Asia-Pacific Consensus On Gastric Cancer Prevention

doi:10.1111/j.1440-1746.2008.05314.
S P E C I A L A RT I C L E
AsiaPacic consensus guidelines on gastric cancer prevention

Kwong Ming Fock,* Nick Talley, Paul Moayyedi, Richard Hunt, Takeshi Azuma, Kentaro Sugano, Shu Dong Xiao,** Shiu Kum Lam, Khean Lee Goh, Tsutomu Chiba, Naomi Uemura, Jae G Kim,*** Nayoung Kim, Tiing Leong Ang,* Varocha Mahachai, Hazel Mitchell, Abdul Aziz Rani, Jyh Ming Liou,**** Ratha-korn Vilaichone and Jose Sollano
*Changi General Hospital, Singapore; Mayo Clinic College of Medicine, Rochester, USA; McMaster University Medical Center, Ontario, Canada; University of Fukui, Fukui, Jichi Medical University, Tochigi, Kyoto University, Kyoto, Kure Kyousai General Hospital, Kure, Japan; **Shanghai Institute of Digestive Disease, Shanghai, University of Hong Kong, Hong Kong, China; University of Malaya, Kuala Lumpur, Malaysia; ***Chung Ang University College of Medicine, Seoul National University College of Medicine, Seoul, Korea; Chulalongkorn University Hospital, Bangkok, Thammasat University Hospital, Pathumthani, Thailand; University of New South Wales, Sydney, New South Wales, Australia; University of Indonesia, Jakarta, Indonesia; ****National Taiwan University Hospital, Taipei, Taiwan; and University of Santo Tomas, Manila, Philippines
Key words gastric cancer, guidelines, Helicobacter pylori, prevention. Accepted for publication 22 November 2007. Correspondence Professor Kwong Ming Fock, Division of Gastroenterology, Department of Medicine, Changi General Hospital, 2 Simei Street 3, Singapore 529889. Email: kwong_ming_fock@cgh.com.sg
Abstract
Background and Aim: Gastric cancer is a major health burden in the AsiaPacic region but consensus on prevention strategies has been lacking. We aimed to critically evaluate strategies for preventing gastric cancer. Methods: A multidisciplinary group developed consensus statements using a Delphi approach. Relevant data were presented, and the quality of evidence, strength of recommendation, and level of consensus were graded. Results: Helicobacter pylori infection is a necessary but not sufcient causal factor for non-cardia gastric adenocarcinoma. A high intake of salt is strongly associated with gastric cancer. Fresh fruits and vegetables are protective but the use of vitamins and other dietary supplements does not prevent gastric cancer. Hostbacterial interaction in H. pylori infection results in different patterns of gastritis and differences in gastric acid secretion which determine disease outcome. A positive family history of gastric cancer is an important risk factor. Low serum pepsinogens reect gastric atrophy and may be useful as a marker to identify populations at high risk for gastric cancer. H. pylori screening and treatment is a recommended gastric cancer risk reduction strategy in high-risk populations. H. pylori screening and treatment is most effective before atrophic gastritis has developed. It does not exclude the existing practice of gastric cancer surveillance in high-risk populations. In populations at low risk for gastric cancer, H. pylori screening is not recommended. Firstline treatment of H. pylori infection should be in accordance with national treatment guidelines. Conclusion: A strategy of H. pylori screening and eradication in high-risk populations will probably reduce gastric cancer incidence, and based on current evidence is recommended by consensus.
Introduction
Gastric cancer is a major public health burden. Globally, it is the fourth most common cancer and the second leading cause of cancer-related death, with 700 000 deaths annually.1 The risk of gastric cancer varies among the countries and populations in the AsiaPacic region. High-risk areas include East Asian countries such as China, Japan and Korea, where the age-standardized incidence rate (ASR) is greater than 20 per 100 000. Intermediate risk
countries (ASR 1119/100 000) include Malaysia, Singapore and Taiwan, while low-risk areas (ASR < 10/100 000) include countries such as Australia, New Zealand, India and Thailand.1 Gastric cancer carcinogenesis is a multifactorial process, related to an interaction of host factors, H. pylori infection and environmental factors such as diet. There is a precancerous cascade, in which the gastric mucosa undergoes a series of changes resulting in gastritis, atrophy, intestinal metaplasia, and dysplasia, before developing eventually into gastric cancer.2 At an early stage,
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Journal of Gastroenterology and Hepatology 23 (2008) 351365 2008 The Authors Journal compilation 2008 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd
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gastric cancer may be clinically silent and, in most countries, patients have advanced cancer at diagnosis. When diagnosed at an early stage, 5-year survival rates for gastric cancer exceed 90%.3,4 In addition, early gastric cancer, depending on the depth of mucosal inltration and degree of differentiation, may also be suitable for endoscopic mucosal resection or submucosal dissection, with lower morbidity, but similar efcacy, when compared to surgery.5,6 However, when diagnosed at an advanced stage, 5-year survival rates may be only in the range of 1020%.7,8 To reduce the morbidity and mortality from gastric cancer, it would be necessary to diagnose gastric cancer at an early stage, and explore means of gastric cancer prevention by addressing modiable environmental risk factors such as diet and H. pylori infection. Currently, a strategy of population screening for gastric cancer is being adopted in Japan,9 Korea10 and Matsu Island in Taiwan.11 No formal programs exist in other countries, either in terms of gastric cancer screening or screening for modiable factors such as H. pylori infection. In order to address this major health problem, the The AsiaPacic Gastric Cancer Consensus Conference was convened in order to review and synthesize the most current information, assess the evidence for current and potential intervention strategies and to decide whether it is timely to adopt a bold proactive approach towards gastric cancer prevention by recommending H. pylori screening and eradication.
Table 1 Level of evidence, classication of recommendations and voting scheme Quality of evidence Ia. Evidence obtained from meta-analysis of randomized trials. Ib. Evidence obtained from at least one randomized controlled trial. IIa. Evidence obtained from at least one well-designed controlled study, without randomization. IIb. Evidence obtained from at least one other type of well-designed quasi-experimental study. III. Evidence obtained from well-designed non-experimental descriptive studies, correlation studies and case studies. IV. Evidence obtained from expert committee reports or opinions and/or clinical experience of respected authorities. Classication of recommendations A. Requires at least one randomized controlled trial as part of a body of literature of overall good quality and consistency addressing the specic recommendation. B. Requires the availability of well-conducted clinical studies, but no randomized clinical trials on the topic of the recommendation. C. Requires evidence obtained from expert committee reports or opinions and/or clinical experience of respected authorities. Indicates an absence of directly applicable clinical studies of good quality. Voting on the recommendations a. Strongly agree b. Agree c. Disagree d. Reject
Accept statement when more than two-thirds of participants voted a or b.
Methods
Nature and extent of background preparation
The AsiaPacic Gastric Cancer Consensus Conference was convened specically to address three main areas relevant to the prevention of gastric cancer and, specically, gastric adenocarcinoma. These areas were: (i) epidemiology, host and bacterial factors; (ii) gastric cancer surveillance and H. pylori screening; and (iii) H. pylori eradication to prevent gastric cancer. The consensus conference was held from 11 to 12 November 2006 in Bangkok, Thailand. The consensus conference was sponsored by the Asian Pacic Association of Gastroenterology. The Journal of Gastroenterology and Hepatology Foundation provided nancial support for the conference through an unrestricted educational grant. Sixteen Asian gastroenterologists and four external experts were invited to participate in the consensus conference on the basis of their expertise (Appendix I). None of the participants were remunerated for their participation in the meeting. Each of the three topics chosen for evaluation and formulation of clinical recommendations was addressed independently. Selected papers relevant to the topics to be discussed were circulated and an overview of each topic based on comprehensive literature searches was presented by selected participants based on their specic expertise. This was followed by a period of discussion, in which the existing data were evaluated and critiqued. At the end of this discussion, a recommendation with specic wording was formulated. For data related to therapeutic interventions, the quality of the evidence and the classication of evidence relative to the recommendation were assessed. Once an acceptable recommendation based on available evidence was established, formal voting for each statement of recommendation was undertaken (Table 1). Acceptance of a statement required that at least
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two-thirds of the votes were in categories a (strongly agree) or b (agree).
Preparation process and format of the report

