Histopathological Change of Oral Malignant Tumour and Epithelial Dysplasia Subjected to Photodynamic Therapy

Objectives: The purpose of this study is to analyze the morphological change of cell nuclei and the change of proliferating activity of oral malignancy and epithelial dysplasia between before and after photodynamic therapy in order to predict recurrence.Material and Methods: We experienced 14 cases of oral squamous cell carcinoma, one case of verrucous carcinoma and seven cases of epithelial dysplasia treated by photodynamic therapy (PDT). The mean nuclear area (NA) and coefficient of variation of the nuclear area (NACV) of 100 nuclei per slide were calculated using computer-assisted image analysis in hematoxylin and eosin stained biopsy specimens before and after PDT. Additionally, proliferating cell nuclear antigen (PCNA) immunohistochemistry was carried out in each specimen.Results: The mean NA after PDT was significantly lower than that before PDT in the nonrecurrent group. However, there was no significant difference in mean NA before and after PDT in the recurrent group. There were no significance differences in NACV before and after PDT in either the nonrecurrent or recurrent group. Furthermore, the PCNA labelling indices of the specimens after PDT was significantly lower than that before PDT in both the nonrecurrent and the recurrent group.Conclusions: Mean nuclear area in the biopsy specimen after photodynamic therapy is likely to be a predictive marker for the recurrence of oral squamous cell carcinoma or epithelial dysplasia subjected to photodynamic therapy, while coefficient of variation of the nuclear area and proliferating cell nuclear antigen labelling indices are less helpful in predicting the recurrence of such lesions

Engineering Bone Formation from Human Dental Pulp- and Periodontal Ligament-Derived Cells.

A robust method for inducing bone formation from cultured dental mesenchymal cells has not been established. In this study, a method for generating bone tissue in vivo from cultured human dental pulp- and periodontal ligament-derived cells (DPCs and PDLCs, respectively) was designed using exogenous bone morphogenetic protein 2 (BMP2). DPCs and PDLCs showed enhanced alkaline phosphatase (ALP) activity and calcified nodule formation in medium containing dexamethasone, beta-glycerophosphate, and ascorbic acid (osteogenic medium). However, the addition of recombinant human bone morphogenetic protein 2 (rhBMP2) to osteogenic medium remarkably increased ALP activity and in vitro calcification above the increases observed with osteogenic medium alone. rhBMP2 also significantly upregulated the expression of osteocalcin, osteopontin, and dentin matrix protein 1 mRNA in both cell types cultured in osteogenic medium. Finally, we detected prominent bone-like tissue formation in vivo when cells had been exposed to rhBMP2 in osteogenic medium. In contrast, treatments with osteogenic medium or rhBMP2 alone could not induce abundant mineralized tissue formation. We propose here that treatment with rhBMP2 in osteogenic medium can make dental mesenchymal tissues a highly useful source of cells for bone tissue engineering. In addition, both DPCs and PDLCs showed similar and remarkable osteo-inducibility.The original publication is available at www.springerlink.co

Epithelium-poor Odontogenic Fibroma with an Unusual Progress

Odontogenic fibroma (OF) is a relatively rare benign tumor derived from odontogenic ectodermal mesenchymal tissue. It is divided into central (COF) or peripheral OF (POF) based on the affected area. Regarding its pathological features, OF can also be classified as epithelium-rich (WHO type) or epithelium-poor (simple type), depending on the amount of odontogenic epithelium in the tumor. There is limited information available about the latter type because of its low incidence. We report case of simple type COF apparently like POF. A 52- year-old Japanese male was suffering from tenderness at the right posterior maxilla during occlusion with his removable partial denture. The lesion was diagnosed as a simple type OF arising at the edentulous region around the right molar site of the maxilla. A tumor resection was performed, and there was no evidence of recurrence at his 18-month follow-up examination. In addition, we provide a review of the literature with the most up-to-date information about this lesion so that it can be diagnosed correctly

Prediction of outcome of patients with oral squamous cell carcinoma using vascular invasion and the strongly positive expression of vascular endothelial growth factors.

