ORIGINAL ARTICLE

Diagnostic ability of magnifying endoscopy with blue laserimaging for early gastric cancer: a prospective study

Osamu Dohi1 • Nobuaki Yagi1 • Atsushi Majima1 • Yusuke Horii1 •

Tomoko Kitaichi1 • Yuriko Onozawa1 • Kentaro Suzuki1 • Akira Tomie1 •

Reiko Kimura-Tsuchiya1 • Toshifumi Tsuji1 • Nobuhisa Yamada1 •

Nobukatsu Bito1 • Tetsuya Okayama1 • Naohisa Yoshida1 • Kazuhiro Kamada1 •

Kazuhiro Katada1 • Kazuhiko Uchiyama1 • Takeshi Ishikawa1 • Tomohisa Takagi1 •

Osamu Handa1 • Hideyuki Konishi1 • Yuji Naito1 • Akio Yanagisawa2 •

Yoshito Itoh1

Received: 20 October 2015 /Accepted: 26 May 2016 / Published online: 13 June 2016

� The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2016

Abstract

Background Blue laser imaging (BLI) is a new image-en-

hanced endoscopy technique that utilizes a laser light source

developed for narrow-band light observation. The aim of this

study was to evaluate the usefulness of BLI for the diagnosis

of early gastric cancer.

Methods This single center prospective study analyzed 530

patients. The patients were examinedwith both conventional

endoscopy with white-light imaging (C-WLI) and magni-

fying endoscopy with BLI (M-BLI) at Kyoto Prefectural

University of Medicine between November 2012 andMarch

2015. The diagnostic criteria for gastric cancer usingM-BLI

included an irregular microvascular pattern and/or irregular

microsurface pattern, with a demarcation line according to

the vessel plus surface classification system. Biopsies of the

lesions were taken after C-WLI andM-BLI observation. The

primary end point of this studywas to compare the diagnostic

performance between C-WLI and M-BLI.

Results We analyzed 127 detected lesions (32 cancers and

95 non-cancers). The accuracy, sensitivity, and specificity of

M-BLI diagnoses were 92.1, 93.8, and 91.6 %, respectively.

On the other hand, the accuracy, sensitivity, and specificity

of C-WLI diagnoses were 71.7, 46.9, and 80.0 %,

respectively.

Conclusions M-BLI had improved diagnostic performance

for early gastric cancer compared with C-WLI. These

results suggested that the diagnostic effectiveness of

M-BLI is similar to that of magnifying endoscopy with

narrow-band imaging (M-NBI).

Keywords Blue laser imaging � Early gastric cancer �Endoscopic diagnosis � Magnifying endoscopy � VSclassification

Introduction

Gastric cancer is the second most common cause of cancer-

associated deaths worldwide [1]. Early detection and

treatment has led to improved survival rates, with esoph-

agogastroduodenoscopy (EGD) proving to be the most

useful method of diagnosis for early gastric cancer (EGC).

However, it is often difficult to detect gastric superficial

adenocarcinomas using conventional endoscopy with

white-light imaging (C-WLI). Many clinical studies have

reported on the diagnostic performance of EGC by image-

enhanced endoscopy (IEE) techniques such as narrow-band

imaging (NBI) [2–9] or flexible spectral imaging color

enhancement (FICE) [10–12]. In particular, magnifying

endoscopy with NBI (M-NBI) is a powerful optical IEE

that has demonstrated accurate real-time diagnostic per-

formance in EGC compared with C-WLI [5, 7].

Recently, Fujifilm developed an endoscope system with a

semiconductor laser as a light source. The system includes

two types of lasers with wavelengths of 410 and 450-nm. The

450-nm laser irradiates phosphor to produce illumination

light similar to that obtained with a xenon lamp. The

& Osamu Dohi

osamu-d@koto.kpu-m.ac.jp

1 Department of Molecular Gastroenterology and Hepatology,

Graduate School of Medical Science, Kyoto Prefectural

University of Medicine, 465 Kawaramachi Hirokoji

Kamigyo-ku, Kyoto 602-8566, Japan

2 Department of Surgical Pathology, Graduate School of

Medical Science, Kyoto Prefectural University of Medicine,

Kyoto, Japan

123

Gastric Cancer (2017) 20:297–303

DOI 10.1007/s10120-016-0620-6

combination of strong 410-nm laser light, weak 450-nm laser

light, and fluorescent light enables blue laser imaging (BLI)

via narrow-band light observation. Magnifying endoscopy

with BLI (M-BLI) is useful for evaluating mucosal surface

information such as surface blood vessel and structure pat-

terns [13–16].