The manuscript was drafted by a working group, and this was then circulated to and reviewed by conference participants, who approved the nal draft.
Consensus statements
Each statement below is followed by a brief summary in which the quality of supporting evidence, a classication of the recommendation and the results of voting are summarized. (N.B. the level of evidence and the grade of recommendation are not included with every statement for the epidemiology section, as many of the statements could not be evaluated by randomized controlled trials.)
Consensus statements
I: Epidemiology, host and bacterial factors
Statement 1: The prevalence of H. pylori infection varies among countries in the AsiaPacic region. This difference is, in general, related to age, socioeconomic circumstances, but also to ethnicity Level of agreement: a, 100%; b, 0%; c, 0%; d, 0%.
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The prevalence of H. pylori infection varies markedly in different Asian countries. The prevalence rates in developing Asian countries such as Bangladesh,12 India,13 Thailand14 and Vietnam15 have been reported to be especially high at 92%, 81%, 74% and 75%, respectively, whereas in more industrialized and developed countries such as Japan,16 Korea17 and Singapore,18 the rates are somewhat lower at 39%, 54% and 31%, respectively. In the AngloCeltic population in Australia, it is approximately 38%.19 Within a country, the seroprevalence rate may vary between geographic regions. In mainland China, the prevalence rate in urban areas was 52% compared to 39% in rural areas,20 whereas in nearby Taiwan, the prevalence rate was 54%.21 There is also a temporal and age-related change in the prevalence rate of H. pylori infection. In Japan,16 the seroprevalence rates decreased from 73% in 1974 to 55% in 1984 and nally to 39% in 1994. In Singapore,18 the seroprevalence of H. pylori infection increased with age from 3% in children below 5 years of age to 71% in adults above 65 years. Within a country, differences in prevalence rates between ethnic groups exist. In Singapore, the prevalence rates in Chinese, Malays and Indians were 46%, 28% and 48%, respectively.22 In Malaysia, the prevalence rates in Chinese, Malays and Indians were 2757.5%, 1229% and 4952%, respectively.23 Statement 2: Gastric cancer is a multifactorial disease Level of agreement: a, 100%; b, 0%; c, 0%; d, 0%. Gastric cancer is a multifactorial disease. Environmental factors such as H. pylori infection and diet are believed to be major contributors to gastric carcinogenesis, but host factors have also been implicated. These factors are individually addressed in the statements that follow. Statement 3: For non-cardia gastric adenocarcinoma, H. pylori is a necessary but not sufcient causal factor Level of agreement: a, 100%; b, 0%; c, 0%; d, 0%. This statement addressed the importance of H. pylori infection as a causal factor for the development of non-cardia gastric adenocarcinoma. It also recognized the fact that not all patients with non-cardia gastric adenocarcinoma are positive for H. pylori, and that other factors are involved as well. As illustrated by a recent study, apart from H. pylori infection, other risk factors such as ethnicity and diet were also independently associated with noncardia gastric adenocarcinoma.24 The relationship of H. pylori with gastric cancer has been examined in a combined analysis of 12 casecontrol studies.25 The prospective design of the studies2637 helped to circumvent the problem of classication bias in retrospective studies, in which H. pylori infection and the circulating antibody response could be lost with development of cancer. In these studies, blood samples for H. pylori serology were collected before diagnosis of gastric cancer. The association with H. pylori was found to be restricted to non-cardia cancers (odds ratio [OR]: 3.0; 95% CI: 2.33.8) and was stronger when blood samples for H. pylori serology were collected more than 10 years before cancer diagnosis (OR: 5.9; 95% CI: 3.410.3). It was concluded that 5.9 was the best estimate of the relative risk of non-cardia cancer associated with H. pylori infection. It was further concluded that based on an average prevalence of H. pylori of 35% in developed countries and 85% in developing countries, an OR of
5.9 would imply that between approximately 65% and 80% of non-cardia gastric cancers were attributable to H. pylori infection and potentially preventable. In Table 2, the seroprevalence of H. pylori infection and the age-standardized incidence rates (ASR) of gastric cancer in selected countries in the AsiaPacic region are listed. It is clear that those countries with high gastric cancer ASR have a high seroprevalence of H. pylori infection. However, there are also populations with a high seroprevalence of H. pylori infection but a purportedly low gastric cancer ASR, such as India and Thailand. These differences are postulated to be related to host genetic factors, bacterial virulence factors38 and other environmental factors. Statement 4: A high intake of salt is strongly associated with gastric cancer in both epidemiological and animal model studies Level of agreement: a, 100%; b, 0%; c, 0%; d, 0%. Salt-preserved food and dietary nitrite are potentially carcinogenic. In animal model studies, salt ingestion has been shown to cause gastritis and enhance the effects of gastric carcinogens.39,40 In an ecological study, the respective importance of high salt and nitrate intake for gastric cancer mortality was assessed at the population level in 24 countries.41 There was a signicant correlation of gastric cancer mortality with sodium as well as nitrate in both men and women. The relationship of gastric cancer mortality with sodium was stronger than with nitrate. In a recent study from Malaysia, a high intake of salted sh and vegetables was found to be signicantly associated with gastric cancer.24 Statement 5: Fresh fruits and vegetables are associated with a reduced risk of gastric cancer Level of agreement: a, 36.8%; b, 63.2%; c, 0%; d, 0%. Level of evidence: I. Grade of recommendation: A. Several prospective studies have reported signicant reductions in gastric cancer risk arising from consumption of fresh fruits and vegetables. In the Cancer Prevention Study II, a high overall plant food intake was associated with reduced risk of gastric cancer in men (relative risk [RR]: 0.79; 95% CI: 0.670.93) but not in women (RR: 1.18; 95% CI: 0.931.50).42 In a prospective cohort study from Japan, the relative risk associated with intake of 1 days per week compared to < 1 day per week was 0.64 (95% CI: 0.450.92) for yellow vegetables, 0.48 (95% CI: 0.250.89) for white vegetables and 0.70 (95% CI: 0.491.00) for fruits.43 In a recent Swedish cohort study, vegetable consumption was inversely associated with risk of gastric cancer, whereas no signicant association was observed for fruit consumption.44 In a multicenter European study, it was observed that for intestinal type non-cardia cancer, a negative association was possible for total vegetable intake and onion and garlic intake.45 A casecontrol study from Malaysia also showed that a high intake of fresh fruits and vegetables was protective against gastric cancer.24 A metaanalysis of cohort studies showed an inverse association between fruit intake and gastric cancer incidence (RR: 0.82; 95% CI: 0.73 0.93) and this was stronger for follow-up periods of 10 years (RR: 0.66; 95% CI: 0.520.83). 46 For vegetables, the RR was 0.88 (95% CI: 0.691.13) using all incidence studies and 0.71 (95% CI:
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Table 2 Country
Prevalence of H. pylori and gastric cancer in the AsiaPacic region Seroprevalence of H. pylori (%) Age-standardized incidence rate (per 100 000) Male Female 6.5 31.7 9.6 6 26.1
Australia19 China20 Changle Hong Kong India13 Japan16
