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S-1 is an anticancer agent that is comprised of tegafur, gimeracil, and oteracil potassium, and is widely used in various carcinomas including oral squamous cell carcinoma (OSCC). Although an established prediction tool is not available, we aimed to develop prediction models for the sensitivity of primary OSCC cases to the preoperative administration of S-1. We performed DNA microarray analysis of 95 cases with OSCC. Using global gene expression data and the clinical data, we developed two different prediction models, namely, model 1 that comprised the complete response (CR) + the partial response (PR) versus stable disease (SD) + progressive disease (PD), and model 2 that comprised responders versus non-responders. Twelve and 18 genes were designated as feature genes (FGs) in models 1 and 2, respectively, and, of these, six genes were common to both models. The sensitivity was 96.3%, the specificity was 91.2%, and the accuracy was 92.6% for model 1, and the sensitivity was 95.6%, the specificity was 85.2%, and the accuracy was 92.6% for model 2. These models were validated using receiver operating characteristic analysis, and the areas under the curves were 0.967 and 0.949 in models 1 and 2, respectively. The data led to the development of models that can reliably predict the sensitivity of patients with OSCC to the preoperative administration of S-1. The mechanism that regulates S-1 sensitivity remains unclear; however, the prediction models developed provide hope that further functional investigations into the FGs will lead to a greater understanding of drug resistance., Genetics; Clinical Genetics; Surgery; Pharmacology; Oncology; anti-tumor agent; 5-fluorouracil; oral squamous cell carcinoma; OSCC; prediction model; S-1.

Both MUC1 and MUC4 are high molecular weight glycoproteins and are independent indicators of worse prognosis in many human epithelial cancers including oral squamous cell carcinoma (OSCC). However, there has been no investigation of the clinical importance of the co-expression of MUC1 and MUC4 in OSCC. The aim of this study was to evaluate the co-expression profile of MUC1/MUC4 and analyze the prognostic significance in OSCC. We examined the expression profile of MUC1 and MUC4 in OSCC tissues from 206 patients using immunohistochemistry. The co-expression profile of MUC1/MUC4 and its prognostic significance in OSCC was statistically analyzed. MUC1 and MUC4 overexpression were strongly correlated with each other (p

Objectives The present study was undertaken to evaluate the anti-fungal activity of amphotericin B (AMPH-B), flucytosine (5-FC), fluconazole (FLCZ), miconazole (MCZ), itraconazole (ITCZ), and micafungin (MCFG) against clinically isolated Candida strains from oral candidiasis (OC) patients and to collect information useful for the treatment of OC. Subjects and methods The study includes 116 strains of Candida isolated from patients. The Candida species were identified by polymerase chain reaction. The minimum inhibitory concentration (MIC) of each drug against each Candida species was determined. Results Of the 106 participants (30 males and 76 females), 57 had OC, including 42 cases of pseudomembranous OC, 11 cases of erythematous OC, 2 cases of hypertrophic OC, and 2 cases of mixed pseudomembranous/erythematous OC. The Candida species isolated were Candida albicans (93 strains), C . glabrata (19 strains), and C. tropicalis (4 strains). AMPH-B and 5-FC had low MIC values against all species of Candida and a low incidence of resistance development. In some species of Candida , FLCZ and ITCZ showed high MICs, but MCZ had a low MIC value. AMPH-B, MCZ, and ITCZ prescribed to OC patients were effective against OC with respect to alleviation of OC symptoms. Conclusion MIC values of anti-fungal drugs against Candida strains isolated from OC patients were obtained and the 3 anti-fungal drugs given to OC patients were found to be effective against OC in spite of differences in their MIC values and in the number of resistant strains (or strains with a high MIC value).

Myofibroblastoma is a rare benign stromal neoplasm with myofibroblastic differentiation most often seen in the breast. In the oral region, only one case of myofibroblastoma has been reported so far; therefore, the diagnostic criteria of this tumor are still controversial in the field of oral pathology. Herein, the authors present a case of myofibroblastoma of the tongue and demonstrate the usefulness of immunohistochemistry in diagnosing this tumor. Histologically, the tumor was composed of interlacing bundles of spindle-shaped or oval cells with hyalinized stroma and amianthoid fibers. Immunohistochemically, the tumor cells showed characteristic features of mammary type myofibroblastoma: diffuse immunoreactivity for desmin, vimentin, and Bcl-2; focal immunoreactivity for α-smooth muscle actin, CD34, and cyclin D1; and no immunoreactivity for h-caldesmon. The pathological diagnosis of myofibroblastoma was made. The authors propose myofibroblastoma as a distinctive entity in the oral region, which should not be confused with other spindle-cell tumors or hamartomatous proliferation with myofibroblastic differentiation, and recommend the inclusion of extramammary myofibroblastoma in the differential diagnosis of soft tissue tumors of the oral cavity.

Purpose To prove that chromatin immunoprecipitation assay can be performed with oral rinse samples and to develop a protocol for comprehensive analysis of functional interactions among DNA methylation, histone modification, and gene expression using such samples. Materials and Methods Eleven cancer cell lines and oral rinse samples from 10 patients with oral squamous cell carcinoma and 3 healthy subjects were examined. The expression of CDKN2A , a tumor suppressor gene, was determined by reverse transcription/polymerase chain reaction and immunohistochemistry. Promoter DNA methylation was assessed by methylation-specific polymerase chain reaction. Chromatin modifications were analyzed by a chromatin immunoprecipitation assay using antibodies for dimethylation and acetylation of lysine 9 of histone H3. Results Epigenetic control of CDK2NA was observed in vitro in 11 cancer cell lines. Using the present protocol, comprehensive epigenetic analysis could be successfully performed with oral rinse samples. All patients were comfortable using the prescribed amount (16 mL) of normal saline to rinse their mouths. Nine patients (90%) and 1 healthy subject (33%) showed dimethylation of lysine 9 of histone H3. Moreover, 8 patients (80%) showed hypoacetylation of lysine 9 of histone H3, which was not observed in healthy subjects. Conclusions The present study showed for the first time that chromatin modifications can be analyzed using oral rinse samples by chromatin immunoprecipitation analysis. To evaluate the contribution of histone modifications for carcinogenesis of oral squamous cell carcinoma, studies including a larger number of subjects should be conducted in the future.

