Address of the study center: University Medical Center, 215 Hong Bang, District 5, Ho Chi Minh City, Vietnam.
Dr Naomi Uemura, Department of Gastroenterology, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655 Japan. Email: email@example.com
Background And Aims: The aims of the present study were to evaluate the role of moderate-to-severe endoscopic gastric atrophy (EGA) on predicting Operative Link on Gastritis Assessment (OLGA) gastritis stage, and to assess the association of high-stage OLGA gastritis with gastric neoplasia in patients with non-ulcer dyspepsia.
Methods: A cross-sectional study was carried out on 280 dyspeptic outpatients. EGA was assessed according to the Kimura–Takemoto classification. Gastritis stage was established according to the OLGA staging system and gastric neoplasia was assessed according to the Vienna classification. The pathologists who read the specimens were kept blind to the endoscopic results.
Results: The mean age of patients was 46.1 years (range 20–78 years) with a male-to-female ratio of 1:1. High-stage gastritis (e.g. stage III or IV) was confirmed in 13 (4.6%) patients. All of these patients were more than 40 years-of-age (P = 0.01), had Helicobacter pylori infection (P = 0.0006) and moderate-to-severe EGA (P < 0.001). Low-grade dysplasia was found in seven patients: 4/13 (30.7%) with high-stage gastritis versus 3/267 (1.1%) with low-stage gastritis (P < 0.001). Six of these patients had moderate-to-severe EGA (P = 0.048). The sensitivity, specificity, positive predictive value and negative predictive value of this endoscopic finding in high-stage gastritis diagnosis were 100%, 57.7%, 10.3% and 100%, respectively.
Conclusions: OLGA high-stage gastritis was associated with gastric dysplasia and was mostly diagnosed in patients with moderate-to-severe EGA. The absence of this endoscopic finding could effectively rule out the possibility of having high-stage gastritis.
A recent advance in the histopathology of gastritis is the replacement of the traditional definition of gastric atrophy, “loss of glands”, with the new definition of gastric atrophy as the “loss of appropriate glands”. By this definition, intestinalized glands represent atrophy when the metaplastic change involves the entire length of the original glandular unit and is considered as metaplastic atrophy. The application of the new definition has resulted in a high level of agreement among gastrointestinal pathologists trained in different cultural contexts.1 As there is obvious evidence that the severity and the extent of gastric atrophy relate to different risk levels of gastric cancer,2–6 an international group of gastroenterologists and pathologists (Operative Link on Gastritis Assessment [OLGA]) has developed a system of histologically reporting gastritis by combining the semi-quantitative scoring scale of the updated Sydney system with the new definition of gastric atrophy. This system expresses the extent of gastric atrophy in terms of gastritis staging. In populations with different risk levels of gastric cancer, the OLGA gastritis stage mirrors the gastric cancer incidence and can identify a subgroup of high-risk patients.7–9 Even in high-risk regions, however, the proportion of this subgroup is very low and taking systemic map biopsies routinely can be a burden. The endoscopic gastric atrophy (EGA) described by Kimura and Takemoto has been reported to be associated with the risk of gastric cancer.2,4,5 This endoscopic evaluation has also been shown to correlate with the histological atrophy according to the traditional definition.10,11 The present study aims (i) to evaluate the role of EGA assessment on predicting OLGA gastritis stage; and (ii) to evaluate the association of high-stage OLGA gastritis with gastric neoplasia in patients with non-ulcer dyspepsia.
The present study was a prospective cross-sectional study carried out at the University Medical Center of Ho Chi Minh City, Vietnam. Between March 2008 and April 2009, we enrolled dyspeptic outpatients who had indications of upper gastrointestinal endoscopy. The patients gave informed consent and information regarding familial history of gastric cancer and smoking status. Exclusion criteria were history of gastric resection, reflux esophagitis, gastric and duodenal ulcer. A total of 282 patients satisfied the criteria and systemic map biopsies were taken. In two patients, the specimens were not qualified enough for pathological examination and were excluded. The remaining 280 patients (142 men and 138 women; mean age, 46 years; range, 20–78) were studied.
All of the endoscopic examinations were carried out and assessed by one experienced endoscopist (DTQ) who had been trained to evaluate EGA at the International Medical Center of Japan. Olympus video scopes (model GIF-160; Olympus, Tokyo, Japan) were used. The endoscopic mucosal atrophy was evaluated according to the location of the endoscopic atrophic border described by Kimura and Takemoto.10 This atrophic border is the boundary between the pyloric and fundic gland regions, which is endoscopically recognized by the difference in color and height of the gastric mucosa between two sides of the border. There are three grades of EGA: marked (O2–O3), moderate (C3–O1) and mild (C1–C2). Six specimens were taken from each patient: five specimens for pathological examination were taken from specific locations according to the updated Sydney system;12 the sixth specimen used for rapid urease test was taken from the greater curvature of the antrum.
