Three-dimensional imaging evaluation of facial swelling after orthognathic surgery with compression and Kinesio taping therapy: a randomized clinical trial.

Background: Postoperative swelling is a common complication of orthognathic surgery. The authors used three-dimensional (3D) image analysis and body surface temperature to determine the effects of compression taping (CT) and Kinesio taping (KT) by the epidermis, dermis, and fascia method (EDF-KT) on postoperative swelling. Materials and methods: The authors conducted a prospective, parallel-group, randomized controlled trial. Among the 162 patients diagnosed with jaw deformity and who underwent orthognathic surgery from August 2020 to October 2022, 105 patients (men: 36, women: 69, mean age: 28.27±8.92) underwent Le Fort type I + sagittal split ramus osteotomy (SSRO) or SSRO and were included in this study. Patients were randomly divided into three groups: EDF-KT group (n=31), CT group (n=41), and no tape group (control group, n=30). All taping was performed immediately postoperatively and removed on postoperative day (POD) 5. Three-dimensional images of the participants' faces were obtained preoperatively and at PODs 3, 7, 30, and 90 using a hand-held 3D imaging system and infrared thermography. Results: No significant difference was observed in postoperative swelling and postoperative body surface temperature between the groups at each time point. The CT group showed a trend towards reduced swelling on PODs 3 and 7 and a trend toward residual swelling on POD 90. The EDF-KT group showed a trend towards an increase in postoperative body surface temperature. Conclusion: CT taping may not be appropriate for postoperative swelling control, suggesting that EDF-KT may affect body surface temperature. Further validation of the efficacy of KT for jaw deformities is needed.

In-House Manufacturing of a Translucent Three-Dimensional Model and Surgical Guide for Marginal Mandibulectomy.

In recent years, intraoperative surgical guides have been widely used in oral and maxillofacial surgery to navigate the resection sites. However, most of them are designed for segmental mandibulectomy and determine only the anterior-posterior cutting sites. In the case of marginal mandibulectomy, the depth and angle of the resection need to be considered in addition to the anterior-posterior cutting site. This report describes a method for creating a translucent mandible model with a colored tumor that enables visualization of the tumor depth and a surgical guide for marginal mandibulectomy with a planned resection angle. If accurate surgical planning and intraoperative navigation are established using this method, personalized surgery is realized according to tumor features and hence avoids over- or under-resection.

Novel frameshift variant of WNT10A in a Japanese patient with hypodontia.

Congenital tooth agenesis is caused by the impairment of crucial genes related to tooth development, such as Wnt signaling pathway genes. Here, we investigated the genetic causes of sporadic congenital tooth agenesis. Exome sequencing, followed by Sanger sequencing, identified a novel single-nucleotide deletion in WNT10A (NC_000002.12(NM_025216.3):c.802del), which was not found in the healthy parents of the patient. Thus, we concluded that the variant was the genetic cause of the patient's agenesis.

Effects of heated tobacco products and conventional cigarettes on dental implant wound healing: experimental research.

Smoking affects wound healing and is associated with dental implant failure. Heated tobacco products (HTPs) appear to be less harmful than conventional cigarettes (CCs); however, there is limited analytical data to support this claim. This study aimed to compare HTPs and CCs for their impact on wound healing using L929 mouse fibroblast cells and evaluate whether HTPs also lead to failure in implant therapy. Materials and methods: Cigarette smoke extract (CSE) was obtained from CCs (Marlboro, Philip Morris) and HTPs (Marlboro Heat Sticks Regular for IQOS, Philip Morris) and initiated a wound-healing assay with a cell-free area created in the centre of a titanium plate by sticking a 2-mm-width line tape. The L929 mouse fibroblast cells were exposed with 2.5 and 5% CSE from HTPs and CCs and then seeded in the titanium plate. A scratch wound-healing assay was initiated when all samples were at 80% confluence. The number of cells migrating to the wound site was counted after 12, 24, and 48 h. Results: Cell migration decreased after CSE exposure from both CCs and HTPs. At each time-point with 2.5% CSE, cell migration in the HTP group was less than that of the CC group. There were significant differences between the 2.5% CC and 2.5% HTP groups and the 5% CC and 5% HTP groups after 24 h. HTPs and CCs had similar effects in the wound-healing assay. Conclusion: Therefore, HTP use may be a risk factor for poor dental implant healing.

