Dermatologic Surgery Made Easy Virendra N Sehgal, Govind Srivastava
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CryosurgeryCHAPTER 1

Sambit N Bhattacharya
Somesh Gupta
Virendra N Sehgal
2
 
INTRODUCTION
Cryosurgery is the term used to describe procedures that achieve surgical outcomes by using freezing temperatures. Tissue destruction and healing by secondary intention usually follow, resulting in tissue/structural change and remodeling. Low temperatures are obtained by cryogens, usually molecules that exist as gases at normal room temperature. They generate the cooling effect by absorbing heat for expansion, evaporation and/or boiling. Non-destructive use of cold temperature to modify disease is termed cryosurgery.
 
HISTORY
Cryotherapy has a long history. 1 The benefits of cold have been appreciated past many thousands of years. Ancient Egyptians and later Hippocrates used cold for its analgesic and anti-inflammatory properties. In early 18th century, James Arnott, an English physician, used mixture of salt and ice to achieve extreme cold in the palliation of tumors.2 The modern cryosurgery began with the discovery of the liquefaction of gases. In 1898, Dewar developed the vacuum flask for storage of liquid gas. The first cryosurgeon in Modern Medicine was an American Dermatologist, White, who used cotton-tipped applicators to apply liquefied air to treat certain skin conditions. Pusey reported use of carbon dioxide snow for cryotherapy.3 Allington first used liquid nitrogen as a cryogen in the year 1950.
 
TERMINOLOGY
Several terminologies have been used. They include cryotherapy, cryocautery, cryocongelation, and cryogenic surgery, but cryosurgery and cryotherpy are in vogue and often used interchangeably. However, some experts restrict the term cryotherapy for non-destructive treatment of skin conditions, such as acne, alopecia areata.4
 
CRYOGENS
Commonly used cryogens are:
Gas (cryogen)
Boiling point (° C)
1. Chlorodifluoromethane
– 41
2. Dimethyl ether and propane
– 24, – 42
3. Solidified carbon-dioxide
– 78
4. Nitrous oxide
– 89
5. Liquid nitrogen
– 196
3
 
Effects of Cooling
Mammalian/ human tissues function optimally in a normal range of temperature, which is maintained by elaborate mechanisms. Extreme variations in temperature progressively results in dysfunction and then death.
Death of living components of a tissue occurs at different temperatures for each cell constituent that is unique to each cell. Keratinocytes are killed at temperatures below –40°C whereas melanocytes succumb at higher temperatures of –5 to –15°C. This differential killing at temperatures between –10°C and –50°C, results in pigment loss as a side-effect of cryotherapy.
The destruction in cryosurgery occurs as a result of cold induced
  1. Vascular injury
  2. Direct cell injury
  3. Immunological/inflammatory injury. Each of these are brought about by:
    1. Formation and expansion of ice-crystals.
    2. Altered osmotic activity due to crystallization of ice extra- and intracellularly.
    3. Molecular structural damage to proteins and lipids inside and on the cell surface.
As non-living structural molecules are not readily damaged by cooling that destroys living cells, they provide a ‘scaffolding’ around which healing occurs, even in peripheral nerves, resulting in the excellent cosmetic and functional results following cryosurgery.
 
Factors Affecting Destruction
The amount of destruction obtained by cryosurgery is determined by the amount of tissue that attains the temperature that is destructive for it. For skin the target temperature is in the region of –50°C (to attain total destruction, important for treating malignant lesions of basal cell carcinoma and squamous cell carcinoma, etc.)
During cryosurgery the factors that determine the amount of destruction are:
  1. Minimum temperature achieved in the frozen area,
  2. Duration for which it is maintained – holding time,
  3. Thawing time and,
  4. Number of freeze thaw cycles.
The extent of the destruction is limited to the area at which ice formation occurs (and the target temperature achieved). The 4cryolesion tends to be spherical around the ‘heat-sink’ area for distances up to 6 mm (the lateral spread is equal to depth) however larger areas of freezing tends to give conical cryolesions of destruction (studied up to 2 cm diameter).
The lower the boiling point of the cryogen the more efficient it is as a cooling agent. Open cooling by direct contact or spray achieves faster and lower temperatures. Closed systems, using cryoprobe heat stinks, tend to achieve temperatures 15° to 20°C higher than the boiling temperature of the cryogen being used. Therefore, cryosurgery using cryogens other than liquid nitrogen may not achieve complete destruction of lesions and are not recommended for treating malignant lesions.
In this section liquid nitrogen cryotherapy/cryosurgery will be highlighted because of its versatility, ease of use and reproducible superior outcomes in all types of dermatological conditions.
 
