Squamous cell carcinoma initially occurring on the tongue dorsum: a case series report with molecular analysis.

BACKGROUND: Squamous cell carcinoma (SCC) of the dorsum of the tongue is extremely rare, and it clinically resembles various benign lesions. Somatic mutations in TP53 and some driver genes were implicated in the development of SCC; however, the somatic genetic characteristics of dorsal tongue SCC remain unknown. With a detailed analysis of gene mutations in dorsal tongue SCC, we aimed to better understand its biology. METHODS: Four cases of SCC initially occurring on the tongue dorsum were evaluated for clinical and histological findings and immunohistochemical expression of p53 and p16. Gene mutations were analyzed using next-generation sequencing with a custom panel of driver genes. RESULTS: We retrospectively investigated 557 cases of tongue SCC, and only four cases of SCC initially occurred on the tongue dorsum. The four patients (cases 1-4) were one woman and three men with a mean age of 53.75 years (range: 15-74 years). Histological analysis revealed well-differentiated SCC. Through molecular analysis, we identified pathogenic somatic mutations, namely, TP53 p.C176F (c.527G > T) in case 3 and TP53 p.R282W (c.844 C > T) in case 4. No pathogenic variants were identified in the PI3K/AKT or RAS/RAF pathways. The p53 immunohistochemical examination revealed a wild-type expression pattern in cases 1-3 and strong expression in case 4. The results of p16 immunostaining were negative in all cases. CONCLUSIONS: We described four previously unreported genetic characteristics of dorsal tongue SCC. Somatic TP53 mutations may contribute to the development of a subset of dorsal tongue SCC; however, more cases with genetic analysis need to be accumulated.

Displacement of lower third molar into floor of mouth: a single institutional experience.

PURPOSE: The displacement of the tooth/tooth fragment into the floor of mouth sometimes happens during the lower third molar surgery and the patients are usually referred to oral and maxillofacial surgeons. To date, however, there is no consensus how to manage the displaced tooth due to the lack of available data. METHODS: In this study, we have retrospectively analyzed the management of the displaced lower third molar into the floor of mouth. Our institute experienced seven cases during 2010 to 2020. RESULTS: Incidence rate of the lingual nerve injury caused by displacement of the lower third molar was 1/7. Six patients out of seven underwent surgical removal of the displaced fragment. The direct approach was used when the fragment was palpable superficially and the fragment was horizontally located away from the lingual plate (2 cases), while when the fragment was not palpable, or was palpable and adjacent to the lingual plate, the lingual mucoperiosteal flap was selected (4 cases). CONCLUSION: We conclude that the palpation and preoperative diagnosis with computed tomographic images are significantly important to decide a better and most effective surgical approach.

A rare anatomical variation of the submental artery.

The submental artery usually runs anteriorly on the inferior surface of the mylohyoid muscle, giving branches to that muscle and to the anterior belly of the digastric muscle, finally supplying the submental skin. Branches of it often perforate the mylohyoid muscle and enter the sublingual space. During a routine anatomy dissection, we encountered a case in which the main trunk of the submental artery perforated the mylohyoid muscle, where the sublingual artery usually runs. No branches coursed anteriorly to supply the submental skin. To our knowledge, this submental artery variation has not been reported in the English literature. Any surgical procedure in the submandibular area, such as the axial pattern submental local flap, requires knowledge of such arterial variations.

A case of langerhans cell histiocytosis of the mandible that spontaneously regressed after biopsy in a child.

In younger patients of LCH, we should consider that the effectiveness of follow-up without aggressive treatment for SS-type LCH in the oral and maxillofacial bone. However, there are very rare case in which an SS-type LCH recurred after showing a healing tendency. Regular follow-up must be performed even after healing.

Comprehensive review of lower third molar management: A guide for improved informed consent.

Lower third molar removal is the most commonly performed dental surgical procedure. Nevertheless, it is difficult to ensure that all the informed consent forms given to patients are based on the best evidence as many newer publications could change the conclusions of previous research. Therefore, the goal of this review article is to cover existing meta-analyses, randomized control trials, and related articles in order to collect data for improved and more current informed consent.

A case of oral cancer with delayed occipital lymph node metastasis: Case report.

Consideration of unexpected metastasis in patients who have undergone neck dissection with advanced tumors must be anticipated with careful follow-up.

High mobility group box 1 induces bone pain associated with bone invasion in a mouse model of advanced head and neck cancer.

