daw
09-03-2003, 11:19 AM
Gastrointestinal Endoscopy
August 2003 (Volume 58, Number 2)
Photodynamic Therapy for Barrett's Esophagus With Dysplasia and/or Early Stage Carcinoma: Long-term Results
Overholt BF, Panjehpour M, Halberg DL
Gastrointestinal Endoscopy. 2003;58(2):183-188
Barrett's esophagus is a clinically important condition because of its link to an increased risk of developing esophageal adenocarcinoma. Although the majority of patients with Barrett's esophagus do not progress to malignancy, a proportion of these patients do. Barrett's esophagus is believed to occur in the setting of long-standing acid reflux.
Primary prevention of Barrett's-related cancer by prohibiting initial development of the Barrett's lesion through control of acid reflux (either surgically or medically) is not viable because Barrett's esophagus generally develops early on in the reflux process, before an individual presents with related symptoms. Therefore, attention must turn toward secondary prevention -- that is, prevention of Barrett's-related esophageal adenocarcinoma ("reversal" of Barrett's esophagus) by eliminating either the reflux or the metaplastic premalignant tissue itself. However, strategies to achieve the former have failed to demonstrate any clinically meaningful results. Thus it appears that for successful reversal of nondysplastic Barrett's esophagus, the "at-risk" metaplastic tissue may need to be eliminated. It is in this setting that the notion of using endoscopic ablation to restore the normal squamous epithelium has emerged.
Photodynamic therapy (PDT) is one such ablative modality that has been investigated as a method for eliminating Barrett's mucosa. PDT uses light to activate a photosensitizing agent (porfimer sodium or 5-aminolevulinic acid) distributed in tissue to generate singlet oxygen. This singlet oxygen is cytotoxic to mucosa that is exposed to a specified wavelength and power of light. Although PDT has demonstrated efficacy in eliminating Barrett's mucosa, long-term results are lacking.
Overholt and colleagues present long-term (5-year) follow-up data after porfimer-PDT for patients with Barrett's esophagus with high-grade dysplasia, low-grade dysplasia, or early cancer. One hundred three patients with Barrett's esophagus underwent porfimer-PDT; patients were followed up from November 1993 through July 2001. An Nd:YAG laser was used to photoablate small areas of residual or untreated Barrett's mucosa. All participants received acid suppressive therapy (omeprazole, 20 mg twice daily) or an equivalent dose of another proton-pump inhibitor. The primary study end point was elimination of dysplasia/cancer.
Overall, results suggest that porfimer-PDT with adjunctive Nd:YAG photoablation and continuous treatment with acid-suppressive therapy decreases the length of Barrett's mucosa (by a mean of 6.9 cm) eliminates high-grade dysplasia and, by comparison with extrapolated historical data, may decrease the expected frequency of esophageal malignancy in patients with Barrett's esophagus and high-grade dysplasia. For the 103 patients initially enrolled in this study, intention-to-treat success rates were 92.9%, 77.5%, and 44.4% for the patient groups with, respectively, low-grade dysplasia, high-grade dysplasia, and cancer. Among those patients followed throughout the length of the study, high-grade dysplasia was eliminated in 95% of cases and Barrett's mucosa eliminated in 68%.
In a related editorial, M. Brian Fennerty, MD, suggests that comparison of the results of this study with other outcomes in other studies as was done by these investigators, does not represent a valid approach to analyzing outcomes. As Fennerty stressed, there are no population-based incidence rates for cancer in patients who have Barrett's esophagus and high-grade dysplasia. Other problems with such cross-study comparisons, Fennerty points out, include characteristics of the populations studied, concomitant treatments that could have affected neoplastic progression, among others. So, the question as to whether use of PDT for treatment of patients with Barrett's esophagus and high-grade dysplasia represents a true advance in management of this disease vs a standard therapeutic option, requires further clarification. And finally, Fennerty emphasized that while it is evident that much if not all of the Barrett's mucosa can be endoscopically eliminated in many patients by using PDT or other endoscopic modalities, it is important that appropriate data are available to justify the use of such (PDT) interventions.
