647
RUGGIERO AND DONOFF
J Oral Maxillofac 49:647-652,
Surg
1991
Bone Regeneration After Mandibular Resection: Report of Two Cases S.L. RUGGIERO,
DMD, MD,* AND R.B. DONOFF, DMD, MDt
Bone, unlike soft tissue and nerve healing, comes the closest to actual tissue regeneration during repair. Osseous tissue, through a series of synthetic and resorptive events, in the presence of various external stimuli achieves a remarkable degree of similarity to the native tissue. Two potential sources of new tissue that operate in bone repair are located at endosteal and periosteal sites. This article focuses on the periosteal response by examining the clinical outcome after mandibular resection in two patients.
Case 2
Report of Cases Case 1 A 27-year-old man underwent a block resection of the right mandibular ramus, with disarticulation and an immediate bone from the left ilium, on December 12, 1978. He had been treated previously for a keratocyst in the area and had presented at this time because of a progressive facial asymmetry with expansion of the right mandibular ramus. Preoperative tomographic studies showed a large radiolucent lesion that encompassed the majority of right mandibular ramus, with extension into the condylar neck (Fig 1). There was evidence of perforation of the medial cortex as well as a fistulous tract in the right retromolar area secondary to a marsupialization procedure 3 years before. The patient underwent a definitive mandibular resection with extension into soft tissue performed via an extraoral approach. Periosteum over the lateral mandible was preserved, but most of the periosteum on the medial side, as well as the inferior alveolar nerve, was taken with the specimen. The Iistulous tract was oversewn after securing the iliac graft and placement of maxillomandibular fixation. Received from the Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, Boston. * Resident. t Professor and Chief. Address correspondence and reprint requests to Dr Donoff: Oral and Maxillofacial Surgery Service, Massachusetts Hospital. Boston, MA 02114. 0 1991 American
Association
geons 0276-2391/91/4906-0016$3.00/O
of Oral
and Maxillofacial
Despite antibiotic prophylaxis, the patient developed an area of drainage at the wound site intraorally and extraorally. The diagnosis of graft sepsis was supported by clinical and radiographic examination. On February 3, 1979, the bone graft was removed, the intraoral area again oversewn, and the external wound closed over a Penrose drain. The patient recovered uneventfully. He refused further reconstruction, but returns for yearly follow-up. Over the next 9 years, he functioned well and radiographic examination demonstrated regeneration of a rudimentary ramus, coronoid process, and a condylar process of the right mandible (Figs 2 and 3). There has been no evidence of recurrent disease.
General
This 27-year-old man presented with a chief complaint of paresthesia in the distribution of the right inferior alveolar nerve. He had a third molar removed in April 1983. In October 1983, he sought attention for right jaw pain, paresthesia of the right chin, and trismus. His pain improved, but because of persistent paresthesia he consulted a neurologist, who found no abnormalities. The pain and paresthesia disappeared without treatment, and he remained asymptomatic until October 1985, when the pain and the paresthesia recurred without swelling. Dilatin was prescribed for the pain, but had to be discontinued because of an allergic rash. Because of the persistence of pain, the patient presented to the Massachusetts General Hospital, where examination showed a fullness in the right medial mandible. Radiographs were nondiagnostic, but suggestive of a bony lesion (Fig 4). A computed tomography scan demonstrated a right mandibular lesion that proved to be Ewing’s sarcoma on biopsy. In March 1986, following a negative metastatic workup, chemotherapy with vincristine, cytoxan, and adriamycin was begun. In May 1986, the patient underwent a disarticulating resection of the right mandible, which included the surrounding periosteum. The contralateral mandible was stabilized with maxillomandibular fixation (Figs 4 and 5). From June through July 1986, the patient received photon therapy to 47.25 Gy and electron therapy to a total dose of 52.25 Gy. Radiotherapy was completed in August 1986. Adjuvant chemotherapy was completed in February 1987, and the patient has been observed since. Radiographs in December 1987 demonstrated remarkable bone regeneration (Fig 6).
Discussion Sur-
Since first discussed by Duhamel’ in 1742, the role of the periosteum in bone formation and graft-
648
BONE REGENERATION
AFTER MANDIBULAR
RESECTION
FIGURE 2. A, Immediate postoperative radiograph following removal of the iliac graft. B, Panoramic radiograph 2 years following resection showing new bone formation.
