DENTAL IMPLANTS
Migration of Alloplastic Bone Graft Material in Infected Conditions: A Case Study and Animal Experiment Hyun Seok, DDS,* Seuk-Keun Lee, DDS, PhD,y Seong-Gon Kim, DDS, PhD,z Tae-Yeon Kang, PhD,x Myung-Jin Lee, MS,k and Weon-Sik Chae, PhD{ Purpose:
Distant migration associated with sinus lifting procedures has not been investigated. In the present study, a case of distant migration of graft material was observed, and the potential mechanisms of migration were analyzed using material analysis and in vivo experiments.
Materials and Methods:
The migrated graft material was biphasic calcium phosphate-based alloplastic material (BCP), and its physical properties were compared with those of xenogenic material (Bio-Oss). The comparisons of the physical properties were performed using scanning electronic microscopic, x-ray diffraction, and Fourier-transform infrared absorbance spectra analysis. The comparative graft migration study was performed using the subcutaneous pocket model in rats (n = 10). The clinical case was analyzed by histologic section and energy dispersive x-ray (EDX) microanalysis.
Results:
The observed diffraction patterns from the Bio-Oss revealed characteristic diffractions for the hydroxyapatite phase, and those from the BCP revealed additional diffractions that could be assigned to the tricalcium phosphate phase. In the animal model, the graft migration distances observed in the BCP group were significantly greater than those observed in the Bio-Oss group (P = .012). In the clinical case, the lymphatic vessels of the submandibular gland contained foreign materials that were morphologically similar to those of the maxillary sinus. EDX microanalysis revealed that the particles in the lymphatic vessels exhibited calcium concentrations that were approximately 200 times greater than those in the adjacent glandular tissue.
Conclusions: In the present study, BCP-based sinus grafts had migrated into the submandibular glandular area by way of the lymphatic chain in the presented clinical case. Ó 2014 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 72:1093.e1-1093.e11, 2014
The restoration of maxillary edentulism has often been challenged by atrophy of the maxillary alveolar ridge and severe pneumatization of the maxillary sinus.1,2 Bone grafting into the maxillary sinus has been an essential procedure for successful reconstruction
of the maxillary dentition. The bone graft material for the sinus lifting procedure can be composed of autogenous, allogenic, xenogenic, or alloplastic materials. Although autogenous graft material has been the reference standard material, it has several
*Resident, Department of Oral and Maxillofacial Surgery, College of Dentistry, Gangneung-Wonju National University, Gangneung, Korea.
The present study was supported by a grant from the NextGeneration BioGreen21 Program (grant PJ009013), Rural Devel-
yProfessor, Department of Oral and Maxillofacial Pathology, College
opment Administration, Republic of Korea.
of Dentistry, Gangneung-Wonju National University, Gangneung, Korea.
Address correspondence and reprint requests to Dr Kim: Depart-
zAssociate Professor and Chairman, Department of Oral and
ment of Oral and Maxillofacial Surgery, College of Dentistry,
Maxillofacial Surgery, College of Dentistry, Gangneung-Wonju
Gangneung-Wonju National University, Gangneung, Gangwondo
National University, Gangneung, Korea.
210-702, Republic of Korea; e-mail: [email protected]
xResearcher, Gangneung Center, Korea Basic Science Institute,
Received October 29 2013
Gangneung, Korea. kResearcher, Gangneung Center, Korea Basic Science Institute,
Ó 2014 American Association of Oral and Maxillofacial Surgeons
Gangneung, Korea.
0278-2391/14/00147-5$36.00/0
{Researcher, Gangneung Center, Korea Basic Science Institute,
Accepted January 24 2014
http://dx.doi.org/10.1016/j.joms.2014.01.021
Gangneung, Korea.
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disadvantages, including donor site morbidity, a limited amount of available bone, and postoperative changes in volume. Alloplastic materials have also been successfully used for sinus lifting procedures.3-5 Most alloplastic materials are composed of inorganic materials, such as hydroxyapatite (HA) or b-tricalcium phosphate (b-TCP). The main complication with the use of alloplastic material after sinus augmentation has been postoperative infection.6 Most alloplastic materials provide ideal conditions for the attachment of microorganisms.7 Therefore, the condition of the recipient site is an important factor for a successful procedure. Graft infections have been associated with preexisting sinus disease.8 Routine computed tomography (CT) examinations have identified 25% of patients as having maxillary sinus disease.9 One survey indicated that 35% of the population had had sinus problems within the previous year.10 Given the high rate of maxillary sinus problems, a patient scheduled to receive a sinus graft must undergo a CT examination. Most investigators have reported that alloplastic materials should not be placed into infected beds.11 If the patient has a seriously infected maxillary sinus, the sinus infection should be treated before the bone graft procedure. Perforation of the sinus mucosa is one of the most frequent intraoperative complications of sinus grafting.12-14 Sinus infections can spread into the perforated mucosa. However, the complications of sinus graft procedures in infected maxillary sinuses have been limited to graft failure.15,16 Although migration of the graft material has been a frequent complication in other areas, distant graft migration after bone grafting procedures in the maxillary sinus has not previously been reported. Recently, we observed a rare case with complications associated with a bone graft procedure in the maxillary sinus. Alloplastic graft material had been placed into the infected maxillary sinus of the patient, and swelling was observed in the buccal and submandibular areas after the grafting procedure. We suspected that the swelling in the submandibular area might have resulted from distant migration of the graft materials from the maxillary sinus, and foreign bodylike materials were collected from the lymphatic vessels of the submandibular gland. To support this hypothesis, scanning electronic microscopic (SEM) images of the specimen from the submandibular gland were collected, and energy dispersive x-ray (EDX) microanalysis was performed to determine the calcium content of the area of interest. Additionally, we evaluated the physical properties of the alloplastic material in relation to those of a well-known xenograft. The migration of these 2 graft materials in the infected condition was compared, and the potential mechanisms responsible for the distant migration were considered.
Materials and Methods X-RAY DIFFRACTION, FOURIER-TRANSFORM INFRARED ABSORBANCE SPECTRA, AND SEM
We purchased the same graft material (GENESIS BCP, Dio Corp, Busan, Korea; abbreviated as BCP) that had been found to migrate to distant locations in the patient reported in the present case study. Although the physical properties of BCP have been previously published,17 the purchased material underwent x-ray diffraction (XRD), Fourier-Transform Infrared (FT-IR) absorption, and SEM examinations for comparison with other commercial products. In brief, the XRD patterns of the samples were recorded using an x-ray diffractometer (X’Pert Pro MPD, PANalytical, Almelo, The Netherlands) using a Cu-Ka (l = 1.5418 A) radiation source. FT-IR measurements were performed using a Vertex 80 spectrometer (Bruker Optics, Ettlingen, Germany) coupled with a Hyperion 3000 microscope (Bruker Optics) equipped with a germaniumattenuated total reflectance objective lens (ATR20) and a liquid nitrogen-cooled mercury cadmium telluride detector. SEM imaging was performed using an electron microscope (SU-70, Hitachi, Tokyo, Japan). The results were compared with those obtained from another commercial product (Bio-Oss, Geistlich, Wolhusen, Switzerland, abbreviated as Bio-Oss). The detailed XRD, FT-IR, and SEM procedures followed those of a previous publication.18 ANIMAL EXPERIMENT
Ten rats (average weight 270 mg, range 250-300) were used in the present study. The institutional animal care and use committee of the Gangneung-Wonju National University approved our experiment (GWNU2013-8). General anesthesia was induced by way of intramuscular injections of a combination of Zoletil 50 (15 mg/kg; Vibac, Carros, France) and Rumpun (0.2 mL/kg; Bayer Korea, Seoul, Korea). The back of the rat was shaved and disinfected with povidone-iodine, and the operation site was infiltrated with 0.5 mL of 2% lidocaine containing 1:100,000 epinephrine. A longitudinal incision approximately 5 mm in length was then made in the skin. A subcutaneous pocket was prepared by blunt dissection. In the experimental group, contaminated BCP was placed into the pockets of 5 rats. The grafts were contaminated with a bacterial culture medium for 5 minutes before grafting. The medium contained 104 colony-forming units of Staphylococcus aureus (ATCC 25923), and these bacteria were kindly provided by Dong-Heun Baek (Dankook University). For comparison, contaminated Bio-Oss was inserted into the pockets of an additional 5 rats. The incisions were closed with 3-0 silk suture. Each rat was individually caged and received food and water. Postoperatively, the rats received gentamycin 1 mg/kg (Kookje, Seoul,
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Korea) intramuscularly 3 times daily for 3 days. All the rats were humanly sacrificed 7 days after the procedure. After death, the specimens were fixed in 10% formalin and underwent histologic evaluation. Local migration of the grafts was evaluated by measuring the distances between the graft site and the most distantly migrated particle. The difference between groups was evaluated using a t test for independent samples. The significance level was set at P < .05. EDX MICROANALYSIS
The specimens from the submandibular gland of the patient were embedded in paraffin. Next, the paraffin block was sliced into 5-mm section and deparaffinized. Unstained 5-mm sections were coated with 0.7 nm of OsO4 (HPC-1SW; Vacuum Device Inc, Mito city, Japan). Each specimen was observed using a scanning electron microscope (SU-70, Hitachi) and underwent EDX microanalysis (EDAX Genesis; Pv 77, EDAX, Mahwah, NJ) to analyze the elements of the area of interest. The compositions of the elements were compared with those of the adjacent area.
