The Impact of Atrophic Gastritis and Intestinal Metaplasia on the Occurrence of Metachronous Gastric Cancer After Endoscopic Resection: A Systematic Review and Meta-analysis

The Impact of Atrophic Gastritis and Intestinal Metaplasia on the Occurrence of Metachronous Gastric Cancer After Endoscopic Resection: A Systematic Review and Meta-analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article The Impact of Atrophic Gastritis and Intestinal Metaplasia on the Occurrence of Metachronous Gastric Cancer After Endoscopic Resection: A Systematic Review and Meta-analysis Younghee Choe, Jae Myung Park, Joon Sung Kim, Yu Kyung Cho, Byung-Wook Kim, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1840349/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background : Metachronous gastric cancer (MGC) can occur after endoscopic resection for gastric cancer. This systematic review and meta-analysis aimed to evaluate the risk of MGC caused by severe atrophic gastritis (AG) and intestinal metaplasia (IM). Methods : We searched the medical literature through May 2022 and identified patients who occurred MGC after endoscopic resection for gastric cancer. We retrieved studies evaluating the degree of AG and the presence or absence of IM and compared the incidence of MGC, respectively. Results : From nine cohort studies, 2,755 patients by 2018. Incidence of MGC was significantly higher in severe AG (RR, 1.64; 95% CI, 1.29–2.07; I 2 =45%) and IM (RR, 7.08; 95% CI, 3.63–13.80; I 2 =0%) than those without. The absolute risk difference of MGC in severe AG and IM was 7.5% and 9.2%, respectively. The difference in incidence rate per 1000 person-years was 17.5 and 22.5 person-years, respectively. However, the H. pylori infection did not affect the MGC occurrence (RR 1.08, 95% CI 0.85–1.39, I 2 =0%). Conclusions : Severe AG or IM had a 1.6-fold and 7.0-fold higher risk of MGC occurrence after endoscopic resection of gastric cancer. Patients with severe AG or IM need more stringent follow-up to monitor MGC occurrences. Endoscopic Mucosal Resection Gastritis Atrophic Meta-Analysis Neoplasms Second Primary Stomach Neoplasms Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Endoscopic resection (ER) for gastric cancer (GC), when small and limited to the mucosa, is now a standard treatment modality. This treatment has no significant difference in short-term outcomes and overall and disease-free survival compared with laparoscopic gastrectomy in early GC. Also, ER has fewer late complications and requires a shorter hospital stay than laparoscopic gastrectomy. 1 , 2 However, local treatments like ER have a high risk for development of metachronous gastric cancer (MGC) in the residual stomach. 3 – 5 There are several risk factors for the occurrence of MGC after ER. Helicobacter pylori ( H. pylori ) infection is the most important factor, but this can be managed. 6 Atrophic gastritis (AG) and intestinal metaplasia (IM) are precancerous GC lesions in the general population. 7 , 8 Since advanced AG and IM have a high risk of gastric adenocarcinoma, endoscopic surveillance is recommended. 9 , 10 Even though the influence of AG or IM is considerable in the development of GC, there is no quantifiable evidence to help predict the risk of MGC occurrence in patients who underwent ER for GC. This study conducted a systematic review and meta-analysis on the risk of MGC occurrence when AG or IM developed after ER for GC. Results Study inclusion and characteristics Through the planned search strategy, 86 documents were identified; after a review of titles and abstracts, 40 studies that appeared to be potentially inclusive were searched and evaluated (Fig. 1). In these, 2,755 patients were included from 9 articles reporting relevant data from 8 individual studies. 18-26 After being diagnosed with GC and undergoing ER, these patients were followed for more than two years at the attending hospital. The patients were evaluated for the presence of IM or degree of AG at the time of ER. The characteristics of studies included by appropriate criteria are presented in Table 1. The proportions of men in the studies ranged from 63% to 82%. At the time of ER, about 67% were negative for H. pylori or had successful eradication treatment of the infection within one year. The shortest and longest median follow-up period was 30 and 62 months, respectively. In this study, the diagnosis of severe atrophy was basically based on the contents defined by the authors of each paper. This study analyzed severe atrophy based on the definition of each paper's authors. Among the studies that defined atrophy endoscopically, five studies were classified based on the Kimura-Takemoto classification. In three studies, open type II and III were defined as severe, one was open type III, and the other was all open type severe. One study did not specifically describe the Kimura classification and only mentioned severe AG. Two studies classified severe atrophy with a low serum pepsinogen I/II ratio, and three studies defined pathologic severe atrophy by updated Sydney classification. In the study where only open type III was evaluated as more extensive atrophy, the serum PG I/II ratio and histology were also investigated. 21 It was evaluated that open type III reflects the most severity. The risk of bias assessments for all included studies was evaluated by the Newcastle-Ottawa Scale for Cohort Study Quality (Supplementary Table S1). Effects of the degree of mucosal atrophy on the occurrence of MGC after ER for GC Data obtained from 8 studies were pooled. 18-26 Of the 2,755 cases, 1,295 cases were classified as severe AG, and 1,250 cases were classified as non-severe AG. The incidence of MGC in GC patients with severe AG and non-severe AG was 186 (14.4%) and 86 (6.9%), respectively (absolute risk difference 7.5%; Table 2). The incidence rate of MGC was 36.9 (95% CI 31.8–42.6) per 1,000 person-years in severe AG and 19.4 (95% CI 15.5–23.9) per 1,000 person-years in non-severe AG, and the difference in incidence rate was 17.5 per 1,000 person-years. Patients with severe atrophy of the background mucosa at the ER had a higher risk of MGC occurrence than patients without severe AG (RR 1.64, 95% CI 1.29–2.07, I 2 =45%; Figure 2). Subgroup analysis was performed to estimate the MGC occurrence according to the parameter for judging the degree of mucosal atrophy. Endoscopically evaluated severe AG had significantly higher MGC occurrence than non-severe AG (RR 1.90, 95% CI 1.25–2.90, I 2 =52%; Figure 3a). In addition, serological (PG I, II) and histological (corpus and antrum) diagnostic methods were also analyzed. Testing for subgroup differences revealed no statistically significant subgroup effect ( P =0.58). However, it was shown that severe AG favored MGC occurrence more than non-severe AG in all subgroups ( P =0.58). Countries were also sub-analyzed to examine the possibility of geographically different outcomes (Figure 3b). Five Japanese studies 18,20-22,25,26 and three Korean studies 19,23,24 were included in this study. In the Japanese study, the number of severe AG patients (n=905, 57.2%) was higher than the number of non-severe AGs, and in the Korean study, the number of severe AGs (n=352, 35.2%) was less classified. The RR for MGC in severe AG was 1.75 (95% CI 1.11–2.73, I 2 =55%) in the Japanese study and 2.09 (95% CI 1.09–4.02, I 2 =26%) in the Korean study. Test for subgroup difference showed no subgroup effect ( P =0.65). Effects of the presence or absence of IM on the occurrence of MGC after ER for GC We investigated whether the presence of IM affects the occurrence of MGC in patients who underwent ER for GC. In four studies, 2,755 patients were included. The median follow-up period after ER was 2.5 to 4.2 years. IM was diagnosed histologically in 3 studies, 19,23,24 , and 1 study was diagnosed grossly during endoscopy. 21,22 In the presence of IM, the absolute risk difference of MGC was higher at 9.2%, and the incidence rate difference per 1,000 person-years was 22.5 (Table 3). In GC patients with IM, the RR of MGC occurrence was significantly higher than in patients without IM (RR 7.08, 95% CI 3.63–13.80, I 2 =0%; Figure 4). Only three studies with histological evaluation of IM out of 4 were performed for subgroup analysis. In patients with IM, the incidence of MGC was significantly increased by 6.94 (95% CI 3.48–13.82, I 2 =0%) compared with those without IM (Supplementary Figure S1). There were two studies in which the biopsy site was divided into antrum and corpus, but the meta-analysis results were the same. Relationship between Helicobacter pylori infection status and MGC A meta-analysis was performed to evaluate the relationship between H. pylori infection status and MGC occurrence (Figure 5). Since many people have not been clearly evaluated for H. pylori eradication in the past, we compared 660 patients with persistent infection and 1,912 patients with negative or eradicated infections. However, there was no significant difference between the risk of MGC occurrence in those with H. pylori -negative or eradicated, and those with persistent infection (RR 1.08, 95% CI 0.85–1.39, I 2 =0%). Analyzes of risk factors affecting the occurrence of MGC We performed an analysis to determine whether the risk of MGC occurrence increases according to demographic factors and characteristics of primary cancer. The risk of MGC occurrence according to demographic factors such as gender, age, drinking history, and smoking history were presented (Supplementary Table S2, Supplementary Figure S2). The risk of developing MGC was significantly higher in men than in women (total number of patients = 2579, RR 1.54, 95% CI 1.07–2.22, I 2 =22%), and there was also a greater incidence of MGC in patients with a history of smoking (total number of patients = 412, RR=2.10, 95% CI 1.25–3.53, I 2 =0%). The risk of developing MGC was higher in alcoholics, but no significant findings were found. There was only one study on the elderly. A forest plot for the occurrence of MGC according to the characteristics of primary cancer was presented (Supplementary Table S3). The primary cancer location, gross type, Lauren's classification, the degree of differentiation, and the depth of invasion were investigated. Supplementary S3 is a meta-analysis for each variable, and no risk factors showed a statistically significant effect on the occurrence of MGC. Discussion This systematic review and meta-analysis showed that the severity of AG and the presence or absence of IM are significant risk factors for the MGC occurrence after ER for GC. The incidence of MGC was significantly increased with severe AG or with IM. This was consistently observed in sub-analyzes according to different methods of evaluating mucosal atrophy and geographical area. There was no significant relationship between H. pylori eradication status and the risk of MGC occurrence in the present study. AG is usually evaluated endoscopically, serologically, and histologically. Endoscopic biopsy is the gold standard method in diagnosing AG. 27 The Kimura-Takemoto classification, the most commonly used method in clinical practice, is reliable and agrees with the Operative Link for Gastritis Assessment (OLGA) staging system. 11 , 28 , 29 Several studies have assessed gastric mucosal atrophy by measuring PG I and II, and PG is a reliable marker for diagnosing gastric mucosal atrophy. 