Cepharanthine and Oral Lichen Planus Efficacy (COLE) study: protocol for a multicentre randomised controlled study assessing the efficacy and safety of cepharanthine with topical corticosteroids in oral lichen planus.

INTRODUCTION: Oral lichen planus (OLP) is a chronic, inflammatory oral condition leading to a range of symptoms from mild discomfort to severe pain, affecting patients' quality of life. Standard therapy involves the use of topical corticosteroids, although some patients respond insufficiently or develop resistance to therapy. We aim to explore if adding cepharanthine, an herbal extract from Stephania cepharantha Hayata, can enhance the efficacy of corticosteroid therapy in symptomatic OLP. METHODS AND ANALYSIS: This open-label, parallel-group, multi-centre, randomised controlled study will be conducted at three Japanese hospitals. It will compare safety and efficacy of integrated oral cepharanthine and corticosteroid therapy versus standard corticosteroid therapy. 50 symptomatic OLP patients will be randomised 1:1 to receive cepharanthine (30 mg/day) plus topical dexamethasone, or topical dexamethasone alone for 8 weeks. The primary outcome will be changed in pain intensity while drinking room-temperature water, measured on a visual analogue scale. The primary outcome is the change in pain intensity from baseline when drinking room-temperature water, evaluated using a visual analogue scale. Secondary outcomes are changes in the longest diameter of the target lesion from baseline to weeks 4 and 8, improvement and deterioration rates according to appearance and severity criteria at weeks 4 and 8, change in pain intensity when drinking room-temperature water from baseline to week 4, changes in pain intensity at rest from baseline to weeks 4 and 8, and the rates of adverse events. ETHICS AND DISSEMINATION: This protocol was approved by the Certified Review Board of Nara Medical University (CRB5200002). Participants will provide informed consent. Results will be disseminated in peer-reviewed journals and conferences. TRIAL REGISTRATION NUMBER: Japan Registry of Clinical Trials (jRCTs051220130).

A Case of Synovial Chondromatosis of Temporomandibular Joint with Numerous Loose Bodies.

Here, we report a case of synovial chondromatosis of the temporomandibular joint (TMJ) with numerous loose bodies. A 56-year-old woman was examined in the oral surgery department for trismus and pain in the left TMJ when opening the mouth. Imaging indicated TMJ synovial chondromatosis, and the patient was referred to our department for further examination. Her facial features were symmetrical, and no occlusal abnormalities were found. The maximum mouth opening was 30 mm, and movement of the left mandibular condyle was restricted and accompanied by pain and joint sounds. Panoramic radiography showed deformation of the left mandibular condyle and radiopaque lesions surrounding it. Computed tomography showed numerous small granules around the left mandibular condyle, some of which were calcified. Magnetic resonance imaging showed anterior disc displacement without reduction in the left TMJ and hypointense lesions on T2-weighted images. Bone scintigraphy showed an accumulation in the area of the left TMJ. Based on the diagnosis of the left TMJ synovial chondromatosis, the lesions were removed, and plastic surgery on the mandibular condyle was performed under general anesthesia. We removed 386 white loose bodies. Histopathologically, the loose bodies were consistent with synovial chondromatosis lesions. The postoperative course was uneventful, with no recurrence or TMJ dysfunction approximately 5 years after the surgery, indicating that open surgery is the best course of intervention in such cases.

Maxillofacial Fractures Associated With Interpersonal Violence.

Interpersonal violence is a major cause of maxillofacial fractures. The aim of this study was to analyze the characteristics of these fractures associated in an effort to develop more effective management. The clinical records and radiographs of 272 patients with maxillofacial fractures associated with interpersonal violence collected during a 36-year period were retrospectively analyzed. Two hundred and nineteen patients were male (80.5%) and 53 (19.5%) were female. The patients ranged in age from 1 to 77 years. Two hundred and two patients (74.3%) were aged 10 to 29 years. The injury was the result of impact by a fist/hand/elbow in 224 patients (82.3%). The fracture site was the mandible in 191 patients (70.2%), the midface in 78 (28.7%), and both sites in 3 (1.1%). One hundred and eight (39.6%) of 273 mandibular fractures were in the angle, 75 (27.5%) were in the symphysis, and 90 (33.0%) were at other sites. Forty-three (53.1%) of 81 fractures in the midface were in the zygoma, 19 (23.5%) were in the maxilla, and 19 (23.5%) were at other sites. Fractures were more common on the left side. Nine patients (3.3%) also had injuries at other body sites. Ninety-five patients (34.9%) were treated by maxillomandibular fixation, 84 (30.9%) by open reduction and internal fixation, 59 (21.7%) by observation, 14 (5.1%) by intramaxillary splinting, 14 (5.1%) by transcutaneous reduction, and 6 (2.2%) by other procedures. Interpersonal violence-related maxillofacial fractures have characteristic features, especially with regard to site and laterality.

