Authorship：Lead author,　Corresponding author   Language：Japanese   Publisher：(一社)日本口腔腫瘍学会  

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: Depressed immune function is a serious adverse effect of long-term immunosuppressant or steroid administration at doses that exceed the physiologically required amount. The purpose of this study was to determine the effects of immunosuppression on carcinogenesis, particularly malignant tumor development, in patients with oral squamous cell carcinoma who had immunosuppression because of immunosuppressant therapy with or without steroid therapy administered for different underlying diseases. MATERIALS AND METHODS: In this retrospective chart review, 886 patients with oral squamous cell carcinoma who received treatment at the authors' department from April 2001 through December 2011 were included. Their clinical characteristics; tumor, node, and metastasis (TNM) stage; initial treatment for the primary cancer; mode of cervical lymph node metastasis; incidence rate of distant metastases; white blood cell, neutrophil, and lymphocyte counts on initial examination; and therapeutic outcomes were evaluated and compared between patients on and those not on immunosuppressant therapy with or without steroid therapy. Survival rates were calculated using the Kaplan-Meier method. RESULTS: Fourteen eligible patients (5 men, 9 women; mean age, 65.2 yr) were identified who were on immunosuppressant therapy with or without steroid therapy. They exhibited considerably more metastases, extracapsular spread, and distant metastases, and the number of metastases and extracapsular spread were statistically significant (P = .0213, P = .042, respectively). In 9 patients, total lymphocyte count in the peripheral blood was no higher than 1,500/μL, indicating the lower limit of the normal range. One patient died of recurrence of the primary tumor. Another patient died of cervical lymph node recurrence. Distant metastases occurred in 2 patients. The cumulative disease-specific 5-year survival rate of patients receiving immunosuppressive therapy was 62.3% and that of patients with cervical lymph node metastasis was 25%. CONCLUSION: The results of this study suggest that patients with oral squamous cell carcinoma on immunosuppression therapy show progression of cervical lymph node metastasis and extracapsular spread and are at high risk of developing distant metastases.

DOI： 10.1016/j.joms.2017.01.006

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Authorship：Lead author,　Corresponding author   Language：Japanese   Publisher：(公社)日本口腔外科学会  

62歳男。右側下顎臼歯部の自発痛を自覚後出現した全身倦怠感を主訴とした。口腔内に急性期の歯性感染巣は認めなかったが、血液検査にて強い炎症反応を認め、入院翌日に体温上昇と異常行動が出現した。CTでは右側頭葉に周囲への浮腫を伴うリング状陰影を認め、MRI拡散強調画像では同部位に高信号領域を認め、下顎歯性感染症から継発した脳膿瘍・硬膜下膿瘍と診断した。保存的治療では症状・画像所見ともに悪化したため、入院15日目に開頭による右側頭葉脳膿瘍および硬膜下膿瘍の排膿術を施行した結果、起炎菌は同定されなかったが術後症状・画像所見は改善した。入院45日目に独歩退院し、後遺症・症状再燃もなく予後良好である。

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Neck dissection is the most reliable treatment for cervical lymph node metastases in head and neck cancer. However, it is unknown whether neck dissection can cause dysphagia. The aim of this study was to evaluate swallowing function after neck dissection. METHODS: By using videofluoroscopic and videoendoscopic methods, swallowing function was evaluated in 17 patients prior to, 1 month after, and 4 months after neck dissection. RESULTS: In comparison with preoperative observations, swallowing function after neck dissection was affected by the following changes: a forward and downward displacement of the hyoid bone at rest and at its highest position, a decrease in the distance traversed by the hyoid bone during swallowing, and an increase in laryngeal penetration. Pharyngeal residue and aspiration were not observed in any of the patients. CONCLUSION: Although swallowing function is affected by neck dissection, serious clinical problems are not likely to occur.

DOI： 10.1002/hed.21275

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Authorship：Lead author   Language：Japanese   Publisher：山梨県立中央病院  

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Basal cell adenocarcinoma arising from the minor salivary gland is extremely rare. We report a 76-year-old Japanese man with basal cell adenocarcinoma originating in the upper gingiva. He underwent subtotal maxillectomy combined with resection of the coronoid process, and reconstruction was performed using a rectus abdominis microvascular flap. The patient has been followed for 40 months after operation without any evidence of disease.

DOI： 10.1016/j.tripleo.2008.11.003

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.jormas.2026.102745

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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

ABSTRACT

Background

Oral appliance (OA) therapy has gained wide acceptance for the management of obstructive sleep apnea (OSA). Although various types of OAs have been developed, the efficacy of the newer devices in patients with mild to moderate OSA remains unclear.

Objective

This systematic review aimed to evaluate the clinical efficacy of customized titratable OAs in improving sleep in adults with mild‐to‐moderate OSA.

Methods

A comprehensive literature search of the Medline, Embase, Scopus, the Cochrane Library, and Web of Science databases for relevant randomized controlled trials (RCTs), published between 2000 and 2025, was performed. The primary outcomes were the apnea–hypopnea index (AHI), oxygen desaturation index (ODI), Epworth Sleepiness Scale (ESS) score, and mean oxygen saturation (SpO ₂ ). The secondary outcomes included sleep efficiency and the percentage of total sleep time.

Results

Of the 1316 articles retrieved in the literature search, 122 fulfilled the inclusion criteria, including 32 RCTs that compared OAs with control interventions. Most studies reported significant improvements in AHI, with mandibular advancement devices demonstrating consistent efficacy across multiple trials. Improvements in the ESS, ODI, and SpO ₂ were also observed in several studies.

Conclusion

Customized, titratable OAs are effective in reducing AHI and improving sleep‐related outcomes in patients with mild‐to‐moderate OSA.

DOI： 10.1111/odi.70351

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/odi.70351

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BACKGROUND: This study aimed to investigate the survival impact and predictive factors of cervical lymph node metastasis (CLNM) in patients with maxillary gingival squamous cell carcinoma (MGSCC). METHODS: This retrospective study included 81 patients with MGSCC who underwent radical surgery from 2008 to 2018. RESULTS: Pathological CLNM was observed in 24 patients, prevalently in levels IB and II on the ipsilateral side. Cox proportional hazards model analysis revealed histologic grade, CLNM, and local recurrence as independent prognostic factors for 5-year disease-specific survival. Multivariate analysis identified tumoral spread to the gingivobuccal sulcus and the maxillary tuberosity as independent risk factors for CLNM. CONCLUSIONS: CLNM is associated with poor survival in patients with MGSCC. Primary tumors extending into the gingivobuccal sulcus or maxillary tuberosity may predict CLNM, particularly at levels IB and II. These findings may provide valuable insights for optimizing neck management strategies.

DOI： 10.1002/hed.70021

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Stevens-Johnson syndrome (SJS) is a rare, potentially life-threatening mucocutaneous disorder, which is often triggered by infections such as Mycoplasma pneumoniae. This report describes a 19-year-old woman who initially presented with oral erosions and painful blisters, along with fever and cough. Oral lesions preceded skin and ocular involvement, and tests confirmed Mycoplasma-associated SJS. She responded to steroid pulse therapy but relapsed at 3 months and was then successfully treated. Oral manifestations may be early SJS indicators; thus, prompt recognition and interdisciplinary care by oral health professionals are vital for improving clinical outcomes.