M-BLI has the potential to diagnose EGC as efficiently

as M-NBI because it uses narrow-band laser light com-

bined with illumination light. However, sufficient data

have not been reported regarding its diagnostic perfor-

mance for EGC. Therefore, we aimed to investigate whe-

ther M-BLI is more effective for diagnostic accuracy of

EGC when compared with C-WLI.

Patients and methods

Patients

A prospective single-center study was conducted at the

Department ofMolecular Gastroenterology andHepatology,

Kyoto Prefectural University of Medicine. A total of 530

consecutive patients with EGC or superficial esophageal

cancer underwent EGD prior to endoscopic submucosal

dissection (ESD) at the University Hospital, Kyoto Prefec-

tural University of Medicine were enrolled in this study

between November 2012 and March 2015. All patients

provided written informed consents to undergo EGD by both

C-WLI and M-BLI. If undetected lesions were found and

diagnosed as gastric adenoma or adenocarcinoma patho-

logically, ESD were performed on the day after obtaining

additional informed consent from the patients.

This study was approved by the Ethical Review Com-

mittee of the Kyoto Prefectural University of Medicine and

carried out in accordance with the Helsinki Declaration of

the World Medical Association. In addition, this study was

registered in the University Hospital Medical Information

Network Clinical Trials Registry (UMIN-CTR) as No.

UMIN000009216.

End points

The primary aim of this study was to compare the diagnostic

performance (accuracy sensitivity, specificity, positive pre-

dictive value, and negative predictive value) betweenC-WLI

and M-BLI. The secondary aim was to evaluate the features

of misdiagnosed lesions by M-BLI.

Endoscopic system and device

All procedures were carried out with optical magnifying

EG-L590ZW endoscopes and the LASEREO endoscopic

system (Fujifilm Medical Co., Tokyo, Japan). BLI can be

applied with the push of a button. In the BLI mode, the

structure enhancement function was constantly set at the

A6 level, with the color mode fixed at level 1. To obtain

magnified endoscopic images of the lesion easily, we

attached a black soft hood (MAJ-1989; Olympus Medical

Systems, Tokyo, Japan) on the tip of the scope.

Participating endoscopists

All examinations were performed by four skilled endo-

scopists who had participated in more than 100 EGC cases

of M-BLI; this minimized diagnostic variation of the

analyses.

Endoscopic examination

In practice, when an elevated or depressive lesion on the

gastric mucosa was diagnosed as cancer or there was a

suspicion of cancer, the lesion was diagnosed by C-WLI as

a target lesion. After the C-WLI diagnosis was complete,

an assistant physician immediately recorded the results in

the case notes. Next, M-BLI was performed and the results

were recorded in the case notes. Afterwards, one forceps

biopsy specimen was taken from each lesion. The follow-

ing lesions were excluded from this study in order to

evaluate the usefulness of M-BLI for diagnoses of the new

detected lesions in daily clinical situation: (1) superficial

gastric lesions with pathological diagnoses (cancer or non-

cancer) before the study, (2) gastric polyps or protruding

lesions, (3) superficial gastric lesions without detailed

observation using M-BLI, (4) superficial gastric lesions

diagnosed using C-WLI as benign with no need of biopsy,

and (5) superficial gastric lesions with indeterminate

pathological diagnoses obtained by biopsy specimen.

Diagnostic criteria

The diagnostic criteria for gastric cancer using C-WLI

were shallow, depressed, or flat elevated lesions with both

an irregular margin and an irregular mucosal area. The

endoscopic diagnostic criteria for gastric cancer using

M-BLI were defined based on previous reports of vessel

plus surface (VS) classification: the presence of either an

irregular microvascular pattern with a demarcation line, or

the presence of an irregular microsurface pattern with a

demarcation line [3].

Pathological diagnosis

Specimens of all lesions were obtained by biopsy or ESD

and were subsequently fixed with 10 % formalin and

evaluated pathologically. The pathological diagnoses were

completed by a highly experienced clinical pathologist (A.

298 O. Dohi et al.

123

Yanagisawa) who was blind to the actual magnified

endoscopic findings, which were categorized according to

the Japanese Classification of Gastric Carcinoma proposed

by the Japanese Gastric Cancer Association [17]. If there

were diagnostic differences between biopsy and ESD

specimens, the final diagnoses were evaluated according to

ESD specimens.

