How to Manage a Patient With Gastric Intestinal Metaplasia: An International Perspective

Abstract

Forty-five years have passed since Correa et al1Correa P. Haenszel W. Cuello C. et al.A model for gastric cancer epidemiology.Lancet. 1975; 2: 58-60Abstract PubMed Scopus (892) Google Scholar proposed their hypothesis on the histopathological cascade leading to gastric adenocarcinoma claiming that gastric cancer usually resulted from chronic gastritis, subsequently leading to gland loss or atrophy, intestinal metaplasia, dysplasia, and eventually invasive cancer. The most common risk factor for gastritis soon revealed to be the colonization with Helicobacter pylori.2Hooi J.K.Y. Lai W.Y. Ng W.K. et al.Global prevalence of Helicobacter pylori infection: systematic review and meta-analysis.Gastroenterology. 2017; 153: 420-429Abstract Full Text Full Text PDF PubMed Scopus (1332) Google Scholar Most infections occur during childhood and remain for life. They are almost invariably associated with chronic gastritis, which may eventually lead to a loss of mucosal glands. This atrophic change usually predominates in the antrum and may spread proximally. Most patients with atrophic gastritis also develop gastric intestinal metaplasia (GIM). This condition can be found in ≥20% of patients undergoing endoscopic biopsy sampling.3Marques-Silva L. Areia M. Elvas L. et al.Prevalence of gastric precancerous conditions: a systematic review and meta-analysis.Eur J Gastroenterol Hepatol. 2014; 26: 378-387Crossref PubMed Scopus (78) Google Scholar GIM is both for endoscopists and pathologists a clearly recognizable and reliable marker of preneoplastic change of the gastric mucosa. Extensive, severe GIM affecting both antrum and corpus is an identifier of patients at the highest risk for development of dysplasia and invasive cancer. As such, GIM is at present the most relevant clinical marker to identify individuals at risk for gastric adenocarcinoma.4Pimentel-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: 365-388PubMed Google Scholar In various surveillance studies from different parts of the world, invasive cancer annually occurred in 0.2%–0.4% of patients harboring GIM. Because GIM is often a multifocal condition and most surveillance studies pooled patients with any degree of GIM, this annual progression rate likely underestimates the true risk for patients with more advanced disease. Both Asia studies based on serologic markers as well as Western studies based on histology stressed that individuals with widespread metaplasia affecting both gastric antrum and body were at higher risk with an absolute risk of 5.8% at 5 years.4Pimentel-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: 365-388PubMed Google Scholar,5Banks M. Graham D. Jansen M. et al.British Society of Gastroenterology guidelines on the diagnosis and management of patients at risk of gastric adenocarcinoma.Gut. 2019; 68: 1545-1575Crossref PubMed Scopus (213) Google Scholar For this reason, the European Society of Gastrointestinal Endoscopy as well as the British Society of Gastroenterology guidelines recommend to offer surveillance with a 3-year interval to patients harboring GIM that affects the antrum and corpus.4Pimentel-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: 365-388PubMed Google Scholar,5Banks M. Graham D. Jansen M. et al.British Society of Gastroenterology guidelines on the diagnosis and management of patients at risk of gastric adenocarcinoma.Gut. 2019; 68: 1545-1575Crossref PubMed Scopus (213) Google Scholar The 3-year interval is also based on studies that showed that surveillance of patients at risk with intervals up to three years allowed for an early diagnosis of gastric cancer and thus improved prognosis.6Pimenta-Melo A.R. Monteiro-Soares M. Libânio D. et al.Missing rate for gastric cancer during upper gastrointestinal endoscopy: a systematic review and meta-analysis.Eur J Gastroenterol Hepatol. 2016; 28: 1041-1049Crossref PubMed Scopus (100) Google Scholar,7Nam J.H. Choi I.J. Cho S.J. et al.Association of the interval between endoscopies with gastric cancer stage at diagnosis in a region of high prevalence.Cancer. 