p62 Is a Potential Biomarker for Risk of Malignant Transformation of Oral Potentially Malignant Disorders (OPMDs).

To determine the intracellular behavior of p62, a marker of selective autophagy, in oral potentially malignant disorders (OPMDs). This retrospective study includes 70 patients who underwent biopsy or surgical resection and were definitively diagnosed with OPMDs. Immunohistochemical staining for p62, XPO1, p53, and ki67 was performed on all samples and positive cell occupancy was calculated. We statistically investigated the correlation between protein expression in OPMDs and the association between malignant transformation, clinicopathological characteristics, and occupancy. ki67 expression was negatively correlated with p62 expression in the nucleus (p < 0.01) and positively correlated with p62 expression in the cytoplasm (p < 0.01). For malignant transformation, the expression of p62 in the nucleus (p = 0.03) was significantly lower in malignant transformation cases, whereas the expression of p62 in the cytoplasm (p = 0.03) and the aggregation expression (p < 0.01) were significantly higher. Our results suggest that the function of p62 is altered by its subcellular localization. In addition, defects in selective autophagy occur in cases of malignant transformation, suggesting that p62 is a potential biomarker of the risk of malignant transformation of OPMDs.

Anterior Maxillary Distraction Osteogenesis With Bone-borne Intraoral Buccal Devices for Maxillary Hypoplasia With Cleft Lip and Palate.

Anterior maxillary distraction osteogenesis (AMDO) surgery for cleft lip and palate involves distraction of a segment of the anterior maxilla and advancement using 2 intraoral buccal bone-borne distraction devices. The anterior part of the maxilla is advanced anteriorly with less relapse which increases maxillary length and does not affect speech. We aimed to evaluate the effects of AMDO, including lateral cephalometric changes. Seventeen patients who had undergone this procedure were included in this retrospective study. The distractors were activated by 0.5 mm twice a day after a 3-day latency period. Lateral cephalometric radiographs were evaluated preoperatively, after distraction and removal of distractors, which were compared using the paired Student's t test. Anterior maxillary advancement was obtained in all patients with a median of 8.0 mm. Complications included nasal bleeding and loosening of distractors; however, there was no tooth damage or abnormal movement. The mean sella-nasion-A point (SNA) angle increased significantly, from 74.91° to 79.66°, the A point-nasion-B point angle from -0.38° to 4.34°, and the perpendicular line from nasion to Frankfort Horizontal (NV)-A point from -5.11 to 0.08 mm. The mean anterior nasal spine-posterior nasal spine length increased significantly from 50.74 to 55.10 mm, and the NV-Nose Tip from 23.59 to 26.27 mm. The mean relapse rate of NV-A was 11.1%. AMDO with bone-borne distractor resulted in less relapse and effectively corrected the maxillary retrusion.

Is Preoperative Plate-Lymphocyte Ratio a Predictor of Deep Vein Thrombosis in Patients With Oral Cancer During Surgery?

PURPOSE: Detecting deep vein thrombosis (DVT) is necessary to reduce the morbidity of venous thromboembolism, and platelet-lymphocyte ratio (PLR) is a novel marker for predicting DVT. This study aimed to investigate the association between preoperative PLR and risk of developing DVT in patients receiving surgical treatment of oral cancer. PATIENTS AND METHODS: We designed a retrospective cohort study, and the source of study sample was patients with oral cancer and who underwent surgery between 2015 and 2019. Patients were excluded if they did not undergo surgical treatment and had preoperative DVT and history of hypercoagulable disorders. The primary predictor variable was PLR. We calculated the receiver operating characteristic curve and area under the curve to determine the best-defined risk groups. The best cutoff value for PLR was 187.4 (area under the curve, 0.772; sensitivity, 75.0%; specificity, 74.2%; P = .002). The primary outcome variable was DVT, and the other variables were patient characteristics, blood examination data, and therapeutic data. A logistic regression analysis was used to adjust the effects of potential confounders. RESULTS: A total of 101 patients were included in this study, and DVT was observed in 12 (11.9%) patients. Free flap reconstructive surgery was performed in 8 of the 12 (66.7%) patients in the DVT group. Statistical analyses showed that DVT was significantly associated with PLR (≤187.4 vs >187.4; P = .001). Logistic multivariate analysis of the preoperative parameters identified the following 2 independent predictive factors for DVT: PLR (≤187.4 vs >187.4) (odds ratio, 13.735; 95% confidence interval, 2.950 to 63.944; P = .001) and free flap reconstructive surgery (odds ratio, 6.584; 95% confidence interval, 1.504 to 28.822; P = .012). CONCLUSIONS: High PLR (>187.4) and free flap reconstructive surgery, considered as preoperative predictive factors, were associated with DVT.

