IntroductionIn 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 analysisThis 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 disseminationThis 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 numberUMIN000027875.
Objective Epithelial–mesenchymal transition (EMT) plays an important role in cancer invasion and metastasis induced by hypoxia. Here, we examined whether phosphorylation of GSK3-β via ...phosphoinositide 3-kinase (PI3 K)/Akt signaling is involved in enhancing the hypoxia-induced EMT in oral squamous cell carcinoma (OSCC). Study Design Experiments were performed in OSCC cell lines (HSC-2, HSC-3, HSC-4, SAS, and HO-1-U-1) under normoxic or hypoxic conditions. The EMT was assessed by Matrigel invasion assays and wound healing assays. OSCC cell lines (HSC-2 and HSC-4) overexpressing hypoxia-inducible factor (HIF)-1α were established to examine the effects of HIF-1α on EMT-related factors. Immunohistochemical staining was performed to examine phosphorylation of GSK3-β in 33 cases of tongue squamous cell carcinoma. Results Under hypoxic conditions, OSCC cell lines exhibited HIF-1α expression and showed evidence of the EMT. In cells overexpressing HIF-1α, the levels of phospho-Akt and phospho-GSK3-β were increased, resulting in induction of the EMT. Inhibition of GSK3-β phosphorylation suppressed these effects. Moreover, the intensity of pGSK3-β staining was significantly increased with cN stage and cTNM stage in patients with tongue squamous cell carcinoma. Conclusions Our data showed that the hypoxia-induced EMT in OSCC was enhanced by GSK3-β phosphorylation, suggesting that GSK3-β may be important in the invasion and metastasis of OSCC.
The most important prognostic factor in oral squamous cell carcinoma (OSCC) is neck metastasis, which is treated by neck dissection. Although selective neck dissection (SND) is a useful tool for ...clinically node-negative OSCC, its efficacy for neck node-positive OSCC has not been established. Sixty-eight OSCC patients with pN1⁻3 disease who were treated with curative surgery using SND and/or modified-radical/radical neck dissection (MRND/RND) were retrospectively reviewed. The neck control rate was 94% for pN1⁻3 patients who underwent SND. The five-year overall survival (OS) and disease-specific survival (DSS) in pN1-3 OSCC patients were 62% and 71%, respectively. The multivariate analysis of clinical and pathological variables identified the number of positive nodes as an independent predictor of SND outcome (OS, hazard ratio (HR) = 4.98, 95% confidence interval (CI): 1.48⁻16.72,
< 0.01; DSS, HR = 6.44, 95% CI: 1.76⁻23.50,
< 0.01). The results of this retrospective study showed that only SND for neck node-positive OSCC was appropriate for those with up to 2 lymph nodes that had a largest diameter ≤3 cm without extranodal extension (ENE) of the neck and adjuvant radiotherapy. However, the availability of postoperative therapeutic options for high-risk OSCC, including ENE and/or multiple positive lymph nodes, needs to be further investigated.
Cholesterol embolism is a condition in which the atheroma in a large vessel wall collapses and cholesterol crystals leak into the bloodstream, causing periphery embolization, which may be caused by ...catheterization or cardiovascular surgery. In this paper, we describe a case of cholesterol embolism after superselective intra-arterial chemotherapy. The patient was an 81-year-old man with right oral-floor carcinoma （T2N1M0, stage Ⅲ）. Since the patient strongly desired to preserve organ function, he underwent a total of four superselective intra-arterial chemotherapy courses by the Seldinger method combined with radiotherapy （66Gy）. Before the fifth superselective intra-arterial chemotherapy course, right toe pain, purple-red spots, and sudden renal function decrease （serum Cr level; 1.92mg/dl, eGFR level; 26.9ml/min） were observed, and a histopathological diagnosis of cholesterol embolism was obtained from the tissue biopsy performed at the department of dermatology. Oral administration of steroids and prostacyclin preparations improved the right toe pain; however, renal function did not improve. After completing steroid therapy, the patient was followed up in the outpatient clinic. After 3 months, cervical lymph node resurgence was observed, and systemic drug therapy was initiated. After 10 months, the patient died of pneumonia. Reportedly, the Seldinger method causes cerebral infarction in approximately 1％ of cases. Conversely, cholesterol embolism, although extremely rare, is a disease with a poor prognosis and high probability of transitioning to hemodialysis. It is suggested that the disease should be fully considered when selecting treatment options.
