Non-Invasive Biomarkers & Mediators of Colorectal Inflammation and Neoplasia

In this thesis, I explore the utility of non-invasive biomarkers and mediators of colorectal inflammation and neoplasia, from the re-evaluation of established biomarkers such as the faecal immunohistochemical test in colorectal cancer surveillance, to the assessment of novel biomarkers for colorectal cancer and the significance of micronutrient deficiency in colorectal neoplasia, to the use of faecal biomarkers to measure severity in COVID-19 infection. Pertinent findings from the thesis include: i) FIT-triaged participants within an organised screening programme demonstrate significantly higher rates of advanced polyps and CRC compared to an age-matched symptomatic cohort. ii) Surveillance represents a significant burden with >30% of all screening colonoscopies performed with a low diagnostic yield of high risk findings. iii) Applying the FIT threshold used for index screening (>45µgHb/gF) or that for symptomatic triage (>10µgHb/gF) in screening surveillance results in suboptimal detection of high risk findings
iv) Caspase-4 represents a novel sensitive biomarker for CRC. v) Caspase-4 shows promise as a biomarker for advanced polyps. vi) Micronutrient deficiency does not impact upon colorectal neoplasia, however higher concentrations of ferritin and copper were associated with CRC. vii) Occult COVID-19 was not detected in a symptomatic IBD cohort reporting LGIS during the SARS-CoV-2 pandemic. viii) Faecal calprotectin may have utility as a biomarker of severity in patients with acute COVID-19 infection. There is a growing role for non-invasive diagnostic tests in the assessment and management of colorectal inflammatory and neoplastic conditions, driven by the increasing demand and limited availability of colonoscopy, advancements in the sensitivity of biomarkers and the challenges posed by the recent pandemic.