doi: 10.2169/internalmedicine.0552-22
Intern Med Advance Publication
http://internmed.jp【 ORIGINAL ARTICLE 】

Clinicopathological Features and the Prevalence of Oxyntic
Gland Neoplasm: A Single-center Retrospective Study
Hikari Asahara 1, Toshitatsu Takao 2, Yumiko Asahara 3, Masakyo Asahara 3,
Douglas Motomura 4, Hiroya Sakaguchi 2, Tetsuya Yoshizaki 2, Nobuaki Ikezawa 2,
Madoka Takao 2, Yoshinori Morita 2, Takashi Toyonaga 2, Masato Komatsu 5, Ryoji Kushima 6
and Yuzo Kodama 2

Abstract:
Objective We explored the clinicopathological characteristics and disease frequency of oxyntic gland neoplasms (OGNs).
Methods We retrospectively evaluated the data of patients pathologically diagnosed with OGN at an internal medicine clinic.
Patients A total of 13,240 upper gastrointestinal endoscopies were performed on 7,488 patients between
December 1, 2017, and March 31, 2021.
Results We identified 27 patients with 30 histopathologically confirmed OGNs, yielding a disease frequency of 0.36% (27/7,488). Furthermore, multiple simultaneous lesions were found in 3 of 27 patients(11%). One (3.3%) of the 30 lesions was present in the antrum, whereas the remaining lesions occurred in
the body of the stomach. Nine (33%) of the 27 patients had no history of Helicobacter pylori infection,
whereas the remaining 18 (67%) were either currently or had been previously infected. Nevertheless, 27/30
lesions (90%) still occurred in non-atrophied regions. After endoscopic treatment, a histopathological examination of the resected specimens revealed submucosal infiltration in 8 (44%) of the 18 lesions; however, noneof the lesions showed submucosal desmoplasia. For all patients with submucosal involvement, only observation was performed. There were no recurrent lesions found on follow-up.
Conclusion The period prevalence of OGN was 0.36%, which is much higher than previously reported. The
discovery of a small submucosal appearing lesion with a faded yellow or white color and dilated microvasculature, especially in a non-atrophic area of the stomach, should raise suspicion for an OGN, which can be endoscopically managed.
Key words: oxyntic gland neoplasm, Gastric adenocarcinoma of fundic-gland type, oxyntic gland adenoma(Intern Med Advance Publication)(DOI: 10.2169/internalmedicine.0552-22)

atrophy, intestinal metaplasia, and then carcinoma. Thus, thevast majority of differentiated gastric adenocarcinoma cases
have an intestinal phenotype and are subsequently named“intestinal-type gastric carcinoma”. However, recent advances in histochemical and immunohistological techniques
have revealed that some gastric neoplasms retain a gastric

Background
Differentiated gastric adenocarcinoma was once thought
to have a stereotypical development cascade, from chronic
gastritis (often Helicobacter pylori-related), progressing to１

Department of Gastroenterology, Kobe Red Cross Hospital, Japan, ２ Department of Gastroenterology, Kobe University Graduate School of
Medicine, Japan, ３ Asahara Clinic, Japan, ４ Division of Gastroenterology, Department of Medicine, University of British Columbia, Canada, ５ Division of Diagnostic Pathology, Kobe University Graduate School of Medicine, Japan and ６ Department of Pathology, Shiga University of Medical Science Hospital, Japan
Received: July 4, 2022; Accepted: December 14, 2022; Advance Publication by J-STAGE: February 15, 2023
Correspondence to Toshitatsu Takao, t.takao1234@gmail.com

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Table 1. Patient Characteristics.

