Digestive Endoscopy 2016; 28: 379–393 doi: 10.1111/den.

12638

Guideline

Magnifying endoscopy simple diagnostic algorithm for early

gastric cancer (MESDA-G)
Manabu Muto,1,2,3 Kenshi Yao,1,2,3 Mitsuru Kaise,1,2,3 Mototsugu Kato,1,2,3 Noriya Uedo,1,2,3
Kazuyoshi Yagi1,2,3 and Hisao Tajiri1,2,3
1
The Japanese Gastroenterological Association, 2Japan Gastroenterological Endoscopy Society, Tokyo, and 3The
Japanese Gastric Cancer Association, Kyoto, Japan

Gastric cancer is the third leading cause of cancer death
worldwide. Early detection and accurate diagnosis of mucosal
cancer is desirable in order to achieve decreased mortality;
cause-specific survival of patients with early gastric cancer is
reported to exceed 95%. Endoscopy is the functional modality to
detect early cancer; however, the procedure is not definitive when
using conventional white-light imaging. In contrast, magnifying
narrow-band imaging (M-NBI), a novel endoscopic technology, is
a powerful tool for characterizing gastric mucosal lesions because
it can visualize the microvascular architecture and microsurface
structure. To date, many reports on the diagnosis of early gastric
cancer by M-NBI, including multicenter prospective random-
ized studies conducted in Japan, have been published in
peer-reviewed international journals. Based on these pub-
lished data, we devised a proposal for a diagnostic strategy
for gastric mucosal cancer using M-NBI to simplify the process
of diagnosis and improve accuracy. Herein, we recommend a
diagnostic algorithm for early gastric cancer using magnifying
endoscopy.
Key words: diagnosis, early cancer, gastric cancer, magnifying
endoscopy, narrow-band imaging

INTRODUCTION that the Japan Gastroenterological Endoscopy Society (JGES),

the Japanese Gastric Cancer Association (JGCA), and the
G ASTRIC CANCER IS the third leading cause of cancer
death worldwide. Effective endoscopic diagnosis of
tumors in their early stages is essential for reducing gastric
World Endoscopy Organization (WEO) jointly devise a
unified international algorithm for ME diagnosis of EGC
(Magnifying Endoscopy Simple Diagnostic Algorithm for
cancer death by curative treatment. As many previous
Gastric cancer [MESDA-G], Fig. 1) using an evidence-based
studies demonstrated that magnifying endoscopy (ME) is
approach.
a highly accurate technique for detecting early gastric
cancer (EGC), this modality is currently the key to its
effective diagnosis and curative treatment. However, be- METHODS
cause many different criteria or algorithms for the diag-
nosis and classification of EGC have been proposed,
there is controversy about which criteria or algorithm
T O PROPOSE THIS algorithm, a PubMed search of the
English language medical literature was conducted for
the period between 1 January 1990 and 10 February
should be used.
2013. We used the following key words for our search:
Therefore, a unified algorithm for general use in the clinical
‘gastric or stomach’ and ‘cancer or carcinoma’ and
setting is necessary for enhancing the efficacy of ME
‘magnifying or magnification or zoom’. In addition, all
diagnosis of EGC. The Japanese Gastroenterological
relevant articles were manually inspected to identify
Association (JGA) established a working group and proposed
publications that may have been missed using the preceding
search terms. Reference lists of all identified studies were
also reviewed, and full original articles were retrieved for
any potentially relevant citations. After this peer-reviewed
Corresponding: Manabu Muto, Department of Therapeutic
Oncology, Kyoto University Graduate School Medicine, 54 process, 169 articles were found by searching PubMed
Kawaharacho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. and 22 more articles were obtained by manual search.
Email: mmuto@kuhp.kyoto-u.ac.jp Among them, randomized controlled studies, observational
Received 3 November 2015; accepted 17 February 2016. studies, case series, and review articles were selected for

© 2016 The Author Digestive Endoscopy published by John Wiley & Sons Australia, Ltd 379
on behalf of Japan Gastroenterological Endoscopy Society
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This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits
use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or
adaptations are made.

380 M. Muto et al.
Figure 1 Magnifying Endoscopy Simple Diagnostic Algorithm
for Gastric cancer (MESDA-G). DL, demarcation line; IMVP,
irregular microvascular pattern; IMSP, irregular microsurface
pattern.
this algorithm. Studies were excluded if they were not
original reports on the diagnosis of EGC or if they were
case reports. After this filtering, 66 articles were selected
for use in this algorithm (57 from PubMed and nine from
the manual search).1–66Among the selected articles, the
most commonly accepted diagnostic system was used for
constructing the diagnostic algorithm for EGC by using
ME.
CANCER DEFINITION AND MACROSCOPIC
CLASSIFICATION
C ANCER DEFINITIONS AND macroscopic
classifications are shown in Figure 2). EGC is defined
as carcinoma confined to the mucosa and submucosa, with
or without regional lymph node metastasis.67 The histological
diagnosis of EGC corresponds to categories 4 (mucosal high-
grade neoplasm) and 5 (submucosal invasion by carcinoma)
according to the Vienna classification.68,69
Endoscopic screening is useful to detect EGC. Macroscopic
classification of the JGCA distinguishes a superficial-type tu-
mor (Type 0) as a typical gross morphological type of EGC.
Type 0 is further subdivided into protruding (Type 0-I), super-
ficial elevated (Type 0-IIa), superficial flat (Type 0-IIb), super-
ficial depressed (Type 0-IIc), and excavated (Type 0-III)
types.70–72 Tumors with <3 mm elevation are usually classi-
fied as Type 0-IIa, whereas more elevated tumors are classified
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Digestive Endoscopy 2016; 28: 379–393
Figure 2 Macroscopic types of early gastric carcinoma by
Japanese Classification of Gastric Carcinoma provided by
Japan Gastric Cancer Association. sup., superficial.
as Type 0-I. In this review, we focused mainly on lesions of 0-
IIa, 0-IIb and 0-IIc, because most of the evidence was from
these lesions.
MAGNIFYING ENDOSCOPY SIMPLE DIAGNOS-
TIC ALGORITHM OF EGC: MESDA-G
F IGURE 1 SHOWS THE MESDA-G algorithm. To diag-
nose EGC, one has to identify any suspicious lesion that
is potentially a neoplasm. To recognize such a lesion, we care-
fully observe the color change (whitish or reddish) or morpho-
logical change (elevated, flat, or depressed) on the gastric
mucosal surface. If we detect a suspicious lesion, identifica-
tion of a demarcation line (DL) between the lesion and the
background mucosa is the first step in distinguishing EGC
from a non-cancerous lesion. If a DL is absent, the diagnosis
of a benign lesion may be made. If a DL is present, the subse-
quent presence of an irregular microvascular (MV) pattern and
an irregular microsurface (MS) pattern should be determined.
If irregular MV and/or MS patterns are present within the de-
marcation line, the diagnosis of EGC can be made.
ENDOSCOPIC IMAGING OF NON-NEOPLASTIC
GASTRIC MUCOSA
U NDERSTANDING THE ENDOSCOPIC finding of the
non-neoplastic gastric mucosa is important for: (i)
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Digestive Endoscopy 2016; 28: 379–393 Diagnostic algorithms for EGC by ME 381

