined. Iliocystoplasty
Mitrofanoff versus transurethrally (18/56 versus was done in 57, colocystoplasty in 2, and ure-
2/30, p = 0.007). Irrigation was “strongly recom- terocystoplasty in 1. All patients were followed
mended” but its impact, if any, was not reported >2 years, with mean of 4.7–5.7 years in the three
(Kispal et al. 2011). cohorts. Stones occurred in no patient on CIC
One retrospective evaluation of 500 children alone, versus five (17 %) of those augmented
after augmentation reported bladder calculi with Mitrofanoff and two (7 %) only augmented,
occurred in 75 (15 %), a mean of 5.6 years post- p = 0.053. The occurrence of stones in augmented
operatively. Recurrent stones developed in 28 patients at a similar rate as reported without sys-
(37 %). There were no differences in stone for- tematic irrigation questioned efficacy of the
mation in ileal versus sigmoid augments, but weekly regimen to reduce stone risk (Brough
both enterocystoplasties had a greater rate than et al. 2009).
did gastric augments, with no stones after stom- Lopez Pereira et al. (2009) stated that all
ach and one in a gastric/ileal composite. patients were instructed to irrigate their aug-
Mitrofanoff channel increased risk for stones mented bladder using saline once daily, using
(OR 2.2, 95 % CI 1.3–3.6). There was no differ- 50–100 cc rinsed three to four times. During fol-
ence in recurrence after cystolithotomy versus low-up a mean of 11 years (8–14.5) in 29 chil-
cystolithotripsy (OR 0.30, 95 % CI 0.06–1.5) dren with ileal (22) or sigmoid (7)
(Metcalfe et al. 2006a). enterocystoplasties, 3 (10 %) developed a stone.
Ventriculoperitoneal Shunt Infection A retrospective review of 500 augmentations

or Dysfunction with minimum follow-up of 2 years and mean of
13 years reported that 43 (9 %) patients rup-
Two retrospective studies report shunt com- tured. A total of 54 perforations occurred (two
plications after augmentation, occurring in in nine patients and three in one patient), one-
15 and 20 %. third within 2 years of surgery and another third
A retrospective analysis included 20 children >6 years postoperatively. One patient death
with myelodysplasia and VP shunts with no resulted from sepsis. There was no difference in
revision within 12 months of augmentation, and rupture based on diagnosis (7/42 [17 %] bladder
having at least 12 months follow-up after aug- exstrophy, 31/336 [9 %] spinal dysraphism,
mentation. Three-day mechanical and antibiotic p = 0.167), but sigmoid augments had a 3.5-fold
bowel preparation had been done, and during sur- increased risk (95 % CI [1.63–7.30]) versus
gery the shunt was packed in gauze away from the ilium. Bladder neck surgery also increased risk
operative field. Postoperative parenteral antibiot- (29/105 [28 %] with versus 13/304 [4 %] with-
ics (not described) continued a mean of 9 days, out, p < 0.05; no information in 91) (Metcalfe
and peritoneal drains were used for a mean of et al. 2006b).
16–18 days. VP shunt infection developed in 4 Four of 86 (5 %) children followed a mean of
(20 %) and presented within 12 months with fever. 8.6 years had perforation occurring up to 11 years
Cultures grew Staphylococcus epidermidis or postoperatively, in one secondary to blunt abdom-
gram-negative organisms (Matthews et al. 1996). inal trauma (Kispal et al. 2011).
Another retrospective study reported that 55
patients with VP shunt had bladder augmenta-
tion for neurogenic bladder, with shunt-related Malignancy
complications developing in 8 (15 %) during
mean follow-up of 60 months (12–111): one A prospective assessment at median follow-up
extruded shunt tip through the former suprapu- 27 years after enterocystoplasty found smok-
bic tube site, five distal obstructions, and two ing and immunosuppression (after renal trans-
exteriorized for bladder rupture. Of the five with plantation), but not augmentation, associated
obstructions, one had a pseudocyst diagnosed with increased malignancy risk.
14 months after augmentation, while the other A matched cohort study also found aug-
four had simultaneous proximal shunt malfunc- mentation did not increase malignancy.
tion at 21–63 months after surgery. Patients Markov modeling raised doubts that annual
underwent 1 day preoperative mechanical bowel screening for malignancy using cystoscopy
preparation using GOLYTELY and oral plus and cytology would be cost-effective.
intravenous antibiotics (not described) as well Prospective data were maintained on 153
as intraoperative shunt isolation using antibi- patients after enterocystoplasty for neurogenic
otic-soaked sponges (not described), with no bladder (97), exstrophy (38), and posterior ure-
acute shunt infections (Yerkes et al. 2001). thral valves (18), with minimum follow-up 10
years and median follow-up, 27 (10–53). Seven
(5 %) developed malignancy at a median time of
Bladder Rupture 32 years (22–52); two smokers had transitional
cell carcinoma, two with renal transplant and
Two series reported perforation of the aug- immunosuppressive medications had adenocarci-
mentation in <10 % of patients during follow- nomas of the bowel segment, and three with blad-
up greater than 8 years. der exstrophy had multifocal adenocarcinoma
One stated risk factors included sigmoid within the bladder, which was considered a
augment (versus ileum), and bladder neck disease-specific risk rather than risk secondary to
procedures. augmentation (Husmann and Rathbun 2008).
In a subsequent study, this population was ment (5–8 cm) was used, there was minimal
compared to a matched 1:1 cohort using intermit- change, with a median capacity gain of 0.14-fold
tent catheterization for similar etiologies of blad- and median compliance loss of −0.11-fold.
der dysfunction, reporting that augmentation did Twenty-three of 24 were considered to need
not increase cancer risk (7 [5 %] augmented ver- re-augmentation. In the remaining 40 children,
sus 4 [3 %] controls, p = 0.54), while renal trans- the entire ureter was used. Six of 9 non-refluxing
plantation and immunosuppressive medications megaureters with preoperative distal ureteral
did (3/20 [15 %] on immunosuppressives versus diameter on ultrasound >1.5 cm had median
8/286 [3 %], p = 0.03) (Higuchi et al. 2010). sixfold capacity increase and 50-fold compliance
Four of 119 (3 %) gastrocystoplasty patients increase, versus 3/9 < 1.5 cm with 0.6 and 0.7-
developed adenocarcinoma (3) or poorly differ- fold changes in capacity and compliance that led
entiated transitional cell carcinoma 11–14 years to re-augmentation in all three. Of 31 cases of
postoperatively in a retrospective report combin- refluxing megaureters, ureterocystoplasty was
ing outcomes from two institutions. Three had successful in those whose preoperative UD had
spina bifida, and one had posterior urethral valves. compliance >20 mL/cm H2O, but 21/26 with
None smoked. One used imminuosuppressives <20 mL/cm H2O compliance had re-augmentation.
after renal transplantation. Two had cystoscopy 1 Fifteen of 64 had progressive upper tract dete-
year before tumor diagnosis, showing “severe rioration associated with decreased bladder
wall inflammation without mass” in one. compliance, and ureterocystoplasty was unsuc-
Diagnosis was made during evaluation for new cessful in each (Husmann et al. 2004).
hydronephrosis or gross hematuria (Castellan
et al. 2007).
Markov modeling compared two screening Mitrofanoff Procedures
strategies, including annual cystoscopy and
cytology, for patients with myelodysplasia fol- Appendix Versus Monti
lowing augmentation. Despite using higher than
expected risks of malignancy and “highly opti- Retrospective case series report the need for
mistic” estimates of efficacy of screening, the additional procedures in >20 % of Mitrofanoff
models found annual screening unlikely to be channels from either appendix or reconfigured
cost-effective at willingness to pay thresholds intestine (Monti).
(Kokorowski et al. 2011). The most common complications are stomal
stenosis and incontinence, with Monti seg-
ments also elongating/angulating or forming
Ureterocystoplasty diverticulum.
Bladder stones occur in approximately
One study reported ureterocystoplasty was not 10–25 % of patients after augmentation with
successful when only a distal ureteral segment Mitrofanoff procedures, as discussed above.
was used for augmentation, when a non-refluxing A retrospective review of 169 children fol-
megaureter was <1.5 cm in distal diameter, or lowed a mean of 5.8 years (8 months to 15 years)
when there was compliance <20 cm H2O preop- with Mitrofanoff procedures for a variety of indi-
eratively with a refluxing megaureter. cations (neurogenic bladder in 36 %) reported
A retrospective study combined all patients that 67 (39 %) had at least one surgical revision:
from five institutions undergoing ureterocysto- 18 % stoma revision at skin level, 4 % revision
plasty over a 15-year period, comprising 64 for mucosa prolapse, 8 % revision beneath the
children with neurogenic bladder (46) or poste- fascia, and injection for incontinence in 8 %.
rior urethral valves (18). When a refluxing (n = 8) Event-to-time analysis showed no significant dif-
or non-refluxing (n = 16) distal megaureter seg- ferences for complications related to appendix
versus Monti channel, or umbilical versus lower into bladder versus bowel. Retrospective case
quadrant stoma, with ³65 % of skin stenoses and series suggest similar outcomes with either
incontinence diagnosed within 3 years (Leslie technique.
et al. 2011). A retrospective review concerned Mitrofanoff
Another retrospective review comprised channels (20 appendix and 12 Monti) implanted
Mitrofanoff procedures in 92 patients from 1994 into bowel (colon in 26 and ilium in 6) rather than
to 1999 for several conditions, including neuro- the bladder, reporting follow-up a mean of 26
genic bladder in 21 (23 %). Appendix was used months. Revision was needed in 6/32 (18 %).
in 69 and small bowel Monti in 25 (8 single-seg- Incontinence occurred in four (12.5 %), due to
ment and 17 double-segment joined end-to-end), short Monti tunnel length in three undergoing
with all stomas except one placed in the right or reoperation; three others had stoma stenosis
left lower quadrants. With mean follow-up of 37 (Franc-Guimond and Gonzalez 2006).
months (6.7–65) after appendicovesicostomy and Another retrospective study included 35
25 months (6–66) after Monti, problems with Mitrofanoff procedures done using appendix in
catheterization occurred in 18 (26 %) appendix 21 and ileal Monti in 14. These channels were
channels versus 15 (60 %) with reconfigured implanted into bladder in 24 and intestinal aug-
small bowel, p < 0.001. However, comparison ment in 11 patients (appendix versus Monti not
of surgical revision rates found no significant stated). With mean follow-up 2.8 years (6 months
differences (10/69 versus 5/25, p = 0.7) to 6 years), reoperation was done for difficult
(Narayanaswamy et al. 2001). catheterization (n = 2), urinary leakage (n = 3), or
A review of 56 Mitrofanoff procedures (48 mucosal prolapse (n = 2), with no difference in
appendix, 2 Monti, 6 ureter) performed in asso- outcomes based on implantation in bladder or
ciation with 86 bladder augmentations (53 [62 %] bowel (Boemers et al. 2005).
for neurogenic bladder), reported 16 (29 %)
required surgical revision at a mean time of 6.6
years (1 month to 16 years) postoperatively. Health-Related Quality of Life
Complications included stoma stenosis (n = 4),
incontinence (n = 4), difficulty with CIC (n = 6), Two surveys found bladder reconstructive
and mucosa prolapse (n = 2), all following appen- surgery did not change reported overall health
dicovesicostomy (Kispal et al. 2011). quality of life in patients.
A retrospective evaluation of 199 Monti chan- Parents in one small survey reported their
nels mostly done in children with neurogenic children to have improved health-related qual-
bladder (88 %), reported complications requiring ity of life after surgery.
surgical revision during a mean 28 months One survey found little difference in self-
follow-up. Stoma revisions were done in 16 (8 %), reported health-related quality of life in sling
mostly for stenosis or mucosa prolapse. These patients with and without augmentation.
stomas had been placed at either the umbilicus The Parkin disease-specific health-related qual-
(105, 53 %) or in lower abdominal quadrants. ity of life score was obtained preoperatively and
Channel or bladder-level problems developed in postoperatively in 31 consecutive children and ado-
17 (8.5 %) for elongated and angulated channels lescents undergoing lower tract reconstructions for
or deficient tunnel length (Cain et al. 2008). urinary incontinence secondary to myelodysplasia.
Despite improved continence, overall scores did not
significantly change, although there were significant
Mitrofanoff into Bladder Versus Bowel improvements in independence and emotional
domains. The authors concluded that a single sys-
No randomized trial or cohort study reports tem change in a multisystem disability might be
outcomes of Mitrofanoff channels reimplanted insufficient to change overall scores, and that
improved continence might only improve caregiver

