Cryosurgery with refrigerant gas as a therapeutic option for the treatment of leukoplakia: a case report Pedro Thalles Bernardo de Carvalho Nogueira, MS ¢ Ozawa Brasil, Jr, MS Antonio Dionízio de Albuquerque Neto, BS ¢ Luciano Leocádio Teixeira Nogueira Filho, BS Bruna Lopes Souza, BS ¢ José Rodrigues Laureano Filho, PhD Leukoplakia is a nondetachable, potentially malignant, alignant lesions of the oral cavity represent 3% of 1 white lesion that is commonly found in smokers of ad- all malignant neoplasms. Like many carcinomas, vanced age. Leukoplakia occurs more frequently in men; squamous cells in the mouth develop from poten- however, there is a higher index of dysplastic changes M tially malignant lesions (PMLs). The correct diagnosis of these and malignant transformation in women. The proposed lesions and their appropriate management are important tar- 1-3 treatments for this disease range from monitoring to gets for cancer prevention. surgical excision. Cryosurgery has been reported as an Leukoplakia is considered a PML, and the diagnosis is alternative to conventional surgery. Cryosurgery destroys essentially clinical. This lesion presents as a white patch that the tissues of a potentially malignant lesion through the is not detachable and is not classified as any other pathologic application of low temperatures. This technique offers condition. Leukoplakia is found in 0.2%-3.6% of the popula- 1-3 a low rate of postsurgical infection, absence of hemor- tion and has a predilection for middle-aged and elderly men. rhage, and ease of application, and it is widely accepted Although leukoplakia occurs more frequently in men, there is a by patients. The most commonly used cryogenic agent, higher index of dysplastic changes and malignant transforma- 3 liquid nitrogen, is costly and difficult to use. The objec- tion in women. tive of this article is to suggest the use of a combination The etiologic agents related to the pathogenesis of leukopla- 1-3 of refrigerant gases (propane and butane), commonly kia include smoking, alcohol, and candidiasis. Other authors employed in pulp sensitivity tests, for cryosurgery of po- have proposed herpes simplex virus and human papillomavi- 2-4 tentially malignant lesions of the oral cavity and to report ruses (HPV-16 and HPV-18) as possible pathogenic sources. a case of leukoplakia treated with this approach. Smokers have a significantly increased risk of leukoplakia. Studies have shown that 80% of these lesions are diagnosed 2-4 Received: November 23, 2015 in patients who smoke. The isolated use of alcohol is not Revised: February 24, 2016 described as an increased risk factor for development of leuko- Accepted: April 11, 2016 plakia; however, consumption of alcohol is well known for a syn- ergistic action with smoking in relation to leukoplakia and oral cancers. A curious fact is that evidence has shown that oral leu- koplakia has a greater probability of malignant transformation in 2-4 nonsmokers than in smokers. The presence of HPV-16 is also 2-4 associated with a higher rate of malignant transformation. The initial treatment of leukoplakia consists of removal of dental irritants, such as dental prostheses, and behavior modi- fications such as cessation of alcohol consumption or smoking. When there is no significant dysplastic change, periodic moni- 2,5 toring can be considered as an option. When histopathologic analysis reveals either moderate or severe dysplasia, complete surgical removal of the lesion is required. This is achieved through conventional excision, electrocauterization, cryosur- 2,5 gery, or laser ablation. Cryosurgery is a therapeutic modality that causes cell destruction by the localized application of low temperatures. The application of refrigerant gases in living tissue causes the Exercise No. 395, p. 65 destruction of the tissue in a few minutes. This mechanism Subject: Oral Medicine, Oral Diagnosis, Oral Pathology (730) is beneficial when used against pathologic tissues. Since it Published with permission of the Academy of General Dentistry. is effective, simple, and easy to apply, this method has been © Copyright 2016 by the Academy of General Dentistry. widely employed in the treatment of skin lesions as well as in All rights reserved. For printed and electronic reprints of this the dental area. There are major advantages in using this tech- article for distribution, please contact [email protected]. nique, such as patient acceptance, absence of transoperative 6-8 hemorrhage, and a low rate of postsurgical infection. www.agd.org/generaldentistry 61 Cryosurgery with refrigerant gas as a therapeutic option for the treatment of leukoplakia: a case report Fig 1. Initial clinical aspect. The white lesion Fig 2. Appearance after the first session of