Photodynamic therapy is nonthermal injury

LETTERS TO THE EDITOR Photodynamic therapy is nonthermal injury In their article regarding changes to the cardia after Barrett’s esophagus ablation, Weston et al1 clearly consider photodynamic therapy to be ‘‘thermal ablation,’’ and imply that this modality should be grouped with other Barrett’s ablation techniques in causing thermal injury as its mechanism of action. Their belief is incorrect. Photodynamic therapy is, in fact, a nonthermal photochemical reaction and does not generate heat as its mechanism of cell injury and ablation. Cell injury and death during photodynamic therapy arises from the nonthermal generation of singlet oxygen and other oxygen free radicals when light of the proper wavelength excites a photosensitizing agent.2,3 Moreover, the light generation process during photodynamic therapy involves a cool light source, typically a cool laser.3 Thus, the implication by Weston et al1 that there is a common thermal pathway as the cause of cardia changes after Barrett’s ablation is incorrect and needs to be revised. Robert A. Ganz, MD Minnesota Gastroenterology Chief of Gastroenterology Abbott-Northwestern Hospital Adjunct Associate Professor of Medicine University of Minnesota Minneapolis, Minnesota, USA REFERENCES 1. Weston AP, Sharma P, Banerjee S, Mitreva D, Mathur S. Visible endoscopic and histologic changes in the cardia, before and after complete Barrett’s esophagus ablation. Gastrointest Endosc 2005;61:515-21. 2. Pass H. Photodynamic therapy in oncology: mechanisms and clinical use. J Natl Cancer Inst 1993;85:443-56. 3. Heier SK, Rothman KA, Heier LM, Rosenthal WS. Photodynamic therapy for obstructing esophageal cancer: light dosimetry and randomized comparison with Nd:YAG laser therapy. Gastroenterology 1995;109: 63-72. doi:10.1016/j.gie.2005.06.010

Response: Yes, photodynamic therapy (PDT) is a nonthermal ablation technique. The generic term ‘‘mucosal ablation’’ and ‘‘Barrett’s ablation’’ were used in many locations throughout the article1 as a general term to include both the thermal ablative techniques of argon plasma coagulation, monopolar electrocautery, and neodymium-yttrium aluminum garnet laser and a nonthermal one, Photofrin (Axcan Scandipharm, Inc, Birmingham, Ala) PDT. However, as Gantz has correctly pointed out, the term ‘‘thermal’’ ablation was inadvertently not removed in 820 GASTROINTESTINAL ENDOSCOPY Volume 62, No. 5 : 2005

several areas (Table 1, Fig. 1, introduction in two locations, second sentence in the results section, and in two places in the discussion section). We appreciate your attentiveness to this oversight. More importantly, however, is our concern over Gantz’s last statement that ‘‘implication by Weston et al that there is a common thermal pathway as the cause of cardia changes after Barrett’s ablation..’’ Unfortunately, we apparently did not effectively convey the primary postulated mechanism to Gantz and, therefore, likely to many other readers. A great majority of the discussion section does not focus on ‘‘thermal’’ injury to the proximal cardia as the mechanism of cardia histology after ablation; this, in fact, is only mentioned as a possible cause in the very last sentence of the very lengthy second paragraph of the discussion. Instead, the mechanism of the histologic changes is postulated to reflect a greater degree of cardia reflux (the anatomic region of stomach) of noxious acid, bile, pancreatic juice, that is likely present to a greater degree in patients with Barrett’s who have high-grade dysplasia (HGD) and cancer compared with nondysplastic and low-grade dysplasia Barrett’s (i.e., paralleling the already well-known increasing severity in quantity, content, and duration of gastric and duodenogastric refluxate into the distal esophagus as one ascends the spectrum from simple nonerosive GERD to erosive GERD to Barrett’s to dysplastic Barrett’s). The vast majority of our discussion section focused on this theory. Serious cardia histologic changes are occurring in a subset of ablated patients; in fact, since the publication of this article, two additional patients with Barrett’s intramucosal adenocarcinoma, who have undergone complete mucosal ablation of Barrett’s have developed focal HGD within the anatomic cardia, picked up as the result of protocol jumbo surveillance biopsies from the cardia in all ablated patients before and after ablation (because the cardia mucosa was visibly normal appearing on standard video white-light endoscopy in both of these cases). It is very important that all centers that conduct ablation of Barrett’s mucosa, especially HGD and early carcinomas, continue endoscopic and histologic surveillance on these patients not only of the neosquamous epithelium but also of the cardia. Allan P. Weston, MD, FACG Gastroenterology Sisters of MercydSt. John’s Clinic Springfield, Missouri, USA REFERENCE 1. Weston AP, Sharma P, Banerjee S, et al. Visible endoscopic and histologic changes in the cardia, before and after complete Barrett’s esophagus ablation. Gastrointest Endosc 2005;61:515-21. doi:10.1016/j.gie.2005.08.005

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