Original Articles 225
Colonic transit
study by radio-opaque markers to investigate constipation:
Validation of a new protocol for a population with rapid gut
transit
Uday C. Ghoshal, Dinesh Gupta, Ashok Kumar, Asha Misra
Abstract
Background. Constipation is a common problem, which
may be due to slow transit or faecal evacuation disorders.
Though the screening test of colonic transit study using
radio-opaque markers given at 0, 24 and 48 hours followed by
abdominal X-ray at 72 hours is a good protocol in the West, it
is not suitable for Indians who have a rapid gut transit.
Methods. Nine patients with adult Hirschsprung disease,
11 with chronic intestinal pseudo-obstruction diagnosed using
standard investigations and 11 healthy subjects were evaluated
by colonic transit study using radio-opaque markers (SGmark),
20 each at 0, 12 and 24 hours followed by an abdominal X-ray
at 36 and 60 hours. The cut-off was determined by using
receiver operating characteristic (ROC) curves, and
sensitivity, specificity, positive and negative predictive
values and diagnostic accuracy were determined.
Results. The total number of markers retained in the
abdomen and those in the right segment at 36 hours in patients
with Hirschsprung disease and chronic intestinal
pseudo-obstruction was higher than that in healthy subjects
though the number in the left and rectosigmoid segments were
comparable. The abdominal X-ray at 60 hours, total number of
markers and number in all segments were higher in patients
with Hirschsprung disease and chronic intestinal
pseudo-obstruction than in healthy subjects. The best cut-off
by ROC curves at 36 and 60 hours was 30 and 14 markers,
respectively. The sensitivity, specificity, positive and
negative predictive values, diagnostic accuracy and area under
the ROC curve at 36 hours were 90%, 82%, 90%, 82%, 87% and
0.9, respectively; the corresponding values at 60 hours were
95%, 100%, 100%, 92%, 97% and 0.99, respectively.
Conclusion. Using the proposed protocol, the colonic
transit study is able to distinguish patients with specific
motility disorders causing constipation such as Hirschsprung
disease and chronic intestinal pseudo-obstruction from healthy
subjects with reasonable sensitivity and specificity, and
shows that an abdominal X-ray at 60 hours is better than one
at 36 hours.
Natl Med J India 2007;20:225
ê9
INTRODUCTION
Constipation is a common problem all over the world. 1
Though in most patients constipation is caused by irritable
bowel syndrome (IBS), in the West, in about half of these
patients, it is caused either by slow transit constipation (STC)
or faecal evacuation disorders (FED).1 A diagnosis of STC and FED in most developing
countries including India may not be easy due to considerable
overlap of the symptoms of these conditions and those of IBS,2
limited utility of tests available to investigate colonic
disorders such as colonoscopy and barium enema,3
and lack of wide availability of investigations used to
diagnose these conditions such as anorectal manometry and
barium defaecography. Colonic transit study (CTS) by
radio-opaque markers is considered a simple screening test to
diagnose STC and FED in the West.4,5
This involves an assessment of gut transit using 20
radio-opaque markers ingested at 0, 24 and 48 hours each,
followed by an abdominal X-ray at 72 hours.6 However, this
method was not found suitable in Indians because at 72 hours
no marker was found retained inside the abdomen due to rapid
gut transit. Therefore, a few investigators attempted to
reduce the interval between ingestion of markers and abdominal
X-ray.7
An earlier CTS used a protocol of administering 20
radio-opaque markers at 0, 12 and 24 hours each followed by an
abdominal X-ray at 12, 24 and 36 hours in 20 healthy Indian
subjects.8
However, in this protocol, patients had to undergo an
abdominal X-ray three times with consequent radiation
exposure. Moreover, no study from India has so far evaluated
such a protocol to differentiate constipation due to STC and
FED and compared it with healthy subjects. Hence, we aimed to
evaluate the clinical utility of a new protocol of CTS in the
diagnosis of constipation caused by STC and FED in India using
radio-opaque markers manufactured locally.
METHODS
Study subjects
Twenty adults with refractory constipation due to
Hirschsprung disease (HD) (n=9) and chronic intestinal
pseudo-obstruction (CIPO, n=11) attending the
Department of Gastroenterology at Sanjay Gandhi Postgraduate
Institute of Medical Sciences (SGPGIMS), Lucknow during a
5-year period (March 2001 to March 2006) and 11 age- and
gender-matched healthy volunteers (authors and staff members)
were included in the study after obtaining informed consent.
Pregnancy was excluded in women of childbearing age. The study
protocol was approved by the Ethics Committee of SGPGIMS.
