Risk factors of medication-related osteonecrosis of the jaw: A clinical investigation.

Medication-related osteonecrosis of the jaw (MRONJ) is an intractable condition caused by drugs such as bisphosphonates and denosumab. This study investigated the changes in the incidence of MRONJ in the previous 10 years and examined the poor prognostic factors during surgery in at-risk patients. We compared 57 and 64 patients diagnosed with MRONJ at our hospital between January 2012 and December 2016 and January 2017 and December 2021, respectively. The disease stage and triggers at the time of initial diagnosis in eligible patients were investigated. Additionally, the adverse prognostic factors were examined in 166 patients at risk of MRONJ who underwent tooth extraction at our department during these 10 years. The results indicated that there was no change in the proportion of patients with osteoporosis and malignancy among those with MRONJ. The number of cases after tooth extraction decreased, and those after dental infections increased on comparing the recent 5 years and the preceding 5 years. The number of MRONJ patients receiving denosumab also increased. Denosumab was a significant post-extraction prognostic factor for delayed healing in the 166 patients at risk of MRONJ. The findings suggest that patients receiving denosumab should be closely monitored when undergoing surgery to prevent MRONJ.

Histological evaluation of tissue destruction in mouse tongues caused by cryosurgery.

Introduction: Cryosurgery is recognized as a treatment option for various types of oral lesions. Although cryosurgery is less invasive and easier to perform than surgical treatments, adverse events, such as stomatitis and scarring can occur if the freezing is excessive. There are few studies regarding the effects of cryosurgery on the surrounding soft tissues. Thus, this study investigated the extent of tissue destruction and healing progress in tongues of mice who underwent cryosurgery. Methods: Eight-week-old male BALB/c mice were used. An instrument cooled with liquid nitrogen was lightly touched on the right side of the tongue for 5 s, and a second test was performed 10 s later. Histological evaluation was performed 3, 7, and 14 days after cryosurgery. Blood vessels were evaluated with India ink at 1, 3, 7, 14, and 21 days after cryosurgery. Results: Destruction of the soft tissue spread to the left side of the tongue after 3 days. At 7 days, it was confirmed that the muscle tissue was in the process of repair and was completely repaired at 14 days. Although blood vessels were not confirmed at 3 days, they were visible after seven days and were confirmed at 21 days all over the tongue. Discussion and Conclusion: These results indicated that the tissue destruction caused by cryosurgery was extensive and suggest that the duration and frequency of freezing should be minimized for clinical use. Lay Summary: Cryosurgery is a treatment method for various types of oral lesions. Freezing the lesion causes the tissue to collapse, resulting in its disappearance. Although cryosurgery is less invasive and easier to perform than surgical treatments, adverse events, such as stomatitis and scarring can occur if the freezing is excessive. This study investigated the extent of tissue destruction and healing progress in tongues of mice who underwent cryosurgery.The right side of mice tongues were frozen by an instrument cooled with liquid nitrogen for 5 s, and a second test was performed 10 s later. The tissue destruction was evaluated at 3, 7, and 14 days after freezing. Blood vessels were evaluated with India ink at 1, 3, 7, 14, and 21 days after freezing. Tissue destruction spread to the left side of the tongue after 3 days. At 7 days, it was confirmed that the muscle tissue was in the process of repair and was completely repaired at 14 days. Blood vessel repair was confirmed at 21 days in the throughout tongue. These results indicated that the tissue destruction caused by cryosurgery was large and suggest that the duration and frequency of freezing should be minimized for clinical use.

Living on the edge: Crayfish as drivers to anoxification of their own shelter microenvironment.

