Effectiveness of intraoral stents in reducing oral adverse events during radiotherapy for maxillary or nasal cavity malignant tumors.

PURPOSE: Many patients experience oral adverse events during head and neck cancer radiotherapy (RT). The methods of management of such events are under debate. One such technique is the intraoral stent (IOS) technique, which removes normal tissue from the irradiation field. This retrospective study examined the factors associated with the occurrence of oral mucositis (OM) and dysgeusia and the efficacy of IOSs in preventing them. METHODS: Twenty-nine patients who underwent RT in the maxilla or nasal cavity between 2016 and 2022 were included. They were investigated for background characteristics, treatment factors (IOS and dose-volume histogram), and oral adverse events (OM and dysgeusia). RESULTS: Significant risk factors for the incidence of grade ≥ 2 (Common Terminology Criteria for Adverse Events v5.0) OM were the non-use of IOSs (p = 0.004) and diabetes (p = 0.025). A significant risk factor for the incidence of grade ≥ 1 dysgeusia was concomitant chemotherapy (p = 0.019). The radiation dose to the tongue was significantly lower in the IOS group than in the non-IOS group. CONCLUSION: Our findings suggest that the use of an IOS during RT reduces the severity of OM by reducing irradiation to the tongue. Therefore, the use of an IOS is recommended during RT performed in the maxilla or nasal cavity.

Definitive radiotherapy for nasopharyngeal carcinoma in Japan: analysis of cases in the National Head and Neck Cancer Registry from 2011 to 2014.

OBJECTIVE: This study aimed to analyze the nationwide prognosis of patients with nasopharyngeal carcinoma who underwent definitive radiotherapy in Japan, utilizing the National Head and Neck Cancer Registry data. METHODS: A total of 741 patients diagnosed with primary nasopharyngeal carcinoma were screened from 2011 to 2014. The inclusion criteria were histologically proven nasopharyngeal squamous cell carcinoma, receiving definitive radiotherapy, and no distant metastases. Patients with unclear prognoses or unknown staging were excluded. The primary endpoint was 5-year overall survival, and secondary endpoints were 5-year progression-free survival and survival by stage. RESULTS: A total of 457 patients met the inclusion criteria. The median age was 60 years, and 80% were male. The proportions of patients with performance status 0, 1, 2 and 3 were 69, 10, 1 and 1%, respectively. Chemoradiotherapy was administered to 84.7%. Radiotherapy modalities were recorded only for 29 patients (three received intensity-modulated radiotherapy and 26 received two/three-dimensional radiotherapy). Of those included, 7.4, 24.7, 35.7, 24.5 and 7.7% had Stage I, II, III, IVA and IVB disease, respectively. The 5-year overall survival was 72.5% for all patients: 82.6, 86.6, 76.0, 51.4 and 66.5% for Stage I, II, III, IVA and IVB disease, respectively. The 5-year progression-free survival was 58.6%: 75.6, 66.8, 61.5, 43.7 and 46.5% for Stage I, II, III, IVA and IVB disease, respectively. CONCLUSIONS: This nationwide survey demonstrated favorable prognoses and provided valuable foundational data for similar future surveys to monitor the penetration of appropriate treatment and changes in clinical structures based on new evidence.

Impact of beta-tricalcium phosphate on preventing tooth extraction-triggered bisphosphonate-related osteonecrosis of the jaw in rats.

Antiresorptive or antiangiogenic drugs can cause medication-related osteonecrosis of the jaw that is refractory. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) may be caused by procedures such as tooth extraction damage the alveolar bone, release bisphosphonates (BPs) and impede healing. This study investigated strategies for BRONJ prevention and molecular mechanisms of its onset. We assessed the effectiveness of filling extraction sockets with beta-tricalcium phosphate (ß-TCP). Rats were administered zoledronic acid (ZA) 1.2 mg/kg once per week for 2 weeks, and a molar was extracted. They were randomly assigned to the ß-TCP group (bone defects filled with 0.01 g of ß-TCP) or control group. Tissue content measurements indicated 2.2 ng of ZA per socket in the ß-TCP group and 4.9 ng in the control group, confirming BP distribution and BP adsorption by ß-TCP in vivo. At 4 weeks after extraction, the ß-TCP group had normal mucosal coverage without inflammation. Moreover, at 8 weeks after extraction, enhanced bone healing, socket coverage, and new bone formation were observed in the ß-TCP group. Connective tissue in the extraction sockets suggested that local increases in BP concentrations may suppress the local autophagy mechanisms involved in BRONJ. Filling extraction sockets with ß-TCP may prevent BRONJ.