However, the BCP had 2 different features. First, additional diffractions were observed (indicated by the asterisks in Fig 2) and were assigned to the TCP phase (ICDD, 01-086-1585). Second, the diffraction peaks, which were narrower than those of the Bio-Oss, indicated the greater crystalline characteristics of the BCP. Figure 3 shows the FT-IR spectra of the Bio-Oss and BCP. Both materials exhibited the typical HA absorption peaks that correspond to the stretching vibration of PO43 (960 to 1,090 cm1) and the stretching and liberation modes of OH-vibration (3,570 cm1 and 630 cm1, respectively). However, the Bio-Oss exhibited a relatively weak OH-vibrational absorption at 3,570 cm1, indicating that the Bio-Oss had low crystallinity. The notable differences between the measured absorption spectra of Bio-Oss and BCP were the presence of HPO42 ions and carbonate (CO32) ions. The absorption spectrum of the BioOss exhibited a weak absorption at 880 cm1, which is related to the P-O-H vibration of HPO42 ions, and the broad absorption bands at 1,350 to 1,550 cm1 can be assigned to the v3 mode of carbonate ions. However, in the case of BCP, no absorption bands were found in either of these regions.
Results MATERIAL ANALYSIS
SEM images of the BCP revealed that differently sized spherical particles with smooth surfaces were gathered together (Fig 1A). However, examination of the Bio-Oss revealed that the differently sized particles were attached to areas of greater mass and that the particles were highly irregularly shaped and had rough surfaces (Fig 1B). The observed diffraction pattern of the BioOss revealed diffraction characteristic of the HA phase (International Center for Diffraction Data [ICDD], 086-0740). The broad diffraction peaks indicated that the Bio-Oss had minimal crystalline characteristics.
IN VIVO EXPERIMENT
Inflammation around the graft sites in both groups was observed, and the degree of inflammation was mild to moderate (Figs 4A,B). Some graft materials were removed during sample processing, because the specimens did not undergo the decalcification process. Some graft materials were found in the distant connective tissues. The distance of graft migration in the BCP and Bio-Oss groups was 1.98 0.63 mm and 0.81 0.14 mm, respectively (Fig 4C). The difference between the groups was statistically significant (P = .012). All the migrated graft material in the Bio-Oss
FIGURE 1. Scanning microscopic images. A, GENESIS biphasic calcium phosphate-based alloplastic material (BCP). B, Bio-Oss (Bio-Oss). Seok et al. Alloplastic Bone Graft Migration and Infection. J Oral Maxillofac Surg 2014.
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FIGURE 2. X-ray diffractions of Bio-Oss and GENESIS biphasic calcium phosphate-based alloplastic material (BCP). Asterisks indicate the tricalcium phosphate [Ca3(PO4)2] phase of the BCP diffractions. Seok et al. Alloplastic Bone Graft Migration and Infection. J Oral Maxillofac Surg 2014.
group was found in the interstitial tissue. However, in the BCP group, some migrated graft material was found in the lymphatic vessels (Fig 4A). The morphology of the migrated graft material in this group was also different. The size of the migrated materials in the Bio-Oss group was mostly larger than 20 mm (Fig 4B). However, the migrated materials of the BCP group were much smaller (2 to 3 mm). Small particles were agglomerated in the lymphatic vessels.
Case Report On May 12, 2012, a 62-year-old man was referred from a private dental clinic to our hospital because of swelling
FIGURE 3. Fourier-transform infrared absorbance spectra of BioOss and GENESIS biphasic calcium phosphate-based alloplastic material (BCP). Seok et al. Alloplastic Bone Graft Migration and Infection. J Oral Maxillofac Surg 2014.
ALLOPLASTIC BONE GRAFT MIGRATION AND INFECTION
in the right buccal and submandibular areas. The patient had previously received a BCP graft in the right maxillary sinus. According to the manufacturer’s specifications, the BCP graft was composed of 60% HA and 40% b-TCP. Dental implants had simultaneously been installed at the right maxillary first and second molar areas. After the surgery, the patient complained of pain and swelling in the right maxilla; however, these symptoms had improved after a few days. The patient exhibited swelling and tenderness in the right submandibular area, and these symptoms had not resolved spontaneously. Enhanced CT was performed for additional evaluation. The CT image revealed 2 enlarged submandibular lymph nodes located in the posterior and lateral areas of the submandibular gland (Fig 5A). Excisional biopsy of the right submandibular gland and the adjacent lymph nodes was performed using the submandibular approach. The removed submandibular gland and lymph nodes exhibited necrotic changes (Fig 5B). After the surgery, the symptoms disappeared, and a histologic examination was performed. The sections of the embedded specimens were stained with hematoxylin-eosin. The specimens contained a submandibular gland and an associated lymph node. The gland exhibited normal features, but swelling was found in the lymph nodes. The lymph nodes exhibited lymphadenitis and atrophic features. Furthermore, a diffuse foreign body reaction was observed in the surrounding connective tissue, which could have caused the lymphadenitis. From the biopsy findings, the condition was determined to be ‘‘lymphadenitis accompanied by a foreign body reaction’’ (Fig 6). According to the pathologist, the origin of the foreign body could have been the right maxillary sinus area. Therefore, granulation tissue and grafted alloplastic particle materials were removed from the right maxillary first and second molar areas in which the dental implants had been installed in the patient under local anesthesia. Histopathologic examinations of the enucleated granulation tissue and alloplastic materials were performed to determine whether the foreign materials found in the submandibular lymph nodes were morphologically the same as those from the maxillary sinus. The samples were stained with hematoxylin-eosin. Numerous particulate materials that were weakly stained with hematoxylin remained in the graft area. The embedded specimens contained degraded bone graft materials that had been infiltrated with inflammatory cells and exhibited foreign body reactions. Biopsy revealed that the area of interest contained poorly organized graft bone tissue and exhibited a foreign body reaction (Fig 7). An SEM image of an unstained 5-mm section of the submandibular gland, as detected by EDX microanalysis, is shown in Fig 8. The left magnified image shows normal gland tissue, and the right is inside the area of
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FIGURE 4. Histologic results (hematoxylin-eosin staining, original magnification 20). A, Graft migration in the experimental group. ‘‘Grafts’’ indicate grafted site. Migrated graft material was found in the lymphatic vessels (magnified image in the box; original magnification 400). B, Graft migration in the control group. ‘‘Grafts’’ indicate grafted site, and graft migration was found near the original graft site. The size of the migrated graft materials in the control group was larger than 20 mm (magnified image in the box; original magnification 400). C, The average distances of graft migration in each group. Seok et al. Alloplastic Bone Graft Migration and Infection. J Oral Maxillofac Surg 2014.
