Association of higher transient receptor potential melastatin 8 expression with higher tumor histologic grades, lymph node metastasis, risk factors, and worse survival in patients with head and neck squamous cell carcinoma.

Background/purpose: Transient receptor potential melastatin 8 (TRPM8), a thermosensitive ion channel known for its role in cold sensation and menthol response, has emerged as a potential regulator in various cancers. This study aimed to investigate expression trends of TRPM8 in head and neck squamous cell carcinoma (HNSCC) cases and oral squamous cell carcinoma (OSCC) cell lines and its association with clinicopathological features. Materials and methods: The noncancerous matched tissues and HNSCC paired tissue samples from 84 HNSCC patients were utilized to evaluate the association of TRPM8 with HNSCC clinicopathological features. TRPM8 expression was examined in HNSCC patient tissues and OSCC cell lines treated with arecoline. Results: Kaplan-Meier survival analysis of TCGA data revealed high TRPM8 expression correlated with unfavorable outcomes and higher tumor histologic grades. TRPM8 mRNA expression was upregulated in HNSCC cell lines and patients' tissue samples. Arecoline treatment led to significantly increased TRPM8 mRNA and protein expression in OSCC cell lines. Lymph node metastasis showed a significant association with upregulated TRPM8 expression in combined OSCC and oropharyngeal squamous cell carcinoma (OPSCC) cases. TRPM8 mRNA expression was upregulated in HNSCC and OSCC patients with alcohol drinking and cigarette smoking habits, but not in betel quid chewing. Conclusion: These findings reveal the involvement of TRPM8 in HNSCC's malignant development and metastasis, suggesting that high expression of TRMP8 may be mutually causal with addiction to tobacco, alcohol, and betel nut in HNSCC patients. Further investigations are needed to determine the underlying pathways of TRPM8 in HNSCC's development and progression.

The Association of Salivary Flow Rate and Sleep Quality among Head and Neck Cancer Survivors after Radiotherapy.

BACKGROUND: Head and neck cancer survivors suffer from xerostomia and sleep disturbances after radiotherapy, both of which affect their quality of life. This study aimed to explore the role of salivary flow in the oral health and sleep quality of head and neck cancer survivors. METHODS: We recruited 120 head and neck cancer survivors who were experiencing symptoms of dry mouth or sleep disturbances post-radiotherapy from a dental clinic. We gathered their socio-demographic and clinical data, measured their salivary flow rate, and recorded their dry mouth score using the summated xerostomia inventory. Additionally, a dentist collected the DMFT (Decayed, Missing, and Filled Teeth) index. The Pittsburgh Sleep Quality Index was employed to assess their sleep quality. RESULTS: In this study, xerostomia was observed in nearly 80% of the cancer survivors. The concurrent prevalence of sleep disturbance and xerostomia was at 55%. After five years post-radiotherapy, there was a significant improvement observed in both the quality of sleep (p = 0.03) and the stimulated salivary flow rate (p = 0.04). Additionally, these improvements were noted to have commenced from the third year onwards. A significant association was found between stimulated salivary flow and dry mouth scores with poor sleep quality (p <  0.05). CONCLUSIONS: We recommend that dental professionals prioritize managing both dental and mental health issues equally for head and neck cancer survivors who have undergone radiotherapy within the past 3 years.

Arecoline Induces ROS Accumulation, Transcription of Proinflammatory Factors, and Expression of KRT6 in Oral Epithelial Cells.

Areca nut is a major contributor to the high prevalence of oral cancer in Asia. The precise mechanisms by which areca nut stimulates mucosal cells and contributes to the progression of oral cancer urgently require clarification. The current study aimed to assess the effects of arecoline on the normal human gingival epithelium cell line S-G. Cell viability, levels of reactive oxygen species (ROS), protein expression, cellular morphology, and gene expression were evaluated using the MTT test, flow cytometry, Western blot analysis, optical or confocal microscopy, and RT-qPCR. Keratin (KRT6) analysis involved matched normal and cancer tissues from clinical head and neck specimens. The results demonstrated that 12.5 µg/mL of arecoline induced ROS production, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) mRNA expression in S-G cells. This activation of the MAPK/ERK pathway increased KRT6 expression while limiting cell migration. In head and neck cancer tissues, KRT6B gene expression exceeded that of normal tissues. This study confirms that arecoline induces ROS accumulation in normal cells, leading to the secretion of proinflammatory factors and KRT6 expression. This impedes oral mucosal healing, thereby promoting the progression of oral cancer.

