The competitive mechanism of EZH1 and EZH2 in promoting oral squamous cell carcinoma.

Enhancer of Zeste Homolog 1 (EZH1) and Enhancer of Zeste Homolog 2 (EZH2) are the key components of polycomb repressive complex 2 (PRC2); however, the roles of these proteins in oral squamous cell carcinoma (OSCC) have yet to be elucidated. In this study, we aimed to determine the respective roles of these proteins in OSCC by investigating the expression levels of EZH1 and EZH2 in OSCC tissues (N = 63) by immunohistochemistry. In addition, we used lentiviruses to construct stable OSCC cell lines that overexpressed EZH1 and EZH2. Then, we investigated these cell lines for cell viability, colony formation capacity, stemness, and epithelial-mesenchymal transition (EMT). Binding competition between EZH1 and EZH2 with PRC2 was further evaluated using Co-immunoprecipitation (Co-IP). Compared with normal tissues, the expression levels of EZH2 in OSCC tissues was up-regulated, while the expression of EZH1 was down-regulated. EZH2 enhanced cell viability, colony formation capacity, stemness, and EMT, while EZH1 did not. Furthermore, analysis indicated that EZH1 and EZH2 bound competitively to PRC2 and influenced the methylation status of H3K27. In conclusion, our findings verified that EZH1 and EZH2 play opposing roles in OSCC and that EZH1 and EZH2 compete as the key component of PRC2, thus affecting the characteristics of OSCC via the methylation of H3K27.

The association of HBV infection and head and neck cancer: a systematic review and meta-analysis.

BACKGROUND: Hepatitis B virus (HBV) infections is an important public health problem worldwide and closely affect extrahepatic cancer. Several recent studies have investigated the relationship between HBV infection and head and neck cancer (HNC), but their findings were inconsistent.In order to address the limitations of small sample sizes, we conducted a meta-analysis to assess the association between HBV and HNC. METHODS: We systematically searched PubMed, Web of Science, Embase, Scopus, Cochrane Library, and China National Knowledge Infrastructure from inception to August 2023. Original articles published as a case-control or cohort study were included. HBV infection was identified by HBsAg, HBV DNA or ICD codes. Review articles, meeting abstracts, case reports, communications, editorials and letters were excluded, as were studies in a language other than English or Chinese. According to the MOOSE guidelines, frequencies reported for all dichotomous variables were extracted by two reviewers independently. Similarly, the outcomes of OR, RR or HR, and 95% CIs after adjusting for age and gender were collected. RESULTS: Thirteen relevant studies and 58,006 patients with HNC were included. Our analysis revealed a positive correlation between HBV and HNC (OR = 1.50; 95% CI: 1.28-1.77). After adjusting for age and gender, the similar result (OR = 1.30; 95% CI: 1.10-1.54) was obtained. Subgroup analysis further demonstrated a significant association between HBV infection and oral cancer (OR = 1.24; 95% CI: 1.05-1.47), as well as nasopharyngeal carcinoma (OR = 1.41; 95% CI: 1.26-1.58). However, due to the limited number of studies included, the statistical significance was not reached for cancer of the oropharynx (OR = 1.82; 95% CI: 0.66-5.05), hypopharynx (OR = 1.33; 95% CI: 0.88-2.00), and larynx (OR = 1.25; 95% CI: 0.69-2.24) after adjusting for age and gender. When excluding the interference of HIV/HCV, smoking and alcohol use, the final outcome (OR = 1.17; 95% CI: 1.01-1.35) got the same conclusion. CONCLUSIONS: Our study confirmed a positive relationship between HNC, specifically oral cancer and nasopharyngeal carcinoma, and HBV infection. However, further investigation is required at the molecular level to gather additional evidence in HNC.

Intratumoral platelet microthrombi in oral squamous cell carcinoma: A marker of lymph node metastasis.