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FIGURE 5. A, Radiographic findings. Preoperative computed tomography image of the right submandibular area. Enlarged submandibular lymph nodes shown (arrows). (Fig 5 continued on next page.) Seok et al. Alloplastic Bone Graft Migration and Infection. J Oral Maxillofac Surg 2014.
the lymphatic duct (Fig 8A). In the lymphatic duct, irregularly shaped material was observed (Fig 8A). EDX microanalysis revealed that the concentrations of calcium (Ca) and carbon (C) were similar in the lymphatic duct (Fig 8B), and the Ca/C ratio was 0.6041. However, the normal gland had a lower concentration of Ca than C, and the Ca/C ratio was 0.0031 (Fig 8C). Analysis of the elements revealed that the Ca/C ratio of the lymphatic duct was 200 times greater than that around the normal gland tissue.
Discussion In the present report, the patient had undergone right maxillary sinus elevation surgery by way of the lateral approach and simultaneous bone augmentation using an alloplastic material. According to the dentist who had referred the patient to our hospital, a discharge of pus was present in the sinus area at grafting. After surgery, the patient complained about
swelling and pain in the right submandibular area. The postoperative inflammation might have resulted from the presence of graft materials in the infected area. In our animal study, BCP was found to migrate farther than Bio-Oss in the infected condition (Fig 4A). This finding might have resulted from differences in the particles’ sizes and compositions. Our element analysis revealed that the foreign bodies in the submandibular lymphatic vessels had a high calcium content (Fig 8B). Collectively, these results have demonstrated that the submandibular swelling resulted from the distant migration of graft materials from the maxillary sinus through the lymphatic chain. Foreign body materials are sometimes found in the lymph nodes of other parts of the body. For example, silicone gel implants for mammoplasty can rupture, which often results in the migration of foreign material to the auxiliary lymph nodes.19 Such migration can cause diseases, including foreign body granuloma and silicone lymphadenopathy.20,21 When silicone prostheses are
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FIGURE 5 (cont’d). B, Macroscopic view of the removed right submandibular gland and lymph nodes. Necrotic changes in the lymph nodes were observed (arrows). Seok et al. Alloplastic Bone Graft Migration and Infection. J Oral Maxillofac Surg 2014.
used to replace metatarsophalangeal joints, silicone elastomer particulate debris can migrate into the ipsilateral femoral lymph nodes and cause foreign body giant cell reactions and lymphadenopathies.22 Lymphatic vessels from the maxillary sinus not only drain through the natural ostia, but certain vessels also exhibit transmural drainage to the nasal lymphatic vessels through bony gaps.23 A number of these vessels drain into the ipsilateral submandibular lymph nodes (Fig 9). Furthermore, the nasal and maxillary sinus lymphatic capillary networks have diameters of 15 to 200 mm.23 According to our histologic findings, particulate materials were present in the submandibular lymphatic channels and connective tissue, in which a diffuse granulomatoid foreign body reaction occurred (Fig 6). The particulate materials were not stained with H&E, but they exhibited slight yellowish-gold color and diameters that ranged from 1 to 50 mm (Fig 6). It might have been possible that the grafted materials migrated from the maxillary sinus to the submandibular lymph nodes through the lymphatic channels. The fine gran-
ular particles were never engulfed by macrophages; however, they somehow induced cytotoxic damage of the macrophages and extracellular matrix. Fibrinoid necrosis and cellular apoptosis of macrophages and fibroblasts frequently appeared in the involved lesion. One extraordinary finding was the presence of iatrogenic destruction of the salivary acinar structures. Some of the damaged salivary acini had gradually degenerated and separated from the main salivary parenchyma (Fig 6). The bone grafting material used in our patient was BCP. BCP is composed of 60% HA and 40% b-TCP.18 BCP has been shown to be an effective bone graft material in animal models. However, b-TCP has a high dissolution rate in acidic conditions.24 In general, b-TCP resorbs and disappears rapidly before new bone formation.25 When b-TCP is used as a bone graft material, it is combined with HA. BCP degrades faster than HA, and the rate of degradation depends on the HA/b-TCP ratio.26 Bio-Oss is an inorganic bovine bone with a composition similar to that of natural bone.27 Bovine bone is composed of 93% HA and 7% b-TCP.28 The
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FIGURE 6. Histologic findings from the removed right submandibular gland and lymph nodes (hematoxylin-eosin staining, original magnification 100). Seok et al. Alloplastic Bone Graft Migration and Infection. J Oral Maxillofac Surg 2014.
proportion of b-TCP in BCP is greater than that of BioOss. Because of these differences, under acidic conditions such as those present during inflammation, BCP might degrade into small particles and migrate into the surrounding tissue more easily than Bio-Oss. Our animal experiments indicated that contaminated BCP
migrated farther than contaminated Bio-Oss (Figs 4A,C). In the present study, Bio-Oss was also found to migrate through the interstitial fibrous tissue in contaminated conditions. The swelling induced by the inflammation might have widened the tissue space and facilitated movement of the graft. However, no clinical
FIGURE 7. Histologic findings of alloplastic bone graft materials and granulation tissues in the right maxillary sinus area (hematoxylin-eosin staining, original magnification 400). Seok et al. Alloplastic Bone Graft Migration and Infection. J Oral Maxillofac Surg 2014.
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FIGURE 8. A, Scanning electron microscopic image of the unstained submandibular gland section (original magnification 10). Lower Right Corner, A magnified image of the lymphatic duct. Upper Left Corner, Image of the acinar portion shown (original magnification 400). B, Energy-dispersive x-ray microanalysis revealing lower concentration of calcium than carbon in the gland tissue. C, Energy-dispersive x-ray microanalysis revealing similar concentrations of calcium and carbon in the lymphatic duct. Seok et al. Alloplastic Bone Graft Migration and Infection. J Oral Maxillofac Surg 2014.
cases of distant migration of Bio-Oss were found in a PubMed search (available at: http://www.ncbi.nlm. nih.gov/PubMed, accessed October 28, 2013), which might have been because most clinicians will not perform grafts into an infected bed and Bio-Oss might not enter the lymphatic vessels. The incidence of maxillary sinusitis after sinus grafting has been reported to be up to 20%.8 In the present case, the patient had pre-existing purulent maxillary sinusitis. Additionally, mucosal perforation occurred during the procedure. In cases of mucosal perforation,
graft materials can become lost in the sinus and induce maxillary sinusitis.29 Microorganisms can potentially invade the graft site through the mucosal perforation, which can worsen the pre-existing maxillary sinusitis. Although the present patient had received the sinus graft by way of the lateral window approach, the dentist did not apply any membrane to the bony window. Owing to the high content of b-TCP, the BCP dissolved in the acidic inflammatory conditions. Thus, the size of the graft materials would have been reduced, and they could migrate through the window
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FIGURE 9. Proposed mechanism for the distant migration from the maxillary sinus to the submandibular gland. When graft material has been introduced into an infected maxillary sinus, the grafted material can migrate though the opened window by way of the lymphatic channel. Migrated graft materials can collect in distant organs, such as the submandibular gland. Seok et al. Alloplastic Bone Graft Migration and Infection. J Oral Maxillofac Surg 2014.
