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Title: Mass spectrometric analysis of volatile organic compounds in oesophago-gastric cancer
Author: Kumar, Sacheen
ISNI:       0000 0004 5349 522X
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2015
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In the UK, oesophago-gastric (OG) cancer remains a disease with poor patient outcomes and only 35% of patients are suitable for potentially curative treatment at first presentation. Early detection of these cancers is necessary with Volatile Organic Compound (VOC) analysis being a promising area to explore for new endogenous biomarkers. In this research, the application of Selected-Ion Flow Tube Mass Spectrometry (SIFT-MS), a real-time technique, for the analysis of VOCs in biofluids and exhaled breath has been investigated. The primary aim of this research was to identify potential VOC biomarkers in oesophago-gastric cancer; the long-term application being the translational development of VOCs as non-invasive diagnostic tests. A total of 13 VOCs emitted from gastric content were investigated in the first study; acetone, formaldehyde, acetaldehyde, hexanoic acid, hydrogen sulphide, acetic acid, hydrogen cyanide and methyl phenol were found to be significantly different between oesophago-gastric cancer and healthy groups. In a study on the headspace of urine, acetaldehyde, acetone, acetic acid, hexanoic acid, hydrogen sulphide, methanol and phenol were found to be at significantly different concentrations between oesophago-gastric cancer, positive control and healthy groups. Methodology experiments including the optimisation of VOC sampling techniques with evaluation of exogenous contamination and variability measures have also been conducted. Investigation of reference ranges for C3-C10 aldehydes in healthy subjects using SIFT-MS have been undertaken for the first time; C4-C10 aldehydes were present in the exhaled breath of healthy persons at concentrations < 3 ppbv. In a study on 210 consecutive patients, increased concentrations of fatty acids, phenols and aldehydes were observed in the exhaled breath of patients with oesophageal and gastric adenocarcinoma. The potential effects of clinical confounding factors have been also assessed and possible explanations for the observed differences have been discussed. The results of the pilot study on acute infection demonstrated minimal influence on the cancer-linked VOCs in OG cancer, except for butanal. The analysis of gastric content, urine and exhaled breath have proven that trace compounds are more influential than abundant metabolites in upper gastro-intestinal malignancy. It is also demonstrated that VOC profiles rather than individual compounds are more accurate in the molecular-orientated diagnosis of oesophago-gastric cancer.
Supervisor: Hanna, George Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral