Introduction
Helicobacter pylori infection is closely associated with gastric carcinogenesis [1]
[2]
[3]
[4]
[5]. The International Agency for Research on Cancer Working Group Report recommends
that all countries should consider the introduction of population-based H. pylori screening and treatment programs as a strategy for gastric cancer prevention [6]. In Japan, the National Health Insurance system covers the H. pylori test and eradication therapy for patients with endoscopically confirmed H. pylori-active gastritis [7]. Endoscopic diagnosis of H. pylori infection in a patient indicates a high risk of developing gastric cancer, and facilitates
provision of H. pylori eradication therapy to reduce morbidity of gastric cancer. In 2014, the Kyoto Classification
of Gastritis was published according to the endoscopic characteristics of gastritis
associated with H. pylori infection to diagnose H. pylori infection accurately and assess the risk factors of gastric cancer [8]
[9]. However, it is often difficult with white light imaging (WLI) to access various
endoscopic features accurately.
Compared with WLI, image-enhanced endoscopy (IEE) improves the accuracy of the endoscopic
diagnosis of H. pylori-active or inactive gastritis. Under thorough examination of the gastric mucosal pattern,
magnifying endoscopy with narrow-band imaging can accurately diagnose mucosal atrophy
and intestinal metaplasia [10]
[11]. Linked color imaging is also useful for diagnosing intestinal metaplasia, diffuse
redness, and map-like redness during routine endoscopy [12]
[13]
[14]
[15]. However, there is no report to investigate the usefulness of IEE for diagnosing
H. pylori gastritis based on the Kyoto Classification of Gastritis.
In 2020, Olympus Medical Systems Corporation (Tokyo, Japan) developed a new IEE called
texture and color enhancement imaging (TXI), which enhances three image factors in
WLI (texture, brightness, and color), improves brightness, and expands color range;
thus, TXI enables easier recognition of slight differences in mucosal color [16]. Given these features, the visibility of endoscopic findings associated with H. pylori infection during routine endoscopy may be improved by TXI. In this study, we aimed
to analyze the efficacy of TXI to diagnose H. pylori-active gastritis in comparison with WLI based on the Kyoto Classification of Gastritis.
Patients and methods
Patients
This retrospective single-center pilot study was conducted at Chiba Cancer Center
in Chiba, Japan. It included 60 consecutive patients who underwent esophagogastroduodenoscopy
with a TXI system at Chiba Cancer Center between January 2021 and June 2021. All were
asymptomatic screening patients. Patients who had a history of prior gastric cancer
or gastrectomy were excluded.
The ethics committee of Chiba Cancer Center approved the study protocol, which was
displayed on the notification board for inpatients and outpatients (R02–252). This
study conformed to the World Medical Association’s Declaration of Helsinki. All patients
had provided informed consent to undergo endoscopy.
Endoscopic procedure
Before the endoscopic examination, all patients received a mixture of 100 mL of water,
20,000 U of Pronase (Kaken Pharmaceutical, Tokyo, Japan), 1 g of sodium bicarbonate,
and 10 mL of dimethicone (20 mg/mL; Kissei Pharmaceutical Co., Ltd., Nagano, Japan).
After the mucus and bubbles were rinsed away, the endoscopic examination was initiated.
We used the new endoscopic system employing the CV-1500 light source equipped with
a TXI system, as well as the GIF-H290Z endoscope (Olympus Medical Systems, Tokyo,
Japan). TXI has two settings: mode 1 (with color enhancement) and mode 2 (without
color enhancement, which appears closer to WLI color tone). This study used the TXI
mode 1. One expert (YK) took all the endoscopic images. Based on the systematic screening
protocol for the stomach (SSS), endoscopic screening was performed with both WLI and
TXI [17].
H. pylori infection status
The H. pylori infection status was evaluated by using the urea breath test (UBT; cutoff value < 2.5 %,
UBIT, Otsuka, Tokyo, Japan) and the serum antibody test (HpAb; cutoff < 10 U/mL, E-plate,
Eiken, Tokyo, Japan). When the UBT or HpAb was positive, the H. pylori infection status was considered as current infection. When both the UBT and HpAb
were negative, the patient had no H. pylori infection. When a H. pylori-negative patient had a definite history of eradication therapy, the H. pylori infection status was regarded as past infection. Absence of H. pylori infection after H. pylori eradication therapy was confirmed using the UBT. Among H. pylori-negative patients, those without a history of eradication therapy were classified
as the noninfection group. Proton pump inhibitor or histamine blocker was stopped
at least 2 weeks prior to the UBT.
