Introduction
Gastric cancer screening endoscopy was established using white light imaging (WLI)
and standard endoscopy via the transoral route. Ultrathin endoscopy (≤ 6 mm diameter)
has been used mainly via the transnasal route since the early 2000s because of minimal
pain and gag reflex during the examination [1]
[2]. It is well tolerated without sedation and is less costly [3]
[4]
[5]. Ultrathin endoscopy via the transnasal route is considered a safer procedure with
less effect on the cardiopulmonary function of elderly patients including blood pressure
and pulse rate [2]
[6]
[7]. Therefore, ultrathin endoscopy is used mainly in private clinics and for routine
health evaluations in Japan [8]. However, there is a trade-off between the resolution of the images and the smaller
caliber endoscope using WLI. The diagnostic accuracy using an ultrathin endoscope
and WLI is lower than with a standard endoscope and WLI for the detection of gastric
neoplasms [9]. There is concern that lower-quality images may result in the inability to diagnose
malignant lesions of the upper gastrointestinal tract in routine outpatient practice,
which has resulted in hesitation to use this modality [8]
[10]
[11]
[12]
[13]. Improvements in optical quality and the incorporation of additional procedures
including chromoendoscopy have been required to enhance visualization [9].
Recently, while standard WLI (that is, a standard-size endoscope using WLI) provides
high-resolution images, image-enhanced endoscopy has progressed for both detailed
examinations and screening for gastrointestinal malignancies. Linked color imaging
(LCI) has been reported to enhance the visibility of early gastric cancer (EGC), esophageal
cancer, and flat colorectal lesions. A prospective multicenter study revealed that
LCI could detect upper gastrointestinal cancers that were missed using WLI [14]. LCI produces enough light to illuminate an area with a large lumen such as in the
stomach and improves the color contrast between a lesion and the surrounding mucosa.
If LCI with an ultrathin endoscope provides a similar advantage, it would be ideal
for gastric cancer screening especially in the elderly and/or patients with cardiopulmonary
dysfunction. Many endoscopists may consider that high-resolution standard endoscopy
is superior to ultrathin endoscopy, to avoid missing EGCs. However, together with
the high color contrast produced by LCI, it is unknown how significant the lower resolution
images obtained with ultrathin endoscopy actually is when compared with standard endoscopy.
It is necessary to determine which is more important during the short amount of time
allotted to screening endoscopy, high-resolution images or high color contrast using
LCI.
This point of uncertainty led to the conduct of this study using prospectively collected
videos using both WLI and LCI modes of EGCs and atrophic gastritis using standard
and ultrathin endoscopes. We designed this study to assess the sensitivity and specificity
for the detection of EGCs with each mode by expert endoscopists as well as visibility.
The objective color differences between malignant lesions and the surrounding mucosa
were then calculated comparing WLI and LCI with both ultrathin and standard endoscopes.
Patients and methods
Study design
The current study was registered as a clinical trial (University Hospital Medical
Information Network Clinical Trials Registry number UMIN 000028328). The study protocol
and its revision (adding an author) were reviewed and approved by the Institutional
Review Board of Jichi Medical University Hospital (Numbers A15–241 and A20–032, respectively).
This was a retrospective analysis of prospectively collected video data including
malignant gastric lesions with chronic gastritis and chronic gastritis alone from
June 2016 to July 2017.
The purpose of this study was to evaluate LCI with ultrathin and standard endoscopy
and its ability to facilitate the detection of EGCs compared with WLI endoscopy.
Study outcome and sample size
The primary endpoint of this study was the sensitivity of EGC detection using LCI
with ultrathin and standard endoscopy. The secondary endpoints included: (1) the color
difference between EGC and surrounding mucosa using WLI and LCI; (2) visibility differences
for EGC comparing images from an ultrathin endoscope and a standard endoscope using
WLI and LCI.
