Three-dimensional Culture Using Atelocollagen Sponge and Self-assembling Peptide Hydrogel.

This study aimed to assess the combined application of two biomaterials, a selfassembling peptide hydrogel (SPH) and an atelocollagen sponge (ACS). The ACS was combined with SPH (PuraMatrixⓇ or PanaceaGelⓇ) and its osteogenic effects on mouse osteoblastic cell line MC3T3 then evaluated. Each type of SPH was successfully incorporated into the ACS. The MC3T3 cells showed uniform distribution within the scaffold. No necrotic cells were observed throughout the experimental procedures. When the SPH was combined with the ACS, the MC3T3 cells differentiated toward the osteo-lineage, expressing Alp, Runx2, Osx, Bsp, and Oc. PanaceaGelⓇ exhibited a stronger osteogenic effect on the cells than PuraMatrixⓇ.

Second Primary Metachronous Malignancies Occurring in Oral Cavity of Young Adult-A Case Report.

The incidence of oral cancer in Japan is increasing. Interestingly, the number of young patients with oral cancer is also rising. A 19-year-old man with no history of smoking or drinking alcohol presented with a 20×15-mm elastic, hard, protruding mass with a white surface on the right-hand margin of the tongue. A biopsy resulted in a diagnosis of a well-differentiated squamous cell carcinoma of the tongue, for which a partial resection was subsequently performed. During regular follow-up, the patient demonstrated no clinical or imaging abnormalities until 4 years and 9 months later, when erosion was observed at the right palatoglossal arch. A malignant tumor of the right palatoglossal arch was diagnosed based on cytology and imaging findings, and total resection of the lesion performed. Histopathological examination of the resected lesion revealed a moderately differentiated squamous cell carcinoma. Epithelial dysplasia on the right-hand margin of the tongue was diagnosed 4 years and 9 months after the second surgery and was subsequently resected. The patient's condition has been favorable for 7 years since the diagnosis of the second cancer, with no noted recurrence. This case emphasizes the importance of follow-up after initial treatment, as even young people, who are likely to have to endure long-lasting consequences from treatment, can develop metachronous cancer in the oral cavity.

Early Detection of Leukoplakic Oral Squamous Cell Carcinoma Using 4NQO-induced Rat Tongue Cancer Model: Study Utilizing Fluorescence Intensity and Histopathological Evaluation.

Early identification of leukoplakic oral squamous cell carcinoma (OSCC) is difficult. The purpose of this study was to determine whether it was possible to detect change from normal epithelium to leukoplakic OSCC using a fluorescence visualization (FV) device in a 4-nitroquinoline 1-oxide (4NQO) -induced rat tongue cancer model. If successful, this would facilitate early detection of OSCC. The rats (3 groups of 5) were administered 50 ppm 4NQO in their drinking water over a period of 10, 15, or 20 weeks. Five non-treated rats were used as a control group. Images of their tongues obtained by FV were analyzed for change in fluorescence intensity (FI) using image analysis software. Immunoreaction for anti-CK13, anti-CK17, and anti-E-cadherin antibodies was also histopathologically evaluated. Receiver operating characteristic (ROC) analysis was used to calculate the cut-off values, sensitivity, specificity, and area under the curve. The most marked change in FI was found between the control and 10-week groups, with an increase observed in its average value and range in the latter. These findings differed from those characteristic of leukoplakia. No significant difference was observed in the positive cell rate for immunoreaction for anti-CK13 or anti-CK17 antibodies between the control and 10-week groups. A significant decrease was observed in the positive pixel ratio of immunoreaction for anti-E-cadherin antibody in the 10-week group in comparison with in the control group (p <0.05). These results showed that disruption of intercellular adhesion could be observed at 10 weeks. In the ROC analysis, the FI cut-off value in the 10-week and control groups was 51.9, sensitivity 95.5%, and specificity 96.9%. This indicated that normal epithelium could be accurately distinguished from low-grade dysplasia with high probability. These results demonstrate that analysis of change in FI as measured by FV could facilitate early detection of leukoplakic OSCC.