Review of endoscopic images
For evaluating endoscopic gastritis, we prepared one image set per patient; each set
had 22 endoscopic images acquired by both WLI and TXI, including the antegrade and
retroflex views of each part of the stomach, according to the SSS [17]. The image sets of WLI and TXI were randomly displayed and independently reviewed
by five skilled endoscopists. These professionals were board certified by the Japanese
Gastrointestinal Endoscopy Society and had over 5 years’ experience using IEE. The
endoscopists were blinded to the H. pylori test results and did not view any of these images before this study. According to
the Kyoto Classification of Gastritis [8]
[9], the reviewers assessed the H. pylori infection status as either current infection, past infection, or noninfection on
endoscopy.
We previously had some consensus meetings, and the endoscopic findings of Kyoto Classification
of Gastritis with each modality were confirmed using an atlas of representative endoscopic
images ([Fig. 1]).
Fig. 1 Representative endoscopic images. Endoscopic images of the regular arrangement of
collecting venules (RAC) in the stomach. a WLI. Venular accumulation is noted with an increase in minute points, and it is regularly
distributed in the body of the stomach. b TXI. Regular tiny veins are depicted more clearly. Endoscopic images of the atrophic
border in the stomach. c WLI. An atrophic border is found at the lesser curvature of the gastric body. d TXI. The atrophic border is more identified. Endoscopic images of intestinal metaplasia
in the stomach. e WLI. Slightly elevated whitish patches are observed in the antrum of the stomach.
f TXI. Whitish patches become more noticeable. Endoscopic images of map-like redness
in the stomach. g WLI. Reddish depressed area is observed in the atrophic area of the gastric body.
h TXI. The reddish depressed area appears more vivid. Endoscopic images of diffuse
redness in the stomach. i WLI. A uniform redness is observed on the non-atrophic mucosa of the fundic gland
in the gastric body. j TXI. Visualization of the reddish area is enhanced.
Outcomes
The primary endpoints were the diagnostic accuracies of WLI and TXI for H. pylori-active gastritis. In addition, the sensitivity, specificity, positive predict value
(PPV), and negative predict value (NPV) were calculated.
We also evaluated the correlation of the endoscopic features with the three H. pylori infection statuses (current infection, past infection, and noninfection) and calculated
the diagnostic odds ratio (OR). It was determined using the following formula: the
diagnostic OR = (true positives/false negatives)/(false positives/true negatives)
[18].
Statistical analysis
The diagnostic accuracies of WLI and TXI for active gastritis were compared using
the McNemar test. The interobserver agreement among the five reviewers for each group
was evaluated using Fleiss’ kappa statistics. We used the arbitrary interpretation
of Landis and Koch [19]. All statistical tests were two-tailed, and P values of less than 0.05 were considered significant. All statistical data were analyzed
using the SPSS software, version 17.0 (SPSS Inc., Chicago, Illinois, United States).
Results
[Table 1] lists patient characteristics. The median patient age was 73 (45–84) years, with
male prevalence (41, 68.3 %). Atrophic gastritis was present in 48 patients (closed
type, 5; open type, 43). Furthermore, 24, 24, and 12 patients had current infection,
past infection, and no infection, respectively.
Table 1
Baseline tumor characteristics.
|
Patient characteristics
|
(n = 60)
|
|
Age, median (IQR), years
|
73 (68–78)
|
|
Sex
|
|
|
41/19
|
|
Atrophy of gastric mucosa, n (%)
|
|
|
12 (20.0)
|
|
|
5 (8.3)
|
|
|
43 (71.7)
|
|
Helicobacter pylori, n (%)
|
|
|
24 (40.0)
|
|
|
24 (40.0)
|
|
|
12 (20.0)
|
|
Acid therapy, n (%)
|
|
|
45 (75.0)
|
|
|
13 (21.7)
|
|
|
2 (3.3)
|
|
NSAIDs, n (%)
|
|
|
53 (88.3)
|
|
|
7 (11.7)
|
IQR, interquartile range; C, closed; O, open; PPI, proton pump inhibitor; H2 blocker, Histamine H2-receptor antagonist; NSAIDs, nonsteroidal anti-inflammatory drugs.
The relationship between endoscopic diagnosis and H. pylori infection status is shown in [Table 2]. The diagnostic performance from each reviewer is shown in Supplementary Table 1.
