|Year : 2016 | Volume
| Issue : 4 | Page : 242-247
Advent and implications of cryosurgery in maxillofacial mucosal lesions
Pathumai Murugadoss, Guru Prasad Thulasidoss, Gnanam Andavan, Raja Krishna Kumar
Department of Oral and Maxillofacial Surgery, SRM Dental College, Chennai, Tamil Nadu, India
|Date of Web Publication||13-Dec-2016|
Uvahai Illam, Plot No. 9, 10, Park Town 6th Street, Madurai - 625 017, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Cryosurgery is the application of cold to the diseased tissue and their destruction. It is an economical and safe method used for the treatment of mucosal lesions. It is well tolerated by patients of all age groups. This paper presents a review on the mechanism of cell death following cryosurgery and its implications in oral mucosal lesions.
Keywords: Cryosurgery, Joule-Thomson effect, oral lesions
|How to cite this article:|
Murugadoss P, Thulasidoss GP, Andavan G, Kumar RK. Advent and implications of cryosurgery in maxillofacial mucosal lesions. SRM J Res Dent Sci 2016;7:242-7
|How to cite this URL:|
Murugadoss P, Thulasidoss GP, Andavan G, Kumar RK. Advent and implications of cryosurgery in maxillofacial mucosal lesions. SRM J Res Dent Sci [serial online] 2016 [cited 2022 May 24];7:242-7. Available from: https://www.srmjrds.in/text.asp?2016/7/4/242/195637
| Introduction|| |
Evolution of cryosurgery
The use of very low temperature for the treatment of diseased tissues and cells dates back to the ancient era where Egyptians first used it as a means of obtaining analgesia. ,, Sir James Arnott used salt and ice mixture to treat breast neoplasms and stated that "a very low temperature would arrest every inflammation which is near enough to the surface to be accessible to its influence." ,,,,, Campbell White was the first person to use it for medical purposes in the year 1899.  The liquid carbon dioxide gas or other liquid cryogens that are pressurized in steel cylinders when allowed to escape, cause rapid expansion, fall in temperature, and ice ball formation. This is called as Joule-Thomson effect ,,,, and is the principle behind cryosurgery. The use of liquid nitrogen and nitrous oxide for cryosurgery began in the 19 th century, and Allington was the first person to use liquid nitrogen for treatment purposes.
Cryogens and cryosurgery equipment
Apart from liquid nitrogen, various other cryogens have been introduced in the market  [Table 1], and even combination of cryogens has proven to have an additive curative effect in treating jaw lesions.  Irrespective of the cryogen or its temperature, the mechanism of tissue destruction is via intra- and extra-cellular ice crystal formation, cell dehydration, and cell death [Figure 1] and [Table 2]. ,,,,,,,
Cryogens can be applied via closed method, open method, or the intralesional method. For large superficial cutaneous lesions, the ideal method of application is open spray technique where the nozzle of the spray is placed 1 cm away from the skin surface, and the lesion is destructed using either paint brush technique or spiral technique [Figure 2]. ,,,,, Discrete, small, round lesions and lesions closer to vital structures are destroyed via a closed spray technique, in which cones are used confining the cryogen to the lesion. ,,,, In oral mucosa, the most commonly applied method is either a dip stick method ,,,,,,, or cryoprobe technique. ,,,,, The significance is that both have a surface contact with the lesion treated, with a difference only in the efficiency of the tip to deliver the cryogen [Figure 3] and [Figure 4]. 