Vascular invasion and lymph node metastasis have been used as histopathological prognosticators of cancers including oral squamous cell carcinoma (OSCC). In addition to metastatic potential via blood vessels, tumor-induced angiogenesis might also be associated with prognosis. However, the efficacy of combined evaluation of vascular invasion and angiogenesis-associated molecules for the prognosis of OSCC remains obscure. This is also the case in lymph node metastasis and lymphovasculogenesis-associated molecules. The aim of this study was to examine factors related to prognosis to improve the accuracy of prognostic prediction of OSCC using vasculogenesis-associated markers. Ninety specimens of patients from 1991 to 2002 with previously untreated OSCC, who underwent either biopsy or surgery, were histopathologically and immunohistochemically analyzed using antibodies for vascular endothelial growth factor (VEGF)-A, VEGF-C, cyclooxygenase (COX)-2 and Midkine. The ninety cases were composed of 72 well-differentiated, 12 moderately differentiated and 6 poorly differentiated OSCC. Efficient models of prognostic prediction were evaluated by extensive statistical analyses. The presence of vascular invasion or lymph node metastasis was confirmed to be significantly associated with poor prognosis in the univariate analysis. Multivariate logic regression analysis suggested that patients with the strongly positive expression of either VEGF-A or VEGF-C had a significant association with poor prognosis even in patients without vascular invasion and in early-stage patients. Neither COX-2 nor Midkine contributed to predict the prognosis of the patients. The strongly positive expression of VEGF-A or VEGF-C was suggested to reinforce the histopathological diagnosis of vascular invasion and improve the accuracy and efficacy of prognostic prediction of OSCC

A clinicopathological study of perineural invasion and vascular invasion in oral tongue squamous cell carcinoma

The risk factors for recurrence of head and neck cancer are classified as being of high or intermediate risk. Those of intermediate risk include multiple positive nodes without extracapsular nodal spread, perineural/vascular invasion, pT3/T4 primary tumours, and positive level IV/V nodes. However, little evidence is available to validate these intermediate risk factors. We analyzed perineural/vascular invasion in 89 patients who underwent radical surgery for oral tongue squamous cell carcinoma, whose records were reviewed retrospectively. Perineural invasion was found in 27.0% of cases and vascular invasion in 23.6%; both had a strong relationship with histopathological nodal status (P = 0.005). The 5-year disease-specific survival (DSS) and overall survival rates of patients with perineural invasion were significantly lower than those of patients without perineural invasion (P < 0.001 and P = 0.002, respectively). The 5-year DSS of UICC stage I and II cases with perineural/vascular invasion was significantly lower than those without (P < 0.001 and P = 0.008, respectively). Perineural invasion and vascular invasion are risk factors for regional metastasis and a poor prognosis. We recommend elective neck dissection when perineural/vascular invasion is found in clinical stage I and II cases. The accumulation of further evidence to consider intermediate risks is required

A New Strategy for Surgical Intervention of Bisphosphonate-Related Osteonecrosis of the Jaw : A retrospective study.

Bisphosphonates (BPs) are now widely used to treat various skeletal complications. Although the number of reported cases ofbisphosphonate-related osteonecrosis of the jaw (BRONJ) is rapidly increasing worldwide, therapeutic strategies remain controversial.Conservative treatments including antibacterial mouth rinses, the systemic administration of antibiotics, and superficial debridement in stage II BRONJ have been recommended by the American Association of Oral and Maxillofacial Surgeons position paper. However, these treatments are only partially successful. We performed a surgical intervention that consisted of osteotomy and primary wound closure in patients with stages II and III BRONJ. Forty-three out of 44 cases were treated effectively by this strategy, leading to improvements in quality of life. All BRONJ patients treated with oral BPs were treated successfully by the surgical intervention. We also proposed a surgical intervention for patients with stage II BRONJ

Immunohistochemical study of vascular endothelial growth factor‑C/vascular endothelial growth factor receptor‑3 expression in oral tongue squamous cell carcinoma: Correlation with the induction of lymphangiogenesis

