CRYOABLATION
TECHNOLOGY
Cryobiology
Cryobiology is the study of living organisms, organs, biological tissues or cells at low temperatures.
The word cryobiology (from the Greek words "cryo" = cold, "bios" = life, and "logos" = science) signifies the science of life at low temperatures. In practice, this field comprises the study of any biological material or system (e.g., proteins, cells, tissues, organs, or organisms) subjected to any temperature below normal (ranging from moderately hypothermic conditions to cryogenic temperatures).
Cryotherapy,
also called cryosurgery or cryoablation refers
to the application of extreme cold to destroy
diseased tissue, including cancer cells. Living
tissue, healthy or diseased, cannot withstand
extremely cold conditions and dies from several
effects following ablation treatments:
• Ice within the cell.
• Ice outside the cell.
• Loss of blood supply.
Once the cells are destroyed, components of the immune system—primarily the white blood cells—clear out the dead tissue. There is some evidence to suggest that this stimulates the immune system to attack remaining cancer cells after cryosurgical ablation.
Intracellular Ice
At approximately -40°C (-40°F) or less, lethal ice crystals begin to form within the cell that will tear apart almost any cell.
Extracellular Ice
As temperatures approach the hypothermic range, extracellular water begins to crystallize and a hyperosmotic extracellular environment that draws water out of the cells is created. As the process continues, extracellular ice crystals grow, cells shrink, and membranes and cell constituents are severely damaged.
Within a short time (minutes), the increased electrolyte concentration is sufficient to destroy the cells. This effect of cell dehydration and solution concentration, called solution-effect injury, is not always lethal to cells; intracellular ice formation is a more significant threat to cell viability and is almost always lethal (Mazur, 1963, 1968, 1977, 1981; Maryman, 1966; Pegg, 1987; Sherman, 1962). Solution-effect injury is associated with low freezing rates, while intracellular ice formation is commonly associated with fast freezing rates.
Although pure water begins to freeze at 0°C, extracellular ice formation is initiated at approximately –7 to -10°C, and by -15°C intracellular ice begins to form (heterogeneous nucleation). By -40°C all metabolic processes are expected to have ceased (homogenous nucleation) (Baust and Change, 1995).
Loss of blood supply
Cells die when their blood supply is choked off by ice forming within small tumor vessels, causing clotting. The loss of circulation and cellular anoxia is commonly considered to be the main mechanism of injury in cryosurgery. The initial response to the cooling of tissue is a decrease in the flow of blood. With freezing, the circulation ceases. As the tissue thaws and the tissue temperature climbs over 0°C, the circulation returns.
The endothelial damage results in increased permeability of the capillary wall, edema, platelet aggregation, and microthrombus formation, which results in stagnation of the circulation. The loss of blood supply deprives all cells of any possibility of survival and results in uniform necrosis of tissue, except at the periphery of the previously frozen volume of tissue.
Thawing
Cryotherapy ablation usually consists of a series of steps in which tumors are repeatedly frozen and thawed.
During thawing, ice crystals fuse
to form large crystals, a process called recrystallization.
In tissues with closely packed cells, the large
crystals are disruptive to cell membranes. As
the ice melts, the extracellular environment is
briefly hypotonic, water rushes into the shrunken,
damaged cell, cell volume increases, and cell
membranes may rupture. After complete thawing,
the previously frozen tissue remains hypothermic
for many minutes and the damaged tissue is subject
to continued metabolic derangement during this
time.
Cryosurgery (freezing)
Cryosurgical treatments require subjecting tissue to freezing temperatures. As explained above, cellular and tissue injury are produced by a sequence of destructive effects, beginning with tissue cooling, metabolic disruption and ice crystal formation. After thawing, microcirculatory failure and the associated ischemia adds to cell death, finally resulting in necrosis.
The basic principles of cryosurgery
for tumors are fast cooling of the tissue
to a lethal temperature, slow thawing, and repetition
of the freeze-thaw cycle to achieve therapeutic
efficacy.
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