Procedure
The procedure can be conducted on an ambulatory basis. Standard patient preparation
includes a 12-hour fast prior to the procedure. Bowel preparation is a matter for
debate. Some experts recommend partial or complete bowel preparation, with polyethylene
glycol administered either the evening prior to the procedure, for example 16 hours
[1] before the recording, or on the same day, at least 2-3 hours before the capsule
examination. However, 80 mg of simethicone 20 minutes before the procedure can be
recommended to all patients, the administration of 2 liters of a polyethylene glycol-based
solution and 10 mg of metoclopramide can be considered optional. The rationale behind
a prep solution is that, as the capsule advances through the small bowel, visualization
of the mucosa may be impaired when there is dark luminal content and bubbles. The
use of prokinetic agents is considered controversial. A recent study showed that erythromycin
had no significant effect on capsule propulsion in the small bowel [2], in contrast to findings elsewhere that metoclopramide may increase the likelihood
of successful small-bowel examination (metoclopramide decreases gastric transit time)
[3]. At this stage, however, recommendations for use of prokinetics are not fully justified.
Patients are allowed to drink clear liquids 2 hours after ingestion of the capsule
and to eat a light meal 4 hours after ingestion.
Currently, two types of video capsules are available for use. The Given Imaging capsule
(PillCam SB) was used to pioneer the technique and employs complementary metal oxide
silicon (COMS) technology. More than 300 000 PillCam capsules have been used worldwide
since the development of this technique and up to now, all published evidence in peer
reviewed journals is based on this form of capsule.
The Olympus capsule endoscope (EndoCapsule EC type 1), with technology based on a
charge-coupled device (CCD) and with electronic enhancement of image quality, was
launched recently (limited data have been presented at a few meetings [4]).
Both capsule systems also provide an external control system (real-time viewer) that
allows real-time checking of the images from the capsule. This system can be used
at the beginning of the examination to avoid the capsule’s being trapped in the esophagus
and/or to shorten transit time in the stomach. The medical benefit of this control
system has yet to be proved in well-designed studies.
Reading the recorded images
Location
The Given Imaging workstation software that is used to process the capsule images
incorporates a locating feature. This makes it technically possible to approximate
the location of any pathological findings within an average range of 3.77 cm, but
the relevance of this feature in clinical practice is unknown. Locating the position
of the capsule in the abdomen is attempted by triangulation from the three closest
sensors; these are identified according to the strength of the signals received from
the capsule by the eight sensors attached to the abdominal wall. The location is then
calculated from the position of these sensors and displayed on the computer screen
as a two-dimensional image.
The Olympus EndoCapsule software provides an antenna (eight antennas combined into
one); the antenna receiving the strongest signal is highlighted, which gives an idea
of the capsule’s position. However in clinical practice, identification of the capsule’s
position is often considered imprecise, and its approximate location is usually guessed
on the basis of sometimes different mucosal patterns in jejunum and ileum and is also
assessed according to the time elapsed from the start of the examination. Furthermore,
it is now possible to directly check the capsule images during the procedure using
the Olympus external viewer.
Software
1. Multiview
Video capsule software has also recently had a ”multiview” feature added for reading
the VCE recordings. This allows for the simultaneous display in adjacent windows of
two or even four consecutive images from the recording. The new software by Given
allows for faster ”quick view” browsing, has a ”rapid atlas” tool for comparing pathological
images, a ”circumferential scale” to estimate the circumferential involvement of a
finding such as a varix or an ulcer, and a new automatic viewing mode. Since software
is constantly updated, guidelines can only report on the present status.
2. The ”suspected blood indicator”
The newer versions of capsule endoscopy include software that detects the color red,
which may help to identify bleeding in the small intestine. Both the PillCam and Olympus
video capsules have this feature. Preliminary reports from a few studies regarding
the accuracy of this feature are conflicting [5]
[6]
[7].
Indications
A Small-bowel diseases
1. Obscure gastrointestinal bleeding
The primary and most frequent indication for VCE of the small bowel has been for the
diagnosis of obscure gastrointestinal bleeding. Obscure gastrointestinal bleeding
accounts for up to 5 % of gastrointestinal bleeding, and is defined as the absence
of an identified source of recurrent or persistent gastrointestinal bleeding after
standard evaluation by upper endoscopy and colonoscopy [8]. Patients with obscure gastrointestinal bleeding may also have obvious bleeding
(overt obscure gastrointestinal bleeding), or positive guaiac stool test results and/or
iron-deficiency anemia (occult obscure gastrointestinal bleeding). The yield of capsule
endoscopy appears highest for patients with ongoing overt bleeding compared with obscure
occult bleeding, as shown in a recent study [9] of 100 consecutive patients with obscure gastrointestinal bleeding. The diagnostic
yield was 92 % and 44 % for overt active bleeding and obscure occult bleeding respectively.