Table 2
Relationship between endoscopic diagnosis and H. pylori infection status
|
|
Helicobacter pylori infection status
|
|
WLI
|
Current infection
|
Past infection
|
Non-infection
|
Total
|
|
Endoscopic diagnosis
|
Current infection
|
63
|
7
|
0
|
70
|
|
Past infection
|
56
|
105
|
7
|
168
|
|
Noninfection
|
1
|
8
|
53
|
62
|
|
Total
|
120
|
120
|
60
|
300
|
|
TXI
|
Current infection
|
Past infection
|
Non-infection
|
Total
|
|
Endoscopic diagnosis
|
Current infection
|
83
|
6
|
1
|
90
|
|
Past infection
|
37
|
107
|
4
|
148
|
|
Noninfection
|
0
|
7
|
55
|
62
|
|
Total
|
120
|
120
|
60
|
300
|
WLI, white light imaging; TXI, texture and color enhancement imaging.
[Table 3] summarizes the diagnostic accuracies of endoscopy with WLI and TXI for H. pylori-active gastritis. The accuracy, sensitivity, specificity, PPV, and NPV were 78.7 %,
52.5 %, 96.1 %, 90.0 %, and 75.2 % for WLI diagnosis, and 85.3 %, 69.2%, 96.1 %, 92.2 %,
and 82.4 % for TXI diagnosis, respectively. Hence, TXI was significantly more accurate
and sensitive than WLI (P = 0.034 and P = 0.012, respectively).
Table 3
Diagnostic accuracy of endoscopy with WLI and TXI for Helicobacter pylori-active gastritis.
|
Accuracy
|
Sensitivity
|
Specificity
|
PPV
|
NPV
|
|
WLI
(95 % CI)
|
78.7
(74.9–81.0)
|
52.5
(47.7–55.4)
|
96.1
(92.9–98.0)
|
90.0
(81.9–94.9)
|
75.2
(72.7–76.7)
|
|
TXI
(95 % CI)
|
85.3
(81.6–87.6)
|
69.2
(64.5–72.0)
|
96.1
(93.0–98.0)
|
92.2
(86.0–96.0)
|
82.4
(79.7–84.0)
|
|
P value
|
0.034
|
0.012
|
1.000
|
0.779
|
0.081
|
CI, confidence interval; PPV, positive predict value; NPV, negative predict value;
WLI, white light imaging; TXI, texture and color enhancement imaging.
For current infection, atrophy, intestinal metaplasia, and diffuse redness had a high
OR using both WLI and TXI ([Table 4]). However, atrophy and intestinal metaplasia also had a high OR for past infection.
Thus, diffuse redness was the only specific observation for current infection using
WLI and TXI (OR, 22.0 and 56.1, respectively). A high OR using WLI and TXI was specifically
observed for map-like redness in past infection (OR 6.3 and 11.0, respectively) and
the regular arrangement of collecting venules (RAC) in noninfection (OR 25.2 and 42.3,
respectively). All the specific endoscopic features associated with H. pylori infection statuses had a higher OR with TXI than with WLI.
Table 4
Diagnostic odds ratio of the endoscopic features.
|
Current infection
|
Past infection
|
Noninfection
|
|
WLI
|
RAC
(95 % CI)
|
0.13
(0.07–0.25)
|
0.70
(0.42–1.16)
|
25.24
(11.70–54.33)
|
|
Atrophy
(95 % CI)
|
64.70
(11.11–375.14)
|
5.81
(2.69–12.50)
|
0.00
(0.00–0.01)
|
|
Intestinal metaplasia
(95 % CI)
|
2.69
(1.66–4.35)
|
1.39
(0.86–2.24)
|
0.00
(0.00–0.08)
|
|
Map-like redness
(95 % CI)
|
0.65
(0.40–1.05)
|
6.29
(3.74–10.50)
|
0.00
(0.00–0.08)
|
|
Diffuse redness
(95 % CI)
|
22.00
(9.31–52.45)
|
0.13
(0.06–0.31)
|
0.00
(0.00–0.19)
|
|
Current infection
|
Past infection
|
Noninfection
|
|
TXI
|
RAC
(95 % CI)
|
0.04
(0.01–0.11)
|
0.74
(0.44–1.26)
|
42.25
(18.61–95.57)
|
|
Atrophy
(95 % CI)
|
69.75
(11.98–404.29)
|
6.20
(2.76–13.90)
|
0.00
(0.00–0.01)
|
|
Intestinal metaplasia
(95 % CI)
|
3.05
(1.90–4.91)
|
1.54
(0.96–2.45)
|
0.01
(0.00–0.07)
|
|
Map-like redness
(95 % CI)
|
0.39
(0.24–0.64)
|
10.97
(6.35–18.98)
|
0.02
(0.00–0.11)
|
|
Diffuse redness
|
56.21
(20.35–154.50)
|
0.04
(0.01–0.13)
|
0.04
(0.01–0.22)
|
CI, confidence interval; WLI, white light imaging; TXI, texture and color enhancement
imaging; RAC, regular arrangement of collecting venules.
