Steps to a faster diagnosis of gastric cancer
In previous blogs we have discussed the fact that gastric cancer is typically diagnosed at a very late stage, leading to extremely poor prognoses, and that these delays have been further exacerbated by the pandemic and resulting strain on endoscopy services. We have also spoken about the key to early diagnosis being the ability to detect pre-cancerous conditions such as atrophic gastritis (AG) and gastric intestinal metaplasia (GIM) before endoscopy, and the issues surrounding how this works in clinical practice.
In this blog we look a little closer at AG and GIM, and show how an understanding of these conditions and their timely diagnosis can both streamline NHS resources and improve patient outcomes.
What is atrophic gastritis?
AG is a high-risk, chronic inflammatory condition of the gastric mucosa that persists with time. Bacterial infection of the stomach lining can cause inflammation, and AG develops when this inflammation has been present for several years. Most often, this is a result of infection by Helicobacter pylori, which disrupts the mucus barrier that helps to protect the stomach lining from the acidic juices that aid digestion. If untreated, the cells in the stomach lining will slowly be destroyed causing thinning of the mucosa and loss of functioning glands such as the acid-producing parietal cells of the corpus. Autoimmune AG can also occur in some cases, when the immune system mistakenly attacks healthy cells of the stomach lining.
H. pylori infection spreads from person to person via direct contact with saliva, vomit or faeces, and can also occur as a result of ingesting contaminated food or water. Most commonly, infection occurs in childhood and worsens if left untreated. It is thought that 41% of gastric cancer cases are caused by H. pylori.
AG is usually asymptomatic, although if H. pylori infection is present then general symptoms such as stomach pain, loss of appetite, nausea/vomiting, anaemia and stomach ulcers may occur. Where the gastric mucosa has been damaged but an individual still has the capacity to secrete gastric acid, the risk of stomach ulcers increases, however as the parietal cell loss becomes widespread in the corpus, this can in turn lead to hypochlorhydria and eventually achlorhydria, which can then cause neurological issues due to nutritional deficiencies.
Most importantly, AG significantly increases the risk of stomach cancer. It has a prevalence of up to 8.3% in western populations, with 18% of AG cases progressing to cancer within 10 years. However, despite being such a high risk factor for gastric cancer, AG’s pre-cancerous lesions are often curable, reinforcing the need for early diagnosis.
What about gastric intestinal metaplasia?
GIM is common in cases of AG and occurs when the cells that create the stomach lining are changed or replaced with cells similar to those that create the lining of the intestines. Like AG, GIM is considered to be a pre-cancerous condition and predisposes individuals to intestinal type gastric adenocarcinoma and neuroendocrine tumours (NETs). H. pylori is again thought to be involved, as the bacteria can produce chemicals from some foods, which in turn cause the stomach cells to change.
GIM is primarily asymptomatic, however in some cases patients may experience H. pylori or acid reflux symptoms. As with AG, H. pylori infection is a risk factor, however smoking is also thought to increase the risk of GIM, as is having a first-degree relative with gastric cancer. Patients with GIM are often over 50 years of age, and it is more common in patients who also have AG.
As both of the above conditions can be either asymptomatic or have very general symptoms, a timely and accurate diagnosis – although crucial to a patient’s prognosis – is often very difficult to achieve. After clinical history and observation e.g. for stomach tenderness, stool antigen tests or urea breath tests for H. pylori infection may be carried out, and in some cases blood tests for levels of pepsinogen and gastrin. Tests for H. pylori can however be misleading as false negatives can often occur if a patient is for example on PPI treatment (even though this is contra-indicated in AG), and they also fail to pick up long-term infections as H. pylori cannot colonise pre-cancerous cells.
The current gold standard for diagnosing AG and GIM is gastroscopy with targeted biopsy histology to risk-stratify patients. Diagnosis of AG and GIM therefore relies heavily on the skilled endoscopist identifying the need for biopsies after the patient has been referred; a situation where 'suspicion' plays a big part. Which is a challenge in itself, because identification of atrophic and metaplastic lesions is difficult using standard white light endoscopy - the miss rate can be as high as 50% - and what's more the resource requirements are considerably greater when applying this subjective approach.
Current practice is not to 'seek out' AG and GIM pre-cancerous cases before endoscopy. This means that individuals with AG and GIM may remain undiagnosed in primary care for prolonged periods as they may not qualify for referral. On the other hand, from those that are referred for endoscopy the diagnostic yield is low. Although endoscopy is frequently used as part of the diagnostic process for AG and GIM, this often takes place too late for many patients – especially in the post-COVID world of clinic backlogs – or in some cases too early to detect to detect any pathological changes.
Meeting the clinical need
As AG and GIM are significant risk factors for gastric cancer, there is clearly a need to identify patients where these diseases are suspected, and prioritise them for endoscopic examination. The GastroPanel blood test from BIOHIT is ideal for this purpose as it diagnoses chronic atrophic gastritis and the associated risks in a primary care setting.
GastroPanel gives detailed information on the structure and function of the stomach mucosa, by quantifying pepsinogen I, pepsinogen II and gastrin-17, and can also differentiate the cause of AG by determining IgG antibodies to H. pylori.
GastroPanel could ideally be used in targeted groups of patients - for example smokers, those with query H. pylori, dyspeptic patients and/or those over 50 years of age – to identify those at most risk of developing gastric cancer and help direct gastroscopies. As it is a non-invasive blood test and can be requested in primary care, higher risk patients who need gastroscopy will be identified and referred. In addition to detecting more cancers at an earlier and more curable stage, reducing the amount of gastroscopies in lower risk patients will reduce both the cost and volume burden on healthcare resources without adversely affecting patient care.
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.
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