DOI： 10.2334/josnusd.25-0254

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Objective Patients with oral squamous cell carcinoma (OSCC) may choose best supportive care (BSC) as initial treatment over active treatment for several reasons. However, no previous reports have compared the clinical characteristics of OSCC patients opting for BSC as initial treatment with those receiving standard treatment. This study retrospectively analyzed these differences to identify the factors influencing this decision. Materials and methods This retrospective study was conducted at Niigata University Medical and Dental Hospital, using medical records within January 2018-December 2022 (follow-up until June 2023). Among 135 patients with primary OSCC, received BSC (BSC group) and underwent standard treatment according to the disease stage (non-BSC group). Data included demographic and tumor characteristics, Eastern Cooperative Oncology Group Performance Status (ECOG-PS), underlying diseases, neutrophil-lymphocyte ratio (NLR), albumin levels, living situation (with family, in a care facility, or alone), rationale for BSC selection (untreatable due to poor general condition or no desire for treatment), overall survival (OS) rate, and disease-specific survival (DSS) rate. Age, NLR, and albumin levels were assessed using Student's t-test. Stage classification, ECOG-PS, and living situation were analyzed using the chi-square test. OS and DDS were calculated using the Kaplan-Meier method and compared using the log-rank test. Multiple logistic regression analysis identified factors associated with BSC. Results  The BSC group included 11 males and 13 females (mean age: 84 years; range: 47-92). The non-BSC group included 67 males and 44 females (mean age: 67.4 years; range: 31-89). Female predominance was higher in the BSC group (male-female ratio: 1:1.2) than in the non-BSC group (1:0.7). Primary sites were the lower gingiva in the BSC and the tongue in the non-BSC group. The BSC group exhibited higher NLR (p=0.50) and a significantly lower albumin level (p<0.001). Stage classification (I/II vs. III/IV) and ECOG-PS (0-1 vs. 2-4) differed significantly between groups (p<0.001). Cardiovascular disease was the most frequent comorbidity in both groups. Living situation exhibited no significant differences (p=0.99). The cumulative one-year OS rate in the BSC group was 29.8%, compared to 97.2% and 81.5% in the non-BSC group at one and five years, respectively. The cumulative one-year DSS rate in the BSC group was 31.9%, and 97.2% and 82.8% at one and five years in the non-BSC group were p<0.001 for OS and DSS. Age (OR: 1.20, 95% CI: 1.10-1.36; p=0.0008), stage classification (I/II vs. III/IV) (OR: 13.79, 95% CI: 2.34-137.75; p=0.0026), psychiatric disorder (OR: 8.73, 95% CI: 2.34-137.75; p=0.021), albumin level (OR: 0.03, 95% CI: 0.002-0.24; p=0.003) were factors in BSC. Among patients aged ≥75 years, stage classification (I/II vs. III/IV) (OR: 19.08, 95% CI: 2.51-321.07; p=0.0027), albumin level (OR: 0.003, 95% CI: 9.0×10-6-0.098; p=0.01) remained significant predictors of BSC. Conclusion Patients opting for BSC tended to be older. Stage classification and albumin level were key factors in BSC across all patients, including those aged ≥75 years. Early diagnosis and timely intervention are vital to improve treatment opportunities. Collaborative discussions among patients, families, and healthcare providers are crucial to develop individualized care plans, ensuring that patients receiving BSC can approach end-of-life care with dignity.

DOI： 10.7759/cureus.89319

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Authorship：Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.7759/cureus.67882

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Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: The accurate assessment of the involvement of mandibular gingival squamous cell carcinoma (SCC) is essential for determining the extent of resection and is also useful for predicting lymph node metastasis and prognosis. The purpose of this study was to investigate the factors for predicting the prognosis. STUDY DESIGN: We reviewed 134 patients with mandibular gingival SCC treated between 2008 and 2017. The clinical findings, TN stage, relationship between radiographical type and histological pattern, and factors affecting the survival rate were investigated. RESULTS: The moth-eaten radiographic type was significantly associated with histologically infiltrative pattern. For all 134 cases, the 5-year OS was 89.5 %, and 5-year DSS was 93.9 %. The 5-year DSS was 95.0 % for cN0 and/or pN0 cases and 90.3 % for pN (+) cases, with a significant difference. The significant risk factors for lymph node metastasis were teeth extractions by previous physicians and moth-eaten radiographic type. CONCLUSION: The risk factor for poor prognosis was lymph node metastasis. In addition, teeth extractions by previous physicians and moth-eaten radiographic type were the risk factors for lymph node metastasis. It is recommended that these cases be treated considering the possibility of cervical lymph node metastasis.

DOI： 10.1016/j.heliyon.2023.e23120

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OBJECTIVES: This study aimed to investigate the relationship between postoperative reconstructed tongue flap volume (RTFV) and body mass index (BMI) and identify factors affecting the flap volume in patients with tongue squamous cell carcinoma. METHODS: Thirty-two patients were evaluated for RTFV from computed tomography images and BMI. The first and second evaluations were done at 6 months and 1.5 years after surgery respectively. RTFV rate changes and BMI differences from the first and second evaluations were calculated. The correlation between RTFV rate change and BMI difference was assessed using Spearman's rank correlation coefficient. Multiple regression analysis evaluated the relationship between the flap volume rate change and age, sex, flap type, and BMI difference to identify influencing factors. RESULTS: The flap volume rate change and BMI difference correlated significantly (r = .594, p < .05). BMI difference and flap type were independent factors that affected reconstructed flap volume rate change in multiple regression analysis (p < .05). CONCLUSION: The flap volume of patients with tongue squamous cell carcinoma correlates with the BMI change in the chronic phase. Patients after tongue reconstruction need to be well nourished to maintain BMI and thus postoperative tongue volume to maintain the quality of life. LEVEL OF EVIDENCE: Level 3.

DOI： 10.1002/lio2.1131

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Wnt signaling plays a crucial role in the progression of various cancers, including oral squamous cell carcinoma (OSCC). However, the tumor microenvironment (TME) regulating Wnt signaling has not yet been fully elucidated. In this study, we investigated whether cancer-associated fibroblasts (CAFs), the primary components of the TME, activate Wnt signaling and promote tumor progression in OSCC. We conducted a Transwell coculture assay using human OSCC cell lines and normal human dermal fibroblasts (NHDFs). NHDFs stimulated WNT7A expression in several OSCC cell lines, especially HO-1-N-1 and HSC-5. An immunohistochemical study using 122 human OSCC samples indicated that high WNT7A expression in tumor cells was significantly associated with invasion depth and poor prognosis. Moreover, WNT7A expression in OSCC cells was positively correlated with α-SMA expression in CAFs. WNT7A knockdown in OSCC cells demonstrated that OSCC cells cocultured with NHDFs significantly promoted tumor cell migration and invasion, which was dependent on WNT7A expression in OSCC cells. We also isolated HSC-5 cells from the coculture and conducted microarray analysis to investigate the factors that promote tumor progression induced by WNT7A. Among the various differentially expressed genes, we identified a downregulated gene encoding CLDN1 and confirmed that WNT7A negatively regulated CLDN1 expression in OSCC cells and CLDN1 knockdown in OSCC cells promoted their migration. Phospho-kinase array analysis showed that WNT7A activates protein kinase B (AKT) phosphorylation. Activating AKT signaling using the SC79 agonist induced CLDN1 downregulation in OSCC cells. In the coculture assay, the AKT inhibitor MK2206 significantly recovered CLDN1 expression downregulated by WNT7A, resulting in OSCC cell migration suppression. These results suggest that CAFs stimulate OSCC cells to produce WNT7A, following CLDN1 expression downregulation by activating AKT signaling, promoting cancer cell migration. These findings highlight the importance of molecular therapies targeting the TME in OSCC.

