Diagnostics
Identifying patients most at risk of gastric carcinogenesis
There is a need for targeted, fast and reliable diagnostics at the point of patient care to identify curable precancerous disease stages that enable timely treatment and better patient outcomes for patients with gastric cancer. Dr. Cinzia Papadia, a Consultant Gastroenterologist at Barts Health NHS Trust and Honorary Senior Lecturer at Queen Mary University of London, discusses the use of a first-line case selection tool for gastric cancer risk.
Gastric cancer is responsible for over 4,000 deaths in the UK every year, and it is estimated that approximately 54 per cent of these cases could have been prevented with earlier detection and prompt intervention.1
In fact,
gastric carcinoma is the fourth most common cancer type worldwide and the second highest cause of death compared to all other malignancies.2,3
It is often diagnosed at a late
stage, which explains its low 5-year survival rate of between 10 and 30 per cent in Europe.4 Gastric cancer arises from the accumulation of
specific genetic changes combined with a mix of environmental influences. This means that there may be opportunities to prevent gastric cancer with strategies such as a healthy diet, therapies targeting H. pylori infection – which is strongly linked to an increased risk – and timely diagnosis through case selection and screening.5–7
Early
detection hinges on comprehensive assessments including endoscopic and histological evaluations, alongside the analysis of biomarkers such as pepsinogen I and II and gastrin-17. These biomarkers serve as a non-invasive tool for assessing gastric cancer risk by indicating atrophic gastritis – characterised by reduced stomach acid, malabsorption issues, anaemia and heightened infection risk – which is the most common preneoplastic condition for both intestinal and diffuse type gastric adenocarcinoma.5,8–10 The 2019 guidelines from the British Society of Gastroenterology (BSG)11
promote these
preventative strategies, recommending regular screening of at-risk populations and prompt intervention when precancerous conditions are detected. Moreover, the guidelines advocate using histologic tools like the updated Sydney System (USS) and Operative Link for Gastritis Assessment (OLGA) staging system to accurately categorise the severity and cancer risk associated with gastritis. Altogether, identifying relevant biomarkers, testing for H. pylori, and assessing gastritis severity through OLGA staging and endoscopic evaluation, make it
possible to detect gastric cancer at an earlier, more treatable stage, thereby improving survival rates.9,12,13
OLGA staging system The OLGA staging system plays a crucial role in standardising the evaluation of gastritis severity, combining histological findings with the distribution of atrophic changes in the gastric mucosa. This approach aims to stratify patients based on their cancer risk, allowing a degree of personalised surveillance and management. The OLGA system uses biopsy samples from the antrum, corpus and incisura angularis, scoring atrophy from 0 (none) to 3 (severe). These scores combine to determine an overall stage from 0 to IV: l Stage 0: no atrophy l Stage I: mild atrophy in the antrum l Stage II: mild to moderate atrophy in antrum and corpus
l Stage III: severe atrophy in the antrum and moderate in the corpus
l Stage IV: severe atrophy in both antrum and corpus
Higher stages (III and IV) correlate with a low ratio of pepsinogen I to pepsinogen II and indicate a significantly increased risk of gastric cancer, requiring close surveillance.12
Pepsinogen I The biomarker pepsinogen I is a precursor to the enzyme pepsin, which is crucial for digesting
proteins in the stomach. It is produced by the chief cells in the gastric glands of the stomach’s fundus and body. Measuring the levels of pepsinogen I in the blood can provide significant insights into gastric health; low levels are associated with atrophic gastritis.8,9
Pepsinogen II Pepsinogen II is another biomarker precursor to pepsin but, unlike pepsinogen I, it is not confined to the fundus and stomach body, but is also found in the antrum and duodenal mucosa. Elevated levels of pepsinogen II are often observed in patients with active H. pylori infection, a major risk factor for gastric cancer. The ratio of pepsinogen I to pepsinogen II is particularly significant; a low pepsinogen I/II ratio (below 3) is indicative of extensive gastric mucosal atrophy, which predisposes the patient to gastric cancer.8,9
Gastrin-17
Gastrin-17 is a hormone primarily produced in the antrum of the stomach that plays a key role in regulating gastric acid secretion by stimulating the parietal cells. Abnormal levels of gastrin-17 can indicate various gastric pathologies. Elevated levels are often associated with hypoacidity, a condition where the stomach produces insufficient acid – frequently due to corpus atrophic gastritis – that can lead to bacterial overgrowth and an increased risk of gastric cancer. Conversely, low levels may suggest hyperacidity or antral atrophy.8,9
H. pylori Pepsinogen I, pepsinogen II and gastrin-17 are all valuable for assessing the state of the gastric mucosa, but identifying H. pylori infection can provide valuable information about the cause of any abnormalities. There is a strong connection between H. pylori and gastrointestinal problems, and the bacterium has been classified as a group I carcinogen by the International
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