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Journal of Cranio-Maxillo-Facial Surgery xxx (2013) 1e5

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Journal of Cranio-Maxillo-Facial Surgery

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Management of locally aggressive mandibular tumours using a gascombination cryosurgery

José Thiers Carneiro a,b, Aline Semblano Carreira Falcão a,b,c,*, Ana Karla da Silva Tabosa a,b,Elio Hitoshi Shinohara a,b,d, Lucas Machado de Menezes a,b

aDepartment of Dentistry (Head: PhD, Fabrício Mesquita Tuji), Ophir Loyola Hospital, Belém, PA, BrazilbAvenida Governador Magalhães Barata (Head: PhD, Fabrício Mesquita Tuji), 992, Belém, PA 66063-240, Brazilc School of Dentistry, Federal University of Pará-UFPA, Belém, PA, BrazildAlbert Einstein Hospital, São Paulo, SP, Brazil

a r t i c l e i n f o

Article history:Paper received 5 February 2012Accepted 21 May 2013

Keywords:CryosurgeryCryotherapyJaw neoplasms

* Corresponding author. Universidade Federal do PSaúde, Faculdade de Odontologia, Avenida Augusto CoBrazil. Tel./fax: þ55 91 32017563.

E-mail address: alinecarreira@hotmail.com (A.S.C.

1010-5182/$ e see front matter � 2013 European Asshttp://dx.doi.org/10.1016/j.jcms.2013.05.033

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a b s t r a c t

This study evaluated the results of curettage followed by cryosurgery using a combination of propane,butane, and isobutane gas for several benign but locally aggressive bone tumours on the mandible.Twenty-nine patients (16 men and 13 women) participated in the study. Patient ages ranged from 6 to 87years (mean, 23.72 years). Before enucleation and cryosurgery, some patients received prior treatmentconsisting of marsupialisation to decrease tumour size. Twenty-seven of the 29 patients (93.10%) showedno evidence of clinical or radiographic recurrence after treatment through enucleation and cryosurgery.Wound dehiscence, which was observed in all cases, healed by second intention. The average follow-upperiod was 70.55 months (range, 53e120 months). These results suggest that enucleation followed bycryosurgery is an effective therapy for managing locally aggressive mandible tumours. In addition, thistreatment is a less expensive intervention than more radical procedures.

� 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rightsreserved.

1. Introduction

Ameloblastoma, myxoma, keratocystic odontogenic tumour,central giant cell lesions, and fibro-osseous lesions are benign yetaggressive and locally recurrent lesions that affect the maxillofacialregion (Salmassy and Pogrel, 1995).

Because conservative treatment may lead to an unacceptablerate of recurrence and radical treatment may compromise functionand aesthetics, management of these lesions remains controversial(Salmassy and Pogrel, 1995).

Cryosurgery is an alternative treatment modality for locallyaggressive instead of invasive lesions (Emmings et al., 1966; Bradleyand Fisher, 1975; Curi et al., 1997; Veth et al., 2005; Gage and Baust,2007). This method uses freezing to induce tissue necrosis (Vethet al., 2005).

Veth et al. (2005) provided an excellent review based on theirconsiderable experience in treating 302 patients with diverse boneand soft tissue tumours. Cryosurgically treated patients included43 with giant cell tumours, 15 with chondroblastoma, 73 with

ará, Instituto de Ciências darrêa 01, Belém, PA 66075-110,

Falcão).

ociation for Cranio-Maxillo-Facial

, et al., Management of locally13), http://dx.doi.org/10.1016

borderline chondrosarcoma, and 44 with grade I chondrosarcoma.In a 2-year follow-up study, 96e100% of patients were disease free,although some patients required repeated treatments.

Several studies have reported successful management of ame-loblastomas (Pogrel, 1993; Salmassy and Pogrel, 1995; Curi et al.,1997; Fregnani et al., 2010), myxomas (Pogrel, 1993; Salmassyand Pogrel, 1995; Rocha et al., 2009), keratocystic odontogenic tu-mours (Jensen et al., 1988; Bradley and Fisher, 1975; Pogrel, 1993;Salmassy and Pogrel, 1995; Schmidt and Pogrel, 2001), and centralgiant cell lesions (Webb and Brockbank, 1986; Pogrel, 1993) withcryosurgery using liquid nitrogen application.

Central giant cell lesions are benign tumours of the jaws. Thera-peutic options have varied greatly over the years (Tosco et al., 2009).The traditional treatment for this lesion is curettage and resection(Shirani et al., 2011), but alternative therapies such as injection ofcorticosteroids in the lesion or subcutaneous administration ofcalcitonin or interferon alpha are described in several case reports,with variable success (de Lange et al., 2007). Furthermore,Webb andBrockbank (1986) reported successful treatment of an aggressivegiant cell lesion of the mandible with curettage and cryotherapy.