OBJECTIVE: A hypercoagulable state exists in patients with oral squamous cell carcinoma (OSCC), but the role of platelets in the tumour microenvironment has not been explored. This study revealed the status of intratumoral plateletmicrothrombi (PLT-MT) and their clinicopathological relevance and predictive value in OSCC. STUDY DESIGN: This study retrospectively evaluated 106 OSCC patients. Tumour and tumour-adjacent tissue specimens were used to stain PLT-MT. Clinicopathological information, patient follow-ups and outcomes and preoperative coagulation and inflammatory hematologic indicators were collected, and their correlation with PLT-MT was analysed. RESULTS: Intratumoral PLT-MT was present in 35 of 106 patients with OSCC who had higher preoperative D-dimer, CRP, FIB and PT levels and lower TT levels. PLT-MT was an independent correlative factor of lymph node metastasis and suggested worse OS in N0 patients. CONCLUSIONS: Intratumoral PLT-MT was found in OSCC and was correlated with a hypercoagulable inflammatory state. PLT-MT was an independent marker of lymph node metastasis and showed potential in prognosis prediction.

Risk of second primary cancer in patients with head and neck squamous cell carcinoma: a systemic review and meta-analysis.

OBJECTIVES: Second primary cancer is a common event in patients with head and neck squamous cell carcinoma. However, the incidence and relevant factors vary by studies. We conducted a systematic review and meta-analysis of observational studies to estimate the incidence and relevant risk factors. MATERIALS AND METHODS: PubMed and Web of Science were searched for studies published between January 2000 and December 2020 that reported the incidence of SPC in HNSCC patients. Per 1000-person-year incidence and odds ratios were used to estimate the incidence and potential risk factors. Due to the high heterogeneity, random-effects models were used to estimate the incidence and 95% confidence interval. RESULTS: Seven thousand seven hundred thirteen articles were identified from the databases, in which 60 studies were included in this meta-analysis. The pooled incidence of the total, synchronous, and metachronous SPC in patients with HNSCC were 29.116 per 1000-person-year, 6.960 per 1000-person-year, and 26.025 per 1000-person-year, respectively. The head and neck region was the most common area where SPC occurred, followed by the lung (7.472 per 1000-person-year) and upper digestive tract (2.696 per 1000-person-year). Smoking, alcohol consumption, betel quid chewing, primary cancer of T1-2, and N0 were risk factors, while HPV infection (OR 0.47, 95% CI 0.30-0.72) was the protective factor. CONCLUSIONS: SPC is frequently observed in HNSCC patients and had great impact on the prognosis. The findings could promote a more individualized follow-up strategy for SPC in HNSCC patients. CLINICAL RELEVANCE: This systemic review and meta-analysis provide sufficient evidence for the establishment of the follow-up strategy for head and neck squamous cancer patients.

The contralateral-based submental artery island flap: feasibility and oncological safety in oral cancer-related defect reconstruction.

OBJECTIVES: Oncologic risk is a serious concern of submental artery island flaps. Here, we introduce the contralateral-based submental artery island flap (C-SAIF) and demonstrate its feasibility and long-term oncological safety in reconstructing oral cancer-related defects. METHODS: An anatomical study was performed concentrating on the pedicle length in seven cadavers. Then, a retrospective study was carried out on C-SAIF patients operated on by a single team. The standard surgical technique of C-SAIF was conducted. Outcomes including operative time, length of hospital stay, volume of intraoperative blood loss, and scores of the Multidisciplinary Salivary Gland Society (MSGS) questionnaire were compared with a similar cohort reconstructed with anterolateral thigh free flap (ALTF). In addition, oncological outcomes were evaluated by the 5-year cumulative survival rate between C-SAIF and ALTF patients. RESULTS: The pedicle length of C-SAIF was sufficient for the flap to be extended to the contralateral oral cavity. Fifty-two patients were included in the retrospective study, and nineteen of them underwent reconstruction with C-SAIF. The operative time of C-SAIF was shorter (p = 0.003), and the intraoperative blood loss was less (p = 0.004) than that of ALTF. There was no difference in MSGS scores. The results of survival analysis revealed comparable survival curves for the two groups in terms of overall survival, disease-specific survival, and disease-free survival. CONCLUSION: C-SAIF is a feasible and reliable flap for reconstructing oral cancer-related defects. Moreover, it is an effective island flap to preserve the perforator and pedicle without compromising oncological safety.

