Introduction
It has been postulated that Helicobacter pylori (H. pylori) infection causes gastric cancer (GC) [1]. In 2013, in order to prevent the development of GC, the national health insurance
program in Japan began to cover eradication therapy for patients with endoscopically
diagnosed chronic gastritis caused by H. pylori infection [2]. Similarly, in 2014 the International Agency for Research on Cancer Working Group
Report recommended that all countries explore the possibility of introducing population-based
H. pylori screening and treatment programs as a strategy for GC prevention [3]. However, long-term studies from Japan showed that eradication of H. pylori does not substantially alter the risk of development of GC [4]
[5].
Based on many studies, it is evident that magnifying narrow-band imaging (NBI) is
useful for the accurate diagnosis of GCs – even for small, depressed-type intramucosal
GCs [6]
[7]
[8]
[9]. It was reported that the macroscopic appearance of gastric neoplasms, including
GC and adenoma, was altered by H. pylori eradication therapy [10]
[11]. Several research groups subsequently reported that GCs are difficult to diagnose
after H. pylori eradication even by magnifying NBI endoscopy because of their indistinct borders
and/or lack of obviously cancerous characteristics [12]
[13]
[14]
[15]. The reason for this may be because an epithelium with low grade atypia or a non-neoplastic
epithelium on GC tissue frequently covers the surface; in addition, the surface structure
was found to have a “gastritis-like” appearance in 44 % of a series of GCs after H. pylori eradication [12]. The features of GC detected after successful eradication therapy were as follows:
small lesion size, location in the non-cardiac part of the stomach, a depressed type,
and differentiated histology [16].
It was reported recently that magnifying blue laser imaging (BLI), a novel image-enhanced
endoscopy (IEE) modality, provided a better diagnostic performance for early GC than
conventional endoscopy with white-light imaging, and the diagnostic effectiveness
of magnifying BLI was described as similar to that of magnifying NBI [17]. However, although endoscopic systems equipped with NBI and BLI are widely used,
only a limited number of cases are subjected to magnifying NBI/BLI endoscopy, even
in hospitals specializing in gastroenterology. Therefore, many gastroenterologists
and endoscopists may be using a conventional non-magnifying (NM)-NBI/BLI endoscope,
which lacks a magnification function, to screen for early GC. There is unfortunately
no reported research on the conventional NM-NBI/BLI of small (≤ 1 cm) early GC. Therefore,
the primary end point of this study was to retrospectively investigate NM-NBI/BLI
findings to discriminate depressed-type GCs from benign depressed lesions (BDLs) in
H. pylori-infected and -eradicated cases using an image analysis system. Secondary end points
were (1) to analyze cutoff indices of NM-NBI/BLI findings for GC diagnosis, and (2)
to elucidate the association between NBI/BLI findings and histological architectures
in GCs.
Materials and methods
This study complied with the Standards for the Reporting of Diagnostic Accuracy Studies
(STARD) initiative [18] and the Declaration of Helsinki. The Ethics Committee of Hyogo College of Medicine
approved this study protocol (No. 2532). Written informed consent was obtained from
all patients who underwent an endoscopic procedure.
Patients
Between April 2013 and March 2017, 346 consecutive patients with a total of 403 early
GCs were treated with endoscopic submucosal dissection (ESD) at Hyogo College of Medicine
Hospital. Among these patients, we enrolled those with images of (1) small (≤ 1 cm)
depressed-type intramucosal GCs, (2) histologically differentiated-type GCs, and (3)
patients whose H. pylori status had been confirmed. Patients with multiple GCs were excluded. [Fig. 1] shows a flow chart of the study patients. As can be seen, 29 consecutive GC cases
(the GC group) were evaluated. In addition, among the 15 713 patients who had been
endoscopically diagnosed as having chronic atrophic gastritis during the same period
at the same hospital, 166 patients with BDLs (the BDL group, i. e. the control group)
whose H. pylori status had been confirmed were selected.
