Liu KSH, Wong IOL, Leung WK. Helicobacter pylori associated gastric intestinal metaplasia: Treatment and surveillance. World J Gastroenterol 2016; 22(3): 1311-1320 [PMID: 26811668 DOI: 10.3748/wjg.v22.i3.1311]
Corresponding Author of This Article
Wai K Leung, MD, Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China. waikleung@hku.hk
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Kevin Sze-Hang Liu, Wai K Leung, Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China
Irene Oi-Ling Wong, School of Public Health, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China
ORCID number: $[AuthorORCIDs]
Author contributions: Liu KSH, Wong IOL and Leung WK prepared literature review and wrote the paper.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Wai K Leung, MD, Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China. waikleung@hku.hk
Telephone: +852-22553348 Fax: +852-28162863
Received: May 12, 2015 Peer-review started: May 14, 2015 First decision: July 14, 2015 Revised: August 4, 2015 Accepted: November 30, 2015 Article in press: November 30, 2015 Published online: January 21, 2016 Processing time: 248 Days and 5.7 Hours
Abstract
Gastric cancer (GC) is one of the leading causes of cancer related death in the world, particularly in East Asia. According to the Correa’s cancer cascade, non-cardia GC is usually developed through a series of mucosal changes from non-atrophic gastritis to atrophic gastritis (AG), intestinal metaplasia (IM), dysplasia and adenocarcinoma. Atrophic gastritis and IM are therefore generally considered to be pre-neoplastic gastric lesions. Helicobacter pylori (H. pylori) infection is an important initiating and promoting step of this gastric carcinogenesis cascade. Emerging long-term data showed that eradication of H. pylori reduced the risk of subsequent cancer development. It however remains confusing whether eradication of the bacterium in individuals with pre-neoplastic gastric lesions could regress these changes as well as in preventing cancer. Whilst H. pylori eradication could likely regress AG, the presence of IM may be a point of no return in this cascade. Hence, surveillance by endoscopy may be indicated in those with extensive IM or those with incomplete IM, particularly in populations with high GC risk. The optimal interval and the best tool of surveillance endoscopy remains to be determined in future studies.
Core tip: Gastric intestinal metaplasia (IM) is generally considered to be a pre-neoplastic gastric lesion, which is usually triggered by chronic Helicobacter pylori (H. pylori) infection. However, the role of H. pylori eradication in treating gastric IM remains controversial. It remains uncertain whether the presence of gastric IM signifies an irreversible step of histological progression. Despite the definite increase in risk of gastric cancer development, the role of endoscopic surveillance remains dubious. This review will summarize the latest literature on treatment and surveillance of gastric IM.
Citation: Liu KSH, Wong IOL, Leung WK. Helicobacter pylori associated gastric intestinal metaplasia: Treatment and surveillance. World J Gastroenterol 2016; 22(3): 1311-1320
Gastric cancer (GC) is one of the most common cancers in the world and is the third leading cause of cancer mortality[1]. Although the incidence of GC is declining worldwide, the number of new cases is still rising due to population growth and the aging population[2]. In particular, the burden of the disease remains high in East Asian countries. In 2012, almost one million new gastric cancers were diagnosed in the world and half of them occurred in East Asia[3]. Since early cancers are usually asymptomatic, two-thirds of the patients presented at an advanced stage when curative resection was not possible. Despite the advances in treatment, the prognosis of patients with advanced gastric cancer remained dismal with a median survival of less than 1 year[4].
The development of GC is generally believed to be a multistep process involving sequential changes of the gastric mucosa from non-atrophic gastritis to atrophic gastritis (AG), intestinal metaplasia (IM), dysplasia and finally carcinoma[5]. The process is thought to be initiated and promoted by Helicobacter pylori (H. pylori) and as a result, this bacterium has been classified by the International Agency for Research on Cancer of the World Health Organization as a class I carcinogen[6]. In a recent meta-analysis, the relative risk (RR) of developing non-cardia GC in H. pylori infected patients was 2.8[7].