Alterations of posterior pharyngeal wall movement during swallowing in postoperative tongue cancer patients: assessment with a videofluoroscopic swallowing study.

This study aimed to determine the association between the progressive contraction of the posterior pharyngeal wall and dysphagia in postoperative patients with tongue cancer. A videofluoroscopic swallowing study (VFSS) was performed in 34 patients after tongue cancer surgery. Images were analyzed using a two-dimensional video measurement software. Cases in which the processes on the posterior pharyngeal wall moved downward from the 2nd to 4th vertebral regions were defined as "normal type", other cases were defined as "abnormal type". Twenty-four patients showed normal movement of the posterior pharyngeal wall, whereas 10 patients showed the abnormal type. The results showed that there was a significant difference in dysphagia scores between the postoperative swallowing type and swallowing dysfunction score. This implies that dysphagia is related to the movement of the posterior pharyngeal wall after tongue cancer surgery. Furthermore, the extent of resection and stage were significantly different between the normal and abnormal groups in the posterior pharyngeal wall movement. There was also a significant difference between the two groups in terms of the following: whether the tongue base was included in the excision range (p < 0.01), whether neck dissection was performed (p < 0.01), or whether reconstruction was not performed (p < 0.01). VFSS results showed that posterior pharyngeal wall movement was altered after surgery in patients with tongue cancer who had severe dysphagia.

Trametinib improves Treg selectivity of anti-CCR4 antibody by regulating CCR4 expression in CTLs in oral squamous cell carcinoma.

Regulatory T-cells (Tregs) play a major role in suppressing anti-tumor immune responses. Mogamulizumab, an anti-CC chemokine receptor type 4 (CCR4) monoclonal antibody, depletes effector Tregs (eTregs). However, the clinical efficacy of mogamulizumab was limited in phase Ia/Ib studies for solid tumors (NCT01929486); the finding suggests that mogamulizumab may also deplete beneficial CCR4+CD8+ T-cells in patients. Therefore, we focused on CTLs and aimed to identify a way to protect CCR4+ CTLs. Here, we evaluated the association of CCR4 expression in cytotoxic T-lymphocytes (CTLs) with antigen and cytokine stimulations and kinase inhibition using cytomegalovirus antigen instead of tumor antigen. CCR4 expression in CTLs was induced by antigen stimulation (mean 3.14-29.0%), enhanced by transforming growth factor-ß1 (TGF-ß1) (mean 29.0-51.2%), and downregulated by trametinib with (mean 51.2-11.4%) or without TGF-ß1 treatment (mean 29.0-6.98%). Phosphorylation of ERK in CD8+ T-cells was suppressed by trametinib. Regarding the effect on immunological function of CTL, trametinib reduced cytokine production but not affected cytotoxicity. Importantly, trametinib alleviated CTL reduction by anti-CCR4 antibody without affecting eTreg depletion because CCR4 expression in eTregs was not downregulated. In conclusion, combination therapy with trametinib may improve the clinical efficacy of mogamulizumab.

MALT lymphoma of the sublingual gland: A case report with current overview of diagnostic and therapeutic strategies.

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) is a low-grade B-cell lymphoma. MALT lymphomas involving the sublingual gland are extremely rare. Herein, we report a case of MALT lymphoma of the sublingual gland. Additionally, we discuss challenging diagnostic aspects as well as current treatment strategies.

Cytotoxic, genotoxic, and toxicogenomic effects of heated tobacco products and cigarette smoke in human primary keratinocytes.

