REVIEWThe Future of Capsule Endoscopy
Jean-Francois Rey

Department of Hepatogastroenterology, Institut Arnault Tzanck, St. Laurent du Var, France(Received for publication on July 9, 2012)(Accepted for publication on October 22, 2012)(Published online in advance on May 27, 2013)

Small-bowel capsule endoscopy (SBCE) was introduced 11 years ago by Given Imaging and is becoming the gold standard for small-bowel examination. This major step in the field of digestive medicine
has opened the possibility of promising non-invasive explorations of the esophagus, stomach, and colon.
SBCE can be used to overcome the inherent limitations of enteroscopy, especially in the West, where
the capsule has been available since 2001. Obscure gastrointestinal (GI) bleeding with normal findings
on upper and lower endoscopy remains the most important indication, and suspected Crohn’s disease isalso a well-accepted indication. Findings from a capsule investigation may warrant therapeutic endoscopy, but in many cases, SBCE avoids this useful but time-consuming endoscopic procedure. The useof a colon capsule for colorectal cancer screening when traditional colonoscopy is contraindicated or
impossible is undergoing clinical trials. Early results seem promising, but control of colonic motility is
still cumbersome, and patient preparation remains the most important drawback. We performed thefirst clinical trial in humans of a magnetically guided gastric capsule that offers the possibility of investigation with a capsule that can be controlled spatially. To date, we have carried out procedures in morethan 400 patients and volunteers, with impressive results compared with high-definition gastroscopy.
Even though endoscopy remains the most important tool in the GI field, capsules offer promising new
possibilities. (doi: 10.2302/kjm.2012-0011-RE; Keio J Med 62 (2) : 41–46, June 2013)

Keywords: capsule endoscopy, guided capsule, digestive endoscopy

Introduction

been using the capsule device since 2004 (Table 1). The
most important indication for the use of SBCE remains
obscure gastrointestinal (GI) bleeding after upper andlower GI endoscopy have shown normal findings. Suspected Crohn’s disease is also a well-accepted indication.
Numerous findings relating to the small bowel have now
been described, whereas, before the advent of SBCE, thesmall bowel was unable to be directly visualized and wasconsidered the “black box” of the digestive tract (Table2). In the near future, we will be able to improve the clinical application of SBCE in three major areas: handlingof the equipment, optical performance, and reduction inreading time.
Handling of the equipment and most of the examination
is carried out by a nurse or an assistant. The sensor arrayand the data recorder are built into a belt that was intro-

Small-bowel capsule endoscopy (SBCE) was introduced 11 years ago by Given Imaging and is becoming agold standard for examination of the small bowel.1 This
major step in digestive medicine allowed promising noninvasive explorations of the esophagus, stomach, andcolon.2 The aim of this review is to highlight future improvements in SBCE and the potential clinical benefits of
its use our patients. 3
Small-bowel Capsule Endoscopy
SBCE can be used to overcome the inherent limitations of enteroscopy, especially in the West, where capsule endoscopy has been available since 2001; we have

Presented at the 1826th meeting of The Keio Medical Society in Tokyo, May 15, 2012.
Reprint requests to: Jean-Francois Rey, MD, Department of Hepatogastroenterology, Institut Arnault Tzanck, St. Laurent du Var 06700,
France, E-mail: jean-francois.rey@wanadoo.fr
Copyright © 2013 by The Keio Journal of Medicine

41

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Rey JF: Future of Capsule Endoscopy

Table 1 Number of examinations performed with different types of capsules at Institut Arnault Tzanck
Given Imaging(PillCam SB)

MiroCam(SBCE)

Olympus(SBCE)

Olympus(MGCE)

Given Imaging(PillCam COLON 2)

7
15
15
24
12
18
21
23
5
140

5
5

26
56
94
32
57
52
59
34
410

85
290
375

2
2
4

2004
2005
2006
2007
2008
2009
2010
2011
2012
Total

SBCE, small-bowel capsule endoscopy; MGCE, magnetically guided capsule endoscopy.

