Prospective observational study of surgery alone for locally advanced oral squamous cell carcinoma: a real-world study.

INTRODUCTION: A prospective observational study was modified to assess the efficacy of surgery alone for the treatment of locally advanced oral squamous cell carcinoma. (LA-OSCC) MATERIALS AND METHODS: This prospective, single-institution, single-arm study involved 174 patients who underwent major surgery for LA-OSCC. Participating patients did not receive postoperative radiation. After initial curative treatment, patients were routinely monitored via clinical examination and imaging. The follow-up period was 3-70 months. Tumour recurrence and death were considered as the Clinical End Point in Research. RESULTS: The 5-year overall survival (OS), disease-free survival (DFS), and locoregional control rates for 174 patients were 66.7% (95% confidence interval [CI], 59.8 to 73.6), 66.1% (95% CI, 59.2 to 73.0), and 82.4% (95% CI, 76.5 to 88.3), respectively. CONCLUSION: A study of patients with LA-OSCC treated with surgery alone may have the optimal therapeutic impact for LA-OSCC, as evidenced by solid data for our next RCT trial. This conclusion still needs to be validated in higher-level RCTs.

Application of anatomy unit resection surgery for lateral basicranial surgical approach in oral squamous carcinoma.

BACKGROUND: The basicranial region lacks definite boundaries and includes various anatomical units. We developed a novel concept of the posterior oral anatomical complex (POAC) to identify these anatomical units in the basicranial region. OSCC with POAC involvement is termed posterior oral squamous cell carcinoma (POSCC) with poor prognosis. The principal aim of this study was to evaluate the effect of anatomy unit resection surgery (AUSR) on patients with POSCC. METHODS: A total of 120 POSCC patients who underwent radical surgical treatment were recruited for this study. These POSCC patients were treated with conventional surgery or AUSR. According to the extent of primary tumor resection in the AUSR group, the lateral basicranial surgical approach can be subdivided into four types: face-lateral approach I, face-lateral approach II, face-median approach or face-median and face-lateral combined approach. Facial nerve function was evaluated according to the House-Brackmann Facial Nerve Grading System. RESULTS: The overall survival rate was 62.5% and 37.5% in the AURS group and conventional group (hazard ratio: 0.59; p < 0.0001), respectively. The disease-free survival rate was 62.5% and 34.3% in the AURS group and conventional group (hazard ratio: 0.43; p = 0.0008), respectively. The local disease control rate in the AURS group (71.4%) was significantly better than that in the conventional group (34.4%) in present study (p < 0.0001). Compared to the conventional group, all the patients undergoing AURS were classified as T4 stage and presented with more lymph node metastasis (71.4%). A total of 20 patients (face-lateral approach I and face-lateral combined approach) were temporarily disconnected from the temporofacial branch of the facial nerve. Fifteen patients exhibited slight paresis, and five patients presented with moderate or severe paresis. The survival rate of zygomatic arch disconnection was 94.6% (54 of 56 patients). CONCLUSION: This lateral basicranial surgical approach based on AUSR improves the survival rate and enhances the local control rate while also preserving a good prognosis without damaging the nerve and zygomatic bone. This surgical approach based on AUSR provides a novel and effective surgical treatment to address POSCC with better prognosis, especially for patients without metastatic lymph nodes.

Postoperative radiotherapy may not be necessary for locally advanced head and neck squamous cell carcinoma: a case-match multicentre study.

BACKGROUND: Some head and neck cancer surgeons found that many patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) without postoperative radiotherapy (PORT) also have a good prognosis. The purpose of this study was to determine the effect of PORT on survival in patients with LA-HNSCC. METHODS: A case-match cohort analysis was performed at two institutions on patients with LA-HNSCC. Patients who received surgery alone were case-matched 1: 1 with patients treated by surgery plus PORT based on pT, pN, tumor subsite etc. RESULTS: 114 patients were matched into 57 pairs, with a median follow-up period of 40.2 months. No difference in overall survival (OS, HR 0.88; 95% CI 0.50-1.58; P = 0.79) or disease-specific survival (DFS, 0.86; 95% CI 0.50-1.50; P = 0.76) was observed with no PORT. CONCLUSIONS: PORT isn't necessary for patients with LA-HNSCC who are treated for the first time as long as the head and neck cancer surgeon adhere to appropriate surgical concepts. The indications of PORT for patients with LA-HNSCC need to be further discussed.

