Skin Cryosurgery

There is more information and experience regarding the effects of cold on the skin than any other organ. Since the skin has long been known to heal well after cold injury a vast array of conditions have been treated by cryosurgery (Fig. 7.1.1-7.1.11); the comprehensive list (Table 7.1.1) reflects those conditions for which good results have been recorded. Cutaneous cryosurgery has come more into the fore during the last 25 years, in part because of improved cryobiological background knowledge, but also because in everyday dermatology, with the ready availability of liquid nitrogen, it has become cheap, quick, easy to perform (5) and can usually be carried out without surgical theatre facilities, and even in the patient’s home under certain circumstances.

Equipment and methods
Liquid nitrogen as a refrigerant is essential for the treatment of pre-malignant and malignant skin lesions because of its ability to give “consistent cell killing”. The simplest technique is the dipstick method. This long-used method employs either a cotton-wool swab (Fig. 7.1.12) or copper disc with insulated handles. The swab or disc is dipped into a robust metal Dewar flask containing liquid nitrogen and then applied to the area to be treated. The time of application depends on the size and nature of the lesions to be treated; to maintain relatively long tissue freezing, repeat dipping and reapplication may be necessary. It is very difficult to standardize this technique in view of the many variables: ambient temperature, the pressure applied, distance the dip instrument travels from Dewar flask to the lesion and “dripping” of liquid nitrogen. This technique is considered to be only suitable for small benign superficial conditions, which includes very many conditions listed in Table 7.1.1 “Artistry” and experience are essential if consistently good cure rates are to be achieved with this method. If pre-malignant and malignant integumentary lesions are to be treated, then modern standardized equipment is required (Fig. 7.1.13 and 7.1.14).

For routine outpatient cryosurgery, most dermatologists prefer a small hand-held spray unit or a compact tabletop unit, capable of either spray or cryoprobe application (Fig. 7.1.13 and 7.1.14), the former are by far the commonest used in clinical practice.

Most units allow for variation in the “width” of the spray and have probe attachments of different sizes to equate with the size of the area to be treated.The probes are generally cylindrical, preferably with flat contact surfaces; they are particularly useful when pressure is needed, for example, with vascular lesions and for areas where “open” spray is a problem around the eye, the mouth and the vagina. Also very small lesions can be treated with pointed probes since spray techniques give too wide an icefield and therefore greater morbidity. Instruments utilizing carbon dioxide snow, or nitrous oxide cooling (Joule-Thomson effect) for dermatological lesions have largely been superseded by liquid nitrogen based methods.

Various items of auxiliary equipment are important if the full range of cryosurgical techniques is to be employed:

Truncated non-conducting cones are frequently employed to limit surface application of the spray. For small lesions, if carefully localized spray is required, auroscope cones can be used. This method gives a very rapid rate of temperature decrease which is probably more destructive than the open spray technique. Some recently introduced machines have an attachable “closed cone” that sprays liquid nitrogen into the cone, which is pressed onto the skin.

To protect the orbit of the eye when eyelid tumors are to be treated, a plastic eyelid retractor is essential; if one is not available, a plastic spoon without coarse edges may suffice – this giving adequate “insulation” against chilling effects on the eyes.

For the treatment of large lesions, especially the superficial type, such as basal cell carcinoma (BCC) and some squamous cell carcinomas (SCC), segmental cryosurgery is usually used. In the first treatment, one half of the tumor is treated with two freeze/thaw cycles with adequate safety margin. One month later the cancer is considerably reduced and is then definitively treated.

When compared with single-session cryosurgery for extensive tumors, the segmental treatments has the following advantages: (1) it permits the treatment of large lesions, under local anesthesia, with less discomfort to the patient; (2) it allows better monitoring of the freezing field and the freeze/thaw times; (3) it carriers a smaller risk of deep necrosis, with involvement of underlying structures; (4) there is less morbidity in the healing process and smaller risk of hypertrophic or retractile scars.

Monitoring devices

If only benign and relatively flat and small pre-malignant and malignant lesions are to be treated, and liquid nitrogen is the refrigerant, then monitoring equipment is unnecessary – since no physical instrument can measure adequate cell death. The treatment of deep or large tumors requires careful “depth close” monitoring equipment – these are most commonly a pyrometer – thermocouple combination; some methods employ electrical impedance or tissue resistant-measuring devices which in principle have the advantage of measuring actual freezing; only thin, inexpensive electrodes are needed, and many areas of the tumor can be monitored with a single probe.

