Bridging the gap in gastric cancer diagnosis
Dyspepsia affects between 20-40 % of the population, with GPs in the UK commonly seeing patients with various symptoms relating to the upper gastrointestinal (GI) tract. Many cases are relatively straight forward to manage at the primary care level, but there can be a gap in the patient pathway for refractory cases where conventional intervention fails, or for those presenting with something potentially more sinister. This blog discusses the current limitations in managing patients with upper GI problems, and a potential solution to help streamline the screening process for gastric cancer.
The clinical puzzle
Chronic or recurrent GI problems can sometimes be a signal of something more serious, such as gastric atrophy (GA) or gastric intestinal metaplasia (GIM) – both precursors to gastric cancer – which are frequently (but not always) initiated by Helicobacter pylori infection. The British Society of Gastroenterology (BSG) recently updated its guidelines for the diagnosis and management of patients at risk of gastric cancer, which clearly state that the key to early cancer detection is to non-invasively detect pre-cancerous conditions, such as GA and GIM, before endoscopy. However the guidelines fall short of setting out a strategy of how this can be achieved in clinical practice.
In current practice there is an ambiguous interface between primary and secondary care in patients presenting with such GI problems. Patients often stay in primary care too long, and are referred at a later, less curable stage. Conversely, they are referred too soon, resulting in a low diagnostic yield with the majority of gastroscopies identifying no pathology. This is worrying to gastroenterologists – who feel they are missing disease cases – and adds to the ever-increasing burden on endoscopy resources, which has amassed a considerable backlog of referrals in the past year due to the COVID-19 pandemic.
These patients need to be investigated but hover in the vast chasm between primary and secondary care. A potential solution is to accurately screen patients with gastric symptoms, or within at-risk groups, in primary care – before referral – to more closely identify those who really need a gastroscopy. In vitro diagnostic tests can play a crucial role here yet in the UK, it seems we are still a long way away from this type of strategy. So what is the current recommendation for testing patients with upper GI symptoms and why should we be looking to change?
Public Health England guidance currently recommends a stool antigen test or urea breath test to identify H. pylori infection. Crucially, however, unless used correctly these tests may produce false-negative results (e.g. where an individual is receiving antacid therapy, or has AG) and they fail to show GA caused by long term H. pylori infection or autoimmune disease. Because AG is the most significant risk factor for gastric cancer, with 18 % of atrophic cases progressing to cancer within 10 years  it is imperative to identify these high-risk patients as early as possible.
Bridging the gap in the patient pathway
In 2019 European guidelines  containing recommendations for the management of precancerous conditions in the stomach were also updated ("MAPS II"). This official statement from an international group of experts comprising the European Society of Gastrointestinal Endoscopy (ESGE), the European Helicobacter and Microbiota Study Group (EHMSG), the European Society of Pathology (ESP), and the Sociedade Portuguesa de Endoscopia Digestiva (SPED), lists and explains recommendations for the diagnosis of precancerous conditions based on expert consensus. Amongst the evidence-based recommendations, one is pertinent to early detection and diagnosis:
"Low pepsinogen I serum levels or/and a low pepsinogen I/II ratio identify patients with advanced stages of atrophic gastritis, and endoscopy is recommended for these patients, particularly if H. pylori serology is negative." 
GastroPanel® is a blood test intended for dyspeptic patients presenting with stomach complaints that offers the solution needed at this interface in care. It enables GPs to confidently identify patients who can be managed symptomatically or otherwise should be referred to a specialist for gastroscopy. This pre-endoscopy non-invasive approach gives detailed information about the health and functionality of the stomach mucosa, as well as H. pylori status, by detecting and quantifying three stomach-specific biomarkers:
In addition, H. pylori IgG antibodies are determined. The results are then fed into a sophisticated algorithm to produce a detailed report with a written interpretation, which GPs can easily understand in primary care. This can help to improve the management of each patient appropriately, and reassures GPs by ruling out the presence of pre-cancerous conditions of the stomach.
The appropriate implementation of GastroPanel still needs to be considered in context to ensure the best use of resources. Widespread population screening is not recommended, but preferably an accepted cohort needs to be established – e.g. dyspeptic patients, >50 years of age, with a history of smoking and/or query H. pylori – to help accurately identify patients at risk of developing gastric cancer. Then, once the criteria have been refined, selectively screening higher risk patients in primary care will benefit patients and the healthcare system alike. Only those who need a gastroscopy will be identified and referred, potentially increasing the diagnostic yield, detecting more cancers at an earlier, more curable stage, and reducing both the cost and volume burden on healthcare resources.
To find out more about BIOHIT's GastroPanel, visit www.biohithealthcare.co.uk/gastropanel
About BIOHIT HealthCare
BIOHIT HealthCare is a Finnish biotech company, headquartered in Helsinki, that specialises in the development, manufacture and distribution of kits and assays for the screening, diagnosis and monitoring of digestive diseases. Its core disease focus areas include stomach health and dyspepsia, reflux and acid dysregulation, Inflammatory Bowel Disease (IBD), functional gastrointestinal disorders (FGID), Irritable bowel syndrome (IBS), and gut microbiota dysbiosis.
Innovating for Health
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Public Health England (2014). Test and treat for Helicobacter pylori (HP) in dyspepsia. Quick reference guide for primary care: For consultation and local adaptation. Available at: https://www.bsg.org.uk/clinical-resource/test-and-treat-for-helicobacter-pylori-hp-in-dyspepsia/ (Accessed: 30/07/2021).
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Pimentel-Nunes P, Libânio D, Marcos-Pinto R, et al. Management of 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 the Sociedade Portuguesa de Endoscopia Digestiva (SPED) guideline update 2019. Endoscopy. 2019; 51: 365–388.