Statistical analysis

In a pilot study, 60 gastric lesions including 12 EGCs were

examined using both C-WLI and M-BLI. Seven of 12

EGCs (58 %) had different diagnoses between C-WLI and

M-BLI. The diagnoses of M-BLI were accurate compared

with those of C-WLI in six of seven EGCs (86 %). These

data indicated that the proportion of cancerous lesions with

a different diagnosis for the response of matched pairs was

58 %, and the proportion of cancerous lesions with an

improved diagnosis for BLI was 86 %. Accordingly, we

needed to study 15 cancerous lesions with different diag-

nostic results to be able to reject a null hypothesis that the

response difference was zero with probability (power) 0.8.

The Type I error probability associated with a study of this

null hypothesis is 0.05. Since the proportion of patients

with a different diagnosis in the response of matched pairs

was 58 %, the sample size was set to 26 cancerous lesions.

The frequency of synchronous or metachronous multiple

gastric cancers in patients with previous gastric cancers

was reported as 3–5 per 100 patient-years [18–20]. More-

over, it was reported that the frequency of synchronous or

metachronous gastric cancers was 7.7 % in patients with

esophageal cancer [21]. Therefore, we hypothesized that

the frequency of cancerous lesions would be 5.0 % for

patients with gastric cancer or esophageal cancer and cal-

culated the required size of the screening sample to be at

least 520 patients.

McNemar’s test was used to analyze the accuracy of

endoscopic diagnosis and biopsy diagnosis. The diagnostic

accuracy of each of the endoscopic findings is presented as

a percentage (95 % confidence interval). A p value of less

than 0.05 was considered statistically significant. All sta-

tistical analyses were performed using SPSS, version 15.0

(SPSS Inc., Chicago, IL, USA).

Results

Between November 2012 and March 2015, 530 patients

were enrolled in this study; 407 patients underwent EGD

for EGC prior to ESD, 123 patients underwent EGD for

superficial esophageal cancer prior to ESD. Among all

patients, 139 previously undiagnosed lesions were detected

during C-WLI in 132 patients. Among these detected

lesions, the M-BLI findings in seven lesions were inap-

propriate due to difficulties in detail observation, and three

lesions were impossible to judge for malignancy or

benignancy on pathological diagnoses, while two lesions

were diagnosed pathologically by biopsy specimens before

the study. Other than these 12 cases, the 127 lesions

comprised 32 gastric cancers, three gastric adenomas, and

92 non-tumorous tissues (86 chronic gastritis and 6

intestinal metaplasia). Resected gastric cancers included 29

well-differentiated adenocarcinomas, two moderately dif-

ferentiated adenocarcinomas, and one poorly differentiated

adenocarcinoma (Fig. 1). The clinicopathological features

of the evaluated lesions are summarized in Table 1. The

frequency of detected synchronous EGCs was 6.8 % (28

EGCs) in 407 patients with EGC prior to ESD and 3.2 % (4

EGCs) in 123 patients with superficial esophageal cancer

prior to ESD.

The outcomes of C-WLI and pathological diagnoses for

the 127 lesions are shown in Table 2. We diagnosed

cancerous lesions in 34 of 127 superficial gastric lesions

with C-WLI. However, only 15 of the 34 lesions diagnosed

as cancers with C-WLI (44.1 %) were diagnosed patho-

logically to be cancers. The outcomes of M-BLI and

pathological diagnoses for all of the 127 lesions evaluated

are shown in Table 3. We diagnosed cancerous lesions for

38 of the 127 superficial gastric lesions with M-BLI; 30 of

these 38 lesions (78.9 %) were diagnosed pathologically to

be cancers. Three of eight of the false-positive lesions were

diagnosed pathologically to be gastric adenomas. The other

five false-positive lesions were shallow depressed lesions

that were diagnosed pathologically to be chronic gastritis.

The sensitivity of M-BLI diagnoses was significantly

higher than that of C-WLI (93.8 vs. 46.9 %, respectively),

as was the specificity (80.0 vs. 91.6 %, respectively),

positive predictive value (44.1 vs. 78.9 %, respectively),

negative predictive value (81.7 vs. 97.7 %, respectively),

and accuracy (71.2 vs. 92.1 %, respectively) (Table 4).

Representative cases

Representative C-WLI and M-BLI images of gastric cancer

and non-cancerous lesions are shown in Figs. 2 and 3.

