Virchows Archiv (2022) 480:759–769

https://doi.org/10.1007/s00428-022-03286-8

ORIGINAL ARTICLE

The OLGA‑OLGIM staging and the interobserver agreement

for gastritis and preneoplastic lesion screening: a cross‑sectional study
Beatriz E. Salazar1 · Tania Pérez‑Cala1 · Sara Isabel Gomez‑Villegas1 · Laura Cardona‑Zapata1 ·
Sebastián Pazos‑Bastidas1 · Alejandra Cardona‑Estepa1 · Diego Enrique Vélez‑Gómez1 ·
José Armando Justinico‑Castro2 · Andrés Bernal‑Cobo2 · Harold Adrián Dávila‑Giraldo2 ·
Juan Carlos Benítez‑Guerra1,3 · Joaquín Tiberio Valencia‑Cárdenas4 · Edgar de Jesús Ospina5 ·
Rodrigo Castaño‑Llano6 · María Mercedes Bravo7 · Juan Carlos Cataño‑Correa8 · Jovanny Zabaleta9 ·
Alba Alicia Trespalacios‑Rangel10 · Ana María Cock‑Botero11 · Miguel Ignacio Roldán‑Pérez1,2 · Alonso Martínez1

Received: 14 September 2021 / Revised: 4 January 2022 / Accepted: 21 January 2022 / Published online: 28 January 2022
© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022

Abstract
Stomach cancer (SC) incidence and mortality are relevant public health issues worldwide. In Colombia, screening for pre-
neoplastic lesions (PNL) and the presence of H. pylori is not routinely performed. Therefore, the aim of this study was to
evaluate OLGA-OLGIM staging and the interobserver agreement in gastritis and preneoplastic lesions in patients with gas-
troduodenal symptoms from Colombia. A cross-sectional study was conducted in 272 patients with gastroduodenal symptoms.
Gastric biopsies were taken following the Updated Sydney System with the OLGA-OLGIM classification, and the results
were evaluated by two pathologists. Chronic gastritis and PNL were reported in 76% and 24% of the patients, respectively.
Furthermore, 25% of the patients with PNL displayed gastric atrophy (GA) and 75% intestinal metaplasia (IM). Agreement
in the histopathological reading for IM was good, whereas for OLGA was variable, and for the H. pylori quantity was poor.
OLGA-OLGIM stages 0-II were the most frequent (96%), while stage III (4%) and SC (4%) were the least frequent. Age
and coffee consumption were associated with a higher prevalence of PNL. This work determined that 4% of the population
is at high risk of developing SC and would benefit from follow-up studies. Reinforcement of training programs to improve
the agreement in histopathology readings is required.

Keywords OLGA · OLGIM · Histopathology · Gastroduodenal diseases

7
* Beatriz E. Salazar Cancer Biology Research Group, National Cancer Institute,
beatriz.salazar@udea.edu.co Bogotá, Colombia
8
1 Internal Medicine Infectious Disease Section, University
Bacteria & Cancer Group, Department of Microbiology,
of Antioquia, Medellín, Colombia
School of Medicine, University of Antioquia, Medellín,
9
Colombia Department of Integrative Oncology and Department
2 of Pediatrics, Stanley S. Scott Cancer Center, Louisiana State
Department of Pathology, School of Medicine, University
University Health Sciences Center, New Orleans, LA, USA
of Antioquia, Medellín, Colombia
10
3 Infectious Disease Group, Department of Microbiology,
Promedan IPS, Medellín, Colombia
Pontificia Universidad Javeriana, Bogotá, Colombia
4
IPS Universitaria, University of Antioquia, Medellín, 11
Cytology and Pathology Unit, Las Vegas Clinic, Medellín,
Colombia
Colombia
5
Somer Clinic, Rionegro, Colombia
6
Cancer Institute, Las Americas Clinic, Medellín, Colombia