Intuitively, eradication of H. pylori may halt the progression of the gastric carcinogenesis cascade and therefore reduce the risk of developing GC. Indirect evidence from populations with very low prevalence of H. pylori, such as Malays in the northeastern region of Malaysia, also support a decreased risk in developing pre-neoplastic lesions and GC in those populations[8]. However, previous studies that examined the role of H. pylori eradication in preventing GC yielded conflicting results, which may be accounted by the heterogeneity in sample size, ethnicity of study population and follow up duration. It remains even more controversial whether the presence of gastric IM is the point of no return in this gastric carcinogenesis cascade. This review examines the latest evidences on the prevention and treatment of H. pylori gastric pre-neoplastic conditions, as well as the role of surveillance of these lesions.
H. PYLORI ERADICATION IN PREVENTION OF GASTRIC CANCER IN INDIVIDUALS WITH BASELINE PRE-NEOPLASTIC LESIONS
Due to the long lag time between H. pylori infection and cancer development, clinical trials design to investigate the effects of H. pylori eradication in preventing GC development are complicated. These trials will require not only prolonged follow-up duration but also large sample size to be conducted in high-risk populations. Several randomized trials have been conducted in the past and the results are summarized in a recent meta-analysis, which showed that eradication of H. pylori resulted in 34% reduction in the incidence of GC[9]. However, the benefits may be more prominent in Asian patients where GC is more prevalent, particularly in Chinese men whom the number needed to treat was as low as 15.
Despite the potential benefits of H. pylori eradication in preventing GC, it remains more controversial whether the presence of pre-neoplastic lesions will preclude the benefits of eradication in cancer prevention. In the subgroup analysis of a randomized trial of H. pylori eradication in preventing gastric cancer in China[10], Wong et al[10] showed that the potential benefits of H. pylori eradication in preventing GC was limited to patients without precancerous lesions at baseline. In a recent meta-analysis, Chen et al[11] looked at the baseline histological changes and the risk of GC after H. pylori eradication. They found that although the risk of GC was lowered in the anti-H. pylori treatment group (RR = 0.64, 95%CI: 0.48-0.85), subgroup analysis in patients with existing IM and dysplasia could not confirm the potential benefits (RR = 0.88, 95%CI: 0.59-1.31). H. pylori eradication also had no effect on regression of these lesions (RR = 0.81, 95%CI: 0.64-1.03). Hence, the presence of IM was believed to be a “point of no return” in the cancer cascade of GC where treatment of H. pylori appears to be of no benefit. Nonetheless, in a more recent subgroup analysis of the 15-year effects of H. pylori treatment on gastric cancer incidence and mortality, Li et al[12] demonstrated that treatment was still associated with a significant reduction in gastric cancer incidence even in patients with baseline IM and dysplasia.
Based on the latest evidence, H. pylori treatment should still be recommended to individuals with existing pre-neoplastic lesions with the hope of reducing the risk of GC. The recent revised guidelines from Eastern countries (China, Japan and Korea) and Europe (Maastricht IV Consensus report) all support H. pylori eradication to reduce the risk of gastric cancer[13-16]. Recommended H. pylori eradication regimen differed slightly in each region because of the difference in local antibiotic resistance profile. Table 1 summarized the recommended first and second line H. pylori eradication regimen from each region. Unfortunately, due to the rising clarithromycin resistance[17], the eradication rate of clarithromycin containing triple therapy is declining globally, sometimes to an unacceptable eradication rate of less than 80%[18]. Several new H. pylori eradication regimens, including sequential therapy and concomitant therapy of three antibiotics given over a period of 10-14 d, have been developed to overcome the problem of antimicrobial resistance.
Table 1 Recommended first and second line Helicobacter pylori eradication regimen.