identification of high-risk individuals who develop gastric
cancer; (ii) distinguishing neoplastic lesions from non-
neoplastic lesions; and (iii) determination of the tumor bound-
ary in order to make treatment decisions. Gastric cancer,
especially the non-cardiac type, usually develops in patients
with chronic Helicobacter pylori (H. pylori) infections;
therefore, the surrounding mucosa is mostly affected by
inflammatory cell infiltration, atrophy, or intestinal metaplasia.
H. pylori-associated chronic gastritis alters the MVarchitecture
and the MS structure of non-neoplastic gastric mucosa.
NORMAL FUNDIC GLAND MUCOSA
epithelium lining crypt opening is visualized as an oval white
belt-like structure which is reported to be the marginal crypt
epithelium (MCE)74 or the white zone8 (Fig. 3b). Capillaries
surrounding each crypt opening form honeycomb-like
subepithelial capillary networks.75–78 These capillaries con-
verge into collecting venules that vertically descend under
the tunica muscularis mucosae and flow into a main vein.
Collecting venules have a starfish-like appearance with a cyan
color.75–78
NORMAL PYLORIC GLAND MUCOSA

A NORMAL FUNDIC gland mucosa indicates a corpus

mucosa without any pathological change such as
inflammation or atrophy as a result of H. pylori infection.
Arterioles that run through the muscularis mucosa lead to
mucosal capillaries forming a network inside the mucosa,
and these capillaries surround the fundic glands and the
surface epithelium of the crypt. Capillaries proceed to the
venous plexus under the covering epithelium and converge
at collecting venules, which vertically descend into the tunica
muscularis mucosae (Fig. 3a).73
ME with narrow-band imaging (NBI) of the normal fundic
gland mucosa is characterized as follows: the surface
A NORMAL PYLORIC gland mucosa refers to a pyloric
mucosa without any pathological changes such as
inflammation or intestinal metaplasia as a result of H. pylori
infection. The crypts in the pyloric gland mucosa form
grooves. The intervening parts between the grooves form
ridges. Arterioles through the muscularis mucosa proceed to
capillary networks inside the mucosa, and these capillaries
exist below the surface epithelium of the ridge-like structure
surrounded by crypts (Fig. 4a). The ME with NBI of the
normal pyloric mucosa shows that the intervening part is lined
with a white belt-like structure,77–79 which is referred to as the
MCE74 or the white zone.8 Coil-shaped subepithelial capillary
networks are observed through the surface epithelium of the

Figure 3 (a) Schematic diagram of the microvascular architecture and the microsurface structure of the normal gastric fundic gland
mucosa corresponding to the surface morphology as visualized by magnifying endoscopy (ME) with narrow-band imaging (NBI). The
microvascular architecture is formed by the capillaries and collecting venules. The morphology of each capillary is that of a polygonal
closed loop. These loops anastomose repeatedly with each other, forming a regular honeycomb-like subepithelial capillary network
pattern. The microsurface structure is made up of the marginal crypt epithelium/white zone (MCE/WZ), and the intervening part in
between. The epithelial morphology is visualized as a semitransparent white belt-like structure (the MCE/WZ), showing a circular or
oval shape at the center of which lies the crypt opening. (b) ME with NBI of normal fundic gland mucosa.

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382 M. Muto et al. Digestive Endoscopy 2016; 28: 379–393

Figure 4 (a) Schematic diagram of the microvascular architecture and the microsurface structure of the normal gastric pyloric gland
mucosa corresponding to the surface morphology as visualized by magnifying endoscopy (ME) with narrow-band imaging (NBI). The
microvascular architecture is formed by capillaries and collecting venules, but the latter are rarely observed from the mucosal surface.
The morphology of each capillary is that of coil-shaped open loops. The mucosal surface structure is made up of the marginal crypt
epithelium/white zone (MCE/WZ) and the intervening parts surrounded by MCE/WZ. The MCE/WZ morphology usually shows
polygonal structures but may be curved or linear. (b) ME with NBI of normal pyloric gland mucosa.

intervening part (Fig. 4b).77–79 The ME finding of the pyloric
gland mucosa is completely different from that of the fundic
gland mucosa.
MUCOSA IN H. PYLORI-ASSOCIATED CHRONIC
GASTRITIS
P ERSISTENT H. PYLORI INFECTION causes inflamma-
tion, atrophy, and intestinal metaplasia in the gastric
mucosa.80 This pathological condition is called chronic
gastritis. The present review will not cover other causes of
chronic gastritis, such as autoimmune gastritis. The ME
images of the fundic gland mucosa with inflammation show
an anomalous form and arrangement of the crypt openings
(Fig. 5a), as well as elliptical or groove-like shapes with white
color (Fig. 5b).76,81,82 Capillaries may or may not be observed
along the crypt opening (Fig. 5a,b).76,81 The ME finding of an
atrophic mucosa shows ridged or villous-to-granular

(a) (b) (c)

Figure 5 (a) Magnifying endoscopy (ME) with narrow-band imaging (NBI) of the fundic gland mucosa with inflammation shows an
anomalous form and arrangement of the crypt openings. (b) ME with NBI of the fundic gland mucosa with inflammation shows
elliptical or groove-like shapes with white color. (c) ME with NBI of atrophic mucosa of the corpus. Yellow arrows indicate a light
blue crest.

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Digestive Endoscopy 2016; 28: 379–393 Diagnostic algorithms for EGC by ME 383

intervening parts encasing dilated, coiled subepithelial capil-
laries (Fig. 5c).83 An atrophic mucosa often involves intestinal
metaplasia which shows a light blue crest (LBC) by ME with
NBI (Fig. 5c, yellow arrows).84
The pyloric gland mucosa is not discussed in the present
review because the characteristic distinction between an
inflammation-free normal mucosa and chronic gastritis by
ME is not clearly elucidated.79
METAPLASTIC MUCOSA
and a groove-type structure in the antrum, whereas the MS
structure of intestinal metaplasia usually shows the groove-
type or villiform structures mimicking the normal antral or
intestinal mucosa (Figs 6c,7c). Upon ME with NBI images,
a fine blue-white line of light is observed on the crests of the
epithelial surface or gyri (an LBC, yellow arrowheads in
Figs 6d,7d).90 The LBC is presumed to originate from the re-
flection of light upon the ciliated structure on the surface of the
intestinal metaplasia (the brush border). Moreover, the epithe-
lium of the intestinal metaplasia (single asterisk in Fig. 6d)
looks cloudy compared to the non-metaplastic mucosa
(double asterisk in Fig. 6d).92

