asia-pacific consensus on gastric cancer prevention[1]

8/13/2019 Asia-Pacific Consensus on Gastric Cancer Prevention[1]

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SPECIAL ART ICL E

AsiaPacic consensus guidelines on gastric cancerpreventionKwong 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; **ShanghaiInstitute 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 UniversityHospital, 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 SantoTomas, Manila, Philippines

AbstractBackground and Aim: Gastric cancer is a major health burden in the AsiaPacic regionbut consensus on prevention strategies has been lacking. We aimed to critically evaluatestrategies for preventing gastric cancer.Methods: A multidisciplinary group developed consensus statements using a Delphiapproach. Relevant data were presented, and the quality of evidence, strength of recom-mendation, and level of consensus were graded.Results: Helicobacter pylori infection is a necessary but not sufcient causal factor fornon-cardia gastric adenocarcinoma. A high intake of salt is strongly associated with gastriccancer. Fresh fruits and vegetables are protective but the use of vitamins and other dietarysupplements does not prevent gastric cancer. Hostbacterial interaction in H. pylori infec-tion results in different patterns of gastritis and differences in gastric acid secretion whichdetermine 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 toidentify populations at high risk for gastric cancer. H. pylori screening and treatment is arecommended gastric cancer risk reduction strategy in high-risk populations. H. pyloriscreening and treatment is most effective before atrophic gastritis has developed. It does notexclude the existing practice of gastric cancer surveillance in high-risk populations. Inpopulations at low risk for gastric cancer, H. pylori screening is not recommended. First-line treatment of H. pylori infection should be in accordance with national treatmentguidelines.Conclusion: A strategy of H. pylori screening and eradication in high-risk populationswill probably reduce gastric cancer incidence, and based on current evidence is recom-mended by consensus.

Key wordsgastric cancer, guidelines, Helicobacter pylori ,prevention.

Accepted for publication 22 November 2007.

CorrespondenceProfessor Kwong Ming Fock, Division ofGastroenterology, Department of Medicine,Changi General Hospital, 2 Simei Street 3,Singapore 529889. Email:kwong_ming_ [email protected]

Introduction

Gastric cancer is a major public health burden. Globally, it is thefourth 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 theAsiaPacic region. High-risk areas include East Asian countriessuch as China, Japan and Korea, where the age-standardized inci-dence rate (ASR) is greater than 20 per 100 000. Intermediate risk

countries (ASR 1119/100 000) include Malaysia, Singapore andTaiwan, while low-risk areas (ASR < 10/100 000) include coun-tries such as Australia, New Zealand, India and Thailand. 1

Gastric cancer carcinogenesis is a multifactorial process, relatedto an interaction of host factors, H. pylori infection and environ-mental factors such as diet. There is a precancerous cascade, inwhich the gastric mucosa undergoes a series of changes resultingin gastritis, atrophy, intestinal metaplasia, and dysplasia, beforedeveloping eventually into gastric cancer. 2 At an early stage,

doi:10.1111/j.1440-1746.2008.05314.x

351Journal of Gastroenterology and Hepatology 23 (2008) 351365 2008 The AuthorsJournal 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 anearly 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 besuitable for endoscopic mucosal resection or submucosal dissec-tion, with lower morbidity, but similar efcacy, when compared to

surgery.5,6

However, when diagnosed at an advanced stage, 5-yearsurvival rates may be only in the range of 1020%. 7,8

To reduce the morbidity and mortality from gastric cancer, itwould be necessary to diagnose gastric cancer at an early stage,and explore means of gastric cancer prevention by addressingmodiable environmental risk factors such as diet and H. pyloriinfection. Currently, a strategy of population screening for gastriccancer is being adopted in Japan, 9 Korea 10 and Matsu Island inTaiwan. 11 No formal programs exist in other countries, either interms of gastric cancer screening or screening for modiablefactors such as H. pylori infection. In order to address this majorhealth problem, the The AsiaPacic Gastric Cancer ConsensusConference was convened in order to review and synthesize themost current information, assess the evidence for current andpotential intervention strategies and to decide whether it is timelyto adopt a bold proactive approach towards gastric cancer preven-tion by recommending H. pylori screening and eradication.

Methods

Nature and extent of background preparation

The AsiaPacic Gastric Cancer Consensus Conference was con-vened specically to address three main areas relevant to theprevention of gastric cancer and, specically, gastric adenocarci-noma. 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 spon-sored by the Asian Pacic Association of Gastroenterology. TheJournal of Gastroenterology and Hepatology Foundation providednancial support for the conference through an unrestricted edu-cational grant. Sixteen Asian gastroenterologists and four externalexperts were invited to participate in the consensus conference onthe basis of their expertise (Appendix I). None of the participantswere remunerated for their participation in the meeting.

Each of the three topics chosen for evaluation and formulationof clinical recommendations was addressed independently.Selected papers relevant to the topics to be discussed were circu-

lated and an overview of each topic based on comprehensiveliterature searches was presented by selected participants based ontheir specic expertise. This was followed by a period of discus-sion, in which the existing data were evaluated and critiqued. Atthe end of this discussion, a recommendation with specicwording was formulated. For data related to therapeutic interven-tions, the quality of the evidence and the classication of evidencerelative to the recommendation were assessed. Once an acceptablerecommendation based on available evidence was established,formal voting for each statement of recommendation was under-taken (Table 1). Acceptance of a statement required that at least

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

Preparation process and format of the reportThe manuscript was drafted by a working group, and this wasthen circulated to and reviewed by conference participants, whoapproved the nal draft.

