Factors affecting progressive facial swelling immediately after orthognathic surgery: A retrospective cohort study.

The aim of this study was to identify clinical factors associated with progressive facial swelling after orthognathic surgery. Patients diagnosed with jaw deformities and undergoing orthognathic surgery were retrospectively evaluated, and those with surgical site infection, Le Fort I osteotomy, or genioplasty only were excluded. Facial swelling volume was calculated by comparing facial volume preoperatively and three days postoperatively using 3D images and image analysis software (VECTRA H2). FXIII was measured within three days after surgery in only patients with unexplained postoperative bleeding or hematoma. The correlation between facial swelling volume and clinical factors was statistically analyzed. Facial swelling volume was examined in 78 patients. Univariate analysis showed a significant difference between facial swelling volume (mean = 41.6 cm3) and operation time (mean = 209.3 min, r = 0.283, p = 0.012), ΔHb level (mean = 1.18 g/dL, r = 0.235, p = 0.039), as well as decreased factor XIII activity (mean = 75.3%, p = 0.012). Multivariate analysis showed a significant difference between facial swelling volume and FXIII deficiency (standard error = 6.44, p = 0.031).Progressive facial swelling immediately after orthognathic surgery may be due to factor XIII deficiency.

The Landscape of MYB/MYBL1- and Peri-MYB/MYBL1-Associated Rearrangements in Adenoid Cystic Carcinoma.

Approximately 60% of adenoid cystic carcinoma (AdCC) cases are positive for MYB::NFIB or MYBL1::NFIB, whereas MYB/MYBL1 oncoprotein, a key driver of AdCC, is overexpressed in most cases. Juxtaposition of superenhancer regions in NFIB and other genes into the MYB/MYBL1 locus is an attractive oncogenic hypothesis for AdCC cases, either negative or positive for MYB/MYBL1::NFIB. However, evidence supporting this hypothesis is insufficient. We examined 160 salivary AdCC cases for rearrangements in MYB/MYBL1 loci and peri-MYB/MYBL1 areas (centromeric and telomeric areas of 10 Mb each) using formalin-fixed, paraffin-embedded tumor sections. For the detection of the rearrangements, we employed conventional fluorescence in situ hybridization split and fusion assays and a 5 Mb fluorescence in situ hybridization split assay. The latter is a novel assay that enabled us to detect any possible splits within a 5 Mb distance of a chromosome. We found MYB/MYBL1- and peri-MYB/MYBL1-associated rearrangements in 149/160 patients (93%). AdCC cases positive for rearrangements in MYB, MYBL1, the peri-MYB area, and the peri-MYBL1 area numbered 105 (66%), 20 (13%), 19 (12%), and 5 (3%), respectively. In 24 peri-MYB/MYBL1 rearrangement-positive cases, 14 (58%) were found to have a juxtaposition of the NFIB or RAD51B locus into the MYB/MYBL1 loci. On comparing with a tumor group positive for MYB::NFIB, a hallmark of AdCC, other genetically classified tumor groups had similar features of overexpression of the MYB transcript and MYB oncoprotein as detected by semiquantitative RT-qPCR and immunohistochemistry, respectively. In addition, clinicopathological and prognostic features were similar among these groups. Our study suggests that peri-MYB/MYBL1 rearrangements may be a frequent event in AdCC and may result in biological and clinicopathological consequences comparable to MYB/MYBL1 rearrangements. The landscape of MYB/MYBL1 and peri-MYB/MYBL1 rearrangements shown here strongly suggests that juxtaposition of superenhancers into MYB/MYBL1 or peri-MYB/MYBL1 loci is an alteration that acts as a key driver for AdCC oncogenesis and may unify MYB/MYBL1 rearrangement-positive and negative cases.

Prognostic scores for patients with salivary adenoid cystic carcinoma without lymph node metastasis.

