This study aims to determine whether a breath test could be used for early detection of oesophageal cancer and Barrett's high grade dysplasia.

Patients who are attending for a planned gastroscopy or who are scheduled to undergo elective resection of histologically confirmed early stage oesophageal adenocarcinoma or dysplasia will be approached to provide a breath sample.

Multi platform mass spectrometry analysis will be performed to establish volatile biomarkers that can discriminate between early stage (T1) oesophageal cancer/ Hight grade dysplasia from non cancer healthy controls/non dysplastic Barrett's cancer.

The incidence of oesophageal adenocarcinoma has been rising over the last decade. Despite improvements in oncological and surgical therapies the associated survival remains poor, mainly due to delays in diagnosis and advanced stage at presentation. Identifying patients at earlier stages as well as those at risk of cancer may lead to survival benefit. Barrett's oesophagus is an established risk factor for the development of oesophageal adenocarcinoma. It has an established histopathologic progression from low-grade, through high-grade dysplasia (HGD) to oesophageal adenocarcinoma (OAC). Barrett's oesophagus patients currently undergo regular endoscopic surveillance to allow earlier detection of oesophageal cancer.

The primary objective is to evaluate the diagnostic accuracy and clinical utility of the volatile organic compounds (VOC) in exhaled breath to detect early stage oesophageal adenocarcinoma and high-grade dysplastic Barrett's oesophagus.

All patients will be fasted for a minimum of 6 hours prior to the breath sample as part of their routine clinical care. Breath collection will be conducted using a previously validated method. Samples of breath (500ml) collected using "breath collecting device utilising bags". Breath samples collected within thermal desorption tubes (Markes International, Llantrisant, UK) will be transferred to a central laboratory for analysis by gas chromatography mass spectrometry (GC-MS) and proton transfer reaction time of flight mass spectrometry (PTR-ToF-MS). Raw data files will be extracted and analysed in accordance with established protocols.

• Oesophageal Cancer
• Barrett Esophagus
• Barretts Esophagus With Dysplasia

• Control group
  Patients who are attending hospital for a gastroscopy as part of their routine clinical care as a 2 week wait rule referral and those on Barrett's surveillance , will be asked to give a sample of their breath prior to the procedure.
  Intervention: Diagnostic Test: Breath test
• Early oesophageal cancer (T1)/ Barrett's high grade dysplasia
  Patients who have known pre-diagnosed T1 oesophageal adenocarcinoma or HGD attending hospital as part of their clinical care will be asked to give a breath sample prior to their endoscopy resection/ cancer operation. Patients will be sampled upon return for follow up endoscopy to assess breath profile changes and correlation with endoscopy findings.
  Intervention: Diagnostic Test: Breath test
• Advanced Oesophageal cancer (T2/3/4)
  Patients who have been diagnosed with oesophageal adenocarcinoma attending hospital as part of their clinical care will be asked to give a breath sample prior to their endoscopy resection/ cancer operation.
  Intervention: Diagnostic Test: Breath test

Inclusion Criteria:

• ≥18 years and ≤90 years of age
• Undergoing gastroscopy or elective resection of histologically confirmed oesophageal adenocarcinoma/ high grade dysplasia
• Fasted >6 hours
• Able to provide informed written consent

Exclusion Criteria:

• Any patient <18 years or >90 years of age.
• Lacks capacity or is unable to provide informed written consent.

• Guts UK
• University College London Hospitals
• Guy's and St Thomas' NHS Foundation Trust
• Oxford University Hospitals NHS Trust
• Nottingham University Hospitals NHS Trust
• University Hospital Birmingham NHS Foundation Trust
• Salford Royal NHS Foundation Trust
• London North West Healthcare NHS Trust