INTRODUCTION: Heated tobacco products (HTPs) appear to be less harmful to health than conventional cigarettes (CCs). However, limited analytical data are available to support this claim. This study aimed to compare the cytotoxic, genotoxic, and toxicogenomic effects of HTPs and CCs in carcinogenesis via multistep gene mutations in the oral mucosal cells. METHODS: Cigarette smoke extract (CSE) was obtained from HTPs and CCs. Primary human oral keratinocytes (HOKs) were treated with 5% and 20% CSE from HTPs and CCs. Cell survival rate assays were performed after 6, 12, and 24 h. After 6 h, DNA double-strand breaks (DSBs) were evaluated using anti-γH2AX antibodies with immunohistochemistry. mRNAs expressions of mediator of DNA damage checkpoint 1 (MDC1) and ataxia telangiectasia and Rad3-related protein (ATR), were analyzed. Expressions of miR-22 and miR-185 were analyzed because miR-22 targets MDC1 and miR-185, ATR. RESULTS: The HOKs had equivalent survival rates after exposure to the same concentrations of CSE from CCs and HTPs. HTPs increased foci formation of γH2AX in HOKs, as did CCs (without CSE vs 20% HTP, p<0.05; without CSE vs 20% CC, p<0.05). Expressions of MDC1 and ATR decreased in cells exposed to CSE from CCs and HTPs (MDC1: without CSE vs 20% HTP, p<0.05; without CSE vs 20% CC, p<0.05; ATR: without CSE vs 20% HTP, p<0.05; without CSE vs 20% CC, p<0.05). Expressions of miR-22 and miR-185 were not significantly increased when exposed to CSE from CCs or HTPs. CONCLUSIONS: HTPs and CCs had similar cytotoxic effects. HTPs are genotoxic, can cause DSBs, and have toxicogenomic damage because they inhibit the MDC1 and ATR-CHK1 DNA repair pathways in the oral mucosa. The miRNA-mRNA axis was not related to these inhibitions.

Oral hygiene status and factors related to oral health in hospitalized patients with schizophrenia.

OBJECTIVE: This study aimed to elucidate the oral hygiene status and the factors associated with poor oral hygiene among patients with schizophrenia. METHODS: The relationships of oral hygiene status (calculus index [CI], debris index [DI]), the mean number of decayed-missing-filled teeth (mean DMFT), and Revised Oral Assessment Guide (ROAG) with related factors (hospitalization, chlorpromazine equivalents [CPZE], age, Barthel Index [BI], frequency of cleaning teeth, and self-oral hygiene ability) among 249 hospitalized schizophrenic patients were investigated. RESULTS: The results for oral hygiene status were as follows: median (range); CI 0.5 (0-6.0), DI 1.7 (0-6.0), ROAG 10.0 (7.0-15.0); and mean DMFT 21.7 ± 7.3. The average CPZE was 524.4 ± 353.6 mg (mean ± SD), and the BI was 76.4 ± 30.7. There was a negative correlation between BI and DI (r = -0.34), and a positive correlation between age and mean DMFT (r = 0.57). Male patients tended to have worse oral conditions (ROAG) than females. The least-squares multiple regression analysis revealed that BI for DI, age for mean DMFT, sex for ROAG, and self-oral hygiene ability for CI, DI, and mean DMFT were factors related to oral health status. CONCLUSION: Patients with schizophrenia tended to have poor oral hygiene. BI, being male, and low activities of daily living were associated with poor oral hygiene. Furthermore, advanced age was associated with an increased risk of dental caries.

Salivary gland polymorphous adenocarcinoma: Clinicopathological features and gene alterations in 36 Japanese patients.

BACKGROUND: Polymorphous adenocarcinoma is a common intraoral minor salivary gland carcinoma in Western countries but is extremely rare in Japan. The current study aimed to characterize the clinicopathological features and status of molecular alterations of polymorphous adenocarcinoma-associated genes, such as PRKD1/2/3, ARID1A, and DDX3X, in a large cohort of Japanese patients with polymorphous adenocarcinoma. METHODS: We examined the cases of 36 Japanese patients with salivary gland polymorphous adenocarcinoma and 26 cases involving histopathological mimics. To detect gene splits, fluorescence in situ hybridization was carried out for polymorphous adenocarcinoma-associated genes. Additionally, we applied a SNaPshot multiplex assay to identify PRKD1 hotspot mutations. RESULTS: This study revealed the indolent clinical course of polymorphous adenocarcinoma with a high 10-year overall survival rate (92.9%), accompanied by occasional local recurrences and cervical lymph node metastasis (23.3%). Twenty cases (55.6%) of polymorphous adenocarcinoma (but none of the mimics) exhibited alterations in at least one polymorphous adenocarcinoma-associated gene. Rearrangement of polymorphous adenocarcinoma-associated genes and PRKD1 E710D were identified in 17 (47.2%) and 4 (11.1%) cases, respectively; one case showed coexisting PRKD3 split and PRKD1 E710D. In the multivariate analysis, high clinical stage (p = 0.0005), the presence of prominent nucleoli (p = 0.0003), and ARID1A split positivity (p = 0.004) were independent risk factors for disease-free survival. CONCLUSION: Japanese patients with polymorphous adenocarcinoma showed clinicopathological features similar to those reported in Western countries. This study disclosed that polymorphous adenocarcinoma-associated genetic alterations were common and specific findings in polymorphous adenocarcinomas. The diagnostic role and possible prognostic significance of polymorphous adenocarcinoma-associated genetic alterations in polymorphous adenocarcinomas were suggested.

