Battersby, Christopher
(2021)
A Clinical and Scientific Study to Investigate the Influence of Statins on Anastomotic Healing in Colorectal Surgery.
Doctor of Medicine thesis, University of Liverpool.
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Abstract
Anastomotic leak remains one of the most devastating complications of colorectal surgery, as it is associated with increased morbidity and mortality, increased need for permanent stoma, increased risk of cancer recurrence, prolonged hospital admission and increased costs of healthcare. Anastomotic leak represents a failure of the complex process of tissue healing, therefore it must be regarded as a multifactorial complication, rather than as a single entity. Statins are amongst the most widely used drugs in the world, prescribed for the primary and secondary prevention of cardiovascular disease. Beyond lipid lowering, statins are known to have pleiotropic effects, which may exert a positive influence on processes fundamental to wound healing. Preliminary data from clinical studies suggests that statins may reduce the incidence of anastomotic leak. Hypothesis and Aims of this Study The hypothesis of this study is that statins promote processes fundamental to healthy tissue healing, and may therefore contribute to reducing the risk of anastomotic leak following colorectal surgery, and that the post-operative outcomes will be improved for patients taking statins. The aims of the study are to investigate whether statins exert an influence on colonic tissue healing. This thesis describes two studies run in parallel: a scientific study to investigate the effects of statins on primary cultured human colonic myofibroblasts, and a clinical study based on prospectively collected data from patients undergoing major colorectal surgery. Outcomes and Conclusions Atorvastatin, in concentrations equivalent to therapeutic doses, was shown to promote both the metabolic activity, and proliferation of primary cultured colonic myofibroblasts. Data was analysed from 113 patients in the clinical study, 38.9% of whom were taking statins at the time of the study. No difference was seen in the incidence of anastomotic leaks in patients taking statins, compared to those patients not taking statins, although the study population represented a relatively small cohort of patients with a low incidence of anastomotic leak (6 leaks out of 113 patients). The outcome from the clinical study raises the possibility that statins may represent a form of pharmacological prehabilitation, by normalising the risk of anastomotic leak in a population of patients with significant comorbidities, and a higher risk of anastomotic leak. The studies described in this thesis suggest that statins have an influence of processes fundamental to colonic tissue healing, and may contribute to reducing the risk of anastomotic leak. The potential direction for further studies to investigate this relationship is described.
| Item Type: | Thesis (Doctor of Medicine) |
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| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 15 Jun 2021 11:15 |
| Last Modified: | 18 Jan 2023 22:47 |
| DOI: | 10.17638/03122511 |
| Supervisors: |
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| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3122511 |
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