Global, regional, and national burden of periodontitis from 1990 to 2019: Results from the Global Burden of Disease study 2019.

BACKGROUND: To evaluate the prevalence and incidence of periodontitis and associated disability-adjusted life years (DALYs) from 1990 to 2019. METHODS: We collected data on periodontitis between 1990 and 2019 from the Global Burden of Disease (GBD) 2019 Study. The global prevalence, incidence, and DALYs attributed to periodontitis were analyzed. The age-standardized rate (ASR) and estimated annual percentage changes (EAPCs) were calculated to quantify the burden of the disease and temporal trends. RESULTS: The ASR of the prevalence, incidence, and DALYs increased worldwide from 1990 to 2019. In 2019, Western Sub-Saharan Africa carried the heaviest burden of periodontitis, whereas the nation with the highest periodontitis burden was Gambia. The burden of periodontitis was negatively associated with the level of socioeconomic development. Although, the majority of periodontitis burden was observed among those aged 55-59 years, the incidence of periodontitis has shown an increasing trend among younger individuals. CONCLUSION: Periodontitis continues to be a global public health problem. Current prevention and control strategies should be enhanced to prevent an increase in periodontitis.

Corrigendum: WGCNA Co-Expression Network Analysis Reveals ILF3-AS1 Functions as a CeRNA to Regulate PTBP1 Expression by Sponging miR-29a in Gastric Cancer.

[This corrects the article DOI: 10.3389/fgene.2020.00039.].

Trends in the incidence of diabetes mellitus: results from the Global Burden of Disease Study 2017 and implications for diabetes mellitus prevention.

BACKGROUD: Diabetes mellitus is a common chronic disease and a severe public health issue. The incidence trends for type 1 diabetes (TIDM) and type 2 diabetes (T2DM) have rarely been studied on a global scale. We aimed to determine the temporal and geographical trends of diabetes globally. METHODS: Data on diabetes mellitus, including incidence, prevalence from 1990 to 2017 were obtained from the 2017 Global Burden of Disease study. We calculated the estimated annual percentage changes (EAPCs) in age-standardized incidence rate (ASIR) of diabetes mellitus according to sex, region, and disease type. RESULTS: The worldwide incident cases of diabetes mellitus has increased by 102.9% from 11,303,084 cases in 1990 to 22,935,630 cases in 2017 worldwide, while the ASIR increased from 234 /100,000 persons (95% UI, 219-249) to 285/100,000 persons (95% UI, 262-310) in this period [EAPC = 0.87, 95% confidence interval (CI):0.79-0.96]. The global ASIRs of T1DM and T2DM both demonstrated significant increase during 1990-2017, with EAPCs of 0.34 (95% CI,0.30-0.39) and 0.89 (95% CI,0.80-0.97), respectively. The ASIR trends also varied considerably by regions and countries. The increase in ASIR was greatest in high sociodemographic index regions (EAPC = 1.05, 95% CI:0.92-1.17) and lowest in low-SDI regions (EAPC = 0.79, 95% CI:0.71-0.88). CONCLUSIONS: Both the number of incident cases and ASIR of diabetes mellitus increased significantly during 1990-2017 worldwide, but the temporal trends varied markedly across regions and countries.

WGCNA Co-Expression Network Analysis Reveals ILF3-AS1 Functions as a CeRNA to Regulate PTBP1 Expression by Sponging miR-29a in Gastric Cancer.

