REVIEW ARTICLE

Screening and surveillance for gastric cancer in the United

States: Is it needed?
Gwang Ha Kim, MD, PhD,1 Peter S. Liang, MD,2 Sung Jo Bang, MD,3 Joo Ha Hwang, MD, PhD2
Busan, Ulsan, Korea; Seattle, Washington, USA

Background and Aims: Although the incidence of gastric cancer in the United States is relatively low, the
incidence of gastric cancer is higher than for esophageal cancer, for which clear guidelines for screening and sur-
veillance exist. With the increasing availability of endoscopic therapy, such as endoscopic submucosal dissection,
for treating advanced dysplasia and early gastric cancer, establishing guidelines for screening and surveillance of
patients who are at high risk of developing gastric cancer has the potential to diagnose and treat gastric cancer at
an earlier stage and improve mortality from gastric cancer. The aims of this article were to review the data
regarding the risk factors for developing gastric cancer, methods for gastric cancer screening, and results of
national screening programs.
Methods: A review of the existing literature related to the aims was performed.
Results: Risk factors for gastric cancer that were identified include race/ethnicity (East Asian, Russian, or South
American), first-degree relative diagnosed with gastric cancer, positive Helicobacter pylori status, and presence of
atrophic gastritis or intestinal metaplasia. Endoscopy has the highest rate of detecting gastric cancer compared
with other gastric cancer screening methods. The national screening program in Japan has demonstrated a
mortality reduction from gastric cancer based on cohort data.
Conclusions: Gastric cancer screening with endoscopy should be considered in individuals who are immigrants
from regions associated with a high risk of gastric cancer (East Asia, Russia, or South America) or who have a
family history of gastric cancer. Those with findings of atrophic gastritis or intestinal metaplasia on screening
endoscopy should undergo surveillance endoscopy every 1 to 2 years. Large prospective multicenter studies
are needed to further identify additional risk factors for developing gastric cancer and to assess whether gastric
cancer screening programs for high-risk populations in the United States would result in improved mortality.
(Gastrointest Endosc 2016;84:18-28.)

Gastric cancer is one of the world’s leading causes of
morbidity and mortality from malignant disease. An estimated
1 million cases of gastric cancer (952,000 cases; 6.8% of all
Abbreviations: AG, atrophic gastritis; CI, confidence interval; EGC, early
gastric cancer; IM, intestinal metaplasia; OR, odds ratio; PG, pepsin-
ogen; UGI, upper GI.
DISCLOSURE: All authors disclosed no financial relationships relevant
to this publication.
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http://dx.doi.org/10.1016/j.gie.2016.02.028
cancers) occurred globally in 2012, making it the fifth most-
common malignancy in the world, after lung, breast, colo-
rectal, and prostate cancers.1,2 More than 70% of gastric
cancer cases occur in the developing world, and approxi-
mately 50% occur in East Asia.3 Gastric cancer is less
common in the United States, with the incidence of gastric
cancer among males and females in the United States at
12.3 and 6.0 per 100,000/year, respectively; however, there
is a disproportionally higher incidence in Asians.4 The
estimated number of new cases of gastric cancer in the
United States in 2015 was 24,590 (1.5% of all cancers) and
10,720 deaths (1.8% of all cancer deaths).5 It should be
noted that the estimated number of new cases of
esophageal cancer in the United States for 2015 was 16,980
(1.0% of all cancers), which is less than the number of new
cases of gastric cancer. Guidelines for esophageal cancer
screening and surveillance of Barrett’s esophagus exist;
however, guidelines for gastric cancer screening and
surveillance of gastric intestinal metaplasia (IM) are lacking.