Application in maxillofacial mucosal lesions
For about a century, cryosurgery has been tried as a treatment option for various oral lesions irrespective of it being benign, malignant, or premalignant. Various authors have tried cryosurgery in a variety of ways, as single stage application ,, or a multistage application at specific intervals till complete remission ,,,, of the lesion is obtained. Observation and analysis of various available literature suggest that the time of application varies, depending on the cryogen in use, , the lesion treated, and the method of application. Lesser the probe temperature reached by the cryogen, lesser is the time taken for freezing, , and also there is evidence to suggest that probe contact method is more effective than the dipstick method. ,
| Benign Conditions|| |
Evidence-based literature for the use of cryosurgery in the management of mucosal benign lesions is not very uncommon. Melanin pigmentation of gingiva is a common condition that presents itself without discrimination of race, gender, or ethnicity. Apart from lasers and surgery, successful depigmentation of gingiva using cryosurgery has been reported by Yeh,  who treated twenty patients with gingival hyperpigmentation with cotton swabs dipped in liquid nitrogen for 20-30 s. Excellent results were noticed with very good patient acceptance and satisfaction.
Yeh  also studied the effect of such low temperatures on oral melanotic macules. These were situated on the vermilion of the lip causing unsightly appearance and esthetic concern for the patients. He treated 15 patients with liquid nitrogen in a similar manner for 30 s with recovery in 7 days. Repigmentation was noted in 6 patients and was retreated in the same manner to obtain complete remission. Slight erythema of the labial mucosa developed immediately after treatment followed by a white slough which was noticed in 4 days that could be separated from the underlying tissue. No postoperative pain, hemorrhage, infection, or scarring occurred in any of these patients.
Arikan and Gürkan used cryogen 1, 1, 1,2-tetrafluoroethane for melanin pigmentation and found it to be as effective as liquid nitrogen for the treatment of 21 patients. Nineteen patients were smokers with a smoking pattern of hyperpigmentation found on the anterior facial gingiva. The temperature of the cotton applicator ranged from −46.7°C to −48.0°C, and freezing zone was continuously maintained for 30-40 s.  This was in contrary to liquid nitrogen where the temperature and timing of application were much less in comparison. 
Inflammatory papillary hyperplasia
Inflammatory papillary hyperplasia is a condition with constant discomfort for the denture wearers that results from hyperplasia of the palatal and labial mucosal tissues along the denture borders. This poses a difficult scenario for the dentist as well as the patient, and hence, various therapies have been tried till date which includes surgery, ,, CO 2 laser ablation,  cryosurgery, ,, and electrocautery. ,, Cryotherapy is an old technique for treatment of this condition and has provided good results with less recurrence. A cotton applicator soaked in liquid nitrogen was positioned onto the hyperplastic tissue for 12-30 s by Amaral et al.  Complete involution was obtained with two to four treatments done at weekly intervals.
Getter and Perez  used Freon, a liquid cryogen for 45 s over the hyperplastic tissue at a temperature of −50°C to −60°C. Multiple visits were required to treat the entire hyperplastic tissue. According to him, cryosurgery was better than electrocautery in producing minimum patient discomfort and no offensive odor.
Bekke and Baart  treated six patients with cryoprobe and found recurrence only in one patient in a follow-up of 33 months. He treated patients by both single and multiple stages depending on the need. Borges et al.  in 2014, reported that of the nine inflammatory papillary hyperplasia cases he treated, three were not responsive to liquid nitrogen cryoprobe thus suggesting the need to have a protocol to treat these. Two 60 s treatment applications were performed, and thawing was allowed to proceed for 2 min. He reported that cryosurgery is an effective therapy only for up to 12 mm long pedunculated hyperplasia.  The simplicity of treatment, relative painlessness, and absence of bleeding are the only advantages over other types of treatment. The efficacy of cryosurgery for those lesions more than 12 mm is still a question.
Narula and Malik  in his study treated three pyogenic granulomas and one fibroma using nitrous oxide closed system to achieve a probe temperature of −70°. Freezing for 2 min followed by thawing for 4 min was done. Two sessions were required for each lesion for their complete regression. Cryosurgery provided a bloodless field with minimal scar formation in comparison with conventional surgical therapy for both the lesions.
