Meta-analysis: capsule enteroscopy vs. conventional modalities in diagnosis of small bowel diseases

Meta-analysis: capsule enteroscopy vs. conventional modalities indiagnosis of small bowel diseases

R. MARMO*, G. ROTONDANO� ,� , R. PISCOPO§, M. A. BIANCO� & L. CIPOLLETTA�*Department of Medicine, Division of Gastroenterology, Hospital L. Curto, Polla, Italy; �Division of General Surgery, Section

of Gastrointestinal Endoscopy, S. Mary’s Hospital, Rocca d’Aspide, Italy; �Department of Gastroenterology and Digestive

Endoscopy, Hospital Maresca, Torre del Greco, Italy; §Division of Internal Medicine, Section of Gastroenterology, Evangelic

Hospital Villa Betania, Naples, Italy

Accepted for publication 29 June 2005

SUMMARY

Background: Prospective trials support the role of capsule

enteroscopy as an improvement in diagnosing mucosal

lesions in the small bowel.

Aim: To determine the diagnostic yield and safety of

capsule enteroscopy vs. alternative diagnostic modali-

ties (such as push enteroscopy, small bowel follow-

through or enteroclysis) in patients with small bowel

diseases.

Methods: A search for prospective studies comparing

capsule enteroscopy vs. other diagnostic tests in adults

was performed between 1966 and 2005. Selected

articles were included in a meta-analysis. Three analy-

ses were run separately, all included studies and studies

having occult gastrointestinal bleeding or Crohn’s

disease as main outcome.

Results: Seventeen studies (526 patients) met inclusion

criteria. The rate difference (i.e. the absolute pooled

difference in the rate of positive findings) between

capsule enteroscopy and alternative modalities for small

bowel disease was 41% (95% CI 35.6–45.9); 37% (95%

CI 29.6–44.1) for occult gastrointestinal bleeding; and

45% (95% CI 30.9–58.0) for Crohn’s disease. Failure to

visualize the caecum occurred in 13%, significantly

more often in occult bleeders (17%) than in patients

with Crohn’s disease (8%) (P < 0.006). Adverse events

were recorded in 29 patients (6%). Capsule retention

was more frequent in patients with Crohn’s disease (3%

vs. 1%, OR 4.37).

Conclusions: Capsule enteroscopy proved significantly

superior to push enteroscopy and small bowel radiology

in the diagnosis of ileal diseases. Capsule enteroscopy is

safe, though prior radiology is still necessary to rule out

small bowel strictures in patients with known or

suspected Crohn’s disease.

BACKGROUND

Capsule endoscopy (CE) is a major advance in visual-

ization of the small intestine. Since the introduction of

CE the indications for the procedure have expanded to

include Crohn’s disease (CD), celiac disease, polyposis

syndromes, monitoring of patients after small-bowel

transplantation, and unexplained abdominal pain, in

addition to obscure gastrointestinal bleeding (OGIB).1–4

Initial prospective trials support the role of CE as an

improvement in the ability to assess and diagnose

mucosal lesions in the small bowel.5–8 CE has been at

least as successful as, and sometimes significantly more

successful than, push enteroscopy in finding the cause

of OGIB in published series, with yields of 55–70%.3, 6 It

has been significantly more successful than barium

studies in finding pathology in the small bowel and has

outperformed barium meal as well as state-of-the-art

Correspondence to: Dr R. Marmo, Via Sottobraida 32, 84037 Sant’Arsenio

(SA), Italy.

E-mail: [email protected]

Aliment Pharmacol Ther 2005; 22: 595–604. doi: 10.1111/j.1365-2036.2005.02625.x

� 2005 Blackwell Publishing Ltd 595

enteroclysis and computed tomographic enteroclysis in

fully published recent studies.4

However, there are few studies that have assessed the

impact of CE on clinical outcome, so that the true value

of this novel technology is less well established. Data are

sparse, the number of patients included in each trial is

often small, different groups of patients are seldom

considered, and conflicting results are sometimes repor-

ted.9, 10

The primary aim of the present study was to assess the

diagnostic yield of CE vs. conventional diagnostic

modalities in patients with OGIB and CD by performing

a quantitative systematic review of the published

controlled trials. The secondary aim was to assess any

negative outcome of CE in these patients.