FIGURE 1. Preoperative radiograph showing a large lesion of the right ramus extending to the condylar and coronoid regions.
ing has been debated. Some authors have reported the necessity of the periosteum for bone healing, whereas others claim its presence interferes with the revascularization of bone grafts. The experiments of Macewen2 in 1912 differentiated between periosteum left without underlying hematoma, which resulted in no new bone formation, and periosteum with underlying hematoma, which allowed bony till of gaps of up to 7 mm. Clinically, fracture repair has been shown to proceed between two widely spaced fragments given the presence of periosteum.3 The importance of a viable and functioning periosteum has been recognized with regard to fracture repair and bone grafting. As defined by Tonna and Cronkite,4 the periosteum is a bilayered membrane surrounding all bony tissues, which is composed of an outer fibroblastic layer and an inner layer of osteoprogenitor cells. This osteogenic layer, in response to trauma or bone continuity defects, is stimulated to differentiate into osteoblasts and chondroblasts, which are crucial to the reparative process (ie, callus formation and new bone production) and restoring bony integrity. The endosteum
also contains osteoprogenitor cells that contribute to the osteogenic process, albeit in a limited capacity as compared to the periosteum in cases of large continuity defects. The cases described in this report support an important role for a periosteal response in healing. In the case of the recurrent keratocyst, the posterior mandible along with the medial periosteum were resected, leaving an intact lateral sleeve of periosteum. Over the course of the next 9 years, bone formation occurred proximally from the distal bony resection margin, resulting in a fully formed and functional condyle and coronoid process. Because this osteogenic process seemed to originate from the most distal bony resection margin, one cannot rule out the possibility of a contributory endosteal process as well. Nonetheless, the intact and viable periosteum probably played a major role in the formation of the proximal mandible. These periosteal remnants, with the stimulation of 9 years of function, produced bone tissue in accordance with the functional matrix theory, suggesting an interaction between the surrounding musculature and a boneproducing organ. The role of mechanical stress as a stimulis for bone regeneration has also been reported by Converse.’ The second case represents an interesting scenario in which bone formation occurred in an irradiated field in which the periosteum was extensively resected. Within 18 months following the initial resection, the patient had reformed the majority of the resected posterior mandible. In this instance, bone formation seems to have begun proximally in
RUGGIERO AND DONOFF
649
FIGURE 3. Panoramic radiograph 8 years postoperative showing the regeneration of a right mandibular ramus complete with a rudimentary condyle and coronoid process.
the region of the resected coronoid and condyle and progressed to the distal resection margin. Bone formation must have originated from periosteal remnants in the region of the temporomandibular joint and zygomatic arch because continuity with the distal mandible was never achieved. This bony apposition occurred within the constraints of a functional matrix and produced a coronoid and a condylar process similar to the first case. Bone production and repair within an irradiated field has been addressed by studies designed to
FIGURE 4. Preoperative radiograph showing a multilocular lesion of the right posterior mandible.
monitor the effect of radiation on the periosteum and the reparative process. These studies have shown that radiation-induced tissue changes were caused by the direct effect of ionizing radiation on the local cells and vasculature resulting in impaired circulation and hypoxia. Despite these local changes, irradiated periosteum still maintained its osteogenic potential (although to a lesser degree than nonirradiated tissue).6 The overall effect of radiation on the proliferative capacity of the periosteum was related to the total dose and the dosing
650
BONE REGENERATION
AFTER MANDIBULAR
RESECTION
FIGURE 5. Immediate postoperative panoramic radiograph of the remaining right mandible with a Penrose drain in place.
intervals. This relationship was addressed by Nathanson and Backstrom,’ who used a single dose of 1,000 to 4,000 rad of 6oCo to the mandible and found no effect on periosteal function with the lowest dose. However, there was a decrease in the osteogenic capacity of the periosteal cells of the outer circumference of the jaw between days 47 and 65 after 2,000 rad. At levels of 2,000 rad or more, there was also increased resorption and interference with cortical bone formation. The amount of radiation damage was demonstrated to be proportional to the dose. The latent period for the damage was inversely proportional to the dose, with blood vessel abnormalities and bone destruction being observed
at 12 weeks after 3,000 rad and at 24 weeks after 2,000 rad. More recently, Jacobsson et al6 quantified the effect of low-dose radiation on bone formation. They demonstrated that at a single dose level of 5,000 rad, the regenerative capacity is signilicantly reduced by 26% as compared with nonirradiated controls. In addition, there was no statistically significant change in the bone regenerative capacity following irradiation at a single dose of 2,500 rad. In contrast to these results, inhibition of the periosteal response did not occur with fractionated doses totaling 5,000 rad when grafts were implanted 18 to 28 days after radiation.’ A possible explana-
FIGURE 6. A panoramic radiograph of the right mandible 18 months postresection that clearly shows regeneration of the right ramus complete with a coronoid and condylar process.