No preferential choice. Options include: (1)PPI, amoxicillin 1 g, clarithromycin 500 mg twice daily (2) PPI, amoxicillin 1 g, levofloxacin 200 mg twice daily (or levofloxacin 500 mg daily) (3) PPI, amoxicillin 1 g, furazolidone 100 mg twice daily (4) PPI, tetracycline 750 mg, metronidazole 400 mg twice daily (or metronidazole 400 mg three times per day) (5) PPI, bismuth 220 mg plus any of the two antibiotics above twice daily
Duration: 7-14 d
GASTRIC PRE-NEOPLASTIC LESIONS AND RISK OF GC
Whilst gastritis is seen in virtually all H. pylori infected subjects, only around 10% of the infected individuals with chronic active gastritis progressed to severe AG[19]. Since this progression is related to chronic inflammation of the gastric mucosa, there is a strong age-associated increase in the prevalence of IM as well[20]. Male gender and those with first-degree family history of GC have been shown to have an increase in risk of developing IM[21]. We have also shown that presence of certain H. pylori genotype (vacA m1) and polymorphisms of the host inflammatory cytokines (interleukin-1β) were associated with the presence of gastric IM in Chinese population[22]. In the meta-analysis by Marques-Silva et al[23], it was also shown that there were wide geographic variations of AG and IM. The prevalence of AG in the worldwide population in general was 33.4% and increased to 42% in countries with high incidence of GC. The prevalence of IM in the worldwide population was 25% whereas extensive IM was found in 13%. In low-prevalence western cohort, the annual incidence of progression to GC is 0.1% for AG, 0.25% for IM and 0.6% for mild to moderate dysplasia[24]. The rate of progression however appears to be higher in Asian population. In a Japanese study, Uemura et al[25] showed that the RR of progression to cancer was 1.7, 4.9 and 6.4 in patients with moderate atrophy, severe atrophy and IM, respectively.
Histologically, IM can be further classified into complete or incomplete as originally proposed by Matsukura et al[26], which depends on the presence of small intestinal digestive enzymes. It is currently separated into complete or incomplete by the resemblance of small intestinal or colonic epithelium, respectively[27]. Another classification was developed by Jass and Flipe[28], which further classified incomplete IM into type II or III by the mucin expressions. Type I, or complete IM, expresses only sialomucins and type III expresses sulfomucins. Type II is a hybrid form which expresses a mixture of gastric and intestinal mucins. These subtyping would require the use of combined high-iron diamine and alcian blue staining which is not widely available in routine service laboratory. It also remains undetermined whether there are sequential changes from type I to type III, and simultaneous expression of different types of mucins are not infrequent[27]. In a recent review by González et al[29], the prevalence of type III IM were significantly higher in GC in 13 of 14 cross-sectional studies and there was a significant association of type III or incomplete IM with GC in 6 of 10 follow-up studies.
Apart from the IM subtypes, the extent of IM is also crucial in determining the subsequent risk of GC. In general, lesions along the lesser curve from the cardia to pylorus [odds ratio (OR) of 5.7] and with diffuse pattern involving essentially the entire gastric mucosa (OR of 12.2) are at higher risk of GC[30]. To this end, the operative link assessment of gastritis assessment (OLGA) staging system was proposed to stage the severity and extent of AG into stages 0 to IV (Table 2)[31]. This staging system was shown to be very useful in predicting the risk of GC development, particularly in patients with stage III-IV AG. While the unequivocal diagnosis of AG is sometimes difficult and IM is more easily recognizable histologically, a modification to the OLGA to the new staging system of operative link for gastric intestinal metaplasia assessment (OLGIM) by replacing AG with IM system was proposed[32]. Although the OLGIM was found to provide a better inter-observer agreement than OLGA, a significant proportion of patients with stage III-IV OLGA were missed if only the OLGIM was applied[33]. In high GC risk population such as Korea, it was found that old age, smoking and H. pylori infection were associated with high risk OLGA and OLGIM stages[33]. High-risk OLGIM stages were infrequent before the age of 40 (2.8%) but increased to 30.1% for those in the 60s.
Table 2 Operative Link for Gastritis Assessment[31].
