The role of capsule sponge testing in early detection of Barrett’s oesophagus and oesophageal adenocarcinoma

Chien, Siobhan (2026) The role of capsule sponge testing in early detection of Barrett’s oesophagus and oesophageal adenocarcinoma. MD thesis, University of Glasgow.

Abstract

Barrett’s oesophagus is the precursor lesion to oesophageal adenocarcinoma (OAC). Barrett’s oesophagus can transform through a stepwise series of dysplastic change prior to evolving into invasive OAC. High-quality surveillance programmes permit early diagnosis of dysplasia, at which point treatment can potentially be endoscopic and improve outcomes in a disease with a dismal 5- year prognosis of <20%. Furthermore, the development of population-based screening programmes for this condition could present an additional opportunity to transform clinical outcomes. At present, Barrett’s surveillance is performed using upper gastrointestinal (UGI) endoscopy. However, endoscopy services are under significant strain across the country, with demand outstripping capacity on a national level. Furthermore, UGI endoscopy is not a perfect test: the rate of abnormalities missed at endoscopy is not insignificant, highlighting the difficulty in maintaining consistent quality with this investigation. Innovative technologies are undoubtedly required to aid endoscopy services.

Capsule sponge testing is one such novel technique that offers promising results in the detection of Barrett’s oesophagus (and potentially OAC) within the clinical trial setting. However, real-world data supporting its use has been lacking to date, and its role in the cohort of patients with an established diagnosis of Barrett’s oesophagus has yet to be critiqued in clinical practice. Scotland was the first country to introduce capsule sponge testing into clinical practice in a national pilot programme triggered by the Coronavirus pandemic for patients undergoing Barrett’s surveillance, as well as those referred to secondary care with symptomatic reflux. This thesis aims to present the results of this national programme and evaluate the role of capsule sponge testing beyond the trial setting, addressing the hypothesis that capsule sponge testing could be utilised as a safe and effective triage tool to UGI endoscopy in the above populations long-term beyond the pandemic.

Chapter 2 presents the results of the Scottish pilot programme in a national pragmatic implementation study in the context of Barrett’s surveillance. Of the 4204 capsule sponge tests performed for Barrett’s surveillance, 608 patients proceeded to UGI endoscopy within 12 months, with 50/608 patients (8.2%) identified as having high grade dysplasia (HGD) or cancer on endoscopic biopsies. 46/50 patients (92.0%) were identified as high-risk on capsule sponge testing, triggering urgent endoscopy. This rose to 100% when insufficient tests were removed from analysis, demonstrating that capsule sponge testing is effectively identifying high-risk patients for dysplasia or cancer that require further investigation with urgent endoscopy.

Chapter 3 then evaluates the impact of delayed Barrett’s surveillance on endoscopic pathology yield, as well as determining if the Scottish pilot programme has reduced delays to surveillance. As surveillance delay increased beyond 24 months, patients were significantly more likely to develop dysplasia or malignancy (p<0.001). In Year 1 versus Year 2 of the programme, there was a longer median delay to surveillance (9 vs. 5 months; p<0.001) and an increased proportion of patients with delayed surveillance (72.6% vs. 57.0%; p<0.001), implying that the Scottish capsule sponge programme has reduced delays to usual Barrett’s surveillance imposed by the pandemic.

Chapter 4 then assesses the impact of capsule sponge testing on Barrett’s dysplasia yield in a single Scottish health board, by comparing the 2-year period pre- and post-implementation of the service, as well as directly comparing endoscopic biopsy results in patients undergoing capsule sponge testing (+/- subsequent endoscopy) versus those undergoing traditional endoscopic surveillance in a single health board. These results demonstrated no significant differences in the rates of HGD, intramucosal cancer (IMC) or invasive cancer diagnosed between the groups, although yield of indefinite for dysplasia (IND) and low grade dysplasia (LGD) cases was higher in the endoscopic surveillance cohort.

Chapter 5 analyses the impact of the introduction of capsule sponge testing on Barrett’s surveillance endoscopy services in a single Scottish health board. These results demonstrated that dysplasia or cancer was significantly more likely to be present in endoscopic biopsies after capsule sponge testing was implemented (p<0.001). This implies that the introduction of capsule sponge testing has refined the local endoscopy service to focus on those most likely to have pathology, with a concurrent reduction in the proportion of endoscopies performed for non-dysplastic Barrett’s oesophagus only. In addition, 28.0% fewer endoscopies were performed for Barrett’s surveillance after capsule sponge testing was introduced.

Chapter 6 then evaluates longer-term follow-up outcomes in the lower risk patients initially undergoing capsule sponge testing for Barrett’s surveillance by comparing those who had UGI endoscopy versus repeat capsule sponge testing as their next follow-up. Again, there were no significant differences in the rates of HGD, IMC and OAC between the groups. Traditional endoscopy detected more cases of IND (4.2% vs. 0.9%; p=0.012) and LGD (3.6% vs. 0.9%; p=0.032). Chapter 6 also compares use of the Cytosponge™ versus EndoSign® capsule sponge devices for the first time. The EndoSign® device detected a higher proportion of trefoil factor 3 (TFF3) positive cases compared to Cytosponge™ (72.3% vs. 48.2%; p<0.001), with both devices demonstrating sound reproducibility.

Moving beyond the Barrett’s surveillance population, Chapter 7 presents the first real-world results of a national prospective cohort study evaluating the clinical application of capsule sponge testing in symptomatic reflux disease based on endoscopic biopsy results. With insufficient tests excluded, 16.6% of patients undergoing UGI endoscopy were found to have IM on endoscopic biopsies, which strongly correlated with positive biomarkers (88.5% vs. 11.5%; p<0.001), including one case of dysplasia. These results suggest that capsule sponge testing is also an effective triage tool to endoscopy in symptomatic reflux patients when combined with clinical assessment.

Finally, Chapter 8 aims to establish whether combining TFF3 result on capsule sponge testing with markers of systemic inflammation, specifically raised neutrophil-lymphocyte ratio (NLR), can effectively rule out Barrett’s oesophagus within the symptomatic reflux population. This study concluded that the combination of TFF3 negativity and normal NLR excluded IM in 99.6% of cases, providing excellent reassurance to clinicians aiming to discharge patients from secondary care and prioritise access to endoscopy resources.

In summary, this thesis has demonstrated positive results for capsule sponge testing in clinical practice on a national level, provisionally supporting its use as a triage tool to endoscopy beyond the pandemic. However, further work focusing on long-term follow-up of these patients is required before capsule sponge testing can be formally integrated into clinical pathways in the future.

• Item Type: Thesis (MD)
• Qualification Level: Doctoral
• Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Supervisor's Name: Glen, Professor Paul and Chang, Professor David
• Date of Award: 2026
• Depositing User: Theses Team
• Unique ID: glathesis:2026-85951
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 21 May 2026 15:01
• Last Modified: 21 May 2026 15:17
• Thesis DOI: 10.5525/gla.thesis.85951
• URI: https://theses.gla.ac.uk/id/eprint/85951

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