In this study, we developed endoscopic scores evaluating the atrophy and metaplasia of gastric mucosa using NBI and NFM and assessed the correlation between the endoscopic scores and histology. Previous studies evaluating atrophy and intestinal metaplasia reported the usefulness of NBI and/or magnifying endoscopy, not diagnostic performance of NFM. Conventional magnifying endoscopy is time consuming for observation and can be performed only by experienced endoscopist. However, near focus function can be used with several additional minutes and easily applicable without special training. In our study, an atrophic border (F-line) could be readily observed by adding an NBI examination and typical findings of intestinal metaplasia (LBC, WOS, and tubular or granular pit of the corpus), which has been previously reported using NBI magnifying endoscopy, and it could also easily be seen with NBI with NFM. When applying endoscopic atrophy scores based on the Kimura-Takemoto classification and the endoscopic metaplasia score based on the typical NBI-magnification view of the metaplasia and the extent, score > 1 was a high-risk group for both atrophy and metaplasia and it showed a strong positive correlation (0.70 for atrophy and 0.75 for metaplasia) with high-risk OLGA and OLGIM staging.
Discrepancies between endoscopic and histologic diagnosis of gastric atrophy and metaplasia have been reported. In a study reporting discrepancies between histological and endoscopic findings for atrophic gastritis in 1330 patients, the sensitivity and specificity of atrophic gastritis in the antrum were 61.5% and 57.7%, and in the corpus were 46.8% and 76.4% [18]. As for intestinal metaplasia, they were 24.0 and 91.9% in the antrum and 24.2.% and 88% in the corpus [19]. In this study, the sensitivities for the diagnosis of endoscopic metaplasia were lower than our results because their diagnosis of metaplasia was evaluated only with white light endoscopy. In a recent multicenter validation study for endoscopic grading of gastric intestinal metaplasia, endoscopic score > 4 correlated with stage III and IV OLGIM with 89.4% of sensitivity, 94.6% of specificity, 79.2% of PPV, and 97.5% of NPV [12]. In the study, the authors used white light endoscopy and NBI (without magnification) and the score ranged from 0 to 10. Our result showed higher sensitivity and PPV whereas lower specificity and NPV than this European study. We assume that a score system with high sensitivity and PPV is more useful to screen gastric cancer in the countries with high prevalence of gastric cancer.
Endoscopic grading of atrophic gastritis according to the Kimura-Takemoto classification is widely used. This system significantly reflects both the extent and severity of gastric atrophy because the extent correlates with the degree of severity. Endoscopic atrophic score was graded as 0 (none, C0 or mild, C1), 1 (moderate, C2 and C3), and 2 (severe, O1, O2, and O3), and when the score was 2, the score correlated well with OLGA Stage III and IV in our result. Recent studies showed the risk of cancer differs according to this grading [20, 21]. In a study evaluating 9378 subjects underwent cancer screening, C0-1, C2-3, and open type showed 0.10%, 0.16%, and 0.31 % of annual rate of gastric cancer occurrence, respectively [21].
H.pylori infection status was also significantly associated with not only high endoscopic atrophy/metaplasia score, but also high OLGA and OLGIM system. Our result is consistent with the date from the previous report evaluating OLGA and OLGIM system according to age and H.pylori status in the Korean population [22]. In the study, the proportion of high OLGA and OLGIM stages was significantly increased with H.pylori infection (OR=8.46) and high risk OLGA and OLGIM stages were uncommon in the H.pylori negative subjects.
We diagnosed endoscopic metaplasia showing at least one finding of LBS, WOS, and tubular/granular pit pattern of the corpus using NBI-NFM. Those findings have been reported as a useful marker for endoscopic diagnosis of intestinal metaplasia with 50–89% sensitivity and 80–100% specificity [10, 13, 23]. However, these findings suggest only the presence of intestinal metaplasia and do not give information about the extent and the severity of intestinal metaplasia. Therefore, we added scores according to the site (antrum or corpus) and severity (whether the findings suggestive of intestinal metaplasia were observed in more than 1/2 area of the picture or not) and our endoscopic metaplasia score showed a good correlation with histologic staging. In a cross-sectional study of 55 patients, the authors developed an endoscopic score using NBI magnifying endoscopy and they combined the scores for the antrum and the corpus mainly based on findings of intestinal metaplasia [8]. The degree of correspondence between the high-risk NBI-ME finding and a high histology score was 89.1%, which was similar to our result.
Our endoscopic atrophic and metaplasia scores tend to overestimate the OLGA and OLGIM system. We speculate that it is because multifocal atrophy or metaplasia could be underestimated on histologic examination if biopsy samples were not taken from the exact site of the atrophy or metaplasia change. In addition, we omitted taking a biopsy sample from the incisura angularis, which could affect the histologic diagnosis. In a study assessing the value of incisura angularis biopsy, a general down-grading of stage by 4.0% for OLGIM and 30–35% downgrading for high-risk OLGA/OLGIM stages were observed if the incisura angularis was excluded from the biopsy [24].
The proportion of high-risk OLGA and OLGIM (stage III or IV) patents was high at 47%. A previous study on the OLGA and OLGIM stage distribution in a Korean screening papulation, high-risk OLGA patients were only 16.6% and high-risk OLGIM, 9.5% [22]. It is inferred that the differences came from the characteristics of our study population. Many of our patients (49%) underwent diagnostic endoscopy because of abnormal EGD findings such as early gastric cancer or dysplasia at a local clinic. In a study evaluating OLGA and OLGIM stage in gastric cancer patients, the proportion of high-risk OLGA and OLGIM patients was similar to our study (46.2% OLGA and 46.1% OLGIM, respectively) [25]. Furthermore, the past history (19.6%) or current infection rate (51%) of H. pylori was relatively high in our population, and this may affect the high proportion of high-risk OLGA and OLGIM staging.
It is known that OLGA staging reliably predicts the risk of developing gastric cancer. In a prospective study of 1755 patients followed up for 5 years, the risk for gastric dysplasia or cancer was null in patients stage 0, 1 and III, while it was 36.5 per 1000 person-years among patients at stage 3 and 63.1 per 1000 person-years among patients at stage IV[26]. In a retrospective cohort study, OLGIM showed a better predictive value for gastric cancer development than OLGA and the standardized incidence rate for high risk OLGIM was 4.0[27]. OLGIM staging has an advantage of high inter-observer agreement, but a substantial proportion of high-risk patients would be missed if only OLGIM staging was applied[24]. Applying both OLGA and OLGIM staging is necessary for accurate prediction of gastric cancer risk. In the same vein, we infer that evaluations of both atrophic gastritis and intestinal metaplasia are necessary to screen high-risk patients for gastric cancer.
This study has several limitations. First, the number of enrolled patients was small. Second, we could not evaluate the inter-observer agreement of the pathologists. Third, we did not take a biopsy of the incisura angularis, which could result in down-grading of histology. However, our prospective study showed the feasibility of applying endoscopic scores using NBI and NFM, and the high-risk scores correlate well with high OLGA and OLGIM staging. Further studies applying these endoscopic scores for large screening populations and evaluating the actual incidence of gastric cancer during long-term follow-up of high-risk patients are needed.
In conclusion, we developed an endoscopic score for gastric atrophy and intestinal metaplasia using NBI-NFM, and the endoscopic scores showed a strong correlation with OLGA/OLGIM staging. Thus, it could be a practical alternative to taking multiple tissue biopsies.