Burrowing is a common trait among crayfish thought to help species deal with adverse environmental challenges. However, little is known about the microhabitat ecology of crayfish taxa in relation to their burrows. To fill this knowledge gap, we assessed the availability of oxygen inside the crayfish shelter by series of in-vivo and in-silico modelling experiments. Under modeled condition, we found that, except for the entrance region of the 200 mm, a flooded burrow microenvironment became anoxic within 8 h, on average. Multiple 12-hour day-night cycles, with burrows occupied by crayfish for 12 h and empty for 12 h, were not sufficient for refreshing the burrow microenvironment. We then examined the degree to which crayfish species with different propensities for burrowing are tolerant of self-created anoxia. From these experiments, primary and secondary burrowers showed best and most consistent tolerance-exhibiting ≥ 64% survival to anoxia and 25-91% survival of ≥ 9 h at anoxia, respectively. Tertiary burrowers exhibited little to no tolerance of anoxia with 0-50% survival to anoxia and only one species exhibiting survival (2%) of ≥ 9 h at anoxia. Results suggest that moderate to strongly burrowing crayfish can quickly draw down the dissolved oxygen in burrow water but appear to have conserved a legacy of strong tolerance of anoxia from their monophyletic ancestors-the lobsters-whereas tertiary burrowers have lost (or never evolved) this ability.

Condyle Fracture Fixed with Custom-Made Titanium Mesh and a Miniplate: A Case Report.

BACKGROUND Open reduction and internal fixation of condyle fractures are sometimes difficult for the upper region. This report presents a case of condyle fracture at the upper neck region treated with a custom-made titanium mesh and a titanium miniplate, which makes it easy to reposition the fragment and keep it in place. CASE REPORT A 20-year-old man was injured during a soccer match and was referred to our hospital with the symptom of trismus and deviation of the mandible to the left with an opened mouth. Fracture of the right condyle neck region was diagnosed; open reduction and internal fixation was planned under general anesthesia. A custom-made titanium mesh was prepared to make it easy to reposition the fragment and keep it in place because the reduction and fixation were expected to be difficult. The fracture region was exposed using the modified Risdon-Strasbourg approach. The segments were gripped with custom-made titanium mesh, and the condyle head was reduced easily. The segments were fixed with titanium mesh, a miniplate, and screws. Nine months after the operation, the mouth opening was good at 40 mm, there was no deviation of the mandible, and there was no breakage on the titanium mesh or plate. CONCLUSIONS This report presents a case of condyle fracture at the upper neck region reduced and fixed with a custom-made titanium mesh and a titanium miniplate, which make it easy to reposition the fragment and keep it in place.

Intramuscular Myxoma of the Intrinsic Muscles of the Tongue: A Case Report with Literature Review.

Myxoma is a benign tumor of mesenchymal origin. It frequently occurs in the muscles of the hip and extremities; however, it rarely occurs in the head and neck region. This report describes the second case of an intramuscular myxoma of the tongue. A 23-year-old woman was referred to our institution for the diagnosis and treatment of a left tongue lesion. T2-weighted magnetic resonance imaging revealed an 8 × 6-mm mass in the tongue. Based on a clinical diagnosis of a tongue tumor, excisional biopsy was performed under general anesthesia. The histopathological diagnosis was an intramuscular myxoma. The postoperative course was uneventful, and there was no evidence of tumor recurrence 3 years after surgery.

Hypoproteinemia Associated with a Gigantic Odontogenic Tumor: A Report of 2 Cases.

BACKGROUND Hypoproteinemia is caused by a decrease in protein level in the blood. This report describes 2 cases of hypoproteinemia associated with a gigantic odontogenic tumor. CASE REPORT Case 1, a 65-year-old man, visited our hospital with the chief concern of swelling in the right mandible, approximately 100 mm in diameter, and ameloblastoma was diagnosed. Abscess drainage was observed in the fistula of the tumors. Total protein and albumin levels were low before surgery. Hemimandibulectomy was performed under general anesthesia. The final pathological diagnosis based on the specimen was ameloblastic carcinoma. After surgery, the total protein and albumin levels improved and remained stable 6 months after the operation. At 21 months after surgery, there were no signs of recurrence. Case 2, a 60-year-old woman, visited our hospital with a chief concern of swelling in the left mandible, approximately 100 mm in diameter, and ameloblastoma was diagnosed. Abscess drainage was observed in the fistula of the tumors. The patient had a history of hypoproteinemia; preoperative levels of total protein and albumin were low, and edema of the body was observed before surgery. Hemimandibulectomy was performed under general anesthesia. The final pathological diagnosis based on the specimen was ameloblastoma. After surgery, the total protein and albumin levels improved, and remained stable 6 weeks after surgery. There were no signs of recurrence 9 months after surgery. CONCLUSIONS These 2 cases indicate the possibility that hypoproteinemia can be caused by plasma leakage from fistulas associated with gigantic odontogenic tumors.

