Around 10% of desmoid tumours (DT) in familial adenomatous polyposis
(FAP) patients grow relentlessly, causing major morbidity and mortality.
Radiological, clinical or cellular predictors of aggressive DT are yet to be
identified. The work described in this dissertation aimed to identify such
predictors by radiological studies, and to develop management guidelines
and identify possible targets for therapy.
Nine FAP patients with DT underwent 64 multi detector computed
tomography (64-MDCT), 1.5 Telsa magnetic resonance imaging (1.5T MRI),
Diffusion Tensor Imaging (DTI), Dynamic Contrast Enhanced MRI (DCE-MRI)
and Fluorine-18 Flurodeoxyglucose Positron Emission Tomography
(18F-FDG PET CT). Direct comparision between 1.5T MRI and 64-MDCT
found that MRI was at least equivalent to MDCT in the assessment of DT. DTI
was feasible and detected an anisotropic diffusion, which was less directional
than in muscle. Metabolic (FDG PET) and vascular imaging (DCE-MRI) of DT
demonstrated a spectrum of findings and found that DT were generally
hypovascular and poorly glucose avid.
A review of nine FAP patients with intra-abdominal desmoid (IAD) and air-fluid
level (AFL) on cross sectional imaging found that either a direct
communication or translocation of microorganism from bowel led to the
development of AFL. Some of these patients could be treated successfully
with antibiotics and/or a percutaneous drain; however, the majority
ultimately required complex surgery.
Full sequence APC mutation analysis performed in three primary DT cell
lines detected ‘second hit’ somatic mutation in only one, confirming the
establishment of a true DT cell line. A study of choline metabolism using
choline kinase alpha (CHKA) as a marker for activation, however, failed to
demonstrate up regulation of choline metabolism in desmoid tumour cells.
Studies of the Wnt signalling pathways confirmed the activation of canonical
Wnt signalling in DT. Interestingly Wnt11, a non-canonical Wnt, was also up
regulated in DT.