Statistical proof of Helicobacter pylori eradication in preventing metachronous gastric cancer after endoscopic resection in an East Asian population

Mohsen Karbalaei,Masoud Keikha

Mohsen Karbalaei,Department of Microbiology and Virology,School of Medicine,Jiroft University of Medical Sciences,Jiroft 78617-56447,Iran

Masoud Keikha,Department of Microbiology and Virology,Faculty of Medicine,Mashhad University of Medical Sciences,Mashhad 13131-99137,Iran

Abstract We conducted a comprehensive literature review and meta-analysis study on the efficacy of Helicobacter pylori (H.pylori) eradication in preventing metachronous gastric cancer after endoscopic resection among an East Asian population.Our results showed that the eradication of this pathogen significantly reduced the risk of susceptibility to metachronous gastric cancer in these patients.However,based on the available evidence,several factors such as increasing age,severe atrophy in the corpus and antrum,and intestinal metaplasia all may increase the risk of metachronous gastric cancer in H.pylori eradicated patients.

Key Words: Helicobacter pylori;Gastric cancer;Eradication rate;Metachronous gastric cancer

TO THE EDlTOR

Helicobacter pylori(H.pylori) is a Gram-negative,microaerophilic,and helical microorganism that colonizes the gastric mucosa in half of the world’s population[1].This bacterium is the main etiologic cause of gastritis,dyspepsia,gastric mucosa-associated lymphoid tissue (MALT) lymphoma,gastric cancer,and peptic ulcer[1-3].According to the literature,H.pylorialso contributes in extragastrointestinal disorders such as insulin resistance,non-alcoholic liver disease,diabetes mellitus,coronary artery disease,and neurodegenerative disease[3,4].In 1994,the International Agency for Research on Cancer (IARC) identified this bacterium as a group I gastric carcinogen[5].There is ample evidence about the positive relationship betweenH.pyloriinfection and gastric cancer;primary infection with this bacterium has been proven to lead to cancer by inducing atrophic gastritis,intestinal metaplasia,and dysplasia[6].According to previous randomized controlled trials (RCTs),it seems that the eradication of this pathogen is not effective in preventing the occurrence of primary gastric cancer[7-12].Doorakkerset al[13] in a recent meta-analysis found that the eradication of this microorganism fundamentally reduced the incidence of primary gastric cancer.

Antrectomy (distal gastric resection) is a rare surgical procedure to treat early distal gastric cancer,in which the pyloric antrum is excised;although the presence ofH.pylorimay be decreased in the residual stomach,both untreated bacterial infection and biliopancreatic reflux damage the residual gastric mucosa,which can be considered as precursors for gastric stump cancer (GSC)[14].Endoscopic resection (ER) procedures such as endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are known as accepted therapeutic strategies for treating early gastric cancer (EGC);although the effect of ER on EGC treatment is greater than that of gastrectomy,the risk of metachronous gastric lesions in the remnant stomach is higher after ER than gastrectomy[15].

Based on documents,the incidence of metachronous gastric cancer (MGC) has been estimated at 2.7%-15.6% in 3-5 years after EGC[16].The efficacy of eradication of infection in the prevention of metachronous recurrence is controversial[15,17].In the present study,we determined the beneficial effect ofH.pylorieradication to prevent the recurrence of MGC after ER in an East Asian population.

We searched scientific databases such as Scopus,PubMed,Google Scholar,Cochrane Library,as well as Embase regardless of restriction in date and language by November 2020.The titles and abstracts of all papers were assessed to select the relevant articles.Then,eligible studies related to the effect of definitive treatment of infection on the recurrence of MGC after ER were collected.The inclusion criteria were: (1) RCTs or cohort studies on the effect of standard bacterial eradication on metachronous recurrence;(2) comparative studies of people with conventionalH.pylorieradication and those who do not receive conventional eradication procedure;and (3) studies on the East Asian population.On the other hand,criteria such as (1) review articles,letters,or congress abstracts;(2) duplication studies;(3) non-clinical studies;and (4) studies with insufficient materials and findings were considered as the exclusion criteria.We collected the essential information using Comprehensive Meta-Analysis software,version 2.2.The incidence of metachronous recurrence was reported in each group as a percentage with 95% confidence interval (95%CI).Moreover,the clinical achievement ofH.pylorieradication in reduction of metachronous recurrence was also measured using odds ratio (OR) with 95%CI.Heterogeneity was determinedvia I2value and Cochran’sQtest;a random-effect model was applied in high heterogeneity cases (I2＞ 25% and Cochran’s-Q P＞ 0.05) according to the Dersimonian and Laird method.The potential study bias was assessed by the Egger’s test and Begg’s test[18,19].

