Mechanisms of cryoablation: Clinical consequences on malignant tumors

Abstract

While the destructive actions of a cryoablative freeze cycle are long recognized, more recent evidence has revealed a complex set of molecular responses that provides a path for optimization. The importance of optimization relates to the observation that the cryosurgical treatment of tumors yields success only equivalent to alternative therapies. This is also true of all existing therapies of cancer that, while applied with curative intent; provide only disease suppression for periods ranging from months to years. Recent research has led to an important new understanding of the nature of cancer, which has implications for primary therapies, including cryosurgical treatment. We now recognize that a cancer is a highly organized tissue dependent on other supporting cells for its establishment, growth and invasion. Further, cancer stem cells are now recognized as an origin of disease and prove resistant to many treatment modalities. Growth is dependent on endothelial cells essential to blood vessel formation, fibroblasts production of growth factors, and protective functions of cells of the immune system. This review discusses the biology of cancer, which has profound implications for the diverse therapies of the disease, including cryosurgery. We also describe the cryosurgical treatment of diverse cancers, citing results, types of adjunctive therapy intended to improve clinical outcomes, and comment briefly on other energy-based ablative therapies. With an expanded view of tumor complexity, we identify those elements key to effective cryoablation and strategies designed to optimize cancer cell mortality with a consideration of the now recognized hallmarks of cancer.

Freeze-thaw decellularization of the trabecular meshwork in an ex vivo eye perfusion model

“…Freeze-thaw cycles, applied here to group F, have been used extensively before to ablate tissues in human diseases (Erinjeri & Clark, 2010;Baust et al, 2014;Chu & Dupuy, 2014) including cyclocryodestruction in glaucoma (Benson & Nelson, 1990). It has also been used in research (Baust et al, 2014;Chan & Ooi, 2016;Liu et al, 2016) and in food production ("Fish and Fishery Products Hazards and Controls Guidance"; Gill, 2006;Craig, 2012).…”

“…It has also been used in research (Baust et al, 2014;Chan & Ooi, 2016;Liu et al, 2016) and in food production ("Fish and Fishery Products Hazards and Controls Guidance"; Gill, 2006;Craig, 2012). The mechanisms of cryoablation in medicine include direct cell injury, vascular injury, ischemia, apoptosis, and immunomodulation (Chu & Dupuy, 2014): cell injury during freezing causes dehydration from the so-called solution effect that causes the earlier freezing extracellular compartment to extract solutes, an osmotic gradient and cell shrinkage (Lovelock, 1953) that can be enhanced by ice crystal formation within the cell, damaging organelles and the cell membrane.…”

Cryoablation and Meriva have strong therapeutic effect on triple-negative breast cancer

“…22 The necrosis observed in the ablated lesion is mediated by mechanical disruption from crystallization, osmotic changes, and vascular stasis. 23 The necrotic tumor lesion remains within the body, and TAA-specific T cells are recruited through the release of multiple TAAs by the cryokilled tumor cells and the release of high mobility group box (HMGB)-1 protein [that binds to the receptor for advanced glycation endproducts (RAGE) and toll-like receptors (TLRs) on DCs], resulting in increased TAA presentation by the DCs. 24 However, these TAA-specific T cells need help because of the strong immune suppression in the TME.…”

Ablative Therapies for the Treatment of Small Renal Masses: a Review of Different Modalities and Outcomes

“…Although CA leads to tissue destruction at −19.4°C, some animal models suggest that lower temperatures are required for cancerous tissues due to increased fibrosis. This ultimately led to a clinical target goal below −40°C [13].…”