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Verruca treatments (cryo)

Discussion in 'General Issues and Discussion Forum' started by *sole_man*, Dec 14, 2005.

  1. *sole_man*

    *sole_man* Member

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    Hi, I run a practice on the south coast and am considering starting cryo for verrucae. I have purchased a liquid nitrogen cryo gun but seem to find differing suggestions as to its effectiveness. I hoped somebody would have experience in using this treatment type and be able to give me a general idea of its effectiveness so that I can tell the patient roughly how many treatments they require and how much to charge them. Thanks, James.
  2. James - the following is a paper I published in 1990 on podiatric cryosurgery which you might find of some use.

    The application of a cryogen or refrigerant to remove body heat in an effort to destroy diseased or malignant tissue has been utilised in medicine for over a century. However, only in the last thirty years has our knowledge of cellular pathogenesis to freezing made cryosurgery an exact science and a commonly found modality in the treatment of benign, precancerous and cancerous tumours.

    Cryosurgery has been popular with chiropodists and podiatrists for a number of years in various forms, namely CO2 dry ice, nitrous oxide pressurised gas systems, and, more recently, with liquid nitrogen systems. The degree of success has varied markedly, depending on the type or system or cryogen used, and, also, because of lack of adequate literature and training available to practitioners, on the most efficient methodologies of incorporating this valuable form of treatment into their clinical regimes. In addition, the majority of cryosurgical units that have been available to podiatrists have generally produced inadequate freezing velocities, or temperatures required to destroy tissue located in the foot. Liquid nitrogen is the only coolant for the effective eradication of podiatric complaints such as verrucae and porokeratosis plantaris discreta. Until recently, the only type of equipment available to practitioners has been the nitrous oxide and carbon dioxide CSUs, and with an operating temperature of -89o this has proved ineffective for plantar tissue which is both thicker and lower in moisture content than, say, epiethelial tissue in the treatment of leucoplakia or in cervical tumours.

    The past few years has seen a great improvement in the technology available for liquid nitrogen cryosurgery, and, conversely, a notable advancement in the treatment of applicable podiatric conditions. As always, it is essential to understand the effects of the application of liquid nitrogen to a lesion, and, as such, there follows a summary on the pathogenesis of the cryolesion followed by techniques employed in podiatric applications.

    Freezing is a physical phenomenon for living tissue or cells, and the withdrawal of heat from this living tissue is the basis for cryosurgery. Freezing represents nothing more than the removal of pure water from solution and its isolation into biologically inert foreign bodies, the ice crystals. All the biochemical, physiologic and anatomical sequelae of freezing are directly or indirectly the consequences of this single physical event. Freezing converts water into ice in a process of crystallisation through dehydration. The size of the crystals and the site of development, whether intracellular or extracellular, are governed by the boiling point of the refrigerant and the rate of freeze. The faster the freeze, the greater the tendency for the formation of microcrystals, which are more lethal than larger crystals. The heat generated during the cooling process with the conversion of water to ice is referred to as the latent heat of fusion. As the water is turned to ice, one can measure the production of heat, equivalent to 80 calories per gram of water. No matter how prolonged or profound the freeze, a small percentage of water within the cells will remain frozen. This is referred to as bound water.

    As tissue is frozen, the iceball within the tissue forms into a hemispherical shape. The depth of freeze approximates the radius of the flat surface of the frozen hemisphere. The ice front close to the cryoprobe is much colder than the margins of the iceball itself. This is referred to as the thermal gradient. The development of the iceball and subsequent evolution of the cryolesion is influenced by these factors:

    1. The thermal conductivity of the tissue.
    2. Tissue blood perfusion tates.
    3. The specific heat of the surrounding tissue.

    One cannot freeze indefinitely, as an equilibrium of temperature transfer is reached between the cryoprobe and the surrounding tissue. The iceball advances until a balance is maintained between the cryogen and the underlying rate of blood flow within the tissue. The development of the cryolesion, and its thermal gradient resulting in the cryonecrotic state of the frozen tissue, is dependent on a number of important factors:

    1. The boiling temperature of the cryogen.
    2. The volume and depth of the tissue to be frozen.
    3. The probe tip size.
    4. The thermal conductivity of the tissue to be frozen.
    5. The cellular composition of the tissue.
    6. The rate of underlying blood flow within the tissue.
    7. The velocity or rate of cooling.