Immune Thrombocytopenic Purpura Detected with Oral Hemorrhage: a Case Report.

Immune thrombocytopenic purpura (ITP) is an immune-mediated acquired disease found in both adults and children. It is characterized by transient or persistent decreases in the platelet count. We report a case of ITP detected based on oral hemorrhagic symptoms. The patient was a 79-year-old female with no significant past medical history. She presented with sudden onset of gingival bleeding and hemorrhagic bullae on the buccal mucosa. Gingival bleeding was difficult to control. Laboratory tests revealed severe thrombocytopenia with a platelet count as low as 2000/µL. Under a provisional diagnosis of a hematological disorder, she was referred to a hematologist. A peripheral smear showed normal-sized platelets. A bone marrow examination revealed increased numbers of megakaryocytes without morphologic abnormalities. The patient was diagnosed with ITP and treated with a combination of pulsed steroid therapy and high-dose immunoglobulin therapy. However, her severe thrombocytopenia was refractory to these treatments. Then, a thrombopoietin receptor agonist was begun as a second-line treatment. Her platelets rapidly increased, and no bleeding complications were reported. Because oral symptoms can be one of the initial manifestations of ITP, dentists should be familiar with the clinical appearance of ITP, and attention must be paid to detect and diagnose unidentified cases.

Trends and characteristics of maxillofacial fractures sustained during sports activities in Japan.

BACKGROUND/AIM: Sports activity increases the risk of maxillofacial fractures. The aim of this study was to analyze trends and characteristics of maxillofacial fractures sustained during sports activity to develop more effective treatments and possibly to prevent injury. MATERIALS AND METHODS: Data of 248 patients with maxillofacial fractures sustained during sports activity were retrospectively analyzed based on their clinical records and radiographs. RESULTS: The patients were 226 males (91.1%) and 22 females (8.9%). Their ages ranged from 6 to 70 years and the majority were in their second decade. The fractures were sustained in various sports which included baseball in 85 patients (34.3%), rugby in 40 (16.1%), soccer in 30 (12.1%), softball in 22 (8.9%), golf in 10 (4.0%), hockey in 8 (3.2%), combat sports in 28 (11.3%), and others in 29 (11.7%). The cause of injuries was collision with another player in 97 patients (39.1%), hit by a ball in 89 (35.9%), intended attack in 20 (8.1%), hit by equipment of another player in 15 (6.0%), a fall in 14 (5.6%), and collision with ground equipment in 13 (5.2%). The site of fractures was the mandible in 145 patients (58.5%), midface in 100 (40.3%), and both in 3 (1.2%). Among 210 fracture sites in the mandible, 77 (36.6%) were in the angle, 68 (32.4%) in the symphysis, and 65 (30.9%) in others. Among 103 fractures in the midface, 58 (56.3%) were in the zygoma, 26 (25.2%) in alveolar bone, and 19 (18.4%) in others. Treatment was observation in 67 patients (27.0%), maxillomandibular fixation in 64 (25.8%), open reduction and internal fixation in 63 (25.4%), intramaxillary splinting in 40 (16.1%), transcutaneous reduction in 10 (4.0%), and other procedures in 4 (1.6%). CONCLUSION: Maxillofacial fractures sustained during sports activity showed characteristic features dependent on the type of sport and cause of injury.

Risks of postextraction bleeding after receiving direct oral anticoagulants or warfarin: a retrospective cohort study.