Speech disorders in patients with Tongue squamous cell carcinoma: A longitudinal observational study based on a questionnaire and acoustic analysis.

BACKGROUND: Speech disorders are common dysfunctions in patients with tongue squamous cell carcinoma (TSCC) that can diminish their quality of life. There are few studies with multidimensional and longitudinal assessments of speech function in TSCC patients. METHODS: This longitudinal observational study was conducted at the Hospital of Stomatology, Sun Yat-sen University, China, from January 2018 to March 2021. A cohort of 92 patients (53 males, age range: 24-77 years) diagnosed with TSCC participated in this study. Speech function was assessed from preoperatively to one year postoperatively using the Speech Handicap Index questionnaire and acoustic parameters. The risk factors for postoperative speech disorder were analyzed by a linear mixed-effects model. A t test or Mann‒Whitney U test was applied to analyze the differences in acoustic parameters under the influence of risk factors to determine the pathophysiological mechanisms of speech disorders in patients with TSCC. RESULTS: The incidence of preoperative speech disorders was 58.7%, which increased up to 91.4% after surgery. Higher T stage (P＜0.001) and larger range of tongue resection (P = 0.002) were risk factors for postoperative speech disorders. Among the acoustic parameters, F2/i/decreased remarkably with higher T stage (P = 0.021) and larger range of tongue resection (P = 0.009), indicating restricted tongue movement in the anterior-posterior direction. The acoustic parameters analysis during the follow-up period showed that F1 and F2 were not significantly different of the patients with subtotal or total glossectomy over time. CONCLUSIONS: Speech disorders in TSCC patients is common and persistent. Less residual tongue volume led to worse speech-related QoL, indicating that surgically restoring the length of the tongue and strengthening tongue extension postoperatively may be important.

Development and validation of multiparametric MRI-based nomogram for predicting occult metastasis risk in early tongue squamous cell carcinoma.

BACKGROUND: Nomograms are currently used in predicting individualized outcomes in clinical oncology of several cancers. However, nomograms for evaluating occult nodal metastasis of patients with squamous cell carcinoma of lateral tongue (SCCLT) have not been widely investigated for their functionality. This retrospective cohort study was designed to address this question. METHODS: This study was divided into primary and validation cohorts. The primary cohort comprised 120 patients diagnosed between 2012 and 2017, whereas the validation cohort included 41 patients diagnosed thereafter. The diagnostic value of multiparametric MRI, including radiologic tumor thickness threshold (rTTT) in three-dimensions, paralingual distance, and sublingual distance were investigated. A nomogram was developed based on stepwise logistic regression of potential predictors associated with nodal metastasis in the primary cohort and then tested for predictive accuracy in the validation cohort using area under the curve (AUC) and goodness-of-fit tests. RESULTS: Multivariate analysis, tumor size (odd ratio [OR] 15.175, 95% confidence interval [CI] 1.436-160.329, P = 0.024), rTTT (OR 11.528, 95% CI 2.483-53.530, P = 0.002), paralingual distance (OR 11.976, 95% CI 1.981-72.413, P = 0.005), and tumor location (OR 6.311, 95% CI 1.514-26.304, P = 0.011) were included in the nomogram to predict the likelihood of having cervical metastasis. A nomogram cutoff value of 210 points (sensitivity 93.8%, specificity 87.5%) was significantly different to classify the patients metastasis risk group (P < 0.001). Nomogram showed predictive accuracy with AUC 0.881 (95% CI 0.779-0.983, P < 0.001) and good calibration after the validation. CONCLUSIONS: A preoperative nomogram incorporating multiparametric MRI demonstrated good prediction and performed adequately in our study. Three-dimensional assessment of occult metastasis risk value obtained from this nomogram can assist in preoperative decision making for individual patients with early-stage SCCLT. The probability of nodal metastasis tended to be greater than 20% in patients with high metastasis risk or nomogram total score > 210 points.