Persistent bone resorption lacunae on necrotic bone distinguish bisphosphonate-related osteonecrosis of jaw from denosumab-related osteonecrosis.

BACKGROUND: Bisphosphonate and denosumab are widely used for the treatment of osteoporosis and bone metastasis of cancer to prevent excessive bone resorption. Osteonecrosis of the jaw is a serious adverse effect of bisphosphonate or denosumab referred to as bisphosphonate-related osteonecrosis of the jaw (BRONJ) or denosumab-related osteonecrosis of the jaw (DRONJ), respectively. Since bisphosphonate and denosumab inhibit bone resorption by different mechanism, we evaluated whether these drug types result in different histopathological characteristics related to bone resorption. MATERIALS AND METHODS: We histopathologically investigated 10 cases of BRONJ, DRONJ, and suppurative osteomyelitis. Paraffin sections prepared from decalcified dissected jaw bones were used for histopathological observation, second harmonic generation imaging, and bone histomorphometry. The samples were also observed by a scanning electron microscope. RESULTS: Numerous bone resorption lacunae were observed on the necrotic bone surface in almost all cases of BRONJ; however, such resorption lacunae were limited in DRONJ and suppurative osteomyelitis. Prominent bone resorption lacunae were also confirmed by second harmonic generation imaging and scanning electron microscopy in BRONJ, but not in DRONJ or suppurative osteomyelitis. As determined by bone histomorphometry, the number of bone resorption lacunae and the length of the erosion surface of resorption lacunae were significantly higher in BRONJ group than in the DRONJ and suppurative osteomyelitis groups. These parameters were correlated between the necrotic bones and the vital bones in BRONJ. CONCLUSIONS: Persistent bone resorption lacunae on the necrotic bone surface are unique to BRONJ, providing a basis for distinguishing BRONJ from DRONJ and OM in histopathological diagnosis.

Three-Dimensional Analysis of Soft and Hard Tissue Changes following Orthognathic Surgery.

Change in soft tissue in relation to that in hard tissue following orthognathic surgery was evaluated. Twenty-five patients were enrolled in the study. The diagnosis in all was jaw deformity (maxillary retrusion and mandibular protrusion) and all underwent a Le Fort I osteotomy and bilateral sagittal splitting ramus osteotomy. Three-dimensional (3D) computer-aided design (CAD) models (polygon models) of the hard and soft tissue of the maxilla and mandible were constructed and superimposed. Reference points were established on the pre- and postoperative hard and soft tissues. Specific elements of each reference point were divided into X, Y, and Z components, respectively, and the distances in each direction and 3D distance (normal distance) measured. The Wilcoxon signed-rank test was used to determine differences in the mean values for the distance moved of each element as the error between pre- and postoperatively. The results revealed statistically significant differences in the Y-direction in the maxilla and the X- and Z-directions in the mandible. A significant difference was also observed in the 3D distances of the maxilla and mandible. Little evidence was found of linearity between the amount of hard and soft tissue movement in the X- and Z-directions in the maxilla. This means that 3D movement in the maxilla was masked more by changes in the morphology of the soft tissue than in the mandible, making it less evident. The results of this study suggest that the 3D analysis method used enables changes in hard and soft tissues to be understood qualitatively, and that it can be used in diagnosis and treatment in orthognathic surgery. It may also be useful in simulation of morphological change in soft tissue.

Three-Dimensional Evaluation of Pharyngeal Morphology in Bimaxillary Surgery with and without Horseshoe Osteotomy in Skeletal Class III Cases.