The most common lesions were angiodysplasia, in 29 %, and inflammatory bowel disease,
in 6 %.
Compared with other diagnostic radiological tests, including barium radiography, push
enteroscopy, and cross-sectional imaging, VCE has a significantly higher yield in
patients with obscure gastrointestinal hemorrhage [9]
[10]
[11]
[12]
[13]
[14]
[15]
[16].
The overall yield for obscure gastrointestinal bleeding is in the range of 50 %-81
% as reported by various studies [9]
[10]
[11]
[12]
[13]
[14]
[15]
[16]. A recent meta-analysis indicated that the incremental yield of VCE over push enteroscopy
and small-bowel barium radiography for clinically significant findings is ≥ 30 % with
a number-needed-to-treat (NNT) of 3 [16]. VCE helps with management decisions with obscure gastrointestinal bleeding and
can replace more complex and risky standard tests [17]
Based on findings from a recent study [10], the optimal timing (higher yield) for a video capsule investigation in obscure
gastrointestinal bleeding is within the first few days post bleeding with the maximum
wait being 2 weeks.
In conclusion, VCE with the Given Imaging PillCam technology has been widely studied,
and is considered to be a very valuable tool for investigating obscure gastrointestinal
bleeding. This can presumably translate to better management outcomes than obtained
with other modalities for patients with obscure gastrointestinal bleeding, although
additional trials are still needed to clarify this issue.
2. Crohn’s disease
Capsule endoscopy has a high yield in findings small bowel lesions in Crohn’s disease,
as illustrated by several comparative studies, and may make the diagnosis in the subset
of patients with clinical suspicion but negative upper and ,lower endoscopy including
inspection of the terminal ileum [18]
[19]
[20]
[21]
[22]
[23]
[24]
[25]. VCE permitted confirmation of the diagnoses of small-bowel Crohn’s disease in both
patients with Crohn’s and in those with suspected Crohn’s disease in which the diagnosis
was not possible by other conventional means of investigation. The diagnostic yield
for this indication ranges from 43 % to 71 %, and according to recent studies VCE
was superior to push enteroscopy [4] and enteroclysis [24]
[25]. VCE detected more proximal and middle small-bowel cases of Crohn’s disease than
computed tomography (CT) enterography and small-bowel follow-through (SBFT) [26]. These results have been used to indicate a role for VCE with regard to early disease
management, but its impact on the management of patients with established CD is not
fully clear. In the studies published, in some patients the medication dosage was
either increased or decreased, with commencement of immunomodulator or anti-tumor
necrosis factor (TNF) therapy, and in other patients surgery was said to be avoided
[22]. Future studies will show which role VCE may have a role in assessing disease prognosis,
activity, and tissue healing post therapy. It is also hoped that VCE may play a role
in the management of Crohn’s disease patients by defining the extent and severity
of the disease in the small bowel [27]
There are still a few issues to be resolved. Firstly, the rate of false-positive and
false-negative results with VCE has not yet been addressed. In other words, not all
ulcers are Crohn’s disease and not all biopsies are confirmatory. The differential
diagnosis for Crohn-like pathologies on VCE should be elaborated, a full history provided,
and relevant tests carried out to confirm the presence or absence of Crohn’s disease.
In addition, one should not overestimate mucosal abnormalities in patients with Crohn’s
disease, especially if the patient is taking nonsteroidal anti-inflammatory drugs
(NSAIDs). The NSAIDS should be stopped 2 months prior to the test. Secondly, from
a technical point of view, VCE does not offer the option of tissue sampling for these
patients and they may ultimately need push enteroscopy or double-balloon endoscopy
for tissue sampling. Thirdly, the gold standard test to compare with VCE is not yet
ideal since, so far, VCE has been proved superior to these conventional tests in terms
of diagnostic yield. Lastly, the interobserver reading variability may be a source
of bias for some cases and confirmation by another gastroenterologist may be needed
but not always possible in some small community hospitals. The risk for retention
in patients with confirmed Crohn’s disease is estimated to be 5 %.