In Situ PD-L1 Expression in Oral Squamous Cell Carcinoma Is Induced by Heterogeneous Mechanisms among Patients.

The expression of programmed death ligand-1 (PD-L1) is controlled by complex mechanisms. The elucidation of the molecular mechanisms of PD-L1 expression is important for the exploration of new insights into PD-1 blockade therapy. Detailed mechanisms of the in situ expression of PD-L1 in tissues of oral squamous cell carcinomas (OSCCs) have not yet been clarified. We examined the mechanisms of PD-L1 expression focusing on the phosphorylation of downstream molecules of epidermal growth factor (EGF) and interferon gamma (IFN-γ) signaling in vitro and in vivo by immunoblotting and multi-fluorescence immunohistochemistry (MF-IHC), respectively. The in vitro experiments demonstrated that PD-L1 expression in OSCC cell lines is upregulated by EGF via the EGF receptor (EGFR)/PI3K/AKT pathway, the EGFR/STAT1 pathway, and the EGFR/MEK/ERK pathway, and by IFN-γ via the JAK2/STAT1 pathway. MF-IHC demonstrated that STAT1 and EGFR phosphorylation was frequently shown in PD-L1-positive cases and STAT1 phosphorylation was correlated with lymphocyte infiltration and EGFR phosphorylation. Moreover, the phosphorylation pattern of the related molecules in PD-L1-positive cells differed among the cases investigated. These findings indicate that PD-L1 expression mechanisms differ depending on the tissue environment and suggest that the examination of the tissue environment and molecular alterations of cancer cells affecting PD-L1 expression make it necessary for each patient to choose the appropriate combination drugs for PD-1 blockade cancer treatment.

Phosphorylation of TRIP13 at Y56 induces radiation resistance but sensitizes head and neck cancer to cetuximab.

Radiation therapy, a mainstay of treatment for head and neck cancer, is not always curative due to the development of treatment resistance; additionally, multi-institutional trials have questioned the efficacy of concurrent radiation with cetuximab, the epidermal growth factor receptor (EGFR) inhibitor. We unraveled a mechanism for radiation resistance; that is, radiation induces EGFR, which phosphorylates TRIP13 (thyroid hormone receptor interactor 13) on tyrosine 56. Phosphorylated (phospho-)TRIP13 promotes non-homologous end joining (NHEJ) repair to induce radiation resistance. NHEJ is the main repair pathway for radiation-induced DNA damage. Tumors expressing high TRIP13 do not respond to radiation but are sensitive to cetuximab or cetuximab combined with radiation. Suppression of phosphorylation of TRIP13 at Y56 abrogates these effects. These findings show that EGFR-mediated phosphorylation of TRIP13 at Y56 is a vital mechanism of radiation resistance. Notably, TRIP13-pY56 could be used to predict the response to radiation or cetuximab and could be explored as an actionable target.

A multicentre tobacco cessation intervention study in the dental setting in Japan.

