Low temperature skin treatment

Although freezing has been a successful method of curing various kinds of skin lesions for at/east 80 years, little progress has been made regarding the techniques and instruments available to the dermatoligist for applying cold. The attempts to improve this technique are reviewed, and the requirements for successful cryotreatment are discussed taking warts as an example. With these requirements in mind, a simple and effective cryoprobe has been developed by the authors. Its design is described, and the experiences from a year's routine application of the probe to the treatment of warts are discussed.

Low temperature skin treatment G. Klipping, A. Krishna, U. Ruppert,

R. Srinivasan, and H. Walter

The use of cryogenics in dermatology is of interest to the medical fraternity as well as to the cryophysicist. The problem of interest to the dermatologist is, whether cryogenics provides a successful alternative to the existing methods of treatment of skin lesions from the point of view of the permanency, the reliability and the reproducibility of the cure, the level of attendant pain, the complexity of the technique and the side effects of the treatment. To a certain extent he is also interested in understanding the nature and extent of the destruction caused in the epidermal and the dermal cells. Matters of interest to the cryophysicist on the other hand are the efficacy with which cold is transmitted from the cold probe to the cutaneous and subcutaneous layers, and the rate at which the cold front moves as a function of the time of application, pressure of the probe on the skin, the nature of the tissue and the extent of vascular blood flow. The optimum design of a cold probe for skin treatment is of interest for both sides. Interactions between cryophysicists and dermatologists appear, however, to be scarcely existent at present. Early reports on the use of cryogenics in surgery generated a lot of expectations. But among the medical fraternity this enthusiasm has noticeably waned, possibly because the controlled application of cold could not be achieved, especially with the techniques available to the dermatologist However, in the last ten years cryogenic techniques have developed rapidly and it is of interest to review the problems involved from the point of view of a cryophysicist. Warts - a classical s u b j e c t f o r c r y o g e n i c t r e a t m e n t

Skin lesions can be classified as malignant (cancerous) and benign (harmless). Needless to say that the treatment of benign lesions by the application of low temperatures provides a greater freedom for experimentation and study without undue risk. Among the benign lesions cryogenic treatment has been practiced most frequently and with success on warts, which therefore will form the main subject of this paper. The authors are interested in developing the necessary understanding for the medical problems involved in order to be able to design optimized equipment. According to the relevant medical literature warts (verrucae) are caused by a viral infection of the skin. The wart virus GK and UR are at the Fachbereich Physik, Freie Universitaet Berlin, Berlin, FRG. HW is at the Fritz-Haber-lnstitut der Max-PlanckGesellschaft, Berlin, FRG. AK is at the Skin and Cosmetology Clinic, Madras, India, and RS is at the Department of Physics, Indian Institute of Technology, Madras, India. Paper received 23 September 1980. 0011-2275/81/003-05 CRYOGENICS . MARCH 1981

attacks the epidermal cells, but how the reaction starts is not known. Warts are transmitted by direct or mediate contact. There are different types of warts. The common type is called verrucae vulgaris, the others are known as verrucae plana, verrucae t'fliformis, verrucae digitatis, verrucae plantaris and condyloma accuminatum. 1 The differences among these warts lie only in their appearance, location and the amount of reaction produced in the host: Verrucae vulgans have a horny surface and a size varying from one millimeter to more than twenty millimeters in diameter. They either occur as solitary warts or in groups, mainly on the dorsa of the hands. They increase in size by coalescence of several small warts. Planar warts are smooth, fiat or slightly raised. They occur on the face or the hands. Filiform warts look like ffmgers on the face and the neck and occur in clusters. Verrucae digitata resemble digits and occur on the scalp and the face. Plantar warts occur on the soles of the feet beneath the pressure point. They are painful and the surface is rough. Condyloma accuminata occur in the genital regions. The cotton swab method

