Observational Study Open Access
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 14, 2021; 27(18): 2238-2250
Published online May 14, 2021. doi: 10.3748/wjg.v27.i18.2238
Standard vs magnifying narrow-band imaging endoscopy for diagnosis of Helicobacter pylori infection and gastric precancerous conditions
Jun-Hyung Cho, Seong Ran Jeon, So-Young Jin, Suyeon Park
Jun-Hyung Cho, Seong Ran Jeon, Digestive Disease Center, Soonchunhyang University Hospital, Seoul 04401, South Korea
So-Young Jin, Department of Pathology, Soonchunhyang University Hospital, Seoul 04401, South Korea
Suyeon Park, Department of Medical Biostatistics, Soonchunhyang University Hospital, Seoul 04401, South Korea
ORCID number: Jun-Hyung Cho (0000-0003-2075-2333); Seong Ran Jeon (0000-0001-6970-9737); So-Young Jin (0000-0002-9900-8322); Suyeon Park (0000-0002-6391-557X).
Author contributions: Cho JH was involved in the study design, performing the study, data collection and analyses, writing and revising the manuscript; Jeon SR and Jin SY were involved in the study design and revising the manuscript; Park S was involved in statistical analyses; all of the authors approved the final version of the manuscript.
Supported by the Soonchunhyang University Research Fund, No. 20200023.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of Soonchunhyang University Hospital (No. SCHUH 2016-05-001).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declare that they have no competing interest.
Data sharing statement: The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.
STROBE statement: The authors have read the STROBE Statement checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jun-Hyung Cho, MD, PhD, Associate Professor, Digestive Disease Center, Soonchunhyang University Hospital, No. 59 Daesagwan-ro, Yongsan-gu, Seoul 04401, South Korea. chojhmd@naver.com
Received: January 27, 2021
Peer-review started: January 27, 2021
First decision: March 29, 2021
Revised: March 31, 2021
Accepted: April 23, 2021
Article in press: April 23, 2021
Published online: May 14, 2021

Abstract
BACKGROUND

Advances in endoscopic imaging enable the identification of patients at high risk of gastric cancer. However, there are no comparative data on the utility of standard and magnifying narrow-band imaging (M-NBI) endoscopy for diagnosing Helicobacter pylori (H. pylori) infection, gastric atrophy, and intestinal metaplasia.

AIM

To compare the diagnostic performance of standard and M-NBI endoscopy for H. pylori gastritis and precancerous conditions.

METHODS

In 254 patients, standard endoscopy findings were classified into mosaic-like appearance (type A), diffuse homogenous redness (type B), and irregular redness with groove (type C). Gastric mucosal patterns visualized by M-NBI were classified as regular round pits with polygonal sulci (type Z-1), more dilated and linear pits without sulci (type Z-2), and loss of gastric pits with coiled vessels (type Z-3).

RESULTS

The diagnostic accuracy of standard and M-NBI endoscopy for H. pylori gastritis was 93.3% and 96.1%, respectively. Regarding gastric precancerous conditions, the accuracy of standard and M-NBI endoscopy was 72.0% vs 72.6% for moderate to severe atrophy, and 61.7% vs. 61.1% for intestinal metaplasia in the corpus, respectively. Compared to type A and Z-1, types B+C and Z-2+Z-3 were significantly associated with moderate to severe atrophy [odds ratio (OR) = 5.56 and 8.67] and serum pepsinogen I/II ratio of ≤ 3 (OR = 4.48 and 5.69).

CONCLUSION

Close observation of the gastric mucosa by standard and M-NBI endoscopy is useful for the diagnosis of H. pylori gastritis and precancerous conditions.

Key Words: Endoscopy, Magnifying narrow-band imaging, Helicobacter pylori, Gastric atrophy, Intestinal metaplasia, Pepsinogen

Core Tip: In Correa’s model of gastric carcinogenesis, Helicobacter pylori infection, gastric atrophy and intestinal metaplasia are linked to gastric cancer development. The low level of serum pepsinogens was known to be highly associated with extensive atrophic gastritis. High-resolution and magnifying narrow-band imaging (M-NBI) facilitate the detailed examination of gastrointestinal mucosa. However, there was no comparative data regarding the usefulness of standard and M-NBI endoscopy for H. pylori infection and gastric precancerous conditions. We found the significant relationship between endoscopic mucosal patterns and degree of gastric precancerous conditions (moderate to severe gastric atrophy and serum pepsinogen I/II ratio of ≤ 3). These results seem to be valuable for identifying a group at risk of gastric cancer using high quality endoscopy.