Corpus
No atrophy (score 0)
Mild atrophy (score 1)
Moderate atrophy (score 2)
Severe atrophy (score 3)
Antrum (including incisura angularis)
No atrophy (score 0)
Stage 0
Stage I
Stage II
Stage II
Mild atrophy (score 1)
Stage I
Stage I
Stage II
Stage III
Moderate atrophy (score 2)
Stage II
Stage II
Stage III
Stage IV
Severe atrophy (score 3)
Stage III
Stage III
Stage IV
Stage IV
H. PYLORI ERADICATION AND CHANGES OF GASTRIC PRE-NEOPLASTIC LESIONS
While eradication of H. pylori could restore the gastric mucosa to normal in individuals with H. pylori associated chronic gastritis alone[34,35], the role of H. pylori treatment in reversing gastric pre-neoplastic changes remain less certain[36]. The presence of IM in the stomach is usually associated with a lower level of H. pylori colonization due to the change in gastric mucus and acidity. Hence, the potential therapeutic effect of H. pylori eradication may be minimal. In our previous randomized controlled trial in Chinese population, we found that progression of IM was more often in those with persistent H. pylori infection, male subjects and those aged more than 45 years[37]. However, eradication of H. pylori alone did not prevent progression in all patients, particularly in those with more extensive and severe IM at baseline. In a meta-analysis that included 16 studies[38], the investigators found that there was significant improvement of AG in the gastric antrum and the gastric corpus after treatment for H. pylori. As for IM, significant improvements were only seen in the antrum but not in the corpus. Yet, two previous meta-analyses did not find any improvement in IM regardless of the location of the lesions[39,40].
Further long-term follow up studies are therefore necessary to determine whether H. pylori eradication could regress gastric IM, particularly those in the corpus. Studies are also needed to address whether there are any changes in gastric IM subtypes after treatment against H. pylori.
OTHER TREATMENTS FOR GASTRIC PRE-NEOPLASTIC LESIONS
Apart from treatment against H. pylori, other agents have been used for treatment of gastric pre-neoplastic lesions including anti-oxidants and cyclooxygenase-2 (COX-2) inhibitor. COX-2 is an enzyme responsible for the conversion of arachidonic acid to prostaglandins. It has been shown to be overexpressed and involved in gastric IM and cancer[41]. Whilst COX-2 selective inhibitors have been shown to reduce the risk of various cancers including colon and breast cancer, the role of COX-2 inhibitors have been tested in two randomized controlled trial in Chinese patients[42,43]. In our previous randomized controlled study, patients with gastric IM after eradication of H. pylori were allocated to receive rofecoxib or placebo for 24 mo. There was no significant difference in the percentage of patients with regression or complete resolution of IM after rofecoxib treatment. In another randomized trial by Wong et al[43] patients with H. pylori infection and advanced gastric lesions including severe chronic AG, IM and dysplasia were assigned to receive different treatment options including eradication of H. pylori, a 2-year course of celecoxib, combination of both or placebo[44]. They found that when compared to placebo, the proportions of patients with regression of gastric lesions were significantly increased in the celecoxib group and the H. pylori treatment group. There was however no significant effect in the group who received both anti-Helicobacter therapy and celecoxib. More importantly, 9 patients developed early gastric cancer in this study and all except one have indefinite dysplasia or dysplasia at baseline. The remaining patient had baseline deep IM. Together, these data do not suggest an additional benefit of COX-2 inhibitor over treatment of H. pylori alone in preventing the progression of gastric IM (Table 3).
Table 3 Pharmacological treatment of gastric intestinal metaplasia.
RCT (H. pylori eradication, vitamins or garlic supplements)
China
3365
Both vitamins and garlic supplements have no effect on gastric precancerous lesion
Vitamins and other anti-oxidants have also been tested in the treatment of gastric precancerous lesions in a randomized trial in China[44]. Subjects were randomly assigned in a factorial design to receive anti-Helicobacter therapy; vitamin C, vitamin E, and selenium (vitamin supplement); or an aged garlic extract and steam-distilled garlic oil (garlic supplement). Although H. pylori eradication significantly reduced the combined prevalence of chronic AG, IM, dysplasia or cancer, vitamin or garlic supplement had no effect on gastric precancerous lesions. Hence, there is so far no compelling evidence to support the routine use of vitamins or anti-oxidants.
Smoking and high salt diet have also been linked to the development of gastric pre-neoplastic lesions[45,46]. As yet, there is no clinical trial to look into the role of smoking cessation or diet manipulation on changes of gastric pre-neoplastic lesions.