C HRONIC INFECTION OF H. pylori induces biomolecu-

lar alteration of the gastric mucosa, causing it to resemble
an intestinal phenotype (intestinal metaplasia).85,86 Intestinal
metaplasia signifies a high risk of gastric cancer. 87–89
On white-light endoscopy, intestinal metaplasia looks
slightly elevated (Fig. 6a) or exhibits whitish flat areas.90 It
can also resemble a flat mucosa with the same color as the
surrounding mucosa (Fig. 7a,b), or else have shallow, de-
pressed reddish areas.91 NBI can contrast the color difference
between metaplastic and non-metaplastic mucosa (Fig. 6b).84
Upon image magnification, the MS structure of the normal
gastric mucosa has a foveolar-type appearance in the corpus
SUSPICIOUS LESION
T HE FIRST STEP in diagnosing EGC is to identify a
suspicious lesion using conventional white-light
endoscopy. In order to detect EGC using this method, it is
important to pay attention to subtle changes of mucosal color
and morphology. Clues of a suspicious lesion include mucosal
discoloration (erythema or pallor), morphological changes of
the mucosal surface (protruding, elevated or depressed),
tapered or interrupted mucosal folds, spontaneous bleeding,

(a) (b)

Figure 6 (a) Gastric intestinal

metaplasia in the antrum looks like a
whitish, slightly elevated area. (b)
Narrow-band imaging (NBI) enhances
the whitish color of the intestinal (c) (d)
metaplasia. (c) In magnifying endoscopy
(ME) with NBI, the metaplastic mucosa
shows a groove-type mucosa (also see
white box in (b)). (d) Magnifying view
of white box in (c). On the crests of
the mucosal surface/gyri, a light blue
crest (yellow arrowheads) is seen (also
see white box in (c)). Note that the
marginal crypt epithelium in the
metaplastic mucosa (white arrow,
single asterisk) is wider and cloudier
than that of the non-metaplastic
mucosa (white arrow, double asterisk).

© 2016 Japan Gastroenterological Endoscopy Society


384 M. Muto et al.
(a) (b)
(c) (d)
localized opacity of the mucosa (abrupt change in background
vascular/mucosal pattern), or loss of mucosal glossiness.93 In
the case with ulcer formation, a suspicious lesion could be
detected as subtle changes of mucosa surrounding an ulcer.
Adequate preparation and use of proper techniques are im-
portant for the detection of EGC.94 Preparation with mucolytic
and defoaming agents, aspiration of fluids, and washing off
any adherent mucus or bubbles using water irrigation facilitate
(a) (b)
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Digestive Endoscopy 2016; 28: 379–393
Figure 7 Gastric intestinal metaplasia
in the corpus appears as a flat mucosa
without any particular finding in (a)
white light imaging and (b) narrow-
band imaging (NBI). (c) In magnifying
endoscopy (ME) with NBI, the mucosa
shows a villiform microsurface
structure (also see white box in (b)). (d)
A light blue crest (yellow arrowheads)
is observed on the surface of the
villiform epithelium (also see white box
in (c)).
careful observation of the mucosal surface. Adequate air insuf-
flation and standardized techniques are necessary to avoid
overlooking a suspicious lesion.95
Subsequent image-enhanced endoscopic observation such
as indigocarmine dye spraying and/or ME with NBI of the sus-
picious lesion improves visualization of mucosal characteristics
to facilitate differentiation of a cancerous lesion from back-
ground mucosa.50 Detection of either a clear border between
Figure 8 Demonstrable case of non-
cancerous lesion. (a) Conventional
endoscopic findings with white-light
imaging. A slightly reddened,
depressed lesion (arrow) is noted at
the gastric antrum. As there are no
irregularities in the color and shape of
the lesion, this lesion does not appear
to be cancerous. (b). Magnifying
endoscopic findings with narrow-band
imaging. When we observe the
marginal part of the lesion, there is no
demarcation line. According to the
diagnostic algorithm, this lesion can
be diagnosed as non-cancer.
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Digestive Endoscopy 2016; 28: 379–393 Diagnostic algorithms for EGC by ME 385

the suspicious lesion and the background mucosa, and/or ir- lesion, increase the likelihood of the growth being
regularity of the color and surface structure of the suspicious cancerous.95 Demonstrable lesions are shown in Figures 8–12.

(a) (b)

Figure 9 Demonstrable case of non-cancerous lesion. (a) Conventional endoscopic findings with white-light imaging. A slightly
reddened, depressed lesion (arrow) is detected in the lower gastric body. As the distribution of the redness is irregular and the
margin of the lesion shows irregularity, cancer cannot be ruled out by this observation alone. (b) Magnifying endoscopic findings
with narrow-band imaging. A clear demarcation line (arrows) between the background mucosa and the lesion is detected (arrows).
Inside the demarcation line, there are regular microvascular and regular microsurface patterns. Because neither an irregular
microvascular nor irregular microsurface pattern is present, this lesion can be diagnosed as non-cancer.

Figure 10 Demonstrable case of

cancerous lesion. (a) Conventional
endoscopic findings with white-light (a) (b)
imaging. A slightly depressed lesion
with discoloration (arrows) is noted at
the anterior wall of the gastric angle.
(b) Conventional white-light endoscopic
findings with the dye (indigocarmine)-
spraying method. After the dye is
sprayed, the subtle lesion can be
clearly visualized. As the margin of
the lesion (arrows) shows irregularity,
this lesion can be diagnosed as
cancer. (c) Magnifying endoscopic
findings with narrow-band imaging. A
clear demarcation line (arrows) is (c) (d)
noted at the margin of the lesion.
Because both irregular microvascular
and irregular microsurface patterns
are present within the demarcation
line, this lesion can be diagnosed as
cancer. (d) Histological findings of
endoscopically resected specimen
shows well- to poorly differentiated
adenocarcinoma limited to the
mucosa. Arrow shows the horizontal
extent of the cancerous tissue.

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386 M. Muto et al. Digestive Endoscopy 2016; 28: 379–393

(a) (b)
Figure 11 Demonstrable case of
cancerous lesion. (a) Conventional
endoscopic findings with white light
imaging. A slightly reddened lesion
with erosion (arrow) is detected at the
gastric antrum. (b). Conventional white-
light endoscopic findings with the dye
(indigocarmine)-spraying method. After
the dye is sprayed, this lesion (arrow)
depicts no signs characteristic of cancer.
(c) Magnifying endoscopic findings
with narrow-band imaging. A clear
(c) (d) demarcation line (arrows) is detected.
Within the demarcation line, a
microvascular pattern is absent because
of the presence of a white opaque
substance, but the microsurface pattern
is irregular. Accordingly, this lesion can
be diagnosed as cancer. (d) Histological
findings of endoscopically resected
specimen demonstrate well-differentiated
adenocarcinoma confined to the
mucosa. Arrow shows the horizontal
extent of the cancerous tissue.