quality of life (MacNeily et al. 2009). Antegrade Continence Enema
In a prospective evaluation of ten children
aged 2–18 years (mean 10) with spina bifida ACE Versus Retrograde Enema
undergoing reconstructive surgery, health-related
quality of life of patients and their parents was Our review found only three studies compar-
separately assessed using the PedsQL 4.0 vali- ing ACE to other bowel managements, includ-
dated health-related quality of life questionnaire ing retrograde enemas. None reported added
both preoperatively and postoperatively. At base- benefit to ACE to achieve fecal continence.
line, children had similar summary scores Two report greater independence with ACE
reported by healthy children except for physical versus retrograde enemas in children.
health and social functioning, which were lower. One reported significantly greater volume
Compared to children with chronic illness, their of tap water for ACE.
summary scores were similar except for physical A multicenter European study retrospectively
functioning, which was lower in patients with reviewed bowel management in 423 children >10
spina bifida. At baseline, parents reported years old (mean 22, 10–47). Three hundred eighty-
significantly lower mean physical and psychoso- two were medically treated with a variety of meth-
cial health and emotional, social, and school ods (digital stimulation, oral laxatives, retrograde
functioning in their children than did parents of enemas), while 47 had ACE and were assessed a
the general population. They also reported lower mean of 3 years postoperatively. Combining “rare”
emotional, social, and school functioning scores and “never” outcomes for soiling, fecal continence
versus parents of children with chronic illnesses. was achieved in 245/382 (64 %) with medical
Postoperatively, children had no significant dif- treatment versus 26/47 (55 %) by ACE, p = 0.3
ferences in summary scores; however, parents (Lemelle et al. 2006).
reported significant improvement in social and Retrospective analysis was done in 80 chil-
school functioning, and psychological social dren with myelodysplasia 5–18 years (mean 13)
health in their children. No demographic or clini- following a treatment algorithm beginning with
cal factors were predictors of health quality of osmotic laxatives, then retrograde water enemas
life in this small sample (Parekh et al. 2006). (self-administered after age 10 years), then ACE,
Another study noted that no validated instru- if unsuccessful. Fecal continence was no soiling,
ment existed to evaluate functional and health achieved in 8 with no treatment, 5/13 (38 %)
status changes after bladder reconstructive sur- using laxatives without enemas, 21/26 (81 %)
gery and so developed a satisfaction question- with retrograde enemas, and 16/20 (80 %) with
naire related to continence, urinary system ACE. Only 12 % using retrograde enemas were
management, and participation in daily activi- independent, versus 50 % following ACE,
ties. Then consecutive patients returning for p = 0.001 (Vande Velde et al. 2007).
follow-up after sling with (n = 18) and without Another retrospective review was done in
(n = 23) augment were analyzed. There were no 25 children with spina bifida, 13 using retro-
differences based on age, gender, ambulatory grade enemas (mean age 8 years, 4–15) and 12
status, or perceived continence between the following ACE (mean age 14 years, 4–23).
two groups. AC use was significantly greater in Those receiving ACE did not first have retro-
the non-augmented patients. Median survey grade enemas, but represented patients under-
scores were the same between groups except going other reconstructive surgery. Warmed
for one question, which asked if patients had tap water was used for irrigation, recommended
“achieved more independence with self- every 2 days but adjusted by families accord-
directed care.” For that question, augmented ing to perceived need (no difference between
patients scored 5 (2–5) versus 4 (1–5), p = 0.02 groups). With mean follow-up at 28 months,
(Snodgrass et al. 2009). fecal continence (no soiling) was 76 % in both
groups. Time to perform enemas was also the A retrospective review included 75 patients,
same at mean 37 min (20–60). Water volume median age 8 years at surgery, 85 % with
was significantly greater for ACE (800 cc spina bifida, assessed at a mean of 3.5 years
[400–1,500] versus 550 cc [300–1,500], (6 months to 11 years). Appendicovesicostomy
p = 0.03). Both had similar abdominal pain dur- was non-imbricated in 67 (51 done laparo-
ing the procedure, 38.5 % retrograde versus scopically) and imbricated in 12 (reasons for dif-
50 % ACE, p = 0.8. Independence performing ferent technique during open surgery not stated).
enemas was greater with ACE, 67 % versus Four not originally imbricated were subsequently
23 %, p = 0.047, in patients who were (three for leakage) and were reported in both cat-
significantly older (Matsuno et al. 2010). egories. Zero of 12 imbricated had leakage, ver-
sus non-imbricated with no leakage (46, 69 %) or
slight leakage £1 episode/month (13, 19 %),
ACE Versus LACE p < 0.001 (Henrichon et al. 2012).
Another retrospective study compared
Systematic literature review found no difference imbricated (n = 34) versus non-imbricated (n = 10)
in fecal continence (approximately 68 %), but ACE in 44 children mostly having anorectal mal-
significantly smaller volume and less toilet time formations; reasons for different surgical man-
(30 versus 50 min) with LACE versus ACE. agement were not explained. In 21 months’ mean
Systematic literature review pooled results follow-up, stomal leakage occurred in 4 (9 %),
from publications between 2002 and 2007 con- p = 0.002 (Lawal et al. 2011).
cerning ACE or LACE: A third retrospective study with 44 consecu-
• LACE, 9 publications reported a total of 93 tive patients having mostly neurogenic bladder
patients at mean age 10 years, 70 % having compared ACE with (n = 25) and without (n = 19)
neuropathic bowel. Mean enema volume was cecal “wrap.” Stomal leakage occurred in six
400 mL (250–600), and mean toilet time was with and zero without at a median 4 months post-
30 min (5–60). Mean follow-up was 15 operatively, p = 0.03 (Koivusalo et al. 2006).
months (1–17) with complete fecal conti-
nence in 72 % achieved at a mean time of 4
months. Bowel Versus Button ACE
• ACE, 16 publications reported 583 patients at
mean age 10 years, 66 % with neuropathic One study found complications requiring
bowel. Mean enema volume was 600 mL reoperation were greater after ACE, but non-
(180–3,000), and mean toilet time was 50 min operative complications were more likely with
(5–60). During follow-up a mean of 29 months a button.
(6–64), complete continence was achieved by Button complications include dislodgement,
81 %; time to continence was not stated. granulation tissue, stool leakage, and infection.
• Enema volume and toilet time were MIC-KEY gastrostomy button was used in
significantly less with LACE, with no differ- 12 children and ACE in another 37 with non-
ence in continence (Sinha et al. 2008). Hirshsprung functional constipation at mean age
10 years. At mean of 18 months, follow-up requir-
ing further surgery only occurred in the ACE
Imbricated Versus Non-imbricated ACE group, in 24 %, with stoma stenosis the most fre-
quent problem occurring in 11 %. Complications
Two retrospective studies reported that cecal not needing surgery were significantly more com-
imbrication of the appendix during ACE mon in the button group (92 % versus 19 %),
significantly reduced stoma leakage, while including stool leakage around the device in
another found significantly greater leakage 42 %, granuloma in 33 %, and pain at the entry
with imbrication. site in 17 % (Cascio et al. 2004).
Button cecostomies (Chait) were performed Eighty-three percent achieved fecal continence
on 69 children at mean age 11 years, 62 % having (no soiling) using a mean of 650 mL (100–1,000)
neuropathic bowel during a 10-year period (Bani-Hani et al. 2008b).
ending in 2007. Tubes were changed annually. Another retrospective analysis stated that
A standardized questionnaire was used before patients were begun on normal saline irrigation
and after insertion. With mean follow-up at 4 and changed to GoLYTELY if not successful.
years, complications developed in 28 (41 %), Of 87 patients using their ACE a median of 61
including tube dislodgement in 9 (13 %), granu- months later, 61 % use GoLYTELY and 31 %
lation tissue in 11 (16 %) or infection at entry site saline (others used tap water). Infusion volume
in 3 (4 %), and pressure sores from the tube in 5 was a mean 850 mL. Success was reported in 66
(7 %). No mention was made of leakage around (76 %) (based on this analysis, but 69 % overall
the tube, nor of patient satisfaction with a tube as discussed below) (Siddiqui et al. 2011).
except to note that overall satisfaction reported
by parents/patients on the questionnaire was 2.7
out of possible 3 (Wong et al. 2008). Long-Term Follow-up
Twenty-nine Chait cecostomies were per-
formed in children mean age 8 years (3–21), Three series with follow-up >5 years reported
mostly having neurogenic bowel or anorectal that 10–45 % of patients no longer use the ACE.
malformation. At review all were at least 1 month Fecal continence ranged from 33 to 70 %.
postoperative, but actual follow-up duration was Consecutive patients who had ACE between
not stated. Two removed the device at 1 and 2.5 1993 and 1999 were contacted for long-term fol-
years when it was no longer needed for stool con- low-up >5 years, with data available in 61 at mean
tinence, leaving 22 with follow-up. Three had age 22 years (15–35) of which 44 % had spina
hypertrophic granulation tissue around the entry bifida. Mean follow-up was 11 years (8–14), and
site, 12 (55 %) had leakage around the tube, and 25 (41 %) reported they no longer used their ACE,
7(32 %) found the button “not very esthetic” 14 (23 %) because it was ineffective and 5 (8 %)
(Becmeur et al. 2008). from complications, including stoma stenosis or
Results of 31 left colon buttons were assessed leakage. Of the 36 still using the ACE, 19 (53 %)
by telephone questionnaire done in 28 at a median reported abdominal pain, with 12 (33 %) rating the
time of 92 months (66–145). Thirteen (46 %) no pain >5 on a visual analog scale of 1–10(very pain-
longer used the device, 7 due to resolution of ful). Ease of use was scored 1–5 (very difficult),
constipation and 6 due to failure. At least 5 had with users rating a median 2. Thirty-two responded
been removed, leaving 23 tubes in place. with information about soiling, with 11 (34 %)
Complications included granulation tissue in six reporting total fecal continence, but of those still
(26 %), leakage in three (13 %), entry site infec- using the ACE, satisfaction scored 1–5 (very) was
tion in one (4 %), and bleeding in one (4 %) 4.1 (overall satisfaction including all 61 patients
(Blackburn et al. 2012). was not reported) (YardLey et al. 2009).
Retrospective chart review was done in 117
patients with ACE, 45 % neuropathic bowel, and
Enema Fluid and Volume median follow-up in 105 of 61 months (mean 68,
7–178). Seventy-two (69 %) had “success,”
Tap water, saline, and GoLYTELY solutions defined as £1 soiling episode/weekly, while 12
have similar results. (11 %) no longer used the ACE. Ninety-three
A retrospective review reported outcomes of a percent had initial success, with late failures
treatment algorithm used in 236 children with occurring a mean of 88 months later (99 months
neurogenic bowel following ACE. Tap water was in spina bifida patients), with reasons for late fail-
instilled beginning with 50 mL nightly, increas- ure not stated. Mean toilet time was 50 min (10–
ing by 50 mL every 3 days until continence. 180) (Siddiqui et al. 2011).
The review by Blackburn et al. (2012) appendix, and had follow-up to a mean of 2.5
described above included 31 children, 19 % with years (2 months to 6 years). Complications
spina bifida, who had left-sided ACE buttons at occurred in seven (17 %), including stoma steno-
median age 7 years (2–17). At median follow-up sis in six, and abscess in one (Webb et al. 1998).
of 92 months (66–145), 28 were reached for tele- Malone reviewed his results in 31 children,
phone questionnaire. Thirteen (46 %) no longer 37 % with neuropathic bowel, operated at a mean
used the device, 7 due to resolution of constipa- age of 8 years (1–18) and with mean follow-up of
tion and 6 due to failure. Of 15 continuing use, 3 years (1–6). Appendix was used in 84 %.
median toilet time was 25 min and 10 (67 %) Complications included stoma stenosis in 17
reported no soiling. (55 %), channel fibrosis in 2 (6 %), and pain dur-
ing irrigation in 18 (58 %). In addition, there
were three (10 %) who developed phosphate tox-
Complications icity from its instillation (Curry et al. 1998).
Patients reported by YardLey et al. (2009)
The most common anatomic complications described above with follow-up over 5 years
are stoma stenosis (15–50 %) and stoma leak- reported that abdominal pain with irrigation (fluid
age (3–35 %). not stated, an earlier publication indicated phos-
Stoma infection was reported in one series phate enemas) persisted and was rated five out of
occurring in 25 % of patients at a mean of 14 a possible ten on a visual analog scale.
months. Review of 29 patients with spina bifida who
Pain during irrigation has been reported in underwent ACE at mean age 9 years and were
several series, occurring in from 17 % to over followed a mean of 4 years (4 months to 7 years)
50 %, but not mentioned by others. Severity reported abdominal pain with irrigation in 21
has been described as mild to severe. Pain was (72 %), described as “severe” in 6 (23 %).
reported in patients using phosphate, saline, “Standard saline and phosphate enemas” were
or tap water enemas. used (Kim et al. 2009).
Retrospective review included 236 patients The retrospective comparison between retro-
with neurogenic bowel and ³6-month follow-up grade enemas and ACE by Matsuno et al. (2010)
(median 50). Appendix was used in 86 %, with mentioned above, in which tap water was used
cecal imbrications, and the stoma was umbilical in for irrigations, found that at 28 months mean
46 % or lower quadrant in 54 %. Other technical follow-up 44 % noted abdominal pain, with no
details, including means of stoma creation, were difference between groups. Severity of pain was
not described. Apparently all were ACE. Of these, not described.
39 (17 %) had revisions for stomal stenosis (32, Another review included 18 patients operated
14 %), stoma leakage (7, 3 %), and channel fibrosis at mean age 13 years, 94 % having neuropathic
(7, 3 %). Channel obliteration occurred significantly bowel. All have LACE, and used either saline
more often in patients with colon flaps or cecal or tap water irrigations. At mean follow-up of
lengthening procedures (Bani-Hani et al. 2008a). 2 years, three (17 %) noted “mild cramping pain or
Another retrospective study with 117 patients nausea” during instillation (Churchill et al. 2003).
(45 % neuropathic bowel) stated that 63 % had
complications during median follow-up of 61
months. Appendix was used in 83 %. Stoma Health-Related Quality of Life
stenosis developed in 44 (38 %) at a mean of 8
months, stoma leakage in 41 (35 %) at a mean of Quality of life surveys following ACE proce-
19 months, and stoma infection in 29 (25 %) at dures generally report improved self-esteem
mean of 14 months (Siddiqui et al. 2011). and independence.
Forty-two patients, mean age 12 years, with The FICQOL (fecal continence and constipa-
spina bifida had ACE procedures, 93 % using tion quality of life) instrument was used to evaluate
23 patients with spina bifida, 23 before and 18 fol- One report stated detrusor overactivity
lowing ACE (5 did not respond). Median age at potentially resolved after detethering, while
surgery was 11 years, and post-surgical survey decreased compliance did not improve.
was done at ³6 months. Soiling decreased from 4 The retrospective review by Macejko et al.
to 0.3 episodes per week, but total time for bowel (2007) described above analyzed all cases of teth-
care remained a constant 45 min. Both patient and ered cord release during a 7-year period to identify
caretaker anxiety regarding soiling significantly infants and children <3 years of age with a primary
reduced (Ok and Kurzrock 2011). tethered cord. UD was obtained in 69/79 patients
Psychosocial functioning and mental health before neurosurgery was done at mean age 10
were assessed preoperatively and at 6 and 16 months months, and was considered normal in 30 (55 %),
following ACE in 20 children mean age 11 years with varying findings in the remainder (overactivity,
with spina bifida, using a structured clinical inter- “hypotonia,” DSD, poor compliance, high voiding
view and three validated questionnaires. Responses pressures). Mean follow-up after tethered cord
were compared to a control group of 20 children release was 5 years (6 months to 11 years), with 49
median age 14 years of age chosen at random from (62 %) described as having no urologic problems,
an epidemiologic study of mental health. Mean toi- 6/43 (14 %) having “delayed toilet training,” and
let time was 50 min. Nineteen reported improved 6/79 (8 %) children requiring CIC. Normal preop-
self-reliance, and 16 (80 %) reported fecal conti- erative UD remained normal in 18/28 (64 %) and
nence or rare soiling. There were significant differ- became abnormal in 10 (36 %) patients having
ences in patients versus controls, with parents of both studies. Abnormal preoperative UD became
patients reporting more behavioral and emotional normal in 8/22 (36 %) and remained abnormal in
problems and patients lower self-esteem. 14 (63 %) having both studies. In total, abnormal
Postoperative patient scores indicated significantly postoperative UDs were found in 24/50 (48 %)
improved self-esteem and close friend ratings that studies (Macejko et al. 2007).
were similar to controls (Aksnes et al. 2002). Nogueira et al. (2004) reported outcomes from
Twenty-five patients who had ACE at mean age tethered cord release in 19 patients at mean age 8
11 years (6–17), 66 % neuropathic bowel, were que- years (8 months to 14 years) diagnosed because
ried by telephone using a quality-of-life instrument of orthopedic anomalies, of which 7 had postop-
6 months to 9 years later (mean not stated). Seven erative UD showing resolution of preoperative
(28 %) were no longer using the ACE due to stomal detrusor overactivity in 2 of 3 and new onset of
complications or perforations in five and two who overactivity in 1. Of 16 patients diagnosed at an
“did not like the idea of it.” Sixteen (64 %) reported earlier age because of cutaneous lesions (mean 1
fecal continence. Mean toilet time was 45 min, year, 1 month to 11 years), postoperative UD in 9
maximum was 90 min, with 8 (32 %) stating the indicated that all 4 with preoperative detrusor
procedure required more than 1 h. Quality of life overactivity had resolution.
was significantly improved from preoperative scor- A third retrospective review included 24
ing, mean 6 (2–9) versus 11.5 (5–14) on a maxi- patients diagnosed with tethered cord, presenting
mum 14-point scale, p < 0.001 (Tiryaki et al. 2010). at median age 6 years (1 month to 12 years) and
undergoing preoperative and postoperative UD (at
mean of 6 months). Seven of 14 toilet-trained
Urologic Outcomes of Surgery were incontinent. Preoperative UD was abnormal
for Tethered Cord in 21(91 %): 17 with detrusor overactivity, and 4
with decreased compliance. Postoperative UD
Primary Tethered Cord showed detrusor overactivity resolved in 10/17;
those with decreased compliance did not improve.
Several retrospective series indicate that nor- Two of 3 with normal preoperative UD had
mal preoperative UD can become abnormal adverse changes postoperatively, one with detru-
after detethering, and that abnormal preop- sor overactivity and the other with decreased com-
erative UD can improve. pliance. Of all 24 patients, postoperative UD was
abnormal in 14. Of the seven with preoperative Bani-Hani AH, Cain MP, Kaefer M, Meldrum KK, King
incontinence, six became continent, and no patient S, Johnson CS, et al. The Malone antegrade continence
enema: single institutional review. J Urol. 2008a;180(3):
had new incontinence (Guerra et al. 2006). 1106–10.
Bani-Hani AH, Cain MP, King S, Rink RC. Tap water irri-
gation and additives to optimize success with the
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University algorithm. J Urol. 2008b;180(4 Suppl):
1757–60. discussion 60.
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with symptomatic tethered cord (flexion contrac- wrap procedures for the treatment of neurogenic
tures, urinary incontinence, UTI) after myelom- sphincteric incontinence. J Urol. 1999;161(1):272–4.
eningocele repair, representing 2.8 % of 1,435 Becmeur F, Demarche M, Lacreuse I, Molinaro F,
Kauffmann I, Moog R, et al. Cecostomy button for
myelodysplastic patients followed. Tethered cord antegrade enemas: survey of 29 patients. J Pediatr
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intractable urinary incontinence in patients with neu-
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Urolithiasis
17
Linda A. Baker and Nicol C. Bush
The initial aim in stone management is relief • Unlike adults, lower pole stones in children
of symptoms. are as effectively treated by SWL as those
Secondary aims: in other renal locations.
1. Achieve stone-free status. • One trial compared monotherapy percuta-
2. Reduce or prevent stone recurrence. neous nephrolithotomy (PCNL) to SWL for
Summary of evidence for these aims: renal stones 1–2 cm, finding stone-free rates
• The most common presenting complaint is greater with PCNL, 95 % versus 85 %.
abdominal pain. Our review found no study • One trial found no difference in stone recur-
evaluating medical therapy to control acute rence in those stone-free versus having
renal colic in children. fragments <5 mm after SWL.
• Although studies in adults conclude that • Recurrence after stone-free status occurred
alpha-blockers promote spontaneous stone in £10–33 % of patients. One study reported
passage, evidence in children is not significantly fewer recurrences with potas-
conclusive. sium citrate therapy.
• Two studies reported spontaneous stone • Low-sodium high-potassium diet resolved
passage in 34 and 47 % of children. hypercalciuria in 50 % of children, but was
• Reported stone-free rates for renal stones difficult to maintain.
<1 cm were 63–86 % for shock wave litho- • Indications and duration of medical ther-
tripsy (SWL) and 50–90 % for ureteroscopy. apy with potassium citrate or thiazides are
Efficiency quotients (EQ) were only reported not defined for children.
for SWL, with approximately 25 % needing • Our review found no study evaluating stone
additional procedures. However, at least a recurrence rates in children with versus with-
third of patients undergoing ureteroscopy out 24-h urine stone-risk profile determina-
needed a period of stenting to dilate the ure- tions in first-time pediatric stone formers.
ter before the stone could be accessed, and
most had postoperative stents, meaning
some had as many as three procedures to Medical Evaluation
achieve stone-free status.
Clinical Presentation
L.A. Baker, M.D. (*) • N.C. Bush, M.D., M.S.C.S.
Department of Pediatric Urology, University of Texas Four retrospective studies reported that pain
was the most common chief complaint.
Center Dallas,1935 Medical District Drive, MS F4.04,
Dallas, TX 75235, USA Hematuria and UTI were other common pre-
e-mail: linda.baker@childrens.com senting complaints of pediatric stones.
260 L.A. Baker and N.C. Bush
Two studies found younger children more 25 %. Chief complaint was flank pain in 63 %,
likely to have renal stones versus ureteral with 49 % having nausea/vomiting, 18 % gross
stones in older patients. hematuria, 10 % lower tract symptoms, and 4 %
Two studies reported spontaneous stone pas- UTI. The diagnosis was “incidental” in 21 %.
sage in 34 % (renal and ureteral) and 47 %. UPJO was found in four (6 %). Spontaneous pas-
Most stones analyzed in children were cal- sage occurred in 47 %, with stones a mean diam-
cium oxalate or phosphate. eter of 4 mm; 35 % had surgical intervention, and
One hundred and twenty-six consecutive chil- 18 % continued with their stone. Of 42 stones
dren referred to a Turkish urology department analyzed, 93 % were calcium oxalate or phos-
with urinary stones were divided into two cohorts phate. During follow-up at a mean of 1.5 years,
based on age at presentation, 48 (58 % male) stones recurred in 21 % of 70 patients (excluding
aged 0–5 years and 78 (63 % male) aged 6–15 two with cystinuria) (Kit et al. 2008).
years. At presentation, kidney/ureteral stone per- Clinical symptoms were described for 197
centages were 65 %/35 % in younger and children (54 % males), mean age 9 ± 4 years,
38 %/62 % in older patients, p = 0.006 (Koyuncu evaluated in a pediatric nephrology unit lacking
et al. 2011). emergency services. Recurrent abdominal pain
A retrospective review identified 80 US chil- was the most common chief complaint in 17 %,
dren (46 % males) evaluated with stones during a acute abdominal pain in 6 %, dysuria in 6 %,
7-year period ending in 2007, 39 <10 years and microscopic hematuria in 6 %, and gross hematu-
41 >10 years of age at presentation. There was no ria in 4 %; the remainder had various combina-
age difference in the chief complaint, which was tions of these (Polito et al. 2012).
pain in 62.5 %, hematuria in 10 %, and UTI in
12.5 %. Stone location was renal in 57 % versus
31 % of younger versus older children, p = 0.02. Prevalence of Metabolic
Mean renal stone size was 7 mm (1–22) in both Abnormalities
groups. Spontaneous passage of these renal
stones occurred in 32 % and 0 % of younger and Stone Formers
older children. Ureteral stones were more com-
mon in those >10 years old, with no differences Two prospective studies evaluating consecu-
by age in stone size, 7 mm versus 5 mm (1–17), tive children with stones reported widely
or spontaneous passage rate of 42 %. Overall divergent results of urine stone risk profiles:
spontaneous passage rate (renal and ureteral one found metabolic abnormalities in 43 % of
stones) was 34 %. During follow-up a mean of 36 stone formers, mostly hypocitraturia, while
months (2–17), new stones occurred in 16 %, the other found 81 % had abnormalities,
with no age difference. There were no differences mostly hypercalciuria.
in stone composition between 17/39 (44 %) and Prospective data were collected in the 126
16/41 (39 %) analyzed in the two age groups, consecutive Turkish children with urinary stones
with 85 % calcium oxalate and 48 % containing reported by Koyuncu et al. (2011) mentioned
calcium phosphate. There were no differences in above, including two to three 24-h urine stone
metabolic assessments done in 59 % and 46 % of risk profiles. Children were divided into two
younger versus older children, with hypercalciu- cohorts based on age at presentation, 48 (58 %
ria in 33 % and hypocitraturia in 62 % (Kalorin male) aged 0–5 years and 78 (63 % male) aged
et al. 2009). 6–15 years. Metabolic evaluation of calcium, cit-
Retrospective review found 72 children (56 % rate, and oxalate reported no significant differ-
males), mean age 11 years, who presented with ences in abnormalities based on age group, 50 %
first known stone disease to a tertiary children’s versus 38 %, for a total of 43 %, but other risk
hospital in Canada over a 5-year period ending in factors, such as low urine volume, cystine, and
2004. Family history was positive for stones in magnesium, were not reported. These comprised
17 Urolithiasis 261
10 % hypercalciuria, 12 % hyperoxaluria, 24 % metabolic evaluation was variable, as reflected