Whilst gastric dysplasia can also be treated by endoscopic resection like endoscopic mucosal resection or endoscopic submucosal dissection, the role of endoscopic treatment for gastric IM is not defined. With the high success of eradicating IM in the esophagus in patients with Barrett’s esophagus[47], we have recently examined the role of endoscopic radiofrequency ablation (RFA) for gastric IM and dysplasia[48]. Although endoscopic RFA could ablate gastric low-grade dysplasia, gastric RFA failed to completely ablate gastric IM. Hence, endoscopic treatment may not be indicated in these patients with gastric IM only.
SURVEILLANCE OF PRE-NEOPLASTIC CONDITIONS
Despite the risk of progression of gastric pre-neoplastic lesions, there is so far no definitive evidence to support the routine surveillance of gastric IM. In a recent Cochrane systemic review of surveillance of gastric IM in the prevention of GC[49], no studies met the inclusion criteria including randomization and a proper comparative group. Hence, there is a genuine need for properly conducted clinical trials to address this issue.
On the other hand, there are several western guidelines published on the recommendation for surveillance of gastric IM. Due to the low risk of gastric cancer in the United States, the American Society for Gastrointestinal Endoscopy does not uniformly recommend surveillance for gastric IM[50]. However, endoscopic surveillance with topographic mapping of the entire stomach in subjects at increased risk of gastric cancer on the basis of ethnic background, immigration from a geographic location with high gastric cancer risk, or family history is recommended. There is also no recommendation on surveillance interval. In 2012, the European Society for Gastrointestinal Endoscopy (ESGE) recommended that patients with IM or GA at both antrum and corpus should be offered surveillance every 3 years[51]. For patients with isolated IM in the antrum, regular surveillance is not recommended. Figure 1 summarizes the management approach recommended by ESGE. It remains to be proven whether this approach is also applicable to Asia where GC is prevalent. In fact, screening of GC is widely practiced in Japan and Korea[52] but there is no national guideline on surveillance of gastric IM. In a recent survey from Korea, it was shown that 95% of specialists perform annual endoscopic surveillance for IM[53].
Figure 1 Flow chart for the management of patients with pre-neoplastic conditions.
Modified from Dinis-Ribeiro et al[51].
Since AG and IM are not uniformly distributed in the stomach, proper mapping of the stomach with biopsies taken from both antrum (including incisura) and corpus are necessary for comprehensive assessment of the extent of the lesions. It remains to be determined whether further classification of IM into different subtypes would have more clinical implications on surveillance strategy. It is however prudent to treat extensive IM and incomplete IM cautiously since the risk of progression to GC appears to be higher than patients with focal IM in the antrum only. Further studies are needed to determine the optimal surveillance strategy for patients with different severities of gastric pre-neoplastic lesions, in a manner similar to what we are practicing for surveillance of different colonic adenoma[54].
Although endoscopic surveillance is recommended by the ESGE, the way how it is performed remains uncertain. Unlike colonoscopy performed for colorectal adenoma detection, there is no reliable quality indicator for gastroscopic examination. Routine white light endoscopy with multiple biopsies taken from the antrum and corpus to map the extent of the disease appears to be the standard approach. A recent study from Singapore showed that endoscopic examination times of longer than 7 min identified a greater number of high-risk gastric lesions including cancer, dysplasia, IM and AG than examinations shorter than 7 min[55]. There was a 2-fold difference in the detection rate of high-risk lesions among slow endoscopists regardless of their seniority. Despite the wide use of chromoendoscopy in Japan for gastric cancer screening, this is not widely practiced in other countries due to various issues including examination time and cost. A recent meta-analysis comparing the diagnostic efficacy of white light endoscopy or magnifying endoscopy with narrow band imaging showed that the latter had a higher diagnostic sensitivity than conventional white light endoscopy[56]. Further support of the use of image-enhanced endoscopy was published from the recent Kyoto Global Consensus Conference[57]. In the consensus report, experts recognized the shortfall of random biopsies using conventional endoscopy and suggested that image-enhanced endoscopy including chromoendoscopy, high-resolution magnification endoscopy and image-enhanced endoscopy combined with magnification to increase the yield from biopsies. Nonetheless, there is a need to define in future studies or guidelines the appropriate endoscopic modality for surveillance of these gastric pre-neoplastic lesions.
