Background: Prognostic biomarkers provide essential information about a patient's overall outcome. However, existing biomarkers are limited in terms of either sample collection, such as requiring tissue specimens, or the process, such as prolonged time for analysis. In view of the need for convenient and non-invasive prognostic biomarkers for oral cancer, we aimed to investigate the prognostic values of neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and platelet-to-lymphocyte ratio in patient survival. We also aimed to explore the associations of these ratios with the clinicopathologic characteristics of Japanese oral squamous cell carcinoma patients. Methods: This study was a non-randomized retrospective cohort study in a tertiary referral center. We included 433 patients (246 men, 187 women) who underwent radical surgery for oral cancers between January 2001 and December 2013. We evaluated various risk factors for poor prognosis including neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and platelet-to-lymphocyte ratio with univariate and multivariate analyses. The disease-specific survival and overall survival rates of patients were compared among the factors and biomarkers. Results: In multivariable Cox proportional hazards analysis, high neutrophil-to-lymphocyte ratio (hazard ratio 2.87, 95% confidence interval 1.59-5.19, P < 0.001), moderately or poorly differentiated histology (hazard ratio 2.37, 95% confidence interval 1.32-4.25, P < 0.001), and extranodal extension (hazard ratio 1.95, 95% confidence interval 1.13-3.35, P = 0.016) were independent predictors of disease-specific survival. High neutrophil-to-lymphocyte ratio (hazard ratio 2.30, 95% confidence interval 1.42-3.72, P < 0.001), moderately or poorly differentiated (hazard ratio 1.72, 95% confidence interval 1.07-2.76, P = 0.025), and extranodal extension (hazard ratio 1.79, 95% confidence interval 1.13-2.84, P = 0.013) were independent predictors of overall survival. Conclusions: Neutrophil-to-lymphocyte ratio might be a potential independent prognostic factor in Japanese oral squamous cell carcinoma patients.

Background/Aim: Tumor lymphangiogenesis plays a key role in lymph node (LN) metastasis in oral squamous cell carcinoma (OSCC). The purpose of this study was to investigate podoplanin and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) and their relationship to nodal metastasis and other clinicopathological variables. Patients and Methods: Podoplanin and LYVE-1 expression of the primary tumor and normal tissue were investigated by means of a quantitative real-time PCR assay and immunohistochemistry in samples from 33 cases of OSCC. Results: The mRNA high expression levels of both genes had a statistically significantly higher rate of LN metastasis (p<0.01) and histological grade (p<0.01 for podoplanin, p<0.05 for LYVE-1). High expression of each gene, as shown by immunohistochemistry, had a statistically significant higher rate of LN metastasis (p<0.01 for podoplanin, p<0.05 for LYVE-1). Conclusion: Podoplanin and LYVE-1 were strongly associated with LN metastasis.

Introduction. In recent years, the tumour immunosuppressive mechanism has attracted attention as a cause of tumour chemoresistance. Although chemoresistance and immunosuppression of tumours have been reported to be associated with a hypoxic environment, effective treatments to improve hypoxia in tumours have not yet been established. We have previously applied carbon dioxide (CO2) to squamous cell carcinoma and have shown that improvement in local oxygenation has an antitumour effect. However, the effects of local CO2 administration on tumour immunosuppression, chemoresistance, and combination with chemotherapy are unknown. In this study, we investigated the effects of local CO2 administration on squamous cell carcinoma and the effects of combined use with chemotherapy, focusing on the effects on tumour immunosuppressive factors. Methods. Human oral squamous cell carcinoma (HSC-3) was transplanted subcutaneously into the back of a nude mouse, and CO2 and cisplatin were administered. After administration twice a week for a total of 4 times, tumours were collected and the expression of tumour immunosuppressive factors (PD-L1, PD-L2, and galectin-9) was evaluated using real-time polymerase chain reaction and immunostaining. Results. Compared with the control group, a significant decrease in the mRNA expression of PD-L1 was observed in both, CO2-treated and combination groups. Similarly, the expression of PD-L2 and galectin-9 decreased in the CO2-treated and combination groups. Furthermore, immunostaining also showed a significant decrease in the protein expression of tumour immunosuppressive factors in the CO2-treated and combination groups. Conclusion. It was confirmed that the tumour immunosuppressive factors decreased due to local CO2 administration to the mouse model. CO2 administration has the potential to improve the hypoxic environment in tumours, and combined use with chemotherapy may also improve tumour immunosuppression.

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Little research has been conducted into hypoesthesia, and no studies have elucidated the risk factors for refractory hypoesthesia and compared treatment modalities. The purpose of this multicentre retrospective cohort study was to investigate the relationships between various risk factors, treatment modalities, and refractory hypoesthesia. Risk factors for refractory hypoesthesia after oral surgery were evaluated using univariate and multivariate analysis. To minimize the selection bias associated with a retrospective data analysis, a propensity score analysis was performed between the medication and non-medication groups (65 sites in each group). Moderate or severe hypoesthesia (odds ratio 13.42) and no or late administration of ATP/vitamin B12 (odds ratio 2.28) were significantly associated with refractory hypoesthesia. In the propensity score analysis, the incidence rate of refractory hypoesthesia in the medication group was lower than that in the non-medication group (P<0.001). This study demonstrated the multivariate relationships between various risk factors, treatment modalities, and refractory hypoesthesia. Moderate or severe hypoesthesia and no or late administration of ATP/vitamin B12 were significantly associated with refractory hypoesthesia. Therefore, clinicians should consider these risk factors and initiate early oral administration of ATP/vitamin B12 in cases of hypoesthesia.