You are in: eMedicine Specialties > Dermatology > SURGICAL CryotherapyArticle Last Updated: Nov 26, 2007AUTHOR AND EDITOR INFORMATIONSection 1 of 10
  Author: Raymond T Kuwahara, MD, Dermatologist, Private Practice Raymond T Kuwahara is a member of the following medical societies: American Academy of Dermatology Editors: Robin Travers, MD, Professor, Department of Dermatology, Boston University School of Medicine; Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University School of Medicine; Consulting Staff, Mountain View Dermatology, PA; Warren R Heymann, MD, Head, Division of Dermatology, Professor, Department of Internal Medicine, University of Medicine and Dentistry of New Jersey; Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania; Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center Author and Editor Disclosure Synonyms and related keywords: cryosurgery, liquid nitrogen, freeze-thaw technique INTRODUCTIONSection 2 of 10
  Cryotherapy, also known as cryosurgery, is a commonly used in-office procedure for the treatment of a variety of benign and malignant lesions. In a recent report, cryotherapy was the second most common in-office procedure after skin excision. The mechanism of destruction is necrosis, which results from the freezing and thawing of cells. Treated areas reepithelialize. Adverse effects are usually minor and short-lived. Dermatologists have used cryotherapy since the turn of the century. After the development of the vacuum flask to store subzero liquid elements, such as nitrogen, oxygen, and hydrogen, the use of cryotherapy dramatically increased. By the 1940s, liquid nitrogen became more readily available, and the most common method of application was by means of a cotton applicator. In 1961, Cooper and Lee1 introduced a closed-system apparatus to spray liquid nitrogen. In the late 1960s, metal probes became available. By 1990, 87% of dermatologists used cryotherapy in their practice. The general advantages of cryotherapy are its ease of use, its low cost, and its good cosmetic results. Most skin cancers are treated with excision or other destructive procedures, such as electrodesiccation and curettage. Superficial basal cell skin cancers and Bowen disease can be treated with cryotherapy. Recurrence rates for primary basal cell carcinoma vary with treatment modality. The 5-year recurrence rate for cryotherapy may be as low as 7.5% if lesions are chosen judiciously.2 This percentage compares favorably with published recurrence rates following other procedures. Published rates include surgical excision, 10.1%; curettage and electrodesiccation, 7.7%; radiation therapy, 8.7%; and all non-Mohs modalities, 8.7%. Because these percentages are derived from various studies, rather than one randomized controlled study comparing the different modalities, they should be viewed as rough approximations. Well-circumscribed tumors are most suitable for cryotherapy. The indolent local growth of these well-circumscribed tumors accounts for the high cure rates quoted in the literature. In most instances, reimbursement for cryotherapy treatment of skin cancers is at the same rate as for destruction of benign lesions. MECHANISM OF ACTIONSection 3 of 10
The mechanism of action can be divided into 3 phases: (1) heat transfer, (2) cell injury, and (3) inflammation. Heat transfer The mechanism by which cryotherapy destroys the targeted cells is the quick transfer of heat from the skin to a heat sink. The most commonly used cryogen is liquid nitrogen, which has a boiling point of -196°C. The rate of heat transfer is dependent on the temperature difference between the skin and the liquid nitrogen. When using the spray technique, the liquid nitrogen is applied directly on the skin, and evaporation (boiling heat transfer) occurs in which the heat in the skin is quickly transferred to the liquid nitrogen. This process results in the liquid nitrogen evaporating (boiling) almost immediately. When using a cryoprobe, conduction heat transfer occurs where the heat is transferred via the copper-metal probe. Cell injury Cell injury occurs during the thaw, after the cell is frozen. Because of the hyperosmotic intracellular conditions, ice crystals do not form until -5°C to -10°C. The transformation of water to ice concentrates the extracellular solutes and results in an osmotic gradient across the cell membrane, causing further damage. Rapid freezing and slow thaw maximize tissue damage to epithelial cells and is most suitable for the treatment of malignancies. Fibroblasts produce less collagen after a rapid thaw.3 Therefore, a rapid thaw may be more suitable for the treatment of keloids or benign lesions in areas prone to scarring. Freeze damage can be seen when a steak is defrosted from the freezer. The steak juices that are seen when fully thawed represent the intracellular liquid that has escaped