Long-term dental outcomes in patients with fibrodysplasia ossificans progressiva: a report of three cases of tooth extraction.

Fibrodysplasia ossificans progressiva (FOP) is an extremely rare autosomal dominant disorder characterized by congenital skeletal malformation and progressive heterotopic ossification. In the oral and maxillofacial region, deformity of the temporomandibular joint is a common feature of FOP, as well as restricted mouth opening derived from heterotopic ossification in the masticatory muscles. Since surgical procedures are generally not recommended because of the risk of flare-ups and increased heterotopic ossification, reports of tooth extractions and their outcomes in patients with FOP are limited. The present article reports the long-term oral outcomes of three Japanese patients with FOP, in whom the teeth were deliberately extracted to avoid the risk of oral inflammation causing further heterotopic ossification. The extractions were conducted under local or general anesthesia, and healing of sockets was nonproblematic with the formation of new bone. Undesirable events, including progression of heterotopic ossification in the oral and maxillofacial region and further restriction of mouth opening, were not apparent. The extractions also alleviated the existing inflammation, contributing to maintaining their oral hygiene. These cases suggest that deliberate planning and judicious surgery could induce favorable healing after tooth extractions in patients with FOP, leading to long-term stability of their oral health status.

Influence of Damage-Associated Molecular Patterns from Chondrocytes in Tissue-Engineered Cartilage.

To obtain stable outcomes in regenerative medicine, the quality of cells for transplantation is of great importance. Cellular stress potentially results in the release of damage-associated molecular patterns (DAMPs) and activates immunological responses, affecting the outcome of transplanted tissue. In this study, we intentionally prepared necrotic chondrocytes that would gradually die and release DAMPs and investigated how the maturation of tissue-engineered cartilage was affected. Necrotic chondrocytes were prepared by a conventional heat-treatment method, by which their viability started to decrease after 24 h. When tissue-engineered cartilage containing necrotic chondrocytes was subcutaneously transplanted into C57BL/6J mice, accumulation of cartilage matrix was decreased compared to the control. Meanwhile, immunohistochemical staining demonstrated that localization of macrophages and neutrophils was more apparent in the constructs of necrotic chondrocytes, suggesting that DAMPs from necrotic chondrocytes could prompt migration of more immune cells. Two-dimensional electrophoresis and mass spectrometry identified prelamin as a significant biomolecule released from necrotic chondrocytes. Also, when prelamin was added to a culture of RAW264, Inos and Il1b were increased in accordance with the content of added prelamin. It was suggested that DAMPs from dying chondrocytes could induce inflammatory properties in surrounding macrophages, impairing the maturation of tissue-engineered cartilage. In conclusion, maturation of tissue-engineered cartilage was hampered when less viable chondrocytes releasing DAMPs were included. Impact statement In regenerative medicine, the quality of cells is of great importance to secure clinical safety. During culture, damage of cells could occur, if not critical enough to cause immediate cell death, but still inducing a less viable status. Damage-associated molecular patterns (DAMPs) are released from necrotic cells, but their influence in regenerative medicine has yet to be clarified. In this study, we elucidated how DAMPs from chondrocytes could affect the maturation of tissue-engineered cartilage. Also, possible DAMPs from necrotic chondrocytes were comprehensively analyzed, and prelamin was identified as a significant molecule, which may serve for detecting the existence of necrotic chondrocytes.

Fibrodysplasia ossificans progressiva: Review and research activities in Japan.

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic skeletal disorder manifesting progressive heterotopic ossification (HO) and congenital malformation of the great toes. Since 2007, we have conducted research on FOP. Here, we review the findings on FOP published to date, including the results of our research. Epidemiological studies in Japan have indicated that FOP has nearly the same prevalence in Japan as in the rest of the world. Basic research on its pathoetiology has progressed rapidly since the identification of the causal gene in 2006. Clinical and radiological findings have been thoroughly researched, including early radiological signs, and diagnostic criteria were established, designating FOP as an intractable disease in Japan. In patients with FOP, the progression of HO is associated with numerous disabilities, often manifesting in vicious cycles that can lead to early mortality. Through cross-sectional and short-term longitudinal studies, we have explored patient education, quality of life, and activities of daily living among Japanese patients. The management of FOP requires education of patients and caregivers, the use of medications to settle inflammation and flare-ups, instructions to ensure proper oral care, and other compensatory approaches that aid in rehabilitation. An avoidance of medical intervention, which may cause HO to progress, is also important. The advent of new drugs to prevent HO could have clinical benefit.

