A Case of Phlebolith in the Tip of Tongue.

The differential diagnosis of a tongue mass containing calcified bodies includes a phlebolith associated with vascular lesions, such as hemangioma and vascular malformation, and diseases such as neoplasm, osseous choristoma and hypercalcemic states, including hyperparathyroidism. The appearance of the calcified bodies on plain radiographs may help to differentiate these entities. Computed tomography, magnetic resonance imaging, and ultrasonography are also useful for differentiating these soft tissue lesions. We report a 40-year-old man with a small mass containing a calcified body in the tip of tongue. The mass was surgically resected and histologically evaluated, confirming the diagnosis of phlebolith. Our case was a rare phlebolith that did not involve a vascular lesion.

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.

Sonographic appearance of syphilitic induration mimicking squamous cell carcinoma in the lower lip: a case report.

BACKGROUND: Syphilis is a sexually transmitted disease caused by the spirochete Treponema pallidum. Recently, its incidence has been increasing worldwide. We encountered a young woman who presented with induration mimicking squamous cell carcinoma in the lower lip, without major medical conditions. CASE PRESENTATION: A 25-year-old Japanese woman presented with a 1-month history of a painless induration in her lower lip. Because squamous cell carcinoma was suspected, a preoperation work up was performed, including laboratory tests, an ultrasonographic examination, and a biopsy. The ultrasonography findings showed an oval-shaped 17 × 11 × 12 mm tumor-like lesion with heterogeneous internal echo and an indistinct border. A pressure test and color Doppler sonography revealed that the lesion was soft with a very abundant blood flow. These findings suggested the possibility of underlying inflammatory causes rather than a neoplastic tumor. Serology tests for syphilis, including the anti-Treponema pallidum antibody and reactive rapid plasma reagin tests, were positive. The biopsy revealed no malignancy. Finally, she was diagnosed as having primary syphilis and treated with amoxicillin for 28 days. The rapid plasma reagin value gradually decreased and the initial induration in her lower lip disappeared. CONCLUSION: This case highlights the need for prompt examinations for possible underlying infective causes, such as syphilis, when seeing a painless induration with ulcer in the lip. Ultrasonography was helpful in the differential diagnosis of a tumor-like lesion and should be included in addition to syphilis serology tests, such as anti-Treponema pallidum antibody and rapid plasma reagin tests.

An analysis of oral microbial flora by T-RFLP in patients undergoing hematopoietic stem cell transplantation.

Even though the hematopoietic stem cell transplantation (HSCT) procedure has been improved, oral mucositis (OM) is still a severe complication of the conditioning regimen. We investigated the association between OM severity and the alteration of oral bacterial flora using 16S rRNA gene-based terminal restriction fragment length polymorphism (T-RFLP) analysis in 19 consecutive patients undergoing HSCT. Oral samples were collected at pre-transplantation, at the peak of mucositis and post-engraftment. T-RFLP profiles for each timepoint were constructed into an X-Y matrix, and the distances between timepoints were calculated. Patients with severe and moderate OM had larger changes in their oral bacterial flora from before HSCT to peak of mucositis than controls (p = 0.031 and 0.016, respectively). Moreover, severe mucositis was significantly associated with an extended period of fever until engraftment, high maximum C-reactive protein levels, and prolonged periods of opioid treatment and intravenous hyper-alimentation. These findings suggest that mucositis severity is associated with the magnitude of change in the oral bacterial flora. This novel finding may help advance strategies for the prevention or treatment of OM after HSCT.

Altered DNA methylation is associated with aberrant stemness gene expression in early­stage HNSCC.