Oculo-facio-cardio-dental (OFCD) syndrome is a rare syndrome characterized by ocular, facial, cardiac, and dental disorders. Only about 20 cases have been reported to date. The most prominent of the various features of this syndrome is canine radiculomegaly. Other features include a long and narrow face, a high nasal bridge, a broad and pointed nose, a bifid nose, ear deformity, cleft palate or submucous cleft palate, maxillary growth retardation, a large gonial angle, open apices, delayed eruption, persistent deciduous teeth, extreme overbite, and constricted maxilla. Orthodontic and prosthodontic treatment has been reported for several patients, but surgical-orthodontic treatment for OFCD has not been reported. An 18-year-old woman with skeletal Class III malocclusion and OFCD syndrome was treated with edgewise appliance therapy combined with orthognathic surgery. We applied a light force during the treatment so as not to induce ankylosis. At the end of the surgical and orthodontic treatments, functional occlusion and an improved facial profile were achieved. After the retention period, stomatognathic function was improved. The results of this treatment suggest that surgical-orthodontic treatment is an effective method for improving skeletal disharmony, facial profile, occlusion, and stomatognathic function in patients with OFCD.

BACKGROUND: DF3/MUC1 mucin is expressed in various cancer tissues, and many in vitro studies have suggested that it may play a role in the aggressive behavior of malignant tumors. However, to the best of the authors' knowledge, the relation between DF3/MUC1 expression and outcome has not yet been investigated in patients with oral squamous cell carcinoma (OSCC). The objective of the current study was to evaluate the prognostic significance of DF3/MUC1 expression in patients with OSCC. METHODS: The expression profile of DF3/MUC1 in OSCC tissues from 206 patients was examined using immunohistochemistry. Its prognostic significance in OSCC was statistically analyzed on the basis of detailed clinicopathologic factors. RESULTS: DF3/MUC1 expression was found to be significantly correlated with tumor aggressiveness, such as pathologic lymph node metastasis (P = .002), advanced tumor stage (P = .02), diffuse invasion of cancer cells (P = .03), and vascular invasion (P = .01). Respectively, the overall survival (OS)and disease-free survival (DFS) rates were significantly worse for patients with DF3/MUC1 expression compared with those without DF3/MUC1 expression (P = .001 and P = .0003, respectively). Multivariate analysis demonstrated that DF3/MUC1 expression was an independent prognostic factor for both OS and DFS (P = .04 for both). In addition, DF3/MUC1 expression was found to be an independent risk factor for subsequent regional lymph node metastasis (P = .03). CONCLUSIONS: Aberrant expression of DF3/MUC1 is an independent prognostic factor indicating poor prognosis in patients with OSCC. DF3/MUC1 expression is a risk factor for subsequent lymph node metastasis in patients with OSCC and therefore may represent an indication for elective neck dissection. Patients with OSCC demonstrating positive expression of DF3/MUC1 should be followed carefully. Cancer 2012. © 2012 American Cancer Society.

BACKGROUND: The early detection of oral squamous cell carcinoma (OSCC) is important, and a screening test with high sensitivity and specificity is urgently needed. Therefore, in this study, the authors investigated the methylation status of tumor-related genes with the objective of establishing a noninvasive method for the detection of OSCC. METHODS: Oral rinse samples were obtained from 34 patients with OSCC and from 24 healthy individuals (controls). The methylation status of 13 genes was determined by using methylation-specific polymerase chain reaction analysis and was quantified using a microchip electrophoresis system. Promoter methylation in each participant was screened by receiver operating characteristic analysis, and the utility of each gene’s methylation status, alone and in combination with other genes, was evaluated as a tool for oral cancer detection. RESULTS: Eight of the 13 genes had significantly higher levels of DNA methylation in samples from patients with OSCC than in controls. The genes E-cadherin (ECAD), transmembrane protein with epidermal growth factor-like and 2 follistatin-like domains 2 (TMEFF2), retinoic acid receptor beta (RARb), and O-6 methylguanine DNA methyltransferase (MGMT) had high sensitivity (>75%) and specificity for the detection of oral cancer. OSCC was detected with 100% sensitivity and 87.5% specificity using a combination of ECAD, TMEFF2, RARb, and MGMT and with 97.1% sensitivity and 91.7% specificity using a combination of ECAD, TMEFF2, and MGMT. CONCLUSIONS: The aberrant methylation of a combination of marker genes present in oral rinse samples was used to detect OSCC with >90% sensitivity and specificity. The detection of methylated marker genes from oral rinse samples has great potential for the noninvasive detection of OSCC. Cancer 2012;118:4298-308. V C 2012 American Cancer Society.

Summary Up to now, we have performed scintigraphy with 201-thallium chloride (201-TlCl) and 99m-Tc-hexakis-2-methoxy-isobutyl-isonitrile (99m-Tc-MIBI) for malignant tumors and lymphoscintigraphy with 99m-Tc-rhenium-colloid (99m-Tc-Re) and 99m-Tc-human-serum-albumin-diethylene-triamine-penta-acetic-acid (99m-Tc-HSA-D) for lymph node metastasis. In this article, we re-evaluated scintigraphic images retrospectively with a hope that the results might be a clue, even if it is small, for dentists to try to improve the accuracy of diagnosis of malignant tumors. From scintigraphy, we obtained the tumor retention index as a factor to estimate the uptake of radioactive agents in tumor cells. Moreover, we estimated transport proteins of Na + /K + -ATPase and permeability-glycoprotein (P-gp) expressed on the cell membrane that might regulate the kinetic condition of radioactive agents. Among the tumor retention index, the transport protein and the histopathologic finding of tumors, there were relatively well correlations. The tumor retention index showed a difference clearly between malignant tumor and benign tumor. The transport protein revealed a distinct expression in accordance with the malignancy of tumor, and the uptake clearly depended upon the expression of transport protein. Moreover, the lymph node metastasis was detected well by lymphoscintigraphy with 99m-Tc-Re and 99m-Tc-HSA-D.

