Helicobacter pylori (Hp) is considered to be a major risk factor for gastric cancer. Other risk factors1 include age, sex, smoking, ethnicity, family history, and so on. At present, it is recommended that once a Hp infection is found, unless for some special reason, it needs to be treated or eradicated.2 In the past, Japanese endoscopists found that the appearance of a large number of red spots in the stomach body was a characteristic discovery in the normal stomach, indicating that the gastric mucosa was not infected with Hp. The discovery was called the “regular arrangement of collecting venules” (RAC).3 Therefore, Japanese endoscopists began to use the RAC to make a preliminary diagnosis of whether the patient was infected with Hp. Many studies have shown that the RAC has good diagnostic efficacy for a normal stomach without an Hp infection.4,5 However, some studies suggest that the effectiveness of this prediction may be affected by the age of the patient or other factors.6 Therefore, we conducted this meta-analysis to systematically evaluate the value of RAC in predicting Hp-negative stomach, and to analyze the value of this predictive efficiency in different ages and ethnicities.

The study selection process is shown in Fig. 1. A total of 242 studies were identified by the database search. After removing 67 duplicates and 134 studies that were not consistent with our purpose, 41 studies were assessed. Among these, 12 studies were conference summaries, 2 studies were duplicates, 12 studies did not provide relevant information, and one study lacked a negative control group. Ultimately, 14 studies with 4070 patients 3–6,12–21were included. The QUADAS-II quality assessment for each study is presented in Table 1. There was unclear bias in our included studies, but none of them were excluded from our meta-analysis. The TP, FP, FN, TN and characteristics of each study are presented in Table 2. Subgroup analysis for pooled sensitivity, pooled specificity, PLR, NLR and DOR are presented in Table 3.

Figure 1.

Flow diagram.

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The pooled sensitivity, pooled specificity, PLR, NLR, DOR and AUC for RAC in predicting an Hp-negative stomach were 0.80 (0.67–0.89), 0.97 (0.93–0.98), 24.8 (12.2–50.8), 0.21 (0.12–0.36), 120 (47–301) and 0.97 (0.19–1.00), respectively. The I2 value was 0.00 (0.00–100.00) for the summary sensitivity and 0.00 (0.00–100.00) for the summary specificity (Fig. 2). Subgroup analysis was conducted for age and ethnicity. The p values of age and ethnicity were greater than 0.05 (Table 3). The pooled estimates for Asian population were as follows: sensitivity, 0.79 (0.67–0.92); specificity, 0.96 (0.93–0.99); Similarly, the corresponding values for other ethnicity were 0.82 (0.60–1.00), 0.99 (0.98–1.00). The RAC had a sensitivity of 0.75 (0.53–0.89), specificity of 0.96 (0.91–0.98), PLR of 18.8 (8.5–41.3), NLR of 0.26 (0.13–0.54) and DOR of 72 (24–213) for patients older than 50. The corresponding values were 0.85 (0.73–0.93), 0.98 (0.91–1.00), 45.3 (8.9–231.6), 0.15 (0.08–0.29) and 303 (55–1669) for patients younger than 50 years of age.

Figure 2.

The I2 for heterogeneity in pooled sensitivity and specificity.

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Sensitivity analysis (Fig. 3) was performed to ensure that our study results were not overly affected by any single included study. Results with and without outliers were compared. The results showed that removing a study19 increased the pooled sensitivity from 0.80 to 0.83 and the DOR from 120 to 136 but reduced the PLR from 24.8 to 23.8 and the NLR from 0.21 to 0.18. The pooled specificity in both cases was 0.97. The I2 for heterogeneity for the pooled sensitivity and specificity in both cases was still 0.00. These results show that our meta-analysis was reliable. Deeks’ funnel plots (Fig. 4) suggest that no evidence of publication bias was found in this meta-analysis.

Figure 3.

Sensitivity analysis of RAC sign in diagnosing non-Hp infection.

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Figure 4.

Publication bias evaluation for RAC sign in diagnosing non-Hp infection.

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According to our systematic meta-analysis, the RAC is a valuable sign for predicting patients without an Hp infection, and the summary result did not show significant heterogeneity. When subgroup analysis was conducted, the performance between Asian and other ethnicities and between the two age groups did not show significant differences. Na S 20showed that the sensitivity and specificity of the RAC in the diagnosis of non-HP infection may be affected by the patient's age. We only divided the age group into two parts; thus, the results of this study need to be further confirmed. In addition, the low H. pylori infection rates in Western countries, combined with the high predictive efficiency of the RAC in predicting an HP-negative stomach, suggest that the RAC can be used to reduce the number of gastric mucosal biopsies performed in this population.

The RAC is considered to be a very simple and effective sign for determining gastric mucosa with non-HP infection. We found that endoscopic physicians observed the RAC from different locations, although a gastritis study in Kyoto, Japan showed that the RAC was generally observed at the lesser curvature and the lower part of the stomach.22 However, Cho14 suggested that it is best to observe the RAC in the corpus at the greater curvature. There is no unified point of view about this matter. Therefore, the best observation position for the RAC remains to be determined. Machado18 suggested that any disease with mucosal infiltration caused by inflammatory cells can lead to the absence of the RAC. However, there is a lack of research to confirm whether this claim is correct, whether it is related to IBD, whether it is affected by the degree of gastritis and the kind of drugs used (PPI, H2 receptor inhibitors, and antibiotics). Machado18 showed that the RAC can be recovered in some patients after the removal of the Hp infection. However, this phenomenon has not been explained. Therefore, it is worth discussing the relationship between the recovery of the RAC and the risk of gastric cancer. Perhaps through further prospective studies, the model for the prediction and treatment of HP infections can be improved.

Our article is the first to systematically evaluate the value of the sign in predicting a Helicobacter pylori-negative stomach. However, the limitations of our study should be recognized. First, we excluded conference abstracts, which may have led to some bias. Second, some detailed descriptions were not found, leading to an “unclear” assessment in QUADAS-II. Third, given the limited information, including multiple age groups and some other factors were not analyzed. Further studies should focus on the patient-relevant characteristics with or without the RAC and whether this sign is associated with gastric cancer.

The RAC is a valuable sign for predicting patients without an Hp infection. No significant differences were found between ethnicities and ages with regard to the predictive ability of the RAC.

They are no conflict of interest.