Introduction

Various countermeasures for gastric cancer have been developed and used in East Asia, where the incidence of gastric cancer is quite high [1]. These measures can be broadly classified into two groups: those that aim to detect gastric cancer itself (cancer screening), and those that aim to evaluate the premalignant condition of gastric mucosa (risk stratification) [2]. Double-contrast upper gastrointestinal barium X-ray radiography (UGI-XR) [3–5] and upper gastrointestinal endoscopy (UGI-ES) [6–8] are the typical measures belonging to the former group, whereas serum markers including anti-Helicobacter pylori (H. pylori) IgG, pepsinogens, gastrin-17, methylation status of several genes, etc. [9–14] are representative measures affiliated with the latter group.

Nowadays, there is a growing tendency to make another new use of UGI-XR and UGI-ES for gastric cancer: namely, UGI-XR as well as UGI-ES are expected not only to detect gastric cancer but also to evaluate atrophic gastritis [2]. Atrophic gastritis is a well-established premalignant condition of gastric mucosa mostly induced by chronic infection of H. pylori [15, 16]. Although UGI-ES and UGI-XR are the two major “no-histological image-based” methods that can evaluate mucosal atrophy of stomach [2, 17–20], very few reports have directly compared their diagnostic accuracy for atrophic gastritis.

Based on the foregoing backgrounds, we have two aims in the present study. The main aim is a direct comparison between UGI-ES and UGI-XR in terms of their accuracy to detect atrophic gastritis. The second aim is to evaluate an association between serum anti-H. pylori IgG titer and “atrophic gastritis” diagnosed by UGI-ES and UGI-XR. In addition, we wish to supply our large-scale raw data from 962 generally healthy subjects that include diagnoses by UGI-ES and UGI-XR, titers of serum anti-H. pylori IgG, values of serum pepsinogens, etc. We believe our results and data will be useful concerning future screening and risk stratification of gastric cancer.

Methods

Study subjects

The study subjects were 962 generally healthy subjects who underwent UGI-XR in 2010 and also underwent UGI-ES within 1 year at our institute for a medical checkup. They agreed to participate in our study, were not users of gastric acid suppressants, and had no history of gastrectomy and eradication for H. pylori.

The seven-grade Kimura–Takemoto classification of UGI-ES-based atrophic gastritis and the four-grade UGI-XR-based atrophic gastritis

According to the Kimura–Takemoto classification [18, 19], atrophic changes of the gastric mucosa diagnosed by UGI-ES were classified into no atrophic change (C0), three closed types of atrophic gastritis (C1, C2, C3), and three open types of atrophic gastritis (O1, O2, O3) based on the endoscopic atrophic border (a boundary between the pyloric and fundic gland areas, and also a boundary between non-atrophic and atrophic gastric mucosae recognized endoscopically by discriminating differences in color and height of the gastric mucosa [21, 22] ).

By referring to several previous reports [23–25], we have recently established the four-grade classification of UGI-XR-based atrophic gastritis judging from the irregular shapes of areae gastricae and their expansion (normal, mild, moderate, and severe) [2]. These two categorizations of image-based atrophic gastritis and double/triple check of the images are minutely described in Fig. 1 and supplementary methods.

Fig. 1
figure 1

Detailed features of the seven-grade Kimura–Takemoto classification of upper gastrointestinal endoscopy (UGI-ES)-based atrophic gastritis and the four-grade types of double-contrast upper gastrointestinal barium X-ray radiography (UGI-XR)-based atrophic gastritis

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Serum anti-H. pylori IgG, serum pepsinogen I and II, and other factors

Serum anti-H. pylori IgG and pepsinogens were measured using commercial kits (E-plate; EIKEN, Tokyo, Japan) [26–30]. According to the manufacturer’s instructions, a titer of anti-H. pylori IgG ≥10 U/ml was considered as positive for H. pylori infection. The ratios of serum pepsinogen I and II were classified into “>3”, “>2”, and ≤3”, and “≤2” [28, 31]. Other factors used in our analyses are minutely described in the supplementary methods.

Statistics

We used SAS 9.1.3 for statistical analyses. To compare the four-grade UGI-XR-based and the seven-grade UGI-ES-based atrophic gastritis, the polychoric correlation coefficient was calculated.

Results

UGI-XR-based atrophic gastritis shows a strong and significant association with UGI-ES-based atrophic gastritis

The characteristics of the present study subjects are shown in Table 1 and Fig. 2. Of the 962 generally healthy subjects, 602 subjects (62.6 %) were diagnosed to be free from atrophic gastritis by both UGI-ES (C0) and UGI-XR (normal), whereas 254 subjects (26.4 %) were diagnosed to have atrophic gastritis by both UGI-ES (C2-O3) and UGI-XR (mild, moderate, or severe).