Based on an expected 25 % difference in the endoscopic detection of EGC with WLI versus
LCI using G power (α = 0.05, β = 0.2), we estimated that a sample size of 56 patients
with EGC would be sufficient to demonstrate a significant difference using StatFlex
version 6.0 software (Artech) [9]. Considering 30 % synchronous lesions and 10 % excluded cases we sought to collect
95 gastric cancer cases. There were 95 EGC cases accrued from June 2016 to July 2017.
We collected consecutive screening videos taken with WLI and LCI including non-cancer
cases.
Patients and endoscopic procedure
One hundred sixty-six consecutive patients requiring detailed upper gastrointestinal
endoscopic examinations referred from smaller clinics or hospitals were enrolled except
patients with a history of gastric surgery. Written informed consent was obtained
from each patient before the procedure. Inclusion criteria included: (1) patients
with a single EGC in the background mucosa with atrophy; and (2) patients with atrophic
gastritis but without a malignant lesion in the stomach. We have excluded cases with
synchronous cancers, advanced cancer, non-atrophic stomach, inadequate video and no
report of ESD pathology.
Repeat informed consent was deemed necessary and eight participants could not be contacted
or chose not to be included in the study. Finally, a total of 81 cases with 52 EGCs
and 29 with atrophic gastritis alone were included in the final analysis ([Fig. 1]).
Fig. 1 Study flowchart. The process from collecting the video of gastric lesions using white
light imaging (WLI) and linked color imaging (LCI) to data analysis evaluated by expert
assessors.
Four experienced endoscopists (HO, YI, YM, and TT) performed gastric screening endoscopy
under the same protocol with an ultrathin endoscope (EG-L580NW, 5.9 mm in diameter),
and a standard endoscope (EG-L590WR, 9.6 mm). Videos were taken with standard WLI,
standard LCI, ultrathin WLI, and ultrathin LCI in order. First, endoscopists observed
from the gastric body to the pyloric ring in an antegrade view followed by antrum
to fornix and inversely in a retrograde view, and subsequently from antrum to upper
body in an antegrade view by withdrawing the endoscope within 90 seconds. Still images
were not taken to decrease the bias of highlighting lesions depending on the location
[15].
Approximately 90 seconds of gastric screening videos ([Video 1]) in each mode were obtained without still images (a total of 4 videos/patient) to
be reviewed later by expert assessors. Subsequently, precise endoscopic examinations
were carried out with the equipment necessary for detailed diagnosis such as a magnifying
endoscope and endoscopic ultrasound. The procedure was carried out under conscious
sedation with intravenous midazolam and pethidine hydrochloride injection.
Video 1 Representative videos of of early gastric cancers obtained
using white light imaging (WLI) and linked color imaging (LCI) by
ultrathin endoscope and standard endoscope.
Evaluation of endoscopic videos
Endoscopic videos were arranged in random order with a wash-out period of 3 weeks
for the same case. Three expert endoscopists with at least 2 years of detailed endoscopic
examination experience using laser endoscopy with no prior knowledge of the study
cases evaluated the videos only once without a time limit with free review. They were
asked to check whether EGC was present and complete a case report form. If they suspected
or detected a malignant lesion, a visibility score was assigned as follows: score
3, excellent (video was viewed one time); score 2, good (video was viewed two times);
score 1, fair (video was viewed three times or more) in reference to a previously
described procedure for the evaluation of endoscopic videos [16]. To make the score descriptions accurate, endoscopists were asked to stop the video,
record the time, and draw the location of the lesion on the screen simulation area
in the case report form. All suspected lesions were carefully double-checked with
corresponding pathology reports and ESD reports. If the lesion was missed the visibility
score was scored as “0”. Representative endoscopic videos are shown in [Video 1].
Endoscopic findings of malignant lesions were defined based on the Japanese gastric
cancer treatment guidelines and the Japanese Classification of Gastric Carcinoma.