Consensus statements

Each statement below is followed by a brief summary in which thequality of supporting evidence, a classication of the recommen-dation and the results of voting are summarized. (N.B. the level of evidence and the grade of recommendation are not included withevery statement for the epidemiology section, as many of thestatements could not be evaluated by randomized controlledtrials.)

Consensus statements

I: Epidemiology, host and bacterial factors

Statement 1: The prevalence of H. pylori infectionvaries among countries in the AsiaPacic region. Thisdifference is, in general, related to age, socioeconomiccircumstances, but also to ethnicity

Level of agreement: a, 100%; b, 0%; c, 0%; d, 0%.

Table 1 Level of evidence, classication of recommendations andvoting scheme

Quality of evidenceIa. 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-designedquasi-experimental study.

III. Evidence obtained from well-designed non-experimentaldescriptive studies, correlation studies and case studies.

IV. Evidence obtained from expert committee reports or opinionsand/or clinical experience of respected authorities.

Classication of recommendationsA. Requires at least one randomized controlled trial as part of a body

of literature of overall good quality and consistency addressing thespecic recommendation.

B. Requires the availability of well-conducted clinical studies, but norandomized clinical trials on the topic of the recommendation.

C. Requires evidence obtained from expert committee reports oropinions and/or clinical experience of respected authorities.

Indicates an absence of directly applicable clinical studies of goodquality.Voting on the recommendations

a. Strongly agreeb. Agreec. Disagreed. Reject

Accept statement when more than two-thirds of participants voted aor b.

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The prevalence of H. pylori infection varies markedly in dif-ferent Asian countries. The prevalence rates in developing Asiancountries such as Bangladesh, 12 India, 13 Thailand 14 and Vietnam 15

have been reported to be especially high at 92%, 81%, 74% and75%, respectively, whereas in more industrialized and developedcountries such as Japan, 16 Korea 17 and Singapore, 18 the rates aresomewhat lower at 39%, 54% and 31%, respectively. In the Anglo-

Celtic population in Australia, it is approximately 38%.19

Withina country, the seroprevalence rate may vary between geographicregions. In mainland China, the prevalence rate in urban areas was52% compared to 39% in rural areas, 20 whereas in nearby Taiwan,the prevalence rate was 54%. 21 There is also a temporal andage-related change in the prevalence rate of H. pylori infection. InJapan, 16 the seroprevalence rates decreased from 73% in 1974 to55% in 1984 and nally to 39% in 1994. In Singapore, 18 theseroprevalence 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 ethnicgroups exist. In Singapore, the prevalence rates in Chinese, Malaysand Indians were 46%, 28% and 48%, respectively. 22 In Malaysia,the prevalence rates in Chinese, Malays and Indians were2757.5%, 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 majorcontributors to gastric carcinogenesis, but host factors have alsobeen implicated. These factors are individually addressed in thestatements 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 adeno-carcinoma. It also recognized the fact that not all patients withnon-cardia gastric adenocarcinoma are positive for H. pylori , andthat other factors are involved as well. As illustrated by a recentstudy, apart from H. pylori infection, other risk factors such asethnicity and diet were also independently associated with non-cardia gastric adenocarcinoma. 24 The relationship of H. pyloriwith gastric cancer has been examined in a combined analysis of 12 casecontrol studies. 25 The prospective design of the studies 2637

helped to circumvent the problem of classication bias in retro-spective studies, in which H. pylori infection and the circulating

antibody response could be lost with development of cancer. Inthese studies, blood samples for H. pylori serology were collectedbefore diagnosis of gastric cancer. The association with H. pyloriwas 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 beforecancer diagnosis (OR: 5.9; 95% CI: 3.410.3). It was concludedthat 5.9 was the best estimate of the relative risk of non-cardiacancer associated with H. pylori infection. It was further con-cluded that based on an average prevalence of H. pylori of 35% indeveloped 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 infectionand 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 regionare listed. It is clear that those countries with high gastric cancerASR have a high seroprevalence of H. pylori infection. However,

there are also populations with a high seroprevalence of H. pyloriinfection but a purportedly low gastric cancer ASR, such as Indiaand Thailand. These differences are postulated to be related to hostgenetic factors, bacterial virulence factors 38 and other environmen-tal factors.

Statement 4: A high intake of salt is stronglyassociated with gastric cancer in both epidemiologicaland animal model studies

Level of agreement: a, 100%; b, 0%; c, 0%; d, 0%.Salt-preserved food and dietary nitrite are potentially carcino-

genic. In animal model studies, salt ingestion has been shown tocause gastritis and enhance the effects of gastric carcinogens. 39,40

In an ecological study, the respective importance of high salt andnitrate intake for gastric cancer mortality was assessed at thepopulation level in 24 countries. 41 There was a signicant corre-lation of gastric cancer mortality with sodium as well as nitrate inboth men and women. The relationship of gastric cancer mortalitywith sodium was stronger than with nitrate. In a recent study fromMalaysia, a high intake of salted sh and vegetables was found tobe signicantly associated with gastric cancer. 24