Figure 12 Demonstrable case of

cancerous lesion. (a) Conventional
endoscopic findings with white light
(a) (b) imaging. A focal pale mucosal lesion
(arrow) is noted at the gastric antrum.
(b) Conventional white-light endoscopic
findings with the dye (indigocarmine)-
spraying method. No finding
characteristic of cancer is detected
(arrow). (c) Arrow indicate pale lesion
in (a). Magnifying endoscopic findings
with narrow-band imaging. A
demarcation line (arrows) is noted. A
microsurface pattern is absent, but
the microvascular pattern is irregular.
Accordingly, this lesion can be
(c) (d) diagnosed as cancer. On the right
side of the figure, slight irregular
microvessels are also seen. However,
they are not located in the well-
demarcated area. Thus, this lesion is
negligible for different diagnosis. (d)
Histological findings of endoscopically
resected specimen depict well- to
moderately differentiated adenocarcinoma
restricted to the mucosa. Arrow
shows the horizontal extent of the
cancerous tissue.

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Digestive Endoscopy 2016; 28: 379–393
DIAGNOSTIC SYSTEM BEHIND THE DIAGNOS-
TIC ALGORITHM
T HE VS (VESSELS plus surface) classification system for
the analysis of ME findings was developed by Yao
et al.55,62 This diagnostic system has proven to be very useful
for correctly diagnosing superficial (0-II) cancer22,40,66,96 and
delineating the margins of EGC.21
Anatomical terms are used to define the MVand MS patterns
as visualized by ME. The MV pattern comprises a subepithelial
capillary, a collecting venule, and pathological microvessels,
whereas the MS pattern is identified by a MCE (white zone),
a crypt opening, and an intervening part between crypts.
According to the VS classification system, the
characteristic ME findings of EGC are the presence of a clear
DL between non-cancerous and cancerous mucosa, and the
presence of an irregular MV pattern and/or irregular MS
Figure 13 Vessels plus surface (VS) classification: The microvascular pattern (V) is classified as regular, irregular, or absent; the
microsurface pattern (S) is also classified as regular, irregular, or absent. Arrows indicate the demarcation line in each panel.
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Diagnostic algorithms for EGC by ME 387
pattern within the DL. On principle, the MV and MS patterns
need to be determined separately.
The definition of a DL is a border between the lesion and
non-lesion areas, discernible through an abrupt change in
MV and/or MS patterns (Figs 13–15).97
Accordingly, two criteria were set for making a diagnosis of
high-grade dysplasia/EGC:62
(i) an irregular MV pattern with a DL; and/or
(ii) an irregular MS pattern with a DL.
If either or both criteria are fulfilled, an endoscopic
diagnosis of EGC can be made and, according to our research,
97% of EGC cases fit these criteria.62 Regarding the algorithm
proposed in the present article, we first need to determine
whether a DL is present between the mucosal lesion and the
background mucosa. If a DL is absent (Figs 13, 14), the lesion
is diagnosed as non-cancerous. If a DL is present, we should
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388 M. Muto et al. Digestive Endoscopy 2016; 28: 379–393

Figure 14 Demonstrable case of an

absent demarcation line. (a)
Conventional endoscopic findings with
white-light imaging. A flat reddened
(a) (b) lesion (arrow) is detected at the gastric
antrum. (b) Magnified endoscopic
findings with narrow-band imaging.
The microvasculature (subepithelial
capillary network) of the lesion is
gradually dilated from the background
mucosa. The microsurface pattern
(marginal crypt epithelium/white zone)
shows no abrupt change between the
lesion and the background mucosa.
Accordingly, no demarcation line is
detected between the lesion and the
background mucosa. Therefore, this
lesion is diagnosed as non-cancer.

next evaluate whether an irregular MV pattern and/or an irreg-
ular MS pattern are present (Figs 13, 15–17).
Three categories of the MV and MS patterns are defined:
regular, irregular, and absent (Fig. 13). In the regular MV
pattern (Figs 13, 15), mucosal capillaries have a uniform shape
that can be closed-looped (polygonal) or open-looped with a
homogeneous morphology, a symmetrical distribution, and a
regular arrangement. In the irregular MV pattern (Figs 13, 16),
the vessels are closed-looped (polygonal), open-looped,
tortuous, branched, or bizarrely shaped, have asymmetrical
distribution and irregular arrangements. Cancer-specific
morphology of irregular microvessels has been described
as dilation, heterogeneity in shape, abrupt caliber alteration,
and tortuousness.33,68 If a MV pattern is not fully visualized
because of the presence of a white opaque substance (WOS)
which obscures subepithelial microvessels, the MV pattern is
described as absent.10,36,62 In cases in which the WOS is
observed, rather than assessing the MVP, morphological
analysis of the WOS could be an alternative marker of MS
pattern.10,36,62 as demonstrated in Figures 11, 13, 17.
In the regular MS pattern (Figs 13, 15), the MCE/WZ is a uni-
form linear, curved, oval, or circular structure with homogeneous
morphology, symmetrical distribution, and regular arrangement.
In the irregular MS pattern (Figs 13, 16), the MCE/WZ is an
irregular linear, curved, oval, circular, or villous structure with
heterogeneous morphology, asymmetrical distribution, and

(a) (b)

Figure 15 Demonstrable case of a visible demarcation line. (a) Conventional endoscopic findings with white-light imaging. A depressed
reddened lesion (arrow) is detected at the gastric antrum. (b) Magnified endoscopic findings with narrow-band imaging. The microvascular
pattern (subepithelial capillary network) and the microsurface pattern (marginal crypt epithelium/white zone) have abruptly disappeared at
the margin of the lesion. Accordingly, a clear demarcation line (arrows) is identified. Inside the demarcation line, both the microvascular
and microsurface patterns are regular. Therefore, this lesion is diagnosed as non-cancer. [Correction added on 15 June, after first online
publication: The captions of Figures 15, 16 and 17 were interchanged and have now been corrected.]