hypocitraturia (Koyuncu et al. 2011). below. Presenting symptoms were pain (47 %),
Prospective 24-h urine stone risk profile data hematuria (33 %), and infection (11 %). Infection-
were recorded in 197 children (54 % males), related stones were diagnosed in 41 (19 %),
mean age 9 ± 4 years, evaluated in an Italian pedi- including 6 patients with bladder stones after
atric nephrology unit by Polito et al. (2012) exstrophy repair. Ten patients had urinary diver-
reported above. Of these, 38 (19 %) had normal sion. Thirty-seven percent of children had a posi-
profiles. There was a positive family history in tive family history for stones.
77 %. Three 24-h urine collections were per- • 49/145 (34 %) Hypercalciuria
formed at home, and highest values were used to • 25/124 (20 %) Hyperoxaluria
classify defects in the 81 % with abnormalities: • 11/32 (34 %) Cystinuria
• 48 % Hypercalciuria • 8/96 (8 %) Hyperuricosuria
• 7 % Hyperoxaluria • 5/54 (9 %) Hypocitraturia (Milliner and
• 4 % Hypocitraturia Murphy 1993)
• 19 % Hyperuricosuria
• 4 % Cystinuria
Another study evaluated 112 children (54 % Stone Formers Versus Controls
males), mean age 4 years (1 month–18 years),
with stones referred to a Turkish pediatric neph- One study showed higher urine calcium and
rology department. Positive family history was super saturation indices in pediatric stone
reported in 55 %. Stones were located in the kid- formers compared to their non-stone-forming
ney in 94 %, ureter in 2 %, and both in 4 %, with siblings and healthy controls, with no differ-
23 % having multiple stones bilaterally. Metabolic ence in other parameters. Two studies com-
evaluation reported abnormalities in 92 %: paring stone formers to controls reported
• 38 % Hypercalciuria patients had significantly increased urinary
• 42 % Hyperoxaluria calcium and oxalate and significantly lower
• 49 % Hypocitraturia urinary citrate. A third study found calcium
• 18 % Hyperuricosuria excretion similar but oxalate higher and cit-
• 4 % Cystinuria rate lower in patients.
More than one risk factor was seen in 22 A study of 129 stone formers (6–17 years)
(20 %) (Gurgoze and Sari 2011). versus 105 non-stone-forming siblings and 183
Retrospective review was done in 104 children healthy children without family history of stones
(53 % males) presenting to a pediatric nephrol- was performed. The stone formers had higher
ogy clinic with stones in Turkey. Metabolic fac- urine calcium excretion (calcium >200 mg versus
tors were analyzed by either two 24-h urine 170 mg versus 140 mg/1.73 m2 in stone formers,
collections or spot urine sampling (percentages siblings, and controls). They also had higher cal-
of each not provided). Fifty percent had a posi- cium super-saturation indices, but similar levels
tive family history. Reported urine abnormalities of hyperoxaluria, hypocitraturia, low urine vol-
were found in 87 %, and included: ume, and abnormal pH (Bergsland et al. 2012).
• 31 % Hypercalciuria A cross-sectional study compared 24-h urine
• 30 % Hyperoxaluria stone risk profiles in 142 children (46 % males),
• 38 % Hypocitraturia median age 14 years (3–18), with newly diag-
• 24 % Hyperuricosuria nosed stones to 210 children, median age 15
• 6 % Citraturia (Alpay et al. 2009) years (3–18), without stones (source of con-
Retrospective review of 221 consecutive chil- trols not described). Stone formers had
dren (108 males, mean 11 years) referred to the significantly increased calcium and oxalate
Mayo clinic for stone evaluation demonstrated and significantly lower citrate than controls
metabolic abnormalities in 42 %; however, 24-h (Spivacow et al. 2008).
A 24-h urine metabolic evaluation was done in recurrence rate in children with versus those
78 stone formers and 24 controls (source not without metabolic abnormalities (50 % versus
described) with similar gender and a mean age of 14 %, p < 0.0001) with average follow-up of 43
7 years. Of patients, 42 % had multiple stones, months.
19 % bilateral stones, and 5 % staghorn stones; A retrospective study analyzed two cohorts,
57 (73 %) were evaluated after a first stone, and children with a single stone at presentation and no
the others had recurrent stones (frequency not recurrence (n = 88) and those with either multiple
stated). Median citrate was lower and median stones at presentation and/or recurrent stone
oxalate higher in stone formers versus controls, (n = 51). Mean age (13 years) and gender were sim-
while calcium excretion was similar. Multivariable ilar, as was follow-up a mean of approximately 3
analysis found only hypocitraturia an indepen- years. The 24-h urine stone risk profiles demon-
dent risk factor for stones (Tekin et al. 2000). strated significantly greater prevalence of hypercal-
A tertiary Scottish referral clinic recruited 24 ciuria (73 % versus 57 %, p = 0.02) and hypocitraturia
stone-formers (62 % males), median age 10 (30 % versus 13 %, p = 0.003) in multiple/recurrent
years (1–17), and 32 controls (41 % males), stone patients (DeFoor et al. 2010).
median age 7 years (1–15), for analysis of The study by Tekin et al. (2000) described
random urine samples tested for creatinine, above included 78 children categorized as first-
calcium, oxalate, urate, citrate, and glycosamin- time stone formers (n = 57, 73 %) or recurrent
oglycans (GAGs). There was no difference in stone formers (frequency not defined). In contrast
ages between stone patients and controls. to DeFoor et al. (2010) above, patients with mul-
Compared to controls, stone formers had tiple stones at presentation were not classified as
significantly lower citrate and significantly recurrent. Multivariable analysis did not find any
higher calcium excretion, as well as higher difference in metabolic defects.
promoter–inhibitor ratios (calcium × oxalate/
citrate × GAGs). Control males and females
showed no differences in parameters. Controls Pediatric Versus Adult Stone Formers
showed significant inverse correlations between
age and all urinary constituents tested expressed One study comparing children mean age 9
as ratios to calcium (MacDougall et al. 2010). years to adults mean age 42 years found most
stones in both age groups were calcium oxalate,
but children were more likely to have hypoci-
Solitary Versus Recurrent Stone traturia versus adults who more likely had
Formers hypercalciuria.
The 24-h urine stone risk profiles were ana-
One study found children with hypocitraturia, lyzed in 71 children (59 % male), mean age 9
hyperoxaluria, and/or hypercalciuria were years (1–14), and 285 adult (59 % male) stone
more likely to have stone recurrence versus formers, mean age 42 years (14–71). Mean stone
children without these risk factors. frequency was 2 (1–4) in children versus 3 (2–8)
One study reported patients with multiple in adults; stones analyzed in 63 and 44 % of
or recurrent stones had significantly greater patients were calcium oxalate in 84 % of children
prevalence of hypercalciuria and hypocitratu- and 75 % of adults. Metabolic factor analysis was
ria than those with a single stone and no abnormal in 90 % of patients in both groups, but
recurrence. with hypocitraturia significantly more often in
Another found no difference in urine risk children (58 % versus 45 %, p = 0.046), and
factors between first-time stone formers and hypercalciuria significantly more often in adults
those with recurrent stones. (51 % versus 27 %, p < 0.01) and no differences
The prospective study by Koyuncu et al. in hyperoxaluria or hyperuricosuria (Karabacak
(2011) described above demonstrated a higher et al. 2010).
17 Urolithiasis 263
Risk for Urolithiasis in Children hypercalciuria. Seventy-four percent of these had

with Hypercalciuria a positive family history for stones. Hypercalciuria
was categorized as renal leak in 33 %, absorptive
Three studies reported onset of urolithiasis in in 41 %, and uncertain in 26 %. All had US at
children diagnosed with hypercalciuria because diagnosis and annually. During follow-up at a
of abdominal pain, hematuria, dysuria, or mean of 3 years (1–6), 16 % developed a stone,
voiding dysfunctions. During 3–7 years of fol- not associated with subtype of hypercalciuria
low-up, stones were diagnosed in 4–16 %. (Garcia et al. 1991).
One study included 104 children without
known urolithiasis who were diagnosed with
hypercalciuria on the basis of abdominal pain, Hypercalciuria and Bone Density
gross or microscopic hematuria, or various void-
ing symptoms as discussed below (Tabel and Mir Two studies found decreased bone mineral
2006). Patients were treated with a diet that density (BMD) in 32–47 % of children with
included sodium restriction, which most did not hypercalciuria ± stones.
comply with, and followed for a mean of 4 years A retrospective chart review was done to
(6 months to 16 years). Systematic renal imaging indentify 98 children with hypercalciuria ± uro-
was not described. A total of seven stones devel- lithiasis (61 without and 37 with stones). BMD
oped in 103 (7 %) treated with diet changes. was obtained in all cases, finding a Z score <−1 in
Another searched a database to identify 94 chil- 47 %, and <−2 in 25 %, numbers representing
dren diagnosed with hypercalciuria without uro- bone density that is >1 and >2 SD below healthy
lithiasis, of which 50 were randomly selected for age, gender, and race-matched controls, respec-
follow-up assessment; 33 (42 % males) with mean tively. Mean BMD for children with normal
age 12 years (8–17) agreed to the follow-up. This scores was 0.4 ± 1.3 versus −2.3 ± 1 for those with
secondary evaluation was done a mean of 7 years low bone density. There were no significant dif-
(4–11) after initial diagnosis, which was made sec- ferences between those with normal versus low
ondary to dysuria/frequency (55 %), incontinence/ BMD in patient age (mean 9 ± 3 years), gender, or
enuresis (18 %), abdominal/flank pain (15 %), and calcium excretion. Stone patients had significantly
hematuria (48 %). Calcium–creatinine ratio was lower bone density scores and a higher percent-
mean 0.32 (0.22–0.45) with 24-h excretion mea- age of Z scores <−2 (Schwaderer et al. 2008).
sured in 22 (67 %) between 4.5 and 9 mg/kg/day. BMD was determined in 88 children (57 %
Initially, renal US showed only two with “mini- male), median age 9 years (2–18), with hypercal-
mal” renal calcifications; no imaging was done in ciuria (three samples with >4 mg/kg/day) versus
seven (21 %). Therapy included increased fluids, 29 normal controls (siblings of the patients but
salt restriction, RDA of calcium and protein; eight without hypercalciuria). Hypercalciuric patients
(24 %) were also prescribed thiazides. At follow- included 49 (56 %) stone formers. There were no
up at 7 years, 21 % still had symptoms considered differences in the groups by gender, age, BMI, or
minor. None continued on medication, and 63 % bone age, but BMD Z scores were significantly
ate an unrestricted diet; the others followed a less in hypercalciuric patients (−0.7, −2.2 to 1.7
“somewhat” salt-reduced and/or low calcium diet. versus 0.0, −0.9 to 1.7), p < 0.001. Thirty-two per-
Only three (9 %) continued high fluid intake. cent of patients had osteopenia (Z score <−2) at
Repeated urine samples showed 48 % to be hyper- diagnosis of hypercalciuria (Penido et al. 2003).
calciuric and 51 % normocalciuric. US was done
in 23 (70 %), finding only one (4 %) “small” renal
calcification. None had symptomatic urolithiasis Hypercalciuria and UTI
(Alon and Berenbom 2000).
A third study of children with hematuria One study reported hypercalciuria in 43 % of
found 58 (71 % male), mean age 8 years, with children mean age 8 years with recurrent UTI.
A prospective study was designed to evaluate