Fig. 1 Flow chart of the study patients with early gastric cancer.
In the BDL group, 47 lesions were positive for H. pylori and 90 were eradicated. The BDLs, i. e. depressed erosions, raised erosions, and
areas of patchy redness, were endoscopically defined based on the Kyoto Classification
of Gastritis [19] and were confirmed histologically as benign lesions. Lesions that underwent a biopsy
before the detection of GC or BDLs were excluded because a biopsy causes morphological
and color changes of the lesions due to the regenerative reaction. Lesions with bleeding
or with a white coating were also excluded, because these conditions make the accurate
judgment of IEE images difficult.
Endoscopy procedure and histology
All individuals underwent NBI or BLI endoscopy (endoscopes: GIF-Q260, H260, H260Z,
H290, HQ290 or H290Z; EG-L590WR or -L600ZW) with an electronic endoscopic system (Elite
CV-290: Olympus Medical Systems, Tokyo; LASEREO: Fujifilm Holdings, Tokyo). The histology,
macroscopic type, and depth of invasion in the resected materials obtained by ESD
and biopsy specimens fulfilled the gastric cancer criteria of the Japanese Gastric
Cancer Association [20].
Image analysis
To assess the NM-NBI/BLI findings objectively, the NBI/BLI of the GCs and BDLs that
underwent ESD or a biopsy was quantified with an image-analytical software program
as described previously [21]. Briefly, NBI/BLI images were converted into Joint Photographic Expert Group images,
and then the GC and BDL areas on the images were manually traced with an image-analytical
software program (ImageJ, ver. 1.48; U.S. National Institutes of Health, Bethesda,
MD, United States). Using the default method, i. e. the “Measure” tool in the “Analyze”
menu, the mean gray value (MGV) of the lesion was calculated, and the MGV of the perilesional
normal mucosa, which corresponds to the peripheral elevation surrounding the depressed
area, was also measured. The ratio of the MGV of the GC or BDL areas against that
of the perilesional areas was defined as the NBI/BLI index ([Fig. 2]; note, a brighter image has a higher NBI/BLI-index).
Fig. 2 Image analysis of NBI/BLI- and C-indices. The mean gray value (MGV) was calculated
in the depressed area surrounded by the red dotted line, and the MGV of the perilesional
area was also determined in the region between the red dotted line and the white dotted
line. a In this lesion diagnosed as a benign depressed lesion (BDL) by biopsy, the NBI/BLI-
and C-indices were 0.80 and 0.40, respectively. b In this gastric cancer case, the depressed area appears more brightly colored than
the surrounding mucosa on magnifying endoscopy in the NBI/BLI mode. The NBI/BLI-index
and C-index were 1.30 and 0.92, respectively, and thus higher than the values in the
BDL.
In addition, the values for shape descriptors of the GCs and BDLs were also calculated
for assessment of their shapes. Briefly, using the default tool “Measure” under the
“Analyze” menu, “Circ.” was adopted as the circularity index (C-index). The C-index
value of a perfect circle is 1; as the shape deviates from perfectly circular, the
C-index value decreases ([Fig. 2]). The C-index thus indicates an overall irregular shape for an entire lesion, but
not local irregularities of the lesion edge. This quantification was performed by
a laboratory assistant (C. I.) who did not have any medical knowledge about endoscopies
or GC, and did not have any information on the patients’ original diagnosis or treatment.
Evaluation of histological architecture
The histopathological images of GCs resected by ESD were evaluated using cellSens
Standard software, ver. 1.8.1 (Olympus, Tokyo). In accordance with a previous report
[22], we analyzed the characteristics of the histopathological findings. Namely, an endoscopist
who was not aware of the information on the NBI/BLI-index randomly selected three
areas of the intervening parts and crypts in the cancerous area, and measured the
length of the intervening part and the depth of the crypt in each lesion. Briefly,
the length of the intervening part was defined as the distance between the crypt and
adjacent crypt. The depth of the crypt was defined as the distance between the bottom
of the crypt and the line that connects the top of the crypt structure ([Fig. 3]).
