Secondary Logo

Journal Logo

REVIEW ARTICLE: REVIEW ARTICLE

Gastric Cancer Risk of Intestinal Metaplasia Subtypes: A Systematic Review and Meta-Analysis of Cohort Studies

Du, Sijing MM1,*; Yang, Yang MD1,*; Fang, Shuangshuang MM1,2,*; Guo, Song MD3,*; Xu, Chuchu MM1,2; Zhang, Ping MD1; Wei, Wei MD1

Author Information
Clinical and Translational Gastroenterology: October 2021 - Volume 12 - Issue 10 - p e00402
doi: 10.14309/ctg.0000000000000402

Abstract

INTRODUCTION

Gastric cancer (GC) remains a major health problem in many countries, with more than 1.22 million incident cases of GC occurring worldwide in 2017, with nearly half of the global incident cases occurring in China (1). GC is the third leading cause of cancer mortality, causing an estimated 783,000 deaths globally in 2018 (2). High mortality in GC is closely related to its silent nature (3). Therefore, early detection and treatment are important approaches to improve the survival of patients with GC.

Intestinal-type gastric adenocarcinoma is the final stage of what is known as the Correa cascade, which pertains to the carcinoma sequence of chronic gastritis to atrophy gastritis, then intestinal metaplasia (IM), to the final dysplasia (4). The stepwise progression of intestinal-type gastric adenocarcinoma allows for the early detection and resection of neoplastic lesions. Histologically confirmed IM is a precancerous condition of GC that has been suggested to be an independent risk factor for GC and is recommended as the most reliable marker of gastric mucosal atrophy in the management of epithelial precancerous conditions and lesions in the stomach (MAPS II) (5).

IM can be classified according to histologic subtypes: complete IM (type I) and incomplete IM (type II or type III) (6). Previous reviews and meta-analyses found that incomplete IM was associated with a higher risk of GC compared with complete IM (7–9); however, additional studies are required before subtyping can be routinely recommended. Previous reviews and meta-analyses were limited to descriptive reviews or subgroup analyses of IM subtypes based on multiple observational studies, including cross-sectional studies; however, incomplete IM is not always found in the gastrectomy specimens of patients with GC (10–12). Instead, a cohort study, where an outcome or disease-free study population is first identified and monitored in time until the disease or outcome of interest occurs, can provide powerful prognostic-related results (13). Thus, we aimed to systematically assess the relationship between IM subtypes and GC risk in cohort studies.

METHODS

The protocol for this systematic review was based on the Meta-Analysis of Observational Studies in Epidemiology (14). The protocol was prospectively registered at PROSPERO (CRD42020176936).

Search strategy

Two reviewers (S.D. and S.F.) independently searched electronic databases, including PubMed, EMBASE, and the Cochrane Library, from inception to May 15, 2021. The search equations were “intestinal metaplasia” AND “(gastric cancer) OR (gastric neoplasm) OR (gastric carcinoma) OR (stomach cancer) OR (stomach neoplasm) OR (stomach carcinoma)” AND “(cohort) OR (follow-up).” In addition, the references of identified articles were also searched for potentially missed articles.

Study selection

After excluding duplicate studies, the 2 reviewers (S.D. and S.F.) screened the titles and abstracts of all retrieved articles to exclude irrelevant studies and then read the full text of the remaining studies to include eligible studies. Disagreements were resolved through discussion or by involving a third reviewer (S.G.) when necessary.

The inclusion criteria were as follows: patients (individuals diagnosed with IM), intervention (being diagnosed with incomplete IM), comparator (being diagnosed with complete IM), outcome (GC and dysplasia incidence in patients with IM subtypes confirmed by pathologic diagnosis or records from government registration), and study design (cohort studies). The exclusion criteria were as follows: (i) insufficient data in original studies, (ii) duplicate publications, (iii) conference abstracts, and (iv) studies published in a non-English language.

Data extraction and quality assessment

Two reviewers (G.S. and C.X.) independently screened all the included studies to extract the following data: name of the first author, publication year, study design, country, study period, sample size, age, sex, duration of follow-up, number of patients with IM subtypes, and numbers of GC and dysplasia. They independently assessed the quality of the included studies according to the Newcastle-Ottawa Quality Assessment Scale. Disagreements were resolved through discussion or by involving a third reviewer (S.D.) when necessary.