August 2003 (Volume 58, Number 2)
Photodynamic Therapy for Barrett's Esophagus With Dysplasia and/or Early Stage Carcinoma: Long-term Results
Overholt BF, Panjehpour M, Halberg DL
Gastrointestinal Endoscopy. 2003;58(2):183-188
Barrett's esophagus is a clinically important condition because of its link to an increased risk of developing esophageal adenocarcinoma. Although the majority of patients with Barrett's esophagus do not progress to malignancy, a proportion of these patients do. Barrett's esophagus is believed to occur in the setting of long-standing acid reflux.
Primary prevention of Barrett's-related cancer by prohibiting initial development of the Barrett's lesion through control of acid reflux (either surgically or medically) is not viable because Barrett's esophagus generally develops early on in the reflux process, before an individual presents with related symptoms. Therefore, attention must turn toward secondary prevention -- that is, prevention of Barrett's-related esophageal adenocarcinoma ("reversal" of Barrett's esophagus) by eliminating either the reflux or the metaplastic premalignant tissue itself. However, strategies to achieve the former have failed to demonstrate any clinically meaningful results. Thus it appears that for successful reversal of nondysplastic Barrett's esophagus, the "at-risk" metaplastic tissue may need to be eliminated. It is in this setting that the notion of using endoscopic ablation to restore the normal squamous epithelium has emerged.
Photodynamic therapy (PDT) is one such ablative modality that has been investigated as a method for eliminating Barrett's mucosa. PDT uses light to activate a photosensitizing agent (porfimer sodium or 5-aminolevulinic acid) distributed in tissue to generate singlet oxygen. This singlet oxygen is cytotoxic to mucosa that is exposed to a specified wavelength and power of light. Although PDT has demonstrated efficacy in eliminating Barrett's mucosa, long-term results are lacking.
Overholt and colleagues present long-term (5-year) follow-up data after porfimer-PDT for patients with Barrett's esophagus with high-grade dysplasia, low-grade dysplasia, or early cancer. One hundred three patients with Barrett's esophagus underwent porfimer-PDT; patients were followed up from November 1993 through July 2001. An Nd:YAG laser was used to photoablate small areas of residual or untreated Barrett's mucosa. All participants received acid suppressive therapy (omeprazole, 20 mg twice daily) or an equivalent dose of another proton-pump inhibitor. The primary study end point was elimination of dysplasia/cancer.
Overall, results suggest that porfimer-PDT with adjunctive Nd:YAG photoablation and continuous treatment with acid-suppressive therapy decreases the length of Barrett's mucosa (by a mean of 6.9 cm) eliminates high-grade dysplasia and, by comparison with extrapolated historical data, may decrease the expected frequency of esophageal malignancy in patients with Barrett's esophagus and high-grade dysplasia. For the 103 patients initially enrolled in this study, intention-to-treat success rates were 92.9%, 77.5%, and 44.4% for the patient groups with, respectively, low-grade dysplasia, high-grade dysplasia, and cancer. Among those patients followed throughout the length of the study, high-grade dysplasia was eliminated in 95% of cases and Barrett's mucosa eliminated in 68%.
In a related editorial, M. Brian Fennerty, MD, suggests that comparison of the results of this study with other outcomes in other studies as was done by these investigators, does not represent a valid approach to analyzing outcomes. As Fennerty stressed, there are no population-based incidence rates for cancer in patients who have Barrett's esophagus and high-grade dysplasia. Other problems with such cross-study comparisons, Fennerty points out, include characteristics of the populations studied, concomitant treatments that could have affected neoplastic progression, among others. So, the question as to whether use of PDT for treatment of patients with Barrett's esophagus and high-grade dysplasia represents a true advance in management of this disease vs a standard therapeutic option, requires further clarification. And finally, Fennerty emphasized that while it is evident that much if not all of the Barrett's mucosa can be endoscopically eliminated in many patients by using PDT or other endoscopic modalities, it is important that appropriate data are available to justify the use of such (PDT) interventions.