A case of solitary neurofibroma in the maxillary gingiva.

Neurofibromas are benign tumors. They are known to be a manifestation of von Recklinghausen's disease (neurofibromatosis type 1) and tend to be generalized and rarely solitary. In this report, we present a case of solitary neurofibroma in the maxillary gingiva. A 39-year-old woman presented with a chief complaint of swollen gingiva. There were no special findings in her medical or family history. After a biopsy was performed under local anesthesia and a diagnosis of neurofibroma was made, tumor resection was performed under general anesthesia. The patient's progress was good, with no recurrence.

Osteosarcoma of the Mandible in an Elderly Patient.

Osteosarcoma is a malignant tumor in which the cancerous cells produce an osteoid matrix or mineralized bone. Jaw bones are affected in 6% of all osteosarcomas and are the fourth most common site of origin. Surgical treatment of osteosarcoma in elderly patients is rarely reported. Here, we report successful treatment of osteosarcoma arising in the mandible of a 90-year-old man. The patient was referred to our institution for diagnosis and treatment of an oral lesion. Intraoral examination revealed that a hard mass measuring 35 × 27 mm was located on the floor of the oral cavity, attached to the bone, and its growth displaced the tongue posteriorly. Therefore, he experienced difficulty in speech and swallowing. Biopsy of the mandibular mass was suspicious for chondrosarcoma. Preoperative examination did not detect critical risks for general anesthesia or surgery. Based on a clinical diagnosis of a malignant bone tumor of the mandible, segmental mandibular resection with reconstruction using a titanium plate was performed. Surgical site infection occurred on postoperative day 12, which was resolved by drainage, local irrigation, and administration of antibiotics. There was no delirium or cardiovascular or pulmonary complications. Surgery resolved the patient's difficulties in speech and swallowing. There was no evidence of tumor recurrence or metastasis 4 years after surgery. This case showed that it was not necessary to exclude surgical treatment merely because the patient was 90 years old. Indications for surgery should be determined individually to improve the patient's quality of life.

Tophaceous pseudogout of the temporomandibular joint extending into the cranium: a case report with literature review.

Pseudogout is a disease characterized by calcium pyrophosphate crystal deposition. Involvement of the temporomandibular joint (TMJ) is rare. We herein report a case of tophaceous pseudogout of the TMJ with cranial extension. An 83-year-old woman was referred to our institution for treatment of right TMJ pain. The patient's medical and family histories were unremarkable. Magnetic resonance imaging showed a mass of about 35 mm in diameter compressing the bottom of the right temporal lobe of the brain. Based on a clinical diagnosis of a right TMJ tumour, biopsy was performed under general anaesthesia. The histopathological diagnosis was pseudogout. Considering the risk of surgically induced brain damage, the patient's advanced age and her relatively good quality of life, the treatment plan simply involved the observation of the lesion. Fourteen months after biopsy, the patient's activities of daily living remained unchanged and she had no TMJ pain.

A case of canalicular adenoma with anemia.

An 81-year-old woman presented with bleeding from a soft elastic bulge on the right buccal mucosa. Her medical history included hypertension, chronic renal failure, hysterectomy and a goiter operation. Certain investigations, such as blood tests, which confirmed the minimum hemoglobin level of 5.3 g/dl, computed tomography and magnetic resonance imaging (MRI), were conducted. MRI revealed features confirming the presence of a tumor involving the right buccal mucosa with high signal in T2-enhanced image. Considering the provisional diagnosis and image findings, the tumor mass was excised and histopathological examination of the biopsy specimen confirmed the diagnosis of a canalicular adenoma. Under the diagnosis of various clinical departments, the anemic state of the patient might be chiefly attributed to the bleeding from the tumor. Herein, we report a rare case of a canalicular adenoma in the right buccal mucosa with anemia due to bleeding from the tumor.

Teriparatide with Octacalcium Phosphate Collagen Composite Stimulates Osteogenic Factors.