cryosurgery. on the dorsum of the tongue is about 2 cm The area presents hyperemia. in its greatest diameter. Cryosurgery directly affects the tissue due to freezing. Freezing asymptomatic white patch on her tongue. The patient stated causes cell disruption, cellular dehydration, electrolyte distur- that the patch first appeared 2 years ago; the patient’s history bances, enzyme inhibition, and modification of proteins. These did not reveal any comorbidities. The extraoral physical exami- cumulative effects cause irreversible damage to the cellular nation showed no change in the cervical lymph nodes, while metabolism, which leaves the cell vulnerable. This process is the intraoral examination found a white patch on the upper followed by a thawing phase, with a sudden entry of water to surface of the tongue, measuring approximately 2 cm in diam- the cell interior, causing damage to the cell membrane. In addi- eter (Fig 1). Scraping showed the lesion to be nondetachable. tion, the thermal shock of increasing temperatures also causes The patient’s current use of a prosthesis was determined to be a damage to the cell membrane. Gage et al demonstrated—both in possible irritant. vitro and in vivo—that cryosurgery causes necrosis in cells from The incisional biopsy for confirmation of the hypothesis the center of a lesion and that the periphery of the lesion under- that was formulated in view of the clinical findings found, as 9 goes apoptosis approximately 12 hours postfreezing. expected, a layer of hyperparakeratosis and mild epithelial dys- The indirect negative effects of cryosurgery are also important plasia, consistent with a clinical diagnosis of leukoplakia. The to consider. These may be caused by vasoconstriction and vas- proposed treatment for the patient was cryosurgery. cular stasis during cold weather, which, after normalization of After administration of local anesthesia, cryosurgery was the blood flow, may lead to the formation of edema. Side effects performed after both intraoral (chlorhexidine gluconate 0.12%) of cryosurgery may also include cardiac tamponade with conse- and extraoral (chlorhexidine gluconate 2%) antiseptics were quent thrombi, ischemia, and hypoxia, resulting in a change in applied to the surgical area. For patient comfort, an anesthetic 9 cellular pH and eventual cell death. block was initiated at the lingual nerve (mepivacaine 2% with The thawing cycle is as important as the freezing cycle. Both epinephrine 1:100,000). phases have their importance for an effective result of cryosurgery. The cryogenic agent used was a combination of propane and Freezing should happen quickly, while thawing preferably should butane gases (Roeko Endo-Frost, Coltène/Whaledent, Inc). First occur slowly, enabling the creation of a liquid medium that is the lesion area was dried with suction and isolated with gauze favorable to intracellular protein denaturation reactions. Another up to the area of leukoplakia. Endo-Frost was then applied to the factor to be taken into consideration is the repetition of this area through the delivery tube in 2 sessions, using high-powered process. The multiple cycles used during cryosurgery may lead to suction to minimize the gas dispersion in the oral cavity (Fig 2). 9-11 deleterious changes and consequent increased tissue damage. Each session consisted of two 1-minute cycles with an interval The cryogenic agents suggested for the treatment of lesions of 2 minutes between cycles. The second session took place 7 are liquid nitrogen, tetrafluoroethane, hydrofluorocarbons, days after the first (Fig 3). and associations of ethane and butane gases, dimethyl ether– The patient reported pain during the postoperative period, 8,12,13 propane, and propane-butane. These systems are used in which was easily controlled with analgesics. After the healing open or closed forms. period, the area presented with color and appeared normal. This The objective of the present article is to describe a case of result was confirmed by incisional biopsy. The patient’s follow- leukoplakia on the tongue treated through cryosurgery with a up at 1 year posttreatment showed no signs of complications or combination refrigerant gas (propane and butane). recurrence (Fig 4). Case report Discussion A 65-year-old woman presented at the Department of Oral PMLs are characterized by a change in the morphology of and Maxillofacial Surgery, Faculty of Dentistry, University benign tissue and a greater than normal risk of malignant trans- 1 of Pernambuco, Camaragibe, Brazil, complaining about an formation. Examples of PMLs are leukoplakia, erythroplakia 62 GENERAL DENTISTRY November/December 2016 Fig 3. Appearance 7 days postoperatively. Fig 4. Final clinical aspect. At the 1-year post- The tongue is in the process