INTRODUCTION

The global prevalence of Helicobacter pylori (H. pylori) infection is reportedly > 50%[1]. In the H. pylori–infected stomach, chronic active inflammation of the mucosa becomes persistent, leading to gastric atrophy and intestinal metaplasia (IM)[2]. According to Correa’s model of gastric carcinogenesis, gastric atrophy and IM are linked to progression to gastric cancer[3]. Advanced gastric atrophy and IM are considered to be precancerous conditions because they correlate with gastric carcinogenesis[4-6]. Accurate diagnosis of gastric precancerous conditions is essential for identifying patients at risk of gastric cancer[7].

Narrow-band imaging (NBI) is an innovative optical method that facilitates detailed examination of the gastric mucosa[8]. Furthermore, magnifying NBI (M-NBI) endoscopy with 80-fold magnification can visualize the fine mucosal structure and microvessels[9]. M-NBI endoscopy can be used to diagnose H. pylori infection and classify gastritis by histological severity[10]. Recent improvements in the resolution (> 1 million pixels) of gastrointestinal endoscopy have enhanced image quality, facilitating characterization of the gastric mucosal pattern[11]. Close observation of the gastric corpus mucosa by standard endoscopy without magnification enables prediction of H. pylori gastritis[12]. Moreover, the severity of gastric atrophy and IM differ according to the endoscopic mucosal pattern. In a systematic review, standard endoscopy was effective as an alternative method for diagnosing H. pylori infection[13]. However, there are no comparative data on the utility of standard and M-NBI endoscopy for diagnosing H. pylori infection, gastric atrophy, and IM.

In this study, we evaluated the diagnostic performance of standard and M-NBI endoscopy for H. pylori infection and advanced gastritis, and investigated the association between the endoscopic mucosal pattern and gastric precancerous conditions.

MATERIALS AND METHODS
Patients and study design

From June 2016 to April 2020, we prospectively enrolled patients who underwent gastroscopy for epigastric symptoms, diagnostic work-up for gastric neoplasia, and gastric cancer screening. Before endoscopic examination, all patients had the informed consents about the evaluation of H. pylori infection status and gastric precancerous conditions. We performed a complete blood cell count, blood chemistry assays, coagulation test, chest X-ray, and electrocardiogram. The exclusion criteria were: Age < 20 or > 80 years, anemia, severe systemic disease, current use of proton pump inhibitors, history of H. pylori eradication, and history of gastric surgery. The study protocol was approved by the Institutional Review Board of our hospital (SCHUH 2016-05-001) and was registered at ClinicalTrials.gov (NCT04489030).

Endoscopic equipment and procedure

Endoscopic procedures were performed using a high-resolution endoscope (GIF-H260Z, H290Z; Olympus, Tokyo, Japan). The whole stomach was examined in a routine manner by a single experienced endoscopist (Cho JH). First, we performed close-up observation of the mucosal patterns at the greater curvature of the middle or lower corpus via non-magnified white-light imaging in structural enhancement mode A5. We captured endoscopic images while maintaining a distance of ≤ 10 mm between the endoscope tip and mucosal surface. We previously classified abnormal mucosal patterns using a simple standard endoscopy technique (Figure 1)[12]. When a regular arrangement of numerous minute red dots (normal pattern) was absent, abnormal patterns were categorized as mosaic-like appearance (type A), diffuse homogenous redness (type B), or irregular redness with groove (type C). After completing the mucosal examination by standard endoscopy, the greater curvature side of the gastric corpus was observed by M-NBI. Before the procedure, a soft black hood was attached to the endoscope tip to fix the distance between the endoscope tip and mucosal surface to about 2 mm. When white-light endoscopic image was magnified 80-fold (Supplementary Figure 1), we pressed the NBI button on the handle for the enhanced visualization of mucosal structures and microvessels[14]. NBI was set in enhancement mode A7 and color mode 2. Next, we classified the M-NBI still images as normal or one of three abnormal patterns according to Yagi’s classification (Figure 2)[15]. A regular arrangement of collecting venules (RAC) and honeycomb-like subepithelial capillary network was considered a normal pattern. If RAC was not visualized by M-NBI endoscopy, abnormal mucosal patterns were classified as regular round pits with polygonal sulci (type Z-1), more dilated and linear pits without sulci (type Z-2), or loss of gastric pits with coiled vessels (type Z-3). In cases of mixed mucosal patterns, the most prominent was reported after discussion with another expert endoscopist (Jeon SR).

