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Liquid nitrogen cryosurgery and immediate bone grafting in the management of aggressive primary jaw lesions
J Oral Maxillofac Surg 53:784-799, 1995
Liquid Nitrogen Cryosurgery and Immediate Bone Grafting in the Management of Aggressive Primary Jaw Lesions DAVID A. SALMASSY, DMD,* AND M. ANTHONY POGREL, MD, DDS'I Purpose: This study evaluated whether simultaneous bone grafting will accelerate healing and reduce the complication rate of aggressive mandibular lesions treated by enucleation and liquid nitrogen cryotherapy. Materials and Methods: Twenty patients with locally aggressive mandibular lesions were evaluated. All were treated by enucleation and liquid nitrogen cryotherapy. Ten received simultaneous bone grafting and 10 did not. Patients were matched as closely as possible for age and size of lesion. Results: None of the patients who received enucleation, cryotherapy, and simultaneous bone grafting developed complications. Of the 10 patients having enucleation, cryotherapy, and no bone grafting, two patients developed pathologic fractures and one developed a wound dehiscence that healed on conservative management. Residual alveolar bone height was 81% of the preoperative level in the grafted group and 78% of the preoperative level in the nongrafted group. Additionally, 15 osseointegrated implants were placed in the group receiving bone grafting whereas none was placed in the group that was not grafted. All complications occurred with lesions greater than 4.0 cm in greatest diameter. Conclusion: For locally aggressive lesions larger than 4.0 cm in greatest diameter, simultaneous cancellous bone grafting following enucleation and liquid nitrogen cryosurgery will decrease the risk of complications and result in greater residual bone height and a better ability to place endosseous dental implants.
The maxillofacial region can be affected by a number of benign yet aggressive and locally recurrent lesions. Examples include the ameloblastoma, myxoma, odontogenic keratocyst, central giant cell granuloma, and some fibre-osseous lesions. The management of these lesions remains controversial with regard to initial surgery and the timing of subsequent reconstructive
procedures. Conservative management may lead to an unacceptable rate of recurrence,1 whereas radical treatment may cause functional and cosmetic compromise. 2 The deliberate destruction of tissue by means of"freeze and thaw cycles was reported first by Arnott in 1851, 3 and has since been referred to as cryosurgery. Gage et al in 19664 published their work on the freezing of segments of long bone in dogs, while Emmings et al5 studied this technique in canine mandibles. Marcove and Miller in 19696 published a series of 50 patients with primary and metastatic bone tumors treated by cryosurgery, and they suggested that its use be confined to low-grade and aggressive primary tumors of bone. The application of this modality in the management of primary intrabony maxillofacial tumors was first reported by Sippel and Emmings in 1969,7 in their management of a recurrent ossifying fibroma of the mandible.
Received from the Department of Oral and Maxillofacial Surgery, University of California at San Francisco, San Francisco, CA. * Chief Resident. ~ Associate Professor and Chair. Address correspondence and reprint requests to Dr Pogre]: Department of Oral and Maxillofacial Surgery, University of California, San Francisco, San Francisco, CA 94143-0440.
© 1995 AmericanAssociationof Oral and MaxillofacialSurgeons 0278-2391/95/5307-000953.00/0
784
SALMASSY AND POGREL Liquid nitrogen, boiling at -196.6°C, achieves a lower temperature than the other two modalities that have been used in cryosurgery (nitrous oxide boils at -89.7°C and carbon dioxide boils at -78.5°C). Therefore, it can achieve a more profound freezing effect. Cell death is believed to occur at temperatures reaching - 2 0 ° C . 8'9 The exact mechanism of mammalian cell death was proposed by Whittaker 1° to be a combination of intracellular and extracellutar ice crystal formation leading to direct cell damage as well as osmotic and electrolyte disturbances across the cell membrane. Most protocols advise that freezing be performed rapidly to cause the maximum intracellular ice crystal formation, followed by a slow thaw period to allow the maximum electrolyte disturbance because both of these situations result in lethal cell effects. 11 When applied to intrabony lesions, liquid nitrogen cryosurgery has the advantage of devitalizing the viable bone while maintaining its inorganic integrity.4'12 Regeneration can occur using the principle of "creeping substitution" as described by Phemister. 13 The net result is represented by the sequential phases of necrosis, osteogenesis, and remodeling. 5'14Techniques using chemical agents such as Carnoy's solution 15 denature the inorganic matrix, destroying its osteogenic and osteoconductive properties. The unique advantage of liquid nitrogen cryosurgery is its ability to devitalize bone in situ. While the exact criteria for its use have not been established, it is thought to be an acceptable method of treatment for benign aggressive bone lesions that have a documented high local recurrence rate following enucleation or curettage. This is of particular importance in the maxillofacial region where there are a number of such lesions. Treatment would consist of local enucleation and curettage of the lesion followed by liquid nitrogen treatment of the residual cavity to devitalize any buds or daughter cells. There are a number of case reports in the literature of the successful management of odontogenic keratocysts, 12'16'~7ameloblastomas, ~6'18giant cell lesions, ~6 and myxomas 16 by the use of liquid nitrogen application. Two different cryosurgical techniques have been described: an open spray technique and a closed cryoprobe technique. The direct spraying of liquid nitrogen has a more profound effect than a closed cryoprobe applicationJ 2 However, a cryoprobe carefully adapted to the tissue contours can give satisfactory results. A variation of the cryoprobe technique uses a water soluble conducting medium such as KY jelly (Johnson & Johnson, Arlington, TX) to fill a small surgical defect, followed by probe application. In this way, the conducting medium will freeze and become, in essence, a perfectly adapted cryoprobe conducting its effect to all bone margins in contact with the medium. The bony necrosis associated with cryotherapy
785 weakens the bone, reaching a maximum at around 8 weeks posttreatment, after which osteogenesis occurs, gradually increasing bone strength to presurgical levels. 19 When the bone is weakened by cryotherapy, it is at risk for pathologic fracture, a phenomenon shown both clinically and experimentally. 16,19Some investigators have therefore suggested simultaneous cancellous bone grafting of larger cavities to provide an early stimulus for osteogenesis in an attempt to override the period of bone weakness. 16 If this cancellous bone grafting is to work in the manner that was intended, it is essential that viable osteoblasts are transplanted to lay down new bone. In this phase I period of osteogenesis, successful grafting is dependent on a favorable vascular bed at the recipient site. 2° At the present time the vascularity of the cryosurgery-treated defect is unknown. Also undetermined is the size of the bone cavity for which bone grafting is advantageous. There are several questions relative to the liquid nitrogen cryosurgery technique that must be resolved before it can be confidently recommended as a therapeutic modality for problematic benign aggressive lesion of the jaws. These include: 1) Does immediate cancellous bone grafting after cryotherapy accelerate the osteogenic process, thereby enhancing bone formation and minimizing the risks of sequestrum formation, wound dehiscence, and pathologic fracture? 2) Is there a critical size of bone cavity beyond which bone grafting has a significant advantage? and 3) Does the immediate placement of an autogenous bone graft in the defect facilitate a final alveolar bone volume that is satisfactory for dental implant placement without further ridge augmentation? This study addresses these questions.
