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Title: Enhancing microsurgical reconstruction after cancer resection
Author: Davis, Christopher Robert
ISNI:       0000 0004 9352 8057
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2020
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After mastectomy for breast cancer, breast reconstruction aims to increase quality of life. However, breast reconstruction offers no oncological advantage, microvascular tissue transfer may fail, microvascular anastomoses are technically challenging and local regional recurrences (LRR) occur. This thesis focuses on four specific aspects to enhance microsurgical reconstruction after cancer resection. Firstly, we used CT angiography to predict venous congestion – the principal cause of flap failure – in 202 patients. We found that atypical venous connections predict postoperative venous congestion (P<0.0001; PPV 83%) and potentially improves operative decisions to maximise flap survival. Secondly, motion analysis technology was applied to track microsurgical instruments during microvascular anastomoses. Results from objective motion analysis could predict surgical experience (Rho, +0.77; P<0.001), correlated with validated training scores (Rho, +89; P<0.001), and had high inter-rater reliability (α = 0.77). Thirdly, a thermoreversible poloxamer was refined for sutureless microvascular anastomosis using an FDA-approved tissue adhesive (2-octyl cyanoacrylate). The intravascular stent (45% P188) had 96kPa stiffness, transition temperature of 25oC, and without bovine serum albumin, which means the poloxamer has more desirable properties for potential clinical translation. Fourthly, gene therapy was used to covert autologous tissue into a novel oncological therapy. In a rodent model of LRR using breast cancer cells (MADB-106-Luc, rat mammary adenocarcinoma), autologous tissue was transduced ex vivo with an adeno-associated viral vector encoding interferon gamma (IFNγ) to create a therapeutic flap. The therapeutic reconstruction released IFNγ-immunotherapy that stimulated M1 macrophages to target cancer cells, decreased tumor burden (P<0.05) and increased survival (33%; P<0.05). Oncological benefits were also demonstrated using human triple-negative breast cancer cells (MDA-MB-231-Luc). These four approaches enhance microsurgical reconstruction after cancer resection with the overall goal of improving flap survival (Chapter 2, Imaging Data) using evidence-based training (Chapter 3, Motion Analysis Data) and a poloxamer stent (Chapter 4, Sutureless Anastomosis Data) to deliver novel oncological immunotherapy using therapeutic breast reconstruction (Chapters 5 & 6, Gene Therapy Data).
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available