MATERIALS AND METHODS

Literature search and identification of primary studies

Relevant papers were identified by searching the

MEDLINE, EMBASE/Excerpta Medica, Current Con-

tents and Cochrane Library databases using ‘capsule

endoscopy’ or ‘wireless capsule endoscopy’ or ‘capsule

enteroscopy’ as search terms. The search was restric-

ted to human studies of adults published in English

and non-English language, between January 1966

and March 2005 inclusive. We also conducted a

manual search of abstracts submitted to the Digestive

Disease Week and United European Gastroenterology

Week covering the same period. In addition, we

hand-searched relevant journals, published articles,

contacted companies and researchers in the field to

seek any ongoing or unpublished studies on the

comparison of diagnostic yield of CE vs. any other

modalities. Articles selected in the search were

reviewed separately by two of the authors (R.M. and

G.R.), and those fulfilling the inclusion criteria were

selected for further analysis. In addition, a fully

recursive search of reference lists of the original

studies was performed to find studies not identified by

the previous searches. Papers recorded in the personal

databases of the authors were also reviewed and

included when appropriate.

Study selection

This is a meta-analysis of the studies comparing CE with

any other diagnostic modality in adults suffering from

suspected small bowel disease. Studies were evaluated

separately by two of the authors. The inclusion criteria

were as follows: (i) Articles or abstracts should report

the results of prospective, comparative trials. (ii) Studies

must include patients with OGIB or CD. (iii) Studies had

to include at least two branches of diagnostic testing, i.e.

CE vs. other modalities. (iv) Explicit reference had to be

given for safety of the tested procedures either in the

text or tables.

A ‘negative outcome’ was defined as any undesired

event directly related to the application of a diagnostic

procedure, according to Fleischer et al.11 In particular,

capsule retention was defined as no evidence of capsule

excretion within 3 days.

When the abstract had no clear reason for exclusion,

the relative full paper was obtained if available.

Where multiple reports of a single trial existed, the

most recent version was obtained. We also reviewed

the references of selected articles and previous clinical

reviews. Data extraction was carried out independ-

ently by two investigators (R.M. and G.R.) using a

standardized form. Decisions regarding inclusion of

articles and data extraction were reached by consen-

sus between the two reviewers. If there was disag-

reement, the papers were jointly evaluated to solve

inconsistency.

Data extraction

The studies were examined with respect to the following

criteria: study design (including methods of reporting

adverse events); inclusion and exclusion criteria; patient

characteristics; technical details of CE and other diag-

nostic procedures; definition of study outcomes and

their monitoring methods.

Quality assessment

Information on objective quality-related characteristics

was also collected and the quality of the studies

included was assessed using 17 of the 22 items of the

CONSORT statement.12 We did not consider the five

items that refer to the process of randomization as all

trials that were evaluated were not randomized. The

final quality score ranged from 0 to 17, with

maximum quality studies rated 17. Results from

the trial reports were reproduced where possible.

The systematic review was performed according to the

QUORUM statement.13

596 R. MARMO et al.

� 2005 Blackwell Publishing Ltd, Aliment Pharmacol Ther 22, 595–604

Statistical analysis

Pooled odds ratio and 95% confidence intervals (CI)

were calculated from the raw study data using the Peto

fixed effect model, which produced a Q-statistic with a

chi-squared distribution with n)1 degrees of freedom,

where n is equal to the number of trials. Data from the

various studies were combined using appropriate

weights. The test of heterogeneity was utilized to

determine whether the fixed effect model or random

effects model was appropriate for calculation of the

weights, used in the meta-analytic estimate, and the

95% CI for this estimate. The chi-square test was

employed to assess whether the variation in diagnostic

effect within trials of the same group was greater than

might be expected. We considered heterogeneity to be

present if P < 0.05. In the absence of statistically

significant heterogeneity, odds ratios and 95% CI by

the fixed effect model only are given in the results.

All calculations were performed with STATA software

(StataCorp, Houston, TX, USA). For studies in which the

constructed 2 · 2 tables contained cells with zero events,

a standard correction factor of 0.5 was added to each cell.

After pooling of data, we calculated the crude and

weighted rate differences (RD), odds ratios (OR) and the

number needed to diagnose (NND) with 95% CI for each

of the trials included in the analysis, based on the raw

data presented in each paper. The NND (1/RD) is a

quantitative estimate of the diagnostic gain: it expresses

the number of patients to be investigated with each of

the procedures under evaluation so as to reach at least

one more positive finding compared with the other

method.14 An intention-to-treat analysis was carried

out, i.e. participants were analysed in the group to

which they were allocated.

