Early Detection of Barrett's Esophagus in Participants With Reflux Symptoms in Primary Care (ELECTRONIC)

Early Detection of Barrett's Esophagus and Esophageal Cancer: Accuracy and Acceptability of a Novel Screening Strategy in Primary Care

In the Netherlands, the incidence of esophageal adenocarcinoma (EAC) is increasing. In addition, EAC has a dismal prognosis. Therefore, screening for Barrett's Esophagus (BE) has stimulated interest. Although BE is a known precursor of EAC, a minority of patients with EAC are known with a previous diagnosis of BE. A non-invasive screening tool, such as breath testing, could select patients at risk for BE, after which unsedated transnasal endoscopy (uTNE) can confirm or exclude the diagnosis. The objective is to determine the accuracy and acceptability of a non-invasive screening strategy i.e. breath testing followed by uTNE for BE and EAC.

The ongoing increasing incidence of esophageal adenocarcinoma (EAC) in the Netherlands during the last few decades and the still dismal prognosis has stimulated interest in screening for Barrett's esophagus (BE). Although BE is a known precursor of EAC, a minority of patients with EAC (<10%) are known with a previous diagnosis of BE, and hence, most cases of BE are undiagnosed. Screening programs to detect BE followed by endoscopic surveillance and treatment of dysplasia or early neoplasia seem able to reduce the incidence of EAC and improve survival. A non-invasive screening tool, such as breath testing, could select patients at risk for BE, after which unsedated transnasal endoscopy (uTNE) can confirm or exclude the diagnosis. uTNE offers the possibility of a more acceptable and accurate endoscopic assessment of the esophagus with almost neglectable risks and lower costs compared to conventional endoscopy. The objective is to determine the accuracy and acceptability of a non-invasive screening strategy i.e. breath testing followed by uTNE for BE and EAC.

The study design is a multi-site prospective cohort study in eight general practices. All participants will receive the breath test with the eNose in the general practice, followed by the uTNE in the hospital.

All participants will receive the breath test with the eNose in the general practice, followed by the uTNE in the hospital.

All participants will receive the breath test with the eNose in the general practice, followed by the uTNE in the hospital.

PPV of the eNose for detecting confirmed BE with the diagnosis made by transnasal endoscopy and upper endoscopy as the reference standard in primary care.

NPV of the eNose for detecting confirmed BE with the diagnosis made by transnasal endoscopy and upper endoscopy as the reference standard in primary care.

Sensitivity of the eNose for detecting confirmed BE with the diagnosis made by transnasal endoscopy and upper endoscopy as the reference standard in primary care.

Specificity of the eNose for detecting confirmed BE with the diagnosis made by transnasal endoscopy and upper endoscopy as the reference standard in primary care.

Patient acceptability consists of two questions regarding discomfort and overall experience of the eNose. Discomfort is measured on a Numeric Pain Rating Scale (NPRS) with 0 being 'none' and 10 being 'severe'. Overall experience is measured on a Numeric Pain Rating Scale (NPRS) with 0 being 'the worst experience', 5 being 'neither pleasant nor unpleasant' and 10 being 'the best experience'.

Patient acceptability consists of two questions regarding discomfort and overall experience of uTNE. Discomfort is measured on a Numeric Pain Rating Scale (NPRS) with 0 being 'none' and 10 being 'severe'. Overall experience is measured on a Numeric Pain Rating Scale (NPRS) with 0 being 'the worst experience', 5 being 'neither pleasant nor unpleasant' and 10 being 'the best experience'.

Patient acceptability (discomfort and overall experience) of conventional endoscopy (if applicable) measured on a NPRS.

Patient acceptability consists of two questions regarding discomfort and overall experience of conventional endoscopy. Discomfort is measured on a Numeric Pain Rating Scale (NPRS) with 0 being 'none' and 10 being 'severe'. Overall experience is measured on a Numeric Pain Rating Scale (NPRS) with 0 being 'the worst experience', 5 being 'neither pleasant nor unpleasant' and 10 being 'the best experience'.

The Cancer Worry Scale (CWS-8) is used to measure cancer worry. Scores are ranging from 8 to 32, and higher scores indicate more cancer worry.

At baseline, 7 days after eNose, 7 days after uTNE, 7 days after conventional endoscopy (if applicable), 30 days after eNose, 30 days after uTNE, 30 days after conventional endoscopy (if applicable), 90 days after last study procedure.

The State-Trait Anxiety Inventory (STAI-6) is used to measure anxiety. Scores are ranging from 6 to 24, and higher scores indicate more anxiety.

At baseline, 7 days after eNose, 7 days after uTNE, 7 days after conventional endoscopy (if applicable), 30 days after eNose, 30 days after uTNE, 30 days after conventional endoscopy (if applicable), 90 days after last study procedure.

The Impact of Event Scale (IES-15) is used to measure impact of event. Scores are ranging from 0 to 75, and higher scores indicate more impact of event.

7 days after eNose, 7 days after uTNE, 7 days after conventional endoscopy (if applicable), 30 days after eNose, 30 days after uTNE, 30 days after conventional endoscopy (if applicable), 90 days after last study procedure.

Inclusion Criteria: Patient aged 50 to 75 years; Recorded diagnosis of reflux symptoms >90 days OR Recorded prescriptions for acid suppressant therapy for this indication for at least 1 year in the past 5 years Written informed consent. Exclusion Criteria: Upper endoscopy in the previous 5 years; A current or previous diagnosis and/or treatment of any type of malignancy (not including basal-cell skin cancer (BCC) and squamous-cell skin cancer (SCC)) within the last five years; Already known with a diagnosis of Barrett's esophagus or gastro-esophageal cancer; Any argument provided by a patient's own general practitioner not to include the patient; Comorbidities precluding transnasal endoscopy (e.g. inability to discontinue oral anticoagulants, history of recurrent epistaxis, allergy to lidocaine derivatives).