15 Cryosurgery

Richard P. Usatine, MD, and Daniel L. Stulberg, MD

Cryosurgery is the most commonly performed dermatologic procedure in the United States. There are many different ways to achieve cold temperatures, but clinically, the end result is to freeze the fluid in cells, which causes crystals that damage the cells, resulting in tissue destruction. Different cell types are destroyed at different temperatures (see Table 15-1). Melanocytes are relatively fragile causing the tendency for hypopigmentation with their death. Cartilage and bone are most resistant to freezing and other cells are in between.

TABLE 15-1 Key Events during Freezing Including Cell Death

Temperature (°C)	Event
+11 to +3	65% of capillaries and 35% to 40% of arterioles and venules develop thrombosis.
−0.6	Freezing begins to occur in tissue.
−4 to −7	Melanocytes die.
−15 to −20	100% of blood vessels develop thrombosis.
−20	Cells in sebaceous glands and hair follicles die.
−21.8	Ice crystals theoretically form in the tissue (the eutectic temperature of sodium chloride solution).
−20 to −30	Keratinocytes and malignant cells die.
−30 to −35	Fibroblasts die.
−50 to −60	All cells die including cartilage cells.

Source: Adapted from Vidimos A, Ammirati C, Poblete-Lopez C. Dermatologic Surgery. London: Saunders; 2008; Table 8-3.

Cryosurgery is an easily mastered technique that is extremely useful for treating benign and premalignant lesions. In experienced hands cryosurgery is also a valuable technique for treating small, nonaggressive nonmelanoma skin cancers (NMSCs).

Indications

Cryosurgery is most often used to treat actinic keratoses and benign conditions. Table 15-2 provides recommended freeze times and margins of freeze for benign conditions (using liquid nitrogen with an open spray technique). Table 15-3 gives recommended freeze times and margins of freeze for vascular conditions (using liquid nitrogen with a closed probe or an open spray technique). Table 15-4 lists recommendations for treating premalignant and malignant conditions (using liquid nitrogen with an open spray technique). Details on how to perform these procedures follow.

TABLE 15-2 Recommended Freeze Times and Margin of Freeze for Benign Conditions Using Liquid Nitrogen with an Open Spray Technique

TABLE 15-3 Recommended Freeze Times and Margin of Freeze for Vascular Conditions Using Liquid Nitrogen with a Closed Probe or an Open Spray Technique

TABLE 15-4 Recommendations for Treating Premalignant and Malignant Conditions Using Liquid Nitrogen with an Open Spray Technique

Contraindications

• Cryosurgery is never an appropriate treatment for melanoma.

• Nevi should not be treated with cryosurgery because if a nevus were to grow back, it might appear malignant and a biopsy could be suspicious for melanoma (pseudomelanoma).

• Cryosurgery should not be used for NMSCs that are aggressive. This includes recurrent basal cell carcinoma (BCC) or squamous cell carcinoma (SCC), any large BCC or SCC, sclerosing BCC, micronodular BCC, poorly differentiated SCC, and any skin cancer with perineural spread. Avoid cryosurgery for cancers on the ala of the nose, the lip, and the ear. If Mohs surgery is indicated, cryosurgery is not.

Contraindications for cryosurgery are listed in Table 15-5.

TABLE 15-5 Contraindications for Cryosurgery

Contraindications	Category
By Lesion
Melanoma	A
Recurrent basal cell carcinoma	A
Sclerosing basal cell carcinoma (BCC)	A
Micronodular BCC	R
Nevus	A
Any undiagnosed lesion suspicious for non-melanoma malignancy (tissue should be sent for pathology first)	R
Morphea	A
By Area
Skin cancer on ala nasi and nasolabial fold	R
Neoplasm of upper lip near vermillion border	R
Neoplasm over the shins	R
By Patient
Previous adverse reaction to cryotherapy (e.g., cold anaphylaxis)	A
Cryoglobulinemia	R
Myeloma, lymphoma	R
Autoimmune disorders (including pyoderma gangrenosum)	R
Raynaud’s disease, especially when lesion is on fingers, toes, nose, ears, penis	R

A, Absolute; R, relative.

Disadvantages of Cryosurgery

As with the advantages of cryosurgery, the disadvantages can also be categorized into those for the clinician and those for the patient. Disadvantages for the clinician include the following:

• Liquid nitrogen needs to be delivered and stored. A liquid nitrogen generator may be purchased. If that is not done, nitrous oxide tanks or other supplies will need to be replenished as needed.