Adenoid cystic carcinoma (AdCC) of salivary gland grows relatively slowly, but occasionally develops distant metastasis. Although cervical lymph node metastasis (LNM) has been reported as a strong prognostic factor, most of AdCC do not have LNM. In this study, we investigated the prognostic factors to predict disease free survival (DFS), distant metastasis free survival (DMFS), and overall survival (OS) for 175 patients surgically treated for AdCC without LNM, and developed prognostic score (PS) determined as number of positive prognostic factors. The following emerged as significant prognostic factors: positive surgical margin in DFS, pT3/4 and positive surgical margin in DMFS, and positive surgical margin and high-histological grade in OS. 10-year DFS rates were 56.4% in PS0, and 19.1% in PS1 (p < 0.0001). 10-year DMFS rates were 86.3% in PS0, 56.4% in PS1, and 30.7% in PS2 (p < 0.0001). 10-year OS rates were 100% in PS0, 73.3% in PS1, and 38.8% in PS2 (p < 0.0001).

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.

Novel WNT10A variant in a Japanese case of nonsyndromic oligodontia.

Congenital tooth agenesis is one of the most common anomalies in humans. Many genetic factors are involved in tooth development, including MSX1, PAX9, WNT10A, and LRP6. Thus, mutations in these genes can cause congenital tooth agenesis in humans. In this study, we identified a novel nonsense WNT10A variant, NM_025216.3(WNT10A_v001):c.1090A > T, which produces a C-terminal truncated gene product, p.(Lys364*), in a sporadic form of congenital tooth agenesis. The variant was not found in the healthy parents and thus was considered to cause congenital tooth agenesis in the case.

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.

Smoking Status and Risk Awareness of Heated Tobacco Product Use among General Dental Practitioners Belonging to the Aichi Dental Association, Japan.

The awareness of healthcare practitioners concerning heated tobacco product (HTP) use risks has been evaluated; however, few studies have investigated general dental practitioners' awareness regarding HTP-use risks. In this cross-sectional study, we investigated dentists' awareness of the risks of smoking, particularly HTP use. A self-administered questionnaire, including eight questions on conventional cigarette and HTP smoking/using status and both knowledge and awareness of HTP-use risks, was posted to 3883 dentists belonging to the Aichi Dental Association, Japan, in August 2019. Statistical analysis was performed using the Statistical Package for Social Sciences; statistical significance was set at p < 0.05. We analyzed the data of 1317 dentists (participation rate, 41.6%). The study group included cigarette smokers (11.5%) and HTP users (8.5%), among whom 41.1% were dual users. HTP users were more likely than never smokers/users to correctly perceive HTP-use risks (p < 0.05). This study indicates that in Japan, the proportion of HTP users is higher than that of the general population. It is important to educate not only smokers/users but also never smokers/users on the risks of smoking and using HTPs. Smoking cessation, including ceasing HTP use, and aiming to quit smoking and HTP use among dentists would contribute to appropriate smoking cessation among patients.

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.

A preliminary deep learning study on automatic segmentation of contrast-enhanced bolus in videofluorography of swallowing.

Although videofluorography (VFG) is an effective tool for evaluating swallowing functions, its accurate evaluation requires considerable time and effort. This study aimed to create a deep learning model for automated bolus segmentation on VFG images of patients with healthy swallowing and dysphagia using the artificial intelligence deep learning segmentation method, and to assess the performance of the method. VFG images of 72 swallowing of 12 patients were continuously converted into 15 static images per second. In total, 3910 images were arbitrarily assigned to the training, validation, test 1, and test 2 datasets. In the training and validation datasets, images of colored bolus areas were prepared, along with original images. Using a U-Net neural network, a trained model was created after 500 epochs of training. The test datasets were applied to the trained model, and the performances of automatic segmentation (Jaccard index, Sørensen-Dice coefficient, and sensitivity) were calculated. All performance values for the segmentation of the test 1 and 2 datasets were high, exceeding 0.9. Using an artificial intelligence deep learning segmentation method, we automatically segmented the bolus areas on VFG images; our method exhibited high performance. This model also allowed assessment of aspiration and laryngeal invasion.

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.

Feasibility of oral microbiome profiles associated with oral squamous cell carcinoma.

