THE AMERICAN JOURNAL OF GASTROENTEROLOGY
1, 2000
© 2000 by Am. Coll. of Gastroenterology
Published by Elsevier Science Inc.
Antral-Type Mucosa in the
Gastric Incisura, Body, and Fundus
(Antralization): A Link Between Helicobacter
pylori Infection and Intestinal Metaplasia?
Harry Hua-Xiang Xia, Ph.D., M.M., Jamshid S. Kalantar, M.B.B.S., F.R.A.C.P.,
Nicholas J. Talley, M.D., Ph.D., F.A.C.G., Jenny Ma Wyatt, M.B.B.S., F.R.C.P.A.,
Stuart Adams, M.B.B.S., F.R.C.P.A., Karen Cheung, M.B.B.S., F.R.C.P.A., and Hazel M. Mitchell, Ph.D.
Department of Medicine, The University of Sydney, Nepean Hospital, Penrith; Department of Anatomical
Pathology, Nepean Hospital, Penrith; and School of Microbiology and Immunology, The University of
New South Wales, Sydney, Australia
OBJECTIVES: Helicobacter pylori is a carcinogen; gastric
carcinoma involves a multistep process from chronic gas-
tritis to atrophy, intestinal metaplasia, and dysplasia. The
aims of this study were to determine the types of mucosa at
different gastric sites in H. pylori-infected and uninfected
patients, and whether the presence of antral-type mucosa in
the incisura, body, and fundus is associated with gastric
atrophy and intestinal metaplasia.
METHODS: Two hundred and sixty-eight patients with dys-
pepsia were enrolled. Eight biopsies (i.e., antrum ⫻3, body
⫻2, fundus ⫻2, and incisura ⫻1) were obtained. One antral
biopsy was used for the CLO-test. Three (each from the
antrum, body, and fundus) were cultured. The remaining
biopsies were examined histologically according to the up-
dated Sydney System after staining with hematoxylin and
eosin and Giemsa. A validated serological test was also
applied.
RESULTS: Overall, 113 (42%) patients were infected with H.
pylori. At the incisura, antral-type mucosa was more prev-
alent in infected than in uninfected patients (84% vs 18%;
odds ratio [OR] ⫽ 23.9, 95% confidence interval [CI] 12.5–
45.8; p ⬍ 0.001). Atrophic gastritis and intestinal metaplasia
at the incisura was present in 19.5% and 13.3%, respec-
tively, of infected, and 4.5% and 3.2%, respectively, of
uninfected patients (both p ⬍ 0.01). Moreover, atrophic
gastritis at the incisura was associated with the presence of
antral-type mucosa at the site (termed antralization); the
prevalence of atrophic gastritis was 19.5% (24/123) in the
presence of antralization, whereas the rate was 2.1% (3/145)
without antralization (OR ⫽ 11.4, 95% CI 3.4 –39.2; p ⬍
0.001). Similarly, at the incisura, 16.3% (20/123) of “an-
tralized” cases and 1.4% (2/145) of “unantralized” cases had
intestinal metaplasia (OR ⫽ 13.8, 95% CI, 3.2– 60.7; p ⬍
0.001). The association between antralization at gastric
Vol. 95, No.
ISSN 0002-9270/00/$20.00
PII S0002-9270(99)00668-1
body and fundus also appeared to be associated with atro-
phic gastritis and intestinal metaplasia at these sites.
CONCLUSIONS: Atrophic gastritis and intestinal metaplasia
occurs predominantly at the gastric antrum and incisura with
H. pylori infection. Antralization of the gastric incisura is a
common event in H. pylori-infected patients, and appears
to be associated with an increased risk of atrophic gas-
tritis and intestinal metaplasia. (Am J Gastroenterol 2000;
95:114 –121. © 2000 by Am. Coll. of Gastroenterology)
INTRODUCTION
The development of gastric cancer in humans has been
shown to be a multistep process, ranging from chronic
gastritis to atrophy, intestinal metaplasia, dysplasia, and
finally invasive cancer (1, 2). Although in 1994, based on
evidence from both clinical and epidemiological studies,
The World Health Organization (WHO) classified Helico-
bacter pylori as a group 1 carcinogen for gastric cancer, as
yet the mechanisms involved in the development of gastric
cancer are unknown (3, 4). Preliminary pathological studies
suggest that H. pylori plays a role in initiating the sequential
stages; i.e., causing chronic gastritis and atrophy (3, 5).
However, how and why H. pylori-induced gastritis progresses
to intestinal metaplasia, a precancerous condition and prob-
ably the irreversible point, is yet to be clarified.