18 GASTROINTESTINAL ENDOSCOPY Volume 84, No. 1 : 2016 www.giejournal.org

Kim et al
TABLE 1. Main risk factors for gastric cancer according to the tumor location
Risk estimates (95% CI)
Noncardia cancer
H pylori infection RR 2.97 (2.34-3.77)
Cigarette smoking RR 1.60 (1.41-1.80)
Alcohol RR 1.07 (.91-1.26)
Obesity (BMI > 30) RR 1.26 (.89-1.78)
Vegetables RR .75 (.59-.95)
Fruit RR .61 (.44-.84)
High salt intake OR 2.05 (1.60-2.62)
Family history of gastric cancer OR 2.82 (1.83-4.46)
Intestinal metaplasia RR 6.4 (2.6-16.1)*
CI, Confidence interval; RR, relative risk; BMI, body mass index; OR, odds ratio.
*In H pylori–positive individuals.
Since the 1970s there have been notable improvements
in the 5-year relative survival rates for gastric cancer in the
United States, from 15% in 1975 to 29% in 2009.6 However,
these low survival rates suggest that most cases (over 65%)
are still diagnosed at an advanced stage.5 The overall 5-year
relative survival rate is about 20% in most parts of the
world, but in Japan and Korea 5-year survival rates above
70% for stage I and II gastric cancer have been re-
ported.7-9 A multicenter retrospective study of 2191
patients with gastric cancer undergoing surgical resection
showed that early gastric cancer (EGC) comprised approx-
imately 20% of all surgically resected cancers in North
America compared with 50% of resected cancers in
Japan.10 Although these differences can be explained by
multiple factors, one of most plausible reasons is the
implementation of a screening program for detection of
EGC in Japan and Korea.
Identification of risk factors involved in carcinogenesis
and interventions to address these risk factors may
reduce the incidence of gastric cancer. Reducing gastric
cancer mortality also requires early identification of
patients who are at high risk for gastric cancer and
management strategies to slow or prevent progression
of gastric cancer. It is likely to be more cost-effective to
detect and treat early-stage gastric cancer with endo-
scopic resection rather than surgical resection. In this
review we discuss risk factors for gastric cancer, define
high-risk groups, and summarize current guidelines for
screening and surveillance strategies for these high-risk
groups. Finally, we propose an algorithm for screening
and surveillance of individuals who are at high risk for
gastric cancer in the United States.
RISK FACTORS FOR GASTRIC CANCER
Gastric cancer is a multifactorial disease involving both
genetic and environmental risk factors. Its risk factors differ
depending on whether cancers arise in the proximal cardia
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Screening and surveillance for gastric cancer
Cardia cancer Reference
RR .99 (.72-1.35) Helicobacter and Cancer Collaborative Group23
RR 1.87 (1.31-2.67) Ladeiras-Lopes et al97
RR .94 (.78-1.13) Tramacere et al98
RR 2.06 (1.63-2.61) Yang et al99
RR .63 (.50-.79) Lunet et al.100
RR .58 (.38-.89) Lunet et al.100
Ge et al.101
Shin et al.27
Uemura et al.37
region or in the distal noncardia region. Advanced age,
male sex, smoking, and family history are common risk
factors for both cardia and noncardia cancers. In terms of
race/ethnicity, whites tend to develop cardia cancer,
whereas Hispanics and Asians tend to develop noncardia
cancer. Helicobacter pylori infection and dietary factors,
such as high intake of salt, increase the risk of noncardia
cancer. On the other hand, obesity and GERD are mainly
associated with cancers arising from the cardia. The
estimates of risk factors for gastric cancer are summarized
in Table 1.
Age
The incidence of gastric cancer increases with age. Be-
tween 2007 and 2011 only 6% of cases occurred in individ-
uals younger than age 45 in the United States, whereas
approximately 70% of cases were diagnosed in individuals
aged 55 to 84.
Sex
Compared with women, men have a higher risk of both
cardia (5-fold) and noncardia (2-fold) gastric cancer.11 The
reason for this difference is unclear, but environmental or
occupational exposures may play a role. Men have
historically tended to smoke more than women, whereas
estrogens may protect against the development of gastric
cancer.12 Delayed menopause and increased fertility may
lower the risk of gastric cancer, whereas antiestrogen
drugs such as tamoxifen may increase the rates of gastric
cancer.13,14 These hormones may protect against gastric
cancer among women of childbearing age, but their effect
is diminished after menopause. Consequently, women
develop gastric cancer in a manner similar to men, albeit
with a 10- to 15-year lag period.15
Race/ethnicity
There is significant variability in the gastric cancer inci-
dence across different ethnicities in the United States.
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Screening and surveillance for gastric cancer Kim et al

450

400

350
Incidence rates (per 100,000/year)

300
White
250 African American
Asian/Pacific Islander
American Indian/Alaska Native
200 Hispanic
Native Korean
Native Japanese
150

100

50

0
15-19
5-19220-24
0-24225-29 30-34 35-39
5-39440-44
0-44445-49 50-54
0-54555-59
5-59660-64
0-64665-69
5-69770-74
0-74775-79
5-79880-84 >85
Age (years)

Figure 1. Incidence of gastric cancers according to age and race in the United States, Japan, and Korea.5,41,42