We performed an orthodontic treatment combined with mandibular distraction osteogenesis in a 15-year-old patient who wanted a correction of a chin deficiency and a protruding upper lip. The patient had an Angle Class II division 1 malocclusion with mandibular retrusion, a low mandibular plane angle, and scissors bite. First, a quad-helix appliance was applied to the mandibular dentition to correct the scissors bite in the bilateral premolar region. Later, a preadjusted edgewise appliance was applied to the maxillary and mandibular teeth. After 3 days, a mandibular distraction osteogenesis was performed. During and after the distraction, the open bite between the upper and lower dental arches was corrected using up and down elastics. The total treatment time with the edgewise appliance was 14 months. A skeletal Class I apical base relationship, good facial profile, and optimum intercuspation of the teeth were achieved with the treatment. The jaw-movement pattern on the frontal view did not change during gum chewing. However, the maximum gap without pain increased. The electromyographic (EMG) activity of the masseter and anterior temporalis muscles, and maximum occlusal force increased. The present case report suggests that an orthodontic treatment combined with mandibular distraction osteogenesis in a patient with mandibular retrusion in the late growth period might be effective for improving stomatognathic function.

It has been reported that the treatment of patients with mental retardation is difficult because their ability to cooperate with the treatment has been insufficient. This case report describes a successful orthodontic treatment with a maxillary advancement and expansion using distraction osteogenesis in an adult female who was mentally retarded, with the intelligence of a person around 9 years old. She was diagnosed as having an Angle Class III malocclusion with a cleft soft palate, maxillary hypoplasia, total crossbite and a skeletal Class III jaw relationship. This case report indicates an effective application of sympathetic nursing care and therapeutic play intervention to patient's psychological stress symptoms during hospitalization, and the treatment results of maxillary distraction and orthodontic treatment.

A case report of angiosarcoma of the tongue is presented. The specimen revealed single and clustered large, pleomorphic, and spindle-shaped cells with a markedly hemorrhagic background. Tumor cells showed expression of thrombomodulin and E-selectin, but no expression of Factor VIII-related antigen, Ulex europaeus agglutinin-1, vascular endothelial growth factor, and CD34. In the current study, immunohistochemical results using antibodies against thrombomodulin and E-selection supported the diagnosis of angiosarcoma.

We reported earlier that hydroxyapatite (HA) formed on/in agarose gels (HA/agarose) produced by alternate soaking process is a bone-filling material possessing osteoconductive and hemostatic effects. This process could allow us to make bone-like apatite that was formed on/in organic polymer hydrogel matrices. Here, we investigated the mechanism of hemostasis induced by HA/agarose and found that HA/agarose, but not agarose or HA powder, significantly shortened activated partial thromboplastin time (APTT). While HA/agarose did not show significant platelet aggregation, it markedly enhanced adenosine diphosphate (ADP)-induced platelet aggregation. Moreover, Western blot analysis revealed selective adsorption of vitronectin onto HA/agarose. We also observed marked differences between HA powder and HA/agarose in their XRD patterns. The crystallinity of HA powder was much higher compared to that of HA/agarose. Furthermore, 50–100 nm of tube-form aggregations was observed in HA powder on the other hand 100–200 nm of particles was observed in HA/agarose by SEM observation. Thus 100–200 nm of low crystallized particles on the surface structure of HA/agarose may play an important role in hemostasis. Our results demonstrated a crucial role of HA/agarose in the mechanism of hemostasis and suggested a potential role for HA/agarose as a bone-grafting material. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006

Calcifying epithelioma (pilomatrixoma) is a benign cutaneous tumor derived from skin appendages, such as pilomatrix. It is usually a solitary tumor and commonly found on the head, neck, and upper extremities inyoung-adult women; multiple occurrences are rare. Histopathologically, the tumor is composed of basophilic cellsand eoshinophilic shadow cells with occasional calcification and bone formation.A 20-year-old woman presented to our clinic with a 4-year history of amass arising in the inferior part of theright auricle. Examinations revealed two other solitary masses on both forearms. The tumor at the inferior part ofthe auricle showed marked calcification and ossification. We also clinicopathologically compared this case withfive previous cases. Wound healing was good 1 year and 6 months after surgery.

BACKGROUND: Oral squamous cell carcinoma develops through a multistep of genetic mutations, and the process can be morphologically recognized as oral epithelial dysplasia. To evaluate the hypothesis that distributional alterations of proliferating and stem cells may be a useful index to estimate the grading and development of epithelial dysplasia, we examined the distribution patterns according to stratified cell layers. METHODS: Sixty-two oral dysplasia cases according to the histological grades were immunohistologically examined and the nuclear expression of Ki-67 and p63 antigens was counted according to epithelial layers as labeling index. RESULTS: The Ki-67 labeling index in the basal and suprabasal layers and that of p63 in the basal layer showed a significant difference between low- and high-grade groups of epithelial dysplasia. CONCLUSION: The architectural alteration of proliferating cell and stem cell distribution in the layers of epithelial dysplasias may provide useful information to evaluate the grading of oral epithelial dysplasias.

Combined epithelial odontogenic tumor was first described by Damm in 1982 as a rare tumor characterized by the presence of calcifying epithelial odontogenic tumor (CEOT) areas in adenomatoid odontogenic tumor (AOT). Histologically, the tumor shows relatively small epithelial nests forming duct-like structures and markedly hyalinized fibrous tissue stroma containing amorphous and irregularly shaped calcified tissue and amyloid-like materials. There are several round-shaped masses that show Liesegang rings. This article describes a case of adenomatoid odontogenic tumor with calcifying epithelial odontogenic tumor-like areas, so-called combined epithelial odontogenic tumor, between the right lateral incisor and the left canine region in the mandible.A 27-year-old woman was referred to our clinic for evaluation of a mixed radiolucent-radiopaque lesion with a well-defined border in the mandible. A computed tomographic scan demonstrated a well-defined large lesion that extended widely, with thinning of the cortical bone of the mandible. The lesion was associated with an impacted canine in the mandible.Surgery was performed with the patient under general anesthesia.The tumor was enucleated completely via an intraoral approach. Wound healing is currently good, 9 months after surgery.