Study protocol
Each patient was evaluated clinically including a detailed
history and physical examination. They were then investigated
based on a standard protocol9 which
included CTS by radio-opaque markers, balloon expulsion test,
anorectal manometry, colonoscopy with biopsy for amyloid
(Congo red stain) and single-contrast barium enema as
indicated. Tests to diagnose systemic diseases causing
constipation such as serum thyroxin and thyroid-stimulating
hormones and postprandial blood sugar were done in all
patients with CIPO.
Criteria for diagnosis
Hirschsprung disease was diagnosed by an absence of or
paradoxical rectoanal inhibitory reflex (RAIR) and a
suggestive single-contrast barium enema. Absence of ganglion
cells in the resected segment of the colon in patients who
underwent surgical treatment at SGPGIMS also supported the
diagnosis in most patients. CIPO was diagnosed by a history of
documented episodes of bowel obstruction and an absence of a
mechanical cause on barium small bowel series, barium enema
and colonoscopy.
CTS
This was done using radio-opaque markers manufactured
locally (SGmark). Subjects were asked to ingest 4
capsules at a time (5 markers in each capsule) at 0, 12 and 24
hours. All the markers at 0 hours were circular, at 12 hours
rectangular and at 24 hours triangular. Subsequently, an
abdominal X-ray was obtained in the
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Fig 1. Colonic transit study using radio-opaque marker (SGmark)
in a 40-year-old woman with refractory constipation and
past history of achalasia cardia successfully treated with
pneumatic dilatation 10 years ago. Note that most of the
radio-opaque markers are retained in rectosigmoid segment
on the abdominal X-ray at 60 hours (A). Anorectal
manometry showed a paradoxical rise in pressure in the
sphincter zone on balloon inflation (B; ‘R’ indicates
deflation of balloon). Single-contrast barium enema
revealed features of Hirschsprung disease (C). The patient
was treated surgically and histological examination of the
narrowed segment showed an absence of ganglion cells
confirming the diagnosis. RS right segment
LS left segment RSS rectosigmoid segment
SZ sphincter zone IR intrarectal port NS
narrow segement TZ transition zone
DS dilated segment |
and the balloon, which had been positioned
inside the rectum, was inflated with an increasing volume of
air (20 ml, 40 ml, 60 ml and so on) and deflated after each
inflation. A reduction in sphincter pressure to <5–10 mmHg
after each balloon inflation and restoration of pressure
following deflation of the balloon was considered as normal RAIR. Failure of the anal sphincter pressure to fall or a
paradoxical rise following balloon inflation was considered
suggestive of HD.
Each patient underwent the balloon expulsion test following
anorectal manometry in the left lateral position using a 4 cm
latex balloon attached to a 2 mm wide tube placed in the
rectum and filled with 60 ml water at room temperature. The
patient was asked to bear down in an attempt to expel the
balloon. If this failed, a weight was suspended on the other
end of the tube in 50 g increments until the balloon was
expelled or up to a maximum of 700 g weight.12
Management and follow up
Patients with HD underwent surgical treatment. The
resected specimens of the colon were examined histologically
for the presence of ganglion cells. Acute episodes of
intestinal pseudo-obstruction in patients with CIPO were
managed after hospitalization with intravenous fluids,
nasogastric suction and intravenous neostigmine. Between these
episodes, they were managed with laxatives and enemas. All
patients were followed up at the Luminal Gastroenterology
Clinic of the Department of Gastroenterology.
Statistical analysis
Numerical data were expressed as median and range.
Categorical and continuous variables were analysed using
Chi-square, Mann–Whitney U and Kruskall–Wallis H tests,
respectively. p values <0.05 were considered significant.
Receiver operating characteristic (ROC) curves were
constructed to evaluate the cut-off value of number of markers
retained that best differentiated healthy subjects from those
with disease. Sensitivity, specificity, positive and negative
predictive values, and diagnostic accuracy were calculated13
taking the best cut-off obtained using ROC analysis. The area
under ROC was also estimated.