Table 2 SBCE findings when investigating the causes of small-bowel bleeding (Reproduced from Pennazio M.)4
Vascular lesions

TumorsOther causes

Angioectasia
Dieulafoy lesion
Telangiectasiaa
Varices
Phlebectasia
Aorto-enteric fistula

AdenomabCrohn’s diseaseDrug-induced small-bowel injury
Ulcers in celiac disease
Chronic ulcerative jejunoileitis
Vasculitis
Radiation enteritis

Aneurysms

Hamartomac
LipomaAdenocarcinoma
Lymphoma
Gastrointestinal stromal tumors(GISTs)
Carcinoid tumors
Vascular tumorsd
Neurofibromae
Metastases

Ischemic injury
Meckel’s diverticulum
Diverticulosis
Zollinger-Ellison syndrome
Endometriosis
Hemosuccus pancreaticus/hemobilia
Infectious causes
Von Willebrand disease

Associated syndromes: aOsler-Weber-Rendu disease, CREST syndrome, Turner’s syndrome; bfamilial adenomatous polyposis;
cPeutz-Jeghers syndrome; dblue rubber bleb nevus syndrome; Klippel-Trenaunay-Weber syndrome; eVon Recklinghausen’sdisease.

duced by Given Imaging for the SB2 model; in general,
second-generation small-bowel capsules are less cumbersome and more reliable than first-generation devices.
Most important is the inclusion of an external viewer, first
introduced by Olympus. It facilitates accurate monitoring of the gastric passage of the capsule, thus informing
decisions about the use of prokinetic agents, and allows
cecal visualization as a marker of complete small-bowel
examination. Expected improvements will allow direct
monitoring of the image from the capsule and also accessto video sequences if, for example, the capsule is blocked
behind a fold or by a pathological stricture.
Image quality relies on multiple factors, such as thefield of view, resolution, brightness, and automatic gain

control, as previously developed in high-definition endoscopy. Image quality is particularly improved with the
SBCE Olympus capsule. Marked technical improvements
are to be expected with the launch of each new generationof capsule. An improved field of view is a particularly
important feature because it will allow a more extensive
image of the lumen of the small bowel and could increase
diagnostic yield.
The reading time of SBCE data is lengthy, which is adrawback for physicians. In addition, we have to bear inmind that capsule imaging does not comprehensively visualize the entire small bowel because of the local effects
of motility, debris, bubbles, absence of insufflation, andpresence of strictures. For example, the papilla of Vater,

Keio J Med 2013; 62 (2): 41–46

43

Table 3 Six types of patient preparation for SBCE (Reproduced from Rey, et al.5)
1
2
3
4
5
6

Standard procedure as indicated by Given Imaging: clear fluid diet the day before the procedure, overnight fasting.
As above, plus simethicone 80 mg and metoclopramide 10 mL (0.1% solution) p.o. 20 min before the procedure.
Clear fluid diet the day before the procedure, 2 L of a PEG-based solution in the afternoon of the day before the procedure. Overnight fasting. Simethicone 80 mg 20 min before the procedure.
Clear fluid diet the day before the procedure, 4 L of a PEG-based solution (2L in the morning, 2L in the afternoon) the day before theprocedure. Overnight fasting. Simethicone 80 mg 20 min before the procedure.
Clear fluid diet the day before the procedure, 2 L of a PEG-based solution in the afternoon of the day before the procedure. Overnight fasting. Metoclopramide 10 mL (0.1% solution) p.o. 20 min before the procedure. Simethicone 80 mg 20 min before theprocedure.
Clear fluid diet the day before the procedure, 4 L of a PEG-based solution (2L in the morning, 2 L in the afternoon of the day before
the procedure). Overnight fasting. Metoclopramide 10 mL (0.1% solution) p.o. 20 min before the procedure. Simethicone 80 mg 20
min before the procedure.

