Photodynamic therapy (PDT) is a treatment that uses a combination of a photosensitizer (a light activated drug) and a laser light to destroy abnormal cells. The primary use of PDT is as an alternative to esophagectomy (the surgical removal of the esophagus) for patients with high-grade dysplasia (HGD) and early cancer in Barrett's esophagus. 

The first step in PDT involves the administration of a chemical photosensitizer, some of which becomes concentrated in the abnormal esophageal mucosa (5-aminolevulinic acid) and some in the stroma (porfimer sodium). The only approved photosensitizer in North America is porfimer sodium (Photofrin® [Axcan Pharma Inc, Birmingham, AL]), which is given intravenously.  Laser light is then delivered two-three days later using a specially designed light delivery balloon.  Activation of the photosensitizer by an endoscopically applied light source at the appropriate wavelength (630 nm for porfimer sodium) induces the generation of singlet oxygen and other cytotoxic species that contribute to the destruction of the abnormal esophageal mucosa, resulting in deep injury that is associated with significant morbidity (11). Photofrin remains in the skin for up to 2 months and thus the patients must avoid direct exposure to sunlight and bright lights during this time, since exposure to light may result in severe sunburn (12).    

Overholt et al. have published extensively regarding their experience of using PDT in 103 patients, most of whom had HGD. The mean follow-up in this group was over 4 years. Of the 65 patients with HGD, 78% had their HGD eliminated. On the basis of an intention-to-treat analysis, 54% had no residual Barrett Esophagus.  The primary complication of PDT for Barrett's esophagus is esophageal stricture, scarring and narrowing of the esophageal lumen. The overall stricture rate for patients treated with PDT was 30%, but for those who required more than one PDT treatment it was 50%.  Such strictures are usually responsive to endoscopic balloon dilation.  Another important finding in patients undergoing PDT with apparent squamous re-epithelialization is the presence of residual patches of subsquamous intestinal metaplasia.  Subsquamous, nondysplastic intestinal metaplasia occurred in 4.9% of patients, but more importantly 3 patients (4.6%) developed subsquamous adenocarcinoma (13).  The occurrence of subsquamous intestinal metaplasia is reported in virtually all studies using PDT: in detailed pathology studies the prevalence is reported to be as high as 51.5% (14). Other side effects reported with PDT include chest pain, dysphagia, odynophagia, pleural effusions, Candida esophagitis, and atrial fibrillation.  In addition, esophageal perforation and tracheoesophageal fistulas have been reported, but are rare (<1%) (15). 

Esophagectomy remains the gold standard treatment for HGD. As techniques and technology improve, it is likely that ablative strategies will become an important part of the armamentarium in the treatment of Barrett’s esophagus (16).  A recent cost-effectiveness analysis of PDT for HGD in Barrett's esophagus found PDT to be a cost-effective alternative to esophagectomy, even though it incurs the greatest lifetime cost (US $47,310) compared with esophagectomy (US $24,045) (17).