Mucous retention cysts
Ranula and mucoceles of the oral cavity can be treated by excision, , CO 2 lasers, , cryosurgery,  electrosurgery,  injecting steroid solution,  sclerosants,  photoelectron radiation,  and marsupialization. Those treated with cryosurgery have yielded satisfactory results. Treatment with cryosurgery resulted in complete resolution of the mucous retention cysts in just a few visits and required freezing cycles of few seconds duration only. Eighteen patients with mucoceles of lower lip and tip of the tongue were treated via dipstick cryosurgery in two visits by Toida et al.  He applied a freezing time of 10-30 s/cycle and thawing period were double the freezing time applied. Only after complete thawing, the next freezing was applied. All lesions disappeared completely in 2-4 weeks' time without scarring.
Similarly, Yeh  treated 33 patients with mucocele by dipstick method for 30-50 s. The secondary application was attempted only if a residual lesion remained in 2-week time. There were recurrences in two patients with a rate of 5.6% which were also treated with cryosurgery to achieve complete resolution. All patients healed by secondary intention.
Manu Prasad et al.  treated twenty mucoceles with this method by freezing for 30 s and thawing for 1 min following it. His study provided complete resolution without any discomfort nor recurrence.  Safety with this modality of treatment is so high that it has been even tried out for mucoceles in babies. A 4-month-old infant was treated for ranula, and a 3-month-old infant was treated for mucocele without any complication. Although various options such as micromarsupialization and surgery are available for pediatric ranulas, the author chose this due to less morbidity.
Hemangiomas have been mostly treated via an open cryosurgery method in the past which eliminated the use of a more sophisticated apparatus. Cryosurgery brings complete regression of cavernous hemangiomas in two freeze-thaw cycles 1½ min each as reported by Leopard.  Nitrous oxide (−89°C), delivered by a unique nitrous oxide cryosurgical apparatus, was used by Gongloff et al. to deliver the freeze cycle for 127 s in comparison to nitrogen system (60 s) due to the temperature difference. Ten patients treated with nitrous oxide cryosurgery showed minimal blood loss and discomfort. Functional impairment or disfigurement described with conventional methods of surgical excision were not noticed.  Yeh treated hemangiomas with cotton swab nitrogen system for 60-70 s in 2-4 consecutive treatments and found no recurrence. 
Karasu  used liquid nitrogen via large contact tip on a single tongue lesion for 60 s and applied it at a rate of two times per area and achieved complete resolution. Cryosurgery has proven itself to be a good alternative to sclerotherapy, laser application, and intralesional steroid therapy owing to less bleeding tendency, infection rate, minimal scarring, and less morbidity. This has encouraged its use even in infants.
| Premalignant States|| |
Leukoplakia is the most common oral potentially malignant disorders. Axell, in 1996, described it as a predominantly white lesion of the oral mucosa that cannot be characterized as any other definable lesions. From times, various treatments have been tried for leukoplakia. The initial treatment for leukoplakia using cryosurgery dates back to 1970 when it was used by Leopard.  He used two freeze-thaw cycles of up to 1½ min and treated 40 patients of which two failed to respond. In the same decade, Sako et al. gave the recurrence rate of cryosurgery on leukoplakia as 20%.  About the same time, Poswillo stressed on the usage of delineating the leukoplakic patches with toluidine blue dye before the application of cryo to give a proper freeze-thaw cycle for the entire patch region without bypassing any. 
Cryosurgery for oral leukoplakia is a promising modality even today. From the usage of an open system for treatment, the transition has shifted to the use of cryoguns for cryotherapy. Although this needs more sophisticated apparatus, the results are far better in terms of treatment outcome as highlighted by Yu et al. ,, Complete regression was achieved in all 54 patients with 60 lesions treated with cryogen cryotherapy and only a few appointments (mean 3.1) were needed for complete eradication of the lesion in comparison to cotton swab cryotherapy done for 60 lesions (mean 6.3). The lesions were sprayed with liquid nitrogen for 7-10 s and allowed to thaw for 20 s. They treated patients once in every 2 weeks till the achievement of complete regression. They stated that the cotton swab carries only a small amount of liquid nitrogen that cannot maintain a constant low temperature in the treated oral leukoplakia lesional tissues and thus is less effective and more treatment cycles are needed to achieve results.