© 2016 Japan Gastroenterological Endoscopy Society

 14431661, 2016, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/den.12638 by Univ of Sao Paulo - Brazil, Wiley Online Library on [03/04/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Digestive Endoscopy 2016; 28: 379–393 Diagnostic algorithms for EGC by ME 389

(a) (b) (c)

Figure 16 Demonstrable case of an irregular microvascular pattern in early gastric cancer. (a) Within the demarcation line (arrows),
the individual shapes of the microvessels show irregular closed loops. Each microvessel exhibits a heterogeneous morphology, an
asymmetrical distribution, and an irregular arrangement. (b) Within the demarcation line (arrows), the individual shapes of the
microvessels show closed, open, or irregularly branched loops. Each microvessel demonstrates a heterogeneous morphology, an
asymmetrical distribution, and an irregular arrangement. (c) Within the demarcation line (arrows), the individual shapes of
microvessels show tiny closed loops. Each microvessel depicts a heterogeneous morphology, asymmetrical distribution, and an
irregular arrangement. Accordingly, this lesion is diagnosed as cancer. [Correction added on 15 June, after first online publication:
The captions of Figures 15, 16 and 17 were interchanged and have now been corrected.]

irregular arrangement. If neither the MCE/WZ is visible my in which tortuous microvessels are isolated like a corkscrew,
ME, the MS pattern is classified as absent (Fig. 13). is characteristic of poorly differentiated adenocarcinoma.
Subclassification of irregular MV patterns was proposed for
predicting histological patterns of gastric cancer.51 Fine net-
LIMITATIONS OF THE ALGORITHM
work pattern (Fig. 18a), in which abundant microvessels are
well connected to one another like a mesh, is characteristic of
differentiated adenocarcinoma. Corkscrew pattern (Fig. 18b), A LTHOUGH THIS ALGORITHM could be expected to
provide high accuracy (95%~), high positive predictive

(a) (b) (c)

Figure 17 Demonstrable case of irregular microsurface patterns in early gastric cancer. (a) Within the demarcation line (arrows), the
individual shape of the marginal crypt epithelium/white zone (MCE/WZ) is curved. Each MCE/WZ demonstrates a heterogeneous
morphology, an asymmetrical distribution, and an irregular arrangement. (b) Within the demarcation line (arrows), the individual
shape of the MCE/WZ is curved. Each MCE/WZ represents a heterogeneous morphology, an asymmetrical distribution, and an
irregular arrangement. (c) Within the demarcation line (arrows), a white opaque substance which obscures the subepithelial
microvascular pattern is present. Each white opaque substance exhibits a heterogeneous morphology, an asymmetrical
distribution, and an irregular arrangement. Thus, this lesion is diagnosed as cancer. [Correction added on 15 June, after first online
publication: The captions of Figures 15, 16 and 17 were interchanged and have now been corrected.]

© 2016 Japan Gastroenterological Endoscopy Society


390 M. Muto et al.
(a)
Figure 18 Representative endoscopic images of the subclassification of irregular microvascular patterns. (a) Fine network pattern and
(b) corkscrew pattern.
value (79%) and high negative predictive value (99%) for
making diagnosis of EGC,22 it has some limitations. The diag-
nostic yield for diffuse-type EGC was unclear, because most
of the evidence was proposed by the results of intestinal type.
The other was that if the lesion showed easy contact bleeding
or was covered by mucus, clear images for accurate diagnosis
were difficult to obtain. Thus, careful and patient observation
to obtain clear images is required in clinical practice.
CONCLUSION
M AGNIFYING ENDOSCOPY HAS proven to be a
key modality for effective diagnosis of EGC. How-
ever, it is not widely used because of the absence of uni-
fied diagnostic criteria. The proposal of a unified
algorithm and classification scheme constructed using
an evidence-based approach, and consensus of the rele-
vant clinical societies, provide a simple and effective
way to diagnose EGC using ME. The clinical societies
hope this algorithm (MESDA-G) and terminology will
be generally and widely used in clinical practice, and
may enhance early diagnosis of gastric cancer, resulting
in reduction of gastric cancer-related death worldwide.
ACKNOWLEDGMENTS
W E GREATLY APPRECIATE the agreement of this
algorithm by Japan Gastroenterological Endoscopy
Society, the Japanese Gastric Cancer Association, and the World
Endoscopy Organization. We acknowledge the secretaries of
Japanese Gastroenterological Association, Ms Tomomi Sasaki
and Ms Yoko Higuchi, for conducting the literature search and
for special assistance in preparing this manuscript.
© 2016 Japan Gastroenterological Endoscopy Society
14431661, 2016, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/den.12638 by Univ of Sao Paulo - Brazil, Wiley Online Library on [03/04/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Digestive Endoscopy 2016; 28: 379–393
(b)
CONFLICTS OF INTEREST
M ANABU MUTO RECEIVED a collaboration research
expense from Olympus Co. Mototsugu Kato has served
in speaking and teaching commitments for Eisai Co., Ltd,
Daiichi Sankyo Company, Ltd, Takeda Pharmaceutical Co.
Ltd, Otsuka Pharmaceutical Co., Ltd and AstraZeneca and
has received scholarship grants from Eisai Co., Ltd, Takeda
Pharmaceutical Co. Ltd, Daiichi Sankyo Company, Ltd,
AstraZeneca and Astellas Pharma Inc. Hisao Tajiri was sup-
ported donations from Olympus Co., Fujifilm Co., and Eisai
Co. Ltd. These funding sources had no role in the design, prac-
tice or analysis of this review. Drs Yao, Kaise, Uedo and Yagi
declare no conflicts of interest for this article.
REFERENCES
1 Kanesaka T, Sekikawa A, Tsumura T et al. Dense-type crypt
opening seen on magnifying endoscopy with narrow-band
imaging is a feature of gastric adenoma. Dig. Endosc. 2014;
26:57–62.
2 Tao G, Xing-Hua L, Ai-Ming Y et al. Enhanced magnifying
endoscopy for differential diagnosis of superficial gastric lesions
identified with white-light endoscopy. Gastric Cancer 2014;
17:122–9.
3 Horiuchi H, Kaise M, Inomata H et al. Magnifying endoscopy
combined with narrow band imaging may help to predict
neoplasia coexisting with gastric hyperplastic polyps. Scand. J.
Gastroenterol. 2013; 48: 626–32.
4 Miyaki R, Yoshida S, Tanaka S et al. Quantitative identification of
mucosal gastric cancer under magnifying endoscopy with flexible
spectral imaging color enhancement. J. Gastroenterol. Hepatol.
2013; 28:841–7.
5 Kobayashi M, Hashimoto S, Nishikura K et al. Magnifying
narrow-band imaging of surface maturation in early

