Cryotherapy also called as Cryosurgery - works by destroying tissue by freezing. Tissue injury results from intra-cellular and extracellular formation of ice, disruption of cell membranes, and circulatory changes in the skin caused by freezing and thawing. Critical factors influencing cellular necrosis are rate of freezing, temperature, duration of freezing, and rate of thawing.


In general, a rapid freeze of tissue to at least -20oC followed by a slow thaw will destroy the tissue of benign lesions. For malignant lesions, tissue needs to be frozen to -50oC to kill the cells1. Critical factors influencing cellular necrosis are rate of freezing, temperature, duration of freezing, and rate of thawing.

Technique - The freezing unit is applied to the skin lesion, freezing begins immediately and can be observed as a whitish discoloration of the skin that spreads peripherally from the point of contact and is known as the lateral spread of freeze. Extent of freezing is estimated by the lateral spread of freeze, which closely approximates depth of freeze. Depth of freeze can be increased by applying pressure on the skin with either a cryoprobe. If liquid nitrogen spray is used, depth of freeze can be increased by prolonging duration of freeze. Successful treatment depends on the lesion's being included in the lethal freeze zone. For this reason, the lateral spread of freeze should extend at least 2 mm beyond the margins of benign lesions and 5mm beyond the margins of malignant lesions1. repeat freeze-thaw cycle, will increase tissue destruction. A slow thaw increases the degree of tissue destruction; frozen tissue should be allowed to thaw gradually at room temperature and should never be warmed artificially.

 The cryosurgery can be of two types - direct cryogens using carbon dixode ice or liquid nitrogen or by cryotherapy machines using nitrous oxide or carbon dioxide as cryogens.

 

Treatment and technique

The cryogens most commonly used are nitrous oxide,  Argon, carbon dioxide, liquid nitrogen, liquid carbondioxide etc.

Cryosurgical units - use cryogens like Nitrous oxide gas / carbon dioxide gas or argon which are sprayed through a special apparatus to produce cooling. . 

Direct application cryogens - The cryogens like liquid nitrogen, liquid carbon dioxide (dry ice) are directly applied to the lesion to create extreme temperatures to destroy the tissue.

 

Cryosurgical Units

These units operate by the Joulc-Thomson effect. This method o f refrigeration results from the principle or the expansion of
the gas through a small opening. Pressurized nitrous oxide advances down the narrow cryogun barrel. When it reaches the hollow cryoprobc tip, the gas rapidly expands, lowering it to a temperature below freezing. Although the cryo-probe tip visibly cools with unit activation, the tip must actually be considered a heat sink. As the tip removes heat from the tissue, the tissue gradually cools. The size, material, composition, and temperature of the probe’s tip determine its capacity' as a heat sink. Other factors, such as tissue moistness, extent of tissue contact, the duration of freeze, and pressure exerted on the probe, affect heat diffusion.

The extent of cryonecrosis is influenced by the speed at which tissue freezes and thaws. A rapid freeze and a slow thaw maximize results. A freeze-thaw-freeze treatment cycle is also more effective than a single freeze technique.


Nitrous oxide


Freezing with nitrous oxide is accomplished with a cryo-gun attached to a nitrous oxide tank. The gas circulates through the gun to a metal probe where rapid expansion of the gas reduces the temperature of the probe to approximately -65oC to -85oC. The probe is applied to the skin lesion through a water-soluble lubricant and held there for an appropriate time. The gas flows continuously to the probe tip while the gun trigger is activated. Thawing begins as soon as the nitrous oxide stops flowing. Nitrous oxide freezing requires longer freeze times because of the higher temperatures and, as a result, there is less likelihood of excessive tissue destruction. It is easy to control freeze times accurately, and a variety of metal probes are available, which means cryoguns can be adapted for treating a variety of lesions. For example, they are often used for gynecologic cryosurgery.
The initial cost of these units is fairly high. The nitrous oxide tanks last a long time, however, and cryogen is not wasted as it might be with liquid nitrogen.

