Effect of early interventions with manual lymphatic drainage and rehabilitation exercise on morbidity and lymphedema in patients with oral cavity cancer.

BACKGROUND: There are clinical and statistical inconsistencies regarding early intervention with manual lymphatic drainage (MLD). The purpose of this study was to compare the short-term effect of early interventions with rehabilitation exercise versus MLD and rehabilitation exercise in terms of pain, range of motion (ROM) and lymphedema in patients with oral cancer after surgery. METHODS: A total of 39 patients who underwent surgery from December 2014 to December 2018 participated in this randomized single-blind study. There were 20 patients in the rehabilitation (R) group and 19 in the MLD (M) plus rehabilitation group. The R group received 30 minutes of rehabilitation intervention; and the M group received 30 minutes of MLD, in addition to 30 minutes of rehabilitation intervention in a work day. Clinical measures, including the visual analog pain scale (VAS), ROM of the neck and shoulder, ultrasonography and face distance for lymphedema, and the Földi and Miller lymphedema scales, were assessed before surgery, before intervention and when discharged from the hospital. RESULTS: The VAS pain score, ROM of the neck, and internal and external rotation of the right shoulder were significantly improved after the interventions. Right-face distance (P = .005), and skin-to-bone distance (SBD) of the bilateral horizontal mandible and left ascending mandibular ramus were significantly improved after the interventions. Left lateral flexion of the neck (P = .038) and SBD of the right ascending mandibular ramus (P < .001) in the MLD group showed more improvement than that of the rehabilitation group. CONCLUSION: Early intervention with MLD and the rehabilitation program were effective in improving ROM of the neck and controlling lymphedema in acute-phase rehabilitation. The preliminary findings suggest a potential therapeutic role for early intervention with MLD, in addition to rehabilitation exercise, in that they yielded more benefits in lymphedema control and improvement of ROM of the neck in acute care.

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.

Clinical Outcomes of Taiwanese Patients with Resected Oral Cavity Squamous Cell Carcinoma Who Underwent Reconstruction with Free Versus Local Flaps.

BACKGROUND: We sought to compare the clinical outcomes of Taiwanese patients with resected oral cavity squamous cell carcinoma (OCSCC) who underwent reconstruction with free versus local flaps. METHODS: From 2011 to 2017, we examined 8646 patients with first primary OCSCC who received surgery either with or without adjuvant therapy. Of these patients, 7297 and 1349 received free and local flap reconstruction, respectively. Two propensity score-matched groups of patients who underwent free versus local flap (n = 1268 each) reconstructions were examined. Margin status was not included as a propensity score-matched variable. RESULTS: Compared with local flaps, patients who received free flaps had a higher prevalence of the following variables: male sex, age < 65 years, pT3-4, pN1-3, p-Stage III-IV, depth ≥ 10 mm, margin > 4 mm, extranodal extension (ENE), and adjuvant therapy (all p < 0.0001). Multivariable analysis identified the reconstruction method (local vs. free flaps, only overall survival [OS]), age ≥ 65 years, pT3-4, pN1-3, p-Stage III-IV, depth ≥ 10 mm (only OS), margins ≤ 4 mm, and ENE as independent adverse prognosticators for disease-specific survival (DSS) and OS. The results of propensity score-matched analyses revealed that, compared with free flaps, patients who underwent local flap reconstruction showed less favorable 5-year DSS (hazard ratio [HR] 1.26, 82%/77%; p = 0.0100) and OS (HR 1.21, 73%/68%; p = 0.0079). CONCLUSIONS: After adjusting for covariates using multivariate models, and also by propensity score modeling, OCSCC patients who underwent free flap reconstruction showed a higher frequency of clear margins and a significant survival advantage compared with those who received local flaps.

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.

Adequate surgical margins for oral cancer: A Taiwan cancer registry national database analysis.

