Cryotherapy and cryosurgery

Cold, like other physical agents, may be used for the local treatment of skin conditions. Its action on given tissues depends on freezing modalities: while slow freezing may be used to preserve tissues (i.e. the principle used for cell preservation), they are destroyed by extremely rapid drops in temperature.

Cryotherapy and cryosurgery are defined as the destruction of given target cells by cold. However, the terms should not be used interchangeably.

Cryotherapy does not require monitoring and does not necessarily lead to total destruction of the target: it is therefore used for benign tumours.

Cryosurgery results in total cryo-destruction and monitoring is therefore essential: it is used to treat pre-malignant and malignant tumours.

The distinction between the two methods, based on accurate interpretation of their respective purposes, conditions the quality and efficacy of the intended result.

1 - METHOD OF ACTION

The destruction process involves application of extreme cold to target tissues which are then allowed to thaw slowly, prolonging the destructive action of the cold. Destruction is achieved through a double process involving crystallisation of tissue water and ischemia caused by vascular thromboses. However, sensitivity to cold varies from one cell to another. Melanocytes, the most fragile cells, are destroyed at a temperature of about –3 °C, which explains scar tissue depigmentation. Normal epidermal cells are destroyed at about –30 °C, and between –30 °C and –50 °C when they are abnormal. The cells of the dermis are resistant to cold, which explains the good quality of dermal scars.

2 - MATERIALS AND TECHNIQUES

2.1 - CRYOGENIC AGENTS

The most common cryogenic agent is liquid nitrogen, which can reduce tissue temperatures to between -25°C and -50°C within 30 seconds. It is the most refrigerant of the cryogenic agents.

Nitrogen protoxide is applied using probes that work on the Joule-Thomson principle. It is the agent used for deep organ cryosurgery.

2.2 - MATERIALS

Liquid nitrogen is stored in an auto pressure-increasing cryogenic container. It is applied directly on the target lesion using either a cryospray or a metal cryoprobe with a closed tip (cryocontact). Different sizes of cryoprobes can be adapted to the container.

2.3 - CONTROL

Extending cryotherapy to cryosurgery entails the use of a special system to control freezing to ensure that the target cells are entirely destroyed. Freezing is thus controlled by measurement of impedance, i.e. the calculation of tissue resistance to cold. Measurement of impedance is a good indicator of tissue degradation and the values required for total tissue destruction range from 500 to 1000 kOhms.

2.4 - THE CHOICE OF TECHNIQUE

It depends more on the lesion to be treated than the operator’s preference. Cryotherapy is used for benign lesions for which cosmetic results are more preferable than complete tissue destruction. Malignant tumours can be treated only by cryosurgery.

3 - CRYOTHERAPY

Useful and competitive for destroying benign tumours [2], cryotherapy is a quick and simple treatment which, unlike excision, electro-coagulation and vaporisation-laser cutting procedures, does not require local anaesthesia. For superficial lesions, the cryospray should be used. Dermal lesions are better treated by cryoprobe.

Cosmetic results are good, particularly when the patient has a light complexion.

A number of tumours can be treated by cryotherapy:

– Epithelial tumours such as seborrheic keratosis, adenomas and sebaceous hyperplasia, hamartoma with verrucous features, etc.

– Vascular tumours such as pyogenic granuloma, senile angiomas, angiokeratomas, lymphangiomas (to improve oozing problems with no risk), etc.

– Mesenchymal tumours: fibrous histiocytoma, cutaneous mucoid or mucinous pseudocysts.

– Inflammtory speudo tumors :

• Nodular prurigo: contact cryotherapy can be use.
• Annular granuloma: excellent results reported, with low relapse rate.
• Facial granuloma: superficial cryotherapy, by cryospray or cryocontact, is an excellent treatment and induces only moderate achromia.
• Keloid: freezing has been shown to modify the behaviour of fibroblasts, which explains why cryotherapy reduces keloid. However, several sessions are required, especially when lesions are large. We suggest, therefore, reducing the scar surgically and immediately freezing the wound, measuring the impedance (1000 kOhms). For 75% of patients, this procedure completely reduces keloid after one session. General or local anaesthesia may be used (depending on the size and site of the lesion and patient preference). Relapse may occur, but the keloid are smaller, less permanent and appear later than when surgery alone is performed. They recur more than a year after treatment and may be treated by the same combination of surgery and cryosurgery. This combined therapy gives stable long-term results and is valuable for a condition for which there are very few effective treatments.
• Pseudo-lymphoma: cryotherapy may be useful to reduce these lesions.
• Infectious pseudo-tumours: cryotherapy is the first-line therapy for viral papilloma. It is particularly indicated for small warts on the hands, even though subungual warts are easier to treat by laser and periungual warts can damage the nail matrix. Deep plantar warts (myrmecia) should not be treated by cryotherapy, or if so, only after careful stripping. Overall, cryotherapy is no better than other therapies for treating papillomavirus lesions.

Cryotherapy is a useful treatment for molluscum contagiosum in immuno-depressed patients and for Kaposi’s sarcoma in HIV-positive patients.