Figure 1
Figure 1 Normal and three abnormal mucosal patterns in the gastric corpus by standard endoscopy. A: Normal pattern, numerous minute red dots; B: Type A, mosaic-like appearance; C: Type B, diffuse homogenous redness; D: Type C, irregular redness with grooves.
Figure 2
Figure 2 Micromucosal patterns in the gastric corpus observed by magnifying narrow-band imaging endoscopy. A: Normal pattern characterized by regular arrangement of collecting venules and honeycomb-like subepithelial capillary network; B: Type Z-1, regular round pits with polygonal sulci; C: Type Z-2, more dilated and linear pits without sulci; D: Type Z-3, loss of gastric pits with coiled microvessels.
Evaluation of H. pylori infection and gastric precancerous conditions

To increase the H. pylori detection rate, a biopsy was taken from the greater curvature of the gastric corpus. H. pylori infection status was confirmed by rapid urease test (Pronto Dry; Gastrex Sarl, Gilly les Citeaux, France) or molecular test (Seeplex® H. pylori-ClaR ACE Detection; Seegene Inc., Seoul, South Korea). For the histological assessment of glandular atrophy and IM, biopsy specimens were obtained from the lesser curvature of the gastric antrum and corpus. The specimens were fixed in 10% formalin and embedded in paraffin wax, and 5-μm sections were stained with hematoxylin and eosin. The gastric atrophy was defined as loss of glandular tissue and scored on a four-point scale in accordance with the updated Sydney System[16]. The degree of atrophy was classified as mild (1-2), moderate (3-4), or severe (5-6) by summing the scores of the antrum (score 0-3) and corpus (score 0-3). IM was diagnosed by the presence of goblet cells in foveolar epithelium[17]. The pathological examination was performed by an expert pathologist (Jin SY), who was blinded to the patients’ data and endoscopic findings.

Before endoscopy, blood samples were collected during a 12-h fasting period. Blood samples were immediately centrifuged at 4 °C and stored at -70 °C until required. Serum pepsinogen (PG) I and PG II levels were measured by latex turbidimetric immunoassay (HiSens; HBI, Anyang, South Korea), and the PG I/II ratio was calculated[18]. A serum PG I level of ≤ 70 ng/mL and PG I/II ratio of ≤ 3 are highly associated with extensive atrophic gastritis[19]. A cutoff PG I/II ratio of ≤ 3 was used to assess the risk of gastric precancerous conditions.

Statistical analysis

Continuous data are presented as means and standard deviations and categorical data as numbers and percentages. The Pearson chi-squared test or linear-by-linear association was used to analyze categorical data. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the two endoscopic classifications were compared by McNemar test. Diagnostic performance was assessed by computing area under the curve (AUC) values. The adjusted odds ratios (ORs) of endoscopic mucosal patterns for predicting gastric precancerous conditions were calculated by logistic regression analysis. Statistical analysis was conducted using SPSS software (version 19.0; IBM Corp., Armonk, NY, United States). A value of P < 0.05 was considered indicative of statistical significance.