The primary sites for intestinal metaplasia as well as
dysplasia and intestinal-type adenocarcinoma have been
shown to be the gastric antral and angulus areas, particularly
along the lesser curvature (6 –11). In addition, studies have
shown that the time-dependent progression of gastritis in
grade (development of atrophy and intestinal metaplasia)
and in extent (spreading of gastritis by pylorocardial exten-
sion) is correlated with the development of gastric cancer in
the distal and angular stomach (2). Based on these findings,
AJG – January, 2000
it is reasonable to hypothesize that the initial events in
gastric carcinogenesis occur at the junction of the oxyntic
and antral mucosae (12). Further, one may hypothesize that
it is the antral-type mucosa that is prone to intestinal meta-
plasia, and therefore expansion of antral mucosa toward the
gastric incisura, body, and fundus (pylorocardial extension),
or migration of antral mucosa at the gastric body or fundus,
that may be associated with an increased risk of developing
intestinal metaplasia. It is conceivable that H. pylori infec-
tion induces the expansion or migration of antral mucosa by
initiating a cycle of damage and regeneration of the gastric
epithelial cells, and precipitates the process of intestinal
metaplasia by increasing proliferation of the gastric epithe-
lial cells.
To explore these issues, we carried out a histological
mapping study to determine the types of mucosa at different
gastric sites in H. pylori-infected and uninfected patients,
and whether the presence of antral mucosa at the incisura,
body, and fundus is associated with atrophic gastritis and
intestinal metaplasia.
MATERIALS AND METHODS
Patients
Two hundred and sixty-eight consecutive patients with dys-
pepsia or reflux symptoms but no history of anti-H. pylori
therapy were enrolled. They were 130 men and 138 women,
with a mean age of 52.1 yr (range, 17– 85 yr). At endoscopy,
53 patients were diagnosed as having peptic ulcer (14 du-
odenal ulcer, 33 gastric ulcer, and six duodenal and gastric
ulcer), 75 patients had gastroesophageal reflux disease
(GERD), 138 had nonulcer dyspepsia (NUD, 80 normal
mucosa, 58 macroscopic gastroduodenitis), and two patients
had gastric cancer. One hundred and three patients had not
received any medications 3 months before endoscopy. Thir-
teen patients had received treatment with single antibiotics,
21 with proton-pump inhibitors, 80 with H2 receptor antag-
onists, 12 with nonsteroidal antiinflammatory drugs (NSAIDs),
and the remaining 39 with two or more previously men-
tioned drugs. None of the patients had undergone previous
gastric surgery. All patients gave informed consent. The
study was approved by the Local Area Health Service Ethics
Committee.
Identification of H. pylori Infection Status
At the time of endoscopic examination, eight biopsies were
obtained from each patient using a standard mapping pro-
tocol. These included three biopsies taken at the antrum
within 2 cm of the pylorus at the lesser curvature (antrum
⫻3), two from midway between the pylorus and cardioe-
sophageal junction at the greater curvature (body ⫻2), two
from the deepest portion of the dome of the fundus when
retroflexing the endoscope (fundus ⫻2), and one from the
angulus at the lesser curvature (incisura ⫻1). One antral
biopsy was used for a rapid urease test (CLO-test; Delta
West Pty Ltd., Bentley, Western Australia). Three biopsies
H. pylori, Antralization, Metaplasia 115
(one each from the antrum, body, and fundus) were cultured
on horse blood agar plates (Becton Dickinson Pty Ltd., Lane
Cove, NSW, Australia) for 5–7 days under microaerophilic
conditions produced by the BBL GasPak CO2 system (Bec-
ton Dickinson and Company, Cockeysville, MD). Colonies
suspected of being H. pylori were Gram stained, and then
urease activity was tested. The remaining four biopsies were
examined by histology according to the revised Sydney
System after staining with hematoxylin and eosin (hema-
toxylin and eosin), as well as Giemsa (13). Serum samples
were also prepared from each of the patients and a validated
enzyme-linked immunosorbent assay (ELISA) test (sensi-
tivity of 97% and specificity of 96%) was used to detect
specific anti-H. pylori IgG antibodies (14)
The H. pylori status was defined as positive if a patient
was shown to be positive by one of the following: serology;
culture; the CLO-test and histology; or histology on at least
two biopsies.