DOI： 10.1016/j.labinv.2023.100228

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The immune checkpoint inhibitor (ICI), nivolumab, has revolutionised the treatment of recurrent and metastatic oral cancer. However, the response rate to ICIs remains low, and identifying predictors of nivolumab response is critical. Although the neutrophil-to-lymphocyte ratio (NLR) has been suggested as a predictive marker of nivolumab response in patients with various types of cancer, its utility in oral squamous cell carcinoma (OSCC) has not been elucidated. In this retrospective multicentre cohort study, we evaluated the association between NLR and outcome of nivolumab treatment in 64 patients with OSCC treated between 2017 and 2020. The objective response and disease control rates were 25.1% and 32.9%, respectively. The rates for complete and partial responses were 15.7% (10/64) and 9.4% (6/64), respectively; stable and progressive disease rates were 7.8% (5/64) and 67.1% (43/64), respectively. Complete and partial responses were classified as responders, and stable and progressive diseases were classified as non-responders. The median (range) pre-treatment NLR among responders was 4.3 (2.8-8.0), which decreased to 4.0 (2.6-6.3) after nivolumab treatment, and the median (range) pre-treatment NLR among non-responders was 5.1 (2.7-7.9), which increased to 6.4 (4.0-14.0) with tumour growth. Moreover, overall survival was significantly worse in the group with a higher post-treatment NLR (≥5) than in the group with a lower NLR (<5). Patients with a post-treatment NLR of ≥6 had worse outcomes for salvage chemotherapy following nivolumab treatment. Thus, post-treatment NLR could be a useful marker for predicting the response to nivolumab treatment or salvage chemotherapy in patients with OSCC.

DOI： 10.1016/j.bjoms.2023.03.012

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BACKGROUND: This study aimed to determine the patterns of invasion of oral squamous cell carcinoma (OSCC) into the bucco-mandibular space (BMS) using detailed histopathological analysis and to assess clinical outcomes. METHODS: Patients with OSCC who underwent segmental mandibulectomy or hemi-mandibulectomy combined with resection of the BMS between 2012 and 2021 were included. The invasions of the BMS were classified into three patterns. Pattern A was defined as a horizontal invasion, Pattern B as a vertical invasion, and Pattern C as an expansive invasion. RESULTS: In total, 109 patients were reviewed. Of these 109 patients, the primary tumor affected the lower gingiva in 78 patients, the buccal mucosa in 18 patients, and was a primary intraosseous carcinoma of the mandible in 13 patients. Invasion of the BMS was significantly associated with a higher pathological T stage, positive/close margins, and lower disease-free survival (DFS) rates. The DFS rates were 86.7% and 66.0% in the BMS non-invasion and invasion groups, respectively. The DFS rates for each type of invasion were 82.1% for Pattern A, 67.4% for Pattern B, and 48.0% for Pattern C (P=0.277). CONCLUSION: Patients with BMS invasion have a poorer prognosis than those without invasion of the BMS. Therefore, adjuvant therapy is necessary, especially in Patterns B and C. Evaluation of preoperative BMS invasion patterns is important for predicting the prognosis of OSCC.

DOI： 10.3389/fonc.2023.1168376

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Language：English  

BACKGROUND: Oral liposarcoma is an extremely rare lesion that is often clinically misdiagnosed as a benign tumor due to its asymptomatic and indolent clinical course. Here, we report a case of massive low-grade myxoid liposarcoma (MLS) of the floor of the mouth. CASE SUMMARY: A 71-year-old man presented with a huge mass in the left floor of the mouth. A biopsy was performed, and a diagnosis of a myxoid tumor suspicious for low-grade MLS or myxoma was made. Gadolinium-enhanced T1-weighted magnetic resonance imaging showed an intensely enhanced tumor lesion that occupies the left sublingual space and extends to the submandibular space. Submandibular dissection, tumor resection, and reconstruction with a radial forearm flap were performed. The surgical specimen exhibited histologically low-grade MLS. Fused in sarcoma (FUS, also known as TLS) and DNA damage-inducible transcript 3 (DDIT3, also known as CHOP) break-apart was not detected in the fluorescence in situ hybridization analysis. The tumor was completely encapsulated and did not require additional treatment. Furthermore, no recurrence was reported 40 mo after surgery. CONCLUSION: We experienced an extremely rare, massive, low-grade MLS emerging from the floor of the mouth. Oftentimes, an MLS of the floor of the mouth lacks significant clinical findings and is often misdiagnosed. Although no FUS-DDIT3 fusion gene was detected, a low-grade MLS was ultimately diagnosed based on the histological findings.

DOI： 10.12998/wjcc.v10.i34.12742

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The present study aimed to investigate the clinical and biological significance of Src‑associated in mitosis 68 kDa (Sam68) in oral squamous cell carcinoma (OSCC). Immunohistochemical analysis was performed on tissue samples obtained from 77 patients with OSCC. Univariate analysis revealed that the high expression of Sam68 was significantly correlated with advanced pathological T stage (P=0.01), positive lymphovascular invasion (P=0.01), and pathological cervical lymph node metastasis (P<0.01). Moreover, multivariate analysis demonstrated that the high expression of Sam68 was an independent predictive factor for cervical lymph node metastasis (odds ratio, 4.39; 95% confidence interval, 1.49‑14.23; P<0.01). These results indicated that high Sam68 expression contributed to tumor progression, especially cervical lymph node metastasis, in OSCC. mRNA sequencing was also performed to assess the changes in the transcriptome between OSCC cells with Sam68 knockdown and control cells with the aim of elucidating the biological roles of Sam68. Gene Ontology enrichment analysis revealed that downregulated differentially expressed genes (DEGs) were concentrated in some biological processes related to epithelial‑mesenchymal transition. Among these DEGs, it was established that vimentin was particularly downregulated in these cells. It was also confirmed that Sam68 knockdown reduced the motility of OSCC cells. Furthermore, the immunohistochemical study of vimentin identified the association between vimentin expression and Sam68 expression as well as cervical lymph node metastasis. In conclusion, the present study suggested that the high expression of Sam68 may contribute to metastasis by regulating vimentin expression and a motile mesenchymal phenotype in OSCC.

DOI： 10.3892/or.2022.8398

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Language：Japanese   Publisher：(一社)日本口腔腫瘍学会  

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Comprehensive genomic profiling (CGP) provides information regarding cancer-related genetic aberrations. However, its clinical utility in recurrent/metastatic head and neck cancer (R/M HNC) remains unknown. Additionally, predictive biomarkers for immune checkpoint inhibitors (ICIs) should be fully elucidated because of their low response rate. Here, we analyzed the clinical utility of CGP and identified predictive biomarkers that respond to ICIs in R/M HNC. We evaluated over 1100 cases of HNC using the nationwide genetic clinical database established by the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) and 54 cases in an institution-based study. The C-CAT database revealed that 23% of the cases were candidates for clinical trials, and 5% received biomarker-matched therapy, including NTRK fusion. Our institution-based study showed that 9% of SCC cases and 25% of salivary gland cancer cases received targeted agents. In SCC cases, the tumor mutational burden (TMB) high (≥10 Mut/Mb) group showed long-term survival (&gt;2 years) in response to ICI therapy, whereas the PD-L1 combined positive score showed no significant difference in progression-free survival. In multivariate analysis, CCND1 amplification was associated with a lower response to ICIs. Our results indicate that CGP may be useful in identifying prognostic biomarkers for immunotherapy in patients with HNC.

DOI： 10.3390/cancers14143476

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BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphatic tumor; however, extranodal DLBCLs that exhibit initial symptoms in the maxilla and mandible are rare. Moreover, DLBCL is clinically classified as a moderate to highly malignant lymphatic tumor that can progress rapidly; therefore, early diagnosis is crucial. However, diagnosis is difficult as the disease causes a diverse range of clinical symptoms with no characteristic imaging findings. We conducted a clinical investigation to clarify the clinical characteristics of DLBCL that exhibits initial manifestation in the maxilla and mandible. METHODS: Of the 2748 patients with malignant tumors of the oral and maxillofacial region examined at our hospital during a period of 11 years between January 2006 and December 2016, 27 primary cases diagnosed with DLBCL based on the chief complaint of symptoms in the gingiva and bone of the maxilla and mandible were enrolled in this study. Evaluations were based on sex, age, whether treatment was provided by a previous physician, symptoms, duration of disease until treatment was sought, clinical diagnosis, laboratory findings, and imaging results. RESULTS: There were 15 cases that involved the maxilla and 12 that involved the mandible. The median duration of disease until treatment was sought was 60 d (3-450 d). All cases exhibited a tumor or a mass, and hypoesthesia of the chin was confirmed in eight cases wherein the mandible was involved. The clinical stages were stage I in eight cases, stage II in ten cases, and stage IV in nine cases. Serum lactate dehydrogenase (LDH) levels were elevated in 13 of 22 patients. The overall survival rate was 63%. CONCLUSIONS: Symptoms associated with nontender swelling and numbness of the lip or chin in the absence of other findings such as dental infections should raise suspicions about DLBCL. Patients should be provided appropriate imaging and accurate biopsy assessments to improve prognosis.