RESULTS
Characteristics of the study population

A total of 254 patients was eligible for the study (Table 1). The mean age was 45.9 (± 14.6) years and the proportion of male patients was 46.9%. The most frequent endoscopic findings were chronic active gastritis (53.1%), peptic ulcer (4.3%), gastric neoplasia (9.8%), and non-neoplastic polyp (7.5%). Current H. pylori infection was confirmed in 64.2% of the patients. According to the degree of gastric atrophy, 117 patients (66.9%) were classified into the none/mild atrophy group, 37 (21.1%) into the moderate atrophy group, and 21 (12.0%) into the severe atrophy group. Regarding the extent of IM, 115 patients (65.7%) had no IM in the antrum or corpus, and 22 (12.6%) and 38 (21.7%) patients had IM in the antrum only and in both the antrum and the corpus, respectively. The mean serum PG I and PG II concentrations and PG I/II ratio were 64.4 ± 32.4 ng/mL, 20.5 ± 14.7 ng/mL, and 4.11 ± 2.2, respectively. The mean serum gastrin concentration was 123.1 ± 149.9 pg/mL.

Table 1 Baseline characteristics of the study population.
Characteristic n = 254
Age (yr, mean ± SD) 45.9 ± 14.6
Sex, male, n (%) 119 (46.9)
Indication for endoscopy, n (%)
Screening 132 (52.0)
Dyspepsia 42 (16.5)
Abdominal pain47 (18.5)
Other33 (13.0)
Endoscopic diagnosis, n (%)
Peptic ulcer11 (4.3)
Gastric neoplasia 25 (9.8)
Non-neoplastic polyp 19 (7.5)
Chronic active gastritis 135 (53.1)
Helicobacter pylori infection, n (%)163 (64.2)
Gastric atrophy, n (%)
None/mild 117 (66.9)
Moderate37 (21.1)
Severe 21 (12.0)
Intestinal metaplasia, n (%)
None115 (65.7)
Antrum only22 (12.6)
Corpus 38 (21.7)
Serum PG (ng/mL, mean ± SD)
PG I64.4 ± 32.4
PG II20.5 ± 14.7
PG I/II ratio 4.11 ± 2.2
Serum gastrin (pg/mL, mean ± SD)123.1 ± 149.9
Diagnostic performance of standard and M-NBI endoscopy

By standard endoscopy, the H. pylori infection rate was 91.5% (n = 43/47) for type A, 100% (n = 84/84) for type B, and 100% (n = 23/23) for type C (Table 2). By M-NBI endoscopy, the proportion of H. pylori infection was 97.6% (n = 124/127) for type Z-1, 96.3% (n = 26/27) for type Z2, and 100% (n = 7/7) for type Z-3. The rate of advanced gastritis was calculated according to the endoscopic mucosal pattern among 175 patients whose samples were subjected to pathologic examination. Moderate to severe gastric atrophy and the presence of IM in the corpus were considered to be advanced gastritis with a high risk of gastric cancer. By standard endoscopy, the proportions of patients with moderate to severe atrophy were 27.3% (n = 9/33) for type A, 74.0% (n = 37/50) for type B, and 50.0% (n = 10/20) for type C. By M-NBI endoscopy, the proportions of patients with moderate to severe atrophy were 45.9% (n = 39/85) for type Z-1, 88.2% (n = 15/17) for type Z-2, and 100% (n = 4/4) for type Z-3. If the gastric mucosal pattern was normal, however, the rate of moderate to severe atrophy was 2.8% (n = 2/72) by standard endoscopy and 0% (n = 0/69) by M-NBI endoscopy. Similarly, the rate of IM in the corpus differed significantly between normal and abnormal mucosal patterns by both standard (types A+B+C, P < 0.001) and M-NBI endoscopy (types Z-1+Z-2 +Z-3, P < 0.001).

Table 2 Helicobacter pylori gastritis, gastric atrophy, and intestinal metaplasia observed by standard and magnifying narrow-band imaging endoscopy.
EndoscopyH. pylori gastritis
Gastric atrophy
Intestinal metaplasia
Negative
Positive
None/mild
Moderate/severe
None/antrum
Corpus