30 , 31 The serum PG I and I/II ratio test for OLGA gastritis also showed a strong correlation with the stage. 4 , 32 A study comparing endoscopic, histologic, and serologic methods together to evaluate AG also showed a statistically significant association between the three. 33 In the present study, analysis was performed to confirm subgroup effects for various methods of evaluating AG. However, most were evaluated endoscopically, and other subgroups included a small number of trials and participants. Due to the uneven covariate distribution, it would have been difficult for the analysis to detect differences in subgroups. However, it was identified that severe AG favored MGC generation rather than non-severe AG in all subgroups. This was consistent with changes according to geographic location. We further evaluated the results of Japan and Korea separately, considering the possibility of inter-observer variation and educational differences between countries in the endoscopic evaluation of mucosal atrophy. There was no statistically significant subgroup effect in this analysis, showing consistent results between AG and MGC. MGC occurs after ER for GC, even in patients who have experienced eradication of H. pylori infection. Therefore, identification of potential risk factors for MGC is essential. IM is a precancerous lesion of GC. 34 , 35 However, to our knowledge, there are no studies that quantify the effect of IM on the occurrence of MGC after ER for GC. The presence of IM can be more meaningful in the group after ER than in the general population. Our present study showed this through meta-analysis of the previous reports. In this study, the small effect of H. pylori on the MGC occurrence after ER for GC is thought to be due to severe AG and IM. IM levels can be a 'point of no return in the Correa cascade.' The effect of H. pylori eradication on GC prevention in the presence of severe AG and IM is limited, and this effect is consistent with the MGC occurrence. 36 , 37 This study has some limitations. First, the included studies might have selection bias as retrospective cohort studies. Second, these studies were conducted only in Japan and Korea. The reason for this is that both counties have a high incidence of GC and perform screening evaluation for GC through a nationwide strategy. Third, the number of patients in whom the presence or absence of IM was confirmed was small. However, since most tissues were evaluated histologically, the results are unlikely to be exaggerated or understated. Fourth, the past infection or eradication history of H. pylori was unknown, so this analysis was limited. In addition, there were limitations in explaining the impact of AG and IM on MGC and the relationship between H. pylori eradication. Fifth, the definition of severe atrophy was not the same between studies, so there was a limitation in subgroup analysis. However, in all analysis results, the occurrence of less MGC was the same in the cases of non-severe AG. Nevertheless, the strength of this study was its focus on factors other than H. pylori infection as risk factors for MGC. As mentioned earlier, compared with H. pylori , AG and IM are more challenging to study and less attractive. However, since there are many H. pylori -negative gastric cancer patients, consideration of other causes is necessary. In conclusion, we found that severe AG and the presence of IM significantly increased the risk of metachronous recurrence in GC patients who underwent ER. In particular, patients with GC with IM occurred about seven times more MGC. These results suggest that patients with severe AG or IM undergo stricter follow-up endoscopy. Future studies in prospective cohorts with adjustment for baseline characteristics such as age and presence of H. pylori infection are needed. Methods Search strategy and Study selection We searched the MEDLINE, Embase, and Cochrane centrally controlled trial registries without language restrictions for studies published from inception through 31 May 2022 to identify potential studies. Suitable studies were investigated for the effects of the degree of mucosal atrophy and the presence or absence of IM on MGC occurrence after ER for GC (Supplementary Table S4). The inclusion criteria for this study were: (i) adults 19 years of age or older with GC who underwent ER, (ii) evaluation of severe AG or IM presence, and (iii) clearly cited evaluation method (endoscopy, histology, or serology). After ER, a follow-up period of at least two years was required for the present study. We extracted all endpoints from the last follow-up using the most recent publication from each trial. Studies in which gastric 'adenoma' were resected or metachronous gastric 'adenoma' occurred were excluded. Studies with ambiguous methods for assessing severe AG or IM were also excluded. Two investigators (YC and JMP) performed literature searches independently of each other. The search terms used are detailed in Supplementary Materials. All potentially relevant references were obtained and evaluated to assess independently the qualifications against the predefined criteria by the investigators. Titles and abstracts were reviewed to extract relevant studies. Full texts were screened to identify eligible studies that met inclusion criteria. We resolved disagreements among investigators through discussion and, if necessary, consultation with a third reviewer who was one of our authors. There were no language restrictions, and foreign language papers were translated when necessary. Outcome assessment The primary outcome was the effect of the presence of IM or severe AG on the occurrence of MGC, which was compared between patients without IM or with mild to moderate AG. IM is histologically defined by the Sydney classification. Mucosal atrophy can be defined variously by three parameters: endoscopy, serology, and histology. Endoscopic evaluation was examined by Kimura-Takemoto classification (closed type I/II/III and open type I/II/III). 11 The included studies evaluated open type II and III as severe AG. Serologically, mucosal atrophy also was evaluated by pepsinogen (PG) I and II. PG is a proenzyme produced in gastric mucosa. When atrophic change occurs, the PG I level produced in chief cells decreases, as does the PG I/II ratio. In general, severe AG is determined when the PG I/II ratio is less than 3.0. 12-14 Histologically, mucosal atrophy was classified into none, mild, moderate, or severe according to the updated Sydney System. 15 Data extraction We extracted all data independently. Two investigators (YC and JMP) did this with dichotomous results (with or without MGC). We also extracted the following data for each trial: geographical location, country of origin, number of centers, number of patients, gender, age, alcohol intake, smoking history, history of H. pylori infection and eradication, follow-up period, number of patients with MGC, presence of IM, the severity of AG at the time of ER, and anatomical, gross and pathological features of primary cancer. Data were extracted using the evaluation parameters of AG and IM. Quality assessment and data synthesis Quality and risk of bias were independently assessed by two investigators (YC and JMP). Because the included studies were non-randomized studies, the ‘Newcastle-Ottawa Scale for Cohort Study Quality’ was used. If there were differences of opinion between the two investigators, the discrepancy was resolved through discussion. We performed a systematic review and meta-analysis following the Preferred Reporting Items for a Systematic Review and Meta-analysis guideline. 16,17 Data for the subsequent development of GC according to the degree of AG and H. pylori infection status were combined using a fixed-effect model and Mantel-Haenszel estimation method. A random-effect model was used for MGC occurrence according to subgroup analyzes of AG and the presence or absence of IM. The Taylor series and Byar method were used for the incidence rate per 1000 person-years of MGC by severe AG and presence of IM. We expressed the effect as a GC risk ratio (RR) of 95% confidence interval (CI) and used I 2 to assess heterogeneity between studies. To define a significant degree of heterogeneity, we evaluated heterogeneity between studies using both the I 2 statistic with a cutoff of ≥ 50% and the χ2 test with a P < 0.10. We used Review Manager V.5.4.1 (RevMan for Windows 2020, Nordic Cochrane Center, Copenhagen, Denmark) and Excel for the analysis. Abbreviations AG, atrophic gastritis; CI, confidence interval; GC, gastric cancer; IM, intestinal metaplasia; MGC, metachronous gastric cancer; OLGA, Operative Link for Gastritis Assessment; PG, pepsinogen; RR, risk ratio Declarations Data availability All data analysed during this study are included in this published article and its supplementary information files. Acknowledgements: The authors gratefully thank for the assistance and comments of analysis to Professors Hyeon Woo Yim and Hyunsuk Jeong, Department of Preventive Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea, for providing advice on meta-analysis. Author contributions Study concept and design: YC and JMP Data analysis and interpretation: YC and JMP Drafting of the manuscript: YC Critical revision of the manuscript for important intellectual content: all authors. Statistical analysis: YC Administrative, technical, or material support: JSK, YKC, BWK and MGC Study supervision: JMP Competing interests : The authors declare no competing interests. Funding : none Writing Assistance: none ORCID Younghee Choe https://orcid.org/0000-0002-9443-2108 Jae Myung Park https://orcid.org/ 0000-0002-1534-7467 Joon Sung Kim https://orcid.org/0000-0001-9158-1012 Yu Kyung Cho https://orcid.org/0000-0002-7297-6577 Byung-Wook Kim https://orcid.org/0000-0002-2290-4954 Myung-Gyu Choi https://orcid.org/0000-0003-4083-5187 References Ryu, S. J. et al. Endoscopic submucosal dissection versus surgical resection for early gastric cancer: a retrospective multicenter study on immediate and long-term outcome over 5 years. Surgical endoscopy 30 , 5283-5289. https://doi.org/10.1007/s00464-016-4877-y (2016). Najmeh, S., Cools-Lartigue, J., Mueller, C. & Ferri, L. E. Comparing laparoscopic to endoscopic resections for early gastric cancer in a high volume North American Center. J Gastrointest Surg 20 , 1547-1553. https://doi.org/10.1007/s11605-016-3176-1 (2016). Liu, Q., Ding, L., Qiu, X. & Meng, F. 