Clinical Findings of a Cantilever Iliac Bone Graft for Secondary Correction of Cleft Lip-Nose Deformities.

The authors performed a cantilever iliac bone graft for the secondary correction of severe cleft lip-nose deformities after the completion of growth. For the purpose of clarifying effects of the cantilever iliac bone grafts and the adverse events with regard to their time course changes after this procedure, the authors retrospectively surveyed long-term morphologic changes in 65 cleft lip, alveolus, and palate patients in whom cleft lip-nose deformities were treated with a cantilever iliac bone graft (age at surgery: 14-45 years old). All postsurgical documents of facial photographs and radiologic images were reviewed to evaluate the effects and adverse events. The main adverse events were deviations of the apex of the nose, excess resorption of the grafted iliac bone, protruding deformations of the grafted iliac bone at the root of the nose, and fracture of the grafted iliac bone. Additional surgery was necessary in 10.7% of patients. Postsurgical changes in facial profiles became favorable, measured on lateral view of cephalometric radiography, achieving morphologic improvements. A cantilever iliac bone graft was effective for improving nasal deformities in cleft lip, alveolus, and palate patients, although the counter measures should be taken to these adverse events.

Three-dimensional changes of noses after transplantation of implant-type tissue-engineered cartilage for secondary correction of cleft lip-nose patients.

INTRODUCTION: We have developed an implant-type tissue-engineered cartilage using a poly-l-lactide scaffold. In a clinical study, it was inserted into subcutaneous areas of nasal dorsum in three patients, to correct cleft lip-nose deformity. The aim of this study was to helping evaluation on the efficacy of the regenerative cartilage. METHODS: 3D data of nasal shapes were compared between before and after surgery in computed tomography (CT) images. Morphological and qualitative changes of transplants in the body were also evaluated on MRI, for one year. RESULTS: The 3D data from CT images showed effective augmentation (>2 mm) of nasal dorsum in almost whole length, observed on the medial line of faces. It was maintained by 1 year post-surgery in all patients, while affected curves of nasal dorsum was not detected throughout the observation period. In magnetic resonance imaging (MRI), the images of transplanted cartilage had been observed until 1 year post-surgery. Those images were seemingly not straight when viewed from the longitudinal plain, and may have shown gentle adaptation to the surrounding nasal bones and alar cartilage tissues. CONCLUSION: Those findings suggested the potential efficacy of this cartilage on improvement of cleft lip-nose deformity. A clinical trial is now being performed for industrialization.

Rescue of lip switch flap at risk of necrosis due to venous congestion for cleft lip deformity.

In a 21-year-old male with bilateral cleft lip who developed marked venous congestion of a lip switch flap, we returned the grafted flap to the donor site to improve blood circulation of the flap and then re-transplanted it, which prevented flap necrosis. Here, we report the procedure and case.

High-risk oral leukoplakia is associated with aberrant promoter methylation of multiple genes.

BACKGROUND: Early detection of oral squamous cell carcinomas (OSCCs) is urgently needed to improve the prognosis and quality of life (QOL) of patients. Oral leukoplakias (OLs), known as the most common premalignant lesions in the oral cavity, often precede OSCCs. Especially, OLs with dysplasia are known to have a high risk of malignant transformation. Here, we searched for the promoter methylation characteristic of high-risk OLs. METHODS: To identify methylation-silenced genes, a combined analysis of methylated DNA immunoprecipitation (MeDIP) - CpG island (CGI) microarray analysis and expression microarray analysis after treatment with a demethylating agent was performed in two OSCC cell lines (Ca9-22 and HSC-2). The methylation statuses of each gene were examined by methylation-specific PCR. RESULTS: A total of 52 genes were identified as candidates for methylation-silenced genes in Ca9-22 or HSC-2. The promoter regions of 13 genes among the 15 genes randomly selected for further analysis were confirmed to be methylated in one or more of five cell lines. In OSCC tissues (n = 26), 8 of the 13 genes, TSPYL5, EGFLAM, CLDN11, NKX2-3, RBP4, CMTM3, TRPC4, and MAP6, were methylated. In OL tissues (n = 24), seven of the eight genes, except for EGFLAM, were found to be methylated in their promoter regions. There were significantly greater numbers of methylated genes in OLs with dysplasia than in those without dysplasia (p < 0.0001). CONCLUSIONS: OLs at high risk for malignant transformation were associated with aberrant promoter methylation of multiple genes.