Fig. 3 Measurement of the histological architecture. A, intervening parts; B, crypt depth
defined as the distance between the bottom of the crypt and the dotted line that connects
the top of the crypt structures.
Diagnosis of H. pylori status
The H. pylori status was analyzed in each patient by three methods: Giemsa staining, urea breath
test, and measurement of the serum level of H. pylori-IgG antibodies with an enzyme-linked immunosorbent assay (ELISA) kit using the E
plate test (Eiken Kagaku, Tokyo, Japan). A patient was regarded as positive for H. pylori if the result of at least one of these methods was positive.
We divided the patients into three groups by H. pylori status: current infection, past infection, and uninfected. We also subdivided the
patients with past infection into two groups: those with successful H. pylori eradication and those with an unknown history of H. pylori eradication (naturally eradicated patients). H. pylori-uninfected patients were defined as those showing negative results in H. pylori examinations and having no atrophic findings on endoscopy based on the Kyoto Classification
of Gastritis [19]. In this study, we excluded the H. pylori-uninfected patients and the patients who were suspected of naturally eradicated H. pylori, since other high-sensitivity and high-specificity tests for H. pylori such as biopsy PCR and fluorescence in situ hybridization [23] were not performed, and thus H. pylori infection could not be completely ruled out in these individuals. We analyzed the
images of GC and BDLs only in patients with current infection of H. pylori or with successful eradication of H. pylori.
Statistical analysis
Continuous and categorical data were reported as means and standard deviations (SDs).
The data were assessed by the Mann-Whitney U test for continuous variables and the chi-squared test or Fisher’s exact test for
categorical variables between two independent groups. To identify the NBI/BLI- and
C-indices indicating the highest diagnostic performance for GC, we performed a receiver
operating characteristic (ROC) curve analysis. The area under the ROC curve (AUC)
was calculated, and the point with the largest AUC was defined as the point that had
the greatest association with GC. Optimal cutoff points were determined on the basis
of the maximum values of the Youden index, calculated as [sensitivity + specificity − 1],
and the minimum values of the square root of [(1 − sensitivity)2 + (1 − specificity)2], which indicates the minimum distance from the upper left corner to the point on
the ROC curve [24]. In the current study, we used the ROC curve analysis to evaluate the efficiency
of the differential diagnosis between GC and BDLs by NBI/BLI- and C-indices in the
H. pylori-infected and -eradicated cases. We used SPSS ver. 22.0 software (IBM Corp., Armonk,
NY, United States) or GraphPad Prism5 (GraphPad Software, La Jolla, CA, United States)
for all analyses. Two-tailed P values less than 0.05 were considered to be statistically significant.
Results
Patients
[Table 1] summarizes the clinical characteristics of the cases. There were no statistically
significant differences in the mean age, gender ratio, or lesion location of patients
between GC and BDLs in either the H. pylori-infected or -eradicated cases.
Table 1
Clinical characteristics of the H. pylori-infected and -eradicated cases.
|
H. pylori-infected cases
|
H. pylori-eradicated cases
|
GC
|
BDLs
|
P value
|
GC
|
BDLs
|
P value
|
No. of lesions
|
15
|
47
|
|
14
|
90
|
|
Age, mean ± SD, y
|
68.8 ± 11.1
|
63.9 ± 15.1
|
0.26
|
71.2 ± 6.5
|
67.6 ± 9.4
|
0.21
|
Female, no. (%)
|
3 (20.0)
|
11 (28.6)
|
0.74
|
3 (21.4)
|
26 (34.2)
|
0.37
|
Tumor size, mean ± SD, mm
|
7.2 ± 1.64
|
–
|
|
6.2 ± 2.71
|
–
|
0.84[1]
|
Location
|
|
2
|
7
|
0.92
|
2
|
11
|
0.74
|
|
6
|
16
|
|
7
|
54
|
|
|
7
|
24
|
|
5
|
25
|
|
|
3
|
18
|
0.44
|
7
|
45
|
0.65
|
|
8
|
16
|
|
1
|
10
|
|
|
2
|
4
|
|
2
|
5
|
|
|
2
|
9
|
|
4
|
30
|
|
GC, gastric cancer; BDLs, benign depressed lesions; SD, standard deviation.