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Severity of gastric intestinal metaplasia predicts the risk of gastric cancer: a prospective multicentre cohort study (GCEP). Gut . https://doi.org/10.1136/gutjnl-2021-324057 (2021). Shichijo, S. et al. Histologic intestinal metaplasia and endoscopic atrophy are predictors of gastric cancer development after Helicobacter pylori eradication. Gastrointestinal endoscopy 84 , 618-624. https://doi.org/10.1016/j.gie.2016.03.791 (2016). Uno, Y. Prevention of gastric cancer by Helicobacter pylori eradication: A review from Japan. Cancer Med 8 , 3992-4000. https://doi.org/10.1002/cam4.2277 (2019). Correa, P. & Piazuelo, M. B. The gastric precancerous cascade. Journal of digestive diseases 13 , 2-9. https://doi.org/10.1111/j.1751-2980.2011.00550.x (2012). Tables Table 1 Study characteristics Study, † year Country No. of center Year of ER No. of Pts. Male sex, N (%) H. pylori status (Persistent vs. Negative or eradicated) Mean age (years, SD) Median follow-up (months, range) Incidence of MGC, N (%) Parameter of IM Parameter of severe AG ‡ Hanaoka 2010 Japan 1 2003‒2006 82 68 (82.9) 10:72 65.2 (8.5) 55 (14‒72) 12 (14.6) ‒ i) Open type on EGD ¶ ii) PG I/II ratio≤1.8 Han 2011 Korea 1 2004‒2007 176 112 (63.6) 22:154 unknown 30 (18‒42) 9 (5.1) Histologic Endoscopic Maehata 2012 Japan 7 1998‒2009 268 194 (72.4) 91:177 69 § (40‒90) 36 (13‒133) 28 (10.4) ‒ Open 2,3 on EGD Iguchi 2016- Moribata 2016 Japan 1 2002‒2013 330 240 (74.6) 82:248 70.7 (9.1) 50 (12‒142) 47 (14.2) Endoscopic i) Open 3 on EGD ii) PG I/II ratio≤3.0 Kim 2016 Korea 1 2005‒2015 433 325 (75.1) 42:215 67 30 15 (3.5) Histologic Endoscopic Han 2018 Korea 1 2005‒2011 565 440 (77.9) 196:369 unknown 60 (12‒122) 50 (8.8) Histologic Histologic Oura 2020 Japan 1 2005‒2018 418 295 (70.6) 28:383 71.6 (8.7) 53 (12‒166) 40 (9.6) ‒ Open 2,3 on EGD Kato 2021 Japan 12 2003‒2010 483 373 (77.2) 189:294 69 § (45‒86) 62.4 (13‒178) 87 (18.0) ‒ Open 2,3 on EGD † All included studies were retrospective studies. ‡ Closed type and open type were classified into Kimura-Takemoto classification endoscopically. § Expressed in median age (range). ¶ It was classified by the Kimura-Takemoto classification. AG, atrophic gastritis; EGD, esophagogastroduodenoscopy; ER, endoscopic resection; H. pylori (Hp) , Helicobacter pylori ; IM, intestinal metaplasia; MGC, metachronous gastric cancer; No., number; PG, pepsinogen; Pts., patients; SD, standard deviation Table 2 The absolute risk and incidence rate per person-years of occurrence of metachronous gastric cancer according to the severity of atrophic gastritis Median follow-up (years) The absolute risk of MGC occurrence according to the degree of atrophy, n/N (%) The absolute risk difference Incidence rate per 1000 person-years (95% confidence intervals) † Non-severe AG Severe AG Non-severe AG 4.7 3/51 (5.9) 9/31 (29.0) 23.1% 12.5 (2.5–36.6) 2.5 3/121 (2.5) 6/55 (10.9) 8.4% 9.9 (2.0–29.0) 3.0 5/103 (4.9) 23/165 (13.9) 9.1% 16.2 (5.2–37.8) 4.2 23/214 (10.7) 24/116 (20.7) 9.9% 25.6 (16.2–38.4) 2.5 7/338 (2.1) 8/95 (8.4) 6.4% 8.3 (3.3–17.1) 4.2 4/115 (3.5) 30/240 (12.5) 9.0% 8.3 (2.3–21.2) 3.3 10/126 (7.9) 30/292 (10.3) 2.3% 24.1 (11.5–44.2) 5.2 31/182 (17.0) 56/301 (18.6) 1.6% 32.8 (22.3–46.5) – 86/1250 (6.9) 186/1295 (14.4) 7.5% 19.4 (15.5–23.9) † Taylor series was used . ‡ Byar method was used. § In 210 patients, the degree of atrophy was unknown. AG, atrophic gastritis; MGC, metachronous gastric cancer Table 3 The absolute risk and incidence rate per person-years of occurrence of metachronous gastric cancer according to the presence or absence of intestinal metaplasia Study, year No. of total subjects Median follow-up (years) Parameter of IM The absolute risk of MGC occurrence according to the presence or absence of IM, n/N (%) The absolute risk difference Incidence rate per 1000 person-years (95% confidence intervals) † Incidence rate difference per 1000 person-years ‡ Absence of IM Presence of IM Absence of IM Presence of IM Han 2011 176 2.5 i) Histologic - antrum ii) Histologic - corpus 1/63 (1.6%) 2/113 (1.8%) 8/108 (7.4%) 5/51 (9.8%) 5.8% 8.0% 6.3 (0.1‒35.3) 7.1 (0.8‒25.6) 29.6 (12.8‒58.4) 39.2 (12.6‒91.5) 23.3 32.1 Iguchi 2016-Moribata 2016 330 4.2 Endoscopic 0/21 (0%) 22/101 (21.8%) 21.8% 0 52.3 (32.8‒79.2) 52.3 Kim 2016 433 2.5 Histologic 5/306 (1.6%) 10/127 (7.9%) 6.2% 6.5 (2.1‒15.3) 31.5 (15.1‒57.9) 25.0 Han 2018 565 4.2 i) Histologic - antrum ii) Histologic - corpus 4/465 (0.9%) 11/430 (2.6%) 44/477 (9.2%) 36/359 (10.0%) 8.4% 7.5% 2.1 (0.6‒5.3) 6.1 (3.1‒11.0) 22.1 (16.1‒29.7) 24.1 (16.9‒33.3) 17.9 Total 1504 ‒ 10/855 (1.2) 84/813 (10.3) 9.2% 4.6 (2.9‒6.9) 27.1 (22.5‒32.2) 22.5 † Taylor series was used. ‡ Byar method was used. IM, intestinal metaplasia; MGC, metachronous gastric cancer Additional Declarations No competing interests reported. Supplementary Files SupplementaryMGCSciRep220706.pdf Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1840349","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":122516698,"identity":"fff2fff6-04b4-44d7-bbe9-70a682517275","order_by":0,"name":"Younghee Choe","email":"","orcid":"","institution":"Catholic University of Korea","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Younghee","middleName":"","lastName":"Choe","suffix":""},{"id":122516699,"identity":"1901405e-06eb-4950-9334-685ff2df60ea","order_by":1,"name":"Jae Myung Park","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABD0lEQVRIie2SsWrDMBBAzwjsRSSrTErTTzgINBHkYxQK6mLI0MWBDpqUxR+Qz+jYUcbQLg5ZHQKFYsic0sVQKJXj0E1txkL1QDo43eN0SAAez9+EAGtDpAACBRdhlxVnKNQA5AroecoRJjoFflPG0brGSfoyx239+v72OKW9yASHBuTcpfDsdiRYeccfdnLE8lLSkAoSZ5Bw5VDQSGJiLRB3CbBcFzS0kw0AUnR1wc3eKp9W2ZakOSnk40elkkTEyiqVLT4poe2SOBW+2hNkTwLjUl5P1rqdZaZ5htKpjPuSDNi9wN5zUVcLPb0cLouiatIb98XsIu1TXpnvnP0D4BS6o+Bgt6FyF3k8Hs8/5wte0lALe2kplgAAAABJRU5ErkJggg==","orcid":"","institution":"Catholic University of Korea","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Jae","middleName":"Myung","lastName":"Park","suffix":""},{"id":122516700,"identity":"34d6d54f-3292-4f38-b206-f0096f7d8c9f","order_by":2,"name":"Joon Sung Kim","email":"","orcid":"","institution":"Catholic University of Korea","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Joon","middleName":"Sung","lastName":"Kim","suffix":""},{"id":122516701,"identity":"51a84161-716b-47d4-87a1-ec0082dd6dbd","order_by":3,"name":"Yu Kyung Cho","email":"","orcid":"","institution":"Catholic University of Korea","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yu","middleName":"Kyung","lastName":"Cho","suffix":""},{"id":122516702,"identity":"d3917f79-1d8a-4a6d-ab0e-a9551b5a1a34","order_by":4,"name":"Byung-Wook Kim","email":"","orcid":"","institution":"Catholic University of Korea","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Byung-Wook","middleName":"","lastName":"Kim","suffix":""},{"id":122516703,"identity":"ecef00d7-7c93-4006-acaf-1a1cbd123195","order_by":5,"name":"Myung-Gyu Choi","email":"","orcid":"","institution":"Catholic University of Korea","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Myung-Gyu","middleName":"","lastName":"Choi","suffix":""}],"badges":[],"createdAt":"2022-07-08 23:14:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1840349/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1840349/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":24357129,"identity":"2a429d31-fe67-4979-8d17-9058dc848f64","added_by":"auto","created_at":"2022-07-26 17:40:57","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":39341,"visible":true,"origin":"","legend":"\u003cp\u003eFlow diagram.\u003c/p\u003e","description":"","filename":"Slide1.png","url":"https://assets-eu.researchsquare.com/files/rs-1840349/v1/1c606cca9beb55393574cf40.png"},{"id":24357128,"identity":"4ac1afbe-47d7-4ccc-bca8-83038230a5f9","added_by":"auto","created_at":"2022-07-26 17:40:57","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":16115,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of the occurrence of metachronous gastric cancer according to the degree of gastric mucosal atrophy. AG, atrophic gastritis\u003c/p\u003e","description":"","filename":"Slide2.png","url":"https://assets-eu.researchsquare.com/files/rs-1840349/v1/5c7f3d335c3b36ea6403c684.png"},{"id":24357393,"identity":"e30d229e-e694-4982-95b3-b68f593f771d","added_by":"auto","created_at":"2022-07-26 17:45:57","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":82307,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of the occurrence of metachronous gastric cancer according to the degree of gastric mucosal atrophy: subgroup analysis. (a) on parameter evaluating atrophy. (b) by country. AG, atrophic gastritis\u003c/p\u003e","description":"","filename":"slide33.png","url":"https://assets-eu.researchsquare.com/files/rs-1840349/v1/35b6c12c760a218746312816.png"},{"id":24357006,"identity":"5d1e33c6-b99b-4167-95b1-b38f05127b92","added_by":"auto","created_at":"2022-07-26 17:35:57","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":13660,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of the occurrence of metachronous gastric cancer according to the presence or absence of intestinal metaplasia. IM, intestinal metaplasia\u003c/p\u003e","description":"","filename":"Slide5.png","url":"https://assets-eu.researchsquare.com/files/rs-1840349/v1/dfc7d20cd5c65bc9f34ea5d3.png"},{"id":24357008,"identity":"399810f0-97ed-44e7-b33f-6295fe40adb3","added_by":"auto","created_at":"2022-07-26 17:35:57","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":16219,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of the occurrence of metachronous gastric cancer according to \u003cem\u003eHelicobacter pylori\u003c/em\u003e infection status.\u003c/p\u003e","description":"","filename":"Slide6.png","url":"https://assets-eu.researchsquare.com/files/rs-1840349/v1/5eba45042a5a6d8e5f6bb768.png"},{"id":27301124,"identity":"e9976d62-e487-4de9-b5ee-44c5f930298c","added_by":"auto","created_at":"2022-10-04 04:59:22","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":863905,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1840349/v1/2c481196-96d7-462c-8776-ac39880fe682.pdf"},{"id":24357011,"identity":"175cd766-8663-4b34-bff3-71bd069a2a73","added_by":"auto","created_at":"2022-07-26 17:35:57","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":295337,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryMGCSciRep220706.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1840349/v1/2362474368a1dfbc9df8d6ed.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The Impact of Atrophic Gastritis and Intestinal Metaplasia on the Occurrence of Metachronous Gastric Cancer After Endoscopic Resection: A Systematic Review and Meta-analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eEndoscopic resection (ER) for gastric cancer (GC), when small and limited to the mucosa, is now a standard treatment modality. This treatment has no significant difference in short-term outcomes and overall and disease-free survival compared with laparoscopic gastrectomy in early GC. Also, ER has fewer late complications and requires a shorter hospital stay than laparoscopic gastrectomy.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e However, local treatments like ER have a high risk for development of metachronous gastric cancer (MGC) in the residual stomach.\u003csup\u003e\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThere are several risk factors for the occurrence of MGC after ER. \u003cem\u003eHelicobacter pylori\u003c/em\u003e (\u003cem\u003eH. pylori\u003c/em\u003e) infection is the most important factor, but this can be managed.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e Atrophic gastritis (AG) and intestinal metaplasia (IM) are precancerous GC lesions in the general population.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e Since advanced AG and IM have a high risk of gastric adenocarcinoma, endoscopic surveillance is recommended.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eEven though the influence of AG or IM is considerable in the development of GC, there is no quantifiable evidence to help predict the risk of MGC occurrence in patients who underwent ER for GC. This study conducted a systematic review and meta-analysis on the risk of MGC occurrence when AG or IM developed after ER for GC.