Identification of driver genes and somatic mutations in cell-free DNA of patients with pulmonary lymphangioleiomyomatosis.

Next-generation sequencing of cell-free circulating DNA (cfDNA) has emerged as promising technique for identifying minimally invasive genomic profiling of tumor cells recently. However, it remains relatively unknown in LAM disease. In our study, paired cfDNA and genomic DNA (gDNA) in blood samples were obtained from 23 LAM patients and seven healthy controls to explore mutations profiles of targeted 70 cancer-related genes. As results, log2-based allele frequencies of mutations in cfDNA were significantly different from those of gDNA. By comparing the mutual mutations identified both in cfDNA and gDNA, a significant correlation was also observed. After removing mutations in gDNA, distinct somatic mutation profiles of cfDNA were observed in LAM patients. Forty of 70 targeted genes had recurrent mutations, of which ATM, BRCA2 and APC showed the highest frequency. Based on the mutation, correlation network constructed of 40 mutated genes, 11 hub genes bearing intensive interactions were highlighted, including BRCA1, BRCA2, RAD50, RB1, NF1, APC, MLH3, ATM, PDGFRA, PALB2 and BLM. Expression of the hub genes showed significant clusters between LAM patients and controls and that RAD50 and BRCA2 had the strongest associations with subject phenotypes. Myogenesis and estrogen response were confirmed to be positively regulated in LAM patients. Collectively, our study provided a landscape of genomic alterations in LAM and discovered several potential driver genes, that is, BRCA2 and RAD50, which shed a substantial light on the clinical application of key molecular markers and potential therapy targets for precision diagnosis and treatment in the future.

Scaffold-Based Delivery of Bone Marrow Mesenchymal Stem Cell Sheet Fragments Enhances New Bone Formation In Vivo.

PURPOSE: Stem cell therapy is becoming a potent strategy to shorten the consolidation time and reduce potential complications during distraction osteogenesis (DO). However, the conventional local injection or scaffold-based delivery of bone marrow mesenchymal stem cell (BMSC) suspension deprives the cells of their endogenous extracellular matrix, which might dampen cell differentiation and tissue regeneration after implantation. Therefore, in our study, a BMSC sheet was established and was then minced into fragments and loaded onto a hydroxyapatite (HA) scaffold for grafting. MATERIALS AND METHODS: The purified and characterized BMSCs were grown into a cell sheet, and bone formation and mineralization capacity, as well as the cell sheet composition, were analyzed. Afterward, the in vivo osteogenic ability of cell sheet fragments (CSFs) was evaluated in immunocompromised mouse and rabbit models of DO. RESULTS: The BMSC sheet exhibited higher alkaline phosphatase activity than osteogenic cell suspension cultures. Alkaline phosphatase activity and mineral particles in the cell sheet increased further after osteogenic induction. Moreover, calcium and phosphorus were present only in the osteogenic cell sheet, along with the common elements carbon, oxygen, chlorine, sodium, and sulfur, as indicated by x-ray photoelectron spectroscopy analysis. In a mouse model, the CSF-HA complex was injected subcutaneously. Micro-computed tomography analysis showed that the osteogenic CSF-HA complex led to a considerably higher bone volume than the BMSC-HA or CSF-HA complex. The osteogenic CSF-HA specimens showed increased angiogenesis and deposition of type I collagen compared with the non-osteogenic CSF-HA or BMSC-HA specimens. Moreover, the osteogenic CSF-HA markedly improved bone consolidation and increased bone mass in DO rabbits. CONCLUSIONS: Collectively, the incorporation of osteogenic BMSC sheets into HA particles greatly promoted bone regeneration, which offers therapeutic alternatives for DO.

A comparison of stromal cell-derived factor-1 expression during distraction osteogenesis and bone fracture in the mandible.

