Large Palatal Pleomorphic Adenoma Complicated by Dysphagia: A Case Report.

A 60-year-old Japanese woman presented with a palatal pleomorphic adenoma measuring 5 cm in size. In addition to impairments during the oral preparatory and oral transport phases, dysphagia with nasopharyngeal closure disorder was observed in the pharyngeal phase. After resection of the tumor, dysphagia resolved, and the patient was immediately able to eat a standard meal. A videofluoroscopic swallowing study confirmed improvement in the movement of the soft palate compared with the pre-operative condition.

Somatic mutations in oral squamous cell carcinomas in 98 Japanese patients and their clinical implications.

INTRODUCTION: The somatic mutational profile of oral squamous cell carcinoma (OSCC) among Japanese patients has been less investigated, partly because of the rarity of the tumor. Moreover, previous studies have either used formalin-fixed paraffin-embedded samples or lacked paired normal tissues. We aimed to determine somatic mutations in the exomes of 76 genes, including 50 driver genes of solid cancers and NOTCH-related genes, some of which are previously reported as frequently mutated in head and neck squamous cell carcinoma or OSCC. MATERIALS AND METHODS: We used fresh-frozen tumor/normal-paired samples from 98 treatment-naïve Japanese patients with OSCC and analyzed their correlations with clinicopathological characteristics and survival. RESULTS: We identified 136 exonic mutations, including 78 non-synonymous mutations, 13 synonymous mutations, 22 nonsense mutations, 2 non-frameshift deletions, 11 frameshift deletion, and 5 each of splice-site and frameshift insertions. The most frequently mutated genes were TP53 (36.7%), FAT1 (9.2%), NOTCH1 (8.2%), CDKN2A (7.1%), ZFHX4 (5.1%), CASP8 (4.1%), EP300 (4.1%), and KMT2D (4.1%). We followed up 90 of the 98 patients for 3 years. Among them, TP53 mutation was associated with significantly shorter 3-year disease-free survival. Most of the identified TP53 mutations occurred in the DNA-binding domain and were functionally deleterious. DISCUSSION: Our findings and the mutation spectra can contribute to the development of a therapeutic strategy for Japanese patients with OSCC.

New PCNT candidate missense variant in a patient with oral and maxillofacial osteodysplasia: a case report.

BACKGROUND: Osteodysplasia of the oral and maxillofacial bone is generally accompanied by systemic bone abnormalities (such as short stature, joint contracture) or other systemic abnormalities (such as renal, dermatological, cardiovascular, optic, or hearing disorders). However, it does not always present this way. Recent reports have suggested that genome-wide sequencing is an effective method for identifying rare or new disorders. Here, we performed whole-exome sequencing (WES) in a patient with a unique form of acquired, local osteodysplasia of the oral and maxillofacial region. CASE PRESENTATION: A 46-year-old woman presented to our hospital with the complaint of gradually moving mandibular teeth (for 6 months), changing facial appearance, and acquired osteolysis of the oral and maxillofacial bones, showing mandibular hypoplasia without family history. Upon skeletal examination, there were no abnormal findings outside of the oral and maxillofacial area; the patient had a height of 157 cm and bone mineral density (according to dual energy x-ray absorptiometry) of 90%. Results of blood and urine tests, including evaluation of bone metabolism markers and neurological and cardiovascular examinations, were normal. We performed WES of genomic DNA extracted from the blood of this patient and her mother, who did not have the disease, as a negative control. We identified 83 new missense variants in the patient, not detected in her mother, including a candidate single nucleotide variant in exon 14 of PCNT (pericentrin). Critical homozygous or compound heterozygous variants in PCNT are a known cause of microcephalic osteodysplastic primordial dwarfism type II accompanied by mandibular hypoplasia, which is similar to the maxillofacial phenotype in this patient. CONCLUSIONS: Protein simulations performed using Polymorphism Phenotyping v2 and Combined Annotation Dependent Depletion software indicated that this missense variant is likely to disrupt the PCNT protein structure. These results suggest that this is a new form of osteolysis related to this PCNT variant.