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eStudy inclusion and characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThrough the planned search strategy, 86 documents were identified; after a review of titles and abstracts, 40 studies that appeared to be potentially inclusive were searched and evaluated (Fig. 1). In these, 2,755 patients were included from 9 articles reporting relevant data from 8 individual studies.\u003csup\u003e18-26\u003c/sup\u003e After being diagnosed with GC and undergoing ER, these patients were followed for more than two years at the attending hospital. The patients were evaluated for the presence of IM or degree of AG at the time of ER.\u003c/p\u003e\n\u003cp\u003eThe characteristics of studies included by appropriate criteria are presented in Table 1. The proportions of men in the studies ranged from 63% to 82%. At the time of ER, about 67% were negative for \u003cem\u003eH. pylori\u003c/em\u003e or had successful eradication treatment of the infection within one year. The shortest and longest median follow-up period was 30 and 62 months, respectively.\u003c/p\u003e\n\u003cp\u003eIn this study, the diagnosis of severe atrophy was basically based on the contents defined by the authors of each paper. This study analyzed severe atrophy based on the definition of each paper\u0026apos;s authors. Among the studies that defined atrophy endoscopically, five studies were classified based on the Kimura-Takemoto classification. In three studies, open type II and III were defined as severe, one was open type III, and the other was all open type severe. One study did not specifically describe the Kimura classification and only mentioned severe AG. Two studies classified severe atrophy with a low serum pepsinogen I/II ratio, and three studies defined pathologic severe atrophy by updated Sydney classification. In the study where only open type III was evaluated as more extensive atrophy, the serum PG I/II ratio and histology were also investigated.\u003csup\u003e21\u003c/sup\u003e It was evaluated that open type III reflects the most severity.\u003c/p\u003e\n\u003cp\u003eThe risk of bias assessments for all included studies was evaluated by the\u0026nbsp;Newcastle-Ottawa Scale for Cohort Study Quality\u0026nbsp;(Supplementary Table S1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEffects of\u0026nbsp;\u003c/strong\u003ethe degree of mucosal atrophy\u003cstrong\u003e\u0026nbsp;on the occurrence of MGC after ER for GC\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData obtained from 8 studies were pooled.\u0026nbsp;\u003csup\u003e18-26\u003c/sup\u003e Of the 2,755 cases, 1,295 cases were classified as severe AG, and 1,250 cases were classified as non-severe AG. The incidence of MGC in GC patients with severe AG and non-severe AG was 186 (14.4%) and 86 (6.9%), respectively (absolute risk difference 7.5%; Table 2). The incidence rate of MGC was 36.9 (95% CI 31.8\u0026ndash;42.6) per 1,000 person-years in severe AG and 19.4 (95% CI 15.5\u0026ndash;23.9) per 1,000 person-years in non-severe AG, and the difference in incidence rate was 17.5 per 1,000 person-years. Patients with severe atrophy of the background mucosa at the ER had a higher risk of MGC occurrence than patients without severe AG (RR 1.64, 95% CI 1.29\u0026ndash;2.07, I\u003csup\u003e2\u003c/sup\u003e=45%; Figure 2).\u003c/p\u003e\n\u003cp\u003eSubgroup analysis was performed to estimate the MGC occurrence according to the parameter for judging the degree of mucosal atrophy. Endoscopically evaluated severe AG had significantly higher MGC occurrence than non-severe AG (RR 1.90, 95% CI 1.25\u0026ndash;2.90, I\u003csup\u003e2\u003c/sup\u003e=52%; Figure 3a). In addition, serological (PG I, II) and histological (corpus and antrum) diagnostic methods were also analyzed. Testing for subgroup differences revealed no statistically significant subgroup effect (\u003cem\u003eP\u003c/em\u003e=0.58). However, it was shown that severe AG favored MGC occurrence more than non-severe AG in all subgroups (\u003cem\u003eP\u003c/em\u003e=0.58).\u003c/p\u003e\n\u003cp\u003eCountries were also sub-analyzed to examine the possibility of geographically different outcomes (Figure 3b). Five Japanese studies\u003csup\u003e18,20-22,25,26\u003c/sup\u003e and three Korean studies\u003csup\u003e19,23,24\u003c/sup\u003e were included in this study. In the Japanese study, the number of severe AG patients (n=905, 57.2%) was higher than the number of non-severe AGs, and in the Korean study, the number of severe AGs (n=352, 35.2%) was less classified. The RR for MGC in severe AG was 1.75 (95% CI 1.11\u0026ndash;2.73, I\u003csup\u003e2\u003c/sup\u003e=55%) in the Japanese study and 2.09 (95% CI 1.09\u0026ndash;4.02, I\u003csup\u003e2\u003c/sup\u003e=26%) in the Korean study. Test for subgroup difference showed no subgroup effect (\u003cem\u003eP\u003c/em\u003e=0.65).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEffects of\u0026nbsp;\u003c/strong\u003ethe presence or absence of\u0026nbsp;\u003cstrong\u003eIM on the occurrence of MGC after ER for GC\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe investigated whether the presence of IM affects the occurrence of MGC in patients who underwent ER for GC. In four studies, 2,755 patients were included. The median follow-up period after ER was 2.5\u0026nbsp;to\u0026nbsp;4.2 years. IM was diagnosed histologically in 3 studies,\u003csup\u003e19,23,24\u003c/sup\u003e, and 1 study was diagnosed grossly during endoscopy.\u003csup\u003e21,22\u003c/sup\u003e In the presence of IM, the absolute risk difference of MGC was higher at 9.2%, and the incidence rate difference per 1,000 person-years was 22.5 (Table 3).\u003c/p\u003e\n\u003cp\u003eIn GC patients with IM, the RR of MGC occurrence was significantly higher than in patients without IM (RR 7.08, 95% CI 3.63\u0026ndash;13.80, I\u003csup\u003e2\u003c/sup\u003e=0%; Figure 4). Only three studies with histological evaluation of IM out of 4 were performed for subgroup analysis. In patients with IM, the incidence of MGC was significantly increased by 6.94 (95% CI 3.48\u0026ndash;13.82, I\u003csup\u003e2\u003c/sup\u003e=0%) compared with those without IM (Supplementary Figure S1). There were two studies in which the biopsy site was divided into antrum and corpus, but the meta-analysis results were the same.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRelationship between \u003cem\u003eHelicobacter pylori\u003c/em\u003e infection status and MGC\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA meta-analysis was performed to evaluate the relationship between \u003cem\u003eH. pylori\u003c/em\u003e infection status and MGC occurrence (Figure 5). Since many people have not been clearly evaluated for \u003cem\u003eH. pylori\u003c/em\u003e eradication in the past, we compared 660 patients with persistent infection and 1,912 patients with negative or eradicated infections. However, there was no significant difference between the risk of MGC occurrence in those with \u003cem\u003eH. pylori\u003c/em\u003e-negative or eradicated, and those with persistent infection (RR 1.08, 95% CI 0.85\u0026ndash;1.39, I\u003csup\u003e2\u003c/sup\u003e=0%).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAnalyzes of risk factors affecting the occurrence of MGC\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe performed an analysis to determine whether the risk of MGC occurrence increases according to demographic factors and characteristics of primary cancer. The risk of MGC occurrence according to demographic factors such as gender, age, drinking history, and smoking history were presented (Supplementary Table S2, Supplementary Figure S2). The risk of developing MGC was significantly higher in men than in women (total number of patients = 2579, RR 1.54, 95% CI 1.07\u0026ndash;2.22, I\u003csup\u003e2\u003c/sup\u003e=22%), and there was also a greater incidence of MGC in patients with a history of smoking (total number of patients = 412, RR=2.10, 95% CI 1.25\u0026ndash;3.53, I\u003csup\u003e2\u003c/sup\u003e=0%). The risk of developing MGC was higher in alcoholics, but no significant findings were found. There was only one study on the elderly.\u003c/p\u003e\n\u003cp\u003eA forest plot for the occurrence of MGC according to the characteristics of primary cancer was presented (Supplementary Table S3). The primary cancer location, gross type, Lauren\u0026apos;s classification, the degree of differentiation, and the depth of invasion were investigated. Supplementary S3 is a meta-analysis for each variable, and no risk factors showed a statistically significant effect on the occurrence of MGC.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis systematic review and meta-analysis showed that the severity of AG and the presence or absence of IM are significant risk factors for the MGC occurrence after ER for GC. The incidence of MGC was significantly increased with severe AG or with IM. This was consistently observed in sub-analyzes according to different methods of evaluating mucosal atrophy and geographical area. There was no significant relationship between \u003cem\u003eH. pylori\u003c/em\u003e eradication status and the risk of MGC occurrence in the present study.\u003c/p\u003e \u003cp\u003eAG is usually evaluated endoscopically, serologically, and histologically. Endoscopic biopsy is the gold standard method in diagnosing AG.\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e The Kimura-Takemoto classification, the most commonly used method in clinical practice, is reliable and agrees with the Operative Link for Gastritis Assessment (OLGA) staging system.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e,\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e Several studies have assessed gastric mucosal atrophy by measuring PG I and II, and PG is a reliable marker for diagnosing gastric mucosal atrophy.\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e,\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e The serum PG I and I/II ratio test for OLGA gastritis also showed a strong correlation with the stage.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e A study comparing endoscopic, histologic, and serologic methods together to evaluate AG also showed a statistically significant association between the three.\u003csup\u003e\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIn the present study, analysis was performed to confirm subgroup effects for various methods of evaluating AG. However, most were evaluated endoscopically, and other subgroups included a small number of trials and participants. Due to the uneven covariate distribution, it would have been difficult for the analysis to detect differences in subgroups. However, it was identified that severe AG favored MGC generation rather than non-severe AG in all subgroups. This was consistent with changes according to geographic location. We further evaluated the results of Japan and Korea separately, considering the possibility of inter-observer variation and educational differences between countries in the endoscopic evaluation of mucosal atrophy. There was no statistically significant subgroup effect in this analysis, showing consistent results between AG and MGC.\u003c/p\u003e \u003cp\u003eMGC occurs after ER for GC, even in patients who have experienced eradication of \u003cem\u003eH. pylori\u003c/em\u003e infection. Therefore, identification of potential risk factors for MGC is essential. IM is a precancerous lesion of GC.