• The clinician must be certain of the diagnosis because no tissue will be sent for pathology.

• Cryosurgery is not as accurate as a scalpel or laser in cosmetic work.

Disadvantages for the patient include:

• Erythema and swelling are the norm. Blistering is common.

• Pain, especially throbbing pain around the nail folds.

• Pain with walking if plantar warts are treated.

• May require multiple visits.

• Hypopigmentation (see the Complications section later in this chapter for more risks).

Equipment for Liquid Nitrogen

• Dewar (holding container) and dispensing device (Figure 15-1)

• Spray guns (Figure 15-2)

• Cryo Tweezers (for skin tags) (Figure 15-3)

• Various tips and probes (Figure 15-4)

• Styrofoam cups for use with Cryo Tweezers.

FIGURE 15-1 (A) Dewar tank and liquid nitrogen dispenser. (B) When the dispenser is placed within the tank and a seal is obtained, the liquid nitrogen rises through the metal tube and comes out through the filter at the end of the blue tube to fill the cryosurgical spray gun.

(A, Copyright Daniel Stulberg, MD; B, Copyright Richard P. Usatine, MD.)

FIGURE 15-2 Two types of cryosurgical spray guns from Brymill (left) and one from Wallach (right).

(Copyright Richard P. Usatine, MD.)

FIGURE 15-3 The Cryo Tweezer at room temperature.

(Copyright Richard P. Usatine, MD.)

FIGURE 15-4 A large assortment of cryosurgical probes, apertures, and spray tips.

(Copyright Richard P. Usatine, MD.)

While we suggest liquid nitrogen as the gold standard, other methods involve the following equipment:

• Compressed gas in tanks or cartridges with appropriate gun or spray tips (nitrous oxide or carbon dioxide)

• Refrigeration—mechanically cooled probe

• Refrigerant liquids that evaporate with associated cones and swabs.

Cryosurgery: Principles and Getting Started

• Factors that affect the freezing of tissue are listed and explained in Table 15-6.

• If you do not know the diagnosis, do not use cryosurgery. Lesions well suited to treatment with cryosurgery are listed in Tables 15-2 to 15-4.

• Advise the patient regarding treatment options and expected results.

• Obtain informed consent at the time of the procedure based on the risks and benefits as laid out in this chapter. Most of the time, verbal consent should be adequate. If the procedure could result in hypopigmentation on the face, written consent should be obtained.

TABLE 15-6 Factors That Affect the Freezing of Tissue

Factor	Key Principles
Rate of tissue freezing	Rapid freezing causes more cell death. In the open spray technique, this is influenced by the rate of liquid nitrogen spray to the skin (aperture and configuration of the spray conduit).
Rate of intermittent spraying	A faster rate for an intermittent spray results in a deeper, but narrower depth of freeze. A slower rate for an intermittent spray results in a more superficial, but wider depth of freeze.
Halo diameter	The wider the halo, the deeper the freeze at the periphery of the lesion.
Distance of spray tip to tissue	The closer the tip is to the tissue, the colder the tissue may become because air is not as good a conductor as tissue.
Tissue temperature	Final tissue temperature of less than −30°C will kill malignant cells.
Duration of freezing	Having the tissue remain adequately frozen for a longer period of time causes more tissue injury. Maximum cell death rate occurs at 100 seconds.
Rate of thawing	Slow thawing causes more cell death.
Repetition of freeze/thaw cycles	More freeze/thaw cycles cause more cell death. Malignant tumors require multiple freeze/thaw cycles. All cellular structures show damage by electron microscopy after two cycles below −30°C.

Source: Adapted from Vidimos A, Ammirati C. Poblete-Lopez C. Dermatologic Surgery. London: Saunders; 2008; Table 8-2.

Cryosurgery Methods

Many different techniques are used to perform cryosurgery. The most common ones are listed in Table 15-7, which explains how the cryogen is applied and its temperature.