Outcomes

The primary outcome was the incidence of GC in patients with IM subtypes. The secondary outcomes were the incidence of dysplasia in patients with IM subtypes and the incidence of GC and dysplasia among patients with IM subtypes in different countries and pathological quality control.

Statistical analysis

We calculated the risk ratios (RRs) and 95% confidence intervals (CIs) using 2 × 2 table data extracted from the original studies. We pooled the results with RRs and 95% CIs using a fixed-effects or random-effects model, depending on study heterogeneity. Heterogeneity in the included studies was assessed using the Cochran Q test and quantity I2. An I2 greater than 50% suggested significant heterogeneity (15). To explore the source of heterogeneity, sensitivity and subgroup analyses were further performed according to the potential effect modification of factors, including country and pathological quality control. Funnel plots were generated to evaluate the possibility of publication bias (16). All statistical analyses were conducted using Review Manager, version 5.3 (Cochrane Reviews).

RESULTS

Literature search

As shown in Figure 1, 928 articles were identified using a search strategy from PubMed, EMBASE, and the Cochrane library, of which 295 were duplicated articles. In the remaining 633 articles, 604 irrelevant articles were excluded after reviewing the titles and abstracts; hence, 29 articles remained. Subsequently, 19 articles were excluded for the following reasons: insufficient data (n = 2), conference abstracts (n = 9), cross-sectional studies (n = 6), no diagnosis of IM subtype (n = 1), and no comparator (n = 1). Two potential articles were included from the reference list. Finally, 12 articles were included in this meta-analysis (17–28).

F1
Figure 1.:
Flow diagram of literature search and study selection.

Study characteristics and quality assessment

The main characteristics of the 12 articles are summarized in Table 1. Among the 12 cohort studies, 10 were prospective cohort studies (18–20,22–28) and 2 were retrospective cohort studies (17,21); 4 studies were conducted in Asia (20,22,25,28), 7 were conducted in Europe (17–19,21,23,24,26), and 1 was conducted in South America (27). In total, 6,498 individuals were included in this meta-analysis, and the sample size of the included studies ranged from 62 to 2,980. All studies included both male and female patients. All the included studies presented the numbers of IM subtypes at baseline and GC at end point, whereas 8 studies presented the numbers of dysplasia at the end point. The numbers of IM subtypes, GC, and dysplasia of the included articles are listed in Table 2. Quality assessment is also summarized in Table 1, where all studies obtained 6 or more stars.

Table 1. - Characteristics of studies included in the meta-analysis
First author Year Design Country Study period Sample size Age, y Sex Follow-up, mo Quality assessment
Ramesar17 1987 RC UK 1976–1987 174 Mean 60.8 53% M 120–132 7
Sossai18 1990 PC Italy None 112 Mean 64.2 57% M 12–88 7
Silva19 1990 PC Portugal 1982–1988 124 31–76 71% M 12–72 7
Fang20 1991 PC China 1982–1987 112 18–70 80% M 15–70 6
Filipe21 1994 RC Slovenia 1967–1986 1,281 NR 65% M 126–234 8
Sun22 2009 PC China 1989–2003 62 NR NR 60–168 6
Gonzalez23 2010 PC Spain 1988–1994
2005–2007
478 Mean 50 47% M Mean 153.6 8
Gonzalez24 2016 PC Spain 1995–2004
2011–2013
649 Mean 52 54% M Mean 144 8
Pittayanon25 2017 PC Thailand 2004–2014 91 63 ± 13.3 51% M 48.6 ± 30 8
Chapelle26 2020 PC France 2000–2015 79 Mean 61 44% M Mean 66 7
Piazuelo27 2021 PC Colombia 1991–2011 356 69 ± 8 45% M 240 8
Lee28 2021 PC Singapore 2004–2010 2,980 59.1 ± 6.7 52% M Mean 52.8 8
NR, not reported; PC, prospective cohort; RC, retrospective cohort.