Three analyses were run separately: the first one for all

included studies, the second one for studies having the

identification of the source of occult GI bleeding as

the main outcome and the last one for studies having

the diagnosis of ileal involvement in CD as their main

outcome.

For a significant meta-analysis finding, publication bias

was defined as the number of additional non-significant

studies that, if included in the meta-analysis, would

have removed the significant meta-analysis finding.

RESULTS

Included and excluded studies

The preliminary search identified 187 potentially rele-

vant papers, of which 160 were excluded. Detailed

reasons for exclusion are outlined in Figure 1. Ten

studies were excluded from further analysis,15–24 the

reasons for which are outlined in Table 1. Seventeen

studies were included in the meta-analysis.5, 8–10, 25–37

The characteristics of the studies are listed in Tables 2–4.

Quality assessment

The articles that were included ranged in quality from 8

to 15. Individual assessment of quality is listed in

Table 2. All studies were published as full papers and

were rated as medium to high in the quality scores.

Review Case series report Safety only (efficacy not investigated) Diseases other than OGIB/CD Descriptive studies Letter to the EditorTechnical aspects onlyGuide-lineEditorialMiscellaneous

Included 27

Potentially relevant papers (n = 187)

Excluded (n = 10)

Retrospective designPartial reportNon-systematic comparisonHistorical controls

Included 17

4633111110

9711

31

5311

Figure 1. Selection process of the included

studies.

META-ANALYSIS: CAPSULE ENDOSCOPY VS. ALTERNATIVE DIAGNOSTIC PROCEDURES 597


Contraindications

A total of 39 of 604 patients had contraindications to

CE (6.5%) (95% CI 4.6–8.7). CE was contraindicated

in patients with OGIB in only eight of 336 cases

(2.4%) (95% CI 1.0–4.6) for the following reasons:

two major abdominal surgery, two diabetes, two

pacemaker and two small bowel strictures (Table 3).

Contraindications to CE in patients with CD were

present in 31 of 268 cases (11.6%) (95% CI 8.0–

16.0); small bowel stricture at pre-CE radiology in 30

cases and previous major abdominal surgery in one

patient (Table 4).

There was a significantly higher probability of having

a contraindication to CE in patients with CD compared

with obscure bleeders (OR 5.36, 95% CI 2.35–13.72)

(P < 0.001). If we consider only the presence of

stricture as contraindication, this chance in patients

with CD rises dramatically (OR 21.05, 95% CI 5.24–

182.83).

Efficacy

A total of 526 patients were evaluated (289 submitted

to CE for obscure bleeding, 237 submitted to CE for

known or suspected CD). The null hypothesis of

homogeneity was not rejected. The P-value for the

Q-statistic for the outcome that was considered (positive

finding) was 1.0.

The results indicate a clinically relevant and statisti-

cally significant advantage for CE over alternative

modalities in the diagnosis of small bowel diseases.

From a fixed effect model, the pooled RD in all the

studies was 40.8% (95% CI 35.6–45.9) (P < 0.0001).

The plot in Figure 2 shows that CE significantly

increases the probability of a positive finding compared

with controls (OR 4.9, 95% CI 3.9–6.4) (P < 0.001).

The calculated NND for this group was 2 (95% CI 2–3),

that is, for every two patients investigated, CE provides

one more diagnosis compared with controls. Publication

bias was 513. Therefore, the significant meta-analysis

finding for diagnosing small bowel pathology could be

removed by including 513 additional studies with non-

significant results.