CRYOSURGICAL EQUIPMENTS
 
Cooling Devices
  • Cryospray nozzle(s)
  • Cryoprobe(s)
  • Cryogun
  • Styrofoam/polystyrene cup and cotton buds
Usually lightweight, portable hand-held devices with a controllable ‘trigger’ or lever to begin and end cooling (Fig. 1.1). Spray guns using liquid nitrogen may have pressure gauge and safety-valve mechanism which lets out pressure automatically should it exceed 70 psi.
The liquid nitrogen spray gun has the spray nozzle that is usually interchangeable with heat-sink cryoprobes of various shapes and sizes with areas up to 1 sq cm.
 
Cryogen Storage Devices
Gaseous cryogens are stored in metal cylinders as compressed gas (Fig. 1.2). Liquid nitrogen is stored in specialized insulated flasks (Dewar's) with inbuilt internal pressure equalization mechanism.
Special handling equipment and techniques are to be followed while transporting, storing and transferring liquid nitrogen as it is a hazardous substance that can cauterize and destroy body parts on which it is accidentally dropped.5
zoom view
Fig. 1.1: Hand-held device for cryosurgery
zoom view
Fig. 1.2: Cryostorage device
Special steel alloys are used in transferring equipment that can withstand abrupt lowering of temperatures without fracturing.
 
Transferring Equipment (IBP)
  • Siphon/Spigot (self-pressurizing)
  • Funnel (stainless steel) and tilting device
  • Insulated gloves
  • Pressure tubing and gauges for connectivity of gas storage cylinder to treatment probes.
6
 
Accessories-optional
Needle thermocouple solid state thermometers reading from –200ºC to 40ºC (not available in India).
 
Indications
 
Benign
  • Acne vulgaris (including nodulocystic)
  • Acne scars
  • Angioma (cherry, strawberry hemangioma)
  • Angiokeratoma
  • Chondrodermatitis nodularis helicis
  • Chromomycosis
  • Condyloma acuminata
  • Dermatofibroma
  • Epidermal nevi
  • Folliculitis keloidalis/sycosis nuchae
  • Granuloma annulare (solitary lesions)
  • Granuloma faciale
  • Granuloma pyogenicum
  • Hemangioma
  • Keloids
  • Keratoacanthoma
  • Leishmaniasis (primary cutaneous)
  • Lentigenes
  • Lymphangioma (circumscriptum)
  • Lymphocytoma cutis
  • Molluscum contagiosum
  • Mucocoele
  • Pearly penile papules
  • Perforating dermatoses (Kyrle's, reactive perforating collagenosis, elastosis perforans serpiginosa and perforating folliculitis)
  • Porokeratosis
  • Rosacea and rhinophyma
  • Sarcoidosis (solitary lesions)
  • Seborrhoeic keratosis
  • Solar lentigo
  • Syringoma
  • Trichoepithelioma
    7
  • Venous lakes
  • Verrucae
  • Xanthoma/xanthelasma
 
Premalignant
  • Actinic cheilitis
  • Actinic keratosis
  • Bowenoid papulosis
  • Leukoplakia
 
Malignant
  • Basal cell carcinoma
  • Bowen's disease
  • Kaposi's sarcoma
  • Squamous cell carcinoma (Delimited to skin, Marjolin's ulcer, etc.).
 
CRYOTHERAPY: STEP BY STEP (USING LIQUID NITROGEN)
 
Preparation
The patient is explained the procedure and the necessity to make the site of operation accessible, visible and held steady. The patient is then made comfortable and any anxiety allayed and analgesic, if felt necessary, administered and given time to take effect. The area (field) is cleaned with iodine/alcohol/acetone and draped. Special care is taken to protect surrounding area with insulation, if spray cooling is being used, by sterile gauze pad covered with surgical tape. If cryoprobe is being used, the appropriate sized, sterilized, cryoprobe is selected and layered thinly with petroleum jelly, as is the lesion surface to allow smooth uniform contact.
 
Cooling (Freezing)
Cooling is applied (either by spray or probe) till ice crystals appear on the lesion and for a few millimeters around the probe (or the cooled target area) and this is maintained for 30 to 60 seconds (holding time).8
In case cryoprobes are being used on a benign lesion, the probe will get attached to the lesion after cooling for 5 to 10 seconds. The probe can then gently be raised a few millimeters above the normal skin level and the attached lesion will thus be raised from surrounding normal skin by a few millimeters, delimiting the damage to the surrounding skin on further cooling.
While using the spray cooling on small lesions, the exposure to the spray can be increased by cutting and applying a cardboard or disposable plastic (neoprene) cone of appropriate size and holding it in position. Care must be taken to protect the hand holding the cone from liquid nitrogen droplet spills.
Spray cooling is achieved by keeping the spray nozzle perpendicularly over the target area, about 1 to 2 cm away and moving the nozzle evenly, in a to and fro manner, over the large target to achieve uniform freezing, seen by the appearance of ice-crystals (which can be confirmed by gentle palpation of the iceball).
 