Age (yr)
MeanMedianSex
Male
FemaleH. pyloriNaïveCurrently infected
previously infected
Atropic gastritis
No
Yes
Antacid
None
PPI
Other
Multiple lesions
No
Yes

n=27

%

67
69 [45-84]

-

15
12

56
44

9
4
14

33
15
52

9
18

33
67

17
9
1

63
33
3.7

24
3

89
11

phenotype without associated metaplasia. This group includes the foveolar, pyloric, and fundic gland types, and iscollectively termed “gastric-type gastric adenocarcinoma”.
In 2007, Tsukamoto et al. reported the first case of a gastric adenocarcinoma with chief cell differentiation (1). In
2010, Ueyama et al. collected similar cases and proposed
the term “gastric adenocarcinoma of the fundic gland type”(GA-FG; chief cell-predominant type) as a new entity ofgastric adenocarcinoma (2). Subsequently, several cases ofgastric-type gastric adenocarcinoma began to be described incase reports and series (3-6). Aatur et al. recommended thename “oxyntic gland polyp/adenoma” in lieu of “gastricadenocarcinoma with chief cell differentiation” owing to its
benign behavior (3). The 2017 Japanese Classification of
Gastric Carcinoma (15th edition) categorized GA-FG as a
special type of gastric cancer that includes not only tumors
invading the submucosa but also intramucosal neoplasms (7). The 2019 World Health Organization (WHO)Classification of Gastric Carcinoma (5th edition) stated thatneoplasms retained within the mucosa are defined as oxyntic
gland adenomas (OGAs), whereas lesions demonstrating
submucosal invasion are referred to as GA-FG (3, 8). In
2020, Ushiku et al. reported 26 cases of oxyntic gland neo-

a

b

c

d

e

Figure 1. Endoscopic findings of multiple lesions of OGN. (a) Conventional endoscopic image. Pale,elevated lesions were observed on the posterior wall of the fundus (yellow and green arrows). (b)Conventional endoscopic image (yellow arrow). (c) Narrow-band imaging with slight magnification(yellow arrow). (d) Conventional endoscopic image (green arrow). (e) Narrow-band imaging withslight magnification (green arrow).
2

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Table 2. Lesion characteristics.

Location
Upper
MiddleLower
Cross sectional location
Greater curvature
Lesser curvature
Anterior wall
Posterior wall
Macroscopic size (mm)MeanMedianMacroscopic typeElevated
Flat
Depressed
Color of lesion
NormalYellow
Faded
Red
Distribution of lesion
Atrophic area
Non-atrophic area

n=30

%

26
3
1

87
10
3

15
3
6
6

50
10
20
20

3.7
3 [2-8]

-

16
13
1

53
43
3.3

5
12
12
1

17
40
40
3

3
27

10
90

The present study examined consecutive cases of OGN ina real-world outpatient cohort and clarified the prevalence
and clinicopathological features of these lesions.

Methods
Between December 1, 2017, and March 31, 2021, patient
records at a high-volume outpatient internal medicine andendoscopy clinic (Asahara Clinic, Akashi, Japan) were reviewed retrospectively. Patients with a diagnosis of OGN via
upper gastrointestinal endoscopy were included in the cohort. Screening tests were performed using high-definition
endoscopy with the GIF-HQ290 or GIF-H290Z (Olympus,
Tokyo, Japan). Conscious sedation was administered in allcases, and carbon dioxide gas was used for insufflation. All
screening tests were performed after thoroughly cleaning thestomach using the waterjet function (OFR-2; Olympus). All
endoscopists had a clinical experience of over 10 years.
All biopsy specimens taken in this study were reevaluated by a gastrointestinal pathologist with expertise in
OGNs (co-author RK). The diagnosis of OGN was confirmed based on the nuclear and cellular atypia of highly
differentiated columnar cells mimicking the fundic glandcells, as well as immunostaining results, such as findings of
MUC5AC, MUC6 pepsinogen-I, and H+/K+-ATPase. In Japan, OGNs are regarded as low-grade cancers, and all patients diagnosed with these lesions were offered endoscopic
treatment. Patients amenable to treatment were referred to
Kobe University Hospital (Kobe, Japan). After resection, a
specialized pathological evaluation was performed in the
Department of Diagnostic Pathology of Kobe University
Graduate School of Medicine. The period prevalence of
OGN was defined as the number of patients with detected
OGNs divided by the total number of patients undergoing
upper gastrointestinal endoscopy over the study period. The
presence of atrophy was noted when areas of faded gastricmucosa and vascular transparency were examined underwhite-light endoscopy. The extent of atrophy was classified
according to the Kimura and Takemoto classification (22).
The presence or absence of H. pylori infection at the time oflesion detection was evaluated using the endoscopic findingsof the background gastric mucosa according to the Kyoto
classification (23). Along with the results of their most recent urea breath test, patients’ H. pylori infection status wasclassified as naive, current, or previous (24).
Endoscopic management varied depending on the lesion
size and location. Endoscopic mucosal resection using a
cap-fitted endoscope (EMRC) was performed for cases inwhich the attending endoscopist deemed margin-negative en
bloc resection (complete R0 resection) feasible with thistechnique (25). In cases where en bloc resection via EMRC
was expected to be difficult, endoscopic submucosal dissection (ESD) was performed instead (26).