Well- and moderately-differentiated tubular adenocarcinoma and papillary adenocarcinoma
were classified as the differentiated type, and poorly differentiated adenocarcinoma
and signet ring cell carcinoma as the undifferentiated type. The locations were classified
according to the trisected portions of the stomach: proximal, middle and distal portions.
The macroscopic classification was as follows: 0-I and/or 0-IIa as elevated type,
0-IIb flat type, 0-IIc and/or 0-III depressed type. Successful eradication was determined
by a history of Helicobacter pylori eradication and confirmed either by serum immunoglobulin level or stool antigen test.
Depth is recorded based on the final pathology report of the resected specimen, tumor
confined to the mucosa or invasion into the muscularis mucosa as M, tumor invasion
within 0.5 mm into the submucosa as SM1 and tumor invasion of 0.5 mm or more deep
into the submucosa as SM2.
Color difference calculations
Similar images of EGCs were captured from the videos and analyzed objectively based
on the L*a*b* (L* = light/dark; a* = red-green; b* = yellow-blue) color values in
the CIELAB system using Adobe Photoshop CC2019 as previously reported [17]
[18]
[19]. The five regions of interest (ROI; 20x20 pixels) were selected at random from malignant
lesions and then their adjacent surrounding mucosae from standard WLI, standard LCI,
ultrathin WLI and ultrathin LCI images. To avoid selection bias as much as possible,
these selections and calculations were performed by a single operator who can recognize
malignant lesions on endoscopic images. The average of five median RGB values for five
sample points was calculated in each region. The L*a*b* values were calculated from
the average RGB values. The color difference (∆E* = [(∆L*)2 + (∆a*)2 + (∆b*)2]1/2) of the pixel values was analyzed to evaluate color contrast between malignant lesions
and surrounding mucosa using ultrathin WLI, ultrathin LCI, standard WLI and standard
LCI, respectively. Color differences were classified based on the size of the malignant
lesion, morphology, location, H. pylori status, histology and depth of lesions histologically evaluated using the resected
specimens.
Resolution measurement of ultrathin and standard endoscopes
The resolution using ultrathin endoscopy compared with standard endoscopy has not
been studied in detail. As an initial investigation, we compared the resolution between
a standard endoscope (EG-L590WR) and an ultrathin endoscope (EG-L580NW) because the
data associated with gastric screening have not been objectively reviewed. The standard
industry testing protocols for image resolution (United States Air Force-1951 test
target) were used to confirm differences in resolution [20]
[21]. The ratios of resolution were measured at a near view of 10 mm, mid-distant view
of 20 mm, and a far-distant view of 50 mm from the resolution chart, simulating the
distance between the endoscope and target gastric mucosa during screening endoscopy
(Supplementary Materials).
Statistical analysis
Statistical analyses were carried out using Stata 16 (version for Windows, StataCorp,
Texas, United States) and Graphpad Prism Version 9 software (Graphpad software, La
Jolla, California, United States). Levels of color differences and values of L*, a*
and b* were expressed as the mean (±standard deviation). Comparisons between four
modes were made using the one-way Analysis of Variance (ANOVA) with Bonferroni post-hoc
test for significance between paired groups. Significant differences were assumed
if P < 0.05 was obtained. The distribution of visibility scores was compared between WLI
and LCI using the linear-by linear chi-squared test. P < 0.05 was considered significant.
Results
Patients
Patient baseline and lesion characteristics are shown in [Table 1]. There were 52 patients with single EGC lesions with atrophic gastritis. Of the
29 patients without gastric malignancy but with gastric atrophy, eight had esophageal
lesions, seven had duodenal lesions, six had gastric submucosal tumors and eight had
atrophic gastritis alone.
