Optimal conditions for successful ablation of high-grade dysplasia in Barrett's oesophagus using aminolaevulinic acid photodynamic therapy.

Photodynamic therapy (PDT) using 5-aminolaevulinic acid (ALA-PDT) is an attractive alternative to PDT with porfimer sodium for the treatment of high-grade dysplasia (HGD) in Barrett's oesophagus (BO) because of the shorter duration of light photosensitivity and low risk of oesophageal stricture formation. Published results, however, show marked variation in its efficacy, and optimum treatment parameters have not been defined. This study investigated how the dose of ALA and the colour of the illuminating light influenced the biological effect. Twenty-seven patients were enrolled into a randomised controlled trial of red versus green (635 nm or 512 nm) laser light activation for the eradication of HGD with ALA-PDT in Barrett's oesophagus. A further 21 patients were subsequently treated with the most effective regimen. Regular endoscopic follow-up with quadrantic biopsies every 2 cm was performed. The primary outcome measure was eradication of HGD. Patient's receiving ALA at 30 mg/kg relapsed to HGD more than those receiving 60 mg/kg (P = 0.03). Additionally, for those treated with ALA 60 mg/kg, red laser light was more effective than green laser light (P = 0.008). Kaplan-Meier analysis of the 21 patients who were subsequently treated with this optimal regimen demonstrated an eradication rate of 89% for HGD and a cancer-free proportion of 96% at 36 months' follow-up. Using an ALA dose of 60 mg/kg activated by 1,000 J/cm red laser light, we found that ALA-PDT was a highly effective treatment for high-grade dysplasia in Barrett's oesophagus.

How light dosimetry influences the efficacy of photodynamic therapy with 5-aminolaevulinic acid for ablation of high-grade dysplasia in Barrett's esophagus.

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.

Photodynamic therapy with m-tetrahydroxyphenyl chlorin for high-grade dysplasia and early cancer in Barrett's columnar lined esophagus.

BACKGROUND: Many patients with high-grade dysplasia and localized adenocarcinoma in Barrett's esophagus have localized disease but are either unfit for major surgery or decline esophagectomy. Photodynamic therapy with the powerful photosensitizer m-tetrahydroxyphenyl chlorin may be a nonsurgical therapeutic option. METHODS: This is a pilot study to evaluate the efficacy and complications of m-tetrahydroxyphenyl chlorin photodynamic therapy. The design is a case series of 19 consecutive patients at a tertiary referral unit with a special interest in photodynamic therapy. The study included 7 patients with high-grade dysplasia and 12 with early esophageal cancer, who had refused or were unfit for esophagectomy. Three days after photosensitization with 0.15 mg/kg m-tetrahydroxyphenyl chlorin, red or green light was delivered endoscopically when using either a bare fiber or a diffuser device. Results were assessed by endoscopic surveillance. RESULTS: By using red light via the diffuser, 4/6 patients with cancer and 3/4 with high-grade dysplasia were successfully treated with photodynamic therapy alone. When using the bare-tipped fiber, there was one procedure-related death and only 1/5 patients with cancers were successfully treated. Two others were downgraded to high-grade dysplasia. With green light delivered via a diffuser, 0/3 patients with high-grade dysplasia are in long-term remission. Two serious complications arose (including one death) from taking multiple biopsy specimens too soon after therapy. Two esophageal strictures occurred. CONCLUSIONS: Photodynamic therapy with m-tetrahydroxyphenyl chlorin is, potentially, a valuable therapeutic option for localized esophageal neoplasia. Red light via a diffuser device appears to be the most effective light-delivery technique. Biopsy specimens should not be taken for at least 2 months after treatment.