BACKGROUND: Margin status and lymph node metastasis are the most important prognostic factors for oral cancers. However, while adequate surgical resection is crucial for local control and prognosis, the definition of clear margins has long been a subject of debate. In this study, we analyzed data from a nationwide population-based cancer registry database and evaluated the impact of surgical margins on cancer-specific survival (CSS) and overall survival (OS) as well as the optimal cutoff of adequate surgical margins. METHODS: This analysis included all cases of oral cancer diagnosed from 2011 to 2017 that were reported to the Taiwan Cancer Registry database. The staging system was converted from American Joint Committee on Cancer (AJCC) version 7 to AJCC version 8. Kaplan-Meier analysis and Cox proportional-hazards regression were performed to identify covariates that were significantly associated with CSS and OS. RESULTS: Between 2011 and 2017, 15,654 of a total of 36,091 cases diagnosed with oral cancers were included in the final analyses. Advanced N stage, positive margins, and advanced T stage are the leading risk factors for poor CSS and OS. When surgical margins were subdivided into 1-mm intervals from 5 mm to positive margin, we found that surgical margins <4 mm and <5 mm predict poor CSS and OS, respectively. CONCLUSIONS: This is the first nationwide, population-based cohort to revisit the question of the adequate surgical margins for oral cancers. We conclude that surgical margins ≥4 mm and ≥5 mm are adequate for good CSS and OS, respectively.

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.

Impact of illness perception, mental adjustment, and sociodemographic characteristics on return to work in patients with head and neck cancer.

PURPOSE: To examine the effects of emotional distress, illness perception, and mental adjustment on return to work (RTW) among patients with head and neck cancer (HNC) and identify factors associated with RTW. METHODS: A cross-sectional study with convenience sampling was conducted in Taiwan. Structured questionnaires were used to collect data on RTW status and to explore possible factors related to RTW. RTW status was assessed by a single question. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale, illness perception was assessed by the Brief Illness Perception Questionnaire, and mental adjustment was assessed using the Mini-mental Adjustment to Cancer Scale. Sociodemographic and disease background data were also collected and analyzed. Factors related to RTW were identified by multivariate logistic regression. RESULTS: A total of 150 patients with HNC were recruited into the study. Of them, 58 (38.7%) returned to work after treatment. Compared to those who did not RTW, patients who did RTW had lower levels of emotional distress (anxiety and depression), better illness perception (cognitive illness representations and illness comprehensibility), and better mental adjustment (hopelessness and helplessness, anxious preoccupation, avoidance, and fatalism). Multivariable analysis indicated that anxiety (OR = 0.863, p < 0.05), avoidance (OR = 1.280, p < 0.001), cognitive illness representations (OR = 0.891, p < 0.01), illness comprehensibility (OR = 1.271, p < 0.05), higher education level (OR = 3.048-3.609, p < 0.05), married status (OR = 5.220, p < 0.05), tumor site in oral cavity (OR = 5.057, p < 0.05), and no reconstruction (OR = 3.415, p < 0.05) were significantly associated with RTW. CONCLUSION: The issue of RTW among patients with HNC is related to multidimensional factors, including sociodemographic, psychological, and disease-related situations. We suggest that programs for emotional rehabilitation and occupational counseling need to be developed to assist patients with HNC to RTW at an early stage.

Correction to: Gamma synuclein is a novel nicotine responsive protein in oral cancer malignancy.

[This corrects the article DOI: 10.1186/s12935-020-01401-w.].

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.

Gamma synuclein is a novel nicotine responsive protein in oral cancer malignancy.

BACKGROUND: The mechanisms of neuronal protein γ-synuclein (SNCG) in the malignancy of oral squamous cell carcinoma (OSCC) are not clear. This study tested the hypothesis that SNCG is involved in nicotine-induced malignant behaviors of OSCC. The effect of nicotine on SNCG expression and epithelial-to-mesenchymal transition (EMT) markers were examined. METHODS: Short hairpin RNA (shRNA) and an antagonist specific for α7-nicotine acetylcholine receptors (α7-nAChRs) were used to examine the role of α7-nAChRs in mediating the effects of nicotine. Knockdown of SNCG in nicotine-treated cells was performed to investigate the role of SNCG in cancer malignancy. The in vivo effect of nicotine was examined using a nude mouse xenotransplantation model. RESULTS: Nicotine increased SNCG expression in a time- and dose-dependent manner. Nicotine treatment also increased E-cadherin and ZO-1 and decreased fibronectin and vimentin expression. After specific knockdown of α7-nAChRs and inhibition of the PI3/AKT signal, the effect of nicotine on SNCG expression was attenuated. Silencing of SNCG abolished nicotine-induced invasion and migration of OSCC cells. The xenotransplantation model revealed that nicotine augmented tumor growth and SNCG expression. CONCLUSION: Nicotine upregulated SNCG expression by activating the α7-nAChRs/PI3/AKT signaling that are participated in nicotine-induced oral cancer malignancy.

