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Introduction: In early-stage oral tongue squamous cell carcinoma (OTSCC), elective neck dissection (END) is recommended when occult lymph node metastasis is suspected; however, there is no unanimous consensus on the risks and benefits of END in such cases. The management of clinically node-negative (cN0) OTSCC remains controversial. This study, therefore, aimed to evaluate the efficacy of END and its impact on the quality of life (QoL) of patients with cN0 OTSCC., Methods and Analysis: This is a prospective, multicentre, nonrandomised observational study. The choice of whether to perform END at the same time as resection of the primary tumour is based on institutional policy and patient preference. The primary endpoint of this study is 3-year overall survival. The secondary endpoints are 3-year disease-specific survival, 3-year relapse-free survival and the impact on patient QoL. Propensity score-matching analysis will be performed to reduce selection bias., Ethics and Dissemination: This study was approved by the Clinical Research Review Board of the Nagasaki University. The protocol of this study was registered at the University Hospital Medical Information Network Clinical Trials Registry. The datasets generated during the current study will be available from the corresponding author on reasonable request. The results will be disseminated internationally, through scientific and professional conferences and in peer-reviewed medical journals., Trial Registration Number: UMIN000027875., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Abstract: The aim of this study is to report the differences in clinicopathological features of oral tongue squamous cell carcinoma (OTSCC) and survival between adolescent and young adult (AYA) patients and elderly patients and to find the prognosticators. The medical records of 101 AYA patients and 175 control patients with OTSCC who underwent surgery were reviewed. Variables related to prognosis and their clinicopathological associations were analyzed. The 5-year overall survival (5y-OS) rates of AYA and control patients with stage I and II OTSCC were 94.4% and 89.6% (P = .353), respectively, and their 5-year disease-free survival (5y-DFS) rates were 82.0% and 76.6%, respectively (P = .476). The 5y-OS rates of patients with stages III and IV OTSCC were 83.3% and 66.7% (P = .333), respectively, and their 5y-DFS rates were 75.0% and 57.1% (P = .335), respectively. Logistic regression analysis revealed that there was no significant clinicopathological difference in AYA and control group. Furthermore, there was no significant difference in 5y-OS rates between patients who underwent elective neck dissection (END) and those who underwent therapeutic neck dissection (TND) in both group (P = 0.717 and 0.688). Overall, the present study revealed the clinicopathological features and prognosis of OTSCC were similar in AYA patients and elderly patients. Moreover, as there was no significant difference in OS between patients who underwent END and those who underwent TND in AYA and control groups, our results suggest that the indication for END in AYA patients with clinical N0 OTSCC is similar to that for elderly patients., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: In patients with advanced oral squamous cell carcinoma (OSCC), surgical treatment is often administered in combination with radiotherapy-based postoperative adjuvant therapy. The aim of the present study was to determine the most appropriate dose by comparing patient outcomes between doses of 50- and 66-Gy for postoperative cervical irradiation., Materials and Methods: This retrospective study included patients who underwent postoperative cervical irradiation following neck dissection for OSCC with lymph nodes metastases, and their primary lesions were controlled. They were divided into the 50- and 66-Gy irradiation groups and were examined for sex, age, primary lesion site, tumor/node/metastasis stage, initial treatment for primary cancer, neck dissection procedure, number of metastatic lymph nodes, presence or absence of extranodal extension (ENE), concomitant anticancer agents, and therapeutic outcomes., Results: A total of 78 patients met the clinical criteria for study enrollment. The 50- and 66-Gy postoperative cervical irradiation groups included 40 and 38 patients, with neck dissection performed at 45 and 38 sites, respectively. Cervical control rate was 97.5% and 97.3% in the 50- and 66-Gy irradiation groups (p = 0.74). The cumulative disease-specific 5-year survival rate was 85.6% and 88.3%, respectively, with no significant difference (p = 0.64)., Conclusion: The findings of our study indicate that the irradiation dose of 50 Gy is appropriate for postoperative cervical irradiation in patients with OSCC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Primary intraosseous carcinoma (PIOC), NOS is an odontogenic carcinoma with unknown etiology. Its diagnosis may be used when central jaw carcinoma cannot be categorized as any other type of carcinoma. Further information on this extremely rare tumor is needed to improve our understanding and evaluate the classification of odontogenic carcinomas., Case Presentation: We herein presented two patients with PIOC, NOS with different clinical and histopathological features and analyzed gene mutations in these patients using next-generation sequencing (NGS). The typical PIOC, NOS case had many histopathological similarities to oral squamous cell carcinoma (OSCC), including the missense point mutations of TP53 Glu285Val, KDR Gln472His, and APC Pro1433Leu, which are similar to those in other cancers; however, no mutations were detected in the other patient with an atypical presentation of PIOC, NOS, which was derived from a precursor cystic lesion with similarities to both ameloblastic carcinoma and OSCC., Conclusions: Genetic analysis suggested that these two PIOC, NOS cases have different features and can be subcategorized.

