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Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse effect of antiresorptive and/or antiangiogenic agents. The standard treatment for MRONJ is conservative treatment and a surgical approach; however, its application remains controversial. This study aimed to identify the risk factors for poor prognosis and to help determine appropriate management. We retrospectively investigated factors associated with the prognosis of MRONJ in 119 patients. Relevant clinical data were obtained for all the patients. In computed tomography images, osteosclerosis, osteolysis, cortical perforation (buccal or lingual), periosteal reaction, and sequestration were observed. Univariate and multivariate analyses were used to evaluate the risk factors for poor prognosis. Multivariate analyses showed statistically significant associations between poor prognosis in patients with MRONJ and conservative treatment alone (hazard ratio [HR] 1.89), osteolysis (HR 4.67), and the absence of sequestration (HR 5.33). These results suggest that conservative treatment alone without clear objectives should be avoided, and osteolytic change could be the criteria for surgical intervention. As the boundary between the lesion and vital bone is indistinct, we recommend extensive surgery in cases which sequestration is unpredictable.

Objectives This study aimed to retrospectively investigate the success and survival rates of dental implants used for dentomaxillary prostheses at our hospital and the risk factors associated with large bone defects. Materials and methods A total of 138 external joint system implants used for dentomaxillary prostheses in 40 patients with large bone defects were included in this study. The alveolar bone at the site of implant insertion was evaluated using panoramic radiography and computed tomography. Various risk factors (demographic characteristics, dental status, and operative factors such as the employment of alveolar bone augmentation, the site, the length, and diameter of implants) for implant failure and complete implant loss were investigated using univariate and multivariate analyses. The associations between the variables and the success and survival rates of dental implants were analyzed using the multivariate Cox proportional hazard models. Results The 10-year overall success and survival rates were 81.3% and 88.4% in this study. Multivariable analysis showed that the male sex (HR 6.22), shorter implants (≤ 8.5 mm) (HR 5.21), and bone augmentation (HR 2.58) were independent predictors of success rate. Bone augmentation (HR 5.14) and narrow implants (≤ 3.3 mm) (HR 3.86) were independent predictors of the survival rate. Conclusion Male sex, shorter or narrow implants, and bone augmentation were independent risk factors for dental implants used in dentomaxillary prostheses in patients with large bone defects. Clinical relevance Clinicians should consider these risk factors and pay close attention to the management of these patients.

Introduction. In recent years, the tumour immunosuppressive mechanism has attracted attention as a cause of tumour chemoresistance. Although chemoresistance and immunosuppression of tumours have been reported to be associated with a hypoxic environment, effective treatments to improve hypoxia in tumours have not yet been established. We have previously applied carbon dioxide (CO2) to squamous cell carcinoma and have shown that improvement in local oxygenation has an antitumour effect. However, the effects of local CO2 administration on tumour immunosuppression, chemoresistance, and combination with chemotherapy are unknown. In this study, we investigated the effects of local CO2 administration on squamous cell carcinoma and the effects of combined use with chemotherapy, focusing on the effects on tumour immunosuppressive factors. Methods. Human oral squamous cell carcinoma (HSC-3) was transplanted subcutaneously into the back of a nude mouse, and CO2 and cisplatin were administered. After administration twice a week for a total of 4 times, tumours were collected and the expression of tumour immunosuppressive factors (PD-L1, PD-L2, and galectin-9) was evaluated using real-time polymerase chain reaction and immunostaining. Results. Compared with the control group, a significant decrease in the mRNA expression of PD-L1 was observed in both, CO2-treated and combination groups. Similarly, the expression of PD-L2 and galectin-9 decreased in the CO2-treated and combination groups. Furthermore, immunostaining also showed a significant decrease in the protein expression of tumour immunosuppressive factors in the CO2-treated and combination groups. Conclusion. It was confirmed that the tumour immunosuppressive factors decreased due to local CO2 administration to the mouse model. CO2 administration has the potential to improve the hypoxic environment in tumours, and combined use with chemotherapy may also improve tumour immunosuppression.