Table 2. - Characteristics of the IM subtypes and GC of studies included
First author Year No. of CIM No. of IIM No. of GC No. of dysplasia Pathological quality control
No. of CIM at baseline No. of IIM at baseline No. of CIM at baseline No. of IIM at baseline
Type I Type II Type III Type I Type II Type III Type I Type II Type III
Ramesar17 1987 16 14 14 0 1 1 NR NR NR NR
Sossai18 1990 71 22 19 0 0 2 9 7 5 NR
Silva19 1990 101 12 11 0 0 1 0 0 3 NR
Fang20 1991 47 34 31 0 0 5 NR NR NR NR
Filipe21 1994 518 197 275 6 5 15 NR NR NR NR
Sun22 2009 19 22 21 0 1 3 6 4 3 NR
Gonzalez23 2010 104 88 1 16 0 0 Yes
Gonzalez24 2016 248 219 8 15 9 13 Yes
Pittayanon25 2017 81 10 0 3 1 2 Yes
Chapelle26 2020 60 13 0 2 2 3 NR
Piazuelo27 2021 134 115 1 7 2 14 Yes
Lee28 2021 302 244 2 13 NR NR Yes
CIM, complete intestinal metaplasia; GC, gastric cancer; IIM, incomplete intestinal metaplasia; NR, not reported.

Based on the 12 studies, the fixed-effects estimated pooled prevalence of incomplete IM among patients with IM was 42% (95% CI, 34%–49%) and complete IM was 58% (95% CI, 50%–66%), presented as forest plots in Supplementary Figures 1 and 2 (see Supplementary Digital Content 1, https://links.lww.com/CTG/A676). In patients with incomplete IM, the fixed-effects estimated pooled prevalence of type II IM was 45% (95% CI, 41%–49%) and type III IM was 55% (95% CI, 51%–59%), presented as forest plots in Supplementary Figures 3 and 4 (see Supplementary Digital Content 1, https://links.lww.com/CTG/A676).

Outcomes

A total of 12 studies with 6,498 participants were included in this meta-analysis to evaluate GC risk in patients with IM subtypes. Compared with complete IM, the pooled relative risk of GC in patients with incomplete IM was 5.16 (95% CI, 3.28–8.12), and GC risk of type III IM was highest with a pooled relative risk of 2.88 (95% CI, 1.37–6.04) compared with type II and 6.42 (95% CI, 3.03–13.62) compared with type I. In addition, GC risk of type II IM was not significantly higher than type I (RR, 2.37; 95% CI, 0.84–6.72). Forest plots of GC risk in the IM subtypes are shown in Figure 2.

F2
Figure 2.:
Forest plots of gastric cancer risk in IM subtypes. IIM, incomplete intestinal metaplasia; CIM, complete intestinal metaplasia; CI, confidence interval; M-H, Mantel-Haenszel.

A total of 7 studies with 1,473 participants were included in this meta-analysis to evaluate dysplasia risk in patients with IM subtypes. Compared with complete IM, the pooled relative risk of dysplasia in patients with incomplete IM was 3.72 (95% CI, 1.42–9.72), and the pooled relative risk in type III IM was 11.73 (95% CI, 2.08–66.08) compared with type I but not significantly higher than type II. Moreover, dysplasia risk of type II IM was not significantly higher than that of type I. Forest plots of GC risk in IM subtypes are shown in Figure 3.

F3
Figure 3.:
Forest plots of dysplasia risk in IM subtypes. IIM, incomplete intestinal metaplasia; CIM, complete intestinal metaplasia; CI, confidence interval; M-H, Mantel-Haenszel.

Subgroup analysis was also performed according to the country of origin and pathological quality control (Table 2). According to the country of origin, the GC risk of incomplete IM was higher in Asia (RR, 8.83; 95% CI, 3.05–25.56), Europe (RR, 4.23; 95% CI, 2.51–7.14), and South America (RR, 8.16; 95% CI, 1.02–65.32) compared with that of complete IM. In addition, 5 studies performed pathological quality control, which indicated a significantly higher GC risk of incomplete IM compared with that of complete IM (RR, 5.45; 95% CI, 3.02–9.84). Forest plots of the subgroup analysis are shown in Figure 4. According to the country of origin, the dysplasia risk of incomplete IM was higher in Europe (RR, 4.05; 95% CI, 1.65–9.93) and South America (RR, 8.16; 95% CI, 1.89–35.14) compared with that of complete IM. Three studies performed pathological quality control, which indicated a significantly higher dysplasia risk of incomplete IM compared with that of complete IM (RR, 4.67; 95% CI, 1.11–19.63). Forest plots of the subgroup analysis are shown in Figure 5.