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Introduction
According to the Global Cancer Observatory (GLO-
BOCAN) for 2020, stomach cancer (SC) ranked fifth in
global incidence (5.6%) and fourth in fatality (7.7%) [1].
In Colombia, SC is the third in incidence (7.3%) and first
in mortality (11.7%) [2]. Helicobacter pylori (H. pylori)
is the major risk factor for developing chronic gastritis
(CG) [3]. The infection is asymptomatic in up to 80% of
cases. Since 1994, the International Agency for Research
on Cancer (IARC) has classified H. pylori as a grade I
carcinogen [4].
The gastric carcinogenesis model described by Correa
et al., in 1975, suggests that H. pylori infection, combined
with genetic and environmental factors, induces inflam-
mation of the mucosa (superficial gastritis), and if the
infection-induced damage persists, it progresses into gas-
tric atrophy (GA), intestinal metaplasia (IM; complete or
incomplete), dysplasia (low-grade and high-grade), and
finally to SC [5]. Both GA and IM are considered preneo-
plastic lesions (PNL) and are associated with an increased
risk to develop SC [6].
SC has a poor prognosis due to its asymptomatic nature
and commonly late diagnosis. The 5-year survival rate is
more than 90% when diagnosed in early stages and 4–36%
in late stages [7]. Due to the slow progression of CG to
SC, it is possible to prevent the development of SC with
an early diagnosis and management of PNL [8, 9]. One
strategy towards SC prevention is the early diagnosis of
PNL by using upper gastrointestinal endoscopy (UGE) fol-
lowed by histopathology [10].
Furthermore, several histologic classifications are used
to categorize gastritis and PNLs, including OLGA (Opera-
tive link on Gastritis Assessment) and OLGIM (Opera-
tive Link on Gastritis/Intestinal-Metaplasia Assessment).
These systems are currently used to determine the indi-
vidual risk of SC. Particularly, OLGA classifies gastritis
in stages based on the severity scale from least to most
significant risk (0 to IV), then determines the presence
of GA, and finally gives a percentage of it in each biopsy
[11–15]. OLGIM classifies IM similarly to the OLGA sys-
tem, and has the advantage of greater reproducibility [11,
14]. Some authors found variations in the interobserver
atrophy reading; thus, they recommend complementing
the OLGA with the OLGIM [11, 14, 16, 17].
Some studies have associated OLGA stages III and IV
with the risk of progression to SC. Satoh et al. found a
correlation between OLGA-III or IV with malignancies in
84% of the cases, while stages I or II were associated with
benign lesions [18]. Additionally, Nam et al. described a
tenfold higher risk for developing SC in patients staged
as OLGA-I and 90-fold higher for stage IV [19]. Using
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Virchows Archiv (2022) 480:759–769
gastric biopsies to be studied with the Updated Sydney and
OLGA systems, Martínez et al. diagnosed more cases of
multifocal atrophic gastritis (MAG) (42%) compared with
gastric biopsies taken to be studied without this protocol
(26%) [20].
Therefore, this study aimed to evaluate OLGA-OLGIM
staging and the interobserver agreement in gastritis and pre-
neoplastic lesions screening in patients with gastroduodenal
symptoms from Colombia.
Material and methods
Sample size and eligibility criteria
Sample size was calculated based on the number of patients
undergoing UGE at participating institutions over a period of
4 months (N = 4024 patients). A sample size of 265 partici-
pants with a 95% confidence interval, 80% power, and 5.8%
precision were estimated. Estimation of the sample size was
conducted using the Epidat software v 3.1. Volunteers aged
18 years or older who underwent UGE in seven healthcare
institutions in Antioquia, Colombia during 2016–2018 and
signed the informed consent form were included. Subjects
were excluded if they were taking proton pump inhibi-
tors (PPIs) and histamine H2-receptor antagonists (within
15 days from UGE) or had any kind of antibiotic treatment
within the last month. Individuals with upper gastrointesti-
nal bleeding, anticoagulation therapy, coagulation disorders,
pregnant women, previous upper digestive tract surgery,
severe chronic disease diagnosis (kidney, liver, decompen-
sated heart failure, and decompensated diabetes mellitus),
or radio-chemotherapy were excluded as well.
Biopsy collection
Two hundred seventy-one participants with UGE and one
with gastrectomy were included. Patients had to fast 7 h
before the UGE. Five samples were taken in accordance
with the recommendations of the Updated Sydney System
following a previously established protocol [21]. A sixth
biopsy was taken in cases where a tumor was evident. Each
sample was stored in conical tubes containing 500 µl of 10%
buffered formalin (Protokimica S.A. S®) and transported to
the Cytology and Pathology Unit Healthcare Provider for
processing and reading.
Biopsy processing
The biopsies submerged in 10% buffered formalin (Pro-
tokimica S.A.S®) were placed in an automatic tissue proces-
sor (Thermo Fisher Scientific®, Kalamazoo, MI). Alcohol
Virchows Archiv (2022) 480:759–769
was used for posterior dehydration; clearance was performed
with xylol and then paraffin inclusion was done (Paraplast
Sigma-Aldrich®) to generate a paraffin block. Histological
sections of 4 µm were obtained. Five biopsies were taken
from every participant, and a block was made from each
of them. Two slides with serial sections were made from
each block, one stained with hematoxylin and eosin (H&E
Merck® Darmstadt, Germany) and the other with modi-
fied Giemsa, Diff Quick (RAL Diagnostics and Siemens
Healthineers®).
Biopsy reading
Four expert gastrointestinal pathologists and one resident
(PGY-3) participated in the study. Each biopsy was assessed
by two pathologists. Pathologist reading 1 = H1 and pathol-
ogist reading 2 = H2, respectively. A report was designed
for the histopathological reading of the five slides, which
included the grading of alterations according to the Visual
Analog Scale described by Dixon [15], the Updated Sydney
System, OLGA [21]. OLGIM system for assessment of IM
described by Rugge et al. [21] and Capelle et al. [17]. For the
OLGA and OLGIM (0-IV) staging, the most severe grade
in any reading (H1 and H2) was considered. A sample was
considered positive if H. pylori was identified in at least one
out of ten slides. The Visual Analog Scale (from absent to
severe) was used for H. pylori quantification.
Helicobacter pylori diagnosis
To confirm H. pylori infection, two additional biopsies (one
from the antrum and one from corpus) were taken. The
antrum biopsy was used to perform the urease biochemical
test. Later, the DNA from antrum and corpus biopsies was
extracted, and a standard PCR was performed to amplify the
vacA and ureA genes [22–24].
Statistical analysis
A database was generated using Microsoft Office Access
2013. Data was analyzed using SPSS v. 25.0, Epidat v. 4.2
and Stata v. 15. Means ± standard deviations were used for
continuous variables; categorical variables were presented
as frequencies and percentages. Interobserver agreement
was analyzed using a Cohen’s kappa coefficient (κ) with
a 95% confidence interval. Values < 0.5, between 0.5 and
0.75, and > 0.75 represented poor, good, and excellent agree-
ment, respectively. To identify risk factors associated with
the development of PNL, a Chi-square test bivariate analy-
sis was performed. For the multivariate analysis, a bino-
mial regression was performed. Unadjusted and adjusted
761
prevalence ratios were estimated with 95% confidence
intervals.
Results
Endoscopic diagnosis and H. pylori frequency
A total of 272 patients were included in the analysis (Sup-
plementary Table 1). UGE was performed in 271 and a gas-
trectomy was performed in one. This study included 7.3%
(20/272) asymptomatic and 92.6% (252/272) symptomatic
subjects. The main reported symptoms were epigastralgia
61.8% (168/272), bloating 61% (166/272), dyspepsia 50.4%
(137/272), and belching 50% (136/272). By UGE, normal
mucosa was observed in 4% (912/271) of the patients. A total
of 92% (250/271) of the patients were diagnosed with CG,
34% (92/271) with esophagitis, 28% (77/271) with hiatal her-
nia, and 9% (23/271) with duodenitis. Other lesions such as
duodenogastric reflux, peptic ulcer, Barrett’s esophagus, and
SC were reported with frequencies < 5%. The frequency of
H. pylori was 60% (163/272) for H1, and 64% (175/272) for
H2. The amount of H. pylori for histopathology was higher
in lesser curvature of the antrum (A1) and incisura angula-
ris (I) (Fig. 1). Similar results were obtained by PCR, 58%
(158/272) in the antrum and 61% (166/272) in the corpus.
However, H. pylori detection for urease biochemical test had
a lower frequency, 47% (128/272) in the antrum.
Frequency of histopathological alterations
and degree of severity
GA showed significant differences between H1 and H2
readings. This was not observed for IM, H. pylori detec-
tion, and CG (Table 1). GA and IM were detected mainly
in samples from A1 and I and the prevalence of PNL was
different between H1 and H2 readings, especially for GA
(Table 2). Multifocal GA incidence, both in the antrum and
I, was 79% (22/28) for H1 and 67% (30/45) for H2. For
corpus, 84% (16/19) and 47% (16/34) are for H1 and H2,
respectively. Diffuse atrophy was reported more frequently
by H2. Multifocal IM in the antrum and I was 88% (29/33)
for both readers, and in the corpus was 95% (20/21) for H1
and 78% (18/23) for H2.
OLGA and OLGIM classification
Histopathological results of biopsies showed that 76%
(207/272) from patients had CG and 24% (65) PNL (GA or
IM or both). All CG samples were categorized as OLGA-0.
An additional biopsy of tumor-like lesions was obtained from
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762 Virchows Archiv (2022) 480:759–769

Fig. 1  Helicobacter pylori

frequency assessed by hema-
toxylin–eosin stain. Category
of absent, mild, moderate, or
severe according to a Visual
Analog Scale. A1 (lesser
curvature antrum), A2 (greater
curvature antrum), I (incisura
angularis), C1 (lesser curvature
corpus), C2 (greater curvature
corpus). H1: histopathology
result 1, H2: histopathology
result 2

Table 1  Comparison between H1 and H2 of H. pylori improved. Agreement for OLGA system reading
Finding H1† H2† p*
was variable (Table 4). There were no significant differences
n (%) n (%) between readings for the OLGIM system.