plasms (OGNs) including OGA and GA-FG (9). In addition,
Ueyama et al. proposed the classification “gastric epithelial
neoplasm of fundic gland mucosa lineage”, which included
OGA and GA-FG but also added GA-FGM, as a new classification in 2021 (10). However, to simplify the varied terminology found in the literature, we have elected to use theterm OGN in this paper.
The typical endoscopic finding of OGN is a flat, elevatedlesion with a submucosal appearance, commonly located in
the upper-to-middle third of the stomach. The lesion is often
whitish in color and can contain dilated vessels with branching architecture (5, 11). The stomach itself is usually nonatrophic, and the rates of H. pylori infection in patients with
OGN are relatively low. In terms of immunohistochemistry,
this type of lesion is positive for pepsinogen-I (a chief cellmarker), H+/K+-ATPase (a parietal cell marker), and MUC6
(a mucous neck cell marker), which are all features of agastric-type tumors (12-14). As mentioned above, the clinical features of OGNs are still being elucidated, and the classification is still developing (7-12). The majority of previous
reports were limited to individual case reports or multicenter
series accumulated at tertiary referral centers. This has led to
uncertainty concerning the real-world frequency of
OGNs (8), as previous reports have described the prevalence
at less than 1/10,000 (<0.01%). Furthermore, the relationship with H. pylori infection, association with oral proton
pump inhibitor (PPI) use, frequency of submucosal invasion,and rate of lymph node metastasis have not yet been clarified (8, 11, 12, 14-21).

Ethics approval

This retrospective study was conducted in accordance3Intern Med Advance Publication

DOI: 10.2169/internalmedicine.0552-22

a

b

c

d

Figure 2. Endoscopic findings of oxyntic gland neoplasm (OGN) without H. pylori infection in the
non-atrophic region. (a) Conventional endoscopic image. A pale, subepithelial tumor-like elevatedlesion was observed in the posterior wall of the fundus. A regular arrangement of collecting venules
in the surrounding mucosa was observed. Dilated vessels were seen in the elevated lesion. (b) Imageafter indigo carmine dye spraying. (c) Narrow-band imaging without magnification. (d) Narrow-band
imaging with slight magnification. Mildly dilated crypt opening and slightly enlarged glands werenoted.

with the ethical principles embodied in the Declaration of
Helsinki (Fortaleza revision) and in compliance with the
Ethical Guidelines for Medical and Health Research Involving Human Subjects in Japan.
In addition, this study was approved by the Institutional
Review Board (IRB) of the Public Health Research Foundation (approval number: 21G0002). The requirement for theacquisition of informed consent from patients was waived
because the analysis used anonymous clinical data. We applied the opt-out method to obtain consent using a paperbased notification. The notification was also approved by the
IRB. The authors have no conflicts of interest to declare.