Objective: Recently, the possibility that oral microbiomes is associated with oral squamous cell carcinoma (OSCC) initiation and progression has attracted attention; however, this association is still unclear. Here, we comprehensively analyze the microbiome profiles of saliva samples using next-generation sequencing followed by determining the association between oral microbiome profiles and OSCC. Materials and Methods: Microbiome profiles in saliva samples from patients with OSCC, oral leukoplakia (OLK), and postoperative OSCC (Post) were analyzed. Candidate OSCC-associated bacteria were identified by comparing the bacterial diversity and relative abundance of each group based on these microbiome profiles, and their applicability as OSCC detection tools were evaluated. Results: There were significant differences in genus abundances (Streptococcus, Aggregatibacter, and Alloprevotella) among the groups from saliva samples. In the OSCC group, compared with the OLK and Post groups, abundances of the genus Fusobacterium, phylum Fusobacteria and phylum Bacteroidetes were markedly increased and that of the genus Streptococcus and phylum Firmicutes were decreased. Conclusion: The results suggested a strong association of these bacteria with OSCC. Especially, phylum Fusobacterium was significantly associated with early recurrence of OSCC. Thus, oral microbiome analysis may have a potential of novel OSCC detection and prognostic tool.

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.

Active Peripheral Osteoma in the Mandibular Notch: A Longitudinal Clinical Report.

Osteomas are benign osteogenic tumors composed of mature compact or cancellous bone and are characterized by slow, painless growth. A peripheral osteoma located in the mandibular notch is extremely rare. Here, we describe the case of a 38-year-old woman with an active peripheral osteoma in the mandibular notch for long-term follow up. Surgical resection of the lesion was performed, which resulted in the improvement of the mandibular function and temporomandibular dysfunction. This is the first report of resection surgery after confirming the activity of peripheral osteoma by bone scintigraphy. Creating a three-dimensional model of the mandible promises an accurate surgical plan.

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.

Salivary mucoepidermoid carcinoma: histological variants, grading systems, CRTC1/3-MAML2 fusions, and clinicopathological features.

AIMS: To investigate the histological diversity of salivary mucoepidermoid carcinoma (MEC), its clinicopathological features, and its associations with CRTC1/3-MAML2 fusions. METHODS AND RESULTS: Salivary MEC cases (n = 177) were examined for CRTC1/3-MAML2 fusions, histological variants were classified, and tumours were graded according to four different grading systems. Adverse histological features considered to be unusual in MEC were also investigated. Of the 177 MEC cases, 110 were positive for CRTC1/3-MAML2 fusions. The classical variant was the most frequent in the fusion-positive case group, the fusion-negative case group, and the total case group. The clear/oncocytic variant was the second most frequent in the fusion-positive and total case groups. Oncocytic, Warthin-like and spindle variants were seen in the fusion-positive case group only. Clear cell, sclerosing, mucinous and central variants were seen in both the fusion-positive case group and the fusion-negative case group. No case was classified as a ciliated variant, as a mucoacinar variant, or as a high-grade transformation. As compared with the classical variant, non-classical variants were characterised by frequent CRTC1/3-MAML2 fusions and a low clinical stage in all cases. Of the four histological features considered to be unusual in MEC, marked nuclear atypia, frequent mitoses (>10/10 high-power fields) and extensive necrosis were found independently of the fusion status, and were present in 3-5% of all cases. However, none of the cases showed overt keratinisation. On comparison, the Armed Forces Institute of Pathology and modified Healey grading systems downgraded tumours, the Brandwein system upgraded tumours, and the Memorial Sloan Kettering system provided a moderate means of assessment. CONCLUSION: Recognition of the histological diversity of MEC, its clinicopathological features and its associations with CRTC1/3-MAML2 fusions is helpful for an accurate diagnosis of this carcinoma.

Efficacy of a deep leaning model created with the transfer learning method in detecting sialoliths of the submandibular gland on panoramic radiography.

OBJECTIVE: This study aimed to compare the performance of 3 deep learning models, including a model constructed with the transfer learning method, in detecting submandibular gland sialoliths on panoramic radiographs. STUDY DESIGN: We used data from 2 institutions (A and B) to create the models for use in institution B. In total, 224 panoramic radiographs with sialoliths were used. Model 1 was created using data from institution A only, model 2 was created using combined data from institutions A and B, and model 3 was created using the transfer learning method by having model 1 transferred and trained in various learning epochs using data from institution B. These models were tested and compared in their detection performance using testing data sets from institution B. RESULTS: Model 2 and model 3 with 300 epochs performed equally well and yielded the highest detection rates (recall: sensitivity of 85%, precision: positive predictive value of 100%, and F measure of 91.9%) for sialoliths on panoramic radiographs. CONCLUSION: The results of this study suggest that use of the transfer learning method with an appropriate number of epochs may be an alternative to sharing patient personal data among institutions.