The location where each specimen was taken was recorded for pathological assessment. Biopsy samples were fixed in formalin 10% and sent to the Department of Surgical Pathology, University Medical Center of Ho Chi Minh City for processing. Sections were cut at 5 µm and stained with Giemsa and hematoxylin–eosin. Two pathologists (HML and TSN), blinded to any clinical and endoscopic information, jointly examined all the specimens and reached a consensus on the score of each of the considered histological variables. Gastric atrophy was defined as the “loss of appropriate glands”. 1 In each single biopsy, atrophy was scored as a percentage of atrophic glands. Non-metaplastic and metaplastic atrophy were considered together. For each biopsy sample, atrophy was scored on a four-tiered scale (no atrophy = 0%, score = 0; mild atrophy = 1–30%, score = 1; moderate atrophy = 31–60%, score = 2; and severe atrophy > 60%, score = 3). The OLGA stage resulted from the combination of the overall “antrum score” with the overall “corpus score”.13
Helicobacter pylori diagnosis
The local rapid urease test used in the present study has been confirmed to have the same accuracy as other validated tests for H. pylori diagnosis, such as 14C breath test (PYtest, Charlottesville, VA, USA) and PyloriTek (Serim Research Corp, Elkhart, IN, USA).14,15 Cases were considered H. pylori positive (Hp+ve) if the bacteria were histologically detected and/or the local rapid urease test was positive.
spss software (version 13.0, SPSS, Chicago, IL, USA) was used. Fisher's exact test and Spearman's rank correlation coefficient were applied. A P-value < 0.05 was considered significant.
The demographic and endoscopic characteristics of patients in the present study are presented in Table 1. The rate of H. pylori infection was 49.6%. A total of 83% (232/280) had OLGA gastritis stage 0 and stage I (Fig. 1). There were 13 (5%) patients with high-stage gastritis (8 in stage III and 5 in stage IV). All of these patients were older than 40 years-of-age (Fisher's exact test, P = 0.012) (Fig. 2) and had H. pylori infection (Fisher's exact test, P < 0.001). We could not find any relationships between OLGA gastritis stage and sex, smoking as well as a familial history of gastric cancer. The severity of EGA significantly correlated with that of OLGA gastritis stage as presented in Table 2 (Spearman correlation coefficient = 0.6, P < 0.001). All of the patients with high-stage OLGA gastritis had moderate-to-severe EGA (Fisher's exact test, P < 0.001). Using moderate-to-severe EGA as the diagnostic criterion for high-stage gastritis, the sensitivity, specificity, positive predictive value and negative predictive value were 100% (95% CI 75.3–100%), 57.7% (95% CI 51.5–63.7%), 10.3% (95% CI 5.6–17%), and 100% (95% CI 97.6–100%), respectively. There were 95 patients who were older than 40 years-of-age and had H. pylori infection in the present study (28 with mild EGA and 67 with moderate-to-severe EGA). In this subgroup of patients, the positive predictive value increased to 19.4% (95% CI 10.8–30.9%). There were seven patients (2.5%) with low-grade dysplasia (3 in stage I, 3 in stage III and 1 in stage IV according to the OLGA gastritis system). All the dysplastic lesions were not endoscopically visible and were detected by systemic map biopsies according to the updated Sydney system. Dysplastic lesions were frequently detected in patients with high-stage gastritis: 4/13 (30.7%) patients with high-stage gastritis versus 3/267 (1.1%) patients with low-stage gastritis (i.e. stage 0–II; Fisher's exact test P = 0.0001; OR = 39.1; 95% CI 6.1–270.8). Dysplastic lesions were also clustered in patients with moderate-to-severe EGA: 6/126 (4.76%) with moderate-to-severe EGA versus 1/154 (0.65%) with mild EGA (Fisher's exact test P = 0.048; OR = 7.7; 95% CI 0.9–170.9).
Table 1. Demographic and endoscopic characteristics
46.1 ± 10.5
Male : female
Familial history of gastric cancer (first degree relatives with gastric cancer)
Helicobacter pylori positive
Endoscopic gastric atrophy
Table 2. The association between endoscopic gastric atrophy and Operative Link on Gastritis Assessment gastritis stage
Operative Link on Gastritis Assessment gastritis stages
EGA, endoscopic gastric atrophy.
The southern area of Vietnam, where this study was carried out, has a moderate incidence of gastric cancer. The age-standardized rate per 100 000 is 16.5 in males.16 The gastritis stage of patients in the present study who were under 40 years-of-age was almost between those in the low-risk and high-risk regions.7 Therefore, the result of the present study suggests that OLGA gastritis staging parallels the gastric cancer risk in our population. However, there was a difference between our result and those from other moderate-risk regions; we found a higher proportion of patients with gastritis stage I–II and no patients with high-stage gastritis, whereas Rugge et al. reported a lower proportion of patients with stage I–II, and a few patients with high-stage gastritis in Hong Kong and Taiwan. Gastric atrophy is more severe among patients with H. pylori infection and tends to increase when the infection is prolonged.17 The present study confirmed that high-stage gastritis is significantly associated with H. pylori infection and advanced age as reported in previous studies and in other populations.8,9 It has been reported that the atrophic progression is not invariable and only appeared in a subgroup of patients with H. pylori. More importantly, all of the new cases of gastric cancer developed in this subgroup.18 Therefore, other factors, such as H. pylori's genetic diversity, environmental factors and host genetic susceptibility, have been suggested to be related to the outcomes.19 The identification of the risk factors of atrophic progression is crucial for developing prevention and surveillance programs for gastric cancer.