(n = 91)
(n = 163)
(n = 117)
(n = 58)
(n = 137)
(n = 38)
Standard
Normal87/100 (87.0)13/100 (13.0)70/72 (97.2)2/72 (2.8)71/72 (98.6)1/72 (1.4)
Type A4/47 (8.5)43/47 (91.5)24/33 (72.7)9/33 (27.3)25/33 (75.8)8/33 (24.2)
Type B0/84 (0)84/84 (100)13/50 (26.0)37/50 (74.0)24/50 (48.0)26/50 (52.0)
Type C0/23 (0)23/23 (100)10/20 (50.0)10/20 (50.0)17/20 (85.0)3/20 (15.0)
M-NBI
Normal87/93 (93.5)6/93 (6.5)69/69 (100)0/69 (0)69/69 (100)0/69 (0)
Type Z-13/127 (2.4)124/127 (97.6)46/85 (54.1)39/85 (45.9)59/85 (69.4)26/85 (30.6)
Type Z-2 1/27 (3.7)26/27 (96.3)2/17 (11.8)15/17 (88.2)7/17 (41.2)10/17 (58.8)
Type Z-30/7 (0)7/7 (100)0/4 (0)4/4 (100)2/4 (50.0)2/4 (50.0)

For the diagnosis of H. pylori gastritis, the sensitivity of standard endoscopy was 92.0%, while the specificity was 95.6%, the PPV was 97.4%, the NPV was 87.0%, and the accuracy was 93.3%. The sensitivity of M-NBI endoscopy was 96.3%, while the specificity was 95.6%, the PPV was 97.5%, the NPV was 93.5%, and the accuracy was 96.1%. The sensitivity of M-NBI endoscopy was significantly greater than that of standard endoscopy (P = 0.016; Table 3). For the diagnosis of moderate to severe atrophy, the sensitivity of standard endoscopy was 96.6%, while the specificity was 59.8%, the PPV was 54.4%, the NPV was 97.2%, and the accuracy was 72.0%. The sensitivity of M-NBI endoscopy was 100%, while the specificity was 59.0%, the PPV was 54.7%, the NPV was 100%, and the accuracy was 72.6%. For diagnosis of IM in the corpus, the sensitivity of standard endoscopy was 97.4%, while the specificity was 51.8%, the PPV was 35.9%, the NPV was 98.6%, and the accuracy was 61.7%. The sensitivity of M-NBI endoscopy was 100%, while the specificity was 50.4%, the PPV was 35.8%, the NPV was 100%, and the accuracy was 61.1%. The diagnostic performance of standard and M-NBI endoscopy for moderate to severe atrophy and IM in the corpus was not significantly different. The AUC values of standard and M-NBI endoscopy were 0.93 and 0.96 for H. pylori gastritis, 0.78 and 0.79 for moderate to severe atrophy, and 0.74 and 0.75 for IM in the corpus, respectively.

Table 3 Diagnostic performance of standard and magnifying narrow-band imaging endoscopy for Helicobacter pylori gastritis, gastric atrophy, and intestinal metaplasia.
EndoscopyDiagnosisSensitivity (%)Specificity (%)PPV (%)NPV (%)Accuracy (%)AUC
StandardH. pylori gastritis92.0a95.697.487.093.30.93
Moderate to severe atrophy96.659.854.497.272.00.78
Intestinal metaplasia, corpus 97.451.835.998.661.70.74
M-NBIH. pylori gastritis96.3a95.697.593.596.10.96
Moderate to severe atrophy10059.054.710072.60.79
Intestinal metaplasia, corpus10050.435.810061.10.75
Association of endoscopic patterns with gastric precancerous conditions

Table 4 shows the relationships between endoscopic mucosal patterns and a serum PG I/II ratio of ≤ 3. Among 127 patients who underwent measurement of serum PG concentration, 44.1% (n = 56) had a PG I/II ratio of ≤ 3. Of patients with a normal mucosal pattern, the rate of a PG I/II ratio of ≤ 3 was 2.6% (n = 1/39) by standard endoscopy and 0% (n = 0/36) by M-NBI endoscopy. By standard endoscopy, the rate of a PG I/II ratio of ≤ 3 was 36.0% (n = 9/25) for type A, 71.7% (n = 33/46) for type B, and 76.5% (n = 13/17) for type C. By M-NBI endoscopy, the rate of a PG I/II ratio of ≤ 3 was 54.2% (n = 39/72) for type Z-1, 86.7% (n = 13/15) for type Z-2, and 100% (n = 4/4) for type Z-3. The rate of a PG I/II ratio of ≤ 3 differed between normal and abnormal mucosal patterns according to two endoscopic classifications (P < 0.001).

