Does phototherapy induce regression of Barrett's columnar lined esophagus?
R. Lambert (Lyons)
Acid suppression alone results in non significant, or no regression, of the metaplastic mucosa of Barrett's esophagus (BE); acid suppression is achieved either by surgical procedures or by proton pump inhibitors.On the other hand, if the Barrett's epithelium is destroyed, acid suppression is required to obtain regeneration of a squamous epithelium replacing the metaplastic mucosa. Various procedures have been proposed, a potent control of acid secretion by proton pump inhibitors in the follow-up, is always added. The techniques for ablating the columnar epithelium depend on the use of thermal or photochemical energy. An associated low morbidity is a requirement because metaplasia without dysplasia is not a considerable risk of cancer. Among procedures using thermal energy [1-7], the most common is the so-called multipolar electrocoagulation with the gold probe, a variant is the monopolar coagulation with the argon plasma coagulator. Laser sources have been employed for their thermal effects: either an Nd:YAG laser at low power, or a contact Nd:YAG laser, or an argon laser
Among photochemical procedures [8-15] photodynamic therapy using the Photofrin® derivative is the most usual. The advantages of the method are the capacity of destruction of large surfaces in a single session, and the capacity to destroy dysplasia or early cancer as well. The drawbacks are the costly drug and material, the long duration of skin sensitization, the poor specificity between normal and tumoral tissue, the presence of the photosensitizer in the submucosa often resulting in deep necrosis and secondary strictures. An alternative photochemical procedure [16-18] has been applied to dysplasia in the columnar lined esophagus; this is the synthesis of an endogeneous photosensitizer (protoporphyrin IX) after oral ingestion of a precursor 5 aminolevulinic acid (60 mg/kg/ bw). The advantages of the method are a very high ratio of concentration of the agent in the tumor vs normal tissue, an excellent fixation in the esophagus, a specific concentration in the mucosa, reducing the alteration of the submucosa, and a short period (30 h) of skin photosensitization. However after ingestion of 5 ALA the concentration in the non neoplastic tissue is low, therefore the application to metaplastic mucosa without dysplasia is uncertain. On the other hand a topical application could be more effective.
To sum up, thermal procedures applied to the destruction of metaplastic epithelium may prove effective in the short type of Barrett, but only when the surface to be destroyed is small; when the surface is large (long type of Barrett) the destruction requires repeated sessions and may be incomplete and ineffective in preventing the risk of cancer. Thermal procedures are not powerful enough to effectively eradicate areas with dysplasia. Phototherapy with the Photofrin® derivative is on the other hand more powerful and adapted to the indication; it may also destroy small areas of metaplasia. In fact, the treatment of high grade dysplasia in BE is always associated to a significant regeneration of squamous epithelium. However, for large areas the destruction is often incomplete. As an exemple in a recent study on 71 patients treated with Photofrin® , complete destruction was achieved in only 23 out of which
12 required in complement thermal laser sessions. Finally the photodynamic therapy with 5ALA, either systemic or topical, is a promising method with a low morbidity.
12. Overholt BF, Panjehpour M. Barrett's esophagus: photodynamic therapy for ablation of dysplasia, reduction of specialized mucosa and treatment of superficial esophageal cancer. Gastrointest Endosc 1995;42:64-70.
14. Overholt BF, Panjehpour M. Photodynamic therapy in Barrett's esophagus: reduction of specialized mucosa, ablation of dysplasia and treatment of superficial esophageal cancer. Semin Surg Oncol 1995;11:372-376.