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PDF file - 746K, Forest plot of overall survival, disease-free survival, locoregional recurrence-free survival, and distant metastasis-free survival in OSCC patients treated with surgery and post-operative radiotherapy with and without TPF induction chemotherapy.

PDF file - 81K, Supplemental table S1: Survival comparison between the cN2 patients treated with and without TPF induction chemotherapy. Supplemental table S2: Univariate Cox model analysis. Supplemental table S3: Multivariate Cox model analysis with interaction analysis. Supplemental table S4: Correlation between cyclin D1 expression and response to TPF induction chemotherapy. Supplemental table S5: Survival comparison between the cN2 patients treated with and without TPF induction chemotherapy according to cyclin D1 expression.

Induction chemotherapy is likely to be effective for biologically distinct subgroups of patients with cancer with biomarker detection. To investigate the prognostic and predictive values of cyclin D1 expression in patients with oral squamous cell carcinoma (OSCC) who were treated in a prospective, randomized, phase III trial evaluating standard treatment with surgery and postoperative radiotherapy preceded or not by induction docetaxel, cisplatin, and 5-fluorouracil (TPF), immunohistochemical staining for cyclin D1 was conducted in pretreatment biopsy specimens of 232 out of 256 clinical stage III/IVA OSCC patients randomized to the clinical trial. Cyclin D1 index was estimated as the proportion of tumor cells with cyclin D1 nuclear staining. A low cyclin D1 expression predicted significantly better overall survival (OS; P = 0.001), disease-free survival (P = 0.005), locoregional recurrence-free survival (P = 0.003), and distant metastasis-free survival (DMFS; P = 0.002) compared with high cyclin D1 expression. Cyclin D1 expression levels were not predictive of benefit from induction TPF in the population overall. However, patients with nodal stage cN2 whose tumors had high cyclin D1 expression treated with TPF had significantly greater OS (P = 0.025) and DMFS (P = 0.025) when compared with high cyclin D1 cN2 patients treated with surgery upfront. Patients with low cyclin D1 level or patients with cN0 or cN1 disease did not benefit from induction chemotherapy. This study indicates that cN2 OSCC patients with high cyclin D1 expression can benefit from the addition of TPF induction chemotherapy to standard treatment. Cyclin D1 expression could be used as a biomarker in further validation studies to select cN2 patients that could benefit from induction therapy. Mol Cancer Ther; 12(6); 1112–21. ©2013 AACR.

PDF file - 3255K, Subgroup analysis of overall survival, disease-free survival, locoregional recurrence-free survival and distant metastasis free-survival in 232 OSCC patients with low and high cyclin D1 expression

PDF file - 2826K, Overall survival (A), disease-free survival (B), locoregional recurrence-free survival (C), and distant metastasis-free survival (D) in 232 OSCC patients with low and high cyclin D1 expression.

PDF file - 10421K, Immunohistochemical staining for cyclin D1, negative (A), weak positive (B), and strong positive staining (C), original magnification �200.

Chemotherapy with docetaxel, cisplatin, and fluorouracil (TPF) has been studied in patients with head and neck cancer. Its impact on patients with oral cavity cancer was not specified.We consecutively reviewed medical files of patients with untreated oral cavity cancer who received neoadjuvant TPF chemotherapy in our department from January 2017 to April 2020. Outcomes included the objective response to TPF chemotherapy, factors associated with the response, and progression and survival in different response groups.A total of 167 patients were included, with half of stage IV disease. Complete or partial response was observed in 51 patients. A total of 91 patients had stable disease, and 25 patients had progressive disease. The response was not associated with age, sex, anatomic subsite, and the tumor's T stage. It was related with N stage (p 0.001) and clinical stage (p = 0.004). Most patients with bulky nodes or nodes with obvious necrosis showed low response or even progressed after neoadjuvant TPF chemotherapy. The planned surgery was conducted in 159 patients. Disease relapse mostly occurred in 2 years after treatment. The 2-year overall survival and the progression-free survival were 89.0% and 85.2% for patients with complete or partial response, 62.4% and 55.6% for patients with stable disease, and 12.5% and 4.2% for patients with progressive disease, respectively.The response of neoadjuvant TPF chemotherapy in patients with oral cavity cancer is related to disease stage, especially the nodal stage. Patients with complete or partial response developed less progression events and better survival.

Pharyngocutaneous fistula (PCF) is one of the most common but stranded complications for salvage laryngectomy. As for localized fistula, there is no convincing standard and method to cure. This paper described a patient who was submitted to extensive resection of mass in right lingual root, total laryngectomy, and pharyngoesophageal reconstruction with an anterolateral thigh flap (ALTF), because of recurred carcinoma of right lingual root which invaded bilateral epiglottis. 2 weeks after surgery, subsequent pharyngocutaneous fistula developed at the junction of the tracheostomy, and maintained over 2 months under conservative treatment. With the assistance of laryngoscope, inner and outer orificiums of fistula were found and sealed by bundled iodoform strip. 9 days after sealing, fistula had been already filled with fresh granulation tissue. During 2 years after surgery, the fistula area dose not recur. This technique provides a safe and effective way for sealing the inner and outer orificiums of fistula.