frequency of OGN was determined to be 0.36% (27/7,488)
per patient. The lesion discovery rate per examination administered was 0.23% (30/13,240). The number of gastriccancers other than OGN detected during the same period
was 132 lesions in 122 patients.
Table 1: summarizes the clinical characteristics of the patients diagnosed with OGNs. There were 15 men and 12
women, with an age range of 45-84 (median: 69) years old.
In terms of the H. pylori infection status, 9 of the patientswere naïve, 4 were currently infected, and 14 had been previously infected. Ten (37%) of the 27 patients were using
proton pump inhibitors (PPIs; n=9) and H2 blockers (n=1)
at the time of lesion discovery. The median duration of use
was 646 (35-5,381) days. Three (33%) of the 9 patients who
had taken PPIs had fundic gland polyps at the time of endoscopy. Three (11%) of the 27 patients had multiple OGNs
simultaneously (Fig. 1).
Table 2: shows the lesion characteristics. The lesions
were located in the upper/middle/lower third of the stomach

Results
Between December 1, 2017, and March 31, 2021, a totalof 13,240 upper gastrointestinal endoscopies were performed
on 7,488 patients. In this cohort, 30 lesions in 27 patientswere pathologically diagnosed as OGN. Thus, the disease4

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D

E

F

G

Figure 3. Endoscopic findings of OGN with current H. pylori infection in the atrophic region. (a)Conventional endoscopic image. The surrounding mucosa was atrophic. A whitish, subepithelial tumor-like elevated lesion was observed at the posterior wall of the fundus. Constriction after a biopsy
was seen in the lesion. (b) Dilated vessels were observed on the elevated lesion, extending from theperiphery towards the center of the tumor. (c) Conventional endoscopic image with slight magnification. (d) Narrow-band imaging with slight magnification.

in 26/3/1 case, respectively. The color of the mucosa wasnormal/yellow/faded/red in 5/12/12/1 case, respectively. The
surface mucosal findings included a pale-yellow tone withdilated microvessels coursing towards the center from theedge of the tumor and slight dilation of the glandular ducts(Fig. 2-4). One lesion was located in the antrum (Fig. 5).
Pigmentation was observed in only one lesion. Twenty-sixof 30 lesions were histopathologically diagnosed as OGN
via a biopsy. In two lesions, the diagnosis was made optically due to the tiny size of the lesion preventing sampling.
The final two lesions were discovered incidentally in patients undergoing endoscopic resection. Because they displayed the typical optical features and were in proximity to
the target lesions, a high probability of synchronous OGN
was considered. These lesions were therefore resected endo-

scopically without a biopsy.
Table 3: shows the treatment and pathological characteristics of the 18 resected lesions. The median pathological size
(width) of the 18 lesions was 3.5 mm (2-8 mm). Ten lesions(54%) were intramucosal, whereas 8 (44%) showed submucosal infiltration (Fig. 6). The median size of the tumors
with submucosal infiltration was5 mm (range: 2-8 mm), andthe depth from the lower end of the muscularis mucosae tothe advanced tumor region was 40 to 950 μm. None of theeight lesions with submucosal infiltration showed desmoplasia in the submucosa around the tumor (Fig. 7). No lymphovascular invasion was observed in any lesions with submucosal infiltration. The median Ki-67 index of the endoscopically resected specimens was 1% (range: 1%-8%). All patients with submucosal infiltration were managed conserva5

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a

b

c

d

Figure 4. Endoscopic findings of OGN with previous H. pylori infection in the non-atrophic region.
(a) Conventional endoscopic image. A small, whitish lesion was seen at the greater curvature of theupper third of the stomach. (b) The surrounding mucosa was not atrophic. A whitish, subepithelial
tumor-like elevated lesion was observed. More dilated microvessels were noted at the periphery of thelesion. (c) Narrow-band imaging without magnification. (d) Narrow-band imaging with slight magnification. Slightly dilated crypt opening was observed on the lesion. Dilated microvessels at the periphery were easily recognized under narrow-band imaging magnification.

tively without additional surgical resection, and none developed metastasis during the follow-up period, which ranged
from 61 to 436 (median: 100) days.

noma (5th edition), the exact prevalence of OGNs is unknown (8). A previous report described a frequency of <0.01% (27) as calculated in a cohort of 30,182 individuals
who underwent yearly checkup endoscopies during the study
period. However, this figure was limited by the inclusion ofa considerable number of patients undergoing multiple procedures. Our prevalence rate is presented per person rather
than per procedure, resulting in a more accurate disease frequency. In addition, our rate of 0.36% was considerably
higher than previously reported, likely due to advances inknowledge concerning these lesions and increased experience with the typical features and optical diagnoses.