Evaluation of soft tissue changes around the nose following subspinal Le Fort â osteotomy.

PURPOSE: This study sought to evaluate the effect of subspinal Le Fort Ⅰ osteotomy (SLFⅠO) and alar base chinch suture (ABCS) in preventing postoperative changes of nasal shape following maxillary movement of advancement-impaction (MAI) or advancement-downward (MAD) by analyzing changes of nasal soft tissue on computed tomography (CT) images. METHODS: Forty-three Japanese patients with dentofacial deformity who underwent orthognathic surgery with SLFⅠO and ABCS were retrospectively examined. Maxillary movement and changes to soft tissues around the nose were analyzed using pre- and postoperative CT. RESULTS: Increased nasal width and alar base width, upturning of the nasal tip and flattening of the nose occurred in both groups, with more prominent changes in MAI. MAD showed horizontal maxillary movement strongly correlated with changes in pronasale and subnasale. Preoperative nasal height correlated negatively with changes to nasal height in both groups, and to nasolabial angle and nasal tip angle in MAD. There were no correlations between the tightness of ABCS during operation and postoperative nasal soft tissue changes including nasal width. CONCLUSION: Postoperative changes to nasal shape following SLFⅠO and ABCS need to be considered with advance movements of the maxilla, regardless of vertical maxillary movement. Postoperative pronasale and subnasale may be estimable from the amount of the maxillary advance movement in MAD. Postoperative changes in nasal shape may be more prominent in cases with low nasal height.

Cepharanthine and Oral Lichen Planus Efficacy (COLE) study: protocol for a multicentre randomised controlled study assessing the efficacy and safety of cepharanthine with topical corticosteroids in oral lichen planus.

INTRODUCTION: Oral lichen planus (OLP) is a chronic, inflammatory oral condition leading to a range of symptoms from mild discomfort to severe pain, affecting patients' quality of life. Standard therapy involves the use of topical corticosteroids, although some patients respond insufficiently or develop resistance to therapy. We aim to explore if adding cepharanthine, an herbal extract from Stephania cepharantha Hayata, can enhance the efficacy of corticosteroid therapy in symptomatic OLP. METHODS AND ANALYSIS: This open-label, parallel-group, multi-centre, randomised controlled study will be conducted at three Japanese hospitals. It will compare safety and efficacy of integrated oral cepharanthine and corticosteroid therapy versus standard corticosteroid therapy. 50 symptomatic OLP patients will be randomised 1:1 to receive cepharanthine (30 mg/day) plus topical dexamethasone, or topical dexamethasone alone for 8 weeks. The primary outcome will be changed in pain intensity while drinking room-temperature water, measured on a visual analogue scale. The primary outcome is the change in pain intensity from baseline when drinking room-temperature water, evaluated using a visual analogue scale. Secondary outcomes are changes in the longest diameter of the target lesion from baseline to weeks 4 and 8, improvement and deterioration rates according to appearance and severity criteria at weeks 4 and 8, change in pain intensity when drinking room-temperature water from baseline to week 4, changes in pain intensity at rest from baseline to weeks 4 and 8, and the rates of adverse events. ETHICS AND DISSEMINATION: This protocol was approved by the Certified Review Board of Nara Medical University (CRB5200002). Participants will provide informed consent. Results will be disseminated in peer-reviewed journals and conferences. TRIAL REGISTRATION NUMBER: Japan Registry of Clinical Trials (jRCTs051220130).

Summary of Japanese clinical practice guidelines for head and neck cancer - 2022 update edited by the Japan society for head and neck cancer.

