Hindawi Publishing Corporation
Diagnostic and Therapeutic Endoscopy
Volume 2013, Article ID 580526, 6 pages
Narrow Band Imaging with Magnification Endoscopy for
Celiac Disease: Results from a Prospective, Single-Center Study
L. De Luca,1L. Ricciardiello,2M. B. L. Rocchi,3M. T. Fabi,1M. L. Bianchi,1
A. de Leone,1S. Fiori,1and D. Baroncini1
1Gastroenterology and Digestive Endoscopy Unit, “San Salvatore” Hospital, Piazzale Cinelli,
1-61121 Pesaro, Italy
2Department of Clinical Medicine, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy
3Department of SUAN, University of Urbino, Via Ca le Suore 2/4, 61029 Urbino, Italy
Correspondence should be addressed to L. De Luca; firstname.lastname@example.org
Received 24 June 2013; Accepted 6 July 2013
Academic Editor: Lars Aabakken
Copyright © 2013 L. De Luca et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
In celiac disease (CD), the intestinal lesions can be patchy and partial villous atrophy may elude detection at standard endoscopy
(SE). Narrow Band Imaging (NBI) system in combination with a magnifying endoscope (ME) is a simple tool able to obtain
targeted biopsy specimens. The aim of the study was to assess the correlation between NBI-ME and histology in CD diagnosis
and to compare diagnostic accuracy between NBI-ME and SE in detecting villous abnormalities in CD. Forty-four consecutive
patientswithsuspectedCDundergoinguppergastrointestinalendoscopy havebeenprospectively evaluated. Utilizing bothSEand
NBI-ME, observed surface patterns were compared with histological results obtained from biopsy specimens using the k-Cohen
agreement coefficient. NBI-ME identified partial villous atrophy in12 patients in whom SE was normal, with sensitivity, specificity,
when compared with SE and histology (kappa score: 0.90 versus 0.46; 푃 = 0.001) in diagnosing CD. NBI-ME could help identify
partial mucosal atrophy in the routine endoscopic practice, potentially reducing the need for blind biopsies. NBI-ME was superior
to SE and can reliably predict in vivo the villous changes of CD.
Standard endoscopy (SE) does not usually allow the visual-
ization of duodenal villouspatterns and may be inaccurate in
patients with celiac disease (CD) [1–4]. In CD the intestinal
damages can have a patchy, “stain-like” distribution, and the
macroscopic features can be more or less dependent on the
degree/severity of the histological lesions . Indeed, at SE,
partial villous atrophy may elude detection, and a normal
endoscopic appearance of the mucosa does not necessarily
imply normal histology.
Several endoscopic features observed during SE reflect
the presence of villous atrophy; however their sensitivity
varies from 50% to 94% [5, 6]. Sensitivity is particularly low
in patients with subclinical CD, partial villous atrophy, or
patchy disease [1, 2, 7]. Improved visual identification of sus-
pected mucosalatrophycouldassist in targetingbiopsiesand
thereby increasing the sensitivity of endoscopy . Different
emerging techniques have been evaluated, alone or in com-
bination, to enhance the ability of the endoscopist to detect
mucosal abnormalities, including chromoendoscopy, water-
or combined with acetic-acid instillation, and optimal band
A previous observation reported the combination of
high-resolution Narrow Band Imaging (NBI) with ME
(NBI-ME) to obtain targeted biopsy specimens indicating
a higher simplicity (with the switch of a button) than
chromoendoscopy, thus reducing the procedure time .
In fact, NBI-ME is a simple tool that allows detection of
2 Diagnostic and Therapeutic Endoscopy
the subepithelial microvascular architecture and mucosal
[14, 15]. To our knowledge there is not a prospective study
that addresses the performance of NBI-ME in evaluating
patients with suspected CD. The aim of this study was to
assess the correlation between NBI-ME and histology and
to compare the diagnostic accuracy between NBI-ME and
SE using histology as gold standard in detecting villous
abnormalities in CD.
2. Materials and Methods
2.1. Subjects and Endoscopic Procedures. Forty-four consec-
utive patients (17 males, 27 females, age range 14–73 years,
mean age 36.5 years) with clinical history suggestive of
anemia, etc.) and serologic suspicion for CD as positive
or borderline antiendomysial (normal values are absent for
both IgA and IgG) and antitransglutaminase antibodies
(normal values 0–10U/mL) were prospectively enrolled in
the study. The presence of severe gastrointestinal or systemic
The study was performed under the local ethics committee
Prior to endoscopy, a written informed consent was
obtained from all participants. In order to prolong the
procedure for the evaluation of the duodenal mucosa with
NBI-ME, a conscious sedation with intravenous midazo-
lam (0.05–0.1mg/Kg) was used before undergoing upper
gastrointestinal (UGI) endoscopy together with induction
of gastrointestinal hypotony (with hyoscine N-butylbromide
All procedures were performed with an Olympus GIFQ
160Z, Exera II (Olympus, America Corp., Melville, NY,
USA), a high-resolution endoscope with adjustable image
magnification to ×115 which included the NBI system. A
secure a single area for focus, thus maintaining an optimum
endoscopist who was blinded to the laboratory data of all
patients. A regular inspection of the duodenum with SE was
performed before switching to the NBI vision. A judgement
on the villous appearance (abnormalities or not) for SE
and for NBI-ME was then expressed. The various duodenal
villous patterns at NBI-ME inspection were classified as
(marked villous atrophy) (Figure 1).
