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White spongiform nevus is an autosomal dominant inherited disorder first reported by Cannon in 1935. It is a rare disease in which the oral mucosa thickens into an edematous and spongy state and is often accompanied by difficult to recognize subjective symptoms. We report a case of multiple non-hereditary white cavernous nevi in the oral mucosa. The subject was a 22-year-old man with a chief complaint of white lesions in his oral cavity. Examination revealed thick edematous and sponge-like white lesions on the bilateral buccal mucosa, upper and lower lip mucosa, and bilateral lingual margins. There was no history of similar lesions in his family or among his relatives. We diagnosed the case as non-hereditary white sponge nevus, based on clinical and histopathological findings. Although difficult to treat, the lesions disappeared with tetracycline ointment application and oral intake of multiple vitamin supplements. No recurrence of the lesion was observed thereafter.

The oral microbiota associated with mucosal diseases, including oral squamous cell carcinoma and oral potentially malignant disorders, have been extensively analyzed at the phylum and genus levels. However, the details of the oral microbiota remain unclear at the species and operational taxonomic unit (OTU) levels. We aimed to determine differences in the microbiota of oral rinse, lesion, and normal site samples of patients with mucosal abnormalities on the tongues. Oral samples were obtained from 10 patients with oral mucosal abnormalities. Alpha and beta diversity at the OTU and genus levels of the microbiota samples were analyzed using OTUs clustered with 99.6% similarity based on 16S rRNA gene sequences obtained using the Sanger method. At the OTU level, the microbiota of the lesions were the least diverse but were different from those of the normal site and oral rinse samples. The OTUs corresponding to Streptococcus infantis, Haemophilus parainfluenzae, and Prevotella scopos were suggested to contribute to the differences between the microbiota of the lesions and normal sites. At the genus level, no significant differences between these microbiota were observed. In conclusion, strict OTU-level microbiota analysis might be able to discriminate lesions from normal sites of patients with mucosal abnormalities.

Peritoneal dialysis can be performed at home, and the transfer of solutes in the blood and other body fluids is slow compared to hemodialysis, reducing the load on the circulatory organs and lessening the frequency of hospital visits. We encountered a male patient in his 70s on peritoneal dialysis for end-stage renal failure who developed obsolete mandibular fracture-associated pseudarthrosis accompanied by osteomyelitis, which was treated with noninvasive reduction and fixation using circumferential wiring after the resolution of inflammation. The inflammation was resolved by an intravenous drip infusion of ampicillin and lavage of the local region through the fistulated region during hospitalization, and sequestrum was removed under local anesthesia. After the disappearance of drainage from the fistula, the mandibular fracture was fixed with circumferential wiring (noninvasive reduction and fixation) using a mandibular resin base (occlusion is possible). For noninvasive reduction and fixation of a midline fracture, a 6-week fixation period is usually necessary after surgery, but in this case it was fixed for 3 months after surgery because of the presence of infection and bone defect. In jaw bone infection in patients on long-term dialysis, high sensitivity to infection and incomplete cure occur due to a decline in cell-mediated immunity, renal osteodystrophy (ROD), and chronic kidney disease (CKD)-mineral and bone disorder. In the present patient, infection complicated the odontogenic source of infection and fracture, which may have protracted the condition. When jaw bone infection is noted in a patient on long-term dialysis, it is important to closely cooperate with the dialysis physician and select the administration method and dose corresponding to the route of administration and metabolism of antimicrobial agents in order to minimize the influence on the renal function. For the local region, infection control by oral hygiene management and cleaning is important, targeting treatment and management while avoiding the use of any antimicrobial agent.

We report a pediatric case aged 10 years with Granulicatella adiacens-associated chronic mandibular osteomyelitis. The causative pathogen was uncertain because polymicrobial species were detected from the bacterial culture in bone marrow fluid. In contrast, G. adiacens was predominantly identified in the clone library analysis of the bacterial 16S rRNA gene sequence. Vancomycin to which G. adiacens was reported to be susceptible was not administrated sufficiently to this patient because of its adverse event, whereas linezolid and ciprofloxacin was alternatively effective for the treatment of chronic mandibular osteomyelitis.