Repositioning of the jaw in orthognathic treatment generates changes in the soft tissues of the maxillofacial region, with consequent changes in the airway. The purpose of this study was to determine how type of orthognathic surgical procedure affected the 3-dimensional morphology of the upper airway. Forty patients were divided into the following 2 groups according to the type of surgical procedure used: a horseshoe osteotomy (HS) group (20 patients, comprising 11 men and 9 women; average age 24.3±4.5 years) who underwent bimaxillary surgery; and a LeFort I osteotomy (LF) group (20 patients, comprising 8 men and 12 women; average age 22.5±4.6 years) who also underwent bimaxillary surgery. Cephalometric measurements were taken and 3-dimensional pharyngeal morphology evaluated in each group. The amounts of maxilla rotation, posterior maxilla impaction, and mandibular setback all revealed a significantly larger value in the HS group. Evaluation of pharyngeal volume revealed a significant decrease in the upper pharyngeal segment in the LF group. A significant decrease in the lower pharyngeal segment was observed in both groups. Differences were noted in postoperative pharyngeal morphology between the two groups. The results of this study suggest that HS has less effect on the upper pharyngeal segment, regardless of the amount of posterior maxilla impaction.

A novel GNAS-mutated human induced pluripotent stem cell model for understanding GNAS-mutated tumors.

A missense mutation of the guanine nucleotide binding protein alpha stimulating activity polypeptide 1 (GNAS) gene, typically Arg201Cys or Arg201His (R201H/R201C), leads to constitutive activation of the Gsα-cyclic AMP (cAMP) signaling pathway that causes several diseases. However, no germline mutations of GNAS have been identified to date, likely due to their lethality, and no robust human cell models have been generated. Therefore, the aim of this study was to generate GNAS-mutated disease-specific induced pluripotent stem cells as a model for these diseases. We then analyzed the functionality of this induced pluripotent stem cell model and differentiated epithelial cells. We generated disease-specific induced pluripotent stem cells by introducing a mutation in GNAS with the clustered regularly interspaced short palindromic repeats (CRISPR) nickase method, which has lower off-target effects than the conventional CRISPR/Cas9 method. We designed the target vector to contain the R201H mutation in GNAS, which was transfected into human control induced pluripotent stem cells (Nips-B2) by electroporation. We confirmed the establishment of GNASR201H-mutated (GNASR201H/+) induced pluripotent stem cells that exhibited a pluripotent stem cell phenotype. We analyzed the effect of the mutation on cAMP production, and further generated teratomas for immunohistochemical analysis of the luminal epithelial structure. GNAS-mutated induced pluripotent stem cells showed significantly higher levels of intracellular cAMP, which remained elevated state for a long time upon hormonal stimulation with parathyroid hormone or adrenocorticotropic hormone. Immunohistochemical analysis revealed that several mucins, including MUC1, 2, and MUC5AC, are expressed in cytokeratin 18 (CK18)-positive epithelial cells. However, we found few CK18-positive cells in mutated induced pluripotent stem cell-derived teratoma tissues, and reduced MUCINs expression in mutated epithelial cells. There was no difference in CDX2 expression; however, mutated epithelial cells were positive for CEA and CA19-9 expression. GNASR201H-mutated induced pluripotent stem cells and GNASR201H-mutated epithelial cells have distinct phenotypic and differentiation characteristics. We successfully established GNASR201H-mutated human induced pluripotent stem cells with increased cAMP production. Considering the differentiation potential of induced pluripotent stem cells, these cells will be useful as a model for elucidating the pathological mechanisms of GNAS-mutated diseases.

Antimicrobial susceptibility surveillance of bacterial isolates recovered in Japan from odontogenic infections in 2013.