The purpose of this study was to evaluate the usefulness of thallium-201-chloride(Tl-201)scintigraphy for the examination of patients with tumors of the head and neck, and to estimate the correlation of the expression of Na + /K + -ATPase with Tl-201 scintigraphy. Tl-201 scintigraphy was performed in 61 patients with squamous cell carcinoma and 10 patients with benign tumors of the salivary gland. The tumor retention index was obtained from the early and delayed dynamic Tl-201 scintigraphies. The expression of Na + /K + -ATPase on the cell membrane was evaluated immunohistochemically. Evaluation of correlations between the histopathological tissue differentiation of tumors, the tumor retention index of Tl-201 scintigraphy and the expression of Na + /K + -ATPase was performed. The tumor retention index of Tl-201 scintigraphy correlated well with the histopathological tissue differentiation of tumors and also showed a good correlation with the expression of Na + /K + -ATPase. In addition, the expression of Na + /K + -ATPase demonstrated a close correlation with the histopathological tissue differentiation of malignant tumors. The tumor retention index could be used for the differentiation of malignant tumors from benign tumors and the expression of Na + /K + -ATPase was estimated as one of the most important factors for Tl-201 accumulation in malignant tumors.

Improved diagnostic and treatment techniques for malignant tumors and increased numbers of elderly patients have led to the detection of greater numbers of multiple primary cancers. We describe our experience with a case of synchronous primary triple cancers. Thyroid cancer was discovered during treatment for tongue cancer, following a bladder cancer.After the diagnosis of tongue cancer, the recurrence of bladder cancer was detected. The recurrent bladder cancer was treated first, followed by the tongue cancer. Radical neck dissection for the tongue cancer revealed occult lymph node metastasis from thyroid cancer. Although thyroidectomy was scheduled to be performed after treatment for the tongue cancer, the second recurrence of bladder cancer was diagnosed. After therapy for this bladder cancer, thyroidectomy was performed.Treatment for synchronous primary triple cancers should be planned to achieve the best outcome for each cancer. Outcome is poorer for patients with multiple primary cancers than for those with single primary cancer. To improve the outcome of synchronous primary cancers, early detection, prompt and effective treatment, and close follow-up of the patient's course, including examination of predilection sites, are considered important.

The present study was designed to evaluate the effects of a hydroxyapatite/agarose (HA/agarose) composite gel formed by a novel alternate soaking process for the treatment of periodontal infrabony defects in three dogs. After creating two-wall infrabony periodontal defects on the medial aspect of the maxillary and mandibular second and forth premolars, the defects were implanted with temporary dental filling material (stopping) to induce inflammatory periodontal disease. Two months later, the mucoperiosteal flaps were raised, and after debridement, the infrabony defects were filled with one of the following three materials: (a) HA/agarose, (b) Bone ject (True-Bone Ceramic-collagen combined bone graft material, Koken, Japan), or (c) no material implantation (negative control). The animals were then randomly scheduled for sacrifice at 1, 2, and 6 months, and samples were taken for histological examination. In the HA/agarose gels, the 2-month postoperative cavities exhibited regeneration to new attachments with the apposition of a new cementum and well-oriented fibers. The neocementum was narrow and acellular, and the new bone apposition was limited. Six months postoperatively, newly formed bone was predominantly observed. The neocementum was wider and cellular. In the negative control, the 2-month postoperative cavities exhibited no regeneration of the cementum, nor any formation of periodontal pockets. The six-month postoperative cavities were nearly the same as the 2-month cavities. The Bone ject, 2-month postoperative cavities exhibited no regeneration of the periodontal tissue, nor any formation of periodontal pockets. Six months postoperatively, inflammatory granulation tissue was observed around the particles. The present study suggests that HA/agarose gels may play an important role in the regeneration of lost periodontal tissue.

Background: Pleomorphic adenoma of the salivary gland (PA) is essentially a benign neoplasm. However, patients with recurrent PA are difficult to manage. There are rare reports on useful immunohistochemical markers to detect a high risk of recurrence when the primary lesions are resected. Aims: To find a new marker to predict the recurrence of PA. Methods: Primary lesions of PA were collected from nine patients showing subsequent recurrence and from 40 patients without recurrence during at least 10 years of follow up of the disease. Paraffin wax embedded tumour samples of the two groups were examined for the expression profiles of MUC1 (differentially glycosylated forms), MUC2, MUC4, MUC5AC, and MUC6 using immunohistochemistry. Several clinicopathological factors were also examined. Results: In univariate analysis of the factors examined, MUC1/DF3 high expression (more than 30% of the neoplastic cells stained) in the primary lesions was seen more frequently in patients with recurrence (four of nine) than in those without recurrence (three of 40; p = 0.011). Larger tumour size (more than 3.0 cm) of the primary PA was also a significant (p = 0.035) risk factor for the recurrence of PA. In multivariate analysis, only high expression of MUC1/DF3 was found to be a significant independent risk factor for the recurrence of PA (p = 0.021). Conclusions: Expression of MUC1/DF3 in PA is a useful marker to predict its recurrence. Those patients with PA showing positive MUC1/DF3 expression should be followed up carefully.

To understand proliferation and suppression in ameloblastoma that exhibit locally invasive growth and recur clinically, the expression of proliferating cell nuclear antigen (PCNA), Ki-67 antigen, topoisomerase IIα, p53 and p21 proteins were analyzed with immunohistochemistry. Sections of archival ameloblastoma tissues were used (16 plexiform and 14 follicular types). Each antigen was labeled by the polymer method with optimal antigen retrieval. The plexiform type exhibited higher expression of PCNA, Ki-67 and topoisomerase IIα antigens than the follicular type. Expression of PCNA correlated significantly with that of the Ki-67 antigen. The plexiform type also exhibited greater expression of p53 and p21 proteins than the follicular type. Expression of p53 protein correlated significantly with that of p21, PCNA, Ki-67 antigen and topoisomerase IIα. Expression of p21 protein did not correlate with that of the proliferation-related antigens. These findings suggest that the plexiform ameloblastoma has higher proliferating activity and malignant potentiality as neoplastic cells than the follicular ameloblastoma.