Lymphoepithelial carcinoma (LEC) is a rare subtype of undifferentiated carcinoma with prominent lymphoid stroma consistently associated with Epstein-Barr virus (EBV) in Asian populations. We ...encountered a case of LEC of the floor of the mouth. In the present LEC, the EBV genome was not detected in tumor cells or tumor-infiltrating lymphocytes (TILs) by in situ hybridization. The invasive pattern of lymphoid infiltration in the present LEC was strongly characteristic. The TILs in this LEC were predominantly CD8+ and CD45RO+ T cells that invaded into and around tumor nests and islands. Moderate numbers of PD-1+ and FoxP3+ cells were also dispersed both within and between the tumor nests and islands. A profuse infiltrate of CD4+ T cells as well as some CD45RO+ T cells and a very few CD20+ B cells was mostly restricted to the tumor stroma. Membranous expression of PD-L1 on the tumor cells was not found in the entire lesion of the present LEC. These findings suggest that TILs in the present EBV-negative LEC might behave as tumor-suppressive immune cells in response to the invasion and proliferation of LEC.
Cases of diverticula of the buccal mucosa are extremely rare. Literature searches of databases such as PubMed/MEDLINE for this condition have revealed only 10 case reports. In this case report, we ...describe our experience in the management of this rare condition and review the previous 10 previously reported cases.
A 66-year-old man presented with a pouch containing inspissated food debris located posterior to the papilla of the parotid duct in his left buccal mucosa. The diagnosis of a diverticulum arising from the buccal mucosa was confirmed based on clinical and radiographic findings. Gross examination of the locally resected tissue specimen revealed a pouch measuring 14 mm in diameter and 8 mm in depth, that was whitish in color and had an elastic, soft, and smooth surface. Microscopic examination revealed a cyst-like lesion lined by stratified squamous epithelium and granulation tissue, with a chronic inflammatory infiltration in the peripheral stromal tissue of the epithelial layer. After surgical excision of the lesion, there was no recurrence during the follow-up period of 5 years and 10 months.
We have presented a rare case of a diverticulum of the buccal mucosa. This is the first report of a case confirmed not only by the clinicopathological findings, but also by computed tomography and magnetic resonance imaging findings. From the magnetic resonance imaging and intraoperative findings, we inferred that the diverticulum was caused by an idiopathic developmental anomaly due to a partial defect of the buccinator muscle.
Low-dose methotrexate is a standard treatment for rheumatoid arthritis (RA). Immunosuppressive therapies, including methotrexate (MTX), for patients with RA have long been implicated in the ...development of lymphoproliferative disorders (LPD), as so-called MTX-associated LPD. However, spontaneous remission of MTX-LPD has been observed after discontinuing MTX therapy for RA. The present study summarizes the clinical features from a review of the literature on patients with MTX-associated diffuse large B-cell lymphoma (DLBCL) and reports a case in which MTX-associated DLBCL showed spontaneous complete remission after withdrawal of MTX therapy.
Methotrexate (MTX) has been reported to be effective for the treatment of rheumatoid arthritis (RA) when a weekly low dose is administered to patients. We carried out microscopic examination of a ...biopsied specimen suspected of being Wegener’s granulomatosis, IgG4-related disease, or malignant lymphoma. Finally we diagnosed a rheumatoid nodule because his medical history included treatment with MTX. Then we immediately discontinued the MTX and his rheumatoid nodule disappeared after 2 months. Rheumatoid nodules are granulomatous nodules that appear subcutaneously and in tendons in the active phase of RA and commonly occur on the exterior part of the elbow joint and the back of the head where subcutaneous tissue is subject to recurrent pressure against bone. The development of an intraoral rheumatoid nodule in the maxillofacial region of a patient with RA who received MTX has not been few reported. To date, this patient has been followed up for 6 years without recurrence.
Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy. It accounts for 5% of all salivary gland tumors and 20% of salivary malignancies and has various clinical outcomes. Its ...prognosis is related to the tumor grade in the WHO classification of head and neck tumors. MEC is divided into high, intermediate and low grades. In general, low-grade MEC with cervical lymph node metastasis is rare, and primary MEC that occurs in a minor salivary gland with cervical lymph node metastasis is very rare. Low-grade lesions have quite different behavior from high-grade ones, leading to differences in the treatment course required for disease control.
MEC is associated with recurring chromosomal translocation t(11;19)(q21;p13). CRTC1-MAML2 gene fusion was identified from the recurring translocation, which is often the sole cytogenetic alteration in this disease. This fusion transcript is detected frequently in MEC and is involved in the transformation of epithelial cells. Detection of the CRTC1-MAML2 fusion transcript is associated with a less advanced clinical stage and low-grade tumor histology. The presence of the transcript is associated with longer disease-free and overall survival periods.
Here, we report a rare case of low-grade MEC with cervical lymph node metastasis. The findings for this patient show that the CRTC1-MAML2 fusion transcript may be specific to MEC, and associated with a distinct MEC subset that exhibits favorable clinicopathologic features.
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