Cryosurgery is a minimally invasive procedure that uses liquified gas (nitrogen or argon) to freeze and destroy diseased tissue or organ. It is also known as cryotherapy, cryoablation, percutaneous cryotherapy, and target cryoablation therapy.
Cryosurgery has a wide range of applications; it can be used to remove simple skin tags as well as dissolve tumors in the liver, bone, breasts, etc. The surgeon uses an instrument called a cryoprobe through which liquid gas is sent in a series of freeze-thaw cycles to the targeted organs; the freezing temperature of the liquid gas (-186 degrees to -196 degrees) destroys the abnormal cells, which get dissolved later on.
What Are the Common Uses of Cryosurgery?
Cryotherapy can be used to treat both benign and non-metastatic malignant tumors; they are:
Benign Lesions - Non-cancerous lesions that can be treated with cryosurgery are seborrheic keratosis (noncancerous skin wart), verruca (viral wart), skin tags, molluscum contagiosum (viral skin infection), solar lentigo (discolored skin patch), and hypertrophic or keloid scars (thick scar). Because of the benign nature of these lesions, one to two rounds of cryosurgery is sufficient to treat them; however, thicker and larger lesions like a verruca will need anywhere between three to six rounds of cryosurgery done at three to four-week intervals to resolve.
Malignant Lesions - Cancerous lesions that are treated with cryosurgery are actinic keratosis (solar keratosis), basal cell carcinoma (epithelial tumor), lentigo maligna melanoma (a type of melanoma), and non-invasive squamous cell carcinoma (cancer that invades only till the second layer of the skin). Malignant tumors that cannot be removed by conservative surgical excision (large and disfiguring)and when present in elderly patients are removed by cryosurgery.
Cryosurgery is not indicated in patients with cryoglobulinemia (abnormal clumping of proteins at normal temperature), multiple myeloma (cancer due to plasma cells), Raynaud’s disease (numbing of fingertips and toes), or cold urticaria (instant skin reaction to cold), because these conditions get exacerbated when exposed to cold. It is also not suggested for patients with a previous history of cold-induced injury and in poorly vascularized sites. When combined with poor vascularization, the vasoconstriction nature of the surgery will lead to necrosis in undesired areas.
How Does Cryosurgery Work?
Cryosurgery uses a cryogen (liquid nitrogen or argon) and a cryoprobe to cool the affected tissue to subzero temperatures. This causes damage to the affected tissue by three mechanisms:
A. Mechanism of Vascular Injury - Lesions or tumors always have a good blood supply, and this is because they secrete growth factors that create new blood vessels from pre-existing ones. The blood through these newly formed vessels provides the necessary nutrients for the tumor to grow in size. During cryosurgery, the liquid gas injected through the cryoprobe damages these blood vessels, which causes tissue ischemia (reduced blood supply), leading to necrosis (death) of the lesion.
B. Mechanism of Immunological Injury - This is an added advantage of cryosurgery compared to the conventional surgical excision of the tumor. During surgical excision, the tumor, along with the antigens (a foreign particle that causes the lesion) causing the tumor, is completely removed, depriving the patient of the immune response that will protect them from recurring malignant cells.
- In cryosurgery, the antigens are retained, which triggers an immune reaction in the body that ultimately destroys them. The information of the entire reaction that disposed of the antigen will be stored in the immune system, which will be reused if and when the body is attacked by the same antigen again, thereby preventing recurrence.
C. Cell Injury During Cryosurgery - Temperature difference and osmosis are the major causative factors for cell death during cryosurgery. Osmosis is the movement of a liquid from its higher concentration to its lower concentration. A lesion or tumor is primarily a mass in which cells are interconnected with the intercellular matrix. When a cryogen is injected into this mass, the intercellular matrix (that contains extracellular fluid) gets frozen first. This leads to the formation of ice crystals in it, which is relatively at a lower temperature compared to the fluid inside the cell.