White in 1899 was the first to treat warts with a cotton swab dipped in liquid nitrogen. 2 The use of carbon dioxide snow for the same purpose was advocated by Pusey. ~ The cotton swab method has till today been followed by some dermatologists with success from the medical point of view, but without any improvement in technique for the last seventy-five years. The cotton swab is pressed on the wart for a time varying between 20 seconds to 2 minutes, till the treated site turns white. The swab is then removed and the lesion allowed to thaw. During the period of thawing some discomfort may be experienced. A blister forms at the end of 24 to 48 hours and then the wart falls off along with the blister. Seldom has scarring been reported in literature. Such single cryotreatment is quite effective for ffliform and flat warts. However, in the case of large common warts and plantar warts a second or third application after a week or two mostly becomes necessary to remove the wart completely. The cotton swab technique is simple but from our point of view as cryophysicists suffers from a number of disadvantages. For controlled and reproducible freezing of the skin the thermal capacity of the probe should be sufficient and the temperature must be precisely determined. This is not the case with the cotton swab technique. Also the area, over which the liquid nitrogen will be applied, cannot be precisely controlled, and therefore unavoidably the area of epidermal cell destruction will be much larger than the area

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of the wart. The liquid nitrogen evaporates rapidly on being brought into contact with the skin and produces a layer of gas between the swab and the lesion, thereby reducing the heat transfer. In our opinion the method of treatment must be such as to allow precisely determined temperature and heat transfer conditions .The dermatologists in general, however, do not seem to worry too much about such controlled conditions and prefer the most simple way of applying cold. Nevertheless, we believe it will pay in the long run to perform cryotreatment of warts under controlled conditions and feel that here the cryophysicist or engineer should help the dermatologist in overcoming the technical problems.

Heat transfer measurements leading to improved cooling techniques Of course, a few dermatologists have realised the disadvantages of the cotton swab treatment and tried to improve the cooling technique. It was found that one cannot produce sub-zero temperatures in layers below 1.5 mm from the surface of the skin. In order to increase the penetration of the cold front, Zacharian has used cylindrical probes of solid copper of 1 cm thickness cooled to liquid nitrogen temperature. 4 By measuring the temperatures at various depths below the skin level in in-vivo tests he showed that with cotton swabs, not only the penetration depth of the cold is limited, but that also the temperatures never fall below - 1 8 to -24°C at the subcutaneous level, while with the copper discs one can reach temperatures between --45 to 75°C. s With copper discs of various diameters also successful treatment of patients with carcinoma of the skin was reported, and a self-pressurised nitrogen spray system was used to treat hyperkeratotic lesions spread over a wide area. 4 Liquid nitrogen spray has also been used by Spiller and Spillers for treating dermatofibromas, while they applied a cryoprobe cooled by circulation of liquid nitrogen (CES cryoderm) for removing facial warts and mucous cysts of the lip. However, even with such improvements over the cotton swab technique one has still not achieved the ideal conditions of well defined temperature at the point of application throughout the period of cryotreatment, optimum heat transfer and minimum damage to healthy areas of the skin around the lesion. In an important paper Rothenborg 7 pointed out the difficulty of ensuring uniformity and reproducibility in cryolesions. He noted that the expectation of producing reproducible and equal cryonecrosis (cryogenic destruction of living cells) by applying a copper cylinder cooled to liquid nitrogen temperature to the skin is not realised in practice. A non-insulated copper cylinder cooled to liquid nitrogen temperature by dipping it into the liquid absorbs about 50% of the heat from the surroundings instead of the skin and the temperature of the metal cylinder increases very fast and in a way dependent on the atmospheric conditions in the room. If the initial temperature difference between the metal cylinder and the skin is very large, about 200°C, the surface of the skin cools very fast, but the motion of the cold front is not uniform. In order to overcome the problems of a variable temperature on the surface of the skin as well as too low temperatures, he used a closed circuit system (CE 4, UCC-Linde Co.) for cooling the copper probe, but found that the thermal iner-

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tia of this cooling system was such that it was imoossible to avoid freezing below -60°C. It is necessary to control the freezing rate of the cryoprobe with a suitable programmer so that overfreezing does not take place. A freezing rate of 30 to 50°C per minute was found to be optimum. A higher freezing rate produces oscillations in the temperature about the freezing curve, while a lower rate results in the formation of ice crystals around the probe in an unpredictable way.

