Cryosurgery in the treatment of oro-facial lesionspain. This clinical application of cryosurgery is known as.[8] Cryoneurotomy is also used for the treatment of intractable neurogenic

Indian Journal of Dental Research, 23(2), 2012

review article

Cryosurgery in the treatment of oro-facial lesions

Ashok Bansal, Shivani Jain, Shipra Gupta1

Received : 01-01-11Review completed : 22-04-11Accepted : 27-09-11

ABSTRACTCryosurgery is a therapeutical method that uses freezing to obtain a tissue inflammatory and/or a destructive response. It has been successfully used for many cutaneous conditions. Its use is increasing for several conditions in the oral cavity. The oral mucosa, because of its characteristics of humidity and smoothness, is an ideal site for this technique. It shows a very good esthetic result and it may be either the first choice or an alternative option to conventional surgery. This article strives to review the modus operandi of cryosurgical instruments, the various indications, limitations and advantages of cryosurgery in the treatment of oral lesions.

Key words: Cryoanalgesia, cryosurgery, freezing, leukoplakia, mucus cysts, oral lesions, thawing

Departments of Oral and Maxillofacial Surgery, Swami Devi Dyal Hospital and Dental College, Barwala, 1Periodontics, Dr. H. S. Judge Institute of Dental Sciences and Hospital, Panjab University, Sector 25, Chandigarh, India

Virtually all biological tissues subjected to a temperature of −20°C or below for a minute or more undergo cryogenic congelation or necrosis.[6] Oral lesions being both warm and moist are ideally suited to this technical procedure.[5,7] It is extremely easy to attack oral lesions repeatedly with the cryoprobe, with only little preliminary preparation of either patient or operative field. Tissues close to the probe freeze quickly, but ice is an efficient insulator, so advance freezing proceeds only slowly. As ice delays the spread of freezing, it reduces the chance of accidental damage to the underlying tissues. Because of the gradient of heat loss, neighboring tissues are unharmed.[5]

In cryosurgery, nothing is excised; rather, the lesion is frozen and the resultant necrotic tissue is allowed to slough spontaneously. Tissue death results from a combination of direct cellular effects, such as formation of ice crystals, cellular dehydration, protein denaturation and disruption of cell membranes and from ischemic infarction resulting from failure of microcirculation. Vascular stasis enhances the direct lethal effect.[5]

Cryosurgery could be used to produce an extended, but reversible, nerve block in the management of intractable facial pain. This clinical application of cryosurgery is known as.[8] Cryoneurotomy is also used for the treatment of intractable neurogenic pain in the temporomandibular joint (TMJ).[9] Cryotherapy is highly regarded in the treatment of localized intraoral tumors overlying bone. After treatment, the tumor is sloughed, exposing the underlying bone. No ill effects result from this exposure even though months pass before the bone is covered by soft tissue again. So, primary tumors of bone might be treated by freezing, without excision or amputation.[10]

Cryosurgery has been recommended as a mode of treatment for a variety of benign and dysplastic intraoral lesions.

Address for correspondence: Dr. Shipra Gupta E-mail: [email protected]

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DOI: 10.4103/0970-9290.100468

The satisfactory removal of diseased or malformed tissues by the surgeon has depended largely upon increasingly sophisticated and complex techniques utilizing the simplest of instruments, the knife.

From time to time, various other methods of tissue destruction have been employed, chemicals, irradiation by X-rays and high-frequency electric current being a few of them. Ideally, any technique in competition with the surgeon’s scalpel should be painless, produce minimal damage to the surrounding tissues, be selective against, for example, malignant cells, be localized and readily controllable and promote rapid and uneventful healing.

According to Arnott,[1-3] low temperatures could be used to destroy cancerous growths. Cryosurgery is a method of local destruction of tissues by freezing in situ “Cryosurgery” is derived from the Greek word “Kryos,” that is, frost, thus literally meaning frost surgery.[4] The local application of low temperature was probably first used as a means of analgesia by the ancient Egyptians.[5] This property of freezing was also exploited for the amputation of limbs during the Franco-Prussian Wars.[5]

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Cryosurgery: A review Bansal, et al.