Histological Assessments of Mucosal Changes
The mucosae of gastric biopsies taken from different sites
were classified as antral (pyloric)-type, body (acid-secreting
or oxyntic)-type, and transitional (junctional)-type accord-
ing to the definitions set out in the updated Sydney System
(13). The characteristic feature of antral-type mucosa is the
presence of coiled and branching antral glands, which are
lined by mucus cells that are interspersed with endocrine
cells (chiefly G and D types), and a few parietal cells. The
glands in body-type mucosa are straight tubes that constitute
hydrochloric acid-producing parietal cells along with scat-
tered mucus cells in their upper portion and mainly chief
cells in their lower portion, with scattered argyrophilic en-
docrine cells. Transitional type mucosa is a mixture of the
architectural features and cell types found in the antral and
body type mucosae (13). The presence of histological find-
ings including chronic and active inflammation, lymphoid
aggregates or follicles, atrophy, and, in particular, intestinal
metaplasia, was determined. Moreover, the grade of intes-
tinal metaplasia was also assessed, using the new visual
analog scale described in the updated Sydney System (13).
The pathologists were blinded to the endoscopic findings.
The slides were read by one of the three histopathologists
(J.M.W., S.A., and K.C.), and reviewed by another. In cases
of discrepancy in determining the grade of histological
changes, an agreement had to be reached by at least two of
the three pathologists. To check the reproducibility in de-
termining the mucosal type at the incisura, two to three
incisura biopsy specimens were taken from each of 30
patients. All 15 cases where two incisura biopsies were
taken showed identical type mucosa, whereas only two of
the 15 cases where three incisura biopsies were taken
showed discrepancy in the mucosal type; one showed antral
and transitional, and another showed transitional and body
mucosa. None showed both antral- and body-type mucosa.
This suggests that a single biopsy taken from the incisura is
representative and reliable.
116 Xia et al.
Table 1. Distribution of Mucosal-Type in Biopsies Taken From Different Gastric Sites in H. pylori-Positive (HP⫹, n ⫽ 113) and
-Negative (HP⫺, n ⫽ 155) Patients
Antral Type
Biopsy Site HP⫹ HP⫺
Antrum 111 (98.7%) 136 (87.7%)*
Incisura 95 (84.1%) 28 (18.1%)‡
Body 4 (3.5%) 2 (1.3%)
Fundus 2 (1.8%) 2 (1.3%)
Comparison between HP⫹ and HP⫺ groups: * p ⬍ 0.01; † p ⬍ 0.05; ‡ p ⬍ 0.001.
Statistical Analysis
Differences in the prevalence of atrophic gastritis and in-
testinal metaplasia among groups of patients were assessed
using the ␹2 test, with Yates’s correction if required. Mul-
tivariate analysis by logistic regression was used to deter-
mine independent risk factors; odds ratios (OR) (and 95%
confidence intervals [CI]) were estimated. The two-sample
t test was used to determine the age difference between
patients with intestinal metaplasia and those without. All p
values calculated were two-tailed; the ␣ level of significance
was set at p ⬍ 0.05.
RESULTS
Detection of H. pylori Infection
Overall, 113 (42.2%) patients were infected with H. pylori.
One hundred patients were positive by both serology and
biopsy-based tests (i.e., culture, histology, or the CLO-test).
Nine patients were positive by serology only. Four patients
were positive by the biopsy based tests but not by serology.
One patient positive by the CLO-test alone was defined as
being negative; the remaining 154 patients were negative by
all the tests. H. pylori-positive patients were older than
-negative patients (53.8 ⫾ 14.8 vs 50.8 ⫾ 16.9), but the
difference was not statistically significant, p ⬎ 0.05). The
prevalence of H. pylori was significantly higher in men than
women (45.4% vs 31.9%, ␹2 ⫽ 5.16, p ⫽ 0.02)
Mucosal-Type: Presence of Antral-Type
Mucosa at Different Sites in the Stomach
Histologically, 92.2% (247/268) of antral biopsies were
associated with the presence of antral-type mucosa, whereas
95.5% (256/268) of body and 97.8% (262/268) of fundus
biopsies had acid-secreting (body-type) mucosa. A striking
difference in mucosal presentation was observed in the
incisura biopsies; antral-type mucosa was more prevalent in
infected patients (84.1%, 95/113) than in uninfected patients
(18.1%, 28/155; OR ⫽ 23.9, 95% CI 12.5– 45.8, ␹2 ⫽
114.7, df ⫽ 1, p ⬍ 0.001). The prevalence of body-type
(acid-secreting) mucosa and transitional mucosa at the in-
cisura in H. pylori-positive and -negative groups was 6.2%
and 43.9% (OR ⫽ 12.5, 95% CI 5.2–27.1, ␹2 ⫽ 46, df ⫽ 1,
p ⬍ 0.001), and 9.7% and 38.1% (OR ⫽ 5.7, 95% CI
2.8 –11.5, ␹2 ⫽ 27.2, df ⫽ 1, p ⬍ 0.001), respectively (Table
1). There was no significant difference in the prevalence of
AJG – Vol. 95, No. 1, 2000
No. (%) of Mucosal Type
Body Type Transitional Type
HP⫹ HP⫺ HP⫺ HP⫺
2 (1.8%) 8 (5.2%) 0 (0) 11 (7.1%)†
7 (6.2%) 68 (43.9%)‡ 11 (9.7%) 59 (38.1%)‡
104 (92.0%) 152 (98.1%)† 5 (4.4%) 1 (0.6%)†
109 (96.5%) 153 (98.7%) 2 (1.8%) 0 (0)
antral-type mucosa between men and women (47.7% vs
44.2%, p ⫽ 0.57). Patients with antral-type mucosa at the
incisura were significantly older than those with transitional
or body type mucosa (55.0 ⫾ 14.5 (mean ⫾ SD) versus
49.4 ⫾ 17.1, t ⫽ 2.88, df ⫽ 266, p ⫽ 0.004). However, the
association between H. pylori infection and the presence of
antral-type mucosa at the incisura persisted after adjustment
for age (OR ⫽ 22.2, 95% CI 11.6 – 42.6, ␹2 ⫽ 88.1, p ⬍
0.001).
