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Liquid nitrogen is stored in dewar containers ranging in size from 5 to 50 L. The nitrogen may be withdrawn using a ladle, a valve system, or a withdrawal tube (Figure 15-1).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):

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:

FIGURE 15-5 Spray tips A through D are arranged in order of largest aperture to the smallest aperture. Two bent spray tips and one straight spray needle (20 gauge).

(Copyright Richard P. Usatine, MD.)

FIGURE 15-6 Acne spray tip next to a tiny E aperture tip.

(Copyright Richard P. Usatine, MD.)

FIGURE 15-7 Closed cryoprobes with different shapes and sizes apply simultaneous pressure and freezing. These are especially helpful when treating vascular lesions. The liquid nitrogen is vented out the white plastic tube.

(Copyright Richard P. Usatine, MD.)

A cryoplate is a transparent plate with four conical openings of various diameters (3, 5, 8, and 10 mm) (Figure 15-8). Used with A – D apertures, the cryoplate provides localization of freezing and protection of sensitive areas such as the eyes. It is good for the novice but is limited by the fact that each opening is round and includes a preset diameter.

FIGURE 15-8 A cryoplate with four different size apertures for controlled freezing diameters.

(Copyright Richard P. Usatine, MD.)

Cryocones come as a set of six Neoprene cones of various sizes used to concentrate spray within a limited area. These can be used for irregularly shaped lesions because they can be shaped to the lesion. Sizes are 6, 11, 16, 25, 30, and 38 mm. Some people use plastic ear specula to control their freeze diameters.

Freezing Times, Thaw Times, and Halo Diameters

The amount of tissue destruction can be estimated by the duration of freezing (freeze time), the amount of thaw time (time until the ice ball is defrosted and is no longer white), and the margin of frozen tissue around the lesion (halo diameter). Factors that affect the freezing of tissue are summarized in Table 15-6.

Figure 15-9 shows how the temperature of the freeze is lowest in the middle of a continuous stationary freeze and why a halo diameter is helpful. Figure 15-10 shows the typical geometry of the hemispherical freeze that occurs in the tissues. Figures 15-11 and 15-12 demonstrate the relationship between depth and temperature of freeze to spraying factors. Intermittent spraying close to the skin can increase the depth and temperature of freeze when it is desirable to treat a deep tumor.

FIGURE 15-9 The liquid nitrogen sprays from the tip at −195.6°C and the cold dissipates in the tissues further from the direct spray. Even the skin at the point of initial contact does not reach the temperature of liquid nitrogen but may get as cold as −60°C.

(Modified from Vidimos A, Ammirati C, Poblete-Lopez C. Dermatologic Surgery. London: Saunders; 2008.)

FIGURE 15-10 A real-life demonstration of the shape of the ice ball produced when liquid nitrogen is sprayed at a single-point of agar. The ice ball spreads out in a hemispherical pattern. The coldest point of the ice ball is the center.

(Copyright Daniel L. Stulberg, MD.)

FIGURE 15-11 Relationship between depth of freeze to spraying factors. (A) The depth of the ice ball is equal to the surface radius of the ice ball. This tends to occur when the spray is intermittent and when the spray tip is close to the skin. (B) The depth of the ice ball is less than the surface radius of the ice ball (R′ < R). This tends to occur when the spray is continuous and when the spray tip is further from the skin. It can also occur when the liquid nitrogen is “painted on” and/or the rate of intermittent spray is too slow. Note that if the depth of the ice ball is too shallow, then the entire tumor may not be destroyed even though the frozen surface margins appear to be adequate. However, this type of freezing is helpful for superficial lesions.

(From Vidimos A, Ammirati C, Poblete-Lopez C. Dermatologic Surgery. London: Saunders; 2008.)

FIGURE 15-12 Relationship between the therapeutically lethal isotherm (TLI) (−30°C) and the edge of the ice ball (0°C isotherm). In both (A) and (B), the sizes and shapes of the ice balls (0°C isotherm) are the same. (A) The TLI is close to the edge of the ice ball. This tends to occur when the spray is intermittent and when the spray tip is close to the skin. (B) The TLI is farther from the edge of the ice ball (Y > X). Note that if the location of the TLI is too far from the edge of the ice ball, the entire tumor may not be destroyed even though the frozen surface margins appear to be adequate.

(From Vidimos A, Ammirati C, Poblete-Lopez C. Dermatologic Surgery. London: Saunders; 2008.)