Statement 5: Fresh fruits and vegetables areassociated 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 andvegetables. In the Cancer Prevention Study II, a high overall plantfood intake was associated with reduced risk of gastric cancer inmen (relative risk [RR]: 0.79; 95% CI: 0.670.93) but not inwomen (RR: 1.18; 95% CI: 0.931.50). 42 In a prospective cohortstudy 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 wasinversely associated with risk of gastric cancer, whereas no sig-

nicant association was observed for fruit consumption. 44 In amulticenter European study, it was observed that for intestinal typenon-cardia cancer, a negative association was possible for totalvegetable intake and onion and garlic intake. 45 A casecontrolstudy from Malaysia also showed that a high intake of fresh fruitsand vegetables was protective against gastric cancer. 24 A meta-analysis of cohort studies showed an inverse association betweenfruit intake and gastric cancer incidence (RR: 0.82; 95% CI: 0.730.93) 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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0.530.94) when considering only those with a longer follow up.However, these epidemiological associations do not establishbeyond doubt that dietary interventions will reduce gastric cancerincidence.

Statement 6: There is a protective role ofascorbic 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 thisstatement, with about half agreeing and half disagreeing. Epide-miological evidence suggested that a diet rich in fresh fruit andvegetables could be a protective factor against gastric cancer. Thespecic nutrients that may be protective remain unclear, but maybe mediated through anti-oxidant vitamins such as ascorbicacid. 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 wereobserved in patients with gastric atrophy and intestinal metaplasia.Mucosal ascorbic acid concentrations were also signicantlylower in patients with H. pylori infection. These ndings mayhave implications in H. pylori -associated carcinogenesis. 47

However, results of specic interventional trials have largely beenunconvincing. Correa et al . conducted a randomized, controlledchemoprevention trial in subjects with histological diagnoses of multifocal atrophy and/or intestinal metaplasia. 48 Individuals wereassigned to receive H. pylori eradication triple therapy and/or

dietary supplementation with ascorbic acid, beta-carotene, or theircorresponding placebos. Ascorbic acid interventions resulted instatistically signicant increases in the rates of regression (RR:5.0; 95% CI: 1.714.4) in subjects with atrophy. Correspondingrelative risk of regression in subjects with intestinal metaplasiawas 3.3 (95% CI: 1.19.5). However, three other randomizedcontrolled trials showed that ascorbic acid supplementation wasnot helpful in preventing progression of gastric precancerouslesions. 4951

Statement 7: The current evidence does not supportthe use of vitamins and other dietary supplements toprevent 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 richin fresh fruit and vegetables could be a protective factor againstgastric cancer, the precise factors involved are probably more thanindividual vitamins and anti-oxidants. Only the study by Correaet al . showed that dietary supplementation with ascorbic acid andbeta-carotene resulted in statistically signicant increases in therates of regression of precancerous gastric lesions. 48 In three otherchemoprevention studies, 4951 dietary interventions had no effecton 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

Table 2 Prevalence of H. pylori and gastric cancer in the AsiaPacic region

Country Seroprevalence of H. pylori (%) Age-standardized incidence rate (per 100 000)

Male Female

Australia 19 38% 13.8 6.5China 20

Changle 86% 81.3 31.7

Hong Kong 58.4% 19.3 9.6India 13 < 5 years: 2257% 8.9 6

> 20 years: 8090%Japan 16 1974: 72.7% 62.1 26.1

1984: 54.6%1994: 39.3%

Korea 17 Overall: 46.6% 58 25Age > 40 years: 78.5%

Malaysia 23

Chinese 26.757.5% 11.9 8.7Malay 11.929.2% 2.6 1.3Indian 49.452.3% 12.9 7.9

Singapore 22

Chinese 46.3% 21.4 10.8

Malay 27.9% 6.6 3.8Indian 48.1% 7.8 6.1

Taiwan 21 54.7% 18.6 10.5Thailand 14 59 years: 17.5% 5.8 2.9

2029 years: 55%3049 years: 75%

Vietnam 15 74.6% 23.7 10.8




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precancerous gastric lesions. 49 There was no statistically signi-cant difference in the progression rate or regression rate betweenvitamin and placebo groups. You et al . conducted a randomizedtrial to test the effect of one-time H. pylori eradication therapy andlong-term vitamin or garlic supplements in reducing the preva-lence of advanced precancerous gastric lesions. 50 No statisticallysignicant favorable effects were seen for garlic or vitamin supple-

ments. Jacobs et al . examined the association between gastriccancer mortality and regular use ( 15 times per month) of vitamin C supplements, vitamin E supplements, and multivita-mins. 51 There was no association between gastric cancer mortalityand regular use of vitamin E or multivitamins regardless of theduration of use. A Finnish study of over 29 000 people also failedto show that any upper aerodigestive cancers were prevented bydaily supplementation with alpha-tocopheryl acetate and/or beta-carotene in older male smokers. 52

Statement 8: Host genetic factors are important in theresponse 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 pepticulcer, 12% develop gastric cancer and a very small proportiondevelop gastric mucosa-associated lymphoid tissue lymphoma. 53 Abody of evidence supports the role of host factors in determiningprogression to gastric cancer in H. pylori infection. The risk of developing gastriccancer is increasedup to three-foldin individualswith an immediate relative suffering from gastric cancer, and 10%of cases of gastric cancer show familial clustering. 54 The observa-tion that relatives of patients with gastric cancer had a higherprevalence of atrophy and hypochlorhydria suggested genetic pre-disposition to the development of atrophy, the precursor of gastriccancer, in thepresence of H. pylori infection. 54 Astrong association

between pro-inammatory polymorphisms in the interleukin(IL)-1b gene cluster and an increased risk of developing gastriccancer has beendemonstrated in Western populations 5557 aswell asin Japan.58 Genetic polymorphisms in tumor necrosis factor(TNF)- a and IL-10, when combined with pro-inammatory IL-1 bgene polymorphisms, were shown to result in a high-risk genotypewith a 27-fold or greater risk of developinggastric cancer. 59 Geneticpolymorphisms of the IL-8 promoter were signicantly associatedwith an increased risk of gastric cancer. 60,61

