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CRYOTHERAPY OF DERMAL ABNORMALITIES
00954543 /97 $0.00
OFFICE PROCEDURES
+ .20
CRYOTHERAPY OF DERMAL ABNORMALITIES David M. Jester, MD
Cryotherapy of the skin is a technique that has been used by physicians since the early twentieth century. The equipment, techniques, and indications have been refined considerably since these early beginnings. The controlled ablation of skin lesions by freezing is the basic principle of cryotherapy. This can be accomplished using many different cryogens, most commonly liquid nitrogen or nitrous oxide. Today, cryosurgery offers the primary care physician a safe, costeffective office procedure capable of treating many benign and premalignant lesions. Some malignant lesions also can be treated by cryotherapy, but other modalities may be preferred. With an understanding of the general principles, proper equipment, and common techniques, physicians can treat many skin lesions safely by cryotherapy. PURPOSE
The purpose of cryotherapy is the controlled ablation of abnormal epidermal cells that require removal. The goal is to accomplish this while preserving the normal surrounding structures, so that healing can occur with minimal scarring. OBJECTIVES
The objective of dermal cryotherapy is to produce a cryoiceball of sufficient depth and linear dimension to encompass the lesion that is being treated. More specifically, the generation of lethal tissue temperatures to From the Department of Family Medicine, Medical College of Georgia School of Medicine, Augusta, Georgia PRIMARY CARE
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VOLUME 24 NUMBER 2 * JUNE 1997
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produce cryonecrosis of the abnormal cells being treated yields a satisfactory outcome. By leaving the dermal matrix intact, healing can occur after the necrotic tissue has sloughed off. To be proficient at cryotherapy, a physician must understand the physiologic effects of freezing on tissue. The temperature of freeze, rate of freeze and thaw, and the number of freeze-thaw-freeze cycles all affect the success of cryotherapy. The two common cryogens, liquid nitrogen and nitrous oxide, produce heat transfer via different mechanisms. Because liquid nitrogen has direct contact with the skin, rapid heat transfer occurs, producing a rapid freeze. Liquid nitrogen also can be applied by using a probe tip that allows conduction to the skin. When nitrous oxide is used, conduction occurs between the skin and the metal cryoprobe and is thus s10wer.~ Liquid nitrogen reduces temperature to - 196"C, whereas nitrous oxide generates a temperature of -89°C. Both of these temperatures are sufficient to provide the desired effect on the skin for effective cryotherapy. It has been shown that at 0" to -20"C, cells begin to freeze but recovery is p~ssible.~ By lowering the temperature beyond - 20"C, tissue destruction occur^.^ Freezing to - 40°C to - 50°C is required for complete destruction of malignant tissue.1° At this temperature the tissue is frozen completely and the chance of recovery is minimal. In achieving the desired effects of cryosurgery it is important to remember the rate of freeze. Rapid freezing produces intracellular freezing and crystal formation that is more destructive than the extracellular crystal formation seen in a slower freeze.'O In addition to the increase in intracellular ice formation with a rapid freeze, there also is trapping of electrolytes intracellularly. This increased concentration of electrolytes produces more intracellular damage during freezing and thawing.'O Therefore it is important to remember that the rate of freeze should be as fast as possible to achieve maximum destruction of tissue. The desired rate of thaw is opposite to that of freezing and should be as slow as possible. With a slow thaw there is time for accumulation of electrolytes in the cells that provide further damage.loThis also allows for the next freeze to achieve a intracellular freeze and complete cellular destruction quickly. The use of repeat or successive freeze-thaw cycles is a technique used by many cryosurgeons. Electron microscopy studies have showed that with a second freeze-thaw cycle the degree of cellular damage increases.'O For this reason at least two cycles (freeze-thaw, freezethaw) generally are recommended. Freezing causes death to all cells that are frozen below - 20°C. Cryotherapy also produces injury to the adjacent microvasculature.1°With vascular injury and thrombosis, any potential recovery of damaged cells is reduced further. Structures with poor vascularity such as stromal cells, collagen, and cartilage are resistant to the effects of freezinglo For this reason, the dermal matrix is left intact, allowing for improved healing of the treated area. INDICATIONS AND CONTRAINDICATIONS
Cryotherapy is indicated for the treatment of many benign, premalignant, and malignant lesions.' With special training in the gynecologic
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applications of cryotherapy, doctors can extend its use to the treatment of cervical dysplasia. Although the list of benign conditions amendable to cryotherapy is long, Acne Adenoma sebaceum Angiokeratomas Angioma Chondrodermatitis nodularis Condyloma acuminatum Granuloma annulare Hemangioma Keloid Leishmaniasis Lentigo Molluscum contagiosum Mucocele Sebaceous hyperplasia Seborrheic keratosis Verrucae the most commonly treated lesions are verucae and actinic keratosis. Premalignant lesions that can be treated with cryotherapy are Actinic cheilitis Actinic keratosis Lentigo maligna Leukoplakia Squamous cell carcinoma and basal cell carcinoma are the malignant lesions most frequently treated with cryotherapy'O: Basal cell carcinoma Kaposi's sarcoma Squamous cell carcinoma Many physicians believe, however, that excision is the preferred method of treatment for squamous cell carcinoma and basal cell carcinoma. Any lesion presumed or known to be a malignant melanoma should not be treated with cryotherapy.'O Cryotherapy can be used in all age groups of patients. Because it is somewhat painful for small children who cannot understand the procedure, one may need to consider other alternative treatment modalities in this population. Elderly patients who are poor surgical candidates often can tolerate cryotherapy. Cryosurgery can be used on almost all parts of the body. Because of a potentially limited amount of scarring, the cosmetic result from cryosurgery may be preferred over a larger surgical scar.7 Even with good patient selection and appropriate technique, cryotherapy can produce sig-
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nificant scarring. Because of the ease of the procedure, multiple sites can be treated at one time with little or no limitation to the patient.l0 There are relatively few contraindications to cryotherapy. Patients who suffer from cold urticaria, cold intolerance, cryofibrinogemenia,and cryoglobulinemia should not have cryotherapy.’O Specific conditions such as malignant melanoma and recurrent basal cells carcinoma also should be treated by other method^.^ Specific areas of the body may be less amenable to cryotherapy. Because of unique anatomic situations, cryotherapy in these areas should be avoided: Areas that overlie nerves Inner canthi Nasolabial folds Nasal ala Periauricular area Vermilion border Patients who suffer from diabetes mellitus or peripheral vascular disease offer unique challenges. It is advisable to avoid treating these patients with cryotherapy on areas with poor cir~ulation.~ This includes the lower leg, ankles, and feet. These areas heal poorly and are at greater risk for infection. Patients with active collagen vascular disease, ulcerative colitis, and hepatitis B are also at risk for poor healing and exaggerated freeze re~ponse.~ Patients who are taking oral steroids may have an exaggerated response to cryotherapy because of immunosuppression.7 It may be advisable to test freeze an area in the axilla to judge the patient’s response so one can determine the duration of freeze better.7
PATIENT PREPARATION
There is little patient preparation needed before cryotherapy. The patient should understand the planned procedure completely. The area to be treated should be clean, dry, and well exposed. The patient should be placed in a comfortable position, allowing the physician easy access to the area to be treated. There is no need for a sterile preparation or draping of the area. Adequate lighting and all necessary equipment should be available.