TABLE 15-7 Forms of Various Cryogens and Temperatures

Cryogens	Form	Temperatures (°C)
Liquid nitrogen	Open spray, closed probes and CTA Tissue temperature is less cold if delivered with CTA	−196
Nitrous oxide in tank	Closed probes on special gun	−89
Solidified CO₂ in tank	Closed probes on special gun	−79
CryoPen	Refrigerated closed probes	−75
Verruca-Freeze (chlorodifluoromethane and propane)	Chemical spray into cones or disposable buds with evaporation producing the cold	−70
Wartner (dimethyl ether and propane)	OTC foam applicator for warts only	−57
Histofreezer (dimethyl ether and propane)	Application is via disposable 2- and 5-mm buds	−55

Liquid Nitrogen

Most dermatologists and many primary care providers have access to liquid nitrogen. It is the gold standard for cryosurgery. Various cryoguns are marketed that efficiently and effectively deliver the liquid nitrogen to the skin at the coldest temperatures.

Liquid nitrogen is stored in dewar containers ranging in size from 5 to 50 L. The nitrogen may be withdrawn using a ladle, a valve system, or a withdrawal tube (Figure 15-1). The withdrawal tube is the most simple and efficient way to extract liquid nitrogen from your storage container.

For those clinicians who are still working with cotton-tipped applicators (CTAs) and liquid nitrogen in a cup, it is possible to do cryosurgery on benign and premalignant conditions. This method does not get cold enough for treating cancer or most vascular lesions. Dip the CTA into the liquid nitrogen and then touch the CTA to the lesion to be treated. The CTA can be unwound a bit and rewound to make a smaller point, or loose cotton from a cotton ball can be wrapped around the CTA for larger lesions to maintain the freezing temperature longer.

A more time-effective and more efficacious approach is to use a cryogun (Figure 15-2). Once filled, the unit can be used to treat many patients rapidly. The spray method allows the clinician to reach tissue temperatures of up to −196°C while the CTA is not likely to get below −20°C. Although there is a cost involved in the purchase of a cryogun, these units can last a clinician’s full career and pay for themselves very quickly. The reimbursement for cryosurgery is excellent for only a few minutes of your time.

Michael D. Bryne developed the first handheld spray device using liquid nitrogen for medical use in 1968. His family continues to run the Brymill Corporation, which sells the most widely used cryoguns. The variety of cryoguns available from Brymill include (Figure 15-2):

• Cry-Ac^®, standard 500-mL capacity—the main workhorse unit

• Cry-Ac-3, smaller capacity of 300 mL—easy handling with shorter holding time

• Cry-Ac Tracker, new device that measures the temperature of the skin when spraying liquid nitrogen using infrared sensor technology.

Wallach makes the UltraFreeze Liquid Nitrogen Sprayer, which comes in 500- and 300-mL sizes. Whatever cryogun you use, it helps to have an assortment of apertures and tips. The tips that are available for the Brymill cryoguns include:

• Four spray tips with round apertures from 0.04 to 0.016 inch, with A being the largest and D the smallest (Figure 15-5). The C tip is a good all-purpose tip.

• Long 20-gauge bent spray with blue cover. This longer tube (3 inches) with an 80-degree angle attenuates the flow of the liquid N₂ (LN2) so that the spray is less shocking to the patient (Figure 15-5). This is good for children and adults who fear this therapy. It also allows for pinpoint accuracy on smaller lesions. It can be helpful for treating anogenital condylomas because it allows the clinician to be further from the lesions being treated.

• Shorter (1.5 inches) 20-gauge bent spray (metallic color). These have similar benefits to the long blue tube but with less attenuation of flow (Figure 15-5). They have a 45-degree angle at the end. This type of tip has one advantage over the long blue tube: it is less likely to become temporarily blocked up with repeated use. Both bent sprays can be rotated 360 degrees for greater precision when treating hard-to-reach lesions.

• Straight spray extensions range from 1.5 to 3 inches long. Straight spray needles have 16-, 18-, and 20-gauge extensions (Figure 15-5). These can be used anywhere or for lesions in body orifices.

• The Advanced Acne Aperture gives a soft, vaporized spray for superficial desquamation of cheeks, forehead, and back area in the treatment of acne (Figure 15-6).

• Closed probes are useful on vascular lesions to compress the lesion and freeze it simultaneously (Figure 15-7). Closed probes come in many sizes and shapes, ranging from 1 to 6 mm and 1 to 2.5 cm in diameter. The probes are available in round flat shapes, conical and spherical shapes, and shapes for use on the cervix. The liquid nitrogen is vented out a plastic tube so that no spray touches the patient. The spray freezes the probe tip for direct application to a lesion. One method to avoid the probe sticking to the skin is to freeze the probe before applying it to the patient. The closed probes have a “low” infection risk since there is no breach of the patient’s skin. Cleaning of the closed probes can be done with an alcohol wipe prior to use.

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