Discussion
This is the first study to report the prevalence of OGN.
The period prevalence based on the consecutive patients undergoing upper gastrointestinal endoscopy was 0.36% (27/7,488). In addition, our results showed that 11% (3/27) of
the patients had multiple OGNs simultaneously. We believethat if OGNs are recognized by more endoscopists and pathologists, the detection rates will increase, and more accurate disease frequencies will be clarified.

Endoscopic findings

The typical endoscopic presentation of OGN is a yellowish, gently rising, elevated lesion characterized by the dilation of microvessels on the surface (19). The manifesta-

Period prevalence

According to the WHO Classification of Gastric Carci6

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a

b

c

d

Figure 5. Endoscopic findings of OGN found in the antrum. (a) Conventional endoscopic image. A
pale, flat lesion was observed in the posterior wall of the gastric antrum. (b) Image after indigo carmine dye spraying. (c) Narrow-band imaging without magnification. (d) Narrow-band imaging withslight magnification. Dilated microvessels at the periphery of the lesion and slightly enlarged glands
were recognized, which raised suspicion for an OGN.

tions of these characteristics may vary based on the size of
the OGN, with these features gaining prominence as the lesion grows. However, at smaller sizes, we found the lesions
to be flat, with colors ranging from a dull, pale yellow tonormal tones, and microvasculature that runs from the periphery towards the center of the tumor (Fig. 2-5). Furthermore, during observation with narrow-band imaging andmagnification, a mildly dilated crypt opening and slightly
enlarged glands appear to support the presence of an OGN,
especially in smaller lesions (Fig. 4). Xanthomas are examples of lesions that are endoscopically similar to OGNs interms of color. However, their surface is finely granular, andthey do not show dilation of microvessels. Conversely, although dilated microvessels are also observed on the surfaceof neuroendocrine tumors, these lesions are more hemispherical and often occur in a background of autoimmune
gastritis, unlike OGN. Therefore, when a xanthoma-like lesion or a neuroendocrine tumor-like lesion is detected in thestomach without atrophy, the possibility of OGN should beconsidered while conducting a careful optical examination.
H. pylori infection and PPI use

Initially, OGNs were reported to be found only in patients
uninfected by H. pylori; however, later reports revealed thatthey were also present in those who had been previously infected (27, 28).
Of the 27 patients in whom we found lesions, 18 (with 20
lesions) had a history of H. pylori infection and atrophic
gastritis (Table 1). However, 17 of the 20 lesions were
found in the non-atrophic areas. Similar to the reports by
Chiba et al. and Tohda et al., the results of our research suggest that OGNs are tumors that are easily detected in endoscopic, non-atrophic regions, regardless of the history of H.
pylori infection (27, 28).
It has also been reported that the histology of some OGN
cases is similar to that of a fundic gland polyp(FGP) (4, 10). Since FGPs may occur with long-term PPIuse, it has been suggested that there may be a relationship7

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Table 3. Pathological Characteristics of theTreated Lesions.
n=18
En bloc resection rate
ESD
6/6
EMRC
11/12
Complications
Perforation0
Postoperative bleeding
0
Pathological tumor size（mm）
Mean
3.9Median3.5 [2-8]
Depth
M
10
SM
8
Horizontal margin
Positive0
Negative
17
Unclear1
Vertical margin
Positive0
Negative
17
Unclear1
Vascular Invasion
Yes
0
No
18
Lymphatic invation
Yes
0
No
18
MUC5AC
Positive
2
Negative
16
MUC6
Positive
17
Negative
1
Pepsinogen
Positive
15
Negative
3
H+/K+-ATPase
Positive
13
Negative5
Ki-67（%）
Mean
2.2Median1 [1-8]