Table 1
Baseline characteristics of study patients.
|
Number of patients, n
|
81
|
|
Gender (male/female)
|
64/17
|
|
Age, median (range)
|
70 (44–89)
|
|
Early gastric cancer, n
|
52
|
|
Location
|
|
|
5/14/33
|
|
Morphology
|
|
|
12/4/36
|
|
Size
|
|
|
14/14/9/15
|
|
H. pylori status
|
|
|
32/14/6
|
|
Histology
|
|
|
48/4
|
|
Depth
|
|
|
41/4/7
|
|
Non-malignant, n
|
29
|
|
|
8
|
|
|
8
|
|
|
7
|
|
|
6
|
|
Atrophy, n
|
|
|
14/67
|
M, tumor confined to the muscularis mucosa or invasion into the muscularis mucosa;
SM1, tumor invasion within 0.5 mm into the submucosa; SM2, tumor invasion of 0.5 mm
or more deep into the submucosa.
Sensitivities and specificities of LCI and WLI for detecting EGC
Ultrathin WLI, ultrathin LCI, standard WLI, and standard LCI showed sensitivities
of 66.0 %, 80.3 %, 69.9 % and 84.0 % and specificities of 67.8 %, 59.3 %, 59.8 % and
50.6 %, respectively for the detection of EGCs ([Table 2]). Sensitivity with ultrathin WLI was slightly lower that with standard WLI similar
to a previous report [9]. Sensitivities with LCI were higher than those with WLI using both ultrathin and
standard endoscopes for all three endoscopists. Sensitivities with ultrathin LCI were
also higher than those with standard WLI for all three endoscopist. Specificities
were lower for LCI than those with WLI and were different among the three endoscopists.
[Fig. 2] shows representative images of EGCs using WLI and LCI, which are captured from the
respective video recordings. The interobserver agreement was measured using the kappa
statistics. The interobserver agreement for standard WLI was 0.51, for standard LCI
was 0.28, for ultrathin WLI was 0.47, and for ultrathin LCI was 0.31 and judged to
have “fair to moderate agreement”.
Table 2
Sensitivity and specificity of white light imaging and linked color imaging with standard
and ultrathin endoscopes.
|
Ultrathin WLI
|
Ultrathin LCI
|
Standard WLI
|
Standard LCI
|
|
Sensitivity (%)
|
66.0 %
|
80.3 %
|
69.9 %
|
84.0 %
|
|
Specificity (%)
|
67.8 %
|
59.3 %
|
59.8 %
|
50.6 %
|
|
Expert endoscopist 1
|
|
Sensitivity (%)
|
75.0 %
|
84.6 %
|
78.8 %
|
88.5 %
|
|
Specificity (%)
|
55.2 %
|
41.4 %
|
48.3 %
|
27.6 %
|
|
Expert endoscopist 2
|
|
Sensitivity (%)
|
65.4 %
|
81.1 %
|
71.2 %
|
82.7 %
|
|
Specificity (%)
|
58.6 %
|
50.0 %
|
44.8 %
|
41.4 %
|
|
Expert endoscopist 3
|
|
Sensitivity (%)
|
57.7 %
|
75.0 %
|
59.6 %
|
80.8 %
|
|
Specificity (%)
|
89.7 %
|
86.2 %
|
86.2 %
|
82.8 %
|
WLI, white light imaging; LCI, linked color imaging.
Fig. 2 Representative images of early gastric cancers obtained using white light imaging
(WLI) and linked color imaging (LCI). a Compared with WLI using an ultrathin endoscope, b LCI produces image with a high color contrast (white arrow) between the malignant
lesion and the surrounding mucosa. Similar images are found using c WLI and d LCI using a standard endoscope.
Visibility scores for malignant lesions
Mean visibility scores for malignant lesions (n = 52) were 1.76 ± 1.15 and 2.32 ± 0.98
for ultrathin WLI and LCI, and 1.94 ± 1.09 and 2.49 ± 0.84 for standard WLI and LCI,
respectively. The distributions of visibility scores were compared using each mode
and evaluated using the linear-by-linear association chi square test ([Fig. 3]). Visibility scores were higher with LCI than with WLI for both ultrathin (P < 0.001) and standard endoscopes (P < 0001). LCI with an ultrathin endoscope resulted in a significantly higher visibility
score than WLI with a standard endoscope (P = 0.001).