Materials and Methods The study group consisted of 10 consecutive patients with locally aggressive mandibular lesions who received enucleation and cryotherapy and simultaneous autogenous bone graft reconstruction, and is referred to as group 1 in Table 1. Group 2 consisted of 10 control patients from the same time period with similar diagnoses who received enucleation and cryotherapy without bone grafting of the defect (Table 2). The control group was selected on the basis of similar age and size of defect. All of the lesions were treated by liquid nitrogen cryotherapy using a Frigitronics CS-76 (Frigitronics, Shelton, CT) cryotherapy unit. For lesions less than 2 cm in largest dimension on a panoramic radiographic survey, a water-soluble conducting medium (KY jelly) was placed in the residual bone cavity following enucleation. The tip of the cryosurgery unit was placed in the center of the medium and a 1-minute freeze cycle initiated, followed by a 5-minute thaw period. This was repeated twice. All other bone cavities
786
CRYOSURGERY A N D BONE GRAFTING
Table 1.
Group 1 (Cryosurgery and Bone Graft)
Patient
Age/Sex
Lesion
Site
A B C D E F G H I J
17/M 77/M 29/F 78/F 27/M 73/F 51/F 17/M 70/M 41/F
OKC Amelo Amelo OKC Amelo Amelo OKC OKC Amelo Myxoma
Left mandible Anterior mandible Left mandible Anterior mandible Anterior mandible Right mandible Left mandible Anterior mandible Anterior mandible Left mandible
Preoperative Measurement
Size (cm) 4 2 2 3.5 3.5 2 2 3 3.5 2.5
× x × x X × x x × ×
(mm)
Postoperative Measurement (mm)
% Preoperative Size
No. of Implants
No. of Complications
40 30 35 38 38 30 28 38 43 35
35 18 26 29 24 22 28 38 31 30
88 67 74 76 63 73 100 100 82 86
1 2 3 -5 2 --2 --
None None None None None None None None None None
6 3 3 8 8 4 3 7.5 8 3
Abbreviations: OKC, odontogenic keratocyst; Amelo, ameloblast0ma.
were treated by direct application of the liquid nitrogen in the form of a spray, until a solid frost was formed over all bone margins. A 5-minute thaw period was allowed before a second and final application was used. The study group received a particulate cancellous bone and marrow (PCBM) graft from the iliac crest to obliterate the cavity. Both groups underwent primary everted wound edge closure by means of vertical mattress sutures. The patients were evaluated for preoperative and postoperative alveolar height on the basis of a panoramic mandibular index similar to the one used by Benson et al. 21 The index was customized for this study by measuring the height from the cortical margin at the inferior mandibular border to the height of the most superior point in the middle of the lesion (Fig 1). Postoperative radiographs were measured in a similar fashion, with the upper limit of the alveolar ridge being directly above the site registered at the inferior border in the preoperative radiograph. An attempt was made to factor out possible errors caused by magnification differences by standardizing these films based on a
Table 2.
constant inferior border cortical bone height. Postoperative complications, including wound dehiscence, sequestrum formation, and pathologic fracture were recorded. The patients in the study group who subsequently received implants in the surgical site were also recorded.
Results The patients in the control and study groups ranged in age from 7 to 79 years. There were 7 females and 13 males. The diagnoses were as follows: odontogenic keratocysts (n = 11), ameloblastomas (n = 6), ossifying fibrrmas (n = 2), and myxoma (n = 1). The average postoperative radiographic follow-up period was 12.6 months with a range of 5 to 21 months. The mean clinical follow-up period was 3.5 years, with a range of 1.1 to 8 years. GROUP 1
(STUDY
GROUP)
The patients receiving cryotherapy combined with PCBM grafting following enucleation showed no post-
Group 2 (Cryosurgery Alone)
Patient
Age/Sex
Lesion
Site
Size (cm)
K L M N O P Q R
79/M 43/M 20/F 13/F 69/M 32/M 51/M 9/M
OKC Myxoma OKC OKC OKC OKC Os Fib OKC
Right mandible Right mandible Right mandible Right mandible Right mandible Right mandible Anterior mandible Left mandible
2 2 2 2 2.5 1.5 1 2
S T
10/M 54/M
Os Fib Amelo
Left mandible Anterior mandible
2.5 x 3 3.5 × 6
x x x X x x X x
3.5 2 2 3 6 3 2 2.5
Preoperative Measurement (mm)
Postoperative Measurement (mm)
% Preoperative Size
26 19 32 25 28 36 31 22
20 20 32 21 19 3428 11
77 105 100 84 68 93 90 50
29 38
13 14
45 37
Abbreviations: OKC, odontogenic keratocyst; Amelo, ameloblastoma; Os Fib, ossifying flbroma.
No. of Complications None None None None Pathologic fracture None None Wound dehiscence, sequestra None Pathologic fracture
SALMASSY AND POGREL
787
FIGURE 3. Patient E with cancellous iliac bone graft placed in the defect before wound closure.