(Fig 9). Mucosal perforation can result in graft migration or loss.30 The graft materials had moved to the submandibular gland through the buccal lymphatic channels. Exposed graft material in cases of chronic bacterial infection should be removed.30 The distant migration of maxillary sinus grafts has not been previously reported. In the present case, the experimental data strongly supported the following conclusions. First, the materials found in the submandibular lymphatic vessel originated from the maxillary sinus. Second, foreign bodies and inflammatory reactions were observable in the submandibular lymph nodes. Third, degraded BCP and a foreign body reaction were found in the specimens from the maxillary sinus. Fourth, BCP had a greater b-TCP content than did the Bio-Oss. Fifth, the animal model demonstrated that BCP could migrate farther than Bio-Oss. Finally, SEM with EDX microanalysis showed
that the foreign bodies in the submandibular lymphatic vessel had calcium contents that were 200-fold greater than those of the adjacent tissue. The limitation of the present study was that the animal model could not exactly simulate the conditions of the presented clinical case. The grafts were placed in skin pockets on the back, and the back has blood supplies and lymphatic drainage pathways that are different from those of the maxillary sinus. We could not use the orthotopic animal model in the present study for the following reasons: 1) the sinus dimensions of the experimental animal were too small to be compared to humans, and 2) the lymphatic drainage pathway from the maxillary sinus of the animal is different from that of humans. Given the different lymphatic drainage systems and the rare specific complication ratio, we believe exactly simulating the conditions of the presented clinical case would
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have been impossible. Additionally, migration of graft material used for the maxillary sinus lifting procedure has not been previously studied. Thus, we used a back skin pocket model of graft migration.31 From our findings, we can conclude that the foreign body materials in the sinus cavity and submandibular lymph nodes were the same. Also, we believe the foreign bodies in the submandibular lymph nodes had migrated from the sinus cavity by way of the lymphatic vessels because the sinus cavity was the only site at which the graft materials had been placed. b-TCP–based materials can easily be resolved in acidic conditions. Therefore, b-TCP–based synthetic materials should not be used in inflamed areas. The application of a membrane over the window could prevent the distant migration of the graft material through the buccal lymphatic chain. Acknowledgments We thank Yong-Tae Park for the collection of the patient’s records and writing of the preliminary case report.
References 1. Fugazzotto PA, Wheeler SL, Lindsay JA: Success and failure rates of cylinder implants in type IV bone. J Periodontol 64:1085, 1993 2. Jaffin RA, Berman CL: The excessive loss of Branemark fixtures in type IV bone: A 5-year analysis. J Periodontol 62:2, 1991 3. Wheeler SL: Sinus augmentation for dental implants: The use of alloplastic materials. J Oral Maxillofac Surg 55:1287, 1997 4. Garlini G, Redemagni M, Donini M, et al: Maxillary sinus elevation with an alloplastic material and implants: 11 Years of clinical and radiologic follow-up. J Oral Maxillofac Surg 68:1152, 2010 5. Kim YK, Yun PY, Lim SC, et al: Clinical evaluations of OSTEONÒ as a new alloplastic material in sinus bone grafting and its effect on bone healing. J Biomed Mater Res B Appl Biomater 86:270, 2008 6. DoudGalli SK, Lebowitz RA, Giacchi RJ, et al: Chronic sinusitis complicating sinus lift surgery. Am J Rhinol 15:181, 2001 7. Jo YJ, Kim KH, Koo KT, et al: Initial adhesion of bone marrow stromal cells to various bone graft substitutes. J Periodontal Implant Sci 41:67, 2011 8. Timmenga NM, Raghoebar GM, Boering G, et al: Maxillary sinus function after sinus lifts for the insertion of dental implants. J Oral Maxillofac Surg 55:936, 1997 9. Havas TE, Motbey JA, Gullane PJ: Prevalence of incidental abnormalities on computed tomographic scans of the paranasal sinuses. Arch Otolaryngol Head Neck Surg 114:856, 1988 10. Lieu JE, Feinstein AR: Confirmations and surprises in the association of tobacco use with sinusitis. Arch Otolaryngol Head Neck Surg 126:940, 2000 11. Alkan A, C ¸ elebi N, Bas¸ B: Acute maxillary sinusitis associated with internal sinus lifting: Report of a case. Eur J Dent 2:69, 2008
1093.e11 12. Jensen O, Shulman L, Block M, et al: Report of the sinus consensus conference of 1996. Int J Oral Maxillofac Implants 13:11, 1998 13. Nolan PJ, Freeman K, Kraut RA: Correlation between schneiderian membrane perforation and sinus lift graft outcome: A retrospective evaluation of 359 augmented sinus. J Oral Maxillofac Surg 72:47, 2014 14. Khoury F: Augmentation of the sinus floor with mandibular bone block and simultaneous implantation: A 6-year clinical investigation. Int J Oral Maxillofac Implants 14:557, 1999 15. Nkenke E, Stelzle F: Clinical outcomes of sinus floor augmentation for implant placement using autogenous bone or bone substitutes: A systematic review. Clin Oral Implants Res 20(suppl 4): 124, 2009 16. Regev E, Smith RA, Perrott DH, et al: Maxillary sinus complications related to endosseous implants. Int J Oral Maxillofac Implants 10:451, 1995 17. Lee SW, Kim SG, Balazsi C, et al: Comparative study of hydroxyapatite from eggshells and synthetic hydroxyapatite for bone regeneration. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 113:348, 2012 18. Yang DH, Park HN, Bae MS, et al: Evaluation of Genesis-BCPTM scaffold composed of hydroxyapatite and b-tricalcium phosphate on bone formation. Macromol Res 20:627, 2012 19. Hausner R, Schoen F, Mendez-Fernandez M, et al: Migration of silicone gel to axillary lymph nodes after prosthetic mammoplasty. Arch Pathol Lab Med 105:371, 1981 20. Cook PD, Osborne BM, Connor RL, et al: Follicular lymphoma adjacent to foreign body granulomatous inflammation and fibrosis surrounding silicone breast prosthesis. Am J Surg Pathol 19:712, 1995 21. Santos-Briz A, L opez-Rıos F, De Agustın P: Granulomatous reaction to silicone in auxiliary lymph nodes. Acta Cytol 43:1163, 2011 22. Sammarco GJ, Tabatowski K: Silicone lymphadenopathy associated with failed prosthesis of the hallux: A case report and literature review. Foot Ankle 13:273, 1992 23. Hosemann W, K€ uhnel T, Burchard A, et al: Histochemical detection of lymphatic drainage pathways in the middle nasal meatus. Rhinology 36:50, 1998 24. LeGeros RZ: Calcium phosphates in oral biology and medicine. Monoqr Oral Sci 15:1, 1990 25. von Arx T, Cochran DL, Hermann J, et al: Lateral ridge augmentation and implant placement: An experimental study evaluating implant osseointegration in different augmentation materials in the canine mandible. Int J Oral Maxillofac Implants 16:343, 2000 26. LeGeros R, Lin S, Rohanizadeh R, et al: Biphasic calcium phosphate bioceramics: Preparation, properties and applications. J Mater Sci Mater Med 14:201, 2003 27. Tamimi FM, Torres J, Tresguerres I, et al: Bone augmentation in rabbit calvariae: Comparative study between Bio-OssÒ and a novel b-TCP/DCPD granulate. J Clin Periodontol 33:922, 2006 28. Ooi C, Hamdi M, Ramesh S: Properties of hydroxyapatite produced by annealing of bovine bone. Ceram Int 33:1171, 2007 29. Kasabah S, Krug J, Simunek A, et al: Can we predict maxillary sinus mucosa perforation? Acta Medica 46:19, 2003 30. Ward BB, Terrell JE, Collins JK: Methicillin-resistant Staphylococcus aureus sinusitis associated with sinus lift bone grafting and dental implants: A case report. J Oral Maxillofac Surg 66: 231, 2008 31. Newman J: Review of soft tissue augmentation in the face. Clin Cosmet Invest Dermatol 2:141, 2009
Migration of Alloplastic Bone Graft Material in Infected Conditions: A Case Study and Animal Experiment Hyun Seok, DDS,* Seuk-Keun Lee, DDS, PhD,y Seong-Gon Kim, DDS, PhD,z Tae-Yeon Kang, PhD,x Myung-Jin Lee, MS,k and Weon-Sik Chae, PhD{ Purpose:
Distant migration associated with sinus lifting procedures has not been investigated. In the present study, a case of distant migration of graft material was observed, and the potential mechanisms of migration were analyzed using material analysis and in vivo experiments.