Gastric cancer (GC) is one of the most common types of human cancers worldwide. However, the detail mechanisms underlying GC progression remained to be investigated. The present study identified 2823 differently expressed mRNAs and 441 differently expressed lncRNAs in GC. WGCNA was conducted to identify highly correlated lncRNAs and mRNAs. Bioinformatics analysis observed that these dysregulated lncRNAs were significantly associated with the regulation of angiogenesis, cell division, cell-cell adhesion, blood vessel development, adaptive immune response, gastric acid secretion, immune response. Co-expression analysis identified ILF3-AS1 was a key lncRNA involved in regulating GC progression. Loss of function assays showed that knockdown of ILF3-AS1 significantly suppressed GC cell proliferation and metastasis. Mechanically, the results indicate that ILF3-AS1 could enhance PTBP3 expression as an miR-29a sponge, thereby promoting the proliferation and metastasis of GC cells. Our work suggests that the ILF3-AS1/miR-29a/PTBP3 axis may be a potential target for the clinical diagnosis and treatment of GC.

Global and regional burdens of oral cancer from 1990 to 2017: Results from the global burden of disease study.

BACKGROUND: Data on the incidence, mortality, and other burden of oral cancer as well as their secular trends are necessary to provide policy-makers with the information needed to allocate resources appropriately. The purpose of this study was to use the Global Burden of Disease (GBD) 2017 results to estimate the incidence, mortality, and disability-adjusted life years (DALYs) for oral cancer from 1990 to 2017. METHODS: We collected detailed data on oral cancer from 1990 to 2017 from the GBD 2017. The global incidence, mortality, and DALYs attributable to oral cancer as well as the corresponding age-standardized rates (ASRs) were calculated. The estimated annual percentage changes in the ASRs of incidence (ASRI) and mortality (ASRM) and age-standardized DALYs of oral cancer were also calculated according to regions and countries to quantify the secular trends in these rates. RESULTS: We tracked the incidence, mortality, and DALYs of oral cancer in 195 countries/territories over 28 years. Globally, the incidence, mortality, and DALYs of oral cancer increased by about 1.0-fold from 1990 to 2017. The ASRI of oral cancer showed a similar trend, increasing from 4.41 to 4.84 per 100,000 person-years during the study period. The ASRM remained approximately stable at about 2.4 per 100,000 from 1990 to 2017, as did the age-standardized DALYs, at about 64.0 per 100,000 person-years. ASRI was highest in Pakistan (27.03/100,000, 95% CI = 22.13-32.75/100,000), followed by Taiwan China, and lowest in Iraq (0.96/100,000, 95% CI = 0.86-1.06/100,000). ASRM was highest in Pakistan (16.85/100,000, 95% CI = 13.92-20.17/100,000) and lowest in Kuwait (0.51/100,000, 95% CI = 0.45-0.58/100,000). CONCLUSIONS: The ASRI of oral cancer has increased slightly worldwide, while the ASRM and age-standardized DALY have remained stable. However, these characteristics vary between countries, suggesting that current prevention strategies should be reoriented, and much more targeted and specific strategies should be established in some countries to forestall the increase in oral cancer.

Differential expression of matrix metalloproteinases and miRNAs in the metastasis of oral squamous cell carcinoma.

BACKGROUND: Our study aimed to reveal the regulatory mechanisms of miRNAs and matrix metalloproteinases (MMPs) in oral squamous cell carcinoma (OSCC). METHODS: The mRNA and miRNA expression profiles of six metastatic tumour samples, six nonmetastatic tumour samples, and six normal tissue samples were used for microarray analysis. Moreover, the important genes and miRNAs were validated by published profiles in Oncomine and by qRT-PCR. RESULTS: MMP7, MMP13, and MMP10 were upregulated, and MMP12 and MMP9 were downregulated in metastatic tumours compared with nonmetastatic tumours. MMP7 was regulated by miR-4697-5p and miR-7109-5p. MMP7 and MMP13 were upregulated in OSCC samples compared with normal samples in Oncomine. Moreover, qRT-PCR revealed that the expression of miR-7109-5p and miR-34b was decreased in metastatic tumours compared with nonmetastatic tumours. CONCLUSIONS: Our study suggested that miR-7109-5p and miR-34b might play important roles in the metastasis of OSCC by regulating MMP7 and MMP13 expression, respectively.