The spot freeze technique involves first defining the size of the field to be treated (as with radiotherapy) and then inducing ice formation within that field by liquid nitrogen spray – large lesions are divided into overlapping circles of 2 cm diameter using a skin marker. The liquid nitrogen spray, e.g., C spray of CryAC Units, Brymill Corp, (Fig. 7.1.13 and 7.1.14) is held approximately 1 cm from the skin surface in the center of a 2 cm circle and spraying commences; the white “ice line” is allowed to extend outwards until it fills the circle – this ice field is then “held” for a measured time by continuing the spray with a sufficient jet pressure to maintain the ice line. The measured time will depend entirely on the nature of the lesion; once the time is completed, spraying is stopped and thawing commences. Each 2 cm circle is treated similarly.

A single freeze and thaw is termed a freeze/ thaw cycle (FTC); malignant lesions usually receive two, sometimes three, FTCs, the intervening thaw time being at least three times the duration of the initial freeze. Evidently treatment fields of less than 2 cm diameter do not require to be divided up.

The time added after ice field formation must be learned by experience, but will vary with the size, site and type of pathology. Viral warts may require as little as 4-5 secs, while malignant lesions need up to 30 secs.Times of less than 30 secs do not usually cause connective tissue distortion and scarring.

As with all surgical treatments, accurate diagnosis is essential before cryosurgery is used, particularly for benign lesions (Table 7.1.1) and many basal cell carcinomas (Fig. 7.1.2 and 7.1.3). As with radiotherapy, wrong diagnosis may lead to serious outcome, for example in patients with melanotic lesions, inappropriate management may facilitate tumor spread before the diagnosis becomes obvious.

Treatment of malignant skin lesions

Theoretically, as with X-irradiation, all skin malignancies could be treated by appropriate cryosurgical techniques; but like radiotherapy, in clinical practice certain tumor types have been found to be amenable to “cold killing” with high cure rates and relatively low morbidity indices (Tables 7.1.5 and 7.1.6). The malignancies which are often treated by cryosurgery are basal cell carcinoma (BCC)(4,12,13,14,15) (Figs. 7.1.2 and 7.1.3), squamous cell carcinoma (SCC)(16)(Figs. 7.1.8 and 7.1.9), carcinoma in situ (Bowen’s disease) of skin and adjacent epithelial surface (16), lentigo maligna (Hutchinson’s freckle) and some cases of lentigo maligma melanoma (1,6,17) (Fig. 7.7.7a and b). In general, malignancy requires two freeze/thaw cycles to ensure consistent cell killing and good success rates. Apart from the examples to be mentioned, it is mandatory to perform a biopsy to obtain tissue diagnosis prior to treatment.

Basal cell carcinoma

Basal cell carcinoma (BCC) is the most common human malignancy. Although BCC has a low mortality, it has a large morbidity. Patients frequently present with difficult to treat BCC because of the lesion itself, the condition of the patient, or both. Satisfactory results have been reported in the cryosurgery of low-risk BCC.

Jaramillo-Ayerbe reported that one hundred and thirty six consecutive patients with 171 difficult to treat BCC (because of size, location, nature, or patient condition) were treated by the mixed technique of curettage followed by liquid nitrogen application. After an average follow-up of 5.2 years (6 months to 9.1 years), a cure rate of 91.8% was achieved. The treatment was well tolerated, widely accepted by the patients, of low cost, and with good functional and cosmetic results. Complications were few and minor. Author considered that cryosurgery is a well-tolerated therapeutic modality that offers an acceptable cure rate and good functional and cosmetic results
in difficult to treat BCC.


Bernardeau et al reported an important series of basal cell carcinoma treated by cryosurgery, with a five year cure rate evaluation. 395 basal cell carcinomas in over 358 patients were treated by cryosurgery between 1981 and 1992.The lesions were mainly located on the face and back. Mean size was 17 mm. Clinical sub-types were known for 178 lesions were morpheaform. 111 tumors were observed for more than 5 years. The 5-year actuarial failure rate was 9% .The 5-year cure rate was not significantly altered by sex, size of lesions, location and clinical sub-type. Complications were rare and esthetic outcome was good. Authors suggested that quickness and low cost of this procedure argue for choosing cryosurgery when treating elderly

Kuflik reported and evaluated the experience of using deep cryosurgery in the management of basal and squamous cell carcinomas on all areas of the body over a 30-year period. 4406 new and recurrent basal and squamous cell carcinomas received cryosurgical treatment and 2932 patients were reviewed. Liquid nitrogen was the cryogen. The open spray technique was mostly employed, and a double freeze-thaw cycle was carried out. The overall 30-year cure rate was 98.6% and was remarkably similar in all locations. A recent 5-year cure rate of 522 cases was 99.0%. There were five recurrences.