651
RUGGIERO AND DONOFF
tion for this discrepancy can be found in the work of Hayashi and Suit,8 who showed that recovery of a fractured femur in mice after a single dose of irradiation was significantly less than after multiple daily doses. Inhibition of callus formation required a higher total radiation level with multiple doses than with a single dose. Thus, the body appears able to activate a reparative mechanism after repeated insults more easily than after a single exposure to irradiation. The work of Altobelli et al9 also reemphasized the importance of the periosteum with regard to bone healing in irradiated beds. Although the type of bone graft implanted into an irradiated bed appeared to play a major role in the soft-tissue integrity, it did not significantly affect the development of a bony union between host and graft bone. The original graft acted originally as a strut in the defect, but the majority of the new bone formation was from the host periosteum, not from the osteocytes transplanted with the microvascular graft or from creeping substitution of the free rib graft. These results support those of Macewen” and those reviewed by Eyre-Brooke.” The cases presented in this report support a major role for the reparative capacity of the periosteurn. The regeneration of the posterior mandibular segment complete with a coronoid process, condyle, and gonial angle indicates bone production in accordance with the functional matrix theory. A similar case was described by Yamashiro et al,” who reported bone regeneration following a subtotal mandibulectomy in a patient with long-standing osteoradionecrosis. In this instance, the author attributed the augmented bone formation to a “periosteal reaction” stimulated by chronic bone inflammation. In an attempt to identify a common denominator in these cases, one is confronted with the remarkable dissimilarities in pathology, treatment, and clinical course. In fact, the only factor common to both patients is the operative procedure itself, including the periosteal resection. Despite the numerous reports in the literature citing the deleterious effects of ionizing radiation on bone repair in general, and the periosteal response in particular, it is conceivable that the radiation exposure in case 2 was responsible for stimulating the periosteum. Such a contention is supported by the work of Kember,i2 which demonstrated an increase in the normal proliferative capacity of bone cells in irradiated periosteum. There is also evidence that bone regeneration in a nonirradiated tissue bed, as in the first clinical case, could represent a normal reparative process within a spectrum of potential periosteal responses. Such augmented periosteal responses have been
documented in the pediatric population.‘3-‘6 In these cases a “residual growth potential” was cited as the factor that enabled these patients to mount such an augmented periosteal response. Other investigators have attributed such cases of bony regeneration to “stimulated” periosteum from chronic endosteal and/or periosteal inflammation. 10,‘7.18With the exception of Yamashiro et al,” nearly all such cases of bone regeneration in the literature were reported in the pediatric age group where petiosteal tissue was left intact. What is remarkable about the second case presented in this report is that bone regeneration occurred in an environment where periosteum was widely resected and exposed to both chemotherapy and radiation. Clinical understanding of such bone regenerative potential may permit less extensive reconstructive procedures to be performed successfully with more reliance on the local periosteal response. What is clear from the cases presented in this report is that the mechanism of the periosteal reparative process and its response to the current modalities of surgery, radiation, and chemotherapy need to be investigated further. References I. Duhamel HL: Sur le development et le true des OS des animaux. Mem Acad Sci 55354. 1742 2. Macewen W: The Growth of Bone. Glasgow, UK, James Maclehose & Sons, 1912 3. Uddstromer L: Periosteal activity in new bone formation and growth of suture-bone grafts: A qualitative and quantitative study in growing rabbits. Uppsala, Sweden, Uppsala Faculty of Medicine, 1977 (dissertation abstr) 4. Tonna EA. Cronkite EP: Autoradiographic studies of cell proliferation in the periosteum of intact and fractured femora of mice utilizing DNA labeling with H3-thymine. Proc Sot Exp Biol Med 107:719, 1960 5. Converse J, Coccaro A, Valauri A: Resection of a giant ossifying fibroma through an intraoral approach in a 9year-old child: Immediate reconstruction and 6year cephalometric follow-up. Plast Reconstr Surg 69:5 1I, 1982 6. Jacobsson M, Jonsson A, Albrektsson T, et ah Alterations in bone regenerative capacity after low level gamma iradiation. A quantitative study. Stand J Plast Reconstr Surg 19:23 I. 1985 7. Nathanson A, Backstrom A: Effects of boCo gamma irradiation on teeth and jaw bone in the rabbit. Stand J Plast Reconstr Surg 12: I, 1978 8. Hayashi S. Suit H: Effect of fractionation of radiation dose on callus formation at the site of fracture. Radiology 101:181. 1971 9. Altobelli D. Lorente C, Handren J, et al: Free and microvascular bone grafting in the irradiated dog mandible. J Oral Maxillofac Surg 45:27, 1987 10. Eyre-Brook A: The periosteum: Its function reassessed. Orthop Rel Res 189:300, 1984
Clin
1I. Yamashiro M, Amagasa T, Horiuchi J, et al: Extensive osteoradionecrosis of the mandible associated with new bone formation. J Oral Maxillofac Surg 45:630, 1987
652
LEIOMYOSARCOMA
12. Kember N: Cell division in endochondral ossification. A study of cell proliferation by the method of tritiated thymidine autoradiography. J Bone Joint Surg 42B824, lY60 13. Shuker S: Spontaneous regeneration of the mandible in a child. J Maxillofac Surg 13:70, 1985 14. Kazanjian V: Spontaneous regeneration of bone following excision of section of mandible. Am J Orthod 34:242, 1948 15. Nwoku A: Unusually rapid bone regeneration following mandibular resection, J Maxillofac Surg 8:309, 1980
J Oral Maxillofac 49:652-655.
