Cytosponge

Cytosponge test for patients with chronic gastro-oesophageal reflux disease (GORD).

Background 

• Heartburn/regurgitation symptoms caused by GORD affect up to 20% of adults leading to significant annual healthcare costs. Most do not have a diagnosis and are treated over many years with acid-suppressant medication therapy. Symptoms of heartburn are important when one considers the link between heartburn and oesophageal adenocarcinoma (OAC). 

• It is estimated that 3–6% of individuals with GOR-predominant symptoms could have the precursor lesion to oesophageal adenocarcinoma, Barrett’s oesophagus. However, only around 20% of patients with Barrett’s oesophagus are diagnosed or known about. Therefore, most cases of oesophageal adenocarcinoma are diagnosed de novo, without the opportunity to prevent Barrett’s progression through surveillance. 
• The incidence of oesophageal adenocarcinoma is six times higher than it was in the 1990s. Oesophageal adenocarcinoma also has a poor prognosis due to late presentation, with an overall 5-year survival of less than 20%, despite advances in neoadjuvant therapy and surgery. 
• Treatment of dysplastic Barrett’s oesophagus prevents progression to adenocarcinoma; however, the optimal diagnostic strategy for Barrett’s oesophagus is unclear.  
• Clinical guidelines recommend urgent referral for an endoscopy in patients with warning symptoms, such as dysphagia and weight loss, and routine referral for an endoscopy in those with symptoms of gastro-oesophageal reflux that persist despite recommended lifestyle and pharmacological management strategies, and those with multiple additional risk factors for the disease. 
• Modelling using data from the USA estimated that the burden of oesophageal adenocarcinoma could be reduced by up to 50% through implementing strategies for the systematic screening and early diagnosis of Barrett’s in individuals with gastro-oesophageal reflux, who would otherwise not have been referred for an endoscopy. 

• Early detection needs to be combined with effective interventions to be clinically beneficial. There have been important advances in outpatient-based endoscopic therapies, which are now recommended for low-grade and high-grade dysplasia in Barrett’s oesophagus, with high rates of success (approx. 90%) and low rates of recurrence. 
• Patients with intramucosal stage I cancers have a survival of more than 90% and can be treated endoscopically, thus mitigating the risks of and side-effects from systemic therapy and an oesophagectomy, which is often required for more advanced disease. 
• The Cytosponge-trefoil factor 3 (TFF3) test (“Cytosponge”) is a non-endoscopic test for Barrett’s oesophagus – see section 3 (below) for details of the procedure. 
• Scottish government has approved and funded the roll out of Cytosponge as an alternative investigative modality to upper GI endoscopy for two groups of patients, the inclusion criteria being:
• Patients with reflux-predominant upper GI symptoms, who have been referred for upper GI endoscopy with concern of Barrett’s oesophagus, pre- or early oesophageal cancer 
• Patients with known Barrett’s oesophagus who are at risk of oesophageal cancer with progressive symptoms and/or who have had significant delay in their upper GI endoscopy.  

1. Cytosponge in NHS Borders

• Cytosponge is now established as our alternative to upper GI endoscopy for Barrett’s surveillance. 
• We are also using cytosponge as an alternative to endoscopy for certain symptomatic patients.

• Exclusion criteria for Cytosponge, as follows:
• Pregnancy 
• Significant dysphagia or swallowing disorders 
• Suspected or known chronic liver disease/cirrhosis 
• Oesophageal or gastric varices 
• Previous or Current Oesophageal Tumour 
• Recent invasive oesophageal procedure within the past 2 months e.g. dilatation, endoscopic mucosal resection (EMR), radiofrequency ablation (RFA) etc. 
• Previous oesophageal surgery including fundoplication  
• Patients in whom results would not influence further management as a result of severe co-morbidities or general fitness 
• Inability to give consent due to lack of capacity 

2. Cytosponge procedure in brief

• The Cytosponge test is performed in an outpatient setting e.g. clinic room. 

• Sedation is not required. 
• Fasting patients are asked to swallow a polyethylene sponge constrained inside a gelatine capsule, attached to a string.   
• Once in the stomach the capsule dissolves in 7 minutes, allowing sponge to expand.  
• It is then withdrawn up the oesophagus and retrieved by the person administering the procedure.  
• The sponge, containing exfoliated cells from the oesophagus, is placed in fixative and sent for laboratory analysis – cytological assessment and staining for expression of TFF-3 (an accurate marker of intestinal metaplasia, a key feature of Barrett’s) and p53 expression (a key marker of dysplasia).  

The entire procedure episode takes 10-15 minutes.  

Cytosponge (panels A,C,E) compared to standard upper GI endoscopy (panels B,D,F).  from Fitzgerald RC et al Lancet 2020;396 (10247):333-344.