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Table
I. Demographic and clinical parameters, and results of
colonic transit study using radio-opaque markers (SGmark)
in patients with Hirschsprung disease (HD), chronic
intestinal pseudo-obstruction (CIPO) and healthy subjects
(HS)
Parameter
HD (n=9) CIPO (n=11)*
HS (n=11) p value†
Age
(years)
29 (17–52) 46 (14–68) 40
(23–47) ns
Men
7 4
7 ns
Duration of symptoms (months)
120 (8–280) 96 (3–168)
— —
Number of markers retained in colonic transit study
At 36 hours
Right segment
22
(5–39) 30 (8–60) 13
(4–16) 0.002‡
Left segment
11
(1–19) 12 (0–27) 5
(0–26) ns
Rectosigmoid segment
9
(0–26) 9 (0–32) 6
(0–12) ns
At 60 hours
Total
44 (10–51) 43 (27–60) 1
(0–16) <0.001‡
Right segment
9
(0–22)§ 21 (13–60)§ 0
(0–10) <0.001‡
Left segment
12
(0–26) 7 (0–16) 0
(0–6) 0.001‡
Rectosigmoid segment
10
(1–42) 7 (0–18) 0
(0–3) <0.001‡
All continuous data are expressed as median and range
*In one patient with paraneoplastic pseudo-obstruction
with gastroparesis, all the markers were retained in the
stomach for weeks;14 for
the purpose of this analysis, it was considered that this
patient retained all markers at 36 and 60 hours †All
continuous data are analysed by Kruskall–Wallis H test and
post-hoc analysis by Mann–Whitney U test and categorical
data by chi-square test ‡ indicates significant
differences by post-hoc tests between all 20 patients as a
group and healthy subjects § indicates significant
differences by post-hoc tests between patients with HD and
CIPO |
RESULTS
Demographic and clinical parameters, and results of CTS of
patients with HD, CIPO and healthy subjects are summarized in
Table I. Patients with HD and CIPO were comparable to healthy
subjects in age and gender. Figures 1 and 2 show the results
of CTS in 2 representative patients, 1 with CIPO due to
amyloidosis and the other with HD, whose anorectal manometry
is also shown.
One patient each with CIPO had amyloidosis (documented by
Congo red staining of rectal biopsy, Fig. 2), parkinsonism,
hypotonic bladder, achalasia cardia and cholangiocarcinoma;
the latter patient also had pseudoachalasia and gastroparesis14
and the other had gastroparesis (documented by radionuclide
gastric emptying for solids in both). No patient had diabetes
mellitus or hypothyroidism. One patient with HD had associated
achalasia cardia. In 8 of 9 patients with HD, symptoms started
after 10 years of age.
The total number of markers retained in the whole abdomen
and those in the right segment at 36 hours in patients with HD
and CIPO was higher than that in healthy subjects though the
numbers in the left and rectosigmoid segments were comparable
(Table I). In the abdominal X-ray done at 60 hours the total
number of markers and number in all segments were higher in
patients with HD and CIPO than in healthy subjects. In the
abdominal X-ray at 60 hours though the number of markers
retained in the distal colonic segments tended to be higher
than those in the proximal colonic segments in patients with
HD than in patients with CIPO, such a difference was not found
in the 36 hours’ abdominal X-ray (Table I).
Anorectal manometry
It was abnormal in all 9 patients with HD. RAIR was absent
in
all of them. The median sphincter length, resting and squeeze
sphincter pressures were 3.9 cm (range 2.3–4.6), 51 mmHg
(19–73) and 83 mmHg (27–143), respectively.
In 6 of 11 patients with CIPO in whom anorectal manometry
was done, RAIR was present in all. The median sphincter
length, resting and squeeze sphincter pressures were 3 cm
(range 2.5–4), 88 mmHg (45–108) and 90 mmHg (75–107),
respectively.
|
Fig 2. Colonic transit
study using radio-opaque marker (SGmark) in a
68-year-old man with peripheral neuropathy and chronic
intestinal pseudo-obstruction. Most of the radio-opaque
markers are retained diffusely in all segments at 36 hours
(A); though at 60 hours
(B) only about half the markers are retained, these are
distributed diffusely. Rectal biopsy showed congophilic
deposits of amyloid
(C). RS right segment LS left segment RSS
rectosigmoid segment |
Balloon expulsion test
Patients with HD expelled the intrarectal
balloon with a median weight of 375 g (range 100–700 g); in
contrast, patients with CIPO expelled it with a median weight
of 150 g (range 100–500 g; p=ns).
Barium enema and histological examination of resected
colonic specimens
In all patients with HD, barium
enema showed a narrow segment followed proximally by a
transition zone and dilated colon. In 3 of 5 patients
undergoing surgical full-thickness biopsy, ganglion cells were
absent. In the other 2 patients occasional ganglion cells were
seen.
ROC curve analysis and determination of
diagnostic performance
Figure 3 shows the diagnostic performance of CTS at 36 and
60 hours. The best cut-off by ROC curve at 36 and 60 hours was
30 and 14 markers, respectively. Sensitivity, specificity,
positive and negative predictive values, and diagnostic
accuracy at 36 hours
Fig 3. Diagnostic performance
of abdominal X-rays at 36 (A) and 60 hours (B) using
cut-offs obtained by ROC analysis (30 markers at 36 hours
and 14 markers at 60 hours, shown by the horizontal line).