OBJECTIVE: The effect of direct oral anticoagulants (DOACs) on the risk of bleeding after tooth extraction remains unclear. This study aimed to evaluate the incidence of postextraction bleeding among patients who received DOAC and vitamin K antagonists (VKAs), such as warfarin. DESIGN: This study was a retrospective cohort analysis. Incidence rates and propensity score-matched regression models were used to compare the risks of bleeding after tooth extractions involving DOACs and VKAs. SETTING: The study took place in a single university hospital in Japan. PARTICIPANTS: Between April 2013 and April 2015, 543 patients underwent a total of 1196 simple tooth extractions. PRIMARY OUTCOME MEASURE: The primary outcome measure was the occurrence of postextraction bleeding, which was defined as bleeding that could not be stopped by biting down on gauze and required medical treatment between 30 min and 7 days after the extraction. RESULTS: A total of 1196 tooth extractions (634 procedures) in 541 patients fulfilled the study criteria, with 72 extractions (41 procedures) involving DOACs, 100 extractions (50 procedures) involving VKAs and 1024 extractions (543 procedures) involving no anticoagulants. The incidences of postextraction bleeding per tooth for the DOAC, VKA and no anticoagulant extractions were 10.4%, 12.0% and 0.9%, respectively. The incidences of postextraction bleeding per procedure for DOACs, VKAs and no anticoagulants were 9.7%, 10.0% and 1.1%, respectively. In comparison to the VKA extractions, the DOAC extractions did not significantly increase the risk of postextraction bleeding (OR 0.69, 95% CIs 0.24 to 1.97; p=0.49). CONCLUSIONS: The risk of postextraction bleeding was similar for DOAC and VKA extractions.

Programmed death ligand 1 (PD-L1) expression and tumor microenvironment: Implications for patients with oral precancerous lesions.

OBJECTIVES: Cancer immunoediting represents a relatively novel concept attempting to explain the process of tumor escape from the host immune system response. Here, we attempted to elucidate the role of programmed death ligand 1 (PD-L1), the tumor microenvironment, and tumor escape mechanisms that allow malignant transformation of oral precancerous lesions. MATERIALS AND METHODS: Patients with oral precancerous lesions managed at the Nara Medical University Hospital, Japan, (n=120) were enrolled in this study. Epithelial dysplasias were graded by experienced pathologists, and subepithelial PD-L1-, CD163-, and CD8-positive cells were counted in the superficial lamina propria of oral mucosa. Epithelial PD-L1 expression was evaluated according to the staining intensity. The association of clinicopathological factors with epithelial dysplasia, malignant-free survival time, and significance of risk factors for malignant transformation were determined. RESULTS: Multivariate analysis showed that the subepithelial CD163-positive cell count was the only significant risk factor for high-grade epithelial dysplasia (P<0.001), while subepithelial CD163- and PD-L1-positive cell counts, and epithelial PD-L1 positivity were significantly associated with malignant-free survival (P=0.004, 0.04, and <0.001, respectively). Subepithelial PD-L1-positive cell count and epithelial PD-L1 positivity were significantly associated with malignant transformation (P=0.01 and 0.04, respectively). CONCLUSION: Our results indicate that PD-L1-expressing dysplastic epithelial and recruited subepithelial cells in oral precancerous legions may evade the host immune system, and that the inhibition of PD-1/PD-L1 pathway may potentially prevent malignant transformation of oral precancerous legions as well as can treat advanced cancers.

A Foreign Body Granuloma of the Buccal Mucosa Induced by Honeybee Sting.

A foreign body granuloma of the buccal mucosa induced by honeybee sting was reported. The patient was an 82-year-old female who presented with a submucous mass at the right buccal mucosa. The mass was 20 mm in diameter, elastically firm, partly mobile without pain or tenderness, and covered with almost normal mucosa. MR image did not delineate the lesion clearly. Under clinical diagnosis of a benign tumor, the lesion was excised under local anesthesia. The excised lesion was 14 × 11 × 9 mm in size and solid and yellowish in cut surface. Histologically, the lesion consisted of granulomatous tissue with a few narrow, curved, eosinophilic structures compatible with decomposed fragments of a honeybee sting and was diagnosed as a foreign body granuloma, although the patient did not recall being stung.

Computed Tomography-Based 3-Dimensional Finite Element Analyses of Various Types of Plates Placed for a Virtually Reduced Unilateral Condylar Fracture of the Mandible of a Patient.