Representative case 1 is a superficial elevated lesion on the

lesser curvature of the middle gastric body. A slight

irregular mucosal lesion is visible on the lesser curvature of

the middle gastric body, but the margin of the lesion is

unclear on C-WLI (Fig. 2a). Thus, the lesion was diag-

nosed as a non-cancerous lesion by C-WLI. The demar-

cation of the lesion is clearly distinguishable because of

both the irregular microvascular pattern and the irregular

microsurface pattern on M-BLI (Fig. 2b), and was thus

diagnosed as a cancer. The lesion was diagnosed as a well-

differentiated adenocarcinoma by ESD specimens

Diagnostic ability of magnifying endoscopy with blue laser imaging for early gastric cancer:… 299

123

(Fig. 2c). Representative case 2 is a superficial depressed

lesion on the lesser curvature of the upper gastric body. A

slight irregular mucosal lesion is visible on the lesser

curvature of the middle gastric body, but the margin of the

Fig. 1 Flow chart showing

enrollment of patients and

analysis of lesions

Table 1 Clinicopathological characteristics of gastric superficial

lesions

Cancer Non-

cancer

p value

No. patients/lesions 28/32 90/95 –

Gender

Male 26 69 0.046

Female 2 21

Median age, years (range) 71 (56–86) 70 (41–91) 0.15

Median lesion size, mm (range) 10 (2–35) 5 (2–25) \0.001

Macroscopic type

Elevated type 19 35 0.044

Flat type 1 14

Depressive type 12 46

Location

U 6 7 0.061

M 18 46

L 8 42

Table 2 Endoscopic diagnoses using C-WLI for gastric superficial

lesions

Pathological diagnosis

Cancer Non-cancer

C-WLI

Cancer 15 19

Non-cancer 17 76

C-WLI conventional endoscopy with white-light imaging

Table 3 Endoscopic diagnoses using M-BLI for gastric superficial

lesions

Pathological diagnosis

Cancer Non-cancer

M-BLI

Cancer 30 8

Non-cancer 2 87

M-BLI magnifying endoscopy with blue laser imaging

Table 4 Diagnostic performance of C-WLI and M-BLI for gastric

superficial lesions

C-WLI M-BLI

% 95 % CI % 95 % CI

Sensitivity 46.9 29.1–65.3 93.8a 79.2–99.2

Specificity 80.0 70.5–87.5 91.6b 84.1–96.3

PPV 44.1 27.2–62.1 78.9 62.7–90.4

NPV 81.7 72.4–89.0 97.7 92.1–99.7

Accuracy 71.7 63.0–79.3 92.1a 86.0–96.2

C-WLI conventional endoscopy with white-light imaging, M-BLI

magnifying endoscopy with blue laser imaging, CI confidence inter-

val, PPV positive predictive value, NPV negative predictive valuea p\ 0.001 vs C-WLI, b p = 0.021 vs C-WLI

300 O. Dohi et al.

123

lesion is clear on C-WLI (Fig. 3a). Thus, the lesion was

diagnosed as a cancer by C-WLI. The demarcation of the

lesion is clearly visible because of both the irregular

microvascular pattern and the irregular microsurface pat-

tern (Fig. 3b). Thus, the lesion was diagnosed as a cancer

by M-BLI. The lesion was diagnosed as fundic and pyloric

gland mucosa with mild edema and inflammatory cell

infiltration by a biopsy specimen (Fig. 3c).

Discussion

This is the first comparative report of M-BLI being useful

for the diagnosis of EGC. In this study, M-BLI clearly

detected microvascular pattern, microsurface pattern, and

demarcation line. Thus, VS classification by M-BLI

correlated well with the pathological diagnoses. The sen-

sitivity, specificity, and accuracy of M-BLI after C-WLI

were excellent at 93.8, 91.6, and 92.1 %, respectively. In

previous reports, Ezoe et al. showed that the sensitivity,

specificity, and accuracy of M-NBI after C-WLI for the

diagnosis of small depressed lesions were excellent at 95.0,

96.8, and 96.6 %, respectively [7]. Yamada et al. showed

that the sensitivity, specificity, accuracy, positive predic-

tive value, and negative predictive value of M-NBI after

C-WLI for the diagnosis of small depressed lesions were

excellent at 95, 97, 97, 79, and 99 %, respectively [8].

Based on our findings, the M-BLI diagnoses using VS

classification were excellent, as were the M-NBI diagnoses.