Fig. 3 Distribution of visibility scores showing the superiority of linked color imaging
(LCI) compared to white light imaging (WLI) as assessed by expert endoscopists. Scores
from 0 to 3 indicate missed, fair, good, and excellent visibility, respectively. Statistical
values are calculated by the linear-by-linear association chi square test.
Color differences between malignant lesion and surrounding mucosa
Color differences with LCI were significantly higher than those with WLI for both
ultrathin and standard endoscopes (P < 0.001) ([Table 3]). LCI with an ultrathin endoscope resulted in significantly higher color differences
than WLI with a standard endoscope (P < 0.001). Significantly higher color difference using ultrathin LCI were found regardless
of H. pylori status and the size of the malignant lesion ([Table 3]). In the mid- and distal stomach, elevated and depressed type, differentiated type,
depth within mucosa, the color difference with ultrathin LCI mode was significantly
higher than with standard WLI ([Table 3]).
Table 3
Comparison of color differences between malignant lesions and the surrounding mucosa
with white light imaging (WLI) and linked color imaging (LCI) (n = 51).
|
Ultrathin WLI
|
Ultrathin LCI
|
Standard WLI
|
Standard LCI
|
P value
|
Ultrathin WLI vs Ultrathin LCI
|
Standard WLI vs Standard LCI
|
Ultrathin LCI vs Standard WLI
|
|
Total lesions (n = 51)
|
|
∆E
|
6.9 (3.6)
|
11 (4.5)
|
6.6 (3.7)
|
12 (4.9)
|
< 0.001[1]
|
< 0.001[1]
|
< 0.001[1]
|
< 0.001[1]
|
|
|
–0.6 (3.6)
|
–0.1 (4.7)
|
–0.01 (3.4)
|
–0.6 (4.8)
|
ns
|
|
|
|
|
|
143.5 (21.1)
|
159.5 (17.6)
|
138 (18)
|
157.2 (17.7)
|
|
|
|
|
|
|
145.1 (20.5)
|
159.5 (16.9)
|
138,4 (18.4)
|
158.6 (19.2)
|
|
|
|
|
|
∆a
|
3.2 (3.9)
|
4.2 (6.3)
|
2.8 (4.4)
|
5.6 (6.3)
|
< 0.001[1]
|
ns
|
< 0.001[1]
|
ns
|
|
|
169.6 (6.1)
|
165.1 (6.3)
|
165.9 (6.2)
|
162.7 (6.9)
|
|
|
|
|
|
|
166.4 (6.1)
|
161 (6.2)
|
163.1 (5.7)
|
157.1 (7.4)
|
|
|
|
|
|
∆b
|
2.5 (4.3)
|
1.3 (8.4)
|
2.7 (3.3)
|
2.1 (8.3)
|
ns
|
|
|
|
|
|
175.5 (7.4)
|
151.6 (7.6)
|
163.1 (7.5)
|
147.5 (7.3)
|
|
|
|
|
|
|
173 (7)
|
150.2 (6.7)
|
160.3 (7.9)
|
145.4 (7.3)
|
|
|
|
|
|
Location ∆E
|
|
|
10.6 (2.5)
|
13.1 (2.8)
|
9.6 (2.6)
|
14.1 (6.8)
|
ns
