Photodynamic therapy of esophageal varices: experimental studies in animal veins, and first clinical cases.

Abstract

Endoscopic injection sclerotherapy and endoscopic variceal ligation have been found to have shortcomings in the treatment of esophageal varices. In this study the effectiveness of photodynamic therapy (PDT) in the obliteration of veins was investigated to evaluate its potential in the treatment of esophageal varices. Auricular margin veins of rabbits were irradiated by copper vapor laser after intravenous injection of 10 mg/kg of hematoporphyrin monomethyl ether (which is a hematoporphyrin derivative) into the rabbits. Control groups included rabbits that received irradiation only, that received injection of photosensitizer only, and that received injection sclerotherapy (using sodium morrhuate). The treated areas were observed macroscopically and also identified using with ultrasonic miniprobe. Biopsies were performed and the specimens were examined microscopically after hematoxylin-eosin staining and Victoria blue staining. In addition, two patients with newly visible veins within the esophageal wall after endoscopic injection sclerotherapy underwent PDT. Intravenous injection of 5 mg/kg of hematoporphyrin monomethyl ether was given, and the newly visible veins were endoscopically irradiated by copper vapor laser. Endoscopic re-examination was performed 1 month later to evaluate the therapeutic effect. Thrombi of the auricular margin vein were formed and blood flow was obstructed after PDT. Thrombus formation and diffused necrosis of adjacent tissue was found after injection of sodium morrhuate. On ultrasonic examination, the lumina of the veins showed a slightly higher echo after PDT compared with a lower echo before treatment, which was another sign of thrombus formation. The rabbit ears showed a diffused low echo after injection of sodium morrhuate, indicating diffuse necrosis. On microscopic observation, destruction of the endothelium and formation of thrombus was seen after PDT. Further observation of specimens stained with Victoria blue showed that the layer of elastic fiber was intact. After injection of sodium morrhuate, extensive necrosis of tissue was seen microscopically. No macroscopic, ultrasonic, or microscopic change was found in the rabbits that received irradiation only or injection of photosensitizer only. The rate of thrombus formation in rabbits that received PDT was significantly higher than that in the rabbits that received irradiation only or injection of photosensitizor only ( P = 0.015, P = 0.015), and comparable to that in the rabbits that received sclerotherapy ( P = 0.467). In the clinical study, at endoscopy 1 month after PDT both the number and the "red sign" of newly visible veins were found to have decreased. No adverse effect was found. PDT can destroy the endothelium of the vein, result in thrombus formation, and eventually obliterate the vein. It is potentially a new method for the treatment of esophageal varices.