Data from the 2002 to 2006 Surveillance, Epidemiology, Helicobacter pylori

and End Results registries show that the incidence of H pylori infection triggers a series of inflammatory
gastric cancer among whites (men, 10.7 per 100,000/year, reactions, which are considered an important cause of
and women, 5.0 per 100,000/year) is approximately chronic gastritis. Progression from chronic gastritis to
half that of Asians/Pacific Islanders (men, 20.8 per gastric atrophy and IM is an early step of mucosal changes
100,000/year, and women, 11.7 per 100,000/year), African in the stomach leading to dysplasia and ultimately cancer.19
Americans (men, 18.4 per 100,000/year, and women, 9.2 H pylori has been classified as a World Health Organization
per 100,000/year), and Hispanics (men, 17.1 per 100,000/ Class I carcinogen since 1994 because several studies have
year, and women, 10.0 per 100,000/year) for both men demonstrated an association between H pylori infection
and women (Fig. 1).4,5 Among Asian American subgroups, and development of gastric cancer, especially intestinal-
Korean and Japanese Americans have an especially high type noncardia gastric cancer.20 Gastric cancer develops
incidence rate (Fig. 2).16 In a study evaluating the effect in approximately 1% of H pylori–infected subjects21;
of immigration on the incidence of gastric cancer among conversely, more than 90% of patients with gastric cancer
Japanese in Hawaii, first-generation participants had high have had current or past H pylori infection.22 In a
rates of gastric cancer17; however, after 2 generations, pooled analysis of 12 prospective studies, which included
gastric cancer rates among Japanese Americans had 762 patients and 2250 control subjects, the odds ratio
decreased to a level that was similar to those of (OR) of H pylori infection for noncardia cancer was 2.97
Americans of European ancestry. (95% confidence interval [CI], 2.34-3.77).23 On the other
By anatomic site, noncardia gastric cancer is approxi- hand, the OR of H pylori infection for cardia cancer was
mately half as common in whites compared with other .99 (95% CI, .40-1.77) in an analysis of 274 patients and
ethnic groups,18 whereas cardia gastric cancer is 827 control subjects.23 When only cases occurring at least
approximately twice as common.11 The risk of noncardia 10 years after the blood draw used for H pylori diagnosis
gastric cancer in the United States is highest among were included in the pooled analysis, the OR increased
Asians/Pacific Islanders, African Americans, and Hispanics to 5.93 (95% CI, 3.41-10.3) for noncardia cancer but
and is least common in whites.6 decreased to .46 (95% CI, .23-.90) for cardia cancer.

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Kim et al Screening and surveillance for gastric cancer

60

50
Incidence rates (per 100,000/year)

40

30 Male
Female

20

10

0
All races Non-Hispanic African Hispanic Asian/Pacific Japanese Korean
White American Islander American American

Figure 2. Age-adjusted incidence rate of gastric cancer by race/ethnicity in the United States.4,16

Family history of gastric cancer TABLE 2. Hereditary syndromes associated with increased risk for
Having a first-degree relative with gastric cancer is asso- gastric cancer
ciated with an OR of 2 to 10 for developing gastric cancer,
Gastric
depending on race.24 Two Western studies showed that a Hereditary syndromes Genes cancer risk
first-degree family history of gastric cancer increased the
risk by 2.6- to 3.5-fold, with a calculated attributable risk Hereditary diffuse gastric CGH1 >80%
cancer
of 8%.25,26 A Korean study examining subjects with first-
degree relatives with gastric cancer found a comparable Lynch syndrome MLH1, MSH2, MSH6, 6%-13%
PMS2, Epcam
adjusted OR of 2.85 (95% CI, 1.83-4.46).27 In addition, in
a meta-analysis studying H pylori infection and gastric Hereditary breast/ovarian BRCA1/2 2.6%-5.5%
cancer syndrome
histology in the first-degree relatives of gastric cancer pa-
tients, individuals with a family history of gastric cancer Li-Fraumeni syndrome p53 2.8%
were approximately twice as likely to have H pylori infec- Familial adenomatous APC .5%-2%
tion, atrophic gastritis (AG), and IM.28 polyposis syndrome
Up to 1% to 3% of gastric cancer cases are thought to be Juvenile polyposis syndrome SMAD4, BMPR1A 21%
related to hereditary syndromes (Table 2).29 Hereditary Peutz-Jeghers syndrome STK11 29%
diffuse gastric cancer is a rare, autosomal dominant,
genetic syndrome characterized by the early onset of
diffuse gastric adenocarcinoma (ie, before age 40), an as hereditary breast and ovarian cancer, Li-Fraumeni, famil-
increased risk of lobular breast cancer and signet-ring cell ial adenomatous polyposis, Peutz-Jeghers, and juvenile
colorectal cancer, and a poor prognosis.30,31 This syndrome polyposis are also associated with an increased risk for
is caused by a germline mutation in the CDH1 gene on chro- gastric cancer.33
mosome 16q22, which encodes for E-cadherin. In hereditary
diffuse gastric cancer families, carriage of the abnormal Atrophic gastritis and intestinal metaplasia
E-cadherin gene confers a greater than 80% lifetime risk of AG and IM are considered precursor conditions of
developing gastric cancer; therefore, carriers of the CDH1 gastric cancer, and both are strongly associated with H
mutation are recommended to undergo prophylactic total pylori infection.19 A nationwide cohort study in the
gastrectomy or endoscopic screening.31 Netherlands reported that the risk of gastric cancer
Gastric cancer risk is also increased in patients with increased in a stepwise manner according to the severity
Lynch syndrome, with affected individuals carrying a 10% of premalignant gastric lesions. Within 5 years of
lifetime risk.29 Most gastric cancers (90%) that develop in diagnosis, the annual incidence of gastric cancer was
patients with Lynch syndrome are intestinal-type cancers .1% for patients with AG, .25% for IM, .6% for mild-to-
and have the same natural history as sporadic intestinal- moderate dysplasia, and 6% for severe dysplasia.34
type gastric cancer.32 Other hereditary syndromes such Although the risk of gastric cancer in individuals with AG