In postoperative patients with head and neck cancer, scar tissue formation may interfere with the healing process, resulting in incomplete functional recovery and a reduced quality of life. Percutaneous application of carbon dioxide (CO2) has been reported to improve hypoxia, stimulate angiogenesis, and promote fracture repair and muscle damage. However, gaseous CO2 cannot be applied to the head and neck regions. Previously, we developed a paste that holds non-gaseous CO2 in a carrier and can be administered transdermally. Here, we investigated whether this paste could prevent excessive scarring and promote muscle regeneration using a bupivacaine-induced rat model of muscle injury. Forty-eight Sprague Dawley rats were randomly assigned to either a control group or a CO2 group. Both groups underwent surgery to induce muscle injury, but the control group received no treatment, whereas the CO2 group received the CO2 paste daily after surgery. Then, samples of the experimental sites were taken on days 3, 7, 14, and 21 post-surgery to examine the following: (1) inflammatory (interleukin [IL]-1β, IL-6), and transforming growth factor (TGF)-β and myogenic (MyoD and myogenin) gene expression by polymerase chain reaction, (2) muscle regeneration with haematoxylin and eosin staining, and (3) MyoD and myogenin protein expression using immunohistochemical staining. Rats in the CO2 group showed higher MyoD and myogenin expression and lower IL-1β, IL-6, and TGF-β expression than the control rats. In addition, treated rats showed evidence of accelerated muscle regeneration. Our study demonstrated that the CO2 paste prevents excessive scarring and accelerates muscle regeneration. This action may be exerted through the induction of an artificial Bohr effect, which leads to the upregulation of MyoD and myogenin, and the downregulation of IL-1β, IL-6, and TGF-β. The paste is inexpensive and non-invasive. Thus, it may be the treatment of choice for patients with muscle damage.

Purpose: Although it is believed that implant-supported removable prostheses (ISrP) improve the quality of life of patients who undergo mandibular reconstruction, few studies have focused on the effect of ISrP in the fibular mandible on the function of the temporomandibular joint. This pilot case series aimed to determine whether four-dimensional computed tomography (4DCT) images allow for the evaluation of changes in condylar movements with and without ISrP.Methods: Three patients who underwent ISrP following segmental mandibulectomy and free-flap reconstruction were evaluated. The participants were instructed to masticate a cookie during the 4DCT scan. The distance between the most anterior and posterior positions of the condyles on the sagittal view of the 4DCT images during chewing of the cookies was measured and compared with and without ISrP. Ethical approval was granted by the Medical Ethics Committee of Kobe University on 25 May, 2020 (No. B200052).Results: Although 4DCT revealed changes in the distances of condylar protrusion with and without wearing ISrP, there were no obvious differences among the three patients.Conclusion: The 4DCT motion analysis allows for the evaluation of the effect of wearing ISrP on condylar movements during mastication in patients with mandibular reconstruction and may become a useful objective evaluation method for the functional evaluation of ISrP.

A standard treatment for osteoradionecrosis (ORN) has not yet been established because of the diversity. Therefore, identifying the risk factors for a poor prognosis is essential. This study retrospectively investigated the factors associated with the prognosis of ORN in 68 patients. Relevant clinical data of all patients were obtained. Of the patients, 16 who underwent extensive surgery underwent histopathological analysis. The necrotic changes of the anterior and posterior margins in the cortical and cancellous bones were investigated. Multivariate analyses showed statistically significant associations between poor prognosis in patients with ORN and high radiation dose (hazard ratio [HR] 1.15), orocutaneous fistula (HR 2.93), and absence of sequestration (HR 2.49). Histopathological analysis showed a viable anterior margin of the middle portion of the cortical bone for all recovered cases; in contrast, most cases (75%) with a poor prognosis showed necrotic changes. The anterior margin of the cancellous bone was viable and resilient to high irradiation, regardless of the prognosis. These results suggest that patients with orocutaneous fistula should receive early surgical intervention, even if the affected area is limited or asymptomatic. In extensive surgery, a sufficient safety margin of necrotic bone, particularly in the anterior region, is required to improve the prognosis.

Purpose: Recurrence in oral squamous cell carcinoma (OSCC) is not rare. Due to lack of studies assessing characteristics of recurrent OSCC, including time to recurrence and outcomes, we sought to investigate its characteristics, time to recurrence, and outcomes in Japanese OSCC patients. Methods: This study was a nonrandomized retrospective cohort study in a tertiary referral centre. It included 208 (117 men and 91 women) patients with recurrent oral cancer who underwent major curative surgery in the Department of Oral and Maxillofacial Surgery at Kobe University Hospital between January 1999 and April 2017. The outcomes were disease-specific survival (DSS) and overall survival (OS). Results: In multivariable Cox proportional hazards analysis, the time to recurrence (hazard ratio [HR] 3.55, 95% confidence interval [CI] 1.69–6.63; P = 0.001), extranodal extension (ENE, HR 2.72, 95% CI 1.51–4.89; P = 0.001), and high T stage (HR 2.00, 95% CI 1.01–3.97; P = 0.046) were independent predictors of DSS. The time to recurrence (HR 3.29, 95% CI 1.82–5.96; P