38% 86% 58.4% < 5 years: 2257% > 20 years: 8090% 1974: 72.7% 1984: 54.6% 1994: 39.3% Overall: 46.6% Age > 40 years: 78.5% 26.757.5% 11.929.2% 49.452.3% 46.3% 27.9% 48.1% 54.7% 59 years: 17.5% 2029 years: 55% 3049 years: 75% 74.6%
13.8 81.3 19.3 8.9 62.1
Korea17 Malaysia23 Chinese Malay Indian Singapore22 Chinese Malay Indian Taiwan21 Thailand14
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11.9 2.6 12.9 21.4 6.6 7.8 18.6 5.8
8.7 1.3 7.9 10.8 3.8 6.1 10.5 2.9
Vietnam15
23.7
10.8
0.530.94) when considering only those with a longer follow up. However, these epidemiological associations do not establish beyond doubt that dietary interventions will reduce gastric cancer incidence. Statement 6: There is a protective role of ascorbic acid Level of agreement: a, 0%; b, 52.6%; c, 47.4%; d, 0%. Level of evidence: Ib. Grade of recommendation: A. This statement was rejected. There was no consensus on this statement, with about half agreeing and half disagreeing. Epidemiological evidence suggested that a diet rich in fresh fruit and vegetables could be a protective factor against gastric cancer. The specic nutrients that may be protective remain unclear, but may be mediated through anti-oxidant vitamins such as ascorbic acid. Ascorbic acid is an important anti-oxidant and may inhibit tumor cell mitotic activity without affecting normal cell growth. Decreased gastric juice dehydroascorbic acid concentrations were observed in patients with gastric atrophy and intestinal metaplasia. Mucosal ascorbic acid concentrations were also signicantly lower in patients with H. pylori infection. These ndings may have implications in H. pylori-associated carcinogenesis.47 However, results of specic interventional trials have largely been unconvincing. Correa et al. conducted a randomized, controlled chemoprevention trial in subjects with histological diagnoses of multifocal atrophy and/or intestinal metaplasia.48 Individuals were assigned to receive H. pylori eradication triple therapy and/or
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dietary supplementation with ascorbic acid, beta-carotene, or their corresponding placebos. Ascorbic acid interventions resulted in statistically signicant increases in the rates of regression (RR: 5.0; 95% CI: 1.714.4) in subjects with atrophy. Corresponding relative risk of regression in subjects with intestinal metaplasia was 3.3 (95% CI: 1.19.5). However, three other randomized controlled trials showed that ascorbic acid supplementation was not helpful in preventing progression of gastric precancerous lesions.4951
Statement 7: The current evidence does not support the use of vitamins and other dietary supplements to prevent gastric cancer Level of agreement: a, 0%; b, 100%; c, 0%; d, 0%. Level of evidence: Ib. Grade of recommendation: A. Although epidemiological evidence suggested that a diet rich in fresh fruit and vegetables could be a protective factor against gastric cancer, the precise factors involved are probably more than individual vitamins and anti-oxidants. Only the study by Correa et al. showed that dietary supplementation with ascorbic acid and beta-carotene resulted in statistically signicant increases in the rates of regression of precancerous gastric lesions.48 In three other chemoprevention studies,4951 dietary interventions had no effect on prevention of precancerous gastric lesions. Plummer et al. examined the effect of dietary supplementation with vitamin C, vitamin E, and beta-carotene on the progression and regression of
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precancerous gastric lesions.49 There was no statistically signicant difference in the progression rate or regression rate between vitamin and placebo groups. You et al. conducted a randomized trial to test the effect of one-time H. pylori eradication therapy and long-term vitamin or garlic supplements in reducing the prevalence of advanced precancerous gastric lesions.50 No statistically signicant favorable effects were seen for garlic or vitamin supplements. Jacobs et al. examined the association between gastric cancer mortality and regular use ( 15 times per month) of vitamin C supplements, vitamin E supplements, and multivitamins.51 There was no association between gastric cancer mortality and regular use of vitamin E or multivitamins regardless of the duration of use. A Finnish study of over 29 000 people also failed to show that any upper aerodigestive cancers were prevented by daily supplementation with alpha-tocopheryl acetate and/or betacarotene in older male smokers.52 Statement 8: Host genetic factors are important in the response to H. pylori infection and disease outcome Level of agreement: a, 0%; b, 100%; c, 0%; d, 0%. H. pylori-infected patients have histological gastritis and approximately 80% are asymptomatic, 1015% develop peptic ulcer, 12% develop gastric cancer and a very small proportion develop gastric mucosa-associated lymphoid tissue lymphoma.53 A body of evidence supports the role of host factors in determining progression to gastric cancer in H. pylori infection. The risk of developing gastric cancer is increased up to three-fold in individuals with an immediate relative suffering from gastric cancer, and 10% of cases of gastric cancer show familial clustering.54 The observation that relatives of patients with gastric cancer had a higher prevalence of atrophy and hypochlorhydria suggested genetic predisposition to the development of atrophy, the precursor of gastric cancer, in the presence of H. pylori infection.54 A strong association between pro-inammatory polymorphisms in the interleukin (IL)-1b gene cluster and an increased risk of developing gastric cancer has been demonstrated in Western populations5557 as well as in Japan.58 Genetic polymorphisms in tumor necrosis factor (TNF)-a and IL-10, when combined with pro-inammatory IL-1b gene polymorphisms, were shown to result in a high-risk genotype with a 27-fold or greater risk of developing gastric cancer.59 Genetic polymorphisms of the IL-8 promoter were signicantly associated with an increased risk of gastric cancer.60,61 Statement 9: Currently identied IL-1b polymorphisms in the AsiaPacic region may not be associated with gastric cancer Level of agreement: a, 47.4%; b, 47.4%; c, 5.2%; d, 0%. The key pathophysiological event in H. pylori infection is the initiation of an inammatory response in which the main mediators are cytokines. IL-1b is a potent proinammatory cytokine and is involved in the hosts response to many antigenic challenges. El Omar et al. studied the correlation of these IL-1b genotypes with hypochlorhydria and gastric atrophy in a Caucasian population of gastric cancer relatives. Genetic polymorphisms in the IL-1 gene cluster signicantly increased the risk of precancerous gastric lesions.62 A positive association between these genotypes and gastric cancer was conrmed in a follow-up study.55
However, the results of Asian studies are conicting. Some studies are in agreement63,64 whereas others did not show any association.6567 However, an association with other genetic markers such as IL-860,61 and TNF-a65 polymorphisms has been proposed. A meta-analysis of the role of IL-1b and IL-1 receptor antagonist gene polymorphisms in gastric cancer risk showed an association in Caucasians, but not in Asians.68
Statement 10: Currently identied cagA genotypes in the AsiaPacic region may not be associated with gastric cancer Level of agreement: a, 10.5%; b, 73.7%; c, 15.8%; d, 0%. Huang et al. conducted a meta-analysis to estimate the magnitude of the risk for gastric cancer associated with cagA seropositivity.69 H. pylori and cagA seropositivity signicantly increased the risk for gastric cancer by 2.3- and 2.9-fold, respectively. Among H. pylori-infected populations, infection with cagApositive strains further increased the risk for gastric cancer 1.6-fold (95% CI: 1.22.2) overall and 2.0-fold (95% CI: 1.23.3) for non-cardia gastric cancer. Gastric cancer of the cardia was not associated with H. pylori infection or cagA-positive strains of H. pylori. However, the prevalence of cagA in Asia is high, and currently identied cagA genotypes in the AsiaPacic region are not associated with gastric cancer.6976