Giuffrida et al showed histologically that single freeze-thaw cryosurgery is an effective cure for well-defined, noduloulcerative BCC of the trunk and upper extremities. Twelve noduloulcerative BCCs of the trunk and proximal upper extremities less than 1 cm were treated with single freeze-thaw cryosurgery using a cryoprobe apparatus with liquid nitrogen.One to 2 months later, the site was excised and examined with horizontal step sections throughout the entire tissue. No tissue specimens had histologic evidence of tumor.


Kokoszka et al reviewed systematically the body of literature reporting on the efficacy of cryosurgery of BCC in terms of recurrence rates and cosmetic results. There were 13 noncontrolled prospective studies and 4 randomized clinical trials comparing cryosurgery to other methods of treatment for BCC. According to the best evidence, recurrence rates of BCC treated with cryosurgery are low (less than 10%). Cosmetic results of cryosurgery treatment reported in literature are described as good by most investigators. Overall, there are sufficient data to consider cryosurgery as a reasonable treatment for BCC.

For recurrent BCC, cryosurgical treatment yields results that compare favorably with other methods of treatment.
Kuflik and Gage treated

54 patients with 56 recurrent BCCs. The treatment consisted of aggressive freezing including an adequate margin of surrounding tissue. RESULTS: Wound healing was favorable and the cosmetic results were excellent. Two recurrences were found and were referred for Mohs micrographic surgery.

Squamous carcinoma (SCC)

Cryosurgery is the most amenable to treatment of carcinoma-in-situ (Boven’s disease) of the skin, some types of external genital lesions in the female and penis erthroplasia of Queyrat (Fig. 7.1.4a and b); of considerable advantage regarding genital skin Bowen’s disease is that the freezing methods used do not cause connective tissue scarring and contracture is a major advantage.

Well-differentiated squamous carcinomas related to sun damage (Figs. 7.1.8 and 7.1.9) require two freeze/thaw cycles to avoid treatment failure, frequent recurrences, or late onset metastases.

Unlike BCC, squamous carcinoma more often invades underlying tissues such as cartilage, lesions on the ear are thus better not treated by freezing. Even though good cure rates can be obtained, loss of ear cartilage and poor cosmetic results are common. The clinical signs of squamous carcinoma in the early stages are less clear cut than BCC.

Therefore prior to treatment of SCC, accurate diagnosis is crucial-evidently this leads to the conclusion that very small lesions are better treated by excision biopsy if primary closure is possible.

Bowen disease

This is a skin cancer in situ.Curettage and cautery and liquid nitrogen cryotherapy are the preferred methods of treatment for Bowen's disease. Ahmed et al reported that eighty lesions in 67 patients (55 female) were given cryotherapy or curettage and cautery. Cryotherapy was performed using a liquid nitrogen spray giving two freeze-thaw cycles, each freeze cycle being maintained for 5-10 s after the formation of an ice ball to the intended margin. In the cryotherapy group (n = 36 lesions), the median time to complete healing was 46 days (range 14-210; mean 69). Twelve lesions took more than 90 days to heal. Infection requiring antibiotics developed in four patients. Thirteen of the treated lesions had recurred by 24 months.

Lentigo maligna (LM) and lentigo maligna melanoma (LMM)

LM and LMM have been treated using freezing techniques for many decades; anecdotal reports have always appeared good. Dawber & Wilkinson published a series with long follow-up observations confirming the long held view that aggressive cryosurgery gives satisfactory cure rates (7).

Because of the marked inflammatory reaction that follows cryosurgery for malignant lesions, it is important to give the patient a suitable advice sheet.

Palliation
Over 150 years ago, the freezing applied to surface malignant lesions was known to decreasing the size of primary and secondary (often fungating) malignancies in the skin,and pain induced by such tumors. Any chronic bacterial infection associated with these lesions usually improved or was cured.