Object The aim of this study was to assess our diagnosis system for cervical node metastasis for oral squamous carcinoma (OSCC) based on the combined results of computed tomography (CT), magnetic resonance imaging (MRI), ultrasonography (US), and 18-fluorodeoxyglucose positron emission ( 18 F-FDG-PET/CT). Methods 106 patients with primary OSCC who underwent surgical treatment were divided into 3 groups. In group 1, cervical node metastasis was diagnosed by disunity combinations of diagnostic devices. In groups 2 and 3, it was assessed according to a set of diagnostic criteria that included the results of the CT/MRI, US and 18 F-FDG-PET/CT. In group 2, node status was considered negative when the results of both CT/MRI and US were negative. In group 3, node status was considered negative when the results of both CT/MRI and US were negative and the maximum standardized uptake value determined via 18 F-FDG-PET/CT was Results 67 patients were diagnosed as cN0. 50 cN0 patients adopted the wait and watch policy, 12 of whom (24.0%) developed cervical node metastasis without recurrence at the primary site. Metastasis rates after surgery improved 33.3%, 23.5%, and 13.3% in groups 1, 2, and 3, respectively. In contrast, positive predict value (PPV) were worst (50.0%, 40.0% and 33.3%). Conclusions Our diagnosis system reduces the rate of cervical lymph node metastasis after surgery.

Background Oral cavity is a reservoir of various respiratory pathogens, and poor oral hygiene is associated with an increase in anaerobic bacteria in oral cavity. In addition, it positively relates higher risk of developing pneumonia and increased pneumonia-related mortality. However, the association between poor oral hygiene and increase in obligate anaerobes in the lungs of pneumonia patients is unclear. Methods A total of 39 patients with pneumonia in whom bronchoscopic examination and oral hygiene evaluation were performed were prospectively enrolled. The microbiota of the bronchoalveolar lavage fluid (BALF) directly obtained from the pneumonia lesion was analysed by the clone library analysis. In addition, oral hygiene evaluations were performed using oral hygiene index (OHI), tongue coating score, oral dryness, and community periodontal index of treatment needs (CPITN). The association between the detection of oral streptococci and obligate anaerobes and oral hygiene status was evaluated. Results Using the clone library analysis of BALF, the phylotypes of oral streptococci and obligate anaerobes were detected in 31 (79.5%) and 26 (66.7%) patients, respectively. Increased oral dryness, OHI, and CPITN, but not the tongue coating score, significantly correlated with higher rate of detection of obligate anaerobes, although no significant associations between the detection of oral streptococci in the lungs and each oral hygiene evaluation were observed. Significantly higher number of obligate anaerobes were detected in the lungs in patients with total oral hygiene score of ≥ 5 (P = 0.008). Conclusion Poor oral hygiene is associated with increased obligate anaerobes in the lungs of patients with pneumonia.

The polypeptide N-acetylgalactosaminyltransferase (GalNAc-Ts) family of enzymes regulates the critical initial steps of mucin-type O-glycosylation. Among GalNAc-Ts that may significantly influence cancer biology, thus affecting cell differentiation, adhesion, invasion, and/or metastasis, GalNAc-T3 exhibits a high expression in several human cancers, closely associated with tumor progression and a poor prognosis. However, the expression pattern of GalNAc-T3 in oral squamous cell carcinoma (OSCC) remains obscure. Since postoperative recurrence of even early stage OSCC (ESOSCC) occurs at an early phase, significantly affecting their clinical course and worse outcome, the identification of clinically significant accurate biomarkers is needed. Therefore, we investigated the correlation between the immunohistochemical GalNAc-T3 expression and various clinicopathological characteristics and recurrence using 110 paraffin-embedded tumor samples obtained from patients with surgically resected ESOSCC (T1–2N0). Recurrence was recognized in 37 of 110 (33.6 %) patients. The GalNAc-T3 expression was considered to be strongly positive when 20 % or more of the cancer cells showed positive cytoplasmic staining. Consequently, a strong expression of GalNAc-T3 was observed in 40 patients (36.4 %), showing a close relationship to poor differentiation, the presence of lymphatic and vascular invasion, and recurrence. Univariate and multivariate analyses further demonstrated that the patients with a strong GalNAc-T3+ status had markedly lower disease-free survival (DFS) rates, especially within the first 2 years postoperatively. Therefore, GalNAc-T3 might play a role in the pathogenesis of ESOSCC recurrence, and its immunohistochemical detection potentially predicts a shorter DFS and may be a useful parameter for providing clinical management against ESOSCC in the early postoperative phase. Electronic supplementary material The online version of this article (doi:10.1007/s13277-015-3928-7) contains supplementary material, which is available to authorized users.