OF THE MANDIBLE
16. Nagase M, Ueda K, Suzuki I, et al: Spontaneous regeneration of the condyle following hemimandibulectomy by disarticulation. J Oral Maxillofac Surg 43:218, 1985 17. Adekeye E: Rapid bone regeneration subsequent to subtotal mandibulectomy. Oral Med Oral Surg Oral Path01 44:521, 1977 18. Elbeshir E: Spontaneous regeneration of the mandibular bone following hemimandibulectomy. Br J Oral Maxillofat Surg 28:128, 1990
Surg
1991
Leiomyosarcoma
of the Mandible:
A Case Report VEJAYAN KRISHNAN, BDS, MS,* CHARLES M. MIYAJI, DMD,t AND ELGENE G. MAINOUS, DDSS Smooth muscle is the prevalent tissue in the gastrointestinal and the genitourinary systems, but it is present in limited amount in the oral cavity. This may account for the low occurrence of smooth muscle neoplasms in the latter region. This article reports a primary, central leiomyosarcoma in the mandible. Report of Case A 27-year-old white man was seen at the Oral Surgery Clinic of the University of Minnesota on January 31, 1989. His chief complaints were pain and swelling in the right anterior mandible, first noticed in June 1988. The pain was localized to the region and was intermittent at first but was continuous for the past 3 months. He had also noticed loosening of the teeth in the region, but reported no altered sensation in his lower lip or chin. A general dentist, who had taken periapical radiographs, had been seen 3 months previously (Fig 1). A diagnosis of advanced chronic periodontitis was made and periodontal surgery was subsequently performed. However, the patient experienced no relief from his symptoms.
The patient’s past medical history was unremarkable with the exception of a history of drug abuse for the past 10 years. Clinical examination showed the presence of an exophytic lesion on the right parasymphysis of the mandible. The surface mucosa was intact but irregular. Buccolingual expansion was observed in the alveolar segment from the lower right lateral incisor to the right first molar. These teeth exhibited 2 + mobility. The area was tender to palpation. Regional lymph nodes were not palpable. A panoramic radiograph showed an ill-defined, diffuse radiolucency in the symphysis and right body of the mandible (Fig 21, measuring 6 cm in length and spanning the height of the mandible from the alveolar crest to 1 cm short of the inferior border. An incisional biopsy was performed under local anesthesia on January 31, 1989. The lesion was found to be firmly adherent to the overlying mucosa, making it difficult to raise a mucoperiosteal flap. The lesion was whit-
Received from the Department of Oral and Maxillofacial Surgery, University of Minnesota, Minneapolis. * Formerly Clinical Fellow; currently, Resident, Oral and Maxillofacial Surgery, University of Texas Health Science Center at Houston. t Resident. $ Formerly, Chairman; currently Chairman, Oral and Maxillofacial Surgery, University of Texas Health Science Center at Galveston. Address correspondence and reprint requests to Dr Krishnan: Oral and Maxillofacial Surgery, the University of Texas Health Science Center at Houston, 6515 John Freeman Ave. Texas Medical Center, PO Box 20068, Houston, TX 77225. 0 1991 American
Association
geons 0278-2391
I91 /4906-0017$3.00/O
of Oral
and Maxillofacial
Sur-
FIGURE 1. Periapical radiograph in the right parasymphysis of the mandible (September 1988). The radiograph shows an illdefined radiolucency and total loss of bony support for the bicuspid teeth.