because of the damage to the cell wall. Low temperature also ensures maximum damage by further concentrating electrolytes intracellularly. Keratinocytes need to be frozen to -50°C for optimum destruction. Melanocytes are more delicate and only require a temperature of -5°C for destruction. This fact is the reason for the resulting hypopigmentation following cryotherapy on darker-skinned individuals. Malignant skin cancers usually need a temperature of -50°C, while benign lesions only require a temperature of -20°C to -25°C. Inflammation The last response to cryotherapy is inflammation, which is usually observed as erythema and edema. Inflammation is the response to cell death and helps in local cell destruction. A thorough cryotherapy treatment causes basement membrane separation, which may result in blister formation. TREATMENT MODALITIES USING CRYOTHERAPYSection 4 of 10
Various methods have been devised in the use of cryotherapy of lesions. They include the spray freeze technique, the applicator technique, the cryoprobe method, and the thermo-coupler method. Liquid nitrogen is the best and universal freezing source because of its low boiling point and its ease of use. Other sources that are used to freeze, such as Freon, carbon dioxide, and nitrous oxide, do exist, but they are not as efficient in destroying lesions because of their higher boiling points. Prior to freezing the lesion, the patient must be informed of the procedure, and verbal or written consent must be obtained. A local anesthetic, such as 1% lidocaine, or a topical anesthetic, such as ELA-Max (Ferndale Pharmaceuticals) or EMLA (Astra Pharmaceuticals), can be used. Young children almost always need some type of anesthetic prior to treatment. Debulking keratotic material with a razor, a No. 11 blade, or a curette by shaving or by curettage facilitates the destruction. Spray technique The spray technique is probably the most commonly used method. This method is suitable for most benign and some superficial neoplastic lesions. Pulsing each spray to avoid an overexpansion of the treatment site prevents complications. A cone spray technique has been suggested in the past by using an apparatus with 2 open ends; however, such accessories are not readily available and, thus, they are not often used.4 The cone attachments are round; therefore, they are most suitable for round lesions. For large, irregularly shaped lesions, sequential freezing is necessary. The use of disposable specula instead of nondisposable cone attachments offers several advantages. Disposable specula can be cut with scissors to vary the size and the shape of the aperture. With the advent of HIV and other communicable diseases, the use of a disposable device, such as the plastic specula, is a convenient and simple solution to the problem of contamination.5 The nozzle tip of the spray gun is held about 1 cm from the treatment site, and liquid nitrogen is sprayed on the lesion until an ice ball is formed. The operator then palpates the lesion to determine the size of the ice ball created. This process is repeated until an ice ball of the desired size is created. The time for which the lesion is frozen is the freeze time. This freeze-thaw cycle can be repeated, depending on the type of lesion being treated. Hypopigmentation is a common complication with cryotherapy. This complication is due to the temperature-sensitive melanocytes, which die at the relatively high temperature of -5°C to -10°C. Feathering, the process of gradually and lightly freezing the area surrounding the ice ball to prevent an abrupt edge, can provide better cosmetic results. Dipstick applicator method6 The dipstick applicator method is the original method used to apply liquid nitrogen to lesions. A cotton-tipped applicator is dipped into liquid nitrogen from a polystyrene cup. The dipstick applicator is then firmly pressed against the lesion for the desired duration. Low temperatures are not achieved in the dipstick applicator method as they are in the spray technique; therefore, this method is suitable only for benign lesions. Adenovirus is capable of survival in liquid nitrogen; therefore, the same source of liquid nitrogen should not be used with different patients. Previously unused liquid nitrogen can be placed in a polystyrene cup and then promptly discarded after use for a single patient. Cryoprobe Manufacturers have devised various metal attachments to serve as heat-conducting probes for cryotherapy. Copper, because of its high conductivity, is typically used. A thin film of white petrolatum can be applied to the treatment site, and the cold probe is firmly pressed against the lesion. Many practitioners do not use the probe because it is cumbersome and time consuming. Thermo-couple device To treat malignant lesions, a temperature probe coupled to a digital thermometer that can read to -75°C can be used. Local anesthetic is injected into the lesion, and a temperature probe is inserted into the estimated depth of the lesion. Usually, a metal or styrene cone is used to concentrate the freeze. The liquid nitrogen is sprayed into the cone until the desired temperature is reached, usually -50°C to -60°C. This process can be repeated until the desired destruction is achieved. CLINICAL APPLICATIONSSection 5 of 10