 

Effects of Cryotherapy / cryosurgery on tissues

Celluar Injury - The cell injury that occurs after freezing is thought to result from a high solute concentration causing cell dehydration. Intracellular ice formation causing intra-cellular organelle and cell membrane disruption has also been implicated. It is known that slow thawing allows solute effects and maximum ice growth during recrystallization to take place. Because solute effects and ice growth are deleterious to cells, complete thawing before the start of another cycle is important in determining the success of cryosurgery for oncological conditions. However, rapid cooling followed by rapid thawing can also be beneficial. During rapid cooling, the ice crystals tend to be small, with high surface energies. The longer the time of thawing, the easier it is for the ice to recrystallize, especially for crystals with high surface energies. The larger ice crystals can be more destructive than the smaller ones, because of the size of the crystals or the forces generated during recrystallization. The hold time – the duration of time the tissue is in the frozen state – is also an important factor in determining the degree of cryoinjury. Another mechanism of direct cell injury is membrane destabilization during freezing and thawing 

Immunological Injury - Another theory is that freezing may stimulate immunological injury. It is believed that the immune system becomes sensitized to the destroyed frozen tissue, and any tissue left behind is attacked by the host’s own immune system after cryosurgery. MECHANISMS OF IMMUNOLOGICAL INJURY - The first theory is the production of antitumour antibodies. When the tumour cells die, the antigens inside the cells are released onto the membrane and phagocytosed by antigen-presenting cells. B cells with antibodies specific for the antigen are stimulated and transformed into plasma cells. Antibody formation induces complement fixation, leading to neutrophil and macrophage chemotaxis. These cells release free radicals and enzymes, which kill tumour cells left behind. The second mechanism of immunological involvement is through the induction of cytotoxic T cells. Normally, intracellular antigens are transferred to the cell membrane and recognized by cytotoxic T cells, which release enzymes and kill the cells. It was proposed that cryosurgery may sensitize the cytotoxic T cells or change the antigen presentation. The third possible mechanism is that cryosurgery may stimulate the activity of natural killer cells 2.

Vascular Injury - It has been theorized that freezing involves vascular injury. The hypothesis is that freezing results in stasis of blood flow, particularly in the capillaries. The resulting ischemia leads to tissue  necrosis.

 


Complications of cryosurgery

In general, cryosurgery is very safe, but some complications do occur.  Cryosurgery is contra-indicated  for patients with cryoglobulinemia, Raynaud's phenomenon, immunosuppression, myeloproliferative disorders such as multiple myeloma, cold intolerance, and various blood dyscrasias.


Severe reaction and tissue destruction following cryosurgery are more likely with lesions on thin skin or skin previously damaged by radiation or sun exposure, with skin lesions over bony prominences, and in patients with impaired vascular supply (such as elderly people).

A short period of moderately intense pain with the freeze and during thawing is followed almost immediately by redness and swelling that might last several hours. Blistering, which often occurs within a few hours of treatment, might be both hemorrhagic and alarmingly large. Blisters tend to dry within 72 hours, and a crust forms. The crust gradually separates over 7 to 14 days.  There can be possibility of  potential hair loss, hypopigmentation, and scarring. steroid ointment can greatly reduce pain and swelling.

 

 

References

  1. Wetmore SJ. Cryosurgery for common skin lesions. Treatment in family physicians' offices. Can Fam Physician. 1999;45:964-974. 
  2. Yiu WK, Basco MT, Aruny JE, Cheng SW, Sumpio BE. Cryosurgery: A review. Int J Angiol. 2007 Spring;16(1):1-6. doi: 10.1055/s-0031-1278235. PMID: 22477240; PMCID: PMC2732998.
  3. Ferris DG, Ho JJ. Cryosurgical equipment: a critical review. J Fam Pract. 1992;35(2):185-193
Go to top