Prevalence of Atrophic Gastritis and Intestinal
Metaplasia and Its Association With H. pylori Infection
Thirty-three patients (12.3%) had histological evidence of
atrophic gastritis in the stomach; 23 of 113 H. pylori-
positive patients and 10 of 155 uninfected patients (20.4%
vs 6.5%, OR ⫽ 3.70, 95% CI 1.69 – 8.14, p ⬍ 0.001) (Fig.
1). There was no difference in the prevalence of atrophic
gastritis between men and women (11.5% vs 13%). The
patients with atrophic gastritis were significantly older than
those without atrophic gastritis (58.4 ⫾ 13.9 yr vs 51.1 ⫾
16.2 yr, t ⫽ 2.5, df ⫽ 266, p ⫽ 0.02). However, adjustment
for age did not affect the association between H. pylori
infection and atrophic gastritis (OR ⫽ 3.48, 95% CI 1.57–
7.69, p ⫽ 0.002).
Intestinal metaplasia was present in 43 (16%) of the 268
patients studied; 25 of 113 H. pylori-positive patients and 18
of 155 uninfected patients (22.1% vs 11.6%, OR ⫽ 2.16,
95% CI 1.11– 4.19, p ⫽ 0.02) (Fig. 1). Despite no significant
difference in the overall rates of intestinal metaplasia be-
tween men (15/130, 17.7%) and women (20/138, 14.5%),
Figure 1. Association of H. pylori infection with atrophic gastritis
and intestinal metaplasia.
AJG – January, 2000 H. pylori, Antralization, Metaplasia 117

Table 2. Relationship Between Presence of Antral Mucosa and Atrophic Gastritis in Biopsies Taken From Different Gastric Sites in
H. pylori-Positive (HP⫹, n ⫽ 113) and -Negative (HP⫺, n ⫽ 155) Patients
Percentage (%) of Atrophic Gastritis in Different Sites According to the Presence of Antral-Type Mucosa
(No. of Cases/No. of Total in Parenthesis)
Antral-type Mucosa Non-Antral-Type Mucosa All Type Mucosa
Biopsy
Site HP⫹ HP⫺ Total HP⫹ HP⫺ Total HP⫹ HP⫺ Total
Antrum 8.1 (9/111) 5.9 (8/136) 6.9 (17/248) 0 (0/2) 0 (0/19) 0 (0/21) 8 (9/113) 5.8 (8/155) 6.3 (17/268)
Incisura 22.1 (21/95) 10.7 (3/28) 19.5 (24/123)*§ 5.6 (1㛳/18) 1.6 (2㛳/127) 2.1 (3/145) 19.5 (22/113) 3.2 (5/155)†§ 10.1 (27/268)
Body 25 (1/4) 0 (0/2) 16.7 (1/6) 2.8 (3/109) 0.4 (1/153) 1.5 (4/262) 3.5 (4/113) 0.6 (1/155) 1.9 (5/268)
Fundus 0 (0/2) 1 (1/2) 25 (1/4)*‡ 0.9 (1㛳/111) 0 (0/153) 0.4 (1/264) 1.8 (2/113) 0 (0/155) 0.7 (2/268)
* Comparing antral and nonantral mucosa; † comparing H. pylori-positive and -negative biopsies; ‡ p ⬍ 0.01; § p ⬍ 0.001; 㛳 one of these cases had transitional mucosa.

