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Next-generation sequencing of oral squamous cell carcinoma (OSCC) has revealed TP53 as the most frequently mutated gene in OSCC mutually exclusive with human papillomavirus infection. Oral epithelial dysplasia (OED) is defined as a precancerous lesion of OSCC by the current World Health Organization (WHO) classification; therefore, it is assumed that TP53 mutations occur in early precancerous conditions such as OED. Here, we conducted an integrated analysis of TP53, including whole coding sequencing of TP53, FISH analysis of the 17p13.1 locus, and immunohistochemical analysis for p53 (p53-IHC), in 40 OED cases. We detected 20 mutations in 16 (40%) OED cases, and four cases, each harbored two mutations. FISH analysis revealed six of 24 cases (25%) had a deletion on 17p13.1, and four cases had concurrent TP53 mutations and 17p13.1 deletion (2-hit). Also, the increased frequency of TP53 mutations in higher degrees of OED implies acquisition of the mutation is a major event toward OSCC. p53-IHC revealed that overall cases could be categorized into four patterns that correlate well with the mutational status of TP53. Especially, two patterns, broad p53 expression type (pattern HI) and p53 null type (pattern LS), strongly correlated with a missense mutation and nonsense mutation, respectively. Furthermore, seven of the 40 cases progressed to SCC, and six of these seven cases presented pattern HI or LS. Therefore, patterns HI and LS have a high risk for malignant transformation if excisional treatment is not performed irrespective of the dysplasia grade. Although the current WHO classification mainly focuses on morphological criteria for the diagnosis of OED, interobserver discrepancy appears in some instances of the OED diagnosis. Our immunohistochemical analysis supports a more accurate pathological diagnosis for OED in cases of low dysplastic changes or of differential diagnosis with non-dysplastic lesions.

Introduction: Due to the development of newly developed anticancer drugs, oral dysesthesia and toothache other than conventional oral mucositis, dry mouth, and dysgeusia are increasing among oral adverse events. The objective of this study was to assess the characteristics of chemotherapy-induced oral dysesthesia and toothache. Materials and Methods: Subjects were patients referred to the oral surgery clinic for oral adverse events related to cancer chemotherapy and with an observation period of more than 1 month after the last course of chemotherapy. Oral adverse events were divided according to the categories of the National Cancer Institute Common Terminology Criteria for Adverse Events, v5.0. Statistical comparison was made using the binomial test. Results: A total of 180 patients were referred to the oral surgery clinic. Oral dysesthesia and/or toothache was found in 15 cases, which included 13 with oral dysesthesia, 4 with toothache, and 2 with both oral dysesthesia and toothache. Of these 15 cases, 13 had concomitant occurrence of peripheral neuropathy (PN) (86.7%, P = 0.0037) and 12 cases had dysgeusia (80.0%, P = 0.0176). Symptoms of oral dysesthesia and/or toothache continued after chemotherapy in 10 of 15 cases with the continuation of accompanied PN (66.7%) and/or dysgeusia and persisted for more than 6 months in 5 cases (33.3%). Discussion: Although oral dysesthesia and toothache are low-grade chemotherapy-induced adverse events, it is suggested that they may be nervous system disorders rather than gastrointestinal disorders. Clinicians should understand that they potentially persist for a long period after the end of chemotherapy.

Objectives This study aimed to investigate the effects of alcohol consumption (AC) on maxillofacial fractures caused by falls on a level surface (simple falls). Material and Methods Patients with maxillofacial fractures caused by falls who visited the Oral and Maxillofacial Surgery Clinic from January 2006 to December 2016 were evaluated. Patients with simple falls were subdivided into those who fell with AC (Falls with AC) and those who fell without AC (Falls without AC). Results Of 180 patients with falls with maxillofacial fractures, 155 had simple falls, and 25 patients had falls from a height. Of the simple falls, 52 were Falls with AC, and 102 were Falls without AC. Falls with AC were significantly more frequent in males (p = .0005). The average number of fracture lines in the mandible was significantly higher in Falls with AC (2.13 ± 0.99 [mean ± SD]) than in Falls without AC (1.76 ± 0.91) (p = .011). The average Facial Injury Severity Scale was significantly higher in Falls with AC (3.08 ± 1.43) than in Falls without AC (2.43 ± 1.29) (p = .007). Conclusions Falls with AC were associated with more severe maxillofacial fractures than Falls without AC.