The aim of the "Japanese Clinical Practice Guidelines for Head and Neck Cancer - 2022 Update" is to review the latest evidence regarding head and neck cancer and to present the current standard approaches for diagnosis and treatment. These evidence-based recommendations were created with the consensus of the Guideline Committee, which is composed of otorhinolaryngologists and head and neck surgeons, together with radiologists, radiation oncologists, medical oncologists, plastic surgeons, dentists, palliative care physicians, and rehabilitation physicians. These guidelines were created by the Clinical Practice Guideline Committee of the Japan Society for Head and Neck Cancer based on the "Head and Neck Cancer Treatment Guidelines 2018 Edition," and the revised draft was compiled after evaluation by the Assessment Committee and public comments. The 'Clinical questions and recommendations' section consists of 13 categories, and 59 clinical questions are described in total. Here we describe 6 clinical questions specific to other sets of guidelines with recommendations and comments.

Comparison of the 8th edition of TNM staging of oral cancer with the 7th edition and its prognostic significance using clinical depth of invasion and extranodal extension.

OBJECTIVES: The 8th edition of the International Union Against Cancer Control/American Joint Committee on Cancer Staging System introduced depth of invasion (DOI) and extranodal extension (ENE) into the staging of oral cavity cancer. We evaluated the prognostic ability of this new staging system compared with the 7th edition using clinical DOI (cDOI) and clinical ENE (cENE). MATERIALS AND METHODS: We retrospectively reviewed and restaged 2,118 patients with oral squamous cell carcinoma treated between 2001 and 2018 using cDOI and cENE. Overall and disease-specific survival were used as endpoints to compare the prognostic outcomes of the 7th and 8th editions using Harrell's concordance index (C-index). RESULTS: In total, 305 (14.4 %) cases were upstaged in the T category, 85 (4.0 %) cases were upstaged in the N category, and 280 (13.2 %) cases were upstaged in the overall TNM stage. The introduction of the cDOI increased the C-index and hazard ratio (HR) for each T category. The introduction of cENE increased the N3b category of 85 cases, bringing the total to 94 cases, thereby widening the differences between each N category. In the 8th edition, the C-index and HR for overall TNM stage increased, and the discrimination between stage groups improved. CONCLUSIONS: The 8th edition of the TNM clinical staging system using cDOI and cENE predominantly identified patients with a high mortality rate, thus improving the ability to discriminate and prognosticate oral cancer.

Measurement of Thickness at the Inferior Border of the Mandible Using Computed Tomography Images: A Retrospective Study including 300 Japanese Cases.

Vascularised fibular free flaps are integral to reconstructive surgery for head and neck tumours. We investigated the morphological characteristics of the mandible to improve the incidence of plate-related complications after surgery. Using standard radiological software, thickness measurements of the inferior or posterior margin of the mandible were obtained from computed tomography images of 300 patients at seven sites: (1) mandibular symphysis, (2) midpoint between the mandibular symphysis and mental foramen, (3) mental foramen, (4) midpoint between the mental foramen and antegonial notch, (5) antegonial notch, (6) mandibular angular apex (gonion), and (7) neck lateral border of the dentate cartilage. Relationships between age, sex, height, weight, the number of remaining teeth in the mandible, and the thickness of each mandible were also investigated. Measurement point 1 had the largest median mandibular thickness (11.2 mm), and measurement point 6 had the smallest (5.4 mm). Females had thinner measurements than males at all points, with significant differences at points 1, 2, 3, 4, and 7 (p < 0.001). Age and number of remaining teeth in the mandible did not correlate with mandibular thickness; however, height and weight correlated at all points except point 6. Thickness measurements obtained at the sites provide a practical reference for mandibular reconstruction. Choosing the fixation method based on the measured thickness of the mandible at each site allows for sound plating.

Volume-based 18F-fluorodeoxyglucose positron emission tomography/computed tomography parameters correlate with delayed neck metastasis in clinical early-stage oral squamous cell carcinoma.