EQUIPMENT AND SUPPLIES
To perform office cryotherapy safely the appropriate equipment and supplies should be available and the physician should be familiar with their use. The first choice one must make is that of a cryogen. The two most commonly used cryogens are liquid nitrogen and nitrous oxide. The type of cryosurgical device also must be considered.
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Office cryotherapy can be performed with liquid nitrogen. It is the most commonly used cryogen because it is colder and more versatile than other methods.' A vacuum-insulated Dewer tank is needed for storage of the liquid nitrogen. Dewer tanks are available in many sizes (10-50 L), depending on the amount of use expected. Depending on the size of the tank, the liquid nitrogen can be stored for 2 to 6 months. Liquid nitrogen continually evaporates from even the best Dewer tank. Because this is not a closed system, one must replace the liquid nitrogen regularly, even if it is not being used. This adds to the expense of using liquid nitrogen. The cost of a Dewer tank is from $400 to $700 depending on size. The cost to refill a tank is $25 to $40 per 10 L of liquid nitrogen. Liquid nitrogen can be applied in several different manners. The simplest way is to emerse a cotton swab in the liquid nitrogen and then apply it to the intended site. All that is needed for this method is a polystyrene plastic (Styrofoam) or metal cup and cotton swabs. Hand-held, self-contained spray devices with multiple tips are available. These devices range in price from $550 to $700.3 Various types of spray-limiting cones are available, but an otoscope cone can suffice and is already available in the office. To use nitrous oxide as one's cryogen one will need a gas cylinder, regulator, pressure gauge, cyrogen, and assorted tips. The gas cylinder generally can be purchased or leased. The cost is approximately $1100 to $1700 for the cylinder, regulator, gauge, cryogen, and three tips.3To refill a cylinder costs $25 to $50.3Special tips for gynecologic cryotherapy are also available. As with all chemicals, liquid nitrogen and nitrous oxide must be handled in accordance with all Occupational Safety and Health Administration regulations. Appropriate labeling, storage, and files must be available before the use of this equipment. Scavenger tubing must be used to evacuate nitrous oxide from the treatment room. There are several other materials that should be available when performing cryotherapy. These include eye protection for the physician if spray is used. Scalpels and curettes may be needed to debulk large lesions before or after freezing. Biopsy instruments and specimen transport containers may be needed before cryotherapy when a tissue diagnosis is needed before treatment. Hemostatic agents should be available as well as suture material. Local anesthesia rarely is needed but should be available.
NORMAL ANATOMY
Before a clinician begins a cryotherapy procedure a review of the underlying anatomy is helpful. Again, the goal being selective destruction of tissue with preservation of surrounding structures, one must evaluate the area to be treated. When performing cryotherapy it is important to understand the anatomy of the skin. The skin is composed of three layers: the epidermis, the
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dermis, and the subcutaneous tissue. Cryotherapy primarily affects the two superficial layers. The epidermis is the most superficial layer of skin and consists of stratified squamous epithelium. The thickness of the epidermis ranges from 0.05 mm to 1.5 mm with the dorsal and extensor surfaces generally thicker than the ventral and flexor surface^.^ The deepest aspect of the epidermis consists of a single layer of nuclear-dense cells called basal cells, followed sequentially toward the surface by parabasal, intermediate, and superficial squamous cells. Melanocytes are present in the epidermis layer. The dermis, beneath the epidermis, consists primarily of connective tissues. It serves to form the framework for the skin's structures. It varies The dermis contains blood vessels, from 0.3 mm to 3 mm in thi~kness.~ nerves, glands, and hair follicles. These structures can be damaged by the thermal injury of cryotherapy. Other unique structures also must be remembered. In the hands and feet, nerves and tendons can be injured by cryotherapy. The epidermis and dermis are separated only by millimeters from the anterior tibia. For these reasons attention always should be given to any unique structures around a lesion to be treated. TECHNIQUES The choice of technique depends on the equipment and the lesion that will be treated. The dipstick method is the simpliest technique for applying liquid nitrogen. It is used commonly for treatment of verrucae, lentigo, and actinic keratosis. It allows for treatment of multiple lesions as well as lesions of different shapes. It is economical because of the low cost of the equipment needed for this technique. To perform the dipstick technique, the liquid nitrogen is placed in a metal or Styrofoam container. The lesion to be treated needs no preparation unless it is large and needs debridement. If this is done, the area should be soaked in warm water and debrided with a scapel blade. A wooden-handled cotton swab with the cotton tip loosened is dipped into the cryogen and placed directly on the lesion with moderate pressure. It is held in place until the desired depth of freeze is achieved. This is estimated by measuring the linear dimension of the lateral iceball. The lesion is allowed to thaw. Further freeze-thaw-freeze cycles can be done based on the size of the lesion. Overlap of successive treatments may be necessary to encompass the entire lesion adequately. A large cotton.swab with the cotton loosened also can be used to allow cryogen to drip onto the lesion without pressure being applied. The same parameters for estimating depth of freeze are used. Spray devices also are used to deliver liquid nitrogen in cryotherapy. This is the most commonly used technique by dermatologists.10When using liquid nitrogen through a spray device a fine spray of the cryogen is emitted onto the lesion. The device is held 1 to 2 cm from the lesion and at a 90" angle. The spray device is triggered while being aimed at the