Distraction osteogenesis (DO) has been a widely applied technique in orthopedics and craniofacial surgery. However, the exact molecular mechanism by which the mechanical stimulus is translated into biological signals is still poorly understood. In this study, we examined and compared the expression of stromal cell-derived factor-1 (SDF-1) during mandibular distraction osteogenesis and fracture in rats, respectively. Forty-eight male Sprague-Dawley rats were divided into 2 groups and received unilateral distraction osteogenesis and rigid internal fixation, respectively, after the osteotomy on the right mandible. The harvested mandibles were examined radiographically, histologically, and immunohistochemically. We found that the expression of SDF-1 was mainly detected in the osteoblasts and blood vessels, and there were more intensive expression of SDF-1 in DO zones than in bone fracture zones. The quantitative analysis by enzyme-linked immunosorbent assay showed that SDF-1 reached a greater peak and maintained a longer period of up-regulation in DO than in fracture healing (P < 0.05). These results suggest that the distraction procedure markedly promotes the high expression of SDF-1 which facilitates the induction of bone formation during DO.

Effects of sympathetic innervation loss on mandibular distraction osteogenesis.

Sympathetic nerve system has been proved to have important regulative effects to bone mass. However, the role of sympathetic nerve system in distraction osteogenesis (DO) is unclear. Here we show that the sympathetic nerve system plays an important role in mandibular DO. Thirty male Sprague-Dawley rats were divided into 2 groups at random. Right-side mandibular DO was performed on the 15 rats in control group (group A). Bilateral transection of cervical sympathetic trunk and right-side mandibular DO were performed on the 15 rats in the experimental group (group B). After operation, quantitative general observations, micro-computed tomography bone morphology analysis, and hematoxylin-eosin staining osseous tissue on new osteotylus in distraction gap were performed at consolidation time of 1, 14, and 28 days. SPSS 12.0 software package was used for statistical analysis. At 1 and 14 days of consolidation time, there was more continuous bone formation in the experimental group than that of the control group as determined by gross observation. Bone formation parameters including bone mineral density, bone volume-total volume ratio, bone trabeculae number as determined by micro-CT, and histological study of the test group were significantly higher than those of the control group (P < 0.05). No significant difference was noted between the 2 groups on consolidation time of 28 days. Our study suggested that the sympathetic innervation loss could improve mandibular DO and new bone formation, and the sympathetic nerve system might negatively regulate the process of DO.

Surgical treatment of a giant neurofibroma.

Neurofibromatosis type 1, an autosomal dominant inherited disease, presents pathologic symptoms of multiple systems, including neurofibromatosis, skeletal dysplasia, café-au-lait spots in skins, and so on. A 45-year-old man with neurofibromatosis type 1 was reported in this article. The patient presented a giant neurofibroma in his head and neck, dysplasia of skull, facial bones and spinal columns, and multiple café-au-lait spots in systematic skins. Satisfactory curative effects were obtained in this case after tumor resection and prosthesis implantation.

Research on a novel rigid internal fixation system.

PURPOSE: The purpose of the present study was to evaluate the efficiency of fixation with a novel (bulge core type system) rigid internal fixation system. MATERIALS AND METHODS: Mandibular linear fractures were created artificially in dogs and fixed using a bulge core type system or a miniplate system in vitro. A 3-point load cell was used to contrast the fixation strength of the 2 systems in vitro. Histologic sections were used to analyze the healing of mandibular linear fractures and to contrast the efficiency of fixation of the 2 systems in vivo. Tetracycline-fluorescein staining technology was used to evaluate the bone healing speed in the mandibular fracture lines during bone healing. RESULTS: In vitro, the 3-point load cell showed that the fixation strength of the bulge core type system was greater than that of the miniplate system (P < .05). In vivo, the histologic sections and tetracycline-fluorescein staining showed that greater and quicker bony healing occurred using the bulge core type system (P < .05) and that the efficiency of fixation of the 2 systems was similar. CONCLUSION: Our results have shown that the bulge core type system can provide sufficient strength for mandibular linear fracture healing.

Accurate reconstruction of discontinuous mandible using a reverse engineering/computer-aided design/rapid prototyping technique: a preliminary clinical study.