A total of 1753 documents were retrieved during the initial literature search.Finally,we selected 23 articles as eligible articles according to the inclusion criteria[20-42].The demographic information such as first author,date of publication,country,follow-up years,metachronous lesions,frequency of metachronous recurrence in both eradicated and persistent cases,and references are summarized in Table 1.These studies were conducted during 1997-2019.Of all the studies,10 were from Korea,and 10 from the Japan.In the current analysis,we evaluated the data of 9233H.pyloripositive cases to determine the efficacy of complete eradication in preventing metachronous events.

Table 1 Characteristics of included studies

The frequency of metachronous recurrence in bothH.pyloriextirpated and persistently infected cases was 7.2% (95%CI: 6.4-8.1,P= 0.01;I2= 81.68,Q= 125.56,P= 0.01;Egger’sP= 0.08,Begg’sP= 0.05) and 17.7% (95%CI: 16.1-19.5,P= 0.01;I2= 92.68,Q= 314.26,P= 0.01;Egger’sP= 0.01,Begg’sP= 0.54),respectively.

According to the statistical analysis,there is an inverse relation betweenH.pylorielimination and metachronous recurrence (OR = 0.53,95%CI: 0.44-0.65,P= 0.01;I2= 39.22,Q= 34.55,P= 0.03;Egger’sP= 0.08,Begg’sP= 0.09).We showed that the eradication ofH.pylorican significantly reduce the risk of metachronous recurrence (Figure 1).

Figure 1 Forest plot for incidence of metachronous gastric cancer between Helicobacter pylori-eradicated group and non-eradicated group in 23 studies.

Although most of included studies had not investigated the positive effect ofH.pylorieradication in reducing MGC in each location of the stomach,in patients withH.pylorieradication,the risk of MGC was significantly associated with other conditions such as severity of corpus atrophy and intestinal metaplasia[21-23,27,39,40].However,Hanet al[39] showed that antrum/body atrophy and old age can meaningfully increase the risk of metachronous cancer afterH.pylorieradication[24].In some studies,there was no significant relationship between this cancer and the eradication ofH.pylori[26,31,36].

Gastric cancer is one of the most prevalent cancers worldwide,especially in East Asian countries;today,the incidence of secondary gastric cancer after ER has become a major public health concern[34].Unfortunately,in some cases,the eradication ofH.pylorihas not been able to prevent MGC in patients with ER.In general,the clinical eradication ofH.pyloriseems to be effective in preventing secondary gastric cancer and improving quality of life and survival of patients with gastric cancer[43].In the present study,using data from 9233H.pyloripositive cases,we showed an inverse association between the elimination ofH.pyloriand progression to MGC in patients with a record of ER.In previous studies,we have shown that eradicatingH.pyloriin patients with gastric ulcers can reduce the risk of gastric cancer[44].In general,it is suggested that eradicatingH.pyloriafter primary gastric cancer can reduce the risk of MGC and increase survival in gastric cancer population[15,34,45].

Unfortunately,there is no detailed information about the location of the stomach where the reduction of gastric cancer can be achieved afterH.pylorieradication.Therefore,in future studies,more research should be done on the recent puzzle.

FOOTNOTES

Author contributions:Karbalaei M and Keikha M contributed to conceptualization,data curation,original drafting,and manuscript review &editing;all authors critically reviewed and approved the final version of the manuscript before submitting.

Conflict-of-interest statement:There are no conflicts of interest to report.

Open-Access:This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers.It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BYNC 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 noncommercial.See: https://creativecommons.org/Licenses/by-nc/4.0/

Country/Territory of origin:Iran

ORClD number:Mohsen Karbalaei 0000-0001-9899-2885;Masoud Keikha 0000-0003-1208-8479.

S-Editor:Chen YL

L-Editor:Wang TQ

P-Editor:Chen YL