Gastric atrophy 34 (12.5) 55 (20.2) 0.001 Population characterization

Intestinal metaplasia 41 (15.1) 42(15.4) 1.000
Chronic gastritis 263 (96.7) 262 (96.3) 1.000
H. pylori detection 163 (59.9) 175 (64.3) 0.082
†
H1 = histopathology 1; H2 = histopathology 2
*
p value < 0.05 McNemar test
n (total) = 272
four patients. By histopathology, these were classified as SC
(one intestinal type, another diffuse, and the other without
determining the type). The patients were classified according
to the OLGA system as one CG (OLGA-0) and three GA (one
OLGA-I and two OLGA-II). According to the OLGIM system,
one was OLGIM-I and three were OLGIM-II. Figure 2 shows
the spectrum of histopathological findings and classifications
according to OLGA and OLGIM are illustrated in Table 3.
Interobserver agreement (kappa coefficient)
Interobserver agreement was determined for H1 and H2. The
variables evaluated are as follows: GA, GA pattern (diffuse or
multifocal), IM, IM pattern (diffuse or multifocal), amount of
H. pylori, and leukocytes. IM showed the highest agreement.
When comparing the reading of each of the five biopsies with
the general reading (considered positive if feature at least in
one out of five biopsies), the agreement for GA and amount
Sociodemographic and clinical variables in relation to the
presence/absence of PNL are shown in Table 5. The highest
prevalence of PNL was observed in individuals > 46 years
of age, with smoking habit (current or previous), and eating
out. According to the subregion where the samples came
from, no differences were found. Sixteen patients were diag-
nosed with GA and IM was diagnosed in 49 participants.
When comparing gastroduodenal signs-symptoms with
the presence of PNL, no differences were observed. When
evaluating different variables (family history of SC, IM,
gastric ulcers, CG, and having relatives who were previ-
ously diagnosed positive for H. pylori), no differences were
observed in the presence/absence of PNL. The variables
gender, age, smoking history, coffee intake, having relatives
diagnosed with H. pylori, and eating out adjusted by region
were included for bivariate and multivariate analysis. Region
was included as a cluster variable. The results showed that
prevalence of PNL was higher in patients > 46 years old and
coffee drinkers (Supplementary Table 2).
Discussion
Using the Updated Sydney with OLGA-OLGIM systems,
76% (207/272) of the patients were diagnosed with CG,
6% (16/272) with GA, and 18% (49/272) with IM. The

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Table 2  Frequency and severity Sample‡ Atrophy Intestinal metaplasia

of atrophy and metaplasia by
†
sample H1 Severity H2 Severity H1 Severity H2 Severity
n (%) (n) n (%) (n) n (%) (n) n (%) (n)

A1 20 L (17) 31 (11) L (18) 25 L (20) 24 L (19)

(7) M (1) M (12) (9) M (2) (9) M (4)
S (2) S (1) S (3) S (1)
A2 9 L (7) 27 L (17) 12 L (9) 12 L (11)
(3) M (1) (9) M (10) (4) M (1) (4) M (1)
S (1) S (0) S (2) S (0)
I 19 L (11) 33 (12) L (23) 22 L (12) 22 L (16)
(6) M (5) M (9) (8) M (6) (8) M (4)
S (3) S (1) S (4) S (2)
C1 14 L (1) 27 L (15) 15 L (11) 17 L (14)
(5) M (0) (9) M (10) (6) M (1) (6) M (1)
S (3) S (2) S (3) S (2)
C2 13 L (11) 23 L (14) 11 L (9) 12 L (11)
(4) M (1) (8) M (8) (4) M (1) (4) M (1)
S (1) S (1) S (1) S (0)
†
Severity of atrophy or metaplasia per sample, (L) low 1–30%, (M) moderate 31–60%, and (S)
severe > 61%
‡
Patients displaying atrophy or metaplasia at least in one of 5 samples
§
n = 272 subjects

frequencies of GA (12.5% and 20.2%) and IM (15.1% and
15.4%) were higher than that reported by Correa et al., 1.7%
for GA and 13.3% for IM [25]. The frequency of GA was
similar (19%), whereas that of IM was lower (11%) com-
pared to what was reported by Bravo et al. [26] and much
lower than the results reported by Luna et al. (43.4% for
GA/IM) [27]. The high percentage of PNL reported by
these authors could be explained by the advanced age of
the patients included in the said studies (median: 53 years,
range: 42–64 years) and the regions studied (Tunja and Bar-
ranquilla, Colombia).
In contrast, Emura et al. determined the usefulness of
systematic chromoendoscopy for diagnosis of PNL and SC,
reporting frequencies of 14.5% and 15.5% for GA and IM,
respectively [28]. They also demonstrated 6.4-fold preva-
lence of PNL in patients > 50 years old, findings similar to
data reported in this study. Evidence suggests that individu-
als > 40 years old should be followed up to avoid develop-
ment of SC because gastric mucosa changes upon aging as
a result of cumulative exposure to pathogens, toxins, envi-
ronmental factors, drugs, and diet [29]. Additionally, MAPS
II (management of epithelial precancerous conditions and
lesions in the stomach) guidelines recommend a follow-up
every 3 years under the Updated Sydney System in indi-
viduals with CG due to persistent H. pylori infection, GA in
the corpus, incomplete IM, and advanced IM with a family
history of SC.
Histopathological diagnosis used routinely for gastroduo-
denal diseases does not determine the risk that a patient with
a PNL has to develop SC. The advantage of the OLGA and
OLGIM staging systems is that they grade the risk for SC.
In consequence, they provide useful information regarding
which patients have more severe PNL and would benefit
from more frequent follow-ups. In this study, 13.8% (9/65)
patients with GA were classified as OLGA-III and 6% (3/49)
with IM were classified in OLGIM-III. These patients are at
high risk for developing SC. Mera et al. evidenced that indi-
viduals in stages OLGA-III-IV presented 19.9-fold risk of
SC than those presented OLGA-0-II (p = 0.005). In addition,
the study showed that the risk of SC doubled (38.2 times)
for patients with OLGIM III-IV compared to OLGIM-0-II
(p < 0.0001) [30].
Additionally, Isajevs et al. found that 8.9% of the stud-
ied patients were classified in OLGA-III-IV and 13.7% in
OLGIM-III-IV. Moreover, they described moderate inter-
observer agreement for GA and excellent for IM. They
conclude that OLGIM is better for staging changes in the
mucosa but should be complemented with OLGA to detect
a greater number of individuals with potential risk of devel-
oping SC [31].
Histopathological diagnosis of H. pylori showed a fre-
quency of 60% and 64% for H1 and H2 respectively. Similar
results were obtained by PCR (58% and 61% for antrum and
corpus, respectively). Correspondingly, Bravo et al. reported
69.1% for Colombia [26]. The different frequencies of H.
pylori in this study may be due to the inclusion of differ-
ent populations and the methodology used to obtain the
biopsies. Helicobacter pylori quantification by histopathol-
ogy is not carried out routinely in Colombia. Dharmesh K
et al. demonstrated that a higher number of bacteria result

