Introduction
Extramural venous invasion (EMVI) is a poor prognostic factor in rectal cancer. It is detected by magnetic resonance imaging (MRI) and histopathological analysis. Neoadjuvant chemoradiotherapy (CRT) is often given to patients with locally advanced disease however the clinical outcomes of EMVI-positive tumours following such treatment remains unknown. This thesis aimed to investigate the radiological, pathological and molecular changes which occur in EMVI-positive tumours following CRT to determine whether these changes can predict prognosis.
Methods
Following a systematic review (SR) of EMVI in rectal cancer, a series of studies were conducted. Patients were identified from a prospectively maintained database of primary rectal cancers who were scheduled for CRT followed by curative surgery between 2006 and 2012. Imaging and pathology samples were reviewed and tissue samples were further processed for molecular profiling using micro-RNA analytical techniques. Data were correlated with disease-free survival (DFS), recurrence rate and patterns of relapse.
Results
SR demonstrated that EMVI is associated with locally advanced tumours, distant disease recurrence and worse overall survival. However there is a variation in technique and definitions which makes interpretation of historical studies problematic. EMVI is an important consideration in the multidisciplinary management of rectal cancer as most clinicians use it to influence treatment decisions. MRI may allow for improved detection rates of EMVI following CRT compared with routine histopathology techniques and it is an independent prognostic factor for recurrence at 3 years. Patients with persistent EMVI following CRT have improved DFS if given adjuvant chemotherapy. Finally, EMVI-positive tumours express specific patterns of microRNA sequences.
Conclusion

EMVI is a poor prognostic factor following CRT. Patients with evidence of EMVI may be considered for intensive adjuvant chemotherapy and more frequent surveillance for distant disease. Unique molecular signatures may hold the key for future management strategies. These results have led to the development of the MARVEL Study.