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lesion until the desired freeze is obtained, again based on the lateral spread of the iceball. This technique is especially useful on irregularly shaped lesions or lesions on curved surfaces. For larger lesions, a paint brush or a spiral pattern can be used.'O If there is a need to limit the area sprayed, a spray-limiting device can be used. An otoscope cone can be placed over the lesion and liquid nitrogen is sprayed into the cone.4This technique can be used to protect surrounding structures such as the eye. It is believed that cryotherapy sterilizes the wound, but some viruses such as human papillomavirus are cold insensitive and the use of a spray limiting device is recommended to prevent lateral spread of the virus? Another technique to pinpoint the delivery of liquid nitrogen is the use of hypodermic needles. A hypodermic needle is attached to a plastic tube, which is attached to the spray d e ~ i c eThe . ~ needle then is placed on the lesion and the cryogen accurately is applied in a fine spray.4 If the physician chooses to use nitrous oxide it is important to have a variety of cryoprobes. Based on the shape of the probe, the shape of freeze can be estimated because the iceball will resemble the probe shape. There are many assorted cryoprobe tips a~ailable.~ The amount of pressure applied to the probe minimally influences the depth of freeze and lateral ~ p r e a d . ~ When treating with nitrous oxide a thin layer of a water-soluble gel is applied to the lesion or the cryoprobe. The gel enhances contact with the lesion and assists in postfreeze release of the probe from the lesion. The physician holds the cryogun in one hand and must be able to activate the controls easily. The other hand is placed on the patient and is used to steady the cryoprobe as it is applied to the lesion. The cryoprobe is placed on the lesion, and the device is activated by squeezing or extending the trigger or lever. After the iceball adheres to the epithelium, the hand steadying the probe is released to prevent injury to the physician. The cryoprobe also is lifted to avoid injury to deep structures. The amount of pressure placed on the probe minimally influences the depth of freeze. The cryoprobe is kept in place until the iceball extends 2 to 3 mm beyond the lesion. Once this is achieved, the cryogun is inactivated, the trigger briefly is flashed to thaw the cryoprobe, contact with the skin is lost, and the cryoprobe is removed. Forceful removal of the cryoprobe can produce injury. There are many ways to judge what is the appropriate freeze for a specific lesion. The easiest and the most precise estimate for depth of freeze is the dimension of the horizontal freeze.'O The depth of freeze roughly corresponds to the lateral spread of freeze from the edge of the cryoprobe. The lateral linear spread of freeze can be seen and measured easily. This measurement is a good estimate of the depth of f r e e ~ eThe .~ recommended estimates are 2 to 3 mm beyond the margin of the lesion for nonmalignant lesions and 3 to 5 mm beyond the margin for malignant lesions.' If one is unsure of the histology of the lesion it is best to ablate the same amount of tissue cryogenically as would have been removed by an incisional technique.' Direct measurement of the temperature of the tissue can be obtained by placing small needles containing thermocouples
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around the lesion. These needles are connected to a thermometer that displays the temperature while the treatment with the cryogen is occurring. Such advanced techniques are not required routinely. Generally, the estimate of the lateral spread of freeze is sufficient. The number of freeze-thaw-freezecycles also can be manipulated. In general, the rapid freeze, slow thaw, then refreeze is the most destructive technique.'O For superficial nonmalignant lesions a single freeze may be sufficient. More than two cycles rarely are needed even for malignant lesions. Judging the degree or adequacy of freeze by freezing time is problematic and not absolute. Freeze timing varies with each lesion, cryogen, patient, and delivery system. For liquid nitrogen from a spray device the time can range from 5 to 60 seconds.lo When nitrous oxide is used this time can be extended to 2 to 3 minutes or longer.'O Although specific treatment times for certain lesions are mentioned, they serve as only a crude estimate of the duration of freeze. It is better to measure the superficial lateral spread of the freeze to determine cryotherapy treatment adequacy. Lesion preparation may be important for cryotherapy. Highly keratinic lesions such as plantar warts may require preparation before application of the cryogen. Simply soaking the foot in warm water followed by sharp dbbridment of the keratin layer works well. A more efficient approach is the use of 40% salacylic acid plaster pads. The salacylic acid preparation is applied to the lesion nightly for 1 to 2 weeks. The patient dbbrides the area before salacylic acid application with a nail file. When the patient returns to clinic the softened keratin layer has been removed perhaps along with the wart. The lesion then may be treated with liquid nitrogen, if necessary. COMMON PATHOLOGIC FINDINGS Because cryotherapy produces the ablation of tissues, pathologic evaluation after therapy is not possible. If a malignant lesion is treated a careful clinical examination and biopsy are needed in follow-up. It is advisable to biopsy all lesions before treatment if the diagnosis is uncertain based on the clinical examination. Common conditions treated with cryotherapy are listed previously. COMPLICATIONS Before one can identify the complications of cryotherapy one first must understand the expected response. The treated area initially responds with erythema and hyperemia. Vesicular and hemorrhagic bullae can form, and the patient should be warned of this to decrease anxiety and allow for proper care of the lesion. During the first 24 to 48 hours edema and exudation occur. Because this is expected, after-care by the patient usually includes a gauze dressing or a simple adhesive bandage.
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If the area is small, minimal care is needed. Within a week the area dries, often with eschar formation. Healing by secondary intention usually occurs with little or no scar formation. The pain associated with cryotherapy is minimal to moderate and occurs at the time of the procedure and during the first 24 hours after the procedure. Although true complications are rare with cryotherapy, they can occur. The complicationsof cryotherapy include pain, delayed bleeding, and infection. Hypertrophic scarring also can occur in sensitive individuals. Damage to underlying structures such as nerves and hair follicles can lead to complications. Although permanent nerve damage is rare, transient neuropathy or paresthesia can occur.1oSome studies have shown full recovery if given adequate time, up to 1 year.l0 Alopecia can occur if a deep freeze destroys the hair follicles. This should be remembered when treating cosmetically important areas. Because deeper freezes can lead to ulcerations and tendon injury, care must be taken in treating hands and feet. The last major complication occurs because of retraction of tissues during the healing process. Complicated areas such as lips, eyebrows, ears, and nasalali can become disfigured, and special care must be taken if these areas are to be treated.' If lesions in these areas are superficial, the risk is minimal. Changes in skin pigmentation may occur after cryotherapy. The result can be an increase or a decrease in pigmentation. It is especially useful to warn patients with darker skin about this side effect before treating a cosmetically important area.
