Diagnostic Performance of Combined Assays for Gastrin-17, Pepsinogen and Anti-helicobacter Pylori Antibodies for Diagnosing Gastric Atrophy.

Gastric atrophy (GA), also referred to as atrophic gastritis, is a pre-neoplastic lesion in the development of intestinal-type gastric cancer (GC). It is defined as the loss of the normal glandular architecture of the stomach. It forms part of the so-called "Correa cascade", first described in 1988. This cascade posits that intestinal-type GC develops along a defined pathway of pre-neoplastic lesions. The initiation of this pathway is triggered by chronic inflammation affecting the gastric mucosa. The cause of this chronic inflammation is most commonly Helicobacter Pylori, although chronic autoimmune gastritis accounts for a minority of cases. The chronic inflammation over time causes the loss of the normal glandular architecture characteristic of gastric atrophy. With the ongoing presence of the initiating factor and persistence of the chronic inflammatory phenotype, the GA can progress to intestinal-type metaplasia and then to dysplasia and, ultimately, intestinal-type gastric cancer.

The precise risk of progression to GC in those with GA is poorly understood, particularly in lower-risk Western countries such as Ireland. In higher-risk countries such as Japan and South Korea, the reported risk may be as high as 0.1 to 0.3% per year. This is similar to the rates of malignant progression seen in low-risk colorectal adenomas and the risk seen in non-dysplastic Barrett's. This has prompted increased interest in the concept of surveilling patients with GA in the hopes of earlier identification of GC. Indeed, there is evidence to suggest that if Helicobacter Pylori is eradicated in patients with GA, the Correa cascade can be halted, and the risk of developing GC can be greatly reduced.

The British Society of Gastroenterology addressed this issue in their guideline document published in 2019. The guideline addresses several issues concerning managing patients at risk of developing Gastric Adenocarcinoma. Central to this is the concept of managing patients with GA. The guideline advocates for increased endoscopist awareness of the macroscopic features of the atrophic stomach. When recognised, the endoscopist should then take targeted biopsies as per the Updated Sydney System. This biopsy regimen involves taking Biopsies from the antrum, both lesser and greater curvature, the incisura and the gastric body again, both lesser and greater curvature. These biopsies should be sent to the lab in separately labelled specimen jars. The histological assessment should then be conducted using the Operative link for Gastritis assessment system, also known as the OLGA system. This classifies the severity of GA into 4 subtypes. There is evidence to suggest that patients with OLGA stage 3 or 4 GA should enter a 3-yearly surveillance program. This pathway is well established and in practice.

The issue currently, however, remains identifying patients with GA. With ever-increasing waiting lists for endoscopic procedures and growing numbers of dyspeptic patients, there is a need to triage referrals to increase the diagnostic yield from oesophagogastroduodenoscopies (OGDs). The use of Biomarkers to identify patients at risk of GA is one such potential pathway.

A panel of biomarkers (commercially available as the GastroPanel), including pepsinogen 1, pepsinogen 2, Gastrin 17, and IgG antibodies to Helicobacter pylori, has been shown to predict GA in high-risk regions. However, their efficacy in identifying GA in lower-risk Western cohorts of patients is less well known. This combination of biomarkers is instructive of the morphological state of the gastric mucosa. Pepsinogen 1 is produced predominantly by the chief cells of the oxyntic mucosa of the corpus and fundus of the stomach. Pepsinogen 2 is similarly produced by the chief cells but also by neck mucous cells, which are found in the oxyntic mucosa and the pyloric mucosa of the antrum and pyloric canal. Thus, in the setting of GA of the oxyntic mucosa, pepsinogen 1 levels will decrease to a greater extent than pepsinogen 2 levels. Gastrin 17 is a peptide produced by the G cells of the diffuse neuroendocrine system located in the pyloric mucosa of the antrum and pyloric canal. Decreased levels of Gastrin 17 are seen in the setting of GA of the pylorus. Thus, by evaluating the levels of these biomarkers, it may be possible to predict both the presence and topological extent of GA.