Healing is usually excellent and the mucosa largely returns to normal by 6 days after treatment.[4]

BRIEF HISTORY OF CRYOSURGERY

The Egyptians were the first to use cold for trauma and inflammation. Since the days of Hippocrates, man has known the therapeutic effects of sub-zero temperatures for the treatment of sprains, the reduction of swelling, the alleviation of pain at operation in per-anesthetic tomes, plus other medical disorders. In the 17th century, Robert Boyle found that cells could be killed by freezing.[11] In the last century, Baron Lorrey observed its utility in anesthesia and sedation for amputation in soldiers.[2,3] In 1977, John Hunter noted that after freezing there was local tissue necrosis and vascular stasis, and that excellent healing of the tissues resulted.[12]

In 1845, James Arnott[1] was the first to report on therapeutic use of low temperatures in malignant disease by means of a salt/ice mixture applied to breast neoplasms. He used it for neuralgia and as a palliative for terminal cancer patients.[2,3]

On Christmas eve, in 1877, Louis Cailletet and Raul Pictet presented experimental papers on the liquefaction of oxygen and carbon monoxide, to the French Academy of Sciences and this historic occasion is regarded by Zacarian[5] as the birth of modern cryogenics. Dewar manufactured vacuum containers for cryogens. White is considered the first cryosurgeon to have used freezing for warts, nevus, precancerous lesions and carcinoma.[2] In the beginning of our century, Whitehouse developed the spray technique, and Zacharian and Torres, in the 60s, developed liquid nitrogen spray equipments for various lesions, including neoplasms.[2,3,13]

From an oral surgery standpoint, cryosurgery began to be seriously considered in early 1960s. Amaral et al.[14] used liquid nitrogen on swabs to treat cases of palatal inflammatory papillary hyperplasia. Mac Donald et al. in 1981 recommended cryosurgery for the treatment of angiomas, hyperplasias of palate, leukoplakia and lichen planus.[15] Barnard in 1981 showed that cryotherapy produces an extended and reversible nerve block in the management of chronic pain and postoperative pain. He emphasized that cryoanalgesia offers advantages over other methods of long-term nerve block or neurectomy and may result in prolonged relief in some patients.[12] Goss in 1988 used cryoneurotomy for the treatment of patients with intractable neuralgic pain in the pre-auricular region.[9]

MECHANISM OF TISSUE DEATH (BIOLOGICAL MECHANISMS OF CRYONECROSIS)

There are various distinct mechanisms by which tissues may be damaged by freezing. These mechanisms co-exist at the time of

a single cryosurgical treatment, and since the preponderance of each varies according to the apparatus used, the physical nature of the tissues being treated, the distance from the cryoprobe, and the rate and degree of cooling, an understanding of these mechanisms enables one to vary the technique according to the nature, site, size and depth of the lesion to be treated.[2] Cold sensitivity varies. Melanocytes are the most susceptible cells, followed by basal cells, keratinocytes, bacteria, connective tissue, axon myelin sheath and virus.[16]

Factors associated with cryodestruction are as follows.[16,17]

Direct effectsIce crystal formation or cellular disruptionWhen the rate of freezing is rapid (greater than 5°C per second), particularly in the immediate vicinity of the probe tip where the cooling rate approaches −70°C per second, ice crystals form in both extracellular and intracellular fluid.[1] The more rapid the cooling rate, the larger the ice crystals formed, and incidentally the greater the degree of adhesion of the tissues to the probe. Large ice crystals produce physical disruption of cell membranes.