The antineutrophil cytoplasmic antibody- (ANCA-) associated vasculitides (AAVs), which include fever of unknown origin (FUO), are rare diseases characterized by necrotizing inflammation of small blood vessels and the presence of ANCAs. Microscopic polyangiitis (MPA) is a subtype of the AAVs. Although the prevalence of AAVs has generally increased over the last 20 years, there have been rare reports from the dental and oral surgery field. In this article, we present a case of MPA suspected to be infective endocarditis (IE) following tooth extraction.

PURPOSE Among previous reports on dental injuries associated with mandibular fractures, there are few investigating the conditions under which dental injuries commonly occur. The aim of this study was to determine specific characteristics of mandibular fractures accompanied by dental injuries. METHODS This retrospective cohort study included dentate patients with mandibular fractures treated at a tertiary trauma center between 2011 and 2019. The data were analyzed according to 2 outcome variables: patients with additional dental injuries and patients without. The predictor variables were patient age, sex, accident mechanism, number and location of mandibular fractures, and presence of submental lacerations. Odds ratios for the risk factors for dental injury were calculated in conjunction with descriptive statistics. Binary logistic regression analysis was also performed to identify the factors associated with dental injuries as dependent variables. RESULTS Of 252 patients who had only mandibular fractures, 95 (37.7%) had associated dental injuries. In the group with dental injuries, 55.8% of mandibular fractures were caused by a fall (P��=��.003). Condyle fractures (77.9%) with dislocation (67.6%) and bilateral involvement (41.9%) were more common than in the group without dental injuries (P < .001). In patients with dental injuries, the incidence of 3 or more fractures (29.5%) was significantly higher than in the group without dental injuries. Dental injuries were more likely to occur in patients with concomitant submental lacerations (confidence interval (CI) 1.135-4.983, P��=��.02), and the risk of dental injury was significantly lower in the presence of angle fractures (CI 0.113-0.999, P��=��.045). CONCLUSIONS A frontal impact involving the anterior part of the mandible is often associated with condyle and multiple mandibular fractures. This seems to be the typical mechanism for concomitant dental injuries. Submental laceration can be considered a prime sign of associated dental injuries.

Background/aim The aim of the study was to evaluate the antitumor potential and combination effects of chemotherapeutic drugs. Materials and methods The cytotoxicity of 20 drip-type classical and molecular-targeted anticancer drugs was examined against 4 human oral squamous cell carcinoma cell lines and 5 human oral normal mesenchymal and epithelial cells. Cell cycle progression was monitored by a cell sorter. Combination effect was evaluated by combination index. Results Most of the classical anticancer drugs showed much higher antitumor activity than molecular-targeted drugs, except bortezomib. Among 12 classical anticancer drugs, taxanes and gemsitabine showed the highest tumor-specificity (TS) and potency-selectivity expression (PSE) values, whereas platinum analogs showed the least TS value. Combination of two classical or a classical and a molecular-targeted drug showed mostly additive or antagonistic effect. 5-FU and cisplatin did not produce a subG1 population, but induced G2/M or G1/S arrest, regardless of the addition of cetuximab. Cetuximab, nibolumab and bortezomib showed potent keratinocyte toxicity. Conclusion The present TS monitoring system may provide useful information for building up the treatment regimens of anticancer drugs.

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Objective The present study aimed to identify the characteristics of dysgeusia caused by cancer chemotherapy. Patients and methods We investigated 181 patients with oral adverse events from cancer chemotherapy who were referred to an oral surgery clinic. Results Oral mucositis, dysgeusia and dry mouth were found in 62 (34.3%), 61 (33.7%) and 28 (15.5%) patients, respectively. Most dysgeusia was grade 1 (95.1%, P Conclusion Dysgeusia tended to occur during treatment with oxaliplatin, paclitaxel and doxorubicin, and an association with PN was also suggested.