Prognostic role of preoperative D-dimer, fibrinogen and platelet levels in patients with oral squamous cell carcinoma.

BACKGROUND: The relationship between cancer and coagulation has been intensively studied in recent years; however, the effects of coagulation factors on oral squamous cell carcinoma (OSCC) have rarely been reported. This study aimed to investigate the relationship between preoperative D-dimer (DD), fibrinogen (FIB), platelets (PLT) and OSCC, as well as the prognostic value of DD, FIB and PLT in OSCC. METHODS: We retrospectively investigated a total of 202 patients with OSCC treated at Guanghua Hospital of Stomatology, Sun Yat-sen University. Baseline demographic and clinicopathological information as well as both preoperative and postoperative DD, FIB and PLT results were collected from each patient, and patients with primary OSCC were followed up for disease progression, death or the end of the study. The correlations between preoperative DD, FIB, PLT and other clinical features, as well as the therapeutic effect and PFS were analysed statistically, and postoperative DD and surgical parameters were also analysed. RESULTS: Preoperative DD was significantly correlated with T stage, N stage, clinical stage and relapse of OSCC (P = 0.000, 0.001, 0.000 and 0.000, respectively). Univariate Cox regression analyses showed that high preoperative DD predicted poor prognosis in patients with OSCC (HR = 2.1, P = 0.033), while FIB and PLT showed no prognostic values. Postoperative DD was significantly correlated with preoperative DD and surgical type but not the duration of surgery (P = 0.005, 0.001 and 0.244, respectively). CONCLUSION: In this study, we suggested that high preoperative DD level may serve as an indicator for synchronous neck dissection in patients with T1, 2 OSCC, and the elevated DD level might be the marker of disease progression in patient follow up.

Dysfunctional role of elevated TIGIT expression on T cells in oral squamous cell carcinoma patients.

OBJECTIVE: This study was aimed to analyze the role of T-cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif domains (TIGIT) expression on T cells in patients with oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMC) and tumor-infiltrating lymphocytes (TILs) were collected from OSCC patients. The correlation between TIGIT expression and clinicopathologic features was analyzed by chi-square test. Phenotypic and functional study of TIGIT+ T cells were performed by flow cytometry. RESULTS: TIGIT was highly expressed on T cells from PBMC and TILs. High expression of TIGIT on CD4+ T cells (19.0%) and CD8+ T cells (35.9%) was also associated with higher T stage and nodal invasion. Moreover, TIGIT+ CD4+ and TIGIT+ CD8+ T cells sorted from OSCC patients showed a dysfunctional phenotype (low cell proliferation and low secretion of IL-2, TNF-α and IFN-γ), and TIGIT+ CD4+ T cells exhibited inhibitory function (high expression of Foxp3 and high amounts of IL-10). Importantly, TIGIT blockade can enhance the proliferation ability and effective cytokine production (IL-2, TNF-α, and IFN-γ) of CD4+ and CD8+ T cells from OSCC patients in vitro. CONCLUSIONS: TIGIT-expressing T cells exhibit a lower effector cytokine-releasing phenotype in OSCC patients.

Prevalence of Dysphagia in China: An Epidemiological Survey of 5943 Participants.

