Pathomorphologic evaluation of pulmonary radiofrequency ablation

Abstract

BACKGROUND.Radiofrequency (RF) ablation is an increasingly applied technique. Promising results of hepatic RF ablation raised expectations of its capabilities for treatment of primary and secondary lung tumors. Because of different thermal and electrical properties of lung tissue, compared with liver tissue, a simple analogy of tissue response is not possible. The authors aimed to evaluate the effectiveness of image‐guided pulmonary RF ablation and to characterize pathomorphology of tissue response.METHODS.RF ablations of 11 pulmonary malignancies in 9 patients were performed under computed tomography (CT)‐guidance. Three days after RF ablation, surgical resection was performed followed by pathologic examination. Specimens were evaluated macroscopically, histologically by hematoxylin and eosin (H & E) staining, terminal deoxy‐nucleotidyl transferase‐mediated nick end‐labeling (TUNEL), and electron microscopy.RESULTS.Tumor tissues and adjacent lung tissues were characterized by double‐strand fragmentation as determined by TUNEL. Ultrastructurally apoptotic bodies were found, indicating apoptotic cells. Criteria for tissue necrosis were not fulfilled by standard histological staining (H & E), showing preserved tissue architecture and only few microscopic cellular details suggestive of tumor regression. Because of DNA fragmentation, as determined by TUNEL and results from electron microscopy, the authors confirmed the tumor tissue to be completely ablated in 10 (90.9%) cases. However, in 2 cases, a safety margin was absent.CONCLUSIONS.CT‐guided pulmonary RF ablation of pulmonary malignancies is a locally effective treatment. Three days after RF ablation, tumor tissue seemed to be thermally fixed still showing characteristics of vital tumor tissue in standard histological staining; however the tissue proved to be in regression toward coagulative necrosis verified ultrastructurally and by TUNEL. Cancer 2008. © 2008 American Cancer Society.

Systemic inflammatory response and downmodulation of peripheral CD25+Foxp3+ T-regulatory cells in patients undergoing radiofrequency thermal ablation for lung cancer

“…Pulmonary RFTA is supposed to induce a coagulative necrosis [4], although evidence of an apoptotic mechanism has been recently provided [36]. Necrotic cell death is associated with an inflammatory response inducing the release of proinflammatory signals, such as heat shock proteins and HMGB1, that can play an important role in the initiation of antitumor immunity by inducing DC stimulation and maturation [37][38][39].…”

Immunologic Response to Tumor Ablation with Irreversible Electroporation

“…Hyperthermia would cause the melting and fusing of cell membranes as well as protein denaturation, in which proteins are transformed from their native state to a more random state of lower organization. The unfolding of the three dimensional protein structure can destroy the structure of antigenic determinants [31], [42]. This means that little of the remaining tumor debris are potential sources of tumor-associated antigens available to stimulate the immune system.…”

More Than Just Tumor Destruction: Immunomodulation by Thermal Ablation of Cancer

“…High temperatures (RF ablation, MWA, HIFU, and LITT) seem rather to sustain antitumor activity whereas both immunomodulatory and immunosuppressive effects have been reported upon cryoablation. Of note, the lesions induced by high-temperature thermoablation are probably not solely of necrotic nature but may also exhibit apoptotic cells [16, 152, 153]. Whether opposite immunological outcomes are hence related to a different balance between apoptosis, necrosis, and secondary necrosis, with apoptotic cells acting more in a tolerizing or immunosuppressive fashion and necrotic cells more immunogenic, is at the moment unclear [138, 139].…”

“…The first patients with cerebral tumors were already treated with RF ablation in the early 20th century, but it took until the 1990s for RF ablation to become an accepted, commonly used treatment option for primarily unresectable tumor lesions in liver, kidney, bones, and lung [15]. During RF treatment, one or more RF applicators are placed in the target tissue and high-frequency alternating current is generated, leading to frictional heating above 60°C up to 100°C inducing coagulative necrosis [2, 16]. Higher temperatures would result in desiccation and subsequent increase in tissue impedance which limits further conduction of electricity into the tissue [12].…”