Cryosurgery with Liquid Nitrogen Spray: Steps and Principles

1. Hold the cryogun relatively upright to avoid having the LN2 come out of the valve and scare everyone in the room.

2. Make sure that the patient is in a stable position and not a moving target. If the lesion is on the hand, see that the hand is resting on the patient or furniture so as not to move.

3. Hold the tip 1 to 2 cm from the lesion, making sure that the spray is perpendicular to the skin. If using a bent spray probe, adjust the position of the cryogun and tip to achieve a 90-degree angle (Figure 15-13). Stabilize your hands and body so that your aim will be accurate and consistent.

4. Compress the trigger to start the spray. The pattern of spray should be determined by the size, elevation, and depth of the lesion. The following techniques are options:

• Steady continuous spray will produce a wider and more shallow freeze zone. This may be sufficient for actinic keratoses and benign lesions.

• Pulsing the spray intermittently in one spot will cause the freeze to stay localized (less lateral spread) and deepen with the duration of spray. This is good for thicker lesions such as common warts, molluscum, dermatofibromas, and keloids.

• Using a paintbrush technique of moving the spray in a spiral or back-and-forth motion will give a more superficial freeze for superficial lesions including actinic keratoses and lentigines. Moving the spray back and forth across the lip may be sufficient for actinic cheilitis (Figure 15-14).

• If you are using the Cry-Ac Tracker, pay attention to the tissue temperature and use this as one extra data point to guide your treatments (Figure 15-15). See Table 15-4 for guidelines on tissue temperature for treating premalignant and malignant conditions.

5. Make sure that the freeze reaches all edges of the lesion with the desired halo diameter (see Tables 15-2 to 15-4). The halo should be symmetrical around the lesion. It may be necessary to move the spray slightly back and forth to achieve an oval or linear pattern instead of a circle.

6. Freeze to the time suggested in Tables 15-2 to 15-4. Smaller lesions on thinner more delicate skin should receive treatments at the lower end of the time range.

7. Watch the thawing. If the area thaws asymmetrically, one area might not have received sufficient freeze time. You can add some freezing to that area. If the whole area thaws faster than expected, consider a second freeze/thaw cycle.

8. If the lesion is hypertrophic (especially with warts) consider paring it down with a scalpel or razor blade so that the base can be more effectively treated (Figure 15-16).

9. If you will be treating a lesion for more than 25 seconds, give the patient a choice to have a local anesthetic first. In particular, if you are treating a malignancy with two 30-second freezes, lidocaine can be very helpful. Two percent lidocaine without epinephrine is a good choice because there is no need for hemostasis or tissue distention.

FIGURE 15-13 A common wart is treated with cryosurgery using the open spray technique and liquid nitrogen. A 2-mm margin of freeze (halo diameter) is achieved to ensure that the periphery of the wart is frozen.

(Copyright Richard P. Usatine, MD.)

FIGURE 15-14 Biopsy-proven actinic cheilitis is being frozen using a bent spray tip and a paintbrush type motion to keep the freeze from going too deep.

(Copyright Richard P. Usatine, MD.)

FIGURE 15-15 The Brymill Cry-Ac Tracker produces two purple lights that will converge to one light when the tracker is at the correct distance for the infrared temperature monitor to work: (A) too far from the skin; (B) correct distance. (C) As the spray freezes the skin, the light turns green when the temperature is below 0°C. The light will turn red when the temperature is below the variable temperature that may be set on the LCD control panel of the tracker.

(Copyright Daniel L. Stulberg, MD.)

FIGURE 15-16 A wart is being frozen after excessive keratin was pared down with a sharp sterile razor.

(Copyright Richard P. Usatine, MD.)

Liquid Nitrogen: Cryo Tweezers

Cryo Tweezers are designed to freeze skin tags without the overspray and inaccuracy inherent in spraying these small raised lesions. The Cryo Tweezers have a Teflon-coated brass tweezer end that holds the cold temperature after dipping them in liquid nitrogen. They have a thin “necked” portion between the heavy tweezer ends and the handle to minimize the cold spread up the handle. The tweezers should be dipped into a Styrofoam cup with LN2 so that the tips are covered, but not the handles. The initial dip should be long enough that the LN2 has stopped boiling away from the originally warm tweezer tips (about 20 seconds). The handles will get very cold, so it helps to wrap them in a 4 × 4 gauze as they are pulled out of the liquid nitrogen. Alternatively, a thick insulated glove can be used to handle the Cryo Tweezers. The skin tags are then grasped and held with the Cryo Tweezers until the freeze margin reaches normal tissue at the skin surface (Figure 15-17). The tweezers can be used to treat many skin tags before they warm up. When treating more than 10 skin tags you may need to redip the tweezers when you note that the freeze time is lengthening.