2012; 118: 4953-4960Crossref PubMed Scopus (47) Google Scholar The recent US guideline recommends against the routine use of endoscopic surveillance of individuals with GIM. Although this may at first seem to be a straightforward message, it creates considerable confusion. The recommendation would be logical if gastric cancer was a rare or rapidly vanishing disease in North America. This is, however, not the case. Gastric cancer remains much more common than some other conditions for which screening and surveillance has been accepted, such as esophageal adenocarcinoma and cervical cancer. In addition, there is a marked disparity in gastric cancer incidence among population subgroups with substantially higher incidences among African American, Hispanic, and American Indian citizens, compared with Caucasians (seer.cancer.gov). In 2018, approximately 11,438 American citizens died from gastric cancer and this number is expected to increase to 17,700 in 2040 (https://gco.iarc.fr/tomorrow). Thus, we need to stress another point that usually is poorly perceived. On one side, the frequency of GIM varies between regions of the globe, in parallel with that for gastric adenocarcinoma precludes screening in all individuals.3Marques-Silva L. Areia M. Elvas L. et al.Prevalence of gastric precancerous conditions: a systematic review and meta-analysis.Eur J Gastroenterol Hepatol. 2014; 26: 378-387Crossref PubMed Scopus (78) Google Scholar However, an individual with GIM merits proper assessment because surveillance of those at risk may well be the only way to improve the dismal prognosis for patients with cancer.6Pimenta-Melo A.R. Monteiro-Soares M. Libânio D. et al.Missing rate for gastric cancer during upper gastrointestinal endoscopy: a systematic review and meta-analysis.Eur J Gastroenterol Hepatol. 2016; 28: 1041-1049Crossref PubMed Scopus (100) Google Scholar It should also be noted that there is no evidence that the risk for progression to gastric cancer among individuals with extensive GIM depends on the ethnicity, age, or gender of the patient. In other words, there is no clinical basis to offer an Asian patient with extensive GIM surveillance, but refrain from doing so in a Caucasian patient with the same condition. The US guideline recommendation to refrain from routine endoscopic surveillance of patients with GIM would also make sense if surveillance in the United States would not have any impact on disease outcome, if outcome of gastric cancer would be much better than for other conditions, or if US clinicians would not be able to recognize and if necessary treat subjects at risk. None of these statements are true. The discrepancy between the US and international guidelines also results from the differences in approach. The US guideline recommends against routine use of surveillance, and then recognizes that there are risk modifiers, namely, extension and family history. These are, however, not incorporated and tackled in further statements. In contrast, the international guidelines start with the recognition that gastric cancer remains an important cause of disease associated with high burden and mortality, that we have gained sufficient understanding of the pathogenesis and risk categorization of gastric cancer, and that we the tools to recognize and if necessary early treat these patients. Based on this approach, international guidelines recommend to spend effort in recognizing preneoplastic changes of the gastric mucosa, use this to risk categorize patients, and offer surveillance to those at the highest risk. This approach essentially resembles our approach to early neoplastic lesions of the esophagus and colon. These criteria allow to select the minority of GIM patients at marked risk for neoplasia (discussed elsewhere in this article). The majority of patients with GIM, those who during high-quality endoscopy were shown to have GIM of limited severity and extent, confined to the antrum, and have a negative family history for gastric cancer do not require surveillance. Some guidelines recommend also including patients with incomplete IM (with ≥31% risk in some studies5Banks M. Graham D. Jansen M. et al.British Society of Gastroenterology guidelines on the diagnosis and management of patients at risk of gastric adenocarcinoma.Gut. 2019; 68: 1545-1575Crossref PubMed Scopus (213) Google Scholar) as well as those with a family history of gastric cancer in this approach.8Marcos-Pinto R. Carneiro F. Dinis-Ribeiro M. et al.First-degree relatives of patients with early-onset gastric carcinoma show even at young ages a high prevalence of advanced OLGA/OLGIM stages and dysplasia.Aliment