Statement 9: Currently identied IL-1 b polymorphismsin the AsiaPacic region may not be associated withgastric 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 media-tors are cytokines. IL-1 b is a potent proinammatory cytokine andis involved in the hosts response to many antigenic challenges. ElOmar et al . studied the correlation of these IL-1 b genotypes withhypochlorhydria and gastric atrophy in a Caucasian population of gastric cancer relatives. Genetic polymorphisms in the IL-1 genecluster signicantly increased the risk of precancerous gastriclesions. 62 A positive association between these genotypes andgastric cancer was conrmed in a follow-up study. 55

However, the results of Asian studies are conicting. Somestudies are in agreement 63,64 whereas others did not show anyassociation. 6567 However, an association with other geneticmarkers such as IL-8 60,61 and TNF- a 65 polymorphisms has beenproposed. A meta-analysis of the role of IL-1 b and IL-1 receptorantagonist gene polymorphisms in gastric cancer risk showed anassociation in Caucasians, but not in Asians. 68

Statement 10: Currently identied cagA genotypes inthe AsiaPacic region may not be associated withgastric 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 magni-

tude of the risk for gastric cancer associated with cagA seroposi-tivity. 69 H. pylori and cagA seropositivity signicantly increasedthe risk for gastric cancer by 2.3- and 2.9-fold, respectively.Among H. pylori -infected populations, infection with cagA -positive 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) fornon-cardia gastric cancer. Gastric cancer of the cardia was notassociated with H. pylori infection or cagA -positive strains of H. pylori . However, the prevalence of cagA in Asia is high, andcurrently identied cagA genotypes in the AsiaPacic region arenot associated with gastric cancer. 6976

Statement 11: The host bacterial interaction inH. pylori infection results in different patterns ofgastritis and consequent differences in gastric acidsecretion 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 out-

comes that range from simple asymptomatic gastritis to seriousconditions such as peptic ulcer disease and gastric neoplasia. Thekey determinants of these outcomes are the severity and dis-tribution of the H. pylori -induced gastritis. Patients with antral-predominant gastritis, the most common form of H. pylorigastritis, are predisposed to duodenal ulcers, whereas patients withcorpus-predominant gastritis and multifocal atrophy are morelikely to have gastric ulcers, gastric atrophy, intestinal metaplasiaand, ultimately, gastric carcinoma. 53 Compared to H. pylori -negative healthy volunteers, patients with H. pylori -related duode-nal ulcers had signicantly higher basal and maximal acidoutput. 77 In contrast, gastritis that involved the acid-secretingcorpus region resulted in hypochlorhydria, progressive gastricatrophy, and an increased risk of gastric cancer. When compared

with controls, the hypochlorhydric subjects had less dense H. pylori colonization, body-predominant colonization and gastri-tis, and increased prevalence of body atrophy and intestinalmetaplasia. 78

Statement 12: Population-based screening for gastriccancer is currently undertaken at the national level intwo countries and at the local level in one country

Currently, population-based screening is being undertaken inJapan, 9 Korea 10 and Matsu island in Taiwan. 11 These are




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populations with high gastric cancer risks. In Japan, screening isperformed in individuals aged over 40 years using double-contrastbarium or endoscopy. In Korea, endoscopy is used, while inTaiwan, individuals are rst screened using serum pepsinogen and,if the level is low, endoscopy is performed.

Statement 13: There is a pressing need for thedevelopment of national policies to reduce theincidence 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, latediagnosis. In Asia, the prevalence of both gastric cancer and H. pylori infection remain high. There is a need to further reducethe incidence of gastric cancer in high-risk populations and thisshould be based on development of national policies. Appropriateapproaches may include screening of high-risk populations, aswell as by addressing known risk factors, in particular, H. pyloriinfection.

Statement 14: A positive family history of gastriccancer 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 associationmay be partly related to clustering of H. pylori infection withinfamilies. For instance, El Omar et al . examined the prevalence of atrophy and hypochlorhydria and their association with H. pyloriinfection in rst-degree relatives of patients with gastric cancer. 62

They found that among the relatives of cancer patients, theprevalence of atrophy and hypochlorhydria was increased only inthose with evidence of H. pylori infection. Eradication of H. pylori infection produced resolution of the gastric inamma-tion in each subject, and resolution of hypochlorhydria andatrophy in 50% of the subjects. In contrast, Brenner et al . carriedout 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 car-cinoma. 79 They found that although H. pylori infection andfamily history were positively related, both were independentlyand strongly associated with a risk for gastric cancer. Comparedwith uninfected subjects without a family history, subjects withboth a positive family history and infection with cagA- positive H. pylori strains had an OR of 8.2 (95% CI: 2.230.4) for gastriccancer overall and an OR of 16 (95% CI: 3.966.4) for non-

cardia gastric cancer.