Background We aimed to explore whether the anatomic extent of lymph node metastases (AE-LNM) could independently predict prognosis of node-positive major salivary gland carcinoma (MaSGC). Methods A total of 376 pathologically node-positive MaSGC patients were identified from the Surveillance, Epidemiology and End Results database and constituted the training cohort. Using the X-Tile program, these patients were divided into three groups based on AE-LNM degrees. Discrimination of overall survival (OS) and disease-specific survival (DSS) was evaluated and compared with the 8th American Joint Committee on Cancer (AJCC) pN classification. The results were externally validated by 220 patients in a Chinese multicenter cohort (Validation cohort). Results Using the training cohort, AE-LNM was divided into Extent 1 (spread to parotid LNs or level I), Extent 2 (spread to level II-IV) and Extent 3 (spread to level V or bilateral LNs or rare LNs). Regarding both OS and DSS, the AE-LNM model revealed clear separation of survival curves, while the pN classification failed to discriminate the prognosis of pN1 and pN2 patients. When we incorporated both the AE-LNM model and AJCC pN classification into the same multivariate Cox analyses, AE-LNM was still an independent prognostic factor, while the AJCC pN classification lost its significance. These results were externally validated by the validation cohort. Conclusion AE-LNM is an independent nodal prognosticator for node-positive MaSGC and may have improved discriminative ability over the current AJCC pN classification. Integration of anatomic extent of LNM into the current AJCC N classification could be considered.

Immediate mandibular reconstruction is always necessary for the patients receiving segmental mandibulectomy to recover the facial contour and function of occlusion. When 3D modeling is unavailable, temporary external fixator is necessary to maintain the occlusion relationship and facial contour. In this study, we introduce the clinical application of temporary external fixator for immediate mandibular reconstruction in patients receiving segmental mandibulectomy, which consists of 2 anchor claws, 2 all-round retentive arms, and 1 central locking structure. From August 2016 to September 2017, temporary external fixator was applied in 13 patients. Clinical data of gender, age, surgical procedure, duration of operation, and clinical outcomes were recorded and analyzed. Among the 13 patients, there were 4 men and nine women whose ages ranged from 21 to 64 (mean 47.7) years old. There were 9 benign and 4 malignant lesions. All lesions expended at the buccal side of mandible. 12 fibular flaps and 1 vascularized iliac bone graft were used. The mandibular defect ranged from 6 to 14 (mean 10) cm. The operation duration of surgery ranged from 5 to 10 (mean 7) hours. All flaps survived with primary healing. The occlusion and facial contour were good, without significant changes of the length of mandibular body and width of mandible before and after surgery. No functional sequelae were noted at the donor sites. From these results, the temporary external fixator is easy to operate; the surgical procedure is simple and time-saving for surgeon when 3D modeling is unavailable. The indication for temporary external fixator usage is the mandibular lesion growing outward to cheek soft tissue.

Large general hospitals currently play an increasingly important role in the diagnosis and treatment for acute critical patients and difficult diseases because of the development of dual referral system and hierarchical diagnosis, as well as the formation of medical treatment alliance. Patients with oral cancers are often associated with systemic diseases, which increases the complexity of the condition. Thus, meeting the demand through the traditional single medical model is difficult. As such, a multidisciplinary team (MDT) model has been proposed and has achieved a good clinical effect. To standardize the application of this model, we organized an event in which relevant experts discussed and formulated a consensus to provide standardized suggestions on the MDT process and the diagnosis and treatment of common systemic diseases as reference for clinical practice.近年来，随着双向转诊、分级诊疗和医联体的建立，大型综合医院承担急危重症和疑难疾病诊疗的功能定位日益凸显，来诊的口腔癌患者常伴有全身情况复杂的系统性疾病，传统的单一诊疗模式难以达到医疗需求。为此，多学科协作诊疗（MDT）模式应运而生并在实践中应用，取得了良好的临床效果。为了进一步规范口腔癌患者的MDT，组织专家制订了本专家共识，对诊疗流程、常见系统性疾病的诊治等给出了规范化建议，供临床医师参考。.

Deformities of the maxillofacial region following trauma and ablative surgery are devastating and not uncommon. Reconstruction of such defects is a surgically challenging procedure. Conventionally, reconstruction of dental arch defects lacks preoperative customised planning and relies heavily on the surgeon experience to ensure optimum surgical outcomes. The restoration of the dental arch shape and function has taken precedence after an extensive tumour resection surgery, especially in the current age of technological advancement. Thus, personalised and accurate reconstruction of dental arch defects has become a new goal. Computer-assisted surgery, especially navigation-assisted surgery, has gained popularity of late, in reconstructing deformities and restoring facial symmetry, appearance and function in the maxillofacial region. This technology provides a clearer three-dimensional visualisation of the area of interest and its relationship with the adjacent vital structures. Together with preoperative virtual surgical planning, it allows more specific and accurate osteotomies, thus reducing the ischemia and total operating times substantially. The risk of complications is also minimised whilst improving the final surgical outcomes. The use of the intraoperative navigation system and other computer-assisted surgical techniques during surgery can significantly improve the precision of the reconstruction of dental arch deformities, and achieve personalised and functional reconstructive goals while enhancing the quality of life of patients postoperatively. The Society of Oral and Maxillofacial Surgery, Chinese Stomatological Association provides the present professional perspective and treatment protocol for navigation-guided reconstruction of dental arch defects, to allow standardisation of the technique while promoting its application among oral and maxillofacial surgeons.