OBJECTIVE: To determine the prevalence of dysphagia among an older population and patients with stroke, head and neck cancers (HNCs) or neurodegenerative diseases (NDDs) in China, to identify the factors associated with this condition, and to explore the relationship between dysphagia and nutritional status. METHODS: This study included participants 65 years and older living in the community or in nursing homes and patients who had sustained a stroke, HNC, or NDD also recruited in hospitals from 14 provinces of China. The presence of dysphagia was determined by use of a questionnaire, water swallowing test, and/or a videofluoroscopic swallowing study. Logistic regression analysis was used to assess the possible associated risk factors. Body mass index was assessed as an indicator of malnutrition. RESULTS: A total of 5943 persons met the inclusion criteria and 2341 (39.4%) were identified with dysphagia, including the following: 51.14% of patients with stroke, 34.4% in HNCs, 48.3% in NDDs, and 19.2% of otherwise healthy older adults. The elderly with comorbidity (OR = 2.90, p < 0.01) and stroke patients (OR = 2.27, p < 0.01) were significantly more likely to exhibit signs of dysphagia. Dysphagic participants were at significantly greater risk of malnutrition (OR = 1.91, p < 0.01) compared to those without dysphagia. CONCLUSION: Dysphagia is prevalent in China among older individuals and people who have suffered a stroke, HNCs, or NDDs. The prevalence of dysphagia increases steadily with increasing age and presence of comorbid disease. People with dysphagia are more likely to suffer from malnutrition.

CA9 transcriptional expression determines prognosis and tumour grade in tongue squamous cell carcinoma patients.

CA9 is a member of the carbonic anhydrases' family, that is often expressed in cancer cells under hypoxic condition. However, the role of CA9 in the molecular mechanisms of tongue squamous cell carcinoma (TSCC) pathogenesis remains unclear. CA9 expression was analysed using the TCGA database, and its influence on survival was performed using Kaplan-Meier, LASSO and COX regression analyses. The correlation between CA9 and immune infiltration was investigated by CIBERSORT and ESTIMATE. Moreover, the relationship between CA9 expression and downstream molecular regulation pathways was analysed by GSEA, GO and WGCNA. CA9 expression correlated with clinical prognosis and tumour grade in TSCC. Moreover, CA9 expression potentially contributes to the regulation of cancer cell differentiation and mediates tumour-associated genes and signalling pathways, including apoptosis, hypoxia, G2M checkpoint, PI3K/AKR/mTOR signalling and TGF-beta signalling pathways. However, the follicular helper T cells, regulatory T cells, immune and stromal scores showed no significance between high and low CA9 expression groups. These findings suggested that CA9 plays a critical role of TSCC prognosis and tumour grade. CA9 expression significantly correlated with the regulation of cell differentiation, various oncogenes and cancer-associated pathways.

MMP-12 regulates proliferation of mouse macrophages via the ERK/P38 MAPK pathways during inflammation.

MMP-12 is a metalloproteinase (MMP) mainly secreted by macrophages and regulating the degradation of the extracellular matrix. MMP-12 is related to several diseases such as emphysema, myocardial infarction and liver fibrosis. However, the functions associated with inflammation of MMP-12 in macrophages have not yet been fully investigated. Therefore, the aim of this study is to elucidate the role of MMP-12 in mouse macrophages during inflammation. Here we show by flow cytometry that MMP-12 was closely associated with the number of F4/80 + macrophages from mouse liver following exposure to LPS. Pro-inflammatory cytokines as well as the proliferation of RAW 264.7 cell line was modulated by MMP-12 knock down as illustrated by qRT-PCR, flow cytometry, CCK-8, Western Blot and EdU staining assays. Furthermore, down-regulation of MMP-12 decreased the expression and the phosphorylation levels of P38 and ERK1/2. Taken together, these data show that MMP-12 contributes to the proliferation of mouse macrophages as well as the secretion of IL-1ß, IL-6, TNF-α, CXCL1 and CXCL3 through the ERK/P38 MAPK signaling pathway.

Prediction of postoperative lower respiratory tract infections in tongue cancer patients based on pretreatment swallowing function.