Table 4 The sensitivity and specificity of colon video capsuleendoscopy (Reproduced from Van Gossum, et al.7)
Condition
Polyps > 6 mm
Advanced adenomas
CancerSensitivity

Specificity

64%
73%
74%

84%
79%
-

Complete examination by colon video capsule endoscopy was possible in 92.8% of 328 patients. Five of 19 carcinomas were missed.

a constant feature of the second part of the duodenum,is seen only in 10% of investigations. Another problem
is that some recorded images are difficult to interpret.
New software technology includes multiple reading
modes, e.g., “QuickView” for Given Imaging capsules,and “overview” or “skip” mode for Olympus capsules,
and these can save up to 30% of reading time. Accurate
detection of abnormally red areas could be an important
advance for accurate diagnosis.
Finally, the anatomic locations of findings are still
known only approximately, and three-dimensional localization needs to be developed. We may expect that in thenear future most patient handling and image reading will
be done by assistants; the physician will focus only on the
final diagnosis from the information on selected images.
We should draw attention to the need for a clear protocol. SBCE was initially described as a patient-friendly
examination for which no patient preparation was required; however, in 25% of examinations, the last partof the ileum is not clearly visible. We have shown, andthis is now generally agreed, that patient preparation with
polyethylene glycol (PEG)5,6 is required for a complete
examination (Table 3). Prokinetics are only importantwhen gastric passage is delayed.

Colon Capsule
The colon capsule is a serious contender for colorectal screening. The results to date are promising, but theyneed to be supported by larger studies. The reported
miss rate of 25% for carcinomas7 is still a concern, eventhough this rate is much lower than that for the current
fecal occult blood test (FOBT) (Table 4). From the diagnostic point of view, polyps smaller than 6 mm are an
important issue. As is also the case for virtual colonoscopy, colon capsule endoscopy has a higher miss rate thanhigh-definition colonoscopy for such lesions. The diagnostic yield is affected by two factors: bowel preparationand large-bowel motility. Currently, bowel preparation
using the following protocol is very demanding for thepatient, even more so than that for colonoscopy:• 5 Days Before: Commence low-fiber diet.
• 2 Days Before: Commence clear fluid diet, 2 L and in theevening: sennoside (Pursennide) 2 × 20mg tablets.
• 1 Day Before: Morning: light breakfast.
o 12:00: pasta then clear liquid diet.
o 19:00–21:00: 2 L PEG.
• Day of Investigation: 06:00–7:00: 1 L PEG.
o 07:45: 20 mg domperidone.
o 08:00–09:00: when capsule is in the stomach, erythromycin 500 mg p.o. or i.v.
o Small-bowel detection: + 30 mL Fleet Phosphosoda + 1 L water (boost I).
o 3 h after boost I, or if capsule in cecum: + 15 mL
Fleet + 1 L water (boost II).
o 2–4 h after boost II: suppository, Bisacodyl (10 mg)
if capsule has not been eliminated.

It is important to note that, unlike colonoscopy, there isno possibility of intraprocedural cleaning and the capsulemoves without guidance through the colon. Regardingcolonic motility, the colon capsule might, for example, remain for several minutes in the cecal area or it might passthrough the transverse colon in a few seconds, pushed on
by strong colonic contractions. For these reasons, comparing the colon capsule with high-definition video colo-

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Rey JF: Future of Capsule Endoscopy

Table 5 Diagnostic accuracy of colon capsule endoscopy for significant findings (polyps 6 mm in size or the presence of 3 or morepolyps)(Reproduced from Spada C, Hassan C, Galmiche J. et al. Colon capsule endoscopy: European Society of Gastrointestinal Endoscopy(ESGE) guideline. Endoscopy 2012; 44: 527-536 8)
Author, year
Eliakim, 2006 [9]aSchoofs, 2006 [10]aVan Gossum, 2009 [7]aGay, 2010 [11]aSacher-Huvelin, 2010 [12]aPilz, 2010 [13]aSpada, 2011 [14]aSpada ; 2011 [15]aEliakim, 2009 [16]bSpada, 2011 [17]b
All studies
CCE-1 studies
CCE-2 studies