Cellular dehydration and electrolyte disruptionWithin the outer zone of ice ball where the temperature is about −10°C, the cooling rate approximates to −1/2°C per second. At such a rate, freezing occurs in the extracellular space only, the cell membranes acting as a barrier to the propagation of ice crystals. This slower freezing captures extracellular water molecules, so that ionic concentration of electrolytes in the extracellular space increases. Intracellular water then passes out of the cells, but in turn becomes trapped in the propagating ice front. The cells thus become dehydrated and undergo physical shrinkage. Moreover, the concentration of electrolytes both inside and outside the cell membranes increases to levels which become irreversibly toxic to cellular function.

Thermal shockIt most likely relates to cell membrane damage caused by rapid freezing rates which in the systems described can be of the order of 1000°C/minute.

Inhibition of enzymesAs each cellular enzyme system operates optimally over a narrow temperature range, sudden cooling acts as an inhibitor. This renders the cells more vulnerable to the metabolic disturbances.

Protein changesLipoprotein complexes in both the cell membranes and mitochondria are denatured by the profound fall in temperature, with consequent damage to cellular metabolism.

The effects of thawingWhen the freezing process stops and the tissues are allowed to rewarm, further damaging effects may take place. If the





intracellular water was supercooled, then on thawing, ice crystals form leading to damage from crystallization. Also, because of raised concentrations of intracellular electrolytes, there is water intake in the cells, which then vacuolate, swell and rupture.[3] A slow thaw prolongs the duration of these damaging effects.

Indirect effectsVascular effectsIschemic necrosis produced by vascular stasis and microthrombus formation is a significant part of the cryodestructive process.[18] Large vessels continue to function, although with increased permeability.

Immunological effectsThese may add to the destruction of a lesion treated by cryosurgery. Such an effect could be due to a massive release of pathological cell antigens and/or changes to the antigenic nature of the frozen and thawed cells, thus making them susceptible to host surveillance mechanisms.

INSTRUMENTATION

The application of cryotherapy to the mouth requires equipment that has the following capabilities:• The cold source (which is really a means of extracting

heat – a heat sink) must be small and sufficiently maneuverable to reach the various parts of the mouth.

• It must be controllable to the extent that selected areas can be frozen without damaging the nearby structures.

• Should maintain the required temperature for as long as required.

• Temperature of the cold source should be variable.• Rate of thawing should be controllable.• Should be fitted with a thermocouple so that temperature

at the tissue surface can be easily read by the surgeon.• Most commonly used cryogens are liquid nitrogen

(−191°C), nitrous oxide (−81°C) and carbon-di-oxide (−79°C).[19]

The available apparatus may be classified into the following:a. Open systems: These involve direct application of

carbon dioxide snow (−79°C) or liquid nitrogen (−196°C) by cotton pledgets or as an open spray. The drop in temperature is profound as the latent heat of vaporization is extracted from the tissues. These are used where control of the depth of destruction is of secondary importance.

b. Closed systems: These offer a greater degree of control but instrumentation is more complex, the depth of freezing being in general less profound than with open systems. These are of different types based on one of the three main principles: [5]

• Thermoelectric• Evaporative

• Joule–Thompson, for example, Ascon cryoprobes (cryopencils)

Variables in cryosurgical techniqueThe variables under the control of the operator are as follows:

The type of apparatusFor most superficial oro-facial lesions, contact probes operating on the Joule–Thompson or evaporative principles are most satisfactory. For hypertrophic, papilliferous or invasive lesions, liquid nitrogen sprays may be preferred since it may be difficult to obtain uniform contact with a probe. Armamentarium used in cryosurgery is depicted in Figures 1 and 2.

The temperature achievedMost effective temperature changes are achieved by selecting a large probe by repeating the freeze–thaw cycle and by ensuring an intimate probe–tissue contact.

The rate of coolingThis is the single most important factor in efficient cryonecrosis. Below −30°C per second, it has been shown that tumor destruction is more efficient with rapid cooling rates, probably because cell damage by intracellular ice crystallization is more lethal than damage by dehydration and electrolyte disturbance.[4,5]

The duration and repetition of freezingMost mucosal leukoplakias respond to two freeze–thaw cycles of 45–60 seconds each. Large cavernous hemangiomas are usually frozen twice for 1–1½ minutes for each freeze, and basal cell carcinoma with raised beaded margins usually responds to two applications (at the same intervention) of about 1½ minutes. Invasive neoplastic tissues require three freeze–thaw cycles, each of 2½–3 minutes duration. During repeated freezing and thawing, tissues are frozen at successively more rapid rates so that each zone is subjected to more than one mechanism of damage.