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Fig. 2  Histopathological alterations. Spectrum of histopathologi-
cal findings detected in gastric mucosa. A Normal gastric mucosa:
lamina propria displays scarce inflammatory infiltration and foveo-
las covered by a mucosal secretory epithelium exhibiting typical
morphology—H&E stain. B Chronic gastritis with increased num-
ber of lymphocytes and plasma cells in a lamina propria inflam-
matory infiltrate—H&E. C and D Helicobacter pylori: bacillary
structures located in the luminal part of the epithelium visualized
by staining, H&E, and Giemsa, respectively. E Atrophic chronic
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Virchows Archiv (2022) 480:759–769
gastritis: decreased number of glandular structures and increased
collagen deposits in the lamina propria were observed—H&E. F
Intestinal metaplasia: small intestine epithelium goblet cells and
cylindrical cells replaced gastric mucosa cells -H&E. G Adenocar-
cinoma according to WHO classification: poorly cohesive (diffuse),
neoplastic cells lose cohesiveness and often reshape into a ring-seal
appearance—H&E. H Adenocarcinoma: tubular (intestinal), neoplas-
tic cells retain light and glandular structure—H&E. Courtesy from
José Armando Justinico Castro MD, Pathologist
Virchows Archiv (2022) 480:759–769 765

Table 3  Agreement between Variable Sample P1-P2 (n = 97) P1-P4 (n = 78) P1-P3 (n = 25) P1-P5 (n = 71)
histopathological evaluation H1
‡ §
and H2 κ 95% ­CI κ 95% CI κ 95% CI κ 95% CI

GA A1 0.6 0.3–0.9 0.0 0.0–0.5 0.5 0.0–1 0.2 − 0.1 to 0.5

¶
A2 1.0 0.10 − 0.1 to 0.3 0.4 − 0.2 to 0.9 0.3 − 0.1 to 0.7
I 0.8 0.5–1.0 0.2 − 0.0 to 0.4 0.6 0.2–1.0 0.7 0.4–1.0
† †
C1 0.6 0.3–0.9 0.6 0.0–1.0 0.7 0.4–1.0
† †
C2 0.6 0.2–0.9 0.5 − 0.1 to 1.0 0.6 0.3–1.0
GA pattern A 0.6 0.3–0.7 0.2 0.0–0.4 0.6 0.2–0.9 0.4 0.2–0.6
† †
C 0.4 0.1–0.6 0.5 0.1–1.0 0.6 0.3–0.9
¶
IM A1 0.8 0.6–1.0 0.9 0.7–1.0 1.0 0.9 0.7–1.0
¶
A2 0.9 0.6–1.0 0.5 − 0.1 to 1.0 1.0 0.8 0.4–1.0
¶
I 0.9 0.7–1.0 0.9 0.6–1.0 1.0 0.9 0.7–1.0
¶
C1 0.7 0.4–1.0 0.8 0.4–1.0 1.0 0.8 0.5–1.0
C2 0.9 0.6–1.0 0.7 0.0–1.0 0.6 0.0–1.0 0.7 0.4–1.0
IM pattern A 0.6 0.3–0.7 0.7 0.5–1.0 0.8 0.5–1.0 0.9 0.7–1.0
C 0.6 0.3–0.8 0.7 0.4–1.0 0.6 0.2–1.0 0.8 0.5–1.0
H. pylori H&E A1 0.4 0.2–0.4 0.5 0.4–0.6 0.4 0.1–0.6 0.4 0.2–0.5
A2 0.4 0.2–0.4 0.6 0.5–0.7 0.7 0.4–0.9 0.4 0.3–0.5
I 0.3 0.2–0.4 0.6 0.4–0.7 0.4 0.2–0.7 0.4 0.3–0.5
C1 0.3 0.1–0.3 0.4 0.2–0.5 0.3 0.1–0.5 0.4 0.3–0.6
C2 0.3 0.2–0.4 0.4 0.3–0.6 0.4 0.1–0.6 0.4 0.2–0.5
PMNL A1 0.6 0.4–0.7 0.7 0.6–0.9 0.6 0.3–0.8 0.4 0.2–0.5
A2 0.6 0.4–0.7 0.7 0.6–0.9 0.5 0.3–0.8 0.4 0.3–0.6
I 0.6 0.4–0.7 0.8 0.6–0.9 0.4 0.1–0.6 0.4 0.3–0.6
C1 0.5 0.3–0.6 0.5 0.4–0.6 0.4 0.2–0.6 0.3 0.2–0.5
C2 0.4 0.3–0.5 0.5 0.4–0.7 0.4 0.2–0.6 0.3 0.2–0.4
GA General 0.7 0.5–0.9 0.2 0.0–0.4 0.7 0.4–1.0 0.6 0.3–0.8
¶
IM 0.8 0.7–0.9 0.8 0.6–0.1 1.0 0.9 0.8–1.0
H. pylori 0.7 0.6–0.8 0.7 0.6–0.9 0.7 0.5–1.0 0.6 0.4–0.8
OLGA 0.6 0.3–0.7 0.2 − 0.0 to 0.3 0.5 0.2–0.8 0.4 0.2–0.6

P pathologist, A1 lesser curvature of the antrum, A2 greater curvature of the antrum, I incisura angularis,
C1 lesser body curvature, C2 greater body curvature, GA Gastric atrophy, IM intestinal metaplasia, H&E
hematoxylin–eosin stain, PMNL polymorphonuclear leukocytes, CG chronic gastritis, OLGA operative link
on gastritis assessment
General = considered positive if featured at least in one out of five samples, pattern = multifocal/diffuse
‡
κ = Cohen’s kappa coefficient, κ < 0.5 poor; 0.5–0.75 good; and > 0.75 excellent agreement
§
95% CI = confidence interval (95%)
¶
95% CI = undetermined
†
No match