Oral rhabdomyosarcoma, a rare malignant tumor mimicking an endodontic-periodontal lesion in an adult patient: a case report.

BACKGROUND: According to previous research, 2.8% of lesions clinically identified as endodontic pathosis were ultimately diagnosed as non-endodontic periapical lesions via histopathology, and 3.7% of these non-endodontic periapical lesions were malignant neoplasms. Rhabdomyosarcoma, a malignant tumor most commonly observed in children, is uncommon in the oral cavity. CASE PRESENTATION: This is a report of a rare case of embryonal rhabdomyosarcoma in a 41-year-old female, in which the lesion was in the maxillary gingiva. The biopsy reports confirmed the diagnosis of embryonal rhabdomyosarcoma. The wide excision of the tumor, free flap reconstruction, chemotherapy, and radiotherapy were performed. Clinical, radiological, and histopathological and management aspects of the neoplasm were also discussed. CONCLUSIONS: This case report aimed to create awareness that rhabdomyosarcoma is one of the differential diagnoses of periapical lesions.

Association of rs9679162 Genetic Polymorphism and Aberrant Expression of Polypeptide N-Acetylgalactosaminyltransferase 14 (GALNT14) in Head and Neck Cancer.

The polypeptide N-Acetylgalactosaminyltransferase 14 (GALNT14) rs9679162 and mRNA expression were associated with treatment outcome in various cancers. However, the relation of GALNT14 and head and neck cancer were nuclear. A total of 199 patients with head and neck squamous cell carcinoma (HNSCC) were collected in this study, including oral SCC (OSCC), oropharyngeal SCC (OPSCC), laryngeal SCC (LSCC), and others. The DNA and RNA of cancer tissues were extracted using the TRI Reagent method. The rs9679162 was analyzed using polymerase chain reaction (PCR) and sequencing methods in 199 DNA specimens, and the mRNA expression was analyzed using quantitative reverse transcription PCR (RT-qPCR) methods in 68 paired RNA specimens of non-cancerous matched tissues (NCMT) and tumor tissues. The results showed that the genotype of TT, TG, and GG appeared at 30%, 44%, and 26%, respectively. Non-TT genotype or G alleotype were associated with alcohol, betel nut, and cigarette using among patients with OSCC, and it also affected the treatment and survival of patients with OSCC and LSCC. High GALNT14 mRNA expression levels increased lymphatic metastasis of patients with HNSCC, and treatment and survival in patients with OPSCC. Overall, the GALNT14-rs9679162 genotype and mRNA expression level can be used as indicators of HNSCC treatment prognosis.

Maximum standardised uptake value is prognostic in patients with early-stage squamous cell carcinoma of the tongue.

The aims of this paper were to evaluate the relation between the preoperative primary tumour maximum standardised uptake value (SUVmax, tSUVmax) and clinicopathological features, including depth of invasion (DOI), recurrence factors, and survival outcomes, and to compare the prognostic value of tSUVmax with that of other factors associated with the recurrence of early-stage oral squamous cell carcinoma (OSCC) of the tongue. We retrospectively analysed data from 155 patients. All patients were treated and regularly monitored at the Changhua Christian Hospital (CCH). Only those who had undergone 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in the 14 days before surgery were included. A tSUVmax of >5.2 was found to be the sole strong predictor of a DOI of >4 mm. A tSUVmax of >7.6 was strongly associated with pT2 SCC of the tongue, more aggressive DOI, and perineural invasion. DOI and tSUVmax could be used to predict disease-free survival (DFS) for early-stage SCC of the tongue, and they showed stronger predictive power than the traditional American Joint Committee on Cancer (AJCC) T stage. Therefore tSUVmax could be a prognostic tool for DFS in AJCC early-stage SCC of the tongue.

Survival and clinicopathological characteristics of cT4b oral squamous cell carcinoma based on different treatment modalities: A single-center retrospective study.