Schmidt and Pogrel (2001) retrospectively evaluated 26 kera-tocystic odontogenic tumours treated with a combination ofenucleation and liquid nitrogen cryotherapy. During the follow-up

Surgery. Published by Elsevier Ltd. All rights reserved.

aggressivemandibular tumours using a gas combination cryosurgery,/j.jcms.2013.05.033

J.T. Carneiro et al. / Journal of Cranio-Maxillo-Facial Surgery xxx (2013) 1e52

period (average, 3.5 years; range, 2e10 years), 23 of 26 (88.5%)patients showed no evidence of clinical or radiographic recurrence.

Rocha et al. (2009) described a case of a recurrent mandibularmyxoma treated with excision and curettage following liquid ni-trogen cryotherapy. After 10 years of postoperative follow-up,the patient showed no clinical or radiographic signs of lesionrecurrence.

Curi et al. (1997) evaluated 36 solid ameloblastomas of the jawtreated with curettage followed by liquid nitrogen cryosurgery.Local recurrence was observed in 11 (30.6%) patients. Postoperativecomplications were wound dehiscence (5.5%), paraesthesia (5.5%),infection (5.5%), and pathologic fracture (11.1%). Despite compli-cations in some cases, the authors suggested that curettage fol-lowed by cryosurgery decreases rate of local recurrences andreduces the initial indication of resection with continuity defects.

Data suggest that additional treatment with liquid nitrogenhelps to decrease rates of recurrences in comparison to treatmentwith curettage alone, especially for lesions with histories ofrecurrence (Schmidt and Pogrel, 2001). Other indications for liquidnitrogen treatment include large and complex mandibular lesions,in which enucleation of the cyst lining might be difficult, and le-sions in which conventional management might involve vitalstructures, such as the inferior alveolar nerve (Schmidt, 2003).

The aim of this treatment modality is to destroy cells associatedwith the lesion (Schmidt, 2003). During cryosurgery, cell and tissuedeath results from intracellular and extracellular ice crystal for-mation, osmotic and electrolyte disturbances, denaturing of lipideprotein complexes, and vascular stasis (Farrant, 1965; Whittaker,1984; Schmidt, 2003).

Cryosurgery produces cellular necrosis in bone while main-taining the inorganic osseous framework (Emmings et al., 1966;Bradley and Fisher, 1975). However, this method weakens the bone

Table 1Site distribution, subtype, sex, age, follow-up, recurrence, pathological fracture, infecticryosurgery using combination propane, butane, and isobutane gas.

Lesion Site Sex Age(years)

Ameloblastoma solid Right body and ramus F 20Ameloblastoma cystic Left body and ramus F 18Ameloblastoma cystic Right ramus M 24Ameloblastoma cystic Left ramus M 07Ameloblastoma solid Left body and ramus M 45Ameloblastoma solid Chin F 16Ameloblastoma solid Left ramus M 26Ameloblastoma cystic Right ramus F 21Ameloblastoma cystic Left ramus M 46Ameloblastoma solid Right ramus F 87Keratocystic odontogenic tumour Left ramus M 15Keratocystic odontogenic tumour Left ramus F 32Keratocystic odontogenic tumour Right ramus F 13Keratocystic odontogenic tumour Left body M 32Keratocystic odontogenic tumour Multiple F 12Keratocystic odontogenic tumour Multiple F 13Keratocystic odontogenic tumour Right ramus M 35Keratocystic odontogenic tumour Right ramus F 33Keratocystic odontogenic tumour Right ramus M 16Myxoma Left body and ramus M 26Myxoma Chin F 23Myxoma Right body M 27Myxoma Right body M 08Myxoma Left body M 06Central giant cell lesion Left body F 15Central giant cell lesion Right body M 11Neurofibroma Right ramus M 26Neurofibroma Right ramus M 12Pindborg Left body F 23Total29

e e Mean23.72

Please cite this article in press as: Carneiro JT, et al., Management of locallyJournal of Cranio-Maxillo-Facial Surgery (2013), http://dx.doi.org/10.1016

and increases the risk of pathologic fracture, a phenomenonobserved both clinically and experimentally (Fisher et al., 1977;Pogrel, 1993).

Tissues freeze at approximately �2.2 �C (Schmidt, 2003). Tem-peratures below�20 �C are believed to cause cell death (Smith andFraser, 1974; Gage et al., 2009). Liquid nitrogen boils at �196 �C(Salmassy and Pogrel, 1995). The mixture of propane, butane, andisobutane gas, which is used to perform endodontic tests,reaches �50 �C. The aim of this study was to evaluate the effec-tiveness of this gas combination in patients with locally aggressivemandibular bone tumours.