A FIGURE 1. Diagram depicting panoramic mandibular index used for preoperative radiographs. Similar measurements were made on the postoperative radiographs with point (B) representing the superior aspect of alveolar ridge. A represents the inferior cortical margin.
operative complications. The average lesion was computed to be 2.8 cm X 5.5 cm in size, with a range of 2 cm to 8 cm in maximum diameter. With an average follow-up and radiographic evaluation period of 12.6 months (range, 5 to 21 months), these patients showed an alveolar height that was 81% of the preoperative state. Fifteen implants were placed in the operative sites of six of the patients. Patients E (Figs 2-4), and C (Figs 5,6) are shown as examples. GROUP 2 (CONTROL GROUP) Three of the patients who were treated with enucleation followed by cryosurgery alone had complications. There were two patients (O and T) who developed pathologic fractures. Patient O (Figs 7,8) acquired
FIGURE 2. Preoperative panoramic radiograph of patient E showing an ameloblastoma in the symphysis of the mandible.
a pathologic fracture of the ascending ramus in the fifth week postoperatively. He was managed on a blenderized diet for 6 weeks and advised to refrain from vigorous activities. Three months following this event, his occlusion remained stable and he had resumed a regular diet. The second pathologic fracture, patient T (Fig 9) occurred 8 weeks after cryosurgery (Fig 10). It was managed by placement of a titanium mesh tray and corticocancellous bone graft from an extraoral approach, and there have been no further sequelae. He is now 6 years postoperation and is without recurrence. One patient (R) developed wound dehiscence on the eighth postoperative day and required local management by means of daily irrigation and sterile gauze packings. This patient developed bone sequestra and, following debridement and sequestrectomy, the wound showed evidence of complete soft tissue coverage by the third week. For the control group of patients, the average radiographic size of the lesion was computed to be 2 cm × 3.5 cm, with a range of 1 cm to 6 cm in maximum diameter. The average follow-up period was 34.9 months (range, 10 to 96 months). Alveolar ridge height
FIGURE 4. Panoramic radiograph 13 months after initial surgery and 7 months after placement of implants. Note fixed removable bar attachment for the prosthesis.
788
CRYOSURGERY AND BONE GRAFFING
FIGURE 7. Preoperativepanoramicradiograph of patient O from group 2 showing large odontogenic keratocyst involving the right ramus and retromolar region of mandible.
FIGURE5. Radiographof patient C showing2 × 3-cm unilocular ameloblastoma of the left mandible before enucleation. averaged 78% of the preoperative value. None of the patients in this group acquired dental implants as part of their treatment plan.
Discussion The process of liquid nitrogen cryosurgery has been shown to have the capacity to devitalize the hard and
FIGURE 6. Close-upview of periapical radiograph from patient C at 1 yearpostoperationshowingthree implants and a goodtrabecular bone pattern.
soft tissues of the maxillofacial region. 5,7"9"HA4A7,18,22 With respect to the soft tissues, the advantages of cryosurgery are ease of application, relative lack of discomfort, no bleeding, and minimal scarring. The disadvantages, however, include an unpredictable degree of postoperative swelling and a lack of precision associated with the extent of tissue destruction at the time of treatment. If the soft tissue margins around a bony lesion are inadvertently exposed to the liquid nitrogen, the resultant soft tissue necrosis may account for wound dehiscence as a postoperative complication. It is known that human bone decreases in density and increases in porosity at the beginning of the third decade of life. 21'23'24 Maximum bone mass has been reported to be reached by about 30 years of age, after which it decreases, usually affecting women at a rate three times that of men, especially in the postmenopausal period. The fractures in this series occurred in patients who were beyond their fifth decade of life. Both were in lesions where one or more of the dimensions measured greater than 4.0 cm. Also, both lesions appeared to involve areas within 1 cm or less of the inferior border of the mandible, yet in different sites. This fact is important because if the correct technique
FIGURE 8. Radiographof patient O at 5 weeks after surgery and application of liquid nitrogen. The a r r o w shows the site of fracture below the right condyle.
SALMASSY AND POGREL
789 Table 3.
Location of the Lesion
Group 1 Group 2 Total
FIGURE 9. Preoperative radiograph of patient T showing large ameloblastoma of the anterior mandible.
is used in application of the liquid nitrogen, the resultant devitalization of bone can be expected to reach at least 2 to 3 m m beyond the margins of the bony cavity. 13,22As previously stated, the maximum bone weakness following cryotherapy appears to be at 8 weeks. In this study, the fractures occurred at or about that time. Both the lesions were in the group that did not receive immediate autogenous reconstruction. In contrast, there were four lesions of greater dimension in the group that received bone graft reconstruction (patients D, E, H, and I), two of whom were in their eighth decade of life at the time treatment was rendered. To assess whether the placement of an immediate bone graft facilitates later implant placement, it is necessary to look at the site of the lesion and its relationship to the crest of the ridge. Table 3 shows whether the lesion involved or violated the crest of the ridge or was confined to some portion below, referred to in the Table as an intrabony defect. In combining both groups, 75% (15 of 20) of the lesions involved the crest of the ridge resulting in a postsurgical defect in this location. None of the patients who had postsurgical complications had isolated intrabony defects. The patients with intrabony defects had an average sized lesion of 2.5 cm × 4.5 cm, with a range of 2 cm to 8 cm in maximum diameter, and retained an average of
Intrabony
Involvementof the Crest of the Alveolus
D, G, H L, M 5
A, B, C, E, F, I, J K, N, O, P, Q, R, S, T 15
96% of the original alveolar height at an average of 12 months after treatment. Two of the three intrabony lesions that were grafted (D and H) had sizes that were 7.5 to 8 cm in their greatest dimension. While the grafts did not contribute to alveolar height, they may have been successful in preventing postoperative pathologic fracture. Fifteen dental implants were placed in the patients in this study, all in group 1. In this group the average lesion was larger, and was destructive to the integrity of the native alveolar crest (7 of 10). Although the majority of odontogenic lesions involve the posterior mandible, five in this group were found in the anterior mandible. Of those, three patients (B, E, and I) accounted for 9 of the 15 implants. This is reasonable because the majotSity of dental implant reconstruction is geared to the anterior region. Only two patients in group 2 (Q and T), had anterior mandibular lesions. Why implants were not placed is unknown. The use of liquid nitrogen cryotherapy for the treatment of locally aggressive lesions of the jaws appears to be effective in preventing recurrence. Five of the 20 patients are at or beyond 5 years after treatment. The combination of cryotherapy with immediate cancellous bone reconstruction of the defect appears to assist in the prevention of postoperative complications such as pathologic fracture and may indeed be effective in preventing wound dehiscence and sequestrum formation, although the numbers in this study axe too small for statistical analysis. The patient that presents with a lesion 4 cm or greater in size, with violation of the crestal alveolus and less than 1 cm of Cortical bone at the inferior margin, may be at risk for pathologic fracture when cryotherapy is used. This certainly applies with respect to older patients, and it may be in their best interest to consider them as candidates for immediate reconstruction with an autogenous cancellous bone graft. The placement of cancellous bone in the surgical defect treated by enucleation combined with cryotherapy lends itself to dental rehabilitation with dental implants when warranted. The residual alveolus has been shown to be a satisfactory site. Whether this is also true for patients treated without a bone graft could not be determined from this study. References
FIGURE 10. Radiograph of patient T with fracture of right body of mandible 8 weeks postsurgery.