Octacalcium phosphate and collagen composite (OCPcol) promotes osteogenic differentiation and angiogenesis, thereby enhancing bone regeneration. Although a newly developed freeze-dried composite of OCPcol and teriparatide (OCPcolTPTD) reinforced bone regeneration more than OCPcol, the mechanism of bone regeneration remains unresolved. In this study, disks containing OCPcolTPTD, OCPcol, or ß-tricalcium phosphate (ß-TCP) col were inserted into rodents with calvarial bone defects, before euthanasia 4 weeks later. Immunohistochemical and histochemical analyses were performed on bone samples to evaluate bone matrix development, angiogenesis, and osteoclast and osteoblast localization. In the OCPcolTPTD and OCPcol groups, bone regeneration was observed at the surface of calvarial dura mater and around acidophilic granular cells with abundant collagenous fiber-containing cells. Furthermore, the newly formed bone in the OCPcolTPTD group showed a larger total area and individual separated area than the other groups. Various osteogenic proteins were detected in the regenerated bone and peri-bone tissues by histochemistry and immunohistochemistry. Although the expression of several osteogenic biomarkers in the OCPcolTPTD group after 4 weeks of implantation was significantly lower than that in the OCPcol group, new bone formation by OCPcolTPTD in the center of the defect, where bone regeneration is difficult, tended to be superior to that by OCPcol. These results suggest that OCPcolTPTD enhanced bone regeneration more evenly and homogenously than OCPcol. Impact statement Our study suggests that octacalcium phosphate and collagen (OCPcol) together with a TPTD enhances bone regeneration in rodents with calvarial bone defects. Furthermore, we believe that composite of OCPcol and teriparatide (OCPcolTPTD) could be developed into novel clinical technique for the regeneration or repair of bone.

Custom-Made Titanium Mesh Tray for Mandibular Reconstruction Using an Electron Beam Melting System.

Mandibular reconstruction using a titanium mesh tray and autologous bone is a common procedure in oral and maxillofacial surgery. However, there can be material problems-such as broken titanium mesh trays-which may undermine long-term functionality. This study was designed to investigate the optimal conditions for a titanium mesh tray with an ideal mandibular shape and sufficient strength, using computer-aided design, computer-aided manufacturing technology, and electron beam additive manufacturing. Specimens were prepared using Ti-6Al-4V extra low interstitial titanium alloy powder and an electron beam melting (EBM) system. The mechanical strength of the plate-shaped specimens was examined for differences in the stretch direction with respect to the stacking direction and the presence or absence of surface treatment. While evaluating the mechanical strength of the tray-shaped specimens, the topology was optimized and specimens with a honeycomb structure were also verified. Excellent mechanical strength was observed under the condition that the specimen was stretched vertically in the stacking direction and the surface was treated. The results of the tray-shaped specimens indicated that the thickness was 1.2 mm, the weight reduction rate was 20%, and the addition of a honeycomb structure could withstand an assumed bite force of 2000 N. This study suggests that the EBM system could be a useful technique for preparing custom-made titanium mesh trays of sufficient strength for mandibular reconstruction by arranging various manufacturing conditions.

Clinical Diagnostic Imaging Study of Osteoradionecrosis of the Jaw: A Retrospective Study.

Radiation therapy (RT) plays a significant role in the management of head and neck malignancies. This study aimed to review the clinical symptoms and various imaging findings of osteoradionecrosis (ORN) and provide a clinical perspective on the development of ORN. The retrospective cohort was composed of 57 sites in 54 patients who had a history of RT and suspected ORN and 48 sites in 45 patients who were confirmed to have ORN. Image analyses included computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET)/CT, bone scintigraphy, and single-photon emission CT (SPECT). The irradiated tissue was damaged by RT, and the extent of damage was correlated with clinical symptoms. The bone marrow showed sclerotic changes and the devitalized bone showed bone resorption after invasive stimulation. Chronic trismus and pathological fracture are considered severe conditions, typically occurring in the last stage of ORN. Furthermore, neurological symptoms were an important sign of tumor recurrence, since diagnostic imaging was difficult. The possible treatment options vary depending on the stage of ORN. We speculate that bone sclerosis reactions and bone resorption are sequential reactions that seem to be protective measures of the bone to radiation injury.

Rhabdomyosarcoma in the maxillary gingiva of a child patient.