INTRODUCTION: Primary surgical treatment for oral squamous cell carcinoma (OSCC) is reserved for T1 to T4a tumors, but not for T4b tumors, according to the present National Comprehensive Cancer Network clinical practice guidelines. In this retrospective study, we aimed to determine the association between the clinicopathological characteristics and different treatment modalities for T4b OSCC based on whether patients received primary surgical treatment. Therefore, we conducted a survival analysis based on different treatment modalities. METHODS: This retrospective cohort study enrolled 125 patients with clinical stage T4b OSCC who received treatment and were followed up at Changhua Christian Hospital between January 1, 2008 and December 31, 2018. RESULTS: Overall, 81 patients received primary surgical treatment and 44 received primary nonsurgical treatment. Comparison of the clinicopathological characteristics between those who did and did not undergo surgery revealed no significant differences in age at tumor diagnosis, tumor location, clinical N stage, and involved tumor area based on computed tomography or magnetic resonance imaging, or stratified Charlson Comorbidity Index scores. In the survival analysis, Kaplan-Meier curves revealed that patients who received treatment modalities including surgery exhibited better survival than those who received treatment modalities that did not include surgery. CONCLUSIONS: In the present study, patients with T4b OSCC treated with primary surgery had a better overall survival rate than those who received nonsurgical treatment. In the future, it will be necessary for clinicians worldwide to report the treatment outcomes of patients with T4b OSCC based on the common criteria.

The relation between NEAT1 expression level and survival rate in patients with oral squamous cell carcinoma.

BACKGROUND/PURPOSE: Numerous studies have shown that long noncoding RNAs (lncRNAs) are involved in cancer progression and chemotherapy resistance. Nuclear enriched abundant transcript 1 (NEAT1) is an lncRNA. It affects tumor cell progression and drug resistance in various tumors. However, the relation of NEAT1 and survival rate in oral squamous cell carcinoma (OSCC) requires further study. MATERIALS AND METHODS: One normal gingival epithelium cell line, SG, three oral cancer cell lines (HSC3, OEC-M1, and SAS), 34 paired non-cancerous matched tissues (NCMT), and OSCC tissues were used in this study. Tri-reagent was used for total RNA extraction. NEAT1 expression was assessed by reverse transcription-quantitative PCR (RT-qPCR). RESULTS: NEAT1 expression in oral cancer cell lines was lower than that in normal cells and was significantly downregulated in OSCC. NEAT1 upregulation reduced the survival rate of patients with OSCC. NEAT1 upregulation also reduced the survival rate of OSCC patients treated with chemotherapy and radiotherapy. CONCLUSION: These results indicate that NEAT1 expression is a valuable biomarker for the prediction and prognosis of oral cancer.

Use of the Cover-Lifting Technique in Mandibular Cemento-Ossifying Fibroma Excision to Preserve the Inferior Alveolar Nerve.

Cemento-ossifying fibroma (also known as ossifying fibroma or cementifying fibroma) is a benign osteogenic neoplasm. Pain and paresthesia are rarely associated with cemento-ossifying fibroma; thus, nerves must be preserved during excision. With the advent of computer-aided techniques, the use of virtual surgical planning and a customized template can improve the precision of resection and reconstruction, reduce operating time, and improve postoperative outcomes. In this report, we describe a case of cemento-ossifying fibroma in a female patient who underwent segmental mandibulectomy and reconstruction with an iliac bone graft. Additionally, we describe a simple and effective way to preserve the inferior alveolar nerve.

Impact on patients with oral squamous cell carcinoma in different anatomical subsites: a single-center study in Taiwan.

The incidence of oral cavity squamous cell carcinoma (OSCC) is particularly high in South Asia. According to the National Comprehensive Cancer Network, OSCC can arise in several subsites. We investigated survival rates and the clinical and pathological characteristics of OSCC in different anatomical subsites in the Taiwanese population. We retrospectively analyzed data for 3010 patients with OSCC treated at the Changhua Christian Hospital. Subsequently, we compared clinical and pathological features of OSCC in different subsites. Pathological T4 stage OSCCs occurred in the alveolar ridge and retromolar trigone in 56.4% and 43.7% of cases, respectively. More than 25% of patients with tongue OSCC and 23.4% of those with retromolar OSCC had lymph node metastasis. The prognosis was worst for hard palate OSCC (hazard ratio 1.848; p < 0.001) and alveolar ridge OSCC (hazard ratio 1.220; p = 0.017). Retromolar OSCC recurred most often and tongue OSCC second most often. The risk for cancer-related mortality was highest for hard palate OSCC, followed by alveolar ridge and retromolar OSCC. We found distinct differences in survival among the different subsites of OSCC. Our findings may also help prompt future investigations of OSCC in different subsites in Taiwanese patients.