the prevalence of intestinal metaplasia was significantly
higher in infected men (19/64, 29.9%) than in infected
women (6/49, 12.2%, ␹2 ⫽ 4.9, p ⫽ 0.03) whereas the
difference in uninfected men (4/66, 6.1%) and women (14/
89, 15.7%) was not statistically significant. A significant
difference in the prevalence of intestinal metaplasia was
observed only between men with and without H. pylori
infection (29.9% vs 6.1%, ␹2 ⫽ 12.5, p ⬍ 0.001). The
patients with intestinal metaplasia were significantly older
than those without intestinal metaplasia (62.1 ⫾ 13.2 yr vs
50.1 ⫾ 15.9 yr, t ⫽ 4.7, df ⫽ 266, p ⬍ 0.001). However, the
association between H. pylori infection and intestinal meta-
plasia persisted after adjustment for age (OR ⫽ 2.0, 95% CI
1.00 –3.98, p ⫽ 0.049).
Topography of Atrophic
Gastritis and Intestinal Metaplasia
Atrophic gastritis was present at the antrum in 17 (6.3%)
patients. The rate was 10.1%, 1.9%, and 0.7%, respectively,
at the incisura, body, and fundus. Atrophic gastritis was
more common at the incisura in patients with H. pylori
infection than in those without the infection (19.5% vs 3.2%,
␹2 ⫽ 19, p ⬍ 0.001). The prevalence of atrophic gastritis at
the body and fundus was also higher in infected patients
than uninfected patients, although the difference was not
statistically significant (Table 2).
Intestinal metaplasia was observed in 12%, 8.2%, 3%,
and 1.1% of gastric antrum, incisura, body, and fundus
biopsy specimens, respectively. Intestinal metaplasia was
present at the antrum in 19.5% (22/113) of infected patients
and 7.7% (12/155) of uninfected groups (␹2 ⫽ 8.1, df ⫽ 1,
p ⫽ 0.004). The prevalence of intestinal metaplasia at the
incisura was also significantly higher in infected patients
(15/113, 13.3%) than in uninfected patients (7/155, 4.5%,
␹2 ⫽ 6.7, df ⫽ 1, p ⫽ 0.01). The prevalence of metaplasia
at the body and fundus were 4.4% (5/113) and 1.8% (2/113),
respectively, in infected patients, and 1.9% (3/155) and
0.6% (1/155), respectively, in uninfected patients (Table 3).
Topographic Association of the
Presence of Antral-Type Mucosa With
Atrophic Gastritis and Intestinal Metaplasia
Atrophic gastritis in the upper (or proximal) stomach (i.e.,
the incisura, body, and fundus) was strongly associated with
the presence of antral-type mucosa (Table 2). The preva-
lence of atrophic gastritis at the incisura was 19.5% (24/123)
in the presence of antral-type mucosa, whereas the rate was
2.1% (3/145) in the absence of antral-type mucosa (OR ⫽
11.4, 95% CI 3.4 –39.2, ␹2 ⫽ 22.4, p ⬍ 0.001). Moreover,
the association between the presence of antral-type mucosa
and atrophic gastritis was significant independently of age
(p ⬍ 0.02). In those with antral-type mucosa at the fundus,
the prevalence of atrophic gastritis at the fundus was also
significantly higher compared with those without antral-type
mucosa at the fundus (25% vs 0.4%, OR ⫽ 87.7, 95% CI
4.38 –1754.4, ␹2 ⫽ 7.57, df ⫽ 1, p ⬍ 0.01) (Table 2).