4 - CRYOSURGERY

Pre-malignant and malignant tumours are treated by cryosurgery. Since they are likely to spread, cryo-destruction must comply with certain rules:

– freezing must be controlled;

– tumours must be superficial; an invasive tumour can only be treated palliatively;

– tumours must have been identified by biopsy;

– poorly circumscribed, recurrent tumours must be examined carefully before any cryosurgery.

• Pre-cancerous lesions

- Pre-epitheliomatous keratosis: cryotherapy has long been the routine, rapid and effective treatment for destroying these tumours which are often on the malignant-benign borderline. The development of such treatments as imiquimod or dynamic phototherapy, has, by treating the cancerous areas, tended to reduce the need for cryotherapy. However it remains effective for pre-cancerous keratosis when the lesions are isolated or infiltrated and the pilar sheath damaged.

- Leucoplakia: an experienced practitioner can obtain good results on leucoplakia lesions of the lips, so long as the cells well beyond the borders of the lesion are destroyed.. 

Results are also satisfactory for oral cavity lesions.

 - Kerato-acanthoma: surgery is the treatment of choice. However, in exceptional circumstances, with large tumours that are difficult to remove at the base, cryosurgery may be an effective replacement therapy..

– Bowen’s disease (intra-epidermal carcinoma) and superficial and multicentric basal cell carcinoma: these tumours occur in the epidermis, with similar clinical features and often with oozing, poorly limited lesions that cause similar damage. Cryosurgery facilitates tissue repair and limits scarring, particularly on the face. It can also be used for Bowen’s disease of the fingers since the scar tissue remains flexible without fibrosis so that tissue mobility is retained. Similarly, for lesions of the balanic mucosa (glans penis), cryosurgery allows for restitutio ad integrum. On the lower limbs and trunk, however, where healing is slow, and scar tissue disfiguring, imiquimod or dynamic phototherapy should be the first-line treatment. If this should fail, superficial cryosurgery may be performed. Dynamic phototherapy and imiquimod can also be used on the face, though dynamic phototherapy is the more painful, whilst imiquimod is more restrictive and both are more expensive than cryosurgery.

- Dubreuilh melanoma: for a tumour that spreads horizontally, the reference treatment remains surgery; but this particular tumour spreads over the skin surface causing large coloured patches. It often occurs on the faces of elderly patients and is very difficult to remove by exeresis. Cryosurgery is a simple alternative, but effective only for intra-epidermal lesions. Treatment leaves a soft, foliate light spot that is cosmetically acceptable.

• Skin carcinoma

Cryosurgery is a major indication for basal cell carcinoma. In exceptional circumstances, and only after a multi-disciplinary discussion, epidermoid carcinomas can be treated when the lesions are well differentiated and have developed on pre-epitheliomatous keratosis.

Often, the decision to perform cryosurgery will depend mainly on the context, since it is quick, easy and well tolerated. Skin carcinoma sufferers are generally elderly and poly-medicated and cryosurgery can be of particular value for them: it is done under local anaesthesia at one session and is compatible with all classes of medicinal products, including anticoagulants. Patients with pacemakers may be treated and rarely is there a hypersensitivity reaction. It is a non-traumatic treatment, despite the slight discomfort induced by marked oedema that occurs around the eyelids, and the weeping of all sites that last for about a week. After cryo-destruction, patients rarely complain of pain for more than a few hours. This means that age is never a contra-indication.

Cryosurgery is particularly indicated for centro-facial tumours which are not always simple to remove because of poor cutaneous reserve, even in elderly patients [1]. On these locations, it is essential to preserve the skin and healing must be excellent, with skin behaving like fresh tissue. The more dispersed the tumours are, the more justified it is to perform cryosurgery, since it can be used without limits and without damaging adjacent skin.

Lesions on the tip and wings of the nose, where the options are limited, are appropriate sites for cryosurgery which should be first-line therapy in these cases [4]. Cryo-resistance of cartilage explains the notches exceptionally occurring on the nostril rim, a risk that cannot be totally excluded. Other indications include lesions along the entire nasal dorsum.

Lesions in the naso-genien groove are less easily treated, but in a difficult context and for a tumour that has been evaluated as non-infiltrating, cryosurgery might be possible if done by an experienced physician.

Canthus tumours are also difficult to treat [3], but they may benefit from cryosurgery which is easy and rapid. Preservation of the lacrymal structures is an advantage since there is no residual tearing, not even late-onset tearing, since the scar is not fibrous. Approach through the free edge of the eyelid may risk the formation of a palpebral notch, but this is rare and can be reduced by fractionated destruction, even of an extensive tumour. Repair of a post-cryosurgical ectropion is facilitated by the flexibility of the reconstituted tissue.

Cryosurgery is also the best treatment for tumours on the pinna, ?but? owing the fact that resistance of healthy cartilage to cold must be taken into account.

Although the treatment of peripheral facial areas is less of a problem, cryosurgery can be very useful if the patient cannot undergo normal surgery.

Besides the benefits for cryosurgery listed above, there is a further one of reduced rate of recurrence to about 5% after five years; bearing in mind the difficulty of comparing heterogeneous series [5, 6 , 7]. These results are obtained only if the criteria with respect to indication and temperature control are fully met. Moreover, the healing process does not preclude further intervention by other techniques; yet another benefit of cryo-destruction.

When properly mastered and well used, cryotherapy and cryosurgery are simple, safe and effective treatment options for patients.