FIGURE 15-17 The Cryo Tweezer is an ideal instrument for quickly freezing small to medium skin tags with minimal pain and no bleeding.

(Copyright Daniel L. Stulberg, MD.)

The Cryo Tweezers are particularly good for skin tags or warts on the eyelids. After grasping the elevated papule, pull the whole lid away from the eye to protect the globe from cryodamage (Figure 15-18). Then continue the freeze until the whole tag or wart is white to the base. This avoids any spray that may enter the eye. Cryo Tweezers can be cleaned between patients by dipping them into the liquid nitrogen again or using an alcohol wipe.

FIGURE 15-18 The Cryo Tweezer can safely treat skin tags or warts on the eyelids. The lesion is grasped carefully and pulled away from the eye; the cold will not be transmitted to the eye itself.

(Copyright Richard P. Usatine, MD.)

Alternatives to Liquid Nitrogen

Condyloma

Condyloma acuminata are generally very responsive to cryosurgery. Many lesions can be treated rapidly without local anesthetic. Consider offering topical or local anesthetic to patients who have larger lesions. The bent spray tips are particularly useful for genital and perianal condyloma because the spray volume and speed are somewhat attenuated (Figure 15-20). While this may require slightly longer freeze times, it improves patient comfort during the procedure. The end of the spray tip should be held within 1 to 2 cm of the lesion to get good focused freezing. The patient may be given a prescription for a topical medication such as podofilox or imiquimod to start 2 weeks after cryosurgery. If the patient cannot afford one of these topical medications, cryosurgery may be repeated every 2 weeks until the lesions are gone.

FIGURE 15-20 An open spray technique is being used to treat condyloma on the glans of a patient’s penis. The spray tip is held close to the mucosa so that the freeze can be carefully controlled.

(Copyright Richard P. Usatine, MD.)

If the perianal lesions are on the anal mucosa or are particularly large, some form of endoscopy should be performed to rule out internal HPV infection in the rectum (Figure 15-21). For perianal lesions in HIV-positive patients, consider a biopsy to rule out squamous cell carcinoma before initiating therapy.

FIGURE 15-21 Condyloma acuminata in the perianal region after liquid nitrogen cryosurgery with a bent tip open spray technique.

(Copyright Richard P. Usatine, MD.)

Make sure you use site-specific billing codes for cryosurgery of the penis, vulva, or perianal area. These do pay at a higher rate (see Table 38-6 in Chapter 38).

Dermatosis Papulosis Nigra

The many small seborrheic keratoses that make up dermatosis papulosis nigra (DPN) can be treated with cryosurgery. Because DPN is more frequently found on the face of women of color, it is important to avoid causing permanent hypopigmentation. This risk should be clearly spelled out and accepted by the patient before starting therapy. This is one time when we suggest getting a written consent signed. It also is prudent to test the cryosurgery out on a few lesions away from the midface to see how the patient will respond before treating many central lesions. The patient in Figure 15-22 was very pleased with her results. She was willing to except some temporary or permanent hypopigmentation just to make sure that her seborrheic keratoses were flattened so they would not show under makeup.

FIGURE 15-22 Dermatosis papulosis nigra that was treated with liquid nitrogen using an open spray technique. (A) Hypopigmentation occurred around many of the treated lesions within the first month. (B) The hypopigmentation was temporary and the patient was delighted with the final result of treatment.

(Copyright Richard P. Usatine, MD.)

Keloids and Hypertrophic Scars

Keloids and hypertrophic scars can be a frustrating and cosmetically disfiguring complication of injury or irritation to the skin. Treatments have included applying silicone sheeting, excising and injecting the margins with steroids, injection alone, and cryotherapy alone or in conjunction with steroid injection. The data on the use of cryotherapy is nicely summarized in Table 15-8.

Molluscum Contagiosum

Cryosurgery is an excellent treatment method for molluscum. The greatest limiting factor is the age and maturity of the patient. This technique should not be used with young and fearful children. For older children and adults, molluscum can be treated using the open spray technique or a small closed probe. Because molluscum can be so small, choose a tip with a small aperture or a probe with a small diameter. The bent spray tips are particularly nice for molluscum. Usually a 5-second freeze time to the edge of the lesion is adequate.