F4
Figure 4.:
Forest plots of subgroup analysis of gastric cancer risk in IM subtypes according to country of origin and pathological quality control. IIM, incomplete intestinal metaplasia; CIM, complete intestinal metaplasia; CI, confidence interval; M-H, Mantel-Haenszel.
F5
Figure 5.:
Forest plots of subgroup analysis of dysplasia risk in IM subtypes according to country of origin and pathological quality control. IIM, incomplete intestinal metaplasia; CIM, complete intestinal metaplasia; CI, confidence interval; M-H, Mantel-Haenszel.

Publication bias

For the risk of GC of incomplete IM vs complete IM, a funnel plot (Figure 6) suggested that publication bias may exist. The results may be related to the small sample size of some included studies and the exclusion of non-English articles and conference abstracts. However, because the abstracts do not contain complete original data, publication bias is inevitable.

F6
Figure 6.:
Funnel plots for the analysis of publication bias.

DISCUSSION

IM is an independent risk factor for GC, with an annual incidence of 12.4 (95% CI, 10.7–14.3) cases of GC per 10,000 persons with IM (9). The Operative Link on Gastritis Assessment (29) and Operative Link on Gastritis Intestinal Metaplasia Assessment (OLGIM) (30) systems have been proposed for staging of atrophy and IM. A meta-analysis revealed that stage III/IV OLGIM system was indeed associated with an increased risk of GC (31). Management of epithelial precancerous conditions and lesions in the stomach II recommended that patients with advanced stages of atrophic gastritis (Operative Link on Gastritis Assessment/OLGIM III/IV) should be followed up with a high-quality endoscopy every 3 years (5). The key issue is that the use of OLGIM has some limitations when only a few biopsies are available for examination, which always happens in clinical practice; thus, other reliable GC risk assessment systems or markers are urgently needed.

The IM subtype may be an easier way to assess the risk of GC. Since the 1970s, investigators have found that there are variants of IM that differ based on morphology and mucin secretion, and they found that some variants were more strongly associated with the risk of intestinal-type gastric adenocarcinoma (32–36). According to the general pathological classification criteria proposed by Jass and Filipe, IM can be classified as complete IM (type I) and incomplete IM (type II or type III) (6). In complete IM (type I), sialomucins are present in goblet cells with no mucins in columnar cells. In type II IM, sialomucins are present in goblet and columnar cells, and sulfomucins are absent in goblet cells. In type III IM, sulfomucins predominate in columnar cells, and goblet cells may contain sialomucins or sulfomucins (37).

Our study provided a comprehensive summary of the relationship between IM subtypes and GC risk and included only cohort studies with high scores of quality assessment (7.33 on average) to ensure the overall quality of evidence. This meta-analysis of cohort studies included 12 studies with 6,498 participants to evaluate the relationship between IM subtypes and GC risk. Compared with complete IM, the pooled relative risks of GC and dysplasia risk of patients with incomplete IM was 5.16 (95% CI, 3.28–8.12) and 3.72 (95% CI, 1.42–9.72), respectively, and the risk of type III IM was the highest. The abovementioned results are more significant in high-incidence areas of GC (Asia and South America). In addition, interobserver agreement between pathologists can improve the accuracy of pathological diagnosis, and research has gradually found that it is poor for AG but moderate or strong for IM (38–40). As reported in the included studies, the abovementioned subtype staining results are easy to identify and distinguish, so the level of interobserver agreement for the IM subtype is likely similarly high. In our study, we conducted a subgroup analysis on whether to perform pathological quality control, which showed that the pooled relative risk (5.45, 95% CI, 3.02–9.84) of pathological quality control was similar to the total pooled results, which proved that the IM subtypes have a high coincidence rate in the pathological diagnosis.