Epithelial-mesenchymal transition (EMT) is an early step in the acquisition of invasiveness by malignant tumors. It has been clarified that the tumor microenvironment affects malignancy in a number of different carcinomas, in particular, that a hypoxic environment induces EMT. Activation of Notch signaling induces EMT, but it remains unclear how the Notch pathway is involved in oral squamous cell carcinoma (OSCC) under hypoxia. Three OSCC cell lines were cultured for examination under hypoxic (1% O2) and normoxic (21% O2) conditions. Expression of E-cadherin was investigated as a hallmark of EMT by immunohistochemical examination. Cell motility and invasion were examined by wound-healing and invasion assays, respectively. The expression of Notch pathway molecules was analyzed by qPCR. Hypoxia increased the mRNA expression of Notch receptors, ligands and target genes, and Snail. Hypoxia decreased the expression of E-cadherin, and increased the motility and invasiveness of OSCC cell lines. γ-secretase inhibitor, a Notch-specific inhibitor, prevented these effects caused by h-ypoxia. These findings suggest that hypoxia induces EMT in OSCC cell lines via activation of Notch signaling, and inhibition of the Notch signaling pathway to suppress EMT may be a useful approach for the treatment of OSCC.

Objective Ameloblastoma has a high risk of bone invasion and local recurrence. However, the mechanisms of bone invasion in ameloblastoma remain unclear. In this study, we established an experimental model for matrix metalloproteinase (MMP) induction and osteoclastogenesis using ameloblastoma-derived cells. Study design We established an ameloblastoma-derived cell line without viral genes and analyzed the expression of all Wnt and Frizzled members and MMPs by real-time reverse transcription-polymerase chain reaction, and analyzed the activity of MMP-2 and MMP-9 by the in-gel-gelatinase assay. Results AM-3, newly established ameloblastoma-derived cells retained the morphology of primary-cultured ameloblastoma cells. AM-3 cells overexpressed the messenger RNA of Wnt-5a, Frizzled-2, MMP-2, and MMP-9 and showed the potential of osteoclastogenesis. In addition, Wnt-3a-treatment induced expression and activation of MMP-9 in AM-3 cells. Conclusions Our study suggests that AM-3 cells retained the characteristics of ameloblastoma, without acquiring typical features of cancer cells. Furthermore, Wnt signaling induced MMP-9 in ameloblastoma cells.

a b s t r a c t Background: As oral neoplasm often originates from epithelium, an immortalized epithelial cell line could be useful for the research of oral carcinogenesis. Although several oral epithelial cell lines were reported, they were either derived from cancer or immortalized by human papilloma virus or simian virus 40 genes, which have the potential to induce carcinogenesis. Materials and methods: We established two immortalized cell lines from human oral epithelium by transducing mutant cyclin dependent kinase 4, cyclin D1, and human telomerase reverse transcrip- tase with or without dominant-negative p53 into primary-cultured normal oral gingival epithelial cells using recombinant lentivirus vectors and named them MOE (mouth-ordinary-epithelium) 1a and MOE1b, respectively. Results: MOE1 cells could be passaged for nine months or more, and the morphology of the cells did not change in comparison with that of fresh primary-cultured epithelial cells. MOE1 cells did not show epithelial-mesenchymal transition. MOE1b cells retain functional p53 and were considered to have less risk of genomic instabilities. Anchorage-independent growth was not observed in MOE1 cells. The expres- sions of cancer-associated genes including keratin-17 were not elevated in MOE1 cells, whereas oral cancer-derived HSC-2 cells showed overexpression of them. Furthermore, interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor-, matrix metalloproteinase (MMP)-2, and MMP-9 were induced in response to lipopolysaccharide or heat-killed bacterium in MOE1 cells. Discussion: MOE1 cells kept the characteristics of normal epithelial cells without acquiring typical features of cancer cells and they could be useful not only for the study of oral neoplasm but also for other oral

