Bissett, IanO'Grady, GregKeane, Celia2021-09-292021-09-292020https://hdl.handle.net/2292/56692Low Anterior Resection Syndrome (LARS) is used to describe bowel dysfunction which patients experience after rectal cancer treatment. There is interest in the field as the accumulating evidence reinforces that LARS is common. However, lack of definition and complex pathophysiological mechanism have limited the ability to progress the understanding of LARS. The overall aims of this thesis are to critically advance the clinical understanding of low anterior resection syndrome (LARS) and propose a consensus definition of LARS. To achieve these aims, it was necessary to explore the current clinical definition, measurement, prevalence, and factors associated with LARS. Clinical and translational research methods were used including review and synthesis of the literature, a case-control study, secondary analyses of randomized control trials, a clinical trial, a Delphi survey and consensus meetings. Cross-sectional measurement of LARS in multiple populations (New Zealand, Australia, Sweden, Denmark) found that the majority of patients suffer from LARS after rectal resection. Cross-sectional assessment in a control group also provided the novel finding that there is a significant rate of similar symptoms in an age- and sex-matched non-operative population (major LARS 26%). Assessment of risk factors in non-controlled populations demonstrated the difficulty differentiating the effect of inter-related factors. Lower anastomotic height and radiotherapy were consistently associated with LARS and there was a suggestion that the use of an ileostomy may also be associated with LARS. Surgical approach showed no association with LARS. Differences in colonic motility after rectosigmoid resection, specifically in the cyclic motor pattern, were found using high resolution manometry. These were more pronounced in patients suffering from LARS supporting the concept of a rectosigmoid brake and offering insights into potential biomarkers and therapeutic options for LARS. An international consensus definition of LARS that incorporates both symptoms and consequences was constructed by reviewing the literature and consulting major stakeholders, including patients. This work provides a series of original contributions to the literature. The international consensus definition will allow future advances to standardise the measurement of LARS. The findings relating to use of an ileostomy and colonic motility may enable future advances in prevention, diagnosis, or treatment of LARS.Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated.Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated.https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htmhttp://creativecommons.org/licenses/by-nc-sa/3.0/nz/Thesis2021-08-02Copyright: The authorhttp://purl.org/eprint/accessRights/OpenAccessQ111963269