FDG-PET predicts bone invasion and prognosis in patients with oral squamous cell carcinoma.

18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) is widely used for tumor staging. This study sought to determine the relationship of preoperative primary tumor SUVmax (tSUVmax) with the clinicopathological features of patients with OSCC and to compare the prognostic ability of tSUVmax with that of other recurrence factors. Data of 340 patients with OSCC who were diagnosed, treated, and followed up at the Changhua Christian Hospital were retrospectively analyzed. Only patients with OSCC arising from gingiva, palate, floor of the mouth, and retromolar trigone and those who had received preoperative FDG-PET within 2 weeks before surgery were included. tSUVmax value > 9.2 was the strong predictor of bone invasion (area under the receiver operating characteristic curve, 0.844). tSUVmax value > 7.2 showed a strong association with advanced pathological T stage and recurrence factors and was associated with poor survival; tSUVmax > 7.2 showed stronger predictive power for poor disease-free survival (DFS) than pT stage and the other recurrence factors related to primary tumor. FDG-PET can be a useful supplement to contrast-enhanced computed tomography or contrast-enhanced magnetic resonance imaging for diagnosing bone invasion by OSCC. The tSUVmax value was an independent predictor of DFS in this study.

Comparison of different lymph node staging systems in patients with positive lymph nodes in oral squamous cell carcinoma.

OBJECTIVES: The evaluation of neck lymph node metastasis is critical for predicting survival after head and neck cancer treatment. However, traditional pathological N staging does not completely correlate with survival; the total number of lymph nodes resected during surgery affects staging, and a minimal number of nodes must be resected to achieve a superior outcome. Thus, the prognostic abilities of various lymph node staging systems for oral cavity squamous cell carcinoma (OSCC)-positive lymph nodes were compared. MATERIALS AND METHODS: Data for 639 patients with OSCC-positive nodes who were treated and monitored at the Changhua Christian Hospital were retrospectively analyzed. The different N staging systems were compared to evaluate their disease-free survival (DFS) predictability. RESULTS: The areas under the receiver operating characteristic curve were as follows: 0.551 for the traditional American Joint Committee on Cancer (AJCC) N staging, 0.60 for lymph node density (LND), 0.596 for log odds of positive lymph nodes (LODDS), and 0.597 for the number of metastatic lymph nodes (nmLN). The LND, LODDS, and nmLN systems could predict DFS better than AJCC N staging. Multivariable analysis for DFS revealed that extranodal spread, level IV or V positive nodes, and tumor invasion deeper than 13 mm were independent prognostic factors in these four models. LND and LODDS predicted DFS better than pathological N staging. CONCLUSION: LND and LODDS staging predicted DFS better than AJCC N staging for OSCC-positive nodes. In the future, the prognostic ability of AJCC staging may be strengthened by LND or LODDS staging.

Survival and clinicopathological characteristics of different histological grades of oral cavity squamous cell carcinoma: A single-center retrospective study.

The TNM staging system for oral squamous cell carcinoma (OSCC) provides clinicians a dependable foundation for patient prognosis and management decisions, but in clinical practice, treatment outcomes of patients with OSCC are sometimes unsatisfactory. This retrospective study investigated the association between survival and clinicopathological characteristics and histological grades of 2535 patients with OSCC. Additionally, the present study aimed to compare the predictive abilities of histological grades with other common prognostic factors. The enrolled patients were divided into three groups by two experienced pathologists into well-differentiated, moderately differentiated, and poorly differentiated groups, according to the WHO classification. Finally, we designed an observational, retrospective study based on the histological grading of tumors to compare their clinicopathological characteristics and conducted survival analysis among the three groups. Advanced tumor stage was diagnosed in 23.9%, 44.0%, and 55.1% of patients with grades 1-3 OSCC, respectively. By T status, T3 or T4 tumors were found in approximately 22%, 34%, and 40% of patients with grades 1-3 OSCC, respectively. By N status, lymph node metastases were found in 6.1%, 29.3%, and 45.9% of patients with grades 1-3 OSCC, respectively. Thus, significant survival differences were observed based on different OSCC histological grades. Meanwhile, in the multivariate (adjusted) analysis, N1 and N2 stages, extranodal spread, and poor differentiation were associated with a higher recurrence risk than the other common prognostic factors. In conclusion, 5% of patients in our study presented with poorly differentiated OSCC at diagnosis. Furthermore, grade 3 OSCC has worse prognosis and is more aggressive than grades 1 and 2 OSCC. In the future, we should focus on modifying individual therapy for poorly differentiated OSCC to achieve improved outcomes.