fined to the mucosa, whereas the remaining 8 (44%, 8/18)
had infiltrated the submucosa. In this study, we did not findany atypia in the foveolar epithelium suggesting GA-FGM.
In our cohort, the median size of intramucosal tumors was
3.9 mm, and the median size of the 8 submucosal infiltrating lesions was 5 (2-8) mm. Chiba et al. reported that 80%
of 10 lesions in 9 patients who underwent ESD exhibited
submucosal infiltration (median tumor diameter: 7 mm,
width: 2-20 mm) (26). Thus, OGNs appear to be unique tumors that frequently infiltrate the submucosa, despite theirvery small size.
There is an ongoing discussion as to the relationship between OGA and GA-FG. In the WHO classification (Page83, oxyntic adenoma section), the description states that “amorphological continuum” exists from OGA to GA-FG (8).
In addition, Ueyama et al. proposed that OGA, GA-FG, and
GA-FGM be regarded as gastric epithelial neoplasms of afundic-gland mucosa lineage (10). They suggested that OGA
and GA-FG were low-grade epithelial neoplasms and that
OGA should be regarded as an intramucosal phase of GAFG.
Furthermore, whether or not the submucosal extension of
GA-FG is true invasion remains controversial. In the present
study, no desmoplastic reaction at the advanced part of thetumor was observed in any of the eight cases with submucosal infiltration (Fig. 7). The Ki-67 labelling indexes werevery low (median value: 1, width: 1-8) in all endoscopicallyresected OGNs (Table 3). This held true even in lesions with
submucosal involvement. These findings may support the
hypothesis that GA-FG shows prolapse-type infiltration oftumors (3, 9) rather than typical submucosal invasion. This
may explain the lack of high-risk histologic features or metastatic disease in both our cohort and the available literature. Considering these findings, GA-FG without stromal reaction may be considered a prolapse-type change in OGA
into the submucosa.

%
100
92
0
0
56
44
0
94
6
0
94
6
0
100
0
100
11
89
94
6
83
17

Treatment outcomes

72
28

Of the 27 patients (with 30 OGN) discovered in the outpatient setting, 17 (with 20 lesions) underwent endoscopic
treatment at Kobe University Hospital. The remaining 10 patients selected conservative management; this cohort included patients whose lesions were too small to be certainof the presence of a residual lesion after a biopsy and thosewith a significantly advanced age. Of the 20 lesions managed endoscopically, 13 were treated by EMRC and 7 ESD.
The en-bloc resection rates were high in both techniques(92% and 100% for EMRC and ESD, respectively) (Table 3). Given the simplicity and efficacy of EMRC, this may
be the method of choice for treating these small lesions andavoiding the technical difficulty and time requirements of
submucosal dissection. In two lesions there was no evidenceof a residual tumor on the final histology, so we concluded
that they had been completely resected at the time of the biopsy, given their small size.
In the present study, all of the OGNs with submucosal in--

between the development of OGN and oral administration of
PPI (19, 29). Chan et al. reported that, in a 12-case series, 7patients had received acid suppressive therapy (6 with PPIs
and 1 with H2 blockers) (29). In our study, 37% (10/27) ofpatients were taking antacids (9 with PPIs and 1 with H2blockers) (median duration of administration: 646 [35-5,381]
days) (Table 1). However, of these nine patients, only three
had concomitant FGP, which calls into question the role of
FGP in the pathogenesis of OGN.
Pathological findings

A pathological study showed that 10 lesions were con8

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a

b

c

d

e

f

Figure 6. An OGN resected by endoscopic submucosal dissection. (a) Conventional endoscopic image. A slightly elevated lesion was observed on the posterior wall of the fundus. The anal side in thelesion was reddish, and the glands were slightly enlarged. In addition, there seemed to be regenerativeor post-inflammatory tissue from previous erosions. (b) Conventional endoscopic image with slightmagnification. (c) Narrow-band imaging without magnification. (d) Narrow-band imaging with slightmagnification. (e) Ulcer bed after the lesion was endoscopically resected en bloc. (f) The resected
specimen.