The aim of the present study was to elucidate the associations between the expression of the vascular endothelial growth factor-C (VEGF-C)/VEGF receptor-3 (VEGFR-3) axis and lymphangiogenesis, regional lymph node metastasis and clinicopathological factors in oral tongue squamous cell carcinoma (OTSCC) using immunohistochemistry. The expression of VEGF-C, VEGFR-3 and podoplanin was immunohistochemically evaluated in specimens obtained from 65 patients with OTSCC (T1-2, N0) who had undergone radical surgery alone. The associations between the expression of VEGF-C, VEGFR-3 and podoplanin, and lymphangiogenesis, regional lymph node metastasis and clinocopathological factors were determined by immunohistochemical analysis. VEGF-C, VEGFR-3 and combined VEGF-C/VEGFR-3 expression was significantly higher in cases with regional recurrence compared with those without lymph node involvement (P<0.001). As regards lymphangiogenesis, a significant correlation was observed between podoplanin expression and VEGF-C, VEGFR-3 and combined VEGF-C/VEGFR-3 expression (P<0.001). Therefore, lymphangiogenesis in the peritumoral stroma was associated with lymph node metastasis. However, podoplanin expression did not exhibit a significant correlation with the progression of lymph node metastasis. The results of the present study suggest that the VEGF-C/VEGFR-3 axis may be associated with lymph node metastasis through lymphangiogenesis. Determining the VEGF-C/VEGFR-3 expression status may help predict which patients will develop regional recurrence and provide novel targets for therapies to suppress lymph node metastasis in the treatment of OTSCC

Prognostic Value of Podoplanin Expression in Oral Squamous Cell Carcinoma―A Regression Model Auxiliary to UICC Classification

Podoplanin, a type I transmembrane glycoprotein with an effect of platelet aggregation, has been reported to be one of the possible prognostic factors of oral squamous cell carcinoma (OSCC). However, the biological significance of podoplanin is largely unclear. The aim of this study was to develop a practical model for the prediction of prognosis using the grade of podoplanin expression, and also to evaluate the biological function of podoplanin. Eighty-two specimens of patients with previously untreated OSCC, who underwent either biopsy or surgery, were histopathologically and immunohistochemically analyzed. These 82 cases were composed of 66 well-differentiated, 10 moderately differentiated and 6 poorly differentiated OSCC. Podoplanin was successfully immunostained in 78 specimens, and was detected in most cases, but the frequency of positive cells varied. The prognosis of patients with more than 50 % podoplanin-positive tumor cells was significantly poorer than that of the other patients. Multivariate hazards regression analysis suggested that a linear combination of covariates, OSCC patients with more or less than 50 % podoplanin expression, age of more or less than 70 years old, mode of invasion and T3, T4 or T2 versus T1 of the UICC T-stage classification was the most effective model for evaluating the prognosis of OSCC patients. Additionally, podoplanin expression had a significant relationship to UICC clinical stage and the expression of Ki-67. An effective regression model using podoplanin expression was developed for evaluating the prognosis of OSCC and the biological significance of podoplanin was suggested to be associated with the growth and/or progression of OSCC

Immunohistochemical Study on Epithelialization of the Fascial Flap in the Oral Cavity of Rats

The immunohistochemical expressions of epidermal growth factor receptor (EGFR) and Proliferating Cell Nuclear Antigen (PCNA) were studied in the epithelialization process of bare flaps, the fascial flap and the deepithelialized mucoperiosteal flap, used for reconstruction of the oral mucosa in rat models. The intense expression of EGFR and PCNA was detected in the tip area of the migrating epithelium during the early period of the healing process in both flaps, and differing distributions of EGFR and PCNA positive cells were identified. In the fascial flap, a significantly high positive rate of EGFR was detected in comparison with the deepithelialized mucoperiosteal flap. The expression of EGFR in both flaps may be attributed to the influences of different connective tissue substrates which induce a control mechanism to maintain the equilibrium between differentiation and proliferation of epithelium