Regarding the association between gastritis stages and endoscopic finding, Rugge et al. reported that all the gastric neoplasia were in OLGA stage III–IV, whereas all of the gastric ulcers were in stage II–III and a majority of duodenal ulcers were in stage 0–I.8 The present study showed that gastric dysplasia also clustered in high-stage gastritis (P < 0.001). Satoh et al. also reported that the gastritis stages in patients with early gastric cancer were significantly higher than those in patients with gastric and duodenal ulcers; 83% of cases with early gastric cancer were in stage III–IV, whereas 83% of cases with duodenal ulcers were in stage 0–I.9 This data explains why the risk of gastric cancer in patients with gastric ulcer is higher than that in patients with duodenal ulcers.2,4,20 Studies from populations with different risk levels of gastric cancer, both from the East and the West, uniformly showed that gastric neoplasia clustered in high-stage gastritis; therefore, patients with high-stage gastritis might be good candidates for a potentially cost-effective surveillance program for detecting early gastric cancer, especially in regions where the prevalence of gastric cancer is not high enough to recommend a population-based screening program. A 12-year clinicopathological follow-up study also showed that gastritis patients could be confidently stratified and managed according to their different cancer risks based on OLGA-staging and H. pylori status.21 Recently, the intestinal metaplasia staging system (operative link on gastric intestinal metaplasia assessment [OLGIM]) has been developed.22 Atrophy in the OLGA is replaced by intestinal metaplasia in OLGIM. This system has been reported to considerably increase interobserver agreement and might result in a smaller and better-defined subpopulation of patients at risk of gastric cancer compared with the OLGA. However, as intestinal metaplasia might be seriously underestimated when taking biopsies according to the updated Sydney system,23 the assessment of OLGIM stage requires an extensive mapping biopsy, which makes this system more difficult to apply in routine clinical practice.
Although non-ulcer dyspepsia is very common in clinical practice, there has been no consensus on the assessment of gastric cancer risk and the surveillance programs. We have reported an incidence of gastric cancer of 4.7% (21/445) among patients with non-ulcer dyspepsia who had H. pylori infection in an 8-year follow-up study in Japan.2 Therefore, identifying patients with high-risk factors is obviously essential. The assessment of EGA is simple and can be established based on standard endoscopic images. There are now also enhanced endoscopic techniques, such as narrow band imaging and i-scan, which make the assessment of this finding much easier. In the present study, we found that the moderate-to-severe EGA had a high sensitivity and negative predictive value for the diagnosis of high-stage gastritis. More than half of the patients in the present study would have been effectively excluded from taking systemic map biopsies if this criterion had been applied. As the prevalence of high-stage gastritis is very low, even in high-risk populations,7 the positive predictive value of this endoscopic finding was also low. The specificity of this finding was just 57.7%, which means that many patients with moderate-to-severe EGA might have OLGA gastritis stages 0–II, and the assessment of EGA cannot replace pathological gastritis staging as the gold standard of atrophy. Because previous studies have shown that moderate-to-severe EGA is related to a high risk of developing gastric cancer,2,4 adding OLGA gastritis staging could further stratify these patients into subgroups with different risk levels of developing gastric cancer.
Regarding dysplastic lesions, Kokkola et al. reported that 68% (57/84) of mild dysplastic lesions in the stomach had no visible endoscopic findings and were only detected by random biopsy specimens.24 Low-grade dysplastic lesions in the present study, not surprisingly, also shared the same characteristics. The detection and surveillance of these lesions are crucial, as a recent study, which is based on data from the Dutch nation-wide histopathology registry, reported that the annual incidence of gastric cancer was 0.6% in the first 5 years.25 Interestingly, the present study showed that 85.7% (6/7) of the dysplastic lesions, like high-stage gastritis, also clustered in patients with moderate-to-severe EGA (P = 0.028). Although moderate-to-severe EGA has been shown to be a risk factor of gastric cancer in several studies,2,4,5 the pathological results of the present study showed that patients with this endoscopic finding could be further stratified into subgroups with different risk levels of gastric cancer. In our opinion, a detailed baseline pathological examination should be carried out in all of these patients, so that individualized follow-up frequencies can be defined for each subgroup.
To conclude, moderate-to-severe EGA has a high sensitivity and negative predictive value for high-stage OLGA gastritis. As gastric neoplastic lesions cluster in patients with high-stage gastritis, this endoscopic finding could select the subgroup of patients who will benefit from taking systemic map biopsies and the appropriate candidates for a potentially cost-effective surveillance program in regions with low-to-moderate incidence of gastric cancer.
We thank Dr Junichi Akiyama, Dr Hung Le and our staff at the Department of Endoscopy and Department of Surgical Pathology, University Medical Center at Ho Chi Minh City for their great support.