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.

Factors Affecting the Occurrence of Complications in the Early Stages After Dental Implant Placement: A Retrospective Cohort Study.

OBJECTIVE: To evaluate the background factors related to the occurrence of complications in the early stages after dental implant placement. MATERIALS AND METHODS: A total of 289 outpatients who received dental implants were retrospectively evaluated for the presence or absence of complications. Background factors, including age, sex, implant width, implant length, implant site, number of implants placed, Periotest values at the time of implant placement, presence/absence of systemic disease (particularly diabetes), and the use of anticoagulation therapy, were compared between patients with and without complications. Logistic regression analysis was performed to identify significant risk factors for the occurrence of complications after dental implant placement. RESULTS: Complications in the early stages after dental implant placement occurred in 25 (8.65%) patients. The patients with complications were older than those without complications (P = 0.003). In addition, the incidence of complications was significantly higher in patients with systemic diseases (P = 0.004) and in those receiving anticoagulation therapy (P = 0.005). Logistic regression analysis revealed that age was a significant risk factor (P = 0.025) for early-stage complications, whereas the number of implants, presence of diabetes, and the use of anticoagulation therapy were not significant risk factors. CONCLUSIONS: Our results show that age is a significant factor influencing the occurrence of complications in the early stages after dental implant placement. Therefore, clinicians should consider this factor when developing their treatment strategies.

A Case of Cholangitis as a Nivolumab-Induced Immune-Related Adverse Event in a Patient with Pulmonary Metastasis After Surgery for Oral Cancer.

We report a case of cholangitis, an immune-related adverse event (irAE), caused by the administration of nivolumab in a patient with lung metastasis of oral cancer. A 72-year-old man developed pulmonary metastasis after surgery for oral cancer. Hepatic enzyme abnormalities were observed after the second session of treatment, and irAE cholangitis was diagnosed based on the results of the blood test results and endoscopy findings. We suggested steroid treatment, but the patient refused it. Therefore, he was treated with ursodeoxycholic acid. The cholangitis gradually deteriorated, the patients' general condition worsened, and he died 169 days after the onset of cholangitis.

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.

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.

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.

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.