Where should gastric biopsies be performed when areas of intestinal metaplasia are observed?

Gastric cancer (GC) remains a major health problem worldwide, with a poor 5-year survival rate, partly due to its late diagnosis. Early detection can significantly increase survival and, therefore, identification of patients with higher GC risk (e. g. premalignant conditions) who may benefit from surveillance is essential for decreasing its mortality [1]. Intestinal-type adenocarcinoma, the most frequent histological type, is preceded by a cascade of precancerous lesions such as atrophic gastritis and gastric intestinal metaplasia (IM). Thus, in the absence of screening strategies in European countries, the MAPS II Guideline recommends opportunistic identification and follow-up of individuals at high risk [1], namely those with advanced stages of atrophic gastritis.

Because the correlation between white light endoscopy (WLE) and histological findings is poor and use of chromoendoscopy is cumbersome, two classifications of advanced atrophic changes based on random biopsies have been proposed: Operative Link for Gastritis Assessment (OLGA) and Operative Link on Gastritis/Intestinal Metaplasia (OLGIM). Some reports have shown that IM is the most reliable marker for this purpose due to its higher interobserver agreement, besides the lack of validated endoscopic pattern of atrophic gastritis. Hence, OLGIM to OLGA is preferable, under European Society of Gastrointestinal Endoscopy Guideline MAPS II, for staging gastritis [1]. However, to improve endoscopic diagnostic accuracy, different real-time techniques using imaging-enhanced endoscopy (IEE) emerged. The major advantages are that they are easy to employ and allow precise observation of the entire gastric mucosa and microvascular pattern. Prior reports evaluated the diagnostic efficacy of these technologies, most of them focusing on narrow-band imaging (NBI). A systematic review showed a pooled sensitivity and specificity of NBI of 0.87 and 0.77, respectively, for IM diagnosis, and 0.90 and 0.83 for dysplasia/cancer diagnosis [2]. More recently, our group reported excellent results in diagnostic yield of NBI in addition to high resolution-WLE (HR-WLE), achieving a global accuracy superior to 90 % in detection of IM and dysplasia [3].

In fact, the concept of random biopsies is now arguable with widespread use of virtual chromoendoscopy (CE) which, at the touch of a button, has been shown to significantly improve endoscopic-histological concordance. Due to the multifocal and patchy distribution presented in most cases of IM, biopsy samples (which represent only a very small part of the entire mucosa) are prone to sampling error, and for these reasons, it seems more logical to rely on endoscopic assessment of the entire mucosa to stratify GC risk instead of depending on random biopsies. But are CE-targeted-biopsies better than Sydney-Houston random biopsies for mapping? Results from some reports suggest that targeted biopsies are not inferior, but random biopsies may detect some cases of IM that are not identified with only NBI [4]. However, this difference does not appear to have a significant clinical meaning because most NBI missed areas will be mild and focal IM, so without necessity of surveillance in most cases. In fact, Buxbaum et al analyzed the diagnostic yield of mapping (biopsies according to the updated Sidney protocol) + WLE vs. NBI + WLE vs. NBI + mapping and the best results were with NBI + mapping (100 % detection of patients with IM and 94.7 % of gastric locations of IM [4]).

Consequently, considering the diagnostic yield of random biopsies and the possibility of missing important changes in the mucosa, this approach is being increasingly questioned and the possibility of replacing random with targeted biopsies is being suggested more and more. In this context, a new endoscopic classification of IM (Endoscopic Grading of Gastric Intestinal Metaplasia [EGGIM classification]) was proposed by our group, and recently validated in a multicenter study, showing a sensitivity of 89.4 % for identifying extensive IM (OLGIM III/IV) if EGGIM > 4 and > 99 % accuracy for excluding advance stages of gastritis if EGGIM 0 [5]. In fact, the MAPS II guideline recommends that whenever possible, virtual CE be used to target biopsies instead of performing random biopsies [1]. It would be reasonable to use a combined approach in which WLE would be followed by NBI examination, with exhaustive inspection of the mucosa and EGGIM calculation, in addition to targeted biopsies from suspicious areas for neoplasia; and if no endoscopic suspicion of IM, random biopsies can be performed (only) for Helicobacter pylori (Hp) diagnosis if applicable. This strategy would vary in accordance with different scenarios.

• References

• 1 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: 365-388
• 2 Kikuste I, Marques-Pereira R, Monteiro-Soares M. et al. Systematic review of the diagnosis of gastric premalignant conditions and neoplasia with high-resolution endoscopic technologies. Scand J Gastroenterol 2013; 48: 108-1117
• 3 Pimentel-Nunes P, Libanio D, Lage J. et al. A multicenter prospective study of the real-time use of narrow-band imaging in the diagnosis of premalignant gastric conditions and lesions. Endoscopy 2016; 48: 723-730
• 4 Buxbaum JL, 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 Endoscopy 2017; 86: 857-865
• 5 Esposito G, Pimentel-Nunes P, Angeletti E. et al. Endoscopic grading of gastric intestinal metaplasia (EGGIM): a multicenter validation study. Endoscopy 2019; 51: 515-521