Takafumi Satomi

A simple evaluation method for early detection of bisphosphonate-related osteonecrosis of the mandible using computed tomography

OBJECTIVES The aim of this study was to establish a simple method for the early detection of bisphosphonate-related osteonecrosis of the jaw (BRONJ) using computed tomography (CT). MATERIALS AND METHODS CT images of the mandible were obtained from a total of 20 patients with BRONJ and 20 control subjects. BRONJ was classified into 2 groups, with bone exposure (Stage 1-3 BRONJ) or without (Stage 0 BRONJ). In each patient, 15 transaxial CT images were selected and 30 configured regions of interest (ROI) were identified. The ANOVA test was applied to test the relationship between the severity of systemic risk factors. RESULTS Regarding the local status of the mandible, significant differences were observed among the Stage 0 BRONJ, Stage 1-3 BRONJ, non-BRONJ and control groups in the cancellous bone CT radiodensity values, but there were no significant differences between the Stage 0 and Stage 1-3 BRONJ groups. In the cortical bone widths, significant differences were observed only between BRONJ and the controls. CONCLUSIONS Measuring cancellous bone CT radiodensity value has the potential to be a simple and quantitative method to detect the early stages of BRONJ.

A successfully treated inflammatory myofibroblastic tumor of the mandible with long-term follow-up and review of the literature

Inflammatory myofibroblastic tumor (IMT) of the oral cavity is an extremely rare clinical and pathological disease entity. It was originally described in the lung but has recently been reported in various anatomic sites. We report such a case of inflammatory myofibroblastic tumor of the mandible in a 14-year-old girl. The patient presented with an aggressive ulcerative soft tissue mass of 3 months duration in the mandibular molar gingiva. Histologically, the lesion was composed of fibroblastic or myofibroblastic spindle cell proliferations with infiltrative margins in an inflammatory background. Immunohistochemically, the fibroblastic or myofibroblastic spindle cells were positive for vimentin, α-smooth muscle actin, and Ki-67 (MIB-1) but negative for desmin, pan-cytokeratin, S-100 protein, CD34, CD68, CD99, bcl-2, β-catenin, estrogen receptor, progesterone receptor, ALK-1, and p53. These spindle cells were focally and weakly Ki-67- (MIB-1-) positive. The MIB-1 labeling index was 5%. The results of in situ hybridization for Epstein-Barr virus-encoded-RNA were negative. The ratio of IgG4+/IgG+ plasma cells was about 10%. A pathological diagnosis of inflammatory myofibroblastic tumor was made. The postoperative course was uneventful, and the patient has had no recurrence in the 10-year follow-up period. Although no evidence of oral inflammatory myofibroblastic tumor recurrence or malignant transformation has been reported, it has been observed that in inflammatory myofibroblastic tumors of other regions, a prolonged follow-up is necessary after surgical resection. No other case of an IMT patient under 20 years of age has appeared in either the English or the Japanese literature.

Cyclo-Oxygenase–2 Expression Is Associated With Vascular Endothelial Growth Factor C Expression and Lymph Node Metastasis in Oral Squamous Cell Carcinoma

PURPOSE Cervical lymph node metastasis in oral squamous cell carcinoma (OSCC) is recognized as a poor prognostic factor, although its mechanism remains unclear. Recently, cyclo-oxygenase-2 (COX-2) level has been found to correlate highly with vascular endothelial growth factor C (VEGF-C) and lymph node metastasis, as in other solid tumors. However, there has been no report of this correlation in OSCC. Therefore, the aim of this study was to investigate whether COX-2 immunohistochemical expression in OSCC was associated with VEGF-C expression, histopathologic parameters, and lymph node metastasis. MATERIALS AND METHODS Lymphatic vessel density, VEGF-C, and COX-2 immunohistochemical expression were examined pathologically in 60 specimens of invasive OSCC. Relations of histopathologic parameters to lymph node metastasis were analyzed. RESULTS Expression levels of VEGF-C and COX-2 and lymphatic vessel density in the lymph node metastatic group were significantly higher than in the nonmetastatic group (P < .01). A significant correlation was found between the expression levels of VEGF-C and COX-2 (r = 0.512; P < .001). COX-2 expression was significantly related to lymph node metastasis (P = .004) and VEGF-C expression (P = .005). Univariate analysis showed that survival time was impaired by higher COX-2 and VEGF-C expression levels. Multivariate survival analysis showed that COX-2 expression was an independent prognostic factor. CONCLUSION This study showed that VEGF-C expression was upregulated by COX-2 in OSCC. High VEGF-C expression appears to promote peritumoral lymphangiogenesis. These data indicated that lymph node metastasis is promoted by COX-2 and VEGF-C in OSCC.