Thermal contact between cryoprobe and skin Rothenborg also points to the problems of insufficient heat transfer between the probe and the skin due to the formation of tiny ice crystals on the probe during the process of transferring it from the liquid nitrogen bath to the surface of the skin. He mentions that the use of a drop of water between the skin and the probe improves the heat transfer. However, this improvement is brought about only if the probe gets welded to the skin by freezing the water uniformly. This is facilitated, if the probe is applied at room temperature and is then gradually cooled by the circulation of liquid nitrogen. If the probe is already much colder than the surface of the skin, the water drop breaks up into tiny ice crystals and a good heat transfer is not obtained. Moreover, the pressure with which the probe is applied to the skin is also an important parameter for heat transfer.

Influence of the thawing rate on cryonecrosis The size of the cryonecrosis not only depends on the freezing rate but also on the thawing rate. Quick thawing reduces cell destruction while slow thawing enhances it. Spontaneous thawing rates are variable over a wide range. Rothenborg 7 recommends quick thawing of the lesions in lukewarm water. Although this reduces cell damage it results in more uniform cryonecrosis. Rothenborg s has also investigated the effect of the arrest of blood flow on the thawing rates of common warts and dermatofibromas cooled by a spray of liquid nitrogen. He finds that the arrest of blood flow considerably slows down the thawing process. It may be mentioned that in another investigation 9 he has shown that during the rapid freezing used in cryosurgery, the arterio-vascular walls do not have time to contract reducing blood flow and the flow ceases only when the temperature falls below 0°C and the blood freezes.

Suitability of cooling method for routine application in a medical practice Since the destruction of living cells can be achieved by rapid cooling to about -20°C to -40°C and slow thawing, it may seem advantageous to develop small closed-cycle refrigerators with freon, which can produce a refrigeration capacity of a few watts at the tip of a cryoprobe. With such a probe one could achieve a temperature of --40°C quickly and maintain this temperature while the probe is in contact with the skin. A cryoprobe using nitrous oxide in a closed cycle producing low temperatures by Joule-Thomson expansion has been described by Barnes l° and Duncan and Parry ~1and has been used in the treatment of cervical erosions and chronic cervicitis. Another example of using a closed-cycle cooled cryoprobe has been given by Rothenborg 7 as mentioned above. He also

CRYOGENICS. MARCH 1981

indicates some problems which may arise in the application of such a system. Though refrigerator-cooled cryoprobes certainly have their domains, for example in surgical clinics, this technique is, from our point of view, not too well suited for the dermatologist's practice, since it is comparatively complicated and expensive. Here, the cryogenic liquid is more favourable as a source of cold. Liquid nitrogen is today used for many purposes and is readily available almost at any place in industrialized countries. Even in developing countries, with the growing interest in artificial insemination of cattle, liquid nitrogen will become more widely available. In modern low-loss transport dewars, liquid nitrogen can be stored over several weeks and can thus almost at any time be kept at hand in a medical practice. An autonomous cryoprobe for surgery using liquid nitrogen as cold source has recently been described by Safrata, Hora, Mgdek and R{ha. ~2 It contains a new type of porous heat exchanger which is supplied from a small volume of liquid nitrogen in the handle. It provides a high cooling rate and controllable cooling power at any desired temperature of the cold tip.

Simple effective cryoprobe for skin treatment A simpler system especially meant for skin treatment has been developed by the authors ~a and, after some practical experience and investigation of its thermal behaviour, has been optimized with regard to the following points: 1. sufficient holding time of temperatures T < 125 K during application, 2. short cool-down time, 3. low consumption of liquid nitrogen, 4. scarce formation of ice at surfaces other than the tip, 5. low weight, 6. handy dimensions, 7. easy handling, 8. long life time, 9. possibility of sterilization, 10. easy production Fig. 1 shows the final design of the cryoprobe. The former long copper rod has been replaced by a comparatively short one (1) with a tip (2) shaped according to the form and size of the wart to be treated. A stainless steel tube (3) is screwed onto the end of the copper rod. At its free end this tube is closed by a threaded plug (4) carrying an electrical feed-through (5) as well as a short piece of a wider brass tube (6), which is provided with an electrical plug connection (7). A platinum resistance thermometer (8) is glued into a bore inside the copper rod and is via the feed-through (5) connected to the plug connection (7). This unit is suspended into a liquid nitrogen dewar such that the rod (1) is fully immersed into the liquid. After cool-down, a jacket tube (9), which over part of its length is knurled for better handling of the probe, is slipped over it and screwed onto the plug (4). This jacket serves two purposes. It prevents burning of the doctor handling the probe and, at the same time, prevents the copper rod (1) from being warmed up too fast and in an uncontrolled way. The experimental investigation of the system showed