\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e,\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e However, to our knowledge, there are no studies that quantify the effect of IM on the occurrence of MGC after ER for GC. The presence of IM can be more meaningful in the group after ER than in the general population. Our present study showed this through meta-analysis of the previous reports. In this study, the small effect of \u003cem\u003eH. pylori\u003c/em\u003e on the MGC occurrence after ER for GC is thought to be due to severe AG and IM. IM levels can be a 'point of no return in the Correa cascade.' The effect of \u003cem\u003eH. pylori\u003c/em\u003e eradication on GC prevention in the presence of severe AG and IM is limited, and this effect is consistent with the MGC occurrence.\u003csup\u003e\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e,\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThis study has some limitations. First, the included studies might have selection bias as retrospective cohort studies. Second, these studies were conducted only in Japan and Korea. The reason for this is that both counties have a high incidence of GC and perform screening evaluation for GC through a nationwide strategy. Third, the number of patients in whom the presence or absence of IM was confirmed was small. However, since most tissues were evaluated histologically, the results are unlikely to be exaggerated or understated. Fourth, the past infection or eradication history of \u003cem\u003eH. pylori\u003c/em\u003e was unknown, so this analysis was limited. In addition, there were limitations in explaining the impact of AG and IM on MGC and the relationship between H. pylori eradication. Fifth, the definition of severe atrophy was not the same between studies, so there was a limitation in subgroup analysis. However, in all analysis results, the occurrence of less MGC was the same in the cases of non-severe AG.\u003c/p\u003e \u003cp\u003eNevertheless, the strength of this study was its focus on factors other than \u003cem\u003eH. pylori\u003c/em\u003e infection as risk factors for MGC. As mentioned earlier, compared with \u003cem\u003eH. pylori\u003c/em\u003e, AG and IM are more challenging to study and less attractive. However, since there are many \u003cem\u003eH. pylori\u003c/em\u003e-negative gastric cancer patients, consideration of other causes is necessary.\u003c/p\u003e \u003cp\u003eIn conclusion, we found that severe AG and the presence of IM significantly increased the risk of metachronous recurrence in GC patients who underwent ER. In particular, patients with GC with IM occurred about seven times more MGC. These results suggest that patients with severe AG or IM undergo stricter follow-up endoscopy. Future studies in prospective cohorts with adjustment for baseline characteristics such as age and presence of \u003cem\u003eH. pylori\u003c/em\u003e infection are needed.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eSearch strategy and Study selection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe searched the MEDLINE, Embase, and Cochrane centrally controlled trial registries without language restrictions for studies published from inception through 31 May 2022 to identify potential studies. Suitable studies\u0026nbsp;were investigated for the effects of the degree of mucosal atrophy and the presence or absence of IM on MGC occurrence\u0026nbsp;after ER for GC (Supplementary Table S4).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe inclusion criteria for this study were: (i) adults 19 years of age or older with GC who underwent ER, (ii) evaluation of severe AG or IM presence, and (iii) clearly cited evaluation method (endoscopy, histology, or serology). After ER, a follow-up period of at least two years was required for the present study. We extracted all endpoints from the last follow-up using the most recent publication from each trial.\u0026nbsp;Studies in which gastric \u0026apos;adenoma\u0026apos; were resected or metachronous gastric \u0026apos;adenoma\u0026apos; occurred were excluded. Studies with ambiguous methods for assessing severe AG or IM were also excluded.\u003c/p\u003e\n\u003cp\u003eTwo investigators (YC and JMP) performed literature searches independently of each other. The search terms used are detailed in Supplementary Materials. All potentially relevant references were obtained and evaluated to assess independently the qualifications against the predefined criteria by the investigators.\u0026nbsp;Titles and abstracts were reviewed to extract relevant studies.\u0026nbsp;Full texts were screened to identify eligible studies that met inclusion criteria. We resolved disagreements among investigators through discussion and, if necessary, consultation with a third reviewer who was one of our authors. There were no language restrictions, and foreign language papers were translated when necessary.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOutcome assessment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe primary outcome was the effect of the presence of IM or severe AG on the occurrence of MGC, which was compared between patients without IM or with mild to moderate AG. IM is histologically defined by the Sydney classification. Mucosal atrophy can be defined variously by three parameters: endoscopy, serology, and histology. Endoscopic evaluation was examined by Kimura-Takemoto classification (closed type I/II/III and open type I/II/III).\u003csup\u003e11\u003c/sup\u003e The included studies evaluated open type II and III as severe AG. Serologically, mucosal atrophy also was evaluated by pepsinogen (PG) I and II. PG is a proenzyme produced in gastric mucosa. When atrophic change occurs, the PG I level produced in chief cells decreases, as does the PG I/II ratio. In general, severe AG is determined when the PG I/II ratio is less than 3.0.\u003csup\u003e12-14\u003c/sup\u003e Histologically, mucosal atrophy was classified into none, mild, moderate, or severe according to the updated Sydney System.\u003csup\u003e15\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData extraction\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe extracted all data independently. Two investigators (YC and JMP) did this with dichotomous results (with or without MGC). We also extracted the following data for each trial: geographical location, country of origin, number of centers, number of patients, gender, age,\u0026nbsp;alcohol intake, smoking history, history of H. pylori infection\u0026nbsp;and eradication, follow-up period, number of patients with MGC, presence of IM, the severity of AG at the time of ER, and anatomical, gross and pathological features of primary cancer. Data were extracted using the evaluation parameters of AG and IM.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eQuality assessment and data synthesis\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eQuality and risk of bias were independently assessed by two investigators (YC and JMP). Because the included studies were non-randomized studies, the \u0026lsquo;Newcastle-Ottawa Scale for Cohort Study Quality\u0026rsquo; was used.\u0026nbsp;If there were differences of opinion between the two investigators, the discrepancy was resolved\u0026nbsp;through discussion. We performed a systematic review and meta-analysis following the Preferred Reporting Items for a Systematic Review and Meta-analysis guideline.\u003csup\u003e16,17\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eData for the subsequent development of GC according to the degree of AG and \u003cem\u003eH. pylori\u003c/em\u003e infection status were combined using a fixed-effect model and Mantel-Haenszel estimation method. A random-effect model was used for MGC occurrence according to subgroup analyzes of AG and the presence or absence of IM. The Taylor series and Byar method were used for the incidence rate per 1000 person-years of MGC by severe AG and presence of IM.\u0026nbsp;We expressed the effect as a GC risk ratio (RR) of 95% confidence interval (CI) and used I\u003csup\u003e2\u003c/sup\u003e to assess heterogeneity between studies. To define a significant degree of heterogeneity, we evaluated heterogeneity between studies using both the I\u003csup\u003e2\u003c/sup\u003e statistic with a cutoff of\u0026nbsp;\u0026ge;\u0026nbsp;50% and the\u0026nbsp;\u0026chi;2 test with a \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.10. We used Review Manager V.5.4.1 (RevMan for Windows 2020, Nordic Cochrane Center, Copenhagen, Denmark) and Excel for the analysis.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAG, atrophic gastritis; CI, confidence interval; GC, gastric cancer; IM, intestinal metaplasia; MGC, metachronous gastric cancer; OLGA, Operative Link for Gastritis Assessment; PG, pepsinogen; RR, risk ratio\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data analysed during this study are included in this published article and its supplementary information files.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e The authors gratefully thank for the assistance and comments of analysis to Professors Hyeon Woo Yim and Hyunsuk Jeong, Department of Preventive Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea, for providing advice on meta-analysis.\u003cstrong\u003e \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e \u003c/p\u003e\n\u003cp\u003eStudy concept and design: YC and JMP\u003c/p\u003e\n\u003cp\u003eData analysis and interpretation: YC and JMP\u003c/p\u003e\n\u003cp\u003eDrafting of the manuscript: YC\u003c/p\u003e\n\u003cp\u003eCritical revision of the manuscript for important intellectual content: all authors.\u003c/p\u003e\n\u003cp\u003eStatistical analysis: YC\u003c/p\u003e\n\u003cp\u003eAdministrative, technical, or material support: JSK, YKC, BWK and MGC\u003c/p\u003e\n\u003cp\u003eStudy supervision: JMP\u003cstrong\u003e \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e: The authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e: none\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWriting Assistance:\u003c/strong\u003e none\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eORCID\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYounghee Choe https://orcid.org/0000-0002-9443-2108\u003c/p\u003e\n\u003cp\u003eJae Myung Park https://orcid.org/ 0000-0002-1534-7467\u003c/p\u003e\n\u003cp\u003eJoon Sung Kim https://orcid.org/0000-0001-9158-1012\u003c/p\u003e\n\u003cp\u003eYu Kyung Cho https://orcid.org/0000-0002-7297-6577\u003c/p\u003e\n\u003cp\u003eByung-Wook Kim https://orcid.org/0000-0002-2290-4954\u003c/p\u003e\n\u003cp\u003eMyung-Gyu Choi https://orcid.org/0000-0003-4083-5187\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eRyu, S. 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B.\u003cem\u003e et al.\u003c/em\u003e Association between \u003cem\u003eHelicobacter pylori\u003c/em\u003e status and metachronous gastric cancer after endoscopic resection. \u003cem\u003eWorld journal of gastroenterology\u003c/em\u003e \u003cstrong\u003e22\u003c/strong\u003e, 9794-9802. https://doi.org/10.3748/wjg.v22.i44.9794 (2016).\u003c/li\u003e\n\u003cli\u003eHan, S. J.\u003cem\u003e et al.\u003c/em\u003e Long-term effects of \u003cem\u003eHelicobacter pylori\u003c/em\u003e eradication on metachronous gastric cancer development. \u003cem\u003eGut and liver\u003c/em\u003e \u003cstrong\u003e12\u003c/strong\u003e, 133-141. https://doi.org/10.5009/gnl17073 (2018).