Thawing
The frozen lesion is then allowed to thaw and get back spontaneously to room temperature after holding the freeze for 30 to 60 seconds. The freeze thaw cycle may need to be repeated again, particularly to ensure complete destruction of malignant lesions. The probe or cone that gets attached to the lesion while freezing should be allowed to spontaneously work loose while thawing and must not be pulled away earlier.
 
After Care
The patient is explained that subsequent to the freezing there will be some pain, blistering and peeling, after crust formation, over the lesion in the next couple of weeks. The patient may be prescribed an non-steroidal anti-inflammatory drug (NSAID) medication for a few days after cryosurgery and some mild antibiotic or antiseptic cream to apply daily after a bath/wash. The patient may be asked to come for follow up, weekly, for evaluation of results, assessment of healing and repeat therapy, if necessary. On exposed, trauma prone areas, light sterile gauze dressing in the initial few days, over antiseptic/disinfectant may need to be prescribed till the lesion dries.
9
 
CRYOSURGERY METHODS
Methods
Advantage(s)
Disadvantage(s)
Cryospray:
a. Liquid nitrogen, slush
Rapid cooling, large area treated simultaneously, very low temperatures achieved at point of contact. Low chance of cross infection.
Difficult to ensure uniform cooling of whole lesion, deep lesions not cooled well at depth.
b. Cryoblast5
Ideal for treating thicker lesions of seborrheic keratosis, verrucae, and smaller squamous cell carcinomas. This is done by removing the standard spray tip from the hand held canister. This is used in short 1 to 2 second pulses until freezing is achieved.
Risk of excessive tissue destruction and complications.
Contact cryotherapy:
a. Cryoprobe Liquid nitrogen Nitrous oxide
Efficient cooling, limited to contact area and narrow surrounding rim, depth cooling uniform, lesional area nearly uniform cooled barring temperature gradient at depth.
Large areas need repeated adjoining application, cooling slower and minimum temperaturereached is significantly higher than boiling point of cryogen, chance of spreading infection exists if probe not well sterilized between patients.
b. Dipstick (Liquid nitrogen)
Quick, easy to perform, minimal accessories required, versatile method.
Outcomes variable based on experience of user, not recommended for malignant lesions freeze temperatures high and are affected by ambient temperature.10
Intralesional cryosurgery
Ideal for larger and deeper lesions, such as large keloids.
More invasive procedure. Lesions may bleed profusely in post-
-cryosurgery
Surface complications are less and cure rates
period. Normal skin at the exit point of the needle
may
are higher.
be frozen and destroyed if proper care is not taken.
 
INTRALESIONAL CRYOSURGERY
Various techniques for use of liquid nitrogen described above involve freezing of the lesion from the surface. With these techniques, freezing up to a depth of 1 to 2 cm can be achieved. Moreover, in these procedures, the major brunt of the lethality falls on the surface epithelium. Therefore, for lesions located in dermis and subcutis, these techniques may not always be successful. To overcome this drawback, Weshahy developed a new technique of intralesional cryosurgery.6 He introduced one or more needles into the skin from one end of the lesion, which run through the deeper part of the lesion and surface on the opposite border. Liquid nitrogen is the passed through the needle, which exits through the other end. During its passage through the needle, liquid nitrogen freezes the deeper tissue, with a relatively less destruction on the surface.7
 
Equipments
Assembling the intralesional cryosurgery device requires a small liquid nitrogen Dewar cylinder with spray tip, an intravenous drip-set, an adhesive tape and single use lumbar-puncture (LP) and/or hypodermic needles. The latex rubber tube with its attached plastic tube is removed from the drip-set and one of its narrow parts is cut. It is then connected to the spray tip and fixed tightly with adhesive tape (Fig. 1.3). The tip of the plastic tube fits snugly on to the single use injection or LP needle.
 