Further large, randomized prospective trials to specifically investigate each factor
will obviously be necessary to define the ultimate role of CE in this setting.
3. Celiac disease
On the evidence of a few studies, capsule endoscopy may be useful in diagnosing celiac
disease [28]
[29]
[30]
[31]
[32]. Since the test is done in the free air-insufflation environment of the small bowel,
the visual images are taken very close to the mucosa and hence clear pictures of the
mucosa are obtained. Furthermore, this technology, with its magnification capacity
of 1 : 8, can provide good quality images of the small bowel, including the villi.
The abnormalities detected include primary changes in small-bowel mucosa, namely villous
atrophy [28] (scalloping, fissuring, mosaic pattern, flat mucosa, loss of the circular folds
and nodularity), and complications related to celiac disease such as ulcerative jejunoileitis,
enteropathy-associated T-cell lymphoma and adenocarcinoma of the small bowel [30].
The sensitivity and specificity of VCE in detection of villous abnormalities can be
high when an experienced capsule endoscopist analyzes the data [28]. This finding shows that a gastroenterologist familiar with VCE may interpret the
data better, making the test more accurate. There are no data comparing VCE with conventional
endoscopy in diagnosing celiac disease in a low prevalence setting, but we know that,
in general, magnification endoscopy is better than conventional endoscopy for such
types of diagnosis [29]. Nevertheless, VCE is a relatively noninvasive test and may be as good as or better
than magnification endoscopy. For this reason, the International Conference on Capsule
Endoscopy (ICCE), sponsored by the company Given Imaging, has reached a consensus
that VCE may be sufficient for establishing a primary diagnosis in patients with strongly
suggestive serological markers for celiac disease who are unwilling or unable to undergo
esophagogastroduodenoscopy (EGD) [33]. Management problems when histology is not performed have not been discussed in
detail yet; further difficulties may arise in patients with positive serological markers
and negative VCE, raising the possibility of partial villous atrophy.
Other potential indications for VCE in celiac disease include complications related
to celiac disease. Patients with celiac disease and non-specific or alarm symptoms
like persistent abdominal pain, anemia, or bleeding will likely benefit from this
investigation that explores all of the small bowel. The yield for detecting endoscopic
findings due to complications related to celiac disease is higher [30] than with other modalities. However, one should ensure that it is determined whether
these entities are related to celiac disease or are a separate phenomenon, although
the management may not differ significantly unless these findings are secondary to
an identifiable culprit such as NSAIDs.
In conclusion, and based on small studies, VCE provides detailed images of the small
bowel in patients with celiac disease. This may facilitate the assessment of celiac
disease and its related complications. Therefore, VCE may be of interest in the initial
work-up of celiac disease (especially in high risk patients), in refractory celiac
disease, and in case of alarm symptoms.
4. Hereditary polyposis syndromes
VCE can be used to detect small-bowel polyps related to hereditary polyposis syndromes.
Recently, VCE has been found to have a higher yield for detecting such polyps than
barium studies [34]. Another study that compared polyp detection by VCE and magnetic resonance imaging
(MRI) in patients with hereditary polyposis found similar accuracy among patients
with polyps larger than 15 mm. However, the detection rate for polyps between 5 and
15 mm was much higher with VCE, and polyps 5 mm and smaller were detected only by
VCE [35]. In this study, MRI, however, was more accurate in determining the exact size and
location of the polyps detected by both studies. Growing evidence from other studies
confirms the usefulness of this technique for detecting polyps in selected patients
with familial adenomatous polyposis (FAP) who have an increased risk of developing
polyps in the distal part of the small bowel, and as a first-line procedure in patients
with Peutz-Jeghers syndrome (PJS) [36]
[37]. The detection by VCE of these polyps in some patients with PJS has led to a change
in management in a significant proportion of them. Capsule endoscopy therefore appears
to be a promising alternative to the SBFT (enteroclysis) series for surveillance in
patients with hereditary polyposis syndromes.
5. Small-bowel tumors
Diagnosis of small-bowel tumors is a new field for capsule endoscopy examination.