RUGGIERO AND DONOFF
J Oral Maxillofac 49:647-652,
Surg
1991
Bone Regeneration After Mandibular Resection: Report of Two Cases S.L. RUGGIERO,
DMD, MD,* AND R.B. DONOFF, DMD, MDt
Bone, unlike soft tissue and nerve healing, comes the closest to actual tissue regeneration during repair. Osseous tissue, through a series of synthetic and resorptive events, in the presence of various external stimuli achieves a remarkable degree of similarity to the native tissue. Two potential sources of new tissue that operate in bone repair are located at endosteal and periosteal sites. This article focuses on the periosteal response by examining the clinical outcome after mandibular resection in two patients.
Case 2
Report of Cases Case 1 A 27-year-old man underwent a block resection of the right mandibular ramus, with disarticulation and an immediate bone from the left ilium, on December 12, 1978. He had been treated previously for a keratocyst in the area and had presented at this time because of a progressive facial asymmetry with expansion of the right mandibular ramus. Preoperative tomographic studies showed a large radiolucent lesion that encompassed the majority of right mandibular ramus, with extension into the condylar neck (Fig 1). There was evidence of perforation of the medial cortex as well as a fistulous tract in the right retromolar area secondary to a marsupialization procedure 3 years before. The patient underwent a definitive mandibular resection with extension into soft tissue performed via an extraoral approach. Periosteum over the lateral mandible was preserved, but most of the periosteum on the medial side, as well as the inferior alveolar nerve, was taken with the specimen. The Iistulous tract was oversewn after securing the iliac graft and placement of maxillomandibular fixation. Received from the Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, Boston. * Resident. t Professor and Chief. Address correspondence and reprint requests to Dr Donoff: Oral and Maxillofacial Surgery Service, Massachusetts Hospital. Boston, MA 02114. 0 1991 American
Association
geons 0276-2391/91/4906-0016$3.00/O
of Oral
and Maxillofacial
Despite antibiotic prophylaxis, the patient developed an area of drainage at the wound site intraorally and extraorally. The diagnosis of graft sepsis was supported by clinical and radiographic examination. On February 3, 1979, the bone graft was removed, the intraoral area again oversewn, and the external wound closed over a Penrose drain. The patient recovered uneventfully. He refused further reconstruction, but returns for yearly follow-up. Over the next 9 years, he functioned well and radiographic examination demonstrated regeneration of a rudimentary ramus, coronoid process, and a condylar process of the right mandible (Figs 2 and 3). There has been no evidence of recurrent disease.
General
This 27-year-old man presented with a chief complaint of paresthesia in the distribution of the right inferior alveolar nerve. He had a third molar removed in April 1983. In October 1983, he sought attention for right jaw pain, paresthesia of the right chin, and trismus. His pain improved, but because of persistent paresthesia he consulted a neurologist, who found no abnormalities. The pain and paresthesia disappeared without treatment, and he remained asymptomatic until October 1985, when the pain and the paresthesia recurred without swelling. Dilatin was prescribed for the pain, but had to be discontinued because of an allergic rash. Because of the persistence of pain, the patient presented to the Massachusetts General Hospital, where examination showed a fullness in the right medial mandible. Radiographs were nondiagnostic, but suggestive of a bony lesion (Fig 4). A computed tomography scan demonstrated a right mandibular lesion that proved to be Ewing’s sarcoma on biopsy. In March 1986, following a negative metastatic workup, chemotherapy with vincristine, cytoxan, and adriamycin was begun. In May 1986, the patient underwent a disarticulating resection of the right mandible, which included the surrounding periosteum. The contralateral mandible was stabilized with maxillomandibular fixation (Figs 4 and 5). From June through July 1986, the patient received photon therapy to 47.25 Gy and electron therapy to a total dose of 52.25 Gy. Radiotherapy was completed in August 1986. Adjuvant chemotherapy was completed in February 1987, and the patient has been observed since. Radiographs in December 1987 demonstrated remarkable bone regeneration (Fig 6).
Discussion Sur-
Since first discussed by Duhamel’ in 1742, the role of the periosteum in bone formation and graft-
648
BONE REGENERATION
AFTER MANDIBULAR
RESECTION
FIGURE 2. A, Immediate postoperative radiograph following removal of the iliac graft. B, Panoramic radiograph 2 years following resection showing new bone formation.