Statement 11: The host bacterial interaction in H. pylori infection results in different patterns of gastritis and consequent differences in gastric acid secretion which determine disease outcome Level of agreement: a, 63.2%; b, 36.8%; c, 0%; d, 0%. H. pylori infection is associated with divergent clinical outcomes that range from simple asymptomatic gastritis to serious conditions such as peptic ulcer disease and gastric neoplasia. The key determinants of these outcomes are the severity and distribution of the H. pylori-induced gastritis. Patients with antralpredominant gastritis, the most common form of H. pylori gastritis, are predisposed to duodenal ulcers, whereas patients with corpus-predominant gastritis and multifocal atrophy are more likely to have gastric ulcers, gastric atrophy, intestinal metaplasia and, ultimately, gastric carcinoma.53 Compared to H. pylorinegative healthy volunteers, patients with H. pylori-related duodenal ulcers had signicantly higher basal and maximal acid output.77 In contrast, gastritis that involved the acid-secreting corpus region resulted in hypochlorhydria, progressive gastric atrophy, and an increased risk of gastric cancer. When compared with controls, the hypochlorhydric subjects had less dense H. pylori colonization, body-predominant colonization and gastritis, and increased prevalence of body atrophy and intestinal metaplasia.78
Statement 12: Population-based screening for gastric cancer is currently undertaken at the national level in two countries and at the local level in one country Currently, population-based screening is being undertaken in Japan,9 Korea10 and Matsu island in Taiwan.11 These are
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populations with high gastric cancer risks. In Japan, screening is performed in individuals aged over 40 years using double-contrast barium or endoscopy. In Korea, endoscopy is used, while in Taiwan, individuals are rst screened using serum pepsinogen and, if the level is low, endoscopy is performed.
Statement 13: There is a pressing need for the development of national policies to reduce the incidence of gastric cancer which is now feasible Level of agreement: a, 73.7%; b, 21%; c, 5.3%; d, 0%. There is considerable morbidity and mortality associated with gastric cancer, due to frequent late presentation and, hence, late diagnosis. In Asia, the prevalence of both gastric cancer and H. pylori infection remain high. There is a need to further reduce the incidence of gastric cancer in high-risk populations and this should be based on development of national policies. Appropriate approaches may include screening of high-risk populations, as well as by addressing known risk factors, in particular, H. pylori infection.
antrum and Brunners glands in the proximal duodenum. As gastritis progresses, mild inammation leads to elevated levels of both PG I and PG II in the circulation initially. However, as disease severity increases further, chief cells are replaced by pyloric glands and the level of PG II remains elevated, while the level of PG I and, consequently, the PG I/II ratio, are reduced. The differential changes in PG levels are indicative of the histological state of the gastric mucosa. Utilizing PG as surrogate markers for gastric atrophy, the EUROGAST Study Group correlated gastric cancer rates with low serum PG levels in men from the same population.83
Statement 16: Low serum pepsinogen I levels and low PG I/II ratio may be useful as a marker to identify populations at high risk for gastric cancer Level of agreement: a, 15.8%; b, 52.6%; c, 31.6%; d, 0% Level of evidence: IIa. Grade of recommendation: B. Since the 1990s, serum PG as a marker for chronic atrophic gastritis has been incorporated into gastric cancer screening programs, on a trial basis, to identify people who would benet most from gastric cancer screening in Japan.8490 The results have shown that PG testing is useful in detecting early-stage gastric cancer. Miki91 performed a meta-analysis of the sensitivity and specicity results from 42 individual studies. PG I level 70 ng/mL and PG I/II ratio 3 had a sensitivity of 77% and false-positive rate of 27%. The positive predictive value was low and varied between 0.77% and 1.25%, but the negative predictive value varied between 99.08% and 99.90%. In a casecontrol study from Thailand, the PG I/II ratio was signicantly lower in the gastric cancer group than in the normal and chronic gastritis groups (OR: 2.3; 95% CI: 1.104.80).92 There are, however, exceptions with respect to the utility of serum pepsinogen levels. A study from Singapore examined whether racial differences in the prevalence of H. pylori and serum PG could account for a racial difference in gastric cancer incidence.22 The H. pylori seroprevalence was similar between Chinese and Indian subjects, but signicantly lower among Malay subjects. The gastric cancer incidence rates correlated with H. pylori seropositivity for the Chinese and Malay subjects, but not for the Indian subjects. The prevalence of low PG was highest in Indian subjects even when adjusted for gender and the presence of H. pylori. This highlighted the limited usefulness of serum PG in the Indian population for gastric cancer screening.
Statement 14: A positive family history of gastric cancer is an important risk factor Level of agreement: a, 15.8%; b, 84.2%; c, 0%; d, 0%. H. pylori infection and a positive family history of gastric cancer are both risk factors for the disease. A familial association may be partly related to clustering of H. pylori infection within families. For instance, El Omar et al. examined the prevalence of atrophy and hypochlorhydria and their association with H. pylori infection in rst-degree relatives of patients with gastric cancer.62 They found that among the relatives of cancer patients, the prevalence of atrophy and hypochlorhydria was increased only in those with evidence of H. pylori infection. Eradication of H. pylori infection produced resolution of the gastric inammation in each subject, and resolution of hypochlorhydria and atrophy in 50% of the subjects. In contrast, Brenner et al. carried out a population-based, statewide casecontrol study in Saarland, Germany, to assess the individual and joint contributions of family history and H. pylori infection to the risk of gastric carcinoma.79 They found that although H. pylori infection and family history were positively related, both were independently and strongly associated with a risk for gastric cancer. Compared with uninfected subjects without a family history, subjects with both a positive family history and infection with cagA-positive H. pylori strains had an OR of 8.2 (95% CI: 2.230.4) for gastric cancer overall and an OR of 16 (95% CI: 3.966.4) for noncardia gastric cancer.
Statement 15: Low serum pepsinogen I levels and low PG I/II ratio reect gastric atrophy Level of agreement: a, 36.8%; b, 57.9%; c, 5.3%; d, 0%. Low serum pepsinogen (PG) has been used as a surrogate marker for atrophic gastritis.8084 PG, the precursor of pepsin, exists as two main types: types I and II. Both are produced by the chief and mucus neck cells in the gastric fundus and corpus. PG II, but not PG I, is also produced by the pyloric glands in the
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Statement 17: Neither cagA serology nor the presence of the cagA gene has been shown to be a useful marker for gastric cancer risk in an individual Level of agreement: a, 78.9%; b, 21.1%; c, 0%; d, 0%. Level of evidence: IIa. The prevalence of cagA in Asia is high, and currently identied cagA genotypes in the AsiaPacic region have not been associated with gastric cancer.7076 As such, there is no role for it as a marker for gastric cancer risk in an individual.
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II. Screening program for H. pylori infection and gastric cancer