OBJECTIVE: There is no known preoperative marker that can effectively predict the risk of delayed neck metastasis (DNM), which is an important factor that determines the prognosis of early-stage oral cancer. In this study, we examined whether 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET)/computed tomography (CT) uptake parameters of primary cancer can predict the risk of DNM in early-stage oral squamous cell carcinoma (OSCC). METHODS: Data from patients with stage I-II OSCC who underwent surgical resection of the primary tumor without elective neck dissection between January 2009 and December 2016 were retrospectively reviewed. Patient characteristics, histopathological factors, and PET/CT parameters (maximum standardized uptake value [SUVmax], metabolic tumor volume [MTV], and total lesion glycolysis [TLG]) were evaluated for their association with DNM. DNM rates were calculated, and the parameters that were statistically significant in the univariate analysis were used as explanatory variables. Independent factors associated with DNM were identified using multivariate analysis. For all statistical analyses, p-values < 0.05 were considered statistically significant. RESULTS: Data from 71 patients were analyzed in the study. The overall DNM rate among all patients was 21.8%. The univariate analysis showed that the T classification, depth of invasion, pattern of invasion, lymphovascular invasion, SUVmax, MTV, and TLG were significant predictors of DNM. However, the multivariate analysis revealed that only the depth of invasion, MTV, and TLG were independent predictors of DNM. CONCLUSION: This study suggests that, in addition to conventional predictors, volume-based PET parameters are useful predictors of DNM in those with early-stage OSCC.

Multicenter retrospective study of the prognosis and the effect of postoperative adjuvant therapy in Japanese oral squamous cell carcinoma patients with close margin.

BACKGROUND: The purpose of this retrospective study was to investigate the prognosis of patients with oral cavity cancer with positive margin (PM) or close margin (CM) divided into pN- and pN+ groups. METHODS: The evaluated endpoints were local control and disease-specific survival (DSS) rates. RESULTS: Higher T classification, lymphovascular space invasion (LVSI), and older age were significant risk factors for DSS in the pN- groups. On the other hand, extranodal extension, multiple lymph node metastases, and LVSI were significant risk factors for DSS in the pN+ groups. Among the CM pN+ patients, no significant differences in the 3-year DSS were observed between the only surgery (51.9%) and adjuvant groups (53.2%). CONCLUSIONS: Higher T classification and LVSI are high-risk features more than PM or CM in the pN- groups for DSS. However, further prospective studies are needed to demonstrate the usefulness of adjuvant treatment in patients with PM or CM.

Radiotherapy Plus Cetuximab for Squamous Cell Carcinoma of the Oral Cavity: A Multicenter Retrospective Study of 79 Patients in Japan.

There are a few reports that focus on radiotherapy (RT) and cetuximab (CET) therapy exclusively for oral cancer. This retrospective study aimed to investigate the efficacy and safety of RT and CET therapy for locally advanced (LA) or recurrent/metastatic (R/M) oral squamous cell carcinoma (OSCC). Seventy-nine patients from 13 hospitals who underwent RT and CET therapy for LA or R/M OSCC between January 2013 and May 2015 were enrolled in the study. Response, overall survival (OS), disease-specific survival (DSS), and adverse events were investigated. The completion rate was 62/79 (78.5%). The response rates in patients with LA and R/M OSCC were 69% and 37.8%, respectively. When only completed cases were examined, the response rates were 72.2% and 62.9%, respectively. The 1- and 2-year OS were 51.5% and 27.8%, respectively (median, 14 months), for patients with LA OSCC, and 41.5% and 11.9% (median, 10 months) for patients with R/M OSCC. The 1- and 2-year DSS were 61.8% and 33.4%, respectively (median, 17 months), for patients with LA OSCC, and 76.6% and 20.4% (median, 12 months) for patients with R/M OSCC. The most common adverse event was oral mucositis (60.8%), followed by dermatitis, acneiform rash, and paronychia. The completion rate was 85.7% in LA patients and 70.3% in R/M patients. The most common reason for noncompletion was an inadequate radiation dose due to worsening general conditions in R/M patients. Although the standard treatment for LA or R/M oral cancer is concomitant RT with high-dose cisplatin (CCRT) and the efficacy of RT and CET therapy for oral cancer is not considered to be as high as that for other head and neck cancers, it was thought that RT and CET therapy could be possible treatments for patients who cannot use high-dose cisplatin.

Changes in strain energy density in the temporomandibular joint disk after sagittal split ramus osteotomy using a computed tomography-based finite element model.