Advanced head and neck cancer (HNC) can invade facial bone and cause bone pain, thus posing a significant challenge to the quality of life of patients presenting with advanced HNC. The present study was designed to investigate HNC bone pain (HNC­BP) in an intratibial mouse xenograft model that utilized an HNC cell line (SAS cells). These mice develop HNC­BP that is associated with an expression of phosphorylated ERK1/2 (pERK1/2), which is a molecular indicator of neuron excitation in dorsal root ganglia (DRG) sensory neurons. Our experiments demonstrated that the inhibition of high mobility group box 1 (HMGB1) by short hairpin (shRNA) transduction, HMGB1 neutralizing antibody, and HMGB1 receptor antagonist suppressed the HNC­BP and the pERK1/2 expression in DRG. It was also observed that HNC­derived HMGB1 increased the expression of the acid­sensing nociceptor, transient receptor potential vanilloid 1 (TRPV1), which is a major cause of osteoclastic HNC­BP in DRG. Collectively, our results demonstrated that HMGB1 originating in HNC evokes HNC­BP via direct HMGB1 signaling and hypersensitization for the acid environment in sensory neurons.

High-mobility group box 1 induces bone destruction associated with advanced oral squamous cancer via RAGE and TLR4.

Bone destruction of maxillary and mandibular bone by invasive oral squamous cell cancer (OSCC) raises various problems in the management of patients, resulting in poor outcomes and survival. However, the mechanism behind bone destruction by OSCC remains unclear. High-mobility group box 1 (HMGB1), a highly conserved ubiquitous nuclear non-histone DNA-binding protein, has been demonstrated to be secreted by aggressive cancers and regulate osteoclastogenesis, a central player during bone destruction. We therefore reasoned that HMGB1 secreted by OSCCs contributes to bone destruction. Our results showed that HMGB1 is produced by human cell lines of OSCC and promotes osteoclastogenesis via up-regulation of the expression of receptor activator of nuclear factor kappa-Β ligand in osteoblasts and osteocytes, and consequently osteoclastic bone destruction in mice. Further, we found that these actions of HMGB1 are mediated via the receptor for advanced glycation end products and toll-like receptors. These findings suggest that HMGB1 of OSCC and its down-stream signal pathways are potential targets for the treatment of bone destruction associated with advanced OSCC.

Maxillofacial Trauma Surgery Patients With Titanium Osteosynthesis Miniplates: Remove or Not?

The authors examined the timing and causes of titanium miniplate removal after maxillofacial trauma surgery. The authors performed a retrospective study of maxillofacial fracture patients in whom maxillofacial osteosynthesis miniplates were inserted or removed at the Kagawa Prefectural Central Hospital, between 2008 and 2017. Predictive variables were age, sex, fracture site distribution, and time to miniplate removal with or without complications in relation to primary outcome variables. Among 185 patients, 440 miniplates were inserted and 272 miniplates were removed. In total, 116 patients (73.4%) had 282 miniplates (64.1%) removed, of which 4.8% fracture sites and 5.7% miniplates were removed because of complications. The mean time to miniplate removal was 630.9 and 258.0 days in patients with and without complications, respectively. There was a statistically significant difference in miniplate removal and miniplate retention relative to age and sex. This difference was not related to the presence or absence of sex- or age-related complications. The miniplates as osteosynthesis material were safe and useful for a long period of time with relatively few complications. Because complications requiring miniplate removal occurred within 1 or after 5 years postoperatively, osteosynthesis miniplate treatments should be decided while considering the patient's age and sex. Long-term follow-up is recommended for miniplates that remain implanted for >1 year.

Evaluation of Open Reduction and Internal Fixation of Mandibular Condyle Fracture by Intraoperative Cone-Beam Computed Tomography in a Hybrid Operating Room.

Condylar fractures are the most common fractures of the mandible, and treatment of mandibular condylar fractures by maxillofacial surgeons is a very important procedure. However, the surgical approaches have anatomical limitations. Therefore, it is difficult to evaluate the reduction achieved in open reduction and internal fixation because of the uncertainty in securing a sufficient operative field. As a potential solution, the authors evaluated the benefits of intraoperative cone-beam computed tomography (CBCT) with high image quality performed in a hybrid operating room. Intraoperative CBCT is easy to perform in a hybrid operating room, and it is possible to quickly evaluate high-quality CT images, including 3D images. Because the state of reduction of mandibular condylar fractures also affects the prognosis of treatment, more precise reduction and fixation should improve prognoses. The use of CBCT in a hybrid operating room also avoids re-operation, and patients benefit from minimum invasive surgery. Intraoperative CBCT is a very useful strategy for evaluation of mandibular condylar fracture surgical treatment.