PURPOSE: To improve the reconstructive surgical outcome of a discontinuous mandibular defect, we used reverse engineering (RE), computer-aided design (CAD), and rapid prototyping (RP) technique to fabricate customized mandibular trays to precisely restore the mandibular defects. Autogenous bone grafting was also used to restore the bony continuity for occlusion rehabilitation. PATIENTS AND METHODS: Six patients who had undergone block resection of the mandible underwent reconstruction using a custom titanium tray combining autogenous iliac grafts. The custom titanium tray was made using a RE/CAD/RP technique. A virtual 3-dimensional model was obtained by spiral computed tomography scanning. The opposite side of the mandible was mirrored to cover the defect area to restore excellent facial symmetry. A bone grafting tray was designed from the mirrored image and manufactured using RP processing and casting. The mandibular defects were restored using the trays in combination of autologous iliac grafting. An implant denture was made for 1 of the 6 patients at 24 weeks postoperatively for occlusion rehabilitation. RESULTS: The trays fabricated using this technique fit well in all 6 patients. The reconstructive procedures were easy and time saving. Satisfactory facial symmetry was restored. No severe complications occurred in the 5 patients without occlusion rehabilitation during a mean 50-month follow-up period. The reconstruction in the patient with occlusion lasted for only 1 year and failed eventually because of bone resorption and infection. CONCLUSIONS: Mandibular reconstruction was facilitated using the RE/CAD/RP technique. Satisfactory esthetic results were achieved. However, the rigidity of the cast tray could cause severe stress shielding to the grafts, which could lead to disuse atrophy. Therefore, some modification is needed for functional reconstruction.

Modified approach to construct a vascularized coral bone in rabbit using an arteriovenous loop.

The most important factor for the survival of thick three-dimensional tissues is the degree of vascularization. In this study, a modified arteriovenous loop (AVL) model was developed to prefabricate an axial vascularized tissue-engineered coral bone. In group A (n = 28), an arteriovenous fistula between rabbit femoral artery and vein was anastomosed to form an AVL. The AVL was placed in a coral block (6 x 8 x 10 mm (3)) as a vascular carrier. The complex was wrapped with polytetrafluoroethylene membrane and implanted subcutaneously. In group B (n = 20), there was no vascular carrier, and the same dimensional coral was directly implanted beneath inguinal skin. After 2, 4, 6, and 8 weeks, the rabbits were perfused with heparinized saline (for scanning electron microscopy), India ink (for histological examination), and ethylene perchloride (for vascular casts) via the abdominal aorta. In group A, histology showed that newly formed vasculature extended over the surfaces and invaded the entire coral blocks. The vascular density was significantly superior to that in group B. Vascular casts showed that new blood vessels robustly sprouted from the AVL. Scanning electron microscopy demonstrated that there were minute sprouting cavities in the vascular endangium. In this model, an axial vascularized coral bone could be effectively constructed.

Expert Consensus for the Treatment Algorithm for Navigationassisted Reconstruction of Maxillofacial Deformities.

Deformities of the maxillofacial region following trauma and ablative surgery are devastating and not uncommon. Reconstruction of such defects is a surgically challenging procedure. Conventionally, reconstruction of dental arch defects lacks preoperative customised planning and relies heavily on the surgeon experience to ensure optimum surgical outcomes. The restoration of the dental arch shape and function has taken precedence after an extensive tumour resection surgery, especially in the current age of technological advancement. Thus, personalised and accurate reconstruction of dental arch defects has become a new goal. Computer-assisted surgery, especially navigation-assisted surgery, has gained popularity of late, in reconstructing deformities and restoring facial symmetry, appearance and function in the maxillofacial region. This technology provides a clearer three-dimensional visualisation of the area of interest and its relationship with the adjacent vital structures. Together with preoperative virtual surgical planning, it allows more specific and accurate osteotomies, thus reducing the ischemia and total operating times substantially. The risk of complications is also minimised whilst improving the final surgical outcomes. The use of the intraoperative navigation system and other computer-assisted surgical techniques during surgery can significantly improve the precision of the reconstruction of dental arch deformities, and achieve personalised and functional reconstructive goals while enhancing the quality of life of patients postoperatively. The Society of Oral and Maxillofacial Surgery, Chinese Stomatological Association provides the present professional perspective and treatment protocol for navigation-guided reconstruction of dental arch defects, to allow standardisation of the technique while promoting its application among oral and maxillofacial surgeons.