Trousseau syndrome in a patient with advanced oral squamous cell carcinoma: a case report.

BACKGROUND: Trousseau syndrome is known as a variant of cancer-associated thrombosis. Trousseau syndrome commonly occurs in patients with lung or prostate cancer. Hypercoagulability is thought to be initiated by mucins produced by the adenocarcinoma, which react with leukocyte and platelet selectins to form platelet-rich microthrombi. This is the first report of Trousseau syndrome in a patient with oral cancer. CASE PRESENTATION: Here, we describe the case of a 61-year-old Japanese man diagnosed as having advanced buccal carcinoma (T4bN2bM1; the right scapula, erector spinae muscles, and the right femur), who experienced aphasia and loss of consciousness. Although magnetic resonance imaging showed cerebral infarction, carotid invasion by the tumor and carotid sheath rupturing, cardiovascular problems, and bacterial infection were not present, which indicated Trousseau syndrome. CONCLUSIONS: Trousseau syndrome in oral cancer is rare, but we must always consider cancer-associated thrombosis in patients with advanced stages of cancer regardless of the primary site of the cancer and take steps to prevent it.

To what extent does the EQ-5D-3L correlate with the FACT-H&N of patients with oral cancer during the perioperative period?

BACKGROUND: The EuroQol 5-dimension scale (EQ-5D) is one of the most frequently used preference-based quality of life (QOL) measures for health technology assessment. The 3-level version of the EQ-5D comprises a descriptive system (the EQ-5D-3L) and a visual analog scale (EQ-VAS). It remains unclear whether this five-item scale correlates with the QOL of patients with oral cancer during the perioperative period. We sought to clarify this point in the present study. METHODS: Participants were 84 patients with oral malignancies who underwent radical treatment and completed the EQ-5D-3L and Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N) at regular intervals over 3 months after treatment. We analyzed the correlations between the EQ-5D-3L, EQ-VAS, and FACT-H&N, and conducted multiple regression analyses to examine how the FACT-H&N subscales relate to the EQ-5D-3L and EQ-VAS. We also investigated whether the EQ-5D-3L shows ceiling effects. RESULTS: The EQ-5D-3L and EQ-VAS were strongly correlated with the FACT-H&N (rs = 0.621 and 0.638, respectively; P < 0.01). Furthermore, the EQ-5D-3L was significantly related with all FACT-H&N subscales except for social/family well-being. Particularly, the physical well-being subscale had the strongest relationship with the EQ-5D-3L. The FACT H&N and EQ-5D-3L showed similar changes over time. The EQ-5D-3L did not have a ceiling effect statistically. CONCLUSIONS: Our results indicate that actual physical performance might be most important for cost-utility analysis, whereas the assessment of familial feelings or friendship seems less important. However, the EQ-5D-3L appears to generally correlate with the FACT-H&N of patients with oral cancer during the perioperative period. Therefore, it is reasonable to assess the cost performance of oral cancer treatment using the EQ-5D-3L in Japan.

Longitudinal changes in the quality of life of oral cancer patients during the perioperative period.

BACKGROUND: There are few quality of life (QOL) studies that have focused on the experiences of oral cancer patients. Therefore, the present study aimed to investigate how the QOL for patients with oral cancer changed perioperatively. METHODS: Eighty-three participants undergoing radical therapy completed assessments of QOL at pre-treatment, treatment completion, and 1-, 3-, and 6-months post-treatment. The Japanese version of the FACT-H&N, comprising the subscales of "physical well-being (PWB)," "social/family well-being (SWB)," "emotional well-being (EWB)," "functional well-being (FWB)," and "additional head- and neck-specific concerns(HN)" was used to assess QOL. There were two study groups: those who required reconstructive surgery (r+, 31 patients) and those who did not (r-, 52 patients). RESULTS: The FACT-H&N, PWB, FWB, and HN, were lowest at treatment completion due to declines; then, it showed significant improvement over time (p < 0.05). SWB was the highest at the completion of treatment, and thereafter decreased significantly until 3 months after treatment (p < 0.05). EWB was the lowest before treatment but improved over time (p < 0.01). HN was significantly lower at 6 months after treatment than before treatment (p < 0.05). The QOL of the r+ group was significantly lower than that of the r- group (p < 0.01). CONCLUSIONS: The treatment-associated declines in subscale area may be compensated for by gains in other subscale areas. Psychological support is better introduced prior to cancer treatment. As it is often difficult to recover from declines in HN functioning subscale, strategies that promote compensation in other areas must be explored. Clinicians should become thoroughly familiar with how patients' QOL changes over time and provide holistic treatments that honor patients' autonomy.