|
|
|
|
|
|
6.4 (3.9)
|
11.3 (4.4)
|
6.9 (4.6)
|
11.1 (4.2)
|
0.0002[1]
|
0.0032[1]
|
0.007[1]
|
0.0158[1]
|
|
|
6.6 (3.4)
|
11 (4.8)
|
6 (3.3)
|
11.9 (4.9)
|
< 0.001[1]
|
< 0.001[1]
|
< 0.001[1]
|
< 0.001[1]
|
|
Morphology ∆E
|
|
|
6.5 (3.7)
|
11.2 (3.9)
|
7 (4.5)
|
12.7 (4.6)
|
0.0002[1]
|
0.0265[1]
|
0.0052[1]
|
0.0287[1]
|
|
|
7.1 (5.7)
|
13.3 (5.2)
|
6.2 (3.7)
|
14.2 (4.5)
|
ns
|
|
|
|
|
|
7.1 (3.4)
|
11.1 (4.7)
|
6.4 (3.5)
|
11.4 (5)
|
< 0.001[1]
|
< 0.001[1]
|
< 0.001[1]
|
< 0.001[1]
|
|
Size ∆E
|
|
|
7.3 (3.4)
|
11.8 (4.8)
|
6.4 (2.9)
|
12.3 (5.3)
|
0.0002[1]
|
0.0009[1]
|
0.0023[1]
|
0.0006[1]
|
|
|
7.1 (4.5)
|
9.7 (3.9)
|
6 (3.8)
|
10.2 (3.8)
|
0.0015[1]
|
0.039[1]
|
0.0075[1]
|
0.0288[1]
|
|
|
6.1 (2.7)
|
11.3 (5.3)
|
6.4 (4.8)
|
12.2 (5)
|
0.0006[1]
|
ns
|
0.02[1]
|
0.0441[1]
|
|
|
7.1 (3.5)
|
12.4 (4.4)
|
7.4 (3.8)
|
13 (5.4)
|
< 0.001[1]
|
0.0013[1]
|
0.004[1]
|
0.0008[1]
|
|
H. pylori status ∆E
|
|
|
6.7 (3.5)
|
11.5 (4.9)
|
6.5 (4)
|
12.5 (5.5)
|
< 0.001[1]
|
< 0.001[1]
|
< 0.001[1]
|
< 0.001[1]
|
|
|
7.6 (4.2)
|
10.9 (4.6)
|
6.6 (3.7)
|
11.2 (3.8)
|
0.0004[1]
|
0.0139[1]
|
0.0027[1]
|
0.0019[1]
|
|
Histology ∆E
|
|
|
6.9 (3.5)
|
11.4 (4.6)
|
6.6 (3.7)
|
12.2 (4.8)
|
< 0.001[1]
|
< 0.001[1]
|
< 0.001[1]
|
< 0.001[1]
|
|
|
7.5 (5.5)
|
9.9 (4.9)
|
6.6 (5.0)
|
8.0 (4.3)
|
0.0447[1]
|
ns
|
ns
|
ns
|
|
Depth ∆E
|
|
|
6.4 (3.5)
|
10.7 (4.6)
|
5.9 (3.4)
|
11.5 (5)
|
< 0.001[1]
|
< 0.001[1]
|
< 0.001[1]
|
< 0.001[1]
|
|
|
7.3 (4.4)
|
13.6 (4.7)
|
8.0 (3.2)
|
14.7 (1.9)
|
ns
|
|
|
|
|
|
9.7 (2.5)
|
13.4 (3.6)
|
9.6 (4.3)
|
12.5 (5.2)
|
0.0265[1]
|
ns
|
ns
|
0.0258[1]
|
One lesion was excluded from analysis because of minute size. Data are shown as mean
(standard deviation).
∆E shows color difference and is calculated from the following formula: [ (∆L*)2 + (∆a*)2 + (∆b*)2]1/2.
L is defined as lightness, a as the red–green component and b as the yellow-blue component.
∆L is obtained from a formula: (absolute L of malignant lesion -absolute L of surrounding
mucosa ) × 100/255.
Values (∆a, ∆b) were obtained by subtracting the value for the surrounding mucosa
from the value for the malignant lesion.
WLI, white light image; LCI, linked color imaging; ns, not significant.