filtration were endoscopically suspected to be intramucosal
lesions prior to resection. We believe it is difficult to optically diagnose submucosal infiltration. OGNs frequently infiltrate the submucosa at a very small size. This may lend
merit to the strategy of offering endoscopic resection to any

detected OGN, regardless of diameter. However, given theindolent nature of these lesions, there is also interest in conservative management (2, 14). In our present study, the eightpatients with submucosal infiltration all elected to receive
continued observation without additional surgical interven9

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a

b

c

d

e

f

g

h

i

Figure 7. Histopathological findings of the OGN shown in Figure 6. (a) Hematoxylin and Eosin(H&E) staining (low-power field). The superficial layer was covered with non-neoplastic mucosa.
Tumor glands proliferated mainly in the middle and deep layers of the mucosa. (b) H&E staining(high-power field). There were tumor glands below the muscularis mucosa. The advanced part of thetumor appeared to have slipped through the muscularis mucosa and infiltrated the submucosa. No
desmoplastic reaction was observed at the advanced part of the tumor. (c) MUC5AC was positive only
in non-neoplastic foveolar epithelial cells on the surface layer. (d) MUC6 was diffusely positive in thetumor. (e) Pepsinogen-I was also diffusely positive in the tumor in the middle and deep layers. (f) H+/
K+-ATPase was positive in the vicinity of the glandular neck. (g) Desmin staining (low-power field)
clearly showed where the muscularis mucosa was. (h) Desmin staining (high-power field) showed thatthe tumor had infiltrated the submucosa without destroying the muscularis mucosa. (i) The Ki-67
index was slightly positive in the tumor. The adjacent regenerative epithelium and inflammatory cells
also seemed to have a positive Ki-67 index on the surface mucosa after erosion healing.

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tion. Thus far, there has been no evidence of recurrence, although the long-term outcomes will need confirmation. The
optimal management strategy for OGN is thus still underconsideration.
Finally, we propose that OGA and GA-FG be collectively
referred to as OGN. The primary reason for this is that thetwo entities appear to have significant clinical overlap. Second, distinguishing between OGA and GA-FG is often impossible endoscopically or with a biopsy specimen. Finally,
the WHO classification and Japanese gastric cancer classification use the term “GA-FG” in different ways, which may
add additional confusion to already complicated nomenclature.

Data availability
The datasets analyzed in this study are available from the corresponding author on reasonable request.

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Limitations

Several limitations associated with the present study warrant mention. First, this was a single-center retrospective
study. The population was only 7,488 people, which may
not be completely representative of the complete Japanese
populace and may limit generalizability in certain cases.
However, the average age of the patients in this study was
only 67 years old. We therefore do not suspect the prevalence rate was falsely elevated due to a significantly elderly
cohort. Second, our follow-up period may have been too
limited to make definitive comments on recurrence rates andlymph node metastases. We are continuing to actively follow
the patients in the cohort to further investigate these questions. Future multicenter studies including a larger databaseof cases will help document these seemingly rare occurrences. Third, this study was unable to fully investigate therelationship between oral PPI use and the development of
OGNs. While we were able to confirm oral PPI use in patients diagnosed with OGNs, this must be compared to theusage rate in all patients who underwent endoscopy in theclinic. As the association between OGNs and PPI use has
been a controversial topic, larger-scale prospective studies
will be necessary to answer these questions.

Conclusion
Our study revealed the period prevalence of OGN to be
0.36%, which is much higher than previously reported in theliterature. These lesions are frequently endoscopically managed with high success rates. Further investigation into thenatural history, risk factors, and post-treatment prognosis isrequired.
The authors state that they have no Conflict of Interest (COI).
Statements
Author contributions
HA and TT collected the data, performed assessments, andwrote the manuscript. TT revised the manuscript as a corresponding author. YA, MA, DM, HS, TY, NI, MT, YM, TT, MK,
RK, and YK revised the manuscript as co-authors. All authors
read and approved the final manuscript.
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DOI: 10.2169/internalmedicine.0552-22

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