Table 4  OLGA and OLGIM Staging Chronic gastritis Preneoplastic lesions Gastric cancer
classification n (%) n (%)
Atrophic gastritis Intestinal metaplasia
n (%) n (%)
OLGA OLGIM OLGA OLGIM OLGA OLGIM OLGA OLGIM

0 203 (100) 203 (100) 0 (0.00) 16 (100) 3 (61.2) 0 (0.00) 1 (25.0) 0 (0.00)
I 0 (0.00) 0 (0.00) 7 (43.8) 0 (0.00) 32 (65.3) 38 (77.6) 1(25.0) 1 (25.0)
II 0 (0.00) 0 (0.00) 5 (31.2) 0 (0.00) 9 (18.4) 8 (16.3) 2 (50.0%) 3 (75.0)
III 0 (0.00) 0 (0.00) 4 (25.0) 0 (0.00) 5 (10.2) 3 (6.12) 0 (0.00) 0 (0.00)
IV 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00)
n = 272 203 (75) 16 (6) 49 (18) 4 (1)

13
766 Virchows Archiv (2022) 480:759–769

Table 5  Demographics of the study population according to preneo- Table 5  (continued)

plastic lesion
Variable Preneoplastic lesions p*
Variable Preneoplastic lesions p*
Positive Negative
Positive Negative
n % n %
n % n %
No 39 24.2 122 75.8
Gender Daily coffee consumption
Male 24 25.3 71 74.7 0.70 Yes 46 27.9 119 72.1 0.05
Female 41 23.2 136 76.8 No 19 17.8 88 82.2
Age Salt addition to meals
46–86 44 28.4 111 71.6 0.05* Yes 13 22.4 45 77.6 0.77
18–45 21 17.9 96 82.1 No 52 24.3 162 75.7
Education Eating out
≤ 5 yr 19 27.1 51 72.9 0.66 Yes 29 19.2 122 80.8 0.04*
6–11 yr 21 26.6 58 73.4 No 36 30.0 84 70.0
12–14 yr 8 20.0 32 80.0 Previous diagnosis of gastric disease
> 15 yr 17 20.5 66 79.5 Yes 34 25.0 102 75.0 0.67
Occupation No 31 22.8 105 77.2
Employed 17 17.2 82 82.8 0.30 Previous diagnosis of H. pylori
Housewife 18 25.4 53 74.6 Yes 18 20.7 69 79.3 0.38
Underemployed/informal 5 23.8 16 76.2 No 47 25.5 137 74.5
Unemployed/student/other 6 27.3 16 72.7 Previous treatment for H. pylori
Retired/self-employed 19 32.2 40 67.8 Yes 15 19.5 62 80.5 0.28
Health insurance coverage No 4 33.3 8 66.7
Private 9 22.5 31 77.5 0.82 Full treatment for H. pylori
Public 56 24.1 176 75.9 Yes 13 18.3 58 81.7 0.51
Wages No 2 28.6 5 71.4
≤ $ 273.06 USD 11 26.2 31 73.8 0.72
Underemployed: type of employment where the employee skills are
$ 273.07 to 546.12 USD 16 26.7 44 73.3
underutilized, the employee works fewer hours, and wages are low.
> $ 546.13 USD 36 22.1 127 77.9 Informal: person who carries out an economic activity under no con-
Socioeconomic stratification tract, outside of tax control, receiving low income, and no health-
Low (1–2) 24 22.4 83 77.6 0.87 care insurance. Other: inmate. Self-employed: person working under
no contract by any employer who makes payments to the healthcare
Medium (3–4) 33 25.4 97 74.6
insurance system by himself. Private: type of bond to the Colombian
High (5–6) 7 24.1 22 75.9 healthcare system whereby an individual or family contribution is
Domestic gas placed by the employee or between the employee and their employer.
Yes 60 24.5 185 75.5 0.49 Public: mechanism whereby the poorest, no payment capacity popula-
tion in the country has access to healthcare services through a sub-
No 5 18.5 22 81.5
sidy offered by the government
Sewer system
Yes 61 23.8 195 76.2 1.00
No 4 25.0 12 75.0 in a lower treatment success (92% success for mild counts,
Drinking water supply 76.9% for moderate counts, and 55.5% for severe counts)
Yes 62 24.8 188 75.2 0.24 [32]. On the other hand, S Khulusi et al. showed a correla-
No 3 16.6 19 86.4 tion between the amount of H. pylori, the severity of lesions,
Use of boiled water and the PMN leukocyte count in the antrum [33].
Yes 6 14.6 35 85.4 0.30 Also, in this study, we found 49 patients that presented
No 11 27.5 29 72.5 intestinal metaplasia; of those 40.5% (15/37) were staged
Not apply 48 25.1 143 74.9 at OLGIM-I while simultaneously being infected with H.
Smoking history (y) pylori. Furthermore, 100% of the patients that were catego-
Yes 25 33.3 50 66.7 0.02** rized at OLGIM-II (8/8) and OLGIM-III (3/3) were positive
No 40 20.3 157 79.7 for H. pylori. That association with this bacterium would
Alcohol intake history indicate that our cases of intestinal metaplasia are associ-
Yes 26 23.4 85 76.6 0.88 ated majorly with preneoplastic mechanisms, which are
consequences of the high prevalence of chronic infection in