Table 4 Serum pepsinogen I/II ratio according to gastric mucosal pattern observed by standard and magnifying narrow-band imaging endoscopy.
PG I/II ratioStandard (%)
M-NBI (%)
NormalType AType BType CNormal
Type Z-1
Type Z-2
Type Z-3
> 3 (n = 71)38/39 (97.4)16/25 (64.0)13/46 (28.3)4/17 (23.5)36/36 (100)33/72 (45.8)2/15 (13.3)0/4 (0)
≤ 3 (n = 56)1/39 (2.6)9/25 (36.0)33/46 (71.7)13/17 (76.5)0/36 (0)39/72 (54.2)13/15 (86.7)4/4 (100)

The age- and sex-adjusted ORs of abnormal mucosal patterns for gastric precancerous conditions were calculated by logistic regression analyses (Table 5). Compared to type A, the OR for moderate to severe atrophy was 5.56 [95% confidence interval (CI): 2.07-14.92, P = 0.001] for types B+C. Compared to type Z-1, the OR for moderate to severe atrophy was 8.67 (95%CI: 1.82–41.30, P = 0.007) for types Z-2+Z-3. Compared to type A, the OR for a serum PG I/II ratio of ≤ 3 was 4.48 (95%CI: 1.60-12.54, P = 0.004) for types B+C. Compared to type Z-1, the OR for a serum PG I/II ratio of ≤ 3 was 5.69 (95%CI: 1.19-27.18, P = 0.029) for types Z-2+Z-3. For IM in the corpus, there was no significant difference in abnormal mucosal patterns according to two endoscopic classifications (type A vs types B+C, P = 0.189; and type Z-1 vs types Z2+Z-3, P = 0.162, respectively).

Table 5 Logistic regression analysis of the associations of endoscopic mucosal patterns with gastric precancerous conditions.
Mucosal patternModerate to severe atrophy
Intestinal metaplasia, corpus
PG I/II ratio ≤ 3
OR (95%CI)
P value
OR (95%CI)
P value
OR (95%CI)
P value
Standard0.0010.1890.004
Type A 1 (ref.)1 (ref.)1 (ref.)
Type B + C 5.56 (2.07-14.92)1.96 (0.72-5.33)4.48 (1.60-12.54)
M-NBI0.0070.1620.029
Type Z-1 1 (ref.)1 (ref.)1 (ref.)
Type Z-2 + Z-3 8.67 (1.82-41.30)2.12 (0.74-6.07)5.69 (1.19-27.18)
DISCUSSION

Pathological examination plays an important role in the diagnosis of gastrointestinal diseases by endoscopy[20]. Endoscopists tend to focus on detecting abnormal lesions, and macroscopic examination by conventional endoscopy has limitations for characterizing mucosal lesions. Therefore, the final diagnosis of detected lesions is dependent on the pathological report. To identify those at risk of gastric cancer, the presence of precancerous conditions is evaluated by non-targeted protocol-guided biopsies in different areas[21]. However, multiple mucosal biopsies increase medical costs and the procedure time.

High-resolution and high-magnification endoscopy facilitate detailed examination of the gastrointestinal mucosa[22]. In 2002, Yagi et al[23] used magnifying endoscopy to show that RAC was a characteristic finding in the normal stomach without H. pylori infection. Abnormal mucosal patterns without RAC were classified as Z-1 to Z-3 in accordance with the degree of mucosal damage in the H. pylori–infected stomach[24]. Anagnostopoulos et al[25] demonstrated that magnifying endoscopic examination could identify normal gastric mucosa, H. pylori–related gastritis, and gastric atrophy in a Western population. The severity of chronic gastritis has been investigated based on the micro-mucosal patterns observed by M-NBI[26]. Kanzaki et al[27] reported that groove-type mucosa had a higher grade of atrophy and IM compared to foveolar-type mucosa. However, M-NBI endoscopy is not available in all endoscopy units and training program is required prior to its clinical application[28].

