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Ileal bladder augmentation and vitamin B12: Levels
decrease with time after surgery
S.C. Blackburn, S. Parkar, M. Prime, L. Healiss, D. Desai, I. Mustaq,
P. Cuckow, P. Duffy, A. Cherian *
Department of Urology, Great Ormond Street Hospital for Children, Great Ormond Street, London WC1N 3JH, UK
Received 30 August 2010; accepted 15 November 2010
Available online 22 December 2010
KEYWORDS
Pediatric;
Bladder augmentation;
Ileocystoplasty;
Enterocystoplasty;
B12
Abstract Objective: We investigated vitamin B12 deficiency following ileocystoplasty in chil-
dren.
Methods: Patients who underwent ileocystoplasty between December 1993 and September 2006
were included and B12 levels were retrospectively analysed. Patients with a serum B12 of less
than 150 pg/ml were considered deficient. The distance of the ileal segment from the ileocaecal
valve was recorded.
Results: There were 105 patients in the series; 61 were male. Mean age at surgery was 7.7 years
(SD Z3.9). The mean interval from surgery to most recent B12 level was 50 months (SD Z30).
None of the patients were on B12 supplementation. Two patients were B12 deficient, both more
than 7 years after surgery; 44% of patients with levels available 7 years after surgery had a B12
below 300 pg/ml. There was a significant negative correlation between B12 level and length of
follow up (Spearman’s rank, P<0.01). Twenty patients with an ileal segment sparing 60 cm from
the ileocaecal valve had a higher mean B12 (524 vs 419, SEM 60 vs 28). This was not statistically
significant.
Conclusion: We demonstrate a reduction in serum B12 level with time following ileocystoplasty.
These patients should have their B12 levels measured in the long term.
ª2010 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.
Introduction
Bladder augmentation using a portion of ileum (ileocysto-
plasty) is the most common method used to achieve a safe
reservoir and continence. Resection of a portion of ileum
and exposing its mucosa to urine leads to a number of
concerns, including the risk of neoplasia[1]. Other potential
complications include metabolic and vitamin deficiencies
[2]. A large number of studies have looked at long-term
outcomes following ileocystoplasty, but few have focused
on vitamin B12 deficiency[3e5].
Absorption of vitamin B12 takes place solely in the
terminal ileum, having been bound to an intrinsic factor in
the stomach. B12 sources are exogenous as it is not synthe-
sized in humans. A recent study by Rosenbaum et al,
* Corresponding author. Tel.: þ44 0207 405 9200.
E-mail address: Cheria@gosh.nhs.uk (A. Cherian).
Journal of Pediatric Urology (2012) 8,47e50
1477-5131/$36 ª2010 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.jpurol.2010.11.007
Author's personal copy
suggested that the development of vitamin B12 deficiency
may be a concern in children who have undergone ileocys-
toplasty[6]. They demonstrated a 21% rate of vitamin B12
deficiency after 7 years of follow up (B12 level <200 pg/ml),
with 41% of patients having ‘low normal’ values (B12
level <300 pg/ml).
In this study, we aimed to investigate the incidence of
B12 deficiency in our own population of patients who had
undergone ileocystoplasty.
Methods
A retrospective review of patients under 16 who had
undergone bladder augmentation between December 1993
and September 2006 was performed. Patients were identi-
fied from departmental records and operating registers.
Case details were retrieved from hospital medical records.
Serum B12 values were obtained from the hospital pathology
records system. Levels are measured annually as part
of postoperative follow up using immunoassay (Immulite
2500). In patients with low B12 values, serum haemoglobin
and mean corpuscular volume were obtained. Patients’
general practitioners were contacted to clarify if any were
on B12 supplementation.
Patients who had undergone augmentation using colon
and those who did not have serum B12 values recorded at
our hospital were excluded from the study. Patients who
had undergone revisional surgery were also excluded,
together with those with a diagnosis of cloacal exstrophy,
as the risk of intestinal failure in these patients puts them
at an independent risk of B12 deficiency before augmen-
tation is undertaken.
Serum B12 levels less than 150 pg/ml were considered to
be low, as this is the lower limit of our laboratory’s normal
range. Data were analysed using a Spearman’s rank correla-
tion coefficient.
One of the surgeons at our institution has pursued
a policy of resecting ileum sparing at least 60 cm from the
ileocaecal valve. These patients were therefore analysed as
a sub-group.
Results
During the period analysed, 236 patients underwent
bladder augmentation. Of these, 112 had undergone ileal
augmentation alone. Seven patients with a diagnosis of
cloacal exstrophy were excluded from analysis. Of the
remaining patients, 105 had B12 levels available for analysis
on our pathology system (64%). Sixty-one patients were
male. The underlying diagnosis was bladder exstrophy in 48
patients (46%), neuropathic bladder in 35 (33%), cloacal
anomaly in 8 (7%), anorectal anomaly in 5 (5%), posterior
urethral valves in 5 (5%), urogenital sinus in 2 (2%) and
bladder malignancy in 2 (2%).
Mean age at operation was 7.7 years (SD Z3.9 years,
range Z3e16 years). The mean interval from surgery to the
most recent serum B12 level was 50 months (SD Z30 months,
range Z2e183 months).
Two patients had low serum B12 levels, both measured at
more than 7 years postoperatively. Proportions of patients
with low B12 levels are shown in Table 1. Values of <200 pg/
ml and <300 pg/ml are included for comparison with the
work of Rosenbaum et al. [6]. B12 levels by diagnosis are
shown in Fig. 1.
A significant negative correlation between length of
follow up and serum B12 level was observed in our data
(Spearman’s rank correlation, P<0.01) (Fig. 2).