Comparisons between four modes were made using the one-way Analysis of Variance (ANOVA)
with Bonferroni post-hoc test for significance between paired groups.
1 Statistically significant.
The purple surrounding mucosae, mainly corresponding to intestinal metaplasia, are
considered to influence the color difference [17]
[18] and we therefore evaluated the ratio of purple color to the entire circumference
of the malignant lesion. The number of lesions with ratios ≤ 50 %,50 % to 75 % and ≥ 75 %
was 31, 3, and 18, respectively. We assessed three cases with gastric cancers missed
using standard WLI by more than two endoscopists but detected by ultrathin LCI ([Fig. 4]). The first case had an inflammatory map-like redness near a small, depressed cancer
on the lesser curvature of the gastric midbody. The second and third cases were flat
and flat-elevated lesion, respectively. These malignant and benign lesions could not
be identified or differentiated by WLI but were visualized as orange-red malignant
lesions and purple inflammatory lesions by LCI.
Fig. 4 EGCs missed using standard white light imaging (WLI) by more than two endoscopists
but detected by ultrathin linked color imaging (LCI). a Small, depressed cancer (white arrow) near inflammatory map-like redness using standard
endoscope, WLI, b ultrathin endoscope, LCI, c,e Standard WLI, d,f ultrathin LCI of flat-elevated and flat lesion respectively.
Difference of resolution between standard and ultrathin endoscope
The resolution using an ultrathin endoscope was compared with that of a standard endoscope
and expressed as a ratio to the value obtained using the standard endoscope (arbitrary
units). The resolution using the ultrathin endoscope was the same as that using the
standard endoscope at a 10-mm view from the resolution chart but was lower at 20-mm
(0.71) and 50-mm (0.89) views simulating the distance between the endoscopic tip and
target gastric mucosa during screening ([Fig. 5]).
Fig. 5 Ratio of resolution of the ultrathin endoscope (EG-L580NW) to the standard endoscope
(EG-L590WR) at each distance between the endoscope tip and the resolution chart. The
resolution using the ultrathin endoscope is lower than when using a standard endoscope
at the 20-mm and 50-mm distances, simulating the distance between the endoscope tip
and the target gastric mucosa at screening.
Discussion
This is the first report to demonstrate that the color contrast between a malignant
lesion and its surrounding mucosa is more important than high-resolution images when
screening for EGCs. These results show both ultrathin LCI and standard LCI improve
the ability to detect EGCs compared with ultrathin WLI and standard WLI, respectively.
Ultrathin LCI had a higher diagnostic sensitivity, significantly higher visibility
scores, and color difference than standard WLI. This suggests that color contrast
is more important than resolution for the identification of EGC. The introduction
of ultrathin LCI seems to be suitable for EGC screening in clinical practice including
routine health examinations.
Ultrathin endoscopy is generally considered to yield low-resolution images compared
with standard endoscopy. Our test of resolution using industry-standard testing protocols
showed that ultrathin endoscopy results in images with a lower resolution at a distant
view. However, sensitivity for detection of EGCs was highest using standard LCI, followed
by ultrathin LCI, standard WLI, and ultrathin WLI. This order implies that endoscopists
are aware of the color contrast between malignant lesions and the surrounding mucosa
as previously reported using ultrathin endoscopy with flexible spectral imaging color
enhancement (FICE) [22]
[23]. LCI accelerates the ability for the early detection of gastric cancers, with the
superiority of ultrathin LCI compared to standard WLI.
The specificity of LCI was lower than WLI both with ultrathin and standard endoscopes.
Most non-malignant gastric lesions such as intestinal metaplasia, erosions and regenerative
epithelium exhibit mucosal changes with lower color contrast to the surrounding mucosa
on WLI, but with high color contrast on LCI, which may result in lower specificity
of LCI compared with WLI. Using LCI, suspicious lesions may increase but blue light
imaging allows endoscopists to differentiate the malignant lesion due to better visualization
of surface patterns without magnification [24]
[25]. The final diagnosis is made by target biopsy. In our experience, we use LCI in
routine clinical practice as the optimal mode for detection of EGC, but not as the
final endoscopic diagnosis tool.