    Cryonecrosis: Cellular response to freezing

    There are several distinct mechanisms whereby freezing causes cellular injury, and within the iceball caused by the cryoprobe application, all of these mechanisms exist. Tissues will freeze at -2.2oC, though a number of factors must coexist to achieve cryonecrosis. After all, many body organs are subjected to extreme temperature when undergoing transplant surgery, and function with no signs of cellular injury after thawing. As stated, the fundamental change during freezing is the conversion of fluid into ice within a cell and its interspaces. The more rapid is this conversion, the greater the degree of hypothermia, and, conversely, the more deleterious the effect on living cells. During the thaw phase, the more rapid this is, the greater the chance of survival, whereas a slow thaw induces a high kill ratio. The changes that take place within a cell subject to freezing are:

    1. Development of extracellular ice formation.
    2. Development of intracellular ice formation.
    3. Abnormal concentration of electrolytes.
    4. Eventual crystallisation of the electrolytes.
    5. Cell dehydration.
    6. Thermal shock.
    7. Denaturation of lipoprotein complexes.

    All of these changes are complex and depend on a number of factors. For example, slow cooling produces large crystals which are not as lethal as the microcrystals that occur with rapid freezing. Remember that freezing temperatures are at varied thermal gradients, and that the velocity of freezing cells closest to the cryoprobe is much greater than those at the periphery of the iceball.

    Immunological effects

    Cryosurgery, in comparison to other forms of therapy, permits the controlled cryogenic destruction of lesions, concomitantly possessing the potential to augment or induce host resistance to the lesion, thus potentiating cryoimmunisation and cryoimmunotherapy. Evidence shows that cell destruction by freezing is accompanied by antigen formation through the liberation of lipoproteins from the cell membrane. This response is tissue specific, and this may explain why, in HPV infection, good cryosurgery technique is so effective, whereas in cauterising surgery, such as electrodesiccation or with CO2 laser surgery, the process tends to denature the protein functions and the response is lost. With many instances of multiple lesions regressing after an initial treatment of one verruca, it would suggest that the antibody response is of vital importance.

    Effect on connective tissue

    An advance of cryosurgery often cited is that of minimal, if any, scar formation postoperatively. Research has shown that the collagen fibre network of the dermis remains largely unaffected by the standard liquid nitrogen freeze times employed by a clinician. The presence of this collagen fibre network enables the skin architecture to return to more or less normal after surgery. However, it has been established that the fibre network loses its structural integrity in the coagulation of protein which occurs after thermal burning, which would explain the incidence of scar formation following electrodesiccation or laser surgery.

    Cryosurgical technique in clinical practice

    Cryosurgery can be employed on the vast majority of patients, and receives a high patient acceptance. In almost all cases, application and treatment can be completed in one visit, and the patient is ambulatory after surgery. In the majority of cases, no anaesthesia need be applied, though with patients who display a low pain threshold, or where the lesion is on a painful site such as a neurovascular heloma, analgesia can be administered in several ways:

    1. Administration of a subcutaneous local anaesthetic such as 2% lignocaine or 4% citanest. With liquid nitrogen cryosurgery, this should not be an infiltration technique, but rather a regional anaesthesia such as posterior tibial block. Freezing of the local anaesthetic with infiltration methods can produce perilesional damage.

    2. Conscious sedation therapy utilising a controllable oxygen/nitrous oxide inhalational mix.

    3. High frequency electrotherapy anaesthesia such as H-Wave neurological stimulation.

    However, not every patient is a candidate for cryosurgery. A patient may present with a condition for which cryosurgery is indicated, but which has, by clinical judgement, progressed beyond the scope for which it would be effective. Conditions such as malignant melanoma or verrucous carcinoma are prime examples of this. In essence, this technique may be employed as a guideline when a patient presents at the surgery.

    1. Assessment and counselling of the patient
    The patient should be fully informed about the cryosurgical process and the postoperative course. An informative handout at the assessment visit will help to reassure any doubts. Clinical judgement will determine whether anaesthesia should be employed for the procedure, and, again, the patient’s suitability has to be considered.

    2. Evaluation of the freeze site
    Careful assessment of the area must be scheduled prior to treatment. Skin type, classification and site of the lesion, along with previous history, all have to be considered in depth. Plantar skin is the most difficult area of the body to freeze, given its thickness and relative dryness compared to epithelial lining such as the cervix or in the oral cavity. Patients with exceptionally dry skin may be advised to soak their feet prior to treatment, or, alternatively, the clinician may opt to apply a 25% salicylic acid preparation to the lesion three days prior to the cryosurgery. The type of lesion is also important. A large solitary HPV1 type of lesion, located on the plantar surface of the heel, may require three repeated freezes of up to 90s each during the visit, whereas a single plane wart located on dorsal skin may require one freeze of only 15s. There are no written rules for freeze times or cycles. Adequate assessment of the site, classification of the lesion, and suitable patient history, combined with operational experience should enable adequate management.