González et al. (7) conducted a review of the evidence including 14 cross-sectional studies and 10 follow-up studies assessing the risk of GC among subjects with different types of IM, and the results showed that the relative risks of GC were 4- to 11-fold higher for the presence of incomplete IM in comparison with complete IM or the absence of incomplete IM. Similarly, Shao et al. (8) observed that incomplete IM (pooled OR = 9.48, 95% CI, 4.33–20.78), but not complete IM (pooled OR = 1.55, 95% CI, 0.91–2.65), was significantly associated with a higher GC risk in a meta-analysis of GC risk among patients with gastric IM. The results of our systematic review and meta-analysis are consistent with the abovementioned research conclusions.

In addition, we found that the fixed-effects estimated pooled prevalence of incomplete IM among patients with IM was 42% (95% CI, 34–49) and complete IM was 58% (95% CI, 50–66), which is consistent with previous research results (41). The widespread distribution of incomplete IM further illustrates the necessity of clinical subtype diagnosis; however, we believe that the main barrier to clinical implementation is the limited reliable evidence-based data, which is mainly caused by the heterogeneity of the research with different study designs, periods, endoscopic and biopsy protocols, and variable follow-up statuses. Fortunately, in recent years, reports of related long-term cohort studies have gradually increased. We, therefore, chose cohort studies for the meta-analysis to obtain more objective results. In clinical practice, Correa et al. (42) suggested that a diagnosis of incomplete IM should be followed by endoscopic topographic mapping to evaluate its extension and rule out more advanced lesions, such as dysplasia or early adenocarcinoma. Shah et al. (37) also promoted the utility of the IM subtype for potential prognostic value and cost-effective pathological operation. In addition, the diagnosis of mixed complete and incomplete IM has not yet been unified, and consensus on pathological diagnosis needs to be formed later.

Our systematic review and meta-analysis had several limitations. First, only 3 electronic databases were searched, and only studies published in English were included, which may have missed potential studies in other databases or those published in other languages. Second, the included studies were from Asia, Europe, and South America; the limited generalizability to global populations cannot be ignored. Third, all the included studies were cohort studies, of which 10 were prospective cohort studies; several biases could not be avoided, particularly follow-up bias. Fourth, we calculated the RRs and 95% CIs by using the 2 × 2 table data extracted from the original studies; hence, confounding factors could not be excluded or matched, such as sex, age, family history of GC, and Helicobacter pylori infection. Finally, all the included studies presented the numbers of IM subtypes at baseline and GC at the end point; only 2 studies reported the hazards ratio of progression to GC for patients with incomplete IM compared with that for patients with complete IM (see Supplementary materials, https://links.lww.com/CTG/A677). However, RR and hazards ratio cannot be pooled even if we calculate the RRs of the remaining 10 studies because the absolute risk of GC in patients with IM is not low (43). A technical review reported that the annual incidence of GC is 12.4 cases per 10,000 persons with IM (9), and a Japanese study reported a higher cumulative incidence of GC at 5 years, reaching 5.3%–9.8% in patients with IM (44). Considering the abovementioned factors, we calculated the RRs and 95% CIs by using the 2 × 2 table data extracted from all the original studies and pooled the results with RRs and 95% CIs.

In conclusion, our systematic review and meta-analysis indicated that the GC risk of incomplete IM, especially type III, was higher than that of complete IM. The current evidence indicates a correlation between IM subtypes and GC risk, which may support the use of IM subtypes in GC surveillance. More population-based prospective cohort studies are warranted to confirm our findings.

CONFLICTS OF INTEREST

Guarantor of the article: Wei Wei, MD.

Specific author contributions: S.D., S.F., P.Z., and W.W: conception and design. S.D. and S.G.: analysis and interpretation of the data. S.D. and Y.Y: drafting of the article. S.D.: critical revision of the article for important intellectual content. all authors: final approval of the article.

Financial support: Science Research Program for TCM Industry (No. 201507001-09) the Fundamental Research Funds for the Central public welfare research institutes (ZZ11-035).

Potential competing interests: None to report.