13
Virchows Archiv (2022) 480:759–769
Colombia (> 60%), which is mostly observed in middle and
low-income countries. In contrast, it has been noted that in
high-income countries, the prevalence of H. pylori infec-
tion has decreased over time, and it has been observed that
most cases of lesions in patients with gastritis are caused
by paraneoplastic mechanisms, such as autoimmune phe-
nomena or drugs [34, 35]. These results can have an impact
in prevention strategies in public health, as policymakers
should design approaches that cater to the main metaplasia
mechanism of the population, whether it is preneoplastic or
paraneoplastic.
Some authors consider that the Updated Sydney System
has disadvantages due to a lack of interobserver agreement
especially for GA [36, 37]. However, others argue that such
variability in histopathology reading decreases if a standard-
ized consensus is established [38]. In this study, a higher
reproducibility was found in the diagnosis of IM compared
to GA, and we also observed a good/excellent interobserver
agreement for IM similar to other authors [37]−[39]. Also, a
wide variability in agreement for GA and H. pylori grading
by H&E is herein reported. Interobserver variability for GA
was similar to data reported by Kim et al. [40] and differed
from what has been recorded by Andrew et al. [41].
In order to reduce the interobserver differences in patho-
logical diagnosis that were found in the study, it is necessary
to take into account certain aspects. Those include optimal
pre-analytical conditions of the sample (size, number, and
orientation of the specimens), peer review of the readings
(especially with unusual findings), the creation and con-
tinuous improvement of new visual scales and formats,
the implementation of new specific professional training
programs, and the use of novel artificial intelligence-based
pathology reading programs [37, 42–44].
SC was diagnosed in four low-risk patients, staged
according to the OLGA and OLGIM systems. Some other
studies also support these results [20, 45]; for example,
Martínez et al. [20] found 2/20 dysplasia patients that were
staged as OLGA-II. To explain this phenomenon, it is impor-
tant to mention that not every type of SC follows Correa’s
cascade (gastritis-atrophy-metaplasia-dysplasia-dysplasia-
cancer) [46]. Some types present various mutations and dif-
ferent oncogenic mechanisms in their development, which
does not necessarily impact the OLGA/OLGIM staging or
the histological findings of the patient [47, 48]. Additionally,
the low OLGA staging in those cases can be explained by
common sampling bias during endoscopy because emphasis
is placed on collecting tumor samples and not on the sur-
rounding mucosa, which has implications in the histopatho-
logical diagnosis. This information not only reinforces that
OLGA-OLGIM help in the detection of PNL in early stages,
but also highlights the importance of including a sample of
lesions such as polyps and tumor-like appearance to improve
the diagnosis of the patient [13].
767
In Colombia, the risk of developing SC is considered
moderate/high [1] as risk factors associated with the pres-
entation of this disease coexist in the country; therefore, the
accurate diagnosis of PNL becomes critical to identify indi-
viduals at a higher risk, meaning that diagnostic evaluation
methods should be sensitive, while allowing to stage the risk
of developing SC, to prioritize the use of UGE. Furthermore,
in most departments in Colombia, the frequency of PNL
remains unknown, and an endoscopic surveillance protocol
has not been established as a secondary prevention strategy
for SC, as the accuracy of the OLGA/OLGIM staging sys-
tems has not been explored locally, and because of incon-
sistencies that can be found in the available literature around
the world [6, 17–19, 21, 49–51]. Moreover, the results of
this study are important not only for our context, but also
for middle-income countries that have similar epidemiology
and conditions to Colombia.
Our study is the first to undertake this approach, while
including other additional testing for the diagnosis of H.
pylori infection. However, as a cross-sectional study with no
monitoring for evolution of the patients and no associated
patient outcomes, it has limitations. As a result, even though
the appropriate staging of patients according to their risk of
SC would facilitate their management and would prioritize
the use of UGE. It is not possible to determine with the
present data if biopsy collection according to the Updated
Sydney System with OLGA-OLGIM would have an impact
on the management and prognosis. Nevertheless, this type
of approach would be particularly useful in a region such as
Antioquia, where the risk of this disease is so variable, and
the availability of UGE is limited.
In conclusion, we report frequencies of GA and IM higher
than those described in other geographic regions of the coun-
try, indicating that the prevalence of PNL associated with
H. pylori infection should continue to be studied. This work
determined that 4% of the population analyzed is at high risk
of developing SC and would benefit from follow-up stud-
ies. Similar studies should be carried out in other regions
where the infection rates and SC prevalence are different.
Implementation of the Updated Sydney, OLGA-OLGIM
systems as public policy will make it possible to improve
the healthcare and to characterize individuals at low risk of
developing SC for whom a control UGE is not required. The
application of these findings in public health policy would
also mean a reduction in costs for unnecessary tests. On the
other hand, in some histopathological parameters, interob-
server variability was observed, demonstrating the need to
standardization and reinforcement of training programs for
gastroenterologists, endoscopists, and pathologists.
Supplementary Information The online version contains supplemen-
tary material available at https://d​ oi.o​ rg/1​ 0.1​ 007/s​ 00428-0​ 22-0​ 3286-8.
13
768
Acknowledgements The authors would like to thank to the Infectious
Disease Group, Department of Microbiology, Pontificia Universidad
Javeriana and Cancer Biology Research Group National Cancer Insti-
tute, for the donation of the reference strain H. pylori. Thanks to Dr.
Zulma Rueda Vallejo for the constructive comments.
Author contribution Funds and resources: Tania Pérez-Cala, Alonso
Martínez, Beatriz E. Salazar, Ana María Cock Botero.
Project administration: Alonso Martínez, Beatriz E. Salazar.