Statement 15: Low serum pepsinogen I levels and lowPG 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 bythe 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

antrum and Brunners glands in the proximal duodenum. As gas-tritis progresses, mild inammation leads to elevated levels of both PG I and PG II in the circulation initially. However, asdisease severity increases further, chief cells are replaced bypyloric glands and the level of PG II remains elevated, while thelevel of PG I and, consequently, the PG I/II ratio, are reduced.The differential changes in PG levels are indicative of the histo-

logical state of the gastric mucosa. Utilizing PG as surrogatemarkers for gastric atrophy, the EUROGAST Study Group cor-related gastric cancer rates with low serum PG levels in menfrom the same population. 83

Statement 16: Low serum pepsinogen I levels and lowPG I/II ratio may be useful as a marker to identifypopulations 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 atrophicgastritis has been incorporated into gastric cancer screening pro-grams, on a trial basis, to identify people who would benet mostfrom gastric cancer screening in Japan. 8490 The results have shownthat PG testing is useful in detecting early-stage gastric cancer.Miki91 performed a meta-analysis of the sensitivity and specicityresults from 42 individual studies. PG I level 70 ng/mL and PGI/II ratio 3 had a sensitivity of 77% and false-positive rate of 27%. The positive predictive value was low and varied between0.77% and 1.25%, but the negative predictive value varied between99.08% and 99.90%. In a casecontrol study from Thailand, thePG I/II ratio was signicantly lower in the gastric cancer groupthan 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 examinedwhether racial differences in the prevalence of H. pylori andserum PG could account for a racial difference in gastric cancerincidence. 22 The H. pylori seroprevalence was similar betweenChinese and Indian subjects, but signicantly lower amongMalay subjects. The gastric cancer incidence rates correlatedwith H. pylori seropositivity for the Chinese and Malay subjects,but not for the Indian subjects. The prevalence of low PG washighest in Indian subjects even when adjusted for gender andthe presence of H. pylori . This highlighted the limited useful-ness of serum PG in the Indian population for gastric cancerscreening.

Statement 17: Neither cagA serology nor the presenceof the cagA gene has been shown to be a usefulmarker 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 identiedcagA genotypes in the AsiaPacic region have not been associ-ated with gastric cancer. 7076 As such, there is no role for it as amarker for gastric cancer risk in an individual.




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II. Screening program for H. pylori infectionand gastric cancer

Statement 18: Population H. pylori screening andtreatment will reduce peptic ulcer disease and itscomplications

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 infec-tion as well as non-steroidal anti-inammatory drug(s) (NSAIDs)use. Eradication of H. pylori infection has been shown to facilitatepeptic ulcer healing, reduce recurrence of peptic ulcers and reduceincidence of bleeding peptic ulcers in clinical trials. This providesevidence that population H. pylori screening and treatment willreduce peptic ulcer disease and its complications.

A recent systemic review of 21 studies involving 10 146patients showed that ulcers were more common in H. pylori -positive than in H. pylori -negative patients (OR: 4.03), irrespectiveof NSAID use, and more common in NSAID users than in non-

users (OR: 3.10), irrespective of H. pylori status. The risk of ulcerwas 17.54-fold higher in H. pylori -positive NSAID users than in H. pylori -negative non-users and the presence of both H. pyloriand NSAIDs increased the risk of bleeding 20.83-fold. 93

In a Cochrane review, eradication therapy was compared toplacebo or pharmacological therapies in H. pylori -positive pepticulcers. 94 In duodenalulcerhealing,eradication therapywassuperiorto acid suppressants (RR of ulcer persisting: 0.66; 95% CI: 0.580.76) and no treatment (RR: 0.37; 95% CI: 0.260.53). In gastriculcer healing, the efcacy was similar between eradication therapyandacidsuppressants(RR: 1.25; 95%CI: 0.881.76). In preventingduodenal ulcer recurrence, no signicant differences weredetectedbetween eradication therapy and maintenance therapy with acidsuppressants (RR of ulcer recurring: 0.73; 95% CI: 0.421.25), buteradication therapy was superiorto no treatment(RR:0.20;95% CI:0.150.26). In preventing gastric ulcer recurrence, eradicationtherapy was superior to no treatment (RR: 0.29; 95% CI: 0.200.42). The efcacy of H. pylori eradication therapy versus anti-secretory therapy for the prevention of recurrent bleeding frompeptic ulcer was assessed in another Cochrane review. 95 It wasshown that treatment of H. pylori infection was moreeffective thanantisecretory therapy (with or without long-term maintenancetherapy) in preventing recurrent bleeding from peptic ulcer. Com-paring H. pylori eradication therapy against antisecretory therapywithout long-term maintenance therapy, the rebleeding rate was2.9% versus 20% (OR: 0.17; 95%CI:0.100.32; numberneeded totreat [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).

Statement 19: Population H. pylori screening andtreatment will result in a modest reduction ofdyspepsia symptoms and costs


The role of H. pylori eradication in the management of dys-pepsia symptoms in patients with functional dyspepsia wasassessed in a meta-analysis. 96 There was a 10% relative risk reduc-tion in the H. pylori eradication group (95% CI: 614%) comparedto placebo. The number needed to treat to cure one case of dys-pepsia was 14 (95% CI: 1025). An economic model suggestedthat this modest benet may be cost-effective. A recent study

investigated the effect of screening for H. pylori on dyspepsia anddyspepsia-related resource use over 10 years. 97 In that study, 2324 H pylori -positive individuals, aged 4049 years, enrolled in acommunity screening program in the UK were randomized toeradication therapy or placebo and followed up after 10 years.There was a signicant 10-year mean saving in total dyspepsia-related costs of US$117 per person (95% CI: 11220). The savingswere greater than the initial cost of H. pylori screening andtreatment.