Older age groups have a high risk for gastric cancer even after H. pylori eradication due to atrophy and intestinal metaplasia in the background mucosa [26]. However, establishing this diagnosis is challenging due to non-neoplastic epithelium
covering the malignant tissue which makes the cancer border indistinct and diminishes
the obvious characteristics of cancer [27]. The current data show that color differences between malignant lesions and the
surrounding mucosa of EGC is significantly higher with ultrathin LCI than standard
WLI regardless of H. pylori infection status. Ultrathin endoscopy reduces pain and panic during the procedure
and is advantageous especially for elderly patients with cardiopulmonary dysfunction
[6]
[7]. Together with the previously reported superiority of LCI for screening in the upper
gastrointestinal tract [14], ultrathin LCI can be suggested as the first choice for gastric screening in the
elderly and/or high-risk patients with cardiopulmonary dysfunction.
Ultrathin endoscopy has been shown to result in poor visibility of malignant lesions
in the proximal stomach using a xenon endoscope [9], but not using laser endoscopy, although it has good visibility around the lesser
curvature of the angle [28]
[29]. In this study, ultrathin LCI showed high visibility scores and significantly higher
color differences in the proximal stomach compared with standard WLI. Of five malignant
lesions in the lesser curvature near the angle, at least two assessors missed malignant
lesions with standard WLI whereas all assessors identified all lesions with ultrathin
LCI. Ultrathin endoscopy has advantages such as allowing direct visualization of these
areas due to a shorter radius at the tip and has the potential to observe the entire
stomach with fewer blind spots. However, all assessors identified all these lesions
even with standard LCI endoscopy, which may suggest the true efficacy of LCI rather
than the physical flexibility of the ultrathin endoscope. Additional studies are necessary
to conclusively evaluate this matter.
We have previously reported that LCI provides images with high color contrast to the
surrounding mucosa for EGC [18]. LCI increased the a* value in the red-green component and/or b* values in the yellow-blue
component in the color space when evaluating color differences between malignant lesions
and the surrounding mucosa [17]
[18]. In this study, most malignant lesions were surrounded by purple mucosa only in
a partial circumferential area (or not at all). The malignant areas and surrounding
mucosa were mostly orange-red and light orange, respectively, resulting in the possibility
to influence a* value in the red-green component rather than b* values related to
purple.
Recent advances in endoscopic treatment such as endoscopic submucosal dissection improves
the prognosis of patients with EGCs and allows patients to maintain a high quality
of life after therapy. It is beneficial to detect cancers when they are as small as
possible to allow the use of endoscopic therapy. The current study showed that the
color difference with ultrathin LCI is higher than with standard WLI even with lesions
at a diameter ≤ 10 mm, suggesting that the advantage was found regardless of lesion
size.
This study has several acknowledged limitations. First, this is a single-center study
with a small number of assessors. Second, the evaluated videos may not be representative
of live endoscopic screening for gastric cancer. Third, the endoscopists who performed
EGC to create the videos were not blinded to patient data or the type of endoscopes.
Multicenter prospective clinical trials are needed to confirm these results. Fourth,
diagnosing EGC in 90 seconds is challenging and thus only expert endoscopists participated.
Conclusions
In conclusion, LCI facilitates the early detection of gastric cancers by providing
high color contrast to the surrounding mucosa regardless of using standard or ultrathin
endoscopes. LCI with a low-resolution ultrathin endoscope is superior to WLI with
a high-resolution standard endoscope for gastric cancer screening. This suggests that
color contrast between malignant lesions and the surrounding mucosa is more important
than high-resolution imaging.