Lateral retropharyngeal lymph node metastasis from squamous cell carcinoma of the upper gingiva: A case report.

Lateral retropharyngeal lymph node (LRPLN) is located between the internal carotid artery and the prevertebral muscles. Metastasis to the LRPLN is frequent in nasopharyngeal cancer, but is rare in oral cancer. The prognosis of patients with oral cancer with LRPLN metastasis is usually poor. The present study reported a patient with LRPLN metastasis from squamous cell carcinoma of the upper gingiva, who survived for >7 years. Docetaxel, cisplatin and fluorouracil (TPF) therapy was performed as induction chemotherapy and it was planned to subsequently conduct chemoradiotherapy or surgery. As the tumor only exhibited a transient response to TPF, surgery was selected. Postoperatively, only radiotherapy was performed and a favorable outcome was achieved.

A mutation in NOTCH1 ligand binding region detected in patients with oral squamous cell carcinoma reduces NOTCH1 oncogenic effect.

NOTCH1 is known as an oncogenic or tumor suppressive gene in solid cancer. NOTCH1 mutations in oral squamous cell carcinoma (OSCC) frequently occur near the ligand-binding region. These mutations change the domain structure of this protein and affect the ligand binding activity. When NOTCH1 is activated by ligand binding, NOTCH1 intracellular domain (NICD) is cleaved from the cell membrane. This study investigated the functional change induced by a NOTCH1 mutation detected in OSCC clinical samples using stable transformant analysis. HEK293 cell lines expressing NOTCH1 wild-type (WT cells) or p.A465T NOTCH1 (A465T cells) were established. NOTCH1 expression was analyzed by flow cytometry, western blotting, and immunofluorescence using an anti-human NOTCH1 antibody. mRNA expression levels in WT and A465T cells were determined by quantitative real-time PCR (qPCR). Cell proliferation was analyzed by using cell growth assays and a xenograft tumor assay. Flow cytometry indicated that NOTCH1 expression on the cell membrane was lower in A465T cells than that in WT cells. NOTCH1 and NICD were both detected by western blot in WT and A465T cells. The immunofluorescence signal for NICD was detected in the nucleus of WT cells, while it was localized mainly in the cytoplasm of A465T cells. HES1 and HEY1 mRNA expression levels were lower in A465T than in WT cells. The cell growth of WT cells was significantly higher than that of HEK293 cells (3-fold, P<0.01), while that of A465T cells was significantly lower than that of HEK293 cells (37%, P<0.01). In a xenograft model, the tumor cell implantation rate of WT cells was 80%, while that of A465T cells was 0%. This study indicates that NOTCH1 acts as an oncogene and that the NOTCH1 mutation (p.A465T) in the ligand-binding region causes the loss of tumorigenicity by downregulating the NOTCH1 pathway.

Saliva pH affects the sweetness sense.

