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We have been investigating PDT with 5 aminolaevulinic acid (ALA) for the treatment of high grade dysplasia (HGD) in
Barrett's oesophagus (BO) for over a decade. This drug has inherent advantages over porfimer sodium (Photofrin), the
current approved photosensitiser in the UK and USA, which causes strictures in 18-50% and light sensitivity for up to
three months. ALA has a lower rate of oesophageal strictures due to its preferential activity in the mucosa, sparing the
underlying muscle, and patients are only light sensitive for 1-2 days.
Within a randomised controlled trial, we demonstrated that an ALA dose of 60mg/kg activated by 1000J/cm red laser
light is the most effective. Using these values we achieved complete reversal of HGD at 1 year in 89% of 27 patients.
A randomised controlled trial of ALA vs porfimer sodium PDT for HGD is currently under way with end points of
efficacy and safety. 50 of 66 patients have been recruited. Preliminary data suggest ALA PDT is safer with a trend to
higher efficacy.
Late relapse can occur in 20% of patients. New prognostic markers, in particular aneuploidy, are helping us to identify
and target patients at risk of late relapse. Furthermore optical biopsy techniques such as elastic scattering spectroscopy
(ESS) may allow detection of nuclear abnormalities in vivo and enable us to target areas of interest whilst reducing
sampling error.
PDT faces new challenges for the treatment of HGD in BO, with the recent introduction of balloon based radiofrequency
ablation. This technique appears simpler and as effective as PDT, but follow up is currently short and long term safety
data is lacking. In our experience ALA PDT is currently the most effective minimally invasive treatment for HGD in
BO.
This work was undertaken at UCLH/UCL who received a proportion of funding from the Department of Health's NIHR
Biomedical Research Centres funding scheme.
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