Expert Consensus on Navigation-guided Unilateral Delayed Zygomatic Fracture Reconstruction Techniques.

The zygoma is located in the medial and lateral parts of the face, supporting the midfacial contour. The forward projection of the zygoma and the zygomatic arch often expose them to injury. Fractures of the zygoma can lead to the displacement of the zygoma and the zygomatic arch, causing facial collapse deformity. For delayed zygomatic fractures, the loss of normal anatomical landmarks caused by the malunion of the fracture lines and remodelling of the bony contour makes it difficult to determine the correct positions of the zygomatic bones. In such cases, ideal and steady outcomes with satisfactory midface symmetry have been difficult to obtain using traditional surgical methods. Nowadays, the application of digital surgical software and surgical navigation helps surgeons to perform accurate preoperative simulations to obtain ideal three-dimensional virtual surgical plans and achieve accurate reduction by intraoperative navigation systems, which increase the accuracy and predictability of fracture reduction outcomes. Experts from the Society of Oral and Maxillofacial Surgery, Chinese Stomatological Association have fully discussed and formulated an expert consensus on navigation-guided unilateral delayed zygomatic fracture reconstruction techniques to standardise the clinical operation procedures and promote the application.

Expert Consensus on Navigation-guided Unilateral Orbital Fracture and Orbital Floor Reconstruction Techniques.

Orbital fracture and orbital floor reconstruction surgery is characterised by limited surgical exposure and high risks. Before the advent of digital technology, the design and implementation of the surgical scheme for orbital floor reconstruction surgery mainly depended on the intuitive understanding of imaging and the clinical experience of surgeons, with strong unpredictability and experience dependence. Surgical navigation systems with real-time positioning and imaging functions, when used in orbital reconstruction surgery, can detect the real-time intraoperative position, avoid risks, and assist in locating the reconstruction position to ensure the accuracy of orbital reconstruction, with the help of a preoperative surgical plan. Many studies have confirmed its effect. Unilateral orbital fracture and orbital floor reconstruction surgery is one of the earliest and most widely used surgical techniques in maxillofacial surgery. Experts from the Society of Oral and Maxillofacial Surgery, Chinese Stomatological Association have fully discussed and formulated this expert consensus on navigation-guided unilateral orbital fracture and orbital floor reconstruction techniques to standardise the clinical surgical procedures and promote its application.

Expert Consensus on Procedures and Operations of Navigation-guided Needle Biopsy Techniques for Skull Base Tumours.

Skull base surgery is an interdisciplinary subject. The anatomical structures in the skull base related to oral and maxillofacial surgery include the parapharyngeal space, the pterygopalatine fossa and the infratemporal space. This operative area is one of the most challenging surgical areas in oral and maxillofacial surgery due to its deep site, complex anatomy and high risk. Obtaining pathological information of the tumour preoperatively may help surgeons optimise their treatment plan. Needle biopsy is one of the major minimally invasive techniques that allows preoperative pathological results to be obtained. The navigation technology, which is developing rapidly nowadays, provides a reliable assistance for deep tissue biopsy surgery. Experts from the Society of Oral and Maxillofacial Surgery, Chinese Stomatological Association formulated an expert consensus on the procedures and operations of navigation-guided needle biopsy techniques for skull base tumours, so as to standardise and promote the application and operation of navigation-guided needle biopsy for skull base tumours.

The association between roofing material and head injuries during the 2008 Wenchuan earthquake in China.