OBJECTIVES: The aim of this study was to establish a prediction system for taste sense according to the biochemical data of saliva. METHODS: The present study included 100 participants ages ≥20 y without physical, mental, or dental disabilities. Saliva samples were collected from the participants and subjected to biochemical analyses. Taste examination (sweetness, saltiness, sourness, and bitterness) was performed using the dropped disk method. Correlation analysis and multiple regression analysis were performed between the taste sense properties and biochemical data of saliva. RESULTS: Multiple regression analysis demonstrated that sweetness sensitivity (in which a higher score indicates lower sensitivity) was significantly affected by various biochemical properties, with the strongest influence being pH. The following prediction equation was determined: Sweetness sensitivity = 1.38 + (-0.12 × low pH [1: If pH <6.7, 0: otherwise]) + (0.80 × high pH [1: If pH >7.3, 0: otherwise]) + (0.04 × Fe [µg/dL]). Analysis of variance showed an overall significant effect of these variables on sweetness sensitivity (R2 = 0.74; P < 0.01). CONCLUSION: Saliva pH most strongly affects the sweetness sensitivity. This prediction can be used for evaluations of variations in dietary choices and to help individuals make healthy food choices to maintain health.

Kikuchi-Fujimoto Disease with 18F-Fludeoxyglucose Uptake in Cervical Lymph Nodes on Dual-time-point Imaging Positron Emission Tomography/Computed Tomography Mimicking Malignant Disease.

Kikuchi-Fujimoto disease (KFD) is a benign but self-limiting disorder. However, KFD is often misdiagnosed as a malignant disease. Although 18F-fludeoxyglucose (FDG) uptake on dual-time-point imaging (DTPI) positron emission tomography (PET)/computed tomography (CT) is useful in distinguishing malignant from benign disease, the latter sometimes mimics malignancy on DTPI PET/CT, resulting in a misdiagnosis. Here, we describe the case of a 30-year-old woman who complained of cervical lymphadenopathy. PET showed increased FDG uptake in multiple lymph nodes, with a maximum standardized uptake value (SUVmax) of 19.0 in the early phase to 21.8 in the late phase. A biopsy was performed, and pathological examination revealed KFD. KFD with FDG uptake in lymph nodes on DTPI PET/CT is rare and difficult to be distinguished from a malignant disease.

Frequent mutations in NOTCH1 ligand-binding regions in Japanese oral squamous cell carcinoma.

Recent studies showed that head and neck squamous cell carcinoma (HNSCC) including oral squamous cell carcinoma (OSCC) of Caucasian, Chinese and Indian patients frequently have NOTCH1 mutations. We found eight of 84 OSCC in Japanese patients have point mutations (9.5%) correspond to the ligand binding region of NOTCH1 protein. Two set of them are the same mutations and all mutations are non-synonymous G>A transitions. In addition, median disease-free survival is significantly longer in patients with NOTCH1-mutated tumors as compared to those without the mutation (P<0.05). The protein structure simulation based on X-ray crystallography indicated that new p.A465T mutation leads to a conformational change of NOTCH1 ligand binding domain as well as the p.G481S mutant NOTCH1 with a loss of flexibility around this residue. These results suggest that NOTCH1 mutation occurs frequently in Japanese OSCC in the vicinity of the ligand binding region and, these mutations cause downregulation of the NOTCH1 function.

MRI analysis of chronological changes in free-flap volume in head and neck reconstruction by volumetry.

OBJECTIVE: To evaluate changes in flap volumes for head and neck cancer patients by MRI. METHODS: MRI examinations of a total of 21 head and neck cancer patients (13 males and 8 females; average age, 67 years) were performed after surgery to monitor changes in flap volumes, including muscle and fat content, using volumetric analysis of T2-weighted images at 1, 3, 6, and 12 months after surgery. RESULTS: Fat-to-muscle ratios of all flaps at 1 month varied (muscle/fat ratio, 0.04-0.96). Flap volumes in all patients decreased at 12 months after surgery. The average final volumes of overall, muscle, and fat volumes reached 76.9% ± 5.2%, 37.1% ± 3.7%, and 85.5% ± 5.7%, respectively. The average fat volume slightly increased between 6 and 12 months, whereas compared with the fat volume, the average muscle volume significantly decreased (p<0.001). CONCLUSIONS: The final overall flap volume in all patients decreased to approximately 25% of the original volume after surgery, which primarily resulted from muscle atrophy. Therefore fat-rich flaps may maintain flap volumes after surgery. MRI is a useful method to evaluate the size and shape of flaps of the head and neck.