Head and neck squamous cell carcinoma (HNSCC) is characterized by morphological and functional cellular heterogeneity, which are properties of progenitor cells, as opposed to cell alterations caused by accidental expression of stem cell­related molecules. The expression levels of stemness molecules and their distribution in HNSCC are unclear. As regards sporadic cellular heterogeneity, methylation is an important factor for transcriptional regulation in tumors. Integrative screening analysis of mRNA expression and altered methylation status was performed with original microarrays in 12 tumor and non­tumor pairs of oral squamous cell carcinoma (SCC) cases. From this data set, genes regulated via aberrant DNA methylation and classified proteins were validated by function clustering. Olfactomedin 4 (OLFM4), known as an intestinal stemness molecule and cell­cell adhesion factor, was found to be highly expressed in tumors, with an mRNA expression ratio [tumor/normal (T/N)] of 40.7686 and low methylation (­18.02%) in the promoter region. In addition, the OLFM4 expression levels increased following treatment with the demethylating agent 5­azacytidine in two HNSCC cell lines. Furthermore, the expression levels of OLFM4 in 59 cases of early­stage tongue SCC were analyzed using immunohistochemistry to examine protein expression corresponding to the histopathological definition of tumors and to evaluate prognosis. The aberrant stemness gene expression caused by altered DNA methylation appeared to regulate early­stage HNSCC characteristics. The results of the present study indicated a correlation between OLFM4 expression and promoter methylation, and suggest that it plays an important role in tumor cell heterogeneity in HNSCC.

Self-study of the non-extension sign in an e-learning program improves diagnostic accuracy of invasion depth of early gastric cancer.

Background and study aims We developed an e-learning program for endoscopic diagnosis of invasion depth of early gastric cancer (EGC) using a simple diagnostic criterion called non-extension sign, and the contribution of self-study quizzes to improvement of diagnostic accuracy was evaluated. Methods We conducted a prospective randomized controlled study that recruited endoscopists throughout Japan. After completing a pretest, the participants watched video lectures and undertook post-test 1. The participants were then randomly allocated to either the self-study or non-self-study group, and participants in the first group completed the self-study program that comprised 100-case quizzes. Finally, participants in both groups undertook post-test 2. The primary endpoint was the difference in post-test 2 scores between the groups. The perfect score for the tests was set as 100 points. Results A total of 423 endoscopists completed the pretest and were enrolled. Post-test 1 was completed by 415 endoscopists and 208 were allocated to the self-study group and 207 to the non-self-study group. Two hundred and four in the self-study group and 205 in the non-self-study group were included in the analysis. Video lectures improved the mean score of post-test 1 from 72 to 77 points. Participants who completed the self-study quizzes showed significantly better post-test 2 scores compared with the non-self-study group (80 vs. 76 points, respectively, P  < 0.0001). Conclusions Our e-learning program showed that self-study quizzes consolidated knowledge of the non-extension sign and improved diagnostic ability of endoscopists for invasion depth of EGC.

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.

Introduction to Kampo medicine for dental treatment - Oral pharmacotherapy that utilizes the advantages of Western and Kampo medicines.

Kampo medicine is a medical system that has been systematically organized based on the reactions of the human body. At present, in Western, herbal medicines means the whole herbal product. It is being called Kampo medicine as a medicinal drug in Japan. Since 2012, the "National Health Insurance Drug Price Standards Related to Dental Treatment" published by the Japan Dental Association have included seven Kampo formulations. In 2015, the Japan Dental Association sent a "Kampo Education Plan for Dentistry" to all dental universities in Japan. Furthermore, the Japanese Society of Oral Therapeutics and Pharmacology compiled a summary of "Evidence for Kampo Treatment in the Field of Oral Surgery." In addition, the phrase "including wakan-yaku" was included in the draft core model curriculum for dental education in 2016. Thus, Kampo medicine is expected to rapidly spread to the field of dental care and dental medical education. Therefore, the training of dentists with knowledge of both Western and Oriental medicine is required for the treatment of oral pain, periodontal disease, stomatitis, xerostomia, and other complaints concerning oral health. It is our hope that this paper provides a footing for dentists who wish to learn about Kampo medicine and incorporate it into clinical practice.

Diagnostic criteria for Patulous Eustachian Tube: A proposal by the Japan Otological Society.