Digestive Endoscopy 2016; 28: 379–393
differentiated-type gastric cancers after Helicobacter pylori
eradication. J. Gastroenterol. 2013; 48:1332–42.
6 Kikuchi D, Iizuka T, Hoteya S et al. Usefulness of magnifying
endoscopy with narrow-band imaging for determining tumor
invasion depth in early gastric cancer. Gastroenterol. Res. Pract.
2013; 2013:217695.
7 Meng XM, Zhou Y, Dang T, Tian XY, Kong J. Magnifying
chromoendoscopy combined with immunohistochemical
staining for early diagnosis of gastric cancer. World J.
Gastroenterol. 2013; 21(19):404–10.
8 Yagi K, Nozawa Y, Endou S, Nakamura A. Diagnosis of Early
Gastric Cancer by Magnifying Endoscopy with NBI from
Viewpoint of Histological Imaging: Mucosal Patterning in terms
of White Zone Visibility and its Relationship to Histology.
Diagn. Ther. Endosc. 2012; 2012:954809.
9 Mochizuki Y, Saito Y, Kobori A et al. Magnifying endoscopy
with narrow-band imaging in the differential diagnosis of gastric
adenoma and carcinoma and identification of a simple indicator.
J. Gastrointest. Liver Dis. 2012; 21: 383–90.
10 Yao K, Iwashita A, Nambu M et al. Nature of white opaque
substance in gastric epithelial neoplasia as visualized by
magnifying endoscopy with narrow-band imaging. Dig. Endosc.
2012; 24: 419–25.
11 Li HY, Dai J, Xue HB et al. Application of magnifying endoscopy
with narrow-band imaging in diagnosing gastric lesions: a
prospective study. Gastrointest. Endosc. 2012; 76: 1124–32.
12 Nonaka K, Namoto M, Kitada H et al. Usefulness of the DL in
ME with NBI for determining the expanded area of early-stage
differentiated gastric carcinoma. World J. Gastrointest. Endosc.
2012; 4: 362–7.
13 Kobara H, Mori H, Fujihara S et al. Prediction of invasion depth
for submucosal differentiated gastric cancer by magnifying
endoscopy with narrow-band imaging. Oncol. Rep. 2012; 28:
841–7.
14 Maki S, Yao K, Nagahama T et al. Magnifying endoscopy with
narrow-band imaging is useful in the differential diagnosis
between low-grade adenoma and early cancer of superficial
elevated gastric lesions. Gastric Cancer 2013; 16: 140–6.
15 Miwa K, Doyama H, Ito R et al. Can magnifying endoscopy with
narrow band imaging be useful for low grade adenomas in
preoperative biopsy specimens? Gastric Cancer 2012; 15: 170–8.
16 Omori T, Kamiya Y, Tahara T et al. Correlation between
magnifying narrow band imaging and histopathology in gastric
protruding/or polypoid lesions: a pilot feasibility trial. BMC
Gastroenterol. 2012; 12: 17.
17 Kosaka R, Tanaka K, Tano S et al. Magnifying endoscopy for
diagnosis of residual/local recurrent gastric neoplasms after
previous endoscopic treatment. Surg. Endosc. 2012; 26: 2299–305.
18 Tsuji Y, Ohata K, Sekiguchi M et al. Magnifying endoscopy with
narrow-band imaging helps determine the management of gastric
adenomas. Gastric Cancer 2012; 15: 414–8.
19 Ang TL, Fock KM, Teo EK et al. The diagnostic utility of narrow
band imaging magnifying endoscopy in clinical practice in a
population with intermediate gastric cancer risk. Eur. J.
Gastroenterol. Hepatol. 2012; 24: 362–7.
14431661, 2016, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/den.12638 by Univ of Sao Paulo - Brazil, Wiley Online Library on [03/04/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Diagnostic algorithms for EGC by ME 391
20 Zhang J, Guo SB, Duan ZJ. Application of magnifying
narrow-band imaging endoscopy for diagnosis of early
gastric cancer and precancerous lesion. BMC Gastroenterol.
2011; 11: 135.
21 Nagahama T, Yao K, Maki S et al. Usefulness of magnifying
endoscopy with narrow-band imaging for determining the
horizontal extent of early gastric cancer when there is an unclear
margin by chromoendoscopy (with video). Gastrointest.
Endosc. 2011; 74: 1259–67.
22 Ezoe Y, Muto M, Uedo N et al. Magnifying narrowband imaging
is more accurate than conventional white-light imaging in
diagnosis of gastric mucosal cancer. Gastroenterology 2011;
141: 2017–25.
23 Araki Y, Sasaki Y, Hanabata N et al. Morphometry for
microvessels in early gastric cancer by narrow band imaging-
equipped magnifying endoscopy. Dig. Endosc. 2011; 23:
233–9.
24 Kobayashi M, Takeuchi M, Ajioka Yet al. Mucin phenotype and
narrow-band imaging with magnifying endoscopy for
differentiated-type mucosal gastric cancer. J. Gastroenterol.
2011; 46: 1064–70.
25 Okada K, Fujisaki J, Kasuga A et al. Diagnosis of undifferentiated
type early gastric cancers by magnification endoscopy with
narrow-band imaging. J. Gastroenterol. Hepatol. 2011; 26:
1262–9.
26 Nonaka K, Arai S, Ban S et al. Prospective study of the evaluation
of the usefulness of tumor typing by narrow band imaging for the
differential diagnosis of gastric adenoma and well-differentiated
adenocarcinoma. Dig. Endosc. 2011; 23: 146–52.
27 Kiyotoki S, Nishikawa J, Satake M et al. Usefulness of
magnifying endoscopy with narrow-band imaging for
determining gastric tumor margin. J. Gastroenterol. Hepatol.
2010; 25: 1636–41.
28 Kato M, Kaise M, Yonezawa J et al. Magnifying endoscopy with
narrow-band imaging achieves superior accuracy in the
differential diagnosis of superficial gastric lesions identified
with white-light endoscopy: a prospective study. Gastrointest.
Endosc. 2010; 72: 523–9.
29 Yokoyama A, Inoue H, Minami H et al. Novel narrow-band
imaging magnifying endoscopic classification for early gastric
cancer. Dig. Liver Dis. 2010; 42: 704–8.
30 Nakamura M, Shibata T, Tahara T et al. The usefulness of
magnifying endoscopy with narrow-band imaging to distinguish
carcinoma in flat elevated lesions in the stomach diagnosed as
adenoma by using biopsy samples. Gastrointest. Endosc. 2010;
71: 1070–5.
31 Ezoe Y, Muto M, Horimatsu T et al. Magnifying narrow-
band imaging versus magnifying white-light imaging for
the differential diagnosis of gastric small depressive
lesions: a prospective study. Gastrointest. Endosc. 2010;
71: 477–84.
32 Kadowaki S, Tanaka K, Toyoda H et al. Ease of early gastric
cancer demarcation recognition: a comparison of four
magnifying endoscopy methods. J. Gastroenterol. Hepatol.
2009; 24: 1625–30.
© 2016 Japan Gastroenterological Endoscopy Society