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Screening and surveillance for gastric cancer
depends on the severity of AG, the adjusted relative risk of
gastric cancer in patients with severe AG was 5.76.35
Gastric cancer incidence in IM patients was reported to
range from 0% to 10% in a systematic review,36 which may
be because of the variation in sample size and follow-up
period in the included studies. A nationwide, histology-
based Dutch study including 61,707 patients with IM
showed that the cumulative 10-year incidence of gastric
cancer was 1.8% (.18% yearly),34 and a large Japanese
study of 1246 H pylori–infected individuals with IM
with a mean follow-up period of 7.8 years showed that
the relative risk of progression to gastric cancer was 6.4
(95% CI, 2.6-16.1).37 The progression from gastric IM to
gastric cancer is highly associated with the histologic
subtype of IM. IM can be subclassified as complete type
or incomplete type. Complete-type IM is characterized
by the presence of a small intestinal-type mucosal pheno-
type with goblet cells containing sialomucin interspersed
among absorptive cells and with a well-defined brush
border, whereas incomplete-type IM is characterized by a
colonic-type mucosal phenotype with tortuous crypts lined
by tall columnar cells containing abundant sulfomucin.
Incomplete type is considered to be a more advanced
stage of IM and has a higher risk of progressing to gastric
cancer.38 In a pooled analysis, 13 of 14 cross-sectional
studies and 6 of 10 cohort studies reported significantly
higher gastric cancer prevalence in the patients with
incomplete-type IM than complete-type IM, with a relative
risk of 4 to 11.37,39 Therefore, patients found to have
incomplete-type IM should undergo surveillance for gastric
cancer.
Other risk factors
Other factors such as cigarette smoking, alcohol,
obesity, fruit/vegetable consumption, and salt intake have
also been investigated. Their effects appear to be modest
compared with the risk factors discussed. Risk estimates
are summarized in Table 1.
Screening for gastric cancer: who and when
Screening can be performed in the general population
(mass screening) or only for individuals identified to
have an increased risk for developing gastric cancer.
Although the effectiveness of mass screening for gastric
cancer still remains controversial,40 it has been
undertaken in Korea and Japan, where there is a high
incidence of the disease.41,42 On the other hand, in
countries with a low incidence of gastric cancer, such as
the United States, mass screening would not be cost-
effective, and only individuals identified to be at high risk
for gastric cancer should be considered for screening.
Abundant evidence shows that H pylori infection, family
history of gastric cancer, and AG/IM are associated with an
increased risk of gastric cancer, and therefore individuals
with these risk factors could be considered high risk. How-
ever, there is significant confusion regarding management
22 GASTROINTESTINAL ENDOSCOPY Volume 84, No. 1 : 2016
Kim et al
of patients with risk factors among practicing gastroenter-
ologists, particularly in Western countries.43 Because of
the low incidence of gastric cancer in the United States,
endoscopic screening is not currently recommended.
However, screening and surveillance strategies are well
established in the United States for Barrett’s esophagus,
which likely has a lower rate of progression to
adenocarcinoma than do the aforementioned risk factors
for progression to gastric cancer.43 Because endoscopic
resection techniques such as EMR and endoscopic
submucosal dissection are becoming increasingly
available in the United States, many EGCs can be
endoscopically resected without the need for surgery.
Given these developments, a change in our approach to
managing individuals at high risk for developing gastric
cancer is needed. Because a high-risk patient population
exists and endoscopic screening can further risk-stratify
patients, the establishment of a screening and surveillance
protocol for high-risk individuals is warranted.
The optimal age to start screening for gastric cancer
is not clear. It has been reported that it would take
44 months for early-stage gastric cancer to develop to
advanced-staged disease.44 Because the incidence of
gastric cancer increases sharply after age 40, it has been
suggested that individuals older than 40 may undergo
screening in high-incidence countries such as Japan and Ko-
rea.45 However, based on evolving data demonstrating a
decreasing incidence of gastric cancer in individuals
between ages 40 and 49 years in Japan, the new national
guidelines in Japan now recommend that screening be
started at age 50. Other authors outside Korea also
recommend screening commencement after age 50.46
Given the incidence of gastric cancer by age and the
incidence threshold used to recommend colorectal cancer
screening in the United States (w50 per 100,000),
endoscopic screening for gastric cancer in asymptomatic
adults from high-risk populations should be considered
starting at age 50. A study evaluating the cost-effectiveness
of screening the general population for upper GI (UGI) can-
cers including EGC in the United States by performing an
upper endoscopy at the time of screening colonoscopy
showed that the incremental cost-effectiveness ratio for
this intervention was $95,559 per quality-adjusted life year
saved; this is comparable with published incremental cost-
effectiveness ratios for other cancer screening interventions
that are commonly performed in the United States.47
Therefore, a screening program targeting a smaller high-
risk population should be substantially more cost-effective.
METHODS FOR GASTRIC CANCER SCREENING
Screening for gastric cancer generally involves 4
methods: UGI series, serum pepsinogen (PG) testing, H
pylori serology, and endoscopy. The ideal screening test
should be simple, safe, validated, and tolerable to patients;
however, there is no single method that meets all these
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Kim et al
TABLE 3. Pros and cons of each screening method for gastric cancer
Pros
H pylori serology Noninvasive
Serum pepsinogen testing Noninvasive
Acceptable sensitivity and specificity
Predicts premalignant lesions
Upper gastrointestinal series Noninvasive
Moderate evidence
Endoscopy Most accurate
Biopsy sampling can be performed
criteria. Pros and cons of each screening method are dis-
cussed below and summarized in Table 3.
H pylori serology
H pylori serology as a screening test for gastric cancer
is limited by low sensitivity and a failure to detect prema-
lignant lesions. It is often negative in the presence of long-
standing AG/IM. Even though H pylori virulence factors
such as Cag A, Vac A, and Bab A may increase its sensitivity
for gastric cancer detection, their sensitivity is still low.48
Therefore, H pylori serology is not useful as a stand-
alone screening test.
Serum PG testing
PG is a precursor of pepsin that is produced in the
gastric mucosa. PG is classified biochemically and immuno-
logically into 2 different isozymes, PG I and PG II. PG I is
produced by chief cells in the gastric fundus and body,
and PG II is produced by the cells throughout the entire
stomach.49,50 A decrease in serum PG I level and PG I/II
ratio is associated with the extent of gastric atrophy and
reduction in gastric acid secretion ability. Stepwise
decrease in the PG I/II ratio is closely correlated with the
progression of gastric atrophy.51,52 Therefore, serum PG
level has been suggested to be a useful marker of AG,
which in turn is a precursor of intestinal-type adenocarci-
noma in the stomach.
To detect gastric cancer, serum PG testing, followed by
endoscopic examination, has been introduced in mass
screenings of high-risk patients for gastric cancer. PG I