Improved treatment of elderly inpatients requires evaluation of their systemic status. We performed open reduction of a mandibular fracture under general anesthesia in a patient who had various underlying diseases, such as hypertension, emphysema, cerebral infarction, diabetes mellitus, and dementia.The patient had presented with dementia before hospitalization. To ensure safety, we paid attention to falling, which had caused the mandibular fracture. However, coronary arterial spasm unexpectedly occurred during operation under general anesthesia. After the planned operation, we prevented the onset of spastic angina, and the patient was discharged without any complications. It is essential to carefully confirm systemic status, including emerging symptoms and disease, to ensure safe perioperative management in elderly patients with many underlying diseases such as hypertension, cerebral infarction, and dementia.

Merkel cell carcinoma, first described by Toker in 1972, is a rare malignant tumour that predominantly occurs in the head and neck region of older patients. This report is of an 86-year-old woman who presented with a mass in the mental region diagnosed as Merkel cell carcinoma. The clinical, histological, and immunohistochemical features of this tumour are described, together with a brief review of the literature.

The biologic behavior of hydroxyapatite formed on/in agarose (HA/agarose) gels with the use of a novel alternate soaking process was compared with commercially available Bone Ject (True-Bone ceramic-collagen combined bone-graft material, Koken, Japan) as a filler for the tooth-extraction sockets of six adult monkeys (Macasa fascicularis). After the monkeys' first premolars were extracted, the defects created were replaced with one of the following materials: (a). HA/agarose created by 12 soaking cycles, (b). HA/agarose created by 9 soaking cycles, (c). Bone Ject, and (d). no material implantation (control). The time of hemostasis in each extraction site was estimated, and the samples were then studied histologically. In the controls, the time of hemostasis was about 5 min. The Bone Ject particles were easily washed out by bleeding, and the time of hemostasis was about 15 min. The HA/agarose gel was densely packed into the bony defect. The hemorrhage from the defects stopped within a few seconds after graft placement. This hemostasis was most likely related to the compactibility and adhesiveness of the material. After 12 weeks of implantation, free Bone Ject particles surrounded by inflammatory cells were observed. The bony defect filled with the HA/agarose gels was completely absorbed and replaced by newly formed bone possessing bone marrow. There was no difference in the biologic behavior of HA/agarose gels created by 9 versus 12 soaking cycles. The present study suggests that HA/agarose gels may play an important role as an alternative biodegradable bone-graft material for autogenous bone in humans.

Gingival fibromatosis is a rare disease characterized by enlargement of the gingiva. The purpose of this study was to analyze a case of idiopathic gingival fibromatosis, using histochemical and immunohistochemical staining and transmission electron microscopy. The patient was a 39-year-old Japanese man, in whom the gingiva was enlarged throughout the entire mandible and maxilla. Specimens of gingival fibromatosis exhibited epithelial hyperplasia and increased amounts of collagen fiber bundles in the connective tissue light-microscopically. Well-developed collagen bundles were strongly stained with Azan and Masson trichrome staining. Immunohistochemically, the gingival connective tissue was specifically stained by type I collagen and vimentin antibodies. Ultrastructurally, the lesion consisted of fibroblasts and mature collagen fibers running in all directions. No myofibroblasts were detected histochemically, immunohistochemically, or ultrastructurally. These findings suggested that this disease may be the result of an increase in collagen synthesis by the fibroblasts and/or that it may be associated with one of the findings of histologic heterogeneity.

Background A standardized neck management strategy for oral cancer patients without clinical nodal metastases remains to be established. Consequently, a decision and sensitivity analysis of two neck management protocols, involving either prophylactic neck dissection or careful observation, was conducted using the Oral Cancer Registry of Kyushu, Japan. Methods We calculated probabilities of subclinical nodal metastases and 5-year survival using the registry data. A two-way sensitive analysis was conducted using the probabilities and parameters of the complete nodal metastasis resection rate (x) and a utility rating that describes the health state induced by dissection (y) compared with the neck condition in a careful-observation group. Results We solved the threshold curve for y and x for the expected utility between the two groups. The results showed that prophylactic neck dissection must guarantee a complete resection of subclinical nodal metastases with no disadvantage to health state to be evaluated as equally satisfactory as careful observation. Conclusions Careful observation involving standardized systematic preoperative and postoperative screening of the neck seems preferable to prophylactic neck dissection for oral cancer patients without subclinical nodal metastases. © 2002 Wiley Periodicals, Inc. Head Neck 24: 582–590, 2002

Objective: The purpose of this study was to evaluate the radiographic findings of malignant fibrous histiocytoma (MFH) and to discuss the contribution of these findings to a differentiation of MFH from other malignant tumors of the head and neck. Study Design: Two cases of MFH of the maxillary sinus affecting the alveolar bone were evaluated radiographically and scintigraphically. Results: We reported the following findings, which have only seldom been described: the presence of fairly well-demarcated bone destruction in the intraoral radiograph; the relatively smooth surface, uniform density, or no necrotic area of the tumor; in computed tomograph images showing the clear separation of the tumor from surrounding soft tissues; bone scintigraphs reflecting the periosteal reaction to tumor invasion; and lymphoscintigraphy of the metastatic lymph nodes. Conclusion: We evaluated the radiographic findings from 2 cases of MFH and describe findings that may aid in the differentiation of MFH. These radiographic features may help dentists differentiate MFH from other malignant tumors in the head and neck, although MFH is a rare disease and there are no radiographic findings that would indicate a specific diagnosis of MFH. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;92:116-23)