1 Indicates tumor size between H. pylori-infected and -eradicated cases.
NBI/BLI- and C-indices in the GC and BDL cases
The mean NBI/BLI- and C-indices were significantly higher in the GC group than in
the BDL group, in both H. pylori-infected and -eradicated cases (P = 0.009 in GC and P < 0.0001 in BDLs for the NBI/BLI-index; P = 0.006 in GC and P = 0.004 in BDLs for the C-index) ([Table 2]). These results indicate that GCs are brighter than the surrounding mucosa and rounder
in shape than BDLs in both the H. pylori-infected and -eradicated cases ([Fig. 1], [Fig. 4], and [Fig. 5]).
Table 2
IEE indices in the H. pylori-infected and -eradicated cases.
|
H. pylori-infected cases
|
H. pylori-eradicated cases
|
GC
|
BDLs
|
P value
|
GC
|
BDLs
|
P value
|
NBI/BLI-index
|
1.03 ± 0.19
|
0.89 ± 0.11
|
0.009
|
1.06 ± 0.13
|
0.87 ± 0.10
|
< 0.0001
|
C-index
|
0.66 ± 0.18
|
0.52 ± 0.15
|
0.006
|
0.67 ± 0.19
|
0.49 ± 0.17
|
0.004
|
IEE, image-enhanced endoscopy; GC, gastric cancer; BDLs, benign depressed lesions.
Fig. 4 Representative non-magnifying NBI image of H. pylori-infected gastric cancer. The depressed area is brighter than the surrounding area.
The NBI/BLI-index and C-index were 1.11 and 0.81, respectively.
Fig. 5 Representative gastric cancer case after H. pylori eradication. The depressed area is a relatively bright area compared to the surrounding
area. The NBI/BLI-index and C-index were 1.26 and 0.86, respectively.
Association between the NBI/BLI-index or C-index and GC or BDLs
The ROC curve for the differential diagnosis between GC and BDLs by the NBI/BLI- and
C-indices in the H. pylori-infected and -eradicated cases is shown in [Fig. 6]. The resulting cutoff value of the NBI/BLI-index was 1.04 (AUC = 0.72, sensitivity
60.0 %, specificity 89.4 %, and P = 0.0001) and that of the C-index was 0.58 (AUC = 0.74, sensitivity 80.0 %, and specificity
66.0 %) for GC in the H. pylori-infected cases. In the H. pylori-eradicated cases, the thresholds for GC were 0.98 in the NBI/BLI-index (AUC = 0.91,
sensitivity 92.9 %, and specificity 92.2 %) and 0.64 in the C-index (AUC = 0.74, sensitivity
71.4 %, and specificity 77.8 %) ([Table 3]). The NBI/BLI and C-indices, which were ≥ 1.04 and ≥ 0.58 in the H. pylori-infected cases, and ≥ 0.98 and ≥ 0.64 in the H. pylori-eradicated cases, were significant predictors of GCs (odds ratio [OR] = 69.0, 95 %
confidence interval [CI] 3.57 – 17.03, P < 0.0001 in the H. pylori-infected cases; OR = 52.2, 95 %CI 5.54 – 34.39, P < 0.0001 in the H. pylori-eradicated cases).
Fig. 6 Receiver operating characteristic curve of the NBI/BLI-index (a) and C-index (b) values of gastric cancer in the H. pylori-positive cases and H. pylori-eradicated cases. The curve is plotted as the sensitivity (y-axis) and (100 − specificity) (x-axis).