In a previous study, we determined H. pylori infection status by close observation of the gastric corpus mucosa by high-resolution endoscopy without magnification[12]. The sensitivity and specificity of all abnormal patterns for predicting H. pylori infection were 93.3% and 89.1%, respectively, and the overall diagnostic accuracy was 91.6%. The inter- and intra-observer agreement for the endoscopic mucosal patterns was 91.7% and 90.0%, respectively. This simplified endoscopic technique has enabled reliable prediction of gastric H. pylori infection in other countries[29,30]. Recent advances in endoscopic imaging technology have increased the diagnostic accuracy for H. pylori infection[13,31]. To our knowledge, this is the first study comparing diagnostic performance between standard and M-NBI endoscopy for H. pylori infection. We also analyzed the degree of gastric atrophy, IM, and serum PG levels according to two endoscopic classifications. A decrease in the serum PG I/II ratio is reportedly a non-invasive marker for advanced corpus gastritis and gastric cancer[32,33]. Wang et al[34] reported that the serum PG level was strongly correlated with the Operative Link for Gastritis Assessment (OLGA) and Operative Link for Gastric Intestinal Metaplasia (OLGIM) stage. Therefore, a serum PG I/II ratio of ≤ 3 is a serologic marker of gastric precancerous conditions.

Except for sensitivity, the diagnostic performance for H. pylori infection was similar between standard and M-NBI endoscopy. Seven patients with a normal pattern by standard endoscopy had H. pylori infection. In contrast, these patients were classified as type Z-1 (n = 4), type Z-2 (n = 2), and type Z-3 (n = 1) by M-NBI endoscopy. This is likely because of the ability of M-NBI to examine the superficial microanatomy of the areae gastricae and the pit pattern, which is not possible with standard endoscopy. Nevertheless, standard endoscopy may enable detection of H. pylori infection in routine clinical practice (diagnostic accuracy, 93.3%).

For diagnosis of gastric atrophy and IM, standard and M-NBI endoscopy had excellent sensitivity, NPV (> 95%), and AUC (> 0.7) values; however, the specificity and PPV values were not acceptable. According to the Kimura–Takemoto classification, gastric atrophy progresses more frequently along the lesser curvature than the greater curvature of the corpus[35]. When atrophic change extends into the anterior and posterior mucosa of the corpus, the topographic pattern of IM becomes more diffuse throughout the stomach[36]. In this study, we focused on the mucosal pattern in the greater curvature of the gastric corpus. Atrophy of the gastric mucosa and transformation to IM occur last at the greater curvature of the corpus, hampering evaluation of gastric precancerous conditions. A systematic screening protocol for the stomach has been developed to ensure high-quality endoscopic evaluation[37], and enables detection of gastric atrophy and IM in various areas of the stomach[38]. Using NBI without magnification, Pimentel-Nunes et al[39] created an endoscopic classification to grade gastric IM; a tubulovillous mucosal pattern was highly concordant with histological IM. However, image-enhanced endoscopic findings for diagnosing and grading gastric atrophy remain to be established[40].

The H. pylori–infected stomach exhibits redness and swelling of the corpus mucosa[41,42]. Histologically, H. pylori infection causes infiltration of neutrophils and mononuclear cells in the gastric mucosa[43]. In biopsy specimens, lymphoid hyperplasia is a specific immunological reaction to H. pylori infection[44]. During long-term H. pylori–induced inflammation, the presence of lymphoid hyperplasia decreased with increasing severity of gastric atrophy and IM. In young women, nodular gastritis is induced by H. pylori infection and lymphoid follicles in nodular lesions can be detected histologically[45]. Miyamoto et al[46] reported that nodular gastritis showed a lower atrophic score than other forms of H. pylori–related gastritis. Similarly, we postulated that a swollen areae gastricae would be present in early stage H. pylori infection. Therefore, type A was used as a reference for evaluating the risk of gastric cancer according to abnormal mucosal pattern by standard endoscopy. By M-NBI endoscopy, type Z-1 was reported to correlate with less severe gastric atrophy and IM compared to other types[27]. In this study, types A and B+C showed significantly different serum PG I/II ratios (3.82 vs 2.74, P = 0.007), as did types Z-1 and Z-2+Z-3 (3.24 vs 2.28, P = 0.005). However, there was no significant difference among abnormal mucosal patterns for IM in the corpus. Based on the multifocal patterns of IM, an endoscopic mucosal examination of the entire stomach is recommended[47]. Marcos et al[48] reported that NBI endoscopic grading of IM was useful for risk assessment of early gastric neoplasia.