PURPOSE: This study was performed to evaluate stresses in various types of plates placed for a virtually reduced unilateral condylar fracture of the mandible using computed tomography-based 3-dimensional finite element (FE) models of a patient to select the optimal plate system. MATERIALS AND METHODS: A computed tomography-based FE model of the mandible of a patient with a unilateral condylar fracture was constructed. The fracture was virtually reduced and fixed with 1 straight titanium plate; 2 straight titanium plates; 2 straight poly-L-lactic acid plates; and 4-hole (box), 5-hole (strut), and 7-hole (lambda) condylar plates. Stresses developing in these plates were analyzed by applying 478.1 N of bite force at the first molar of the contralateral side of the mandible. RESULTS: The magnitudes of tensile stress were within the tensile strength in all types of plates. However, the magnitudes of compressive stress in 1 straight titanium plate and 2 straight poly-L-lactic acid plates were beyond the compressive strength. The tensile and compressive stresses of the 5-hole (strut) plate were the smallest among the 3 types of condylar plates. CONCLUSIONS: Fixation by 2 straight titanium plates or any type of condylar plate was biomechanically indicated for the condylar fracture of this patient. Among these plates, the 5-hole (strut) plate was considered optimal. FE analysis is useful in selecting the optimal fixation method in the individual patient.

Chronic Maxillary Sinusitis Caused by Denture Lining Material.

We report a case of chronic maxillary sinusitis caused by denture lining material entering through an oroantral fistula after tooth extraction. The patient was an 80-year-old female who visited us with a complaint of pus discharge from the right posterior maxilla. She had extraction of the upper right second molar and had her upper denture relined with silicone lining material. The patient noticed swelling of the right cheek and purulent rhinorrhea 20 days before her first visit to our clinic. Oral examination showed an oroantral fistula with a diameter of 3 mm in the posterior alveolar ridge of the right maxilla. Computed tomography revealed a hyperdense foreign body in the right maxillary sinus and thickening of the mucosal lining. Under diagnosis of maxillary sinusitis caused by a foreign body, endoscopic maxillary surgery was performed simultaneously with the removal of the foreign body. The foreign body removed was 12 × 6 mm in size, oval in shape, light pink in color, and compatible with silicone denture lining material. During the follow-up it was observed that the oroantral fistula closed spontaneously after the removal of the foreign body. The maxillary sinus was in a good shape without recurrence of sinusitis seven months after surgery.

Trend and Characteristics of 2,636 Maxillofacial Fracture Cases over 32 Years in Suburban City of Japan.

Trend and characteristics of maxillofacial fractures in 2,636 patients over 32 years were analyzed retrospectively. Patients comprised 1,764 males and 872 females with ages ranging from 0 to 99 years. Patients younger than 30 years consisted of 60% maxillofacial fractures in the early period but decreased to 40% in the late period. In contrast, patients older than 60 years gradually increased to 30%. In terms of cause, traffic accidents consisted of more than 50%, predominantly motorcycle accidents, but gradually decreased to 40%. In contrast, falls markedly increased from less than 10 to 30%. Fractures occurred in the midface in 938 patients, in the mandible in 1,490, and in both in 208. In the midface, zygoma fractures consisted of 50% throughout the period. In the mandible, condyle fractures were observed in 40%, followed by fractures of the symphysis and angle. The ratio of condylar fractures slightly increased. Open reduction and internal fixation (ORIF) were performed in 782 patients, followed by observation in 716, maxillomandibular fixation (MMF) in 605, intramaxillary splinting (IMS) in 294, transcutaneous reduction (TCR) in 126, and others in 113. MMF markedly decreased from more than 30 to less than 5% and observation increased from 20 to 40%.

Routine removal of the plate after surgical treatment for mandibular angle fracture with a third molar in relation to the fracture line.