BACKGROUND MUC1 mucin is a transmembrane, mucin-like glycoprotein encoded by the MUC1 gene. Although MUC1 expression has been identified in a variety of neoplastic tissues, to the authors' knowledge, few studies have examined MUC1 expression in premalignant and malignant oral lesions. METHODS A total of 36 specimens of oral epithelial dysplasia, 12 carcinoma in situ (CIS) specimens and 77 specimens of oral squamous cell carcinoma (OSCC), were examined by both light and electron microscopy using immunohistochemical staining of MUC1 mucin. Relations between staining patterns and clinicopathologic findings also were examined. RESULTS Distinct membrane MUC1 mucin staining patterns were identified in epithelial dysplasia (33.0%), CIS (50.0%), and OSCC (59.7%) cases. A predominantly cytoplasmic staining pattern was detected in epithelial dysplasia (5.6%), CIS (41.7%), and OSCC (32.5%) cases. Significant positive correlations were found between MUC1 mucin membranous immunoreactivity and disease progression from epithelial dysplasia to OSCC (P < 0.01), mode of tumor invasion (P < 0.02), and lymph node metastasis (P < 0.01). Furthermore, the malignant transformation of oral epithelium, tumor invasion, and tumor metastasis were associated with higher MUC1 mucin expression in the cytoplasm (P < 0.01). In addition to the usual cell surface expression, cytoplasmic expression of MUC1 mucin was confirmed by colloidal gold labeling with transmission electron microscopy. CONCLUSIONS The results of the current study suggest that determination of MUC1 mucin expression may be a parameter in the diagnosis of premalignant and malignant lesions arising in the oral cavity and that this expression may affect the malignant behavior of OSCC. MUC1 mucin expression may be a useful diagnostic marker for prediction of the invasive/metastatic potential of OSCC. Cancer 2000;88:245–54. © 2000 American Cancer Society.

Ganglioside GM2 is expressed on the surface of neuroblastoma and glioblastoma cells, and may also be detected on lung cancer cells. We reported previously that anti-ganglioside GM2 antibody exhibited strong in vitro anti-tumor activity against adriamycin-resistant cancer cells, which overexpressed ganglioside GM2. In the present study, we examined the in vivo anti-tumor effect of the chimeric anti-ganglioside GM2 antibody, KM966, against human lung and breast carcinoma cells, SBC-3 and MCF-7, and respective adriamycinresistant clones, SBC-3/ADM and AdrR MCF-7 in BALB/c nu/nu mice. Ratios of tumor volume (T/C) between KM966treated group and control group were 0.01 for SBC-3, 0.00 for SBC-3/ADM, 0.85 for MCF-7 and 0.34 for AdrR MCF-7 cells, respectively. Nude mice, which were pretreated with antiasialo GM1 antibody to remove natural killer cells, were transplanted with 4 3 10 7 of SBC-3 and SBC-3/ADM subcutaneously. Seven days later, when tumors had grown to a diameter of over 8 mm, mice began to receive intravenous treatment of 120 mg/mouse KM966 daily. Fourteen daily treatments induced regression to less than 4-mm diameter in 4/5 SBC-3 tumors and 5/5 of SBC-3/ADM tumors. All SBC-3/ ADM tumors disappeared completely, suggesting that KM966 exerts a strong in vivo anti-tumor effect on ganglioside GM2-expressing cancer cells. In KM966-treated mice, the surface of the tumor cells stained positive with anti-human IgG. In addition, numerous leukocytes had infiltrated into the tumor mass. Antibody-dependent cell-mediated cytotoxicity (ADCC) of KM966 against tumor cells was examined in vitro by 51 Cr-release assay and revealed that KM966 induces ADCC activity against ganglioside GM2-expressing tumors. Our results suggest that immunotherapy using KM966 may be useful for the treatment of ganglioside GM2-expressing solid tumors. Int. J. Cancer 82:759‐764, 1999. r 1999 Wiley-Liss, Inc.

九州地区口腔癌懇話会は, 多施設共同研究により, 口腔とその隣接領域の悪性腫瘍に関する臨床研究の向上, 治療成績の改善を目的として1994年4月に発足した。口唇, 口腔, 中咽頭 (UICC分類) の癌腫, 顎骨中心性癌を有する患者データを記録する全施設共通の記録用紙 (共通カルテ) が作成された。共通カルテには以下の項目が含まれている。1) 年齢, 性, 未治療, 既治療など, 患者に関する一般的情報。2) 診断日, p分類を含むTNM分類, 診断に関連した項目。3) 初回治療日, 治療法, 治療後の経過 (腫瘍制御, 再発) 。4) 原発腫瘍および転移病巣に対する手術, 放射線治療, 化学療法, その他の治療法の詳細。5) 多発癌と重複癌, 同時性癌と異時性癌。6) 治療法のまとめ, 観察期間, 生存状態や死因などの患者の転帰。共通カルテで使用した用語のうち, 議論のある幾つかの用語についての私たちの取り決め, 共通カルテを使用した経験, 共通カルテに今後必要と思われる内容を述べた。共通カルテのデータは, これに対応したソフトを用いて容易にコンピュータへ入力でき, 同時にデータベースソフト (ファイルメーカーPro ver.3.0) 内に蓄積される。

Thrombomodulin (TM) is a glycoprotein that was originally identified on vascular endothelium and characterized as a natural endothelial anticoagulant. We reported previously that TM was also expressed at cell-cell boundaries of squamous epithelium, except in the basal layer cells and upper granular layer cells. The expression pattern of TM in the squamous cells implies that this molecule might be associated with keratinocyte differentiation, as well as being a potent anticoagulant. In the present study we examined TM expression immunohistochemically in biopsy specimens from 65 patients with primary oral squamous cell carcinoma (OSCC), and compared the results with the biological behavior of the carcinomas. The patients with intense TM expression in the carcinoma showed a significantly lower frequency of lymph node metastasis and significantly more favorable survival than those with negative TM expression. The TM expression was a better marker than the other prognostic factors, such as differentiation degree, tumor size and invasion mode. When TM expression was compared between the primary and metastatic lesions in the 36 patients who had lymph node metastasis, 14 (39%) showed decreased TM expression, 19 (53%) showed no change, and 3 (8%) showed an increase in the metastatic lesions. Wilcoxon's signed-rank test indicated that tumor cells positive for TM expression were significantly rarer in the metastatic lesions than in the primary tumors (P < 0.05). These results indicate that reduced expression of TM is associated with metastasis of carcinoma cells. The reduction of TM expression seems to play an important role in the metastatic process of OSCC, and to be related with a poor outcome for the patients.