Seborrheic Keratosis

Seborrheic keratoses are frequently treated with cryosurgery. Very good cosmetic results can be obtained with cryosurgery of seborrheic keratoses from the scalp down to the legs. The open spray technique is a very fast and easy method of treating one or many seborrheic keratoses. The freeze time should be determined by the thickness and location of the seborrheic keratosis. It is better to underfreeze and have to do a second freeze than to overfreeze and cause permanent hypopigmentation, scarring, or atrophy. Some clinicians combine curettage with cryosurgery just as curettage is combined with electrodesiccation in the treatment of seborrheic keratoses. Large seborrheic keratoses can be treated in multiple sessions if needed.

Solar Lentigines

Solar lentigines may be quite responsive to depigmentation with cryosurgery. However, there is a risk of hypopigmentation or postinflammatory hyperpigmentation. It may be best to try this treatment on the dorsum of the hand before performing it on the face. For facial lesions you should obtain written consent and make sure the patient understands the potential risks. Make sure you are certain of the diagnosis before proceeding. Visual diagnosis may be adequate in most cases and a dermatoscope can help confirm the clinical impression. While it is possible to perform cryosurgery on a lentigo maligna, it is best to know what you were treating because a lentigo maligna is a precancer and can go on to lentigo maligna melanoma. Because solar lentigines can be large and superficial, a paintbrush method with an open spray technique is useful.

Syringomas

Syringomas are benign tumors that occur bilaterally around the eyes, usually on the lower eyelids. They can be treated with cryosurgery using a bent spray method. One simple way to protect the eye is to place a wooden tongue depressor between the syringomas being treated and the closed eye (Figure 15-23).

FIGURE 15-23 Syringoma are being treated with a bent tip open spray. A wooden tongue depressor is used as a barrier to protect the eye from the spray. Although patients are always directed to close their eyes, the tongue depressor provides additional security.

(Copyright Richard P. Usatine, MD.)

Warts

Warts are covered in detail in Chapter 33, Procedures to Treat Benign Conditions.

Vascular Lesions

Hemangiomas

Small or large hemangiomas can be compressed with an adherent cryoprobe and then frozen destroying the vascular tissue. Freeze the cryoprobe first before applying when using liquid nitrogen (Figure 15-24). By freezing the probe first, the probe will not stick to the skin and can be moved to other parts of the hemangioma if the probe is smaller than the hemangioma.

FIGURE 15-24 A 31-year-old man requested treatment of a strawberry hemangioma that he had had since infancy. Because he could not afford laser treatment, he was offered cryosurgery. The initial treatment is being performed with a closed probe and liquid nitrogen. (A) The closed probe is frozen first before touching the skin to avoid sticking to the skin. (B) The probe compresses the hemangioma while additional liquid nitrogen is used to keep the probe at a low temperature. (C) The larger hemangioma is treated with a larger probe using the same technique. Note the freeze ball and the compression obtained. The probe did not stick to the skin. Cryosurgery was repeated two times and the patient was happy with the final result.

(Copyright Richard P. Usatine, MD.)

Pyogenic Granuloma

While the success rate for treating a pyogenic granuloma should be higher with a shave excision and electrosurgical destruction, some children will allow you to freeze their lesion but will not permit you to inject local anesthetic for the preferred surgical method. In these cases cryosurgery with a closed probe is preferred over the open spray technique. Because the closed probe can compress the pyogenic granuloma, the freeze can reach the base to decrease the chance of recurrence (Figure 15-25). An alternative is to compress the lesion with a Cryo Tweezer (Figure 15-26).

FIGURE 15-25 A closed probe is about to be applied to a pyogenic granuloma in a 7-year-old boy. While he was unwilling to allow an injection of local lidocaine for electrosurgical treatment, he was able to tolerate a cryosurgery with no anesthesia. The closed probe was chosen to compress the vascular tissue of this lobulated hemangioma.

(Copyright Richard P. Usatine, MD.)

FIGURE 15-26 (A) Pyogenic granuloma on the face of a young girl. (B) The Cryo Tweezer is freezing and compressing the pyogenic granuloma laterally. Note the end of the 4 × 4 gauze wrapped around the handle of the Cryo Tweezer to prevent a freezing injury to the clinician’s hand.

(Copyright Richard P. Usatine, MD.)

Venous Lakes

Venous lakes are vascular tumors that appear most commonly on the lower lip. They can be compressed with an adherent cryoprobe and then frozen, destroying the venous lake. Freeze the cryoprobe with liquid nitrogen first before applying (Figure 15-27) so that the probe does not stick to the lip when the freeze is complete.