Statement 20: Population H. pylori screening andtreatment will increase antibiotic resistance in thecommunity

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 antibioticresistance in the community with population H. pylori screeningand eradication. The widespread use of antimicrobials constitutesa risk for antimicrobial resistance. 98 This will be especially so inthe context of non-compliance to treatment. This may potentiallyimpact on the efcacy of H. pylori eradication regimens as well asthe efcacy of antibiotics against other infections. An associationhas been found between the consumption level of antibiotics andthe rate of bacterial resistance to antimicrobials. 99102 In Europe,a trend toward a higher resistance of H. pylori to macrolideswas noted in countries with the highest consumption of thesedrugs. 103,104 Ensuring compliance to treatment would be importantin preventing the selection of resistant strains, and public healthmeasures to monitor the patterns of drug resistance would beneeded.

Statement 21: Population H. pylori screening willincrease 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, therewas a strong concern by the participants of the meeting that H. pylori screening could possibly increase cancer anxiety, espe-cially to a level disproportionate to the actual risk of disease. Arecent paper on public awareness of breast cancer and screeningshowed that increased awareness led to increased referrals andscreening for breast cancer, without an actual increase in detectionrates, leading the authors to conclude that while it was encourag-ing that media campaigns raised awareness, there may be a detri-mental effect with increased radiation exposure, anxiety andcancer phobia. 105




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Statement 22: H. pylori eradication does not increasereux symptoms in the community


Labenz et al . initially suggested that an increase in the preva-lence of gastroesophageal reux disease (GERD) occurred after H. pylori eradication. 106 However, subsequently, a post hoc meta-analysis of eight double-blind studies of H. pylori eradication 107

and a large post hoc analysis of the peptic ulcer trials, GU MACHand DU MACH 108,109 showed that H. pylori eradication for ulcerdisease did not lead to development of erosive esophagitis or newsymptomatic GERD or worsening of symptoms in patients withpre-existing GERD.The results were similar for studies conductedin patients with pre-existing GERD 110112 and in the general popu-lation. 113,114 These data support the statement that H pylori eradi-cation does not increase reux symptoms in the community.

Statement 23: Current data suggest that

population-based H. pylori screening andtreatment does not increase the risk foresophageal 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. pyloriinfection and GERD or Barretts esophagus. 115117 There are epi-demiological studies that showed H. pylori CagA seropositivitywas inversely and strongly associated with a risk of esophagealadenocarcinoma, 118,119 although this has not been a universal obser-vation. 120 There was consensus that since there was no associationbetween GERD and H. pylori , the association with Barretts

esophagus may be spurious and the benets of H. pylori eradica-tion would almost certainly outweigh any theoretical impact onBarretts cancer.

III. H. pylori eradication and gastric cancer

Statement 24: H. pylori eradication reduces the risk ofdeveloping gastric cancer


The potential benet of H. pylori eradication in reducing the

risk of gastric cancer can be considered indirectly from studies thatassessed its effect on precancerous lesions and directly from itseffect on cancer development.

Correa et al . assessed the effect of H. pylori eradication therapyon intestinal metaplasia, multifocal atrophy and dysplasia in a highgastric cancer risk region of Colombia. 121 Results of the 6-yearfollow-up evaluation showed that H. pylori eradication produced asignicant increase in the rates of regression for intestinal meta-plasia and gastric atrophy. These ndings were subsequently con-rmed at the end of the 12-year follow-up period. 122 Those whowere H. pylori negative had, on average, 15% more regression and

14% less progression of precancerous gastric lesions than subjectswho were H. pylori positive. Another prospective, placebo-controlled, randomized study was performed by Leung et al .123 At5 years follow up, subjects with persistent H. pylori infection hada signicantly higher risk of progression to intestinal metaplasiathan 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 similarconclusions. 50,124

Uemura et al . rst provided evidence that H. pylori eradicationhad a direct impact on gastric cancer occurrence. 125 They con-ducted a non-randomized H. pylori eradication trial in patientswith early gastric cancer treated by endoscopic resection. After a3-year follow-up period, metachronous gastric cancer developedin 9% of those not treated, compared with 0% in patients with H. pylori eradicated. In a prospective observational study, thesame group also showed that gastric cancer developed in personsinfected with H. pylori , but not in uninfected persons. 126 A recentnon-randomized, interventional trial evaluated gastric cancerdevelopment after 3 years in H. pylori -positive subjects and inthose in whom H. pylori was eradicated. 127 At the end of thefollow-up period, signicantly more patients (4% vs 1.5%) in the H. pylori -positive group developed gastric cancer. To date, verandomized placebo-controlled H. pylori eradication trials havebeen conducted in Asia to address this issue. 50,128131 There werefour studies 50,128130 evaluating H. pylori screening and treatment inthe general population and all showed a non-signicant trendtowards risk reduction for gastric cancer with H. pylori eradica-tion. One Japanese study in patients having endoscopic mucosalresection for gastric adenocarcinoma did show a signicant effectof H. pylori eradication in the prevention of subsequent gastricneoplasia. 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 meta-analysis relies on the results of two studies 128,131 that have yet to bepublished in peer-reviewed journals, the consensus meeting con-cluded that the evidence is very suggestive.