The re-warming phaseAs actively damaging events take place during the thawing of frozen tissues, a slow thaw is more effective than a rapid thaw.

The volume of tissue treatedThis may be increased by firmly pressing the probe to invaginate the surface before freezing commences or decreased by applying traction on the probe as soon it has adhered to the surface.

Other ancillary measuresThe freezing effect may be enhanced by reducing the blood supply to the part by prior injection of vasoconstrictor agents, digital compression of afferent vessels, etc.





SCOPE OF CRYOSURGERY IN DENTISTRY

Cryosurgery and oro-facial lesions[13,20,21]

Vascular malformationsCavernous hemangioma: Cryosurgery produces complete regression of these malformations, whether of skin or of mucosa, with minimal scarring. Two freeze–thaw cycles of 1½ minutes each are usually sufficient. The nevi are emptied by compression with the probe before and during treatment. Cryosurgery is very effective in cases of strawberry nevi where there is lot of bleeding, ulceration or overwhelming parental demands.

Capillary nevi respond to cryosurgery.[22] The most satisfactory technique is to freeze the entire nevus site by site for 2–3 seconds only. A second freeze is applied for approximately 10 seconds. By restricting the duration of freezing, scarring is avoided.

Lymphangiomas, especially those with moderate fibrous element, are less responsive to cryosurgery. A combined excisional and cryosurgical approach is sometimes useful.

Hyperkeratosis and leukoplakiaWide excision may be difficult in areas such as tongue, lips and commissures, and there is always the possibility of further changes developing in adjacent areas. Cryosurgery is a simple and effective means for fissured or granular types of leukoplakia and also for thick plaques as well as in cases in which candida are found. Following biopsies, each area is given two freeze–thaw cycles of up to 1½ minutes depending on the site and thickness of the lesion. Thick irregular plaques are planed with a surgical blade and the area is moistened with saline prior to freezing. In extensive or multifocal leukoplakia, the toluidine blue test helps to establish the priority of one area over another.[5] Figures 3 and 4 show one such case of leukoplakia being treated with cryosurgery.

Granulomatous and hyperplastic conditionsCryosurgery is a satisfactory alternative to excision or cautery for the treatment of papillary hyperplasia of the palate, fibrous epulis, fibroepithelial polyps, myeloid epulides and viral warts.[5,20]

Hyperplastic conditionsDenture hyperplasia: In the lower labial sulcus, hyperplastic folds may be multiple and relatively broad based. Simple excision in these cases leads to loss of sulcus depth, which may necessitate more radical approach to the problem, such as vestibuloplasty. In the elderly and debilitated, cryosurgery may be used. Necrosis of the hyperplastic tissue may be achieved with minimal alteration of sulcus depth.[5]

Mucus cysts and polypsMucus retention cysts respond to cryosurgery without recurrence and detectable scarring and are better accepted by children. Toida M, Ishimaru JI, and Hobo N treated 12

female and 6 male patients with mucus cysts on the lower lip and the tip of the tongue, by direct application of liquid nitrogen with a cotton swab. Each lesion was exposed to four or five cycles composed of freezing of 10–30 seconds and thawing of double the freezing time. No anesthesia was required. All lesions had disappeared completely 2–4 weeks after one or two treatment courses of cryosurgery. In all cases, neither scarring nor recurrence was noted during the 6 months to 5 years of follow-up. [23] Figures 5 and 6 show one such mucocele being treated with cryosurgery.

Antral polyps commonly form in relation to oro-antral fistulae where they impair antral drainage and may also be troublesome in antral fenestration cavities in relation to obturators. They respond readily to cryosurgery, permitting improved antral toilet pending either closure of the fistulae or adjustment of the obturator.