the possible relationship between recurrent UTI Medical Management
and hypercalciuria in 75 children >5 years of age
(mean 8 years). The mean of ³3 random morning Stone Expulsion Therapy
urine calcium–creatinine ratios was used to define
hypercalciuria; UTI was >105 CFU/cm3 in mid- Although alpha-blocker therapy in adults
stream urine and recurrent UTI was two or more significantly improves spontaneous stone pas-
infections with an intervening sterile culture and sage, one trial in children comparing dox-
symptom-free interval. Febrile versus non-febrile azosin to controls reported no difference in
infection was not stated. All had renal US and either rate of spontaneous passage or time to
DMSA for renal scar, with VCUG if either upper passage of distal ureteral stones.
tract test was abnormal. All had recurrent UTI, Another pediatric trial compared tamsu-
and 83 % of patients were female. Hypercalciuria losin to placebo, reporting increased spontane-
(mean calcium–creatinine ratio 0.5 ± 0.2 mg/mL, ous stone passage and decreased time to passage,
mean 24-h calcium excretion 6.5 mg/kg/day) was but 45 % of treated patients had residual frag-
found in 32 (43 %). There were no differences in ments after SWL or PCNL, while all those on
voiding dysfunction (73 %, means to diagnose placebo presented with ureteral stones.
not described) or in anatomic anomalies (27 %) Systematic literature review of alpha-antagonist
between hypercalciuric and normocalciuric chil- (16 studies) and calcium channel blocker therapy
dren (Biyikli et al. 2005). (9 studies) reported that these agents significantly
improve spontaneous stone passage in adults >18
years of age:
Urine Stone Risk Profiles in Tube-Fed • Alpha-antagonists RR 1.6 (95 % CI 1.4–1.7),
Children with Stones number need to treat three
• Calcium channel blockers RR 1.5 (95 % CI
One retrospective evaluation comparing tube- 1.3–1.7), number needed to treat four
fed patients to otherwise healthy stone-forming Side effects from alpha-blockers were noted
controls reported similar rates of hypercalciu- in 4 % (Singh et al. 2007).
ria and hypocitraturia but significantly higher One trial in children 2–14 years old with
urine pH and more calcium phosphate stones distal ureteral stones <10 mm randomized
in those who were tube-fed. patients to 20 controls receiving ibuprofen ver-
A retrospective review was done comparing 16 sus 19 receiving doxazosin 0.03 mg/kg/day.
stone patients with gastrostomy feeding to 32 age- Mean follow-up was 19 days. There was no
matched controls who formed stones but were difference in spontaneous stone passage rates,
considered otherwise healthy. Ninety-four percent 70 % versus 84 %, or in time to passage, 6 days
of gastrostomy patients were immobile, and dura- in both groups. No gender differences were
tion of tube feeding prior to stone onset was mean noted in response either. The authors stated
of 35 months (4–96), with no apparent differences that there were fewer pain episodes with alpha-
between enteral formulas used. A 24-h urine col- blocker therapy, but added that this was not
lection was done in 10/16 patients and 28/32 stone- objectively assessed. There were no reported
forming controls, finding similar rates of complications from alpha-blocker treatment
hypercalciuria (29 %), hypocitraturia (13 %) and (Aydogdu et al. 2009).
low urine volume (65 %, <40 cm3/kg/day). Another trial randomized 61 children (59 %
However, urine pH was significantly higher (mean males), mean age 8 ± 7 years, with distal ureteral
6.9 versus 6.2) in gastrostomy patients, and stone stones to either tamsulosin (0.2 mg daily if <4
composition was significantly more likely calcium years; 0.4 mg if >4 years of age) or placebo.
phosphate stones in gastrostomy patients versus Patient groups were similar for gender, age, and
calcium oxalate in controls (Smith et al. 2011). stone size. However, 45 % of tamsulosin patients
17 Urolithiasis 265
had ureteral fragments after SWL or PCNL, • Only 27 % had normal calcium–creatinine and
with none of these randomized to the placebo Na–K ratios on the first spot urine after begin-
group. Tamsulosin treatment resulted in ning dietary management.
increased spontaneous passage, 88 % versus • Hypercalciuria resolved with diet in 65 (50 %),
64 %, and decreased time to passage, 8 days but then recurred in 30 (time to recurrence,
versus 14.5 days, p < 0.001. Patients receiving dietary habits at recurrence not stated).
tamsulosin reported significantly fewer pain • Hypercalciuria persisted in 50 (38 %), all with
episodes (1.4 ± 1.2 versus 2.2 ± 1.4); 25 % also high Na–K ratios.
reported “mild” somnolence and nasal conges- • Nineteen (95 %) thiazide-treated patients
tion (Mokhless et al. 2012). resolved hypercalciuria, but four discontinued
therapy for symptoms, and hypercalciuria
recurred in a total of ten (apparently when
Hypercalciuria medication stopped).
• Eight of 104 (8 %) without stones at presenta-
Two studies found diet changes (decreased tion developed stones, including 1 treated with
sodium, increased potassium) resolved hyper- thiazide.
calciuria in 33–50 %; one reported that hyper- The authors stated that most patients did
calciuria recurred in half of responders due to not comply with sodium restriction (Tabel and
difficulties maintaining a low-sodium diet. Mir 2006).
Most non-responders treated with either A pediatric nephrology unit identified 33 chil-
thiazides or potassium citrate became dren (from a group of 44, 55 % male, mean age
normocalciuric. 10 years) with known urolithiasis diagnosed with
Optimal duration of medication therapy is hypercalciuria by 24-h urine collection or spot
unknown. urine calcium–creatinine ratios if not toilet-
Hypercalciuria diagnosed on the basis of cal- trained. Treatment included high fluid intake (not
cium–creatinine ratio >0.21 in three consecutive defined), and a low-sodium, high-potassium, and
morning urinalyses or urinary calcium >4 mg/kg/ RDA protein diet. Those with persistent hyper-
day on 24-h collections (percentages of each not calciuria were then treated with thiazide (15–
stated), in children evaluated in a pediatric neph- 25 mg/kg/day) and/or potassium citrate
rology clinic for abdominal pain (60 %), hematu- (1–1.5 mEq/kg/day). Of the 33 patients:
ria (56 %), or urination disturbance including • Thirteen had diet changes alone; two had per-
UTI (24 %), dysuria (45 %) or enuresis (14 %). sistent “mild” hypercalciuria (not defined).
There was a total of 131 children (53 % male), • Fifteen used potassium citrate.
mean age 3 years (1–15). Fifty-five percent of • Four started thiazide, but one added and two
patients had a family history of urolithiasis. changed to potassium citrate.
Stones were diagnosed in 27 (20 %) at presenta- Thirty-one (94 %) became normocalciuric.
tion. All were recommended a diet with liberal No new stones developed on therapy. Three
fluids (>1,500 mL/m2/day), decreased sodium ending or stopping medication had recurrent
(1–2 mg/kg/day) and increased potassium hypercalciuria and new stones. Recommended
(“according to RDA”) and followed by calcium– duration of medication treatment was not stated
creatinine and sodium–potassium (Na–K) rates (Alon et al. 2004).
in spot urines monthly for 3 months and then
every 3 months. Hydrochlorothiazide (1–2 mg/kg
for a mean of 8 months, 3–18) was prescribed for Hypocitraturia
20 children (19 with stones) subcategorized with
renal leak hypercalciuria unresponsive to dietary One study reported that potassium citrate
treatment after 1 year. Mean follow-up was 4 significantly increased urine pH and citrate
years (6 months to 16 years): and decreased urinary calcium.
A retrospective chart review reported A retrospective study considered SWL efficacy

potassium citrate treatment (1 mEq/kg/day) for for varying stone burdens in 260 children mean
hypocitraturia (< 320 mg/1.73 m2/day) in 64 age 7 years (3 months to 16 years) and 279 renal
consecutive children (65 % males), median age units treated with the Lithostar Modularis. Mean
7 years (1–15), with stones. With mean follow- stone burden was 1 cm2, mean number of ses-
up of 22 months (3–67), no adverse drug reac- sions was 1.4 (1–3), and mean shock waves
tions were recorded. Therapy resulted in per session was 2,260 (500–3,500). IVP or non-
significant median changes from baseline at contrast CT were done in all patients (numbers of
both 3 months and at last visit, including pH each not stated) 3 months after the last treatment.
(5.3 ± 0.3 to 6.3 ± 0.5), citrate (197 ± 72 to Stone-free rate was 77 % with SWL. Additional
621 ± 173), and calcium (3.5 ± 2.7 to 2.7 ± 2.4). postoperative procedures (double-J stent, PCNL,
Of the children, 20 (31 %) had recurrent stones or ureteroscopy) were included in an EQ calcula-
at entry; during follow-up, 93 % had no new tion. Overall success was 87.5 %, with EQ of
stones or stone growth, while 3 with prior his- 0.62. There was a significant decrease in stone-
tory of recurrent stones had additional recur- free rates and EQ as stone burden increased:
rence. Recommended duration of therapy was <1 cm2 87 %, 0.71; 1–2 cm2 74 %, 0.61; >2 cm2
not discussed (Tekin et al. 2002). 33 %, 0.29. There were no procedure-related
complications. Steinstrasse occurred in 28 (11 %)
patients, 4 treated with a second SWL and the
Surgical Therapy others “conservatively” managed (Turunc et al.
2010a).
Renal Stones Another review included 149 children, mean
age 14 years (3–17), with mean total stone diam-
Shock Wave Lithotripsy eter of 1.4 cm (0.2–9) who had SWL using
Several retrospective analyses reported SWL Medirex Tripter X1 or Medstone STS. No single
achieved stone-free status after one treatment stone was >2 cm diameter. Mean time to imaging
in 50–80 % of kidneys. after SWL was 21 days (13–93), but imaging
Stone-free rates were consistently found to modalities used were not stated. One-session
be significantly greater with stones <1 cm ver- stone-free status was 71 %, with 8 % undergoing
sus >2 cm, 63–86 % versus 25–62.5 %. a second session; EQ was 0.63. Multivariable
One study contrasted results in children analysis showed stone diameter related to suc-
younger than 6 versus those 7–15 years of age, cess, but not age, gender, BMI, or stone location
and found that younger patients had significantly (lower pole versus others). Stone-free rates and
higher stone-free rates after one treatment. EQ were 80 %, 0.74 for stones <1 cm; 59 %, 0.5
Two studies reported both stone-free rates for stones 1–2 cm; and 45 %, 0.35 for those
and EQ (taking into account additional post- >2 cm (McAdams et al. 2010a).
operative procedures). Both indicated that A third retrospective study reported SWL
secondary procedures were needed in approx- using the HM3 machine in 157 children mean
imately 25 % for stones <1 cm. age 6 years (10 months to 12 years) with mean
One study reported that Houndsfield Units stone diameter 1.5 cm and maximum 5.5 cm.
determined from the stone center predicted Stent or nephrostomy was placed before treat-
SWL success, with significantly greater clear- ment in 42 % of patients for stones >2 cm, stag-
ance for those <1,000 HU. horn stones, or high-grade obstruction. Stone-free
Only one reviewed study reported the fre- rates were determined 3 months after SWL, but
quency with which US, KUB, and CT were imaging was not described. Overall 80 % were
used to determine stone-free status. stone-free apparently after one session, with oth-
Steinstrasse occurred in from 0.6 to 11 % of ers having one to two additional SWL sessions.
patients. Stone-free rates after one session for those <1 cm
17 Urolithiasis 267
were 86 % versus 62.5 % if >2 cm, p = 0.03. One not described) from 2 weeks to 3 months. While
un-stented patient developed steinstrasse, leading univariate analysis showed both stone size and
to nephrostomy tube and spontaneous stone pas- attenuation to predict stone-free rates, multivari-
sage (Landau et al. 2009). able analysis showed that only attenuation was an
SWL using the Compact Delta was reported in independent factor. For successful versus failed
101 children, mean age 10.5 years (10 months to cases, mean attenuation was 710 ± 294 HU versus
19 years), with mean stone diameter of 8 mm and 994 ± 379 HU, p = 0.007. Stone-free rate was
a solitary stone in 76 %. Of these, one session was 77 % for stones <1,000 HU versus 33 % for
done in 78 % (mean size not stated) and mean >1,000 HU (McAdams et al. 2010b).
shock waves per session was 2,250. Outcome
assessment was done at a mean of 5 months, using Percutaneous Nephrolithotomy
US in 92 % of cases. Stone-free rate after one ses- Three reviewed retrospective studies reported
sion was 50 %, and 59 % overall, more likely with stone-free rates after PCNL ranging from 61
stones <1 cm (63 % versus 25 %, p = 0.01). Hospital to 86 % of kidneys.
admission was needed in 3 % of sessions—for None reported EQ to take into account
febrile UTI (fUT) in three and ureteral obstruction additional procedures, including second looks.
in two (Nelson et al. 2008). Complications included postoperative fever,
Retrospective analysis was done in 164 chil- renal pelvis perforation, and blood loss requir-
dren, mean age 46 months (4–178), treated with ing transfusion (4–15 %).
SWL monotherapy using the PeizoLith 3000 lith- PCNL was reported for 169 children (188 kid-
otripter for solitary renal calcium stones <2.5 cm neys) ranging in age from 1 to16 years with mean
in length. Patients were divided into two cohorts stone burden ranging from 19 to 33 mm. Single
by age <6 years (mean 28 months) versus those access was used in 94 %, with a 17-Fr scope in
7–15 years (mean 119 months). Follow-up 71 % and a 26-Fr scope in the others. Postoperative
included KUB, renal US, and/or CT (relative use imaging was not described. Sixty-one percent
within the two cohorts not stated). There were no were stone-free using only PCNL; second looks
differences in stone location, mean stone size were not described, and SWL was used for addi-
(10 mm, 5–25), mean shock waves per session tional therapy. Postoperative fever lasting £48 h
(2,233 versus 2,147), or mean energy applied occurred in 49 % of patients, and seven (4 %) had
(0.6 mJ/mm2 versus 0.7 mJ/mm2): transfusion (Samad et al. 2006).
• The number of sessions was significantly less Results of PCNL were reviewed in 45 chil-
in the younger children, mean 1.6 (1–5) versus dren, mean age 6 ± 4 years, with 51 treated kid-
2.9 (1–6). neys. Procedures were all done using a 20-Fr
• Stone-free rate after one session was 68 % access sheath and 170-Fr nephroscope, with one
versus 39 % for younger versus older children, access in 43 (84 %) kidneys. Indications were
p = 0.04. SWL-resistant stones and those >2 cm2, and were
• Stone-free rates between younger and older single in 27, multiple in 12, and staghorn in 12
patients were similar for all locations except kidneys. Postoperative imaging included KUB
the lower pole calyx, where one session was and renal US at £4 weeks, 6 months, and annu-
effective in 36 % versus 78 %, p = 0.2. ally with mean follow-up of 16 ± 12 months.
• Overall stone-free rate was the same—93 % Forty-four (86 %) kidneys were stone-free.
for the entire group (Goktas et al. 2012). Analysis in 43 patients showed calcium oxalate
Preoperative stone attenuation was studied in stones in 79 % and struvite in 21 %. Complications
53 children, mean age 10 years (1–18), undergo- included blood loss requiring transfusion in three
ing SWL for stones a mean of 1 cm (4 mm–4 cm) (7 %), colon perforation “treated conservatively”
in diameter. Attenuation was determined in HU in one, and “prolonged” urine leak in one, as well
from the center of the stone. Stone-free rates were as fever in six (13 %, duration not stated) (Dogan
reported based on US, KUB, or CT (relative use et al. 2011b).
Another retrospective series included 26 Stone-free rates ranged from 50 to 97 %.