70 ng/L and PG I/II ratio
3.0 are associated with an
increased risk for gastric cancer.53-55 In a pooled meta-
analysis assessing approximately 300,000 people, the sensi-
tivity and specificity of serum PG testing for gastric cancer
screening were 77% and 73%, respectively.56 In a case-
control study using serum PG level for gastric cancer
screening, the ORs for death from gastric cancer among
control subjects screened within 1 and 2 years were .24
(95% CI, .06-.93) and .38 (95% CI, .16-.91), respectively.57
These results suggest that gastric cancer screening using
serum PG level may decrease gastric cancer mortality;
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Screening and surveillance for gastric cancer
Cons
Very low sensitivity
Does not detect premalignant lesions
Optimal cut-off values can be affected by
several factors (age, sex, race)
Requires endoscopy for confirmation
Exposure to radiation
Requires endoscopy for confirmation
Invasive and expensive
Low evidence
however, the evidence was not considered to be strong
enough to incorporate serum PG testing into the
national screening program in Japan.58 The limitations of
using serum PG include variable proposed cut-off values
for PG I and the PG I/II ratio, lack of sensitivity and speci-
ficity, variability of PG I and the PG I/II ratio (depending on
age, sex, and race), and scant and inconclusive data outside
of Japan.
Combining H pylori serology and serum PG testing may
provide additional information for predicting the develop-
ment of gastric cancer. It has been reported that a combi-
nation of low PG I or PG I/II ratio with negative H pylori
serology antibodies suggests the highest risk for gastric
cancer,53 because it may indicate extensive atrophy
where the H pylori burden in the stomach is reduced.
UGI series
The barium meal indirect radiograph examination was
introduced as a mass screening program for gastric cancer
in the 1960s in Japan.59 In a meta-analysis including 5
case-control studies and 2 cohort studies, gastric cancer
screening using UGI series was reported to be useful,60
but the evidence is weak.61 The sensitivity of UGI series
ranged from 60% to 80%, whereas the specificity and true
positive rate were 90% and .7% to 2.0%, respectively.62
Case-control studies conducted in Japan showed that
screening by UGI series resulted in a 40% to 60% reduction
in gastric cancer mortality, which is the primary reason
this remains an accepted method for the national gastric
cancer screening programs in Japan and Korea.63,64
Endoscopy
Endoscopy is the only method available for direct visual
examination of the gastric mucosa, and it allows for biopsy
sampling so that histologic evaluation can be performed.
Endoscopy is the criterion standard test for diagnosing
gastric cancer because of its high detection rate. Although
UGI series was the initial tool for mass screening of gastric
cancer, a cohort analysis demonstrated that endoscopy
resulted in a 3- to 5-fold higher detection rate for
EGC compared with UGI series and was also more
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Screening and surveillance for gastric cancer
cost-effective.65,66 The sensitivity of endoscopy for identi-
fying gastric cancer is reported to be 78% to 84%.67,68 In
Japan and Korea, endoscopy has become the primary
method for gastric cancer screening given its superior
test characteristics, availability, and affordability (EGD costs
approximately U.S.$40 in Korea).66 However, the use of
endoscopy for gastric cancer screening in the United
States does have several potential limitations, such as
the need for additional trained endoscopists to meet
the increased demand, potential adverse events of
endoscopy, patient acceptance, and cost.62
Several studies suggest that advanced endoscopic imag-
ing modalities such as chromoendoscopy or narrow-band
imaging can increase accuracy for diagnosing gastric
neoplasia compared with standard white light endoscopy.
Chromoendoscopy using indigo carmine and acetic acid
has been demonstrated to clarify subtle mucosal irregular-
ities and to delineate the lateral extent of EGCs.69,70 Meth-
ylene blue magnification chromoendoscopy was shown
to identify IM and intestinal dysplasia with sensitivities of
76% and 97% and specificities of 87% and 81%, respec-
tively, and good interobserver agreement (k Z .74).71
Narrow-band imaging and digital-based image enhance-