Similarly, intestinal metaplasia in the upper stomach was
also strongly associated with the presence of antral-type
mucosa. At the incisura, 20 (16.3%) of 123 cases with
antral-type mucosa and two (1.4%) of 145 cases without

Table 3. Relationship Between Presence of Antral Mucosa and Intestinal Metaplasia in Biopsies Taken From Different Gastric Sites in
H. pylori-Positive (HP⫹, n ⫽ 113) and -Negative (HP⫺, n ⫽ 155) Patients
Percentage (%) of Intestinal Metaplasia in Different Sites According to the Presence of Antral-Type Mucosa
(No. of Cases/No. of Total in Parenthesis)
Antral-Type Mucosa Non-Antral-Type Mucosa All Type Mucosa
Biopsy
Site HP⫹ HP⫺ Total HP HP⫺ Total HP⫹ HP⫺ Total
Antrum 19.8 (22/111) 8.8 (12/136) 13.8 (34/247) 0 (0/2) 0 (0/19) 0 (0/21) 19.5 (22/113) 7.7 (12/155)†‡ 12.7 (34/268)
Incisura 15.8 (15/95) 17.8 (5/28) 16.3 (20/123)*§ 0 (0/18) 1.8 (2/127) 1.4 (2/145) 13.3 (15/113) 4.5 (7/155)†‡ 8.2 (22/268)
Body 25 (1/4) 50 (1/2) 33.3 (2/6)*‡ 3.7 (4/109) 1.3 (2/153) 2.3 (6/262) 4.4 (5/113) 1.9 (3/155) 3 (8/268)
Fundus 50 (1/2) 50 (1/2) 50 (2/4)*§ 0.9 (1㛳/111) 0 (0/153) 0.4 (1/264) 1.8 (2/113) 0.6 (1/155) 1.1 (3/268)
* Comparing antral and nonantral mucosa; † comparing H. pylori-positive and -negative biopsies; ‡ p ⬍ 0.01; § p ⬍ 0.001; 㛳 this case had transitional mucosa.
118 Xia et al.
antral-type mucosa had intestinal metaplasia (OR ⫽ 13.8,
95% CI 3.2– 60.7, ␹2 ⫽ 19.6, df ⫽ 1, p ⬍ 0.001). Moreover,
the presence of antral-type mucosa at the incisura and H.
pylori infection in the stomach were both associated with
intestinal metaplasia at the incisura independently of age
(p ⬍ 0.01 and p ⬍ 0.001, respectively). The strong associ-
ation between the presence of antral-type mucosa and in-
testinal metaplasia also existed in the gastric body (33.3% vs
2.3%, OR ⫽ 21.3, 95% CI 3.25–139.9, ␹2 ⫽ 19.5, df ⫽ 1,
p ⬍ 0.001) and fundus mucosa (50% vs 0.4%, OR ⫽ 263.0,
95% CI 16.4 – 4215.8, ␹2 ⫽ 87.7, df ⫽ 1, p ⬍ 0.001) (Table
3).
Atrophic gastritis, when present, was mild in most cases.
The grade of atrophy appeared to be similar at the antrum
(1.18 ⫾ 0.39, mean ⫾ SD, n ⫽ 17), incisura (1.19 ⫾ 0.40,
n ⫽ 27), body (1.20 ⫾ 0.45, n ⫽ 5), and fundus (1.0, n ⫽
2). The grade of atrophic gastritis in the upper stomach was
similar between cases with antral-type mucosa at the inci-
sura, body, or fundus (1.29 ⫾ 0.48) and those without
(1.16 ⫾ 0.37).
The grade of intestinal metaplasia appeared to increase
from the distal to the proximal stomach; it was 1.38 (⫾ 0.70)
at the antrum (n ⫽ 34), 1.91 (⫾ 0.87) at the incisura (n ⫽
22), 2.13 (⫾ 0.99) at the body (n ⫽ 8), and 2.33 (⫾ 1.16)
at the fundus (n ⫽ 3). However, the grade of intestinal
metaplasia in the upper stomach, including the incisura,
body, and fundus, was similar between cases with and
without the presence of antral-type mucosa at these sites
(2.00 ⫾ 0.94 vs 2.08 ⫾ 0.91, p ⬎ 0.05).
Association Between the Presence of Antral-Type
Mucosa at the Incisura and Endoscopic Findings
The presence of antral-type mucosa at the incisura was seen
in 71.4%, 57.6%, and 66.7% of patients with duodenal ulcer,
gastric ulcer, and duodenal and gastric ulcer, respectively,
giving an overall rate of 62.3% (33/53) in patients with
peptic ulcer disease. The prevalence of the presence of
antral-type mucosa at the incisura was 47.8% (66/138) in
patients with NUD (compared with peptic ulcer patients,
NS), whereas the rate was 38.6% (22/75) in those with
GERD, which was significantly lower than that in peptic
ulcer patients (␹2 ⫽ 13.7, df ⫽ 1, p ⬍ 0.001). When H.
pylori-negative patients were excluded, the prevalence of
the presence of antral-type mucosa at the incisura was
93.1% (27/29), 83.3% (50/60), and 72.7% (16/22), respec-
tively, in patients with peptic ulcer disease, NUD, and
GERD; the difference in the rate between peptic ulcer dis-
ease and GERD remained statistically significant (p ⬍
0.05). Both patients with gastric cancer were H. pylori
positive and had antral-type mucosa at the incisura.
The prevalence of atrophic gastritis was 14.3%, 22.2%,
33.3%, 10.9%, and 9.3%, respectively, in duodenal ulcer,
gastric ulcer, duodenal and gastric ulcer, NUD, and GERD.