2. Materials and methods

This retrospective review was approved by the ethical com-mittee of the University Hospital João de Barros Barreto, FederalUniversity of Pará. Consent was obtained through a written docu-ment explaining in detail the procedures to be performed and wassigned by each patient who participated in the study.

Twenty-nine patients (16 men and 13 women) participated inthe study. The average patient age was 23.72 years (range, 6e87years). Diagnoses included ameloblastoma (n ¼ 10), keratocysticodontogenic tumour (n ¼ 9), myxoma (n ¼ 5), central giant celllesion (n ¼ 2), neurofibroma (n ¼ 2), and tumour of Pindborg(n ¼ 1).

Most tumours were located on the mandible: 9 involved thebody (right side, 5; left side, 4), 12 involved the ramus (right side, 8;left side, 4), and 4 involved both the body and ramus (right side, 1;left side, 3). Two tumours were observed on the chin (Table 1).

Each patient was treated by the same surgeon using a stan-dardized technique. Before enucleation and cryosurgery, cystic le-sions were marsupialised to decrease the tumour size. This

on and wound dehiscence in locally aggressive mandibular tumours treated with

Follow-up(months)

Recurrence Pathologicalfracture

Infection Wounddehiscence

72 No No No Yes60 No No No Yes60 No No No Yes120 No No No Yes67 No No No Yes86 No No No Yes60 No No No Yes60 No No No Yes66 No No No Yes74 No No No Yes54 No No No Yes54 No No No Yes55 No No No Yes108 No No No Yes120 Yes No No Yes54 No No No Yes54 No No No Yes54 Yes No No Yes66 No No No Yes54 No No No Yes93 No No No Yes58 No No No Yes62 No No No Yes54 No No No Yes54 No No No Yes53 No No No Yes99 No No No Yes86 No No No Yes89 No No No YesMean70.55

e e e e

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J.T. Carneiro et al. / Journal of Cranio-Maxillo-Facial Surgery xxx (2013) 1e5 3

treatment required 4months to 1 year, depending on the size of thelesion.

The surrounding tissues were then protected using sterilewooden tongue depressors and Vaseline gauze, while the cavitywas sprayed with a combination of propane, butane, and isobutanegas (Endo FrostTM, Roeko, Langenau, Germany) for 1 min (Fig. 1).The surrounding soft tissues were irrigated with warm saline so-lution to decrease the possibility of thermal injury. The mucosawasthen closed with vertical mattress sutures to ensure adequate softtissue apposition.

3. Results

Twenty-seven of the 29 patients (93.10%) showed no evidence ofclinical or radiographic recurrence, pathologic fracture, or infectionafter enucleation and cryosurgery using a combination of propane,butane, and isobutane gas (Figs. 2 and 3). The good control achievedwith the equipment enabled application of liquefied gas only inbone tissue, while the mucosal tissue remained protected byVaseline gauze.

During the first 72 h, the tissue surrounding the lesions washyperaemic with no ulceration. However, the cavity was exposeddue to bone dehiscence. Regions of exposed bone healed by secondintention, and within 2 weeks, the region had re-epithelialized.

The mean follow-up period was 70.55 months (range, 53e120months). Wound dehiscence, which was observed in all cases, wastreated by irrigating the area with 0.2% chlorhexidine for 1 week,followed by irrigation with physiological saline solution until thewounds healed (Table 1).

Two patients developed recurrence after treatment. One patientwas re-treated using the same approach described above and theother patient we will schedule a resective surgery.

Fig. 2. Panoramic radiograph of an 18-year-old woman showing an ameloblastoma inthe left body and ramus of the mandible (A). Postoperative panoramic radiographobtained 3 years and 5 months after performing enucleation and cryosurgery usingcombination propane, butane, and isobutane gas (B).

4. Discussion

Cryosurgery is a recently accepted treatment option for eradi-cating undesirable tissues, especially tumour tissues. Cryosurgery isparticularly attractive because it is minimally invasive. Successfulcryosurgery destroys the majority of undesired tissues by creating acryolesion and spares the surrounding normal tissues from injury(Zhao et al., 2007). Cryosurgery has thus become an adjunct toconventional treatment of locally invasive lesions (Emmings et al.,1966; Bradley and Fisher, 1975; Curi et al., 1997; Veth et al., 2005;

Fig. 1. Cryosurgery using a combination of propane, butane, and isobutane gas. The surround

Please cite this article in press as: Carneiro JT, et al., Management of locallyJournal of Cranio-Maxillo-Facial Surgery (2013), http://dx.doi.org/10.1016

Gage and Baust, 2007). The results are comparable to those ach-ieved with en bloc excision.

Several studies have reported successful management of locallyaggressive lesions of the jaw by cryosurgery with liquid nitrogenapplication (Bradley and Fisher, 1975; Webb and Brockbank, 1986;Jensen et al., 1988; Pogrel, 1993; Salmassy and Pogrel, 1995; Curiet al., 1997; Schmidt and Pogrel, 2001; Rocha et al., 2009;Fregnani et al., 2010).