The kappa values of interobserver agreement among the five reviewers were fair to
substantial for WLI, and moderate to substantial for TXI ([Table 5]). Additionally, TXI had higher kappa values than the WLI among the five reviewers,
except for one pair.
Table 5
Interobserver agreement among the five reviewers.
|
Kappa values for TXI
|
Kappa values for WLI
|
Endoscopist
|
|
0.52
|
0.30
|
A to B
|
|
0.68
|
0.71
|
A to C
|
|
0.77
|
0.28
|
A to D
|
|
0.65
|
0.44
|
A to E
|
|
0.57
|
0.53
|
B to C
|
|
0.66
|
0.41
|
B to D
|
|
0.62
|
0.46
|
B to E
|
|
0.67
|
0.55
|
C to D
|
|
0.71
|
0.51
|
C to E
|
|
0.72
|
0.57
|
D to E
|
WLI, white light imaging; TXI, texture and color enhancement imaging.
Discussion
This study revealed that TXI significantly improved endoscopic diagnostic accuracy
for active gastritis compared with WLI. Additionally, all the specific endoscopic
features associated with H. pylori infection statuses had a higher OR with TXI than with WLI.
The recently developed Kyoto Classification of Gastritis provides 16 endoscopic findings
that are useful for differentiating H. pylori infection statuses [8]
[9]. Among the endoscopic features, diffuse redness, which pathologically correlates
with neutrophil and mononuclear cell inflammation, is an important feature of active
H. pylori infection [12]
[14]
[20].
In the present study, diffuse redness showed a high OR using both WLI and TXI in patients
with current infection. It was also strongly related to current infection using TXI
compared with using WLI. This result can be explained by the imaging principle of
TXI, which enhances color to greatly accentuate color tone differences of mucosal
surfaces, thereby enhancing the mucosal redness. In addition, TXI is more useful for
visualizing gastric mucosal atrophy [21] because it strengthens the contrast between the non-atrophic mucosa showing diffuse
redness and the atrophic mucosa. Considering the relationship between endoscopic diagnosis
and H. pylori infection status, we speculate that H. pylori-active cases were misdiagnosed as past infections with WLI, because of the possibility
that WLI could miss diffuse redness. TXI can detect diffuse redness accurately, thereby
improving diagnostic sensitivity and accuracy for active H. pylori infection compared with WLI. Good accuracy for current infection is vital; those
who are not diagnosed as having current infection may miss the opportunity of H. pylori eradication therapy and surveillance for gastric cancer.
In a multicenter observation study conducted by Kawamura et al., endoscopic atrophy,
invisible RAC, intestinal metaplasia, and map-like redness were high-risk endoscopic
findings in the Kyoto Classification of Gastritis [22]. In our study, map-like redness correlated with past infection, whereas RAC correlated
with noninfection. As with diffuse redness, these endoscopic features were strongly
associated with H. pylori infection statuses using TXI compared with using WLI. The reason is that TXI improves
the visibility of map-like redness and RAC by enhancing the reddish color, resulting
in a stronger contrast.
Among the five reviewers, the interobserver agreement with WLI was fair to substantial
(0.28–0.71), whereas that with TXI was moderate to substantial (0.52–0.77). Hence,
TXI seems a more reliable modality for diagnosing H. pylori infection than WLI. Therefore, through TXI, the endoscopists could assess various
endoscopic features of H. pylori-related gastritis more precisely.
However, the present study has some limitations. The diagnostic performance of the
two modalities was compared using stored images; thus, this study did not assess real-time
diagnostic performance, and the possibility of selection bias remains. Considering
that all image sets were reviewed in a single session, another bias is possible because
of the previous display of the same images in different modalities. The proportion
of current infection was higher than that normally seen in the clinical practice.
Although the UBT or stool antigen test would be better to evaluate the H. pylori infection status, some cases with current infection were determined based on the
HpAb. We could not perform the histologic examination for atrophy and intestinal metaplasia.
However, additional examinations could not be performed because the endoscopic procedures
were part of routine screening. Interobserver agreement between one pair was higher
in WLI than in TXI. Furthermore, this study has a small sample size, was conducted
in a single center, and is retrospective in design. Thus, a prospective, randomized,
multicenter study is required to validate our findings.
Conclusions
Nonetheless, the present study demonstrated the efficacy of TXI in accurately diagnosing
H. pylori infection on endoscopy under the same conditions.
In conclusion, TXI can be a useful modality for the accurate endoscopic diagnosis
of H. pylori infection.