Statement 18: Population H. pylori screening and treatment will reduce peptic ulcer disease and its complications Level of agreement: a, 90%; b, 10%; c, 0%; d, 0%. Level of evidence: I. Grade of recommendation: A. Peptic ulcers are independently related to both H. pylori infection as well as non-steroidal anti-inammatory drug(s) (NSAIDs) use. Eradication of H. pylori infection has been shown to facilitate peptic ulcer healing, reduce recurrence of peptic ulcers and reduce incidence of bleeding peptic ulcers in clinical trials. This provides evidence that population H. pylori screening and treatment will reduce peptic ulcer disease and its complications. A recent systemic review of 21 studies involving 10 146 patients showed that ulcers were more common in H. pyloripositive than in H. pylori-negative patients (OR: 4.03), irrespective of NSAID use, and more common in NSAID users than in nonusers (OR: 3.10), irrespective of H. pylori status. The risk of ulcer was 17.54-fold higher in H. pylori-positive NSAID users than in H. pylori-negative non-users and the presence of both H. pylori and NSAIDs increased the risk of bleeding 20.83-fold.93 In a Cochrane review, eradication therapy was compared to placebo or pharmacological therapies in H. pylori-positive peptic ulcers.94 In duodenal ulcer healing, eradication therapy was superior to acid suppressants (RR of ulcer persisting: 0.66; 95% CI: 0.58 0.76) and no treatment (RR: 0.37; 95% CI: 0.260.53). In gastric ulcer healing, the efcacy was similar between eradication therapy and acid suppressants (RR: 1.25; 95% CI: 0.881.76). In preventing duodenal ulcer recurrence, no signicant differences were detected between eradication therapy and maintenance therapy with acid suppressants (RR of ulcer recurring: 0.73; 95% CI: 0.421.25), but eradication therapy was superior to no treatment (RR: 0.20; 95% CI: 0.150.26). In preventing gastric ulcer recurrence, eradication therapy was superior to no treatment (RR: 0.29; 95% CI: 0.20 0.42). The efcacy of H. pylori eradication therapy versus antisecretory therapy for the prevention of recurrent bleeding from peptic ulcer was assessed in another Cochrane review.95 It was shown that treatment of H. pylori infection was more effective than antisecretory therapy (with or without long-term maintenance therapy) in preventing recurrent bleeding from peptic ulcer. Comparing H. pylori eradication therapy against antisecretory therapy without long-term maintenance therapy, the rebleeding rate was 2.9% versus 20% (OR: 0.17; 95% CI: 0.100.32; number needed to treat [NNT]: 7; 95% CI: 511). Comparing H. pylori eradication against antisecretory therapy with long-term maintenance therapy, the rebleeding rate was 1.6% versus 5.6% (OR: 0.25; 95% CI: 0.080.76; NNT: 20; 95% CI: 12100).
The role of H. pylori eradication in the management of dyspepsia symptoms in patients with functional dyspepsia was assessed in a meta-analysis.96 There was a 10% relative risk reduction in the H. pylori eradication group (95% CI: 614%) compared to placebo. The number needed to treat to cure one case of dyspepsia was 14 (95% CI: 1025). An economic model suggested that this modest benet may be cost-effective. A recent study investigated the effect of screening for H. pylori on dyspepsia and dyspepsia-related resource use over 10 years.97 In that study, 2324 H pylori-positive individuals, aged 4049 years, enrolled in a community screening program in the UK were randomized to eradication therapy or placebo and followed up after 10 years. There was a signicant 10-year mean saving in total dyspepsiarelated costs of US$117 per person (95% CI: 11220). The savings were greater than the initial cost of H. pylori screening and treatment.
Statement 20: Population H. pylori screening and treatment will increase antibiotic resistance in the community Level of agreement: a, 95%; b, 5%; c, 0%; d, 0%. Level of evidence: III. Grade of recommendation: C. There was concern about the problem of increased antibiotic resistance in the community with population H. pylori screening and eradication. The widespread use of antimicrobials constitutes a risk for antimicrobial resistance.98 This will be especially so in the context of non-compliance to treatment. This may potentially impact on the efcacy of H. pylori eradication regimens as well as the efcacy of antibiotics against other infections. An association has been found between the consumption level of antibiotics and the rate of bacterial resistance to antimicrobials.99102 In Europe, a trend toward a higher resistance of H. pylori to macrolides was noted in countries with the highest consumption of these drugs.103,104 Ensuring compliance to treatment would be important in preventing the selection of resistant strains, and public health measures to monitor the patterns of drug resistance would be needed.
Statement 21: Population H. pylori screening will increase cancer anxiety in the population Level of agreement: a, 0%; b, 75%; c, 25%; d, 0%. Level of evidence: IV. Grade of recommendation: C. There are no published data on the association of cancer anxiety in the population with H. pylori screening. However, there was a strong concern by the participants of the meeting that H. pylori screening could possibly increase cancer anxiety, especially to a level disproportionate to the actual risk of disease. A recent paper on public awareness of breast cancer and screening showed that increased awareness led to increased referrals and screening for breast cancer, without an actual increase in detection rates, leading the authors to conclude that while it was encouraging that media campaigns raised awareness, there may be a detrimental effect with increased radiation exposure, anxiety and cancer phobia.105
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Statement 19: Population H. pylori screening and treatment will result in a modest reduction of dyspepsia symptoms and costs Level of agreement: a, 10%; b, 70%; c, 20%; d, 0%. Level of evidence: I. Grade of recommendation: A.
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Statement 22: H. pylori eradication does not increase reux symptoms in the community Level of agreement: a, 45%; b, 55%; c, 0%; d, 0%. Level of evidence: I. Grade of recommendation: A. Labenz et al. initially suggested that an increase in the prevalence of gastroesophageal reux disease (GERD) occurred after H. pylori eradication.106 However, subsequently, a post hoc metaanalysis of eight double-blind studies of H. pylori eradication107 and a large post hoc analysis of the peptic ulcer trials, GU MACH and DU MACH108,109 showed that H. pylori eradication for ulcer disease did not lead to development of erosive esophagitis or new symptomatic GERD or worsening of symptoms in patients with pre-existing GERD. The results were similar for studies conducted in patients with pre-existing GERD110112 and in the general population.113,114 These data support the statement that H pylori eradication does not increase reux symptoms in the community.
Statement 23: Current data suggest that population-based H. pylori screening and treatment does not increase the risk for esophageal adenocarcinoma Level of agreement: a, 0%; b, 100%; c, 0%; d, 0%. Level of evidence: III. Grade of recommendation: C. Some data suggested an inverse association between H. pylori infection and GERD or Barretts esophagus.115117 There are epidemiological studies that showed H. pylori CagA seropositivity was inversely and strongly associated with a risk of esophageal adenocarcinoma,118,119 although this has not been a universal observation.120 There was consensus that since there was no association between GERD and H. pylori, the association with Barretts esophagus may be spurious and the benets of H. pylori eradication would almost certainly outweigh any theoretical impact on Barretts cancer.
14% less progression of precancerous gastric lesions than subjects who were H. pylori positive. Another prospective, placebocontrolled, randomized study was performed by Leung et al.123 At 5 years follow up, subjects with persistent H. pylori infection had a signicantly higher risk of progression to intestinal metaplasia than those with successful eradication, with an OR of 2.13 (95% CI: 1.413.24). Two other prospective, randomized, double-blind, placebo-controlled studies conducted in China reached similar conclusions.50,124 Uemura et al. rst provided evidence that H. pylori eradication had a direct impact on gastric cancer occurrence.125 They conducted a non-randomized H. pylori eradication trial in patients with early gastric cancer treated by endoscopic resection. After a 3-year follow-up period, metachronous gastric cancer developed in 9% of those not treated, compared with 0% in patients with H. pylori eradicated. In a prospective observational study, the same group also showed that gastric cancer developed in persons infected with H. pylori, but not in uninfected persons.126 A recent non-randomized, interventional trial evaluated gastric cancer development after 3 years in H. pylori-positive subjects and in those in whom H. pylori was eradicated.127 At the end of the follow-up period, signicantly more patients (4% vs 1.5%) in the H. pylori-positive group developed gastric cancer. To date, ve randomized placebo-controlled H. pylori eradication trials have been conducted in Asia to address this issue.50,128131 There were four studies50,128130 evaluating H. pylori screening and treatment in the general population and all showed a non-signicant trend towards risk reduction for gastric cancer with H. pylori eradication. One Japanese study in patients having endoscopic mucosal resection for gastric adenocarcinoma did show a signicant effect of H. pylori eradication in the prevention of subsequent gastric neoplasia.131 A meta-analysis was performed (Moayyedi P, unpubl. data, 2007) using the raw data from these ve studies. With H. pylori eradication, the pooled relative risk of developing gastric cancer was 0.56 (95% CI: 0.40, 0.8). Even though this metaanalysis relies on the results of two studies128,131 that have yet to be published in peer-reviewed journals, the consensus meeting concluded that the evidence is very suggestive. Statement 25: Eradication of H. pylori has been shown to reduce the incidence of gastric cancer development even at a late age Level of agreement: a, 10%; b, 85%; c, 0%; d, 5%. Level of evidence: I. Grade of recommendation: A. As elaborated in the discussion following statement 24,121130 the results of both randomized and non-randomized studies suggested that in a subpopulation of treated subjects, H. pylori eradication prevented the progression of precancerous gastric lesions. However, H. pylori eradication seemed to reduce the incidence of gastric cancer in patients without baseline precancerous gastric lesions.129 Hence, the issue of the optimal population age cut-off for treatment of infection to prevent cancer remains unknown. The choice of an arbitrary age cut-off for population screening and eradication for H. pylori infection would depend on local resources and ethical considerations. The sole rejection in the voting was made on the basis that the actual age of cut-off remained unknown.
III. H. pylori eradication and gastric cancer