DOI： 10.1186/s12903-022-02056-x

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BACKGROUND: Metastasis of infradiaphragmatic tumors to the left supraclavicular lymph node is reported to be rare. When metastasis is detected in the left supraclavicular node in patients with head and neck carcinoma, locating the primary cancer remains a difficult and time-consuming challenge despite the dramatic development of screening technologies and treatment methods. CASE PRESENTATION: We report three cases of malignant infradiaphragmatic tumor diagnosed following an initial finding of left supraclavicular node metastasis after surgery for tongue squamous cell carcinoma (follow-up period, range 18-62 months). In these cases, adenocarcinoma was diagnosed based on left supraclavicular node biopsies, and a second primary tumor was found, in a 78-year-old Japanese woman with a diagnosis of cholangiocarcinoma, a 64-year-old Japanese man with a diagnosis of bladder carcinoma, and a 61-year-old Japanese man with a diagnosis of prostate carcinoma. In the cholangiocarcinoma case, carbohydrate antigen 19-9 and alpha-fetoprotein levels helped to diagnose cholangiocarcinoma. Palliative care only was given, with survival for 11 months after diagnosis of lymph node metastasis. In the bladder carcinoma case, pathological analysis of fine-needle aspiration biopsy specimen of the metastatic cervical lymph node showed atypical cells with slight squamous differentiation. Hematoxylin-eosin staining of the bladder lesion did not identify a clear glandular or squamous component, and we could not make a definitive diagnosis of whether the lesion was poorly differentiated squamous cell carcinoma, adenocarcinoma, or high-grade urothelial carcinoma. GATA3 staining aided in the diagnosis of urothelial bladder cancer with left supraclavicular node metastasis. He survived for 2 months after diagnosis of left supraclavicular lymph node metastasis. In the prostate carcinoma case, 18F-fluorodeoxyglucose uptake was weak. Prostate-specific antigen levels and magnetic resonance imaging findings aided the diagnostic process. This patient underwent bilateral orchiectomy and adjuvant hormonal therapy and survived for 47 months after diagnosis of left supraclavicular node metastasis. CONCLUSIONS: Pathological diagnosis on the basis of immunohistochemistry and specific diagnosis methods such as radiological and serological assessments are important for providing rapid diagnosis and appropriate treatment.

DOI： 10.1186/s13256-022-03261-6

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Patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M HNSCC) have a poor prognosis. Recently, the use of immune checkpoint inhibitors (ICIs) for drug treatment has been expanding . However, the response rate to immunotherapy is low. Therefore, the identification of predictive biomarkers of response and resistance to ICIs is required for various types of malignant tumors. We report the case of a patient with recurrent and metastatic HNSCC who simultaneously showed different responses to nivolumab in metastatic lesions. After administering nivolumab, metastasis to the multiple cervical lymph node metastases showed a significant reduction, whereas a new metastasis to the right axillary lymph node occurred . Each surgical specimen was analyzed using the cancer gene panel test (FoundationOne CDx) to elucidate why treatment response is distinct among the same patient. Next-generation sequencing revealed MYC amplification and programmed cell death-1 loss in the right axillary lymph nodes but not cervical lymph nodes. Furthermore, t he histopathological findings suggested that MYC amplification regulated programmed death-ligand 1 expression and was involved in a decreased response to ICIs. This result is expected to help predict the efficacy of ICI treatment and select therapeutic agents.

DOI： 10.1016/j.oraloncology.2021.105666

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OBJECTIVE: The study aimed to evaluate the clinical characteristics and outcomes of patients with metastatic tumors in the oral region. STUDY DESIGN: We conducted a retrospective study of 14 patients (11 men and 3 women; median age, 70.5 years) with metastatic tumors in the oral region diagnosed between 2005 and 2018. RESULTS: The primary tumors were located in the lung (n = 7), kidney (n = 3), renal pelvis (n = 1), thyroid (n = 1), stomach (n = 1), and bladder (n = 1). The most common histologic type of the tumor was adenocarcinoma (n = 6). The metastatic sites were the mandible (n = 7), tongue (n = 4), upper gingiva (n = 2), and maxilla (n = 1). In 6 patients, metastatic tumors were found in the oral region before the primary tumors were detected. The primary tumors were detected by positron emission tomography/computed tomography in 5 patients and by computed tomography alone in one patient. Seven patients received treatment for metastatic tumors in the oral region. The overall 1- and 5-year survival rates were 35.7% and 10.7%, respectively. CONCLUSIONS: It is important to detect metastatic tumors in the oral region and primary tumors as early as possible. Radical or palliative treatment should be performed if possible, considering the condition of the primary tumor and its metastasis to other organs.

DOI： 10.1016/j.oooo.2021.04.007

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Epithelial-myoepithelial carcinoma (EMC) is a rare salivary gland tumor that is histologically characterized by biphasic tubular structures composed of inner ductal and outer clear myoepithelial cells, which is especially uncommon in the minor salivary glands (MSG). Because of its histologic variety, complexity, and heterogeneity, it is sometimes challenging to make the accurate diagnosis. Here, we report a literature review of EMC of the MSGs with our experience of two cases. Incisional biopsy was suggestive of pleomorphic adenoma in Case 1 and pleomorphic adenoma or a low-grade salivary gland carcinoma in Case 2. Both cases were performed intraoral tumor resection, and they have good postoperative courses and are alive with no evidence of local recurrence or metastasis at 31 and 16 months, respectively. Considering that the anatomy, structure, and size of salivary glands are quite different from MSGs, it might be difficult to predict EMCs of the MSG similarly to EMCs of the major salivary glands. This comprehensive review also reports the features of EMC of the MSG cases and the trends of diagnosis and discusses treatment strategy.

DOI： 10.3390/diagnostics11112124

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The purpose of this study was to evaluate which radiological depth of invasion (r-DOI) measurement is the most concordant to clinical DOI (c-DOI) derived from correction for the shrinkage rate of the histopathological specimens. We retrospectively reviewed 128 patients with tongue carcinoma who had undergone glossectomy between 2006 and 2019. At first, the width shrinkage rate during formalin fixation and preparation process of histopathological specimens was evaluated. From the shrinking rates, a formula to calculate c-DOI from pathological DOI (p-DOI) was developed. The correlation between c-DOI and r-DOI was evaluated. The specimen shrinkage rate during the histopathological specimen preparation process was 10.3%. Based on that, we yielded the correct formula for c-DOI based on p-DOI and preparation shrinkage rate: c-DOI = p-DOI × 100/89.7. The regression equations for the association of c-DOI with r-DOI measured by ultrasound (n = 128), MRI before biopsy (n = 18), and MRI after biopsy (n = 110) were y = 1.12 * x + 0.21, y = 0.89 * x - 0.26, and y = 0.52 * x + 2.63, respectively, while the coefficients of determination were 0.664, 0.891, and 0.422, respectively. In conclusion, r-DOI using MRI before biopsy most strongly correlated with c-DOI.