A retrospective comparative study of mandibular fracture treatment with internal fixation using reconstruction plate versus miniplates.

PURPOSE: This study compared the clinical success rates of mandibular fracture treatment using reconstruction plates or miniplates and clarified the selection criteria for reconstruction plates. METHODS: All patients who had surgically-treated mandible fractures from 2008 to 2017 with sufficient follow-up were retrospectively analyzed for information about the fracture condition, treatment, and outcomes. RESULTS: A total of 126 surgically-treated mandible fractures without mandibular condylar fracture in 105 patients (76 male, 29 female) were included. Reconstruction plates were used in 32 fractures with very good postoperative occlusal function. Four cases with complications requiring reoperation were treated using only miniplates. Variables that were statistically associated with follow-up surgery included simple versus comminuted mandible fracture, and the absence of teeth that could be used for intermaxillary fixation (P < 0.05). In the miniplates treatment for comminuted fracture, there was a significant difference in the treatment outcome depending on the number of free bone-fragments and the presence of bone-fragments requiring removal within 1 cm (P < 0.05). CONCLUSION: Reconstruction plates provided better treatment outcomes for comminuted fractures and fractures without teeth. Selecting a reconstruction plate that is capable of sufficiently overloading is important in comminuted fractures with multiple free bone-fragments and bone-fragments requiring removal.

Which fixation methods are better between three-dimensional anatomical plate and two miniplates for the mandibular subcondylar fracture open treatment?

PURPOSE: To compare the clinical outcomes of a single three-dimensional (3-D) anatomical plate versus two conventional straight miniplates for the open treatment of mandibular subcondylar fractures. METHODS: This retrospective clinical study included patients with mandibular subcondylar fractures treated by the retromandibular transparotid approach using a 3-D plate or two straight miniplates. Outcome variables included preoperative conditions of patients and fractures, extent of postoperative bone healing, and incidence of complications. Other variables included age, sex, fracture site, and follow-up duration. Variables were evaluated using descriptive statistics and compared between groups. RESULTS: Twenty-eight fractures were analyzed: 13 fractures using 3-D plate and 15 fractures using two straight miniplates. None of the assessed variables showed significant differences between the two groups (p < 0.05). Unfortunately, in the 3-D plate group, reoperation was necessary for nonunion owing to plate breakage in one case with a bone defect around the fracture. CONCLUSION: The 3-D plate and two straight miniplates were equally effective for the surgical management of mandibular subcondylar fractures. Although a 3-D plate is sufficient for a typical simple fracture, in cases with a bone defect around the fracture, selection of the plate fixation method should be carefully considered.

What are the risk factors for postoperative infections of third molar extraction surgery: A retrospective clinical study?

Background: This study aimed to identify (1) the predilection site of postoperative infection after third molar extraction surgery, (2) risk factors associated with postoperative infection, and (3) the cause of the difference between delayed- and early-onset infections. Material and Methods: This retrospective study included 1010 patients (396 male, 614 female) who had ≥1 third molars extracted (2407; 812 maxilla, 1595 mandible). The risk factors were classified as attributes, general health, anatomic, and operative. Outcome variables were delayed- and early-onset infections. Results: Postoperative infection was completely absent in the maxilla, and all infections occurred in the mandible, with a probability of 1.94% (31/1595). Bivariate analysis for postoperative infection showed depth of inclusion and intraoperative hemostatic treatment to be significantly associated with the development of infections. Bivariate analysis for delayed- and early-onset infections showed simultaneous extraction of the left and right mandibular third molars to be prominent risk factors. Conclusions: Postoperative infection occurs mainly in the mandible, and that in the maxilla is very rare. The risk of postoperative infection in the mandible was found to be related to the depth of inclusion and intraoperative hemostatic treatment. Simultaneous extraction of the left and right mandibular third molars appear to increase the risk of delayed-onset postoperative infection

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Endoscope-Assisted Resection of Intramuscular Cavernous Hemangioma Within the Temporal Muscle.