Materials and Methods:
The migrated graft material was biphasic calcium phosphate-based alloplastic material (BCP), and its physical properties were compared with those of xenogenic material (Bio-Oss). The comparisons of the physical properties were performed using scanning electronic microscopic, x-ray diffraction, and Fourier-transform infrared absorbance spectra analysis. The comparative graft migration study was performed using the subcutaneous pocket model in rats (n = 10). The clinical case was analyzed by histologic section and energy dispersive x-ray (EDX) microanalysis.
Results:
The observed diffraction patterns from the Bio-Oss revealed characteristic diffractions for the hydroxyapatite phase, and those from the BCP revealed additional diffractions that could be assigned to the tricalcium phosphate phase. In the animal model, the graft migration distances observed in the BCP group were significantly greater than those observed in the Bio-Oss group (P = .012). In the clinical case, the lymphatic vessels of the submandibular gland contained foreign materials that were morphologically similar to those of the maxillary sinus. EDX microanalysis revealed that the particles in the lymphatic vessels exhibited calcium concentrations that were approximately 200 times greater than those in the adjacent glandular tissue.
Conclusions: In the present study, BCP-based sinus grafts had migrated into the submandibular glandular area by way of the lymphatic chain in the presented clinical case. Ó 2014 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 72:1093.e1-1093.e11, 2014
The restoration of maxillary edentulism has often been challenged by atrophy of the maxillary alveolar ridge and severe pneumatization of the maxillary sinus.1,2 Bone grafting into the maxillary sinus has been an essential procedure for successful reconstruction
of the maxillary dentition. The bone graft material for the sinus lifting procedure can be composed of autogenous, allogenic, xenogenic, or alloplastic materials. Although autogenous graft material has been the reference standard material, it has several
*Resident, Department of Oral and Maxillofacial Surgery, College of Dentistry, Gangneung-Wonju National University, Gangneung, Korea.
The present study was supported by a grant from the NextGeneration BioGreen21 Program (grant PJ009013), Rural Devel-
yProfessor, Department of Oral and Maxillofacial Pathology, College
opment Administration, Republic of Korea.
of Dentistry, Gangneung-Wonju National University, Gangneung, Korea.
Address correspondence and reprint requests to Dr Kim: Depart-
zAssociate Professor and Chairman, Department of Oral and
ment of Oral and Maxillofacial Surgery, College of Dentistry,
Maxillofacial Surgery, College of Dentistry, Gangneung-Wonju
Gangneung-Wonju National University, Gangneung, Gangwondo
National University, Gangneung, Korea.
210-702, Republic of Korea; e-mail: [email protected]
xResearcher, Gangneung Center, Korea Basic Science Institute,
Received October 29 2013
Gangneung, Korea. kResearcher, Gangneung Center, Korea Basic Science Institute,
Ó 2014 American Association of Oral and Maxillofacial Surgeons
Gangneung, Korea.
0278-2391/14/00147-5$36.00/0
{Researcher, Gangneung Center, Korea Basic Science Institute,
Accepted January 24 2014
http://dx.doi.org/10.1016/j.joms.2014.01.021
Gangneung, Korea.
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disadvantages, including donor site morbidity, a limited amount of available bone, and postoperative changes in volume. Alloplastic materials have also been successfully used for sinus lifting procedures.3-5 Most alloplastic materials are composed of inorganic materials, such as hydroxyapatite (HA) or b-tricalcium phosphate (b-TCP). The main complication with the use of alloplastic material after sinus augmentation has been postoperative infection.6 Most alloplastic materials provide ideal conditions for the attachment of microorganisms.7 Therefore, the condition of the recipient site is an important factor for a successful procedure. Graft infections have been associated with preexisting sinus disease.8 Routine computed tomography (CT) examinations have identified 25% of patients as having maxillary sinus disease.9 One survey indicated that 35% of the population had had sinus problems within the previous year.10 Given the high rate of maxillary sinus problems, a patient scheduled to receive a sinus graft must undergo a CT examination. Most investigators have reported that alloplastic materials should not be placed into infected beds.11 If the patient has a seriously infected maxillary sinus, the sinus infection should be treated before the bone graft procedure. Perforation of the sinus mucosa is one of the most frequent intraoperative complications of sinus grafting.12-14 Sinus infections can spread into the perforated mucosa. However, the complications of sinus graft procedures in infected maxillary sinuses have been limited to graft failure.15,16 Although migration of the graft material has been a frequent complication in other areas, distant graft migration after bone grafting procedures in the maxillary sinus has not previously been reported. Recently, we observed a rare case with complications associated with a bone graft procedure in the maxillary sinus. Alloplastic graft material had been placed into the infected maxillary sinus of the patient, and swelling was observed in the buccal and submandibular areas after the grafting procedure. We suspected that the swelling in the submandibular area might have resulted from distant migration of the graft materials from the maxillary sinus, and foreign bodylike materials were collected from the lymphatic vessels of the submandibular gland. To support this hypothesis, scanning electronic microscopic (SEM) images of the specimen from the submandibular gland were collected, and energy dispersive x-ray (EDX) microanalysis was performed to determine the calcium content of the area of interest. Additionally, we evaluated the physical properties of the alloplastic material in relation to those of a well-known xenograft. The migration of these 2 graft materials in the infected condition was compared, and the potential mechanisms responsible for the distant migration were considered.
Materials and Methods X-RAY DIFFRACTION, FOURIER-TRANSFORM INFRARED ABSORBANCE SPECTRA, AND SEM
We purchased the same graft material (GENESIS BCP, Dio Corp, Busan, Korea; abbreviated as BCP) that had been found to migrate to distant locations in the patient reported in the present case study. Although the physical properties of BCP have been previously published,17 the purchased material underwent x-ray diffraction (XRD), Fourier-Transform Infrared (FT-IR) absorption, and SEM examinations for comparison with other commercial products. In brief, the XRD patterns of the samples were recorded using an x-ray diffractometer (X’Pert Pro MPD, PANalytical, Almelo, The Netherlands) using a Cu-Ka (l = 1.5418 A) radiation source. FT-IR measurements were performed using a Vertex 80 spectrometer (Bruker Optics, Ettlingen, Germany) coupled with a Hyperion 3000 microscope (Bruker Optics) equipped with a germaniumattenuated total reflectance objective lens (ATR20) and a liquid nitrogen-cooled mercury cadmium telluride detector. SEM imaging was performed using an electron microscope (SU-70, Hitachi, Tokyo, Japan). The results were compared with those obtained from another commercial product (Bio-Oss, Geistlich, Wolhusen, Switzerland, abbreviated as Bio-Oss). The detailed XRD, FT-IR, and SEM procedures followed those of a previous publication.18 ANIMAL EXPERIMENT
Ten rats (average weight 270 mg, range 250-300) were used in the present study. The institutional animal care and use committee of the Gangneung-Wonju National University approved our experiment (GWNU2013-8). General anesthesia was induced by way of intramuscular injections of a combination of Zoletil 50 (15 mg/kg; Vibac, Carros, France) and Rumpun (0.2 mL/kg; Bayer Korea, Seoul, Korea). The back of the rat was shaved and disinfected with povidone-iodine, and the operation site was infiltrated with 0.5 mL of 2% lidocaine containing 1:100,000 epinephrine. A longitudinal incision approximately 5 mm in length was then made in the skin. A subcutaneous pocket was prepared by blunt dissection. In the experimental group, contaminated BCP was placed into the pockets of 5 rats. The grafts were contaminated with a bacterial culture medium for 5 minutes before grafting. The medium contained 104 colony-forming units of Staphylococcus aureus (ATCC 25923), and these bacteria were kindly provided by Dong-Heun Baek (Dankook University). For comparison, contaminated Bio-Oss was inserted into the pockets of an additional 5 rats. The incisions were closed with 3-0 silk suture. Each rat was individually caged and received food and water. Postoperatively, the rats received gentamycin 1 mg/kg (Kookje, Seoul,
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Korea) intramuscularly 3 times daily for 3 days. All the rats were humanly sacrificed 7 days after the procedure. After death, the specimens were fixed in 10% formalin and underwent histologic evaluation. Local migration of the grafts was evaluated by measuring the distances between the graft site and the most distantly migrated particle. The difference between groups was evaluated using a t test for independent samples. The significance level was set at P < .05. EDX MICROANALYSIS
The specimens from the submandibular gland of the patient were embedded in paraffin. Next, the paraffin block was sliced into 5-mm section and deparaffinized. Unstained 5-mm sections were coated with 0.7 nm of OsO4 (HPC-1SW; Vacuum Device Inc, Mito city, Japan). Each specimen was observed using a scanning electron microscope (SU-70, Hitachi) and underwent EDX microanalysis (EDAX Genesis; Pv 77, EDAX, Mahwah, NJ) to analyze the elements of the area of interest. The compositions of the elements were compared with those of the adjacent area.