We report on the findings of the first antimicrobial susceptibility surveillance study in Japan of isolates recovered from odontogenic infections. Of the 38 facilities where patients representing the 4 groups of odontogenic infections were seen, 102 samples were collected from cases of periodontitis (group 1), 6 samples from pericoronitis (group 2), 84 samples from jaw inflammation (group 3) and 54 samples from phlegmon of the jaw bone area (group 4) for a total of 246 samples. The positivity rates of bacterial growth on culture were 85.3%, 100%, 84% and 88.9%, respectively, for groups 1, 2, 3 and 4. Streptococcus spp. isolation rates according to odontogenic infection group were 22% (group 1), 17.7% (group 3) and 20.7% (group 4). Anaerobic isolation rates were 66.9% (group 1), 71.8% (group 3) and 68.2% (group 4). Drug susceptibility tests were performed on 726 strains excluding 121 strains that were undergrown. The breakdown of the strains subjected to testing was 186 Streptococcus spp., 179 anaerobic gram-positive cocci, 246 Prevotella spp., 27 Porphyromonas spp., and 88 Fusobacterium spp. The isolates were tested against 30 antimicrobial agents. Sensitivities to penicillins and cephems were good except for Prevotella spp. The low sensitivities of Prevotella spp is due to ß-lactamase production. Prevotella strains resistant to macrolides, quinolones, and clindamycin were found. No strains resistant to carbapenems or penems were found among all strains tested. No anaerobic bacterial strain was resistant to metronidazole. Antimicrobial susceptibility testing performed on the S. anginosus group and anaerobic bacteria, which are the major pathogens associated with odontogenic infections, showed low MIC90 values to the penicillins which are the first-line antimicrobial agents for odontogenic infections; however, for Prevotella spp., penicillins combined with ß-lactamase inhibitor showed low MIC90 values.

Which Factors Affect the Long-Term Survival of Patients With Oral Squamous Cell Carcinoma With Distant Metastasis?

PURPOSE: The development of distant metastases (DMs) in patients with oral squamous cell carcinoma (OSCC) leads to dismal prospects for survival. The present study aimed to identify the risk factors for DM development and long-term survival. PATIENTS AND METHODS: The present study was a retrospective cohort study of patients with OSCC at a single institution. The predictor variables were age, gender, lymph node classification, histologic grade, neck dissection, infiltrative growth pattern (INF), vascular/lymphatic invasion, perineural invasion (PI), extranodal extension, local recurrence, nodal metastasis, DMs, interval to the diagnosis of DMs, and surgery for DMs. The primary outcome variables were the 5-year overall survival (OS) and median survival time (MST), which were estimated using the Kaplan-Meier method. Cox hazard models were used to identify the risk factors for DM development. RESULTS: The cohort included 526 patients; the data from 402 were available for analysis. Of these 402 patients, 37 developed DMs. On multivariate analysis, clinical N1 (cN1)-cN2 (hazard ratio [HR], 3.36), moderate/poor differentiation (HR, 2.51), INFc (HR, 3.27), vascular/lymphatic invasion (HR, 2.95), and PI (HR, 2.17) were independent predictors of DM development. The 5-year OS was 84.6% for the non-DM patients and 9.7% for the DM patients, with a MST of 16.9 months. In those with DMs with cN0, the 5-year OS was 18.2% and the MST was 37.2 months. For those with DMs with cN1-cN2, the 5-year OS was 4.7% and the MST was 12.9 months. In patients with an interval to the DM diagnosis of 10.0 months or longer, the 5-year OS was 20.0% and the MST was 38.6 months. In the patients with an interval to the DM diagnosis of less than 10.0 months, the MST was 11.7 months. The 5-year OS of the patients who had undergone pulmonary metastasectomy was 60.0% and the MST of the nonsurgery group was 16.0 months. CONCLUSIONS: In the patients with DMs, stage cN0 and a late interval to DM diagnosis were associated with long-term survival. Pulmonary metastasectomy could be worth considering to improve survival.

Target Capture/Next-Generation Sequencing for Nonsyndromic Cleft Lip and Palate in the Japanese Population.