Purpose This study retrospectively investigated relationships among risk factors and post-hepatectomy surgical site infection (SSI) and other complications in patients who underwent hepatectomy for hepatocellular carcinoma (HCC). Methods We included 334 patients who underwent hepatectomies for liver cancers between January 2011 and December 2015 in this study. We evaluated risk factors for SSI and other post-hepatectomy complication, including demographic factors, preoperative factors, and preoperative intervention including oral management, perioperative factors, and length of hospital stay, with univariate and multivariate analyses. The oral management intervention included self-care instructions, extraction of infected teeth, removal of dental plaques and calculus (scaling), professional mechanical teeth cleaning, removal of tongue coating, and cleaning of dentures. SSI was defined in accordance with the guideline issued by the Centers for Disease Control and Prevention; it included purulent discharge from any incision or organ space within 30 days postoperatively, with or without microbiological evidence. Complications of grade II or greater, according to the Clavien-Dindo classification, were regarded as postoperative complications. Results We found bacterial infection of ascites (Odds ratio (OR) = 13.72), lack of preoperative oral management intervention (OR = 10.17), and severe liver fibrosis (OR = 2.76) to be associated with SSI and severe liver fibrosis (OR = 2.28), hypoalbuminemia (OR = 2.02), blood transfusion (OR = 1.86), and longer operation time (OR = 1.80) to be associated with postoperative complications. Conclusions Preoperative oral management may reduce the risk of SSI in patients with HCC who undergo hepatectomy.

Objectives One of the treatment goals for osteonecrotic lesions of the jaw, such as medication-related osteonecrosis of the jaw (MRONJ) or osteoradionecrosis (ORN), is restoration of quality of life (QOL). This study aimed to identify symptoms that negatively affect QOL in patients with unhealed MRONJ or ORN. Study Design This cross-sectional study included patients who were previously diagnosed with MRONJ or ORN and who underwent treatment at the Kobe University Hospital between June 2015 and February 2016. Patient QOL was measured by using the Oral Health Impact Profile (OHIP-14). The predictor variable was disease status (stage and healing). The outcome variable was OHIP-14. One-way analysis of variance and Tukey’s test were performed. Results The study included 74 patients (37 men and 37 women; mean age 70 years). Although there was no significant difference between the OHIP-14 scores of unhealed MRONJ and ORN (stages 1–3) and those of healed ones, the “worsened sense of taste” resulted in significant differences among stages in patients with unhealed MRONJ (P = .027) and the “painful mouth aching” in patients with unhealed ORN (P = .041). Conclusions Worsened sense of taste and pain negatively affected QOL in patients with unhealed MRONJ and ORN.

Objective. The present study investigated the effect of low-intensity pulsed ultrasound (LIPUS) on long-term osseous healing of the cleavage space between bone fragments after intraoral vertical ramus osteotomy (IVRO). Study Design. Patients undergoing IVRO were randomly assigned to the LIPUS group (n = 12) or the control group (n = 9) after surgery. LIPUS treatments were applied daily to the cleavage space between bone fragments for 3 weeks. We observed 3-dimensional quantitative color mapping of the whole mandible created by computed tomography (CT) data at 1 month, 6 months, and 1 year postoperatively. On the basis of CT values, the color grades were classified as D1 to D5 by using the Misch criteria. We then calculated mean CT values and rated each color grade in different selection ranges. Results. The mean CT values of the LIPUS group were significantly higher than those of the control group at 1 month, 6 months and 1 year postoperatively (P

Mechanical stress induces a variety of biochemical and morphological reactions in bone cell biology. This study aimed to investigate appropriate pressures of osteogenesis on the biological responses of 3-dimensional cultured human mandibular fracture haematoma-derived cells by compressive loading. Six patients with mandibular fractures who underwent open reduction and internal fixation were included in the study. During the operation, fracture haematomas that formed fibrin clots were manually removed before irrigation. First, pressures were applied to human mandibular fracture haematoma-derived cell-seeded collagen sponges. The sponges were subjected to mechanical compression using loading equipment applied at no compression, 0.5, or 1 mm. Compressive loading was applied to the samples prior to compression for 0, 6, 12, or 24 hours. Collagen sponge samples were collected for quantification of mRNA using several parameters including alkaline phosphatase (ALP), osteopontin (OPN), osterix (OSX), runt-related gene 2 (RUNX2), protein level, and immunocytochemistry (anti-sclerostin). Among these the 0.5 mm compression group compared with the control and 1.0 mm compression groups upregulated mRNA expression of OPN and OSX after 24 hours. Additionally, compared with the control group, a significantly higher OSX gene expression was observed in both the 0.5 mm and 1.0 mm groups after 6, 12, and 24 hours of compression (p lt; 0.05). However, no significant differences were observed regarding ALP and RUNX2 expression. These results indicated increased stimulation of osteogenesis of the mandibular fracture-line gap in the 0.5 mm compression group compared with the control and 1.0 mm compression groups.

Osteoradionecrosis of the jaw is the most refractory disease, which is caused by medical treatment such as radiotherapy and inhibitors of bone resorption. Recent researchers revealed that early resection of necrotic jawbone allows one to complete the treatment in a short period of time. The resection area in necrotic jawbone is determined by physician’s subjective diagnosis using pre-operative images. It takes a long time for the surgical planning and often differs from the intra-operative findings. This research aims to propose resection area of the jawbone accurately. Therefore, we automatically register pathological images to pre-operative head CT image. In the pre-operative head CT image and resected jawbone CT image registration, we proposed a two-step registration method using three manually acquired keypoints, and obtained normalized cross-correlation of 0.953 in the five subjects. The proposed two-step registration method achieved dice coefficient of 0.700 in the resected jawbone CT image and pathology image registration.

Schwannomas commonly occur in the head and neck region as acoustic neuromas. Facial nerve schwannomas are rare and usually occur in the temporal region. A 57-year-old woman presented with a mass at the right mandibular margin. Magnetic resonance imaging revealed a schwannoma located immediately caudal to the mental foramen. We were initially uncertain whether it arose from the trigeminal nerve or the facial nerve. Excision was performed under general anesthesia. The mass was encapsulated and easily detached from the surrounding tissue. The nerve of origin was identified proximal to the tumor. A facial nerve origin was confirmed as the muscles supplied by the marginal mandibular branch of the facial nerve moved on nerve stimulation. Nerve fibers were not found distal to the tumor, possibly because they had been cut during excision. We believe that this is the first report of a schwannoma arising from the peripheral facial nerve.

Introduction: Scarring and pain are postoperative complications in patients after head and neck cancer treatment; however, there is no effective treatment. These complications are affected by local blood flow disorders, and it is well known that the transcutaneous application of carbon dioxide (CO2) improves local blood flow. Previously, we have shown that the transcutaneous application of carbon dioxide causes absorption of CO2 and increase the oxygen (O2) pressure in the treated tissue; it is expected that the application of CO2 may reduce scarring and pain caused by cancer treatment. We newly introduced the CO2 paste as a new CO2 application method, which does not need to use CO2 gas directly. In this study, we aimed to apply of CO2 paste to healthy people and to investigate its usefulness, safety and feasibility by analysing the increase in blood flow and frequency of adverse events. Methods: We applied carbon dioxide paste to skin over the sternocleidomastoid and gastrocnemius muscles of eight healthy volunteers. The changes in blood flow before and after the CO2 paste application using dynamic MRI, and changes in the vital signs were evaluated. Results: In the neck area and middle layer of the lower leg, the signal intensity (SI) significantly increased 60 seconds after application. In the surface layer of the lower leg, the SI was significantly increased 60 and 300 seconds after paste application. Although mild heat was noted after the paste application, no obvious adverse events occurred. Conclusion: We demonstrated the increase in SI by dynamic MRI at the site of the carbon dioxide paste application, which indicates the paste application is effective in improving the blood flow.

In recent years, osteotomy has been used as a treatment for osteomyelitis of the jaw. However, the extent of osteomyelitis that can be determined from preoperative images is ambiguous, which causes problems such as lengthy surgery. Therefore, it is necessary to estimate the resection area with high accuracy. In this study, we proposed a method that combines deep metric learning and anomaly detection to estimate the area of osteomyelitis before surgery. As a result of experiments, we were able to estimate the presence or absence of osteomyelitis with F value of 0.85.

Evaluation of the inner aspect of the maxillary sinus is important for the success of a sinus lift procedure. The most common surgical complication is perforation of the Schneiderian membrane, which is thought to occur because of the presence of maxillary sinus septa. Therefore, we retrospectively investigated the incidence and morphology of maxillary sinus septa using multiplanar reformatted computed tomographic (CT) images from dentate Japanese patients. A total of 276 patients and 552 maxillary sinus segments were evaluated. The maxillary sinus septa were divided into four locations: forefront, anterior, middle, and posterior. The heights of the septa were measured at three sites from the deepest point of the sinus floor: lateral, mid-point, and medial. Sinus septa were identified in 191 of 552 (34.6%) maxillary sinus segments obtained from 111 of 276 (40.2%) patients. One unilateral septum was most commonly detected, and the sinus septa were most often located in the middle of the maxillary sinus. The average height of the identified septa was 8.69 ± 4.68 mm (mean ± standard deviation). Multiplanar reformatted CT images can identify maxillary sinus septa in any plane. The height of maxillary sinus septa in the dentate maxillae was higher than detected in previous studies. Appropriate treatment planning using CT images should be considered to prevent surgical complications.