Table 2. Characteristics of the study trial

included in the meta-analysisReference Disease investigated

Procedure compared

with CE

Quality

assessment

Adler et al.25 Obscure bleeding Push enteroscopy 11

Buchman et al.10 Known Crohn SBFT 8

Chong Ho et al.26 Known + suspected Crohn Enteroclysis 15

Costamagna et al.8 Small bowel diseases SBFT 10

Eliakim et al.27 Suspected Crohn SBFT 9

Ell et al.28 Obscure bleeding Push enteroscopy 12

Fireman et al.5 Suspected Crohn SBFT 8

Ge et al.29 Suspected Crohn SBFT 8

Hartmann et al.30 Obscure bleeding Push enteroscopy 13

Herrerias et al.31 Suspected Crohn SBFT 12

Lewis and Swain32 Obscure bleeding Push enteroscopy 11

Marmo et al.34 Known Crohn Enteroclysis 15

Mata et al.33 Obscure bleeding Push enteroscopy 12

Mylonaki et al.35 Obscure bleeding Push enteroscopy 13

Saurin et al.36 Obscure bleeding Push enteroscopy 15

Van Gossum et al.9 Obscure bleeding Push enteroscopy 9

Voderholzer et al.37 Known Crohn CT enteroclysis 10

CE, capsule endoscopy; SBFT, small bowel follow through; CT, computed tomography. No

study had randomized design.

Table 1. Reasons for excluding articles

Reference Reasons for exclusion

Mata et al.15 Preliminary results of Mata et al.33

Eliakim et al.16 Preliminary results of Eliakim et al.27

Voderholzer et al.17 Preliminary results of Voderholzer et al.37

May et al.18 Non-systematic comparison

with double balloon enteroscopy

Liangpunsakul et al.19 Retrospective design

Hara et al.20 Retrospective design

Caunedo et al.21 Retrospective design

Rastogi et al.22 Retrospective design

Mow et al.23 Retrospective design

Ge et al.24 Historical controls

598 R. MARMO et al.


In the subgroup analysis of studies of OGIB (Figure 3),

the pooled RD was 36.9% (95% CI 29.6–44.1)

(P < 0.0001). All the studies but one had push

enteroscopy as comparator investigation. CE significantly

increases the probability of a positive finding in such

patients compared with push enteroscopy (OR 4.3, 95%

CI 3.1–6.0) (P < 0.001). The calculated NND for this

subgroup was 3 (95% CI 3–5). Publication bias was 146.

Table 3. Clinical features of patients with obscure gastrointestinal bleeding

Reference

No. patients with

contraindication

to CE/included

No. patients submitted

to either diagnostic

procedure

Overt

bleeding

Occult

bleeding

Duration

of disease

Mean Hb

level (g/dL)

Adler et al.25 No data 20 11 9 n.d. 7.5 (4.0–12.1)

Ell et al.28 2/65 32 0 32 29 ± 2.4 months 5.9 (±1.4)

Van Gossum et al.9 No data 21 5 16 n.d. 9.8 (5.2–11.2)

Hartmann et al.30 0/33 33 33 0 30 ± 36 months 6.5 (±1.6)

Lewis and Swain32 4/25 21 9 12 36.5 (2–144) months 6.4 (2–8)

Mata et al.33 No data 42 26 16 n.d. 7.8 (±2.1)

Mylonaki et al.35 0/50 50 11 39 4.2 (0.5–20) years n.d.

Saurin et al.36 0/60 60 32 28 24.8 ± 21.7 months 9.4 (±2.5)

Costamagna et al.8 2/20 13 n.d. n.d. n.d. n.d.

CE, capsule endoscopy; n.d., not declared; Hb, haemoglobin. Values are mean (±standard deviation or range). See text for details of contraindi-

cations.

Table 4. Clinical features of patients with

Crohn’s disease

Reference

No. patients with

contraindication

to CE/included

No. patients submitted

to either diagnostic

procedure

Time interval between

diagnosis of CD and

CE examination

Eliakim et al.27 0 35 At initial diagnosis

Fireman et al.5 0 17 At initial diagnosis

Herrerias et al.31 0 21 At initial diagnosis

Ge et al.29 0 20 At initial diagnosis

Voderholzer et al.37 15/56 41 At initial diagnosis*

Buchman et al.10 12/42 30 5.5 ± 6.5 years

Chong Ho et al.26 2/45 43 At initial diagnosis*

Marmo et al.34 2/33 31 11 days

CD, Crohn’s disease; CE, capsule endoscopy. See text for details of contraindications.

* These two studies include patients with suspected CD (CE performed for initial diagnosis) and

also patients with known or surgically treated CD (CE performed not for diagnosis but for

staging).