Is Lymph Node Ratio a Prognostic Factor for Patients With Oral Squamous Cell Carcinoma?

PURPOSE: Lymph node ratio (LNR), defined as the ratio of positive resected lymph nodes (LNs) to the total number of resected LNs, predicts survival for some solid tumors. This study investigated the value of LNR in the prognosis and postsurgical management of oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: The authors designed a retrospective cohort study and enrolled a sample of patients who were diagnosed with OSCC and treated by neck dissection. The predictor was LNR and the outcome variable was overall survival (OS). Other variables were dissection type, postsurgical management, number of positive LNs, pN stage, nodal disease area, extracapsular spread, perineural invasion, vascular invasion, and lymph duct invasion. Differences in OS rate were analyzed by log-rank test. A Cox proportional hazards model was used to adjust for the effects of potential confounders. Differences with a P value less than .05 were considered statistically significant. RESULTS: In 95 patients with OSCC, the LNR cutoff value for predicting overall OS was 0.04 (area under the curve, 0.705; P = .010). There was a significant difference in OS when patients were stratified according to LNR (rate for low LNR, 90.5%; rate for high LNR, 68.8%; P = .014). Univariate analyses showed close correlations between OS and LNR, pT stage, number of positive LNs, and nodal disease area (levels IV and V). Cox multivariate analysis identified LNR (hazard ratio [HR] = 2.889; 95% confidence interval [CI], 1.032-8.087; P = .043) and area of nodal disease (levels IV and V; HR = 5.149; 95% CI, 1.428-18.566; P = .012) as independent predictive factors for OS. OS differed significantly between the high-LNR and low-LNR groups treated by surgery alone (P = .027). CONCLUSIONS: As a predictive factor, high LNR (>0.04) was associated with decreased survival, and intensive adjuvant therapy could improve the prognosis for patients with high LNR.

MicroRNA-155-5p is associated with oral squamous cell carcinoma metastasis and poor prognosis.

BACKGROUND: Abnormal miRNA expression was recently implicated in the metastasis of oral squamous cell carcinoma (OSCC) and with a poor prognosis. The initiation of the invasion-metastasis cascade involves epithelial-mesenchymal transition (EMT). Our aim was to clarify how miRNA, especially miR-155-5p misexpression contributes to OSCC metastasis through EMT. METHODS: We collected tumor samples from 73 subjects with OSCC. The samples were analyzed by quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and correlations between miR-155-5p levels and clinical characteristics were investigated. OSCC cell lines were analyzed by miRNA microarray and by transfection with a miR-155-5p mimic or inhibitor, followed by proliferation and wound-healing migration assays. qRT-PCR analyses of EMT makers in cells transfected with miR-155-5p inhibitor were performed. RESULTS: We found high miR-155-5p expression in tissue samples from subjects with OSCC that had metastasized to cervical lymph nodes. HSC-3 cells also strongly expressed miR-155-5p. The epithelial marker E-cadherin was strongly expressed in HSC-3 cells transfected with miR-155-5p inhibitor, and we observed elevated SOCS1 and decreased STAT3 expression in these cells. CONCLUSIONS: Our results suggest that miR-155-5p causes OSCC to metastasize, and could serve as a novel therapeutic target for OSCC.

Epstein-Barr Virus-Positive Mucocutaneous Ulcer With Medication-Related Osteonecrosis of the Jaw Arising in the Mandible of a Rheumatoid Arthritis Patient: A Case Report.