OBJECTIVES: This study investigated the predictive role of pretreatment swallowing function and surgical factors on postoperative and nosocomial lower respiratory tract infections (PN-LRTIs). SUBJECTS AND METHODS: A retrospective study for predicting PN-LRTIs from January 2017 to December 2018 at Hospital of Stomatology, Sun Yat-sen University. Patients who were newly diagnosed with tongue squamous cell carcinoma (TSCC) were enrolled. Presurgical swallowing function was assessed using water swallow test (WST) and the M.D. Anderson Dysphagia Inventory (MDADI). RESULTS: A total of 83 patients were recruited to the study. Of which 54 were men (65.1%) and 29 were women (34.9%), with the mean age of 51 years old. Thirteen (15.7%) developed PN-LRTIs. On univariate analysis, the outcomes of WST, the MDADI scores, T stage, tongue resection range, operative time, segmental mandibulectomy, and type of neck dissection exhibited a statistical significance (p < .05). On multivariate analysis, abnormal group of WST (odds ratio [OR], 15.88; 95% CI, 2.13-118.64) and total glossectomy (OR, 12.20; 95% CI, 2.01-68.32) was demonstrated to be independent risk factors. CONCLUSIONS: The WST together with the resection range of tongue can predict the postoperative risk of PN-LRTIs collaboratively. Clinically, preventive measures and intensified care should be taken for patients with abnormal WST outcome before surgery and management of total glossectomy.

Temporomandibular joint disorders contribute to anxiety in BalB/C mice.

Despite a high comorbidity between these two disorders, the physiological association between temporomandibular joint disorders (TMDs) and anxiety remains unknown. This study aimed to investigate whether TMDs contribute to anxiety through the induction of oligodendrogenesis in the hippocampus using a mouse model of TMD. Forty 8-week-old male BalB/C mice were used in the experiments. The mice were randomly divided into 4 groups: (1) control group (N group); (2) elevated occlusion group (E group); (3) restriction group (R group); and (4) elevated occlusion and restriction group (ER group). The mice were subjected to behavior tests of open field tests and elevated plus maze analysis. The serum corticosterone levels and expression of mature oligodendrocyte marker MBP and the oligodendrocyte marker RIP were analyzed. All data were statistically analyzed using by one-way analysis of variance. The TMD group showed condylar degeneration compared with the control group. Additionally, exposure to chronic restraint stress for 3 weeks after TMD significantly exacerbated anxiety-like behavior and resulted in a significant increase in serum corticosterone levels and in the expression of MBP and RIP in the dentate gyrus (DG) and CA3 in the hippocampus. Taken together, these data suggest that TMD lead to increased oligodendrogenesis in the hippocampus, which contributes to the development of anxiety-like behavior. TMD could contribute to anxiety by inducing oligodendrogenesis in the hippocampus.

Role of Noxa in proliferation, apoptosis, and autophagy in human adenoid cystic carcinoma.

BACKGROUND: Noxa, which is subset of the Bcl-2 family of proteins, was previously reported to have considerable therapeutic potential in diverse cancers. However, its expression and role in salivary gland adenoid cystic carcinoma (ACC) have not been well studied. This study aimed to elucidate the expression and role of Noxa in salivary gland ACC. MATERIALS AND METHODS: The expression levels of NOXA and its association with overall survival in salivary gland ACC were analyzed by quantitative real-time PCR. We next examined the effects of Noxa overexpression or inhibition on colony formation, proliferation, apoptosis, and autophagy of salivary gland ACC cells. Furthermore, promoter analysis was performed to identify the potential transcriptional activator of NOXA. RESULTS: NOXA was markedly down-regulated and significantly correlated with a more aggressive phenotype and poor overall survival of salivary gland ACC. Ectopic expression of Noxa suppressed the viability and growth of ACC cells, which involved the induction of apoptosis and autophagy. Moreover, the transcriptional activity of NOXA gene could be enhanced by p53. CONCLUSION: The findings of this study indicate that Noxa, activated transcriptionally by p53, suppress the progression of ACC, whereby it regulates proliferation, apoptosis, and autophagy.

Interaction of cancer cell-derived Foxp3 and tumor microenvironment in human tongue squamous cell carcinoma.