The oral microbiota plays an important role in the human microbiome and human health, and imbalances between microbes and their hosts can lead to oral and systemic diseases and chronic inflammation, which is usually caused by bacteria and contributes to cancer. There may be a relationship between oral bacteria and oral squamous cell carcinoma (OSCC); however, this relationship has not been thoroughly characterized. Therefore, in this study, we compared the microbiota compositions between tumor sites and opposite normal tissues in buccal mucosal of 50 patients with OSCC using the 16S rDNA sequencing. Richness and diversity of bacteria were significantly higher in tumor sites than in the control tissues. Cancer tissues were enriched in six families (Prevotellaceae, Fusobacteriaceae, Flavobacteriaceae, Lachnospiraceae, Peptostreptococcaceae, and Campylobacteraceae) and 13 genera, including Fusobacterium, Alloprevotella and Porphyromonas. At the species level, the abundances of Fusobacterium nucleatum, Prevotella intermedia, Aggregatibacter segnis, Capnocytophaga leadbetteri, Peptostreptococcus stomatis, and another five species were significantly increased, suggesting a potential association between these bacteria and OSCC. Furthermore, the functional prediction revealed that genes involved in bacterial chemotaxis, flagellar assembly and lipopolysaccharide (LPS) biosynthesis which are associated with various pathological processes, were significantly increased in the OSCC group. Overall, oral bacterial profiles showed significant difference between cancer sites and normal tissue of OSCC patients, which might be onsidered diagnostic markers and treatment targets. Our study has been registered in the Chinese clinical trial registry (ChiCTR1900025253, http://www.chictr.org.cn/index.aspx).

BACKGROUND Platelet-derived growth factor alpha (PDGFRA) is a gene encoding tyrosine kinase receptor and both EGFR and PDGFRA activate tyrosine kinases. The implication of PGFRA in many cancers and its prognostic significance irrespective to EGFR status in spinal chordoma, gliomas, and uterine cancers have shown a need for its investigation in oral squamous cell carcinoma (OSCC). We investigated the prognostic value of PDGFRA mRNA expression in OSCC. PATIENTS AND METHODS The study was conducted in the department of oral maxillofacial surgery-head and neck oncology, at a tertiary hospital. The data on PDGFRA mRNA expression and immunohistochemical staining status in primary OSCC patients treated for curative surgery from 2010 to 2012 were analyzed. Univariate and multivariate analyses were performed with other cofactors for survival. RESULTS A total of 114 consecutive patients with primary OSCC who received treatment were studied. Thirty-one patients died of the disease. Strong PDGFRA immunohistochemical staining and high expression of PDGFRA mRNA were associated with positive pN status (P

Background Venous thromboembolism (VTE) is a preventable complication in which early ambulation is expected after head and neck surgery. Thus, the role of VTE prophylaxis is questionable and needs further assessment. The purpose of this study was to specify the relative contributing risk factors for patients who underwent head and neck cancer ablation with immediate reconstruction. Methods A retrospective analysis was conducted of consecutive head and neck cancer ablations with immediate reconstructions between 2008 and 2013. Dextran and prostaglandin E2 (PGE2) were routinely given as flap thromboprophylaxis. Logistic regression was applied to analyze the potentially significant risk factors. Results Of 1953 subjects, the incidence of symptomatic VTE was 2.2% with 0.1% mortality rate. Prolonged surgery (>592.5 minutes; P = .048), immobilization (>4 days; P = .019), and subjects without postoperative flap thromboprophylaxis (P = .002) are significant risk factors for VTE development. Conclusion Our flap thromboprophylaxis regime might have played a crucial role in keeping the incidence of VTE low. Despite prolonged immobilization in fibula flap reconstruction, the incidence of VTE remained low when flap thromboprophylaxis was given.

The white blood cell (WBC) indices have been reported to have a prognostic impact in cancer of multiple organs including head and neck cancer; however; site and stage stratification was not attempted, and compelling evidence has shown that early cancers have a different distribution and prognostic ability than late-stage cancers. We studied the prognostic importance of WBC indices in early oral tongue cancers.The retrospective data of primary pT1N0 to pT2N0 oral tongue cancers treated between 2009 and 2013 were charted. WBC indices such as the neutrophil count, lymphocyte count (LC), platelet count (PC), and monocyte count, along with derived indices such as the neutrophil-lymphocyte ratio, platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR), were analyzed by multivariate analysis with other clinicopathologic prognostic factors.A total of 133 patients fulfilled the inclusion criteria; the minimum follow-up period for living patients was 36 months. A total of 22 patients reported disease relapse, and 11 patients died of disease. Multivariate analysis showed LC (hazard ratio [HR], 0.206; 95% confidence interval [CI], 0.092 to 0.46; P.001), PC (HR, 1.011; 95% CI, 1.001 to 1.021; P = .026), PLR (HR, 1.012; 95% CI, 1.008 to 1.016; P.001), and LMR (HR, 0.721; 95% CI, 0.596 to 0.872; P = .001) are significant independent prognostic factors for disease-free survival. Distant metastasis (HR, 9.014; 95% CI, 2.303 to 38.914; P = .004), LC (HR, 0.091; 95% CI, 0.015 to 0.558; P = .01), PC (HR, 1.023; 95% CI, 1.006 to 1.041; P = .009), PLR (HR, 1.016; 95% CI, 1.004 to 1.027; P = .002), and LMR (HR, 0.58; 95% CI, 0.387 to 0.868; P = .008) are significant independent prognostic factors for overall survival.Low pretreatment LMR and high PLR indicate poor survival in patients with early tongue cancer. We suggest close follow-up for this subgroup despite radical resection with clear margins.