PURPOSE: The purpose was to analyze the clinical course of surgically treated mandibular angle fractures from the viewpoint of routine removal of the plate because these fractures are associated with high rates of complications and plate removal. SUBJECTS AND METHODS: The subjects were 40 patients with unilateral mandibular angle fracture, which was intraorally reduced and principally fixed with a single miniplate on the external oblique ridge. The third molar in relation to the fracture line was extracted in seven patients during the surgery. Clinical course was evaluated in terms of removal of the plate, preservation of the third molar and complications. RESULTS: One patient showed a wound infection postoperatively, and two patients developed pericoronitis during the follow-up. These were managed with medication and local irrigation. One patient with a preserved third molar did not make a required visit and was lost from the follow-up. Removal of the plates was performed in 39 patients after confirmation of good fracture healing, mostly within a year. Twenty-four of 32 preserved third molars were simultaneously extracted. These procedures were generally performed under local anesthesia on an outpatient basis, and they did not cause any complications. CONCLUSIONS: Routine removal of the plate after surgical treatment for mandibular angle fractures, simultaneously with extraction of the third molar if indicated, may be beneficial to avoid complications related to the plate and the third molar later in life.

Clinical analysis of midfacial fractures.

PURPOSE: To analyze the features of midfacial fractures. METHODS: Data of 320 patients treated for midfacial fractures during the past 10 years were retrospectively analyzed. RESULTS: Patients were 192 male and 128 female. Their age ranged from 1 to 96 years old with the average of 42.1. Injury most frequently occurred by traffic accidents in 168 patients, followed by falls in 78, assaults in 31 and sports in 25. Pattern of the fractures was classified into zygoma in 159 patients, alveolus in 60, multiple sites in 54, maxilla in 45 and nasal bone in 2. Facial injury severity scale ranged from 1 to 12 with the average of 1.52. Injuries to other sites of the body were found in 90 patients. Fractures of multiple sites showed higher facial injury severity scale and were associated with injuries to other sites of the body at a higher rate. Observation was most frequently chosen in 153 patients, followed by open reduction and internal fixation in 72, intramaxillary fixation in 43 and transcutaneous reduction in 26. CONCLUSIONS: Midfacial fractures showed a variety of features in terms of the site and severity and associated injuries. Understanding these features is important to manage these patients properly.

Distribution of corticosteroid receptors in mature oligodendrocytes and oligodendrocyte progenitors of the adult mouse brain.

The expression of glucocorticoid receptors (GRs) was investigated immunohistochemically in two different lineages of oligodendrocytes, using carbonic anhydrase (CA) II and neuron glial antigen (NG) 2 as markers of mature oligodendrocytes and oligodendrocyte progenitors, respectively. We focused on the gray matter regions, including CA1, CA3 and the dentate gyrus of the hippocampus, the primary somatosensory cortex barrel field and the basolateral amygdala, and the white matter regions, including the corpus callosum, external capsule and fimbria of the hippocampus. More than 80% of CAII-immunoreactive (IR) cells and more than 95% of NG2-IR cells expressed GRs in various regions of the brain. In contrast, neither CAII-IR cells nor NG2-IR cells expressed mineralocorticoid receptors (MRs) in the same regions. The intensity of GR expression was drastically reduced in CA II-IR cells and NG2-IR cells in the same regions in adrenalectomized mice. Finally, steroid receptor co-activator (SRC)-1 and p300, both of which are cofactors for GR, were expressed in the gray and white matter regions in NG2-IR cells, but not in CAII-IR cells. These results suggest that the expression of GRs in oligodendrocytes and their progenitor cells mediates several functions in vivo, including differentiation and myelination, as a major target of glucocorticoids and their cofactors.

A keratocyst in the buccal mucosa with the features of keratocystic odontogenic tumor.

A 74-year-old male patient consulted us for an elastic firm mass in the right buccal mucosa. CT examination revealed a well-circumscribed oval cystic lesion in the anterior region of the masseter muscle. On MRI, the lesion showed a low signal on T1-weighted image and a high signal on T2-weighted image. Aspiration biopsy demonstrated the presence of squamous cells in whitish liquid. Under the diagnosis of epidermoid cyst, the lesion was intraorally extirpated under general anesthesia. The lesion was cystic at the size of 30 × 25mm. Histologically, the cyst wall was lined with parakeratinized squamous epithelium corrugated on its surface, the basal layer of which consisted of cuboidal cells showing palisading of the nuclei. Immunohistochemically, the lining epithelium was positive for CK17 and negative for CK10. The basal and suprabasal cells were labeled for Ki-67 at a relatively high rate. These features are compatible with those of keratocystic odontogenic tumor.

