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Prevalence and detection of serrated colorectal neoplasia in a screened population

Ramaraj, Rajeswari 2023. Prevalence and detection of serrated colorectal neoplasia in a screened population. MD Thesis, Cardiff University.
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Introduction: Serrated lesions (SL), precursors of colorectal cancer (CRC), account for 15 to 30% of all CRC cases. Post-colonoscopy CRC (PCCRC) may occur due to missed proximal serrated neoplasia. Existing heterogeneity in SL reporting and detection makes the actual prevalence uncertain. This study aims to assess the feasibility of introducing enhanced colonoscopy and estimating proximal SL detection and prevalence. Method: A multicentre randomised controlled trial was conducted in bowel cancer screening centres in Wales. Participants aged 60-74, testing positive for faecal occult blood, were randomised to undergo standard white light colonoscopy or chromocolonoscopy. All removed proximal colon polyps were centrally reviewed by expert pathologists. Data analysis included serrated neoplasia detection rate, procedural time, resource utilisation, and interobserver variability among pathologists. A subsequent genetics exploratory study was conducted using Next Generation sequencing. Results: The study recruited 741 patients, achieving 82% patient participation and 87% colonoscopists. The chromocolonoscopy procedure was marginally longer (6.3 minutes) and showed enhanced detection rates for proximal sessile serrated lesions (11.8% vs 6.4%) and significant serrated lesions (4.2% vs1.9%). Central histopathology review revealed a higher prevalence of significant serrated neoplasia in the proximal colon (7.6% vs 3.3%). There was good concordance for non-dysplastic SLs however this was fair for dysplastic SLs. Lastly, an exploratory study revealed the feasibility of extracting DNA from FFPE blocks with a weak mutational signature in ex-smokers, albeit with significant background noise. Conclusions: This study demonstrated that chromocolonoscopy could be implemented in a UK-based population bowel screening programme for improved detection of proximal serrated neoplasia with acceptable time and resource usage, and bias minimisation. Further trials and longitudinal studies to assess clinical effectiveness, economic evaluation, translational studies, and the impact on surveillance and reducing PCCRC is necessary.

Item Type: Thesis (MD)
Date Type: Completion
Status: Unpublished
Schools: Medicine
Date of First Compliant Deposit: 8 March 2024
Last Modified: 08 Mar 2024 11:49

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