However, the BCP had 2 different features. First, additional diffractions were observed (indicated by the asterisks in Fig 2) and were assigned to the TCP phase (ICDD, 01-086-1585). Second, the diffraction peaks, which were narrower than those of the Bio-Oss, indicated the greater crystalline characteristics of the BCP. Figure 3 shows the FT-IR spectra of the Bio-Oss and BCP. Both materials exhibited the typical HA absorption peaks that correspond to the stretching vibration of PO43 (960 to 1,090 cm1) and the stretching and liberation modes of OH-vibration (3,570 cm1 and 630 cm1, respectively). However, the Bio-Oss exhibited a relatively weak OH-vibrational absorption at 3,570 cm1, indicating that the Bio-Oss had low crystallinity. The notable differences between the measured absorption spectra of Bio-Oss and BCP were the presence of HPO42 ions and carbonate (CO32) ions. The absorption spectrum of the BioOss exhibited a weak absorption at 880 cm1, which is related to the P-O-H vibration of HPO42 ions, and the broad absorption bands at 1,350 to 1,550 cm1 can be assigned to the v3 mode of carbonate ions. However, in the case of BCP, no absorption bands were found in either of these regions.
Results MATERIAL ANALYSIS
SEM images of the BCP revealed that differently sized spherical particles with smooth surfaces were gathered together (Fig 1A). However, examination of the Bio-Oss revealed that the differently sized particles were attached to areas of greater mass and that the particles were highly irregularly shaped and had rough surfaces (Fig 1B). The observed diffraction pattern of the BioOss revealed diffraction characteristic of the HA phase (International Center for Diffraction Data [ICDD], 086-0740). The broad diffraction peaks indicated that the Bio-Oss had minimal crystalline characteristics.
IN VIVO EXPERIMENT
Inflammation around the graft sites in both groups was observed, and the degree of inflammation was mild to moderate (Figs 4A,B). Some graft materials were removed during sample processing, because the specimens did not undergo the decalcification process. Some graft materials were found in the distant connective tissues. The distance of graft migration in the BCP and Bio-Oss groups was 1.98 0.63 mm and 0.81 0.14 mm, respectively (Fig 4C). The difference between the groups was statistically significant (P = .012). All the migrated graft material in the Bio-Oss
FIGURE 1. Scanning microscopic images. A, GENESIS biphasic calcium phosphate-based alloplastic material (BCP). B, Bio-Oss (Bio-Oss). Seok et al. Alloplastic Bone Graft Migration and Infection. J Oral Maxillofac Surg 2014.
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FIGURE 2. X-ray diffractions of Bio-Oss and GENESIS biphasic calcium phosphate-based alloplastic material (BCP). Asterisks indicate the tricalcium phosphate [Ca3(PO4)2] phase of the BCP diffractions. Seok et al. Alloplastic Bone Graft Migration and Infection. J Oral Maxillofac Surg 2014.
group was found in the interstitial tissue. However, in the BCP group, some migrated graft material was found in the lymphatic vessels (Fig 4A). The morphology of the migrated graft material in this group was also different. The size of the migrated materials in the Bio-Oss group was mostly larger than 20 mm (Fig 4B). However, the migrated materials of the BCP group were much smaller (2 to 3 mm). Small particles were agglomerated in the lymphatic vessels.
Case Report On May 12, 2012, a 62-year-old man was referred from a private dental clinic to our hospital because of swelling
FIGURE 3. Fourier-transform infrared absorbance spectra of BioOss and GENESIS biphasic calcium phosphate-based alloplastic material (BCP). Seok et al. Alloplastic Bone Graft Migration and Infection. J Oral Maxillofac Surg 2014.
ALLOPLASTIC BONE GRAFT MIGRATION AND INFECTION
in the right buccal and submandibular areas. The patient had previously received a BCP graft in the right maxillary sinus. According to the manufacturer’s specifications, the BCP graft was composed of 60% HA and 40% b-TCP. Dental implants had simultaneously been installed at the right maxillary first and second molar areas. After the surgery, the patient complained of pain and swelling in the right maxilla; however, these symptoms had improved after a few days. The patient exhibited swelling and tenderness in the right submandibular area, and these symptoms had not resolved spontaneously. Enhanced CT was performed for additional evaluation. The CT image revealed 2 enlarged submandibular lymph nodes located in the posterior and lateral areas of the submandibular gland (Fig 5A). Excisional biopsy of the right submandibular gland and the adjacent lymph nodes was performed using the submandibular approach. The removed submandibular gland and lymph nodes exhibited necrotic changes (Fig 5B). After the surgery, the symptoms disappeared, and a histologic examination was performed. The sections of the embedded specimens were stained with hematoxylin-eosin. The specimens contained a submandibular gland and an associated lymph node. The gland exhibited normal features, but swelling was found in the lymph nodes. The lymph nodes exhibited lymphadenitis and atrophic features. Furthermore, a diffuse foreign body reaction was observed in the surrounding connective tissue, which could have caused the lymphadenitis. From the biopsy findings, the condition was determined to be ‘‘lymphadenitis accompanied by a foreign body reaction’’ (Fig 6). According to the pathologist, the origin of the foreign body could have been the right maxillary sinus area. Therefore, granulation tissue and grafted alloplastic particle materials were removed from the right maxillary first and second molar areas in which the dental implants had been installed in the patient under local anesthesia. Histopathologic examinations of the enucleated granulation tissue and alloplastic materials were performed to determine whether the foreign materials found in the submandibular lymph nodes were morphologically the same as those from the maxillary sinus. The samples were stained with hematoxylin-eosin. Numerous particulate materials that were weakly stained with hematoxylin remained in the graft area. The embedded specimens contained degraded bone graft materials that had been infiltrated with inflammatory cells and exhibited foreign body reactions. Biopsy revealed that the area of interest contained poorly organized graft bone tissue and exhibited a foreign body reaction (Fig 7). An SEM image of an unstained 5-mm section of the submandibular gland, as detected by EDX microanalysis, is shown in Fig 8. The left magnified image shows normal gland tissue, and the right is inside the area of
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FIGURE 4. Histologic results (hematoxylin-eosin staining, original magnification 20). A, Graft migration in the experimental group. ‘‘Grafts’’ indicate grafted site. Migrated graft material was found in the lymphatic vessels (magnified image in the box; original magnification 400). B, Graft migration in the control group. ‘‘Grafts’’ indicate grafted site, and graft migration was found near the original graft site. The size of the migrated graft materials in the control group was larger than 20 mm (magnified image in the box; original magnification 400). C, The average distances of graft migration in each group. Seok et al. Alloplastic Bone Graft Migration and Infection. J Oral Maxillofac Surg 2014.