Pharmacol Ther. 2012; 35: 1451-1459Crossref PubMed Scopus (60) Google Scholar For individuals with GIM affecting both the antrum or corpus and with a family history of gastric adenocarcinoma the interval for surveillance may be adjusted for 1–2 years.4Pimentel-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: 365-388PubMed Google Scholar,5Banks M. Graham D. Jansen M. et al.British Society of Gastroenterology guidelines on the diagnosis and management of patients at risk of gastric adenocarcinoma.Gut. 2019; 68: 1545-1575Crossref PubMed Scopus (213) Google Scholar Also, for those individuals with a single site with IM but positive family history, incomplete IM or autoimmune gastritis diagnosed (or H pylori persistently present), a 3 years should be recommended.4Pimentel-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: 365-388PubMed Google Scholar,5Banks M. Graham D. Jansen M. et al.British Society of Gastroenterology guidelines on the diagnosis and management of patients at risk of gastric adenocarcinoma.Gut. 2019; 68: 1545-1575Crossref PubMed Scopus (213) Google Scholar In summary, clinicians and patients should be aware that GIM is a relevant marker for gastric adenocarcinoma and that surveillance of patients with marked and extensive GIM may lead to early diagnosis of gastric cancer and therefore improve prognosis and patients’ survival. These individuals at risk merit the proper surveillance every 3 years. The European Society of Gastrointestinal Endoscopy, in a recent position statement, recommended determining the quality of upper GI endoscopy by means of several parameters. These include time registration, adequate photodocumentation, standardized reporting, and the use of high-resolution/definition scopes.9Bisschops R. Areia M. Coron E. et al.Performance measures for upper gastrointestinal endoscopy: a European Society of Gastrointestinal Endoscopy (ESGE) Quality Improvement Initiative.Endoscopy. 2016; 48: 843-864Crossref PubMed Scopus (159) Google Scholar Adherence to these parameters is considered critical to ensure the quality of upper GI endoscopy and thus to decrease the frequency of missed neoplasias.6Pimenta-Melo A.R. Monteiro-Soares M. Libânio D. et al.Missing rate for gastric cancer during upper gastrointestinal endoscopy: a systematic review and meta-analysis.Eur J Gastroenterol Hepatol. 2016; 28: 1041-1049Crossref PubMed Scopus (100) Google Scholar Moreover, clinicians are now being supported by classifications for endoscopic assessment of the gastric mucosa with virtual chromoendoscopy, both by means of narrow band imaging10Esposito G. Pimentel-Nunes P. Angeletti S. et al.Endoscopic grading of gastric intestinal metaplasia (EGGIM): a multicenter validation study.Endoscopy. 2019; 51: 515-521Crossref PubMed Scopus (59) Google Scholar,11Buxbaum J.L. Hormozdi D. Dinis-Ribeiro M. et al.Narrow-band imaging versus white light versus mapping biopsy for gastric intestinal metaplasia: a prospective blinded trial.Gastrointest Endosc. 2017; 86: 857-865Abstract Full Text Full Text PDF PubMed Scopus (49) Google Scholar and blue light imaging.12Castro R.1 Rodriguez M. Libanio S. et al.Reliability and accuracy of blue light imaging for staging of intestinal metaplasia in the stomach.Scand J Gastroenterol. 2019; 3: 1-5Google Scholar These techniques allow visual determination of the presence of GIM and its extension. An endoscopic grading system for GIM was proposed and validated with both technologies. GIM can by virtual chromoendoscopy be recognized as the presence of regular mucosal pattern with tubulovillous changes (Figure 1). The extension of these changes can be determined in the antrum, incisura and corpus, both in the lesser and the greater curvature. If GIM is endoscopically determined during a first endoscopy, targeted biopsies should be done to histologically confirm and assess the type and extension of IM and the presence of H pylori infection. If no GIM is seen, biopsies may be done randomly at the lesser and greater curvature of the antrum and corpus with the same purposes. If GIM is present both in the antrum and corpus or incomplete IM is noted, a 3-year surveillance endoscopy should be offered. If any concerns are raised regarding the adequacy of the baseline gastroscopy quality, repeat gastroscopy should be considered with a 1-year interval. H pylori is the single most relevant risk factor for stomach adenocarcinoma and consistently all guidelines support that H pylori eradication should be offered to patients with GIM.13Sugano K. Tack J. Kuipers E.J. et al.Kyoto global consensus report on Helicobacter pylori gastritis.Gut. 2015; 64: 1353-1367Crossref PubMed Scopus (941) Google Scholar, 14Malfertheiner P. Megraud F. O'Morain C.A. et al.Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report.Gut. 2017; 66: 6-30Crossref PubMed Scopus (1763) Google Scholar, 15Mahachai V. Vilaichone R.K. Pittayanon R. et al.Thailand Consensus on Helicobacter pylori Treatment 2015.Asian Pac J Cancer Prev. 2016; 17: 2351-2360PubMed Google Scholar However, this is not the only measure that can contribute to the primary prevention of gastric cancer. Stopping smoking is an important additional factor. A change in smoking habits together with the decrease in H pylori prevalence is thought to have had the largest impact on gastric cancer incidence in the United States.16Yeh J.M. Hur C. Schrag D. et al.Contribution of H. pylori and smoking trends to US incidence of intestinal type noncardia gastric adenocarcinoma: a microsimulation model.PLoS Med. 2013; 10e1001451Crossref PubMed Scopus (30) Google Scholar In a prospective European study, adoption of a healthy diet and lifestyle was estimated to lead to a 47% and 77%, respectively, decreased incidence of distal and proximal gastric cancers.17Buckland G. Travieri N. Huerta J.M. et al.Healthy lifestyle index and risk of gastric adenocarcinoma in the EPIC cohort study.Int J Cancer. 2015; : 598-606Crossref PubMed Scopus (85) Google Scholar We aimed to provide clinicians a pragmatic approach to patients with gastric cancer precursors including adequate information regarding healthy habits and to acknowledge the potential of targeted surveillance (Table 1). In contrast with colorectal cancer, yet similar to esophageal cancer, population screening for gastric cancer and its precursors is not recommended in most Western regions. However, all upper GI endoscopies for any indication should include gastric cancer as an outcome to prevent. With an aging population that still commonly carries H pylori, gastric cancer will become a more prevalent problem with a prognosis that continues to be dismal.Table 1Pratical Approach to a Patient With GIM1. Check the completeness of baseline data to decide on the management of an individual patient; this should include the quality of baseline endoscopy, H pylori status, family history, extension, and type of GIM.2. Always provide state-of-art gastroscopy as an opportunity to determine the presence of gastric neoplasia and its precursors,3. Become familiar with the current classifications for VCE of the stomach.4. In all patients with GIM, treat H pylori and promote healthy habits (stop smoking, reduce salt intake and alcohol).5. If baseline data are incomplete or suboptimal in anyway, consider repeating the gastroscopy to provide assurance regarding missed lesions, H pylori status and staging of GIM in 1–3 years.6. In the absence of a positive family history, follow those patients with GIM affecting both antrum and corpus or incomplete IM every 3 years.7. For those with a family history of gastric cancer, a gastroscopy should be proposed every 1–2 years.8. For those with a negative family history, negative H pylori status and no GIM or GIM confined to the antrum, no surveillance should be proposed.9. During surveillance endoscopy exclude gastric cancer and, if negative for H pylori, use VCE to determine the condition of the gastric mucosa, while abstaining from biopsy sampling.GIM, gastric intestinal metaplasia; VCE, virtual chromoendoscopy. Open table in a new tab GIM, gastric intestinal metaplasia; VCE, virtual chromoendoscopy. Worldwide gastroenterologists may consider that the current available endoscopic equipment allow, after proper training, to easily detect individuals at risk (those with multifocal, extensive IM) that may likely benefit from targeted clinical management. Whenever individuals with such phenotype are identified a 3-year interval surveillance high-quality endoscopy should be proposed, if no further risk factors exist. These subjects only form a minority of all patients undergoing upper GI endoscopy and, therefore, a significant burden of care is not expected. On the contrary, prevention by easy measures may decrease the clinical burden owing to advanced disease.