Not only genetic changes, such as tumor suppressor gene mutation, proto-oncogene activation and genomic instability, but also epigenetic modifications play fundamental roles in cancer development. The most common examples of epigenetic modifications include DNA methylation, histone modification, small non-coding RNAs, and others.

Our studies have identified several G protein-coupled receptors (GPCRs) as prognostic factors for head and neck squamous cell carcinoma (HNSCC). Significant epigenetic silencing of GPCR expression by DNA methylation, including that of Galanin (25%), GALR1 (38%), GALR2 (33%), TAC1 (49%), TACR1 (34%), SST (81%) and SSTR1 (64%), has been found in HNSCC than in normal tissue, which is also known to be significantly correlated with the clinical behavior. The group with hypermethylation (more than 4 out of 7 genes) showed a significantly higher percentage of cases with advanced disease, reduced disease-free survival, and a higher recurrence rate.

We detected frequent methylation of p16 (44%), RASSF1A (18%), E-cadherin (54%), H-cadherin (35%), MGMT (35%), DAPK (53%), DCC (42%), COL1A2 (44%), TAC1 (61%), SST (64%), and GALR1 (44%) in HNSCC. The disease-free survival was lower in patients with 6-11 methylated genes than in those with 0-5 methylated genes. In a multivariate Cox proportional hazards analysis, methylation of E-cadherin, COL1A2, TAC1 and GALR1 was associated with a poor survival. In a joint analysis of these four genes, early-stage HNSCC patients with 2-4 methylated genes had a significantly lower survival rate than those with 0-1 methylated genes.

Epigenetic modifications can be reversible and therefore be targeted therapeutically by the enzymes involved in DNA methylation and histone modifications. Further study of epigenetic alterations in HNSCC may pave the way for the development of new treatments and/or for elucidation of the carcinogenetic pathway.

This retrospective study was performed to clarify the relation between orthostatic blood pressure elevation (OBPE) and dizziness. Data of 188 outpatients who visited Kure Medical Center in 2013 for dizziness were analyzed. OBPE was defined as a greater than 5 mmHg increase of the systolic blood pressure just after and/or 10 minutes after the patient stood up in the Schellong test. OBPE without any other significant findings on routine examination was diagnosed in 24 patients. Tofisopam, which is known to normalize sympathetic nerve hypersensitivity, was administered to 4 of the 24 patients. In 3 of these 4 patients, the Schellong test was repeated after two weeks of treatment with tofisopam. Both the dizziness and OBPE had resolved completely by this time in all of the 3 patients. All of these 3 patients reported being exposed to some kind of chronic stress. Our findings suggest that sympathetic nerve hypersensitivity might cause both OBPE and dizziness, and that chronic stress might induce sympathetic nerve hypersensitivity.

A 64-year-old Japanese man presented with a 2-year-history of an itchy skin swelling of the right ear helix. Ultrasonography revealed no abnormalities of the salivary glands or lymphadenopathy. Although the swelling was solitary and small, blood examination revealed eosinophilia and a high serum IgE level. Surgical resection of the ill-defined lesion measuring 3 cm in diameter was performed. Histopathological examination of the resected lesion revealed the characteristic findings of Kimura’s disease, namely, numerous lymph follicles with germinal centers and profuse eosinophilic infiltration of the thickened dermal tissue. IgE staining revealed reticular reaction in the germinal centers. Because of the similarity of the histopathological findings and site of predilection around the ear, this condition should be differentiated from angiolymphoid hyperplasia with eosinophilia (ALHE).

Pleomorphic adenomas most commonly arise in the major salivary glands, and only rarely in the nasal cavity. We reported herein on a case of a pleomorphic adenoma originating from the nasal septum.

A 49-year-old female complained of left nasal obstruction. A tumor had arisen from the left nasal septum, and it was covered with smooth mucosa and showed vasodilation. The CT scan showed a 20×20 mm soft tissue mass in the posterior left nasal cavity. MRI imaging showed that the mass was a well-defined and hyperintense in T2-weighted images, and isointense in T1-weighted images. The tumor was removed with endoscopic surgery, and the pathological diagnosis was a pleomorphic adenoma.

Including the present cases, 99 cases of pleomorphic adenoma arising from the nasal cavity have been reported in Japan. Of these 79 (79.8%) arose from nasal septum and 18 (18.2%) arose from lateral nasal wall. Four cases (4.3%) have been reported as demonstrating malignancy and 4 (4.3%) as recurrent tumors. Cases of pleomorphic adenoma of nasal cavity have characteristics unlike those of the major salivary gland adenomas in that symptoms such as nasal obstruction and epistaxis appear early, and sufficient resection is possible. The treatment of choice for pleomorphic adenomas is resection. Careful follow-up for a longer period is necessary.

Ameloblastoma is one of the most common odontogenic tumors that arise most commonly from the mandible, but rarely arise from the maxilla. We report the case of a 32 year-old male patient with ameloblastoma of the maxilla. The patient visited our hospital complaining of a swelling in the left cheek. Computed tomography revealed a solid bony tumor measuring about 4 cm in diameter in the left maxillary sinus. Gallium-67 scintigraphy showed a hot spot in the region of the tumor. We performed resection of the tumor, and histopathologic examination of the resected tumor revealed the diagnosis of ameloblastoma, desmoplastic type. As at time of writing, the patient remains alive, with no recurrence.