PURPOSE: We evaluated the changes in the strain energy density (SED) in the temporomandibular joint (TMJ) disk after sagittal split ramus osteotomy (SSRO) at three time points. A finite element model (FEM) based on real patient-based computed tomography (CT) data was used to examine the effect of SSRO on the TMJ. METHODS: Measurements of the condylar position and angulation in CT images and FEM analyses were performed for 17 patients scheduled to undergo SSROs at the following time points: before surgery, immediately after surgery, and 1 year after surgery. SED on the entire disk was calculated at each of the three time points using FEM. Furthermore, the relationship between individual SED values and the corresponding condylar position was also evaluated. RESULTS: No significant change was observed in the condylar position at the three time points. The FEM analysis showed that SED was the highest and lowest immediately after and 1 year after surgery, respectively. A possible SED distribution imbalance between the left and right joints was improved 1 year after SSRO. Concerning the effect of fossa morphometry and condylar position, wide and deep glenoid fossae and a more posterior condylar position tended to show lower SED. CONCLUSION: SED in the articular disk temporarily increased after surgery and significantly decreased 1 year after surgery compared with that before surgery. SSRO generally improved the imbalance between the left and right joints. Thus, SSRO, which improves maxillofacial morphology, may also improve components of temporomandibular disorders.

Peri-operative hemostatic management of tooth extraction in patients with hemophilia A, with and without inhibitors, receiving emicizumab prophylaxis.

INTRODUCTION: Emicizumab treatment may allow patients with hemophilia A without (PwHA) and with inhibitors (PwHA-I) to undergo some minor surgeries, such as tooth extraction, without peri-operative factor infusions. However, criteria for determining the necessity of factor infusions before minor surgeries are unknown. AIM: We report the peri-operative hemostatic management and outcomes of emicizumab-treated PwHA and PwHA-I cases who underwent tooth extractions using our institutional protocol. METHODS: We retrospectively evaluated PwHA and PwHA-I who underwent tooth extraction with emicizumab prophylaxis at our institution. Local bleeding risk was assessed based on the method, number, and site of tooth extraction. Hemostasis was monitored peri-operatively by rotational thromboelastometry (ROTEM). Hemostatic agents and a mouth splint were used. RESULTS: Twenty-nine extractions (17 interventions) were performed in eight PwHA and two PwHA-I. Based on ROTEM, pre-operative factor infusions were used in ten PwHA and four PwHA-I interventions. Among nine low local bleeding risk interventions, three (33.3%) each received no infusions, one dose of factor infusion pre-operatively, and pre- and post-operative factor infusions. All eight high local bleeding risk interventions involved planned factor infusions. Absorbable hemostats were used in all extractions. A mouth splint was used in 21/25 (84.0%) PwHA and in 4/4 (100%) PwHA-I extractions. No post-extraction bleeding or thrombotic events occurred. CONCLUSIONS: Use of a systemic hemostatic treatment plan according to the local bleeding risk, peri-operative coagulation status assessment using ROTEM, filling the extraction socket with hemostats, and use of a mouth splint can achieve effective and safe hemostatic management in emicizumab-treated PwHA and PwHA-I.

The Impact of Pretreatment Low Body Mass Index on Cause-Specific Mortality in Patients with Squamous Cell Carcinoma of the Oral Cavity.

The association between the pretreatment body mass index (BMI) and oral squamous cell carcinoma (SCC) outcomes is controversial. We aimed to examine the association between BMI and cause-specific mortality due to cancer of the oral cavity and patterns of failure that correlate with increased mortality. We enrolled 2,023 East Asian patients in this multicenter cohort study. We used the cumulative incidence competing risks method and the Fine-Gray model to analyze factors associated with cause-specific mortality, local recurrence, regional metastasis, and distant metastasis as first events. The median follow-up period was 62 mo. The 5-year cause-specific mortality for patients with underweight was 25.7%, which was significantly higher than that for patients with normal weight (12.7%, P < 0.0001). The multivariate model revealed that underweight was an independent risk factor for cause-specific mortality and regional metastasis (P < 0.05). Moreover, patients with underweight displayed a 51% and 55% increased risk of cause-specific mortality and regional metastasis, respectively, compared with their normal weight counterparts. Local recurrence was not associated with the BMI categories; however, the incidence of distant metastasis inversely decreased with BMI value. In summary, being underweight at diagnosis should be considered a high-risk mortality factor for oral SCC.