ment technologies such as computed virtual chromoendo-
scopy have been reported to increase the diagnostic yield
and accuracy for the detection of gastric neoplasia; howev-
er, imaging criteria are inconsistent between studies and
comparative or validation studies have yet to be per-
formed.72-77 Furthermore, because of the rapid develop-
ment of imaging technologies (including the resolution
of white-light endoscopy), it is difficult to make any defin-
itive conclusions regarding any of the advanced imaging
technologies. A consensus on criteria for characterizing
mucosal patterns is needed to further study the role of
mucosal enhancement imaging technologies to obtain an
accurate assessment of their validity and performance.
Further studies are required to assess the ability of new
imaging technologies to identify gastric IM and EGCs.
Based on the existing evidence and ease of use, it is
reasonable to apply technologies such as narrow-band
imaging or digital-based image enhancement technologies
in addition to high-definition white-light endoscopy to
examine the gastric mucosa and target biopsy sampling.
RESULTS OF NATIONAL SCREENING
PROGRAMS
In Japan, annual gastric cancer screening for all resi-
dents aged 40 years and older with UGI series was initiated
in 1983.60 In 2015 the Japanese guidelines were updated to
allow screening to be performed with either UGI series or
endoscopy based on studies from Japan demonstrating a
decrease in mortality from gastric cancer when screening
is performed with either method.58,78-81 In addition,
screening starting at age 50 and performed every 2 to 3
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Kim et al
TABLE 4. Suggested intervals of surveillance endoscopy in individuals
at high risk for gastric cancer
Country/ Indication for Surveillance Reference and
region surveillance interval (y) year
Australia IM 1-3 Busuttil et al,38
2009
United Extensive AG/IM* 3 Correa et al,92
States 2010
Italy High-risk IMy 1 Zullo et al,90
2012
Low-risk IM 2-3
Europe Extensive AG/IM 1 Dinis-Ribeiro
et al,91 2012
Korea AG/IM or family history of 1 Yoon et al,82
gastric cancer 2015
IM, Intestinal metaplasia; AG, atrophic gastritis.
*Definition of extensive AG: serum PG I level < 70 mg/L and a PG I/PG II ratio < 3;
definition of extensive IM: (1) IM present in at least 2 gastric locations or (2) moderate
or marked IM in at least 2 biopsy specimens.
y(1) IM extension > 20%, (2) the presence of incomplete type IM, (3) first-degree
relative of gastric cancer patients, and (4) smokers.
years is now recommended. The proportion of EGC in
Japan is more than 50% of all gastric cancers diagnosed,
whereas in Europe EGC only comprises 15% of all cases.82
Similarly, in Korea the National Cancer Screening Program
for gastric cancer screening that began in 1999
recommends endoscopy or UGI series for individuals aged
40 years and older every 2 years.83 As a result
approximately 46% to 67% of gastric cancers are detected
at an early stage by screening,84 and the 5-year survival
rate has increased from 43% in 1993 to 1995 to 69% in
2006 to 2011; however, reduction in mortality from gastric
cancer as a result of screening has yet to be demonstrated.41
These data from Japan and Korea support the effectiveness
of screening for gastric cancer in high-risk populations.
Screening intervals
Few studies have addressed the optimal interval for
endoscopic screening for gastric cancer, and no guidelines
exist. In a prospective study in which population-based
screening using endoscopy was performed twice over a
5-year interval in China, which also has a high incidence
of gastric cancer, no reduction in mortality from gastric
cancer was observed.85 On the other hand, in a Japanese
study the 5-year survival rate for patients who had under-
gone endoscopy within 2 years before the detection of
gastric cancer was significantly higher than that for patients
who had not undergone endoscopy within 2 years.86
However, the survival rates were not different between
the patients who had undergone endoscopy within 1
year before the detection of gastric cancer and the
patients who had undergone endoscopy between 1 and
2 years. These results suggest that every 2 years may
be an optimal interval for endoscopic screening for
gastric cancer. Another Korean study also showed that
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Kim et al Screening and surveillance for gastric cancer