DOI： 10.1038/s41598-021-00398-0

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Squamous cell carcinoma (SCC) of the tongue rarely metastasizes to the lingual lymph nodes (LLNs), which are inconstant nodes and often situated outside the areas of basic tongue tumor surgery. The current study evaluated the clinicopathological features and prognostic impact of LLN metastasis (LLNM), compared to that of cervical lymph node metastasis, in patients with tongue SCC. A total of 608 patients underwent radical surgery for tongue SCC at our department between January 2001 and December 2016. During neck dissection, we scrutinized and resected lateral LLNs, when present. Of the 128 patients with lymph node metastasis, 107 had cervical lymph node metastasis and 21 had both cervical lymph node metastasis and LLNM. Univariate analysis demonstrated that LLNM was significantly associated with the adverse features of cervical lymph node metastasis. The 5-year disease-specific survival (5y-DSS) was significantly lower in patients with LLNMs than in those without LLNMs (49.0% vs. 88.4%, P < 0.01). Moreover, Cox proportional hazards model analyses revealed that cervical lymph node metastasis at level IV or V and LLNM were independent prognostic factors for 5y-DSS. LLNM has a strong negative impact on survival in patients with tongue SCC. An advanced status of cervical lymph node metastasis may predict LLNM.

DOI： 10.1038/s41598-021-99925-2

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BACKGROUND: The scapular flap is the most versatile composite flap used for mandibular reconstruction. The purpose of this study was to review and summarize findings of cases of mandibular reconstruction with a scapular flap and describe associated outcomes and complications. METHODS: A total of 208 microvascular scapular free flaps were performed for mandibular reconstruction in a total of 205 patients from 2003 to 2018. This study involved a retrospective review of all eligible patients' medical records. RESULTS: There were seven cases (3.4 percent) of microvascular thrombosis. Postoperative bone union was achieved by 201 patients, except for five with total flap necrosis and two with partial flap necrosis. There were four cases (1.9 percent) of mandibular condyle dislocation. Two major types of complications were observed at the donor site, including four cases of infection and six cases of scapular body fracture. Postoperative denture prosthesis was introduced to 97 patients (47.3 percent). Implant treatment was performed in 10 patients (4.9 percent). Functional and aesthetic outcomes were good to excellent. CONCLUSIONS: The scapular composite free flap for mandibular reconstruction was associated with favorable outcomes and demonstrated satisfactory results. Although scapular bone fracture is rare, patients who have undergone mandibular reconstruction using a scapular flap should be monitored for its presence. . CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

DOI： 10.1097/PRS.0000000000008301

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BACKGROUND: Currently, sequential morphological changes of vascularized scapular bone for mandibular reconstruction have remained unreported. METHODS: We retrospectively analyzed 18 patients with defects on the lateral segment of the mandible who underwent postoperative computed tomography (CT) scanning at 1, 6, 12, and 24 months postoperatively. Using the cross-sectional coronal CT images during each assessment, we measured the height and thickness of the grafted scapular bone at points 10 and 30 mm away from the mesial segment and evaluated their differences over time. Then, the relationship between the morphological changes of the grafted scapular bone and the distance from the mesial bone segment, the number of occlusal supports on the contralateral side of the mandible, and the correlation of sex and age were evaluated. RESULTS: The height of the grafted scapular bone decreased by approximately 11% and its thickness increased by 14% within 24 months postoperatively. The bone thickness increase was greater at point 30 mm from the mesial bone segment. Patients with two occlusal contacts (premolar and molar) on the contralateral side had a significantly higher rate of bone thickness increase. Furthermore, the graft morphology was not associated with age or sex. CONCLUSION: A vascularized scapular bone thickens over time, which depends on the distance from the mesial bone segment and the occlusal contact regions on the contralateral side of the mandible.

DOI： 10.1016/j.bjps.2021.02.009

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The incidence of oral cancer in Japan accounts for 1% of all cancers, with oral tongue cancer accounting for 60% of oral cancers based on the subsite. The most common histologic type is squamous cell carcinoma. This study aimed to evaluate the series of surgical treatments for 432 patients with oral tongue squamous cell carcinoma (OTSCC). Initial surgical treatments for the primary site included partial glossectomy, hemiglossectomy, and total or subtotal glossectomy in 348, 58, and 26 patients, respectively. Therapeutic neck dissection, elective neck dissection, and subsequent neck dissection were performed in 74, 53, and 37 patients, respectively. Patients with advanced cases had level IIb, IV, and V metastasis and outside regional lymph node metastases. The cumulative 5-year disease-specific survival rate for OTSCC was 92.8%, and the rates for each stage were 96.6%, 93.9%, 84.1%, and 79.0% in stages I, II, III, and IV, respectively. The recurrence rate, overall salvage rate for recurrent cases, and rate for the additional surgical group were 10.4%, 46.7%, and 78.6%, respectively. Patients with multiple cervical lymph node metastases, extranodal extension, metastases to multiple levels, and lower neck metastases had poor prognosis. In conclusion, careful follow-up is necessary to detect recurrence of primary tumors at a stage when surgical treatment can be performed, and cervical lymph node status is one of the most important prognostic factors in OTSCC.

DOI： 10.35772/ghm.2020.01084

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BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory oral mucosa disease that is recognized as an oral potentially malignant disorder. However, the potentially malignant nature of OLP remains unclear. METHODS: We designed this study to examine the demographic and clinical characteristics of patients with OLP and evaluate the associated malignant transformation rate. A total of 565 patients with a clinical and histopathological diagnosis of OLP who presented at our department between 2001 and 2017 were retrospectively studied. Patients who had clinical and histopathological features of oral lichenoid lesions (OLLs) classified as oral lichenoid contact lesions, oral lichenoid drug reactions and oral lichenoid lesions of graft-versus-host disease were excluded. RESULTS: The study population included 123 men and 442 women aged 21-93 years (mean ± standard deviation, 60.5 ± 11.8). The 565 patients were followed up for a duration of 55.9 ± 45.3 months, during which 4 (0.7%) patients developed squamous cell carcinoma (SCC). In three of these 4 patients who developed SCC, the clinical type of OLP was the red type. CONCLUSIONS: Our results suggested that OLP was associated with a low risk of malignant transformation. We recommend regular follow-up for OLP patients and clear differentiation of oral epithelial dysplasia and OLLs to enable early detection of malignant transformation. Further investigation of the clinical risk factors associated with malignant transformation is necessary.

DOI： 10.1186/s12903-021-01652-7

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The control of distant metastasis in oral squamous cell carcinoma is an important determinant of improved prognosis. The study aimed to identify risk factors for distant metastasis in patients with locoregionally controlled oral carcinoma. We identified 982 patients with oral squamous cell carcinoma treated at our hospital between January 2008 and December 2017. After excluding patients with distant metastasis at initial treatment, patients with metastasis to the oral cavity, those receiving palliative treatment, and those lacking follow-up data, 941 patients were selected. Finally, among these 941 patients, 887 with locoregionally controlled oral squamous cell carcinoma were included in the study. Among the 887 patients, 36 had confirmed distant metastasis (4.1%), and the lung was the most common site (31/36 patients, 86.1%). Multivariate analysis showed that the incidence of primary intraosseous carcinoma of the mandible, cervical lymph node metastasis at levels IV and V, and the presence of pathological extranodal extension were significant risk factors for distant metastasis. When treating patients with oral squamous cell carcinoma who are positive for the aforementioned risk factors, the possibility of developing distant metastases must be accounted for, and aggressive treatment should be planned accordingly.

DOI： 10.1038/s41598-021-84704-w

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OBJECTIVE: The objective of this study was to investigate the prognostic effects of clinical and histologic findings in patients with mucoepidermoid carcinoma (MEC) of minor salivary glands. STUDY DESIGN: This retrospective clinical review included 63 patients (30 males, mean age 52.8 years) with minor salivary gland MEC treated at our hospital from 1994 to 2019. Overall survival (OS) or disease-free survival was determined using the Kaplan-Meier limit method. Correlations between different factors and survival rates were assessed using chi-square tests. RESULTS: The 10-year OS rate was 91.2%. Low- or intermediate-grade MEC had a good prognosis regardless of the surgical margin, whereas high-grade MEC had a poor 10-year OS rate (64.2%). Ten patients developed recurrence or metastasis after primary surgical resection, of whom 6 were diagnosed with a high-grade tumor. The most frequently affected site was the palate, whereas the mandibular gingiva was the most commonly affected site during recurrence. Of 4 patients who received chemotherapy and/or radiotherapy postsurgery, 2 had local recurrence and/or neck lymph node metastasis and 1 died from MEC. CONCLUSION: Patients with low- or intermediate-grade MEC exhibited satisfactory survival after surgery. In patients with high-grade tumors, it has been suggested that survival rates are poor and do not improve following adjuvant therapy.