Technique
  • Local anesthesia with 2 percent lignocaine
    11
  • The single-use inj./LP needles are inserted both transversely and longitudinally from one end to the other end
  • The distance between adjacent needles is kept between 1.5 and 3 cm
  • The first needle is connected to the modified device and liquid nitrogen is passed through the needle
  • Care should be taken to protect the skin at the entry and exit points of the needles from liquid nitrogen by keeping the bevel end of needle facing upwards and additionally by covering it by plastic/rubber sheet
  • The diameter of ice cylinder is observed at the entry and exit points
  • Freezing is kept on for a period of 10 to 30 seconds depending on the size and nature of the lesion
  • Freezing is done serially in all the needles. After finishing the task in the last needle, the procedure is repeated in all the needles, if required
  • The procedure is safe because freezing up to 30 to 40 seconds does not produce untoward effects like surface ulcerations, however depigmentation is common.
 
Complications of Cryosurgery
  1. Common:
    1. Early: pain, blistering, edema (almost invariable).
    2. Late: hypopigmentation/depigmentation – lesional and peripheral hyperpigmentation are frequent.
  2. Rare: Infection, delayed healing, atrophy, hypertrophic scar, milia, sensory impairment, cicatricial alopecia (in hair bearing areas).
 
Contraindications
Absolute contraindications to cryotherapy are relatively few, and include the following:
  • Cryoglobulinemia
  • Cryofibrinogemia
  • Raynaud's disease
  • Compromised vasculature.
Relative: Dark skinned individuals are more likely to have permanent hypopigmentation/depigmentation.
12
 
Advantages of Cryosurgery over Other Ablative Procedures
  • Safe and simple technique
  • Short duration of freezing/procedure
  • Low cost
  • Repeatable and as outpatient's procedure
  • No admission or hospital stay
  • No anesthesia required
  • Good healing and cosmetic results
  • Few contraindications, can be done on debilitated, old or “poor-risk” patients palliatively
  • Safe in all trimesters of pregnancy
  • Mild non life-threatening complications, if any
  • Minimal special technique/drugs/equipment
  • Easy to acquire skill/learn technique.
 
SPECIAL ISSUES
 
Cryosurgery for Infectious Diseases
Cryosurgery is a useful modality for the treatment of certain infectious diseases of skin, such as condyloma accuminata, verruca vulgaris, molluscum contagiosum, Kaposi's sarcoma, chromoblastomycosis and Leishmaniasis.8 The advantage of cryosurgery is that it is a bloodless procedure, therefore, can be used safely in patients with HIV or hepatitis B infections. Certain modifications have been used for treatment of infectious lesions. Disposable hypodermic needles of various gauges can be used in place of probes. The needle can be attached with to cryoprobe stem with a plastic tube (Fig. 1.3). Otoscope cones may be used to limit lateral spread of the cryogen. Only small, thin lesions of Kaposi's sarcoma on the face, ear, hands, and forearms should be treated with cryosurgery. A cure rate of 80 percent can be achieved, though cosmetic improvement occurs only in 50 percent of the patients.9
Cryosurgery has advantage due to its less invasive nature in molluscum contagiosum. These are common in HIV seropositive patients. These lesions require spraying of liquid nitrogen with a fine needle, for a shorter duration (5 to 10 seconds).
Randomized trials have shown that for external genital warts, cryosurgery is more effective than podophyllin treatment, better than or equal to trichloroacetic acid, but less effective than electrodesiccation or surgical removal.
13
zoom view
Fig. 1.3: Hypodermic needle attached to cryoprobe stem
For common warts, weekly cryotherapy produced more rapid cures, but the overall cure rate depended on number of treatments. Plantar warts require two freeze-thaw cycles of 30 to 60 seconds and paring before freezing to improve the cure rate.10,11 Periungual warts require 10 to 15 seconds freeze using cryospray. A 2 to 3 mm halo surrounding the wart should be achieved in order to bring about the complete eradication of the wart.12 Irreversible matrix destruction can occur with prolonged freezing, which may lead to permanent nail atrophy.13
 
Skin Tags
Multiple skin tags can be easily frozen with a cotton bud or a spray technique, however, care should be taken to avoid freezing the surrounding skin, which may lead to unsightly pigmentary changes.
 
Seborrheic Keratosis
These superficial lesions are easily treatable with a single freeze of 5 to 10 seconds. Bulky lesions of seborrheic keratosis may require more freeze-thaw cycles of 10 to 20 seconds.
 
