Studies of the gastro-oesophageal junction in normal and overweight healthy volunteers

Robertson, Elaine V. (2016) Studies of the gastro-oesophageal junction in normal and overweight healthy volunteers. MD thesis, University of Glasgow.

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Introduction: Oesophageal adenocarcinoma has increased dramatically in incidence over the past three decades with a particularly high burden of disease at the gastro-oesophageal junction. Many cases occur in individuals without known gastro-oesophageal reflux disease and in the absence of Barrett’s oesophagus suggesting that mechanisms other than traditional reflux may be important.

Distal squamous mucosa may be prone to acid damage even in the absence of traditional reflux by the mechanism of distal opening of the lower oesophageal sphincter. This is splaying of the distal segment of lower oesophageal sphincter allowing acid ingress without traditional reflux.

It has been suggested that the cardiac mucosa at the gastro-oesophageal junction, separating oesophageal squamous mucosa and acid secreting columnar mucosa of the stomach may be an abnormal mucosa arising as a consequence of acid damage. By this theory the cardiac mucosa is metaplastic and akin to ultra-short Barrett’s oesophagus.

Obesity is a known risk factor for adenocarcinoma at the gastro-oesophageal junction and its rise has paralleled that of oesophageal cancer. Some of this excess risk undoubtedly operates through stress on the gastro-oesophageal junction and a predisposition to reflux. However we sought to explore the impact of obesity on the gastro-oesophageal junction in healthy volunteers without reflux and in particular to determine the characteristics of the cardiac mucosa and mechanisms of reflux in this group.

Methods: 61 healthy volunteers with normal and increased waist circumference were recruited. 15 were found to have a hiatus hernia during the study protocol and were analysed separately. Volunteers had comprehensive pathological, physiological and anatomical assessments of the gastro-oesophageal junction including endoscopy with biopsies, MRI scanning before and after a standardised meal, prolonged recording of pH and manometry before and after a meal and screening by fluoroscopy to identify the squamo-columnar junction.

In the course of the early manometric assessments a potential error associated with the manometry system recordings was identified. We therefore also sought to document and address this on the benchtop and in vivo.

Key Findings:
1. In documenting the behaviour of the manoscan we described an immediate effect of temperature change on the pressure recorded by the sensors; ‘thermal effect’ and an ongoing drift of the recorded pressure with time; ‘baseline drift’. Thermal effect was well compensated within the standard operation of the system but baseline drift not addressed. Applying a linear correction to recorded data substantially reduced the error associated with baseline drift.

2. In asymptomatic healthy volunteers there was lengthening of the cardiac mucosa in association with central obesity and age. Furthermore, the cardiac mucosa in healthy volunteers demonstrated an almost identical immunophenotype to non-IM Barrett’s mucosa, which is considered to arise by metaplasia of oesophageal squamous mucosa. These findings support the hypothesis that the cardia is metaplastic in origin.

3. We have demonstrated a plausible mechanism of damage to distal squamous mucosa in association with obesity. In those with a large waist circumference we observed increased ingress of acid within but not across the lower oesophageal sphincter; ‘intrasphincteric reflux’

4. The 15 healthy volunteers with a hiatus hernia were compared to 15 controls matched for age, gender and waist circumference. Those with a hiatus hernia had a longer cardiac mucosa and although they did not have excess traditional reflux they had excess distal acid exposure by short segment acid reflux and intrasphincteric acid reflux.

Conclusions: These findings are likely to be relevant to adenocarcinoma of the gastro-oesophageal junction

Item Type: Thesis (MD)
Qualification Level: Doctoral
Keywords: Cardiac mucosa, Gastro-oesophageal junction, obesity, oesophageal cancer, hiatus hernia, thermal driftng.
Subjects: R Medicine > RC Internal medicine
Colleges/Schools: College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Supervisor's Name: McColl, Professor K.E.L
Date of Award: 2016
Depositing User: Dr E.V Robertson
Unique ID: glathesis:2016-7491
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 25 Aug 2016 07:38
Last Modified: 28 Sep 2016 13:52

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