In addition to the verified mechanisms of tissue damage during cryosurgery there is anecdotal evidence that cryosurgery may result in a beneficial systemic immunological response. There is no doubt that a normal immune response exists in response to the tissue injury which freezing produces. The usefulness of this immune response in treating metastatic tumors has been proved.
Recently a new concept was developed that has the potential for increasing the destructive effect of freezing. It has been observed that a family of proteins known as "antifreeze proteins" has the ability to modify the structure of ice crystals. These proteins, found in a large number of cold tolerant animals and plants inhibit non-colligatively the freezing temperature of solutions. However, when the solutions eventually freeze in the presence of these antifreeze proteins, they modify the structure of ice crystals. At certain concentrations these ice crystals can become needle like and lethal to cells. In cryosurgery experiments, in which the antifreeze proteins were introduced in tissue prior to the procedure, it was found that the cells were destroyed by freezing throughout the tissue regardless of the thermal history employed during freezing. The mechanism of damage appears to be mechanical and related to the interaction between the ice crystals and the cells. It appears that the antifreeze proteins induce intracellular ice formation at high subzero temperatures, regardless of the thermal history during freezing. Obviously the use of antifreeze proteins as chemical adjuvant to cryosurgery may become important. The destruction of frozen tissue may potentially become independent of the thermal history that the cells have experienced during freezing.
PROCEDURE
The technique requires sophisticated equipment, which generally uses argon gas or liquid nitrogen as the cryogenic material. The tumors are localized by untrasound or CT. The general approach is to avoid direct puncture of the tumor and to try to have some noncancerous tissue interposed between entry point and the tumor tissue. An 18-gauge needle is placed in the centre of tumor. The needle position is confirmed in both imaging planes. A J-shaped guide wire is positioned in the tumor through the needle. A sheathed dilator (3-8mm) is introduced into the tumor over the guide wire. The dilator is removed, and the sheath is left in place. Cryogenic probes are then placed into tumor through the sheath. The sheath is then pulled back. Cryogenic material is circulated through the probes. The iceball created by this treatment is visualized and monitored by real-time untrasonography or CT, as the leading edge of the iceball echogenic. The tumors are frozen at maximum flow rate for 15 minutes, and are thawed for 5 minutes, and then refrozen for another 10 minutes. If the initial ice balls are not large enough to encompass the entire length of the tumor, then the probes are pulled back for 2-5cm, depending on the length of the tumors. The cryogenic probes are turned on maximum flow rate for an additional 15 minutes, thawed for 5 minutes, and then refrozen for 10 minutes. The entire process may be repeated for very large tumors.