This study presents a rare case of an Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU) co-existing with medication-related osteonecrosis of the jaw (MRONJ) in the mandible of a 54-year-old Japanese man who complained of painful swelling of the left mandibular gingiva over the past three months. The patient had a history of methotrexate (MTX) and bisphosphonates (BPs) use. Intraoral examination revealed a 35 mm large ulcerative lesion with marginal gingival swelling and bone exposure on the left side of the mandible. A biopsy was performed, confirming the diagnosis of EBVMCU with MRONJ. Due to the enlargement of the bone exposure, marginal resection of the mandible was performed under general anesthesia as a treatment for residual MRONJ. At the two-year follow-up, no evidence of recurrence was observed.

Involvement of submandibular gland in oral squamous cell carcinoma.

BACKGROUND: The submandibular gland (SMG) is sacrificed during neck dissection in patients undergoing curative surgery for oral squamous cell carcinoma (OSCC). This may cause a decrease in the production of saliva and result in xerostomia. PURPOSE: This study aimed to determine the incidence, invasion patterns, risk factors, and prognosis of SMG involvement in OSCC. METHODS: The primary predictor variable in this study was SMG involvement, and the secondary predictor was prognosis. MAIN FINDINGS: The primary outcome variables were patient characteristics and pathological results for extranodal extension (ENE), perineural invasion (PNI), and pN stage. Four out of 173 patients (2.23 %) showed SMG involvement. Of these cases, one (25 %) was from the primary lesion and three (75 %) were from the metastatic neck lymph nodes (LNs). The primary lesion was located on the lower gingiva, and the other three were from level-Ib LNs with ENE. The pathological PNI was observed in three of the four patients, and ENE was observed in three of the four patients. Preoperative CT and MR revealed SMG invasion and contact in two patients. There were significant differences in the ENE and pN stages between patients with and without SMG involvement (P<0.05). There was a significant difference in the overall survival between patients with (25.0 %) and without (71.5 %) SMG involvement (P = 0.011). CONCLUSIONS: SMG involvement was associated with ENE, pN stage, and poor prognosis.

The inflammatory markers and locoregional pathological results both have an impact on the prognosis of oral squamous cell carcinoma in patients who have undergone neck dissection.

BACKGROUND: Locoregional surgical pathology, with surgical margins at the primary site and lymph node (LN) metastasis, particularly extranodal extension (ENE), plays an important role in the prognosis of oral squamous cell carcinoma (OSCC). In addition, systemic inflammatory response and nutritional status are associated with poor prognosis. PURPOSE: This study aimed to comprehensively assess the effect of inflammatory markers and locoregional factors on the prognosis of patients with OSCC who underwent neck dissection (ND). METHODS: This retrospective cohort study included patients who had undergone ND for OSCC between 2013 and 2021. The primary predictive variables were the weighted lymph node ratio (WLNR) and inflammatory markers. Primary outcome variables were overall survival (OS) and disease-free survival (DFS). RESULTS: Among 153 patients (99 males, 54 females), 55 (35.9 %) had LN metastasis and 11 (7.2 %) exhibited ENE. The inflammatory markers lymphocyte/monocyte ratio (LMR), monocyte/albumin ratio (MAR), C-reactive protein/albumin ratio (CAR), and WLNR demonstrated significant cut-off values for survival, with values of 4.805, 104.72, 0.041, and 0.0235, respectively. The Cox proportional hazards model revealed significant differences in age, WLNR, LMR, MAR, CAR, and vascular, lymphatic, and perineural invasion (Pn). Multivariate analysis indicated that the hazard ratios (95 % confidence intervals) for WLNR (3.416; 1.542-7.566), MAR (2.404; 1.254-4.607), and Pn (2.516; 1.291-4.905) were independent variables for OS. CONCLUSIONS: In patients with OSCC who underwent ND, the inflammatory marker MAR and locoregional factors WLNR and Pn were simultaneously identified as prognostic factors.

Predictors of Occult Metastasis and Prognostic Factors in Patients with cN0 Oral Cancer Who Underwent Elective Neck Dissection.