The forkhead transcription factor, Foxp3, has been proved essential for differentiation and activation of regulatory T cells (Tregs). Recently, Foxp3 expression in tumor cells (cancer cell-derived Foxp3) has gained increasing interest, but the function has yet to be confirmed. In the current investigation, we identified the interaction of cancer cell-derived Foxp3 and tumor microenvironment in human tongue squamous cell carcinoma(TSCC) by various in vitro methods. We detected cancer cell-derived Foxp3 was closely associated with the infiltration of Foxp3 + lymphocytes in TSCC lesions using immunohistochemical staining. The cytokines secretion (IFN-γ, TGFß, IL-2, IL-6, IL-1ß, IL-10, IL-8, IL-17, IL-23) of PBMC and differentiation of CD4 +T cells were modulated by the expression of Foxp3 in TSCC, shown by ELISA and flow cytometry. As feedback, increasing TGFß and decreasing IL-17 further up-regulated cancer cell-derived Foxp3. Furthermore, CHIP on chip assay showed that both TGFß and IL-17 decreased the number of Foxp3-binding genes in TSCC. GO and pathway analysis suggested that, treated with TGFß or Th17, Foxp3-binding genes were inclined to the negative regulation of TGFß signal pathway. Taken together, this study showed cancer cell-derived Foxp3 contributed to Tregs expansion in TSCC microenvironment with positive and negative feedbacks.

Long-Term Quality of Life in Patients With Maxillofacial Malignancies Who Have Undergone Craniofacial Resection: A Cross-Sectional Survivorship Study.

PURPOSE: The purposes were to investigate the postoperative, long-term quality of life (QoL) of patients with maxillofacial malignancies who underwent craniofacial resections that involved the skull base and to screen for potential predictors of QoL. PATIENTS AND METHODS: We reviewed all patients who had undergone craniofacial resections as identified by the electronic medical record system from 2013 onward; we then applied our eligibility criteria to generate the study cohort. Each patient was asked to complete the Skull Base Inventory, a questionnaire that is scored from 0 to 100, during his or her regular postoperative follow-up. All demographic information and clinicopathologic variables were then collected and analyzed. RESULTS: A total of 25 patients who received treatment between March 2013 and March 2018 were consecutively enrolled and surveyed at 6 to 42 months (median, 15 months). The age at diagnosis ranged from 23 to 81 years (median, 42 years), with a female-to-male ratio of 1.1:1.0. The mean score for QoL was 67.56 ± 16.35. Univariate analysis found that being in the subgroup aged 20 to 40 years (ß = -12.87 [95% confidence interval (CI), -25.54 to -0.21], P = .047), having the mesenchymal pathologic subtype (ß = -18.80 [95% CI, -34.05 to -3.54], P = .018), and having involvement of the middle skull base (ß = -15.00 [95% CI, -28.33 to -1.68], P = .029) could all significantly impact long-term QoL. A multiple linear regression model (R2 = 36.4%, P = .007) included the latter 2 factors (ß = -16.82 [95% CI, -31.06 to -2.59], P = .023, and ß = -13.14 [95% CI, -25.35 to -0.94], P = .036, respectively). CONCLUSIONS: The location of the involved skull base may be used as a guide for the surgical approach or incision design to improve patients' long-term QoL. However, this should not take precedence over the nature of malignancies as the pathologic subtype implied that patients with mesenchymal malignancies may pay the price of better QoL to survive.

Elevated hydrostatic pressure promotes ameloblastoma cell invasion through upregulation of MMP-2 and MMP-9 expression via Wnt/ß-catenin signalling.