A 2-Stage Reconstruction of the Jaw Using Vascularized Bone and Secondary Alveolar Ridge Augmentation With Particulate Cancellous Bone and Marrow.

PURPOSE: To present the novel technique for reconstruction of the jaw, that facilitates occlusal restoration using dental implants, in cases with wide bony defects from tumor resection. MATERIALS AND METHODS: After alveolar ridge is augmented using titanium mesh tray and particulate cancellous bone and marrow (PCBM) from iliac bone on reconstructed bone, by way of improvement of maxillomandibular relationship for dental implants. RESULTS: This 2-stage surgery underwent successfully in 3 cases. After 2-stage surgery and occlusal reconstruction using dental implant, the patients experienced no complications, and received satisfaction with results functionally and aesthetically. CONCLUSIONS: Our results suggest that, in cases where bone defect is over a wide area, in addition to vascularized bone grafts, secondary alveolar ridge augmentation using a titanium mesh tray and PCBM on grafted bone can provide satisfactory occlusion further to improvement of facial form.

Computed tomographic evaluation of novel custom-made artificial bones, "CT-bone", applied for maxillofacial reconstruction.

INTRODUCTION: We fabricated custom-made artificial bones using three-dimensionally layered manufacturing (3D printing) process, and have applied them to patients with facial deformities. We termed this novel artificial bone the "CT-bone". The aim of the present study was to evaluate the middle- and long-term safety and effectiveness of the CT-bones after transplantation. METHODS: The subject areas involved were 23 sites of 20 patients with facial bone deformities due to congenital abnormality, tumor, or trauma. The CT-bones were used for augmentation; they were evaluated by CT images, minimally for 1 year and maximally for 7 years and 3 months (3 years and 1 month on average) after transplantation. RESULTS: No serious systemic events due to the CT-bone graft were found during the observation period (1 year postoperatively). In 4 sites of 4 patients, the CT-bones were removed due to local infection of the surgical wounds at 1-5 years postoperatively. Compatibility of the shapes between the CT-bone and the recipient bone was confirmed to be good during the operation in all of the 20 cases, implying that the CT-bones could be easily installed onto the recipient sites. During the CT evaluation (<7 years and 3 months), no apparent chronological change was seen in the shape of the CT-bones. Sufficient bone union was confirmed in 19 sites. The inner CT values of the CT-bones increased in all the sites. The longer the postoperative period, greater increases in the CT values of the CT-bones tended to be observed. CONCLUSIONS: The CT-bone showed maintenance of the original shape and good bone replacement, based on the middle- and long-term follow-ups. In the future, we would make an intelligent type of artificial bones in which bone regeneration is induced by gradually releasing angiogenesis-inducing factors and/or bone-regeneration-inducing factors at the three-dimensionally controlled positions.

Clinical experience of full custom-made artificial bones for the maxillofacial region.

INTRODUCTION: Autologous, allogeneic, and artificial bones are clinically applied as graft materials for bone reconstruction, with each having their own advantages and disadvantages. Although artificial bones with various shapes are currently available, a product with a morphology that may be freely modified by operators has not yet been developed. In the present study, we developed a full custom-made artificial bone, and applied it to form the maxillofacial region. We herein report treatment outcomes. METHODS: An artificial bone was prepared on a 3-dimensional solid model, and data of its shape was collected on CT. A full custom-made artificial bone was prepared by laminating α-tricalcium phosphate powder using an aqueous polysaccharide curing solution and the ink-jet powder-laminating device, Z406 3D Printer (DICO, USA). Subjects comprised patients who underwent maxillofacial plasty using this artificial bone between March 2006 and September 2009. RESULTS: Maxillofacial plasty using the full custom-made artificial bone was applied to 23 regions in 20 patients (14 females and 6 males). The recipient region was the maxilla in 3, mandibular ramus in 13, mental region in 7, and frontal bone in 1. Postoperative courses were favorable in 18 out of the 23 regions; however, the fit was insufficient in 2 regions and the recipient regions were exposed within 1 year after surgery. Three regions were exposed 1 year or more after surgery. CONCLUSION: We developed a novel reconstruction method using a full custom-made artificial bone. Its fit with the recipient bone was considered to be important, since an ill fit between the recipient and artificial bones potentially resulting in the artificial bone being detached. Therefore, fixation is important in order to prevent the detachment, and careful course observations are required when an ill fit is concerned during the follow-up period.

