Should Complete Ablation of Barrett’s Esophagus Be the Goal of Photodynamic Therapy?

Abstract

Background: Photodynamic therapy (PDT) is extensively evaluated for the treatment of superficial neoplasia arising in Barrett’s esophagus (BE). Several reports have demonstrated marked reduction of neoplastic tissue post PDT, but only a few have included a systematic pathologic assessment. Methods: Forty-nine BE patients (M:41, F:8) with high-grade dysplasia (HGD, n = 21), intramucosal carcinoma (IMC, n = 25), and invasive carcinoma (InvCa, n = 3) were treated with PDT. Photosensitizing agents were porfimer sodium (2 mg/kg; n = 45) or 5-aminolevulinic acid (30 mg/kg; n = 4). Biopsies were taken with jumbo forceps from 4-quadrant every 2 cm over the length of the BE. During follow-up, the protocol surveyed the length of the original BE, including areas of squamous re-epithelialization. Acid suppression with proton pump inhibitors was maintained in all patients. Results: Mean length of BE was 6.63 cm (range, 1–13). Mean follow-up was 27.7 months (range, 6–85). PDT was successful after one session in 15 patients (30.6%; HGD 9, IMC 6) with no recurrence during follow-up (mean 19.9 months, range 7–32). Thirty-four patients were treated with additional PDT alone (n = 1), in combination with mucosal fulguration (n = 19), or fulguration alone (n = 13). One patient refused additional treatment. In toto, neoplasias were eradicated in 39 patients (79.6%; HGD 17, IMC 21, InvCa 1) with a mean disease-free interval of 12.8 months (0–32). The neoplastic lesions were downgraded in 2 patients (HGD to LGD, InvCa to IMC), unchanged in 7 (14.3%; HGD 3, IMC 3, InvCa 1), or progressed in one (IMC to InvCA). Thirteen of 24 patients (54.2%) with neoplasias spanning less than 3 cm were successfully treated by one course of PDT. Conversely, it was successful in only 2 of 25 patients (8%) with neoplasia spanning over 3 cm. Residual neoplasias were more common in the distal (n = 9) or middle (n = 8) than in the proximal (none) segment of BE. Patches of BE covered by squamous epithelium were found in 30 patients (61.2%), and foci of buried neoplasia were found in 18 (36.7%) patients after PDT, while they were observed in only 17 (34.7%) and 5 (10.2%) before PDT, respectively. Conclusion: Post PDT detailed pathologic evaluation reveals a high frequency of persistent neoplasia. Diffuseness and distal location of the lesions are associated with treatment failure. Residual neoplasia is often covered by unremarkable squamous epithelium. These characteristics underline the importance of close follow-up. Background: Photodynamic therapy (PDT) is extensively evaluated for the treatment of superficial neoplasia arising in Barrett’s esophagus (BE). Several reports have demonstrated marked reduction of neoplastic tissue post PDT, but only a few have included a systematic pathologic assessment. Methods: Forty-nine BE patients (M:41, F:8) with high-grade dysplasia (HGD, n = 21), intramucosal carcinoma (IMC, n = 25), and invasive carcinoma (InvCa, n = 3) were treated with PDT. Photosensitizing agents were porfimer sodium (2 mg/kg; n = 45) or 5-aminolevulinic acid (30 mg/kg; n = 4). Biopsies were taken with jumbo forceps from 4-quadrant every 2 cm over the length of the BE. During follow-up, the protocol surveyed the length of the original BE, including areas of squamous re-epithelialization. Acid suppression with proton pump inhibitors was maintained in all patients. Results: Mean length of BE was 6.63 cm (range, 1–13). Mean follow-up was 27.7 months (range, 6–85). PDT was successful after one session in 15 patients (30.6%; HGD 9, IMC 6) with no recurrence during follow-up (mean 19.9 months, range 7–32). Thirty-four patients were treated with additional PDT alone (n = 1), in combination with mucosal fulguration (n = 19), or fulguration alone (n = 13). One patient refused additional treatment. In toto, neoplasias were eradicated in 39 patients (79.6%; HGD 17, IMC 21, InvCa 1) with a mean disease-free interval of 12.8 months (0–32). The neoplastic lesions were downgraded in 2 patients (HGD to LGD, InvCa to IMC), unchanged in 7 (14.3%; HGD 3, IMC 3, InvCa 1), or progressed in one (IMC to InvCA). Thirteen of 24 patients (54.2%) with neoplasias spanning less than 3 cm were successfully treated by one course of PDT. Conversely, it was successful in only 2 of 25 patients (8%) with neoplasia spanning over 3 cm. Residual neoplasias were more common in the distal (n = 9) or middle (n = 8) than in the proximal (none) segment of BE. Patches of BE covered by squamous epithelium were found in 30 patients (61.2%), and foci of buried neoplasia were found in 18 (36.7%) patients after PDT, while they were observed in only 17 (34.7%) and 5 (10.2%) before PDT, respectively. Conclusion: Post PDT detailed pathologic evaluation reveals a high frequency of persistent neoplasia. Diffuseness and distal location of the lesions are associated with treatment failure. Residual neoplasia is often covered by unremarkable squamous epithelium. These characteristics underline the importance of close follow-up.