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
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
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
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.
Elastic scattering spectroscopy (ESS) may be used to detect high-grade dysplasia (HGD) or cancer in Barrett's esophagus (BE). When spectra are measured in vivo by a hand-held optical probe, variability among replicated spectra from the same site can hinder the development of a diagnostic model for cancer risk. An experiment was carried out on excised tissue to investigate how two potential sources of this variability, pressure and angle, influence spectral variability, and the results were compared with the variations observed in spectra collected in vivo from patients with Barrett's esophagus. A statistical method called error removal by orthogonal subtraction (EROS) was applied to model and remove this measurement variability, which accounted for 96.6% of the variation in the spectra, from the in vivo data. Its removal allowed the construction of a diagnostic model with specificity improved from 67% to 82% (with sensitivity fixed at 90%). The improvement was maintained in predictions on an independent in vivo data set. EROS works well as an effective pretreatment for Barrett's in vivo data by identifying measurement variability and ameliorating its effect. The procedure reduces the complexity and increases the accuracy and interpretability of the model for classification and detection of cancer risk in Barrett's esophagus.