These preliminary results show that elastic scattering spectroscopy has the potential to target conventional biopsies in Barrett's surveillance saving significant endoscopist and pathologist time with consequent financial savings. This technique now requires validation in prospective studies.

Photofrin photodynamic therapy (PDT) is a licenced treatment for Barrett's oesophagus (BE) with high-grade dysplasia (HGD) but causes strictures and photosensitivity and complete reversal of dysplasia (CR-HGD) by 50 % at 5 years. 5-Aminolaevulinic acid (ALA) is an alternative treatment with non-randomised data suggesting 85 % CR-HGD and a low risk of side effects. We aimed to compare efficacy and side effect profile between the drugs. A single-centre randomised controlled trial was conducted. Presence of HGD was confirmed on three occasions by two specialist GI pathologists. Stratification was by length of BE and extent of dysplasia. Standard protocols for ALA and Photofrin-PDT were followed. Endoscopic follow-up with 2-cm four-quadrant biopsy was at 6 weeks, 4 months, and then annually. All adverse event data were collected. Sixty four patients were randomised, 34 ALA and 30 Photofrin-PDT. Median follow-up is 24 months. On intention-to-treat analysis, CR-HGD was 16/34 (47 %) with ALA-PDT and 12/30 (40 %) with Photofrin-PDT. The overall cancer incidence was 14 % (9/64). On sub-group log-rank analysis, for BE ≤ 6 cm, CR-HGD was significantly higher with ALA-PDT than Photofrin-PDT (χ(2) =5.39, p=0.02). Strictures and skin photosensitivity were significantly more common after treatment with Photofrin-PDT than ALA-PDT (33 vs. 9 % and 43 vs. 6 %, respectively, p<0.05). The rate of buried glands with either drug was significantly higher post-PDT (48 % of patients) than pre-PDT (20 %). ALA-PDT has a better risk profile than Photofrin-PDT. In patients with BE length ≤ 6 cm, preliminary results show ALA-PDT is associated with significantly higher CR-HGD. In longer segments of BE, neither PDT drug is sufficiently efficacious to warrant routine use.

BACKGROUND AND AIMS: DNA ploidy abnormalities (aneuploidy/tetraploidy) measured by flow cytometry (FC) are strong predictors of future cancer development in untreated Barrett's oesophagus, independent of histology grade. Image cytometric DNA analysis (ICDA) is an optical technique allowing visualisation of abnormal nuclei that may be undertaken on archival tissue. Our aim was to determine the accuracy of ICDA vs FC, and evaluate DNA ploidy as a prognostic biomarker after histologically successful treatment with photodynamic therapy (PDT). METHODS: Nuclei were extracted from 40 mm sections of paraffin-embedded biopsies and processed for ICDA at UCL and FC at UW using standardised protocols. Subsequently, DNA ploidy was evaluated by ICDA on a cohort of 30 patients clear of dysplasia 1 year after aminolaevulinic acid PDT for high-grade dysplasia (HGD). The results were correlated with long-term outcome. RESULTS: In the comparative study, 93% (41 out of 44) of cases were classified identically. Errors occurred in the near-diploid region by ICDA and the tetraploid region by FC. In the cohort study, there were 13 cases of late relapse (7 cancer, 6 HGD) and 17 patients who remained free of dysplasia after a mean follow-up of 44 months. Aneuploidy post-PDT was highly predictive for recurrent HGD or cancer with a hazard ratio of 8.2 (1.8 -37.8) (log-rank P ¼ 0.001). CONCLUSIONS: ICDA is accurate for the detection of DNA ploidy abnormalities when compared with FC. After histologically successful PDT, patients with residual aneuploidy are significantly more likely to develop HGD or cancer than those who become diploid. DNA ploidy by ICDA is a valuable prognostic biomarker after ablative therapy. British Journal of Cancer (2010) The incidence of oesophageal adenocarcinoma is rising rapidly in the developed world. Barrett's oesophagus (BE) is a precursor lesion that confers an increased risk of oesophageal adenocarcinoma, with incidence rates of 0.4 -2% per annum (Cameron et al, 1985;Robertson et al, 1988;Hameeteman et al, 1989;Williamson et al, 1991). Progression seems to occur through a metaplasiadysplasia -carcinoma sequence (Weston et al, 1999;Montgomery et al, 2001). High-grade dysplasia (HGD) confers a high probability of cancer, with rates varying between 31 and 59% over 5 years (Reid et al, 2000a;Buttar et al, 2001;Overholt et al, 2007). In recent years, there has been a paradigm shift in the treatment of HGD in BE from oesophagectomy to endoscopic therapy, with focal ablation of nodular disease (endoscopic mucosal resection (EMR)) and field ablation of residual flat dysplasia (photodynamic therapy (PDT), argon plasma coagulation, radiofrequency ablation and cryotherapy). The effectiveness of these approaches in eradicating HGD and reducing the risk of progression to cancer has been shown in randomised controlled trials (Overholt et al, 2007;Shaheen et al, 2009).Although complete ablation of a Barrett's segment is the ideal response to treatment, complete reversal of HGD at 1 year is currently used as a marker of ...

Photodynamic therapy (PDT) with 5-aminolaevulinic acid (ALA) is a novel treatment for high-grade dysplasia (HGD) in Barrett's esophagus (BE). Our aim was to evaluate the effectiveness of differing light doses. Patients with HGD in BE received oral ALA (60 mg/kg) activated by low (500 J/cm), medium (750 J/cm), high (1,000 J/cm), or highest (1,000 J/cm x2) light dose at 635 nm. Follow-up was by regular endoscopy with quadrantic biopsies. Twenty-four patients were treated. Successful eradication of HGD was significantly correlated with light dose (log rank, p < 0.01). Six of eight patients (75%) treated with the highest light dose, one of two treated with high dose (50%), two of nine (22%) receiving medium light dose, and zero of five receiving low light dose had successful eradication of HGD (median follow-up 45 months, range 1-78 months). No skin photosensitivity or esophageal strictures occurred. The efficacy of ALA-PDT for eradication of HGD in BE is closely related to the light dose used. With a drug dose of 60 mg/kg and light at 635 nm, we recommend a minimum light dose of 1,000 J/cm of esophagus. This dose appears safe.