Nonvascularized Iliac Bone Reconstruction for the Mandible Without Maxillofacial Skin Scarring.

PURPOSE: There are many methods to reconstruct the mandible, but they are often accompanied by trauma, which can lead to scarring of the maxillofacial skin. The purpose of this study was to show the utility of a minimally invasive method for reconstruction of the mandible with nonvascularized iliac bone grafts without a skin scar, as well as to evaluate the success rate and complications. PATIENTS AND METHODS: This was a retrospective case series. We retrospectively analyzed patients who underwent transoral resection of benign mandibular pathologies, followed by nonvascularized iliac bone graft reconstruction. The primary outcome variable was the success rate of the bone grafts. Secondary outcome variables were postoperative complications at the grafted bone recipient and donor sites, the long-term absorptivity of grafted bone, and the type of mandibular defect. We computed descriptive statistics or performed the χ2 test for each variable. RESULTS: Overall, 54 patients were included in the study, including 21 male and 33 female patients, with an age range of 10 to 65 years. The complete survival rate was 87.0% (47 of 54 patients), and the partial survival rate was 98.1% (53 of 54). The average bone absorption rate 3 years after surgery was 1.8 to 30.7%. We propose a new classification method for mandibular defects based on the extent of the tumor, location of the osteotomy, and degree of surgical difficulty. CONCLUSIONS: Intraoral nonvascularized iliac bone grafting is a highly successful minimally invasive method for mandibular reconstruction. It is also one of the best methods for mandibular reconstruction in patients with benign mandibular tumors without soft tissue involvement.

Global, regional, and national burden of nasopharyngeal carcinoma from 1990 to 2017-Results from the Global Burden of Disease Study 2017.

BACKGROUND: The aim of this study is to estimate the incidence, mortality, and disability-adjusted life years (DALYs) of nasopharyngeal carcinoma from 1990 to 2017. METHODS: We collected detailed information on nasopharyngeal carcinoma from 1990 to 2017 based on data from Global Burden of Disease (GBD) study 2017. The global incidence, mortality, and DALYs attributable to nasopharyngeal carcinoma was reported, as well as the age-standardized rates (ASRs). RESULTS: The ASR of nasopharyngeal carcinoma incidence decreased from 1.88 (95% UI: 1.76-2.00) in 1990 to 1.35 (95% UI: 1.28-1.42) in 2017. The ASR of mortality decreased from 1.19 (95% UI: 1.13-1.25) in 1990 to 0.86 (95% UI: 0.82-0.89) in 2017, while ASR-DALYs decreased from 38.2 (95% UI: 35.9-40.2) in 1990 to 25.4 (95% UI: 24.4-26.5) in 2017. CONCLUSIONS: The ASR of incidence, mortality, and DALYs of nasopharyngeal carcinoma have decreased slightly worldwide. East Asia carried the heaviest burden of nasopharyngeal carcinoma. The majority of nasopharyngeal carcinoma burden was observed in men, especially among male aged 55 to 69 years.

HOXC10 promotes migration and invasion via the WNT-EMT signaling pathway in oral squamous cell carcinoma.

As a master regulator of embryonic morphogenesis, homeodomain-containing gene 10 (HOXC10) has been found to promote progression of human cancers and indicate poor survival outcome. Therefore, we concentrate on elucidating the role of HOXC10 in progression of oral squamous cell carcinoma (OSCC). In our study, the expression of HOXC10 was significantly increased in human OSCC samples and was significantly correlated with TNM stage and lymph node metastasis. Upregulation of HOXC10 indicated a poor overall survival of OSCC patients according to the Kaplan-Meier survival curves. Furthermore, HOXC10-knockdown dramatically suppressed migration, invasion, and expression of N-Cadherin, Vimentin and Snail, as well as increased E-cadherin level both in vivo and in vitro. Bioinformatics and cellular study further confirmed that HOXC10 may promote invasion and migration of OSCC cells by regulating the WNT/epithelial-mesenchymal transition (EMT) signaling pathway. These findings suggest that HOXC10 plays a pivotal role in the metastasis of OSCC and highlight its usefulness as a potential prognostic marker or therapeutic target in human OSCC.

