Tucker, Emily C.
(2015)
Development of novel methods of assessment in oesophageal and gastric function.
DM thesis, University of Nottingham.
Abstract
The objective of this thesis was to develop new methodologies to assess upper gastro-intestinal function in health and disease. Several different technologies were studied in a range of upper gastro-intestinal diseases and adapted to try and provide more meaningful insights. The thesis has three main sections.
In the first section, High Resolution Oesophageal Manometry (HRM) was used to assess unexplained upper gastro-intestinal symptoms in a group of patients referred to a tertiary centre. 46 patients were diagnosed with rumination syndrome following HRM. A retrospective review was completed of these patients case notes and HRM data. The predominant aim of this section was to identify if common mechanisms exist within rumination and its variations and to establish if the variety of presenting symptoms is due to different underlying problems or a common behavioural response to a variety of stimuli, with symptoms being dependent on the circumstance the behaviour exists in. This would support a generic biofeedback technique being useful regardless of presenting complaint.
Comparing the variety of symptoms, exhibited behaviour and manometric findings, a new classification system for rumination was then developed;
1. Primary or “classical” rumination
a. Increase in abdominal strain with corresponding rise in intra-gastric pressure and return of gastric contents to the mouth
2. Secondary or reflux-related rumination
a. Reflux event causes the patient to respond with increase in intra-abdominal muscle strain and subsequent rumination
3. Supra-gastric belching independent of meals.
a. Rise in intra-gastric pressure whilst a closed gastro-oesophageal junction, therefore producing rapid belching of air from the oesophagus without any return of gastric contents
Generic biofeedback therapy was used (regardless of presenting symptoms) to control the abnormal behavioural response to symptoms. 20/46 patients reported full resolution of their symptoms and a further 13 / 46 reported improvement in their symptoms with this, while underlying mechanisms were targeted e.g. reflux with proton pump inhibitors, pain in functional dyspepsia.
In the second main section of this thesis, gastro-oesophageal reflux disease (GORD) is considered. GORD is currently diagnosed by 24 hour pH studies. These are often difficult for patients to tolerate and require time off medication. A more attractive method would be for diagnosis to occur at the same time as gastroscopy. A novel instrument is the EndoFLIP® device. This measures cross-sectional area (CSA) and distensibility at the gastro-oesophageal junction (GOJ) via a long catheter with a balloon at the end that straddles the GOJ. It has been hypothesised that these measurements will be increased in those with GORD, as the GOJ is more distensible, allowing more retrograde movement of gastric contents. The aim of this section of the thesis was to establish if GOJ CSA and distensibility differentiate between healthy volunteers (HV) and GORD patients based on i) symptoms and ii) prolonged oesophageal acid exposure.
21 HV and 18 patients with GORD (based on symptoms) had EndoFLIP® measurements and wireless pH studies to assess this. 14% of HV and 50% GORD patients had pathological acid exposure. CSA and distensibility were both significantly higher in the HV’s compared to GORD patients. However, there was an inverse correlation between CSA and body mass index (BMI) which was significantly higher in the patient population. This may explain differences seen due to corresponding higher intra-abdominal pressure in those individuals with a high BMI, sub-sequentially affecting the CSA and distensibility. The complex structure of the GOJ and multiple factors involved in the pathogenesis of GORD present difficulties in using EndoFLIP® to diagnose GORD. It may find applications in other areas, such as serial measurements in single patients.
In the final section of this thesis, gastric emptying is the focus and its pathogenesis in functional dyspepsia (FD). Current gastric emptying studies only find abnormalities in approximately 40% of patients with FD. Gamma scintigraphy is used in routine clinical practice for gastric emptying studies. Magnetic resonance imaging (MRI) is emerging as a modality in gastric emptying assessment and potentially provides additional information.
This thesis hypothesised that standard gastric emptying studies may not be measuring the parameters reflective of underlying pathophysiology in FD. Also, most have a relatively small meal size that may be too small to trigger dysfunction. MRI may provide additional insights as can assess gastric contents and surrounding structure (unlike GS). To investigate these a 400ml test meal was utilised and gastric emptying parameters i) gastric contents volume at time 0 (GCV0, representative of early emptying), ii) gastric emptying rate at the time taken for half the meal volume to empty (GE rate @T50, representative of later emptying) and the more traditional measurement iii) time taken for half the gastric contents to empty (T50) in bopth GS and MRI studies. The hypothesis of this study is that early emptying is more rapid in FD due to impaired accommodation (therefore a lower GCV0) leading to a slower later emptying (therefore a lower GE rate @ T50). Following validation studies in a large healthy population (n=53), GS and magnetic resonance imaging (MRI) studies with a test meal of 400ml were used in 8 FD patients and 24 matched HV (from the pool of HV) . FD had a significantly lower BMI. Early emptying (represented by gastric contents volume after ingestion of meal (GCV0)) was significantly lower in GS for FD patients but higher in MRI. Time for half the meal to empty (T50) and gastric emptying rate at T50 (GE rate @T50) were similar. The difference between the two modalities was thought to be due to increased secretion production in the patients, which is measureable in MRI but not in GS. A further study with a solid component of 12 non-nutrient agar beads in addition to the liquid component was completed. 24 HV’s, 17 FD patients and 11 gastro-oesophageal reflux disease (GORD) patients were studied. FD patients and GORD patients had rapid early gastric emptying in comparison to HV in gamma scintigraphy (represented by GCV0) but higher GCV0 in MRI (significantly so between HV and GORD), suggesting increased secretion production is present in both conditions. These findings do support impaired fundal accommodation within the FD population but that other factors, such as secretion production and the rate of this in comparison to gastric emptying are important in the later stages of emptying. Further work is ongoing within the MRI department to quantify and measure the emptying of these secretions.
This thesis explores how existing and new technologies can be applied to clinical conditions to identify possible pathophysiology and potential targets for treatment. Only by these ongoing efforts can we endeavour to improve the care we deliver to our patients.
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