OUTCOMES When the outcome of lesions treated by cryotherapy is evaluated, physicians must consider if the lesion is malignant or nonmalignant. In malignant lesions such as basal cell and squamous cell carcinoma, cure rates are reported at 95% to 98Y0.l~For benign lesions such as lentigo maligna, cure rates are around 90%.'O For verrucae, cure rates approach 97% depending on the type and the number of treatments used.IoAll this helps to validate cryotherapy as a useful tool in clinical practice.
FOLLOW-UP Because of the high success rate and low incidence of complication, routine follow-up is not always needed, especially for benign lesions. The proper follow-up interval is variable but should occur after healing has occurred, generally 2 to 3 weeks. Patients who have received treatment of malignant lesions must be reexamined following the treatment. Followup may be needed for large, nonmalignant lesions that may require multiple treatments. Each patient should be educated about the expected effects, side effects, and possibility for recurrence. With this information, in
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addition to the suggestion of the treating clinician, the patient can decide if follow-up is needed. PATIENT EDUCATION/COUNSELING
As with any procedure the patient must be counseled on other available treatment options. These can include cryotherapy, excision, or electrodesiccation. For benign lesions, cosmetic benefits may be the only indication for treatment. The benefits of each option should be discussed with the patient. These can include the need for histologic evaluation, which is only possible after excision, or cosmetic reasons, which depend on the area being treated. Next, one needs to discuss the procedure that is to be performed. A step-by-step description of the technique to be used should be discussed in simple terms to ensure patient understanding. In addition to the procedure, it is important that the patient understands the condition being treated. The expected response to cryotherapy of erythema, hyperemia, bullae formation, and sloughing also should be reviewed. The signs of infection should be reviewed. The risk of delayed bleeding and home management options should be discussed. Complications such as hyperpigmentation or hypopigmentation, alopecia, and injury to underlying structures appropriate to the area being treated should be clear to the patient. It is also important to discuss the degree of posttreatment pain the patient could expect. This is usually minimal and is treated easily with acetaminophen or ibuprofen. Treatment to large or sensitive areas may require mild narcotics such as codeine. Before any therapy it is important for the patient to be clear about the follow-up that is needed. Again, this is determined by the condition being treated and the judgment of the physician. The patient also should have a clear understanding of how and when to contact his or her physician. DOCUMENTATION/CONSENT
As with any office procedure, proper documentation of cryotherapy is essential. Informed consent should be obtained first. The consent form should include the following: name of procedure, disease/condition being treated, prognosis after treatment, prognosis without treatment, alternative treatment options, complications, and the ability of the patient to ask questions. The consent form should be signed by a witness, the patient, and the physician, then dated and placed in the chart. An appropriate history and physical examination should be documented in the chart. The physical examination should include a histologic or clinical diagnosis of lesion as well as the location, number, size, and description of each lesion. If underlying structures are of concern, they also should be mentioned in the examination. A procedure note also should be included in the patient’s chart. It
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should address diagnosis, location, number, and size of each lesion that was treated. Informed consent should be mentioned. The method of treatment should be expressed. The width, estimated depth, and temperature of freeze (if temperature is measured) also should be recorded, especially for malignant lesions. When multiple lesions are treated a diagram is often helpful. PROCEDURE CODES
The appropriate procedural codes for cryotherapy can be found in the American Medical Association’s Physicians Current Procedural Terminology CPT’96 under ”Destruction, Benign or Premalignant Lesions.” A summary of these listing follows. For benign lesions 17000 is used for destruction of benign facial lesions other than cutaneous vascular proliferative lesions. For two or more lesions, 17001 is used. For complicated lesions, 17010 is appropriate. For lesions not on the face and for non-vascular proliferative lesions 17100 is used for the first lesion, 17101for the second, 17102 for 2 to 15 lesions and 17104 for more than 15 lesions. Complicated lesions are coded as 17105. This includes common and plantar warts. For flat warts, molluscum contagiosum, and milia 17110 is used. Retreatment is billed as an office visit. Up to 15 fibrocutaneous tags is a 17200 with each additional 10 lesions being a 17201. For malignant lesions of the arms, legs, or trunk that are less than 0.5 cm 17260 is used, for lesions 0.6 to 1 cm--17261, 1.1 to 2 cm--17262, 2.1 to 3 cm-17263,3.1 to 4 cm-17264, more than 4 cm--17266. For malignant lesions on the scalp, neck, hands, feet, and genitalia the 17271 series is used, again based on the size of the lesion. Malignant lesions of the face, ears, eyelids, nose, lips, or mucous membranes require the 17280 series. In summary, cryosurgery is a technique used for the destruction of benign and malignant lesions of the skin. Because of its effectiveness, few complications, broad application, and cost-effectiveness it is a worthwhile procedure. References 1. Drake LA: Guidelines of care for cryosurgery. J Am Acad Dermatol31:648-653,1994 2. Ferris D: Cryotherapy precision. Clinician’s estimate of cryosurgical ice ball lateral spread of freeze. Arch Fam Med 2:269-274,1993 3. Ferris DG: Cryosurgical equipment: A critical review. J Fam Pract 35:185-193,1992 4. Graham GF: Cryosurgery: A useful tool in the treatment of selected infectious diseases. Int J Dermatol33:107-108,1994 5. Habif T: Clinical Dermatology, ed 2. St Louis, Mosby, 1990, pp 9-10 6. Hocutt JE: Cryosurgery I. Family Practice Bulletin 1:67-70, 1988 7. Hocutt JE: Skin surgery for the family physician. Am Fam Physician 48:445452,1993 8. Hong J S MR imaging assisted temperature calculations during cryosurgery. Magn Resona Imaging 12:1021-1031,1994 9. Kirschner C, Davis S, Jackson J, et al: Physician’s Current Procedural Terminology. Chicago, American Medical Association, 1996, pp 69-70 10. Kuflick EG: Cryosurgery updates. J Am Acad Dermatol31:925-944, 1994
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11. Kuflick EG, Gage AA: Cryosurgical Treatment for Skin Cancer. New York, Igaku-Shoin, 1990 12. Torre D, Labritz R, Kuflick E: Practical Cutaneous Cryosurgery. Norwalk, Appleton and Lange, 1988
Address reprint requests to David M. Jester, MD Department of Family Medicine Medical College of Georgia School of Medicine 1120 15th Street, HB-3018 Augusta, GA 30912-3500
OFFICE PROCEDURES
+ .20
CRYOTHERAPY OF DERMAL ABNORMALITIES David M. Jester, MD
Cryotherapy of the skin is a technique that has been used by physicians since the early twentieth century. The equipment, techniques, and indications have been refined considerably since these early beginnings. The controlled ablation of skin lesions by freezing is the basic principle of cryotherapy. This can be accomplished using many different cryogens, most commonly liquid nitrogen or nitrous oxide. Today, cryosurgery offers the primary care physician a safe, costeffective office procedure capable of treating many benign and premalignant lesions. Some malignant lesions also can be treated by cryotherapy, but other modalities may be preferred. With an understanding of the general principles, proper equipment, and common techniques, physicians can treat many skin lesions safely by cryotherapy. PURPOSE