Application of a new classification of chimeric anterolateral thigh free flaps.

BACKGROUND: The anterolateral thigh free flap is one of the most commonly used flaps in reconstructive procedures. The purpose of this study was to assess this new classification of chimeric anterolateral thigh free flaps. METHODS: Sixty-five patients underwent free anterolateral thigh chimeric free flap reconstruction of defects in the head and neck region. We summarized the anatomic features of perforators, including the number and origin of the perforators. RESULTS: Sixty-five cases of femoral anterolateral double island flaps were divided into 3 types: trunk type (type I), 11 cases (16.9%), in which the perforators of two flaps originated in the descending branch and the transverse branch of the lateral femoral circumflex artery; branch type (type II), 45 cases (69.3%), in which both the perforators originated in the descending branch or the transverse branch of the lateral femoral circumflex artery; and bifurcation type (type III), 9 cases (13.8%), in which two perforators originated in the bifurcation of one perforator that originated in the descending branch or the transverse branch of the lateral femoral circumflex artery. All 65 flaps survived and none showed partial necrosis. CONCLUSIONS: The anterolateral thigh chimeric flap can be divided into 3 types: trunk type (I type), branch type (II type) and bifurcation type (III type).

Prediction of Flap Compromise by Preoperative Coagulation Parameters in Head and Neck Cancer Patients.

PURPOSE: Studies on coagulation parameters (including activated partial thromboplastin time, prothrombin time, thrombin time, fibrinogen [FIB], platelet count, and D-dimer) in flap compromise are limited. The aim of the present study was to compare coagulation parameter variables in patients with and without flap compromise. MATERIALS AND METHODS: In this retrospective cohort study, patients were recruited from the Department of Oral and Maxillofacial Surgery at the Second Xiangya Hospital (Changsha, Hunan, China) from July 2016 through July 2017. The primary predictor variable was a set of coagulation parameters. The primary outcome variable was flap compromise. The other variables were age, gender, tumor stage, smoking, and prior radiotherapy. Descriptive, bivariate, receiver operating characteristic (ROC) curves and regression statistics were computed. Statistical significance was set at less than .05 with 95% reliability. RESULTS: A total of 503 patients with 42 compromised flaps were identified in this study. Venous thrombosis, arterial thrombosis, or no confirmed reason for compromise was observed in 28, 5, or 9 compromised flaps, respectively. Only FIB was associated with flap compromise or venous thrombosis at adjusted analyses, although the predictive values were low at ROC analysis. For patients with D-dimer lower than 0.4 µg/mL, the likelihood of venous thrombosis was greater than that for patients with D-dimer of at least 0.4 µg/mL (P = .0414). For patients with FIB lower than 3.5 g/L, the likelihood of venous thrombosis was greater than that for patients with FIB of at least 3.5 g/L (P = .0336). CONCLUSION: Decreased FIB was associated with a higher rate of flap compromise. In patients with D-dimer lower than 0.4 µg/mL or FIB lower than 3.5 g/L, the risk of venous thrombosis was higher.

Reconstruction design before tumour resection: A new concept of through-and-through cheek defect reconstruction.

OBJECTIVE: To explore a new method of reconstruction of through-and-through cheek defects and to evaluate this method's efficacy and patient prognosis. MATERIALS AND METHODS: This retrospective study included 70 patients who underwent reconstruction of through-and-through cheek defects. The surgical approach, design of facial skin incisions, selection and design of flaps, postoperative quality of life and prognosis of patients were recorded and reported. RESULTS: Postoperative quality of life gradually increased over time, and the mean scores of University of Washington Quality of Life (UW-QOL) Questionnaire was more than 80 at 1-year postoperatively. The appearance, oral competence, chewing, swallowing, speech and other oral functions were well recovered in about 90% of patients at 1-year postoperatively. CONCLUSION: This new idea of reconstruction before tumour resection, brings the effect of plastic and reconstructive surgery to a new height.

