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The investigation of pressurised intraperitoneal aerosolised therapeutics for peritoneal metastases

Tate, Sophia 2021. The investigation of pressurised intraperitoneal aerosolised therapeutics for peritoneal metastases. MD Thesis, Cardiff University.
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Peritoneal metastases are a feature of many cancers. Cancer surveillance statistics in the UK do not record the incidence of specific metastatic locations so it is not possible to define the overall burden of disease. Patient outcomes from peritoneal metastases are generally poor, and current treatments have limitations. Peritoneal metastases therefore represent an area of unmet clinical need, and new therapeutic options are needed. Pressurised Intraperitoneal Aerosolised Chemotherapy (PIPAC) is a recent innovation. It involves a laparoscopic operation to deliver aerosolised chemotherapy into the peritoneal cavity. The systematic investigation of new surgical procedures like PIPAC in clinical trials is challenging. The IDEAL Framework is a paradigm for surgical innovation proposed by the Balliol collaboration to try and address the shortcomings of research in surgery. A service evaluation of the management of peritoneal metastases from colorectal cancer at Cardiff and Vale University Health Board was performed, allowing the incidence of peritoneal metastases in colorectal cancer patients over the period evaluated, and the treatments provided to be assessed. A systematic review of the literature on PIPAC was carried out, and the evolution of PIPAC, and its introduction to surgical practice was examined with reference to the IDEAL Framework. This work underpinned the introduction of PIPAC to the UK in Cardiff in 2018. An audit of the first cases was carried out using standards identified from the literature. This demonstrates that PIPAC is feasible and can be performed safely in an NHS setting. Pressurised Intraperitoneal Aerosolisation represents a potential delivery route for other therapeutics. Oncolytic adenoviruses are a promising strategy for cancer therapy. The feasibility of using the technique to administer viral vectors was assessed in vitro and in vivo. Adenovirus vectors were unaffected by aerosolisation, and retained their ability to transduce cells in vitro. Further investigation of this delivery method is warranted.

Item Type: Thesis (MD)
Date Type: Completion
Status: Unpublished
Schools: Medicine
Date of First Compliant Deposit: 16 August 2021
Last Modified: 16 Aug 2021 15:38

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