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FIGURE 5. A, Radiographic findings. Preoperative computed tomography image of the right submandibular area. Enlarged submandibular lymph nodes shown (arrows). (Fig 5 continued on next page.) Seok et al. Alloplastic Bone Graft Migration and Infection. J Oral Maxillofac Surg 2014.
the lymphatic duct (Fig 8A). In the lymphatic duct, irregularly shaped material was observed (Fig 8A). EDX microanalysis revealed that the concentrations of calcium (Ca) and carbon (C) were similar in the lymphatic duct (Fig 8B), and the Ca/C ratio was 0.6041. However, the normal gland had a lower concentration of Ca than C, and the Ca/C ratio was 0.0031 (Fig 8C). Analysis of the elements revealed that the Ca/C ratio of the lymphatic duct was 200 times greater than that around the normal gland tissue.
Discussion In the present report, the patient had undergone right maxillary sinus elevation surgery by way of the lateral approach and simultaneous bone augmentation using an alloplastic material. According to the dentist who had referred the patient to our hospital, a discharge of pus was present in the sinus area at grafting. After surgery, the patient complained about
swelling and pain in the right submandibular area. The postoperative inflammation might have resulted from the presence of graft materials in the infected area. In our animal study, BCP was found to migrate farther than Bio-Oss in the infected condition (Fig 4A). This finding might have resulted from differences in the particles’ sizes and compositions. Our element analysis revealed that the foreign bodies in the submandibular lymphatic vessels had a high calcium content (Fig 8B). Collectively, these results have demonstrated that the submandibular swelling resulted from the distant migration of graft materials from the maxillary sinus through the lymphatic chain. Foreign body materials are sometimes found in the lymph nodes of other parts of the body. For example, silicone gel implants for mammoplasty can rupture, which often results in the migration of foreign material to the auxiliary lymph nodes.19 Such migration can cause diseases, including foreign body granuloma and silicone lymphadenopathy.20,21 When silicone prostheses are
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FIGURE 5 (cont’d). B, Macroscopic view of the removed right submandibular gland and lymph nodes. Necrotic changes in the lymph nodes were observed (arrows). Seok et al. Alloplastic Bone Graft Migration and Infection. J Oral Maxillofac Surg 2014.
used to replace metatarsophalangeal joints, silicone elastomer particulate debris can migrate into the ipsilateral femoral lymph nodes and cause foreign body giant cell reactions and lymphadenopathies.22 Lymphatic vessels from the maxillary sinus not only drain through the natural ostia, but certain vessels also exhibit transmural drainage to the nasal lymphatic vessels through bony gaps.23 A number of these vessels drain into the ipsilateral submandibular lymph nodes (Fig 9). Furthermore, the nasal and maxillary sinus lymphatic capillary networks have diameters of 15 to 200 mm.23 According to our histologic findings, particulate materials were present in the submandibular lymphatic channels and connective tissue, in which a diffuse granulomatoid foreign body reaction occurred (Fig 6). The particulate materials were not stained with H&E, but they exhibited slight yellowish-gold color and diameters that ranged from 1 to 50 mm (Fig 6). It might have been possible that the grafted materials migrated from the maxillary sinus to the submandibular lymph nodes through the lymphatic channels. The fine gran-
ular particles were never engulfed by macrophages; however, they somehow induced cytotoxic damage of the macrophages and extracellular matrix. Fibrinoid necrosis and cellular apoptosis of macrophages and fibroblasts frequently appeared in the involved lesion. One extraordinary finding was the presence of iatrogenic destruction of the salivary acinar structures. Some of the damaged salivary acini had gradually degenerated and separated from the main salivary parenchyma (Fig 6). The bone grafting material used in our patient was BCP. BCP is composed of 60% HA and 40% b-TCP.18 BCP has been shown to be an effective bone graft material in animal models. However, b-TCP has a high dissolution rate in acidic conditions.24 In general, b-TCP resorbs and disappears rapidly before new bone formation.25 When b-TCP is used as a bone graft material, it is combined with HA. BCP degrades faster than HA, and the rate of degradation depends on the HA/b-TCP ratio.26 Bio-Oss is an inorganic bovine bone with a composition similar to that of natural bone.27 Bovine bone is composed of 93% HA and 7% b-TCP.28 The
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FIGURE 6. Histologic findings from the removed right submandibular gland and lymph nodes (hematoxylin-eosin staining, original magnification 100). Seok et al. Alloplastic Bone Graft Migration and Infection. J Oral Maxillofac Surg 2014.
proportion of b-TCP in BCP is greater than that of BioOss. Because of these differences, under acidic conditions such as those present during inflammation, BCP might degrade into small particles and migrate into the surrounding tissue more easily than Bio-Oss. Our animal experiments indicated that contaminated BCP
migrated farther than contaminated Bio-Oss (Figs 4A,C). In the present study, Bio-Oss was also found to migrate through the interstitial fibrous tissue in contaminated conditions. The swelling induced by the inflammation might have widened the tissue space and facilitated movement of the graft. However, no clinical
FIGURE 7. Histologic findings of alloplastic bone graft materials and granulation tissues in the right maxillary sinus area (hematoxylin-eosin staining, original magnification 400). Seok et al. Alloplastic Bone Graft Migration and Infection. J Oral Maxillofac Surg 2014.
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FIGURE 8. A, Scanning electron microscopic image of the unstained submandibular gland section (original magnification 10). Lower Right Corner, A magnified image of the lymphatic duct. Upper Left Corner, Image of the acinar portion shown (original magnification 400). B, Energy-dispersive x-ray microanalysis revealing lower concentration of calcium than carbon in the gland tissue. C, Energy-dispersive x-ray microanalysis revealing similar concentrations of calcium and carbon in the lymphatic duct. Seok et al. Alloplastic Bone Graft Migration and Infection. J Oral Maxillofac Surg 2014.
cases of distant migration of Bio-Oss were found in a PubMed search (available at: http://www.ncbi.nlm. nih.gov/PubMed, accessed October 28, 2013), which might have been because most clinicians will not perform grafts into an infected bed and Bio-Oss might not enter the lymphatic vessels. The incidence of maxillary sinusitis after sinus grafting has been reported to be up to 20%.8 In the present case, the patient had pre-existing purulent maxillary sinusitis. Additionally, mucosal perforation occurred during the procedure. In cases of mucosal perforation,
graft materials can become lost in the sinus and induce maxillary sinusitis.29 Microorganisms can potentially invade the graft site through the mucosal perforation, which can worsen the pre-existing maxillary sinusitis. Although the present patient had received the sinus graft by way of the lateral window approach, the dentist did not apply any membrane to the bony window. Owing to the high content of b-TCP, the BCP dissolved in the acidic inflammatory conditions. Thus, the size of the graft materials would have been reduced, and they could migrate through the window
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FIGURE 9. Proposed mechanism for the distant migration from the maxillary sinus to the submandibular gland. When graft material has been introduced into an infected maxillary sinus, the grafted material can migrate though the opened window by way of the lymphatic channel. Migrated graft materials can collect in distant organs, such as the submandibular gland. Seok et al. Alloplastic Bone Graft Migration and Infection. J Oral Maxillofac Surg 2014.