Unit resection of buccal squamous cell carcinoma: Description of a new surgical technique.

This study characterized the infiltration of primary tumors along the muscles, fascia and spaces of the maxillofacial region in buccal squamous cell carcinoma (BSCC) and suggested a new surgical strategy that is suitable for most stages. Based on the anatomic characteristics and infiltration of the primary tumor a new surgical approach - unit resection buccal surgery (URBS) - was developed. We evaluated this new surgical strategy, across a cohort of 127 BSCCs: 60 cases treated with URBS and 67 cases treated with conventional surgery. Notably there was no statistical difference in the clinicopathological variables between the two groups. After initial treatment with curative intent, the patients were regularly followed-up with clinical examination and imaging. URBS proved suitable for almost all stages of BSCC, and was particularly advantageous for advanced stages of BSCC. At 2 years post-treatment, the rates of overall survival were 83.3% in the URBS group and 60.1% in the conventional surgery group, respectively (hazard ratio 0.38; 95% CI 0.20 to 0.75; P=0.005). Similarly, the rates of disease-free survival were 76.6% and 51.9% in the URBS group and the conventional surgery group, respectively (hazard ratio 0.42; 95% CI 0.23 to 0.75; P=0.003). The principles of URBS are suitable for almost all stages of BSCC, especially advanced stages. URBS may improve the prognosis of BSCC patients.

CD73 is associated with poor prognosis in HNSCC.

CD73 is a cell surface immunosuppressive enzyme involved in tumor progression and metastasis. While patients whose cancer cells express elevated CD73 are typically associated with an unfavorable outcome, the clinical impact of CD73 expression in patients with Head and neck squamous cell carcinoma (HNSCC) remains unclear. In the present study, we investigated the prognostic significance of CD73 in HNSCC using gene and protein expression analyses. Our results demonstrate that high levels of CD73 are significantly associated with reduced overall survival in patients with HNSCC. We also investigated the functional role of CD73 in vitro and demonstrated that CD73 promotes HNSCC migration and invasion through adenosine A3R stimulation and the activation of EGF/EGFR signaling. Moreover, in vivo xenograft studies demonstrated that CD73 promotes tumorigenesis. In conclusion, our study highlights a role for CD73 as a poor prognostic marker of patient survival and also as a candidate therapeutic target in HNSCCs.

CD73 as a novel marker for poor prognosis of oral squamous cell carcinoma.

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.

Clinical Application of an Original Vascular Anastomosis: A Clinical Multicenter Study.

PURPOSE: Vascular anastomosis is the most important technical step required for the possibility of free tissue transfer, and mismatch of the donor and recipient vessel size is the most common surgical challenge. As recent reports have described a new method (Ren anastomosis) to resolve this challenge, the goal of this study was to assess these newly described microvascular anastomosis methods. PATIENTS AND METHODS: The study was conducted at 2 institutes in China in different periods. Patients were recruited from the Second Xiangya Hospital between February and May 2013 and from the Shanghai Ninth People's Hospital between March and May 2015. All patients who participated in this study needed free flaps for oral and maxillofacial defects. Patients were divided into the experimental group and the control group. In the experimental group, isometric double-notch end-in-end microvascular anastomosis (Ren anastomosis) was performed, whereas end-to-end anastomosis was performed in the control group. Statistical differences were assessed by use of χ2 and t tests. RESULTS: A total of 148 patients (108 men and 40 women) were treated over the course of this study. There was a statistically significant difference (P < .001) in the operation time for the microscopic artery anastomosis between the experimental group (70 cases; 5.6 ± 1.8 minutes) and the control group (78 cases; 14.6 ± 3.7 minutes). In each group, 1 case of artery compromise was observed. CONCLUSIONS: The Ren anastomosis was time-saving, straightforward, efficient, and easy to learn, with a high patency rate.