Aggressive lesions of the jaw, including ameloblastomas, myx-omas, giant cell tumours, and keratocystic odontogenic tumourshave all been successfully treated by cryosurgery with liquid

ing tissues were protected with sterile wooden tongue blades and gauze with Vaseline.

aggressivemandibular tumours using a gas combination cryosurgery,/j.jcms.2013.05.033

Fig. 3. Panoramic radiograph of an 8-year-old boy showing a myxoma in the rightbody of the mandible (A). Postoperative panoramic radiograph obtained 4 years and 2months after performing enucleation and cryosurgery using combination propane,butane, and isobutane gas (B).

J.T. Carneiro et al. / Journal of Cranio-Maxillo-Facial Surgery xxx (2013) 1e54

nitrogen (Webb and Brockbank, 1986; Curi et al., 1997; Schmidt andPogrel, 2001; Veth et al., 2005; Rocha et al., 2009). The results of ourstudy demonstrate that these lesions can be successfully treatedwith a combination of propane, butane, and isobutane gas. Inaddition, few studies have investigated the management of Pind-borg tumours and neurofibromas with cryotherapy. To ourknowledge, this is the first report of Pindborg tumour and neuro-fibroma treated with cryosurgery.

Despite the successful use of curettage and cryosurgery usingliquid nitrogen to treat benign and locally aggressive bone tumours,a high rate of pathologic fractures was observed in these cases (Curiet al., 1997; Pogrel et al., 2002).

The use of propane, butane, and isobutane gas combination maybe a better option for cryosurgery. This combination reaches tem-peratures capable of causing cell lysis (�50 �C), but does not reachtemperatures as low as those of liquid nitrogen (�196 �C), reducingthe risk of pathological fracture and infection. We have previouslydemonstrated that the use of propane, butane, and isobutanegas combination for the treatment of ameloblastomas was effectivein preventing recurrence, pathological fracture and infection(Carneiro et al., 2012).

Bone cells are very sensitive to freezing, but the present casesshowed no pathologic fractures as a result of the treatment weemployed. The use of bone grafts or other supporting agents mayadd strength and facilitate bone healing (Gage et al., 2009). Ac-cording to Salmassy and Pogrel (1995), bone grafts performed afterenucleation and cryotherapy decrease the risk of complications andresult in greater residual bone heights.

The results of our study suggest that the use of this gas com-bination for locally aggressive lesions of the jaw is effective inpreventing recurrence within 5 years of treatment.

Fregnani et al. (2010) showed that the recurrence rate aftercurettage and cryotherapy of ameloblastomas is 31%. Because thisrate is considered high, this form of treatment should be selectedfor small or unicystic lesions. Curettage and cryotherapy have been

Please cite this article in press as: Carneiro JT, et al., Management of locallyJournal of Cranio-Maxillo-Facial Surgery (2013), http://dx.doi.org/10.1016

suggested as treatment for the solid tumour counterpart (Pogreland Montes, 2009), but long-term studies are not available.

According to Schmidt (2003), cryotherapy should not be thetreatment of choice for every patient with keratocystic odontogenictumour. There are clear indications for this technique which are thecases of recurrences, large complex mandibular lesions, and whenthe conventional treatment might involve vital structures andnoncompliant patient.

The average recurrence rate of myxomas is 25%, especially whenmore conservative treatments are used. Lesion excision andcurettage with liquid nitrogen cryotherapy is an alternative toradical en bloc resection. Although complications may occur due tobone-freezing, they do not affect the success of the treatment(Rocha et al., 2009).

Webb and Brockbank (1986) suggested that central giant celltumours are amenable to conservative curettage and cryosurgery.However, few case reports describe the use of this technique inthese lesions.

Wound dehiscence was observed in all cases with partial expo-sure of bone cavity and frequently developed during the first 10 days.Extended antibiotic therapy was not necessary in these cases.

Treating patients with a combination of propane, butane, andisobutane gas offers additional advantages. First, the equipment,which comprises a bottle and a small thin tube, is easily manipu-lated. This provides better control and lower risk of injury to theadjacent soft tissue. Second, this treatment represents a lessexpensive intervention than more radical procedures.

5. Conclusion

For locally aggressive mandible tumours, treatment withenucleation and cryosurgery using a combination of propane,butane, and isobutane gas could be a safe, effective, and low-costtherapy, when precise conditions are present.

Sources of supportNone.

Conflict of interest statementNone declared.

Acknowledgements

This study was performed at University Hospital João de BarrosBarreto, Federal University of Pará (Belém, Pará, Brazil) and at theOphir Loyola Hospital (Belém, Pará, Brazil).

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