OBJECTIVE: The pathogenesis of nonsyndromic cleft lip with or without cleft palate (NSCL ± P) and nonsyndromic cleft palate only (NSCP) may be associated with genetic factors. Although some predisposing genes/loci have been reported, their attributable risk is too small to be clinically meaningful. To clarify the genetic causes and mechanisms of NSCL±P or NSCP, we conducted mutation analysis of target genes using a next-generation sequencing (NGS) approach. METHODS: The target genes, IRF6, WNT5A, WNT9B, TP63, MSX1, TFAP2A, PAX9, DLX3, DLX4, and MN1, were selected based on previous reports of potential associations with the development of NSCL±P or NSCP from genome-wide association studies and candidate gene analyses. Mutation analysis was conducted using NGS on 74 Japanese trios (patient and parents) and 18 Japanese patients only families. RESULTS: We detected single-nucleotide variants (SNVs) for 7 genes: IRF6, DLX4, WNT5A, TFAP2A, WNT9B, TP63, and PAX9. The SNVs found on IRF6 and DLX4 were missense mutations, whereas those identified on WNT5A, TFAP2A, WNT9B, TP63, and PAX9 were rare variants in the noncoding region; no de novo mutation was identified in the trio samples. The amino acid change on DLX4 was detected within the highly conserved homeodomain and was predicted to have a deleterious impact on the protein function by in silico analysis. CONCLUSIONS: The DLX4 missense mutation c.359C>T (Pro120Leu) was found in 1 Japanese patient with NSCL±P and was located in the homeodomain region. This mutation likely plays a role in the development of NSCL±P in the Japanese population.

Actinin-4 Expression Predicts Poor Disease-free Survival and Correlates with Delayed Lymph Node Metastasis in Patients with Completely Resected Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma is generally characterized by poor prognosis, and biomarkers are needed for development and selection of therapy. The purpose of this study was to assess expression of actinin-4, which has been implicated in cancer invasion and metastasis, to determine its viability as a prognostic indicator in oral squamous cell carcinoma. Clinical factors and tumor samples immunohistochemically stained for actinin-4 were retrospectively investigated in 55 patients who underwent curative surgery for oral squamous cell carcinoma. Overall survival and disease-free survival were estimated by Kaplan-Meier analysis. Significant differences were detected using the Pearson's chi-square and Fisher's exact tests. Univariate and multivariate analyses were performed with the Cox regression model. No association was found between expression of actinin-4 and clinical factors, including age or sex, or histopathological factors, including vascular invasion, lymphatic invasion, stage, mode of invasion, or histological atypicality. Expression of actinin-4 showed a positive correlation with delayed cervical lymph node metastasis. Disease-free survival was significantly lower in patients who were positive for expression of actinin-4 (p=0.010); overall survival showed no difference between patients with or without expression of actinin-4, however. The results revealed that actinin-4 was an independent prognostic factor for disease-free survival. Expression of actinin-4 showed a 73% sensitivity and 68% specificity for prediction of delayed cervical lymph node metastasis. In conclusion, actinin-4 may potentially be a useful biomarker for prediction of delayed cervical lymph node metastasis.

Luminal, Intramural Unicystic Ameloblastoma with Marked Fluid-Fluid Level: Validity of CT and MRI Findings.

We report herein a case of a luminal and intramural unicystic ameloblastoma (UA) with a marked fluid-fluid level. The validity of imaging findings in diagnosing UA in the present case is discussed in reference to the literature. The patient was a 50-year-old woman who presented with swelling of the gingiva in the region of the left mandibular third molar and numbness in the lower lip. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a large mass lesion with a unilocular appearance and a biphasic aspect, suggesting liquid content. Contrast-enhanced MRI (CE-MRI) and dynamic contrast-enhanced MRI (DCE-MRI) demonstrated that the biphasic aspect indicated a fluid-fluid level with no blood pooling/flow; it also revealed a thick rim-enhanced margin with mural protrusion. Postoperatively, the lesion was histopathologically diagnosed as a luminal and intramural UA. In conclusion, extensive imaging including both standard CT and MRI together with CE-MRI and DCE-MRI allowed mural protrusions or nodules on a thick cystic wall and liquid content to be correctly identified. This suggests that such imaging can play an important role in diagnosing a UA, even though the results were at first misleading due to the marked fluid-fluid level.