\u003c/li\u003e\n\u003cli\u003eOura, H.\u003cem\u003e et al.\u003c/em\u003e Long-term use of proton pump inhibitors does not affect ectopic and metachronous recurrence of gastric cancer after endoscopic treatment. \u003cem\u003eScandinavian journal of gastroenterology\u003c/em\u003e \u003cstrong\u003e55\u003c/strong\u003e, 209-215. https://doi.org/10.1080/00365521.2020.1720796 (2020).\u003c/li\u003e\n\u003cli\u003eKato, M.\u003cem\u003e et al.\u003c/em\u003e \u003cem\u003eHelicobacter pylori\u003c/em\u003e eradication prevents secondary gastric cancer in patients with mild-to-moderate atrophic gastritis. \u003cem\u003eJournal of gastroenterology and hepatology\u003c/em\u003e \u003cstrong\u003e36\u003c/strong\u003e, 2083-2090. https://doi.org/10.1111/jgh.15396 (2021).\u003c/li\u003e\n\u003cli\u003eRugge, M.\u003cem\u003e et al.\u003c/em\u003e Gastritis staging in clinical practice: the OLGA staging system. \u003cem\u003eGut\u003c/em\u003e \u003cstrong\u003e56\u003c/strong\u003e, 631-636. https://doi.org/10.1136/gut.2006.106666 (2007).\u003c/li\u003e\n\u003cli\u003eRugge, M.\u003cem\u003e et al.\u003c/em\u003e OLGA gastritis staging for the prediction of gastric cancer risk: a long-term follow-up study of 7436 patients. \u003cem\u003eThe American journal of gastroenterology\u003c/em\u003e \u003cstrong\u003e113\u003c/strong\u003e, 1621-1628. https://doi.org/10.1038/s41395-018-0353-8 (2018).\u003c/li\u003e\n\u003cli\u003eKotelevets, S. M., Chekh, S. A. \u0026amp; Chukov, S. Z. Updated Kimura-Takemoto classification of atrophic gastritis. \u003cem\u003eWorld J Clin Cases\u003c/em\u003e \u003cstrong\u003e9\u003c/strong\u003e, 3014-3023. https://doi.org/10.12998/wjcc.v9.i13.3014 (2021).\u003c/li\u003e\n\u003cli\u003eKim, E. H.\u003cem\u003e et al.\u003c/em\u003e The optimal serum pepsinogen cut-off value for predicting histologically confirmed atrophic gastritis. \u003cem\u003eDigestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver\u003c/em\u003e \u003cstrong\u003e47\u003c/strong\u003e, 663-668. https://doi.org/10.1016/j.dld.2015.05.014 (2015).\u003c/li\u003e\n\u003cli\u003eLee, S. Y. Endoscopic gastritis, serum pepsinogen assay, and \u003cem\u003eHelicobacter pylori\u003c/em\u003e infection. \u003cem\u003eKorean J Intern Med\u003c/em\u003e \u003cstrong\u003e31\u003c/strong\u003e, 835-844. https://doi.org/10.3904/kjim.2016.166 (2016).\u003c/li\u003e\n\u003cli\u003eWang, X.\u003cem\u003e et al.\u003c/em\u003e The correlation between histological gastritis staging- \u0026apos;OLGA/OLGIM\u0026apos; and serum pepsinogen test in assessment of gastric atrophy/intestinal metaplasia in China. \u003cem\u003eScandinavian journal of gastroenterology\u003c/em\u003e \u003cstrong\u003e52\u003c/strong\u003e, 822-827. https://doi.org/10.1080/00365521.2017.1315739 (2017).\u003c/li\u003e\n\u003cli\u003eLee, J. 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J.\u003cem\u003e et al.\u003c/em\u003e Severity of gastric intestinal metaplasia predicts the risk of gastric cancer: a prospective multicentre cohort study (GCEP). \u003cem\u003eGut\u003c/em\u003e. https://doi.org/10.1136/gutjnl-2021-324057 (2021).\u003c/li\u003e\n\u003cli\u003eShichijo, S.\u003cem\u003e et al.\u003c/em\u003e Histologic intestinal metaplasia and endoscopic atrophy are predictors of gastric cancer development after \u003cem\u003eHelicobacter pylori\u003c/em\u003e eradication. \u003cem\u003eGastrointestinal endoscopy\u003c/em\u003e \u003cstrong\u003e84\u003c/strong\u003e, 618-624. https://doi.org/10.1016/j.gie.2016.03.791 (2016).\u003c/li\u003e\n\u003cli\u003eUno, Y. Prevention of gastric cancer by \u003cem\u003eHelicobacter pylori\u003c/em\u003e eradication: A review from Japan. \u003cem\u003eCancer Med\u003c/em\u003e \u003cstrong\u003e8\u003c/strong\u003e, 3992-4000. https://doi.org/10.1002/cam4.2277 (2019).\u003c/li\u003e\n\u003cli\u003eCorrea, P. \u0026amp; Piazuelo, M. B. The gastric precancerous cascade. \u003cem\u003eJournal of digestive diseases\u003c/em\u003e \u003cstrong\u003e13\u003c/strong\u003e, 2-9. https://doi.org/10.1111/j.1751-2980.2011.00550.x (2012).\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003ctable border=\"0\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"12\" width=\"100%\"\u003e\n \u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e\u003c/p\u003e\n \u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eStudy characteristics\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.77720207253886%\"\u003e\n \u003cp\u003eStudy,\u003csup\u003e\u0026dagger;\u003c/sup\u003e year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.839378238341969%\"\u003e\n \u003cp\u003eCountry\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.9067357512953365%\"\u003e\n \u003cp\u003eNo. of center\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.808290155440414%\"\u003e\n \u003cp\u003eYear of ER\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.937823834196891%\"\u003e\n \u003cp\u003eNo. of Pts.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.9067357512953365%\"\u003e\n \u003cp\u003eMale sex, N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.740932642487047%\"\u003e\n \u003cp\u003e\u003cem\u003eH. pylori\u003c/em\u003e status\u0026nbsp;\u003cbr\u003e\u0026nbsp;(Persistent vs. Negative or eradicated)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.875647668393782%\"\u003e\n \u003cp\u003eMean age (years, SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.875647668393782%\"\u003e\n \u003cp\u003eMedian follow-up (months, range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.875647668393782%\"\u003e\n \u003cp\u003eIncidence of MGC,\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eN (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.808290155440414%\"\u003e\n \u003cp\u003eParameter of IM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.647668393782384%\"\u003e\n \u003cp\u003eParameter of severe AG\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.77720207253886%\"\u003e\n \u003cp\u003eHanaoka 2010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.839378238341969%\"\u003e\n \u003cp\u003eJapan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.9067357512953365%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.808290155440414%\"\u003e\n \u003cp\u003e2003‒2006\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.937823834196891%\"\u003e\n \u003cp\u003e82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.9067357512953365%\"\u003e\n \u003cp\u003e68 (82.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.740932642487047%\"\u003e\n \u003cp\u003e10:72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.875647668393782%\"\u003e\n \u003cp\u003e65.2 (8.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.875647668393782%\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003cp\u003e(14‒72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.875647668393782%\"\u003e\n \u003cp\u003e12 (14.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.808290155440414%\"\u003e\n \u003cp\u003e‒\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.647668393782384%\"\u003e\n \u003cp\u003ei) Open type on EGD\u003csup\u003e\u0026para;\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eii) PG I/II ratio\u0026le;1.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.77720207253886%\"\u003e\n \u003cp\u003eHan 2011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.839378238341969%\"\u003e\n \u003cp\u003eKorea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.9067357512953365%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.808290155440414%\"\u003e\n \u003cp\u003e2004‒2007\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.937823834196891%\"\u003e\n \u003cp\u003e176\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.9067357512953365%\"\u003e\n \u003cp\u003e112 (63.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.740932642487047%\"\u003e\n \u003cp\u003e22:154\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.875647668393782%\"\u003e\n \u003cp\u003eunknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.875647668393782%\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003cp\u003e(18‒42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.875647668393782%\"\u003e\n \u003cp\u003e9 (5.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.808290155440414%\"\u003e\n \u003cp\u003eHistologic\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.647668393782384%\"\u003e\n \u003cp\u003eEndoscopic\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.77720207253886%\"\u003e\n \u003cp\u003eMaehata 2012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.839378238341969%\"\u003e\n \u003cp\u003eJapan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.9067357512953365%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.808290155440414%\"\u003e\n \u003cp\u003e1998‒2009\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.937823834196891%\"\u003e\n \u003cp\u003e268\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.9067357512953365%\"\u003e\n \u003cp\u003e194 (72.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.740932642487047%\"\u003e\n \u003cp\u003e91:177\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.875647668393782%\"\u003e\n \u003cp\u003e69\u003csup\u003e\u0026sect; \u0026nbsp;\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e(40‒90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.875647668393782%\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003cp\u003e(13‒133)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.875647668393782%\"\u003e\n \u003cp\u003e28 (10.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.808290155440414%\"\u003e\n \u003cp\u003e‒\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.647668393782384%\"\u003e\n \u003cp\u003eOpen 2,3 on EGD\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.77720207253886%\"\u003e\n \u003cp\u003eIguchi 2016- Moribata 2016\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.839378238341969%\"\u003e\n \u003cp\u003eJapan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.9067357512953365%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.808290155440414%\"\u003e\n \u003cp\u003e2002‒2013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.937823834196891%\"\u003e\n \u003cp\u003e330\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.9067357512953365%\"\u003e\n \u003cp\u003e240 (74.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.740932642487047%\"\u003e\n \u003cp\u003e82:248\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.875647668393782%\"\u003e\n \u003cp\u003e70.7 (9.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.875647668393782%\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003cp\u003e(12‒142)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.875647668393782%\"\u003e\n \u003cp\u003e47 (14.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.808290155440414%\"\u003e\n \u003cp\u003eEndoscopic\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.647668393782384%\"\u003e\n \u003cp\u003ei) Open 3 on EGD \u0026nbsp; \u0026nbsp;ii) PG I/II ratio\u0026le;3.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.77720207253886%\"\u003e\n \u003cp\u003eKim 2016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.839378238341969%\"\u003e\n \u003cp\u003eKorea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.9067357512953365%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.808290155440414%\"\u003e\n \u003cp\u003e2005‒2015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.937823834196891%\"\u003e\n \u003cp\u003e433\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.9067357512953365%\"\u003e\n \u003cp\u003e325 (75.