Over the last decade, there are increasing research on the relationship between genetic alterations and GC development. A number of genes whose functional effects range from inflammation to signal transduction and cell cycle regulation had been identified[58]. For the studies that examined H. pylori and pre-neoplastic changes, they generally showed positive association with the frequency of the specific genetic polymorphism with increased severity of changes in gastric mucosa. One particular genome wide association study by Maran et al[59] showed specific single nucleotide polymorphisms (SNPs), namely UFM1, THBS4, CYP2C19 and MGST1 genes, were associated with AG, complete IM, incomplete IM and dysplasia, respectively. This may provide an indirect method on surveillance of pre-neoplastic changes and avoid the sampling error from random gastric biopsies. Unfortunately, the genetic polymorphisms association may only be applicable to certain ethnic group. Therefore, the findings of these SNPs changes with different degree of pre-neoplastic changes need to be validated in a different cohort of patients before it can be applied globally.
Another less invasive and simple strategy for surveillance of gastric pre-neoplastic lesions is the use of serum pepsinogen (PG) levels. PGI is secreted by chief and mucous neck cells in the corpus and fundic glands, whereas PGII is secreted by these cells as well as cells in the pyloric glands and Brunner’s glands. Hence, any reduction in PGI levels is strongly associated with corpus atrophy. Unlike endoscopic examination that is invasive and skill dependent, measurement of serum PG levels is non-invasive and mass population screening is also possible. In Japanese series, a low serum PGI or a PGI/II ratio is a reliable marker for predicting risk of GC[60]. The use of serum PG screening was also found to be more effective than endoscopic screening in a recent cost-effective analysis[61].
Further non-invasive testing of pre-neoplastic gastric lesions and GC via exhaled breath is being investigated. Amal et al[62] demonstrated that by applying nanoarray analysis on the exhaled volatile organic compounds could accurately differentiate normal gastric mucosa, pre-neoplastic gastric lesions (based on OLGIM staging system) and GC. The results were encouraging and could be used as a future screening and surveillance tool for gastric pre-neoplastic lesions.
COST EFFECTIVENESS ANALYSIS OF H. PYLORI ERADICATION AND SURVEILLANCE OF PRE-NEOPLASTIC CONDITIONS FOR GC PREVENTION
Cost-effectiveness analysis with the use of mathematical model is the mainstream method for economic evaluation in health technology assessment in recent decades[63]. This method is particularly useful to policy makers for making decisions related to healthcare intervention assessment and resource allocations in view of increased healthcare costs and limited budget. Such model is able to simulate disease evolution (i.e., provide insights into those uncertain aspects of the natural history of the disease concerned), present a comprehensive epidemiologic model by means of model-based estimates and to improve the basis for projecting the future course of the disease burden. Under such mathematical framework, multiple and diverse data sources on costs, clinical effects, and health-related issues concerning the effects of alternative strategies on one’s quality of life are synthesized to estimate intermediate and long-term clinical outcomes. This serves as one of the valuable tools to extend the time horizon of existing clinical trials to assess public health policies than in a single trial, and to evaluate incremental costs and effectiveness of alternative strategies to reduce disease burden[64]. Although primary preventive strategies such as eradicating H. pylori infection have been shown in both Caucasian and Asian populations[65-70] to be cost-effective by using the mathematical modeling approach with a population screening scenario, special attention must be paid for the secondary prevention which focuses on surveillance of precancerous lesions in preventing GC. With the huge variations in the GC incidence, prevalence of H. pylori infection and pre-neoplastic lesions as well as the cost of screening, the results may not be applicable to all countries. A recent systematic review summarized that there was no consistent evidence on cost-effectiveness of endoscopic surveillance for premalignant gastric conditions[51,71]. Hassan et al[72] study concluded that yearly endoscopy surveillance was not cost-effective compared to non-surveillance policy in American patients with IM [incremental cost-effectiveness ratio (ICER) of US$72519 per life-year gained]. Similarly, Yeh et al[73] work demonstrated that endoscopic surveillance of less advanced lesions (for IM) did not appear to be cost-effective (ICER of US$544500 per quality-adjusted life-year (QALY) for endoscopic mucosal resection with surveillance every 10 years) for a cohort of US men with a recent incidental diagnosis of gastric precancerous lesions (AG, IM or dysplasia), except possibly for immigrants from high risk countries. Conversely, Areia et al[74] study suggested that endoscopic surveillance every 3 years of patients with premalignant conditions was cost-effective compared to no surveillance in a Portuguese population (ICER of Euro$18336 per QALY). The inconsistent results might be likely due to different parameter estimates on progression rates (e.g., rates from IM to dysplasia, from dysplasia to gastric cancer) and costing data (e.g., endoscopy) being used[51]. There is also no cost-effectiveness analysis study conducted in high-risk population such as Chinese. More research on cost-effectiveness of endoscopic surveillance in IM patients and high-risk groups are warranted.