    3. Freezing of the target site
    With verrucae infections, the overlying hyperkeratosis is removed prior to application. It is advisable to mark on the skin an area around 4 mm beyond the margins of the lesion. In the initial stages this will enable to clinician to gauge the size of the iceball formation in comparison to the target tissue. This close monitoring will also prevent the most common cause of failure – under-freeze of the lesion. Selecting a probe tip similar in size to the lesion, a water-soluble gel is applied to the freeze site, the probe is place in position perpendicular to the tissue, and freezing is commenced. When the tissue iceball progresses to the 4 mm border, one can assume that the lesion is within the lethal zone for cryonecrosis. The employment of a water-soluble gel enhances the thermal transfer, and gives good adherence to the skin whilst the procedure is performed.

    4. Postoperative care
    A sterile gauze dressing should be applied after the procedure, and deflective padding is useful where the lesion is on a weight bearing area. The reaction of the tissue following cryosurgery will vary between patients. In some cases a haematoma may form fully within a 12-24 hour period, whereas in others, a small intradermal bulla may not be apparent for up to five days post-operatively. In general, one should schedule the follow-up visit some three to five days after treatment, being prepared to see the patient at short notice should a haematoma develop. There is much debate on the care of blister formation. Some clinicians prefer to leave the lesion in situ, and wait until the necrosed skin sloughs off after a period of time. Others will prefer to excise the lesion at the blister stage and then debride the base. Both methods have their merits, and individual choice and preference will ensue with experience. Healing time will vary depending on the size of the lesion treated and the general health of the patient. On average, complete granulation and healing will take place between ten and twenty one days following the procedure.

    Cryosurgical equipment

    There has been much development in the technology available to chiropodists and podiatrists utilising the modality of cryosurgery within their clinical regime over the past ten years. In general, equipment can be classified into three main categories:

    1. Closed probe Joule Thomson equipment, which encompasses the pressurised gas systems using carbon dioxide or nitrous oxide gas to expand rapidly within a restricted probe tip area. Such systems are largely ineffective for podiatric conditions due the slow cooling velocities and modest probe tip temperatures of, at best, -89oC. This combination results in low success rates for the management of plantar verrucae where probe tip temperatures of below -120oC should be attained, and where freezing velocities in excess of -200oC/minute are required.

    2. Direct cryogen application. The provision of liquid nitrogen spray guns operating at a pressure between 8psi and 30psi have allowed practitioners to incorporate, what is established, as the ideal cryogen into clinical practice. These units are relatively inexpensive at around £450,00 to £600.00 per unit and are simple to use and maintain. They are ideal when a superficial freeze is required such as in the treatment of mosaic warts or in the removal of tattoos, though as the cryogen comes into contact with the tissue, film boiling takes place and the cryogen is dissipated over the surrounding tissues causing a large superficial freeze. Due to the thickness of the plantar skin this type of application is seldom adequate to ensure sufficient depth of freeze and local formation of an iceball, giving only moderate success. The boiling of the cryogen on the skin can also be extremely painful and the clinician may also wish to consider the use of a local/regional anaesthetic.

    3. Closed probe liquid nitrogen systems. Recognised as the ultimate in design for cryosurgical applications, this system incorporates the benefits of indirect thermal transfer through a closed probe system with the ultra-low operating temperatures of liquid nitrogen at -196˚C. Giving a controlled freeze on the target tissue with freezing velocities of up to -720˚C per minute and a stable tip temperature of -190˚C, this is recognised to be the most efficient system for the eradication of the majority of podiatric conditions. Modern units incorporate an efficient electronic management system which monitors cryogen flow/pressure and is designed to deliver a constant tip temperature of -190˚C whilst economising the consumption of the cryogen by operating at a low pressure of between 1psi and 3psi. The more sophisticated models incorporate an automatic defrost control for easy removal from the freeze site thus eliminating unwarranted perilesional damage. More expensive than the direct spray units at between £1,500.00 and £2,900.00, their costs should be weighed against the success rate of around 96% eradication with a single procedure.


    In summary, it can be stated that cryosurgery has a number of benefits and advantages not shared by other operative procedures in the treatment of cutaneous anomalies presented in the podiatric sphere. It is a simple and safe procedure with a high clinical success rate and is also well tolerated by patients. With the advent of the latest generation of cryosurgical equipment we can anticipate predictable, desirable results for a variety of conditions where previous methodologies were costly and time consuming. However, it would be incorrect to assume that cryosurgery was a panacea for cutaneous skin conditions in podiatric practice. Common sense, combined with a comprehensive knowledge of diagnosis and pathophysiology is paramount for utilisation of today’s technology. In specialising and refining their cryosurgical technique, clinicians will have added a valuable ally to their armament in clinical practice.

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