Our study included both elevated and depressed lesions;

thus, the sensitivity, specificity, and accuracy of M-BLI

might be slightly lower score than that of M-NBI. In

Fig. 2 A positive case with M-BLI diagnosis (case 1). Superficial

elevated lesion on the lesser curvature of the middle gastric body.

a C-WLI image shows a slight irregular mucosal lesion with unclear

margin (arrowhead). b M-BLI image shows both irregular microvas-

cular pattern and irregular microsurface pattern with a clear

demarcation line (arrows). c Histopathological image of biopsy

specimen shows a well-differentiated adenocarcinoma. C-WLI con-

ventional endoscopy with white-light imaging, M-BLI magnifying

endoscopy with blue laser imaging

Diagnostic ability of magnifying endoscopy with blue laser imaging for early gastric cancer:… 301

123

addition, the positive predictive value of M-BLI was

slightly low at 78.9 % when compared with other scores.

Moreover, we investigated the reasons why eight non-

cancerous lesions were incorrectly diagnosed as cancers

using M-BLI. In five non-tumorous lesions, the finding of

irregular microvascular and microsurface pattern prompted

a cancer diagnosis. In three other adenomas, flat-elevated

lesions with focal irregular microsurface pattern and reg-

ular microvasuclar pattern were diagnosed as cancers using

M-BLI. The difficulty of diagnosing these lesions was a

limitation of M-BLI using VS classification.

It was previously reported that the sensitivity and

specificity of the gastrofiberscopic biopsy method for

gastric malignancies were 93.8 and 99.6 %, respectively,

and the overall accuracy for all the patients was 97.4 %

[22]. In our study, the sensitivity of M-BLI was as high as

biopsy method. When the lesion is diagnosed to be a cancer

by M-BLI, taking a biopsy specimen is highly

recommended to confirm the pathology. On the other hand,

specificity and negative predictive value of M-BLI was

high in our study. When the lesion is not suspected to be a

cancer by M-BLI, we could decrease the number of

unnecessary biopsies.

Our study has a major limitation. This study provided

only a limited evaluation of M-BLI and the VS classifi-

cation system, which is a diagnostic tool for M-NBI. We

previously reported the evaluation of endoscopic image

between M-BLI and M-NBI. M-BLI could detect

microvascular pattern and microsurface pattern the same as

M-NBI. With VS classification criteria, the accuracy of

M-NBI and M-BLI were 94.1 and 95.3 %, respectively.

There was not significantly difference in appearance of

microvascular pattern [23]. However, the number of

patients was small and the data were gathered from a single

center. Therefore, further multi-institutional studies with a

large number of cases are required to evaluate the

Fig. 3 A false-positive case with M-BLI diagnosis (case 2). Super-

ficial depressed lesion on the posterior wall of the upper gastric body.

a C-WLI image shows a reddish irregular mucosal lesion with clear

margin (arrowhead). b M-BLI image shows both irregular microvas-

cular pattern and irregular microsurface pattern with a demarcation

line (arrows). c Histopathological image of biopsy specimen shows a

fundic and pyloric gland mucosa with mild edema and inflammatory

cell infiltration. C-WLI conventional endoscopy with white-light

imaging, M-BLI magnifying endoscopy with blue laser imaging

302 O. Dohi et al.

123

diagnostic accuracy and findings using VS classification for

EGC between M-BLI and M-NBI. Thus, a multi-institu-

tional prospective study (UMIN-CTR 000007300) has

already been done and the data processing is now ongoing.

In conclusion, M-BLI had greater diagnostic perfor-

mance for early gastric cancer than C-WLI. These results

suggest that the diagnostic effectiveness of M-BLI is

similar to that of M-NBI.

Acknowledgments We thank all members of the Department of

Molecular Gastroenterology and Hepatology, Graduate School of

Medical Science, Kyoto Prefectural University of Medicine, for

helping conduct this study. We also thank Kubo Masahiro and all

personnel who assisted with operation of the Fujifilm LASEREO

system.

Compliance with ethical standards

Conflict of interest Y. Naito received collaboration research funding

from Fujifilm Medical Co., Ltd. (J132001115, J132001139). N. Yagi

and Y. Itoh were affiliated with a department that was partially funded

by Fujifilm Medical Co., Ltd. (J082003006). Fujifilm Medical Co.,

Ltd. had no role in the design, conduct, data collection, data inter-

pretation, or reportage of the study.

Human rights statement and informed consent All procedures

followed were in accordance with the ethical standards of the

responsible committee on human experimentation (The Ethical

Review Committee of the Kyoto Prefectural University of Medicine

and national) and with the Helsinki Declaration of 1964 and later

versions. Informed consent or substitute for it was obtained from all

patients included in the study.

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