VOLUME 57, NO. 7, 2003 GASTROINTESTINAL ENDOSCOPY 897 During the last 3 decades, photodynamic therapy (PDT) has been investigated in preclinical and clin- ical trials as a potentially attractive technique for the treatment of malignant tumors. 1,2 Technologic improvements in light sources, light delivery sys- tems, and clinical procedures, as well as the devel- opment of new photosensitizers, have contributed to an increase in the application of PDT, including treatment of esophageal lesions. Photodynamic therapy has been applied in the esophagus as an experimental treatment for early stage superficial squamous cell carcinoma and for premalignant changes associated with Barrett’s esophagus with curative intent, 3,4 and advanced invasive malignan- cies as a palliative treatment. 5,6 Based on clinical experience thus far, it appears that PDT is most appropriate for localized superficial lesions with an infiltration depth of less than a few millimeters where the risk of lymph node metastasis is almost nil. 7,8 Several studies have confirmed the efficacy of PDT for in situ and microinvasive squamous cell carcinoma of the esophagus, as well as dysplastic changes and early stage adenocarcinoma in Barrett’s esophagus. 9-11 Early stage carcinomas are defined as either in situ (i.e., intraepithelial) with no invasion of the basement membrane, or microinva- sive (T1a, i.e., with no invasion beyond the muscu- laris mucosae). However, severe complications, such Received May 15, 2002. For revision October 1, 2002. Accepted February 26, 2003. Current affiliations: Department of Otolaryngology, Head and Neck Surgery, CHUV Hospital, CH-1011 Lausanne, Switzerland, Institute of Environmental Engineering, EPFL, CH-1015 Lausanne, Switzerland, Institute of Pathology, CHUV Hospital, CH-1011 Lausanne, Switzerland. Grant support provided by the Swiss National Fund and Scotia Pharmaceuticals Limited (Stirling, UK). Reprint requests: Alexandre Radu, MD, Department of Otolaryngology, Head and Neck Surgery, CHUV Hospital, CH- 1011, Lausanne, Switzerland. Copyright © 2003 by the American Society for Gastrointestinal Endoscopy 0016-5107/2003/$30.00 + 0 doi:10.1067/mge.2003.275 Mucosal ablation with photodynamic therapy in the esophagus: optimization of light dosimetry in the sheep model Alexandre Radu, MD, Ramiro Conde, PhD, Charlotte Fontolliet, MD, Georges Wagnieres, PhD, Hubert Van den Bergh, PhD, Philippe Monnier, MD Lausanne, Switzerland Background: Photodynamic therapy is an attractive technique for mucosal ablation in patients with superficial squamous cell carcinoma of the esophagus, or high-grade dysplasia or early stage adenocarcinoma arising in Barrett’s esophagus. Although illumination with green light is assumed to be safe, choice of the light has been empirical in clinical studies; light dose is often reduced to avoid potential complications.The present study assessed the safety of green and blue lights dur- ing photodynamic therapy in the esophagus by progressively administrating increasing doses in an attempt to standardize the dose and determine a safe upper limit. This would considerably sim- plify photodynamic therapy and improve therapeutic results. Methods: The sheep model was chosen because of similarities with humans regarding the thick- ness and histologic structure of the esophagus. Irradiation with a 180° windowed cylindrical light distributor was performed in 19 sheep 4 days after injection of 0.15 mg/kg of tetra(m-hydroxy- phenyl) chlorin. Light doses ranged from 10 to 500 J/cm 2 at 514 nm (argon ion laser) and from 5 to 250 J/cm 2 at 413 nm (krypton laser). Results: Follow-up endoscopies revealed a tissue response with a fibrinous area at almost all light doses, whereas application of extremely high light doses tended to induce circumferential necro- sis with subsequent stenosis. Three months after irradiation with green light, histologic examina- tion of the resected specimens revealed transmural scarring at doses higher than 100 J/cm 2 . After illumination with blue light, partial or more extensive fibrosis of the muscular layer was observed only at light doses of 175 to 250 J/cm 2 . Conclusions: Application of high doses of green light after sensitization with tetra(m-hydroxy- phenyl) chlorin led to severe complications in the esophagus of the sheep that are highly likely to occur in humans as well. Blue light causes significantly less damage than green light and may, therefore, be considered as an alternative for photodynamic therapy of early stage superficial esophageal cancer. (Gastrointest Endosc 2003;57:897-905.)