Photodynamic therapy for Barrett’s esophagus: does light still have a role?

Potential of photodynamic therapy

Photodynamic therapy consists of three elements [2]. There is a drug, which can be administered either orally or intravenously, that is supposed to be preferentially taken up within the Barrett’s mucosa. The most commonly used oral drug, 5-aminolevulinic acid (ALA), generally is administered within 4 hours of photoradiation, while the intravenous drug sodium porfimer must be given 48 hours before photoradiation. The oral medication certainly would make therapy simpler but is not used in the United States except as a topical application. Once adequate concentrations of the drug are achieved, photoradiation can be applied. This generally uses “red” wavelengths (630 – 635 nm) of light, which activate the drug. The drug interacts with molecular oxygen, causing it to form a singlet oxygen state, which then can interact with the tissue, causing cell death ([Fig. 1]).

Fig. 1 Photodynamic therapy in its current iteration. Light is used to activate a drug in the tissue. The drug absorbs the light energy and interacts with oxygen causing singlet oxygen which mediates cell death.

Although this sounds complicated, this is one of the simplest methods by which phototherapy can be delivered. Technically, it is a very easy procedure to perform which ensures that treatment can be performed without much variation in response due to variation in endoscopic skills. The administration of light can be done through very small fibers that can fit through any endoscope or even potentially come from nonendoscopic light sources. In addition, the photoradiation periods are relatively short and do not require much endoscope motion, which makes the therapy easily tolerated by most patients. The simplicity of this treatment would indicate that it has the highest chance of being effectively introduced into community practice. A great deal of the ablative therapies currently available are fairly complex and are suitable only for tertiary referral centers where the expertise exists to utilize these therapies.

This situation is analogous to esophagectomy where, if it is performed in expert centers, mortality rates are often less than 3 %, even in the older population of patients who are prone to Barrett’s esophagus [3]. If one examines, though, the mortality rate in the community, they can easily approach 18 % in centers where esophagectomy is not often performed. The same issues will most likely apply to complicate complex endoscopic procedures. In fact, this type of cancer therapy is probably more translatable to practice, not only in this country, but also in countries with limited healthcare resources where more complex modalities are difficult to deliver.