The purpose of cryotherapy is the controlled ablation of abnormal epidermal cells that require removal. The goal is to accomplish this while preserving the normal surrounding structures, so that healing can occur with minimal scarring. OBJECTIVES
The objective of dermal cryotherapy is to produce a cryoiceball of sufficient depth and linear dimension to encompass the lesion that is being treated. More specifically, the generation of lethal tissue temperatures to From the Department of Family Medicine, Medical College of Georgia School of Medicine, Augusta, Georgia PRIMARY CARE
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VOLUME 24 NUMBER 2 * JUNE 1997
269
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JESTER
produce cryonecrosis of the abnormal cells being treated yields a satisfactory outcome. By leaving the dermal matrix intact, healing can occur after the necrotic tissue has sloughed off. To be proficient at cryotherapy, a physician must understand the physiologic effects of freezing on tissue. The temperature of freeze, rate of freeze and thaw, and the number of freeze-thaw-freeze cycles all affect the success of cryotherapy. The two common cryogens, liquid nitrogen and nitrous oxide, produce heat transfer via different mechanisms. Because liquid nitrogen has direct contact with the skin, rapid heat transfer occurs, producing a rapid freeze. Liquid nitrogen also can be applied by using a probe tip that allows conduction to the skin. When nitrous oxide is used, conduction occurs between the skin and the metal cryoprobe and is thus s10wer.~ Liquid nitrogen reduces temperature to - 196"C, whereas nitrous oxide generates a temperature of -89°C. Both of these temperatures are sufficient to provide the desired effect on the skin for effective cryotherapy. It has been shown that at 0" to -20"C, cells begin to freeze but recovery is p~ssible.~ By lowering the temperature beyond - 20"C, tissue destruction occur^.^ Freezing to - 40°C to - 50°C is required for complete destruction of malignant tissue.1° At this temperature the tissue is frozen completely and the chance of recovery is minimal. In achieving the desired effects of cryosurgery it is important to remember the rate of freeze. Rapid freezing produces intracellular freezing and crystal formation that is more destructive than the extracellular crystal formation seen in a slower freeze.'O In addition to the increase in intracellular ice formation with a rapid freeze, there also is trapping of electrolytes intracellularly. This increased concentration of electrolytes produces more intracellular damage during freezing and thawing.'O Therefore it is important to remember that the rate of freeze should be as fast as possible to achieve maximum destruction of tissue. The desired rate of thaw is opposite to that of freezing and should be as slow as possible. With a slow thaw there is time for accumulation of electrolytes in the cells that provide further damage.loThis also allows for the next freeze to achieve a intracellular freeze and complete cellular destruction quickly. The use of repeat or successive freeze-thaw cycles is a technique used by many cryosurgeons. Electron microscopy studies have showed that with a second freeze-thaw cycle the degree of cellular damage increases.'O For this reason at least two cycles (freeze-thaw, freezethaw) generally are recommended. Freezing causes death to all cells that are frozen below - 20°C. Cryotherapy also produces injury to the adjacent microvasculature.1°With vascular injury and thrombosis, any potential recovery of damaged cells is reduced further. Structures with poor vascularity such as stromal cells, collagen, and cartilage are resistant to the effects of freezinglo For this reason, the dermal matrix is left intact, allowing for improved healing of the treated area. INDICATIONS AND CONTRAINDICATIONS
Cryotherapy is indicated for the treatment of many benign, premalignant, and malignant lesions.' With special training in the gynecologic
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applications of cryotherapy, doctors can extend its use to the treatment of cervical dysplasia. Although the list of benign conditions amendable to cryotherapy is long, Acne Adenoma sebaceum Angiokeratomas Angioma Chondrodermatitis nodularis Condyloma acuminatum Granuloma annulare Hemangioma Keloid Leishmaniasis Lentigo Molluscum contagiosum Mucocele Sebaceous hyperplasia Seborrheic keratosis Verrucae the most commonly treated lesions are verucae and actinic keratosis. Premalignant lesions that can be treated with cryotherapy are Actinic cheilitis Actinic keratosis Lentigo maligna Leukoplakia Squamous cell carcinoma and basal cell carcinoma are the malignant lesions most frequently treated with cryotherapy'O: Basal cell carcinoma Kaposi's sarcoma Squamous cell carcinoma Many physicians believe, however, that excision is the preferred method of treatment for squamous cell carcinoma and basal cell carcinoma. Any lesion presumed or known to be a malignant melanoma should not be treated with cryotherapy.'O Cryotherapy can be used in all age groups of patients. Because it is somewhat painful for small children who cannot understand the procedure, one may need to consider other alternative treatment modalities in this population. Elderly patients who are poor surgical candidates often can tolerate cryotherapy. Cryosurgery can be used on almost all parts of the body. Because of a potentially limited amount of scarring, the cosmetic result from cryosurgery may be preferred over a larger surgical scar.7 Even with good patient selection and appropriate technique, cryotherapy can produce sig-
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nificant scarring. Because of the ease of the procedure, multiple sites can be treated at one time with little or no limitation to the patient.l0 There are relatively few contraindications to cryotherapy. Patients who suffer from cold urticaria, cold intolerance, cryofibrinogemenia,and cryoglobulinemia should not have cryotherapy.’O Specific conditions such as malignant melanoma and recurrent basal cells carcinoma also should be treated by other method^.^ Specific areas of the body may be less amenable to cryotherapy. Because of unique anatomic situations, cryotherapy in these areas should be avoided: Areas that overlie nerves Inner canthi Nasolabial folds Nasal ala Periauricular area Vermilion border Patients who suffer from diabetes mellitus or peripheral vascular disease offer unique challenges. It is advisable to avoid treating these patients with cryotherapy on areas with poor cir~ulation.~ This includes the lower leg, ankles, and feet. These areas heal poorly and are at greater risk for infection. Patients with active collagen vascular disease, ulcerative colitis, and hepatitis B are also at risk for poor healing and exaggerated freeze re~ponse.~ Patients who are taking oral steroids may have an exaggerated response to cryotherapy because of immunosuppression.7 It may be advisable to test freeze an area in the axilla to judge the patient’s response so one can determine the duration of freeze better.7
PATIENT PREPARATION
There is little patient preparation needed before cryotherapy. The patient should understand the planned procedure completely. The area to be treated should be clean, dry, and well exposed. The patient should be placed in a comfortable position, allowing the physician easy access to the area to be treated. There is no need for a sterile preparation or draping of the area. Adequate lighting and all necessary equipment should be available.