1st or 2nd generation immigrant from high-incidence region†, No

or No screening
family history of gastric cancer

Yes

EGD at age 50*

HP(-) HP(+)
AG/IM(+) OR
AG/IM(-) AG/IM(-)
FHx(+)
FHx(-) FHx(-)

Eradicate HP If HP(+), eradicate

AG/IM(-) AG/IM(+)
No follow-up EGD in 3-5 yrs EGD every 1-2 yrs

Figure 3. Suggested screening algorithm for gastric cancer in the United States. yEast Asia, Russia, and South America. *If there is a first-degree relative
with gastric cancer, start screening 10 years before the age at diagnosis in the first-degree relative or age 50 (whichever is earlier).
HP, H pylori; FHx, family history of gastric cancer; AG, atrophic gastritis; IM, intestinal metaplasia.

endoscopic screening every 2 years decreased the
incidence of gastric cancer and that endoscopic resection
could be applied to more patients who underwent EGD
screening within 2 years.87
Appropriateness of the above-mentioned interval for
surveillance endoscopy is not well documented in Western
countries. However, 2 cohort studies in England88 and
Italy89 showed that only 36% and 38% of detected gastric
cancers were in an early stage when the endoscopic
surveillance interval was 1 or 2 years, respectively. Based
on these results, it seems that a 3-year interval follow-up
is not appropriate in clinical practice. Therefore, a Euro-
pean review article proposed that annual endoscopic
surveillance would appear justified in all patients with IM
having at least 1 of following additional risk factors: IM
extension > 20%, presence of incomplete-type IM, first-
degree relative with gastric cancer, and smokers.90 In the
remaining IM patients, surveillance endoscopy with a 2-
to 3-year interval is recommended. According to the
consensus guidelines from the European Gastroenterology
Societies, it is recommended that patients with extensive
AG and/or IM should be offered surveillance endoscopy
once every 3 years.91
Correa et al92 proposed that U.S. patients with extensive
gastric IM (defined as IM present in at least 2 gastric
locations or moderate or marked IM in at least 2 biopsy
specimens) or incomplete-type IM found on index endos-
copy undergo surveillance endoscopy with mapping or
serum PG testing at 1 year and then repeat surveillance
endoscopy every 3 years if extensive AG/IM or
incomplete-type IM persists.
At the present time there are no well-defined guidelines
regarding screening for gastric cancer or surveillance of
gastric intestinal metaplasia in the United States. The
2015 American Society for Gastrointestinal Endoscopy
guidelines suggest that surveillance endoscopy be per-
formed in patients with gastric intestinal metaplasia who
are at an increased risk of gastric cancer because of ethnic
background or family history and that surveillance intervals
should be individualized.93 Table 4 summarizes previously
proposed intervals for endoscopic surveillance in
individuals at high risk for gastric cancer.
PROPOSED ALGORITHM FOR SCREENING AND
SURVEILLANCE OF GASTRIC CANCER IN THE
UNITED STATES
Based on the aforementioned evidence and guidelines,
we propose the following simplified strategy for gastric