CRYOGENICS. MARCH 1981

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8

I

IO

Fig. 1

4

3

5

6

9

Design of the cryoprobe

that the latter effect can be considerably improved by providing a second shorter jacket tube (10) inside the jacket (9), which advantageously is covered by some layers of superinsulation. The same jacket is used for several probes. For operation, the probe without the jacket tube is dipped into a dewar vessel with liquid nitrogen as mentioned above. Of course, a number of probes with tips of different shapes can be cooled down at the same time in a wide necked dewar or glass dewar. The probe shown in Fig. 1 cools down to liquid nitrogen temperature in about 1.5 min. Even without temperature measurement, readiness for cryotherapy is indicated by a sudden increase in bubbling of the liquid nitrogen and a hissing noise wlfich suddenly stops. The probe is then taken out of the dewar, the jacket is slipped over it and fastened, and it is ready for use. During several minutes the knurled end of the jacket used for handling remains suitably warm due to the heat transferred from the hand of the person holding it. For fast warmup of the probe and removal of the ice crystals, wlfich unavoidably condense on the free surface of the tip, the jacket is removed and the probe is immersed into water. It then attains room temperature in a few seconds and is again ready for use. Characteristic design features and performance data of such optimized cryoprobes are given in Table 1. Fig. 2 shows warm-up curves for the same probe. The temperature of the copper rod (1) and the ~ip (2) during cool-down and application is measured by the platinum resistor (8) and is indicated by a suitable temperature measuring device. Of course, the provision of the temperature sensor and the temperature measuring device will considerably increase the investment of the dermatologist for such a cryoprobe. After extended practical experience, however, a kind of calibration of the cryoprobe should be possible. Then it could also be produced and used without temperature measurement and could thus be made cheaper, which especially for developing countries may be of importance.

Experiences from n~dieal application of the cryoprobe For the past year in the skin clinic of one of the authors, the cryoprobe described has been employed for the routine treatment of warts except in the case of bizzare confluent warts of the vulgaris type and irregular plantar mosaic warts. The equipment is provided with the temperature sensor and is routinely connected to the temperature measuring device during operation for standardization of technique. It has become apparent,

183

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Warm up curves for the cryoprobe

however, that the procedure of therapy is reproducible with the cryoprobe alone. With the hand holding the probe near the lower part of the outer jacket in the manner of a pen or pencil, the tip of the probe is applied with a certain amount of pressure, just to depress the wart, and kept in position. The temperature remaL,as below 125 K, normally for about 50 to 70 s by which time the tissue is frozen adequately to induce cryonecrosis. It has shown to be useful to keep the probe in contact with the wart for another 60 to 90 s to slow thawing and thus enhance the cell destruction being induced.

As compared to electro-surgical removal of warts, a standard method practiced by the majority of dermatolo. gists, cryo-therapy with this probe has the following advantages: an operation theatre set-up as, though minimal, required for electro-surgery is eliminated;absence of the need for local inf'tltration anesthesia in the patient; the number of post therapy check-ups of the patient is reduced to two or three from four to six that are needed in the case of electro-surgery, depending on the size of the wart treated;post therapy surgical dressings are avoided, and, in the co-author's technique of leaving the blisters induced to dry up on their own and get peeled off, the need for surgical dressings to the area under treatment is totally eliminated; the final scarring is minimal with good cosmetic results and high degree patient acceptability. It has been the experience of the co-author that therapy by cold always gives less scarring as compared to the dessication of tissue by heat. Conclusions