Patulous Eustachian Tube (PET) is of increasing importance in otology. However, despite the abundance of diseases requiring a differential diagnosis from PET, such as superior semicircular canal dehiscence syndrome, perilymphatic fistula, acute low-tone sensorineural hearing loss, etc., there are currently no established diagnostic criteria for PET. In view of these circumstances, the Japan Otological Society (JOS) Eustachian Tube Committee proposed the diagnostic criteria for Patulous Eustachian Tube in 2012, in order to promote clinical research on PET. A revision was made in 2016, maintaining the original concept that the criteria should be very simple, avoid any contamination of "Definite PET" with uncertain cases. Moreover, it was also intended to minimize the number of cases that could be accidentally excluded even in the presence of some suspected findings ("Possible PET"). The criteria can be used by all otolaryngologists even without using the Eustachian tube function test apparatus. However, the use of such an apparatus may increase the chances of detecting "Definite PET". The algorithm for the diagnosis of PET using the criteria has also been described. The JOS diagnostic criteria for Patulous Eustachian Tube will further promote international scientific communication on PET.

A Case of Early Pneumoparotid Presenting With Oral Noises.

A 53-year-old man presented with the chief complaint of oral noises. No lesion could be observed in the oral cavity. Ultrasound detected several high-echogenicity areas inside the bilateral parotid ducts, and the initial stage of pneumoparotid was diagnosed. It was considered that air had entered each duct in retrograde fashion through the parotid papilla because of repeated compression of the bilateral parotid glands by the patient who had the habit of compressing the buccal region. This case suggests that ultrasound is effective for diagnosing the initial stage of pneumoparotid.

A Study of Adjuvant Chemoradiotherapy with Tri-weekly Cisplatin for Postoperative High-risk Oral Squamous Cell Carcinoma.

OBJECTIVE: The aim of this study was to assess the feasibility and safety profile of concurrent chemoradiotherapy with cisplatin in Japanese patients with postoperative high-risk oral cancer. METHODS: Patients with high-risk pathological features were selected from patients with oral squamous cell carcinoma who underwent surgery at the Department of Oral and Maxillofacial Surgery, Tokai University Hospital. Patients were given adjuvant chemoradiotherapy with tri-weekly cisplatin (100 mg/m2) (66 Gy/33 Fr), and the treatment completion rate was examined. RESULTS: A total of 27 patients were enrolled between April 2011 and December 2012, including 19 males and 8 females. The median follow-up period was 36 months, and the protocol completion rate was 81.5%. Grade 3 or higher adverse events included leukopenia in 16 patients (59.3%), anemia in 7 patients (25.9%), mucositis in 2 patients (7.4%), increased creatinine in 1 patient (3.7%), nausea in 4 patients (14.8%), and anorexia in 12 patients (44.4%). The 3-year overall survival rate was 66.7%, relapse-free survival rate was 63.0%, and locoregional control rate was 77.8%. CONCLUSION: The feasibility and safety profile of concurrent chemoradiotherapy with cisplatin in Japanese patients with postoperative high-risk oral cancer were comparable to pivotal phase III trials.

Analgesic efficacy of celecoxib in patients after oral surgery: special reference to time to onset of analgesia and duration of analgesic effect.

PURPOSE: Cyclooxygenase-2 inhibitor celecoxib is also used in the dental field for analgesia. However, there are few reports on the time to onset and duration of analgesia. We investigated the analgesic effect of celecoxib after oral surgery. METHODS: A total of 138 patients undergoing unilateral mandibular third molar surgery under local anesthesia were enrolled. After surgery, the patients who felt pain and requested an analgesic were instructed to take celecoxib 400 mg and to record the time. Primary efficacy outcome measures were time to onset of analgesia. In addition, the conditions of pain at the time of taking celecoxib, at the onset time of analgesia, and 2 and 6 h after taking the drug were recorded. Pain assessments were evaluated using a 10-cm visual analog scale and four-point verbal rating score. These data were documented in the questionnaire forms handed to the patients and retrieved by post. RESULTS: Effective responses without missing were returned from 103 patients. The median time to onset of the efficacy was 35 min. The pain scales at celecoxib administration was significantly higher compared with the time of onset of analgesia, 2 hours after administraton and 6 hours hours administration (P<0.05, respectively). The pain scales at the onset time of analgesia were significantly higher compared to that after 2 or 6 h of taking the drug (P<0.05, respectively). There were no statistically significant differences in the pain scales between 2 and 6 h after taking the drug (P>0.05). CONCLUSION: The analgesic effect of celecoxib was exhibited quickly and sustained after oral surgery.