The nitrogen-fixing actinomycete Frankia coexists with actinorhizal plants via nodules and supplies nitrogen compounds to the plants. Although communication has been suggested to exist through chemical substances in this nodule symbiosis, the details underlying this mechanism remain elusive. The biphenyl-type diarylheptanoids (BP-CDHs), alnusonol, and alnusdione, previously isolated from the actinorhizal plant A. sieboldiana branch wood, are secondary metabolites that accumulate in a limited number of plant species. However, since relatively widely distributed in actinorhizal plants, we investigated whether adding A. sieboldiana root extracts and these BP-CDHs could affect plant seedlings inoculated with Frankia. The results showed that the addition of root extract or alnusonol significantly increased the number of nodules and lobes more than two times compared with that upon Frankia supplementation only. We also proved that the extracted components of this plant affected nodule symbiosis. Finally, we confirmed through LC-MS that the root extract component contained BP-CDH, alnusonol. The above-described results indicate that BP-CDHs, at leaset alnusonol, might function as signal compounds from the plant side of the actinorhizal symbiosis between A. sieboldiana and Frankia.

Pyogenic granuloma (PG) refers to a common, acquired, benign, and vascular tumor that arises in tissues such as the skin and mucous membranes. However, it is extremely rare for PG to arise from an empty socket after tooth extraction. Herein, we describe a rare case of PG that arose from the empty extraction socket of the second molar adjacent to a dentigerous cyst of the left mandibular wisdom tooth in a 57-year-old man. The patient’s second molar was extracted during the same procedure in which the wisdom tooth and cyst were removed. Subsequently, at 42 days after surgery, an exophytic mass was found in the socket of the second molar. An excisional biopsy was performed, and the histopathological diagnosis was PG. Since the PG recurred 90 days after the surgery, a complete excision with bone curettage was performed. During the 12 months of follow-up, there has been no recurrence observed. In conclusion, as tooth extraction is a routine dental practice, clinicians should be aware that PGs can also develop from an extraction socket.

Objective. An angiogenesis inhibitor can cause medication-related osteonecrosis of the jaw (MRONJ). To our knowledge, there has been no report that an angiogenesis inhibitor causes delayed healing of tooth extraction socket. Here, we describe a case of delayed healing of tooth extraction sockets associated with an angiogenesis inhibitor, ramucirumab, which showed characteristics similar to MRONJ. Materials and Methods. A 76-year-old male patient, who was diagnosed with gastric cancer with liver metastasis, received tooth extraction twice during continuous chemotherapy comprising paclitaxel and ramucirumab. Results. The first extraction was performed 30 days after ramucirumab discontinuation without complication. The second extraction was conducted without ramucirumab discontinuation. Although tooth socket healing was finally achieved, it took about 150 days. Discussion. This case was considered to be delayed healing of dry sockets rather than MRONJ due to ramucirumab. Dentists and oral surgeons need to be aware that angiogenesis inhibitors can cause not only MRONJ but also dry sockets after tooth extraction.

Immune checkpoint inhibitors (ICI) have shown positive results in patients with hepatocellular carcinoma (HCC). As liver function contributes to prognosis, its precise assessment is necessary for the safe prescribing and clinical development of ICI in HCC. We tested the accuracy of the albumin-bilirubin (ALBI) grade as an alternative prognostic biomarker to the Child-Turcotte-Pugh (CTP). In a prospectively maintained multi-centre dataset of HCC patients, we assessed safety and efficacy of ICI across varying levels of liver dysfunction described by CTP (A to C) and ALBI grade and evaluated uni- and multi-variable predictors of overall (OS) and post-immunotherapy survival (PIOS). We studied 341 patients treated with programmed-death pathway inhibitors (n = 290, 85%). Pre-treatment ALBI independently predicted for OS, with median OS of 22.5, 9.6, and 4.6 months across grades (p &lt, 0.001). ALBI was superior to CTP in predicting 90-days mortality with area under the curve values of 0.65 (95% CI 0.57&ndash, 0.74) versus 0.63 (95% CI 0.54&ndash, 0.72). ALBI grade at ICI cessation independently predicted for PIOS (p &lt, 0.001). Following adjustment for ICI regimen, neither ALBI nor CTP predicted for overall response rates or treatment-emerging adverse events (p &gt, 0.05). ALBI grade identifies a subset of patients with prolonged survival prior to and after ICI therapy, lending itself as an optimal stratifying biomarker to optimise sequencing of systemic therapies in advanced HCC.