Rhabdomyosarcoma (RMS) is a rare, rapidly growing and aggressive malignant neoplasm mainly affecting children. However, mean age at the diagnosis of patients with gingival RMS is 26.9 years. A 12-year-old girl presented to our clinic with a chief complaint of trismus. The examination findings indicated a malignant tumor in the left maxillary gingiva. We performed a biopsy of the tumor, and the histopathological diagnosis was RMS. We report a rare case of primary RMS of the maxillary gingiva in a child patient.

Segmental Bone Reconstruction by Octacalcium Phosphate Collagen Composites with Teriparatide.

Octacalcium phosphate and collagen composite (OCPcol) demonstrated superior bone regeneration and has been commercialized recently in Japan. Teriparatide (TPTD) is a bioactive recombinant form of parathyroid hormone that is approved for osteoporosis treatment. Because mandibular bone reconstruction after segmental resection is a key clinical problem, it was examined whether single-dose local administration of OCPcol with TPTD can affect recovery after this procedure. OCPcol was prepared, and a commercially available hydroxyapatite and collagen composite (HAPcol) was used as a control. A 15 mm length segmental bone defect was made in the mandibular region of male beagle dogs. The experimental animals were divided in four groups. OCPcol treated with TPTD (OCPcol + TPTD), OCPcol, HAPcol treated with TPTD (HAPcol + TPTD), or HAPcol was implanted into the defect. The radiopaque areas of the implanted site were measured and statistically analyzed, and histological examination was performed after 6 months. The value of radiopaque area in total region of OCPcol + TPTD was highest (90.8 ± 7.3 mm2), followed in order by OCPcol (49.3 ± 21.8 mm2), HAPcol + TPTD (10.6 ± 2.3 mm2), and HAPcol (6.4 ± 2.3 mm2), and that of OCPcol + TPTD was significantly higher than that of HAPcol + TPTD or HAPcol. All segmented mandibles of OCPcol + TPTD and a part of those of OCPcol were bridged with newly formed bone, whereas no bone bridges were observed in HAPcol + TPTD or HAPcol. These results suggested that OCPcol treated with TPTD enabled bone reconstruction after segmental mandibular resection more than other three groups.

Radiation Esophagitis in a Patient with Oral Carcinoma and Bone Metastasis.

Radiation esophagitis requiring endoscopic evaluation occurs quite rarely, affecting <1% of patients undergoing radiation treatment. Acute radiation esophagitis develops within 3 weeks of radiation therapy. We describe herein a case of radiation esophagitis in a patient with oral carcinoma with multiple general bone metastases. Cisplatin, fluorouracil, and cetuximab were given for 3 cycles. Radiation therapy (30 Gy) to the thoracic vertebrae and lumbar vertebrae was prescribed to prevent worsening of bone metastases and relieve pain. Neutropenia was also observed due to chemotherapy. After the end of radiation therapy, the patient experienced chest pain, heartburn, and dysphagia. Upper gastrointestinal endoscopy revealed severe radiation esophagitis of endoscopic Fukui Acute Radiation Esophagitis grade 4. Oral food was discontinued and an intravenous proton-pump inhibitor was administered. After 3 weeks, upper gastrointestinal endoscopy showed improvement of radiation esophagitis, with scars. The symptoms of chest pain, heartburn, and dysphagia had also disappeared. This is the first case to be reported of acute radiation esophagitis in a patient with oral carcinoma with bone metastasis who experienced dramatic improvement of endoscopic findings. Neutropenia appears to be associated with more severe acute radiation esophagitis.

Cystadenoma of the tongue: report of a case with long-term follow-up.

Cystadenoma is a rare benign salivary gland neoplasm characterized by a predominantly multicystic growth pattern. The parotid gland is involved in about 45-50% of cystadenoma cases, with the minor glands of the lip and buccal mucosa being the next most common sites. The tongue is rarely involved; only one congenital case is reported in the literature. Here, we report a 63-year-old man who was referred to our hospital for a nodule on the right edge of his tongue that developed into an elastic soft mass, 4 mm in diameter. It was clinically diagnosed as a benign tumour and removed under local anaesthesia. Microscopically, the lesion was composed of multiple cysts of various sizes and shapes, with or without papillary intraluminal short projections. It was diagnosed as cystadenoma. The postoperative course was uneventful, and we found no evidence of recurrence at the postoperative 14-year follow-up.