Various lesions have been treated with liquid nitrogen. Because of the histologic differences in lesions, different freeze-thaw cycles are used to successfully destroy them. For most of these lesions, cryotherapy is not the only and often not the best modality for treatment. However, it does represent a valuable alternative for selected patients. For some lesions, such as actinic keratoses, warts, and seborrheic keratoses, cryotherapy is the standard first-line therapy. The time estimates given below must be adjusted depending on the skin temperature, local circulation, skin pigment, and method of delivery. Overfreezing can produce permanent hypopigmentation and scarring. Pigmented lesions For melasma, a light, uniform freeze with feathering completed every 4-6 weeks can produce a good cosmetic result in some patients. Other modalities, such as topical depigmenting agents, sunscreens, and chemical peels, are more commonly used to treat melasma. For tattoos, two 30-second freeze-thaw cycles with 1-mm margins performed every 4-6 weeks can improve some lesions. Newer modalities, especially laser therapy, are more suitable for most tattoos. Idiopathic guttate hypomelanosis can be treated with one 5-second freeze with feathering performed every 4-6 weeks. Lentigo can be treated with one 5- to 10-second freeze with feathering completed every 4-6 weeks until resolved. Often, one treatment is all that is required. Vascular lesions AIDS-related Kaposi sarcoma can be treated by performing two 30-second freeze-thaw cycles with 3-mm margins every 4 weeks. A venous lake can be treated with one 10-second freeze-thaw cycle with a 1-mm margin; usually, 1 cycle is all that is required. Cherry angiomas can be treated with one 10-second freeze-thaw cycle with a 1-mm margin. Capillary hemangioma can be treated with two 30-second freeze-thaw cycles with a 1-mm margin. Cysts and tumors One 10-second freeze-thaw cycle with a 1-mm margin can be used to treat acne cysts. This method is usually adequate to cause exfoliation and to open pores. For milia, a short freeze-thaw cycle of 5-10 seconds is usually adequate. Skin tags can be treated with one 10-second freeze-thaw cycle. Seborrheic keratosis can be treated with one 10-second freeze-thaw cycle. Other lesions One 15- to 30-second freeze-thaw cycle with a 1-mm margin can be used to treat keloids.7 Cryotherapy of keloids can be painful. Other modalities, such as intralesional corticosteroid injection, are more commonly used. Rhinophyma can be treated with two 30-second freeze-thaw cycles of the entire nose at 4-week intervals. Most nonmelanoma skin cancers, such as squamous cell carcinomas and basal cell carcinomas, should be treated by excision with sufficient margins, by Mohs surgery, or with radiation. The freeze time for actinic keratoses is highly variable, depending on skin temperature and the thickness of the lesion. Warts can usually be treated with two 15- to 30-second freeze-thaw cycles, depending on the thickness. COMPLICATIONSSection 6 of 10
As with any procedure, complications can occur. Complications can be divided into (1) acute, (2) delayed, (3) prolonged-temporary, and (4) permanent. Acute complications include headache, pain, and blister formation. Delayed complications include hemorrhage, infection, and excessive granulation tissue formation. Prolonged-temporary complications include milia, hyperpigmentation, and change in sensation. Permanent complications include alopecia, atrophy, keloids, scarring, hypopigmentation, and ectropion formation. CONTRAINDICATIONSSection 7 of 10
Contraindications can be divided into 2 groups: relative contraindications and absolute contraindications. Relative contraindications include cold intolerance, cold urticaria, cryoglobulinemia, history of pyoderma gangrenosum, and Raynaud disease. Absolute contraindications include the use of cryotherapy near the eye margins. CONCLUSIONSection 8 of 10
Cryotherapy is a safe and easy to use treatment to destroy many benign and malignant lesions. The cryotherapy operator must be aware of the complications associated with this modality; for example, a complication is hypopigmentation (dark-skinned individuals are prone to hypopigmentation). One needs to be aware of the fact that lesions may need to be treated multiple times before resolution. MULTIMEDIASection 9 of 10
REFERENCESSection 10 of 10
Article Last Updated: Nov 26, 2007 | |||||||||||||||||||||||||||||||||||||||||||||||