(Fig 9). Mucosal perforation can result in graft migration or loss.30 The graft materials had moved to the submandibular gland through the buccal lymphatic channels. Exposed graft material in cases of chronic bacterial infection should be removed.30 The distant migration of maxillary sinus grafts has not been previously reported. In the present case, the experimental data strongly supported the following conclusions. First, the materials found in the submandibular lymphatic vessel originated from the maxillary sinus. Second, foreign bodies and inflammatory reactions were observable in the submandibular lymph nodes. Third, degraded BCP and a foreign body reaction were found in the specimens from the maxillary sinus. Fourth, BCP had a greater b-TCP content than did the Bio-Oss. Fifth, the animal model demonstrated that BCP could migrate farther than Bio-Oss. Finally, SEM with EDX microanalysis showed
that the foreign bodies in the submandibular lymphatic vessel had calcium contents that were 200-fold greater than those of the adjacent tissue. The limitation of the present study was that the animal model could not exactly simulate the conditions of the presented clinical case. The grafts were placed in skin pockets on the back, and the back has blood supplies and lymphatic drainage pathways that are different from those of the maxillary sinus. We could not use the orthotopic animal model in the present study for the following reasons: 1) the sinus dimensions of the experimental animal were too small to be compared to humans, and 2) the lymphatic drainage pathway from the maxillary sinus of the animal is different from that of humans. Given the different lymphatic drainage systems and the rare specific complication ratio, we believe exactly simulating the conditions of the presented clinical case would
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have been impossible. Additionally, migration of graft material used for the maxillary sinus lifting procedure has not been previously studied. Thus, we used a back skin pocket model of graft migration.31 From our findings, we can conclude that the foreign body materials in the sinus cavity and submandibular lymph nodes were the same. Also, we believe the foreign bodies in the submandibular lymph nodes had migrated from the sinus cavity by way of the lymphatic vessels because the sinus cavity was the only site at which the graft materials had been placed. b-TCP–based materials can easily be resolved in acidic conditions. Therefore, b-TCP–based synthetic materials should not be used in inflamed areas. The application of a membrane over the window could prevent the distant migration of the graft material through the buccal lymphatic chain. Acknowledgments We thank Yong-Tae Park for the collection of the patient’s records and writing of the preliminary case report.
References 1. Fugazzotto PA, Wheeler SL, Lindsay JA: Success and failure rates of cylinder implants in type IV bone. J Periodontol 64:1085, 1993 2. Jaffin RA, Berman CL: The excessive loss of Branemark fixtures in type IV bone: A 5-year analysis. J Periodontol 62:2, 1991 3. Wheeler SL: Sinus augmentation for dental implants: The use of alloplastic materials. J Oral Maxillofac Surg 55:1287, 1997 4. Garlini G, Redemagni M, Donini M, et al: Maxillary sinus elevation with an alloplastic material and implants: 11 Years of clinical and radiologic follow-up. J Oral Maxillofac Surg 68:1152, 2010 5. Kim YK, Yun PY, Lim SC, et al: Clinical evaluations of OSTEONÒ as a new alloplastic material in sinus bone grafting and its effect on bone healing. J Biomed Mater Res B Appl Biomater 86:270, 2008 6. DoudGalli SK, Lebowitz RA, Giacchi RJ, et al: Chronic sinusitis complicating sinus lift surgery. Am J Rhinol 15:181, 2001 7. Jo YJ, Kim KH, Koo KT, et al: Initial adhesion of bone marrow stromal cells to various bone graft substitutes. J Periodontal Implant Sci 41:67, 2011 8. Timmenga NM, Raghoebar GM, Boering G, et al: Maxillary sinus function after sinus lifts for the insertion of dental implants. J Oral Maxillofac Surg 55:936, 1997 9. Havas TE, Motbey JA, Gullane PJ: Prevalence of incidental abnormalities on computed tomographic scans of the paranasal sinuses. Arch Otolaryngol Head Neck Surg 114:856, 1988 10. Lieu JE, Feinstein AR: Confirmations and surprises in the association of tobacco use with sinusitis. Arch Otolaryngol Head Neck Surg 126:940, 2000 11. Alkan A, C ¸ elebi N, Bas¸ B: Acute maxillary sinusitis associated with internal sinus lifting: Report of a case. Eur J Dent 2:69, 2008
1093.e11 12. Jensen O, Shulman L, Block M, et al: Report of the sinus consensus conference of 1996. Int J Oral Maxillofac Implants 13:11, 1998 13. Nolan PJ, Freeman K, Kraut RA: Correlation between schneiderian membrane perforation and sinus lift graft outcome: A retrospective evaluation of 359 augmented sinus. J Oral Maxillofac Surg 72:47, 2014 14. Khoury F: Augmentation of the sinus floor with mandibular bone block and simultaneous implantation: A 6-year clinical investigation. Int J Oral Maxillofac Implants 14:557, 1999 15. Nkenke E, Stelzle F: Clinical outcomes of sinus floor augmentation for implant placement using autogenous bone or bone substitutes: A systematic review. Clin Oral Implants Res 20(suppl 4): 124, 2009 16. Regev E, Smith RA, Perrott DH, et al: Maxillary sinus complications related to endosseous implants. Int J Oral Maxillofac Implants 10:451, 1995 17. Lee SW, Kim SG, Balazsi C, et al: Comparative study of hydroxyapatite from eggshells and synthetic hydroxyapatite for bone regeneration. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 113:348, 2012 18. Yang DH, Park HN, Bae MS, et al: Evaluation of Genesis-BCPTM scaffold composed of hydroxyapatite and b-tricalcium phosphate on bone formation. Macromol Res 20:627, 2012 19. Hausner R, Schoen F, Mendez-Fernandez M, et al: Migration of silicone gel to axillary lymph nodes after prosthetic mammoplasty. Arch Pathol Lab Med 105:371, 1981 20. Cook PD, Osborne BM, Connor RL, et al: Follicular lymphoma adjacent to foreign body granulomatous inflammation and fibrosis surrounding silicone breast prosthesis. Am J Surg Pathol 19:712, 1995 21. Santos-Briz A, L opez-Rıos F, De Agustın P: Granulomatous reaction to silicone in auxiliary lymph nodes. Acta Cytol 43:1163, 2011 22. Sammarco GJ, Tabatowski K: Silicone lymphadenopathy associated with failed prosthesis of the hallux: A case report and literature review. Foot Ankle 13:273, 1992 23. Hosemann W, K€ uhnel T, Burchard A, et al: Histochemical detection of lymphatic drainage pathways in the middle nasal meatus. Rhinology 36:50, 1998 24. LeGeros RZ: Calcium phosphates in oral biology and medicine. Monoqr Oral Sci 15:1, 1990 25. von Arx T, Cochran DL, Hermann J, et al: Lateral ridge augmentation and implant placement: An experimental study evaluating implant osseointegration in different augmentation materials in the canine mandible. Int J Oral Maxillofac Implants 16:343, 2000 26. LeGeros R, Lin S, Rohanizadeh R, et al: Biphasic calcium phosphate bioceramics: Preparation, properties and applications. J Mater Sci Mater Med 14:201, 2003 27. Tamimi FM, Torres J, Tresguerres I, et al: Bone augmentation in rabbit calvariae: Comparative study between Bio-OssÒ and a novel b-TCP/DCPD granulate. J Clin Periodontol 33:922, 2006 28. Ooi C, Hamdi M, Ramesh S: Properties of hydroxyapatite produced by annealing of bovine bone. Ceram Int 33:1171, 2007 29. Kasabah S, Krug J, Simunek A, et al: Can we predict maxillary sinus mucosa perforation? Acta Medica 46:19, 2003 30. Ward BB, Terrell JE, Collins JK: Methicillin-resistant Staphylococcus aureus sinusitis associated with sinus lift bone grafting and dental implants: A case report. J Oral Maxillofac Surg 66: 231, 2008 31. Newman J: Review of soft tissue augmentation in the face. Clin Cosmet Invest Dermatol 2:141, 2009