In the modern age, Narula and Malik  treated ten patients with leukoplakia using nitrous oxide system. He treated all lesions in of 1½ min freeze and 3 min thaw. Depending on the size of the lesion, the number of sessions required range from two to three.
Lichen planus is a premalignant condition that has both cutaneous and mucous manifestation. Oral lichen planus (OLP) presents itself with bilateral white striae, papules, or plaques that may be present in buccal mucosa, tongue, or gingiva. They have been treated using topical steroids, lasers, antifungal mouthwashes, surgical excision, and cryosurgery.
Narula and Malik  treated ten patients with cryosurgery using nitrous oxide system by applying two freeze-thaw cycles each area. Freezing time was 1½ min followed by a 3 min thaw. The number of sessions required depended on the size of the lesion. Two of his patients came with recurrence. He hence suggested that cryosurgery is a good treatment option if not for complete cure it is palliative for lichen planus. Amanat et al.  compared the treatment of cryosurgery and steroids for thirty patients with bilateral OLP lesions. From each patient, a lesion on one side was chosen randomly for a single session of cryotherapy with nitrous oxide gas and the lesion on the other side received triamcinolone acetonide 0.1% ointment in orabase. At the end of the treatment, they noted that cryosurgery with nitrous oxide gas was as effective as steroid application. However, in patients with overlying systemic conditions that contraindicate the usage of steroids, cryosurgery is the best treatment option. Another added advantage is that no supra added infections such as candidiasis occur with cryosurgery.
| Malignancy|| |
Various case reports have been published with the successful usage of cryogens on initial stages of oral carcinomas, but they are only a part of the history now. There are no recent works of cryo on oral carcinomas as a treatment option. However, it is used as a palliative treatment option in various parts of the world. Hausamen treated 16 patients with oral squamous cell carcinoma and stated that cryosurgery can only be used for locally extensive superficial lesions but is not suitable for deep infiltrating carcinomas. 
| Sequelae Following Application|| |
Irrespective of the type, size, site of the lesion, or the time of freeze cycle, the healing is the same and occurs by secondary intention.  Immediately following application, there are hyperemia and swelling of the area in contact with the probe.  Very rarely, a vesicle may form immediately after the procedure in an hour's time and ruptures the next day.
In 3-4 days' time, there is necrotic slough formation that peels off from the underlying surface. The reepithelialization takes a due course of 4-5 weeks to revert to its normal state. ,,, During the course of healing, minimal inflammation is evident, but patients generally complain of increase in pain between 1 st and 3 rd week which subsides completely by the 5 th week.
| Advantages and Limitations|| |
Apart from the advantages discussed above, cryosurgery can be used in very apprehensive patients in an outpatient basis. It is not a very technique sensitive procedure making even a less skilled person to use it confidently and is also economical. Very rarely, complications such as blister formation, hypopigmentation,  and hyperpigmentation do occur, but nothing leads to severe debilitating states. However, they do have certain limitations. Their use in the presence of cold sensitive conditions such as cryoglobulinemia,  cold intolerance,  cold urticaria,  cryofibrinogenemia,  dysfibrinogenemia,  and Raynaud's phenomenon , is absolutely contraindicated.
| Conclusion|| |
Cryosurgery has been in use for a long time for treatment of various soft and hard tissue lesions. Cryosurgery can thus be considered a promising modality in treating oral mucosal lesions with less morbidity. The minimal discomfort in handling the apparatus and a longer healing time  can definitely be overlooked considering its benefits.
Cryosurgery with its ability to produce very low temperatures causes effective tissue destruction. It has been utilized for oral cavity lesions of the infants, elderly patients and also immunocompromised patients. With a wide variety of cryogens that have come in the market and by combining these cryogens, better treatment protocols and freezing times have been established, producing excellent results.
We would like to acknowledge the Department of Oral and Maxillofacial Surgery, SRM Dental College, and Department of Oral Pathology, SRM Dental College.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2]