Octacalcium phosphate collagen composite (OCP/Col) enhance bone regeneration in a rat model of skull defect with dural defect.

Cranial bone defects are a major issue in the field of neurosurgery, and improper management of such defects can cause cosmetic issues as well as more serious infections and inflammation. Several strategies exist to manage these defects clinically, but most rely on synthetic materials that are prone to complications; thus, a bone regenerative approach would be superior. We tested a material (octacalcium phosphate collagen composite [OCP/Col]) that is known to enhance bone regeneration in a skull defect model in rats. Using a critical-sized rat skull defect model, OCP/Col was implanted in rats with an intact dura or with a partial defect of the dura. The results were compared with those in a no-treatment group over the course of 12 weeks using computed tomographic and histological analysis. OCP/Col enhanced bone regeneration, regardless of whether there was a defect of the dura. OCP/Col can be used to treat skull defects, even when the dura is injured or removed surgically, via bone regeneration with enhanced resorption of OCP/Col, thus limiting the risk of infection greatly.

Clinical study of octacalcium phosphate and collagen composite in oral and maxillofacial surgery.

Octacalcium phosphate and its collagen composite have been recognized as bone substitute materials possessing osteoconductivity and biodegradation properties. We evaluated the effectiveness of octacalcium phosphate and its collagen composite used for bone augmentation in major oral and maxillofacial surgeries in a clinical trial. Octacalcium phosphate and its collagen composite were used in cases of sinus floor elevation in 1- and 2-stage, socket preservation, cyst, and alveolar cleft procedures. A total of 60 patients were evaluated for effectiveness after the implantation of octacalcium phosphate and its collagen composite. Although sinus floor elevation in 1-stage, cyst, and alveolar cleft cases met the criteria for the judgment of success, sinus floor elevation in 2-stage and socket preservation groups did not meet the criteria in the initial evaluation. However, an additional evaluation for reconfirmation revealed the effectiveness of octacalcium phosphate and its collagen composite in those groups, and all evaluation results ultimately indicated the success of this clinical trial. Therefore, this clinical trial suggested that application of octacalcium phosphate and its collagen composite for oral and maxillofacial surgery was safe and effective and that octacalcium phosphate and its collagen composite could be a bone substitute candidate instead of autologous bone.

Octacalcium phosphate collagen composite stimulates the expression and activity of osteogenic factors to promote bone regeneration.

OBJECTIVE: This study investigated the bone regenerative properties of an octacalcium phosphate collagen composite (OCP/Col) in a rat calvarial bone defect model. DESIGN: An OCP/Col or ß-tricalcium phosphate (ß-TCP)/Col disk was implanted into the critical-sized calvarial defects and fixed 2 or 4 weeks later. The radiopacity of defects was examined after disk implantation by the radiographic examination and micro-computed tomography (µ-CT). Immunohistochemical and histochemical analyses were carried out to assess the bone matrix maturation, neovascularization, and osteoclast and osteoblast distribution in the neonatal bone. RESULTS: Radiographic and µ-CT examination of the area of implanted OCP/Col indicated the newly formed bone and no difference from those of the original bone. Osteopontin, osteocalcin, Runt-related transcription factor 2, type 1 collagen, vascular endothelial growth factor, and alkaline phosphatase or tartrate-resistant acid phosphatase in the newly formed calvarial bone and the surrounding connective tissue were detected by immunohistochemistry and histochemistry. Biomarker expression was not significantly elevated at the defect site; the area of which was calculated by dividing the distance from the healthy bone margin or calvarium and dura mater surface. There was no difference in the expression of these biomarkers in the OCP/Col group at 2 and 4 weeks after surgery. In addition, the expression levels of all markers were higher in the OCP/Col group than in the ß-TCP/Col group at 2 and 4 weeks after surgery. CONCLUSIONS: The OCP/Col as a bone regeneration material not only exhibits osteoconductive activity that is dependent on residual healthy bone tissue, but also has osteoinductive capacity, which promotes angiogenesis and osteogenic cell invasion from host tissue into the bone defect.