OBJECTIVE: The objective of this study was to assess the efficacy of a tobacco cessation intervention conducted by different dental specialists directed at a group of patients with tobacco-related oral diseases or undergoing implant treatment. METHODS: The study design was a multicentre, nonrandomized prospective cohort study to examine the effects of smoking cessation. The target patients were current smokers (aged ≥20 years) with an oral potentially malignant disorder or periodontitis and those seeking dental implants. A total of 74 patients were enrolled in the study. All dental specialists who participated in the trial completed an e-learning Japan Smoking Cessation Training Outreach Project (J-STOP) tobacco cessation education programme. Nicotine dependence was evaluated by the Fagerstrom Test for Nicotine Dependence. Cessation status was verified biochemically by measurement of salivary cotinine or exhaled carbon monoxide. Tobacco cessation intervention was implemented for 8 weeks with or without nicotine replacement therapy with follow-up for 12 months. RESULTS: A total of 61 patients agreed to the tobacco cessation intervention. The mean biochemically confirmed tobacco abstinence rate was 37.7% at month 3, 34.4% at month 6, and 32.8% at month 12. The highest rate of biochemically confirmed tobacco abstinence at month 12 was among patients receiving implant treatment (42.9%) followed by patients with oral potentially malignant disorder (37.1%), and those with periodontitis (21.1%). CONCLUSION: This interventional study demonstrates the challenges encountered and the feasibility of tobacco cessation intervention among Japanese patients attending dental specialists who had completed an e-learning course on smoking cessation. Making tobacco cessation an integral part of patient management by dental specialists requires further evaluation.

Improving function of cytotoxic T-lymphocytes by transforming growth factor-ß inhibitor in oral squamous cell carcinoma.

Immunotherapy with immune-checkpoint therapy has recently been used to treat oral squamous cell carcinomas (OSCCs). However, improvements in current immunotherapy are expected because response rates are limited. Transforming growth factor-ß (TGF-ß) creates an immunosuppressive tumor microenvironment (TME) by inducing the production of regulatory T-cells (Tregs) and cancer-associated fibroblasts and inhibiting the function of cytotoxic T-lymphocytes (CTLs) and natural killer cells. TGF-ß may be an important target in the development of novel cancer immunotherapies. In this study, we investigated the suppressive effect of TGF-ß on CTL function in vitro using OSCC cell lines and their specific CTLs. Moreover, TGFB1 mRNA expression and T-cell infiltration in 25 OSCC tissues were examined by in situ hybridization and multifluorescence immunohistochemistry. We found that TGF-ß suppressed the function of antigen-specific CTLs in the priming and effector phases in vitro. Additionally, TGF-ß inhibitor effectively restored the CTL function, and TGFB1 mRNA was primarily expressed in the tumor invasive front. Interestingly, we found a significant negative correlation between TGFB1 mRNA expression and the CD8+ T-cell/Treg ratio and between TGFB1 mRNA expression and the Ki-67 expression in CD8+ T-cells, indicating that TGF-ß also suppressed the function of CTLs in situ. Our findings suggest that the regulation of TGF-ß function restores the immunosuppressive TME to active status and is important for developing new immunotherapeutic strategies, such as a combination of immune-checkpoint inhibitors and TGF-ß inhibitors, for OSCCs.

Salivary CCL20 Level as a Biomarker for Oral Squamous Cell Carcinoma.

BACKGROUND/AIM: This study investigated the utility of C-C motif chemokine ligand 20 (CCL20) expression in saliva as a biomarker for oral squamous cell carcinoma (OSCC) and also examined the associated microbiome. MATERIALS AND METHODS: The study group included patients with OSCC or oral potentially malignant disorder (OPMD), and healthy volunteers (HVs). microarray and qRT-PCR were used to compare salivary CCL20 expression levels among groups. Data on CCL20 levels in oral cancer tissues and normal tissues were retrieved from a public database and examined. Furthermore, next-generation sequencing was used to investigate the salivary microbiome. RESULTS: A significant increase in the expression level of CCL20 was observed in both OSCC tissues and saliva from patients with oral cancer. Fusobacterium was identified as the predominant bacteria in OSCC and correlated with CCL20 expression level. OSCC screening based on salivary CCL20 expression enabled successful differentiation between patients with OSCC and HVs. CONCLUSION: CCL20 expression may be a useful biomarker for OSCC.

Salivary CPLANE1 Levels as a Biomarker of Oral Squamous Cell Carcinoma.

BACKGROUND/AIM: This study aimed to identify novel biomarkers for oral squamous cell carcinoma (OSCC) screening to improve the survival rate of patients with oral cancer. MATERIALS AND METHODS: We investigated differential salivary gene expression in patients with OSCC, those with oral potentially malignant disorders (OPMDs), and healthy volunteers (HVs). CPLANE1 was selected for further investigation by microarray analysis. We used quantitative reverse transcription PCR (qRT-PCR) to determine CPLANE1 expression levels in the saliva. The expression of CPLANE1 in normal and oral cancer tissues was analyzed using the Gene Expression database of Normal and Tumor tissues. RESULTS: qRT-PCR analysis of saliva samples showed that CPLANE1 expression levels were significantly higher in OSCC patients than in HVs and OPMDs patients. Furthermore, we developed a screening test for OSCC using CPLANE1 and showed that it had good accuracy. CONCLUSION: Salivary CPLANE1 could be a useful biomarker for OSCC screening and early detection.