The prevalence of intestinal metaplasia was 7.1%, 33.3%,
33.3%, 15.5%, and 13.6%, respectively, in these groups.
The highest prevalence of atrophic gastritis and intestinal
AJG – Vol. 95, No. 1, 2000
metaplasia was in patients with gastric ulcer, although the
difference was not statistically significant compared with
other groups. Atrophic gastritis and intestinal metaplasia
was present in one of the two gastric cancer cases.
DISCUSSION
The finding that atrophic gastritis and intestinal metaplasia
occurred predominantly at the gastric antrum and incisura is
consistent with previous observations (6 –11). In the present
study, it was also found that the prevalence of intestinal
metaplasia was significantly higher at the gastric antrum of
patients with H. pylori infection, compared with uninfected
cases. Moreover, the prevalence of atrophic gastritis and
intestinal metaplasia was significantly higher at the gastric
incisura of infected patients than in those without infection.
Studies before the H. pylori era showed that gastritis first
affected the distal part of the stomach, tended to be more
severe at the antrum, and showed pylorocardial extension
with greater involvement of the gastric angulus in particular
(15, 16). Development of intestinal metaplasia is closely
related to the acid-secreting function in the stomach, i.e., the
frequency and extent of intestinal metaplasia increases when
the acid-secreting area decreases (17). In the present study,
we observed that among patients without H. pylori infec-
tion, most (82%) biopsies taken from the incisura had acid-
secreting (44%) or transitional (38%) mucosa whereas 18%
had antral-type mucosa. In contrast, as many as 85% of H.
pylori-positive patients had incisura biopsies with antral-
type mucosa; only 6% had acid-secreting mucosa. We have
coined the term “antralization” to describe this change; i.e.,
mucosa altered from transitional or acid-secreting type to
antral type. Antralization also occurred at the body and
fundus in a few patients; four of six antralized body biopsies
and the two of four antralized fundus biopsy were associated
with H. pylori infection. This finding suggests that H. pylori
infection may lead to expansion of the gastric antral-type
mucosa toward the upper stomach, or retreat of the oxyntic
mucosa, which is then replaced by antral mucosa.
Notably, there were 21 (8%) cases where biopsies taken
from the antrum showed acid-secreting (n ⫽ 10) or transi-
tional mucosa (n ⫽ 11); 19 of these 21 patients were H.
pylori negative and two were H. pylori positive. It is pos-
tulated that in the absence of H. pylori infection, transitional
or body-type mucosa may exist in the anatomical location of
gastric antrum in a few cases. In our mapping protocol,
biopsy specimens were always taken carefully at the antrum
within 2 cm of the pylorus along the lesser curvature.
Therefore, we believe that our observations are unlikely to
represent sampling error.
More importantly, we found that antralization of the
incisura, body, and fundus was associated with an increased
risk of having gastric atrophy and intestinal metaplasia,
suggesting that antralization is an important step (or marker)
in the process of gastritis progressing to gastric atrophy and
intestinal metaplasia. Even in patients without infection,
AJG – January, 2000
antralization at the incisura was strongly associated with
gastric atrophy and intestinal metaplasia. This could be
explained, in part, by the fact that gastric atrophy and
intestinal metaplasia creates a hostile environment for H.
pylori, and thus it is likely that some of these patients might
have been infected with H. pylori in the past, but the
organisms were lost after the development of gastric atrophy
and intestinal metaplasia (18 –21). Therefore, it is suggested
that H. pylori-associated antralization is related to the de-
velopment of gastric atrophy and intestinal metaplasia in
most cases.
How H. pylori infection might lead to antralization and
the subsequent development of gastric atrophy and intestinal
metaplasia has yet to be understood. Eidt and Stolte (22)
have suggested that H. pylori probably promotes mucosal
regeneration, and the prolonged stimulatory effect on regen-
eration could then, over the course of time, lead to an
increasing likelihood of development of gastric atrophy and
intestinal metaplasia. Recently, Miwa et al. (23) reported
that the proliferative zone in antral specimens with intestinal
metaplasia was deeper and larger than in nonintestinalized
antral mucosa, indicating that dislocation of the proliferative
zone with an increase in its size is a hallmark of gastric
intestinal metaplasia. Thus, increased proliferation of antral
mucosa appears to be associated with the development of
intestinal metaplasia. Indeed, Cahill et al. (24) observed that
patients with chronic atrophic gastritis, intestinal metapla-
sia, or gastric cancer had increased gastric antral epithelial
cell proliferation, compared with normal mucosa. Although
H. pylori status was not associated with these results, in
gastritis associated with H. pylori infection there was in-
creased epithelial cell proliferation, compared with normal
controls or subjects with H. pylori-negative gastritis, sug-
gesting an initial role for H. pylori infection in the process
(24). Moreover, this group also found that successful erad-
ication of H. pylori infection in patients with gastritis re-
duced the gastric antral epithelial cell proliferation to nor-
mal levels (25).