392 M. Muto et al.
33 Kaise M, Kato M, Urashima M et al. Magnifying endoscopy
combined with narrow-band imaging for differential diagnosis
of superficial depressed gastric lesions. Endoscopy 2009; 41:
310–5.
34 Yoshizawa M, Osawa H, Yamamoto H et al. Diagnosis of
elevated-type early gastric cancers by the optimal band imaging
system. Gastrointest. Endosc. 2009; 69: 19–28.
35 Yao K, Takaki Y, Matsui T et al. Clinical application of
magnification endoscopy and narrow-band imaging in the upper
gastrointestinal tract: new imaging techniques for detecting and
characterizing gastrointestinal neoplasia. Gastrointest. Endosc.
Clin. N. Am. 2008; 18: 415–33.
36 Yao K, Iwashita A, Tanabe H et al. White opaque substance
within superficial elevated gastric neoplasia as visualized by
magnification endoscopy with narrow-band imaging: a new
optical sign for differentiating between adenoma and
carcinoma. Gastrointest. Endosc. 2008; 68: 574–80.
37 Tanaka K, Toyoda H, Kadowaki S et al. Surface pattern
classification by enhanced-magnification endoscopy for identifying
early gastric cancers. Gastrointest. Endosc. 2008; 67: 430–7.
38 Areia M, Amaro P, Dinis-Ribeiro M et al. External validation of a
classification for methylene blue magnification
chromoendoscopy in premalignant gastric lesions. Gastrointest.
Endosc. 2008; 67: 1011–8.
39 Osawa H, Yoshizawa M, Yamamoto H et al. Optimal band
imaging system can facilitate detection of changes in depressed-
type early gastric cancer. Gastrointest. Endosc. 2008; 67: 226–34.
40 Yao K, Iwashita A, Tanabe H et al. Novel zoom endoscopy
technique for diagnosis of small flat gastric cancer: a
prospective, blind study. Clin. Gastroenterol. Hepatol. 2007; 5:
869–78.
41 Dinis-Ribeiro M Chromoendoscopy for early diagnosis of gastric
cancer. Eur. J. Gastroenterol. Hepatol. 2006; 18: 831–8.
42 Fukui H, Shirakawa K, Nakamura T et al. Magnifying
pharmacoendoscopy: response of microvessels to epinephrine
stimulation in differentiated early gastric cancers. Gastrointest.
Endosc. 2006; 64: 40–4.
43 Tanaka K, Toyoda H, Kadowaki S et al. Features of early gastric
cancer and gastric adenoma by enhanced-magnification
endoscopy. J. Gastroenterol. 2006; 41: 332–8.
44 Tamai N, Kaise M, Nakayoshi T et al. Clinical and endoscopic
characterization of depressed gastric adenoma. Endoscopy 2006;
38: 391–4.
45 Kuznetsov K, Lambert R, Rey JF. Narrow-band imaging:
potential and limitations. Endoscopy 2006; 38: 76–81.
46 Ohashi A, Niwa Y, Ohmiya N et al. Quantitative analysis of the
microvascular architecture observed on magnification
endoscopy in cancerous and benign gastric lesions. Endoscopy
2005; 37: 1215–9.
47 Yagi K, Aruga Y, Nakamura A, Sekine A, Umezu H. The study of
dynamic chemical magnifying endoscopy in gastric neoplasia.
Gastrointest. Endosc. 2005; 62: 963–9.
48 Yao K, Iwashita A, Kikuchi Y et al. Novel zoom endoscopy
technique for visualizing the microvascular architecture in
gastric mucosa. Clin. Gastroenterol. Hepatol. 2005; 3: S23–6.
© 2016 Japan Gastroenterological Endoscopy Society
14431661, 2016, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/den.12638 by Univ of Sao Paulo - Brazil, Wiley Online Library on [03/04/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Digestive Endoscopy 2016; 28: 379–393
49 Yoshida T, Kawachi H, Sasajima K, Shiokawa A, Kudo SE. The
clinical meaning of a nonstructural pattern in early gastric
cancer on magnifying endoscopy. Gastrointest. Endosc. 2005;
62: 48–54.
50 Sugano K, Sato K, Yao K. New diagnostic approaches for early
detection of gastric cancer. Dig. Dis. 2004; 22: 327–33.
51 Nakayoshi T, Tajiri H, Matsuda K, Kaise M, Ikegami M,
Sasaki H. Magnifying endoscopy combined with narrow band
imaging system for early gastric cancer: correlation of vascular
pattern with histopathology (including video). Endoscopy 2004;
36: 1080–4.
52 Sumiyama K, Kaise M, Nakayoshi T et al. Combined use of a
magnifying endoscope with a narrow band imaging system and
a multibending endoscope for en bloc EMR of early stage
gastric cancer. Gastrointest. Endosc. 2004; 60: 79–84.
53 Otsuka Y, Niwa Y, Ohmiya N et al. Usefulness of magnifying
endoscopy in the diagnosis of early gastric cancer. Endoscopy
2004; 36: 165–9.
54 Tajiri H, Doi T, Endo H et al. Routine endoscopy using a
magnifying endoscope for gastric cancer diagnosis. Endoscopy
2002; 34: 772–7.
55 Yao K, Oishi T, Matsui T, Yao T, Iwashita A. Novel magnified
endoscopic findings of microvascular architecture in
intramucosal gastric cancer. Gastrointest. Endosc. 2002; 56:
279–84.
56 Yang HJ, Wang JT, Wang TH, Lin JT, Sun CT. Diagnosis of
gastric polypoid lesions by magnifying endoscopy and dye
endoscopy. J. Formos. Med. Assoc. 1991; 90: 371–4.
57 Ueo T, Yonemasu H, Yada N et al. White opaque substance
represents an intracytoplasmic accumulation of lipid droplets:
immunohistochemical and immunoelectron microscopic
investigation of 26 cases. Dig. Endosc. 2013; 25: 147–55.
58 Yoshizawa M, Osawa H, Yamamoto H et al. Newly developed
optimal band imaging system for the diagnosis of early gastric
cancer. Gastrointenst. Endosc. 2008; 67: 226–34.
59 Niwa Y, Ohashi A, Miyahara R, Ohmiya N, Goto H. Differential
diagnosis of gastric lesions by magnifying endoscopy. Dig.
Endosc. 2005; 17: S20–2.
60 Endo T, Nosho K, Arimura Yet al. Study of the tumor vessels in
depressed-type early gastric cancers using narrow band imaging
magnifying endoscopy and cDNA array analysis. Dig. Endosc.
2005; 17: 210–7.
61 Tobita K. Study on minute surface structures of the depressed-
type early gastric cancer with magnifying endoscopy. Dig.
Endosc. 2001; 13: 121–6.
62 Yao K, Anagnostopoulos GK, Ragunath K. Magnifying
endoscopy for diagnosing and delineating early gastric cancer.
Endoscopy 2009; 41: 462–7.
63 Yao K, Iwashita A, Yao T. Early Gastric Cancer: Proposal for a
new diagnostic system based on microvasular architecture as
visualized by magnified endoscopy. Dig. Endosc. 2004; 16:
S110–7.
64 Yagi K, Nakamura A, Sekine A, Umezu H. Magnifying
endoscopy with narrow band imaging for early differentiated
gastric adenocarcinoma. Dig. Endosc. 2008; 20: 115–22.