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.740932642487047%\"\u003e\n \u003cp\u003e42:215\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.875647668393782%\"\u003e\n \u003cp\u003e67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.875647668393782%\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.875647668393782%\"\u003e\n \u003cp\u003e15 (3.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.808290155440414%\"\u003e\n \u003cp\u003eHistologic\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.647668393782384%\"\u003e\n \u003cp\u003eEndoscopic\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.77720207253886%\"\u003e\n \u003cp\u003eHan 2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.839378238341969%\"\u003e\n \u003cp\u003eKorea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.9067357512953365%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.808290155440414%\"\u003e\n \u003cp\u003e2005‒2011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.937823834196891%\"\u003e\n \u003cp\u003e565\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.9067357512953365%\"\u003e\n \u003cp\u003e440 (77.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.740932642487047%\"\u003e\n \u003cp\u003e196:369\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.875647668393782%\"\u003e\n \u003cp\u003eunknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.875647668393782%\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003cp\u003e(12‒122)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.875647668393782%\"\u003e\n \u003cp\u003e50 (8.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.808290155440414%\"\u003e\n \u003cp\u003eHistologic\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.647668393782384%\"\u003e\n \u003cp\u003eHistologic\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.77720207253886%\"\u003e\n \u003cp\u003eOura 2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.839378238341969%\"\u003e\n \u003cp\u003eJapan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.9067357512953365%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.808290155440414%\"\u003e\n \u003cp\u003e2005‒2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.937823834196891%\"\u003e\n \u003cp\u003e418\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.9067357512953365%\"\u003e\n \u003cp\u003e295 (70.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.740932642487047%\"\u003e\n \u003cp\u003e28:383\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.875647668393782%\"\u003e\n \u003cp\u003e71.6 (8.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.875647668393782%\"\u003e\n \u003cp\u003e53\u003c/p\u003e\n \u003cp\u003e(12‒166)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.875647668393782%\"\u003e\n \u003cp\u003e40 (9.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.808290155440414%\"\u003e\n \u003cp\u003e‒\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.647668393782384%\"\u003e\n \u003cp\u003eOpen 2,3 on EGD\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.77720207253886%\"\u003e\n \u003cp\u003eKato 2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.839378238341969%\"\u003e\n \u003cp\u003eJapan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.9067357512953365%\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.808290155440414%\"\u003e\n \u003cp\u003e2003‒2010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.937823834196891%\"\u003e\n \u003cp\u003e483\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.9067357512953365%\"\u003e\n \u003cp\u003e373 (77.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.740932642487047%\"\u003e\n \u003cp\u003e189:294\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.875647668393782%\"\u003e\n \u003cp\u003e69\u003csup\u003e\u0026sect;\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(45‒86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.875647668393782%\"\u003e\n \u003cp\u003e62.4\u003c/p\u003e\n \u003cp\u003e(13‒178)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.875647668393782%\"\u003e\n \u003cp\u003e87 (18.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.808290155440414%\"\u003e\n \u003cp\u003e‒\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.647668393782384%\"\u003e\n \u003cp\u003eOpen 2,3 on EGD\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"12\" width=\"100%\"\u003e\n \u003cp\u003e\u003csup\u003e\u0026dagger;\u003c/sup\u003eAll included studies were retrospective studies.\u003c/p\u003e\n \u003cp\u003e\u003csup\u003e\u0026Dagger;\u003c/sup\u003eClosed type and open type were classified into Kimura-Takemoto classification endoscopically.\u003c/p\u003e\n \u003cp\u003e\u003csup\u003e\u0026sect;\u003c/sup\u003eExpressed in median age (range).\u003c/p\u003e\n \u003cp\u003e\u003csup\u003e\u0026para;\u003c/sup\u003eIt was classified by the Kimura-Takemoto classification.\u003cbr\u003eAG, atrophic gastritis; EGD, esophagogastroduodenoscopy; ER, endoscopic resection; \u003cem\u003eH. pylori (Hp)\u003c/em\u003e, \u003cem\u003eHelicobacter pylori\u003c/em\u003e; IM, intestinal metaplasia; MGC, metachronous gastric cancer; No., number; PG, pepsinogen; Pts., patients; SD, standard deviation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" style=\"width: 49.8145%;\" width=\"100%\"\u003e\n \u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003eTable 2\u003c/strong\u003e\u003c/p\u003e\n \u003cp style=\"text-align: center;\"\u003e\u0026nbsp;The absolute risk and incidence rate per person-years of occurrence of metachronous gastric cancer according to the severity of atrophic gastritis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 5.9775%;\" width=\"9.433962264150944%\"\u003e\n \u003cp\u003eMedian follow-up (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 28.5314%;\" width=\"32.94629898403483%\"\u003e\n \u003cp\u003eThe absolute risk of MGC occurrence according to the degree of atrophy, n/N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 7.8863%;\" width=\"12.336719883889696%\"\u003e\n \u003cp\u003eThe absolute risk difference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.0676%;\" width=\"34.25253991291727%\"\u003e\n \u003cp\u003eIncidence rate per 1000 person-years\u003cbr\u003e(95% confidence intervals)\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14.2657%;\" width=\"27.228915662650603%\"\u003e\n \u003cp\u003eNon-severe AG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.316%;\" width=\"27.228915662650603%\"\u003e\n \u003cp\u003eSevere AG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.9458%;\" width=\"27.228915662650603%\"\u003e\n \u003cp\u003eNon-severe AG\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 5.9775%;\" width=\"11.504424778761061%\"\u003e\n \u003cp\u003e4.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.2657%;\" width=\"20%\"\u003e\n \u003cp\u003e3/51 (5.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.316%;\" width=\"20%\"\u003e\n \u003cp\u003e9/31 (29.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.8863%;\" width=\"15.044247787610619%\"\u003e\n \u003cp\u003e23.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.9458%;\" width=\"20%\"\u003e\n \u003cp\u003e12.5 (2.5\u0026ndash;36.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 5.9775%;\" width=\"11.504424778761061%\"\u003e\n \u003cp\u003e2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.2657%;\" width=\"20%\"\u003e\n \u003cp\u003e3/121 (2.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.316%;\" width=\"20%\"\u003e\n \u003cp\u003e6/55 (10.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.8863%;\" width=\"15.044247787610619%\"\u003e\n \u003cp\u003e8.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.9458%;\" width=\"20%\"\u003e\n \u003cp\u003e9.9 (2.0\u0026ndash;29.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 5.9775%;\" width=\"11.504424778761061%\"\u003e\n \u003cp\u003e3.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.2657%;\" width=\"20%\"\u003e\n \u003cp\u003e5/103 (4.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.316%;\" width=\"20%\"\u003e\n \u003cp\u003e23/165 (13.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.8863%;\" width=\"15.044247787610619%\"\u003e\n \u003cp\u003e9.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.9458%;\" width=\"20%\"\u003e\n \u003cp\u003e16.2 (5.2\u0026ndash;37.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 5.9775%;\" width=\"11.504424778761061%\"\u003e\n \u003cp\u003e4.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.2657%;\" width=\"20%\"\u003e\n \u003cp\u003e23/214 (10.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.316%;\" width=\"20%\"\u003e\n \u003cp\u003e24/116 (20.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.8863%;\" width=\"15.044247787610619%\"\u003e\n \u003cp\u003e9.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.9458%;\" width=\"20%\"\u003e\n \u003cp\u003e25.6 (16.2\u0026ndash;38.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 5.9775%;\" width=\"11.504424778761061%\"\u003e\n \u003cp\u003e2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.2657%;\" width=\"20%\"\u003e\n \u003cp\u003e7/338 (2.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.316%;\" width=\"20%\"\u003e\n \u003cp\u003e8/95 (8.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.8863%;\" width=\"15.044247787610619%\"\u003e\n \u003cp\u003e6.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.9458%;\" width=\"20%\"\u003e\n \u003cp\u003e8.3 (3.3\u0026ndash;17.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 5.9775%;\" width=\"11.504424778761061%\"\u003e\n \u003cp\u003e4.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.2657%;\" width=\"20%\"\u003e\n \u003cp\u003e4/115 (3.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.316%;\" width=\"20%\"\u003e\n \u003cp\u003e30/240 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.8863%;\" width=\"15.044247787610619%\"\u003e\n \u003cp\u003e9.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.9458%;\" width=\"20%\"\u003e\n \u003cp\u003e8.3 (2.3\u0026ndash;21.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 5.9775%;\" width=\"11.504424778761061%\"\u003e\n \u003cp\u003e3.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.2657%;\" width=\"20%\"\u003e\n \u003cp\u003e10/126 (7.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.316%;\" width=\"20%\"\u003e\n \u003cp\u003e30/292 (10.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.8863%;\" width=\"15.044247787610619%\"\u003e\n \u003cp\u003e2.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.9458%;\" width=\"20%\"\u003e\n \u003cp\u003e24.1 (11.5\u0026ndash;44.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 5.9775%;\" width=\"11.504424778761061%\"\u003e\n \u003cp\u003e5.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.2657%;\" width=\"20%\"\u003e\n \u003cp\u003e31/182 (17.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.316%;\" width=\"20%\"\u003e\n \u003cp\u003e56/301 (18.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.8863%;\" width=\"15.044247787610619%\"\u003e\n \u003cp\u003e1.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.9458%;\" width=\"20%\"\u003e\n \u003cp\u003e32.8 (22.3\u0026ndash;46.