1. Toiler PA: Newer concepts of odontogenic cysts. Int J Oral Surg 1:3, 1972
790
DISCUSSION
2. Bramley PA: Treatment of cysts of the jaws. Proc R Soc Med 64:547, 1971 3. Arnott J: On the Treatment of Cancer by Regulated Application of an Anesthetic Temperature. London, England, J Churchill, 1851, p 32 4. Gage A, Green G, Neiders M, et al: Freezing bone without excision. An experimental study of bone-cell destruction and manner of regrowth in dogs. JAMA 196:720, 1966 5. Emmings F, Neiders M, Green G, et al: Freezing of the mandible without excision. J Oral Maxillofac Surg 24:145, 1966 6. Marcove RC, Miller TR: Treatment of primary and metastatic bone tumors by cryosurgery. JAMA 207:1890, 1969 7. Sippel HW, Emmings FG: Cryotherapy in the treatment of recurrent ossifying fibroma: Report of a case. J Oral Surg 27:32, 1969 8. Smith JJ, Fraser J: An estimation of tissue damage and thermal history in the cryolesion. Cryobiology 11:139, 1974 9. Rosen G, Vered IY: Cryosurgery for basal cell carcinoma of the head and neck. S Afr Med J 56:26, 1979 10. Whittaker DK: Mechanisms of tissue destruction following cryosurgery. Ann R Coll Surg Engl 66:313, 1984 11. Le Pivert PJ: Basic considerations of the cryolesion, in Albin RJ (ed): Handbook of Cryosurgery. New York, NY, Dekker, 1980, p 22 12. Bradley PF, Fisher AD: The cryosurgery of bone: An experimental and clinical assessment. Br J Oral Surg 13:111, 1975 13. Phemister DB: The fate of transplanted bone and regenerative powers of its various constituents. Surg Gynecol Obstet 19:393, 1914 14. Bradley PF: Modern trends in cryosurgery of the maxillofacial region. Int J Oral Surg 7:405, 1978
15. Voorsmit RA: The art of treating keratocysts: Fixation before enucleation. Paper presented at the 8th Congress of European Association for Maxillofacial Surgery held in Madrid, Spain, June 14-18, 1986 16. Pogrel MA: The use of liquid nitrogen cryotherapy in the management of locally aggressive bone lesions. J Oral MaxiUofac Surg 51:264, 1993 17. Webb J, Brockbank J: Treatment of odontogenic keratocysts by combined enucleation and cryosurgery. Int J Oral Surg 13:506, 1984 18. Emmings FG, Gage A, Koepf SW: Combined curettage and cryotherapy for recurrent ameloblastoma of the mandible. J Oral Surg 29:41, 1971 19. Fisher AD, Williams DF, Bradley PF: The effect of cryosurgery on the strength of bone. Br J Oral Surg 15:215, 1977 20. Marx RE, Kline SN: Principles and techniques of bony reconstruction in cancer patients, in Fonseca RJ, Davis WH (eds): Major Prosthetic Surgery. Philadelphia, PA, Saunders, 1986, p 347 21. Benson BW, Pirhoda TJ, Glass BJ: Variations in adult cortical bone mass as measured by a panoramic mandibular index. Oral Surg Oral Med Oral Pathol 71:349, 1991 22. Bradley PF: The cryosurgery of bone in the maxillofacial region, in Bradley PF (ed): Cryosurgery of the Maxillofacial Region, vol II. Boca Raton, FL, CRC 1986, pp 55-91 23. von Wowern N: Microradiographic and histomorphometric indices of mandibles for the diagnosis of osteopenia. Scand J Dent Res 90:47, 1982 24. Kribbs PJ, Smith DE, Chestnut CH: Oral findings in osteoporosis. Part II. Relationship between residual ridge and alveolar bone resorption and generalized skeletal osteopenia. J Prosthet Dent 50:719, 1983
d Oral Maxillofac Surg 53:790, 1995
Discussion Liquid Nitrogen Cryosurgery and Immediate Bone Grafting in the Management of Aggressive Primary Jaw Lesions Fred G. Emmings, DDS, P h D Pittsford, NY The preceding article supports the hypothesis that simultaneous grafting at the site of locally aggressive jaw tumors treated by enucleation and freezing decreases subsequent vulnerability to fracture at these sites. While the number of patients reported are inadequate to justify a definitive conclusion, the results certainly encourage simultaneous grafting. The addition of particulate cancellous bone and marrow (PCBM) to the matrix left after freezing likely hastens osteogenesis, which apparently strengthens the nonvital segment before it reaches its weakest condition around 8 weeks after freezing. It is not surprising that PCBM grafting is most applicable to larger lesions in older patients. In the past clinicians using freezing and enucleation simply applied maxillomandibular fixation during the fourth to tenth postoperative weeks. Grafting should clearly prove to be a better option. Although these clinical observations suggest that initiation of osteogenesis in the P C B M graft produces beneficial ef-
fects, experiments are needed to confirm that notion. The graft bed is nonvital and, although freezing spares larger vessels, smaller vessels are certainly occluded. In the graft bed, only the surrounding soft tissues have been protected from freezing. Studies need to be done to define the source of circulatory support for the graft, to confirm the presence of osteogenesis, and to compare osteogenesis in frozen tissues to that in nonfrozen recipient sites. The P C B M grafts did not contribute to preservation of alveolar ridge height. However, more than 80% of the original ridge height was present in both groups. This suggests that it might be feasible to install dental implants at the time of enucleation/freezing/grafting. Simultaneous grafting with implant placement has been successful in nonfrozen sites and might work when only 2 to 3 m m of bone has been devitalized around the recipient site. This is another reason we need the information generated by the studies proposed above. This is a clinical study reporting a small number of patients. Follow-up is insufficient in many of these cases to determine the efficacy of the treatment, but that was not the author's purpose. Neither was there adequate follow-up to draw many conclusions regarding the implants. Therefore, only modest inferences can be added to our knowledge base. However, the results are consistent with and support previously published advances.