Patients with significant findings,n (%)

Sensitivity

Specificity

PPV

NPV

16 (19)13 (36)87 (27)67 (53)112 (21)
6 (10)
13 (33)7 (15)
18 (19)45 (41)384 (20)321 (19)63 (30)

50%
77%
64%
76%
39%
50%
62%
100%
89%
84%
63%
58%
86%

82%
70%
84%
76%
88%
75%
85%
95%
76%
64%
83%
85%
71%

40%
59%
60%
78%
47%
19%
67%
78%
46%
62%
57%
57%
56%

88%
84%
86%
74%
85%
93%
82%
100%
97%
85%
86%
86%
92%

PPV, positive predictive value; NPV, negative predictive value, aFirst-generation colon capsule endoscopy (CCE-1) studies, bSecond-generation(CCE-2) studies.

noscopy, the results from the colon capsule must still be
improved (Table 5); however, in comparison with FOBT,
the colon capsule gives acceptable results.8,18
Based on this analysis, practitioners must accept thecurrent indications for capsule colonoscopy, i.e., if colonoscopy is impossible for technical reasons, if there aretemporary contraindications to colonoscopy, or if the patient is highly reluctant to undergo high-definition colonoscopy. With respect to the last indication, the patient
should be aware of the necessity for colonoscopy if there
are positive findings from the colon capsule. A final disadvantage to use of the colon capsule relates to cost: eachcolon capsule costs US$700 plus the medical fee, and in
most countries healthcare providers do not provide reimbursement. This is why, in our opinion, it seems too early
to draw up official guidelines.
The Guided Gastric Capsule
Passive video capsule endoscopy is considered a gold
standard for the small bowel, and it has been investigatedclinically for use in the esophagus and colon; however,it was considered impossible to devise a clinical trial
for gastric exploration because of the inherent technicallimitations. To overcome some of the limitations of passive capsules, magnetically guided capsule endoscopy(MGCE) was developed jointly by Olympus Medical Systems Corporation and Siemens Healthcare. A comparative study between high-definition gastroscopy (Olympus
Exera II 180) and MGCE was carried out in 85 patientswith clinical indications for gastric examination. The
guidance system, in which a capsule is steered by a low-

Fig. 1 Possible maneuvers of the video capsule using magnetic
guidance.

level magnetic field, was designed by Siemens Healthcare, and images were obtained using a two-sensor video
capsule built by Olympus Medical Systems Corporation(Fig. 1). The trial was carried out at the Institut Arnault
Tzanck (St. Laurent du Var, France) with close cooperation with three Japanese universities: Keio University
School of Medicine (Tokyo), Jikei University School of
Medicine (Tokyo), and Showa University Northern Yo-