Statement 24: H. pylori eradication reduces the risk of developing gastric cancer Level of agreement: a, 90%; b, 10%; c, 0%; d, 0%. Level of evidence: I. Grade of recommendation: A. The potential benet of H. pylori eradication in reducing the risk of gastric cancer can be considered indirectly from studies that assessed its effect on precancerous lesions and directly from its effect on cancer development. Correa et al. assessed the effect of H. pylori eradication therapy on intestinal metaplasia, multifocal atrophy and dysplasia in a high gastric cancer risk region of Colombia.121 Results of the 6-year follow-up evaluation showed that H. pylori eradication produced a signicant increase in the rates of regression for intestinal metaplasia and gastric atrophy. These ndings were subsequently conrmed at the end of the 12-year follow-up period.122 Those who were H. pylori negative had, on average, 15% more regression and
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Statement 26: Gastric cancer can still occur despite eradication of the infection Level of agreement: a, 80%; b, 20%; c, 0%; d, 0%. Level of evidence: I. Grade of recommendation: A. Even though H. pylori eradication may represent a primary chemopreventive strategy, gastric cancer may still develop despite successful eradication therapy. This is clear from studies that used occurrence of precancerous gastric lesions as a surrogate outcome measure for gastric cancer development, as well as those that directly assessed the incidence of gastric cancer. The effect of H. pylori eradication therapy on precancerous gastric lesions such as intestinal metaplasia, multifocal atrophy and dysplasia was assessed by several studies. In a study from Colombia, at the end of the 12-year follow-up period, although those who were H. pylori negative had more regression and less progression of precancerous gastric lesions than subjects who remained H. pylori positive, approximately one-third of the patients successfully treated still experienced progression of precancerous gastric lesions.122 In a study by Leung et al., progression of intestinal metaplasia was found in approximately one-third of patients in whom H. pylori was successfully eradicated.123 In another prospective randomized trial, after a follow-up period of 7 years, You et al. noted that progression of precancerous lesions occurred in 45% in the active treatment group versus 49% in the placebo group.50 Similar ndings were noted by Zhou et al.124 Collectively, these data suggest that although H. pylori eradication was able to induce regression of precancerous gastric lesions, particularly in those with early and non-severe lesions, up to 45% of treated subjects would still show disease progression. The occurrence of gastric cancer after successful H. pylori eradication has also been assessed. Ogura et al. reported that at the 3-year follow up, 4% in the H. pylori-positive group and 1.5% in the H. pylori-negative group developed gastric cancer.127 In the study by Wong et al. during the period of follow-up of 7.5 years, 0.9% of treated subjects and 1.3% of placebo developed gastric cancer.129
Statement 28: In high gastric cancer-risk populations in the AsiaPacic region, population screening and treatment of H. pylori infection is the strategy of choice Level of agreement: a, 10%; b, 90%; c, 0%; d, 0%. Level of evidence: I. Grade of recommendation: A. To date, all randomized controlled trials on H. pylori eradication to prevent precancerous gastric lesions and gastric cancer have been conducted in high-risk populations. In the long term, if H. pylori infection were to be eradicated, it may even mean that endoscopic surveillance for gastric cancer may no longer be necessary, if this eradication occurred before the development of advanced precancerous gastric lesions. For developing countries in the AsiaPacic region, affordability would be a major concern and, on a national level, individual strategies need to be developed. Statement 29: H. pylori screening and treatment does not exclude the existing practice of gastric cancer surveillance in high-risk populations such as in Japan and Korea Level of agreement: a, 75%; b, 25%; c, 0%; d, 0%. Level of evidence: IV. Grade of recommendation: C. Current evidence suggests that H. pylori eradication might represent a primary chemopreventive strategy in a subset of subjects without advanced precancerous gastric lesions. However, H. pylori eradication in those patients who have already developed advanced precancerous gastric lesions does not prevent gastric cancer development and, as such, in high-risk populations such as Japan and Korea, endoscopic surveillance may continue to be performed. Statement 30: In populations at low risk for gastric cancer, screening for H. pylori is not recommended Level of agreement: a, 0%; b, 100%; c, 0%; d, 0%. Level of evidence: IV. Grade of recommendation: C. To date, the limited published data on H. pylori eradication and gastric cancer prevention have been from high-risk populations. Even within these high-risk populations, the benet is not universal because advanced precancerous changes may continue to progress. Hence, it is not recommended at this time to adopt a strategy of H. pylori screening and eradication with the aim of decreasing the already low incidence of gastric cancer in low-risk populations. However, quite apart from gastric cancer prevention, there are data that suggest that screening for H pylori and eradicating it would reduce total dyspepsia-related health-care costs.97 Statement 31: Opportunistic testing and treating of H. pylori infection offers the possibility to reduce the risk of peptic ulcer disease and gastric cancer Level of agreement: a, 20%; b, 80%; c, 0%; d, 0%. Level of evidence: I. Grade of recommendation: A. In light of the data concerning the relationship between
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Statement 27: H. pylori screen and treat is a gastric cancer risk reduction strategy in high-risk populations Level of agreement: a, 55%; b, 45%; c, 0%; d, 0%. Level of evidence: I. Grade of recommendation: A. Based on the results of the published data on H. pylori eradication and its impact on the progression of precancerous gastric lesions and occurrence of gastric cancer discussed earlier,121130 it was felt that screening for H. pylori infection and eradicating it in high-risk populations would have an impact on reduction of gastric cancer incidence. All these studies were conducted in high-risk populations. By targeting high-risk populations, there would be a better return for the economic resources that need to be committed for such a strategy. Indeed, economic modeling using efcacy data from the meta-analysis presented in statement 24 and randomized controlled trial data97 with Asian costs applied suggested this strategy would be cost-effective in developed countries where gastric cancer rates were high.
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H. pylori and gastric cancer,25 and peptic ulcer disease,94 and the data that showed reduced occurrence of gastric cancer125,126 and peptic ulcer disease94 after H. pylori eradication, it was felt that opportunistic testing and treating of H. pylori infection offered a possibility to reduce the risk of peptic ulcer disease and gastric cancer. However, the issue of costs and affordability of this strategy of screening and subsequent treatment for H. pylori eradication have not been addressed in the region.
optimal because H. pylori strains differ across geographic locations.134
Statement 35: Childhood screening of H. pylori infection to prevent gastric cancer is not recommended Level of agreement: a, 75%; b, 20%; c, 5%; d, 0%. Level of evidence: IV. Grade of recommendation: C. Childhood screening of H. pylori infection to prevent gastric cancer is not recommended. H. pylori infection is usually acquired in childhood, and as children would not have not harbored the organism for long enough to have developed precancerous lesions, childhood is theoretically an attractive time for H. pylori eradication and, thus, could help prevent gastric cancer later in life. However, as H. pylori prevalence and the incidence of gastric cancer are low in childhood, widespread population screening programs would be enormously expensive and not justiable at a national level.135,136 There is also an increased risk of reinfection after successful eradication therapy in childhood when compared to adulthood.137 The interval between screening and preventing gastric cancer would be lengthened and therefore payers for the program would have to wait a longer time before seeing any return on their investment. The program would therefore also be less nancially attractive from a third-party payer perspective.