Table 1 Characteristics of the total 962 study subjects, 602 subjects without atrophic gastritis, and 254 subjects with atrophic gastritis based on UGI-ES and UGI-XR
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Fig. 2
figure 2

Comparison between UGI-ES-based atrophic gastritis and UGI-XR-based atrophic gastritis using the data of 962 generally healthy subjects

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When UGI-ES-based atrophic gastritis was considered to be the standard, the sensitivity and specificity of UGI-XR-based atrophic gastritis were 92.0 % (254/276) and 92.8 % (602/649), respectively (Fig. 2). A high polychoric correlation coefficient value (r = 0.9069) demonstrated that there is a strong and significant association between the seven-grade UGI-ES-based atrophic gastritis (Kimura–Takemoto classification) and the four-grade categories of UGI-XR-based atrophic gastritis.

The titer of serum anti-H. pylori IgG cannot reliably detect atrophic gastritis that is diagnosed by UGI-ES and UGI-XR

We next evaluated the association between the serum titer of anti-H. pylori IgG and atrophic gastritis diagnosed by UGI-ES and UGI-XR. Distributions of the serum anti-H. pylori IgG titers in the 602 subjects without atrophic gastritis and the 254 subjects with atrophic gastritis are shown in Fig. 3a, b. Values of pepsinogen I, pepsinogen II, and pepsinogen I/II ratio are also shown in Figures S1 and S2.

Fig. 3
figure 3

Distribution of the serum anti-Helicobacter pylori IgG titers in the 602 subjects without atrophic gastritis (a, c) and that in the 254 subjects with atrophic gastritis (b, c), based on UGI-ES and UGI-XR

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We next examined whether the positive titer of serum anti-H. pylori IgG could predict atrophic gastritis diagnosed by UGI-ES and UGI-XR, because atrophic gastritis is predominantly induced by chronic infection of H. pylori [17, 22]. On the basis of UGI-ES/UGI-XR-based diagnoses, the sensitivity and specificity to detect atrophic gastritis with the positive titer of anti-H. pylori IgG were 89.4 % (227/254) and 99.8 % (601/602), respectively (Fig. 3c). Our results also revealed that the positive and negative predictive values were 99.6 % (227/228) and 95.7 % (602/628), respectively (Fig. 3c).

Discussion

Presently, detection of chronic H. pylori infection is thought to be important for predicting the risk of gastric cancer [32–35]. For endoscopic observation, atrophic gastritis is established as the most typical and frequent appearance of gastric mucosa with H. pylori infection [22, 35, 36]. Therefore, a strong association between “UGI-ES-based” and “UGI-XR-based” diagnoses suggests that detection of UGI-XR-based atrophic gastritis can lead to evaluation of chronic H. pylori infection. In the case of the positive titer for serum anti-H. pylori IgG, mucosal atrophy was observed with 99.6 % accuracy (Fig. 3c): this indicates that chronic H. pylori infection can be diagnosed almost completely by UGI-XR. In contrast, in the case of negative titer for serum anti-H. pylori IgG, as many as 4.3 % had atrophic gastritis (Fig. 3c): this indicates that other factors may have some critical role in the development of UGI-ES/UGI-XR-based atrophic gastritis, or that serum anti-H. pylori IgG titer is insufficient to diagnose H. pylori infection. In either case, our results reveal that UGI-ES/UGI-XR-based atrophic gastritis can be overlooked when the serum titer of anti-H. pylori IgG alone is used as an indicator.

Internationally standard risk stratification methods for gastric cancer are still histological evaluation of random biopsy specimens such as OLGA [37, 38], OLIGM [39], etc. In contrast, endoscopic diagnosis of premalignant atrophic gastritis is widely conducted in Japan [35]. The Kimura–Takemoto classification of atrophic gastritis by UGI-ES is the most widely used method, which has been validated by several reports showing the reliable association between endoscopic findings and histological appearances [18, 19, 22, 40]. In this study, we showed a significantly strong association between UGI-ES-based atrophic gastritis and UGI-XR-based atrophic gastritis (Fig. 2). Taking all these into consideration, UGI-XR-based atrophic gastritis should reflect the premalignant histological condition of gastric mucosa, which is mostly induced by H. pylori infection. Based on these results, we are now planning to evaluate the clinical meaning of UGI-XR-based atrophic gastritis from the aspect of predicting future gastric cancer development.

In Table S1, we provide all the data of our 962 study subjects, which include the Kimura–Takemoto classification of UGI-ES-based atrophic gastritis, the four-grade types of UGI-XR-based atrophic gastritis, serum titers of anti-H. pylori IgG, age, gender, body mass index, smoking history, alcohol use, serum pepsinogens, the ABCD risk classification of gastric cancer [9], the three-grade types of UGI-XR-based enlarged folds [24, 25], etc. Extracted data of the 602 subjects without UGI-ES/UGI-XR-based atrophic gastritis and those of the 254 subjects with UGI-ES/UGI-XR-based atrophic gastritis are also provided in Tables S2 and S3. We believe these data will be helpful for future research concerning the screening and risk stratification of gastric cancer.

Conclusion

The four-grade categories of UGI-XR-based atrophic gastritis showed a strong and significant association with the seven-grade Kimura–Takemoto classification of UGI-ES-based atrophic gastritis. UGI-ES/UGI-XR-based atrophic gastritis can sometimes be overlooked when the serum titer of anti-H. pylori IgG alone is used as an indicator.