EQUIPMENT AND SUPPLIES
To perform office cryotherapy safely the appropriate equipment and supplies should be available and the physician should be familiar with their use. The first choice one must make is that of a cryogen. The two most commonly used cryogens are liquid nitrogen and nitrous oxide. The type of cryosurgical device also must be considered.
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Office cryotherapy can be performed with liquid nitrogen. It is the most commonly used cryogen because it is colder and more versatile than other methods.' A vacuum-insulated Dewer tank is needed for storage of the liquid nitrogen. Dewer tanks are available in many sizes (10-50 L), depending on the amount of use expected. Depending on the size of the tank, the liquid nitrogen can be stored for 2 to 6 months. Liquid nitrogen continually evaporates from even the best Dewer tank. Because this is not a closed system, one must replace the liquid nitrogen regularly, even if it is not being used. This adds to the expense of using liquid nitrogen. The cost of a Dewer tank is from $400 to $700 depending on size. The cost to refill a tank is $25 to $40 per 10 L of liquid nitrogen. Liquid nitrogen can be applied in several different manners. The simplest way is to emerse a cotton swab in the liquid nitrogen and then apply it to the intended site. All that is needed for this method is a polystyrene plastic (Styrofoam) or metal cup and cotton swabs. Hand-held, self-contained spray devices with multiple tips are available. These devices range in price from $550 to $700.3 Various types of spray-limiting cones are available, but an otoscope cone can suffice and is already available in the office. To use nitrous oxide as one's cryogen one will need a gas cylinder, regulator, pressure gauge, cyrogen, and assorted tips. The gas cylinder generally can be purchased or leased. The cost is approximately $1100 to $1700 for the cylinder, regulator, gauge, cryogen, and three tips.3To refill a cylinder costs $25 to $50.3Special tips for gynecologic cryotherapy are also available. As with all chemicals, liquid nitrogen and nitrous oxide must be handled in accordance with all Occupational Safety and Health Administration regulations. Appropriate labeling, storage, and files must be available before the use of this equipment. Scavenger tubing must be used to evacuate nitrous oxide from the treatment room. There are several other materials that should be available when performing cryotherapy. These include eye protection for the physician if spray is used. Scalpels and curettes may be needed to debulk large lesions before or after freezing. Biopsy instruments and specimen transport containers may be needed before cryotherapy when a tissue diagnosis is needed before treatment. Hemostatic agents should be available as well as suture material. Local anesthesia rarely is needed but should be available.
NORMAL ANATOMY
Before a clinician begins a cryotherapy procedure a review of the underlying anatomy is helpful. Again, the goal being selective destruction of tissue with preservation of surrounding structures, one must evaluate the area to be treated. When performing cryotherapy it is important to understand the anatomy of the skin. The skin is composed of three layers: the epidermis, the
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dermis, and the subcutaneous tissue. Cryotherapy primarily affects the two superficial layers. The epidermis is the most superficial layer of skin and consists of stratified squamous epithelium. The thickness of the epidermis ranges from 0.05 mm to 1.5 mm with the dorsal and extensor surfaces generally thicker than the ventral and flexor surface^.^ The deepest aspect of the epidermis consists of a single layer of nuclear-dense cells called basal cells, followed sequentially toward the surface by parabasal, intermediate, and superficial squamous cells. Melanocytes are present in the epidermis layer. The dermis, beneath the epidermis, consists primarily of connective tissues. It serves to form the framework for the skin's structures. It varies The dermis contains blood vessels, from 0.3 mm to 3 mm in thi~kness.~ nerves, glands, and hair follicles. These structures can be damaged by the thermal injury of cryotherapy. Other unique structures also must be remembered. In the hands and feet, nerves and tendons can be injured by cryotherapy. The epidermis and dermis are separated only by millimeters from the anterior tibia. For these reasons attention always should be given to any unique structures around a lesion to be treated. TECHNIQUES The choice of technique depends on the equipment and the lesion that will be treated. The dipstick method is the simpliest technique for applying liquid nitrogen. It is used commonly for treatment of verrucae, lentigo, and actinic keratosis. It allows for treatment of multiple lesions as well as lesions of different shapes. It is economical because of the low cost of the equipment needed for this technique. To perform the dipstick technique, the liquid nitrogen is placed in a metal or Styrofoam container. The lesion to be treated needs no preparation unless it is large and needs debridement. If this is done, the area should be soaked in warm water and debrided with a scapel blade. A wooden-handled cotton swab with the cotton tip loosened is dipped into the cryogen and placed directly on the lesion with moderate pressure. It is held in place until the desired depth of freeze is achieved. This is estimated by measuring the linear dimension of the lateral iceball. The lesion is allowed to thaw. Further freeze-thaw-freeze cycles can be done based on the size of the lesion. Overlap of successive treatments may be necessary to encompass the entire lesion adequately. A large cotton.swab with the cotton loosened also can be used to allow cryogen to drip onto the lesion without pressure being applied. The same parameters for estimating depth of freeze are used. Spray devices also are used to deliver liquid nitrogen in cryotherapy. This is the most commonly used technique by dermatologists.10When using liquid nitrogen through a spray device a fine spray of the cryogen is emitted onto the lesion. The device is held 1 to 2 cm from the lesion and at a 90" angle. The spray device is triggered while being aimed at the