21/3020/302004Buchmann

21/424/422005Chong Ho

25/4112/412005Voderholzer

22/318/312005Marmo

13/200/202004Ge

9/210/212003Herrerias

12/170/172003Fireman

27/358/352004Eliakim

4/131/132002Costamagna

40/5822/582003Saurin

34/5016/502003Mylonaki

31/428/422004Mata

11/206/202004Lewis

25/337/332003Hartmann

13/2116/212003Van Gossum

21/329/322002Ell

14/204/202004Adler

VCEOther Procedure

YearAuthor

Pooled (fixed effect) 4.992 (3.898 / 6.392)

1/161/64 1/4 1 4 16 64

Better controls Better VCE

141/526 343/526

Figure 2. Meta analysis: capsule enteros-

copy vs. alternative procedures in small

bowel disease (overall population).



In the subgroup analysis concerning studies performed

in patients with known or suspected CD, there was

significant heterogeneity between the studies (Q ¼17.41, P < 0.01). From a random effect model, pooled

RD was 44.5% (95% CI 30.9–58.0) (P < 0.0001). As

shown in Figure 4, in these patients, CE provided a

significant diagnostic gain over both enteroclysis (OR 5.4,

95% CI 3.0–9.9) and small bowel follow-through (OR

13.0, 95% CI 2.3–71.4) with an overall sevenfold

increase in diagnostic capability against controls (OR

7.2, 95% CI 3.2–16.3) (P < 0.0001). The calculated

NND for this subgroup was 2 (95% CI 2–3). Publication

bias was 105.

Safety

Failure to visualize the caecum. Overall, in 526 patients

submitted to CE, the caecum was not visualized in 68

patients (12.9%, 95% CI 10.2–16.1). Such bad outcome

occurred in 48 patients investigated for OGIB (16.6%,

95% CI 12.5–21.4) (Table 5) and 20 investigated for

CD (8.4%, 95% CI 5.2–12.7) (Table 6). This difference

of 8.2% (95% C.I. 2.8–13.8) was statistically significant

(P < 0.006).

Adverse events. Adverse events were recorded in 29

patients (5.5%) (95% CI 3.7–7.8). In the population with

OGIB, there were 15 adverse events related to CE (5.2%,

95% CI 2.9–8.4) (Table 5). Capsule retention occurred

in two patients (0.7%, 95% CI 0.08–2.5) with one

surgical and one endoscopic removal. In the population

with CD, there were seven adverse events (3%, 95% CI

1.2–6.0), all related to capsule retention. Of these, five

necessitated a surgical removal, one endoscopic retrieval

and in one case there was a spontaneous passage after

3 days of steroid therapy (Table 6). The risk of capsule

retention was higher in the CD subgroup (OR 4.37, 95%

CI 0.82–43.37).

VCE: video capsule enteroscopy; REM: random effect model; FEM: fixed effect model; SBFT: small bowel follow-through

VCE 1/64 1/16 1/4 1 4 16 64Other procedure

YearN. Author

Better other procedures Better VCE

82/12328/123

52/237 150/237

SubGroup(REM)

(FEM)

68/11424/114SubGroup

SBFT

(REM)

(FEM)

Pooled(REM)

(FEM)

21/3020/302004Buchmann

21/424/422005Chong Ho

25/4112/412005Voderholze

22/318/312005Marmo

Enteroclysis

14

15

16

10

11

12

17

13

9/210/21

0/20

2003Herrerias

12/17

13/20

0/172003Fireman

27/358/352004

2004Ge

Eliakim

5.467 (3.014/9.917)

5.092 (2.988/8.678)

7.235 (3.210/16.310)

6.012 (4.132/8.748)

13.006 (2.369/71.412)

7.074 (4.174/11.990)

Figure 4. Meta analysis: capsule enterosco-

py vs. alternative procedures in patients

with suspected small bowel Crohn’s disease.

VCE, video capsule enteroscopy; REM, ran-

dom effect model; FEM, fixed effect model;

SBFT, small bowel follow-through.

VCE: video capsule enteroscopy; REM: random effect model; FEM: fixed effect model; SBFT: small bowel follow-through

4/131/13

4/131/13

89/289 193/289

Better other procedures

2002Costamagna

40/5822/582003Saurin

SubGroup 88/276 189/276

SBFT

(REM)

(FEM)

SubGroup(REM)

(FEM)

Pooled(REM)

(FEM)

34/5016/502003Mylonaki

31/428/422004Mata

11/206/202004Lewis

25/337/332003Hartmann

13/2116/212003Van Gossum

21/329/322002Ell

14/204/202004Adler1

Push enteroscopy

2

3

4

5

6

7

8

9

VCE 1/64 1/16 1/4 1 4 16 64

4.328 (2.399/7.808)

4.331 (3.101/6.048)

3.947 (0.518/30.907)

4.173 (0.616/28.257)

4.314 (2.487/7.483)

4.326 (3.113/6.011)

Better VCE

Other procedure

YearN. Author

Figure 3. Meta analysis: capsule enterosco-

py vs. alternative procedures in patients

with obscure gastrointestinal bleeding. VCE,

video capsule enteroscopy; REM, random

effect model; FEM, fixed effect model; SBFT,

small bowel follow-through.