Liquid Nitrogen Cryosurgery and Immediate Bone Grafting in the Management of Aggressive Primary Jaw Lesions DAVID A. SALMASSY, DMD,* AND M. ANTHONY POGREL, MD, DDS'I Purpose: This study evaluated whether simultaneous bone grafting will accelerate healing and reduce the complication rate of aggressive mandibular lesions treated by enucleation and liquid nitrogen cryotherapy. Materials and Methods: Twenty patients with locally aggressive mandibular lesions were evaluated. All were treated by enucleation and liquid nitrogen cryotherapy. Ten received simultaneous bone grafting and 10 did not. Patients were matched as closely as possible for age and size of lesion. Results: None of the patients who received enucleation, cryotherapy, and simultaneous bone grafting developed complications. Of the 10 patients having enucleation, cryotherapy, and no bone grafting, two patients developed pathologic fractures and one developed a wound dehiscence that healed on conservative management. Residual alveolar bone height was 81% of the preoperative level in the grafted group and 78% of the preoperative level in the nongrafted group. Additionally, 15 osseointegrated implants were placed in the group receiving bone grafting whereas none was placed in the group that was not grafted. All complications occurred with lesions greater than 4.0 cm in greatest diameter. Conclusion: For locally aggressive lesions larger than 4.0 cm in greatest diameter, simultaneous cancellous bone grafting following enucleation and liquid nitrogen cryosurgery will decrease the risk of complications and result in greater residual bone height and a better ability to place endosseous dental implants.
The maxillofacial region can be affected by a number of benign yet aggressive and locally recurrent lesions. Examples include the ameloblastoma, myxoma, odontogenic keratocyst, central giant cell granuloma, and some fibre-osseous lesions. The management of these lesions remains controversial with regard to initial surgery and the timing of subsequent reconstructive
procedures. Conservative management may lead to an unacceptable rate of recurrence,1 whereas radical treatment may cause functional and cosmetic compromise. 2 The deliberate destruction of tissue by means of"freeze and thaw cycles was reported first by Arnott in 1851, 3 and has since been referred to as cryosurgery. Gage et al in 19664 published their work on the freezing of segments of long bone in dogs, while Emmings et al5 studied this technique in canine mandibles. Marcove and Miller in 19696 published a series of 50 patients with primary and metastatic bone tumors treated by cryosurgery, and they suggested that its use be confined to low-grade and aggressive primary tumors of bone. The application of this modality in the management of primary intrabony maxillofacial tumors was first reported by Sippel and Emmings in 1969,7 in their management of a recurrent ossifying fibroma of the mandible.
Received from the Department of Oral and Maxillofacial Surgery, University of California at San Francisco, San Francisco, CA. * Chief Resident. ~ Associate Professor and Chair. Address correspondence and reprint requests to Dr Pogre]: Department of Oral and Maxillofacial Surgery, University of California, San Francisco, San Francisco, CA 94143-0440.
© 1995 AmericanAssociationof Oral and MaxillofacialSurgeons 0278-2391/95/5307-000953.00/0
784
SALMASSY AND POGREL Liquid nitrogen, boiling at -196.6°C, achieves a lower temperature than the other two modalities that have been used in cryosurgery (nitrous oxide boils at -89.7°C and carbon dioxide boils at -78.5°C). Therefore, it can achieve a more profound freezing effect. Cell death is believed to occur at temperatures reaching - 2 0 ° C . 8'9 The exact mechanism of mammalian cell death was proposed by Whittaker 1° to be a combination of intracellular and extracellutar ice crystal formation leading to direct cell damage as well as osmotic and electrolyte disturbances across the cell membrane. Most protocols advise that freezing be performed rapidly to cause the maximum intracellular ice crystal formation, followed by a slow thaw period to allow the maximum electrolyte disturbance because both of these situations result in lethal cell effects. 11 When applied to intrabony lesions, liquid nitrogen cryosurgery has the advantage of devitalizing the viable bone while maintaining its inorganic integrity.4'12 Regeneration can occur using the principle of "creeping substitution" as described by Phemister. 13 The net result is represented by the sequential phases of necrosis, osteogenesis, and remodeling. 5'14Techniques using chemical agents such as Carnoy's solution 15 denature the inorganic matrix, destroying its osteogenic and osteoconductive properties. The unique advantage of liquid nitrogen cryosurgery is its ability to devitalize bone in situ. While the exact criteria for its use have not been established, it is thought to be an acceptable method of treatment for benign aggressive bone lesions that have a documented high local recurrence rate following enucleation or curettage. This is of particular importance in the maxillofacial region where there are a number of such lesions. Treatment would consist of local enucleation and curettage of the lesion followed by liquid nitrogen treatment of the residual cavity to devitalize any buds or daughter cells. There are a number of case reports in the literature of the successful management of odontogenic keratocysts, 12'16'~7ameloblastomas, ~6'18giant cell lesions, ~6 and myxomas 16 by the use of liquid nitrogen application. Two different cryosurgical techniques have been described: an open spray technique and a closed cryoprobe technique. The direct spraying of liquid nitrogen has a more profound effect than a closed cryoprobe applicationJ 2 However, a cryoprobe carefully adapted to the tissue contours can give satisfactory results. A variation of the cryoprobe technique uses a water soluble conducting medium such as KY jelly (Johnson & Johnson, Arlington, TX) to fill a small surgical defect, followed by probe application. In this way, the conducting medium will freeze and become, in essence, a perfectly adapted cryoprobe conducting its effect to all bone margins in contact with the medium. The bony necrosis associated with cryotherapy
785 weakens the bone, reaching a maximum at around 8 weeks posttreatment, after which osteogenesis occurs, gradually increasing bone strength to presurgical levels. 19 When the bone is weakened by cryotherapy, it is at risk for pathologic fracture, a phenomenon shown both clinically and experimentally. 16,19Some investigators have therefore suggested simultaneous cancellous bone grafting of larger cavities to provide an early stimulus for osteogenesis in an attempt to override the period of bone weakness. 16 If this cancellous bone grafting is to work in the manner that was intended, it is essential that viable osteoblasts are transplanted to lay down new bone. In this phase I period of osteogenesis, successful grafting is dependent on a favorable vascular bed at the recipient site. 2° At the present time the vascularity of the cryosurgery-treated defect is unknown. Also undetermined is the size of the bone cavity for which bone grafting is advantageous. There are several questions relative to the liquid nitrogen cryosurgery technique that must be resolved before it can be confidently recommended as a therapeutic modality for problematic benign aggressive lesion of the jaws. These include: 1) Does immediate cancellous bone grafting after cryotherapy accelerate the osteogenic process, thereby enhancing bone formation and minimizing the risks of sequestrum formation, wound dehiscence, and pathologic fracture? 2) Is there a critical size of bone cavity beyond which bone grafting has a significant advantage? and 3) Does the immediate placement of an autogenous bone graft in the defect facilitate a final alveolar bone volume that is satisfactory for dental implant placement without further ridge augmentation? This study addresses these questions.