REFERENCES

1. GBD 2017 Stomach Cancer Collaborators. The global, regional, and national burden of stomach cancer in 195 countries, 1990-2017: A systematic analysis for the Global Burden of Disease study 2017. Lancet Gastroenterol Hepatol 2020;5:42–54.
2. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394–424.
3. Tan P, Yeoh KG. Genetics and molecular pathogenesis of gastric adenocarcinoma. Gastroenterology 2015;149:1153–62.e3.
4. Correa P. Human gastric carcinogenesis: A multistep and multifactorial process: First American cancer society award lecture on cancer epidemiology and prevention. Cancer Res 1992;52:6735–40.
5. Pimentel-Nunes P, Libânio D, Marcos-Pinto R, et al. Management of epithelial precancerous conditions and lesions in the stomach (MAPS II): European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter and Microbiota Study Group (EHMSG), European Society of Pathology (ESP), and Sociedade Portuguesa de Endoscopia Digestiva (SPED) guideline update 2019. Endoscopy 2019;51:365–88.
6. Jass JR, Filipe MI. The mucin profiles of normal gastric mucosa, intestinal metaplasia and its variants and gastric carcinoma. Histochem J 1981;13:931–9.
7. González CA, Sanz-Anquela JM, Gisbert JP, et al. Utility of subtyping intestinal metaplasia as marker of gastric cancer risk. A review of the evidence. Int J Cancer 2013;133:1023–32.
8. Shao L, Li P, Ye J, et al. Risk of gastric cancer among patients with gastric intestinal metaplasia. Int J Cancer 2018;143:1671–7.
9. Gawron AJ, Shah SC, Altayar O, et al. AGA technical review on gastric intestinal metaplasia-natural history and clinical outcomes. Gastroenterology 2020;158:705–30.e5.
10. Conchillo JM, Houben G, de Bruïne A, et al. Is type III intestinal metaplasia an obligatory precancerous lesion in intestinal-type gastric carcinoma? Eur J Cancer Prev 2001;10:307–12.
11. Matsukura N, Onda M, Tokunaga A, et al. Mucosal IgA antibody against Helicobacter pylori in chronic gastritis and intestinal metaplasia detected by the Tes-Tape method in resection specimens after gastrectomy for gastric cancer. Cancer 1995;75:1472–7.
12. Silva S, Filipe MI. Intestinal metaplasia and its variants in the gastric mucosa of Portuguese subjects: A comparative analysis of biopsy and gastrectomy material. Hum Pathol 1986;17:988–95.
13. Song JW, Chung KC. Observational studies: Cohort and case-control studies. Plast Reconstr Surg 2010;126:2234–42.
14. Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of observational studies in epidemiology: A proposal for reporting. Meta-analysis of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000;283:2008–12.
15. Higgins JP, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-analyses. BMJ 2003;327:557–60.
16. Egger M, Davey Smith G, Schneider M, et al. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629–34.
17. Ramesar KC, Sanders DS, Hopwood D. Limited value of type III intestinal metaplasia in predicting risk of gastric carcinoma. J Clin Pathol 1987;40:1287–90.
18. Sossai P, Barbazza R. Intestinal metaplasia and dysplasia in gastric ulcer and its tissue repair. Am J Gastroenterol 1990;85:829–32.
19. Silva S, Filipe MI, Pinho A. Variants of intestinal metaplasia in the evolution of chronic atrophic gastritis and gastric ulcer. A follow up study. Gut 1990;31:1097–104.
20. Fang DC, Liu WW. Subtypes of intestinal metaplasia and gastric carcinoma. A clinicoendoscopic follow-up of 112 cases. Chin Med J (Engl) 1991;104:467–71.
21. Filipe MI, Muñoz N, Matko I, et al. Intestinal metaplasia types and the risk of gastric cancer: A cohort study in Slovenia. Int J Cancer 1994;57:324–9.
22. Sun Y, Li ZW, Feng GS, et al. Long-term follow-up study on gastric intestinal metaplasia subtype and its relation to expression of P53, Bcl-2 and PCNA. Chin J Cancer Res 2009;21:272–7.
23. González CA, Pardo ML, Liso JM, et al. Gastric cancer occurrence in preneoplastic lesions: A long-term follow-up in a high-risk area in Spain. Int J Cancer 2010;127:2654–60.