BACKGROUND Platelet-derived growth factors alpha (PDGFA) is a tyrosine kinase receptor activator which is known to be amplified in the malignancies, and their expression levels are correlated to tumor progression and reduced overall survival. The expression of PDGFRA is different among the tumors and normal tissues; furthermore, their expression level is site specific. Under a physiological condition, PDGFRA and its ligand are expressed in distinct cell populations and activated in a paracrine manner. Nevertheless, heterodimer characteristic of PDGFRA allows it to be trans-activated by non-specific ligands or via autocrine manner. The future of cancer therapy can be based on PDGFRA receptor blockade and therefore warrants further investigation to determine the differing expression of PDGFRA between controls and patients with oral squamous cell carcinoma (OSCC). METHODS We performed a case-control study of 111 patients with newly diagnosed tongue squamous cell carcinoma and 111 control subjects without a cancer diagnosis, matched for age and gender, to evaluate the association between PDGFRA expression levels in oral mucosa. We then performed smoking stratification in each cohort. Independent t test analysis was applied for case-control comparisons. RESULTS Mean value of PDGFRA mRNA level (-ΔCt) for normal cohort is -30.242, whereas mean value of PDGFRA mRNA level for patients with OSCC is -11.516. PDGFRA mRNA level (-ΔCt) was significantly higher in oral cancer cohort, P

Ecto-5'-nucleotidase [cluster of differentiation (CD)73] has important functions in several types of cancer, however, its expression in squamous cell carcinoma (SCC) remains unknown. The present study was designed to investigate CD73 expression in SCC. CD73 expression was assessed by immunohistochemistry in 113 patients with oral SCC (OSCC). The association between CD73 expression and clinicopathological features, overall survival (OS) and disease-free survival (DFS) times of patients were statistically analyzed. CD73 expression was detected in 58.4% (66/113) of OSCC patients, with the immunostaining predominantly localized in the cytomembrane and a little in the cytoplasm. Statistical analysis revealed that CD73 expression was more frequently detected in patients with larger tumors (P=0.021). The overexpression of CD73 was significantly associated with clinical stage (P=0.047). Furthermore, immunohistochemical staining showed that overexpression of CD73 was inversely correlated with DFS (P=0.002) and OS (P=0.002) times. Multivariate Cox regression analysis revealed that CD73 expression was an independent prognostic factor for poor DFS (P=0.018) and OS (P=0.021). The current study is the first to evaluate the clinical significance and prognostic value of CD73 in patients with OSCC. The findings suggest that CD73 is a potential prognostic marker for OSCC.

Oral squamous cell carcinomas (OSCCs) are a growing problem in the world. The various existing treatments have not markedly improved the survival rate of patients with OSCC during the past three decades. Novel treatment strategies are required. Sex determining region Y-box 2 (SOX2) is a transcription factor that is involved in the maintenance of embryonic stem cell pluripotency and in multiple developmental processes. SOX2 expression was indicated to act as a prognostic factor in various types of tumors, including breast, colorectal, gastric and lung cancer and glioblastoma, and as a link between malignancy and stemness. Cancer stem cells (CSCs) may be responsible for the genesis, growth and metastatic spread of tumors. The poor survival outcomes for OSCC patients may be attributable to a poor selection of target cells for treatment, as current oral cancer therapies are generally aimed at the global mass of tumor. Therefore, the consideration that novel approaches to oral cancer may be targeted using SOX2 and CSCs appears reasonable. In order to better understand the oncogenic roles and the corresponding signal transduction pathways of the SOX2 protein, the present study emphasizes the role of SOX2 in OSCC, including the proteins associated with OSCC, and reviews the literature regarding the role of SOX2 in lymph node metastasis. The aim of the present study is to provide a reference for future studies that engage in research on the aforementioned subject.

BACKGROUND Computer-aided design/computer-aided manufacturing (CAD/CAM) surgical templates allow precise mandibular reconstructive surgery. However, their clinical accuracy is limited by manual plate bending. Digitally hydroformed plates maintain a digital workstream in virtual planning. METHODS Twelve patients with Brown's class IIc mandibular defects were randomized into two groups: group I (experimental), the reconstruction plate was digitally hydroformed, and group II (control), surgeries were performed CAD/CAM guided with the reconstruction plate manually prebent. The linear and angular deviations of reconstruction outcomes were compared to surgical simulation in both groups. RESULTS The mean linear and angular deviations of middle and posterior segments were 2.14 ± 0.79 mm, 3.71 ± 0.95 mm, 8.73° ± 1.91°, and 9.06° ± 0.96° in group I and 4.31 ± 0.78 mm, 6.74 ± 1.40 mm, 16.35° ± 0.72°, and 31.48° ± 3.38° in group II, respectively. Measurements in group I were significantly lower than group II (P < .005). CONCLUSION Digital hydroforming for plate prebent is a reliable method that helps improving the clinical accuracy of CAD/CAM-guided mandibular reconstruction surgery.