The major vault protein (MVP) is the major constituent of the vault particle, the largest ribonuclear protein complex described to date and is identical to lung resistance-related protein (LRP). Although MVP is also expressed in several normal tissues, little is known about its physiological role. MVP played a protective role against some xenobiotics and other stresses. We thus investigated the effect of osmotic stress on MVP expression by treating human colon cancer SW620 cells with sucrose or NaCl. The expression level of both MVP protein and MVP mRNA was increased by the osmostress. Sucrose or sodium chloride could also enhance MVP promoter activity. Inhibition of p38 MAPK in SW620 cells by SB203580 inhibited the expression of MVP under hyperosmotic stress. These findings suggested that osmotic stress up-regulated the MVP expression through p38 MAPK pathway. Down-regulation of MVP expression by MVP interfering RNA (RNAi) in SW620 cells increased the sensitivity of the cells to hyperosmotic stress and enhanced apoptosis. Furthermore, MVP RNAi prevented the osmotic stress-induced, time-dependent increase in phosphorylated Akt. These findings suggest that the PI3K/Akt pathway might be implicated in the cytoprotective effect of MVP. Our data demonstrate that exposure of cells to hyperosmotic stress induces MVP that might play an important role in the protection of the cells from the adverse effects of osmotic stress.

We describe the successful use of medical leeches to relieve venous congestion of a free forearm flap after reconstruction in a patient with intraoral carcinoma.A 63-year-old woman consulted our clinic because of an ulcer on the left buccal mucosa. Histopathological examination revealed squamous cell carcinoma. After 60Co radiotherapy of with a total dose of 34 Gy, she underwent bilateral upper neck dissection and resection of the carcinoma. The cheek mucosa was reconstructed by transplantation of a free forearm flap.Because the flap became swollen and black, suggesting venous congestion, the vein connected to the flap was unsutured and anastomosed again on the 5 th day after the operation. However, the patient's condition did not improve.Leech therapy was started on the 4 th day after reanastomosis. A medical leech was applied to the flap for 40 minutes twice daily. After 10 leeches were used in 5 days, the flap apparently recovered and nearly healed.Hirudin contained in the saliva of leech is reported to have various effects, such as vasodilation, anticoagulation, and local anesthesia. The anticoagulative effect was considered the most important for improving the congestion in our patient.

To ensure reliable surgical margins, intraoperative frozen section histological analysis (FS) has been performed since October, 2005 as follows: i) the orientation at the anatomical position and extent of the tumor are shared between oral pathologists and oral surgeons using imaging evaluations and pathological pictures and the planned site of sampling for intraoperative FS is confirmed; ii) a tumor team is organized and the team marks the tumor area and sets the resection range to correct the setting errors of the resection range among operators; iii) vital Lugol staining is applied to the lesion prior to tumor resection, the surgical margin is set based on the non-stained region and the extent of the tumor is macroscopically confirmed in the maximum cross-sectional surface of the resected specimen; and iv) FS is performed using samples from resected specimens to confirm the mucoepithelium and safety margin of the deep stump. The aim of this study was to evaluate the usefulness of our FS method. The treatment outcomes of oral squamous cell carcinoma were retrospectively investigated in patients treated prior to (Group 1) and after (Group 2) the introduction of our FS method. The recurrence rate of the primary lesions was high (17.3%) in Group 1, but decreased significantly in Group 2 (6.9%). Regarding clinicopathological factors, the condition of the surgical margins was associated with recurrence of the primary lesion in Group 1, but not in Group 2. In conclusion, our FS method appears to be useful for resecting tumors with reliable safety margins.

