## 1 Introduction
### Cryotherapy  
The target of the treatment is tumor removal with no recurrence. Taking into consideration that the GCT is usually located in close proximity to a joint, great care must be taken to preserve the articular surface. Historically, these aims were approached by performing an intralesional curettage of the tumoral tissue by filling the resulting cavity using morselized iliac bone autograft. The major problems of this therapy were the high recurrence rates of up to 50% [6], most likely because residual tumoral cells may still remain even with an accurate surgical procedure. In order to lower the risk of recurrence, the excision margins need to be enlarged. This can be done surgically, but in many cases the proximity of the joint will probably lead to sacrificing the articular surface and functional disability, or by using local adjuvants [7]. The first use of an adjuvant therapy in conjunction with orthopedic surgery is attributed to [PERSON] and [PERSON] at Memorial Sloan Kettering Cancer Center in New York (1969), who used an \"open system\" that allowed pouring liquid nitrogen (LN) directly into a tumor cavity. They treated a 48-year-old male with a painful metastatic lung carcinoma in the proximal humerus that was resistant to radiation therapy. The patient experienced complete relief of his pain following treatment. LN was shown to achieve local tumor control with minimal bone and function loss, and cryosurgery was soon practiced in conjunction with surgery for a large variety of bone tumors [8]. Other local adjuvants used for marginal tumor necrosis are phenol, ethanol, hydrogen peroxide (H\({}_{2}\)O\({}_{2}\)) and bone cement (polymethyl methacrylate (PMMA)) supplemented with antiblastics. Perhaps the most used and the most efficient method when completing tumoral excisions is argon beam coagulation, based on thermal ablation, which can be delivered even on small surfaces with cryoprobes [8]. All of these agents are used in order to achieve better results following surgical curettage of the tumor by eliminating any remaining neoplastic cells. Margin status of the curettage is associated mostly with an increased risk of local recurrence. The application of a tumoricidal agent as a local adjuvant to the tumor bed has been shown to decrease local recurrence rates. LN is a liquefied gas (cryogenic liquid) stored under pressure in purposely designed storage vessels. LN is intended for use as a cryogen in medical applications due to the cold temperature of the liquid. The boiling point of liquid nitrogen is \(-196\)\({}^{\circ}\)C. Nitrogen is stored and transported at \(-197\)\({}^{\circ}\)C in its liquid state as the most cost-effective way to provide product supply. In medicine, LN can be used either to preserve tissues or for controlled necrosis depending on the cycles of freezing and thawing. Usually, a quick freeze followed by a slow thaw will lead to destruction of human cells, and a slow freeze followed by a quick thaw is used to preserve tissues [9; 10]. There are several mechanisms that converge to cellular death during cryosurgery. Rapid exposure to extreme cold temperatures will lead to direct cellular destruction due to the formation of intracellular ice crystals and membrane destruction; increasing the temperature after the delivery of LN (freeze-thaw cycle) will lead to secondary necrosis for the tumoral cells. Thermal shock, toxic electrical imbalance, intracellular dehydration, microvascular alterations and disruption of the cell membrane are all produced by the increase in temperature following the freezing phase. Repetitive freeze-thaw cycles increase the amount of necrosis, but the response to cryotherapy is different depending on the distinct characteristics of the tissue (type, tissue vascularization, density, number of freeze-thaw cycles and absolute temperature) and is proportional to the time of exposure. Temperature range for necrosis of the cells is between \(-21\) and \(-60\)\({}^{\circ}\)C; beyond this, the percentage of necrosis does not increase [11].