Adverse effects

The patient usually feels a burning sensation during freezing and thawing. Any pain experienced is usually transient due to the anesthetizing effect of freezing. Local anesthesia is not required for short freeze times but may be indicated when treating malignant lesions or for patients thought to have a low pain threshold. Deep treatments on the forehead may occasionally produce migraine like headaches, and periungual treatment produces relatively greater discomfort than other digital sites.

Some degree of erythema and edema is to be expected with cryosurgery treatments and in areas where the skin is lax-periorbital skin (Fig. 7.1.15), lips, labia majora and penis-ederma may be pronounced. Prolonged freezing schedules may produce blister formation (Fig. 7.1.6); even short freeze times may cause such changes in atrophic skin.

Because this acute inflammation was thought to be unnecessary to obtain good cure rates, for many years the author advocated pre- and post treatment (3-5 days) anti-inflammatory therapy with solute Aspirin 300-600mg up to four times daily or Ibuprofen 800mg twice daily; and Dermovate (clobetasol propionate) cream daily to the treated area. The value of this has been confirmed by objective assessment. Some authorities recommend systemic corticosteroids to minimize the acute inflammation.

Obviously many of the conditions listed in Table 7.1.1 as being by cryosurgery are also amenable to other surgical methods; the modality chosen will often depend on the skills available in the department to which the patient has been referred. Cryosurgery has the advantage over all other modes of being quick, cheap and easy to learn and to carry out; usually sterile surgical facilities are not required and treatment can be initiated even in the presence of bacterial infection, e.g., ingrowing toenail. The fact that post-treatment connective tissue distortion does not generally occur (1) makes cryosurgery advantageous where scarring would be progressively troublesome, e.g., perianal, penile, vulva and periorbital skin; also over joints where a full range of movement can be expected to be retained even after treatment can be expected to be retained even after treatment of malignancy with two or three freeze/thaw cycles.

Cartilage necrosis is extremely rare after freezing; therefore ear, eyelid and many nasal lesions give good cosmetic results after cryosurgery. It should be remembered that the only consistent exception to this dogma is cartilage already invaded by tumor,even if good cure is obtained, a cartilage defect may occur, e.g., squamous carcinoma of the ear.

Anything but the shortest freeze schedules will give pigment changes in the treatment area. Hypopigmentation occurs after prolonged freezing, e.g., approximately 10secs after ice field formation, and may be permanent.

In general, cryosurgery is not recommended for the treatment of lesions on sites with coarse terminal hair (20). Hair follicles are easily damaged by cryodurgery and permanent alopecia is not uncommon (Fig. 7.11.6).

Temporary impairment of sensation in the treatment area is common after freezing; only rarely will the patient be aware of this. Such nerve ending damage can be expected to disappear within a few months. At sites such as the lip margin, permanent sensory loss may give important functional impairment, but in other sites it is generally of no significance. Though nerve trunk damage and “distant” sensory and tumor loss have been recorded they are rare and reversible, usually within a few months.

A rare side-effect of cryosurgery is delayed bleeding; this may be due to granulation tissue formation (Fig. 7.1.18) as in pyogenic granuloma, or from erosion of a small artery. The former may require no more than pressure to abort it, or chemical hemostasis or electrocautery; a patent bleeding artery requires tying off with an appropriate suture.

Discussion

Cryosurgery has been demonstrated to be an excellent alternative for the treatment of benign, premalignant and malignant lesions of the skin. It is a practical, safe, effective and inexpensive modality. For small tumors, cryosurgery can usually be performed in a single session, in the out-patient clinic, without anesthesia, or, in some instances, under local anesthesia. Larger lesions require two or more sessions. When treating extensive tumors, segmental cryosurgery is usually used.

Combination of cryosurgery with other modalities may give rise better results. There are evidences that debulking with excision, electrodessication and curetting,and radiofrequency before cryosurgery affect the efficacy of treatment.

Prior debulking of skin cancers by curettage, are used to prepare the large lesion for cryosurgical treatment. Nordin performed a 5-year follow-up study.60 auricular non-melanoma skin cancers were treated by a thorough curettage with different sized curettes followed by cryosurgery in a double freeze-thaw cycle. Forty-seven basal cell carcinomas (BCCs), nine squamous cell carcinomas (SCCs), three Bowen's disease and one basisquamous cancer were included. The mean diameter of the malignancies was 18 mm (range 5-70). Morphoeiform BCCs, recurrent BCCs with fibrotic component and most of the SCCs were selected for Mohs' micrographic surgery. Forty-two patients with 47 tumours were followed-up for at least 5 years with only one recurrence. Thirteen patients, followed-up for 2-4 years, died from other causes with no sign of recurrence at their last visit. No major problems after treatment were registered and the cosmetic result was good or acceptable in all patients.