References

• 1 Siersema P D. Photodynamic therapy for Barrett"s esophagus: not yet ready for the premier league of endoscopic interventions.  Gastrointestinal Endoscopy. 2005;  62 503-507
• 2 Wilson B C, Patterson M S, Wilson B C, Patterson M S. The physics, biophysics and technology of photodynamic therapy.  Phys Med Biol. 2008;  53 61-R109
• 3 Birkmeyer J D, Stukel T A, Siewers A E. et al . Surgeon volume and operative mortality in the United States.  N Engl J Med. 2003;  349 2117-2127
• 4 Lightdale C J, Heier S K, Marcon N E. et al . Photodynamic therapy with porfimer sodium versus thermal ablation therapy with Nd:YAG laser for palliation of esophageal cancer: a multicenter randomized trial.  Gastrointest Endosc. 1995;  42 507-512
• 5 Dougherty T. Photodynamic therapy for early esophageal cancer [abstract]. International Photodynamic Therapy Association Meeting 1990. 
• 6 Laukka M A, Wang K K. Initial results using low-dose photodynamic therapy in the treatment of Barrett’s esophagus.  Gastrointest Endosc. 1995;  42 59-63
• 7 Overholt B F, 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
• 8 Overholt B F, Lightdale C J, Wang K K. et al . Photodynamic therapy with porfimer sodium for ablation of high-grade dysplasia in Barrett’s esophagus: international, partially blinded, randomized phase III trial. [Erratum appears in Gastrointest Endosc 2006; 63 : 359].  Gastrointest Endosc. 2005;  62 488-498
• 9 Overholt B F, Wang K K, Burdick J S. et al . Five-year efficacy and safety of photodynamic therapy with Photofrin in Barrett’s high-grade dysplasia.  Gastrointest Endosc. 2007;  66 460-468
• 10 Pech O, Gossner L, May A. et al . Long-term results of photodynamic therapy with 5-aminolevulinic acid for superficial Barrett’s cancer and high-grade intraepithelial neoplasia.  Gastrointest Endosc. 2005;  62 24-30
• 11 Hage M, Siersema P D, van Dekken H. et al . 5-aminolevulinic acid photodynamic therapy versus argon plasma coagulation for ablation of Barrett’s oesophagus: a randomised trial.  Gut. 2004;  53 785-790
• 12 Peters F, Kara M, Rosmolen W. et al . Poor results of 5-aminolevulinic acid-photodynamic therapy for residual high-grade dysplasia and early cancer in Barrett esophagus after endoscopic resection.  Endoscopy. 2005;  37 418-424
• 13 Mackenzie G D, Jamieson N F, Novelli M R. et al . How light dosimetry influences the efficacy of photodynamic therapy with 5-aminolaevulinic acid for ablation of high-grade dysplasia in Barrett’s esophagus.  Lasers in Med Sci. 2008;  23 203-210
• 14 Hur C, Nishioka N S, Gazelle G S. Cost-effectiveness of photodynamic therapy for treatment of Barrett’s esophagus with high grade dysplasia.  Dig Dis Sci. 2003;  48 1273-1283
• 15 Shaheen N J, Inadomi J M, Overholt B F, Sharma P. What is the best management strategy for high grade dysplasia in Barrett’s oesophagus? A cost effectiveness analysis.  Gut. 2004;  53 1736-1744
• 16 Comay D, Blackhouse G, Goeree R. et al . Photodynamic therapy for Barrett’s esophagus with high-grade dysplasia: a cost-effectiveness analysis.  Can J Gastroenterol. 2007;  21 217-222
• 17 Comay D, Blackhouse G, Goeree R. et al . Photodynamic therapy for Barrett’s esophagus with high-grade dysplasia: a cost-effectiveness analysis.  Can J Gastroenterol. 2007;  21 217-222
• 18 Prasad G A, Wang K K, Buttar N S. et al . Predictors of stricture formation after photodynamic therapy for high-grade dysplasia in Barrett’s esophagus.  Gastrointest Endosc. 2007;  65 60-66
• 19 Prasad G A, Wang K K, Buttar N S. et al . Long-term survival following endoscopic and surgical treatment of high-grade dysplasia in Barrett’s esophagus.  Gastroenterology. 2007;  132 1226-1233
• 20 Sharma V K, Wang K K, Overholt B F. et al . Balloon-based, circumferential, endoscopic radiofrequency ablation of Barrett’s esophagus: 1-year follow-up of 100 patients.  Gastrointest Endosc. 2007;  65 185-195
• 21 Mörk H, Barth T, Kreipe H H. et al . Reconstitution of squamous epithelium in Barrett’s oesophagus with endoscopic argon plasma coagulation: a prospective study.  Scand J Gastroenterol. 1998;  33 1130-1134
• 22 Van Laethem J L, Cremer M, Peny M O. et al . Eradication of Barrett’s mucosa with argon plasma coagulation and acid suppression: immediate and mid term results.  Gut. 1998;  43 747-751
• 23 Cheung R, Solonenko M, Busch T M. et al . Correlation of in vivo photosensitizer fluorescence and photodynamic-therapy-induced depth of necrosis in a murine tumor model.  J Biomed Optics. 2003;  8 248-252
• 24 Solonenko M. In vivo reflectance measurement of optical properties, blood oxygenation and motexafin lutetium uptake in canine large bowels, kidneys and prostates.  Phys Med Biol. 2002;  47 857-873
• 25 Sessler J L, Miller R A. Texaphyrins: new drugs with diverse clinical applications in radiation and photodynamic therapy.  Biochem Pharmacol. 2000;  59 733-739
• 26 Vargas A, Eid M, Fanchaouy M. et al . In vivo photodynamic activity of photosensitizer-loaded nanoparticles: formulation properties, administration parameters and biological issues involved in PDT outcome.  Eur J Pharm Biopharm. 2008;  69 43-53
• 27 Saw C L, Heng P W, Olivo M. et al . Potentiation of the photodynamic action of hypericin.  J Environ Pathol Toxicol Oncol. 2008;  27 23-33
• 28 Minnes R, Weitman H, You Y. et al . Dithiaporphyrin derivatives as photosensitizers in membranes and cells.  J Phys Chem B. 2008;  112 3268-3276
• 29 Cole C D, Liu J K, Sheng X. et al . Hypericin-mediated photodynamic therapy of pituitary tumors: preclinical study in a GH4C1 rat tumor model.  J Neurooncol. 2008;  87 255-261
• 30 Trachtenberg J, Bogaards A, Weersink R A. et al . Vascular targeted photodynamic therapy with palladium-bacteriopheophorbide photosensitizer for recurrent prostate cancer following definitive radiation therapy: assessment of safety and treatment response.  J Urol. 2007;  178 1974-1979; discussion 1979
• 31 Taquet J P, Frochot C, Manneville V. et al . Phthalocyanines covalently bound to biomolecules for a targeted photodynamic therapy.  Curr Med Chem. 2007;  14 1673-1687
• 32 Prasad G A, Wang K K, Halling K C. et al . Utility of biomarkers in prediction of response to ablative therapy in Barrett’s esophagus.  Gastroenterology. 2008;  135 370-379