Prior to the use of the video capsule, small-bowel tumors were considered rare (found
in about 1 % of patients according to radiological imaging studies) [38]. These tumors have often been diagnosed late in their stage of development or incidentally
during a laparotomy or biopsy. With the advent of video capsule endoscopy, this could
change. Some studies [38]
[39]
[40] have reported small-bowel tumors in 6 % - 9 % of patients - many more than previously
expected. The most common indication for video capsule endoscopy in patients with
small-bowel tumors was obscure gastrointestinal bleeding/anemia (80 %). Video capsule
endoscopy detected small-bowel tumors after patients had undergone an average of 4.6
negative procedures. The majority of the detected small-bowel tumors were malignant
(60 %), consisting of adenocarcinomas, carcinomas, melanomas, lymphomas, and sarcomas.
The benign small-bowel tumors (40 %) were gastrointestinal stromal tumors (GISTs),
hemangiomas, hamartomas, and adenomas. Therefore, in cases of unclear obscure gastrointestinal
bleeding, the possibility of small-bowel tumor should be considered and the patient
assessed with video capsule endoscopy [38]
[39]
[40]
[41]
[42]
[43]
[44]
[45].
6. NSAID-related conditions
Considerable side effects and pathological lesions related to the gastrointestinal
tract can be caused by NSAID use. VCE was useful in a recent study to detect lesions
caused mainly by NSAIDs [46]. The most common lesions were mucosal breaks, seen in 40 % of patients. Other lesions
were reddened folds, petechiae, denuded mucosa, blood in the lumen, ulcers, and intestinal
diaphragm.
In another similar study [47], VCE was able to detect small-bowel mucosal breaks in 55 % of patients using naproxen,
16 % of those using celecoxib, and in 7 % of placebo patients with a normal baseline
VCE prior to the study. VCE showed that NSAID damage is more frequent and extensive
than suggested by studies of NSAID-associated small-bowel injury shown by ileoscopy
performed at the time of colonoscopy or in autopsy examination [48]. Subsequent studies are needed to investigate whether there is a pattern of damage
associated with outcomes such as unexplained iron-deficiency anemia or hypoalbuminemia
among chronic NSAID users [48].
7. Miscellaneous
Different small-bowel lesions have been described using video capsule endoscopy. Case
reports have demonstrated the possible usefulness of VCE in the diagnosis of Meckel’s
diverticulum, tuberculosis, Ascaris infection, and aortoduodenal fistulas [49]
[50]
[51]
[52]. Some centers have also evaluated capsule endoscopy for the study of gastrointestinal
tract motility disorders, the assessment of bowels in post transplant patients, in
unexplained abdominal pain and diarrhea. The usefulness of this technique for such
indications has not yet been established.
8. Pediatrics
Capsule endoscopy has been used less frequently in pediatric populations for to some
of the indications mentioned above (e. g. obscure bleeding and Crohn’s disease); information
has mainly been obtained from case reports and small series studies. The video capsule
was superior to conventional studies (gastroscopy, colonoscopy with ileoscopy, and
SBFT examinations) in finding lesions suggestive of Crohn’s disease, in a small study
involving patients between the ages of 12 and 16 [53]. In a recent small study, VCE was used in to examine children over the age of 10
with obscure small-bowel lesions; it was found that VCE is an accurate and noninvasive
approach for diagnosing these lesions [54]. Safety issues may limit the use of VCE in the younger age group given that in this
group there may be difficulties passing the capsule through the gastrointestinal tract,
particularly through the pylorus and ileocecal valve.
B Esophageal capsule (PillCam ESO) investigation
The PillCam ESO, which was specifically designed to investigate esophageal diseases,
has recently been evaluated and released [55]
[56]
[57]
[58]
[59]. Because there is only a short transit time in the esophagus, the video capsule
is equipped with miniature sensors at both ends to improve image quality.
The patient is asked to fast for 2 hours prior to the procedure. The patient swallows
the capsule while supine, maintains this position for 2 minutes, and is then asked
to rise slowly to a 30-degree angle and then to increase the angle by 30 degrees every
2 minutes over a period of about 6 minutes until sitting upright (improvements in
the ingestion procedure have recently been presented [60]. During this time, the capsule camera flashes 14 times per second to capture images
from both ends of the capsule which are then transmitted to the three sensor arrays
that are placed on the patient’s chest.