As a result of this temperature change, fluid inside the cell is drawn to the intercellular matrix to balance the temperature difference causing shrinkage of the cells. As the cryogen infiltrates more into the mass, ice crystals start forming inside the cells, which will rupture them.
Next comes the thawing process, which starts first in the intercellular matrix. During thawing, the extracellular fluid's temperature increases in the matrix, but the inside of the cell is still at a low temperature compared to the extracellular fluid. To balance this, fluid from the intercellular matrix enters the cells causing them to swell and burst.
Ideally, cryosurgery starts with cooling, followed by freezing, and then thawing, but most surgeons prefer to use the freeze-thaw cycle, which is rapid cooling followed by slow thawing (freeze-thaw cycle). This is because the quantity of damaged cycles increases with each free-thaw cycle. Ideally, the temperature to destroy benign lesions is around -20 degrees, and for malignant lesions, it is -50 degrees.
The surface area that gets frozen during cryosurgery is known as an isotherm. Therefore, a cryo surgeon needs to know the concept of isotherm to achieve the required temperature at the required depth and width for the lesion to damage and dissolve.
How Is Cryosurgery Done?
The most frequently used technique for cryosurgery is the open approach, during which the cryogen (liquid nitrogen or argon) is sprayed onto the target lesion; a few other techniques are:
Periodic release of liquid gas gives controlled and precise application at the target site.
The semi-open technique is preferred for papular lesions, where a cone or a plate is used to direct the cryogen to the area that needs to be cooled.
The closed technique is where the cryoprobe comes into the picture; it is a wand-like device with inbuilt nitrous oxide cartridges. They deliver liquid nitrogen directly at the target site; occasionally, the probe will freeze to the skin and, when tried to remove forcefully, will rip off the skin leading to bleeding. When this happens, it is suggested to use warm water to separate the probe from the skin.
A modified closed technique would cool the tip of the forceps/needle drivers and then use the frozen forceps to grasp the pedunculated lesions.
The type of approach depends on the location of the lesion. The duration of cryosurgery is decided based on the type of lesion; for benign lesions, the target temperature is -5 degrees for pigmented lesions and -25 degrees for keratinocytic lesions.
One freeze-thaw cycle is sufficient for most of them; they are frozen till the white halo extends one millimeter to two millimeters beyond the border of the lesion, and the thawing is done till the white frost completely disappears. Benign lesions are always undertreated to prevent damage to the melanocytes, which can cause hypopigmentation.
For malignant lesions, the freezing temperature can be extended to -50 degrees, requiring multiple free-thaw cycles. In addition, the freezing is extended five millimeters beyond the border of the lesion to include any remnant malignant cells that might cause future recurrence. As a caution, malignant lesions are always overtreated because there is no way to ensure that the entire margin has been cleared.
What Are the Complications of Cryosurgery?
Cryosurgery is done to damage the tissue, which will heal by secondary intention, so pain, erythema, and edema are expected. Apart from these, a few complications that are seen due to cryosurgery are:
Dyspigmentation, either hypopigmentation or hyperpigmentation, happens due to the destruction of melanocytes during cryosurgery.
Alopecia is a temporary side-effect due to cold-induced destruction of hair bulge cells.
Pseudoepitheliomatous hyperplasia is also seen after cryosurgery; no treatment is needed for this as it will resolve spontaneously once the effects of cryosurgery wear off.
Depressed scars are often seen in deep cryosurgery, the depth and the scar depend on the lesion, and it takes time to resolve these scars.
Besides the complications mentioned above, tissue distortion, like nail dystrophy and notching in the cartilage, is also seen after cryosurgery.
Cryosurgery is a well-tolerated procedure with satisfactory results. The procedure's success depends on choosing the right patient and understanding the mechanism of selective tissue destruction. Patients should be counseled on expected outcomes before the procedure. Although cryotherapy is a slow treatment that requires multiple sessions, an efficient interprofessional team of clinicians and nurses will produce the best results and provide continuous follow-up.