A Case of Odontogenic Infection by Streptococcus constellatus Leading to Systemic Infection in a Cogan's Syndrome Patient.

Odontogenic infection in immunocompromised patients tends to extend systemically beyond the oral cavity. Our case report presents a patient with sepsis due to a Streptococcus constellatus (S. constellatus) odontogenic infection in a 64-year-old-immunocompromised woman with Cogan's syndrome. She had been suffering from chronic mandibular osteomyelitis which was thought to have been caused by dental caries and/or chronic periodontitis with furcation involvement of the left mandibular first molar. We suspect that the acute symptoms of the chronic osteomyelitis due to S. constellatus led to the systemic infection. This infection could be accelerated by the use of a corticosteroid and an alendronate. This is the first report which represents the potential association between odontogenic infection and Cogan's syndrome.

Correction of upturned nasal tip with a costal cartilage graft in bilateral cleft lip patients.

We used a piece of costal cartilage as a cartilaginous strut to correct the upturned nasal tip in patients with bilateral cleft lip. The grafted cartilage provides more definition of the tip and improves the obtuse nasolabial angle. Neither the septal cartilage nor the ear cartilage has enough strength to shape the tip. This method of correction has consistently produced favorable, long-lasting results in adults and has improved the contour of the nasal tip in younger patients.

Surgical management of odontogenic myxoma: a case report and review of the literature.

BACKGROUND: Odontogenic myxoma is a benign odontogenic tumor with locally aggressive behavior, and is relatively rare in the oral cavity. There are currently no clear surgical management guidelines for odontogenic myxoma, and a variety of approaches may be used. This study evaluated the literature concerning the surgical management of odontogenic myxoma, and reports the long-term outcome of a case managed by using a more conservative surgical approach. CASE PRESENTATION: We managed a 40-year-old Japanese man with odontogenic myxoma in the right mandible by enucleation and curettage, a relatively conservative approach that has proved to have been justified by a lack of recurrence over 10 years. Our strategy was compared with others reported in the literature, which was identified by a PubMed search using the term "odontogenic myxoma". Articles without full text or with missing data were excluded. The age and sex of patients, the tumor location (maxilla/mandible), treatment (conservative/radical), recurrence, and follow-up period were compared in the reported cases that we evaluated. From the initial 211 studies identified, 20 studies qualified as mandibular cases of odontogenic myxoma. Recurrence was reported in three cases that had been treated with a more conservative surgical approach. CONCLUSIONS: Enucleation and curettage has proved an effective approach in several cases in ours there has been no recurrence more than 10 years after surgery but the risk of recurrence appears to be higher. We discuss the important factors that must be considered when determining the correct management approach to odontogenic myxoma.

Reconstruction of a complex midface defect from excision of a squamous cell carcinoma, according to regional aesthetic units.

Extensive squamous cell carcinoma involving the skin of the upper lip, nasal ala, and cheek is relatively rare. Although numerous reconstruction techniques for the midface including lip, nose, and cheek have been described in the literature, reconstruction of large defects in this area continues to be challenging, as it is difficult to obtain satisfactory results with single-stage surgery. This case report concerns a 53-year-old woman with squamous cell carcinoma extending from the upper lip to the alar base and the cheek. It describes a step-by-step surgery undertaken according to defined regional aesthetic units of the face using several reconstruction methods, including a microvascular free flap, forehead flap, and conchal cartilage graft, rather than multistage reconstruction surgeries after first immediate reconstruction. Satisfactory functional and aesthetic results were achieved despite the extensive facial defects.

Clinical presentation of epignathus teratoma with cleft palate; and duplication of cranial base, tongue, mandible, and pituitary gland.

A 2-day-old girl was diagnosed with an oral epignathus teratoma and an uncommon combination of orofacial malformations including cleft palate; tongue, mandible, cranial base, cervical vertebrae, lower lip, and pituitary gland duplications; and fistula of the glabella and lower lip. Computed tomography revealed that the mass within the nasal cavity had tooth-like calcifications and protruded into the nasopharynx and oral cavity. It was implanted on the anterior wall of the body of the sphenoid bone and was accompanied with mandibular duplication. Magnetic resonance imaging detected duplication of the pituitary gland and confirmed the absence of intracranial communication of the nasopharyngeal mass. The teratoma did not cause respiratory obstruction; however, the patient required continuous nasogastric tube feeding. Usually, an epignathus teratoma is associated with few midline defects and can be corrected with multiple interventions at different time points. The current study describes the surgical procedure comprising excision of the tumor along with reconstructive surgeries of the mandible, tongue, and fistulae undertaken when the infant reached 7 months of age. The cleft palate was repaired at 18 months of age using the Kaplan buccal flap method. Histopathologic examination confirmed a grade 0 teratoma covered with keratinized skin and containing pilosebaceous and sweat glands, adipose tissue, and smooth muscle. The long-term success of this intervention was determined at the follow-up examination conducted at 3 years of age, with no signs of the teratoma recurrence observed.