Desmoplastic ameloblastoma is an unusual type of ameloblastoma that was first reported at 1984. Ameloblastoma is considered as a benign tumor, however, as numerous casea of recurrence have been reported prompt and effective treatment is very important. Complete tumorectomy is desirable as resection of the mandible would be associated with cosmetic disfigurement.

Ours was a case of desmoplastic ameloblastoma, which is rarely known to recure; we propose to follow up the patient carefully.

Chronic invasive fungal sinusitis is recognized as one type of fungal sinusitis, however, there are few case reports of this disease and patients with this disease are rare. We report herein on a 60-years-old male patient with chronic invasive fungal sinusitis treated by surgery and an antifungal drug. The patient had been suffering from lacrimation and slight pain of the right eye for three years. Right maxillary sinusitis was detected on brain magnetic resonance imaging (MRI) and he was referred to our hospital. Computed tomography (CT) detected opacity of the right maxillary area with calcification. Both T1-weighted and T2-weighted MRI showed a low signal lesion of the right maxillary sinus with invasion of the right nasolacrimal duct. Blood chemistry revealed that β-D glucan levels were high (42.1 pg/ml). Because the time course of the disease had been very long and the nasolacrimal duct was invaded, chronic invasive fungal sinusitis in the right maxillary sinus was the final diagnosis. A lateral rhinotomy was performed with reconstruction of right nasolacrimal duct and voriconazole was administered for 8 days after the operation. The pathological sample revealed major fungal invasion of the sinus mucosa shown to be Aspergillus with immunostaining. The patient has now been without recurrence for 21 months. A standard treatment of chronic invasive fungal sinusitis has not been established and has varied in the few case reports available; one of them reported treatment with only an operation and the other reported treatment with an operation and an antifungal drug. Our results showed that the combination of an operation and an antifungal drug was effective in the treatment of chronic invasive fungal sinusitis.

We report four patients with intractable recurrent oropharyngeal ulcers, including two with idiopathic oropharyngeal ulcers, one with intestinal Behcet’s disease, and one with mucous membrane pemphigoid. The diagnosis of intestinal Behcet’s disease was confirmed by gastrointestinal endoscopy, and the diagnosis of mucous membrane pemphigoid was confirmed by skin biopsy. However, no causative disease could be identified in the two cases with idiopathic oropharyngeal ulcers on the basis of any of the clinical findings, blood examinations or histological analysis. The patients with idiopathic oropharyngeal ulcers were treated by steroids combined or not combined with colchicine. The patient with intestinal Behcet’s disease was treated with infliximab. The patient with mucous membrane pemphigoid was treated using a combination of steroids with diaminodiphenyl sulfone and rituximab. During clinical observation over an average period of 7 years, all the patients have maintained a good course without a recurrence of severe ulcers.

We report herein on a case of undifferentiated carcinoma of the thyroid with a high serum G-CSF level. A 78-year-old woman was referred to hospital in respiratory discomfort that caused by large neck mass. A cytological examination from an aspiration biopsy disclosed papillary carcinoma of the thyroid. CT and MRI examinations revealed thyroid carcinoma with laryngeal infiltration and lung metastasis. We diagnosed it as papillary carcinoma of the thyroid (T4aN1aM1 Stage IVc) and suggested surgery with radiation therapy. However, she and her family were not expecting treatment, so we performed only a tracheostomy. Four years later, she was admitted to our hospital because of a rapidly enlarging tumor, anorexia and general malaise. She died a month later after admission. Marked elevation of the number of leukocytes to 178,900/mm³ was observed during the clinical course, and an increase in the G-CSF level (139 pg/dl) was demonstrated in the serum. We discuss the clinical course and prognosis of this tumor based on our case with reference to the literature.

S-1 consists of tegafur and two biochemical modulators and reduces adverse effects such as neuro- and cardiac toxicity, hand-foot syndrome and gastrointestinal (GI) toxicity. It can be used as a relatively safe anti-cancer agent for various types of cancers in not only the head and neck region but also the GI, breasts, lungs and so forth.

At our center, we have used concurrent chemoradiotherapy with S-1 in combination with nedaplatin in patients with head and neck squamous cell cancer and obtained favorable feasibility; recently, however, three GI-related serious adverse events that were considered to be due to S-1 occurred in series. One case was a lower GI hemorrhage accompanied with hemorrhagic shock. The remaining two cases were GI perforations, including one fatal outcome.

We have been evaluating various factors that could contribute to GI adverse events including medication, patient and healthcare personnel factors to establish a more appropriate therapeutic plan and supportive care.

We have encountered four cases of infantile otitis media caused by multidrug-resistant Haemophilus influenzae, including to the newer quinolones. The antimicrobial sensitivity of each bacterial isolate was tested on the basis of the minimum inhibitory concentration (MIC). Each isolate was then tested using the polymerase chain reaction (PCR) to investigate whether the TEM β-lactamase production gene was present, and to detect mutations in the penicillin-binding protein (PBP) genes and mutations leading to amino acid substitutions in the quinolone resistance-determining region (QRDR). The isolates were found to be classifiable into two types according to the amino acid-substitution mutations. Molecular epidemiological analysis by pulsed field gel electrophoresis (PFGE) revealed different electrophoretic patterns in all the H. influenzae isolates, suggesting that the four patients were infected by different strains.