Investigation of Surgical Site Infections and Bacteria Detected Following Neck Dissection in Patients with Oral Cancer.

During dissection for oral cancer, there is a high probability of bacteria indigenous to the oral cavity migrating to the surgical field in the neck due to the opening of new pathways of communication with the oral cavity. The risk of postoperative surgical site infection (SSI) in such patients is high due to malnutrition arising from perioperative eating disorders and dysphagia. Neck infections after neck dissection in oral cancer patients were investigated to elucidate the development of SSIs and their relationship with the results of bacterial culture.A total of 86 patients with oral squamous cell carcinoma who underwent neck dissection between January 2012 and December 2016 were enrolled. Ten factors were selected for investigation: (1) sex; (2) age; (3) primary site; (4) type of dissection; (5) whether or not there was a new pathway of communication between the oral cavity and the neck; (6) operative time; (7) blood loss; (8) number of drainage days; (9) amount of drainage at the time of drain removal; and (10) whether or not there was an SSI. Bacteria isolated from the catheter tip on drain removal were also investigated. Significant differences were observed between patients with and without SSIs (p-0.010) according to the presence of a new pathway of communication between the oral cavity and the neck (p-0.004); operative time (p-0.007); number of drainage days (p-0.029); or the amount of drainage at the time of drain removal. The present results indicate that selecting antibiotics appropriate to each patient and administering perioperative oral care are important in preventing SSIs.

A Case of Fibrolipoma of the Hard Palate.

An extremely rare case of fibrolipoma in the hard palate is presented and discussed with reference to the literature. An 85-year-old woman visited the Tokyo Dental College Chiba hospital in September 2016 with the chief complaint of a mass in the hard palate. The patient had first become aware of this mass several years earlier. An examination at another hospital in June 2009 resulted in a clinical diagnosis of lipoma. Regular examinations followed every 6 months until September 2014, at which time she stopped attending these appointments because there was no change. In August 2016, however, the patient realized that the tumor was increasing in size. Although there was no pain, awareness of a foreign body in the oral cavity when eating or talking was increasing, so she decided to visit our clinic for detailed examination and treatment. At this point, the mass extended from the center to the left side of the hard palate. It measured 15 mm along the major axis, and had a clear border; nearly spherical, its surface was smooth and glossy, and was of a slightly yellowish color. The mass was painless, elastic, and soft. Computed tomography and magnetic resonance imaging revealed a tumorous lesion. Based on a clinical diagnosis of lipoma, it was subsequently excised under general anesthesia in January 2017. The tumor lay under the palatal mucosa, extending from the center to the left side of the hard palate. It was surrounded by a single-layered membranous structure, and had not adhered to the surrounding tissues. Healthy palatal mucosa and periosteum were also removed en bloc with the tumor within a safety margin of approximately 5 mm. No pressure absorption of palatine bone was seen. Histopathologically, proliferation of mature adipose tissue was observed. This was surrounded by a thin, single-layer membrane within the subepithelial connective tissue, which was covered by stratified squamous epithelium. Proliferation of fibrotic connective tissue was seen between the adipocytes. The final diagnosis was fibrolipoma. To date, at 18 months postoperatively, no recurrence has been observed and progress has been satisfactory.

Monitoring of cancer patients via next-generation sequencing of patient-derived circulating tumor cells and tumor DNA.