Background/aim Although chemotherapy agents, such as oxaliplatin, cisplatin, paclitaxel and bortezomib frequently cause severe peripheral neuropathy, very few studies have reported the effective strategy to prevent this side effect. In this study, we first investigated whether these drugs show higher neuropathy compared to a set of 15 other anticancer drugs, and then whether antioxidants, such as sodium ascorbate, N-acetyl-L-cysteine, and vitamin B12 have any protective effect against them. Materials and methods Rat PC12 cells were induced to differentiate into neuronal cells by repeated overlay of serum-free medium supplemented with nerve growth factor. The cytotoxic levels of anticancer drugs against four human oral squamous cell carcinoma cell lines, three normal oral cells, and undifferentiated and differentiated PC12 cells were determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Cells were sorted for apoptotic cells (distributed into subG1 phase) and cells at different stages of cell cycle (G1, S and G2/M). Results All 19 anticancer drugs showed higher cytotoxicity against PC12 compared to oral normal cells. Among them, bortezomib showed the highest cytotoxicity against both undifferentiated and differentiated PC12 cell and, committed them to undergo apoptosis. Sodium ascorbate and N-acetyl-L-cysteine, but not vitamin B12, completely reversed the cytotoxicity of bortezomib. Conclusion Bortezomib-induced neuropathy might be ameliorated by antioxidants.

The aim was to determine changes in various parameters indicating physical conditions and nutritional status of patients during surgical and conservative treatment of mandibular fractures. A round by a nutrition support team was done once postoperatively for the surgical treatment group. For the conservative treatment group, three rounds were performed during the period of intermaxillary fixation. Data obtained from the rounds were compared between the groups. There were 29 patients surgically and 30 patients conservatively treated. A significant weight loss was observed in both groups postoperatively. The mean weight loss of the surgical treatment group measured at the postoperative round was 1.73 kg (SD ± 1.78) (P 0.001) and that of the conservative treatment group at the third round was 2.74 kg (SD ± 2.35) (P 0.001). During the entire treatment period, weight loss, body fat percentage, skeletal muscle percentage, grip strength and parameters indicating body composition and nutritional status of the conservative treatment group did not substantially differ from those of the surgical group. The influence of the conservative procedure on the nutritional condition of the patients seems to be limited and reversible at the end of the treatment. The weight loss observed here suggests that systematic nutrition support is necessary during both surgical and conservative treatment.

The oral hygiene and oral status of children with severe disabilities with both nutritional and respiratory complications who were institutionalized at Karugamonoie (KNI), a facility for children with disabilities, were investigated in this study. Their oral hygiene management was solely dependent on caregivers and nurses at the institution. Thirty children (13 females, 17 males; average age, 7.6 years) who had a tracheotomy and feeding tube (gastrostomy, nasogastric, or jejunostomy feeding tube) were included in the study. As for oral characteristics, poor control of tongue movement, anterior open-bite, abnormal strain of facial muscles, dry mouth, and swallowing dysfunction were found in 63.3%, 63.3%, 13.3%, 20.0%, and 100.0%, of the children, respectively. The mean ± standard deviation Decayed, Missing, Filled Teeth score was 0.13 ± 0.57. The Gingival Index (GI) showed that the children had mild (53.3%) to moderate (46.7%) gingivitis. The Simplified Oral Hygiene Index was excellent in 50.0% of the children, good in 23.3%, fair in 20.0%, and poor in 6.7% of the children. These indices were satisfactory in general except for GI management, which may have been hampered by abnormal oral functions and anterior open-bite. In conclusion, oral hygiene management of children with nutritional and respiratory complications at KNI was shown to be of high quality even without on-site intervention by dental specialists.