Elective neck dissection (END) is recommended for the management of patients with oral squamous cell carcinoma (OSCC) because of the risk of occult metastasis (OM). We hypothesized that some factors predict poor prognosis regardless of a cN0 END. This study aimed to investigate the predictors of OM and prognostic factors in patients with cN0 OSCC who underwent supraomohyoid neck dissection (SOHND). A retrospective cohort study design was created and implemented. The primary predictive variables in this study were OM and risk factors for poor prognosis after SOHND. A Cox proportional hazard model was used to adjust for the effects of potential confounders on the risk factors for poor prognoses. Among 86 patients with OSCC, OMs were observed in 9 (10.5%). The neutrophil-to-lymphocyte ratio (NLR) and vascular invasion are good markers for detecting OM. A Cox multivariable analysis identified two independent predictors of overall survival: pathologic node (pN) and laterality of END. An independent predictive factor for disease-free survival, the surgical margin, was also identified in this study. According to the pN classification, pN1 patients had a worse survival rate than pN2 patients. Therefore, in the case of pN1, regardless of being cN0, additional adjuvant therapy may be necessary.

Sequencing-based study of neural induction of human dental pulp stem cells.

Techniques for triggering neural differentiation of embryonic and induced pluripotent stem cells into neural stem cells and neurons have been established. However, neural induction of mesenchymal stem cells, including dental pulp stem cells (DPSCs), has been assessed primarily based on neural-related gene regulation, and detailed studies into the characteristics and differentiation status of cells are lacking. Therefore, this study was aimed at evaluating the cellular components and differentiation pathways of neural lineage cells obtained via neural induction of human DPSCs. Human DPSCs were induced to neural cells in monolayer culture and examined for gene expression and mechanisms underlying differentiation using microarray-based ingenuity pathway analysis. In addition, the neural lineage cells were subjected to single-cell RNA sequencing (scRNA-seq) to classify cell populations based on gene expression profiles and to elucidate their differentiation pathways. Ingenuity pathway analysis revealed that genes exhibiting marked overexpression, post-neuronal induction, such as FABP7 and ZIC1, were associated with neurogenesis. Furthermore, in canonical pathway analysis, axon guidance signals demonstrated maximum activation. The scRNA-seq and cell type annotations revealed the presence of neural progenitor cells, astrocytes, neurons, and a small number of non-neural lineage cells. Moreover, trajectory and pseudotime analyses demonstrated that the neural progenitor cells initially engendered neurons, which subsequently differentiated into astrocytes. This result indicates that the aforementioned neural induction strategy generated neural stem/progenitor cells from DPSCs, which might differentiate and proliferate to constitute neural lineage cells. Therefore, neural induction of DPSCs may present an alternative approach to pluripotent stem cell-based therapeutic interventions for nervous system disorders.

Analysis of predictors of fever after aortic valve replacement: Diabetic patients are less likely to develop fever after aortic valve replacement, a single-centre retrospective study.

BACKGROUND: Postoperative temperature dysregulation affects the length of hospital stay and prognosis. This study evaluated the factors that influence the occurrence of fever in patients after aortic valve replacement surgery. METHODS: Eighty-seven consecutive patients who underwent aortic valve replacement surgery were included. Patients' age, sex and body mass index; presence of diabetes mellitus; operation time; blood loss; blood transfusion volume; preoperative and postoperative laboratory findings; presence or absence of oral function management; and fever >38°C were retrospectively analysed through univariate and multiple logistic regression analyses. RESULTS: Among the variables, only diabetes mellitus status was significantly associated with fever ⩾38°C. Postoperatively, patients with diabetes mellitus were significantly less likely to develop fever above 38°C and a fever rising to 38°C. CONCLUSIONS: This study shows that the presence of comorbid diabetes mellitus decreases the frequency of developing fever >38°C after aortic valve replacement surgery.

A Case of Tooth Extraction in a Patient with Food-Dependent Exercise Induced Anaphylaxis.

A 29-year-old Japanese man with food-dependent exercise-induced anaphylaxis (FDEIA) underwent tooth extraction under general anesthesia. FDEIA is a rare condition in which anaphylaxis occurs due to exercise load or oral administration of NSAIDs after ingestion of allergens. Wheat is often the cause in FEDIA, defined as wheat-dependent exercise-induced anaphylaxis (WDEIA). It is an allergy that is not well known in the dental field. Patients may ingest the causative food on a regular basis because they do not develop without factors such as exercise. Post extraction period was uneventful as the patient was instructed not to ingest wheat before the treatment or while he was taking NSAIDs. We were able to safely extract teeth without causing anaphylaxis.