To evaluate the temporal trend of inpatients with smoking-associated oral cancer in Shanghai and its surrounding areas and to forecast the public health burden in the next decade.Data of inpatients with oral cancer were retrieved from Shanghai Ninth People's Hospital during a 15-year period. The annual numbers of inpatients were compared by Chi-test. The hospitalization expenditures were compared by Student's t test. The trend analysis and inpatient forecasting were performed by exponential smoothing, regression models, and the forecasting function in Excel software. The financial burden of smoking-associated oral cancer was calculated by polynomial equation.The annual number of inpatients with oral cancer increased during the study period. Most male patients were reported to have a smoking habit. Among the three estimation methods, polynomial regression model was most fitted to the existing data. By a conservative estimation, the public health burden of smoking-associated oral cancer patients will be 120 million RMB by the year 2026, not including the cost by prevalent patients and the patients' family members.Smoking-associated oral cancer will cost a lot of public resource in the next decade. Efforts should be made to lower the amount of tobacco consumption.

Background The clinical degradation rate and strength of biodegradable implant exposed to postoperative radiotherapy (PORT) are unknown. Methods A prospective randomized control trial of 40 consecutive mandibulotomy patients randomly divided into titanium and biodegradable cohorts. All patients received PORT. The following parameters were compared: maximal mouth opening, occlusal force, center of force trajectory, occlusal status, radiographic evidence of bony union, mandibular function impairment questionnaire (MFIQ), overall satisfaction score, and complication rates. Results Both the mandibular function and occlusal status parameter of the biodegradable and the titanium groups were not significantly difference. Biodegradable cohort showed better MFIQ scores (P = .08) and overall satisfaction scores (P = .64) but was not statistically significant. Of note, 40% of patients in the titanium cohort complained of plate palpability/cold intolerance and required plate removal (P = .02); 10% of patients in the titanium cohort developed osteoradionecrosis. Conclusion Biodegradable osteosynthesis is as reliable as titanium osteosynthesis for mandibulotomy fixation. PORT did not increase the complication rate in the biodegradable group.

Previously, we conducted a randomized phase III trial of TPF (docetaxel, cisplatin, and 5-fluorouracil) induction chemotherapy in surgically managed locally advanced oral squamous cell carcinoma (OSCC) and found no improvement in overall survival. This study reports long-term follow-up results from our initial trial. All patients had clinical stage III or IVA locally advanced OSCC. In the experimental group, patients received two cycles of TPF induction chemotherapy (75mg/m2 docetaxel d1, 75mg/m2 cisplatin d1, and 750mg/m2/day 5-fluorouracil d1-5) followed by radical surgery and post-operative radiotherapy; in the control group, patients received upfront radical surgery and post-operative radiotherapy. The primary endpoint was overall survival. Among 256 enrolled patients with a median follow-up of 70 months, estimated 5-year overall survival, disease-free survival, locoregional recurrence-free survival, and distant metastasis-free survival rates were 61.1%, 52.7%, 55.2%, and 60.4%, respectively. There were no significant differences in survival rates between experimental and control groups. However, patients with favorable pathologic responses had improved outcomes compared to those with unfavorable pathologic responses and to those in the control group. Although TPF induction chemotherapy did not improve long-term survival compared to surgery upfront in patients with stage III and IVA OSCC, a favorable pathologic response after induction chemotherapy may be used as a major endpoint and prognosticator in future studies. Furthermore, the negative results observed in this trial may be represent type II error from an underpowered study. Future larger scale phase III trials are warranted to investigate whether a significant benefit exists for TPF induction chemotherapy in surgically managed OSCC.

Background Men and women share a common maxillary morphology with heterogeneity in size. This indicated that our technique of reconstruction with a rhomboid-shaped iliac crest bone flap incorporating a 30° vertical wedge osteotomy may be widely used for Brown's class III maxillectomy defect reconstruction among a population with class I skeletal profile. The reconstruction of Brown's class III maxillary defects is extremely challenging. The purpose of this study was to closely study the maxilla geometrically in order to establish a standardized maneuver, which facilitates conversion of the iliac bone flap into a natural maxilla's contours. Methods We evaluated the geometries of 40 adult maxillas. The perimeter lengths of perinasal and infraorbital subunits were analyzed, in addition to the intersecting angle (δ) of both subunits. Sex variation was evaluated using the Student's t test. Results In the 80 studied unilateral maxillas (40 maxillas from 18 men and 22 women), there were no significant sex differences for δ (P = .1527). In addition, both sexes shared common morphological features, hence, in surgical reconstruction, the δ can be constantly set at 150°. Perimeter of bone segments had a greater intersubject variability (coefficient of variation [CV] of approximately 4.5-11). From both cadaveric dissections and clinical applications, our results have shown that our standard maneuver was reproducible and reliable in reestablishing natural facial contours. Conclusion Our standard maneuver can serve as a universal guideline, with individualized perimeter manipulations, to yield an aesthetically natural and functional outcome.