Erosive conditionsA few cases of longstanding erosive lichen planus have been successfully treated with cryosurgery.

Cryosurgery and intractable facial painLloyd et al.[24] reported the use of cryoanalgesia in various forms of chronic facial pain. A reliable, prolonged, reversible nerve block is achieved by a simple technique which does not appear to aggravate symptoms. Postoperative pain is minimal following cryosurgery. More significant is the return of normal sensation in the distribution of peripheral nerves which have become incidentally incorporated in the cryolesion. Bradley et al. reported the return of sensory function of the inferior alveolar nerve over 3–6 months following cryosurgery.[10]

Cryosurgery and intractable temporomandibular joint painAN Goss used cryoneurotomy to the TMJ capsule and/or great auricular nerve. The patients had severe pain complicated by failed previous treatment, analgesic abuse or psychiatric problems. The patients had excellent pain relief for 1 year following cyroneurotomy.[9]

Cryosurgery and oral cancerIn established oral carcinoma, cryosurgery is at best a means of localized tissue destruction in superficial accessible lesions. Its use has been mainly confined to recurrent or persistent growths following surgery and/or radiotherapy. According to Holden, cryosurgery is the treatment of choice in recurrent nasopharyngeal carcinoma.[25] It should not be the primary treatment of oral cancer except in very early lesions of anterior part of palate and in patients who are considered unfit for other forms of treatment.[26]

Cryosurgery and basal cell carcinomaAlthough surgical excision and radiotherapy are well tried and carry a good prognosis, in certain circumstances, there is danger to surrounding structures, for example, rodent





Figure 5: Mucus retention cysts in the lower lip Figure 6: Frozen appearance of the cyst after cryosurgery

Figure 3: Leukoplakia lesion at the angle of mouth being treated using cryoprobe Figure 4: Frozen appearance of lesion after cryosurgery

Figure 2: Armamentarium: Cryogun

Figure 1: Armamentarium: Cryosurgery using liquid nitrogen

ulcers at the inner canthus. Similarly, in cases where there are multiple lesions, cryosurgery is a sound alternative to surgery and radiotherapy provided the tumor has not invaded deeper structures.

Cryosurgery and herpetic or aphthous ulcersUsed for their eradication, presumably by conversion of a specific ulceration to a non-specific “traumatic” ulcer which is expected to heal more rapidly.





Chin-Jyh Yeh performed cryosurgical treatment for 92 patients who had 102 benign oral lesions. The procedure was performed by direct application of liquid nitrogen to the lesion using a cotton swab on an outpatient basis. This treatment required no sophisticated equipment and gave very satisfactory results. There was no intra- or postoperative bleeding, no surgical defects, minimal scarring, and no infection following treatment.[27]

ADVANTAGES OF CRYOSURGERY

• Minimal general disturbance to the patient, particularly well accepted by the elderly.

• Low complication rate.• Reasonably predictable volume of tissue destruction.

Particularly suited to extensive superficial lesions.• Treatment may be repeated as often as necessary

without increase in scarring. This is particularly important in facial skin and in anatomical sulci.

• Of great value in the treatment of wide areas of premalignant change.

• May be used as an adjunct to surgery and/or radiotherapy in palliative tumor control.

• Cryosurgery is a very safe, easy to perform, and relatively inexpensive technique for treating various oral lesions in an out-patient clinic.[7]

PROBLEMS, LIMITATIONS AND COMPLICATIONS ASSOCIATED WITH CRYOSURGERY OF ORAL TISSUES

• Difficulty in judging the extent of the cryolesion can lead to involvement of an inadequate amount of tissue, resulting in persistence of the pathologically changed epithelium and re-establishment of the lesion. So, one should be quite certain that normal tissues beyond the margins of the lesion are adequately frozen.[28]

• Volume of the lesion might be beyond the freezing capacity of the available instrument so that arrangements for repeated cryosurgery procedures or an alternative method of treatment need to be made.[28]

• Healing of cryosurgery wounds occurs slowly. However, they should be closely observed to overcome the possibility of slow healing being related to the persistence of a lesion, particularly if neoplastic. Slow healing and associated inflammatory lymphadenopathy can mask and mimic malignant involvement of cervical lymph nodes.[29]

• Cryosurgery of tongue can produce swellings that might severely interfere with swallowing and sometimes respiration.