DOI： 10.1016/j.oooo.2020.10.012

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BACKGROUND: Floor of the mouth (FOM) squamous cell carcinoma (SCC) accounts for approximately 10% of all oral SCCs. FOM SCC can be classified into the anterior and posterior types according to their site of origin, but few studies have compared these types. This study sought to clarify differences in clinicopathological characteristics between these two types. METHODS: A total of 1,220 patients with oral SCC were treated at our department from January 2001 to December 2015. Among these patients, 62 had FOM SCC. The FOM SCCs were classified into two groups: the anterior type and the posterior type. The anterior and posterior types were defined by the boundary connecting the spaces between the canine and the first premolar bilaterally. We retrospectively compared the sex, age, smoking and drinking history, clinical stage, treatment, histopathological diagnosis, multiple primary cancers, and outcomes of the two groups. RESULTS: Among the 62 patients, 32 had the anterior type, while 30 had the posterior type. The anterior type was found more significantly in men (p = 0.01) and individuals with a smoking history than the posterior type (p = 0.04). pN2-3 cervical lymph node metastasis was significantly more common in the anterior type than in the posterior type (p = 0.01). The median depth of invasion in the anterior type was 4 mm. Multivariate analysis showed that the anterior type was an independent risk factor for multiple primary cancer development in FOM SCC (p = 0.02). The cumulative 10-year disease-specific survival rates of the anterior and posterior types were 92.8 and 95.0%, respectively, while the overall survival rates were 65.4 and 95.0%, respectively. In the anterior type FOM SCC, a lower overall survival rate was associated with multiple primary cancers and smoking-related diseases. CONCLUSION: Smoking cessation and adequate systemic screening for multiple primary cancers are needed to improve the prognosis of FOM SCC, particularly the anterior type.

DOI： 10.3389/fonc.2021.682428

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Language：Japanese   Publisher：(公社)日本口腔外科学会  

血管吻合による遊離組織移植後に生じた皮弁のうっ血に対し、medical leechを使用した9例(男性4例、女性5例、平均64.9歳)について臨床的検討を行った。原疾患は口腔癌7例、放射線性下顎骨骨髄炎2例であった。うっ血確認までの時間は平均17.3時間、medical leechの使用日数は平均4.3日、使用数は平均12.6匹であった。静脈再吻合術を施行したが皮弁のうっ血が残存したためmedical leechを使用した4例の皮弁は生着した。吻合部血栓を認めなかった5例のうち3例は救済されたが、腹直筋皮弁と前外側大腿皮弁のそれぞれ1例が皮弁壊死をきたした。救済された3例と壊死した2例を比較検討したが、うっ血を確認するまでの時間、medical leechの使用日数と使用数において統計学的有意差は認めなかった。Medical leech療法は遊離皮弁術後のうっ血の改善に対して有効な治療法であると考えられた。

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Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Oral and Maxillofacial Surgeons  

DOI： 10.5794/jjoms.66.200

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症例は49歳女性で、健康診断で甲状腺の腫大を指摘された。甲状腺専門病院で甲状腺腫と診断され、6ヵ月ごとに経過観察を行っていた。1年半後に左側耳前部に腫瘤を認めたため某病院形成外科を受診、造影CTおよびMRIにて甲状腺左葉および左側下顎骨関節突起の腫瘤、両肺の多発結節を認めた。左側下顎骨関節突起の腫瘤の精査依頼にて当科初診となった。各種検査所見から左側甲状腺癌(T2N0M1、Stage IVC)、左側下顎骨関節突起転移、肺転移と診断した。甲状腺全摘、下顎の病変を切除後に肺転移に対して放射性ヨウ素内用療法を行う方針とした。甲状腺専門病院にて甲状腺全摘を施行し、その後全身麻酔下に下顎半側切除術を施行した。筋突起と下顎孔を含み、腫瘍から1cmの安全域を付与した高さで下顎枝を離断した。さらに、術後6ヵ月で甲状腺専門病院にて肺転移に対し放射性ヨウ素内用療法を開始した。病理組織学的に甲状腺濾胞癌の左側下顎骨関節突起転移と診断した。

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OBJECTIVE: Extraoral primary cancers (EPCs) can appear in patients with oral cancer. This study investigated the use of positron emission tomography/computed tomography (PET/CT) to detect EPCs and to identify characteristics of these cancers. The disease-specific survival rate and the overall survival rate were calculated. STUDY DESIGN: We studied records for 891 patients with oral cancer who underwent PET/CT between January 2006 and December 2016 for the detection of EPCs. RESULTS: A total of 35 EPCs were detected by PET/CT in 34 patients with primary oral carcinoma (3.8%). Of this total, 33 patients had 1 EPC and 1 patient had 2 EPCs. The extraoral lesions were found in the upper gastrointestinal tract (11), colon (6), lung (5), kidney (3), liver (2), prostate (2), breast (2), bladder (1), thyroid (1), pancreas (1), and hypopharynx (1). The disease-specific survival rate was 84.8% and the overall survival rate was 64.6%. CONCLUSIONS: PET/CT was useful for early detection of EPCs. The use of PET/CT for the early detection and treatment of EPCs with no symptoms can improve treatment outcomes.

DOI： 10.1016/j.oooo.2019.09.001

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PURPOSE: The buccinator and mandibular nodes belong to the facial lymph node group, and metastasis of oral cancer to these nodes is extremely rare. The purpose of this study was to examine particularly rare metastatic cases in which treatment was administered for the buccinator or mandibular nodes. PATIENTS AND METHODS: The authors identified 1,479 cases of oral squamous cell carcinoma treated at their hospital from April 2001 to December 2016. After excluding cases with distant metastasis at initial treatment, perioperative mortality, and lack of follow-up data, the final study population consisted of 1,406 cases. RESULTS: Six patients were identified who had pathologic metastasis to the buccinator or mandibular node (3 men and 3 women; age range, 45 to 72 yr; average age, 59.3 yr). The primary sites were the lower gingiva in 2 cases and the buccal mucosa in 4 cases. There were 2 cases of metastasis to the buccinator nodes and 4 cases of metastasis to the mandibular nodes. There were no cases of metastasis to the buccinator and mandibular nodes. Each case also involved submandibular node metastasis. The outcomes were disease-free survival in 4 cases and death from cancer in 2 cases; the cumulative disease-specific 5-year survival rate was 62.5%. CONCLUSIONS: The possibility of metastasis to the buccinator and mandibular nodes should be considered in oral cancer when primary tumor invasion reaches the buccinator muscle with submandibular node metastasis.

DOI： 10.1016/j.joms.2018.11.023

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BACKGROUND: Malignancies occur in approximately 1:1000 pregnancies; the most common being breast (46%) and hematological (18%) malignancies. Oral cancers account for only 2% of all cancers in pregnant women, and there are no standard guidelines for the treatment of oral cancer during pregnancy. METHODS: Between 2007 and 2014, our department managed 1109 patients with oral cancers; four (0.4%) had tongue carcinomas during pregnancy. These cases were retrospectively reviewed. RESULTS: The four women were aged 29-39 (median 32.5) years. Two underwent partial glossectomy at 39 and 40 weeks' gestation, respectively, one received radiotherapy at 17 weeks' gestation, and one underwent supraomohyoid neck dissection and hemi-glossectomy with a forearm flap reconstruction. CONCLUSION: In addition to tumor factors, the wishes of the patient and her family, gestational age, and fetal and maternal conditions are important factors in deciding on a treatment protocol. Moreover, treatment decisions require multidisciplinary approach.