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 5.9775%;\" width=\"11.504424778761061%\"\u003e\n \u003cp\u003e\u0026ndash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.2657%;\" width=\"20%\"\u003e\n \u003cp\u003e86/1250 (6.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.316%;\" width=\"20%\"\u003e\n \u003cp\u003e186/1295 (14.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7.8863%;\" width=\"15.044247787610619%\"\u003e\n \u003cp\u003e7.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.9458%;\" width=\"20%\"\u003e\n \u003cp\u003e19.4 (15.5\u0026ndash;23.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" style=\"width: 52.9942%;\" width=\"100%\"\u003e\n \u003cp\u003e\u003csup\u003e\u0026dagger;\u003c/sup\u003eTaylor series was used\u003csup\u003e. \u0026Dagger;\u003c/sup\u003eByar method was used. \u003csup\u003e\u0026sect;\u003c/sup\u003eIn 210 patients, the degree of atrophy was unknown.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" style=\"width: 52.9942%;\" width=\"100%\"\u003e\n \u003cp\u003eAG, atrophic gastritis; MGC, metachronous gastric cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"10\" width=\"100%\"\u003e\n \u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003eTable 3\u003c/strong\u003e\u003c/p\u003e\n \u003cp style=\"text-align: center;\"\u003e The absolute risk and incidence rate per person-years of occurrence of metachronous gastric cancer according to the presence or absence of intestinal metaplasia\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" width=\"10.78838174273859%\"\u003e\n \u003cp\u003eStudy, year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" width=\"6.846473029045643%\"\u003e\n \u003cp\u003eNo. of total subjects\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" width=\"6.431535269709544%\"\u003e\n \u003cp\u003eMedian follow-up (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" width=\"15.145228215767634%\"\u003e\n \u003cp\u003eParameter of IM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" width=\"22.510373443983404%\"\u003e\n \u003cp\u003eThe absolute risk of MGC occurrence according to the presence or absence of IM, n/N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" width=\"7.8838174273858925%\"\u003e\n \u003cp\u003eThe absolute risk difference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" width=\"22.510373443983404%\"\u003e\n \u003cp\u003eIncidence rate per 1000 person-years (95% confidence intervals)\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" width=\"7.8838174273858925%\"\u003e\n \u003cp\u003eIncidence rate difference per 1000 person-years\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.963133640552996%\"\u003e\n \u003cp\u003eAbsence of IM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.036866359447004%\"\u003e\n \u003cp\u003ePresence of IM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.963133640552996%\"\u003e\n \u003cp\u003eAbsence of IM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.036866359447004%\"\u003e\n \u003cp\u003ePresence of IM\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.78838174273859%\"\u003e\n \u003cp\u003eHan 2011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.846473029045643%\"\u003e\n \u003cp\u003e176\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.431535269709544%\"\u003e\n \u003cp\u003e2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.145228215767634%\"\u003e\n \u003cp\u003ei) Histologic - antrum\u003cbr\u003e\u0026nbsp;ii) Histologic - corpus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.78838174273859%\"\u003e\n \u003cp\u003e1/63 (1.6%)\u003cbr\u003e\u0026nbsp;2/113 (1.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.721991701244812%\"\u003e\n \u003cp\u003e8/108 (7.4%)\u003cbr\u003e\u0026nbsp;5/51 (9.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8838174273858925%\"\u003e\n \u003cp\u003e5.8%\u003cbr\u003e\u0026nbsp;8.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.78838174273859%\"\u003e\n \u003cp\u003e6.3 (0.1‒35.3)\u003cbr\u003e\u0026nbsp;7.1 (0.8‒25.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.721991701244812%\"\u003e\n \u003cp\u003e29.6 (12.8‒58.4)\u003cbr\u003e\u0026nbsp;39.2 (12.6‒91.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8838174273858925%\"\u003e\n \u003cp\u003e23.3\u003cbr\u003e\u0026nbsp;32.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.78838174273859%\"\u003e\n \u003cp\u003eIguchi 2016-Moribata 2016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.846473029045643%\"\u003e\n \u003cp\u003e330\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.431535269709544%\"\u003e\n \u003cp\u003e4.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.145228215767634%\"\u003e\n \u003cp\u003eEndoscopic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.78838174273859%\"\u003e\n \u003cp\u003e0/21 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.721991701244812%\"\u003e\n \u003cp\u003e22/101 (21.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8838174273858925%\"\u003e\n \u003cp\u003e21.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.78838174273859%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.721991701244812%\"\u003e\n \u003cp\u003e52.3 (32.8‒79.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8838174273858925%\"\u003e\n \u003cp\u003e52.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.78838174273859%\"\u003e\n \u003cp\u003eKim 2016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.846473029045643%\"\u003e\n \u003cp\u003e433\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.431535269709544%\"\u003e\n \u003cp\u003e2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.145228215767634%\"\u003e\n \u003cp\u003eHistologic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.78838174273859%\"\u003e\n \u003cp\u003e5/306 (1.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.721991701244812%\"\u003e\n \u003cp\u003e10/127 (7.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8838174273858925%\"\u003e\n \u003cp\u003e6.2%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.78838174273859%\"\u003e\n \u003cp\u003e6.5 (2.1‒15.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.721991701244812%\"\u003e\n \u003cp\u003e31.5 (15.1‒57.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8838174273858925%\"\u003e\n \u003cp\u003e25.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.78838174273859%\"\u003e\n \u003cp\u003eHan 2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.846473029045643%\"\u003e\n \u003cp\u003e565\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.431535269709544%\"\u003e\n \u003cp\u003e4.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.145228215767634%\"\u003e\n \u003cp\u003ei) Histologic - antrum\u003cbr\u003e\u0026nbsp;ii) Histologic - corpus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.78838174273859%\"\u003e\n \u003cp\u003e4/465 (0.9%)\u003cbr\u003e\u0026nbsp;11/430 (2.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.721991701244812%\"\u003e\n \u003cp\u003e44/477 (9.2%)\u003cbr\u003e\u0026nbsp;36/359 (10.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8838174273858925%\"\u003e\n \u003cp\u003e8.4%\u003cbr\u003e\u0026nbsp;7.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.78838174273859%\"\u003e\n \u003cp\u003e2.1 (0.6‒5.3)\u003cbr\u003e\u0026nbsp;6.1 (3.1‒11.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.721991701244812%\"\u003e\n \u003cp\u003e22.1 (16.1‒29.7)\u003cbr\u003e\u0026nbsp;24.1 (16.9‒33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8838174273858925%\"\u003e\n \u003cp\u003e17.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.78838174273859%\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.846473029045643%\"\u003e\n \u003cp\u003e1504\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.431535269709544%\"\u003e\n \u003cp\u003e‒\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.145228215767634%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.78838174273859%\"\u003e\n \u003cp\u003e10/855\u0026nbsp;(1.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.721991701244812%\"\u003e\n \u003cp\u003e84/813\u0026nbsp;(10.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8838174273858925%\"\u003e\n \u003cp\u003e9.2%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.78838174273859%\"\u003e\n \u003cp\u003e4.6 (2.9‒6.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.721991701244812%\"\u003e\n \u003cp\u003e27.1 (22.5‒32.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.8838174273858925%\"\u003e\n \u003cp\u003e22.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"10\" width=\"100%\"\u003e\n \u003cp\u003e\u003csup\u003e\u0026dagger;\u003c/sup\u003eTaylor series was used. \u003csup\u003e\u0026Dagger;\u003c/sup\u003eByar method was used.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"10\" width=\"100%\"\u003e\n \u003cp\u003eIM, intestinal metaplasia; MGC, metachronous gastric cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Endoscopic Mucosal Resection, Gastritis, Atrophic, Meta-Analysis, Neoplasms, Second Primary, Stomach Neoplasms","lastPublishedDoi":"10.21203/rs.3.rs-1840349/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1840349/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: Metachronous gastric cancer (MGC) can occur after endoscopic resection for gastric cancer. This systematic review and meta-analysis aimed to evaluate the risk of MGC caused by severe atrophic gastritis (AG) and intestinal metaplasia (IM).\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: We searched the medical literature through May 2022 and identified patients who occurred MGC after endoscopic resection for gastric cancer. We retrieved studies evaluating the degree of AG and the presence or absence of IM and compared the incidence of MGC, respectively.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: From nine cohort studies, 2,755 patients by 2018. Incidence of MGC was significantly higher in severe AG (RR, 1.64; 95% CI, 1.29–2.07; I\u003csup\u003e2\u003c/sup\u003e=45%) and IM (RR, 7.08; 95% CI, 3.63–13.80; I\u003csup\u003e2\u003c/sup\u003e=0%) than those without. The absolute risk difference of MGC in severe AG and IM was 7.5% and 9.2%, respectively. The difference in incidence rate per 1000 person-years was 17.5 and 22.5 person-years, respectively. However, the \u003cem\u003eH. pylori\u003c/em\u003e infection did not affect the MGC occurrence (RR 1.08, 95% CI 0.85–1.39, I\u003csup\u003e2\u003c/sup\u003e=0%).\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e: Severe AG or IM had a 1.6-fold and 7.0-fold higher risk of MGC occurrence after endoscopic resection of gastric cancer. Patients with severe AG or IM need more stringent follow-up to monitor MGC occurrences.\u003c/p\u003e","manuscriptTitle":"The Impact of Atrophic Gastritis and Intestinal Metaplasia on the Occurrence of Metachronous Gastric Cancer After Endoscopic Resection: A Systematic Review and Meta-analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-07-26 17:35:55","doi":"10.21203/rs.3.rs-1840349/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"184ba72e-19b7-4a63-a4eb-631fae60f0fc","owner":[],"postedDate":"July 26th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-10-04T04:59:12+00:00","versionOfRecord":[],"versionCreatedAt":"2022-07-26 17:35:55","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1840349","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1840349","identity":"rs-1840349","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}