Table 3
Parameters of the ROC curves for gastric cancer diagnosis.
|
H. pylori-infected cases
|
H. pylori-eradicated cases
|
NBI/BLI-index
|
C-index
|
NBI/BLI-index
|
C-index
|
Cutoff point
|
1.04
|
0.58
|
0.98
|
0.64
|
AUC
|
0.72
|
0.74
|
0.91
|
0.74
|
SE
|
0.09
|
0.08
|
0.05
|
0.08
|
95 %CI
|
0.54 – 0.91
|
0.58 – 0.90
|
0.81 – 1.02
|
0.59 – 0.89
|
P value
|
0.009
|
0.006
|
< 0.0001
|
0.004
|
Sensitivity (%)
|
60.0
|
80.0
|
92.9
|
71.4
|
Specificity (%)
|
89.4
|
66.0
|
92.2
|
77.8
|
PPV (%)
|
64.3
|
42.9
|
65.0
|
33.3
|
NPV (%)
|
87.5
|
91.2
|
98.8
|
94.6
|
Accuracy (%)
|
82.3
|
69.4
|
92.3
|
76.9
|
|
OR 69.0, 95 %CI 3.57 – 17.03, P < 0.0001
|
OR 52.2, 95 %CI 5.54 – 34.39, P < 0.0001
|
ROC, receiver operating characteristic; AUC, area under the ROC curve; SE, standard
error; CI, confidence interval; PPV, positive predictive value; NPV, negative predictive
value; OR, odds ratio.
Diagnostic accuracy at various thresholds of the NBI/BLI- and C-indices in the H.
pylori-infected and -eradicated cases
In 2012, the American Society for Gastrointestinal Endoscopy (ASGE) established recommended
thresholds for the Preservation and Incorporation of Valuable Endoscopic Innovations
(PIVI) to eliminate the need for random mucosal biopsies during the endoscopic surveillance
of patients with a non-dysplastic Barrett’s esophagus. According to the PIVI document
released by the ASGE, the recommended performance thresholds were as follows: imaging
technology with targeted biopsies should have a per-patient sensitivity of ≥ 90 %
and a negative predictive value (NPV) of ≥ 98 % for detecting high grade dysplasia
or early esophageal adenocarcinoma, compared with the current standard protocol [25]. Thus, based on these thresholds – because there is no PIVI document with regard
to GC – we analyzed the diagnostic accuracy of GC by applying a few useful cutoff
points of the NBI/BLI- and C-indices as diagnostic parameters for GC ([Table 4]). When we set the reference values of the NBI/BLI-index for GC at ≥ 0.69 with the
C-index at ≥ 0.21 in the H. pylori-infected cases, and the values of the NBI/BLI-index at ≥ 0.80 with the C-index at
≥ 0.32 in the H. pylori-eradicated cases, the sensitivity and NPV for early GC were both 100 %.
Table 4
Diagnostic values for gastric cancer using the criteria of the NBI/BLI-index and C-index.
Diagnostic parameters for GC
|
|
|
|
|
|
NBI/BLI-index
|
C-index
|
Sensitivity (%)
|
Specificity (%)
|
PPV (%)
|
NPV (%)
|
Accuracy (%)
|
H. pylori-infected cases
|
(≥ 0.69)
|
(≥ 0.21)
|
|
|
|
|
|
+
|
+
|
100
|
4.3
|
25.0
|
100
|
27.4
|
+
|
–
|
0
|
97.9
|
0
|
75.4
|
74.2
|
–
|
+
|
0
|
97.9
|
0
|
75.4
|
74.2
|
(≥ 0.69)
|
(≥ 0.38)
|
|
|
|
|
|
+
|
+
|
86.7
|
19.1
|
25.5
|
81.8
|
35.5
|
+
|
–
|
6.7
|
83.0
|
11.1
|
73.6
|
64.5
|
–
|
+
|
6.7
|
97.9
|
50.0
|
76.7
|
75.8
|
H. pylori-eradicated cases
|
(≥ 0.80)
|
(≥ 0.32)
|
|
|
|
|
|
+
|
+
|
100
|
34.4
|
19.2
|
100
|
43.3
|
+
|
–
|
0
|
85.6
|
0
|
84.6
|
74.0
|
–
|
+
|
0
|
83.3
|
0
|
84.3
|
72.1
|
(≥ 0.98)
|
(≥ 0.64)
|
|
|
|
|
|
+
|
+
|
64.3
|
96.7
|
75.0
|
94.6
|
92.3
|
+
|
–
|
28.6
|
95.6
|
50.0
|
89.6
|
86.5
|
–
|
+
|
7.1
|
81.1
|
5.6
|
84.9
|
71.2
|
GC, gastric cancer; PPV, positive predictive value; NPV, negative predictive value.