Digestive Endoscopy 2016; 28: 379–393
65 Yao K. How is the VS (vessel plus surface) classification system
applicable to magnifying narrow-band imaging examinations of
gastric neoplasias initially diagnosed as low-grade adenomas?
Gastric Cancer 2012; 15: 118–20.
66 Yamada S, Doyama H, Yao K et al. An efficient diagnostic
strategy for small, depressed early gastric cancer with
magnifying narrow-band imaging: a post-hoc analysis of a
prospective randomized controlled trial. Gastrointest. Endosc.
2014; 79: 55–63.
67 Murakami T. Early cancer of the stomach. World J. Surg. 1979; 3:
685–92.
68 Schlemper RJ, Riddell RH, Kato Yet al. The Vienna classification
of gastrointestinal epithelial neoplasia. Gut 2000; 47: 251–5.
69 Dixon MF. Gastrointestinal epithelial neoplasia: Vienna revisited.
Gut 2002; 51: 130–1.
70 Japanese Gastric Cancer Association. Japanese classification of gas-
tric carcinoma: 3rd English edition. Gastric Cancer 2011; 14:101–12
71 The Paris endoscopic classification of superficial neoplastic le-
sions: esophagus, stomach, and colon: November 30 to December
1, 2002. Gastrointest. Endosc. 2003; 58: S3–43.
72 Endoscopic Classification Review Group. Update on the Paris
classification of superficial neoplastic lesions in the digestive
tract. Endoscopy 2005; 37: 570–8.
73 Gannon B, Browning J, O’Brien P, Rogers P. Mucosal
microvascular architecture of the fundus and body of human
stomach. Gastroenterology 1984; 86: 866–75.
74 Yao K, Nagahama T, Matsui T, Iwashita A. Detection and
characterization of early gastric cancer for curative endoscopic
submucosal dissection. Dig. Endosc. 2013; 25: S44–54.
75 Yagi K, Nakamura A, Sekine A. Comparison between
magnifying endoscopy and histological, culture and urease
test findings from the gastric mucosa of the corpus.
Endoscopy 2002; 34: 376–81.
76 Yagi K, Aruga Y, Nakamura A, Sekine A. Regular arrangement of
collecting venules (RAC): a characteristic endoscopic feature of
Helicobacter pylori-negative normal stomach and its
relationship with esophago-gastric adenocarcinoma.
J. Gastroenterol. 2005; 40: 443–52.
77 Singh R, Lee SY, Vijay N, Sharma P, Uedo N. Update on narrow
band imaging in disorders of the upper gastrointestinal tract. Dig.
Endosc. 2014; 26: 144–53.
78 Yao K, Oishi T. Microgastroscopic findings of mucosal
microvascular architecture as visualized by magnifying
endoscopy. Dig. Endosc. 2001; 13: S27–33.
79 Yagi K, Nakamura A, Sekine A. Characteristic endoscopic and
magnified endoscopic findings in the normal stomach without
Helicobacter pylori infection. J. Gastroenterol. Hepatol. 2002;
17: 39–45.
80 Kuipers EJ, Uyterlinde AM, Pena AS et al. Long-term sequelae of
Helicobacter pylori gastritis. Lancet 1995; 345: 1525–8.
81 Yagi K, Honda H, Yang JM, Nakagawa S. Magnifying endoscopy
in gastritis of the corpus. Endoscopy 2005; 37: 660–6.
14431661, 2016, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/den.12638 by Univ of Sao Paulo - Brazil, Wiley Online Library on [03/04/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Diagnostic algorithms for EGC by ME 393
82 Yagi K, Saka A, Nozawa Y, Nakamura A. Prediction of
Helicobacter pylori status by conventional endoscopy, narrow-
band imaging magnifying endoscopy in stomach after endoscopic
resection of gastric cancer. Helicobacter 2014; 19: 111–5.
83 Kawamura M, Abe S, Oikawa K et al. Topographic differences in
gastric micromucosal patterns observed by magnifying
endoscopy with narrow band imaging. J. Gastroenterol.
Hepatol. 2011; 26: 477–83.
84 Uedo N, Ishihara R, Iishi H et al. A new method of diagnosing
gastric intestinal metaplasia: narrow-band imaging with
magnifying endoscopy. Endoscopy 2006; 38: 819–24.
85 Mutoh H, Hakamata Y, Sato K et al. Conversion of gastric mucosa
to intestinal metaplasia in Cdx2-expressing transgenic mice.
Biochem. Biophys. Res. Commun. 2002; 294: 470–9.
86 Busuttil RA, Boussioutas A. Intestinal metaplasia: A
premalignant lesion involved in gastric carcinogenesis.
J. Gastroenterol. Hepatol. 2009; 24: 193–201.
87 Mutoh H, Sakurai S, Satoh K et al. Development of gastric
carcinoma from intestinal metaplasia in Cdx2-transgenic mice.
Cancer Res. 2004; 64: 7740–7.
88 Uemura N, Okamoto S, Yamamoto S et al. Helicobacter pylori
infection and the development of gastric cancer. N. Engl. J.
Med. 2001; 345: 784–9.
89 de Vries AC, van Grieken NC, Looman CW et al. Gastric cancer
risk in patients with premalignant gastric lesions: a nationwide
cohort study in the Netherlands. Gastroenterology 2008; 134:
945–52.
90 Kaminishi M, Yamaguchi H, Nomura S et al. Endoscopic
classification of chronic gastritis based on a pilot study by the
Research Society for Gastritis. Dig. Endosc. 2002; 14: 138–51.
91 Nagata N, Shimbo T, Akiyama J et al. Predictability of Gastric
Intestinal Metaplasia by Mottled Patchy Erythema Seen on
Endoscopy. Gastroenterol. Res. 2011; 4: 203–9.
92 An JK, Song GA, Kim GH et al. Marginal turbid band and light
blue crest, signs observed in magnifying narrow-band imaging
endoscopy, are indicative of gastric intestinal metaplasia. BMC
Gastroenterol. 2012; 12: 169.
93 Yoshida S, Yamaguchi H, Saitoh D. Endoscopic diagnosis: latest
trends. In: Nishi M (ed). Gastric Cancer. Tokyo: Springer
Verlag, 1993; 246–262.
94 Ono H. Early gastric cancer: diagnosis, pathology, treatment
techniques and treatment outcomes. Eur. J. Gastroenterol.
Hepatol. 2006; 18: 863–6.
95 Yao K. The endoscopic diagnosis of early gastric cancer. Ann.
Gastroenterol. 2013; 26: 11–22.
96 Yao K, Doyama H, Gotoda T et al. Diagnostic performance and
limitations of magnifying narrow-band imaging in screening
endoscopy of early gastric cancer: a prospective multicenter
feasibility study. Gastric Cancer 2014; 17: 669–79.
97 Yao K. The vessel plus surface (VS) classification system in the
diagnosis of early gastric cancer. In: Yao K (ed). Zoom
Gastroscopy. Tokyo: Springer, 2014; 89–98.
© 2016 Japan Gastroenterological Endoscopy Society