FIGURE 1. Preoperative radiograph showing a large lesion of the right ramus extending to the condylar and coronoid regions.
ing has been debated. Some authors have reported the necessity of the periosteum for bone healing, whereas others claim its presence interferes with the revascularization of bone grafts. The experiments of Macewen2 in 1912 differentiated between periosteum left without underlying hematoma, which resulted in no new bone formation, and periosteum with underlying hematoma, which allowed bony till of gaps of up to 7 mm. Clinically, fracture repair has been shown to proceed between two widely spaced fragments given the presence of periosteum.3 The importance of a viable and functioning periosteum has been recognized with regard to fracture repair and bone grafting. As defined by Tonna and Cronkite,4 the periosteum is a bilayered membrane surrounding all bony tissues, which is composed of an outer fibroblastic layer and an inner layer of osteoprogenitor cells. This osteogenic layer, in response to trauma or bone continuity defects, is stimulated to differentiate into osteoblasts and chondroblasts, which are crucial to the reparative process (ie, callus formation and new bone production) and restoring bony integrity. The endosteum
also contains osteoprogenitor cells that contribute to the osteogenic process, albeit in a limited capacity as compared to the periosteum in cases of large continuity defects. The cases described in this report support an important role for a periosteal response in healing. In the case of the recurrent keratocyst, the posterior mandible along with the medial periosteum were resected, leaving an intact lateral sleeve of periosteum. Over the course of the next 9 years, bone formation occurred proximally from the distal bony resection margin, resulting in a fully formed and functional condyle and coronoid process. Because this osteogenic process seemed to originate from the most distal bony resection margin, one cannot rule out the possibility of a contributory endosteal process as well. Nonetheless, the intact and viable periosteum probably played a major role in the formation of the proximal mandible. These periosteal remnants, with the stimulation of 9 years of function, produced bone tissue in accordance with the functional matrix theory, suggesting an interaction between the surrounding musculature and a boneproducing organ. The role of mechanical stress as a stimulis for bone regeneration has also been reported by Converse.’ The second case represents an interesting scenario in which bone formation occurred in an irradiated field in which the periosteum was extensively resected. Within 18 months following the initial resection, the patient had reformed the majority of the resected posterior mandible. In this instance, bone formation seems to have begun proximally in
RUGGIERO AND DONOFF
649
FIGURE 3. Panoramic radiograph 8 years postoperative showing the regeneration of a right mandibular ramus complete with a rudimentary condyle and coronoid process.
the region of the resected coronoid and condyle and progressed to the distal resection margin. Bone formation must have originated from periosteal remnants in the region of the temporomandibular joint and zygomatic arch because continuity with the distal mandible was never achieved. This bony apposition occurred within the constraints of a functional matrix and produced a coronoid and a condylar process similar to the first case. Bone production and repair within an irradiated field has been addressed by studies designed to
FIGURE 4. Preoperative radiograph showing a multilocular lesion of the right posterior mandible.
monitor the effect of radiation on the periosteum and the reparative process. These studies have shown that radiation-induced tissue changes were caused by the direct effect of ionizing radiation on the local cells and vasculature resulting in impaired circulation and hypoxia. Despite these local changes, irradiated periosteum still maintained its osteogenic potential (although to a lesser degree than nonirradiated tissue).6 The overall effect of radiation on the proliferative capacity of the periosteum was related to the total dose and the dosing
650
BONE REGENERATION
AFTER MANDIBULAR
RESECTION
FIGURE 5. Immediate postoperative panoramic radiograph of the remaining right mandible with a Penrose drain in place.
intervals. This relationship was addressed by Nathanson and Backstrom,’ who used a single dose of 1,000 to 4,000 rad of 6oCo to the mandible and found no effect on periosteal function with the lowest dose. However, there was a decrease in the osteogenic capacity of the periosteal cells of the outer circumference of the jaw between days 47 and 65 after 2,000 rad. At levels of 2,000 rad or more, there was also increased resorption and interference with cortical bone formation. The amount of radiation damage was demonstrated to be proportional to the dose. The latent period for the damage was inversely proportional to the dose, with blood vessel abnormalities and bone destruction being observed
at 12 weeks after 3,000 rad and at 24 weeks after 2,000 rad. More recently, Jacobsson et al6 quantified the effect of low-dose radiation on bone formation. They demonstrated that at a single dose level of 5,000 rad, the regenerative capacity is signilicantly reduced by 26% as compared with nonirradiated controls. In addition, there was no statistically significant change in the bone regenerative capacity following irradiation at a single dose of 2,500 rad. In contrast to these results, inhibition of the periosteal response did not occur with fractionated doses totaling 5,000 rad when grafts were implanted 18 to 28 days after radiation.’ A possible explana-
FIGURE 6. A panoramic radiograph of the right mandible 18 months postresection that clearly shows regeneration of the right ramus complete with a coronoid and condylar process.