Relationship between NBI/BLI-index and histological architecture
From the group of patients with GC who underwent resection by ESD, we selected 20
resected specimens for which the histological architecture could be correctly examined
in sagittal sections. The length of the intervening part and the depth of crypts ([Fig. 3]) did not show a significant difference in cutoff points of the NBI/BLI-index between
< 1.04 and ≥ 1.04 in the H. pylori-infected cases ([Table 5]). In the H. pylori-eradicated cases, however, the length of the intervening parts tended to be wider
in lesions with ≥ 0.98 as the cutoff point compared to those with < 0.98 as the cutoff
point (P = 0.09), but the depth of crypts was not significantly different.
Table 5
Correspondence between the NBI/BLI-index and histological architecture in gastric
cancer.
|
H. pylori-infected case (n = 9)
|
H. pylori-eradicated case (n = 11)
|
Cutoff point
|
Cutoff point
|
< 1.04
|
≥ 1.04
|
P value
|
< 0.98
|
≥ 0.98
|
P value
|
Length of intervening parts
|
192.7 ± 153.0
|
183.9 ± 65.2
|
0.49
|
130.7 ± 93.4
|
197.3 ± 97.6
|
0.09
|
Depth of crypts
|
201.4 ± 110.2
|
195.9 ± 89.2
|
0.85
|
121.1 ± 37.8
|
120.7 ± 63.6
|
0.90
|
Discussion
GC after H. pylori eradication is often difficult to diagnose, even by magnifying NBI/BLI endoscopy
[11]
[12]
[13]
[14]
[15]. However, the present study clearly demonstrated the possibility of detecting small
depressed-type early GCs in both H. pylori-infected and -eradicated cases by NM-NBI/BLI endoscopy with objective indicators.
Several recent studies reported the potential quantitative diagnosis of early GC by
computer-aided/computer-based diagnosis and deep learning [26]
[27]
[28]
[29]. However, those studies investigated the identification and delineation of early
GCs using magnifying NBI or BLI, and they did not suggest a region of interest during
NM-endoscopy, nor did they attempt to capture GCs during such screening NM-endoscopy
using IEE [26]
[27]
[28]
[29].
Our present analyses revealed that both NBI/BLI- and C-indices calculated using NM-NBI/BLI
images were significantly higher in the GC group than in the BDL group in both the
H. pylori-infected and -eradicated cases, indicating that (1) the depressed area in GCs is
a relatively bright color against the color of the surrounding perilesional area,
and (2) GCs are rounder in shape than BDLs. However, the AUC of the NBI/BLI-index
was sufficiently higher in the H. pylori-eradicated cases (0.91) than in the H. pylori-infected cases (0.72). Like the NBI/BLI-index, the C-index also showed a high accuracy
rate for GC diagnosis in the H. pylori-eradicated cases (76.9 %) when the appropriate cutoff point was applied. Commonly,
early depressed-type GC, especially differentiated-type adenocarcinoma, exhibits a
reddish and irregularly shaped depression [30]
[31]. Although the irregularity, i. e. the spine-like appearance, at the edge of the
depression is a predictive indicator of depressed GC, the C-index evaluated in our
study indicates the irregular shape of the entire lesion rather than just its edge.