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.

α7-Nicotine acetylcholine receptor mediated nicotine induced cell survival and cisplatin resistance in oral cancer.

OBJECTIVE: To investigate the effect of nicotine on cell survival and cisplatin resistance in oral cancer and the possible involvement of α7-nicotinic acetylcholine receptors (α7-nAChRs). DESIGN: The effects of nicotine on cell survival and cisplatin-induced apoptosis were assessed. Knockdown of α7-nAChRs by short hairpin RNA and the specific antagonist methyllycaconitine (MLA) was used to examine the involvement of α7-nAChRs in modulating the effects of nicotine. Apoptosis signal molecules were examined in nicotine- and cisplatin-treated cells. RESULTS: Nicotine increased the survival of the oral cancer cells YD8 and OEC-M1 in a dose- and time-dependent manner. Nicotine treatment accelerated cell cycle progression in the oral cancer cells, and significantly reduced cisplatin-induced cell apoptosis. In the α7-nAChR-silenced cells, the prosurvival effect of nicotine in the cisplatin-treated cells was attenuated. Co-treatment of cisplatin and nicotine attenuated the effect of cisplatin on Bcl-2 expression. In addition, the effect of nicotine on cell survival under cisplatin treatment was attenuated with the addition of the Bcl-2 inhibitor ABT-737. CONCLUSIONS: Treating oral cancer cells with nicotine increased cell survival and cisplatin resistance, in which α7-nAChRs were involved.

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.

A rare case of oral tumor presenting as first sign of immunoglobulin G4-related disease.

Immunoglobulin G4 (IgG4)-related disease is an idiopathic autoimmune disease characterized by elevated serum and tissue IgG4 levels, organ enlargement, and a clinical response to immunosuppressants. We present such a case in a 39-year-old female, whose lesion was located in the right buccal space involving the minor salivary gland. After the tumorlike growth was removed, diagnosis was confirmed with histopathologic slides showing lymphoid cell infiltration, dense fibrotic stroma, and IgG4-positive plasma cells. The patient underwent steroid therapy, and there has been no recurrence since. Rarely do we see IgG4-related sclerosing disease involve the buccal minor salivary gland in its early stages. Thus, it is important to include IgG4-related disease in the differential diagnosis when considering autoimmune diseases with oral manifestations.

Sequential therapy of neoadjuvant biochemotherapy with cetuximab, paclitaxel, and cisplatin followed by cetuximab-based concurrent bioradiotherapy in high-risk locally advanced oral squamous cell carcinoma: Final analysis of a phase 2 clinical trial.

BACKGROUND: The prognosis of advanced oral squamous cell carcinoma is poor. We investigated the effect of cetuximab-based sequential therapy as a primary treatment. METHODS: Forty-seven treatment-naive patients with advanced tumors originating from the oral cavity or oropharynx were enrolled. Neoadjuvant cetuximab, paclitaxel, and cisplatin were administered, followed by cetuximab-based radiotherapy. Immunohistochemical staining was applied to study the tissues. RESULTS: The best overall response rate was 70.2%, including 4 patients with a complete response and 29 with a partial response. The median progression-free and overall survival rates were 10.3 and 15.2 months, respectively. Patients with more than 50% tumor reduction with neoadjuvant therapy had better survival outcomes. Twenty-two patients had severe adverse events with mostly dermatological complications. Of the 16 patients who received operations, 9 had increased PD-L1 staining compared to pretreatment biopsy in the post hoc study. CONCLUSION: The regimen was effective in selected patients. Increased PD-L1 suggested altered tumor features.

Adjuvant radiotherapy after curative surgery for oral cavity squamous cell carcinoma and treatment effect of timing and duration on outcome-A Taiwan Cancer Registry national database analysis.