24. González CA, Sanz-Anquela JM, Companioni O, et al. Incomplete type of intestinal metaplasia has the highest risk to progress to gastric cancer: Results of the Spanish follow-up multicenter study. J Gastroenterol Hepatol 2016;31:953–8.
25. Pittayanon R, Rerknimitr R, Klaikaew N, et al. The risk of gastric cancer in patients with gastric intestinal metaplasia in 5-year follow-up. Aliment Pharmacol Ther 2017;46:40–5.
26. Chapelle N, Péron M, Quénéhervé L, et al. Long-term follow-up of gastric precancerous lesions in a low GC incidence area. Clin Transl Gastroenterol 2020;11:e00237.
27. Piazuelo MB, Bravo LE, Mera RM, et al. The Colombian chemoprevention trial: 20-year follow-up of a cohort of patients with gastric precancerous lesions. Gastroenterology 2021;160:1106–17.e3.
28. Lee JWJ, Zhu F, Srivastava S, et al. Severity of gastric intestinal metaplasia predicts the risk of gastric cancer: A prospective multicentre cohort study (GCEP). Gut 2021. [Epub ahead of print May 11, 2021.]
29. Rugge M, Genta RM. Staging and grading of chronic gastritis. Hum Pathol 2005;36:228–33.
30. Dixon MF, Genta RM, Yardley JH, et al. Classification and grading of gastritis. The updated sydney system. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol 1996;20:1161–81.
31. Yue H, Shan L, Bin L. The significance of OLGA and OLGIM staging systems in the risk assessment of gastric cancer: A systematic review and meta-analysis. Gastric Cancer 2018;21:579–87.
32. Teglbjaerg PS, Nielsen HO. Small intestinal type and colonic type intestinal metaplasia of the human stomach, and their relationship to the histogenetic types of gastric adenocarcinoma. Acta Pathol Microbiol Scand A 1978;86a:351–5.
33. Jass JR, Filipe MI. A variant of intestinal metaplasia associated with gastric carcinoma: A histochemical study. Histopathology 1979;3:191–9.
34. Jass JR. Role of intestinal metaplasia in the histogenesis of gastric carcinoma. J Clin Pathol 1980;33:801–10.
35. Sipponen P, Seppälä K, Varis K, et al. Intestinal metaplasia with colonic-type sulphomucins in the gastric mucosa; its association with gastric carcinoma. Acta Pathol Microbiol Scand A 1980;88(4):217–24.
36. Segura DI, Montero C. Histochemical characterization of different types of intestinal metaplasia in gastric mucosa. Cancer 1983;52:498–503.
37. Shah SC, Gawron AJ, Mustafa RA, et al. Histologic subtyping of gastric intestinal metaplasia: Overview and considerations for clinical practice. Gastroenterology 2020;158:745–50.
38. Isajevs S, Liepniece-Karele I, Janciauskas D, et al. Gastritis staging: Interobserver agreement by applying OLGA and OLGIM systems. Virchows Arch 2014;464(4):403–7.
39. Leja M, Funka K, Janciauskas D, et al. Interobserver variation in assessment of gastric premalignant lesions: Higher agreement for intestinal metaplasia than for atrophy. Eur J Gastroenterol Hepatol 2013;25:694–9.
40. Capelle LG, de Vries AC, Haringsma J, et al. The staging of gastritis with the OLGA system by using intestinal metaplasia as an accurate alternative for atrophic gastritis. Gastrointest Endosc 2010;71:1150–8.
41. Altayar O, Davitkov P, Shah SC, et al. AGA technical review on gastric intestinal metaplasia-epidemiology and risk factors. Gastroenterology 2020;158:732–44.e16.
42. Correa P, Piazuelo MB, Wilson KT. Pathology of gastric intestinal metaplasia: Clinical implications. Am J Gastroenterol 2010;105:493–8.
43. Greenland S. Quantitative methods in the review of epidemiologic literature. Epidemiol Rev 1987;9:1–30.
44. Shichijo S, Hirata Y, Niikura R, et al. Histologic intestinal metaplasia and endoscopic atrophy are predictors of gastric cancer development after Helicobacter pylori eradication. Gastrointest Endosc 2016;84:618–24.

Supplemental Digital Content

© 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology