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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

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.

BACKGROUND/AIM Tumor lymphangiogenesis plays a key role in lymph node (LN) metastasis in oral squamous cell carcinoma (OSCC). The purpose of this study was to investigate podoplanin and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) and their relationship to nodal metastasis and other clinicopathological variables. PATIENTS AND METHODS Podoplanin and LYVE-1 expression of the primary tumor and normal tissue were investigated by means of a quantitative real-time PCR assay and immunohistochemistry in samples from 33 cases of OSCC. RESULTS The mRNA high expression levels of both genes had a statistically significantly higher rate of LN metastasis (p

Purpose This study aimed to evaluate the occurrence and treatment outcome of late complications after free fibula osteocutaneous flap reconstruction for mandibular osteoradionecrosis (ORN). Methods We enrolled 15 consecutive patients (14 men, one woman; median age 65 years, range 57-80 years) who underwent free fibula reconstruction for advanced mandibular ORN during 2013-2017 with two or more years of follow-up. Late complications included infection, plate exposure, and recurrence at the resection margin. The effect of perioperative antibiotic administration on late complications was also assessed. Results Late complications occurred in 33.3% (5/15) of patients, including two infections (local and distant), two plate exposures, and two recurrences (plate exposure and recurrence occurred in one patient). Perioperative antibiotic administration duration did not significantly affect the occurrence of postoperative late complications. All late complications were treated without problems. Conclusions Late complications after ORN reconstructive surgery are not uncommon, but can be treated properly.

Advanced mandibular osteoradionecrosis (ORN) sometimes requires extended resection (e.g., hemimandibulectomy). Bacterial infection contributes to ORN pathogenesis. To control infection and determine the extent of debridement required, an understanding of bacterial spread within sites of mandibular ORN is important. The current study used a histopathological approach to assess bacterial colonization in the mandibular condyle and elucidate possible paths of bacterial spread towards the mandibular condyle. Four hemimandibulectomy specimens were selected. Areas of bone destruction were macroscopically assessed and confirmed using hematoxylin and eosin staining. Bacterial presence within mandibular condyle was confirmed with Gram staining. Bone exposure was observed in the molar area in all specimens. Macroscopic bone destruction was apparent especially near the medial side of the cortical wall. Gram staining revealed bacterial colonization of the mandibular condyle in three of the four specimens. In conclusion, bacteria tended to spread posteriorly and through the medial side of the mandibular cortical wall. In patients with advanced ORN, the potential for bacterial colonization of the mandibular condyle should be considered during treatment.

Background Prognostic biomarkers provide essential information about a patient’s overall outcome. However, existing biomarkers are limited in terms of either sample collection, such as requiring tissue specimens, or the process, such as prolonged time for analysis. In view of the need for convenient and non-invasive prognostic biomarkers for oral cancer, we aimed to investigate the prognostic values of neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and platelet-to-lymphocyte ratio in patient survival. We also aimed to explore the associations of these ratios with the clinicopathologic characteristics of Japanese oral squamous cell carcinoma patients. Methods This study was a non-randomized retrospective cohort study in a tertiary referral center. We included 433 patients (246 men, 187 women) who underwent radical surgery for oral cancers between January 2001 and December 2013. We evaluated various risk factors for poor prognosis including neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and platelet-to-lymphocyte ratio with univariate and multivariate analyses. The disease-specific survival and overall survival rates of patients were compared among the factors and biomarkers. Results In multivariable Cox proportional hazards analysis, high neutrophil-to-lymphocyte ratio (hazard ratio 2.87, 95% confidence interval 1.59–5.19, P P P = 0.016) were independent predictors of disease-specific survival. High neutrophil-to-lymphocyte ratio (hazard ratio 2.30, 95% confidence interval 1.42–3.72, P P = 0.025), and extranodal extension (hazard ratio 1.79, 95% confidence interval 1.13–2.84, P = 0.013) were independent predictors of overall survival. Conclusions Neutrophil-to-lymphocyte ratio might be a potential independent prognostic factor in Japanese oral squamous cell carcinoma patients.

Purpose In maxillary wisdom tooth extraction, the necessity of CT is unknown. The purpose of this study was to investigate whether CT adding to orthopantomography is useful for predicting oroantral perforation during maxillary third molar extraction. Methods Various risk factors for oroantral perforation during maxillary third molar extraction were investigated by univariate and multivariate analyses. We analyzed those of all patients and the patients who underwent CT, respectively. The proximity of the roots to the maxillary sinus floor (root-sinus [RS] classification) and Archer classification were assessed using panoramic radiography. The number of roots and vertical relationship were assessed using CT. Results A total of 604 out of 3299 patients underwent CT adding to orthopantomography. In all cases, multivariate analyses except for CT findings showed that the RS classification type III/IV and the Archer classification Type B/C/D in panoramic findings were significantly correlated with oroantral perforation as radiological findings. In cases for which CT was performed, multivariate analyses showed that one root (OR 12.87) and the vertical relationship Type D (OR 5.63) in CT findings, besides the RS classification type III/IV (OR 4.47) in panoramic findings, were significantly related to oroantral perforation. Conclusion The RS classification and the Archer classification in panoramic findings can predict the risk of oroantral perforation. The usefulness of CT adding to orthopantomography is limited. However, when the relationship between the upper wisdom tooth and maxillary sinus floor (RS classification) is unclear, to check whether the number of roots is one and the apex of one root is projecting into the maxillary sinus in CT findings, is useful for the prediction.

Introduction: Delayed wound healing after surgery lowers the long-term quality of a patient's life and leads to discomfort and pain. However, treatments for wound healing are often difficult and have not yet been fully established. In this study, we investigated the effect of a special paste that can be administered transdermally and holds a non-gaseous carbon dioxide (CO2) source in its carrier, which can be applied to the head and neck region for wound healing in a rat skin defect model. Methods: Forty-eight Sprague Dawley rats were randomized into control and CO2 groups. We punched a 6.2-mm wound on the back of each rat. The control rats were left untreated, whereas rats in the CO2 group were treated with the CO2 paste every day after surgery. We evaluated wound healing 3, 7, 14, and 21 days after wounding by analyzing the diameter of the wound, gene expression of inflammatory markers vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β, hypoxia-inducible factor (HIF)-1α, interleukin (IL)-1β, and IL-6 using quantitative real-time polymerase chain reaction, hematoxylin and eosin, and immunohistochemical staining patterns. Results: Rats in the CO2 group showed accelerated wound healing compared to those in the control group. Furthermore, VEGF and TGF-β were overexpressed, whereas HIF-1α, IL-1β, and IL-6 were downregulated in the rats treated with CO2. Immunohistochemical analysis also revealed similar patterns of expression. Conclusion: Taken together, the CO2 paste promoted wound healing by regulating the hypoxic environment, reducing inflammation, and accelerating angiogenesis.

Purpose: The appearance of osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ) is similar, but clinically important differences between ORN and MRONJ exist. The aim of this study was to compare the clinical data between ORN and MRONJ and to reveal the critical differences between these diseases. Methods: We retrospectively reviewed the epidemiological data, clinical findings, and treatment in 27 ORN and 61 MRONJ patients. Radiographic signs before the initiation of treatment were also assessed. Results: The median age (P = 0.0474) and the ratio of female to male patients (P

Most head and neck lymphoepithelial carcinomas (LECs) arise in the nasopharynx and harbor Epstein–Barr virus (EBV). LEC is also a rare subtype of the oral squamous cell carcinoma (SCC). Morphologically, LEC is defined as resembling non-keratinizing nasopharyngeal carcinoma, undifferentiated subtype. The histological features and pathogenesis of oral LEC are not established. We describe a case of tongue LEC with histopathological diagnostic difficulties. A 72-year-old Japanese female presented with a whitish change on her left-side tongue. The diagnosis was atypical epithelium; neoplastic change could not be ruled out by a biopsy. Although the lesion was monitored at our hospital per her request, invasive carcinoma was detected 11 months later. Microscopically, conventional SCC was observed with the characteristic features as LEC confined to the deep part of the lesion. We briefly discuss this unusual histological finding and make a novel proposal for distinguishing oral LEC from LECs in other regions based on these histological findings.

Accepted: 2017-03-30, 資料番号: SA1160356000

Background/aim We recently investigated the contribution of the iPS-related genes SOX2, OCT4, and Nanog to de-differentiation by assaying for their mRNA levels. Given that mRNA expression does not always correlate with the protein levels, the aim of this study was to retrospectively determine the expression of these four iPS-related factors in human OSCC specimens by immunohistochemistry and examine their association with patient prognosis. Materials and methods iPS cell-related gene expression in 89 OSCC patients by tissue microarray, and its correlation with clinicopathological factors, differentiation, metastasis, and poor prognoses were investigated. Results No evidence of statistically significant relationships was found between the expression of iPS cell-related genes and clinicopathological parameters. However, our data indicated that KLF4 expression was associated with survival, and poor tumor differentiation. In addition, high expression of KLF4 was an independent poor prognostic factor (p=0.004) for OSCC patients. Conclusion In preoperative biopsies, higher KLF4 and poor differentiation may be clinically effective predictors for the prognosis of oral cancer.

Background This prospective study investigated the change of swallowing ability using the Swallowing Ability Scale System (SASS) and swallowing-related quality of life (QOL) by Performance Status Scale for Head and Neck Cancer patients (PSS-H&N). This study also investigated the risk factors for postoperative dysphagia in patients who received reconstructive surgery for oral cancer. Subjects and Methods This study included 64 patients (33 men and 31 women) who underwent radical surgery with neck dissection and reconstructive surgery for oral cancers between July 2014 and February 2018. We evaluated risk factors for poor swallowing ability after treatment, including demographic factors, preoperative factors and perioperative factors, with univariate and multivariate analyses. The change of swallowing ability by the SASS and swallowing-related QOL by PSS-H&N were evaluated prospectively prior to the initiation of surgery within 1 week and at 1 and 3 months after treatment. Results Advanced T stage (T3, 4) (odds ratio (OR) = 79.71), bilateral neck dissection (OR = 20.66) and the resection of unilateral or bilateral suprahyoid muscles (OR = 17.00) were associated with poor swallowing ability after treatment. The scores for time for food intake and Eating in Public were associated with decrease of QOL in the poor group. Conclusions We propose that clinicians consider the risk factors identified in this study and pay close attention to the management of oral cancer patients with reconstructive surgery. Graphical abstract

Oral squamous cell carcinoma (OSCC) is the most common form of oral cancers. Recent studies have shown that the malignant transformation of various carcinomas, including OSCC, is associated with epithelial-mesenchymal transition (EMT), and that expression of the EMT factors are significantly associated with tumor invasion, tumor metastasis, and survival rates in OSCC patients. Hence, there is a possibility that EMT suppression may improve the prognosis of OSCC patients. Hypoxia inducible factor-1α (HIF-1α) is a crucial microenvironmental factor in tumor progression, which induces the expression of EMT factors. We previously reported that transcutaneous CO2 suppresses both human OSCC tumor growth and metastasis to the regional lymph nodes by improving hypoxia in treated tissue. According to this background, we hypothesized that increased EMT with HIF-1α expression may increase the progression and the metastatic potential of OSCC, and that decreased hypoxia by transcutaneous CO2 could suppress EMT. In the present study, in vitro studies showed that hypoxic conditions increased the expression of HIF-1α and EMT factors in OSCC cells. In addition, in vivo studies revealed that transcutaneous CO2 increased E-cadherin expression with the decreased expression of HIF-1α, Snail, Slug, N-cadherin, and Vimentin in tumor treatment. These results suggest that transcutaneous CO2 could suppress EMT by improving hypoxia, resulting in the reduction of metastatic potential of OSCC. The findings indicate that transcutaneous CO2 may be able to improve the prognosis of OSCC patients through the suppression of EMT.

Omics analysis is a versatile approach for understanding the conservation and diversity of molecular systems across multiple taxa. In this study, we compared the proteome expression profiles of four yeast species (Saccharomyces cerevisiae, Saccharomyces mikatae, Kluyveromyces waltii, and Kluyveromyces lactis) grown on glucose- or glycerol-containing media. Conserved expression changes across all species were observed only for a small proportion of all proteins differentially expressed between the two growth conditions. Two Kluyveromyces species, both of which exhibited a high growth rate on glycerol, a nonfermentative carbon source, showed distinct species-specific expression profiles. In K. waltii grown on glycerol, proteins involved in the glyoxylate cycle and gluconeogenesis were expressed in high abundance. In K. lactis grown on glycerol, the expression of glycolytic and ethanol metabolic enzymes was unexpectedly low, whereas proteins involved in cytoplasmic translation, including ribosomal proteins and elongation factors, were highly expressed. These marked differences in the types of predominantly expressed proteins suggest that K. lactis optimizes the balance of proteome resource allocation between metabolism and protein synthesis giving priority to cellular growth. In S. cerevisiae, about 450 duplicate gene pairs were retained after whole-genome duplication. Intriguingly, we found that in the case of duplicates with conserved sequences, the total abundance of proteins encoded by a duplicate pair in S. cerevisiae was similar to that of protein encoded by nonduplicated ortholog in Kluyveromyces yeast. Given the frequency of haploinsufficiency, this observation suggests that conserved duplicate genes, even though minor cases of retained duplicates, do not exhibit a dosage effect in yeast, except for ribosomal proteins. Thus, comparative proteomic analyses across multiple species may reveal not only species-specific characteristics of metabolic processes under nonoptimal culture conditions but also provide valuable insights into intriguing biological principles, including the balance of proteome resource allocation and the role of gene duplication in evolutionary history.

Purpose Few studies exist that focus on the details of perioperative antibiotic administration for surgery to treat medication-related osteonecrosis of the jaw (MRONJ). The regime and duration of perioperative antibiotics applied in published studies were reviewed to clarify appropriate perioperative antibiotic use in MRONJ surgery. Methods A literature search was conducted using the MEDLINE database via PubMed. Results The search resulted in 453 hits on PubMed. After reading the downloaded full-text articles, 17 articles met the inclusion and exclusion criteria. The most common perioperative antibiotic used for MRONJ surgery was a combination of penicillin-based antibiotics and β-lactamase inhibitor (52.9%), and the second most common regime was penicillin-based antibiotics with metronidazole (17.6%). The duration of administration was 2 weeks postoperatively in nine studies, whereas four studies applied long-term administration (2-6 weeks postoperatively). Conclusions Oral and maxillofacial surgeons mostly prefer penicillin-based antibiotics plus β-lactamase inhibitor or metronidazole for MRONJ surgery. The duration of administration of these medications may be based on empirical experience.

Radiotherapy (RT) is one of the main treatment modalities for oral squamous cell carcinoma (OSCC), however, radioresistance is a major impediment to its clinical success and poses as a concern that needs to be addressed. Tumor hypoxia is known to be significantly associated with radioresistance in various malignancies, hence, resolving the hypoxic state of a tumor may improve the antitumor effect of RT on OSCC. We have previously revealed that transcutaneous CO2 induced mitochondrial apoptosis and suppressed tumor growth in OSCC by resolving hypoxia. Considering the previous study, we hypothesized that transcutaneous CO2 may enhance the antitumor effect of RT on OSCC by improving intratumoral hypoxia, thereby overcoming radioresistance. In the present study, the combination of transcutaneous CO2 and RT significantly inhibited tumor growth compared with other treatments. This combination therapy also led to decreased expression of HIF-1α in parallel with increased expression of the cleaved forms of caspase-3-8-9 and PARP, which play essential roles in mitochondrial apoptosis. Additionally, the combination therapy increased the expression of ROS modulator 1 and subsequent mitochondrial ROS production, compared to RT alone. These results indicated that transcutaneous CO2 could potentially improve the antitumor effect of RT by decreasing the intratumoral hypoxia and increasing the mitochondrial apoptosis. Our findings indicated that CO2 therapy may be a novel adjuvant therapy in combination with RT for OSCC.

Objectives Transient receptor potential cation channel (subfamily V, members 1–4) (TRPV1–4) are expressed in skin and neurons and activated by external stimuli in normal mucosae of all oral cavity sites. The oral cavity is exposed to various stimuli, including temperature, mechanical stimuli, chemical substances, and changes in pH, and, notably, the risk factors for oncogenic transformation in oral squamous epithelium are the same as the external stimuli received by TRPV1–4 receptors. Hence, we examined the relationship between oral squamous cell carcinoma (SCC) and TRPV1–4 expression. Materials and Methods Oral SCC patients (n = 37) who underwent surgical resection were included in this study. We investigated the expression of TRPV1–4 by immunohistochemical staining and quantification of TRPV1–4 mRNA in human oral mucosa. In addition, we compared the TRPV1–4 levels in mucosa from patients with SCC to those in normal oral mucosa. Results The receptors were expressed in oral mucosa at all sites (tongue, buccal mucosa, gingiva, and oral floor) and the expression was stronger in epithelia from patients with SCC than in normal epithelia. Furthermore, alcohol consumption and tobacco use were strongly associated with the occurrence of oral cancer and were found to have a remarkable influence on TRPV1–4 receptor expression in normal oral mucosa. In particular, patients with a history of alcohol consumption demonstrated significantly higher expression levels. Conclusion Various external stimuli may influence the behavior of cancer cells. Overexpression of TRPV1-4 is likely to be a factor in enhanced sensitivity to external stimuli. These findings could contribute to the establishment of novel strategies for cancer therapy or prevention.

Background/aim Cancer stem cells are suspected to contribute to malignancy in tumors. Hypoxia affects cell differentiation and induces stem-cell-like characteristics in malignancies. Induced pluripotency was demonstrated in mouse fibroblasts by reprogramming with four transcriptional factors: Oct3/4, Sox2, c-Myc, and Klf4. Conversely, oncogenic transformations frequently express transcriptional factors and Nanog. Therefore, cancer cells present some similarities with induced pluripotent stem (iPS) cells. Materials and methods We investigated the expression of iPS-related genes in vitro and in clinical samples to identify their relationships with hypoxia and tumorigenesis. Results Oral squamous cell carcinoma (SCC) cells were used to show that expression levels of Oct3/4, Sox2, and Nanog were significantly increased in hypoxic condition in vitro and in moderately- and poorly-differentiated samples. Conclusion We propose that Oct3/4, Sox2 and Nanog are associated with tumor hypoxia characterized in oral SCC and that these factors may also contribute to the undifferentiated potency observed in oral SCC clinically.

Dental rehabilitation with osseointegrated implants in reconstructed mandibles is a common procedure, but the technique still requires improvement, especially in its reliability and technical simplification. We herein report dental rehabilitation of a free fibula-reconstructed mandible with scar contracture. A vestibuloplasty technique with application of a polyglycolic acid (PGA) sheet is described. The implants were inserted into a viable fibula flap with severe scar contracture of the overlying epithelium resulting from vascular instability in skin paddle. Only the fibula periosteum was sutured after implant insertion; exposed surfaces were covered with a combination of PGA sheet and fibrin sealant. The area with PGA sheet coverage gradually healed with moderate contracture. The epithelium around the almost implants became immobilized. The implant-supported removable partial denture with custom titanium bar was acceptable. Dental rehabilitation is possible for reconstructed mandibles with severe scar contracture. Application of a PGA sheet may be useful for vestibuloplasty in patients with reconstructed mandibles.