FIGURE 15-27 (A) Venous lake on the lip. (B) Venous lake being frozen with liquid nitrogen and a closed probe.

(Copyright Richard P. Usatine, MD.)

Premalignant Lesions

Actinic Keratoses

Actinic keratoses (AKs) are very amenable to treatment with cryosurgery. Any of the open spray techniques can be used with the cryogun. The smaller lesions can be treated for 5 to 10 seconds, whereas the thicker more hypertrophic lesions should be treated for 10 to 20 seconds. A single freeze cycle should be adequate unless the thaw time appears too short. Table 15-9 shows the percentage cure of actinic keratoses with a single freeze/thaw cycle. Tissue destruction increases if longer freeze times or repeated freeze thaw cycles are performed.³

TABLE 15-9 Actinic Keratoses of the Face and Scalp Larger Than 5 mm—Cure Rates with a Single Freeze³

Single Freeze Time (s)	Cure Rate (%)
<5	39
5–20	69
>20	83

The most efficient method of treating many AKs is to have your cryogun with you in the exam room when examining a patient with many AKs. Once you and the patient determine that cryosurgery is to be done, freeze each AK as you find it so that you do not need to find each AK twice (once without and once with the cryogun). Also if you look closely, you will see that the borders of the AK become more visible as the freezing is occurring. Another option is to mark the location of AKs because they are often more easily palpated than seen (Figure 15-28).

FIGURE 15-28 Multiple actinic keratoses being treated with a “C” aperture tip. The AKs were marked first prior to treatment.

(Copyright Daniel L. Stulberg, MD.)

Count your AKs as you go because you are paid individually for each AK until you reach 15. Then one global CPT code is used for 15 AKs and above.

Malignant Lesions

After developing proficiency with all kinds of benign lesions, it is reasonable to consider using cryosurgery for the least aggressive nonmelanoma skin cancers. Studies have shown that cryosurgery has similar effectiveness to electrodesiccation and curettage for correctly chosen BCCs. The most commonly recommended regimen is to maintain a freeze for 30 seconds, allow full thawing, and then repeat the 30-second freeze.⁴ Clinical cure rates are approximately 90%, so appropriate follow-up is important.⁴ If the lesion recurs after treatment, surgical excision or Mohs surgery may be indicated. These longer freeze times can be painful and difficult to tolerate, so inject with lidocaine for anesthesia prior to treatment. Efficacy and appearance are not as highly rated as surgical management, and after treatment there will likely be a prolonged period (weeks) of erythema, exudate, and healing, so judgment should be used in picking cryotherapy over surgical management.⁴ It is typical to have some hypopigmentation and skin atrophy after healing.

The Cry-Ac Tracker can help the clinician develop confidence in the treatment of appropriate skin cancers with cryosurgery. The Cry-Ac Tracker allows the clinician to see and read the tissue temperatures during treatment. It also has a stopwatch timer and at the end of one burst of treatment will provide the number of seconds in which the coldest temperature was maintained. Previous studies recommending specific temperatures for cancer treatment were based on the use of thermocouples. The Cry-Ac Tracker measures surface temperature using infrared technology. Based on expert opinion and previous thermocouple data, it appears that skin cancers should be treated to a temperature below −30°C. The 30-second pulses are based on total freeze time and not a freeze time of less than −30°C. To reach a cold temperature faster, use a B or C tip aperture or a straight needle tip. All three of these choices work well with the Cry-Ac Tracker. Do not use a bent spray tip for treating skin cancer because the flow rate of liquid nitrogen is slower and the Cry-Ac Tracker does not work with the geometric configuration of a bent tip spray.

Use a surgical marker and circle the full skin cancer. If the margins are not clear, do not use cryosurgery for treatment. Measure 5 mm around the border and draw the desired halo diameter (Figure 15-29). Start the freeze and a stopwatch simultaneously—do not just estimate the 30-second freeze time. It helps to have a second person in the room to watch the time on a watch, smart phone, or the Cry-Ac Tracker. In most cases the spray can be held wide open, and intermittent pulsing only needs to be initiated if the freeze ball extends beyond the halo diameter.

FIGURE 15-29 A small biopsy-proven squamous cell carcinoma in situ was found on the face. The patient chose cryosurgery as his method of treatment. The lesion was circled and a 5-mm margin was drawn around it. Some local anesthetic was injected and the patient received two 30-second freeze cycles. Each thaw cycle was over 60 seconds in length.

(Copyright Richard P. Usatine, MD.)