• Extensive cryosurgery procedures may produce considerable scarring. Following healing by secondary intention, loss of normal anatomy can lead to limitation of mouth opening, speech disturbances and prosthetic problems.

• Following extensive cryosurgery as in the case of widespread keratoses, severe pain can be troublesome and narcotic analgesics may be required.

• If a biopsy is not taken prior to cryosurgery, the true nature of the lesion may not be ascertained.

• Cryosurgery is non-specific in its destructive effects.[5] Because of the flow rate in larger arteries, it is virtually impossible to freeze these structures using surface contact probes.

COMPLICATIONS

• After pain• Vesicle formation• Exposure of bone if probe applied to areas with thin

mucoperiosteal surfaces such as mucosa over lingual aspect of mandible. Although healing may be delayed in such cases, the devitalized exposed bone remains unaffected and pain free, until sequestration and/or resorption have occurred, and the area is covered by mucosa again.

• Scarring of facial skin if freezing is done for longer than 20–30 seconds. Healing occurs with reduction in pigmentation in such cases. However, after a few months, it may be difficult to detect.

• Peripheral nerve fibers may be painful following moderate freezing of adjacent structures, possibly due to the action of cellular breakdown products. More profound freezing causes Wallerian degeneration which is followed by regeneration, as the nerve sheath architecture remains intact. This is also the reason for reduced sensation following cryosurgery.

• The la te compl icat ions are appearance of pseudoepitheliomatous hyperplasia, post-surgical infection, fever, and pyogenic granuloma. There are also some permanent complications such as hypopigmentation, atrophy, alopecia and ectropion, when performed near the eyes.[30-32]

There are some contraindications such as cold intolerance, cold urticaria, cryoglobulinemia, agammaglobulinemia, dysfibrinogenemia, Raynaud’s and collagen diseases, pyoderma gangrenosum, patients undergoing hemodialysis or immunosuppressive therapy, patients with platelet alterations or with multiple myeloma.[21,33]

CONCLUSION

Cryosurgery is a very safe, easy to perform, and relatively inexpensive technique for treating various oral lesions in an out-patient clinic. It is an atraumatic form of therapy in comparison to conventional surgery. Liquid nitrogen spray or cryoprobe have been used alone or associated with other surgical methods in various types of oral lesions such as pyogenic granuloma, angioma, actinic cheilitis, keratoacantoma, fibroma, human papillomavirus (HPV)





lesions in HIV and non-HIV patients, hypertrophic lichen planus, leukoplakia and erythroplakia, verrucous carcinoma, mucus cysts, and papillary hyperplasia of the palate, among others, with resultant good patient acceptance. We can expect a considerable increase in the use of cryotherapy in oral surgery, along with a much better understanding of the basic principles and techniques related to this form of treatment.

REFERENCES

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3. Shepherd J, Dawber RP. The historical and scientific basis of cryosurgery. Clin Exp Dermatol 1982;7:321-8.

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9. Goss AN. Cryoneurotomy for intractable TMJ pain. Br J Oral and Maxillofac Surg 1988;26:26-31.

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32. Faber WR. Side effects and complications in cryosurgery. Dermatol Monatsschr 1993;179:247-51.


How to cite this article: Bansal A, Jain S, Gupta S. Cryosurgery in the treatment of oro-facial lesions. Indian J Dent Res 2012;23:297.Source of Support: Nil, Conflict of Interest: None declared.



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Cryosurgery in the treatment of oro-facial lesionspain. This clinical application of cryosurgery is known as.[8] Cryoneurotomy is also used for the treatment of intractable neurogenic