Prognostic prediction using maximum standardized uptake value ratio of lymph node-to-primary tumor in preoperative PET-CT for oral squamous cell carcinoma.

This study aimed to calculate the ratio of maximum standardized uptake values of cervical lymph nodes to maximum standardized uptake values of primary tumors measured by preoperative fluorodeoxyglucose positron-emission tomography in oral cancer patients, and to retrospectively examine the prognostic association and evaluate whether it could be a prognostic factor. We retrospectively examined consecutive Japanese patients diagnosed with oral squamous cell carcinoma who underwent oral cancer resection and cervical dissection between January 2014 and December 2018. The study included 52 patients aged 39-89 years (median age 66.5 years), excluding non-cervical dissection surgery and/or non-underwent preoperative positron-emission tomography. The maximum standardized uptake value of the cervical lymph nodes and primary tumor was measured, and the ratio of maximum standardized uptake values of the lymph nodes to that of the primary tumor was calculated. The median follow-up of 52 patients was 1,465 days (198-2,553 days), and overall survival was significantly worse in patients with a high lymph node-to-tumor standardized uptake values ratio (>0.4739) (5 years, 58.8% vs. 88.2%; P<0.05). Pretreatment lymph node-to-tumor standardized uptake values ratio can be easily calculated, and as a predictor of prognosis, it may be of assistance when considering the treatment strategy for oral cancer.

Postoperative Deep Sedation after Microvascular Reconstructive Surgery for Oral Cancer Increases the Risk of Early Postoperative Pneumonia.

This study investigated the effect of postoperative deep sedation after oral cancer reconstructive surgery on the occurrence of early postoperative pneumonia and early postoperative delirium. We obtained medical records of 108 consecutive patients who underwent microvascular reconstructive surgery at Tsukuba University Hospital for oral cancer between January 2013 and December 2021. Forty-six of them woke soon after surgery. Ten of these forty-six patients were restless and required immediate sedation within 3 h after surgery. The comparison between sedation group and no sedation group revealed early postoperative pneumonia in the no sedation group; however, sedation was not related to early postoperative delirium. The preoperative albumin levels of patients with postoperative pneumonia were significantly different (p = 0.03) than those of patients without postoperative pneumonia. The performance status (p = 0.02), preoperative albumin level (p = 0.02), and age 75 years or older (p = 0.02) were significantly associated with postoperative delirium. Restless patients and those who could not be sedated experienced delirium and pneumonia. The risk of pneumonia was increased for patients who were difficult to sedate.

A Case of Primary Intraosseous Squamous Cell Carcinoma Arising in Dentigerous Cyst of Mandible.

Primary intraosseous squamous cell carcinoma (PISCC) arising from dentigerous cysts (DCs) is rare. Herein, we present a rare case of a 35 year-old Japanese man with PISCC arising from a DC. Clinicians should be aware of the potential for malignant changes to SCC in asymptomatic DCs and should conduct follow-up. Moreover, histological examination of the entire specimen should be performed even if the lesion is suspected to be benign.

A Case of Tophaceous Pseudogout with Destruction of the Skull Base at the Temporomandibular Joint.

We report a case of tophaceous pseudogout that occurred in the temporomandibular joint (TMJ) and presented with skull base destruction. The patient was a 73-year-old woman, who complained of an obstructed ear sensation in December 2021. The otolaryngological examination was unremarkeable, and a computed tomography scan revealed a calcified lesion in the left TMJ. Suspected of having osteochondroma, the patient was brought to our hospital. She was performed tumor resection as much as possible under general anesthesia revealed nodular pseudogout. The patient refused to undergo total resection due to the necessary craniotomy and the risk of postoperative complications. Instead, the patient decided to undergo following-up. One year and 4 months have passed since the biopsy operation, but there is no tendency to re-increase.

A Case of Primary Intraosseous Adenoid Cystic Carcinoma of the Mandible.