Intravitreal injection of melphalan for intraocular retinoblastoma.

PURPOSE: To investigate the safety and efficacy of intravitreal injection of melphalan for retinoblastoma. METHODS: A retrospective chart review of all patients who were administered intravitreal injections of melphalan for retinoblastoma between 1990 and 2011. A total of 264 eyes of 250 patients were included. All ocular adverse events, systemic prognosis, ocular prognosis, and visual acuity were investigated. RESULTS: The total number of intravitreal injections administered was 1,067; each eye received between one and 25 injections. A postoperative subconjunctival tumor developed in one eye. None of the eyes suffered infections or uveitis, and all other adverse events including chorioretinal atrophy displayed incidences of less than 1.5 %. At 5 postoperative years, the cumulative incidence of cataract surgery was 3.1 % among the eyes that were treated without ocular hyperthermia. Distant metastasis or intracranial invasion occurred in 11 patients, all of whom had high-risk pathological factors for metastasis such as optic nerve invasion, but refused to receive adjuvant chemotherapy. Sixty-eight percent of the eyes achieved complete vitreous seed remission, but recurrence occurred in 19 % of these eyes after 10.0 ± 4.9 months. In addition, 47 and 27 % of the eyes without primary macular tumors retained visual acuity of >0.5 and >1.0, respectively. CONCLUSIONS: The risk of extraocular tumor spreading following intravitreal injections is low, and other adverse events are rare. Sixty-eight percent of the treated eyes achieved complete vitreous seed remission, and about half of them retained practical levels of vision. The intravitreal injection of melphalan is a safe and effective treatment for vitreous seeds.

Severe retinopathy following radiation therapy with a moderate dose for orbital mucosa-associated lymphoid tissue lymphoma.

Mucosa-associated lymphoid tissue (MALT) lymphoma is a radiosensitive malignancy. We report on a case of severe retinopathy following radiation therapy with a moderate dose for orbital MALT lymphoma. A 69-year-old woman with orbital MALT lymphoma received definitive radiation therapy with a total dose of 36 Gy in 18 fractions. The patient showed complete response but had severe retinopathy along with marked deterioration in visual acuity at 2 years after irradiation. Although the patient underwent treatments for retinopathy, including laser photocoagulation and steroid injection, improvement of the visual acuity was modest. This case developed severe radiation-induced retinopathy after radiation therapy with the moderate dose of 36 Gy that is considered to be usually safe.

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.

Left ventricular endocardial dysfunction in patients with preserved ejection fraction after receiving anthracycline.

BACKGROUND: Anthracycline chemotherapy generates progressive dose-dependent left ventricular (LV) dysfunction associated with a poor prognosis. Early detection of minor LV myocardial dysfunction caused by the cardiotoxicity of anthracycline is thus important for predicting global LV dysfunction. METHODS: Fifty patients with preserved ejection fraction (all ≥55%) after receiving anthracycline chemotherapy were recruited for this study. Two-dimensional speckle tracking was used to assess global radial and circumferential strains from mid-LV short-axis views and global longitudinal strain from the apical four- and two-chamber view as peak global strain curves. Three-dimensional (3D) radial, circumferential, and longitudinal myocardial function was quantified as a peak global strain curve using 3D speckle tracking from all 16 LV segments. 3D speckle tracking imaging was used to evaluate LV endocardial area change ratio (area strain) quantified as peak global area strain curve (3D-GAS) to determine LV endocardial function. Twenty age-, gender-, and EF-matched normal volunteers were studied for comparisons. RESULTS: Only 3D-GAS and peak 3D global circumferential strains of the anthracycline group were significantly worse than those of the control group (-43.3 ± 3.1 vs. -45.8 ± 4.3% and -31.6 ± 3.5% vs. -34.4 ± 4.2%, respectively; P = 0.008, P = 0.004) even though global LV systolic and diastolic functions were similar. 3D-GAS correlated significantly with the cumulative doxorubicin dose (r = 0.316, P = 0.026). It was noteworthy that multivariate analysis showed only 3D-GAS (ß = 0.323, P = 0.025) was independently associated with cumulative doxorubicin dose. CONCLUSIONS: Three-dimensional speckle tracking area strain was found useful for early detection of minor LV endocardial dysfunction associated with the use of anthracycline, and may thus prove to be clinically useful for predicting global LV dysfunction.