Our previous phase 3 trial (NCT01542931) failed to demonstrate improved survival when docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy was introduced prior to surgery and postoperative radiotherapy in patients with locally advanced oral squamous cell carcinoma (OSCC). The aim of the present study was to investigate the long-term predictive value of GDF15 expression for potential personalized treatment strategies in OSCC. A total of 256 patients with stage III/IVA OSCC from our phase 3 trial were enrolled in the present study. Immunohistochemical staining against GDF15 was performed in the biopsy samples from 230/256 patients. Kaplan-Meier analysis, followed by the log-rank test, and the Cox proportional hazards model were used for outcome analysis using the statistical SPSS 18.0 software package for Windows. Among the 230 patients, low GDF15 expression was detected in 68 patients and high GDF15 expression was detected in 162 patients. With a median follow-up period of 67 months, the patients with low GDF15 expression exhibited a higher survival rate than those with high GDF15 expression, including 5-year overall survival (73.4 vs. 57.7%; P=0.059), 5-year disease-free survival (64.5 vs. 49.2%; P=0.033), 5-year locoregional recurrence-free survival (66.0 vs. 51.5%; P=0.043) and 5-year distant metastasis-free survival (73.4 vs. 56.6%; P=0.038) rates. Furthermore, the cT3/4N0M0 patients with high GDF15 expression benefited significantly from TPF induction chemotherapy, including overall survival (HR=0.233; P=0.02), disease-free survival (HR=0.296; P=0.014), locoregional recurrence-free survival (HR=0.347; P=0.035) and distant metastasis-free survival (HR=0.212; P=0.013) rates. The results of the present study suggested that elevated GDF15 expression may be used as a long-term prognostic biomarker for poor clinical outcomes in patients with locally advanced OSCC. Elevated GDF15 expression in cT3/4N0M0 patients predicts significant long-term benefit of survival from TPF induction chemotherapy.

With the increasing maturation of 3D printing technology, as well as its application in various industries, investigation of 3D printing technology into clinic medical education becomes an important task of the current medical education. The teaching content of oromaxillofacial head and neck surgical oncology is complicated and diverse, making lower understanding/memorizing efficiency and insufficient skill training. To overcome the disadvantage of traditional teaching method, it is necessary to introduce 3D printing technique into teaching of oromaxillofacial head and neck surgical oncology, in order to improve the teaching quality and problem solving capabilities, and finally promote cultivation of skilled and innovative talents.

Curcumin, a phytochemical derived from the rhizome of Curcuma longa, has shown anticancer effects against a variety of tumors. In the present study, we investigated the effects of curcumin on the miR-9 expression in oral squamous cell carcinoma (OSCC) and explored the potential relationships between miR-9 and Wnt/β-catenin pathway in curcumin-mediated OSCC inhibition in vitro. As the results shown, the expression levels of miR-9 were significantly lower in clinical OSCC specimens than those in the adjacent non-tumor tissues. Furthermore, our results indicated that curcumin inhibited OSCC cells (SCC-9 cells) proliferation through up-regulating miR-9 expression, and suppressing Wnt/β-catenin signaling by increasing the expression levels of the GSK-3β, phosphorylated GSK-3β and β-catenin, and decreasing the cyclin D1 level. Additionally, the up-regulation of miR-9 by curcumin in SCC-9 cells was significantly inhibited by delivering anti-miR-9 but not control oligonucleotides. Downregulation of miR-9 by anti-miR-9 not only attenuated the growth-suppressive effects of curcumin on SCC-9 cells, but also re-activated Wnt/β-catenin signaling that was inhibited by curcumin. Therefore, our findings would provide a new insight into the use of curcumin against OSCC in future.

The pedicled latissimus dorsi myocutaneous flap (PLDMF) is not the first-line reconstructive option for most clinicians; however, when treating salvage patients or those with depleted neck vessels, the PLDMF provides a valuable armamentarium. Unlike the pectoralis major myocutaneous flap or the lower island trapezius flap, the PLDMF has greater versatility in soft tissue design and a longer arc of rotation. These advantages are of great importance in managing advanced reconstructive cases.

This study was designed to investigate the effects of local delivery of adipose-derived stem cells (ADSCs) transfected with transcription factor osterix (OSX) on bone formation during distraction osteogenesis. New Zealand white rabbits (n=54) were randomly divided into three groups (18 rabbits per group). A directed cloning technique was used for the construction of recombinant plasmid pEGFP-OSX, where EGFP is the enhanced green fluorescence protein. After osteodistraction of the right mandible of all experimental rabbits, rabbits in group A were treated with ADSCs transfected with pEGFP-OSX, group B with ADSCs transfected with pEGFP-N1, and group C with physiological saline. Radiographic and histological examinations were processed after half of the animals within each group were humanely killed by injection of sodium pentothal at Week 2 or 6 after surgery. The distraction bone density was measured as its projectional bone mineral density (BMD). Three parameters were measured, namely, the thickness of new trabeculae (TNT), and the volumes of the newly generated cortical bone (NBV1) and the cancellous bone (NBV2) of the distracted regions. Good bone generation in the distraction areas was found in group A, which had the highest BMD, TNT, and NBV in the distraction zones among the groups. There was no significant difference in bone generation in the distraction areas between groups B and C. The results indicate that the transplantation of ADSCs transfected with pEGFP-OSX can effectively promote bone generation during distraction in vivo.

ResumenObjetivoRealizar una revisión de la situación actual en el tratamiento del melanoma de mucosa oral (MMO).Describir el protocolo de tratamiento que haya demostrado mejores resultados dada la experiencia y los estudios realizados por la institución de referencia.Material y métodosLos autores realizan una amplia revisión de la literatura abordando las nuevas líneas terapéuticas de investigación.ResultadosDescripción del protocolo de tratamiento que siguen en uno de los centros con mayor cáustica en la literatura internacional.ConclusionesEl MMO es una neoplasia maligna poco frecuente, con etiología y patogenia desconocida y un pronóstico infausto. El tratamiento debe basarse en un diagnóstico temprano y un abordaje multidisciplinar.AbstractObjectiveTo review the current situation in the treatment of oral mucosal melanoma. To describe the treatment protocol that has shown better results, given the experience and studies by the reference institution.MethodsThe authors conducted an extensive review of the literature addressing the new lines of therapeutic research.ResultsDescription of the treatment regimen followed at one of the most experienced centers in the international literature.ConclusionsOral mucosal melanoma is a rare malignancy with an unknown etiology and pathogenesis and poor prognosis. Treatment should be centered on early diagnosis and a multidisciplinary approach.