CONCLUSION
H. pylori is one of the most important causes of GC as well as pre-neoplastic gastric lesions. Eradication of H. pylori appears to be the best approach in preventing the development and subsequent progression of gastric pre-neoplastic lesions. Treatment of H. pylori should ideally be given at an early stage prior to the development of gastric pre-neoplastic lesions to have the best long-term outcome, but encouraging results are still seen in more recent data of subgroup analysis of older patients with advanced gastric lesions. On the other hand, the role of endoscopic surveillance of these advanced gastric lesions remain uncertain. Universal surveillance is unlikely to be helpful, particularly in low risk population. A selected group of patients at high risk of GC development as identified by proper mapping and staging of gastric histology by OLGA or OLGIM would be the likely sustainable surveillance strategy. More clinical data is desperately needed to characterize the best screening tool as well as the optimal surveillance interval for patients with gastric pre-neoplastic lesions.
Footnotes
P- Reviewer: Gucin Z, Kim GH, Lee YY, Ruiz-Bustos E S- Editor: Yu J L- Editor: A E- Editor: Zhang DN
Ford AC, Forman D, Hunt RH, Yuan Y, Moayyedi P. Helicobacter pylori eradication therapy to prevent gastric cancer in healthy asymptomatic infected individuals: systematic review and meta-analysis of randomised controlled trials.BMJ. 2014;348:g3174.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 423][Cited by in F6Publishing: 412][Article Influence: 41.2][Reference Citation Analysis (1)]
Wong BC, Lam SK, Wong WM, Chen JS, Zheng TT, Feng RE, Lai KC, Hu WH, Yuen ST, Leung SY. Helicobacter pylori eradication to prevent gastric cancer in a high-risk region of China: a randomized controlled trial.JAMA. 2004;291:187-194.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 1015][Cited by in F6Publishing: 995][Article Influence: 49.8][Reference Citation Analysis (0)]
Malfertheiner P, Megraud F, O’Morain CA, Atherton J, Axon AT, Bazzoli F, Gensini GF, Gisbert JP, Graham DY, Rokkas T. Management of Helicobacter pylori infection--the Maastricht IV/ Florence Consensus Report.Gut. 2012;61:646-664.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 1541][Cited by in F6Publishing: 1520][Article Influence: 126.7][Reference Citation Analysis (4)]
Mégraud F, Lamouliatte H. Review article: the treatment of refractory Helicobacter pylori infection.Aliment Pharmacol Ther. 2003;17:1333-1343.
[PubMed] [DOI][Cited in This Article: ]
Matsukura N, Suzuki K, Kawachi T, Aoyagi M, Sugimura T, Kitaoka H, Numajiri H, Shirota A, Itabashi M, Hirota T. Distribution of marker enzymes and mucin in intestinal metaplasia in human stomach and relation to complete and incomplete types of intestinal metaplasia to minute gastric carcinomas.J Natl Cancer Inst. 1980;65:231-240.