Hemangiomas are benign vascular soft tissue tumors, which most frequently occur in the skin or subcutaneous tissue. Intramuscular hemangiomas typically occur in the trunk and extremities and less frequently in the head and neck. Among these, those occurring in the temporalis muscle are extremely rare. The authors report the case of a 43-year-old Japanese male with a mass in his left temporal fossa. Computed tomography images showed no erosion of the zygomatic bone, and magnetic resonance imaging revealed an ovoid well-marginated mass within the temporal muscle. The lesion was surgically excised with an endoscopy procedure used for minimally invasive lesions and complete removal. Histopathological examination confirmed the diagnosis of intramuscular cavernous hemangioma. The postoperative clinical course was good, with no indications of temporary nerve paralysis. No signs of local recurrence were observed postoperatively. Therefore, a cavernous hemangioma should be suspected when a mass occurs in the temporal region with accompanying radiologic findings suggesting vascular origin. In surgical treatment, the endoscopy-assisted technique is very useful to achieve complete tumor resection and prevent relapse while avoiding serious complications due to surgical procedures.

Retinoic Receptor Signaling Regulates Hypertrophic Chondrocyte-specific Gene Expression.

BACKGROUND/AIM: Retinoid signaling is important for the maturation of growth-plate chondrocytes. The effect of retinoid receptor gamma (RARγ) signaling on the expression of genes in hypertrophic chondrocytes is unclear. This study investigated the role of RARγ signaling in regulation of hypertrophic chondrocyte-specific genes. MATERIALS AND METHODS: The gene expression in mouse E17.5 tibial cartilage was examined by in situ hybridization analysis. Real-time reverse transcription-polymerase chain reaction (RT-PCR) and immunoblotting were used for analysis of mRNA and phosphorylated mitogen-activated protein kinase (MAPK). RESULTS: mRNA expression of Rarg and connective tissue growth factor (Ccn2) was detected in maturing chondrocytes throughout the cartilaginous skeletal elements. In chondrogenic ATDC5 cells, an RARγ agonist induced the gene expression of type-X collagen (Col10A1), transglutaminase-2 (Tg2), matrix metalloproteinase-13 (Mmp13), and Ccn2 mRNA, whereas a retinoic acid pan-agonist suppressed RARγ agonist-stimulated gene expression. Phosphorylated extracellular signal regulated-kinases (pERK1/2), p-p38, and phosphorylated c-Jun N-terminal kinase (pJNK) MAPK were time-dependently increased by RARγ agonist treatment. Experimental p38 inhibition led to a severe drop in the RARγ agonist-stimulated expressions of Col10A1, Tg2, Mmp13, and Ccn2 mRNA. CONCLUSION: RARγ signaling is required for the differentiation of hypertrophic chondrocytes, with differential cooperation with p38 MAPK.

Complications of a poly-L-lactic acid and polyglycolic acid osteosynthesis device for internal fixation in maxillofacial surgery.

The purpose of this study was to retrospectively evaluate and examine the incidence of complications using poly-L-lactic acid and polyglycolic acid (PLLA/PGA) copolymer plate system in maxillofacial osteosynthesis. The retrospective study included 87 patients (50 men, 37 women), who needed maxillofacial surgery. We examined the proportion of complications and their factors from clinical data. A comparison was also made for plate decomposition using the molecular weight of the plate without plate exposure and complications. Osteosynthesis sites healed in all patients. Ten cases (11.5%) showed plate exposure-related complications, with all occurring at intraoral surgical sites. There was no significant difference in molecular weight changes of plates in resorbable process. Statistical analysis of study variables between patients with and without exposed plates showed that the plate thickness was significantly associated with the risk of exposed plates (p < 0.05). The commercially available PLLA/PGA device could be a useful rapid resorbable material for maxillofacial osteosynthesis. When thick plates are used on the intraoral site, it may be necessary to pay attention to the complication of plate exposure. Even if exposure-related complications have occurred, resorption and degradation of this material proceeds, suggesting the ease of appropriate risk management.

Low-intensity pulsed ultrasound stimulation promotes osteoblast differentiation through hedgehog signaling.

Low-intensity pulsed ultrasound (LIPUS) has been used as an adjunct to fracture healing therapies, but the mechanisms underlying its action are not known. We reported that sonic hedgehog (SHH) signaling was activated in osteoblasts at the dynamic remodeling site of a bone fracture. Mechanical stimulation is a crucial factor in bone remodeling, and it is related to the primary cilia as a sensor of hedgehog signaling. Here we observed that LIPUS promoted callus formation in accord with Gli2-positive cells after 14 days at the mouse femur fractured site compared with a control group. An immunofluorescence analysis showed that the numbers of primary cilia and cilia/osterix double-positive osteoblasts were increased at the fracture site by LIPUS. LIPUS stimulated not only the number and the length of primary cilia, but also the levels of ciliated protein, Ift88 mRNA, and SHH, Gli1, and Gli2 in MC3T3-E1 cells. Further experiments revealed that LIPUS stimulated osteogenic differentiation in the presence of smoothened agonist (SAG) treatment. These results indicate that LIPUS stimulates osteogenic differentiation and the maturation of osteoblasts by a primary cilium-mediated activation of hedgehog signaling.