Materials and Methods The study group consisted of 10 consecutive patients with locally aggressive mandibular lesions who received enucleation and cryotherapy and simultaneous autogenous bone graft reconstruction, and is referred to as group 1 in Table 1. Group 2 consisted of 10 control patients from the same time period with similar diagnoses who received enucleation and cryotherapy without bone grafting of the defect (Table 2). The control group was selected on the basis of similar age and size of defect. All of the lesions were treated by liquid nitrogen cryotherapy using a Frigitronics CS-76 (Frigitronics, Shelton, CT) cryotherapy unit. For lesions less than 2 cm in largest dimension on a panoramic radiographic survey, a water-soluble conducting medium (KY jelly) was placed in the residual bone cavity following enucleation. The tip of the cryosurgery unit was placed in the center of the medium and a 1-minute freeze cycle initiated, followed by a 5-minute thaw period. This was repeated twice. All other bone cavities
786
CRYOSURGERY A N D BONE GRAFTING
Table 1.
Group 1 (Cryosurgery and Bone Graft)
Patient
Age/Sex
Lesion
Site
A B C D E F G H I J
17/M 77/M 29/F 78/F 27/M 73/F 51/F 17/M 70/M 41/F
OKC Amelo Amelo OKC Amelo Amelo OKC OKC Amelo Myxoma
Left mandible Anterior mandible Left mandible Anterior mandible Anterior mandible Right mandible Left mandible Anterior mandible Anterior mandible Left mandible
Preoperative Measurement
Size (cm) 4 2 2 3.5 3.5 2 2 3 3.5 2.5
× x × x X × x x × ×
(mm)
Postoperative Measurement (mm)
% Preoperative Size
No. of Implants
No. of Complications
40 30 35 38 38 30 28 38 43 35
35 18 26 29 24 22 28 38 31 30
88 67 74 76 63 73 100 100 82 86
1 2 3 -5 2 --2 --
None None None None None None None None None None
6 3 3 8 8 4 3 7.5 8 3
Abbreviations: OKC, odontogenic keratocyst; Amelo, ameloblast0ma.
were treated by direct application of the liquid nitrogen in the form of a spray, until a solid frost was formed over all bone margins. A 5-minute thaw period was allowed before a second and final application was used. The study group received a particulate cancellous bone and marrow (PCBM) graft from the iliac crest to obliterate the cavity. Both groups underwent primary everted wound edge closure by means of vertical mattress sutures. The patients were evaluated for preoperative and postoperative alveolar height on the basis of a panoramic mandibular index similar to the one used by Benson et al. 21 The index was customized for this study by measuring the height from the cortical margin at the inferior mandibular border to the height of the most superior point in the middle of the lesion (Fig 1). Postoperative radiographs were measured in a similar fashion, with the upper limit of the alveolar ridge being directly above the site registered at the inferior border in the preoperative radiograph. An attempt was made to factor out possible errors caused by magnification differences by standardizing these films based on a
Table 2.
constant inferior border cortical bone height. Postoperative complications, including wound dehiscence, sequestrum formation, and pathologic fracture were recorded. The patients in the study group who subsequently received implants in the surgical site were also recorded.
Results The patients in the control and study groups ranged in age from 7 to 79 years. There were 7 females and 13 males. The diagnoses were as follows: odontogenic keratocysts (n = 11), ameloblastomas (n = 6), ossifying fibrrmas (n = 2), and myxoma (n = 1). The average postoperative radiographic follow-up period was 12.6 months with a range of 5 to 21 months. The mean clinical follow-up period was 3.5 years, with a range of 1.1 to 8 years. GROUP 1
(STUDY
GROUP)
The patients receiving cryotherapy combined with PCBM grafting following enucleation showed no post-
Group 2 (Cryosurgery Alone)
Patient
Age/Sex
Lesion
Site
Size (cm)
K L M N O P Q R
79/M 43/M 20/F 13/F 69/M 32/M 51/M 9/M
OKC Myxoma OKC OKC OKC OKC Os Fib OKC
Right mandible Right mandible Right mandible Right mandible Right mandible Right mandible Anterior mandible Left mandible
2 2 2 2 2.5 1.5 1 2
S T
10/M 54/M
Os Fib Amelo
Left mandible Anterior mandible
2.5 x 3 3.5 × 6
x x x X x x X x
3.5 2 2 3 6 3 2 2.5
Preoperative Measurement (mm)
Postoperative Measurement (mm)
% Preoperative Size
26 19 32 25 28 36 31 22
20 20 32 21 19 3428 11
77 105 100 84 68 93 90 50
29 38
13 14
45 37
Abbreviations: OKC, odontogenic keratocyst; Amelo, ameloblastoma; Os Fib, ossifying flbroma.
No. of Complications None None None None Pathologic fracture None None Wound dehiscence, sequestra None Pathologic fracture
SALMASSY AND POGREL
787
FIGURE 3. Patient E with cancellous iliac bone graft placed in the defect before wound closure.