To avoid insufficient sampling, as recommended by
previous investigators , 4 to 6 biopsy specimens were
taken from the descending duodenum and from any other
area of irregular appearing duodenal mucosa by using stan-
dard biopsy forceps. If no abnormality was macroscopi-
cally evident, random biopsy specimens were obtained. The
histopathological evaluation was performed according to the
Marsh classification, modified by Oberhuber . Samples
disposable polyethylene cap was applied on the distal end of
the endoscope to prevent slippage of the mucosa and to help
were evaluated by a pathologist who was blinded to the
clinical data and the endoscopic findings.
2.2. Statistical Analysis. The relationship between NBI-ME
and SE findings was compared with histology using the
k-Cohen agreement coefficient. Sensitivity, specificity, and
positive and negative predictive values (PPV-NPV) for both
techniques were calculated using histology reports as the
gold standard. The efficacy of NBI-ME for predicting villous
abnormalities in CD was evaluated by the area under the
Receiver Operating Characteristic (ROC) curve analysis.
Statistical significance was established at 푃 < 0.05 for all the
3. Results and Discussion
3.1. Results. A diagnosis of CD was histologically made in
17 (38.6%) of 44 enrolled patients, while the remaining 27
with CD, 7 (41%) showed endoscopic features of disease
After switching to NBI-ME, a diagnosis of mucosal
were the same as those found at SE, had a complete absent
duodenal villous pattern, while 12 displayed an abnormal
duodenal villous pattern. Two cases showing abnormal vil-
lous patterns at NBI-ME were subsequently classified as neg-
ative for CD at histology (Table 1). NBI-ME identified patchy
specificity, PPV, and NPV of 100%, 93%, 89%, and 100%,
100%, and 73%, respectively (Table 2). The area under the
under the ROC was 0.706 for SE (푃 = 0.023) (Figure 2).
ROC curve for NBI-ME was 0.978 (푃 = 0.0005), indicating
The overall agreement between NBI-ME and histology was
significantly higher when compared with SE and histology
an excellent agreement with the histological results. The area
(kappascore:0.90versus0.46;푃 = 0.001)indeterminingCD
The mean additional time for single NBI-ME procedure
functional dyspepsia, irritable bowel syndrome, or overlap
was 4 minutes and 30 seconds (±1 minute).
3.2. Discussion. The first report on the use of ME with
chromoendoscopy to highlight duodenal villous pattern was
published by Siegel et al.  demonstrating an increased
detection rate of focal villous atrophy as well as partial
villous atrophy compared with SE in patients with malab-
to difficulty in achieving a complete and an even coating
of the mucosal surface with the dye , increased cost
and procedure time, and the lack of visualization of the
vascular pattern have prevented the widespread use of vital
dye staining chromoendoscopy techniques. Recently a new
technology called “Fuji Intelligent Color Enhancement,” a
virtual chromoendoscopy, was introduced to enhance the
contrast of the mucosal surface without the use of dyes,
Diagnostic and Therapeutic Endoscopy3
Figure 1: (a, b, and c) Normal villous patterns. Visualization of normal duodenal mucosa at white light SE (a). Regular villi appear well
represented, thick, with a finger-like appearance at NBI system and ME (b and c). (d, e, and f) Abnormal villous patterns. Partial villous
atrophy view at SE (d); NBI-ME showing a low-density of villi which appear irregular, disoriented, and with an initial pattern of surface
destruction (e and f). (g, h, and i) Absent villous patterns. Marked villous atrophy with NBI system and ME (g); the surface is flat (h),
“foveolar-like,” with total villi absence and wide circles (i: black arrow).
through the ability to select better spectral images decom-
posed from ordinary endoscopic images . Cammarota
et al.  published an original open, prospective, single-
centre trial on the potential of a similar system, the optimal
band imaging (OBI), for predicting the duodenal villous
morphologic characteristics in patients with suspected CD.
The authors concluded that the OBI system, in association
with ME, allows clear visualization of the duodenal pattern,
with a potential role in optimizing the diagnostic accuracy of
endoscopy in CD.