DOI： 10.1186/s40463-019-0331-1

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OBJECTIVE: Odontogenic myxoma (OM) is a rare benign tumor that is frequently nonencapsulated and invades the surrounding bone, resulting in a high risk of recurrence. However, the optimal surgical technique and appropriate surgical margin remains controversial. Here, we report our clinical investigation of 12 patients with OM diagnosed histopathologically. STUDY DESIGN: We retrospectively reviewed the records of 12 patients treated at our institution. Osteotomy or bone shaving with enucleation was generally performed with 5-mm bony margins from the radiologic extent of the tumor. RESULTS: One half of the cases occurred in the maxilla and the other half in the mandible. Treatment for maxillary OM was enucleation in 2 patients and maxillectomy in 4 patients. Treatment for mandibular OM was enucleation with shaving of the surrounding bone in 1 patient and segmental mandibulectomy in 5 patients. Radiographs of surgical specimen removed by segmental mandibulectomy indicated that the mean distance between the tumor and the margin was 5.4 (range 3.4-7.0) mm. Tumor recurrence was noted in 1 patient who had undergone enucleation alone. CONCLUSION: The 1-cm surgical margin for OM, as reported conventionally, might not be necessary. A prospective study is needed to determine the appropriate surgical margin for OM.

DOI： 10.1016/j.oooo.2018.06.002

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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The interaction between cancer cells and the cancer stroma plays a crucial role in tumor progression and metastasis in diverse malignancies, including oral cancer. However, the mechanism underlying this interaction remains incompletely elucidated. Here, to investigate the interaction between oral cancer cells and fibroblasts, which are major cellular components of the tumor stroma, we conducted an in vitro study by using human oral squamous cell carcinoma (OSCC) cell lines and normal human dermal fibroblasts (NHDFs). The results of transwell assays revealed that the migration and invasion of 2 OSCC cell lines, HO1-N-1 and HSC3, were markedly stimulated upon coculturing with NHDFs. To investigate the factors that promote tumor invasion, we isolated NHDFs from cocultures prepared with HO1-N-1 cells and performed microarray analysis. Among the various genes that were upregulated, we identified the gene encoding leukemia inhibitory factor (LIF), and we focused on LIF in further analyses. We confirmed that all OSCC-derived conditioned media potently upregulated LIF expression in NHDFs, and the results of our transwell analysis demonstrated that NHDF-induced OSCC migration and invasion were inhibited by LIF-neutralizing antibodies. Furthermore, immunohistochemical analysis of patient samples revealed that in 44 out of 112 OSCC cases, LIF was expressed in the tumor stroma, particularly in cancer-associated fibroblasts (CAFs), and, notably, clinicopathological analyses confirmed that LIF expression in CAFs was significantly correlated with increased depth of tumor invasion. Collectively, our results suggest that OSCC stimulates fibroblasts to produce LIF, which, in turn, participates in cancer-cell invasion. Our finding offers a potential therapeutic strategy targeting the cancer stroma for the treatment of OSCC patients.

DOI： 10.1371/journal.pone.0191865

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OBJECTIVE: Analysis of the incidence and clinical relevance of neck failure after elective neck dissection (END) in patients with oral squamous cell carcinoma (OSCC). STUDY DESIGN: A retrospective study of 188 patients with OSCC without cervical lymph node metastases was conducted; these patients had undergone END from 2005 to 2015. The most common primary tumor location was lower gingiva, followed by tongue. RESULTS: Supraomohyoid neck dissection (SOHND) was the most common procedure. Neck failure developed in 4 pathologic negative (pN[-]) and 3 pathologic positive (pN[+]) patients. The site of neck recurrence was beyond the dissected field in all cases. The site of recurrence in pN(-) patients was ipsilateral in 2 patients and contralateral in 2, whereas the site in pN(+) patients was ipsilateral in 1 patient and contralateral in 2. CONCLUSIONS: Although neck failure after END can occur, SOHND is appropriate for END for OSCC. For tongue carcinoma, level IV dissection is recommended, and for tumors close to the midline, contralateral neck dissection is also recommended.

DOI： 10.1016/j.oooo.2017.03.003

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OBJECTIVE: We studied complications following multiple free flap reconstructions in the head and neck. METHODS: In this cohort, 26 patients (14 men and 12 women) who underwent multiple microvascular free flap reconstructions were included in the study. The reasons for secondary reconstruction were recurrence of tumor (12 cases), necrosis of transferred skin and/or bone (6 cases), reconstruction plate fracture or exposure (4 cases), and others (4 cases). A third reconstruction in 4 cases and a fourth reconstruction in 1 case were performed. RESULTS: No flap necrosis occurred. Postsurgical infections occurred at only secondary reconstructions in 7 patients. Although 4 cases with a history of external radiation therapy were anastomosed at contralateral side, those 4 cases suffered from severe pre-and postsurgical infection of the ipsilateral side. Postsurgical infection occurred in 2 cases with anastomoses at the ipsilateral side of the neck and required drainage after secondary surgery. CONCLUSIONS: A history of external radiation therapy and the existence of severe preoperative infection affected complications after multiple reconstructions.

DOI： 10.1097/GOX.0000000000001337

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48歳男。左側耳前部の腫瘤を主訴に受診した。腫瘤は直径22mm大、弾性やや硬で、皮膚との癒着は認めなかった。造影CTでは比較的境界明瞭な腫瘤として描出され、CT値は筋と同程度で均一であり、腫瘤辺縁に造影効果を認めた。MRIでは、T1強調像で腫瘤内部不均一な高信号、T2強調像で内部不均一な低信号を呈した。FDG-PET/CTで腫瘤部にFDGの軽度集積を認めた。これらの所見から「顎関節部腫瘍疑い」と臨床診断し、摘出術を行った。摘出標本の病理組織所見は、腫瘤周囲が線維性被膜に覆われ、被膜内側に毛細血管の増生や炎症細胞浸潤を伴う肉芽組織の増生を認めた。内部には赤血球成分を混じえたフィブリン網と凝血塊を認め、腫瘍性病変は認めなかった。これらより慢性拡張性血腫と診断した。術後経過は良好で、3年後の現在まで再発は認めていない。

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Recent studies have shown that Notch signaling is involved in many types of cancers, including oral squamous cell carcinomas (OSCCs). However, the role of Notch signaling in the tumor microenvironment is not yet fully understood. In this study, we investigated the roles of NOTCH3 signaling in cancer associated fibroblasts (CAFs) in OSCCs. Immunohistochemical study of 93 human tongue OSCC cases indicated that about one third of OSCCs showed NOTCH3 expression in CAFs, and that this expression significantly correlated with tumor-size. In vitro study showed that OSCC cell lines, especially HO1-N-1 cells stimulated NOTCH3 expression in normal human dermal fibroblasts (NHDFs) through direct cell-to-cell contact. Immunohistochemical and morphometric analysis using human OSCC samples demonstrated that NOTCH3 expression in CAFs significantly correlated with micro-vessel density in cancer stroma. In vitro angiogenesis assays involving co-culture of NHDFs with HO1-N-1 and human umbilical endothelial cells (HUVECs), and NOTCH3 knockdown in NHDFs using siRNA, demonstrated that HO1-N-1 cells significantly promoted tube formation dependent on NOTCH3-expression in NHDFs. Moreover, NOTCH3 expression in CAFs was related to poor prognosis of the OSCC patients. This work provides a new insight into the role of Notch signaling in CAFs associated with tumor angiogenesis and the possibility of NOTCH3-targeted molecular therapy in OSCCs.