The main potential indication for PillCam ESO investigation is for patients with gastroesophageal
reflux disease (GERD) and Barrett’s esophagus. It was approved by the US Food and
Drug Administration (FDA), following a study by Eliakim et al. published in abstract
form [55]. The sensitivity and specificity for both indications were very high (e. g. 100
% and 80 % respectively). This was subsequently confirmed by a larger multicenter
study carried out by the same group which re-emphasized the previous findings [59]. Recently, a new device with an image production capability of 14 fps (frames per
second) has been developed. This device has been compared with a 4-fps device in a
recent study, and proved to be superior in terms of sensitivity and specificity for
GERD, Barrett’s esophagus, and for visibility of the upper esophageal sphincter [56].
Presumably, other esophageal diseases could also be detected by the PillCam ESO. Small
pilot studies suggest that it is comparable to EGD in detecting esophageal varices
and assessing portal hypertension in cirrhotic patients [57]
[58]. However, this comparison between VCE and EGD can be misleading in some cases for
a few reasons. The EGD provides a more extensive area for examination including the
stomach and small bowel, and has the advantage of allowing intervention, compared
with the esophageal imaging only that is allowed by the capsule. On the other hand,
in the studies comparing the two devices a regular EGD instrument was used (the XP
in one study, type not mentioned in the other), as opposed to new-generation EGD devices
with high magnification, which provide better imaging than regular EGD instruments.
Additionally, the studies did not fully address issues such as detection and accuracy
rate for short-segment compared with long-segment Barrett’s esophagus, using the esophageal
VCE technique. The problem of uncontrolled image production in VCE may play a significant
role in the misdiagnosis of short-segment Barrett’s esophagus in high-risk patients.
On the other hand, esophageal VCE has been proved to be excellent for detection of
erosive esophagitis. However, patients with nonerosive esophagitis who continue to
have symptoms will likely require EGD for better evaluation.
In patients with pacemakers, there is a risk of interference with the pacemaker because
of the proximity of the sensor arrays placed on the patient’s chest when the esophageal
capsule is used. This has not yet been confirmed by any trials.
In conclusion, use of the esophageal capsule should be determined on a case by case
basis, depending on the patient’s presentation. Those with suspected Barrett’s esophagus
should undergo EGD so that a biopsy can be obtained. The role of the esophageal capsule
for other indications needs to be clarified further by larger prospective studies.
The issue of the relative cost-effectiveness of esophageal capsule examination and
EGD in such indications will also need to be clarified by further study.
Limitations and risks
Generally, VCE is very well tolerated by patients. However, there are a few limitations
and risks which should be taken into consideration.
Capsule retention is defined as having an endoscopy capsule remain in the digestive
tract for a minimum of 2 weeks [63]. This problem has been reported especially among patients with Crohn’s disease and
among those with a high risk for stricture formation, such as NSAID users and ischemic
colitis (associated with small-bowel tumors, radiation enteritis, surgical anastomotic
strictures). The occurrence of this problem is variable and largely dependent upon
the nature and extent of the disease and the degree of stenosis. The rate has been
reported as 1 % - 2 % [64]
[65]. Recently, a ”patency capsule,” of similar size to the video capsule and able to
dissolve spontaneously as it is mainly composed of lactose, has been developed to
assess bowel patency and degree of stenosis. When passage of the patency capsule is
blocked, the capsule dissolves in 40 - 100 hours. The safety and efficacy of this
capsule has been questioned [66]. There is a risk that the capsule itself will exacerbate the stenosis and surgical
intervention has been reported, especially among patients with Crohn’s disease (mainly
those with a high degree of stenosis) [66]
[67].
For this reason, if VCE is indicated, careful consideration must be given before performing
VCE in high risk patients. VCE should be preceded by imaging tests to exclude stenosis
in patients with suspected Crohn’s disease. Patients with a history of abdominal obstruction,
abdominal surgery, and abdominal or pelvic area radiation exposure should be excluded.
Medical treatment with corticosteroids or infliximab can release a trapped capsule
but in some cases endoscopic or surgical removal is required.
The extent of false-negative results may be an issue, given the fact that VCE is largely
dependent on peristalsis which affects its image angle accuracy. This is attributed
to an ”image skip” phenomenon since the visual field of the camera does not cover
360 degrees.
VCE should not be used in patients with swallowing disorders, due to the risk of aspiration.
The safety of its use during pregnancy has not yet been studied. Electromagnetic interference
with pacemakers can occur; however, this is without clinical significance and no potential
dangerous inhibition of pacemakers was observed in a recent study [68]. The absence of reimbursement for the procedure in the majority of European countries
is still a major drawback.