Statement 32: In a high-risk population, screening for H. pylori infection is most effective before atrophic gastritis has developed Level of agreement: a, 5%; b, 95%; c, 0%; d, 0%. Level of evidence: IIa. Grade of recommendation: B. The participants based their decision on the indirect evidence from the randomized controlled study by Wong et al.129 During the period of follow up, the incidence of gastric cancer development at the population level was similar between those who received H. pylori eradication and controls. However, in the subgroup of patients with no precancerous lesions (gastric atrophy, intestinal metaplasia, or gastric dysplasia) at presentation, no patient developed gastric cancer after H. pylori eradication compared to 6% in controls (P = 0.02). The occurrence of precancerous lesions may represent a stage of irreversibility in the pathogenesis of gastric cancer.
Statement 33: In high-risk populations, screening for H. pylori infection is recommended 1020 years before the take-off age for gastric cancer Level of agreement: a, 0%; b, 100%; c, 0%; d, 0%. Level of evidence: IV. Grade of recommendation: C. The unanimous consensus was based on knowledge that the occurrence of gastric cancer goes through a cascade, and that it takes time for precancerous lesions to occur. It was felt that screening for H. pylori infection 1020 years before the take-off age for gastric cancer in the population would allow H. pylori eradication before the onset of irreversible precancerous changes. This strategy assumes reinfection would be low in adults successfully treated.132,133
Statement 36: Repeated testing for H. pylori infection as part of the screening strategy is not necessary Level of agreement: a, 20%; b, 80%; c, 0%; d, 0%. Level of evidence: III. Grade of recommendation: B. The targeted group for H. pylori screening are the adults in high-risk populations. Infections are generally acquired during childhood.53 Serological tests, in particular antibodies against the specic antigen CagA, are immunogenic and long-lasting, for which reason they are useful for epidemiological studies.138,139 As such, the risk of false-negative results are minimal and do not justify the costs of repeated testing for H. pylori infection.
Statement 37: First-line treatment of H. pylori infection should be in accordance with national treatment guidelines Level of agreement: a, 100%; b, 0%; c, 0%; d, 0%. Level of evidence: I. Grade of recommendation: A. It was unanimously agreed that rst-line treatment of H. pylori infection should be in accordance with national treatment guidelines. Standard rst-line H. pylori eradication regimens are based on triple therapy comprising twice daily proton pump inhibitors, clarithromycin and amoxicillin or metronidazole for at least 7 days. These rst-choice H. pylori treatments are recommended worldwide. However, it is recognized that the exact choice of antimicrobials may differ based on local patterns of antibiotic resistance, and that the decision to treat for 1 or 2 weeks would also depend on the results of locally validated data.134
Statement 34: A serological test for H. pylori that has been locally validated is recommended for population screening Level of agreement: a, 25%; b, 65%; c, 10%; d, 0%. Level of evidence: IIb. Grade of recommendation: B. Serological tests for diagnosis of H. pylori infection rely on the detection of immunoglobulin (Ig)G antibodies to H. pylori antigens. They are widely available and inexpensive, and were used in population screening for H. pylori infection in epidemiological studies.83 Overall, the diagnostic accuracy is low at approximately 8084%. However some kits have a high accuracy rate (> 90%) and may be used when locally validated. Local validation is
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Populations with a high or intermediate risk of gastric cancer Patients with dyspepsia Asymptomatic individuals (1860 years)
Investigate dyspepsia
One-off screening with locally validated serology test for H. pylori
negative
positive
Continue program of gastric cancer surveillance based on national guidelines
Qualified reassurance; perform 2nd test on individualized basis.
Eradicate H. pylori
One-off treatment according to local guideline; e.g. 1-week triple therapy.
On a case-by-case basis, one may assess the success of H. pylori eradication by using non-serological tests at least 4 weeks posttherapy and institute a second-line therapy in the event of treatment failure.
Figure 1 Strategy of H. pylori screening and eradication in populations at high or intermediate risk for gastric cancer.
Statement 38: Conrmation of H. pylori eradication is not practical or cost-effective to consider on a population basis Level of agreement: a, 35%; b, 60%; c, 5%; d, 0%. Level of evidence: IV. Grade of recommendation: C. For the individual patient, there should be conrmation of the success of H. pylori eradication by using non-serological tests, which should be performed at least 4 weeks after treatment has been completed.134 In clinical practice, approximately 20% of patients will fail to eradicate H. pylori infection with the recommended treatment regimens. Major causes of treatment failure are poor patient compliance and antibiotic resistance.140 However, at the population level, because of the costs involved and the resources required, conrmation of H. pylori eradication is not practical or cost-effective to consider. One may however, consider retesting and follow-up therapy on a case by case basis, such as in patients with dyspepsia symptoms and those who request conrmation of successful H. pylori eradication.
gastric cancer, and it has come time to try and intervene to prevent this cancer at the population level. Current evidence suggests that H. pylori eradication can prevent the progression of precancerous gastric lesions and, in those without advanced precancerous lesions, H. pylori eradication probably reduces the incidence of gastric cancer. A strategy of H. pylori screening and eradication in high-risk populations (Fig. 1) should reduce gastric cancer incidence and is recommended by this consensus conference. This approach may be considered in intermediate-risk populations, although it is acknowledged that supporting data are lacking and such a strategy is not recommended at this time. Finally, screening in low-risk populations is not currently recommended. At the same time, the current gastric surveillance programs in populations at high risk for gastric cancer such as in Japan and Korea should be continued.
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Conclusion
After carefully reviewing the literature and weighing the evidence and uncertainties, this consensus conference has concluded that there is a denite causal link between H. pylori infection and
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Appendix I
List of participants and contributors
Australia: Professor Nick Talley, Professor Mitchell Hazel; Canada: Professor Paul Moayyedi, Professor Richard Hunt; China: Professor Shu Dong Xiao, Professor Shiu Kum Lam; Indonesia: Professor Abdul Aziz Rani; Japan: Professor Takeshi Azuma, Professor Kentaro Sugano, Tsutomu Chiba, Naomi Uemura; Korea: Professor Jae G Kim, Professor Nayoung Kim; Malaysia: Professor Khean Lee Goh; Philippines: Professor Jose Sollano; Singapore: Professor Kwong Ming Fock, Dr Tiing Leong Ang; Taiwan: Dr Jyh Ming Liou; Thailand: Professor Varocha Mahachai, Dr Ratha-korn Vilaichone, Dr Sombat Treeprasertsuk, Dr Ongard Praisontarangkul.
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doi:10.1111/j.1440-1746.2008.05314.