STUDY OBJECTIVE: We analyze the spectrum of earthquake-related head injuries resulting in hospitalization and arising from the 2008 Wenchuan Earthquake in China. An additional objective is to assess injury patterns associated with 2 types of roofing structures found in this region of China. METHODS: This descriptive study included data on trauma patients at 8 hospitals in Jiangyou for the 14 days immediately after the earthquake. The patients were either from Jiangyou County, which experienced a modified Mercalli intensity level of VIII, or from Beichuan County (Mercalli intensity level of X). Of the 5,775 earthquake-related injuries, 1,484 (25.7%) involved the head and were classified into 4 categories. Seven injury mechanisms were also analyzed to determine the association with the 4 types of head injuries. RESULTS: Scalp injuries (43%) were the most common type of head injuries, followed by facial injuries, 482 (32%), intracranial injuries, 218 (15%), and skull fractures, 117 (8%). Differences in injury type and cause were apparent, with scalp injuries being more common (49%) in Jiangyou than in Beichuan (30%) and falling clay tiles contributing more (40%) to this injury in the former city than the latter (6%). In contrast, precast concrete plank roofing caused 20% of scalp injuries in Beichuan compared with 3% in Jiangyou. CONCLUSION: Scalp injuries were the most common head injury type. Falling clay roofing tiles and precast concrete plank roofs are important injury mechanisms, and their contribution may reflect differences in building construction.

Tisssue responses in corticotomy- and osteotomy-assisted tooth movements in rats: histology and immunostaining.

INTRODUCTION: The purpose of this histologic study was to examine underlying cellular responses to corticotomy- and osteotomy-assisted tooth movements. METHODS: Thirty-six rats were divided into 5 groups: corticotomy-assisted tooth movement (CO + TM), sham corticotomy without tooth movement (CO alone), osteotomy-assisted tooth movement (OS + TM), sham osteotomy without tooth movement (OS alone), and unassisted tooth movement (TM alone). Standard orthodontic springs were activated to produce mesial tooth movement. The rats were killed at 3, 21, and 60 days after activation for osteoclast and blood vessel counts, and immunostaining with proliferating cell nuclear antigen (PCNA), transforming growth factor beta 1 (TGF beta 1), vascular endothelial growth factor (VEGF), and osteocalcin were performed. RESULTS: The CO + TM group had significantly more osteoclasts at 3 days (P <0.005) compared with the OS + TM group. The alveolar bone surrounding the dental roots was replaced with multicellular tissue at 21 days in the CO + TM group but was intact in the OS + TM group with the exception of a distal distraction site. At day 21, immunostaining with PCNA, TGF beta 1, VEGF, and osteocalcin occurred at the mesial border of bone in the CO + TM group, whereas a diffuse pattern was observed in the distal distraction sites at 21 and 60 days in the OS + TM group. CONCLUSIONS: Corticotomy-assisted tooth movement produced transient bone resorption around the dental roots under tension; this was replaced by fibrous tissue after 21 days and by bone after 60 days. Osteotomy-assisted tooth movement resembled distraction osteogenesis and did not pass through a stage of regional bone resorption.

In vitro transdifferentiation of adipose tissue-derived stem cells into salivary gland acinar-like cells.

Current clinical approaches to treat irradiation-induced salivary gland hypofunction are ineffective. We previously reported that adipose-derived stem cell (ADSC)-based therapy ameliorates damaged salivary gland function in mice and that the effects were enhanced when the therapy was co-administrated with platelet-rich fibrin (PRF). We examined the feasibility of ADSC transdifferentiation into salivary gland acinar-like cells (SGALCs) and analyzed the potential of PRF to promote the transdifferentiation process in vitro. Salivary gland cells (SGCs) and ADSCs were indirectly co-cultured using Transwell inserts, and increasing concentrations of PRF-conditioned medium were applied to the co-culture system. The expression of α-amylase and AQP-5 were used to evaluate ADSC transdifferentiation. Notably, on day 7, 14, and 21, expression of both α-amylase and AQP-5 were detected in the co-cultured ADSCs. Additionally, PRF increased α-amylase and AQP-5 levels in ADSCs that were co-cultured for 7 days. These data demonstrate that ADSCs have the potential to transdifferentiate into SGALCs and that PRF can promote the transdifferentiation process. Therefore, these data reveal a possible mechanism to treat irradiation-induced salivary gland hypofunction and have translational medicine implications.

A novel strategy for prefabrication of large and axially vascularized tissue engineered bone by using an arteriovenous loop.