Relationship between age and sex and the numbers of ingestions and swallows for foods of different textures among healthy adults.

BACKGROUND: The number of swallows needed per single ingestion of food is an important index when assisting a patient with dysphagia in eating. While providing meal assistance, the caregiver may assume that one ingestion is completed with one swallow and then may administer the next ingestion even if the individual's mouth still has remaining food from the previous ingestions, increasing the risk for aspiration and choking. OBJECTIVE: The objective of this pilot study was to clarify the differences in foods ingested and swallowed because of influencing factors such as age and gender among healthy adults. METHODS: The study enrolled 110 healthy adults (47.4 ± 15.8 years; 57 males, 53 females). The numbers of ingestions and swallows were counted and evaluated by food type (pilaf, 100 g; yogurt 80 g; and sponge cake, 35 g) and participant age and sex and analyzed by least-squares multiple regression analysis. RESULTS: The mean numbers of ingestion/swallows were pilaf, 12.5 ± 3.2/13.4 ± 4.2; yogurt, 8.8 ± 2.1/10.8 ± 2.1; and sponge cake, 5.8 ± 2.1/7.0 ± 2.1. The mean number of ingestions and swallows for all foods were higher for female participants compared with male participants. Statistical analysis identified sex as a significant influencing factor for the number of ingestion for all foods. For the number of swallows, the significant influencing factors were sex for sponge cake and age for pilaf and yogurt. CONCLUSION: For the test foods of different textures, sex and age were significant influencing factors for the numbers of ingestions and swallows. Further research is needed to elucidate the problem areas in this pilot study.

Automatic detection of cervical lymph nodes in patients with oral squamous cell carcinoma using a deep learning technique: a preliminary study.

OBJECTIVE: To apply a deep learning object detection technique to CT images for detecting cervical lymph nodes metastasis in patients with oral cancers, and to clarify the detection performance. METHODS: One hundred and fifty-nine metastatic and 517 non-metastatic lymph nodes on 365 CT images in 56 patients with oral squamous cell carcinoma were examined. The images were arbitrarily assigned to training, validation, and testing datasets. Using the neural network, 'DetectNet' for object detection, the training procedure was conducted for 1000 epochs. Testing image datasets were applied to the learning model, and the detection performance was calculated. RESULTS: The learning curve indicated that the recall (sensitivity) for detecting metastatic and non-metastatic lymph nodes reached 90% and 80%, respectively, while the model performance recall by applying the test dataset was 73.0% and 52.5%, respectively. The recall for detecting level IB and Level II metastatic lymph nodes was relatively high. CONCLUSIONS: A system that has the potential to automatically detect cervical lymph nodes was constructed.

Salivary NUS1 and RCN1 Levels as Biomarkers for Oral Squamous Cell Carcinoma Diagnosis.

BACKGROUND/AIM: Oral cancer may become advanced because of delay in diagnosis. In order to promote oral cancer screening, simple and highly reliable screening methods that can be implemented at general dental clinics are required. Herein we investigated differential salivary gene expression between oral squamous cell carcinoma (OSCC) patients and healthy volunteers (HV) to identify new biomarkers for OSCC detection. MATERIALS AND METHODS: Candidate genes were selected by microarrays, nuclear undecaprenyl pyrophosphate synthase 1 (NUS1) and reticulocalbin 1 (RCN1) were selected for further investigation. We used real-time quantitative reverse transcription PCR (qRT-PCR) to determine NUS1 and RCN1 expression levels in saliva and tissues. RESULTS: qRT-PCR analysis of clinical samples revealed that OSCC patients had significantly higher expression of salivary NUS1 and RCN1 than HV. CONCLUSION: A combination of NUS1 and RCN1 accurately distinguished patients from controls, and this combination can be implemented as a screening test for OSCC.