Primary intraosseous adenoid cystic carcinoma (PIACC) of the jaw is rare. To our knowledge, only 51 cases have been reported in the English literature. We present a rare case of PIACC arising in the mandible with multiple bone metastases and review the previous articles. A 70-year-old woman presented with paresthesia of the right chin and lower gingiva for 4 months. Radiography revealed an irregular radiolucent region on the right side of the ramus, infiltrating to the mandibular canal. Biopsy revealed a pathological diagnosis of adenoid cystic carcinoma. Multiple bone metastases were present in the sternum, scapula, and thighs. The treatment effect was progressive disease for chemotherapy; therefore, best supportive care was provided for 3 years.

Positive impact of perioperative oral management on the risk of surgical site infections after abdominal surgery: Sixteen universities in Japan.

Surgical site infections (SSI) are associated with increased morbidity and mortality rates. This study aimed to investigate the ability of perioperative oral management (POM) to reduce the risk of SSI in abdominal surgery Real-world data collected from 16 university hospitals in Japan were reviewed. The medical records of consecutive 2782 patients (1750 men and 1032 women) who underwent abdominal surgery under general anesthesia at 16 university hospitals were retrospectively reviewed. Detailed information about SSI was assessed and compared between patients with and without POM in univariate and multivariate analyses. SSI were observed in 275 patients (incidence rate:9.9%), and POM was administered to 778 patients (28.0%). Univariate analyses revealed that diabetes mellitus, Eastern Cooperative Oncology Group performance status, American Society of Anesthesiologists classification, surgical site, preoperative Prognostic Nutritional Index score, POM, extent of surgery, operation time, and intraoperative blood loss were significantly associated with postoperative SSI (Chi-square or Mann-Whitney U test, P < .01). Multivariate analysis revealed that POM had significant preventive effects against postoperative SSI (estimate: -0.245, standard error: 0.080, P < .01). Surgical site, American Society of Anesthesiologists classification, and operation time were also significant and independent clinical predictors of SSI. The analysis of real-world data from 16 university hospitals revealed that, regardless of the content and degree of the problem, the addition of POM has significant beneficial effects in reducing the risk of SSI in patients who undergo abdominal surgery. Medical records from each hospital and data from the Health Care Payment Fund were collected and analyzed retrospectively.

Macrophage specific restoration of the Nrf2 gene in whole-body knockout mice ameliorates steatohepatitis induced by lipopolysaccharide from Porphyromonas gingivalis through enhanced hepatic clearance.

Lipopolysaccharide (LPS) derived from Porphyromonas gingivalis (P.g.), which causes periodontal disease, contributes to the development of non-alcoholic steatohepatitis (NASH). We investigated the role of Nrf2, an antioxidative stress sensor, in macrophages in the development of NASH induced by LPS from P.g. We generated macrophage-specific Nrf2 gene rescue mice (Nrf2-mRes), which express Nrf2 only in macrophages, using the cre/loxp system. Wild-type (WT) mice, whole body Nrf2-knockout (Nrf2-KO) mice, and Nrf2-mRes mice were fed a high-fat diet for 18 weeks, and LPS from P.g. was administered intraperitoneally for the last 6 weeks. Nrf2-KO mice developed severe steatohepatitis with liver inflammation and fibrosis compared with WT mice, and steatohepatitis was ameliorated in Nrf2-mRes mice. The mRNA expressions of Toll-like receptor (Tlr)-2, which activates inflammatory signaling pathways after LPS binding, and α-smooth muscle actin (αSma), which promotes hepatic fibrosis, were reduced in Nrf2-mRes mice compared with Nrf2-KO mice. The protein levels of LPS-binding protein in livers were increased in Nrf2-KO mice compared with WT mice; however, the levels were reduced in Nrf2-mRes mice despite similar numbers of F4/80 positive cells, which reflect macrophage/Kupffer cell infiltration into the livers. Nrf2 in macrophages ameliorates NASH through the increased hepatic clearance of LPS.

Osseous Choristoma of the Tongue: A Case Report.

We report a case of a 40-year-old Japanese woman with a benign tongue tumor diagnosed as osseous choristoma of the tongue. Resection of the tongue tumor was performed under general anesthesia. The gross examination of the resected specimen showed a bone-like mass measuring 5 × 5 × 3 mm, surrounded by soft tissue. Based on the findings, a histopathological diagnosis of osseous choristoma was established. There was no evidence of tumor recurrence or distant metastasis during the 3-year follow-up.