Background: Positron emission tomography with 2-deoxy-2-[18F] fluoro-d-glucose integrated with computed tomography (FDG-PET/CT) is a useful method to evaluate patients with oral squamous cell carcinoma (OSCC). However, the prognostic significance of FDG-PET/CT for assessing early OSCC remains unclear., Methods: Pretreatment FDG-PET/CT of 205 consecutive patients (125 men, 80 women, mean age 59.7 year old) with early OSCC (cT1-2N0M0) between June 2010 and December 2014 were retrospectively analyzed. FDG avidity in primary lesions was assessed by visual interpretation. Thereafter, maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured in primary lesions. The relationship between each parameter and recurrence free survival (RFS) was assessed using the log-rank test. The performance of FDG-PET/CT for diagnosing metastatic lesions and synchronous cancer was also assessed., Results: During the follow-up period (mean 32.9 months), 43 patients developed recurrences (21.0%). Patients with visually positive FDG uptake in primary lesions showed significantly shorter RFS than the others (63.0 months vs. 52.9 months, P = 0.005). In those patients, greater SUVmax, MTV, and TLG did not significantly predict shorter RFS. The sensitivity and specificity of FDG-PET/CT for cervical nodal metastases detection were 32.3% and 77.6%, respectively. FDG-PET/CT detected eight synchronous cancers (3.9%) and overlooked six synchronous cancers (2.9%)., Conclusions: Although its utility for detecting cervical nodal metastases and synchronous cancers is limited, FDG-PET/CT is a potentially prognostic indicator in early OSCC.

This clinico-statistical study includes 597 cases of oral squamous cell carcinoma treated at the Maxillofacial Surgery Section of Tokyo Medical and Dental University between January 2002 and December 2011. There were 373 male and 224 female patients (male to female ratio, 1.7 : 1), and the median age was 67 years. The tongue (53.3%) was the most commonly affected site. The 5-year disease-specific survival rate was 84.8%. Survival rates by clinical stage were as follows : Stage 1, 92.1% (n=195).; Stage , 86.0% (n = 221) ; Stage III, 77.7% (n=65) ; and Stage IV, 73.8% (n =116). Survival rates by primary site were as follows: tongue, 85.4% (n=318) ; lower gingiva, 82.8% (n =114) upper gingiva, 83.7% (n=59) ; buccal mucosa, 89.1% (n 54) ; oral floor, 81.4% (n=49) ; and hard palate, 100% (n=3). According to clinical growth patterns of Stage I / I tongue cancer cases, the 5-year disease-specific survival rate was significantly higher for patients with the exophytic/superficial type (97.3%, n =173) than for those with the endophytic type (77.5%, n=145). Among Stage I/II tongue cancer cases, the corresponding survival rate was significantly higher for patients who had not previously undergone invasive treatments (n=201), such as tooth extraction, compared to those who had previously done so (n=54) (92.7% and 79.7%, respectively). In addition, the incidence of secondary cervical lymph node metastasis was significantly higher in patients who had previously undergone invasive treatments.

To explore the mechanism of bone destruction associated with oral cancer, we identified factors that stimulate osteoclastic bone resorption in oral squamous cell carcinoma. Two clonal cell lines, HSC3-C13 and HSC3-C17, were isolated from the maternal oral cancer cell line, HSC3. The conditioned medium from HSC3-C13 cells showed the highest induction of Rankl expression in the mouse stromal cell lines ST2 and UAMS-32 as compared to that in maternal HSC3 cells and HSC3-C17 cells, which showed similar activity. The conditioned medium from HSC3-C13 cells significantly increased the number of osteoclasts in a co-culture with mouse bone marrow cells and UAMS-32 cells. Xenograft tumors generated from these clonal cell lines into the periosteal region of the parietal bone in athymic mice showed that HSC3-C13 cells caused extensive bone destruction and a significant increase in osteoclast numbers as compared to HSC3-C17 cells. Gene expression was compared between HSC3-C13 and HSC3-C17 cells by using microarray analysis, which showed that CXCL2 gene was highly expressed in HSC3-C13 cells as compared to HSC3-C17 cells. Immunohistochemical staining revealed the localization of CXCL2 in human oral squamous cell carcinomas. The increase in osteoclast numbers induced by the HSC3-C13-conditioned medium was dose-dependently inhibited by addition of anti-human CXCL2-neutralizing antibody in a co-culture system. Recombinant CXCL2 increased the expression of Rankl in UAMS-32 cells. These results indicate that CXCL2 is involved in bone destruction induced by oral cancer. This is the first report showing the role of CXCL2 in cancer-associated bone destruction., (Copyright © 2012 Elsevier Inc. All rights reserved.)

To determine whether staining with iodine solution provides an efficient criterion for determining the area of resection for the lesions surrounding squamous cell carcinoma (SCC) and leukoplakia of the tongue, we determined the optimum density of iodine solution and staining procedure and analyzed the color of lightly stained lesions (LSLs) in relation to the histopathologic findings. Sixty-five patients with SCC or leukoplakia of the tongue were divided into two groups: lesions stained with 3% Lugol solution and restained with either 5% Lugol solution (n=38) or 10% iodine glycerin (n=27). Among the lesions stained with 5% Lugol solution, significant differences were found in all color values. Color difference values (DeltaE*ab) using 3% and 5% Lugol solutions were significantly different between epithelial hyperplasia/mild epithelial dysplasia and moderate to severe dysplasia (P < 0.05). According to the evaluations of five clinicians in 46 LSLs, a distinctive boundary was most often obtained using 5% Lugol solution. These results suggest that the most effective method for obtaining a clear boundary and distinguishing moderate to severe dysplasia from mild or no epithelial dysplasia according to the measured color value was to stain with 3% followed by 5% Lugol solution.