Project supervision: Alonso Martínez, Beatriz E. Salazar.
Academic advising: Alonso Martínez, Alba Alicia Trespalacios-
Rangel, Maria Mercedes Bravo, Juan Carlos Cataño-Correa, Jovanny
Zabaleta.
Methodology design: Alonso Martínez, Tania Pérez-Cala, Beatriz
E. Salazar, Alba Alicia Trespalacios.
Data collection: Beatriz E. Salazar, Tania Pérez-Cala, Sara Gómez
Villegas, Laura Cardona-Zapata, Sebastián Pazos-Bastidas, Juan Carlos
Benítez Guerra, Joaquin Tiberio Valencia Cárdenas, Edgar de Jesús
Ospina, Rodrigo Castaño Llano.
Laboratory tests: José Justinico Castro, Andrés Felipe Bernal Cobo,
Harold Dávila, Miguel Ignacio Roldan, Ana María Cock Botero, Beat-
riz E. Salazar.
Database management: Alejandra Cardona-Estepa, Diego E. Vélez,
Alba Alicia Trespalacios-Rangel, Maria Mercedes Bravo, Juan Carlos
Cataño-Correa, Jovanny Zabaleta, Beatriz E. Salazar.
Statistical data analysis: Diego E. Vélez, Beatriz E. Salazar.
Manuscript writing: all authors.
Funding This study was funded by Comité Para el Desarrollo de la
Investigación (CODI) Universidad de Antioquia, grant number 2014–
1062 and National Doctoral Scholar by Ministerio de Ciencia, Tec-
nología e Innovación (Minciencias), grant number 617–2013.
Data availability The data are available without any patient identifica-
tion upon request, emailing beatriz.salazar@udea.edu.co (correspond-
ing author).
Code availability Not applicable.
Declarations
Ethics statement The consent and survey were approved by the Bioeth-
ics Committee of the Faculty of Medicine of the University of Antio-
quia – Colombia (ethics approval number: 013–2016). Each participant
signed the consent form and approved the publication of the results.
Conflict of interest The authors declare no competing interests.
Disclaimers The funding sources have not been involved in the design,
conduct, or presentation of the study.
References
1. Sung H, Ferlay J, Siegel RL et al (2021) Global Cancer Statis-
tics 2020: GLOBOCAN estimates of incidence and mortality
worldwide for 36 cancers in 185 countries. CA Cancer J Clin
71:209–249. https://​doi.​org/​10.​3322/​caac.​21660
2. International Agency for Research on Cancer W (2020) Colombia,
Globocan 2020. In: https://​gco.​iarc.​fr/​today/​data/​facts​heets/​popul​
ations/​170-​colom​bia-​fact-​sheets.​pdf
13
Virchows Archiv (2022) 480:759–769
3. Dorer MS, Talarico S, Salama NR (2009) Helicobacter pylori’s
unconventional role in health and disease. PLoS Pathog 5 https://​
doi.​org/​10.​1371/​journ​al.​ppat.​10005​44
4. IARC (1994) Schistosomes, Liver Flukes and Helicobacter pylori.
IARC Monogr Eval Carcinog risk to Hum 61:121–162
5. Correa P, Piazuelo MB (2012) The gastric precancerous cascade1.
Correa P, Piazuelo MB. The gastric precancerous cascade. J Dig
Dis. 2012;13(1):2–9. J Dig Dis 13:2–9. https://​doi.​org/​10.​1111/j.​
1751-​2980.​2011.​00550.x
6. Park YH, Kim N (2015) Review of atrophic gastritis and intestinal
metaplasia as a premalignant lesion of gastric cancer. J Cancer
Prev 20:25–40. https://​doi.​org/​10.​15430/​jcp.​2015.​20.1.​25
7. Lee Y, Chiang T, Liou J et al (2016) Mass eradication of Helico-
bacter pylori to prevent gastric cancer : theoretical and practical
considerations. Gut Liver 10:12–26. https://d​ oi.o​ rg/1​ 0.5​ 009/g​ nl15​
091
8. Wang Z, Graham DY, Khan A et al (2018) Incidence of gastric
cancer in the USA during 1999 to 2013: a 50-state analysis. Int J
Epidemiol 47:966–975. https://​doi.​org/​10.​1093/​ije/​dyy055
9. Rugge M, Genta RM, Graham DY et al (2016) Chronicles of a
cancer foretold: 35 years of gastric cancer risk assessment. Gut
65:721–725. https://​doi.​org/​10.​1136/​gutjnl-​2015-​310846
10. Chen F, Liu Y, Tsay A et al (2019) Hit or a miss: concordance
between histopathologic-endoscopic findings in gastric mucosal
biopsies. Ann Diagn Pathol 38:106–114. https://d​ oi.o​ rg/1​ 0.1​ 016/j.​
anndi​agpath.​2018.​12.​002
11. Rugge M, Capelle LG, Fassan M (2014) Individual risk stratifi-
cation of gastric cancer: evolving concepts and their impact on
clinical practice. Best Pract Res Clin Gastroenterol 28:1043–1053.
https://​doi.​org/​10.​1016/j.​bpg.​2014.​09.​002
12. Yue H, Shan L, Bin L (2018) The significance of OLGA and
OLGIM staging systems in the risk assessment of gastric cancer: a
systematic review and meta-analysis. Gastric Cancer 21:579–587.
https://​doi.​org/​10.​1007/​s10120-​018-​0812-3
13. Rugge M, Genta RM, Fassan M et al (2018) OLGA gastritis stag-
ing for the prediction of gastric cancer risk: a long-term follow-
up study of 7436 patients. Am J Gastroenterol 113:1621–1628.
https://​doi.​org/​10.​1038/​s41395-​018-​0353-8
14. Pimentel-Nunes P, Libânio D, Marcos-Pinto R et al (2019)
Management of epithelial precancerous conditions and lesions
in the stomach (MAPS II): European Society of Gastrointesti-
nal Endoscopy (ESGE), European Helicobacter and Microbiota
Study Group (EHMSG), European Society of Pathology (ESP),
and Sociedade Port. Endoscopy 51:365–388. https://​doi.​org/​10.​
1055/a-​0859-​1883
15. Dixon MF, Genta RM, Yardley JH, Correa P (1996) Classifica-
tion and grading of gastritis. The updated Sydney System. Inter-
national Workshop on the Histopathology of Gastritis, Houston
1994. Am J Surg Pathol 20:1161–1181
16. Sipponen P, Price AB (2011) The Sydney System for classification
of gastritis 20 years ago. J Gastroenterol Hepatol 26:31–34
17. Capelle LG, de Vries AC, Haringsma J et al (2010) The staging of
gastritis with the OLGA system by using intestinal metaplasia as
an accurate alternative for atrophic gastritis. Gastrointest Endosc
71:1150–1158. https://​doi.​org/​10.​1016/j.​gie.​2009.​12.​029
18. Satoh K, Osawa H, Yoshizawa M et al (2008) Assessment of
atrophic gastritis using the OLGA system. Helicobacter 13:225–
229. https://​doi.​org/​10.​1111/j.​1523-​5378.​2008.​00599.x
19. Nam JH, Choi IJ, Kook M-C et al (2014) OLGA and OLGIM
stage distribution according to age and Helicobacter pylori status
in the Korean population. Helicobacter 19:81–89. https://​doi.​org/​
10.​1111/​hel.​12112
20. Martínez D, Otero W, Ricaurte O (2016) Impacto del sistema
OLGA en la detección de gastritis crónica atrófica en Colombia :
un estudio de casos y controles. Rev la Asoc Colomb Gastroen-
terol 31:360–367
Virchows Archiv (2022) 480:759–769
21. Rugge M, Correa P, Di Mario F et al (2008) OLGA staging for
gastritis: a tutorial. Dig Liver Dis 40:650–658. https://​doi.​org/​10.​
1016/j.​dld.​2008.​02.​030
22. Atherton JC, Cao P, Peek RM et al (1995) Mosaicism in vacuolat-