Conduct an accurate risk assessment of resected oral cavity squamous cell carcinoma (OSCC) patients by accessing a nationwide systemic investigation is pivotal to improve treatment outcomes. In this article, we tried to determine the impact of different prognostic factors for OSCC patients who received adjuvant radiotherapy (RT) after curative surgery, using Taiwan's national cancer registry database (TCR). A nationwide, large population-based study was conducted using TCR with patients identified from 2007 to 2015. The study variables included age, gender, cancer subsites, stage, histology grade, margin and extra-nodal extension (ENE) status, treatment type, surgery to RT interval (ORI), total RT treatment time (RTT), and RT dose. Univariate and multivariate analysis were performed to identify predictors of the variables associated with overall survival (OS), cause-specific survival (CSS), local-regional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS). 8986 OSCC patients treated with surgery and adjuvant RT were analyzed. In multivariate analysis, worse outcomes were associated with males, older age, subsite in the oral tongue, advanced stage, higher histologic grade, involved margin, and positive ENE. ORI only showed an adverse trend in LRFS, when exceeding 7 weeks (P = .06). RTT >8 weeks was a significant poor predictor in OS, CSS and LRFS (P < .001). Extreme RT dose (>70 Gy or ≤50 Gy) also demonstrated an adverse impact on the outcomes. Prolonged RT treatment time and extreme RT doses were identified as significantly poor prognostic predictors in OSCC patients who received adjuvant RT after curative surgery.

Laser Sintered Magnesium-Calcium Silicate/Poly-ε-Caprolactone Scaffold for Bone Tissue Engineering.

In this study, we manufacture and analyze bioactive magnesium-calcium silicate/poly-ε-caprolactone (Mg-CS/PCL) 3D scaffolds for bone tissue engineering. Mg-CS powder was incorporated into PCL, and we fabricated the 3D scaffolds using laser sintering technology. These scaffolds had high porosity and interconnected-design macropores and structures. As compared to pure PCL scaffolds without an Mg-CS powder, the hydrophilic properties and degradation rate are also improved. For scaffolds with more than 20% Mg-CS content, the specimens become completely covered by a dense bone-like apatite layer after soaking in simulated body fluid for 1 day. In vitro analyses were directed using human mesenchymal stem cells (hMSCs) on all scaffolds that were shown to be biocompatible and supported cell adhesion and proliferation. Increased focal adhesion kinase and promoted cell adhesion behavior were observed after an increase in Mg-CS content. In addition, the results indicate that the Mg-CS quantity in the composite is higher than 10%, and the quantity of cells and osteogenesis-related protein of hMSCs is stimulated by the Si ions released from the Mg-CS/PCL scaffolds when compared to PCL scaffolds. Our results proved that 3D Mg-CS/PCL scaffolds with such a specific ionic release and good degradability possessed the ability to promote osteogenetic differentiation of hMSCs, indicating that they might be promising biomaterials with potential for next-generation bone tissue engineering scaffolds.

Environmental heavy metal as a potential risk factor for the progression of oral potentially malignant disorders in central Taiwan.

OBJECTIVE: Oral cancer (OC) is a leading cause of death from cancer in men between the ages of 25 and 44 years in Taiwan. The overall 5-year survival rates for the four OC stages (I-IV) in Taiwan are approximately 70%, 30%, 20%, and 10%, respectively, indicating the importance of the early diagnosis of oral potentially malignant disorders (OPMDs). Previous studies indicated an association between the OC incidence and certain environmental heavy metal concentrations. If these associations do exist for OC, they may also be observed for OPMD. The purpose of this study is to explore the association between the development of OPMD to OC and environmental heavy metals. Oral submucous fibrosis (OSF) and oral leukoplakia (OL) are two major types of OPMD in Taiwan. MATERIALS AND METHODS: A retrospective cohort study was conducted by Changhua Christian Hospital, the sole medical center in Changhua County, where 2725 male adult patients diagnosed with either OSF or OL between 2000 and 2014 were recruited. Data were analyzed by Cox regression and adjusted for smoking and betel-quid chewing. RESULTS AND DISCUSSION: OPMD patients who resided in areas with high nickel concentrations (polluted levels) exhibited hazard ratios of 1.8-2 for OC relative to those who lived in areas with low nickel levels (P<0.01). Meanwhile, smokers with OPMDs had a hazard ratio of 2.8-2.9 relative to non-smokers. Betel-quid chewers had a 2.2-2.3 hazard ratio relative to non-chewers. Smoking, betel-quid chewing, and environmental nickel exposure are associated with an increased risk of OC development in OPMD patients. This study provides valuable findings on the environmental effects of heavy metals on human health. Enhanced surveillance of the condition of OPMD patients who have been exposed to high nickel concentrations may be crucial for OC prevention.