In 117 patients with oral cancer who were examined scintigraphically and histopathologically, the tumor blood flow was estimated scintigraphically immediately after administration of99mTc-Hydroxymethylene-diphosphate (99mTc-HMDP). The radioactivity was measured in the venous phase (30 to 40 seconds after administration) and in the blood pool phase (1 to 3 minutes), and the radioactivity ratios of the tumor to the control region in both phases, (venous ratio, VR and blood pool ratio, BPR, respectively) were calculated. The early image with99mTc-HMDP (early image) was obtained 5 minutes after administration, and the image with67Ga-citrate (Ga-image) was obtained 3 days after administration. Among the tumor classified histopathologically as showing rich, intermediate and poor vascularity, those with poor vascularity showed small VR (M±SD=0.97±0.08) and BPR (1.02±0.04), whereas those with rich vascularity showed large VR (1.39±0.01) and BPR (1.31±0.16). Early image demonstrating tumor was frequent among tumors with large VR (78%) and with large BPR (100%). Of tumors under 3 cm in diameter, 65% showed intermediate or rich vascularity and positive early image for tumor blood flow. These results suggest that the detection of small soft tissue tumors can be improved by combining the early image with the Ga-image.

Orthognathic surgery was performed on 180 patients from 1984 to 1993 in our clinic. There were 42 male and 138 female patients with a mean age of 20 years. 154 patients (85.5%) were diagnosed with mandibular prognathism. 160 patients (88.9%) underwent sagittal splitting ramus osteotomy (Obwegeser-Dal Pont's method). 29 patients underwent Le Fort I osteotomy. The average time of operation and the average blood loss during operation were 3 hr 41 min and 583 ml for sagittal splitting ramus osteotomy with tongue reduction, 3 hr 13 min and 580 ml for sagittal splitting ramus osteotomy, 4 hr 51 min and 926 ml for Le Fort I osteotomy, 5 hr 49 min and 1, 091ml for two jaw surgery. Tongue reduction (Egyedi-Obwegeser's method) was carried out on 113 patients (62.8%) 169 patients (93.9%) received autologous blood transfusion, and 72% of blood loss was replenished by autologous blood transfusion.

Standards for stored autologous blood transfusion were established recently based on the clinical experience and research data for 140 autologous blood transfusions, which have been carried out in orthognathic surgery patients between 1985 and 1992 at the First Department of Oral and Maxillofacial Surgery, Kagoshima University Dental Hospital, Japan. Regarding standards designed to avoid anemia after phlebotomy, one time collection volume was decided using the following formula: predicted Hb level after collection=(circulating blood volume-one time collection volume) ÷circulating blood volume×Hb level before collection ≥10 g/dl. Fifteen female patients with mandibular prognathism were studied hematologically following a 400 ml autologous blood collection and a transfusion to evaluate the efficiency of this new standard.Two units of whole blood were collected 15 days before each patient's operation. All units of collected blood were transfused without homologous blood transfusion. RBCs, Hb and Hct, which were reduced after the phlebotomy, normalized the day before operation. The rate of reticulocytes was tended to increase during the period of blood storage and for one week after operation. The iron level in the serum was minimum on the day following operation, suggesting the need for postoperative iron supplementation. Increased serum erythropoietin levels, similar to reticulocytes, showed high erythropoietic activity from the first day following the phlebotomy to the postoperative period. There were no differences between the actual minimum Hb level and the predicted Hb level after blood collection of 400 ml. The Hb level on the first day after operation was significantly higher than the calculated Hb level on the same day without blood transfusion (p

DF3/MUC1 mucin is expressed in various cancer tissues, and many in vitro studies have suggested that it may play a role in the aggressive behavior of malignant tumors. However, to the best of the authors' knowledge, the relation between DF3/MUC1 expression and outcome has not yet been investigated in patients with oral squamous cell carcinoma (OSCC). The objective of the current study was to evaluate the prognostic significance of DF3/MUC1 expression in patients with OSCC.The expression profile of DF3/MUC1 in OSCC tissues from 206 patients was examined using immunohistochemistry. Its prognostic significance in OSCC was statistically analyzed on the basis of detailed clinicopathologic factors.DF3/MUC1 expression was found to be significantly correlated with tumor aggressiveness, such as pathologic lymph node metastasis (P = .002), advanced tumor stage (P = .02), diffuse invasion of cancer cells (P = .03), and vascular invasion (P = .01). Respectively, the overall survival (OS)and disease-free survival (DFS) rates were significantly worse for patients with DF3/MUC1 expression compared with those without DF3/MUC1 expression (P = .001 and P = .0003, respectively). Multivariate analysis demonstrated that DF3/MUC1 expression was an independent prognostic factor for both OS and DFS (P = .04 for both). In addition, DF3/MUC1 expression was found to be an independent risk factor for subsequent regional lymph node metastasis (P = .03).Aberrant expression of DF3/MUC1 is an independent prognostic factor indicating poor prognosis in patients with OSCC. DF3/MUC1 expression is a risk factor for subsequent lymph node metastasis in patients with OSCC and therefore may represent an indication for elective neck dissection. Patients with OSCC demonstrating positive expression of DF3/MUC1 should be followed carefully.