Stem cell self-renewal factors Bmi1 and HMGA2 in head and neck squamous cell carcinoma: clues for diagnosis.

Head and neck squamous cell carcinoma (HNSCC) includes both morphological and functional cellular heterogeneity, as would be expected if it arose from dysregulated stem or progenitor cells as opposed to the simple clonal expansion of a mutated cell; however, stemness molecule expression levels and distribution in HNSCC remain unclear. To clarify this, stemness molecule expressions were determined in HNSCC, as well as their properties and prognosis. Two proto-oncogenic chromatin regulators, Bmi-1 and high-mobility-group A2 (Hmga2), were identified in 12 pair cases of HNSCC tumor regions by comparison with their non-cancerous background tissues using cDNA microarray. Both Bmi-1 and Hmga2 are known to promote stem cell self-renewal by negatively regulating the expressions of Ink4a and Arf tumor suppressors. Despite similar targets, Bmi-1 protein was expressed in an early cancerous region and HMGA2 protein was expressed in a region showing more progression. Similarly, Bmi1 expression had no significance with regard to overall survival (P=0.67), whereas HMGA2 expression was associated with decreased overall survival (P=0.05). Quantitative real-time reverse transcription polymerase chain reaction analyses also correlated with protein levels. These findings suggest that Bmi-1 is an early detection marker to distinguish cancerous from non-cancerous regions, whereas HMGA2 is presumed to be a tumor prognosis marker. Among our HNSCC analyses, these stemness molecules expressed fewer primitive rare cells in the tumor than all other cells in the tumor. HNSCC cells with high expression of stemness molecules partly behave like stem cells.

Peripheral ameloblastoma of the lower molar gingiva: a case report and immunohistochemical study.

Peripheral ameloblastoma (PA) is a rare extraosseous odontogenic tumor with histological characteristics similar to those of the common intraosseous ameloblastoma. Two questions regarding PA remain: its histogenic origin and how to differentiate between PA and intraoral basal cell carcinoma. We describe a patient with PA. The result of immunohistochemistry showed cytokeratin (CK) 7-, CK14+, CK19+, AE1/AE3+, CAM5.2-, 34 ß E12+, epithelial membrane antigen-, Ber-EP4-, p53-, p63+, and low Ki-67, that was similar to those of 4 cases of intraosseous ameloblastoma. Our results suggest that a PA originates from odontogenic epithelial remnants, rather than from the oral epithelium.

Concurrent onset of an eosinophilic ulcer of the oral mucosa with peripheral eosinophilia in a human T-cell leukemia virus type I carrier.

We present a case of a 46-year-old Japanese woman with an eosinophilic ulcer of the oral mucosa (EUOM), located in the buccal mucosa, who was found by various examinations to be a human T-cell leukemia virus type I (HTLV-1) carrier with peripheral eosinophilia. Her peripheral eosinophilia and EUOM promptly improved in response to oral corticosteroid therapy. EUOM has been described to be possibly associated with trauma, but its etiology has not been fully elucidated to date. In the present case, the presence of peripheral eosinophilia in addition to the EUOM indicated possible influence of certain immune system abnormalities associated with HTLV-1 infection.