Difference between Female and Male Patients with Oral Squamous Cell Carcinoma: A Single-Center Retrospective Study in Taiwan.

There is a distinct male predominance in head and neck cancers. The present study aimed to investigate the clinical and pathological features of male and female patients with oral squamous cell carcinoma (OSCC), and to simultaneously conduct a survival analysis. Patients (n = 2573) were identified between January 2008 and December 2018, and subsequently analyzed for characteristics such as age at squamous cell carcinoma diagnosis, lifestyle factors (smoking habit, betel nut chewing and alcohol consumption), pathological American Joint Committee on Cancer (AJCC) anatomic site, AJCC TNM stage, pathological recurrence factor and interval from first diagnosis to recurrence. A case-matched comparison between female (n = 122) and male (n = 2451) patients was conducted. Significant gender differences were noted in age at diagnosis, anatomic site of the tumor, smoking habit, betel nut chewing and alcohol consumption (p < 0.001). There were no significant gender differences in the other clinical and pathological characteristics and survival conditions. In conclusion, female patients with OSCC were older than male patients with OSCC, and mostly had tumors of the oral tongue. Once patients develop OSCC, there was no difference in survival between men and women in a Taiwanese population.

Barrel-shaped design of the forearm free flap for lower lip reconstruction: a pilot case-control study.

BACKGROUND: Radial free forearm flaps is indicated patients with total or near-total defects in their lower lip. The purpose of our study was to evaluate a simple and effective barrel-shaped design of the radial free forearm flap for lower lip reconstruction and to compare its clinical outcomes with those of a conventional rectangular shaped free forearm flap. METHODS: Twenty-two patients with a lower lip carcinoma who underwent radial forearm free flap reconstructive surgery were enrolled in this study between January 1, 2012, and December 31, 2017. A barrel-shaped design of radial forearm free flap for reconstruction was used in 8 patients (case group), and a rectangular design was used in 14 patients (control group). The patients' quality of life was evaluated preoperatively and postoperatively in all the patients using the European Organization for Research and Treatment of Cancer Quality of Life (EORTC-HN35) questionnaire. We analyzed the differences in the EORTC QLQ-HN35 scores pre- and postoperatively between the case and control group. RESULTS: The patients in the case group had better outcomes in swallowing, speech, social eating, social contact, and dry mouth than the control group at 1-year follow-up (P < 0.05). CONCLUSIONS: The use of a barrel-shaped design free forearm flap for lower lip reconstruction is an effective procedure and can achieve better results than the use of rectangular free forearm flap.

Head and neck cancer in living donor liver transplant recipients: Single center retrospective study.

The purpose of this study was to investigate the incidence and risk factors of head and neck cancer in living donor liver transplant (LDLT) recipients.This is a retrospective cohort study. A case-matched (1:4) comparison between recipients with and without developed head and neck cancer after LDLT was conducted. The differences between 2 groups were analyzed.The incidence of head and neck malignancy in our cohort was 9 of 453 (1.98%). Their cumulative survival rate was below 60% at 24 months after the diagnosis of head and neck cancer, and no recipients lived for more than 2 years after being diagnosed with stage IV cancer. In the case-control study, univariate analysis revealed that alcohol consumption (odds ratio [OR] = 8.75, 95% confidence interval [CI]: 1.55-49.56) and smoking (OR = 6.71, 95% CI: 1.20- 37.44) were factors associated with the incidence of head and neck cancer after LDLT.In the conclusion, recipients with head and neck cancer after LDLT may have a rather poor prognosis, especially those who are initially diagnosed with advanced-stage disease. Alcohol consumption and smoking may be the predisposing factors to head and neck cancer in LDLT recipients.