children, median age 3 years (6 months to 6 years), Each reported inability to access the upper
treated by PCNL using 14-Fr access sheaths for tract initially in from 30 to 43 % of patients, in
stone burden ranging from 100 to 1,380 mm2. some despite active dilation of the distal ure-
Three (12 %) patients needed two to three access ter, managed by double-J stent placement.
sites. Twenty-four of 28 (86 %) kidneys were Two reported postoperative double-J stent-
stone-free after one session. Complications ing in all cases.
included need for transfusion in four (15 %) and None reported EQ to take into account
leakage from insertion site requiring double-J unsuccessful initial access or need for an addi-
stent in one (Bilen et al. 2010). tional anesthetic to retrieve a stent.
Prospectively entered data were analyzed in
167 children (89 boys) mean age 5 years (3
SWL Versus PCNL months to 18 years) who had a mean stone bur-
den of 6 mm (3–24) and underwent flexible uret-
One review compared treatments in renal eroscopy. Of these, 101 stones were above the
stones 1–2 cm, finding higher stone-free rates UPJ. Access was not possible at initial attempt in
for PCNL, with one patient needing transfusion 57 % of patients, who then had a ureteral stent
after PCNL versus one steinstrasse after SWL. placed for passive dilation for 1–2 weeks; active
One retrospective study evaluated 166 children dilation was not done. All were stented after ure-
undergoing either SWL or PCNL for renal stones teroscopy, with approximately 50 % having a
1–2 cm in size according to surgeon preference, retrieval string. Stone-free rate for renal stones
with SWL done in 91 (93 kidneys, 53 %) and was 97 % with one intervention. Mean follow-up
PCNL in 75 (82 kidneys). SWL was done using was 20 months (6–39); no complications were
electromagnetic Lithotriptor S, and a maximum of reported, but postoperative imaging was not dis-
three sessions was used with maximum 2,000 cussed (Kim et al. 2008).
shock waves each. PCNL used 22-Fr access A retrospective study found 80 children (69
sheaths and ultrasonic lithotripsy or 30-Fr access males), mean age 9.5 years (6–12), who had ure-
with intact extraction (in “older” children, age not teroscopy for upper ureteral or UPJ stones with a
stated). Mean age was similar at 6 years, as was mean stone burden of 10 mm (7–16). Retrograde
mean stone diameter of 14 mm (11–20) and loca- access included active dilation using cone-tipped
tion (pelvis, calyces, both). Stone-free rates were metal dilators followed by flexible ureteroscopy
reported using US (and CT, number not stated) at (scope size not stated) in 65 %, while another
3 months. One-session stone-free rates were 87 % 31 % had pretreatment double-J stenting for pas-
for PCNL and 45 % for SWL. PCNL monotherapy sive dilation (when unable to dilate or pass the
stone-free rate was 95 % versus 85 % for SWL, ureteroscope). The number with stents after uret-
p = 0.05. Complications included bleeding needing eroscopy was not reported. Postoperative imag-
transfusion and renal pelvic perforation requiring ing was at the discretion of the operating surgeon.
4 days nephrostomy diversion in two patients Single-session stone-free rate was reported as
after PCNL versus one steinstrasse treated with 90 %, with no perforations or other major com-
ureteroscopy after SWL. Postoperative fever plications noted (Nerli et al. 2011).
developed in two (3 %) PCNL and zero SWL A retrospective review was reported in 50 chil-
patients. During follow-up a mean of 31 months dren (52 kidneys), mean age 8 years (1–14), after
(6–84), recurrence in prior stone-free patients was ureteroscopy using a 7.5-Fr flexible scope, with
similar (10 %) (Shokeir et al. 2006). holmium:YAG lithotripsy done in 54 %.
Ureteroscopy was initial therapy in 90 %, with
Ureteroscopy 54 % having stones in the renal pelvis and 25 % in
Three studies reported ureteroscopy for renal the lower pole. Mean stone size was 8 mm (1–16).
stones, all with mean size £1 cm. In 33 % of cases, a 4.8-Fr or 6-Fr stent was placed
17 Urolithiasis 269
solely to passively dilate the ureter before with complete (n = 6) or partial staghorn stones
intervention a mean of 21 days (7–40) later. Ureteral with two or more caliceal branches. Stone burden
dilation was done in 35 %, and an access sheath was >2 cm in 91 %. Treatment used either a
used in 48 %. Stents were left in all but one ureter, Sonolith 3000 or Nova machine and a maximum
with retrieval strings in 57 %, while a second anes- of 3,000 shocks per session, with no difference in
thetic solely to remove the stent was needed in five results. Double-J stent was used in five (22 %)
(10 %). Postoperative imaging was by US in 24 children, all >6 years of age. One-session stone-
(46 %), CT in 14 (27 %), and KUB in 4 (10 had no free rate was 14/23 (61 %), and overall stone-free
imaging because of second look or were lost to rate with SWL monotherapy was 19 (83 %). There
follow-up). Stone-free status was 25 (50 %) patients were no steinstrasse (Lottmann et al. 2001).
with a single session. Patient age, gender, or stone PCNL was used in 12 children mean age 12
location did not predict need for additional inter- years (4–16) for “branched stones occupying
vention, but 50 % of stones >6 mm had additional more than 1 portion of the collecting system”
treatment versus none <6 mm. There were no com- (AUA guideline definition for staghorn) that
plications (Tanaka et al. 2008). ranged in size from 300 to 1,150 mm2. The 24-Fr
Another series evaluated ureteral access for sheaths were placed, and a pneumatic lithoclast
renal/proximal ureteral stones in 30 children. All was used. Flexible renoscopy was not done.
had active dilation using an 8/10-Fr coaxial dila- KUB ± renal US or CT was obtained on postop-
tor. Ureteroscopy was then possible in 18 (60 %); erative day 1, with second-look procedures only
no differences were seen in mean age (10 years) done for known fragments. Seven patients (58 %)
between those that were successful and those that were considered stone-free after one session
were not. Failure was due to a small ureteral using one access. Additional procedures included
orifice (n = 3), difficulty passing the iliac vessels three second looks (two with additional access),
(n = 4), a narrow UPJ (n = 3), and various other one SWL, and one ureteroscopy to become stone-
problems, such as reimplanted ureter or duplica- free in 11 (92 %). Complications included one
tion anomaly (n = 2). A 3.7-Fr or 4.8-Fr stent was abdominal urinoma; mean hemoglobin loss was
left for 1–2 weeks for passive dilation in those 1 mg % (apparently none transfused). Stone com-
with failed access, apparently with subsequent position was only reported in six, with five cal-
ability to reach the kidney. Early complications cium oxalate monohydrate and one struvite.
included two ureteral perforations, one requiring Follow-up after treatment was not described
percutaneous urinoma drainage. At mean follow- (Kumar et al. 2011).
up of 8 months with imaging by US (44 %), CT A retrospective review was done in patients
(23 %), or KUB (31 %), no obstruction was noted with PCNL, identifying 51 children with 53 com-
(Corcoran et al. 2008). plex stones (staghorn, or stones >300 mm2, involv-
ing more than one calyx, upper ureteral or in an
anomalous kidney). Tract dilation was done to
Staghorn Stones 20–30-Fr, and fragmentation used ultrasonic and
pneumatic lithotripters. A single tract was sufficient
One study reported SWL monotherapy to be in 60 % of renal units. Antegrade nephrostograms
successful after one session in 61 %, and over- were obtained 48 h after the procedures. One treat-
all in 83 % of staghorn stones. ment session was successful in 39 (74 %) renal
Three studies using PCNL reported one- units. Complications included 17 % transfusions,
session success in 58–74 %. Complications 6 % urine leaks (after nephrostomy tube removal,
included urinoma, urine leak requiring stent- required double-J stenting), and 2 % hydro-
ing, hydro-pneumothorax, hyponatremia with pneumothorax (Ozden et al. 2008).
seizure, and transfusions. One other retrospective review included 38
SWL monotherapy was reported for 23 chil- children (69 % male), mean age 8 years (1–13),
dren ranging from 5 months to 12 years of age with 45 renal units having a mean stone burden
of 3 cm who underwent PCNL. A complete Ureteroscopy for lower pole stones was
staghorn stone was present in 12. “Stone-free” reviewed in 21 children, mean age 15 years
was defined as absent fragments or fragments (1–20), having mean stone burden of 12 mm. In
<4 mm on KUB or renal US 2 weeks post-proce- 11 (52 %), the procedure was secondary to prior
dure. Single 26–30-Fr access sheaths were used SWL, ureteroscopy, or PCNL. Preoperative stent-
to place pneumatic or ultrasonic lithotripters. ing was done in 38 % (reasons, decision-making
Simultaneous transurethral lithotripsy was done not described). Active dilation with balloons or
in nine (24 %) but not further described. Based dilators was used in 81 and 43 % when the scope
on their definition of success, 67 % were consid- would not pass. Postoperative stenting was done
ered stone-free after one treatment. Complications in 71 %. Time for analysis to determine stone-
included transfusion in one, hyponatremia with free status was not stated; overall follow-up was
seizure in one (sterile water was used for irriga- mean 11 ± 14 months. Stone-free status appar-
tion in all cases), and fever for 1–7 days in eight ently was achieved in 13 (62 %) after one treat-
(Etemadian et al. 2012). ment and overall in 76 %. Total number of
procedures, including that to place and retrieve
stents, was not stated. No “major” complications
Lower Pole Stones occurred (Cannon et al. 2007).
In contrast to adults, lower pole stones in chil-

dren are just as effectively treated by SWL as Anomalous Kidneys
stones in the renal pelvis or other calyces.
One study compared SWL for lower pole One report indicated that PCNL could be
stones (n = 50) versus those in other locations effectively and safely performed in children
for 131 children (157 kidneys) mean age 8 years with horseshoe, malrotated or cross-fused
(1–16). Median stone burden was 0.6 cm2 in the kidneys.
lower pole. A Lithostar machine was used for PCNL was described for six children, mean
one to three sessions with a mean of 1,500 shock age 7 years (5–12), with anomalous kidneys,
waves per session. Outcomes were assessed at including three horseshoe, two malrotated, and
12 weeks using US or IVP. Single-session stone- one cross-fused. Indications were failed SWL in
free rate for lower pole stones was 42 %, which two and large stone burden in the others, mean
was not different from those in other locations. surface area of 3 cm2. All procedures were done
Total stone-free rate and EQ was 71.5 and 43 % prone in one session, including access and litho-
for the lower pole, which was also not different tripsy, with mean operating time of 43 min (25–
from stones elsewhere. One patient with a lower 70). One treatment achieved stone-free status in
pole stone developed a steinstrasse (Demirkesen five, while a second look was needed in one. No
et al. 2006). child needed transfusion, and one had puncture
SWL specifically for lower calyceal stones of the renal pelvis treated with 5 days nephros-
<2.5 cm was compared between adults (n = 282, tomy diversion (Abdeldaeim et al. 2011).
mean age 48 ± 13 years) and children (n = 54, mean
age 48 ± 42 months) in a retrospective review.
Mean stone size was 8 mm (5–25), apparently not Treatment Effects on Renal Function
different between groups. The PiezoLith 3000 was
used; post-treatment imaging included KUB and Three studies reported pre- and post-SWL
renal US ± CT (relative use in the two cohorts not renal function and scarring using nuclear
described), with final assessment for stone-free renography. None reported new renal scar.
status at 3 months. Sixty-seven percent versus Two reported no decrease in ipsilateral func-
28 % of children versus adults were stone-free tion, while another reported transient decrease
after one session, p = 0.001 (Goktas et al. 2011). in 2 % and decrease without recovery in 1 %.
17 Urolithiasis 271
One retrospective review reported 6 % of time during follow-up between 6 and 72 months,
patients had ≥10 % ipsilateral renal function and were described as showing “no significant
decrease after PCNL, but did not describe gross cortical scarring.” DTPA scans apparently
access sheath size or number of access sites. were done both preoperatively and postoperatively,
A prospective study included 100 children with four (6 %) demonstrating a ³10 % function
mean age 8 years (3–14) who had DMSA and loss (data not shown) (Dawaba et al. 2004).
DTPA pre- and 6 months post-SWL (for those
stone-free). Mean number of sessions was 1.5
(1–3), with a mean of 2,000 (800–2,600) shocks Stone Fragments After SWL
per session. Average stone size was 1 cm
(8 mm–2.7 cm). Eighty-eight percent were stone- One trial reported no difference in new stone
free, and none demonstrated new renal cortical formation in patients with versus those with-
scar on DMSA. Ipsilateral GFR was measured by out fragments after SWL. Both groups had
DTPA and also unchanged in all patients (Fayad significantly fewer recurrences on potassium
et al. 2010). citrate therapy (6 %) than observation alone
SWL was used in 182 children mean age 5 (33 %).
years (5 months to 20 years) over a 20-year Ninety-six children (60 % males) had SWL,
period, for which there was pre- and ³6 month with 52 becoming stone-free and 44 having per-
posttreatment DMSA in 94 (52 %), who were all sistent stone fragments <5 mm by 4 weeks post-
stone-free at follow-up imaging. Of these, three treatment. These patients were then randomized
(3 %) had >5 % decrease in function, which into two groups, one receiving potassium citrate
recovered in two from a transient 8 % decrease. 1 mEq/kg/day for 1 year (n = 48, mean age 9
None developed new cortical scars. The number years), or another receiving no medication or
of treatment sessions for the entire group was one other preventative measures (n = 48, mean age 7
to four (mean not stated) with median 3,000 years). Stone growth was not defined other than
shocks per session (IQR 2,600–3,005), but data as “enlargement” during follow-up. All radio-
specific to those with DMSA were not provided logic assessment was by US and KUB. Duration
(Griffin et al. 2010). of follow-up was mean 24 months (12–36):
SWL was used for 23 complete or partial stag- • In stone-free children, recurrence was reported
horn stones by Lottmann et al. (2001) described in 8 % on therapy versus 35 % observed,
above, in 21 children ranging from 5 months to p = 0.04.
12 years of age with complete (n = 6) or partial • In residual fragment patients, recurrence was
staghorn stones with ³2 caliceal branches. Stone found in 5 % on therapy versus 32 % observed,
burden was >2 cm in 91 %. Treatment used either p = 0.04.
a Sonolith 3000 or Nova machine and a maxi- • There was no difference in new stone forma-
mum of 3,000 shocks per session. Total sessions tion in patients who were stone-free versus
used were one (n = 12, 52 %), two (n = 8, 35 %), 3 those with residual fragments after SWL.
(n = 1), and four (n = 2). DMSA was obtained pre- Although 24-h urine stone risk profiles were
SWL and at 6 months after treatment, with no done in each patient, results were only provided
scars of “significant changes in renal function for those with residual fragments, with none hav-
attributable to SWL.” ing hypercalciuria, 81 % having hypocitraturia,
PCNL effects on renal function were studied in and 31 % hyperoxaluria. It was not stated if ran-
65 children (72 kidneys), mean age 6 years domization resulted in equal balance of patients
(9 months to 16 years). Sizes of access sheaths with metabolic abnormities into the two groups
were not described, nor were number of sites (Sarica et al. 2006).
per kidney. Lithotripsy was done in 57 %, while the A retrospective review had 25 children, mean
remainder had stones removed intact. DMSA age 9 years (3–14), and 26 renal units with
scans were obtained only postoperatively, some- residual fragments £5 mm after SWL ± additional
procedures. Metabolic evaluation was done in 20, Ureteroscopy