(C) Area under ROC curves for abdominal X-ray at 36 (0.90,
shown by the thick dotted line) and 60 hours (0.99, shown
by the continuous line) are compared. Thin dotted line
indicates area under the curve below 0.5, which is by
chance. |
were 90%, 82%, 90%, 82% and 87%,
respectively; the corresponding values at 60 hours were 95%,
100%, 100%, 92% and 97%, respectively. The area under ROC
curve tended to be more at 60 hours than that at 36 hours
(0.99 v. 0.9, respectively, Fig. 3c; p=0.06).
Management and follow up
Five of 9 patients with HD underwent surgical treatment
(modified Duhamel in 3 and colostomy with full-thickness
biopsy in 2). The other patients declined surgical treatment
and were lost to follow up.
Ten of 11 patients with CIPO presented with recurrent
episodes of intestinal pseudo-obstruction, which were managed
after hospitalization with nil by month, intravenous fluids,
nasogastric suction and rectal tube. Four of 11 patients
required intravenous neostigmine for treatment of acute
episodes of CIPO. One patient underwent colectomy for
persistent obstructive symptoms. One other patient with
paraneoplastic pseudo-obstruction died with advanced
malignancy.14
DISCUSSION
Our study shows that in India, CTS using
radio-opaque markers given at 0, 12 and 24 hours followed by
an abdominal X-ray at 36 and 60 hours can distinguish patients
with specific motility disorders causing constipation from
healthy subjects with reasonable sensitivity and specificity.
Also, an abdominal X-ray at 60 hours was better than that at
36 hours.
Although the present protocol distinguished patients with
HD or CIPO from healthy subjects with reasonable accuracy, it
was poor in differentiating between the 2 diseases (Table I).
This is possibly because of secondary dysfunction of the
proximal colon in cases of distal obstruction due to stasis
and increased pressure, which may be reversible after relief
of obstruction.15 However, an abdominal X-ray taken at 60
hours differentiated HD and CIPO quite well.
As per the protocol followed in the West, radio-opaque
markers are given at 0, 24 and 48 hours and an abdominal X-ray
obtained at 72 hours.1,9 However, the western protocol is not
appropriate for Indian subjects as Indians have a rapid
colonic transit7,16,17 Subsequently, CTS have been done on
healthy Indian subjects8 but no study has validated these in
patients with STC and FED and compared them with healthy
subjects. Our study shows that the present protocol for
performing CTS is effective in differentiating between STC and
FED such as HD from healthy subjects and therefore, has
potential clinical value. However, we have compared patients
with severe abnormalities causing constipation with healthy
subjects. Therefore, further studies are needed to determine
the best cut-off to differentiate a mild abnormality such as
constipation predominant IBS from healthy subjects.
Most criteria that are used to positively diagnose IBS have
been designed to differentiate IBS from organic diseases such
as colon cancer.18 Therefore, when patients present to a
clinician with severe constipation, neither these criteria nor
colonoscopy help to exclude specific motility disorders such
as STC or FED.19,20 Our data and other studies4,5 show that
marker studies help clinicians to decide whether to
investigate these patients further with specialized tests such
as anorectal or colonic manometry and defaecography.21 Though
in our study CTS was less accurate in differentiating FED from
STC, being a screening test, it would help clinicians to
decide whether to do other tests such as anorectal or colonic
manometry and defaecography.
Colonic transit depends on several factors. It is slower in
old age22 and in women, who more often suffer from
constipation.21 However, the patients included in our study
were comparable with the healthy subjects in age and gender.
Rarely, multiple markers may get stuck to one another making
it difficult to identify and count them. Using markers of
different shapes at different times may help clinicians to be
more confident in deciding whether the colonic transit in a
given patient is really slow. Rarely, it may be difficult to
differentiate perpendicularly lying rectangular and triangular
markers on an abdominal X-ray and hence the quality of the
abdominal X-ray is important in the optimal interpretation of
a CTS.
In conclusion, CTS using the proposed protocol is useful to
clinically diagnose constipation caused by STC or FED in an
Indian population and a single X-ray at 60 hours may be
sufficient. Hence, an X-ray at 36 hours may be avoided to
reduce unnecessary exposure to radiation.
ACKNOWLEDGEMENT
We thank Mr Raghunath of the Department of Gastroenterology,
SGPGIMS for technical help.
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