AIM: To clarify human papillomavirus (HPV) involvement in carcinogenesis of the upper digestive tract of virological and pathological analyses. METHODS: The present study examined the presence of HPV in squamous cell carcinomas of the oral cavity (n = 71), and esophagus (n = 166) collected from Japan, Pakistan and Colombia, with different HPV exposure risk and genetic backgrounds. The viral load and physical status of HPV16 and HPV16-E6 variants were examined. Comparison of p53 and p16INK4a expression in HPV-positive and HPV-negative cases was also made. RESULTS: HPV16 was found in 39 (55%) oral carcinomas (OCs) and 24 (14%) esophageal carcinomas (ECs). This site-specific difference in HPV detection between OCs and ECs was statistically significant (P < 0.001). There was a significant difference in the geographical distribution of HPV16-E6 variants. Multiple infections of different HPV types were found in 13 ECs, but multiple infections were not found in OCs. This difference was statistically significant (P = 0.001). The geometric means (95% confidence interval) of HPV16 viral load in OCs and ECs were 0.06 (0.02-0.18) and 0.12 (0.05-0.27) copies per cell, respectively. The expression of p16INK4a proteins was increased by the presence of HPV in ECs (53% and 33% in HPV-positive and -negative ECs, respectively; P = 0.036), and the high-risk type of the HPV genome was not detected in surrounding normal esophageal mucosa of HPV-positive ECs. CONCLUSION: Based on our results, we cannot deny the possibility of HPV16 involvement in the carcinogenesis of the esophagus.

1976年1月から1990年12月までの15年間に, 鹿児島大学医学部歯科口腔外科および鹿児島大学歯学部第1口腔外科において, 治療を行った悪性腫瘍患者285例を対象として臨床統計的観察を行い, 以下の結果を得た。1.対象症例285例中, 癌腫は267例 (93.7％) , 肉腫は16例 (5.6％) , その他は2例 (0.7％) であり, また, 性別は男性173例, 女性112例で, 男女比は1.5: 1であった。初診時年齢は21～92歳, 平均59.8歳, 年齢分布では60歳台 (30.9％) が最も多かった。2.癌腫267例の初発症状としては, 疼痛 (29.6％) , 腫瘤 (27.9％) , びらん・潰瘍形成 (20.0％) が多く, 一方, 一次症例271例の発生部位では, 舌が103例 (38.0％) と圧倒的に多かった。3.組織型別では, 扁平上皮癌が234例に達し, 全体の82.1％, 癌腫の87.6％を占めていた。4.治療法としては, 術前化学療法後に手術を行ったものが87例 (30.5％) , 手術単独が85例 (29.8％) などであった。5.一次症例271例の5年累積生存率は66.3％, 組織型別では, 癌腫は67.1％, 肉腫は45％, その他の悪性腫瘍は100％であった。

We made a retrospective study on the usefulness of autologous blood transfusion conducted by using stored autologous blood with or without blood dilution in orthognathic surgery. Ninety-six patients had received autotransfusion in our department from 1985 through 1991.Their mean age was 19.8 years.Females predominated over males in the ratio of about three to one.The main disorder of the patients was prognathism (90cases);the major method of operation was a sagittal splitting ramus osteotomy.The average volume of autologous blood donation was 525.1ml, and 72% of blood loss was covered by autologous blood transfusion.Hematologically postoperative anemia of the patients was recovered with autotransfusion, and serum erythropoietin levels in autologous donors increased significantly (P

Background and Objective: Matrix metalloproteinase (MMP)-13 has wide substrate specificity compared with other MMPs and appears to be involved in periodontitis. Previously, we reported that roxithromycin (RXM) inhibits vascular endothelial growth factor expression induced by tumour necrosis factor-α in human periodontal ligament cells, but little is known about the effect of RXM on MMP-13 expression in human gingival epithelial cells. We therefore examined the effect of RXM on MMP-13 mRNA expression and production in cultured human gingival epithelial cells. Material and Methods: Human epithelial cell lines (Ca9-22, TU4, SCCTF and HSC-3) were plated in tissue culture dishes. Then, the culture supernatants and sediments were collected and the production of MMP-13 was analysed using enzyme-linked immunosorbent assay; the expression of MMP-13 mRNA and runt-related gene 2 mRNA was assessed using reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time RT-PCR. We also studied the effect of Runx2 short interfering RNA (siRNA) on the induction of MMP-13. Results: Roxithromycin downregulated the induction of MMP-13 in Ca9-22 cells. Roxithromycin suppressed the expression of MMP-13 mRNA not only in Ca9-22 cells, but also in other human epithelial cell lines. Roxithromycin strongly inhibited the expression of Runx2 mRNA. Furthermore, Runx2 siRNA inhibited the induction of MMP-13 in Ca9-22 cells. Conclusion: These results indicate that RXM suppresses MMP-13 via the downregulation of Runx2 in human gingival epithelial cell cultures.

Carcinoma in pleomorphic adenoma (CPA) of salivary gland origin is a relatively uncommon neoplasm. CPA accounts for 3 % to 10% of all tumors arising in the salivary glands.Recently, we encountered a case of CPA metastasizing from the right parotid gland to the left side of the mandible in a 70-year-old woman.She had swelling and spontaneous pain of the left side of the mandible. At initial examination, the clinical diagnosis of the parotid gland was pleomorphic adenoma, and that of the mandible was a malignant tumor. Surgical removal of these tumors was performed, and the histopathological diagnosis was CPA in the parotid gland and mandible.The patient must be followed up for a long time and local recurrence must be controlled.

An eosinophilic granuloma was discovered in the region of the ramus of the mandible. This case occured in a very rare location limited only to the ramus, and showed similar features resembling osteomyelitis or malignant neoplasm at different stages of the disease. The radiographic findings indicated a diagnosis of malignant neoplasm and the scintigraphic manifestations showed that of osteomyelitis. The histopathological examinations showed different manifestations in accordance with the respective stages of the disease. This case was finally diagnosed as eosinophilic granuloma showing rapid regression.

Verrucous carcinoma, a variant of squamous cell carcinoma, was first described as a distinct clinical and histopathological entity by Ackerman in 1948. In this paper, two cases of verrucous carcinoma of the oral cavity are reported. One case was treated by surgical excision, but the other rejected the treatment. The first case is free from recurrence as of today, 4 years and 4 months after surgery.Ultrastructural observations demonstrated that gap junctions and desmosomes were numerously found in the verrucous carcinoma.A well preserved intercellular junction might be rclatcd to a better prognosis of this lesion in comparison with invasive carcinomas.