Oral Squamous Cell Carcinoma-derived Sonic Hedgehog Promotes Angiogenesis.

BACKGROUND: Sonic hedgehog (SHH) signaling is related to the pathogenesis of oral squamous cell carcinoma (OSCC), but its role in OSCC is not yet well understood. In this study, we analyzed the role of SHH signaling in OSCC. MATERIALS AND METHODS: We examined the expression pattern of SHH and its signal proteins in clinically resected OSCC samples by immunohistochemistry. We also evaluated the function of SHH signaling using the hedgehog signaling inhibitor cyclopamine in vivo and in vitro by proliferation, migration and angiogenesis analyses. RESULTS: We found that SHH was highly expressed in human tongue OSCC, whereas patched (PTCH1), glioma-associated oncogene 1 (GLI1) and GLI2 proteins were expressed in the microvascular cells in the tumor invasive front. Administration of cyclopamine to mice suppressed the growth and angiogenesis of OSCC xenografts in vivo. Moreover, cyclopamine inhibited endothelial cell proliferation and migration, and reduced aorta vascular length in the rat. CONCLUSION: These findings suggest that OSCC-derived SHH stimulates angiogenesis at the tumor invasive front.

Use of an intraoperative navigation system and piezoelectric surgery for styloidectomy in a patient with Eagle's syndrome: a case report.

BACKGROUND: Elongated styloid process syndrome (Eagle's syndrome) is the term given to the symptomatic elongation of the styloid process or the mineralization of the stylohyoid or stylomandibular ligament. The two commonly used approaches for the surgical treatment of this syndrome are the transcervical and transoral approaches. Both have their limitations and specific intraoperative risks. Here, we report the treatment of a patient with Eagle's syndrome using the transoral approach in conjunction with piezoelectric surgery, surgical planning, and intraoperative navigation to reduce the risk of complications. CASE PRESENTATION: The elongated styloid process was resected in a 45-year-old Japanese man using a minimally invasive approach with an intraoperative navigation system. Preoperative preparation involved the use of a custom interocclusal splint to produce the mouth opening conditions required during surgery. Using the three-dimensional position of the navigation probe, the location of the elongated styloid process was identified. After confirmation of the resection spot via the transoral approach, the styloid process was dissected by piezoelectric surgery. Follow-up examination showed an uneventful recovery with no associated complications. CONCLUSION: The resection of the styloid process using an intraoperative navigation system and a custom interocclusal splint during a transoral approach, together with a piezoelectric cutting device, is safe and effective for the treatment of Eagle's syndrome.

Biomechanical Loading Evaluation of Unsintered Hydroxyapatite/poly-l-lactide Plate System in Bilateral Sagittal Split Ramus Osteotomy.

OSTEOTRANS MX® (Takiron Co., Ltd., Osaka, Japan) is a bioactive resorbable maxillofacial osteosynthetic material composed of an unsintered hydroxyapatite/poly-l-lactide composite, and its effective osteoconductive capacity has been previously documented. However, the mechanical strength of this plate system is unclear. Thus, the aim of this in vitro study was to assess its tensile and shear strength and evaluate the biomechanical intensity of different osteosynthesis plate designs after sagittal split ramus osteotomy by simulating masticatory forces in a clinical setting. For tensile and shear strength analyses, three mechanical strength measurement samples were prepared by fixing unsintered hydroxyapatite/poly-l-lactide composed plates to polycarbonate skeletal models. Regarding biomechanical loading evaluation, 12 mandibular replicas were used and divided into four groups for sagittal split ramus osteotomy fixation. Each sample was secured in a jig and subjected to vertical load on the first molar teeth. Regarding shear strength, the novel-shaped unsintered hydroxyapatite/poly-l-lactide plate had significantly high intensity. Upon biomechanical loading evaluation, this plate system also displayed significantly high stability in addition to bioactivity, with no observed plate fracture. Thus, we have clearly demonstrated the efficacy of this plate system using an in vitro model of bilateral sagittal split ramus osteotomy of the mandible.