reporting hypercalciuria in 7 and cystinuria in 3
(12 %). History of stone activity before SWL was Three retrospective studies discussed
not reported. Follow-up was a mean of 48 months, ureteroscopy for ureteral stones in children.
with stone growth determined using US or KUB Two reported stone-free success greater for
and considered an increase in diameter of ³50 %. distal than proximal stones.
Nine stones met this criteria, but seven were in One study described passive ureteral dila-
patients with metabolic conditions. Excluding tion with a double-J stent in 54 %, while active
these, 4/17 (24 %) had renal colic, and 3 had orifice dilation was done in 8 and 31 % in the
gross hematuria. Eight stones were stable, and other two.
four passed (Afshar et al. 2004). Two reported 1 and 4 % distal ureteral inju-
ries with ureterovesical junction obstruction.
A retrospective multicenter analysis was done
Ureteral Stones in Turkey for 642 children mean age 90 ± 51 months
managed with semi-rigid ureteroscopy and having
SWL Versus Ureteroscopy 72 % distal, 11 % middle, and 14 % proximal ure-
teral stones. Mean stone burden was 9 mm (3–32).
One trial randomized children with distal ure- Instrument size was <8-Fr in 42 % of cases.
teral stones, mean burden 36 mm2, to either Preoperative stenting was not described for these
ureteroscopy or SWL, reporting that stone- patients, although orifice dilation was done in 31 %.
free rates from one treatment were significantly Lithotripsy was pneumatic in 55 %, holmium:YAG
better with ureteroscopy (82 % versus 62 %). in 21 %, and basketing in 24 %. Mean operative
One patient needed reimplant following time was 46 min (10–180). Mean postoperative
perforation during ureteroscopy. stenting used in 62 % was 28 ± 29 days. Stone-free
EQ for the two procedures was not reported. status was determined by KUB ± US at £4 weeks.
A RCT allocated 100 consecutive children At mean follow-up of 13 months (1–120), 93 %
with distal ureteral stones to either SWL using were stone-free, with significantly greater success
the Compact Delta II (mean 1,530 shock waves for distal versus proximal stones, 96 % versus
per session) or ureteroscopy using a 6-Fr (48 82.5 % p < 0.01. EQ was reported to be 0.93 versus
cases) or 8.5-Fr semirigid scope with holmium 0.85 in distal versus proximal stones, but reconcili-
laser or pneumatic lithotripsy. Post-treatment ation of that calculation with procedures involving
imaging included US at 2 weeks and IVP at 3 stents was not discussed. Complications occurred
months, with success defined as no stones. There in 8 % of patients, including inability to access the
were no differences in age (mean 6 years), gender stone (1 %), ureteral perforation (1 %), and UVJO
(56 males), or stone burden (mean 36 mm2). (1 %) (Dogan et al. 2011a).
Stone-free rates at 3 months were significantly Another retrospective review included 61 con-
greater after one treatment by ureteroscopy ver- secutive patients mean age 8 years (6 months to
sus SWL, 82 % versus 62 %, p = 0.001. In con- 16 years) with ureteral stones a mean of 8 mm
trast to series described above and in the following (4–20) that were in the distal ureter in 75 %, mid-
section, the authors state that they did not encoun- dle in 14 %, and upper in 11 %. An 8-Fr rigid
ter difficulties with access for ureteroscopy. In ureteroscope was used, with balloon dilation to
addition, they did not report postoperative ure- 15-Fr done in five (8 %). Pretreatment stenting, if
teral stenting. Ureteral perforation occurred in done, was not described; post-treatment stenting
two patients, one managed with a double-J stent was done in 55 %, with subsequent removal under
and the other by reimplantation. Steinstrasse anesthesia in 1–2 weeks. Stone-free rates were
occurred in three following SWL but was not determined 1 day after surgery using KUB,
described, and management was not mentioned reported as 90 % for distal, 67 % for middle, and
(Basiri et al. 2010). 71.5 % for upper ureteral stones (significantly
17 Urolithiasis 273
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Index
A oral, 235
ACE. See Antegrade continence enema (ACE) UD, 230
Acupuncture, enuresis, 62–63 Artificial urinary sphincter (AUS)
Acute scrotum and CIC, 239–240
abdominal pain, 92 description, 238
color Doppler, 95 retrospective study, 238–239
cremasteric reflex, 93 simultaneous augmentation, 238
elevated testicular position, 93 “sphincteric incompetence”, 238
nausea and vomiting, 92 Ascending testes, 70–71
scrotal swelling, 93 Aspirin therapy for heart disease, 157
testicular torsion vs. torsed appendage, 91 Attention deficit/hyperactivity disorder
urine cultures, 91 (ADHD), 58
ADHD. See Attention deficit/hyperactivity disorder AUA Reflux Guidelines
(ADHD) BBD observations, 24
Adjunctive hormonal therapy, 72–73 unilateral reimplantations, 29
Adverse events, enuresis, 62 VUR (see Vesicoureteral reflux (VUR))
Alarm conditioning, 60–61 Augmentation
Alpha-adrenergic blockers, 46 bladder, 240
ALSPAC. See Avon Longitudinal Study of Parents and bladder compliance changes (see Bladder
Children (ALSPAC) compliance)
Anesthesia, circumcision, 155 retrospective studies, 233
Anorchia surgical technique, 238
bilateral nonpalpable testes, 69 AUS. See Artificial urinary sphincter (AUS)
diagnosis, 69 Avon Longitudinal Study of Parents and Children
Anorectal malformations, 225–226 (ALSPAC), 37, 54, 56
Antegrade continence enema (ACE)
bowel vs. button, 251–252
complications, 253 B
enema fluid and volume, 252 Balanitis xerotica obliterans (BXO)
health-related quality of life, 253–254 circumcision, 161–162
imbricated vs. non-imbricated, 251 diagnosis, 160
vs. LACE,251 incidence, 160–161
long-term follow-up, 252–253 tacrolimus ointment, 161
vs. retrograde enema, 250–251 topical steroids, 161
Antibiotic prophylaxis Balloon dilation, 202
continuous, 25–26 BBD. See Bladder and bowel dysfunction (BBD)
voiding dysfunction, 24 Bedwetting. See Infrequent bedwetting
Antibiotic therapy Behavioral interventions, 60
duration, 11–12 Bell clapper deformity, 98
immediate vs. delayed therapy, 12 Betamethasone
intravenous vs. oral therapy, 11 circumcision reduction, 153
Anticholinergics primary phimosis, 154
CIC and, 233 retraction vs. placebo, 154
intravesical, 236 secondary phimosis, 155, 158
OAB treatment, 45–46 Bilateral nonpalpable testes, 69
DOI 10.1007/978-1-4614-6910-0, © Springer Science+Business Media New York 2013
276 Index
Biofeedback BXO. See Balanitis xerotica obliterans (BXO)

diurnal incontinence, 35 Byar’s flaps, 130
dysfunction voiding, 39
RCT recruited patients, 45
Birth to toilet-training age C
CIC and anticholinergics, 233 Cambridge Baby Growth Study, 70
Cochrane review, 232 CAP. See Continuous antibiotic prophylaxiz (CAP)
febrile UTI, 234 Catheterized vs. voided specimens, 2
imaging-based observation, 232–233 Cerebral palsy, 225
newborn assessment and management, 232 Children and adolescents, testicular torsion
treatments, 232 abdominal pain, 92
UD-based selective therapy, 233–234 “acute scrotum”, 91
Bladder and bowel dysfunction (BBD) clinical algorithms, 94
alpha-adrenergic blockers, 46 cremasteric reflex, 93
anticholinergics, 45–46 high testicular position, 93
biofeedback, 45 nausea and vomiting, 92
botulinum A toxin injection, 47 pain duration, 92–93
constipation management, 47 parameters, prediction, 91–92
diagnosis criteria, 36 patient age, 92
dysfunctional voiding, impact, 47–49 scrotal reaction, 93–94
ICCS definition, 36–37 Chiropractor adjustment, enuresis, 62–63
and KUB, 41–42 Chronic renal failure (CRF)
nerve stimulation, 46 defined, 209
placebo/timed voiding/urotherapy, 44–45 and ESRD (see End-stage renal disease
prevalence, 37–38 (ESRD))
questionnaires, 38 GFR vs., 209
spinal cord MRI, 42–43 prenatal vs. postnatal diagnosis, 208
ultrasound-determined rectal diameter, 42 Circumcision, neonatal
urodynamics, 40–41 AAP policy statement, 2012, 158
uroflowometry, 39–40 anesthesia, 155
UTI/VUR, 43–44 aspirin therapy for heart disease, 157
voiding diary/pad tests, 39 bleeding disorders, 156–157
wall thickness/post-void residual, 40 complications, 157–158
Bladder compliance Gomco and Plastibell, 155–156
AUS without augmentation, 243 HIV infection, reduction, 158
bladder neck surgery, 242 HPV prevalence, 158–159
LMS/sling without augmentation, 242–243 HSV-2 infection, reduction, 159
neck injection, 244 Mogen Clamp, 156
Bladder dysfunction, 7–8, 196 secondary phimosis, 158
Bladder function UTI reduction (see Urinary tract infection (UTI))
alpha-blocker therapy, 215 Clean intermittent catheterization (CIC )
capacity and compliance, 214 and AC, 228
dysfunction, 214 and anticholinergics (see Anticholinergics)
functional characteristics, 214 UTI, 234
medical bladder therapy, 216–217 Cohen technique. See Ureteral reimplantation
UD (see Urodynamics (UD)) Color Doppler ultrasound
urinary continence, 216 acute scrotum, 91, 95
Bladder neck revision, 237 prenatal and perinatal torsion, 90–91
Bleeding disorders, 156–157 sensitivity/specificity, testicular torsion, 94, 95
Bone density, hypercalciuria and, 263 Communicating hydrocele
Botox injections, 236 definition, 81
Botulinum A toxin injection, 47 prevalence, 81–82
Bowel and bladder dysfunction (BBD), 24 repair, 82
B12 vitamin deficiency resolution, 82
bladder calculi, 245–246 Comprehensive Hospital Abstract Reporting System, 157
bladder rupture, 247 Congenital reflux nephropathy, 21, 27
malignancy, 247–248 Constipation
serum homocysteine/methylmalonic acid, 245 enuresis, 56–57
short-term study, 245 ICCS definition, 36–37
ventriculoperitoneal shunt infection/dysfunction, 247 KUB, 41
Index 277
management, 47 E
prevalence, 37 Ectopic ureters
Continence management upper tract surgery, 193–194
AUS (see Artificial urinary sphincter (AUS)) ureteroceles and (see Ureteroceles)
bladder compliance changes (see Bladder compliance) Encopresis, 55
bladder neck closure, 240–241 End cutaneous ureterostomy, 202
bladder neck injection, 240 Endopyelotomy, 178–179
LMS, 237 Endoscopic injection
medical therapy, 236 reflux resolution, 30–31
salle bladder neck repair, 239–240 VUR, surgical correction, 27–28
sling, 237–238 Endoscopic puncture
sphincteric incompetency (see Sphincteric incompetency) antibiotic prophylaxis, 192
Continuous antibiotic prophylaxis (CAP), 25–26 UTI, 192
Contralateral torsion, 98 Endoureterotomy
Cosmesis, 134–135, 147–148 balloon dilation, 201
Cranberry supplements, 12–13 distal narrowed segment, 202
Cremasteric reflex, 93, 94 HN, 201
CRF. See Chronic renal failure (CRF) non-refluxing megaureters, 202
Cutaneous ureterostomy, 202 renal function, 202
Cycled cystography, 9–10 ureters, 202
Cystography, 9–10, 22 VUR, 202
End-stage renal disease (ESRD)
“bladder dysfunction”, 211
D and CRF (see Chronic renal failure (CRF))
Daytime urinary incontinence (DUI), 37 fUTI, 210
Daytime wetting, 8, 55 multivariable logistic regression analysis, 209
DES. See Dysfunctional elimination syndrome (DES) prenatal vs. postnatal diagnosis, 208
Desmopressin, 61–62 urinary extravasation, 211
Detrusor leak point pressure (DLPP) valve ablation, 208
Dietl’s crisis, 172–173 Enterocystoplasty
Differential renal function bladder augmentation, 244
analysis, 175–176 bowel contractions, 244–245
estimation, 167 metabolic acidosis, 245
integral method, 167, 168 retrospective review, 244
Rutland/ Patlak plot analysis, 167 Enuresis
Dipstick, 3 adverse events, 62
Diuretic renography drainage, 176–177 alarm conditioning, 60–61
DMSA scintigraphy alternative therapies, 62–63
acute, 3 attention deficit/hyperactivity disorder, 58
age, 13 behavioral interventions, 60
children, 13 constipation, 56–57
preoperative and postoperative, 27 desmopressin, 61–62
renal defects, 12 European Association of Urology
renal scars, 13, 228–229 guidelines, 60
repeat, 3 evaluation, 60
scintigraphy, 228 family history, 55–56
VUR diagnosis, 21 FDA adverse events reporting, 62
Double-J stenting, 201 ICCS guidelines, 60
Double oral anticholinergic therapy, 235 imipramine, 62
DUI. See Daytime urinary incontinence (DUI) infrequent bedwetting, 54
Dysfunctional elimination syndrome (DES), 8, 43 mono-symptomatic nocturnal, 54
Dysfunctional voiding NICE guidelines, 60
baseline uroflowometry, 39–40 oxybutynin, 62
bladder behavioral modification program, 38 poly-symptomatic, 54–55
impact, 47–49 psychologic impact, 59
LUTS, 35 secondary enuresis, 55
overt, 43 self-esteem, therapy impact, 63–64
symptom score, 38, 44 sleep-disordered breathing, 57–58
urodynamics, 40 spontaneous resolution, 59–60
VUR, 24–25 therapy order, 63
278 Index
Epididymitis contralateral exploration, 85–86