The repair of bone defects remains a major clinical challenge because none available reconstruction methods and biomaterials have been proved completely satisfactory. As a promising approach for bone regeneration, tissue engineered bone has become a technically feasible method to repair small to moderate sized bone defects in clinical practice, but it is difficult to repair large one, particularly when the recipient site is scarred by infection or radiation injury. Construction of large and vascularized tissue engineered bone may overcome the problems since vascularization is an essential prerequisite for the constructs to survive and integrate with existing host tissue. On the other hand, prefabrication large artificial bone in vivo bioreactor and axial vascularization by means of arteriovenous loop model in soft tissue have been proved to be feasible. Therefore, we hypothesize that combination of cells, solid scaffold, growth factors, and arteriovenous loop may eventually generate a large and vascularized tissue engineered bone flap in vivo bioreactor. Like vascularized autologous bone grafts, the new constructs could be transferred to the defect site by using microsurgical techniques. The strategy would facilitate clinical translation in bone tissue engineering and offer new therapeutic strategies for reconstruction of extended bone defects if the hypothesis proved to be practical.

The role of bone morphogenetic protein-2 in vivo in regeneration of peripheral nerves.

We investigated the effects of bone morphogenetic protein-2 (BMP-2) and some other BMPs on regeneration of peripheral motor nerves in vivo. The facial nerves of 24 New Zealand rabbits were crushed to examine a series of retrograde changes in the facial nuclei and axons, in what has been called the "axon reaction". The facial nerves of the experimental group were treated with epineurial coaptation and BMP-2 after the injury. Nerves not treated with BMP-2 were regarded as controls. The expression of BMP-2 was investigated by in situ hybridisation in the neurons of facial nuclei. The electrophysiology, image analysis and transmission electron microscopy were used to evaluate the level of the recovery of facial nerves. The results showed that the axons in the experimental group were thicker and denser than those in the control group four weeks later. The expression of BMP-2 in the neurons of facial nuclei increased after injury. The electron microscopic observations showed that the axons' degeneration in the experimental group was less than that in the control group. Despite the morphological difference between the two groups, there was no apparent difference between them in nerve conduction velocity. These findings suggest that BMP-2 might be involved in the regeneration of facial nerves, and might function as a potential neurotrophic factor.

Nuclear Multidrug Resistance-Related Protein 1 Is Highly Associated with Better Prognosis of Human Mucoepidermoid Carcinoma through the Suppression of Cell Proliferation, Migration and Invasion.

OBJECTIVES: Multidrug resistance-related protein 1 (MRP1) overexpression is a well acknowledged predictor of poor response to chemotherapy, but MRP1 also correlated to better prognosis in some reports, especially for patients not pretreated with chemotherapy. In our previous study, we found nuclear translocation of MRP1 in mucoepidermoid carcinoma (MEC) for the first time. The purpose of this study was to further investigate the function of nuclear MRP1 in MEC. MATERIALS AND METHODS: Human MEC tissue samples of 125 patients were selected and stained using immunohistochemistry. The expression level of total MRP1/nuclear MRP1 of each sample was evaluated by expression index (EI) which was scored using both qualitative and quantitative analysis. The correlations between the clinicopathologic parameters and the EI of nuclear MRP1 were analyzed using Spearman's rank correlation analysis, respectively. The effects of RNAi-mediated downregulation of nuclear MRP1 on MEC cells were assessed using flow cytometric analysis, MTT assay, plate colony formation assay, transwell invasion assay and monolayer wound healing assay. RESULTS: In this study, we found the EI of nuclear MRP1 was negatively correlated to the pathologic grading (r = -0.498, P<0.01)/clinical staging (r = -0.41, P<0.01)/tumor stage (r = -0.28, P = 0.02)/nodal stage (r = -0.29, P<0.01) of MEC patients. The RNAi-mediated downregulation of nuclear MRP1 further proved that the downregulation of nuclear MRP1 could increase the cell replication, growth speed, colony formation efficiency, migration and invasion ability of MEC cells. CONCLUSION: Our results suggested that nuclear MRP1 is highly associated with better prognosis of human mucoepidermoid carcinoma and further study of its function mechanism would provide clues in developing new treatment modalities of MEC.