But the main inconveniences of curettage procedure are the nearly always inevitable hemorrhage and the time necessary to control it. Goncalves et al performed a study consisting of debulking skin tumors with radiofrequency prior to cryosurgery, on a series of 38 patients (31 basal cell carcinomas, six squamous cell carcinomas, and one Bowen's disease.Authors considered the radiofrequency debulking has the advantages over the traditional debulking by curettage: easy and fast control of the bleeding, easily performance in one single session and on an out-patient regimen.

Photodynamic therapy(PDT) is used for superficial skin malignancies. Combination of PDT and cryosurgery may be complementary for treatment of skin cancer.It was reported that treatment of Bowen's disease using PDT with topically applied delta-aminolaevulinic acid (ALA) to be at least as effective as cryosurgery and to be associated with fewer adverse effects.Wang et al compared ALA-PDT and cryotherapy in the treatment of histopathologically verified basal cell carcinomas (BCCs) in a non-blinded, prospective phase III clinical trial.One lesion from each of 88 patients was included. The BCCs were divided into superficial and nodular lesions. The follow-up period was restricted to 1 year with close follow-up for the first 3 months. Clinical recurrence rates were only 5% (two of 44) for PDT and 13% (five of 39) for cryosurgery,however histopathologically verified recurrence rates in the two groups were statistically comparable and were 25% (11 of 44) for ALA-PDT and 15% (six of 39) for cryosurgery. Additional treatments, usually one, had to be performed in 30% of the lesions in the PDT group. The healing time was considerably shorter and the cosmetic outcome significantly better with PDT. Pain and discomfort during the treatment session and in the following week were low, and were equivalent with the two treatment modalities.

Conclusion
Cryosurgery is a successful modality for destruction of skin tumors,such as basal and squamous cell carcinomas. There is a trend toward more aggressive freezing of lesions and treatment of selected difficult tumors. The standard method of treatment is used with aggressive freezing of the lesion. The cure rate of cryosurgery is high and the cosmetic results are good to excellent. It is considered that the results of cryosurgery are comparable with other modalities. It may be preferable or advantageous for some patients because of the quickness and safety of the procedure and its low cost.

References

Jaramillo-Ayerbe F.Cryosurgery in difficult to treat basal cell carcinoma. Int J Dermatol. 2000 ;39(3):223-9.

Bernardeau K, Derancourt C, Cambie M, Salmon-Ehr V, Morel M, Cavenelle F, Leonard F, Kalis B, Bernard P.Cryosurgery of basal cell carcinoma: a study of 358 patients. Ann Dermatol Venereol. 2000 Feb;127(2):175-9.

Kuflik EG.Cryosurgery for skin cancer: 30-year experience and cure rates. Dermatol Surg.2004;30(2pt2):297-300

Giuffrida TJ, Jimenez G, Nouri K.Histologic cure of basal cell carcinoma treated with cryosurgery. J Am Acad Dermatol. 2003 ;49(3):483-6.

Kokoszka A, Scheinfeld N.Evidence-based review of the use of cryosurgery in treatment of basal cell carcinoma. Dermatol Surg. 2003;29(6):566-71.

Kuflik EG, Gage AA.Recurrent basal cell carcinoma treated with cryosurgery. J Am Acad Dermatol. 1997 Jul;37(1):82-4

Ahmed I, Berth-Jones J, Charles-Holmes S, O'Callaghan CJ, Ilchyshyn A.Comparison of cryotherapy with curettage in the treatment of Bowen's disease: a prospective study. Br J Dermatol. 2000 Oct;143(4):759-66.

Nordin P.Curettage-cryosurgery for non-melanoma skin cancer of the external ear: excellent 5-year results. Br J Dermatol. 1999 Feb;140(2):291-3.

Goncalves JC, Martins C.Debulking of skin cancers with radio frequency before cryosurgery. Dermatol Surg. 1997 Apr;23(4):253-6; discussion 256-7.