600 R. MARMO et al.


DISCUSSION

The small intestine is relatively inaccessible to endo-

scopic examination because of length, location and

tortuosity. Conventional imaging with barium radiol-

ogy fails to detect flat lesions, such as angiodysplasia,

and is an insensitive method of detecting fine mucosal

disease and raised lesions. The clinical need for more

detailed small bowel imaging has been recently

fulfilled by the introduction of wireless capsule

enteroscopy. CE has opened up a new world of

diagnoses and possibilities to the gastroenterologist,

providing him/her with images of small intestinal

abnormalities which were not possible until recently.

It has been particularly successful in finding the cause

of OGIB and evaluating patients with inflammatory

bowel diseases.2–4 Nonetheless, there is a paucity of

data on the ultimate clinical impact of CE in small

Table 6. Negative outcomes in patients

with CDReference

No.

patients Adverse events of CE

CE failure to reach

the caecum

Eliakim et al.27 35 0 No data

Fireman et al.5 17 0 No data

Herrerias et al.31 21 0 0

Ge et al.29 20 3 (capsule retention)* 2

Voderholzer et al.37 41 2 (capsule retention)* 10

Buchman et al.10 30 2 (capsule retention) 0

Chong Hoet al.26 42 0 6

Marmo et al.34 31 0 2

CD, Crohn’s disease; CE, capsule endoscopy.

* One passed 3 days after steroid therapy and one successfully removed by push enteroscopy.

In this subgroup of CD patients enteroclysis could not be completed in six patients because of

intolerance to naso-jejunal tube.

Table 5. Negative outcomes in patients with OGIB

Reference

No.

patients Adverse events of CE

Adverse events of

push enteroscopy

CE failure to

reach the caecum

Adler et al.25 20 0 0 0

Ell et al.28 32 2

Technical defect (1)

Vision obscured by active bleeding (1)

0 n.d.

Van Gossum et al.9 21 1

Capsule blocked in an appendiceal stump

0 1

Hartmann et al.30 33 0 0 22

Lewis and Swain32 20 1

Long oesophageal transit

0 3

Mata et al.33 42 3

Capsule retention (1)

Long oesophageal transit (1)

Capsule malfunction (1)

0 3

Mylonaki et al.35 50 5

Long oesophageal transit (1)

Temporary electrical disconnection (1)

Battery dysfunction (1)

1

No advance beyond

duodenal bulb

16

Saurin et al.36 58 2

Battery dysfunction (1)

Error to transfer data (1)

0 3

Costamagnaet al. 8 13 1

Battery dysfunction

NA 0

OGIB, obscure gastrointestinal bleeding; CE, capsule endoscopy; NA, not applicable as in this study CE was compared with small bowel follow-

through. n.d., not declared.



bowel disease, especially concerning changes in

management that lead to enduring positive outcomes.

Depending on the indication for which CE is per-

formed, however, a negative capsule study can be

reassuring and might potentially limit further diag-

nostic tests.38 Much of the available literature (mostly

abstracts) indicates that, although the initial diagnos-

tic yield of CE might be high, the proportion of

patients with changes in management is less, and the

proportion of patients with successful long-term

outcomes is even less.35, 39 Compared with push

enteroscopy, CE increases the diagnosis yield in

patients with OGIB and allows modification on

therapy strategy in up to 66% of cases.3, 6, 9, 25, 28, 30

In such patients, who have undergone multiple prior

procedures, even a much lower sustained long-term

success rate of 15–20% might be quite favourable. In

patients with known or suspected CD, CE has a higher

yield than push enteroscopy and enteroclysis when

small bowel mucosal disease is suspected.5, 27, 33, 37

Capsule examination alters the knowledge of the

presence and/or extension of disease in about half of

the patients with CD, leading to a relevant change in

therapeutic strategy.34

Capsule endoscopy is considered a simple, non-inva-

sive procedure, which can be universally performed,

even in out-patients. Nonetheless, our data show that

6.5% of patients who may potentially benefit from this

examination, actually have a contraindication to CE,

mainly related to radiological detection of small bowel

stricture during the pre-CE diagnostic work up.