Statement 25: Eradication of H. pylori has been shownto reduce the incidence of gastric cancer developmenteven at a late age


As elaborated in the discussion following statement 24, 121130

the results of both randomized and non-randomized studies sug-

gested that in a subpopulation of treated subjects, H. pylori eradi-cation prevented the progression of precancerous gastric lesions.However, H. pylori eradication seemed to reduce the incidence of gastric cancer in patients without baseline precancerous gastriclesions. 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 screeningand eradication for H. pylori infection would depend on localresources and ethical considerations. The sole rejection in thevoting was made on the basis that the actual age of cut-off remained unknown.




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Statement 26: Gastric cancer can still occur despiteeradication of the infection


Even though H. pylori eradication may represent a primarychemopreventive strategy, gastric cancer may still develop despitesuccessful eradication therapy. This is clear from studies that usedoccurrence of precancerous gastric lesions as a surrogate outcomemeasure for gastric cancer development, as well as those thatdirectly assessed the incidence of gastric cancer.

The effect of H. pylori eradication therapy on precancerousgastric lesions such as intestinal metaplasia, multifocal atrophyand dysplasia was assessed by several studies. In a study fromColombia, at the end of the 12-year follow-up period, althoughthose who were H. pylori negative had more regression and lessprogression of precancerous gastric lesions than subjects whoremained H. pylori positive, approximately one-third of thepatients successfully treated still experienced progression of pre-cancerous gastric lesions. 122 In a study by Leung et al ., progres-

sion of intestinal metaplasia was found in approximatelyone-third of patients in whom H. pylori was successfullyeradicated. 123 In another prospective randomized trial, after afollow-up period of 7 years, You et al . noted that progression of precancerous lesions occurred in 45% in the active treatmentgroup versus 49% in the placebo group. 50 Similar ndings werenoted by Zhou et al .124 Collectively, these data suggest thatalthough H. pylori eradication was able to induce regression of precancerous gastric lesions, particularly in those with early andnon-severe lesions, up to 45% of treated subjects would still showdisease progression. The occurrence of gastric cancer after suc-cessful H. pylori eradication has also been assessed. Ogura et al .reported that at the 3-year follow up, 4% in the H. pylori -positivegroup and 1.5% in the H. pylori -negative group developed gastriccancer. 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 27: H. pylori screen and treat isa gastric cancer risk reduction strategy inhigh-risk populations


Based on the results of the published data on H. pylori eradi-cation and its impact on the progression of precancerous gastric

lesions and occurrence of gastric cancer discussed earlier, 121130 itwas felt that screening for H. pylori infection and eradicating it inhigh-risk populations would have an impact on reduction of gastriccancer incidence. All these studies were conducted in high-risk populations. By targeting high-risk populations, there would be abetter return for the economic resources that need to be committedfor such a strategy. Indeed, economic modeling using efcacy datafrom the meta-analysis presented in statement 24 and randomizedcontrolled trial data 97 with Asian costs applied suggested this strat-egy would be cost-effective in developed countries where gastriccancer rates were high.

Statement 28: In high gastric cancer-risk populationsin the AsiaPacic region, population screeningand treatment of H. pylori infection is the strategyof choice


To date, all randomized controlled trials on H. pylori eradica-tion to prevent precancerous gastric lesions and gastric cancer havebeen conducted in high-risk populations. In the long term, if H. pylori infection were to be eradicated, it may even mean thatendoscopic surveillance for gastric cancer may no longer be nec-essary, if this eradication occurred before the development of advanced precancerous gastric lesions. For developing countries inthe AsiaPacic region, affordability would be a major concernand, on a national level, individual strategies need to be developed.

Statement 29: H. pylori screening and treatment doesnot exclude the existing practice of gastric cancersurveillance in high-risk populations such as in Japanand Korea


Current evidence suggests that H. pylori eradication might rep-resent a primary chemopreventive strategy in a subset of subjectswithout advanced precancerous gastric lesions. However, H. pylorieradication in those patients who have already developed advancedprecancerous gastric lesions does not prevent gastric cancer devel-opment and, as such, in high-risk populations such as Japan andKorea, endoscopic surveillance may continue to be performed.

Statement 30: In populations at low risk for gastriccancer, screening for H. pylori is not recommended


To date, the limited published data on H. pylori eradication andgastric cancer prevention have been from high-risk populations.Even within these high-risk populations, the benet is not univer-sal because advanced precancerous changes may continue toprogress. Hence, it is not recommended at this time to adopt astrategy 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 eradi-cating it would reduce total dyspepsia-related health-care costs. 97

Statement 31: Opportunistic testing and treating ofH. pylori infection offers the possibility to reduce therisk of peptic ulcer disease and gastric cancer


In light of the data concerning the relationship between




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H. pylori and gastric cancer, 25 and peptic ulcer disease, 94 and thedata that showed reduced occurrence of gastric cancer 125,126 andpeptic ulcer disease 94 after H. pylori eradication, it was felt thatopportunistic testing and treating of H. pylori infection offered apossibility to reduce the risk of peptic ulcer disease and gastriccancer. However, the issue of costs and affordability of this strat-egy of screening and subsequent treatment for H. pylori eradica-

tion have not been addressed in the region.