BACKGROUND: The process of marsupialization involves the release of intracystic pressure and the fluid contained within. Marsupialization of cystic ameloblastoma is controversial; therefore, we investigated how hydrostatic pressure influences biological behaviours of ameloblastoma cells and its underlying mechanisms. MATERIALS AND METHODS: An ameloblastoma epithelial cell line, hTERT+ -AM, was exposed to different hydrostatic pressures with or without Dickkopf-related protein 1 (also known as DKK), a canonical Wnt signalling pathway inhibitor. A CCK-8 assay, a monolayer wound assay, and a Transwell assay were used to determine cell proliferation, migration and invasion, respectively. qRT-PCR and Western blot were used to detect expression of MMP-2, MMP-9, RANKL and other downstream targets of Wnt signalling. RESULTS: Elevated hydrostatic pressure promoted migration and invasion of ameloblastoma cells, but inhibited proliferation. Expression of MMP-2, MMP-9, LEF-1, cyclin D1, c-Jun and c-Myc was significantly upregulated under elevated hydrostatic pressure, and these effects could be abolished by DKK1. Expression of RANKL, which is thought to be a downstream target of Wnt signalling, did not significantly change under elevated hydrostatic pressure. CONCLUSIONS: This study indicates that elevated hydrostatic pressure promotes the migration and invasion of ameloblastoma cells by activating the Wnt/ß-catenin pathway, thereby increasing expression of MMP-2, MMP-9 and other Wnt signalling downstream targets. This suggests that marsupialization may reduce invasiveness and reverse the bone resorption process by lowering intracystic hydrostatic pressure in cystic ameloblastoma.

Synergistic effects of ischemic preconditioning and immediate post-conditioning in the protection against ischemia/reperfusion injury in rabbit submandibular glands.

Submandibular gland autotransplantation is an effective approach for treating severe keratoconjunctivitis sicca. However, ischemia/reperfusion (I/R) injury, which inevitably occurs during transplantation, is involved in the hypofunction and structural damage that occur early after transplantation. Therefore, it is critical to identify effective strategies to ameliorate I/R injury in submandibular glands. In this study, we investigated the ability of immediate post-conditioning combined with ischemic preconditioning to attenuate I/R injury. We observed that after I/R injury, the level of reactive oxygen species was increased, inflammatory response was strengthened, and severe apoptosis had occurred. In addition, the salivary flow rate was greatly decreased. However, the pathogenesis of I/R injury was significantly ameliorated by ischemia post-conditioning or ischemia preconditioning treatments. In addition, the combination of ischemia preconditioning and post-conditioning achieved synergistic protective effects against I/R injury compared with ischemia preconditioning or ischemia post-conditioning alone. The secretion function was restored in the combination group. Furthermore, the combination treatment involved the same mechanisms of ischemia preconditioning or ischemia post-conditioning, including suppression of the inflammatory reaction and neutrophil accumulation, attenuation of oxidation stress, and inhibition of apoptosis. In conclusion, the combination of ischemia preconditioning and ischemia post-conditioning treatment is a simple and effective approach for treating I/R injury in submandibular glands.

Microvascular Submandibular Gland Transplantation for Severe Keratoconjunctivitis Sicca: A Single-Institution Experience of 61 Grafts.

PURPOSE: Keratoconjunctivitis sicca (KCS) is a relatively common disease that results in discomfort, tear film instability, visual impairment, and ocular surface damage. Artificial tear substitutes may be suitable for the treatment of mild KCS, but no effective treatment currently exists for severe KCS. Therefore, this study evaluated the effectiveness of autologous microvascular submandibular gland transplantation in the treatment of severe KCS. PATIENTS AND METHODS: A total of 61 eyes (56 patients) with severe KCS were treated with autologous submandibular gland transplantation from June 2002 to June 2017. The cephalic vein or the great saphenous vein was applied to solve the problem of unmatched veins. RESULTS: In 53 cases (53 of 56, 94.6%), 58 glands (58 of 61, 95.1%) were transplanted successfully. The mean Schirmer I test value improved from 0.78 ± 0.84 mm preoperatively to 18.83 ± 5.72 mm in the stable period after transplantation. Epiphora (14 of 58, 24.14%) was the most common complication of this procedure. Other postoperative complications included venous thrombosis (6 of 61, 9.84%), local infection (2 of 58, 3.45%), xerostomia (2 of 53, 3.77%), duct fistula (1 of 58, 1.72%), sialolithiasis (1 of 58, 1.72%), and ranula (1 of 58, 1.72%). CONCLUSIONS: Autologous microvascular submandibular gland transplantation is a credible and effective solution for severe KCS.