Although the commercially available M2A device lists

the presence of pacemakers and use in children as

contraindications to its use, some groups including our

own have used the capsule in patients in both of these

settings.

The results of the present meta-analysis indicate that

the diagnostic gain of CE vs. all other procedures in the

assessment of OGIB and CD is both clinically relevant

and statistically significant. In obscure bleeders, CE

provides a fourfold chance of a positive finding. Such

superiority is consistent and homogeneous throughout

the studies and is witnessed by the huge number of void

or negative trials necessary to render meaningless the

meta-analysis. In patients with known or suspected CD,

the chance of a positive finding further rises to

sevenfold, independently of which investigation is

the comparator (from fivefold when compared with

enteroclysis to 13-fold when compared with SBFT).

However, the presence of significant heterogeneity

among studies prevents generalizability of results to

the whole population. Subgroup of patients such as

those with long-standing disease, surgically treated,

with indication to CE to monitor therapeutic response,

may represent the target of additional studies. CE will

likely not provide the answer if the clinician’s question

is preoperative assessment of ileal involvement and/or

extension. Such a question at the moment is still

answered by radiological imaging.

There is little doubt that bowel preparation may affect

sensitivity of CE examination. The optimal bowel

preparation for video CE has yet to be determined.

Given imaging recommends a 10-h fasting without

bowel purge. Data from the literature document that

bowel preparation accelerates small bowel capsule

transit, leads to a higher rate of complete endoscopic

examination and improves visualization of the small

bowel. Several different regimens have been tested: 2 L

polyethylene glycol (PEG) given 16 h before capsule

ingestion,40 ‘colonoscopy-type preparation’ with so-

dium picolax,35 sodium phosphate bowel preparation41 or 4 L PEG-based electrolyte solution (3 L during the

evening and 1 L 3 h before CE).42 Independently of the

type of bowel cleansing, all the authors agree that bowel

preparation before CE improved both the quality of

images and the diagnostic yield of the examination.

For a procedure to be recommended, both efficacy and

safety must be known as every endoscopic procedure

may induce complications. Despite the importance of

this matter, available studies fail to address the safety of

CE satisfactorily. Clinical trials typically assess only a

small number of patients and thus the chances of

detecting rare or delayed adverse events are small. The

present systematic review proved that 4.2% of patients

submitted to CE experience a negative outcome because

of technical problems and that 13% of patients do not

have a complete ileal exploration because of capsule

failure to reach the caecum. Such bad outcome

occurred more frequently in patients with OGIB

(16.6%) than in patients with CD (8.4%). We do not

have a clear explanation for this: alterations in gastric

emptying and/or gut motility, influence of co-prescrip-

tions and/or comorbidities, bowel preparation, etc. may

all be contributing factors. This observation may

attenuate the enthusiastic opinion on the ability of CE

to fully explore the small bowel. Further technical

refinement and or development will have to address this

issue.

602 R. MARMO et al.


The main complication associated with capsule use is

that is can get stuck in strictures. Capsule retention is

infrequent (0.7–3%) but still happens even in a selected

population. The four times higher risk of capsule

retention in the subgroup of patients with CD is

clinically relevant and does not reach statistical signi-

ficance probably due to a beta error. In the work up of

small bowel disease, because of safety reasons, radiology

cannot initially be replaced if the clinical suspicion is CD

to assess potential contraindication to CE. Nonetheless,

the risk that barium studies also may fail to detect

strictures, especially in early CD, should not be over-

looked. The use of a bio-fragmentable capsule (patency

capsule) may overcome these limitations, but needs to

be validated with proper investigations.

In conclusion, the diagnostic advantage of CE over all

other current diagnostic modalities is such that CE

should be considered as the procedure of choice in the

evaluation of patients with obscure bleeding and

suspected small bowel CD.

ACKNOWLEDGEMENT

The authors are indebted to Gioacchino Leandro, MD,

for his valuable help in statistical calculation.

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Meta-analysis: capsule enteroscopy vs. conventional modalities in diagnosis of small bowel diseases

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