abdominal pain, 92 definition, 81
color Doppler, 91 incarceration incidence, 82–83
high testicular position, 93 indirect vs. direct hernias, 84
nausea/vomiting, 92 one-instrument percutaneous sac ligation,
patient age, 92 laparoscopy, 85
scrotal reaction, 93 open vs. laparoscopic repair, 84
urine cultures, 91 premature infants, 83
ESRD. See End-stage renal disease (ESRD) prevalence, 81–82
Excisional tapering, 203 sutured vs. skin adhesive wound closure, 86
Extraordinary daytime urinary frequency, 36 testicular atrophy, 83
three-instrument laparoscopic repair, 84–85
vasal injury, 83
F VP shunts (see Ventriculoperitoneal (VP) shunts)
Febrile UTI (fUTI) Herniorrhaphy, unilateral, 85
infants, antimicrobial prophylaxis, 26 Herpes simplex virus type 2 (HSV-2) infection, 159
pyelonephritis vs., 3–4 Hidden incision endoscopic surgery (HIdES),
recurrent infection, 21 174–175
renal scar vs., 15 HIdES. See Hidden incision endoscopic surgery
Fertility, 78 (HIdES)
Fetal ultrasound, 207 Hinman’s syndrome, 36
Fetal urine analysis, 206–207 HN. See Hydronephrosis (HN)
Fistulas Homeopathy, enuresis, 62–63
prevention, 136–137 Hormonal monotherapy, 72
treatment, 137–138 Hormone therapy
Foley drainage, 29 androgens, 120–121
Foreskin glans width, 119–120
BXO, 160 testosterone, 120
separation, 153 HPV. See Human papillomavirus (HPV)
status, 153 Human papillomavirus (HPV), 158–159
Fowler-Stephens orchiopexy Hydrocele
intra-abdominal testes, 76 circumcision, 81, 82
nonpalpable testes, 75 communicating (see Communicating hydrocele)
one-stage, 76 definition, 81
Furosemide, drainage, 167–168 prevalence, 81–82
fUTI. See febrile UTI (fUTI) resolution, 82
Hydronephrosis (HN)
extent, 165
G prenatal, 165–166
Giggle incontinence, 36 Hypercalciuria
Glans dehiscence, 138 and bone density, 263
Glenn-Anderson reimplantation, 28–29 calcium-creatinine, 265
Gomco circumcision, 155–156 dietary treatment, 265
Graft diet changes, 265
dermal, 125 low-sodium high-potassium diet, 259
inlay graft reoperations, 143, 144 medication therapy, 265
one-and two-stage preputial, 130–131 pediatric nephrology, 265
oral mucosal inlay graft, 140 potassium citrate, 265
SIS, 125–126 risk, urolithiasis, 263
tunica vaginalis, 126 stone recurrence vs. children, 262
two-stage buccal grafting, 144–145 and UTI, 263–264
Gram stain, 3 Hypertension
description, 186
newborns and children, 187
H retrospective review, 187
Heminephrectomy series without HTN, 187
pyelopyelostomy, 194 Hypnosis, enuresis, 62–63
upper pole ureteral tailoring, 195 Hypocitraturia
upper tract surgery, 197 vs. adults, 262
Hernia. See also Incarcerated hernia calcium super-saturation indice, 261
Index 279
metabolic abnormalities, 260–261 definition, 81

potassium citrate, 265 OHR, 85
retrospective chart review, 266 testicular atrophy, 83
Hypospadias Infertility
adult outcomes, prepubertal repair, 146–147 contralateral testis biopsy, 100
cosmesis (see Cosmesis) hormonal assays, 100
diverticula, 140–141 palpable varicoceles, 109
fistulas (see Fistulas) right testis, 109
Glans dehiscence, 138 semen analysis/sperm antibodies, 99–100
intraoperative assessment and management semen parameters, 106
dermal graft, 125 testicular size, 104
dorsal plication, 124–125 unilateral varicocele, 108
perioperative antibiotics, 123 varicocele, 108
single vs. multiple ventral corporotomies, Infrequent bedwetting
126–127 definition, 53
SIS graft, 125–126 prevalence, 54
sutures, 122–123 Intermittent torsion, 100–101
tunica vaginalis flap, 126 International Reflux Study
tunica vaginalis graft, 126 patients surgery, 28
UP ± urethral elevation, 126 ureteral reimplantation, 26–27
urethral plate (UP), 123–124 VUR resolution, 26–28
urethroplasty (see Urethroplasty) Intrascrotal testis, 73
VC (see Ventral curvature (VC)) Intravenous pyelogram (IVP)
ventral lengthening vs. dorsal plication, 125 hemi-nephrectomy, 194
meatal stenosis, 139 lesions, chronic pyelonephritis, 196
postoperative management and assessment ureteral reimplantation, 194
bandages, 131 Intravenous vs. oral therapy, 11
calibration, 132 Intravesical anticholinergics, 236
follow-up duration, 132 Involution, 185
preventing erections, 131–132 Isolated vs. syndromic hypospadias, 118
urinary diversion, 131 IVP. See Intravenous pyelogram (IVP)
preoperative assessment and management
adjuvant hormonal therapy, 119–120
imaging, 119 K
isolated vs. syndromic, 118 Karyotyping, 118–119
karyotyping, 118–119 Kidney, ureter, and bladder (KUB), 41–42
outcomes, 121
prevalence and familial risk, 118
response to androgens, 120–121 L
side effects, 121 LACE. See Left-colon antegrade continence enema
timing, surgery, 121–122 (LACE)
reoperations Laparoscopic hernia repair
buccal inlay, 141–144 description, 84
skin flaps, 146 SEAL, 85
TIP, 141 three-instrument, 84–85
two-stage buccal grafting, 144–145 Laparoscopic pyeloplasty
risk factors, 135–136 cosmesis, 174–175
sexual function, 147 surgical outcomes, 174
strictures, 139–140 Leadbetter/Mitchell bladder neck revision plus sling
urinary function (LMS), 237
symptoms, 147 Left-colon antegrade continence enema (LACE)
uroflowometry, 147 vs. ACE, 251
uroflowometry (see Uroflowometry) irrigation volume, 224
Lich-Grigoir. See Ureteral reimplantation
Likelihood ratio (LR)
I colony counts, 2
Imipramine, enuresis, 62, 64 positive, 3
Immediate vs. delayed therapy, 12 Lower urinary tract symptoms (LUTS), 35
Incarcerated hernia LR. See Likelihood ratio (LR)
bowel resection, 83 LUTS. See Lower urinary tract symptoms (LUTS)
280 Index
M Nephrectomy
MAG-3 renography BP normalization, 183
database review, 168 duct carcinoma, 188
differential renal function, estimation, 167 hypertension, 188
diuretic, 176 palpable mass, 188
mean differential renalfunction, 176 retrospective review, 187
patient observation, 171 Nephrostomy drainage, 173, 178
postnatal HN, 166 Nerve stimulation, BBD, 46
Manchester Scar Scale, 175 Neurogenic bladder
MCDK. See Multicystic dysplastic kidney (MCDK) ACE (see Antegrade continence enema (ACE))
Meatal stenosis ACE procedures, 223
description, 139 birth to toilet-training age, 232–234
diagnosis, 159–160 B12 vitamin deficiency, 245–248
meatotomy, 160 definition, 224
occurrence, 157 diagnosing and management, 223
prevalence, 160 DLPP, 223
prevention, 139 DMSA-based acquired renal damage (see DMSA)
treatment, 139 enterocystoplasty (see Enterocystoplasty)
Meatotomy etiologies, 225–226
meatal stenosis, 159–160 LACE, 224
uroflowometry, 159 leak point pressure, 227–228
Metabolic abnormalities, urolithiasis management, continence (see Continence
hypercalciuria, 263 management)
pediatric vs. adult stone formers, 262 medical management, 234–236
solitary vs. recurrent stone formers, 262 Mitrofanoff procedures (see Mitrofanoff procedures)
stone formers, 260–261 newborn assessment (see Newborn assessment)
stone formers vs. controls, 261–262 optimal medical management, 223
Metachronous hernia, 85–86 quality of life, 249–250
Mitrofanoff procedures renal scar, 223
appendix vs. monti, 248–249 spinal cord anomalies (see Spinal cord anomalies)
bladder vs. bowel, 249 tethered cord (see Tethered cord)
Mono-symptomatic nocturnal enuresis, 54 UD (see Urodynamics)
Multicystic dysplastic kidney (MCDK) ureterocystoplasty, 248
age and gender, 183 Newborn assessment
contralateral renal function, 183 high-risk vs. low-risk UD, 231–232
contralateral renal hypertrophy, 184 imaging and UD, 229–230
hypertension, 186–187 retrospective study, 230
increased size, 185–186 UD-based selective therapy, 230, 231
involution, 185 UTI and VUR, 230
malignancy, 188 Nonfunctioning renal segments
nephrectomy, 188 chronic inflammatory changes, 195–196
prevalence and presentation, 184 IVP, 196
renal function, 187–188 upper pole, 195
renal US, 184 Nonpalpable testis
renography, 183–184 management, 73–75
sports participation, 188–189 MRI, 71
sports-related renal injury, 184 unilateral, 72
UTI/VUR, 186 Non-refluxing megaureter
VCUG, 185 abdominal/flank pain, 199
antibiotic prophylaxis, 199, 200
conservative patients, 200
N Dietl’s crisis, 201–203
Nadir creatinine distal ureteral diameter, 199
CRF, 209 fUTI, 199
ESRD, 209 HN grade, 200
renal functions, 205 retrospective analysis, 200
valve ablation/vesicostomy, 211 retrospective study, 200
National Health and Nutrition Examination Survey SFU grade, 200–201
(NHANES), 54 surgical rates, 199
Neonatal circumcision. See Circumcision, neonatal trimethoprim, 200
Index 281
Nuclear renography Phimosis

abnormal contralateral kidney, 188 foreskin status, 153
description, 185 grading, 155
technical factors, impact, 166–167 Kayaba grading scale, 154
timing, 166 medical therapy, 154
pediatrician report, 153–154
prepuce (see Prepuce)
O prevalence and history, 153–154
OAB. See Overactive bladder (OAB) secondary, 158
“Oozing”, 156 steroids, 154–155
Oral anticholinergics, 235 Placebo, 44–45
Orchiopexy Plastibell neonatal circumcision, 155–156
cancer risk, 67 Plication, 202–203
contralateral, 98 Politano-Leadbetter. See Ureteral reimplantation
detorsion, 99 Poly-symptomatic enuresis, 54–55
Fowler-Stephens (see Fowler-Stephens orchiopexy) Posterior urethral valves (PUV)
intermittent torsion, 100 ablation technique, 212
intra-abdominal, 76 bladder function (see Bladder function)
laparoscopic, 75 cohort study, 205
pain duration, 95 diagnosis and management, 205
prenatal and perinatal torsion, 90 ESRD, 205
puberty, 77 nephrectomy, 219
rates, 70 postnatal parameters, 208–211
recurrent torsion, 98–99 prenatal assessment (see Prenatal
reoperative, 77 assessment, PUV)
scrotal, 73 prenatal diagnosis, 205–206
surgical reports, 67 prenatal intervention vs. observation, 207
testicular salvage rates, 97 prenatal vs. postnatal diagnosis, 208
testicular viability rates, 97 radiologic changes (see Valve ablation)
timing, 73 renal transplantation, 219–220
two-stage, 76 TUR valves vs. urinary diversion, 214
Overactive bladder (OAB) ureteral reimplantation, endoscopic injection,
Cochrane review, 45–46 218–219
ICCS definition, 35–36 ureterovesical junction obstruction, 219
placebo, 34 urethral stricture after ablation, 213–214
prevalence, 37 valve ablation (see Valve ablation)
resolution, 47 VCUG (see Voiding cystourethrogram
Oxybutynin, 62 (VCUG))
Postnatal parameters, PUV
age, diagnosis, 208–209
P nadir serum creatinine, 209
Palpable testes renal ultrasound parameters, 209
management, 73 UTI, 210
nonpalpable vs., 68 valve bladder, 210–211
UDT location, 68–69 VUR, 209–210
Patient Scar Assessment Scale, 175 VURD, 211
PCNL. See Percutaneous nephrolithotripsy (PCNL) Pregnancy, VUR impact, 25
Pediatric Committee of the European Association of Prenatal assessment, PUV
Nuclear Medicine, 166, 167 fetal ultrasound, 207
Percutaneous nephrolithotripsy (PCNL) fetal urine analysis, 206–207
postoperative procedures, 266 vs. observation, 207
renal function, 271 vs. postnatal diagnosis, 208
stone-free rates, 259 postnatal parameters (see Postnatal parameters, PUV)
SWL vs., 268 Prenatal hydronephrosis
ureteral fragments, 265 differential renal function, estimation, 167
Perinatal torsion drainage after furosemide, 167–168
color Doppler, 90, 91 nuclear renography (see Nuclear renography)
orchiopexy, 90 postnatal evaluation, 165–166
testicular salvage, 90 supranormal renal function, 168
Perioperative antibiotics, hypospadias surgery, 123 ultrasound timing, 166
282 Index
Prenatal torsion UTI, 13

color Doppler, 90, 91 VUR, 14, 21
contralateral torsion, 89 Renal stones
orchiopexy, 90 percutaneous nephrolithotomy, 267–268
unilateral nonpalpable testis, 89 SWL (see Shock wave lithotripsy (SWL))
Prepuce SWL vs. PCNL, 268
BXO, 160 ureteroscopy (see Ureteroscopy)
retractability, 154 Renal transplantation, 219–220
retraction, 161 Renal ultrasound and VCUG, 9
status, 154 Renal ultrasound parameters, 209
Preputial flap Reoperative orchiopexy, 77
diverticulum, 140 Reoperative pyeloplasty, 178
one-and two-stage grafts, 130–131 Retractile testis, 70
onlay, 128–129 Retrograde endopyelotomy, 179
postoperative, 134 Ring block. See Circumcision, neonatal
tubularized, 129–130 Robotic pyeloplasty, 178
two-stage (see Byar’s flaps)
Pseudohermaphroditism, 119
Psychotherapy, enuresis, 62–63 S
PUV. See Posterior urethral valves (PUV) Salle bladder neck repair, 239–240
Pyelonephritis, 3–4 Sclerotherapy
Pyeloplasty antegrade, 109–111
failed, 177 retrograde, 109, 110
imaging after, 175 Scrotal orchiopexy, 73
laparoscopic, 174–175 SEAL. See Subcutaneous endoscopically assisted
reoperative, 178 ligation (SEAL)
robotic reoperative, 178 Secondary enuresis, 55
SFU grade 3 and 4 HN kidneys, 169 Semen analysis
UPJO, 170–171 abnormal vs. normal, 108
adolescents, varicocele, 105
artery-sparing vs. non-sparing laparoscopic
R varicocelectomy, 111
Randomized controlled trial (RCT) grades 2 and 3 varicoceles, 106
children, ureteral reimplantation, 26 preoperative and postoperative, 112
meta-analysis, 25–26 testicular size discrepancy, 108–109
Reflux Sexual function, hypospadias
lower pole, 191 ejaculation, 147
VUR, 194 erectile dysfunction, 147
Reimplantations sexual satisfaction, 147
intravesical vs. extravesical, 28–29 Shock wave lithotripsy (SWL)
reflux resolution, 28 HM3 machine, 266
unilateral, 29 Houndsfield units, 266
ureteral, 26–27 Medirex Tripter X1/Medstone
Renal function STS, 266
fetal ultrasound, 207 vs. PCNL, 268
fetal urine analysis, 206–207 preoperative stone attenuation, 267
Renal hypertrophy retrospective analysis, 267
compensatory, 184 stone-free rates, 266
contralateral, 184 vs. ureteroscopy, 272
Renal scar Sibling and offspring screening, 20
antibiotic therapy, 12 Sleep-disordered breathing, 57–58
children,VUR, 19 Sling, 237–238
DMSA scintigraphy, 13 Social Readjustment Rating Scale, 55
IVP-based diagnosis, 14 Solitary kidney
low birth weight, 25 regional trauma registry, 189
negative DMSA, after, 21–22 renal trauma, 188
preeclampsia, 25 sports-related renal injuries, 189
pregnancy, 25 Sphincteric incompetency
reported febrile UTI, 15 AMS, 238
surgical VUR correction, 26 definition, 236–237
Index 283
persistent incontinence, 236 surgery vs. conservative management, torsed