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lesion until the desired freeze is obtained, again based on the lateral spread of the iceball. This technique is especially useful on irregularly shaped lesions or lesions on curved surfaces. For larger lesions, a paint brush or a spiral pattern can be used.'O If there is a need to limit the area sprayed, a spray-limiting device can be used. An otoscope cone can be placed over the lesion and liquid nitrogen is sprayed into the cone.4This technique can be used to protect surrounding structures such as the eye. It is believed that cryotherapy sterilizes the wound, but some viruses such as human papillomavirus are cold insensitive and the use of a spray limiting device is recommended to prevent lateral spread of the virus? Another technique to pinpoint the delivery of liquid nitrogen is the use of hypodermic needles. A hypodermic needle is attached to a plastic tube, which is attached to the spray d e ~ i c eThe . ~ needle then is placed on the lesion and the cryogen accurately is applied in a fine spray.4 If the physician chooses to use nitrous oxide it is important to have a variety of cryoprobes. Based on the shape of the probe, the shape of freeze can be estimated because the iceball will resemble the probe shape. There are many assorted cryoprobe tips a~ailable.~ The amount of pressure applied to the probe minimally influences the depth of freeze and lateral ~ p r e a d . ~ When treating with nitrous oxide a thin layer of a water-soluble gel is applied to the lesion or the cryoprobe. The gel enhances contact with the lesion and assists in postfreeze release of the probe from the lesion. The physician holds the cryogun in one hand and must be able to activate the controls easily. The other hand is placed on the patient and is used to steady the cryoprobe as it is applied to the lesion. The cryoprobe is placed on the lesion, and the device is activated by squeezing or extending the trigger or lever. After the iceball adheres to the epithelium, the hand steadying the probe is released to prevent injury to the physician. The cryoprobe also is lifted to avoid injury to deep structures. The amount of pressure placed on the probe minimally influences the depth of freeze. The cryoprobe is kept in place until the iceball extends 2 to 3 mm beyond the lesion. Once this is achieved, the cryogun is inactivated, the trigger briefly is flashed to thaw the cryoprobe, contact with the skin is lost, and the cryoprobe is removed. Forceful removal of the cryoprobe can produce injury. There are many ways to judge what is the appropriate freeze for a specific lesion. The easiest and the most precise estimate for depth of freeze is the dimension of the horizontal freeze.'O The depth of freeze roughly corresponds to the lateral spread of freeze from the edge of the cryoprobe. The lateral linear spread of freeze can be seen and measured easily. This measurement is a good estimate of the depth of f r e e ~ eThe .~ recommended estimates are 2 to 3 mm beyond the margin of the lesion for nonmalignant lesions and 3 to 5 mm beyond the margin for malignant lesions.' If one is unsure of the histology of the lesion it is best to ablate the same amount of tissue cryogenically as would have been removed by an incisional technique.' Direct measurement of the temperature of the tissue can be obtained by placing small needles containing thermocouples
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around the lesion. These needles are connected to a thermometer that displays the temperature while the treatment with the cryogen is occurring. Such advanced techniques are not required routinely. Generally, the estimate of the lateral spread of freeze is sufficient. The number of freeze-thaw-freezecycles also can be manipulated. In general, the rapid freeze, slow thaw, then refreeze is the most destructive technique.'O For superficial nonmalignant lesions a single freeze may be sufficient. More than two cycles rarely are needed even for malignant lesions. Judging the degree or adequacy of freeze by freezing time is problematic and not absolute. Freeze timing varies with each lesion, cryogen, patient, and delivery system. For liquid nitrogen from a spray device the time can range from 5 to 60 seconds.lo When nitrous oxide is used this time can be extended to 2 to 3 minutes or longer.'O Although specific treatment times for certain lesions are mentioned, they serve as only a crude estimate of the duration of freeze. It is better to measure the superficial lateral spread of the freeze to determine cryotherapy treatment adequacy. Lesion preparation may be important for cryotherapy. Highly keratinic lesions such as plantar warts may require preparation before application of the cryogen. Simply soaking the foot in warm water followed by sharp dbbridment of the keratin layer works well. A more efficient approach is the use of 40% salacylic acid plaster pads. The salacylic acid preparation is applied to the lesion nightly for 1 to 2 weeks. The patient dbbrides the area before salacylic acid application with a nail file. When the patient returns to clinic the softened keratin layer has been removed perhaps along with the wart. The lesion then may be treated with liquid nitrogen, if necessary. COMMON PATHOLOGIC FINDINGS Because cryotherapy produces the ablation of tissues, pathologic evaluation after therapy is not possible. If a malignant lesion is treated a careful clinical examination and biopsy are needed in follow-up. It is advisable to biopsy all lesions before treatment if the diagnosis is uncertain based on the clinical examination. Common conditions treated with cryotherapy are listed previously. COMPLICATIONS Before one can identify the complications of cryotherapy one first must understand the expected response. The treated area initially responds with erythema and hyperemia. Vesicular and hemorrhagic bullae can form, and the patient should be warned of this to decrease anxiety and allow for proper care of the lesion. During the first 24 to 48 hours edema and exudation occur. Because this is expected, after-care by the patient usually includes a gauze dressing or a simple adhesive bandage.
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If the area is small, minimal care is needed. Within a week the area dries, often with eschar formation. Healing by secondary intention usually occurs with little or no scar formation. The pain associated with cryotherapy is minimal to moderate and occurs at the time of the procedure and during the first 24 hours after the procedure. Although true complications are rare with cryotherapy, they can occur. The complicationsof cryotherapy include pain, delayed bleeding, and infection. Hypertrophic scarring also can occur in sensitive individuals. Damage to underlying structures such as nerves and hair follicles can lead to complications. Although permanent nerve damage is rare, transient neuropathy or paresthesia can occur.1oSome studies have shown full recovery if given adequate time, up to 1 year.l0 Alopecia can occur if a deep freeze destroys the hair follicles. This should be remembered when treating cosmetically important areas. Because deeper freezes can lead to ulcerations and tendon injury, care must be taken in treating hands and feet. The last major complication occurs because of retraction of tissues during the healing process. Complicated areas such as lips, eyebrows, ears, and nasalali can become disfigured, and special care must be taken if these areas are to be treated.' If lesions in these areas are superficial, the risk is minimal. Changes in skin pigmentation may occur after cryotherapy. The result can be an increase or a decrease in pigmentation. It is especially useful to warn patients with darker skin about this side effect before treating a cosmetically important area.
