Application of photodynamic therapy in gastrointestinal disorders

Photodynamic therapy (PDT) is minimally invasive, highly selective for cancer, and has good patient compliance due to the simplicity of the procedure. Therefore, PDT is used as a treatment for patients with various gastrointestinal malignancies. However, drawbacks of PDT including suboptimal efficacy, phototoxicity and high cost have reduced initial enthusiasm for this procedure in the treatment of GI malignancies.(1) PDT is approved for the curative endoscopic treatment of superficial esophageal squamous cell carcinoma and palliative treatment of patients with symptomatic obstructive esophageal cancer in Korea. However, the development of endoscopic submucosal resection, which can confirm histologic success, has greatly limited PDT practice in esophageal cancer. Recently good results have been reported when used as salvage therapy for local failure after definitive chemoradiotherapy for esophageal cancer.(2-6) In unresectable cholangiocarcinoma, PDT in combination with bile duct stents is a promising palliative treatment. A recent meta-analysis found that PDT had better overall survival and 30-day mortality than remission with RFA and/or stents alone.(7) The combination of PDT and chemotherapy can improve patient survival for unresected cholangiocarcinoma without increased side effects. A recent clinical report of PDT for treating unresectable pancreatic cancer also shows promising results.(8, 9) PDT can be used as an effective adjuvant therapy for endoscopic treatment of early gastric cancer.(10) For patients with inoperable advanced gastric cancer, especially those with peritoneal metastases(11) and cardiac or pyloric obstruction, PDT can be used in palliative care to improve the patient's quality of life. Recently, many researchers have made great efforts to expand the application of PDT. The application of PDD and PDT is being newly illuminated with good results in the fields of early diagnosis, salvage treatment of local failure, and palliation of gastrointestinal cancer. Novel integration of PDT with existing technologies such as molecular imaging, and nanotechnology may make PDT a feasible and desirable option for GI cancer treatment. Several new approaches for local delivery of PDT targeting GI tumors have also been developed. These include spraying through the working channel of an endoscope, endoscopic ultrasound-guided photodynamic therapy, and the use of photosensitizer-coated stents. Based on these new developments, PDT is likely to re-emerge as a useful technology for the treatment of various gastrointestinal cancers. In addition to therapeutic modality of cancer, PDT has been used in various fields such as the treatment of infectious diseases. We focused on methylene blue, which is approved for human use and can be used as a photosensitizer. We found that the combined implementation of methylene blue-based PDT and hydrogen peroxide through the endoscopic working channel may be appropriate to prevent early colonization and biofilm formation in the endoscopic and post-endoscopic outbreak. Methylene blue induces cell death efficiently, has excellent safety, and can be directly applied to the intestinal mucosa by spraying through the working channel of the endoscope.(12) We developed a novel duodenal mucosal resurfacing method using PDT after methylene blue spray in an animal model. Duodenal PDT showed specific destruction of the duodenal mucosal layer without complications. As a result, duodenal PDT induced significant reduction in body weight and glycemic control. Duodenal PDT with methylene blue has shown a feasible therapeutic modality for diabetes or morbid obesity.