Submucous cleft palate: variations in bony defects of the hard palate.

We have analysed bony defects of the hard palate in patients with submucous cleft palate to find out whether velopharyngeal insufficiency (VPI) is dependent on the extent of these defects. We evaluated the maxillofacial structures associated with cleft palate by 3-dimensional computed tomography (CT) in 23 children diagnosed with submucous cleft palate. Bony defects of the hard palate were divided into Type I, defined as absent posterior nasal spine (n=12), Type II, V-shaped bony notch (moderate, n=7), and Type III, as bony defect extending into the incisive foramen (severe, n=4) defects, respectively. VPI was found in 10, 3, and 4 patients, respectively. Neither VPI nor the degree of bifid uvula was significantly associated with the types of bony defects.

Evaluation of mandibular hypoplasia in patients with hemifacial microsomia: a comparison between panoramic radiography and three-dimensional computed tomography.

OBJECTIVE: To compare the accuracy of three-dimensional computed tomography (3D-CT) and panoramic radiography in the evaluation of mandibular hypoplasia in patients with hemifacial microsomia (HFM). DESIGN: Retrospective study of imaging data. Setting : Images selected from the archives of the University of Tokyo Hospital. SUBJECTS: Twenty patients with unilateral HFM who had undergone both panoramic radiography and 3D-CT in the same period. METHOD: Mandibular deformities were classified according to the Pruzansky classification; eight patients had Grade I deformity and 12 patients had Grade II deformity. Ramus heights were measured on both panoramic radiographs and 3D-CT. MAIN OUTCOME MEASURES: Magnification in panoramic radiographs and extent of mandibular asymmetry as estimated by the affected/unaffected side ratio based on two methods were examined. The Pearson product-moment correlation coefficient was used to estimate correlations between parameters. RESULTS: The magnification of ramus heights on panoramic radiographs showed large variations in Grade II patients. The affected/unaffected side ratio estimated by the two methods showed a strong correlation in Grade I patients (correlation coefficient 0.99; p < .0001). Conversely, a weak correlation was seen in Grade II patients (correlation coefficient 0.77; p  =  .0036), and affected/unaffected side ratios from panoramic radiographs were both over- and underestimated. CONCLUSIONS: The accuracy of evaluation using panoramic radiography was fairly reliable in Grade I patients. Conversely, accuracy was poor in Grade II patients, and evaluation using 3D-CT seems preferable. The combination of two methods with careful consideration is recommended for clinical applications.

Anatomical study of the external carotid artery and its branches for administration of superselective intra-arterial chemotherapy via the superficial temporal artery.

BACKGROUND: The branching patterns of the external carotid artery vary among individuals, and consideration of the proximity of nerves is important during catheter insertion in superselective intra-arterial infusion via the superficial temporal artery. We aimed to evaluate the anatomy of the external carotid artery and its surrounding nerves for safe and accurate administration of superselective intra-arterial chemotherapy via the superficial temporal artery. METHODS: We analyzed the external carotid artery and its branches morphometrically in 28 Japanese cadavers (56 sides). RESULTS: Vascular tortuosity in the preauricular region of the catheter insertion site was observed in 42.9% of the sides; the main trunk of the external carotid artery was excessively tortuous in 25.0% of the sides, primarily in the preparotid region. Faciolingual and superior thyrolingual trunks were observed in 28.6 and 1.8% of the sides, respectively. The superior thyroid, lingual, facial, occipital, and maxillary arteries branched from the external carotid artery above the carotid bifurcation in 41.1% of the sides. The mean distance between the insertion site and maxillary artery was 39.5 mm, indicating the extent of catheter insertion. The auriculotemporal nerve was observed near the superficial temporal artery in the preauricular region in 44.6% of the sides; however, the clearly identifiable nerves in the exposed area were difficult to avoid. CONCLUSION: Because of the branching variations observed in individuals and sides, preoperative angiography is extremely important for avoiding complications.