ing cytotoxin alleles of helicobacter pylori. Association of specific
vacA types with cytotoxin production and peptic ulceration. J Biol
Chem 270:17771–17777
23. Van Doorn LJ, Figueiredo C, Sanna R et al (1998) Expanding
allelic diversity of Helicobacter pylori vacA. J Clin Microbiol
36:2597–2603
24. Peek RM, Miller GG, Tham KT et al (1995) Detection of Heli-
cobacter pylori gene expression in human gastric mucosa. J Clin
Microbiol 33:28–32
25. Correa S, Cardona A, Correa T et al (2016) Prevalencia de Heli-
cobacter pylori y características histopatológicas en biopsias
gástricas de pacientes con síntomas dispépticos en un centro de
referencia de Medellín Biopsies from Patients with Dyspeptic
Symptoms at a Referral Center in Medellin. Asoc Colomb Gas-
troenterol 31:9–15
26. Bravo LE, Cortés A, Carrascal E et al (2003) Helicobacter pylori:
patología y prevalencia en biopsas gástricas en Colombia. Colomb
Med 34:124–131
27. Flores-Luna L, Bravo MM, Kasamatsu E et al (2020) Risk factors
for gastric precancerous and cancers lesions in Latin American
counties with difference gastric cancer risk. Cancer Epidemiol
64:101630. https://​doi.​org/​10.​1016/j.​canep.​2019.​101630
28. Emura F, Mejia J, Mejia M et al (2010) Utilidad de la cromoen-
doscopia sistemática en el diagnóstico del cáncer temprano y
lesiones gástricas premalignas. Resultado de dos campañas masi-
vas consecutivas de tamización en Colombia (2006–2007). Rev
Col Gastroenterol 25:19–30
29. Sonnenberg A, Genta RM (2015) Changes in the gastric mucosa
with aging. Clin Gastroenterol Hepatol 13:2276–2281. https://d​ oi.​
org/​10.​1016/j.​cgh.​2015.​02.​020
30. Mera R, Bravo L, Camargo MC et al (2017) Dynamics of Helico-
bacter pylori infection as a determinant of progression of gastric
precancerous lesions: 16-year follow-up of an eradication trial.
Physiol Behav 176:139–148. https://​doi.​org/​10.​1016/j.​physb​eh.​
2017.​03.​040
31. Isajevs S, Liepniece-Karele I, Janciauskas D et al (2014) Gastritis
staging: interobserver agreement by applying OLGA and OLGIM
systems. Virchows Arch 464:403–407. https://​doi.​org/​10.​1007/​
s00428-​014-​1544-3
32. Shah DK, Jain SS, Mohite A et al (2015) Effect of H. pylori
density by histopathology on its complications and eradication
therapy. Trop Gastroenterol 36:101–106
33. Khulusi S, Mendall MA, Patel P et al (1995) Helicobacter pylori
infection density and gastric inflammation in duodenal ulcer and
non-ulcer subjects. Gut 37:319–324. https://​doi.​org/​10.​1136/​gut.​
37.3.​319
34. Neumann WL, Coss E, Rugge M, Genta RM (2013) Autoimmune
atrophic gastritis—pathogenesis, pathology and management. Nat
Rev Gastroenterol Hepatol 10:529–541. https://​doi.​org/​10.​1038/​
nrgas​tro.​2013.​101
35. Lenti MV, Rugge M, Lahner E, et al (2020) Autoimmune gastritis.
Nat Rev Dis Prim 6https://​doi.​org/​10.​1038/​s41572-​020-​0187-8
36. Aydin O, Egilmez R, Karabacak T, Kanik A (2003) Interobserver
variation in histopathological assessment of Helicobacter pylori
gastritis. World J Gastroenterol 9:2232–2235. https://​doi.​org/​10.​
3748/​wjg.​v9.​i10.​2232
769
37. Kasamatsu E, Bravo LE, Bravo JC et al (2010) Reproducibility
of histopathologic diagnosis of precursor lesions of gastric car-
cinoma in three Latin American countries. Salud Publica Mex
52:386–390. https://d​ oi.o​ rg/​10.​1590/S​ 0036-​363420​ 10000​ 50000​ 5
38. Bravo LE, Bravo JC, Realpe JL et al (2008) Fuentes de variabili-
dad en el diagnóstico de gastritis atrófica multifocal asociada con
la infección por Helicobacter pylori. Colomb Med 39:58–65
39. Tepeš B, Ferlan-Marolt V, Juteršek A et al (1999) Interobserver
agreement in the assessment of gastritis reversibility after Heli-
cobacter pylori eradication. Histopathology 34:124–133. https://​
doi.​org/​10.​1046/j.​1365-​2559.​1999.​00604.x
40. Kim HJ, Kim N, Yun CY, Lee HS (2019) The clinical meaning of
the “indefinite for atrophy” lesions within gastric mucosa biopsy
specimens in a region with a high prevalence of gastric cancer.
Helicobacter 24:1–9. https://​doi.​org/​10.​1111/​hel.​12605
41. Andrew A, Wyatt JI, Dixon MF (1994) Observer variation in the
assessment of chronic gastritis according to the Sydney system.
Histopathology 25:317–322. https://d​ oi.o​ rg/1​ 0.1​ 111/j.1​ 365-2​ 559.​
1994.​tb013​49.x
42. Miwata T, Quach DT, Hiyama T, et al (2015) Interobserver and
intraobserver agreement for gastric mucosa atrophy. BMC Gas-
troenterol. 15
43. Jansen M, Waddingham W, Graham D, Banks M (2018) The
evolving role of endoscopy in the diagnosis of premalignant gas-
tric lesions [version 1; referees: 4 approved]. F1000Research 7:.
https://​doi.​org/​10.​12688/​f1000​resea​rch.​12087.1
44. Guarner J, Herrera-Goepfert R, Mohar A et al (2001) Gastric atro-
phy and extent of intestinal metaplasia in a cohort of Helicobacter
pylori-infected patients. Hum Pathol 32:31–35. https://d​ oi.o​ rg/1​ 0.​
1053/​hupa.​2001.​20889
45. Ramírez-Mendoza P, Hernández-Briseño L, Casarrubias-Ramírez
M, et al [Atrophy in the mucosa neighboring an intestinal-type
gastric adenocarcinoma by comparing the Sydney vs. OLGA sys-
tems]. Rev médica del Inst Mex del Seguro Soc 53:584–90
46. Correa P, Cuello C, Duque E, et al (1976) Gastric cancer in
Colombia. III. Natural history of precursor lesions the precursor
role of CAG in the etiology of gastric cancer has beén suspected
for a long time (1, 2 ); this view has received increasing support
from studies of the pathology and e. 57:
47. Businello G, Angerilli V, Parente P et al (2021) Molecular land-
scapes of gastric pre-neoplastic and pre-invasive lesions. Int J Mol
Sci 22:9950. https://​doi.​org/​10.​3390/​ijms2​21899​50
48. Conchillo JM, Houben G, de Brune A, Stockbrügger R (2001) Is
type III intestinal metaplasia an obligatory precancerous lesion in
intestinal-type gastric carcinoma? Eur J Cancer Prev 10:307–312.
https://​doi.​org/​10.​1097/​00008​469-​20010​8000-​00003
49. Cho S-J, Choi IJ, Kook M-C et al (2013) Staging of intestinal- and
diffuse-type gastric cancers with the OLGA and OLGIM staging
systems. Aliment Pharmacol Ther 38:1292–1302. https://​doi.​org/​
10.​1111/​apt.​12515
50. Ohata H, Kitauchi S, Yoshimura N et al (2004) Progression
of chronic atrophic gastritis associated with Helicobacter
pylori infection increases risk of gastric cancer. Int J Cancer
109:138–143
51. Rugge M, Meggio A, Pennelli G et al (2007) Gastritis staging
in clinical practice: the OLGA staging system. Gut 56:631–636.
https://​doi.​org/​10.​1136/​gut.​2006.​106666
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