In the present study we show that the NBI system,
conventional endoscopy in detecting mucosal abnormali-
ties on otherwise normal appearing duodenal mucosa. We
found high sensitivity and specificity values with an over-
all agreement between NBI-ME and histology significantly
duodenal villous pattern features. Moreover, the ROC curve
analysis demonstrated that the NBI-ME performance was
greater than SE, showing an excellent agreement with the
The NBI system consists of a sequential electronic endo-
scope system that can select better spectral images using
particular luminous bands, thus enabling to filter incidence
light resulting in some kind of “coloration without coloring.”
Since the gastrointestinal tract is mainly composed of blood
vessels and mucosa, narrow band illumination, which is
strongly absorbed by hemoglobin and penetrates only the
surface of tissues, is ideal for enhancing the contrast between
However, our results have some limitations. First, we
did not assess the inter- or intraobserver reliability of the
4 Diagnostic and Therapeutic Endoscopy
Table 1: Histological diagnosis and corresponding endoscopic
§7 absent villous patterns.
12 abnormal villous patterns.: 2 negative, histology for CD.
NBI + ME
Table 2: Diagnostic accuracy of SE and NBI with ME.
NBI + ME
Table 3: Overall agreement (k-Cohen coefficient) between endo-
scopic findings and histology reports.
NBI + ME and histology
SE and histology
∗푃 = 0.001 (Student’s 푡-test).
mucosal patterns. Consequently, although duodenal villous
classified patterns were normal, abnormal, or absent, we
have not evaluated the correlationbetween partial or marked
villous atrophy with histological score. In fact, our main
objective was to establish the presence or absence of CD. A
previous report by Badreldin et al.  on the potential role
villous atrophy showed a sensitivity of 90.7% and specificity
of 63%. In their study the main disagreement between zoom
endoscopy and histopathology was the distinction between
normal tall villi and morphologically normal but shortened
villi, which depends on the assessment of villus height.
More recently another study, using a simplified classification,
demonstrated the feasibility of using NBI-ME for the detec-
tion of villous atrophy in patients presenting with suspected
Second, among the criticisms that have been raised for
including conscious sedation, for routine application. We
observed an additional mean procedure time of 4 minutes
and 30 seconds.
Third, as reported by other authors , all patients
who underwent UGI endoscopy had clinical history of
malabsorption or serologic suspicion for CD, thus having a
high pretest probability for duodenal abnormalities.
Fourth, we have found two false-positive cases at NBI-
ME which reduced the specificity. It is possible that this
CD in open access endoscopy is likely to be underestimated,
with missed diagnose, ranging from less than 1% to 16%
. The ideal diagnostic technique approach for CD should
saving, and repeatable, and not be time consuming .
Source of the curve
AUC for NBI-ME = 0.978
AUC for SE = 0.706
Figure 2: Receiver operating characteristic curves of NBI-ME and
SE for diagnosing CD.
Furthermore, other endoscopic options, such as con-
focal endomicroscopy  and optical coherence tomog-
raphy , that were studied in patients with suspected
CD achieved good results. However, these techniques are
hampered by technical problems. In particular, difficulty
of image acquisition/stability, with potential distortion and
artifacts, and a long learning curve would restrict their wide
use on the basis of the local availability of equipment and
expertise. Moreover, according to Fedeli and colleagues ,
the combination of two or more simple new endoscopic
approaches, such as OBI together with ME, during water-
immersion would obtain outstanding images of the villous
have proposed an algorithm to minimize the need for duo-
denal biopsy in patients with suspected CD in particular for
that could involve patients who are on anticoagulation ther-
apy and that cannot be safely interrupted . As suggested
in a correspondence , we believe that it is not possible, at
and for followup. In fact it is not possible to make a precise
differential diagnosis of Giardia lamblia infection or Crohn’s
disease (where there could also be changes of serological
markers)  and eosinophilic jejunitis or HIV enteropathy
; furthermore, the histological evaluation is fundamental
because it allows verifying improvement of duodenal lesions
after gluten-free diet or the absence of mucosal recovery that
needs an analysis of molecular markers in the suspicion of a
T-cell dysplasia lymphoma .
Diagnostic and Therapeutic Endoscopy5
In conclusion, our findings show that the NBI with ME
represents a simple technique that could help identify patchy
areas of partial mucosal atrophy and then estimate the
extension, even considering frequently mixed patterns. With
these tools it is also possible to predict, in a reliable manner,
“minimal changes” of duodenal villi in CD occurring in vivo
and, importantly, improve biopsy sampling by potentially
reducing the need for blind biopsies and false-negative cases.
Conflict of Interests
The authors certify that there is no conflict of interests with
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