Acne
Cryotherapy has some role in cystic acne. Individual cysts can be treated with liquid nitrogen spray for 5 to 10 seconds. A small Eschar is formed which dries in about a week.14
 
Keloid and Hypertrophic Scars
Cryosurgery has been used for years in the treatment of keloids. The therapeutic effect of cryosurgery in keloids depends on direct cell damage as well as on changes in the microcirculation. The resulting anoxia causes tissue necrosis and sloughing, followed by tissue flattening. Liquid nitrogen is the suitable cryogen. Freeze time varies depending on the characteristic of the individual lesion. Approximately 1 cm3 lesion requires 10 to 30 seconds freeze. Larger lesions require longer duration freezing and lesions on cosmetically prominent sites should be treated with a shorter duration freezing. Rusciani et al obtained good results in 73.8 percent of the lesions.14 Success rates are even more when cryosurgery is combined with intralesional triamcinolone injections. Many experts use cryofreezing to cause mild tissue edema enabling easier injection of intralesional steroids.15 However, there is a risk of permanent hypopigmentation, especially in patients with darker skin types. Many patients may not return for follow-up cryosurgery because of the post-operative pain, morbidity and slow healing.
 
Basal Cell Carcinoma and Other Non-melanoma Skin Cancers
Cryosurgery is an effective treatment modality for non-melanoma skin cancers. The procedure is done under local anesthesia. Preliminary curettage should be carried out and the lesion is treated with open spray technique using liquid nitrogen.
zoom view
Figs 1.4A and B: (A) Superficial BCC (B) Complete remission with cryosurgery Note: Re-pigmentation taking place from the margins
15
Recommended freezing time ranges from 40 to 90 seconds depending on the size and thickness of the skin cancer. The frozen area should extend at least 3 to 5 mm beyond the margin of the cancer. In most reported studies, the cure rate for non-melanoma skin cancers is more than 90 percent (Figs 1.4A and B).16,17
REFERENCES
  1. Cooper SM, Dawber RPR. The history of cryosurgery. J Royal Soc Med 2001;94:196–201.
  1. Bird H James, Arnott MD (Aberdeen). 1797–1883, a pioneer in refrigeration. Anaesthesia 1949;4:10–7.
  1. Pusey W. The use of carbon dioxide in the treatment of nevi and other skin diseases. JAMA 1907;49:1354–6.
  1. Kuflik EG. Cryosurgery updated. J Am Acad Dermatol 1994;34:925–44.
  1. Callaway SR, Ratz JL. Surgical pearl: cryoblast, a modified cryosurgical technique for thick lesions. J Am Acad Dermatol 2004;51:458–9.
  1. Weshahy AH. Intralesional cryosurgery. A new technique using cryoneedles. J Dermatol Surg Oncol 1993;19:123–6.
  1. Gupta S, Kumar B. Intralesional cryosurgery using lumbar puncture and/or hypodermic needles for large, bulky, recalcitrant keloids. Int J Dermatol 2001;40:349–53.
  1. Graham GF. Cryosurgery: a useful tool in the treatment of selected infectious diseases. Int J Dermatol 1994;33:107–8.
  1. Tappero JW, Berger TG, Kaplan LW, et al. Cryotherapy for Kaposi's sarcoma associated with acquired immune deficiency syndrome (AIDS): a phase II treatment. J Acqu Immu Defic Syndr 1991;4:839–46.
  1. Wetmore SJ. Cryosurgery for common skin lesions. Treatment in family physicians' offices. Can Fam Physician 1999;45:964–74.
  1. Graham GF. Cryosurgery. Clin Plast Surg 1993;20:131–47.
  1. Kuflik EG. Misconception about cryosurgery in warts of the nail unit. Dermatol Surg 2002;28:301–3.
  1. Tosti A, Piraccini BM. Warts of the nail unit: surgical and nonsurgical approaches. Dermatol Surg 2001;27:235–9.
  1. Rusciani L, Rossi G, Bono R. Use of cryotherapy in the treatment of keloids. J Dermatol Surg Oncol 1993;19:529–34.
  1. Kelly AP. Medical and surgical therapies for keloids. Dermatol Ther 2004;17:212–8.
  1. Kuflik EG. Cryosurgery for skin cancer: 30 year experience and cure rates. Dermatol Surg 2004;30:297–300.
  1. Kokoszka A, Scheinfeld N. Evidence-based review of the use of cryosurgery in treatment of basal cell carcinoma. Dermatol Surg 2003;29:566–71.
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FURTHER READING
  1. Ferris Dg, Ho JJ. Cryosurgical equipment: a critical review. J Fam Practice 1992;35:185–93.
  1. Hoffmann NE, Bischof JC. The crybiology of cryosurgical injury. Urology 2002;60(Suppl):40–9.
  1. Jackson AD. Cryosurgery: a guide for GPs. Practitioner 1999;243:131–6.
  1. Kuflik EG. Cryosurgery updated. J Am Acad Dermatol 1994;34:925–44.
  1. Sandison GA. Future directions for cryosurgery computer treatment and planning. Urology 2002;60(Suppl):50–5.
  1. Zouboulis C. Cryosurgery in dermatology. Eur J Dermatol 1998;8:466–74.