Long-term results of mandibular reconstruction of continuity defects with fibula free flap and implant-borne dental rehabilitation.

PURPOSE: This study evaluated the retrospective outcomes of implant-borne dental rehabilitation in patients with mandibular defects reconstructed with a fibula free flap. MATERIALS AND METHODS: Patients with segmental mandibular defects were enrolled in this cohort study. Defects in these patients were caused by oral neoplasm, trauma, and osteoradionecrosis. The patients were treated with a fibula free flap procedure and dental implant-borne prostheses between 1988 and 2010. Clinical and radiographic data were evaluated; Kaplan-Meier survival analysis and Poisson regression analysis were used to evaluate implant survival parameters. The statistical significance (α = .05) of the results was determined. RESULTS: Seventy-four patients were selected in this study. All patients were available for continuous follow-up. Nine patients (12.1%) developed fibular graft complications postoperatively: 3 in donor sites and 6 in recipient sites. One hundred ninety-two implants were inserted, and 18 implants failed (9.3%). Overall implant survival in patients was 90.1%, 83.1%, and 69.3% after 5, 10, and 20 years, respectively. In 152 implants, probing depth (PD) ranged from 2 to 3 mm. In 31 implants, PD was greater than 5 mm. In 9 implants, PD was greater than 7 mm. The highest implant failure rates were expected for men (odds ratio [OR] = 2.948; 95% confidence interval [CI], 1.10 to 7.85; P = .031), patients receiving primary fibula free flap reconstruction (OR = 3.696; 95% CI, 1.16 to 11.73; P = .027), and patients receiving radiotherapy (OR = 5.269; 95% CI, 1.40 to 19.7; P = .014). CONCLUSION: Fibula free flap procedures and implant-borne prostheses proved to be reliable approaches for rehabilitation of mandibular defects and oral function. The overall postoperative fibula free flap and peri-implant complication rates proved to be low. Regular follow-up visits and proper oral hygiene maintenance contributed to the long-term successful treatments.

Long-Term Results of Mandibular Reconstruction of Continuity Defects with Fibula Free Flap and Implant-Borne Dental Rehabilitation.

Purpose: This study evaluated the retrospective outcomes of implant-borne dental rehabilitation in patients with mandibular defects reconstructed with a fibula free flap. Materials and Methods: Patients with segmental mandibular defects were enrolled in this cohort study. Defects in these patients were caused by oral neoplasm, trauma, and osteoradionecrosis. The patients were treated with a fibula free flap procedure and dental implant-borne prostheses between 1988 and 2010. Clinical and radiographic data were evaluated; Kaplan-Meier survival analysis and Poisson regression analysis were used to evaluate implant survival parameters. The statistical significance (α = .05) of the results was determined. Results: Seventy-four patients were selected in this study. All patients were available for continuous follow-up. Nine patients (12.1%) developed fibular graft complications postoperatively: 3 in donor sites and 6 in recipient sites. One hundred ninety-two implants were inserted, and 18 implants failed (9.3%). Overall implant survival in patients was 90.1%, 83.1%, and 69.3% after 5, 10, and 20 years, respectively. In 152 implants, probing depth (PD) ranged from 2 to 3 mm. In 31 implants, PD was greater than 5 mm. In 9 implants, PD was greater than 7 mm. The highest implant failure rates were expected for men (odds ratio [OR] = 2.948; 95% confidence interval [CI], 1.10 to 7.85; P = .031), patients receiving primary fibula free flap reconstruction (OR = 3.696; 95% CI,1.16 to 11.73; P = .027), and patients receiving radiotherapy (OR = 5.269; 95% CI, 1.40 to 19.7; P = .014). Conclusion: Fibula free flap procedures and implant-borne prostheses proved to be reliable approaches for rehabilitation of mandibular defects and oral function. The overall postoperative fibula free flap and peri-implant complication rates proved to be low. Regular follow-up visits and proper oral hygiene maintenance contributed to the long-term successful treatments.