There is good evidence that H. pylori infection increases
basal acid output in most patients with duodenal ulcer (26 –
28). However, in a proportion of infected individuals with-
out duodenal ulcer, local acid secretion is decreased, al-
though the underlying mechanisms remain poorly
understood (29, 30). It is known that hypochlorhydria is
associated with gastric atrophy and intestinal metaplasia, but
whether it is a cause or a consequence of these lesions is still
controversial (30 –33). We hypothesize that antralization in
the upper stomach may have affected local acid secretion
(although it is possible that local acid secretion may also
have an influence on antralization in the upper stomach).
The degree of influence may depend on the severity and
extent of antralization, as well as the ability of the oxyntic
mucosa to compensate. It is likely that the majority of
individuals with H. pylori-associated antralization but with-
out duodenal ulcer may, to some extent, have reduced acid
secretion, as the acid-secreting area is decreased (17, 30).
H. pylori, Antralization, Metaplasia 119
However, because the outcome of H. pylori infection de-
pends on a complex interaction between the host and infec-
tion, changes in local acid secretion may be variable (26, 27,
30). Although we were not able to directly evaluate the
association between antralization and local acid secretion in
this study, we tried to correlate the prevalence of antraliza-
tion, atrophic gastritis, and intestinal metaplasia with endo-
scopic findings. Previous studies have suggested that gastric
atrophy and intestinal metaplasia are more prevalent in
gastric ulcer, which is believed to be associated with a low
local acid secretion, than duodenal ulcer and other endo-
scopic findings (34, 35). These observations were confirmed
in the present study. The highest prevalence of atrophic
gastritis and intestinal metaplasia was in gastric ulcer (22%
and 33%, respectively) and the lowest prevalence of atro-
phic gastritis was in GERD (9%), which is usually associ-
ated with normal acid secretion; the lowest prevalence of
intestinal metaplasia was in duodenal ulcer (7%), where the
local acid secretion is usually high to normal. Moreover, a
higher prevalence of antralization at the incisura was found
in patients with gastric ulcer than in those with GERD.
However, a high prevalence of antralization at the incisura
was also observed in patients with duodenal ulcer. Further-
more, a significant difference in the prevalence of antraliza-
tion between the patients with peptic ulcer diseases and
those with GERD remained even when H. pylori-positive
status was taken into account. Therefore, more studies are
required to elucidate the relationship between antralization
and local acid secretion.
Conflicting results have been reported on the association
of H. pylori infection with atrophic gastritis, intestinal meta-
plasia, and gastric cancer, probably due to the disappearance
of the organisms in many of these histological lesions (18 –
21). In the present study, five of the nine patients who were
positive by serology but negative by other biopsy based tests
had intestinal metaplasia. Thus, identification of an earlier
stage before these late lesions may help us to understand the
process of the development of gastric cancer and clarify the
role of the infection in carcinogenesis. Atrophy, intestinal
metaplasia, and dysplasia probably do not reverse after
successful eradication of H. pylori infection, although this is
controversial (21, 36 – 44). For example, whether antraliza-
tion at the gastric incisura is a marker for the risk of gastric
cancer that will be reversible with H. pylori eradication is
unknown but feasible.
Based on the findings in the present study as well as
previous studies described here, it is concluded that antral-
ization at the junctional area between the anatomical antrum
and body along the lesser curvature is related to H. pylori
infection and is a marker for the development of atrophic
gastritis and intestinal metaplasia. Further histological and
pathophysiological studies on populations with a high risk
of intestinal metaplasia or gastric carcinoma and clinical
trials evaluating the effect of eradication of H. pylori infec-
tion on the antralization process are now needed to further
understand this condition.
120 Xia et al.
ACKNOWLEDGMENT
We thank Dr. Laurence Brooks, Dr. Andrew Keegan, and
the staff of the Endoscopy Unit, Nepean Hospital, for their
assistance and cooperation.
Reprint requests and correspondence: Nicholas J. Talley, M.D.,
Professor of Medicine, Department of Medicine, The University of
Sydney, Nepean Hospital, P. O. Box 63, Penrith, NSW 2751,
Australia.
Received Apr. 3, 1999; accepted Aug. 18, 1999.
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