AsiaPacic consensus guidelines on gastric cancer prevention

AsiaPacic gastric cancer consensus

two-thirds of the votes were in categories a (strongly agree) or b (agree).

Preparation process and format of the report

AsiaPacic gastric cancer consensus

AsiaPacic gastric cancer consensus

Australia19 China20 Changle Hong Kong India13 Japan16

13.8 81.3 19.3 8.9 62.1

11.9 2.6 12.9 21.4 6.6 7.8 18.6 5.8

8.7 1.3 7.9 10.8 3.8 6.1 10.5 2.9

AsiaPacic gastric cancer consensus

AsiaPacic gastric cancer consensus

AsiaPacic gastric cancer consensus

II. Screening program for H. pylori infection and gastric cancer

AsiaPacic gastric cancer consensus

III. H. pylori eradication and gastric cancer

AsiaPacic gastric cancer consensus

AsiaPacic gastric cancer consensus

optimal because H. pylori strains differ across geographic locations.134

AsiaPacic gastric cancer consensus

One-off screening with locally validated serology test for H. pylori

Continue program of gastric cancer surveillance based on national guidelines

Qualified reassurance; perform 2nd test on individualized basis.

One-off treatment according to local guideline; e.g. 1-week triple therapy.

AsiaPacic gastric cancer consensus

AsiaPacic gastric cancer consensus

AsiaPacic gastric cancer consensus

AsiaPacic gastric cancer consensus

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