DOI： 10.1371/journal.pone.0154112

PubMed

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PURPOSE: This study aimed to evaluate the coverage of oral wounds using either a polyglycolic acid (PGA) sheet or split-thickness skin grafting (STSG). MATERIALS AND METHODS: A total of 119 cases of wound coverage using a PGA sheet and fibrin glue spray as well as 132 cases of wound coverage cases using STSG were reviewed retrospectively. The site of the excision area, perioperative conditions, and postoperative functional problems were evaluated. RESULTS: The PGA group had significantly shorter operation time, earlier start of oral intake, and shorter hospitalization than the STSG group. If the PGA sheet over the wound with exposed bone could be protected by a surgical sprint, oral food intake could be started on the day after surgery at the earliest. When the size of the wound in the buccal excisional area was classified into two groups (<6 or ≥6 cm2), mouth opening in the STSG group was significantly larger at 3 months postoperatively. When the size of the wound in the tongue and floor of mouth was classified into two groups (<12 or ≥12 cm2), the STSG group had a significantly higher score in postoperative speech intelligibility. CONCLUSION: Selection of a PGA sheet or STSG based on the consideration of defect size, tumor location, patients' local and general condition and tolerance for surgery could reduce the patients' postsurgical dysfunctional problems.

DOI： 10.4103/2231-0746.200346

PubMed

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVES: This study aimed to clarify the clinical characteristics of multiple primary carcinomas of the oral cavity. MATERIALS AND METHODS: We retrospectively reviewed the cases of 1015 patients who were treated during follow up for oral cancer at Tokyo Medical and Dental University between March 2001 and December 2012. We compared the clinical characteristics of 961 patients who developed single primary oral squamous cell carcinoma (SCC) during follow up and 54 patients who subsequently developed multiple primary carcinomas in the oral cavity. RESULTS: Mean age at first diagnosis was significantly higher in patients with multiple primary carcinomas than single primary carcinoma. Multiple primary carcinomas showed a female predilection, were most prevalent in the gingiva, and tended to show earlier tumor and nodal stages than single primary carcinoma. The local recurrence rate was higher for multiple primary carcinomas than single primary carcinoma, and it increased with the number of multiple primary occurrences. The disease-specific survival rate at 10 years for patients with single primary carcinoma was 85.3% and that for patients with multiple primary carcinomas was 79.6%. The cumulative incidence rate for metachronous second multiple primary carcinomas after the onset of first carcinoma at 10 years was 8.0%. The recurrence of multiple primary carcinomas did not decrease the survival rate. CONCLUSION: Differences were found in the clinical characteristics between patients with single oral SCC and those with multiple primary oral carcinomas. Early diagnosis and treatment as well as close long-term follow up are needed for patients with multiple primary oral carcinomas.

DOI： 10.1016/j.oraloncology.2014.11.013

PubMed

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Language：English  

Chronic mandibular osteomyelitis is an intractable disease. In recent years, some case reports have related this disease process to synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome, which is chronic with frequent remissions and exacerbations. This report describes a case of chronic mandibular osteomyelitis suspected to be SAPHO syndrome. A 68-year-old woman presented with pain on the left side of the mandible. On the basis of clinical and radiological findings, chronic mandibular diffuse sclerosing osteomyelitis was initially diagnosed. We administrated oral clarithromycin (400 mg daily) and levofloxacin (500 mg daily), and her pain subsequently resolved. On (99m)Tc-labeled methylene diphosphonate scintigraphy, tracer uptake in the asymptomatic mandible was unchanged, but there was increasing tracer uptake in the sternocostal and sternoclavicular joints, compared with (99m)Tc-labeled methylene diphosphonate scintigraphic findings of the first visit. We diagnosed SAPHO syndrome and administrated oral sodium risedronate hydrate (2.5 mg daily). Although there has been no pain or swelling in the area of the left mandibular lesion, we have followed up on other skin and osteoarticular manifestations in conjunction with other medical departments.

DOI： 10.2147/JIR.S29981

PubMed

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Language：Japanese   Publisher：(一社)日本口腔腫瘍学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：Japanese Society of Oral and Maxillofacial Surgeons  

Cavernous hemangiomas rarely arise in the submandibular gland. We report a case of cavernous hemangioma in the submandibular gland that had atypical clinical symptoms and imaging findings.<BR>A 27-year-old man presented with intermittent pain and swelling in the right submandibular region in August 2007. Three years 6 months ago the patient had had colicky pain during a meal and was given a diagnosis of submandibular sialolithiasis at another university hospital. Extraoral examination revealed an elastic soft mass with well-demarcated borders in the right submandibular region. On oral examination, salivation from the right Wharton's duct was normal, and other findings were unremarkable. MRI demonstrated a well-demarcated tumor in the submandibular gland, which showed low-signal intensity on Tl-weighted images and heterogeneous highsignal intensity on T2-weighted images. Enhanced CT showed a poorly-defined intraglandular lesion and enlarged submandibular and upper jugular lymph nodes. On the basis of these preoperative findings, a malignant tumor was included in the differential diagnosis. The submandibular gland was extirpated to remove the tumor with intraoperative frozen section examination in October 2007. The tumor was histopathologically diagnosed as a cavernous hemangioma with chronic sialadenitis.<BR>Factors such as the characteristic blood flow of the cavernous hemangioma and the intraglandular location of the tumor may have caused the atypical features of this case.

DOI： 10.5794/jjoms.54.572

CiNii Article

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Other Link： https://jlc.jst.go.jp/DN/JALC/00320552326?from=CiNii

Language：Japanese   Publisher：(一社)日本口腔腫瘍学会  

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：English   Publisher：(一社)日本癌治療学会  

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J-GLOBAL

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J-GLOBAL

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(一社)日本顎関節学会  

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：English   Publisher：(一社)日本病理学会  

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：(一社)日本摂食嚥下リハビリテーション学会  

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Language：Japanese   Publisher：(一社)日本摂食嚥下リハビリテーション学会  

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Language：Japanese   Publisher：(一社)日本摂食嚥下リハビリテーション学会  

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Language：English   Publishing type：Research paper, summary (international conference)  

DOI： 10.1016/j.oraloncology.2013.03.194

Web of Science

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Language：English   Publishing type：Research paper, summary (international conference)  

DOI： 10.1016/j.oraloncology.2013.03.139

Web of Science

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：(一社)日本摂食嚥下リハビリテーション学会  

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：(一社)日本口腔腫瘍学会  

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Language：Japanese   Publisher：(一社)日本摂食嚥下リハビリテーション学会  

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(公社)日本口腔外科学会  

27歳男。3年前に右側顎下部から頸部にかけて疼痛を自覚し、その後も疼痛を繰り返していた。右側顎下腺に一致して弾性軟、可動性良好な3.5×3.0cmの腫瘤を触知した。MRIで腫瘍はT1強調像で低信号、T2強調像で内部不均一な高信号を呈し、ダイナミックMRIではGdにより経時的に辺縁から中心部に向かい不均一に造影された。造影CTでは腫瘍は内部不均一で顎下腺組織との境界不明瞭で、また右側顎下リンパ節および上内頸静脈リンパ節の腫大を認めた。術前の諸検査で悪性腫瘍の可能性を否定できず、摘出術を施行した。病理組織学的所見で、腫瘍に被膜は認めず、周囲の小葉を島状に解離し分け入るように増殖していた。腫瘍部には一層の扁平な内皮細胞により裏打ちされた大小不規則な血管腔を認め、内腔には赤血球の貯留を認めた。また腫瘍に隣接する顎下腺組織には腺房の萎縮・消失を認め、リンパ球を主体とする軽度の炎症性細胞浸潤を伴う広範囲な線維化がみられた。病理組織学的診断は慢性顎下腺炎を伴う顎下腺海綿状血管腫であった。術後8ヵ月経過して再発はない。

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Language：Japanese   Publisher：(公社)日本口腔外科学会  

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Language：Japanese   Publisher：(公社)日本口腔外科学会  

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Language：Japanese   Publisher：(公社)日本口腔外科学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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