Though cryotherapy has been recognized as highly effective, especially in the treatment of benign skin lesions (the cure rate being 80% and above), all over the world it is not practiced extensively,t4 During the early years of cryotherapy in the developed countries and even now in the developing countries, its limited use can partly be ascribed to difficulties in the free availability of liquid nitrogen or solid carbon dioxide. However, in the meantime almost everywhere the necessary cooling agents are accessible. The continuing reluctance to try this therapy on the part of the dermatologists is therefore probably due to their

Keeping the probe on the wart under treatment for 2 to 2.5 min without interruption has been found adequate for the great majority of warts, except the large periungual and confluent warts of long duration. A single treatment of this kind has been found sufficient for curing of warts up to 5 - 6 mm in diameter, under which category most warts coming in for treatment will fall. Compared with the regular method of cotton swab application of liquid nitrogen, the present cryoprobe brings Table 1.

in a great degree of reproducibility and standardization of technique and helps saving time as well. The need for repeated application of liquid nitrogen every few seconds necessary with the cotton swab is eliminated along with its concomitant vagueness of the procedure including unnecessary and excessive damage to wide peripheral areas of healthy tissues on the surface around the wart.

Design features and performance data of an optimized cryoprobe for skin treatment Copper rod

Design

Performance

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Probe

Length mm

Diameter mm

Total length mm

Total weight g

80

9

260

100

Cool-down with copper rod completely immersed

Warm-up of probe from 78 K under different conditions

Cool-down time 300 K -~ 78 K

Holding time at 78 K

Horizontal in air -+ 125/150 K

Tip pressed on wet sponge -+ 125/150 K

s

s

s

s

58

12

62/122

39/69

CRYOGENICS. MARCH 1981

unfamiliarity with modern cryogenic techniques. On the other hand, also the physicists and engineers working in cryogenics may not be aware of the dermatologist's need for support. The authors want to emphasize the need for close co-operation from both sides in order to make the advantages o f modern cryogenics available tor medical application.

6

7 8 9

References 1 2 3 4 5

Fischer, T. Metoder foer behandling av vartor Laekartidningen 71 (1974) 3917-8 White, A.C. Liquid air in medicine and surgery M Rec 56 (1899) 109-114 Pusey, W.A. Use of carbon dioxide snow in the treatment of nevi and other skin lesionsJAMA 49 (1907) 1354-1357 Zacharian, S.A. Cryosurgery in dermatologylnt Surgery '47 (1967) 528-534 Zacharian, S.A., Adham, M.I. Cryotherapy of cutaneous malignancy Cryobiology 2(1966) 212-218

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13 14

Spiller, W.F., Spiller, R.F. Cryosurgery in dermatologie office practice: special reference to dermatofibroma and mucous cyst of the lip. Southern Medical Journal 68 (1975) 157-160 Rothenborg, H.W. Standardization of cryosurgical lesions Cryogenics 15 (1975) 4-7 Rothenborg, H.W. The influence of blood flow on freezing and thawing rates of living tissues Cryobiology 6 (1970) 512-514 Rothenborg, H.W. Cutaneous circulation in rabbits and humans before, during and after cryosurgical procedures measured by xenon 133 clearance Cryobiology 6 (1970) 507 Barnes,J. Cryosurgery in gynaecology Nursing Tunis (June 20, 1974) 947-948 Duncan, G.R., Parry, G.K. Cryosurgical treatment of the benign cervix New Zealand Medical Journal (1974) 57-59 M~lek,Z., Hora, O., Jelihek, J., Zoba~, L., Soukop, F., Safrata, R.S., Riha, J., Kr~sel, I. An improved method of controlled cryo-destruction of pathological tissue by a high rate of cooling. Proceedings ICEC 8 Genova (1980) 549-553 Klipping, G., Lakshmi, G., Srinivasan, R. Cryogenic treatment of warts, Indian J Cryog 3 (1978) 43-48 Fraser, J. Cryogenic techniques in surgery, Cryogenics 19 (1979) 375-81

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