Nineteen patients had the ileal segment utilized for the
augment sparing at least 60 cm from the ileacaecal valve.
These patients had a higher serum B12 at follow up (mean:
524 v 419, SEM: 60 v 28). This difference did not approach
statistical significance. The interval between follow up and
surgery for these patients was shorter (30 vs 50 months).
Discussion
We have demonstrated a 2% rate of B12 deficiency. Our
absolute B12 levels are similar to those quoted by Rose-
nbaum et al. [6], with 9% of patients having serum B12
levels of less than 200 pg/ml and 35% having levels less than
300 pg/ml. In those patients followed up for more than
7 years, 33% of patients had a B12 level less than 200 pg/ml.
This compares to 20% in the previous study.
Our series contain a large number of patients who
underwent ileal bladder reconstruction as children. The
fact that we have demonstrated a strong trend towards
a decrease in serum B12 with time after surgery indicates
that ongoing follow up of the serum B12 levels in these
patients is necessary to prevent the complications of
deficiency.
Table 1 Number of patients with serum B12 less than
300 pg/ml, 200 pg/ml and 150 pg/ml after ileocystoplasty.
All patients >5 years
post op.
>7 years
post op.
Total no. 105 31 9
B12 <300 35 (33%) 15 (48%) 4 (44%)
B12 <200 9 (9%) 5 (16%) 3 (33%)
B12 <150 2 (2%) 2 (6%) 2 (22%)
Figure 1 Scatter graph showing B12 level in pg/ml, for the
five principle diagnostic groups in the series.
48 S.C. Blackburn et al.
Author's personal copy
There are several limitations to our methods which
require discussion. The recording of B12 levels occurred in
most patients on an annual basis; however, as data collection
was incomplete a potential bias was introduced, as not all
patients undergoing bladder augmentation had B12 levels
measured at our hospital. In addition, it is possible that this
population of patients have an impairment of the preoper-
ative ability of the liver to store B12. This study would,
therefore, have been strengthened if preoperative B12 levels
were available [7]. Although the segment of ileum harvested
for augmentation was consistently 25e30 cm, only one
surgeon measured the distance of the ileal segment from the
ileocaecal valve. These patients were analysed as a sub-
group. More precise details of the location of ileal segment
used in the remaining patients would have been of use.
Although no patients with B12 deficiency developed
megaloblastic anaemia, we have no data relating to the
neurological status of these patients. As it is recognised that
neurological complications of B12 deficiency can occur in the
absence of anaemia or a macrocystosis[8], this study would
have been enhanced by information from neurological exam-
ination documenting the incidence of complications of B12
deficiency amongst our patients with low serum B12 values.
The implication of our study, and that of Rosenbaum
et al. [6], is that B12 deficiency is the result of the exclu-
sion of ileum from the intestinal tract. Pancreatic insuffi-
ciency, diet, bacterial overgrowth and medication are,
however, also possible aetiologies[7].
The question remains as to which patients would benefit
from supplementation. It is important not to underestimate
the potentially devastating consequences of B12 deficiency,
which include peripheral neuropathy, loss of position and
vibration sense, and dementia. The absolute value of serum
B12 is of limited use, as patients have been observed to have
neurological complications of B12 deficiency with a serum
B12 level greater than 150 pg/ml
8
. Given that some of the
patients undergoing bladder augmentation have concurrent
neurological impairment, it is important that B12 deficiency
is considered as a possible cause of neurological deteriora-
tion. Measurement of methylmalonic acid and homocysteine
in these patients may be a more sensitive way of detecting
those at risk of complications of deficiency, as B12 serves as
a coenzyme in their metabolism. An alternative strategy
would be to assess intestinal absorption of B12 using a Schil-
ling test. Rosenbaum et al. suggest that all patients with
values of less than 300 should be considered for supple-
mentation on the basis that the trend of decreasing B12
values in this patient population leads to a probability of B12
deficiency developing at a later date [6]. Vanderbrink et al.
have recently demonstrated that serum B12 in this patient
population can be increased using oral B12 supplementation
[9]. Prophylactic administration of oral B12 to this population
at risk of B12 deficiency may, therefore, be a practical way of
avoiding the complications of deficiency.
It is unclear from our data to what extent surgical
technique affects the development of B12 deficiency. Adult
studies have suggested that B12 deficiency is principally
associated with the use of the ileocaecal region for urinary
reconstruction[5]. In the paediatric population, it has
previously been recognised that the use of a long segment
of ileum, such as in a Koch reservoir, is associated with the
development of B12 deficiency[10]. Our study is limited in
that the details of precisely which segment of ileum was
used were not available to us in all patients. The consensus
view of the surgeons involved in our study, however, is that
the ileocaecal region should be avoided, with one surgeon
measuring the distal limit of the resection at least 60 cm
from the ileocaecal valve. Patients treated by this surgeon
had a higher B12 level, although this difference was not
significant. This may be due to the shorter follow up of this
sub-group of patients.
Conclusions
We demonstrate a reduction in serum B12 level with time
after surgery in our study. Patients who have undergone
ileal bladder reconstruction should have their B12 levels
regularly checked and be appropriately supplemented to
avoid the complications of deficiency. This is particularly
important from 5 years postoperatively.
Figure 2 Scatter graph showing serum B12 plotted against length of postoperative follow up in months. This plot shows
a negative correlation between serum B12 and length of follow up. Spearman’s rank, P<0.01. Patients in whom 60 cm of ileum was
definitely spared are shown as square data points.
Ileal bladder augmentation and vitamin B12 49
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Funding
None.
Conflict of interest
None.
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