Maxillofacial fractures in children.

Maxillofacial fractures in Japanese children were retrospectively analyzed. The subjects were 287 patients aged 15 years and younger seeking treatment for maxillofacial fractures in the Department of Oral and Maxillofacial Surgery, Nara Medical University. The patients were 186 males and 101 females. Injuries most frequently occurred as a result of traffic accidents in 125 patients, 92 of which were bicycle-related accidents. Injuries by falling from one level to another were found in 49, primarily in younger children. One hundred seventy-nine fractures occurred in the mandible, 100 in the midface, and 8 in both. In the mandible, fractures most frequently occurred in condyle followed by symphysis. In the midface, alveolus was mostly involved. The facial injury severity scale ranged from 1 to 9 with an average of 1.83 and was higher in traffic accidents. Injury to other sites of the body was found in 33 patients, 28 of which occurred in traffic accidents. Observation was most frequently chosen in 84 patients. Intramaxillary fixation was chosen in 79, primarily for alveolar fractures and in younger children. Maxillomandibular fixation was chosen in 62 for mandibular fractures in older children. Open reduction and internal fixation was performed in 40, primarily in older children. The facial injury severity scale was higher in patients treated by open reduction and internal fixation and maxillomandibular fixation. Maxillofacial fractures in Japanese children showed characteristic features primarily depending on their age in terms of etiology, patterns, and treatment modalities.

Maxillofacial fractures of pedestrians injured in a motor vehicle accident.

Maxillofacial fractures of pedestrians injured in a motor vehicle accident were retrospectively analyzed. The patients were 38 males and 26 females, and their age was distributed almost evenly from 1 to 91 years old (average 45.9 ± 24.8 years old). Motor vehicle collisions were with an automobile in 46 patients (71.9%), a motorcycle in 17 (26.6%), and a train in 1 (1.6%). The midface was involved in 32 patients (50.0%), the mandible in 19 (29.7%), and both the mandible and the midface in 13 (20.3%). Fractures were frequently observed in the zygoma and alveolus in the midface and in the condyle, symphysis, and body in the mandible. The facial injury severity scale (FISS) rating ranged from 1 to 9 (average 2.30 ± 1.79). Injuries to other sites of the body occurred in 29 patients (45.3%). Observation was most frequently chosen in 26 patients (40.6%), followed by open reduction and internal fixation (ORIF) in 18 (28.1%), and maxillomandibular fixation (MMF) in 8 (12.5%). The FISS rating was higher in patients treated with ORIF and MMF. Injuries to other sites of the body were observed at a higher rate in patients who collided with an automobile and were also treated by ORIF.

A dilated odontoma in the second molar region of the mandible.

A case of dilated odontoma in the second molar region of the mandible was reported. The patient was a 14-year-old female. Panoramic X-ray and CT examination revealed an oval ring-shaped radiopaque lesion accompanying a radiolucent area in the center at the left second molar region of the mandible. The left second molar and all third molars were not found. The lesion was diagnosed as odontoma and extirpated under general anesthesia. The lesion was a spherical mass of 12x9mm. Histologically, the mass was composed of dentin arranged in an oval ring shape with dentinal tubules. Inside the dentin, immature enamel was present. The central area of the mass was filled with fibrous tissue with a small nest of bone and cementum. Bone tissue was also observed in contact with the immature enamel layer. These morphological and histological features are compatible with those of a dilated odontoma.

Nicorandil-induced oral ulceration: report of 3 cases and review of the Japanese literature.

Nicorandil-induced oral ulceration in 3 Japanese patients is reported. The patients were men aged 86, 81, and 91 years. Ulcers of 15, 10, and 12 mm in diameter, respectively, were observed at the border of all of the patients' tongues. These were painful and persistent but not indurated. Irritation by the teeth or dentures was not evident. They had been administered nicorandil at a dose of 15 mg for 22, 54, and 90 months, respectively; therefore, ulceration induced by nicorandil was suspected. In consultation with the doctor, nicorandil was withdrawn. The ulcers disappeared 5, 8, and 9 weeks, respectively, after the cessation of nicorandil. No relapse of the ulcer was noted. The findings suggest that these were the examples of nicorandil-induced oral ulceration.