Multicenter retrospective study of nivolumab for recurrent/metastatic oral squamous cell carcinoma.

OBJECTIVES: Immunotherapy with nivolumab for patients with recurrent/metastatic oral squamous cell carcinoma has not been evaluated. Here, we aimed to examine the efficacy, safety, and prognostic factors of nivolumab in these patients. MATERIALS AND METHODS: This multicenter retrospective observational study involved patients who received nivolumab between April 2017 and June 2019. The patient characteristics were evaluated for association with progression-free and overall survival. Progression-free and overall survival rates were calculated; parameters that were significant in the univariate analysis were used as explanatory variables. Independent factors for progression-free and overall survival were identified using multivariate analysis. RESULTS: Totally, 143 patients were included. The overall response and disease control rates were 27.3% and 46.2%, respectively. The median, 1- and 2-year progression-free survival rates were 2.7 months, 25.4%, and 19.2%, respectively; those for overall survival were 11.2 months, 47.3%, and 33.6%, respectively. The independent factors affecting progression-free survival were performance status and immune-related adverse event occurrence, whereas those affecting overall survival were performance status, target disease, and number of previous lines of systemic cancer therapy. Eight patients reported grade ≥3 immune-related adverse events. CONCLUSION: Nivolumab was effective for recurrent/metastatic oral squamous cell carcinoma treatment and was well tolerated by patients.

Examination of Suprahyoid Muscle Resection and Other Factors Affecting Swallowing Function in Patients With Advanced Oral Cancer After Surgical Resection and Reconstruction.

Dysphagia is one of the most common adverse effects associated with oral cancer therapy and could greatly impair postoperative quality of life. The objective of this study was to analyze postoperative swallowing outcomes and factors influencing postoperative swallowing function in patients with advanced oral cancer who underwent primary reconstruction after surgical resection to identify patients at risk of experiencing severe dysphagia after immediate reconstruction of surgical defects, and to determine an ideal approach to provide appropriate perioperative interventions. The swallowing status was evaluated at 4 week postoperatively using the Functional Oral Intake Scale. We also analyzed the effects of patient, tumor, surgical, and other factors on postoperative swallowing function. The study included 67 patients. At 4 weeks postoperatively, 11 patients showed reduced swallowing function, whereas 56 patients showed good swallowing function. The number of resected suprahyoid muscles (odds ratio, 1.55; 95% confidence interval, 1.03-2.32; P=0.035) was an independent factor influencing postoperative swallowing function. Thus, among patients who underwent radical resection of oral cancer with primary reconstruction, those with extensive resection of the suprahyoid muscles were at higher risk of developing postoperative dysphagia. These findings are expected to facilitate increased vigilance for dysphagia, better counseling, and appropriate rehabilitation interventions.

An Axis between the Long Non-Coding RNA HOXA11-AS and NQOs Enhances Metastatic Ability in Oral Squamous Cell Carcinoma.

Long non-coding RNAs (lncRNAs) play critical roles in human cancers. HOXA11 anti-sense RNA (HOXA11-AS) is an lncRNA belonging to the homeobox (HOX) gene cluster that promotes liver metastasis in human colon cancer. However, its role and mechanism of action in human oral squamous cell carcinoma (OSCC) are unclear. In this study, we investigated HOXA11-AS expression and function in human OSCC tissues and cell lines, as well as a mouse model of OSCC. Our analyses showed that HOXA11-AS expression in human OSCC cases correlates with lymph node metastasis, nicotinamide adenine dinucleotide (NAD)(P)H: quinone oxidoreductase 1 (NQO1) upregulation, and dihydronicotinamide riboside (NRH): quinone oxidoreductase 2 (NQO2) downregulation. Using the human OSCC cell lines HSC3 and HSC4, we demonstrate that HOXA11-AS promotes NQO1 expression by sponging microRNA-494. In contrast, HOXA11-AS recruits zeste homolog 2 (EZH2) to the NQO2 promoter to suppress its expression via the trimethylation of H3K27. The upregulation of NQO1 enzymatic activity by HOXA11-AS results in the consumption of flavin adenine dinucleotide (FAD), which reduces FAD-requiring glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity and suppresses glycolysis. However, our analyses show that lactic acid fermentation levels are preserved by glutaminolysis due to increased malic enzyme-1 expression, promoting enhanced proliferation, invasion, survival, and drug resistance. In contrast, suppression of NQO2 expression reduces the consumption of NRH via NQO2 enzymatic activity and increases NAD levels, which promotes enhanced stemness and metastatic potential. In mouse tumor models, knockdown of HOXA11-AS markedly suppressed tumor growth and lung metastasis. From these findings, targeting HOXA11-AS may strongly suppress high-grade OSCC by regulating both NQO1 and NQO2.