surgery, 236 appendages, 101
Spina bifida ultrasonography, 94–95
ACE procedures, 253 viability factors, 95
retrospective series, 223 Testis cancer, 77–78
sacral anomalies, 226 Tethered cord
Spinal cord anomalies primary, 254–255
lipomeningocele, 224 secondary, 255
myelodysplasia, 224 Timed voiding, 44–45
primary tethered cord, 224–225 TIP. See Tubularized incised plate (TIP)
sacral agenesis/caudal regression, 224 Tonsillectomy and adenoidectomy (T&A), 57
Spinal cord MRI, 42–43 “Top-Down” Imaging, DMSA scintigraphy, 10–11
Spontaneous resolution Topical steroids, 161
renal units, 169 Torsed appendage
SFU 1 and 2 HN, 169 mean age, 92
SFU 3 and 4 HN, 170 predictive value, 92
Staghorn Stones scrotal erythema/edema, 93
description, 269 surgery vs. conservative management, 101
PCNL, 269 vs. testicular torsion, 91
retrospective review, 269–270 Transcutaneous electrical nerve stimulation (TENS), 45
“stone-free”, 270 Tubularized incised plate (TIP)
Stone expulsion therapy, 264–265 distal hypospadias, 127
Subcutaneous endoscopically assisted ligation (SEAL) distal-midshaft, 131
hernia, 85 distal repair, 122, 123, 127
nonabsorbable suture, 85 fistulas, 127, 139
pediatric inguinal hernia, 85 glansplasties, 138
suture ligation, 85 vs. Mathieu, 127
Supranormal renal function, 168 midshaft, 122
Suprapubic aspiration, 1–2 postoperative, 133–134
Swedish reflux trial, 15, 22 prepubertal patients, 121
SWL. See Shock wave lithotripsy (SWL) proximal hypospadias, 128
Symptomatic stumps, 196–197 reoperative, 141, 142
UP characteristics, 123
urethroplasty, 131, 135
T T1/2 washout
T&A. See Tonsillectomy and adenoidectomy (T&A) diuretic renography drainage, 176
Tacrolimus, 161 UTI occurrence, 172
TENS. See Transcutaneous electrical nerve stimulation
(TENS)
Testicular hypotrophy, 108, 109, 112 U
Testicular salvage rates, detorsion and orchiopexy, 97 UD. See Urodynamics (UD)
Testicular torsion UDT. See Undescended testes (UDT)
bell clapper deformity, 98 Ultrasound-determined rectal diameter, 42
children and adolescents (see Children and Underactive bladder
adolescents, testicular torsion) bladder wall thickness, 40
contralateral torsion, 98 ICCS definition, 36
duration of symptoms, 95 Undescended testes (UDT)
goals, diagnosis and management, 89 adjunctive hormonal therapy, 72–73
infertility, 99–100 anorchia diagnosis, 71–72
intermittent torsion, 100–101 ascending testes, 70–71
intraoperative tests, 96–97 bilateral nonpalpable, 69
investigational tools, 95 cancer risk, 77–78
manual detorsion, 96 cosmetic results, 76
prenatal and perinatal torsion, 89–91 extra abdominal testes, 75
preoperative US, 96 fertility, 78
prosthesis, 98 history and physical examination, 69–70
psychologic impact, unilateral orchiectomy, 100 hormonal monotherapy, 72
recurrent torsion, orchiopexy, 98–99 imaging, 71
salvage rates, detorsion and orchiopexy, 97 intra-abdominal orchiopexy, 76
scrotal reaction, 96 nonpalpable testis (see Nonpalpable testis)
284 Index
Undescended testes (UDT) (cont.) robotic reoperative pyeloplasty, 178

orchiopexy timing, 73 spontaneous resolution (see Spontaneous resolution)
palpable (see Palpable testes) supranormal renal function, 168
prevalence, 68 symptoms, 177
reoperative orchiopexy, 77 ultrasonography, 175
retractile testis vs., 70 ultrasound timing, 166
surgical success, 76 UTI, risk, 172
ultrasound, 71 Ureteroscopy
unilateral nonpalpable, 69 postoperative double-J stenting, 268
Unilateral hernia, 85–86 postoperative imaging, 269
Unilateral nonpalpable testes, 69 renal/proximal ureteral stones, childrens, 269
Unilateral reimplantation, contralateral, 29 renal stones sizes, 268
UP. See Urethral plate (UP) retrospective study, 268
UPJO. See Ureteropelvic junction obstruction (UPJO) vs. SWL, 272
Ureteral duplication, 119 Ureteroureterostomy (UU)
Ureteral folding, 203 description, 195
Ureteral reimplantation duplex systems, 195
perforation and, 201 fUTI, 195
Starr plication, 203 hydronephrosis, 195
ureteral dilation, 202 and reimplantation, 195
VUR after plication, 202 Urethral plate (UP)
Ureteral stones pre-incision width, 123
SWL vs. ureteroscopy, 272 shallow, 123
ureteroscopy, 272–273 TIP repair, 123
Ureteral stump Urethral stricture
symptomatic, 196–197 after ablation, 213–214
VUR, 194 newborns and infants, 212
Ureteral tapering retrospective series, 213
excisional, 203 Urethroplasty
retrospective studies, 201 distal hypospadias, 127
Ureteroceles one-and two-stage preputial grafts, 130–131
endoscopic management, 192–193 onlay preputial flap, 128–129
lower tract surgery, 194 proximal hypospadias, 127–128
selective observation, 191–192 tubularized preputial flap, 129–130
upper and lower tract reconstruction, 194–195 two-stage preputial flaps, 130
upper tract surgery, 193–194 Urethroplasty complication
Ureterocystoplasty, 248 distal hypospadias, 127
Ureteropelvic junction obstruction (UPJO) fistulas, 123, 129, 144
associated comorbidities, 165 follow-up, 132
bilateral, management, 173–174 glans dehiscences, 123, 129
Dietl’s crisis, 172–173 meatal stenoses, 123, 144
differential renal function (see Differential renal onlay preputial flap, 128
function) postoperative bandages, 131
diuretic renography drainage, 176–177 postoperative preputial flaps, 134
endopyelotomy, 178–179 preoperative topical DHT vs. no therapy, 120
etiologies, 168–169 reoperations, two-stage graft, 145
failed pyeloplasty, 177 risk factors, 135–136
furosemide, drainage, 167–168 “shallow” UP, 123
imaging after pyeloplasty, 175 timing of surgery, 121–122
incidence and pathophysiology, 177 TIP vs. Mathieu, 127
laparoscopic pyeloplasty, 174–175 tubularized preputial flap, 129
management, 173 two-stage buccal grafting, 144
nuclear renography (see Nuclear renography) two-stage preputial flaps, 130
observational management, 169 Urge syndrome, 36
postnatally detected, 172–173 Urinary continence
prenatal hydronephrosis, postnatal evaluation, bladder dysfunction, 216
165–166 diurnal incontinence, 216
pyeloplasty, 170–171 valve ablation/supravesical diversion, 216
renal function loss, risk, 171 valve ablation vs. urinary diversion, 216
reoperative pyeloplasty, 178 Urinary incontinence
Index 285
coated vs. uncoated catheters, 234 renal stones, 266–269

single-use vs. multiple-use, 234 retrospective studies, 259
sterile vs. clean CIC, 234 Staghorn stones (see Staghorn Stones)
VUR and, 228 stone expulsion therapy (see Stone expulsion therapy)
Urinary tract infection (UTI) stone fragments after SWL, 271–272
age, 13 stone management, 259
anatomic anomalies, 7 treatment effects, renal function, 270–271
antibiotic therapy (see Antibiotic therapy) Turkish urology department, 260
bladder dysfunction, 7–8 ureteral stones (see Ureteral stones)
catheterized vs. voided specimens, 2 urine stone risk profiles, 264
circumcision status, 9 UTI and hypercalciuria, 263–264
colony counts, 2 Urotherapy, 44–45
constipation, 8–9 UTI. See Urinary tract infection (UTI)
cranberry supplements, 12–13 UU. See Ureteroureterostomy (UU)
cystography, diagnostic accuracy, 9–10
data regarding recurrent, 5–6
diagnosis, 209 V
ESRD, 210 Valve ablation
fUTI, 210 “bladder dysfunction”, 211
fUTIs, vs. number, 14–15 bladder function, 205
gram stain, dipstick, and microscopy, 3 initial management
incidence, 4–5 positive/negative predictive value, 213
in newborns, 192 post-ablation cystoscopy, 213
prevalence, 4 retrospective report, 212–213
pyelonephritis vs. febrile, 3–4 urethral ratios, 213
recurrent, initial infection, 5–7 VCUG and repeat cystoscopy, 213
renal scar, 13 nadir serum creatinine, 209
renal ultrasonography, 5 prenatal bladder, 207
renal ultrasound and VCUG, 9 radiologic changes
scar risk, 15 hydronephrosis, 218
“Top-Down” Imaging, DMSA scintigraphy, 10–11 posterior urethral dilation, 217
urinary retention, 208 VUR, 217–218
VUR, 14 “residual valves”, 212
Urine gram stain, 2 vs. supravesical diversion, 212
Urodynamics (UD) vesicostomy/supravesical diversion, 212
bladder capacity, 227 Valve bladder
description, 226 defined, 210
detrusor pressures, 216 dysfunction, 211
DLPP, 226 retrospective analysis, 211
ESRD, 215 urinary continence, 211
ICCS recommendations, 227 Varicocele
infusion, childrens, 227 fertility in adults, 107–108
retrospective analysis, 215 fertility, surgery, 109
room vs. body temperature, 227 persistent, management of, 113–114
spinal dysraphism, 227 prevalence, 103–104
supravesical diversion, 215 semen analysis, 105–106
urethral catheter and medical treatment, 215 surgical outcomes
Urodynamic test, 60 cosmetic improvement, 113
Uroflowometry meta-analysis, 112
postoperative preputial flaps, 134 pain resolution, 113
postoperative TIP, 133–134 semen parameters, 112
preoperative, 133 testicular size discrepancy, 112–113
Urolithiasis testicular growth
anomalous kidneys, 270 resolution, size discrepancy, 106–107
clinical symptoms, 260 size discrepancy development, 107
hypercalciuria (see Hypercalciuria) volume changes, 106
hypercalciuria and bone density, 263 testicular size assessment, 104
lower pole stones, 270 testicular size discrepancy, 108–109
metabolic abnormalities (see Metabolic testicular volume discrepancy, 105
abnormalities, urolithiasis) varicocelectomy (see Varicocelectomy)
286 Index
Varicocelectomy recurrent fUTI, LR, 21

antegrade sclerotherapy, 110–111 recurrent infection, 5
artery-sparing vs. non-sparing laparoscopic, 111 reflux resolution, reimplantation, 28
lymph vessel sparing vs. non-sparing laparoscopic, renal scarring, 21
111–112 renal scar, risk, 1, 13–14
vs. observation, 110 resolution, 22–23
open vs. laparoscopic, 110, 111 risk factor, 5
retrograde sclerotherapy, 110 sibling and offspring screening, 20
VC. See Ventral curvature (VC) significant, 10
VCUG. See Voiding cystourethrogram (VCUG) spontaneous resolution, 22
Ventral curvature (VC) surgical correction, 26–28
dermal grafting, 125 unilateral injection, contralateral, 31
distal hypospadias, 117, 124 unilateral reimplantation, contralateral, 29
dorsal plication, 128 ureteral reimplantation, 26–27
proximal hypospadias, 117, 124, 126 valve ablation
recurrent, 124, 125 consecutive patients, 218
reoperation, 125 observational study, 217–218
SIS graft, 125–126 retrospective review, 218
UP elevation, 126 ureters, 218
Ventriculoperitoneal (VP) shunts Vesicoureteral reflux into dysplastic kidney
hernia risk, 83 (VURD)
inguinal hernia surgery, 83 defined, 211
Vesicoureteral reflux (VUR) “pop-off” mechanisms, 211
AUA Refux Guidelines data, 20 PUV, 211
CAP, 25–26 retrospective review, 211
contralateral, 22–24 Voiding cystourethrogram (VCUG)
cycled cystography, 9–10 “adequate valve ablation”, 212
cystography, annual, 22 consecutive newborns, 184
diagnosis, 7 cystoscopy and, 213
DMSA scintigraphy, 21 diagnosis, 211–212
dysfunction voiding, 24–25 “profuse bleeding”, 213
endoscopic injection (see Endoscopic injection) ureter detection, 183
febrile UTI (see Febrile UTI (fUTI)) urologic assessment, 219
intravesical vs. extravesical, reimplantation, 28–29 valve/posterior urethral dilation, 213
management, 25 vaporization, 212
and PBS, 206 Voiding diary/pad tests, 39
postnatal parameters VP shunts. See Ventriculoperitoneal (VP) shunts
ESRD, 210 VUR. See Vesicoureteral reflux (VUR)
multivariable logistic regression, 210 VURD. See Vesicoureteral reflux into dysplastic kidney
normal vs. reduced renal function, 210 (VURD)
retrospective analysis, 209
pregnancy, impact, 25
prenatal hydronephrosis, 20–21 W
prevalence, 20 Wound Evaluation Scale, 175

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Pediatric Urology Evidence

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Warren T.

Evidence for Optimal

ISBN 978-1-4614-6909-4 ISBN 978-1-4614-6910-0 (eBook)

Library of Congress Control Number: 2013934223

© Springer Science+Business Media New York 2013

Printed on acid-free paper

Springer is part of Springer Science+Business Media (www.springer.com)

Management of various conditions by pediatric urologists has been chal-

Two authors have advanced degrees of relevance, one a Master’s in Public

Dallas, TX, USA Warren T. Snodgrass

1 Urinary Tract Infection ............................................................... 1

Index ...................................................................................................... 275

Linda A. Baker Department of Pediatric Urology, University of Texas

Table 1.1 Recurrent UTI in patients on no antibiotic prophylaxis after UTI

5 days/month), or control for 6 months. The Versus Age at UTI

Two studies report risk <5 %, and one study, References

Most detected VUR is low grade, with

Spontaneous Resolution A retrospective review was done in 167 children

Table 2.1 Percent chance of VUR resolutiona

VCUG post-injection. During mean follow-up of Glenn-Anderson in 10 % and “other modifications”

Endoscopic Injection: Reﬂux Resolution cystogram in 70 % of 168 patients and 78 % of

Two studies reported approximately 10 % of References

Table 3.1 Criteria for Diagnosis Commonly Referenced

Urge syndrome. frequent attacks of urinary Dysfunctional voiding. habitual contraction of

• No trial included children. dysfunction) in 25 %, normal in 17 %, and lazy

Three studies reported constipated children Spinal Cord MRI

abnormal MRI findings (tethered cord, thick

• DES occurred in 43 % of children with UTI

Biofeedback One placebo-controlled trial in children with

Botulinum A Toxin Injection significant decrease in diurnal incontinence

One RCT reported 45 % of patients had Impact of Voiding Dysfunction

girls (4 vs. 2 % at age 7.5 years) (Butler and

In the cross-sectional epidemiological study The prospective case–control study of 170

and psychological risk factors (such as divorce,

failure (<14 consecutive dry nights) in 250 of 260

A RCT enrolled children with enuresis and

found descent to have occurred in 44 %, leaving

Ultrasound Basal LH and FSH levels >3× normal are con-

Intra-abdominal Orchiopexy 1,000/1,126 (89 %) extra-abdominal testes had

Reoperative Orchiopexy was attempted in the remaining 25 based on an

The primary reason to operate on hernias is to • Meta-analysis of laparoscopic versus open

A prospective determination of the preva- A retrospective review of 110 infants presenting

Scrotal Reaction A retrospective review included 61 patients

despite scrotal reaction in all patients (Bush and

Three retrospective studies were reviewed that

decompression (fasciotomy) with tunica vaginalis Makela E, Lahdes-Vasama T, Rajakorpi H, Wikstrom S. A

cele had testicular size discrepancy, whereas 24

Two population-based studies reported that

Primary goals in hypospadias repair: of proximal hypospadias. Short-term stud-

without hypospadias had chromosome analysis. Imaging

was a mean of 14 mm (11–19), while mean padias to receive a mixture of testosterone

Impact on Hypospadias Outcomes

Retrospective review of 12 patients with proxi- UP ± Urethral Elevation

of 27 months vs. 19 months, respectively complications ranged from 0 to 24 %, with 25

Table 9.1 One-stage proximal hypospadias repair using preputial flaps

Table 9.2 Proximal Byar’s flap outcomes

(18–30), complications developed in three Two retrospective studies reported compli-

Postoperative Management Bandages

Uroﬂowometry One study that reported that 49 % were

complication risk (OR 1.79 [95 % CI 1.34–2.40]), Fistulas