| dc.description.abstract | Introduction
The assessment and management of rectal cancer is complex, involving clinicians
from several specialities, with a broad and expanding range of therapeutic options.
As oncological outcomes have improved, the preservation of functioning sphincters
with avoidance of long-term functional problems, and the negative impact that these
have on quality of life, is a priority in the management of rectal cancer.
Aims and objectives
This thesis aimed to discover what determines the ability to preserve functioning
sphincters during the management of low rectal cancer.
Objectives were (1) to systematically review the evidence base for treatment of rectal
cancer (2) to determine the proportion of patients following anterior resection in the
UK with low anterior resection syndrome (LARS) and identify risk factors (3) to
determine ability of measures derived from diffusion-weighted MRI (DWI) to
predict and assess response to neoadjuvant chemoradiotherapy (CRT) in rectal
cancer (4) to identify microRNA targets with potential as predictive biomarkers of
response to CRT and (5) to define altered sphincter function following anterior
resection and CRT using high-resolution anorectal manometry (HRAM).
Methods
Objective 1: A systematic review of the current literature. Objective 2: A prospective
epidemiological cohort study using LARS and QLQ-C30 quality of life
questionnaires. Objective 3: A retrospective cohort study of patients undergoing
DWI for rectal cancer. Objective 4: A retrospective MicroRNA profiling using pretreatment
rectal cancer biopsies. Objective 5: A prospective cohort study of rectal
cancer patients undergoing HRAM.
Results
A review of the literature showed that there is data on oncological outcomes
following sphincter preserving rectal cancer surgery, but data on functional
4
outcomes is limited. 1093 participants completed the LARS questionnaire, 22% had
minor LARS and 41% major LARS. The risk factors for LARS identified by the study
were neoadjuvant radiotherapy, defunctioning stoma, female gender and younger
age. The DWI study included 39 patients and found that use of DWI was feasible and
that measures derived from DWI show potential as non-invasive biomarkers for
predicting and assessing response to CRT in rectal cancer. The laboratory study
confirmed that analysis of microRNA expression from rectal biopsy tissue from 28
patients was feasible and that, with further study, microRNAs could possibly act as
predictive biomarkers for response to neoadjuvant therapy. 51 patients underwent
HRAM, which showed potential for being a tool to help improve assessment and
understanding of pre and post treatment sphincter function in patients with rectal
cancer.
Conclusions
Patients undergoing sphincter-preserving surgery for rectal cancer are at risk of
developing LARS. This has a long-term impact on quality of life. Neoadjuvant
therapy significantly increases risk of LARS. Imaging and laboratory studies
confirmed that DWI and microRNA analysis are feasible approaches to the
identification of potential biomarkers; with further study these could meet the aim of
individualised therapy and limit use of neoadjuvant therapy to preserve anorectal
function where possible. The exact pathophysiology behind LARS remains
unexplained; HRAM can be used as an investigative tool to improve this
understanding with the aim to preserve function. Multicentre prospective studies
incorporating all of these methods are required. | en_US |