Purpose To evaluate induction chemotherapy with docetaxel, cisplatin, and fluorouracil (TPF) followed by surgery and postoperative radiotherapy versus up-front surgery and postoperative radiotherapy in patients with locally advanced resectable oral squamous cell carcinoma (OSCC). Patients and Methods A prospective open-label phase III trial was conducted. Eligibility criteria included untreated stage III or IVA locally advanced resectable OSCC. Patients received two cycles of TPF induction chemotherapy (docetaxel 75 mg/m2 on day 1, cisplatin 75 mg/m2 on day 1, and fluorouracil 750 mg/m2 on days 1 to 5) followed by radical surgery and postoperative radiotherapy (54 to 66 Gy) versus up-front radical surgery and postoperative radiotherapy. The primary end point was overall survival (OS). Secondary end points included local control and safety. Results Of the 256 patients enrolled onto this trial, 222 completed the full treatment protocol. There were no unexpected toxicities, and induction chemotherapy did not increase perioperative morbidity. The clinical response rate to induction chemotherapy was 80.6%. After a median follow-up of 30 months, there was no significant difference in OS (hazard ratio [HR], 0.977; 95% CI, 0.634 to 1.507; P = .918) or disease-free survival (HR, 0.974; 95% CI, 0.654 to 1.45; P = .897) between patients treated with and without TPF induction. Patients in the induction chemotherapy arm with a clinical response or favorable pathologic response (≤ 10% viable tumor cells) had superior OS and locoregional and distant control. Conclusion Our study failed to demonstrate that TPF induction chemotherapy improves survival compared with up-front surgery in patients with resectable stage III or IVA OSCC.

OBJECTIVES: This study aimed to evaluate the stability of prostheses supported by zygoma implants and remaining teeth for subjects who had undergone hemi-maxillectomy. METHODS: Ten patients were included in the study. Oral rehabilitation was performed using a temporary prosthesis that was supported by remaining teeth for the first three months. Then, a zygoma implant was placed to provide support for a final prosthesis in addition to the remaining teeth. Each prosthesis was tailor-made according to biomechanical three-dimensional finite element analysis results. The patients were assessed using the prosthesis functioning scale of the Memorial Sloan-Kettering Cancer Center. In addition, retention and bite force were recorded for both the temporary prosthesis and the final prosthesis. RESULTS: The mean bite force of the prosthetic first molar was increased to 69.2 N. The mean retentive force increased to 13.5 N after zygoma implant insertion. The bite force on the prosthetic first molar was improved to 229.3 N. CONCLUSION: Bite force increased significantly with the support of a zygoma implant. The use of zygoma implants in the restoration of maxillary defects improved functional outcome and patient satisfaction.

Summary Owing to rarity and awareness deficiency towards inflammatory myofibroblastic tumor (IMT), we sought to review on its clinicopathological features; arising awareness to achieve early diagnosis; exploring prognostic factors and then establishing a treatment protocol. Retrospective study was performed on patients with histological proven IMT between January 2003 and December 2010. Their demographic data, clinical and histological presentations were recorded. Overall survival (OS) and progression-free-survival (PFS) were estimated via Kaplan–Meier method. Cox regression model was applied to determine the significant of prognostic factors. Logistic regression model was established to predict the probability of relapse. A total of 28 patients. Five-year PFS was 65%. Surgical margins primarily and independently determined the survival, followed by size, pseudocapsule of the lesion, intra-lesional necrosis and lastly Ki-67 and ALK overexpression. Logistic model in prediction of relapse was established, with the formula as probability of relapse = 1/(1 + e − z ) where e = exponential function, z = constant value (3.9) + B *margin + B *size + B *immunohistochemical expression + B *pseudocapsule + B *intra-lesional necrosis. Immunohistochemical overexpression was significant if Ki-67 was strongly expressed with a conditioned ALK overexpression simultaneously. Staining intensity must be at least moderate for those ALK nuclear staining was less than 25%. Weak ALK staining intensity is only significant if nuclear staining was more than 25%. Diagnosis of IMT is achieved via exclusion. Radical resection and obtaining negative margins remains the mainstay of treatment. Both high and moderate-risk groups required post-operative radiotherapy. In low-risk group, post-operative radiotherapy was recommended if the lesion is larger than 5 cm in diameter with a conditioned ALK & Ki-67 overexpression.

Induced pluripotent stem cells (iPSCs) can differentiate into mineralizing cells and thus have a great potential in application in engineered bone substitutes with bioactive scaffolds in regeneration medicine. In the current study we characterized and demonstrated the pluripotency and osteogenic differentiation of mouse iPSCs. To enhance the osteogenic differentiation of iPSCs, we then transduced the iPSCs with the potent transcription factor, nuclear matrix protein SATB2. We observed that in SATB2-overexpressing iPSCs there were increased mineral nodule formation and elevated mRNA levels of key osteogenic genes, osterix (OSX), Runx2, bone sialoprotein (BSP) and osteocalcin (OCN). Moreover, the mRNA levels of HoxA2 was reduced after SATB2 overexpression in iPSCs. The SATB2-overexpressing iPSCs were then combined with silk scaffolds and transplanted into critical-size calvarial bone defects created in nude mice. Five weeks post-surgery, radiological and micro-CT analysis revealed enhanced new bone formation in calvarial defects in SATB2 group. Histological analysis also showed increased new bone formation and mineralization in the SATB2 group. In conclusion, the results demonstrate that SATB2 facilitates the differentiation of iPSCs towards osteoblast-lineage cells by repressing HoxA2 and augmenting the functions of the osteoblast determinants Runx2, BSP and OCN.