651
RUGGIERO AND DONOFF
tion for this discrepancy can be found in the work of Hayashi and Suit,8 who showed that recovery of a fractured femur in mice after a single dose of irradiation was significantly less than after multiple daily doses. Inhibition of callus formation required a higher total radiation level with multiple doses than with a single dose. Thus, the body appears able to activate a reparative mechanism after repeated insults more easily than after a single exposure to irradiation. The work of Altobelli et al9 also reemphasized the importance of the periosteum with regard to bone healing in irradiated beds. Although the type of bone graft implanted into an irradiated bed appeared to play a major role in the soft-tissue integrity, it did not significantly affect the development of a bony union between host and graft bone. The original graft acted originally as a strut in the defect, but the majority of the new bone formation was from the host periosteum, not from the osteocytes transplanted with the microvascular graft or from creeping substitution of the free rib graft. These results support those of Macewen” and those reviewed by Eyre-Brooke.” The cases presented in this report support a major role for the reparative capacity of the periosteurn. The regeneration of the posterior mandibular segment complete with a coronoid process, condyle, and gonial angle indicates bone production in accordance with the functional matrix theory. A similar case was described by Yamashiro et al,” who reported bone regeneration following a subtotal mandibulectomy in a patient with long-standing osteoradionecrosis. In this instance, the author attributed the augmented bone formation to a “periosteal reaction” stimulated by chronic bone inflammation. In an attempt to identify a common denominator in these cases, one is confronted with the remarkable dissimilarities in pathology, treatment, and clinical course. In fact, the only factor common to both patients is the operative procedure itself, including the periosteal resection. Despite the numerous reports in the literature citing the deleterious effects of ionizing radiation on bone repair in general, and the periosteal response in particular, it is conceivable that the radiation exposure in case 2 was responsible for stimulating the periosteum. Such a contention is supported by the work of Kember,i2 which demonstrated an increase in the normal proliferative capacity of bone cells in irradiated periosteum. There is also evidence that bone regeneration in a nonirradiated tissue bed, as in the first clinical case, could represent a normal reparative process within a spectrum of potential periosteal responses. Such augmented periosteal responses have been
documented in the pediatric population.‘3-‘6 In these cases a “residual growth potential” was cited as the factor that enabled these patients to mount such an augmented periosteal response. Other investigators have attributed such cases of bony regeneration to “stimulated” periosteum from chronic endosteal and/or periosteal inflammation. 10,‘7.18With the exception of Yamashiro et al,” nearly all such cases of bone regeneration in the literature were reported in the pediatric age group where petiosteal tissue was left intact. What is remarkable about the second case presented in this report is that bone regeneration occurred in an environment where periosteum was widely resected and exposed to both chemotherapy and radiation. Clinical understanding of such bone regenerative potential may permit less extensive reconstructive procedures to be performed successfully with more reliance on the local periosteal response. What is clear from the cases presented in this report is that the mechanism of the periosteal reparative process and its response to the current modalities of surgery, radiation, and chemotherapy need to be investigated further. References I. Duhamel HL: Sur le development et le true des OS des animaux. Mem Acad Sci 55354. 1742 2. Macewen W: The Growth of Bone. Glasgow, UK, James Maclehose & Sons, 1912 3. Uddstromer L: Periosteal activity in new bone formation and growth of suture-bone grafts: A qualitative and quantitative study in growing rabbits. Uppsala, Sweden, Uppsala Faculty of Medicine, 1977 (dissertation abstr) 4. Tonna EA. Cronkite EP: Autoradiographic studies of cell proliferation in the periosteum of intact and fractured femora of mice utilizing DNA labeling with H3-thymine. Proc Sot Exp Biol Med 107:719, 1960 5. Converse J, Coccaro A, Valauri A: Resection of a giant ossifying fibroma through an intraoral approach in a 9year-old child: Immediate reconstruction and 6year cephalometric follow-up. Plast Reconstr Surg 69:5 1I, 1982 6. Jacobsson M, Jonsson A, Albrektsson T, et ah Alterations in bone regenerative capacity after low level gamma iradiation. A quantitative study. Stand J Plast Reconstr Surg 19:23 I. 1985 7. Nathanson A, Backstrom A: Effects of boCo gamma irradiation on teeth and jaw bone in the rabbit. Stand J Plast Reconstr Surg 12: I, 1978 8. Hayashi S. Suit H: Effect of fractionation of radiation dose on callus formation at the site of fracture. Radiology 101:181. 1971 9. Altobelli D. Lorente C, Handren J, et al: Free and microvascular bone grafting in the irradiated dog mandible. J Oral Maxillofac Surg 45:27, 1987 10. Eyre-Brook A: The periosteum: Its function reassessed. Orthop Rel Res 189:300, 1984