Keio J Med 2013; 62 (2): 41–46

kohama Hospital (Yokohama). Japanese physicians performed capsule and endoscopy examinations on French
patients.19 The Japanese physicians were included in thetrial to develop the protocol and review the data.
The patients, who all gave their informed consent, underwent high-definition gastroscopy under propofol sedation and then underwent a capsule examination on thefollowing day. A total of 97 patients were included, and85 patients completed the trial. One patient had minor abdominal pain that resolved spontaneously.
Step 1, which involved the first 24 patients, was regarded as our learning-curve experience for capsule examination. Step 2 was the comparative study of the next 61 patients; comparative examinations were carried out blindly
by two physicians by gastroscopy and then by capsuleinvestigation. Using the guided gastric capsule, visualization of the gastric pylorus, antrum, body, fundus, andcardia was assessed as complete in 88.5, 86.9, 93.4, 85.2,
and 88.5% of patients, respectively. In 12 patients, visualization was incomplete: in 4 patients this resulted fromearly pyloric passage of the capsule, and in the remaining
8 patients there were a variety of causes such as resistantmucus, excessive gastric motility, and incomplete gastricexpansion. Visualization by guided gastric capsule wasachieved in a mean total examination time of 17.4 min(range 9.9–26.4 min). The examination time became
shorter with better understanding of navigation and withincreasing familiarity with previously unseen perspectives of the stomach, such as panoramic views of the lesser curve and the appearance of the closed cardia. In total,
108 gastric findings (e.g., gastritis, angioma, polyp) wereidentified. Of these, 63 lesions were seen on both gastroscopy and capsule examination, 31 lesions were detectedby capsule but were missed by conventional endoscopy,
and 14 lesions were detected by gastroscopy but were
missed by the capsule examination.20
This first clinical trial raised some points about capsulenavigation:• Cleanliness of the stomach: Stomach lavage with 900 mLof mineral water ingested in two steps is required to obtain a clear view using MGCE. A clean gastric environment without bubbles, residue, or mucus is needed. Bile
reflux can also impair gastric visibility.
• Expansion of the stomach: This is the main purpose of
the final step in patient preparation, i.e., ingestion of
400 mL mineral water at 35°C, because an air–waterinterface is required for navigation of the capsule. Thisapproach was effective in 84.2% of all patients; it wasineffective in 20% of male patients but in only 9.1% offemale patients.
• Gastric motility: This could also impair navigation, especially in the antrum in the case of strong contractions.
Antispasmodic drugs will be used in a further clinical
trial on volunteers. In addition, MGCE could be a useful tool for assessing motility disorders in patients with

45

unexplained gastric pains.

Because these preliminary results were promising, asecond study was carried out with 50 volunteers to improve the gastric lavage and distension protocol, and thena technical trial was carried out in 50 patients for training
and to improve guidance. This was followed by a second scientific study in which the capsule examination
was performed initially, and then a few hours later thefindings were verified by high-definition endoscopy (214patients).
Esophageal Capsule
The initial results for the esophageal capsule engendered an enthusiastic response,21 and a few months later,a well-known multinational pharmaceutical company exhibited a device at their booth devoted to proton pumpinhibitors. However, a technical difficulty remains to be
overcome, namely, the best way to steady the capsule in
the Z line area. Appropriate positioning of patients andtethering of the capsule have been proposed, but results
have not been reproducible. Currently, esophageal capsule endoscopy is not recommended by scientific societies, even for follow-up of varices or Barrett’s esophagus.
Reimbursement
Although small-bowel capsule endoscopy is well accepted in the scientific community and is considered
to be a major advance in small-bowel diagnosis, reimbursement is still an obstacle. Intensive marketing by
the leading manufacturer has led to some reluctance to
use the device in many countries, so that reimbursement
for SBCE is limited, even though its clinical use in routine investigations is fully approved. Usually, obscure
GI bleeding and suspected Crohn’s disease are the only
indications accepted for reimbursement. For other indications, the price of the device (about US$700) and the
medical fees must be borne by the patient.
The costs of newer capsule types have not yet been considered for reimbursement: the colon capsule is undergoing clinical trials, and the guided gastric and the esophageal capsules are still at the stage of preliminary researchstudies.
Conclusion
SBCE is a major advance in small-bowel exploration;
in most cases it is performed before enteroscopy. It is thegold standard for small-bowel diagnosis. The colon capsule is still at the stage of clinical trials; in the near future
it might be the first step in colorectal cancer screening, butbowel preparation and the use of prokinetics must be considered. Capsule endoscopy for the esophagus and stomach is still at the research stage. In the future, a magnetic
guidance system could be included in all capsule designs.

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Rey JF: Future of Capsule Endoscopy

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