Liquid biopsy of circulating tumor cells (CTC) and circulating tumor DNA (ctDNA) is gaining attention as a method for real-time monitoring in cancer patients. Conventional methods based upon epithelial cell adhesion molecule (EpCAM) expression have a risk of missing the most aggressive CTC subpopulations due to epithelial-mesenchymal transition and may, thus, underestimate the total number of actual CTC present in the bloodstream. Techniques utilizing a label-free inertial microfluidics approach (LFIMA) enable efficient capture of CTC without the need for EpCAM expression. In this study, we optimized a method for analyzing genetic alterations using next-generation sequencing (NGS) of extracted ctDNA and CTC enriched using an LFIMA as a first-phase examination of 30 patients with head and neck cancer, esophageal cancer, gastric cancer and colorectal cancer (CRC). Seven patients with advanced CRC were enrolled in the second-phase examination to monitor the emergence of alterations occurring during treatment with epidermal growth factor receptor (EGFR)-specific antibodies. Using LFIMA, we effectively captured CTC (median number of CTC, 14.5 cells/mL) from several types of cancer and detected missense mutations via NGS of CTC and ctDNA. We also detected time-dependent genetic alterations that appeared during anti-EGFR therapy in CTC and ctDNA from CRC patients. The results of NGS analyses indicated that alterations in the genomic profile revealed by the liquid biopsy could be expanded by using a combination of assays with CTC and ctDNA. The study was registered with the University Hospital Medical Information Network Clinical Trials Registry (ID: UMIN000014095).

A Multicenter Retrospective Study of Elective Neck Dissection for T1-2N0M0 Tongue Squamous Cell Carcinoma: Analysis Using Propensity Score-Matching.

BACKGROUND: This multicenter retrospective study aimed to determine whether elective neck dissection (END) can be performed for T1-2N0M0 tongue cancer. METHODS: Patients with T1-2N0M0 tongue squamous cell carcinoma who received treatment between January 2000 and December 2012 were enrolled at 14 multicenter study sites. The 5-year overall survival (OS) and 5-year disease-specific survival (DSS) were compared between the propensity score-matched END and observation (OBS) groups. RESULTS: The results showed that the OS rates among the 1234 enrolled patients were 85.5% in the END group and 90.2% in the OBS group (P = 0.182). The DSS rates were 87.0% in the END group and 94.3% in the OBS group (P = 0.003). Among the matched patients, the OS rates were 87.1% in the END group and 76.2% in the OBS group (P = 0.0051), and the respective DSS rates were 89.2% and 82.2% (P = 0.0335). CONCLUSION: This study showed that END is beneficial for T1-2N0M0 tongue cancer. However, END should be performed for patients with a tumor depth of 4-5 mm or more, which is the depth associated with a high rate of lymph node metastasis. The use of END should be carefully considered for both elderly and young patients.

Antiresorptive Agent-Related Osteonecrosis of the Jaw (ARONJ): A Twist of Fate in the Bone.

Bisphosphonates (BPs) have been used as antiresorptive agents to treat patients with osteoporosis or metastatic bone cancer, each of which is characterized by bone loss due to the increased bone resorption. However, BPs could cause osteonecrosis of the jaw (ONJ), known as bisphosphonate-related osteonecrosis of the jaw (BRONJ). ONJ is associated with severe pain and deteriorated quality of life. ONJ is also caused by administration of denosumab, a monoclonal antibody against receptor activator of NFκB ligand (RANKL), that functions as a powerful antiresorptive agent. Accordingly, antiresorptive agent-related ONJ (ARONJ) has been advocated, the incidence of which is continuing to increase in Japan as a super-aging society. Importantly, the jawbone is more susceptible to infection compared with bones in other parts of the body, due to the unique anatomical and physiological characteristics; for example, the jawbone with a high remodeling rate is stimulated by teeth during mastication. The risk factors of ARONJ include dental infection, poor occlusal or oral hygiene status, and bone-invasive dental treatment, such as tooth extraction, dental implants, and dentures. Proper collaboration between doctors and dentists is of utmost importance to understand the current status of ARONJ and prevent developing ARONJ. It is also important to ensure that the patients treated with BPs or denosumab can receive appropriate dental treatment. More recently, angiogenesis inhibitors were reported to cause ONJ; thus, medication-related ONJ (MRONJ) has been advocated. This article overviews the concept of MRONJ by focusing on antiresorptive agents and the status of BRONJ in Japan.