Statement 32: In a high-risk population, screening forH. pylori infection is most effective before atrophicgastritis 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 evidencefrom the randomized controlled study by Wong et al .129 During theperiod of follow up, the incidence of gastric cancer development atthe 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, intestinalmetaplasia, or gastric dysplasia) at presentation, no patient devel-oped gastric cancer after H. pylori eradication compared to 6% incontrols ( P = 0.02). The occurrence of precancerous lesions mayrepresent a stage of irreversibility in the pathogenesis of gastriccancer.

Statement 33: In high-risk populations, screening forH. pylori infection is recommended 1020 years beforethe take-off age for gastric cancer


The unanimous consensus was based on knowledge that theoccurrence of gastric cancer goes through a cascade, and that ittakes time for precancerous lesions to occur. It was felt that screen-ing for H. pylori infection 1020 years before the take-off age forgastric cancer in the population would allow H. pylori eradicationbefore the onset of irreversible precancerous changes. This strat-egy assumes reinfection would be low in adults successfullytreated. 132,133

Statement 34: A serological test for H. pylori thathas been locally validated is recommended forpopulation 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 thedetection of immunoglobulin (Ig)G antibodies to H. pylori anti-gens. They are widely available and inexpensive, and were used inpopulation screening for H. pylori infection in epidemiologicalstudies. 83 Overall, the diagnostic accuracy is low at approximately8084%. However some kits have a high accuracy rate ( > 90%)and may be used when locally validated. Local validation is

optimal because H. pylori strains differ across geographiclocations. 134

Statement 35: Childhood screening of H. pylori infection to prevent gastric cancer is notrecommended


Childhood screening of H. pylori infection to prevent gastriccancer is not recommended. H. pylori infection is usually acquiredin childhood, and as children would not have not harbored theorganism for long enough to have developed precancerous lesions,childhood is theoretically an attractive time for H. pylori eradica-tion and, thus, could help prevent gastric cancer later in life.However, as H. pylori prevalence and the incidence of gastriccancer are low in childhood, widespread population screeningprograms would be enormously expensive and not justiable at anational level. 135,136 There is also an increased risk of reinfectionafter successful eradication therapy in childhood when comparedto adulthood. 137 The interval between screening and preventinggastric cancer would be lengthened and therefore payers for theprogram would have to wait a longer time before seeing any returnon their investment. The program would therefore also be lessnancially attractive from a third-party payer perspective.

Statement 36: Repeated testing for H. pylori infectionas 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 inhigh-risk populations. Infections are generally acquired duringchildhood. 53 Serological tests, in particular antibodies against thespecic antigen CagA, are immunogenic and long-lasting, forwhich reason they are useful for epidemiological studies. 138,139 Assuch, 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 nationaltreatment 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 guide-lines. Standard rst-line H. pylori eradication regimens are basedon triple therapy comprising twice daily proton pump inhibitors,clarithromycin and amoxicillin or metronidazole for at least 7days. These rst-choice H. pylori treatments are recommendedworldwide. However, it is recognized that the exact choice of antimicrobials may differ based on local patterns of antibioticresistance, and that the decision to treat for 1 or 2 weeks wouldalso depend on the results of locally validated data. 134




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Statement 38: Conrmation of H. pylori eradication is

not practical or cost-effective to consider on apopulation basis


For the individual patient, there should be conrmation of thesuccess of H. pylori eradication by using non-serological tests,which should be performed at least 4 weeks after treatment hasbeen completed. 134 In clinical practice, approximately 20% of patients will fail to eradicate H. pylori infection with the recom-mended treatment regimens. Major causes of treatment failure arepoor patient compliance and antibiotic resistance. 140 However, atthe population level, because of the costs involved and the

resources required, conrmation of H. pylori eradication is notpractical or cost-effective to consider. One may however, considerretesting and follow-up therapy on a case by case basis, such as inpatients with dyspepsia symptoms and those who request conr-mation of successful H. pylori eradication.

ConclusionAfter carefully reviewing the literature and weighing the evidenceand uncertainties, this consensus conference has concluded thatthere is a denite causal link between H. pylori infection and

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 precancerousgastric lesions and, in those without advanced precancerouslesions, H. pylori eradication probably reduces the incidence of gastric cancer.A strategy of H. pylori screening and eradication inhigh-risk populations (Fig. 1) should reduce gastric cancer inci-dence and is recommended by this consensus conference. Thisapproach may be considered in intermediate-risk populations,although it is acknowledged that supporting data are lacking andsuch a strategy is not recommended at this time. Finally, screeningin low-risk populations is not currently recommended.At the sametime, the current gastric surveillance programs in populations athigh risk for gastric cancer such as in Japan and Korea should becontinued.

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treatment of early gastric cancer: surgical techniques and long-termsurvival. Langenbecks Arch. Surg. 2004; 389 : 6974.

Patients with dyspepsia

Investigatedyspepsia Continue

program ofgastric cancer

surveillancebased onnational

guidelines

One-off screening withlocally validated

serology test for H. pylori

EradicateH. pylori

positivenegative

One-off treatment

according to localguideline; e.g. 1-weektriple 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 post-

therapy and institute a second-line therapy in the event of treatmentfailure.

Populations with a high or intermediate risk ofgastric cancer

Asymptomatic individuals(1860 years)

Qualified reassurance;perform

2nd test onindividualized

basis.

Figure 1 Strategy of H. pylori screening and eradication in populations at high or intermediate risk for gastric cancer.




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