Objective: To investigate the effects and potential mechanisms of preconditioning of tricarbonyldichlororuthenium (III) dimer (CORM-2)-liberated CO on LPS-induced activation of endothelial cells (HUVEC). Methods: HUVEC were pretreated with CORM-2 at the concentration of 50 or 100μM for 2 hrs, washed and stimulated with LPS (10μg/ml) for additional 4 hrs. Activation (oxidative stress) of HUVEC was assessed by measuring intracellular oxidation of DHR 123 or nitration of DAF-FM, specific H2O2 and NO fluorochromes, respectively. The expression of HO-1, iNOS (Western blot) and ICAM-1 (cell ELISA) proteins and activation of inflammation-relevant transcription factor, NF-κB (EMSA) were assessed. In addition, PMN adhesion to HUVEC was also assessed. Results: The obtained data indicate that pretreatment of HUVEC with CORM-2 results in: 1) decrease of LPS-induced production of ROS and NO; 2) up-regulation of HO-1 but decrease in iNOS at the protein levels; 3) inhibition of LPS-induced activation of NF-κB; and 4) downregulation of expression of ICAM-1, and this was accompanied by a decrease of PMN adhesion to LPS-stimulated HUVEC. Conclusions: Preconditioning of CO liberated by CORM-2 elicited its anti-inflammatory effects by interfering with the induction of intracellular oxidative stress. In addition, it also supports the notion that CO is a potent inhibitor of iNOS and NF-κB.

To investigate the clinical and pathological features of jaw ameloblastomas in 890 patients, in order to provide reference for clinical diagnosis and treatment.Eight hundred and ninty cases with jaw ameloblastomas treated in our department from January 2003 to June 2014 were retrospectively analyzed, including their gender, age, primary sites, pathological subtypes and therapies.The age of patients ranged from 6 to 101 years old, with a mean age of 40.15 years. The distribution between males and females were 61.91% (551/890) males to 38.08% (339/890) females (1.62:1). 724 (81.35%) were located in the mandible, 166 (18.65%) were located in the maxilla. The occurrence of jaw ameloblastomas in this series of 890 patients was same in both sides of the jaw. Jaw ameloblastomas occurred in any parts of the jaw. Solid (378/890) and unicystic ameloblastoma (427/890) were the most common pathological subtypes. 414 cases underwent curettage, 212 cases underwent decompression, and 264 cases underwent mandibulectomy or maxillectomy.Jaw ameloblastoma mainly happens in mandible and young people. Men are more vulnerable to suffer from than women. The most common sites are mandibular molar region and ramus. Curettage is the most commonly used treatment for ameloblastomas. Supported by Scientific Research Fund of Oromaxillofacial Head and Neck Surgery of Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine.

Summary Purpose To investigate the biomechanics of the mandible following reconstruction with autogenous bone grafts. Material Computerized tomography scan images of a human mandible, fibula and iliac crest were collected and used to build models on a PC. Methods Four finite-element analysis (FEA) models of mandibles reconstructed with autogenous bone were created. The principal stresses of marked points, the Von Mises stresses at anatomical index regions, and the force values of temporo-mandibular joints and masticatory muscles were calculated. Results Compared with the normal mandible, the one repaired with a fibula had greater Von Mises stresses on the grafted bone; the one repaired with iliac crest bone had the similar distribution of the Von Mises stresses as in the normal mandible. The principal stresses in the autograft varied between tensile and compressive stresses from the right graft/bone binding interface to the left in all reconstructed mandibles. On the whole, the maximum Von Mises stress was greater on the mandible reconstructed with fibula than that reconstructed with iliac crest. Conclusion Mandibles repaired with iliac crest grafts have more mechanical properties similar to normal than those repaired with fibula grafts.

Fibrous dysplasia (FD) as an abnormal bone growth is one of the common fibro-osseous leasions (FOL) in oral and maxillofacial region, however, its etiology still remains unclear. Here, we performed gene expression profiling of FD using microarray analysis to explore the key molecule events in FD development, and develop potential diagnostic markers or therapeutic targets for FD. We found that 1,881 genes exhibited differential expression with more than two-fold changes in FD compared to normal bone tissues, including 1,200 upregulated genes and 681 downregulated genes. Pathway analysis indicated that obviously activated pathways are Ribosome and ECM-receptor interaction pathways; downregulated pathways are “Hepatitis C” and “cancer” signaling pathways. We further validated the expression of ADAMTS2, one of most differentiated expressed genes, by Immunohistochemistry (IHC) in 40 of FD cases. Results showed that ADAMTS2 was significantly overexpressed in FD tissues, but rarely expressed in normal bone tissues, suggesting that ADAMTS2 could be a potential biomarker for FD. Thus, this study uncovered differentially expressed candidate genes in FD, which provides pilot data for understanding FD pathogenesis, and developing novel biomarkers for diagnosis and targeting of FD.