A FIGURE 1. Diagram depicting panoramic mandibular index used for preoperative radiographs. Similar measurements were made on the postoperative radiographs with point (B) representing the superior aspect of alveolar ridge. A represents the inferior cortical margin.
operative complications. The average lesion was computed to be 2.8 cm X 5.5 cm in size, with a range of 2 cm to 8 cm in maximum diameter. With an average follow-up and radiographic evaluation period of 12.6 months (range, 5 to 21 months), these patients showed an alveolar height that was 81% of the preoperative state. Fifteen implants were placed in the operative sites of six of the patients. Patients E (Figs 2-4), and C (Figs 5,6) are shown as examples. GROUP 2 (CONTROL GROUP) Three of the patients who were treated with enucleation followed by cryosurgery alone had complications. There were two patients (O and T) who developed pathologic fractures. Patient O (Figs 7,8) acquired
FIGURE 2. Preoperative panoramic radiograph of patient E showing an ameloblastoma in the symphysis of the mandible.
a pathologic fracture of the ascending ramus in the fifth week postoperatively. He was managed on a blenderized diet for 6 weeks and advised to refrain from vigorous activities. Three months following this event, his occlusion remained stable and he had resumed a regular diet. The second pathologic fracture, patient T (Fig 9) occurred 8 weeks after cryosurgery (Fig 10). It was managed by placement of a titanium mesh tray and corticocancellous bone graft from an extraoral approach, and there have been no further sequelae. He is now 6 years postoperation and is without recurrence. One patient (R) developed wound dehiscence on the eighth postoperative day and required local management by means of daily irrigation and sterile gauze packings. This patient developed bone sequestra and, following debridement and sequestrectomy, the wound showed evidence of complete soft tissue coverage by the third week. For the control group of patients, the average radiographic size of the lesion was computed to be 2 cm × 3.5 cm, with a range of 1 cm to 6 cm in maximum diameter. The average follow-up period was 34.9 months (range, 10 to 96 months). Alveolar ridge height
FIGURE 4. Panoramic radiograph 13 months after initial surgery and 7 months after placement of implants. Note fixed removable bar attachment for the prosthesis.
788
CRYOSURGERY AND BONE GRAFFING
FIGURE 7. Preoperativepanoramicradiograph of patient O from group 2 showing large odontogenic keratocyst involving the right ramus and retromolar region of mandible.
FIGURE5. Radiographof patient C showing2 × 3-cm unilocular ameloblastoma of the left mandible before enucleation. averaged 78% of the preoperative value. None of the patients in this group acquired dental implants as part of their treatment plan.
Discussion The process of liquid nitrogen cryosurgery has been shown to have the capacity to devitalize the hard and
FIGURE 6. Close-upview of periapical radiograph from patient C at 1 yearpostoperationshowingthree implants and a goodtrabecular bone pattern.
soft tissues of the maxillofacial region. 5,7"9"HA4A7,18,22 With respect to the soft tissues, the advantages of cryosurgery are ease of application, relative lack of discomfort, no bleeding, and minimal scarring. The disadvantages, however, include an unpredictable degree of postoperative swelling and a lack of precision associated with the extent of tissue destruction at the time of treatment. If the soft tissue margins around a bony lesion are inadvertently exposed to the liquid nitrogen, the resultant soft tissue necrosis may account for wound dehiscence as a postoperative complication. It is known that human bone decreases in density and increases in porosity at the beginning of the third decade of life. 21'23'24 Maximum bone mass has been reported to be reached by about 30 years of age, after which it decreases, usually affecting women at a rate three times that of men, especially in the postmenopausal period. The fractures in this series occurred in patients who were beyond their fifth decade of life. Both were in lesions where one or more of the dimensions measured greater than 4.0 cm. Also, both lesions appeared to involve areas within 1 cm or less of the inferior border of the mandible, yet in different sites. This fact is important because if the correct technique
FIGURE 8. Radiographof patient O at 5 weeks after surgery and application of liquid nitrogen. The a r r o w shows the site of fracture below the right condyle.
SALMASSY AND POGREL
789 Table 3.
Location of the Lesion
Group 1 Group 2 Total
FIGURE 9. Preoperative radiograph of patient T showing large ameloblastoma of the anterior mandible.
is used in application of the liquid nitrogen, the resultant devitalization of bone can be expected to reach at least 2 to 3 m m beyond the margins of the bony cavity. 13,22As previously stated, the maximum bone weakness following cryotherapy appears to be at 8 weeks. In this study, the fractures occurred at or about that time. Both the lesions were in the group that did not receive immediate autogenous reconstruction. In contrast, there were four lesions of greater dimension in the group that received bone graft reconstruction (patients D, E, H, and I), two of whom were in their eighth decade of life at the time treatment was rendered. To assess whether the placement of an immediate bone graft facilitates later implant placement, it is necessary to look at the site of the lesion and its relationship to the crest of the ridge. Table 3 shows whether the lesion involved or violated the crest of the ridge or was confined to some portion below, referred to in the Table as an intrabony defect. In combining both groups, 75% (15 of 20) of the lesions involved the crest of the ridge resulting in a postsurgical defect in this location. None of the patients who had postsurgical complications had isolated intrabony defects. The patients with intrabony defects had an average sized lesion of 2.5 cm × 4.5 cm, with a range of 2 cm to 8 cm in maximum diameter, and retained an average of
Intrabony
Involvementof the Crest of the Alveolus
D, G, H L, M 5
A, B, C, E, F, I, J K, N, O, P, Q, R, S, T 15
96% of the original alveolar height at an average of 12 months after treatment. Two of the three intrabony lesions that were grafted (D and H) had sizes that were 7.5 to 8 cm in their greatest dimension. While the grafts did not contribute to alveolar height, they may have been successful in preventing postoperative pathologic fracture. Fifteen dental implants were placed in the patients in this study, all in group 1. In this group the average lesion was larger, and was destructive to the integrity of the native alveolar crest (7 of 10). Although the majority of odontogenic lesions involve the posterior mandible, five in this group were found in the anterior mandible. Of those, three patients (B, E, and I) accounted for 9 of the 15 implants. This is reasonable because the majotSity of dental implant reconstruction is geared to the anterior region. Only two patients in group 2 (Q and T), had anterior mandibular lesions. Why implants were not placed is unknown. The use of liquid nitrogen cryotherapy for the treatment of locally aggressive lesions of the jaws appears to be effective in preventing recurrence. Five of the 20 patients are at or beyond 5 years after treatment. The combination of cryotherapy with immediate cancellous bone reconstruction of the defect appears to assist in the prevention of postoperative complications such as pathologic fracture and may indeed be effective in preventing wound dehiscence and sequestrum formation, although the numbers in this study axe too small for statistical analysis. The patient that presents with a lesion 4 cm or greater in size, with violation of the crestal alveolus and less than 1 cm of Cortical bone at the inferior margin, may be at risk for pathologic fracture when cryotherapy is used. This certainly applies with respect to older patients, and it may be in their best interest to consider them as candidates for immediate reconstruction with an autogenous cancellous bone graft. The placement of cancellous bone in the surgical defect treated by enucleation combined with cryotherapy lends itself to dental rehabilitation with dental implants when warranted. The residual alveolus has been shown to be a satisfactory site. Whether this is also true for patients treated without a bone graft could not be determined from this study. References
FIGURE 10. Radiograph of patient T with fracture of right body of mandible 8 weeks postsurgery.