Surgical Management of Median Cleft Lip Extending as Far as Alveolus Using Bone Grafting.

Median clefts, which run through the midline of the upper lip, and alveolus are considered a type of craniofacial cleft. A Tessier number 0 median cleft lip is the rarest, and there are few reports concerning its surgical management. Here, we describe the case of a 6-year-old boy who presented at our hospital with a median cleft and alveolus of the upper lip with a shortened bifid frenulum. Inverted-V and Z-plasty incisions were performed for the median cleft and iliac bone grafting for the midline alveolus. At 1 year 5 months later, the postoperative course was uneventful, and proper approximation of the orbicularis oris muscle and vermilion were achieved, with a symmetrical Cupid's bow and labial tubercle and philtrum.

Evaluation of Liquid Based Cytology for Tongue Squamous Cell Carcinoma: Comparison with Conventional Cytology.

Oral exfoliative cytology is now used by general practitioners in Japan to screen for oral cancer. With conventional cytology, however, the number of cells that can be sampled is small. Moreover, cell deformation and piling of cells when preparing specimens has been reported. The purpose of this study was to compare conventional and liquid based cytology (LBC), which has been employed with increasing frequency in recent years. We believe that identifying potential pitfalls in oral exfoliative cytology will help improve diagnostic accuracy. A total of 153 patients with tongue squamous cell carcinoma who were diagnosed and treated initially at our hospital between January 2000 and December 2010 were included. Of these, 124 underwent conventional cytology, while the remaining 29 underwent LBC. Histopathological and clinical findings were used as criteria. Conventional cytology yielded a positive rate of 54.8% and LBC 79.3%, while values of 28.2% and 13.8% were obtained for a suspected positive rate, respectively. Liquid based cytology yielded a significantly higher percentage of accurate diagnoses and fewer suspected positives (p<0.05) in cases clinically classified as endophytic and those classified as ulcerative in terms of clinical growth pattern. No significant difference was observed between conventional cytology and LBC in cases of an infiltrative growth pattern, however.The present results suggest that LBC is superior to conventional cytology in achieving an accurate diagnosis based on oral exfoliative cytology. The present findings also suggest that exophytic type, and especially leukoderma type clinical growth patterns constitute pitfall cases in oral exfoliative cytology.

Ten-year Clinical Trends among 575 Consecutive Oral Cancer Patients at Tokyo Dental College Oral Cancer Center.

The facilities comprising Tokyo Dental College (TDC) -the college itself and its medical institutions at Suidobashi, Ichikawa, and Chiba - have been officially recognized as a center for treating oral cancer. The TDC Oral Cancer Center (OCC) was established on April 1, 2006. It provides comprehensive medical care, including that aimed at recovery of postoperative function, such as restoration of stomatognathic function, dysphagia therapy, and placement of maxillary prostheses. The purpose of this study was to investigate patient trends at TDC-OCC over the 10 years following its establishment in order to determine how the safe and high-quality cancer care already provided might be even further improved. Oral cancer patients attending TDC-OCC between April 2007 and March 2017 were investigated. Clinical information was obtained from medical records and analyzed, including that on patient numbers, age, sex, primary site of tumor, clinical stage, and surgery provided. There were 758 new cases, and the number of new cases showed an annual increase. Among the total number of new patients, 575 (75.9%) represented primary cases. The number of operations also showed an increase, which correlated with the increase in the number of patients. The incidence in oral cancer has increased in several countries, including Japan. Oral cancer can be observed macroscopically and touched. In contrast to with cancers at many other sites, and despite various diagnostic devices for early detection having been developed, however, cases are often advanced when first encountered. Many advanced cases were treated at TDC-OCC, and the number of reconstructive operations following progressive cancer also increased over time.