This study had several limitations. First, we did not evaluate the severity of gastric atrophy and IM using the OLGA and OLGIM staging systems. Second, only H. pylori treatment-naïve patients were enrolled. Therefore, the results may be not be applicable to endoscopic surveillance after H. pylori eradication. Finally, this study was conducted in a single center. A multicenter trial involving endoscopists with varying levels of experience is required to confirm the reliability of the results.

CONCLUSION

In conclusion, close observation of the gastric corpus mucosa by standard and M-NBI endoscopy enables diagnosis of H. pylori infection and gastric precancerous conditions. Furthermore, our results suggest an association of endoscopic mucosal patterns with moderate to severe atrophy and a serum PG I/II ratio of ≤ 3.

ARTICLE HIGHLIGHTS
Research background

In Correa’s model of gastric carcinogenesis, Helicobacter pylori (H. pylori) infection, gastric atrophy and intestinal metaplasia (IM) are linked to gastric cancer development. The low level of serum pepsinogens (PG) was known to be highly associated with extensive atrophic gastritis.

Research motivation

High-resolution and magnifying narrow-band imaging (M-NBI) facilitate the detailed examination of gastrointestinal mucosa. M-NBI endoscopy can be used to diagnose H. pylori infection and classify gastritis by histological severity. Moreover, recent improvements in the resolution (> 1 million pixels) of gastrointestinal endoscopy have enhanced image quality, facilitating characterization of the gastric mucosal pattern. Close observation of the gastric corpus mucosa by standard endoscopy without magnification enables prediction of H. pylori gastritis and precancerous lesions.

Research objectives

To date, there was no comparative data regarding the usefulness of standard and M-NBI endoscopy for H. pylori infection and gastric precancerous conditions. We compared the diagnostic performance of standard and M-NBI endoscopy for H. pylori gastritis and precancerous conditions.

Research methods

In total, 254 patients who underwent gastroscopy were prospectively enrolled. Standard endoscopy findings of the gastric mucosal surface were classified into mosaic-like appearance (type A), diffuse homogenous redness (type B), and irregular redness with groove (type C). Gastric mucosal patterns visualized by M-NBI endoscopy were classified as regular round pits with polygonal sulci (type Z-1), more dilated and linear pits without sulci (type Z-2), and loss of gastric pits with coiled vessels (type Z-3). We evaluated the utility of the two endoscopic classifications for the diagnosis of H. pylori gastritis, gastric atrophy, IM, and a serum PG I/II ratio of ≤ 3.

Research results

The diagnostic accuracy of standard and M-NBI endoscopy for H. pylori gastritis was 93.3% and 96.1%, respectively. Regarding gastric precancerous conditions, the diagnostic accuracy of standard and M-NBI endoscopy was 72.0% vs 72.6% for moderate to severe atrophy, and 61.7% vs 61.1% for IM in the corpus, respectively. Compared to type A and Z1, types B+C and Z-2+Z-3 were significantly associated with moderate to severe atrophy [odds ratio (OR) = 5.56, P = 0.001; OR = 8.67, P = 0.007] and a serum PG I/II ratio of ≤ 3 (OR = 4.48, P = 0.004; OR = 5.69, P = 0.029).

Research conclusions

Close observation of the gastric corpus mucosa by standard and M-NBI endoscopy enables diagnosis of H. pylori infection and gastric precancerous conditions. Furthermore, our results suggest an association of endoscopic mucosal patterns with moderate to severe atrophy and a serum PG I/II ratio of ≤ 3.

Research perspectives

By gastric mucosal observation in detail, optical diagnosis of H. pylori–related gastritis may be achieved in real time. In the future, a multicenter trial is required to confirm the reliability of our results.

Footnotes

Manuscript source: Invited manuscript

Specialty type: Gastroenterology and hepatology

Country/Territory of origin: South Korea

Peer-review report’s scientific quality classification

Grade A (Excellent): 0

Grade B (Very good): B, B, B

Grade C (Good): 0

Grade D (Fair): 0

Grade E (Poor): 0

P-Reviewer: Peruhova M, Ulaşoğlu C S-Editor: Yan JP L-Editor: A P-Editor: Wang LL

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