1. Toiler PA: Newer concepts of odontogenic cysts. Int J Oral Surg 1:3, 1972
790
DISCUSSION
2. Bramley PA: Treatment of cysts of the jaws. Proc R Soc Med 64:547, 1971 3. Arnott J: On the Treatment of Cancer by Regulated Application of an Anesthetic Temperature. London, England, J Churchill, 1851, p 32 4. Gage A, Green G, Neiders M, et al: Freezing bone without excision. An experimental study of bone-cell destruction and manner of regrowth in dogs. JAMA 196:720, 1966 5. Emmings F, Neiders M, Green G, et al: Freezing of the mandible without excision. J Oral Maxillofac Surg 24:145, 1966 6. Marcove RC, Miller TR: Treatment of primary and metastatic bone tumors by cryosurgery. JAMA 207:1890, 1969 7. Sippel HW, Emmings FG: Cryotherapy in the treatment of recurrent ossifying fibroma: Report of a case. J Oral Surg 27:32, 1969 8. Smith JJ, Fraser J: An estimation of tissue damage and thermal history in the cryolesion. Cryobiology 11:139, 1974 9. Rosen G, Vered IY: Cryosurgery for basal cell carcinoma of the head and neck. S Afr Med J 56:26, 1979 10. Whittaker DK: Mechanisms of tissue destruction following cryosurgery. Ann R Coll Surg Engl 66:313, 1984 11. Le Pivert PJ: Basic considerations of the cryolesion, in Albin RJ (ed): Handbook of Cryosurgery. New York, NY, Dekker, 1980, p 22 12. Bradley PF, Fisher AD: The cryosurgery of bone: An experimental and clinical assessment. Br J Oral Surg 13:111, 1975 13. Phemister DB: The fate of transplanted bone and regenerative powers of its various constituents. Surg Gynecol Obstet 19:393, 1914 14. Bradley PF: Modern trends in cryosurgery of the maxillofacial region. Int J Oral Surg 7:405, 1978
15. Voorsmit RA: The art of treating keratocysts: Fixation before enucleation. Paper presented at the 8th Congress of European Association for Maxillofacial Surgery held in Madrid, Spain, June 14-18, 1986 16. Pogrel MA: The use of liquid nitrogen cryotherapy in the management of locally aggressive bone lesions. J Oral MaxiUofac Surg 51:264, 1993 17. Webb J, Brockbank J: Treatment of odontogenic keratocysts by combined enucleation and cryosurgery. Int J Oral Surg 13:506, 1984 18. Emmings FG, Gage A, Koepf SW: Combined curettage and cryotherapy for recurrent ameloblastoma of the mandible. J Oral Surg 29:41, 1971 19. Fisher AD, Williams DF, Bradley PF: The effect of cryosurgery on the strength of bone. Br J Oral Surg 15:215, 1977 20. Marx RE, Kline SN: Principles and techniques of bony reconstruction in cancer patients, in Fonseca RJ, Davis WH (eds): Major Prosthetic Surgery. Philadelphia, PA, Saunders, 1986, p 347 21. Benson BW, Pirhoda TJ, Glass BJ: Variations in adult cortical bone mass as measured by a panoramic mandibular index. Oral Surg Oral Med Oral Pathol 71:349, 1991 22. Bradley PF: The cryosurgery of bone in the maxillofacial region, in Bradley PF (ed): Cryosurgery of the Maxillofacial Region, vol II. Boca Raton, FL, CRC 1986, pp 55-91 23. von Wowern N: Microradiographic and histomorphometric indices of mandibles for the diagnosis of osteopenia. Scand J Dent Res 90:47, 1982 24. Kribbs PJ, Smith DE, Chestnut CH: Oral findings in osteoporosis. Part II. Relationship between residual ridge and alveolar bone resorption and generalized skeletal osteopenia. J Prosthet Dent 50:719, 1983
d Oral Maxillofac Surg 53:790, 1995
Discussion Liquid Nitrogen Cryosurgery and Immediate Bone Grafting in the Management of Aggressive Primary Jaw Lesions Fred G. Emmings, DDS, P h D Pittsford, NY The preceding article supports the hypothesis that simultaneous grafting at the site of locally aggressive jaw tumors treated by enucleation and freezing decreases subsequent vulnerability to fracture at these sites. While the number of patients reported are inadequate to justify a definitive conclusion, the results certainly encourage simultaneous grafting. The addition of particulate cancellous bone and marrow (PCBM) to the matrix left after freezing likely hastens osteogenesis, which apparently strengthens the nonvital segment before it reaches its weakest condition around 8 weeks after freezing. It is not surprising that PCBM grafting is most applicable to larger lesions in older patients. In the past clinicians using freezing and enucleation simply applied maxillomandibular fixation during the fourth to tenth postoperative weeks. Grafting should clearly prove to be a better option. Although these clinical observations suggest that initiation of osteogenesis in the P C B M graft produces beneficial ef-
fects, experiments are needed to confirm that notion. The graft bed is nonvital and, although freezing spares larger vessels, smaller vessels are certainly occluded. In the graft bed, only the surrounding soft tissues have been protected from freezing. Studies need to be done to define the source of circulatory support for the graft, to confirm the presence of osteogenesis, and to compare osteogenesis in frozen tissues to that in nonfrozen recipient sites. The P C B M grafts did not contribute to preservation of alveolar ridge height. However, more than 80% of the original ridge height was present in both groups. This suggests that it might be feasible to install dental implants at the time of enucleation/freezing/grafting. Simultaneous grafting with implant placement has been successful in nonfrozen sites and might work when only 2 to 3 m m of bone has been devitalized around the recipient site. This is another reason we need the information generated by the studies proposed above. This is a clinical study reporting a small number of patients. Follow-up is insufficient in many of these cases to determine the efficacy of the treatment, but that was not the author's purpose. Neither was there adequate follow-up to draw many conclusions regarding the implants. Therefore, only modest inferences can be added to our knowledge base. However, the results are consistent with and support previously published advances.