Based on the established PIVI thresholds for imaging in Barrett’s esophagus [25], lesions with high sensitivity and a high NPV (such as the NBI/BLI-index of ≥ 0.69
with the C-index at ≥ 0.21 in the H. pylori-infected cases and the NBI/BLI-index of ≥ 0.80 with the C-index at ≥ 0.32 in the
H. pylori-eradicated cases) should be biopsied in order to compensate for low specificity (4.3 – 34.4 %)
and accuracy (27.4 – 43.3 %). Since the diagnosis of early GC after successful H. pylori eradication is not necessarily satisfactory even by magnifying endoscopy with NBI/BLI
[12]
[13]
[14]
[15], our diagnostic strategy may be appropriate. Although it is undeniable that magnifying
NBI/BLI is an important modality for finding the irregular microvascular and microsurface
patterns in the diagnosis of GC [6]
[7]
[8]
[9], the NBI/BLI-index calculated by NM-NBI/BLI endoscopy reflects a “mixed whole image”
of microvascular and microsurface features. In daily endoscopy, we often find depressed
lesions, and occasionally multiple depressed lesions. Therefore, our objective data
may provide useful information on the future use of artificial intelligence (AI),
including computer-aided/computer-based diagnosis and deep learning, for the detection
and diagnosis of GC.
Interestingly, the bright color image of the depressed area compared to the surrounding
perilesional color, which corresponds to an NBI/BLI-index ≥ 0.98 derived from the
ROC analysis, was associated with a greater length of the intervening part in the
H. pylori-eradicated cases, although this relationship did not reach the level of statistical
significance. This trend of association might be ascribed to the fact that, in cases
of differentiated-type GC after H. pylori eradication, an epithelium with low grade atypia or non-neoplastic epithelium covers
the GC tissue [11]
[12]
[13]
[14]
[15]. However, we observed no significant difference in the association between the length
of the intervening part and the NBI/BLI-index in the H. pylori-infected cases in the present study. Therefore, the infiltration of inflammatory
cells in the cancerous mucosa in the H. pylori-infected cases may have contributed to the difference in the NBI/BLI findings in
addition to the length of the intervening part. In contrast, the depth of crypts was
not involved in the color difference in either the H. pylori-infected or -eradicated cases.
The present study had a methodological advantage, as all NBI/BLI- and C-indices were
evaluated by a single laboratory assistant (C. I.) who did not have endoscopy expertise
and was unaware of the lesion groups. Therefore, the proposed method could lead to
future AI research for early GC diagnosis. However, our investigation also had some
limitations. First, this was a study from a single institution with a small number
of cases. Second, because all BDLs could not be selected during the study period,
the BDL group was vulnerable to selection bias, while there were no significant differences
in the clinical characteristics, including the sex ratio, mean age, lesion location,
and H. pylori status, between GC and BDLs. Third, it was not possible to examine all lesions by
both modalities, i. e. NM-NBI and -BLI endoscopy. However, when we analyzed the “ratio”
of the MGV of the GC or BDL areas against the perilesional areas by NBI or BLI, the
difference in modality did not appear to substantially affect the results of the NBI/BLI-index.
Fourth, the endoscopic images of the GCs and BDLs were selected by experienced endoscopists
and were reviewed retrospectively. To overcome these limitations, further investigations
with larger sample sizes including differentiated-type early GCs and BDLs are needed
to validate our endoscopic findings and the objective indicators, followed by a multicenter
and prospective study to exclude selection bias.
In conclusion, the brighter color and rounder shape of small depressed lesions determined
by the NBI/BLI- and C-indices in non-magnifying IEE images may increase the index
of suspicion of early GC in both H. pylori-infected and -eradicated patients, thus these lesions should be biopsied for histological
diagnosis.