Epithelial–mesenchymal transition (EMT), a key process in the tumor metastatic cascade, is characterized by the loss of cell–cell junctions and cell polarity as well as the acquisition of migratory and invasive properties. However, the precise molecular events that initiate this complex EMT process are poorly understood. Snail is a regulator of EMT that represses E-cadherin transcription through its interaction with proximal E-boxes in the promoter region of target genes. To investigate the role of Snail in EMT, we generated stable Snail transfectants using the oral squamous cell carcinoma cell line HSC-4 (Snail/HSC-4). Snail/HSC-4 cells had a spindle-shaped mesenchymal morphology, and enhanced migration and invasiveness relative to control cells. Consistent with these EMT changes, the downregulation of epithelial marker proteins, E-cadherin and desmoglein 2, and the upregulation of mesenchymal marker proteins, vimentin and N-cadherin were detected. Despite these observations, the mRNA levels of E-cadherin and desmoglein 2 did not decrease significantly. Although E-cadherin and desmoglein 2 proteins were stable in parental HSC-4 cells, these proteins were rapidly degraded in Snail/HSC-4 cells. The degradation of E-cadherin, but not desmoglein 2, was inhibited by dynasore, an inhibitor of dynamin-dependent endocytosis. Therefore, in HSC-4 cells Snail regulates levels of these proteins both transcriptionally and post-translationally.

The glandular odontogenic cyst (GOC) is a rare odontogenic cyst which is still controversial in regard to classification, terminology, and origin. The first Japanese case of GOC is reported. Immunohistochemical examination for expression of cytokeratins and epithelial membrane antigen by monoclonal antibodies suggested that the lining epithelium was of odontogenic origin with metaplastic mucus-laden cells. We have reviewed the literature and compared the clinicopathological findings of the reported case of GOC with those of botryoid odontogenic cysts (BOC). The anatomical location, age range, and sex of GOC cases were very similar to those of BOC. GOC appears to be a multiocular and mucoepidermoid variant of non-keratinizing odontogenic cysts, which also includes BOC. GOC should be separated from the other types of odontogenic cyst and central mucoepidermoid tumours of salivary gland origin.

We introduced concurrent neoadjuvant chemoradiotherapy (CCRT) with S-1, an oral fluoropyrimidine, as treatment for oral squamous cell carcinoma (OSCC) from October 2005. The clinical usefulness and medical safety of CCRT with S-1 (S-1 group) for OSCC were analyzed and compared with CCRT using super-selective intra-arterial infusion (AI group). The subjects in the S-1 group underwent external irradiation, at a total dose of 30 Gy, with S-1 chemotherapy. The AI group received cisplatin (CDDP) or carboplatin (CBDCA) combined with daily radiotherapy at a total dose of 40 Gy. The histological effects and disease-specific survival rates were almost equivalent in the S-1 and AI groups. Adverse events were less frequent in the S-1 group, while hematological toxicity, including anemia, thrombopenia and pharyngeal edema, was observed in the AI group. The results of this study indicate that CCRT combined with S-1 is a more effective and safer treatment for OSCC than AI.

A Clinical evaluation was carried out on 68 patients who underwent orthognathic surgery from 1981 for 10 years in the Second Department of Oral and Maxillofacial Surgery, Kagoshima University. The results were as follows:1. The male-female ratio was 1: 2.2. The average age was 20, 8 years.3. Mandibular prognathism was the most predominant diagnosis (66%). Ten (14%) out of 68 patient were accompanied with cleft palate.4. The extent of mandibular set back in sagittal splitting osteotomy was 10.5mm on the right side and 10.1mm on the left side in average.5. Excision on the tongue in patients with possible macroglossia. The excised areas were 274.2mm2 in average (ranged from 180mm2 to 400mm2).6. In sagittal splitting osteotomy, rigid fixation by use of metal or sapphire screws were employed with the maneuver for repositioning the mandibular condyle. In Le Fort I osteotomy, iliac bone graft and fixation with a miniplate and zygomatic suspension were employed.7. The operation time for sagittal splitting mandiblectomy was 5hr. 41min. in average (ranged from 3hr. 12min. to 8hr. 26min.), and in bimaxillary osteotomy was 7hr. 12min. in average (ranged from 7hr. 17min. to 9hr.58min.).8. The mean blood loss was 537.2ml in the sagittal splitting mandiblectomy (ranged from 114m1 to 2140ml), 1041ml in bimaxillary surgery (ranged from 494ml to 2910ml).9. The routine period of intermaxillary fixation in our department was 14 days for sagittal splitting mandiblectomy, and 21 days for Le Fort I osteotomy.

