ABSTRACT
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.
Subject(s)
Aminolevulinic Acid/therapeutic use , Barrett Esophagus/therapy , Laser Therapy/methods , Photochemotherapy/methods , Photosensitizing Agents/therapeutic use , Aged , Aged, 80 and over , Aminolevulinic Acid/administration & dosage , Barrett Esophagus/pathology , Dose-Response Relationship, Radiation , Female , Humans , Laser Therapy/adverse effects , Laser Therapy/instrumentation , Light , Male , Middle Aged , Photochemotherapy/instrumentation , Photosensitizing Agents/administration & dosage , Prospective Studies , Treatment OutcomeABSTRACT
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.