OUTCOMES When the outcome of lesions treated by cryotherapy is evaluated, physicians must consider if the lesion is malignant or nonmalignant. In malignant lesions such as basal cell and squamous cell carcinoma, cure rates are reported at 95% to 98Y0.l~For benign lesions such as lentigo maligna, cure rates are around 90%.'O For verrucae, cure rates approach 97% depending on the type and the number of treatments used.IoAll this helps to validate cryotherapy as a useful tool in clinical practice.
FOLLOW-UP Because of the high success rate and low incidence of complication, routine follow-up is not always needed, especially for benign lesions. The proper follow-up interval is variable but should occur after healing has occurred, generally 2 to 3 weeks. Patients who have received treatment of malignant lesions must be reexamined following the treatment. Followup may be needed for large, nonmalignant lesions that may require multiple treatments. Each patient should be educated about the expected effects, side effects, and possibility for recurrence. With this information, in
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addition to the suggestion of the treating clinician, the patient can decide if follow-up is needed. PATIENT EDUCATION/COUNSELING
As with any procedure the patient must be counseled on other available treatment options. These can include cryotherapy, excision, or electrodesiccation. For benign lesions, cosmetic benefits may be the only indication for treatment. The benefits of each option should be discussed with the patient. These can include the need for histologic evaluation, which is only possible after excision, or cosmetic reasons, which depend on the area being treated. Next, one needs to discuss the procedure that is to be performed. A step-by-step description of the technique to be used should be discussed in simple terms to ensure patient understanding. In addition to the procedure, it is important that the patient understands the condition being treated. The expected response to cryotherapy of erythema, hyperemia, bullae formation, and sloughing also should be reviewed. The signs of infection should be reviewed. The risk of delayed bleeding and home management options should be discussed. Complications such as hyperpigmentation or hypopigmentation, alopecia, and injury to underlying structures appropriate to the area being treated should be clear to the patient. It is also important to discuss the degree of posttreatment pain the patient could expect. This is usually minimal and is treated easily with acetaminophen or ibuprofen. Treatment to large or sensitive areas may require mild narcotics such as codeine. Before any therapy it is important for the patient to be clear about the follow-up that is needed. Again, this is determined by the condition being treated and the judgment of the physician. The patient also should have a clear understanding of how and when to contact his or her physician. DOCUMENTATION/CONSENT
As with any office procedure, proper documentation of cryotherapy is essential. Informed consent should be obtained first. The consent form should include the following: name of procedure, disease/condition being treated, prognosis after treatment, prognosis without treatment, alternative treatment options, complications, and the ability of the patient to ask questions. The consent form should be signed by a witness, the patient, and the physician, then dated and placed in the chart. An appropriate history and physical examination should be documented in the chart. The physical examination should include a histologic or clinical diagnosis of lesion as well as the location, number, size, and description of each lesion. If underlying structures are of concern, they also should be mentioned in the examination. A procedure note also should be included in the patient’s chart. It
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should address diagnosis, location, number, and size of each lesion that was treated. Informed consent should be mentioned. The method of treatment should be expressed. The width, estimated depth, and temperature of freeze (if temperature is measured) also should be recorded, especially for malignant lesions. When multiple lesions are treated a diagram is often helpful. PROCEDURE CODES
The appropriate procedural codes for cryotherapy can be found in the American Medical Association’s Physicians Current Procedural Terminology CPT’96 under ”Destruction, Benign or Premalignant Lesions.” A summary of these listing follows. For benign lesions 17000 is used for destruction of benign facial lesions other than cutaneous vascular proliferative lesions. For two or more lesions, 17001 is used. For complicated lesions, 17010 is appropriate. For lesions not on the face and for non-vascular proliferative lesions 17100 is used for the first lesion, 17101for the second, 17102 for 2 to 15 lesions and 17104 for more than 15 lesions. Complicated lesions are coded as 17105. This includes common and plantar warts. For flat warts, molluscum contagiosum, and milia 17110 is used. Retreatment is billed as an office visit. Up to 15 fibrocutaneous tags is a 17200 with each additional 10 lesions being a 17201. For malignant lesions of the arms, legs, or trunk that are less than 0.5 cm 17260 is used, for lesions 0.6 to 1 cm--17261, 1.1 to 2 cm--17262, 2.1 to 3 cm-17263,3.1 to 4 cm-17264, more than 4 cm--17266. For malignant lesions on the scalp, neck, hands, feet, and genitalia the 17271 series is used, again based on the size of the lesion. Malignant lesions of the face, ears, eyelids, nose, lips, or mucous membranes require the 17280 series. In summary, cryosurgery is a technique used for the destruction of benign and malignant lesions of the skin. Because of its effectiveness, few complications, broad application, and cost-effectiveness it is a worthwhile procedure. References 1. Drake LA: Guidelines of care for cryosurgery. J Am Acad Dermatol31:648-653,1994 2. Ferris D: Cryotherapy precision. Clinician’s estimate of cryosurgical ice ball lateral spread of freeze. Arch Fam Med 2:269-274,1993 3. Ferris DG: Cryosurgical equipment: A critical review. J Fam Pract 35:185-193,1992 4. Graham GF: Cryosurgery: A useful tool in the treatment of selected infectious diseases. Int J Dermatol33:107-108,1994 5. Habif T: Clinical Dermatology, ed 2. St Louis, Mosby, 1990, pp 9-10 6. Hocutt JE: Cryosurgery I. Family Practice Bulletin 1:67-70, 1988 7. Hocutt JE: Skin surgery for the family physician. Am Fam Physician 48:445452,1993 8. Hong J S MR imaging assisted temperature calculations during cryosurgery. Magn Resona Imaging 12:1021-1031,1994 9. Kirschner C, Davis S, Jackson J, et al: Physician’s Current Procedural Terminology. Chicago, American Medical Association, 1996, pp 69-70 10. Kuflick EG: Cryosurgery updates. J Am Acad Dermatol31:925-944, 1994
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11. Kuflick EG, Gage AA: Cryosurgical Treatment for Skin Cancer. New York, Igaku-Shoin, 1990 12. Torre D, Labritz R, Kuflick E: Practical Cutaneous Cryosurgery. Norwalk, Appleton and Lange, 1988
Address reprint requests to David M. Jester, MD Department of Family Medicine Medical College of Georgia School of Medicine 1120 15th Street, HB-3018 Augusta, GA 30912-3500