Clin
1I. Yamashiro M, Amagasa T, Horiuchi J, et al: Extensive osteoradionecrosis of the mandible associated with new bone formation. J Oral Maxillofac Surg 45:630, 1987
652
LEIOMYOSARCOMA
12. Kember N: Cell division in endochondral ossification. A study of cell proliferation by the method of tritiated thymidine autoradiography. J Bone Joint Surg 42B824, lY60 13. Shuker S: Spontaneous regeneration of the mandible in a child. J Maxillofac Surg 13:70, 1985 14. Kazanjian V: Spontaneous regeneration of bone following excision of section of mandible. Am J Orthod 34:242, 1948 15. Nwoku A: Unusually rapid bone regeneration following mandibular resection, J Maxillofac Surg 8:309, 1980
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OF THE MANDIBLE
16. Nagase M, Ueda K, Suzuki I, et al: Spontaneous regeneration of the condyle following hemimandibulectomy by disarticulation. J Oral Maxillofac Surg 43:218, 1985 17. Adekeye E: Rapid bone regeneration subsequent to subtotal mandibulectomy. Oral Med Oral Surg Oral Path01 44:521, 1977 18. Elbeshir E: Spontaneous regeneration of the mandibular bone following hemimandibulectomy. Br J Oral Maxillofat Surg 28:128, 1990
Surg
1991
Leiomyosarcoma
of the Mandible:
A Case Report VEJAYAN KRISHNAN, BDS, MS,* CHARLES M. MIYAJI, DMD,t AND ELGENE G. MAINOUS, DDSS Smooth muscle is the prevalent tissue in the gastrointestinal and the genitourinary systems, but it is present in limited amount in the oral cavity. This may account for the low occurrence of smooth muscle neoplasms in the latter region. This article reports a primary, central leiomyosarcoma in the mandible. Report of Case A 27-year-old white man was seen at the Oral Surgery Clinic of the University of Minnesota on January 31, 1989. His chief complaints were pain and swelling in the right anterior mandible, first noticed in June 1988. The pain was localized to the region and was intermittent at first but was continuous for the past 3 months. He had also noticed loosening of the teeth in the region, but reported no altered sensation in his lower lip or chin. A general dentist, who had taken periapical radiographs, had been seen 3 months previously (Fig 1). A diagnosis of advanced chronic periodontitis was made and periodontal surgery was subsequently performed. However, the patient experienced no relief from his symptoms.
The patient’s past medical history was unremarkable with the exception of a history of drug abuse for the past 10 years. Clinical examination showed the presence of an exophytic lesion on the right parasymphysis of the mandible. The surface mucosa was intact but irregular. Buccolingual expansion was observed in the alveolar segment from the lower right lateral incisor to the right first molar. These teeth exhibited 2 + mobility. The area was tender to palpation. Regional lymph nodes were not palpable. A panoramic radiograph showed an ill-defined, diffuse radiolucency in the symphysis and right body of the mandible (Fig 21, measuring 6 cm in length and spanning the height of the mandible from the alveolar crest to 1 cm short of the inferior border. An incisional biopsy was performed under local anesthesia on January 31, 1989. The lesion was found to be firmly adherent to the overlying mucosa, making it difficult to raise a mucoperiosteal flap. The lesion was whit-
Received from the Department of Oral and Maxillofacial Surgery, University of Minnesota, Minneapolis. * Formerly Clinical Fellow; currently, Resident, Oral and Maxillofacial Surgery, University of Texas Health Science Center at Houston. t Resident. $ Formerly, Chairman; currently Chairman, Oral and Maxillofacial Surgery, University of Texas Health Science Center at Galveston. Address correspondence and reprint requests to Dr Krishnan: Oral and Maxillofacial Surgery, the University of Texas Health Science Center at Houston, 6515 John Freeman Ave. Texas Medical Center, PO Box 20068, Houston, TX 77225. 0 1991 American
Association
geons 0278-2391
I91 /4906-0017$3.00/O
of Oral
and Maxillofacial
Sur-
FIGURE 1. Periapical radiograph in the right parasymphysis of the mandible (September 1988). The radiograph shows an illdefined radiolucency and total loss of bony support for the bicuspid teeth.