In recent years, electric toothbrushes have become widespread. However, injuries caused by electric toothbrushes have rarely been reported. We describe three cases of oral penetrating injuries caused by electric toothbrushes. Case 1 occurred in a disabled boy while brushing due to unexpected movement. In Case 2, a mother using an electric toothbrush had fallen when bumped by her child. Case 3 involved a man using the toothbrush while taking a bath, who slipped in the bathtub. Cases 1 and 3 were using sonic toothbrushes, and Case 2 was using an oscillating-rotating toothbrush. Electric toothbrushes can cause oral penetrating injuries and infections in the same manner as manual toothbrushes. Prevention of oral trauma requires familiarity with the form and function of electric toothbrushes. Some room for improvement remains in optimizing the form of electric toothbrushes.

Background & Aims Tumour mutational burden (TMB) predicts improved response and survival to immunotherapy. In this pilot study, we optimized targeted next‐generation sequencing (tNGS) to estimate TMB in hepatocellular carcinoma (HCC). Methods We sequenced 48 non‐paired samples (21 fresh‐frozen [FF] and 27 paraffin‐embedded [FFPE]), among which 11 FFPE samples were pretreated with uracil‐DNA glycosylase (UDG). Thirty samples satisfied post‐sequencing quality control. High/low TMB was defined by median number of mutations/Mb (Mut/Mb), across different minimum allele frequency (MAF) thresholds (≥0.05, ≥0.1 and ≥0.2). Results Eligible patients (n = 29) were cirrhotic (84%) with TNM stage I‐II HCC (75%). FFPE samples had higher TMB (median 958.39 vs 2.51 Mut/Mb, P < .0001), estimated deamination counts (median 1335.50 vs 0, P < .0001) and C > T transitions at CpG sites (median 60.3% vs 9.1%, P = .002) compared to FF. UDG‐treated samples had lower TMB (median 4019.92 vs 353 Mut/Mb, P = .041) and deamination counts (median 6393.5 vs 328.5, P = .041) vs untreated FFPE. At 0.2 MAF threshold with UDG treatment, median TMB was 5.48 (range 1.68‐16.07) and did not correlate with salient pathologic features of HCC, including survival. Conclusion While tNGS on fresh HCC samples appears to be the optimal source of tumour DNA, the low median TMB values observed may limit the role of TMB as a predictor of response to immunotherapy in HCC.

We investigated the damage evolution behaviors of binary Fe–28–40Mn alloys (mass%) from 93 to 393 K by tensile testing. The underlying mechanisms of the microstructure-dependent damage evolution behavior were uncovered by damage quantification coupled with in situ strain mapping and post-mortem microstructure characterization. The damage growth behaviors could be classified into three types. In type I, the Fe–28Mn alloy at 93 K showed premature fracture associated with ductile damage initiation and subsequent quasi-cleavage damage growth associated with the $$\upvarepsilon $$ -martensitic transformation. In type II, the Fe–28Mn alloy at 293 K and the Fe–32Mn alloy at 93 K showed delayed damage growth but did not stop growing. In type III, when the stacking fault energy was $$>\,$$ 19 $$\hbox {mJ/m}^{2}$$ , the damage was strongly arrested until final ductile failure.

Peripheral neuropathy is the major adverse event during administration of the taxanes, including paclitaxel and docetaxel. Among oral adverse events, oral mucositis is relatively common, but the occurrence of trigeminal nerve disorders is rare. Two cases of trigeminal nerve disorders, one involving the inferior alveolar nerve, the buccal nerve and the lingual nerve and the other the lingual nerve, caused by docetaxel are presented.