Do We Need Multiple Biopsies for Assessing Gastric Cancer Risk?

Abstract

It is widely accepted that differentiated-type gastric cancers evolve through a multistep process starting with Helicobacter pylori-associated superficial gastritis, followed by atrophy, intestinal metaplasia (IM), dysplasia, and finally carcinoma [1]. Thus, the identification of such precancerous condition and follow-up of patients in whom they are found could lead to the diagnosis of gastric cancer at early stage and improved patient survival. However, diagnosis of atrophy and IM by conventional white light endoscopy has high inter-observer variability [2] and a poor correlation with histological findings [3]. Consequently, the diagnosis of atrophy or IM is currently based on histology of biopsy specimens from certain anatomic locations of the gastric mucosa, i.e., the updated Sydney system [4]. This system recommends taking at least five biopsy specimens (two from the antrum, two from the corpus and one from the incisura angularis) to grade severity of neutrophils (activity) and lymphocytic infiltration (inflammation), glandular atrophy (atrophy), and intestinal metaplasia. A recent Western publication proposes a staging system to classify gastric cancer risk in clinical practice on the basis of the histological findings of multiple biopsies [5]. The reason for taking biopsies from multiple sites in the stomach is that the grade and distribution of gastritis are different at each site of the stomach in a patient with chronic atrophic gastritis. Mapping studies of biopsy findings suggested that chronic atrophic gastritis develops from the lesser curvature of the lower gastric body and extends upward and laterally in the corpus [6]; therefore, knowledge of the biopsy site is important to interpret histological finding of gastritis in multiple biopsy specimens. When we investigated association between gastric cancer risk and histological grade of gastritis at the each biopsy site in the stomach, the presence of IM in the lesser curvature of the corpus had the strongest association with cancer risk among other findings of gastritis in the other sites [7]. Although gastritis is regarded as a histological entity, many attempts have been made to diagnose the disease macroscopically during esophagogastroduodenoscopy (EGD). Kimura et al. [8] suggested that the endoscopic finding of atrophic mucosa was pale yellowish mucosa with increased mucosal vessel visibility, indicating that it was related to histological finding of atrophy of fundic gland (pseudo-pylorization) by step-wise biopsy across the endoscopic atrophic border. When the atrophic border remained on the lesser curvature of the corpus, the diagnosis was made as closed-type atrophic gastritis (antral predominant gastritis), whereas when the atrophic border no longer exists on the lesser curvature and extends along the anterior and posterior walls of the stomach, the diagnosis was made as open-type atrophic gastritis (pangastritis or corpus predominant gastritis). This endoscopic diagnostic criterion is commonly accepted and practically used for the diagnosis of chronic atrophic gastritis in Japan. Actually, Uemura et al. [9] indicated that extent of mucosal atrophy diagnosed by endoscopy was associated with risk for development of gastric cancer in a large-scale cohort study. In contrast to point evaluation of gastritis by biopsy, endoscopy is advantageous to evaluate the actual extent and distribution of atrophy or IM in the gastric mucosa that is related to gastric carcinogenesis. Ahn et al. [10] showed that mucosa in patients with open-type atrophic gastritis had more IM and Cdx2 N. Uedo (&) Department of Gastrointestinal Oncologym, Endoscopic Training and Learning Center, Osaka Medical Center for Cancer and Cardiovascular Diseases, 3-3 Nakamichi 1-chome, Higashinari-ku, Osaka 537-8511, Japan e-mail: uedou-no@mc.pref.osaka.jp