Protocol for a multicentre, prospective observational study of elective neck dissection for clinically node-negative oral tongue squamous cell carcinoma (END-TC study).

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.

Oral melanoma: a multicenter study of 69 patients from Japan.

OBJECTIVES: The purpose of this multicenter retrospective study was to investigate the demographic characteristics and treatment outcomes of patients with mucosal malignant melanoma (MM) of the oral cavity. MATERIALS AND METHODS: This was a multicenter study involving 8 Japanese universities. The medical records of 69 patients who were diagnosed with primary oral MM between January 2000 and December 2020 were retrospectively analyzed. Overall survival (OS) and prognostic factors for OS were analyzed statistically. RESULTS: There were 40 (58.0%) males and 29 (42.0%) females, and their mean (range) age was 69.8 ± 14.6 (22-96) years old. The most common primary site was the palate (30 patients, 43.5%). Stage IVA was the most common disease stage (36 patients, 52.2%). Radical therapy was performed in 55 patients (79.7%). The 2-year and 5-year OS rates of the 69 patients were 64.6% and 42.5%, respectively. The 2-year and 5-year OS rates of the stage III patients were 85.9% and 72.5%, respectively, and those of the stage IVA patients were 56.3% and 26.0%, respectively. The 1-year OS rate of the stage IVB/IVC patients was 26.7%. The 2-year and 5-year OS rates of the radical therapy group were 74.1% and 50.5%, respectively, whereas the 2-year OS rate of the non-radical therapy group was 26.0%. An advanced T classification was the only identified prognostic factor for OS (hazard ratio: 6.312, 95% confidence interval: 1.133-38.522, p < 0.05). CONCLUSIONS: Early detection and radical treatment are essential for improving the prognosis of oral MM patients. CLINICAL RELEVANCE: Early detection and adequate radical therapy leads to the better prognosis of oral MM patients.

Prevalence of and risk factors for postoperative complications after lower third molar extraction: A multicenter prospective observational study in Japan.

Lower third molar extraction is the most common surgical treatment among routine dental and oral surgical procedures. while the surgical procedures for lower third molar extraction are well established, the difficulty of tooth extraction and the frequency of postoperative complications differ depending on the patient's background. To establish a management protocol for the lower third molars, the prevalence of and risk factors for postoperative complications after lower third molar extraction were investigated in a large number of Japanese patients in a multicenter prospective study. During 6 consecutive months in 2020, 1826 lower third molar extractions were performed at the 20 participating institutions. The medical records of the patients were reviewed, and relevant data were extracted. The prevalence of and risk factors for postoperative complications were analyzed. The prevalence of postoperative complications after lower third molar extraction was 10.0%. Multivariate analysis indicated that age (≤32 vs >32, odds ratio [OR]: 1.428, 95% confidence interval [95% CI]: 1.040-1.962, P < .05), the radiographic anatomical relationship between the tooth roots and mandibular canal (overlapping of the roots and canal vs no close anatomical relationship between the roots and the superior border of the canal, OR: 2.078, 95% CI: 1.333-3.238, P < .01; overlapping of the roots and canal vs roots impinging on the superior border of the canal, OR: 1.599, 95% CI: 1.050-2.435, P < .05), and impaction depth according to the Pell and Gregory classification (position C vs position A, OR: 3.7622, 95% CI: 2.079-6.310, P < .001; position C vs position B, OR: 2.574, 95% CI: 1.574-4.210, P < .001) are significant independent risk factors for postoperative complications after lower third molar extraction. These results suggested that higher age and a deeply impacted tooth might be significant independent risk factors for postoperative complications after lower third molar extraction.