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Screening and surveillance for gastric cancer
cancer screening and surveillance of high-risk individuals
(excluding those with hereditary diseases) according to
race, H pylori infection status, family history of gastric can-
cer, and AG/IM status (Fig. 3). We recommend endoscopic
screening for gastric cancer starting at age 50 for
individuals who are first- or second-generation immigrants
from high-incidence regions (East Asia, Russia, and South
America). Individuals with a family history of gastric
cancer are recommended to begin endoscopic screening
10 years before diagnosis in the affected relative, similar
to recommendations for colorectal cancer.94 At the time
of screening endoscopy, at least 5 nontargeted biopsy
specimens should be obtained according to the updated
Sydney System, which includes 2 biopsy samples from
the antrum (lesser and greater curvature), 1 biopsy
sample from the incisura angularis, and 2 biopsy samples
from the body (lesser and greater curvature).95 Biopsy
specimens should be submitted for pathologic evaluation
in separate vials labeled by region of the stomach
(antrum, incisura angularis, and body). This biopsy
protocol has been demonstrated to be both sensitive for
the identification of H pylori infection and AG/IM when
performed in a population considered to be at high risk
for gastric preneoplastic lesions.96 Additional targeted
biopsy samples of visible lesions should also be obtained
and submitted in separate vials.91
After screening EGD, those with no H pylori infection,
no family history of gastric cancer, and no AG/IM identified
on screening endoscopy require no further follow-up.
Those with H pylori infection alone should be treated for
H pylori eradication therapy with confirmation of eradica-
tion and then undergo endoscopic examination in 3 to 5
years to evaluate for progression to AG/IM. If there is no
evidence of progression to AG/IM, then surveillance can
be discontinued because the risk of gastric cancer is low
in the absence of AG/IM. Additionally, those at high risk
(family history of gastric cancer or presence of AG/IM)
should undergo endoscopy every 1 to 2 years with eradica-
tion therapy in patients with H pylori infection. Prospec-
tive studies are needed to assess whether this screening
and surveillance protocol for gastric cancer in the United
States will produce a survival benefit similar to that
observed in Korea and Japan.
CONCLUSIONS
Comprehensive U.S. guidelines for gastric cancer
screening and surveillance of high-risk individuals are war-
ranted. The optimal gastric cancer prevention program will
combine risk stratification for screening and surveillance
for high-risk groups. Because race, H pylori infection, fam-
ily history of gastric cancer, and AG/IM are significant risk
factors for gastric cancer, the initial approach should be
to identify individuals with these risk factors. Although
large, prospective, multicenter studies are needed to
26 GASTROINTESTINAL ENDOSCOPY Volume 84, No. 1 : 2016
Kim et al
evaluate the effectiveness of screening and surveillance
strategies to detect gastric cancer, it would be reasonable
to begin screening individuals who are at high risk for
developing gastric cancer and then to perform surveillance
endoscopy at 1- or 2-year intervals if IM is identified on
screening endoscopy or if the patient has a family history
of gastric cancer. Gastric cancer screening in the appro-
priate population will likely lead to an increase in the
detection of EGCs, which may improve the likelihood of
being able to intervene with endoscopic therapy, such as
endoscopic submucosal dissection, and reduce mortality
from gastric cancer.
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Received November 24, 2015. Accepted February 19, 2016.
Current affiliations: Department of Internal Medicine, Pusan National
University School of Medicine and Biomedical Research Institute, Pusan
National University Hospital, Busan, Korea (1), Division of Gastroenter-
ology, Department of Medicine, University of Washington, Seattle, Wash-
ington, USA, (2), Department of Internal Medicine, Ulsan University
Hospital, University of Ulsan College of Medicine, Ulsan, Korea (3).
Reprint requests: Joo Ha Hwang, MD, PhD, Division of Gastroenterology,
Department of Medicine, University of Washington, 325 Ninth Avenue,
Seattle, WA 98104.
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