[PubMed] [DOI][Cited in This Article: ]
Jass JR, Filipe MI. The mucin profiles of normal gastric mucosa, intestinal metaplasia and its variants and gastric carcinoma.Histochem J. 1981;13:931-939.
[PubMed] [DOI][Cited in This Article: ]
Capelle LG, de Vries AC, Haringsma J, Ter Borg F, de Vries RA, Bruno MJ, van Dekken H, Meijer J, van Grieken NC, Kuipers EJ. The staging of gastritis with the OLGA system by using intestinal metaplasia as an accurate alternative for atrophic gastritis.Gastrointest Endosc. 2010;71:1150-1158.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 301][Cited by in F6Publishing: 339][Article Influence: 24.2][Reference Citation Analysis (0)]
Valle J, Seppälä K, Sipponen P, Kosunen T. Disappearance of gastritis after eradication of Helicobacter pylori. A morphometric study.Scand J Gastroenterol. 1991;26:1057-1065.
[PubMed] [DOI][Cited in This Article: ]
Genta RM, Lew GM, Graham DY. Changes in the gastric mucosa following eradication of Helicobacter pylori.Mod Pathol. 1993;6:281-289.
[PubMed] [DOI][Cited in This Article: ]
Hojo M, Miwa H, Ohkusa T, Ohkura R, Kurosawa A, Sato N. Alteration of histological gastritis after cure of Helicobacter pylori infection.Aliment Pharmacol Ther. 2002;16:1923-1932.
[PubMed] [DOI][Cited in This Article: ]
Correa P. Human gastric carcinogenesis: a multistep and multifactorial process--First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention.Cancer Res. 1992;52:6735-6740.
[PubMed] [DOI][Cited in This Article: ]
Leung WK, Tong DK, Leung SY, Chan FS, Ho RS, Chu KM, Law SY. Treatment of gastric metaplasia or dysplasia by endoscopic radiofrequency ablation: A pilot study.Hepatogastroenterology. 2015;62:748-751.
[PubMed] [DOI][Cited in This Article: ]
Dinis-Ribeiro M, Areia M, de Vries AC, Marcos-Pinto R, Monteiro-Soares M, O’Connor A, Pereira C, Pimentel-Nunes P, Correia R, Ensari A. Management of precancerous conditions and lesions in the stomach (MAPS): guideline from the European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter Study Group (EHSG), European Society of Pathology (ESP), and the Sociedade Portuguesa de Endoscopia Digestiva (SPED).Endoscopy. 2012;44:74-94.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 442][Cited by in F6Publishing: 451][Article Influence: 37.6][Reference Citation Analysis (0)]
Levin B, Lieberman DA, McFarland B, Andrews KS, Brooks D, Bond J, Dash C, Giardiello FM, Glick S, Johnson D. Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology.Gastroenterology. 2008;134:1570-1595.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 1423][Cited by in F6Publishing: 1431][Article Influence: 89.4][Reference Citation Analysis (0)]
Watabe H, Mitsushima T, Yamaji Y, Okamoto M, Wada R, Kokubo T, Doi H, Yoshida H, Kawabe T, Omata M. Predicting the development of gastric cancer from combining Helicobacter pylori antibodies and serum pepsinogen status: a prospective endoscopic cohort study.Gut. 2005;54:764-768.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 290][Cited by in F6Publishing: 298][Article Influence: 15.7][Reference Citation Analysis (0)]
Goldie SJ. Chapter 15: Public health policy and cost-effectiveness analysis.J Natl Cancer Inst Monogr. 2003;102-110.
[PubMed] [DOI][Cited in This Article: ]
Parsonnet J, Harris RA, Hack HM, Owens DK. Modelling cost-effectiveness of Helicobacter pylori screening to prevent gastric cancer: a mandate for clinical trials.Lancet. 1996;348:150-154.
[PubMed] [DOI][Cited in This Article: ]
Wong IO, Schooling CM, Cowling BJ. Cost-effectiveness of Helicobacter pylori screening and treatment for gastric cancer in Hong Kong: a decision analytic approach.Hong Kong Med J. 2014;20 Suppl 7:13-15.
[PubMed] [DOI][Cited in This Article: ]