The aim of this study was to analyze the relationship between the maximum standardized uptake value (SUVmax) of 18F-fluoro-2-deoxyglucose-positron emission tomography (FDG-PET) and the effects of neoadjuvant chemoradiotherapy in oral squamous cell carcinoma (OSCC), and to identify the possible biological background of this association. Thirty-seven patients with OSCC, who underwent preoperative FDG-PET followed by cancer treatment with neoadjuvant chemoradiotherapy, were enrolled in this study. The various histological effects following neoadjuvant chemoradiotherapy were compared to the SUVmax in the primary OSCC. These effects were also compared to the immunohistochemical staining score of hypoxia-inducible factor-1alpha (HIF-1alpha), glucose membrane transporter (GLUT)-1 and vascular endothelial growth factor (VEGF) in the biopsy specimen. Furthermore, we analyzed the chemosensitivity of KB-3-1 cells to cisplatin under hypoxic conditions using the MTT assay. A negative correlation was observed between the SUVmax and the histological effects following neoadjuvant chemoradiotherapy (p

The constitutive activation of the Notch pathway has been demonstrated in various types of malignancies. However, it remains unclear how the Notch pathway is involved in the pathogenesis of oral squamous cell carcinoma (OSCC). We investigated the expression of Notch pathway molecules in OSCC cell lines and biopsy specimens and examined the effect of Notch pathway inhibition. Reverse transcription-polymerase chain reaction revealed upregulation of Notch1, Notch2, Jagged1, HES1 and HEY1 in both OSCC cell lines and biopsy specimens. Immunohistochemical examination showed that the Notch intracellular domain accumulates in the nucleus of cells in OSCC cell lines and biopsy specimens. In addition, Jagged1 is expressed in the cytoplasm of cells in OSCC cell lines and biopsy specimens. Furthermore, Notch pathway inhibition using a gamma-secretase inhibitor prevented the growth of OSCC in vitro. These findings suggest that inhibition of the Notch pathway suppresses OSCC growth and may be a useful approach for the treatment of patients with OSCC.

Small cell carcinoma (SCC) in the head and neck region is an extremely rare high-grade malignant tumor. The authors report a case of an SCC occurring in the left buccal region. An 85-year-old man exhibited left cheek swelling that rapidly increased in size. Histopathological examination revealed invasive growth of an SCC into the musculo-adipose tissue. Immunohistochemically, the tumor cells were positive for cytokeratin (AE1/AE3), neuron-specific enolase (NSE) and CD56, but negative for cytokeratin 20. The patient received chemotherapy and radiotherapy, which resulted in marked regression of the tumor. Surgical resection was performed. The serum levels of NSE and pro-gastrin-releasing peptide (pro-GRP) increased and multiple metastases of the tumor occurred 1 month after surgery. SCCs tend to exhibit aggressive invasion and metastasis so chemotherapy for the whole body is recommended to prevent dissemination of the tumor cells. Serum levels of NSE and pro-GRP are considered to be useful tumor markers for understanding the status of the tumor and the clinical symptoms.

A clinico-statistical analysis was carried out on the 341 patients with primary cleft lip and palate who visited our clinic during the 10-year period since 1981.The results were as follows:1. The body weight at birth of 324 patients averaged 3, 061. 6 g (ranged from 1, 350 to 4, 380 g). The incidence of low-weight babies less than 2, 500 g accounted for 10. 8 percent of the patients, which was higher than in the normal.2. The mean age of the 290 mothers at delivery was similar to the normal distribution. High-aged mothers over 35 years old accounted for 6. 6 percent. No relationship was suggested between the mother's age and the occurrence of cleft lip and palate.3. Bottle feeding was being used in most patients at the first medical examination (72.4% of 301 patients).4. Other congenital malformations were detected in 71 patients (20.8% of all 341patients). The cleft palate (CP) group showed the highest incidence among the three (CP, CL and CLP) groups.5. A family history was found in 49 (14. 4%) of 341 patients.

An osseous choristoma occurring on the tongue of a Japanese 11-year-old girl is reported. The lesion was a polypous mass, measuring about 8×8×5 mm, in the centroposterior region of the tongue. The lesion was removed under general anesthesia.Histologically, the lesion consisted of dense lamellar bone with Haversian canals and bone marrow. It was surrounded by a thin layer of fibrous conective tissue and covered by stratified squamous epithelium. The origin of this lesion was discussed briefly, referring to the literature.