Preventive effect of rebamipide gargle on chemoradiotherpy-induced oral mucositis in patients with oral cancer: a pilot study.

ABSTRACT Objectives To assess the efficacy and safety of rebamipide in preventing chemoradiotherapy-induced oral mucositis in patients with oral cancer. Material and Methods Patients with oral cancer treated with chemoradiotherapy (daily radiotherapy plus docetaxel hydrate once a week) were enrolled for this study. They were assigned in a double-blind fashion to receive either rebamipide gargle or placebo on the days of chemoradiotherapy. Oral mucositis was assessed using the WHO grading system. The primary endpoint of this study was the incidence of grade 3 - 4 mucositis after exposure to 40 Gy radiation (4 weeks). The secondary endpoint was the effect of rebamipide gargle on tumour response to chemoradiotherapy. Results Twenty-four patients were randomly assigned to receive rebamipide gargle (n = 12) or placebo-gargle (n = 12) during chemoradiotherapy. The number of patients with severe mucositis (WHO ≥ 3) was higher in the placebo group than in the rebamipide group (83.3% vs. 33.3%, P = 0.036). In addition, no effect of rebamipide gargle on tumour response to chemoradiotherapy was recognized compared with the placebo group. Conclusions For patients with oral cancer undergoing chemoradiotherapy, rebamipide gargle may contribute to decrease the severity of oral mucositis.

Indications of Potassium Titanyl Phosphate Laser Therapy for Slow-Flow Vascular Malformations in Oral Region.

Background: Indications for laser therapy for slow-flow vascular malformations in the oral and maxillofacial regions have not been clearly documented. The authors aimed to estimate the frequency of resolution of slow-flow vascular malformations and to identify risk and prognostic factors associated with resolution in potassium titanyl phosphate (KTP) laser treatment. Methods: This study was designed as a prospective cohort study. Patients who had diagnosed slow-flow vascular malformations were continuously assigned to receive KTP laser therapy. All patients had intralesional laser photocoagulation performed under local anesthesia. Administered power of the KTP laser was fixed at 2 watts throughout the procedure in all patients. The primary endpoint was to understand the frequency of resolution of slow-flow vascular malformations in KTP laser treatment. Secondary endpoints were: treatment outcomes based on lesion size; treatment outcomes based on location; treatment outcomes based on total energy in joules; types of complications. Treatment outcomes were judged by a clinical assessment as well as reduction in lesion size on magnetic resonance imaging. Results: Data were obtained from 26 patients (9 men, 17 women) with 38 lesions. The average lesion size was 13.5 ± 7.7 mm. Treatment outcomes based on lesion size showed that cure and regression were obtained in lesions less than 30 mm in size. However, lesions larger than 30 mm showed no response. Lesions in the tongue and lips showed higher cure rates than in other areas. Treatment outcomes based on administered total energy in joules showed that 68% of lesions were treated and responded well at less than 400 joules. Complication rate was relatively high in the buccal mucosal lesions. Immediate postoperative complications such as necrosis were more common in high-energy administration than in low-energy administration. Conclusion: Our results indicated that KTP laser therapy was effective for slow-flow vascular malformations less than 30 mm in size without significant side effects.BACKGROUND Indications for laser therapy for slow-flow vascular malformations in the oral and maxillofacial regions have not been clearly documented. The authors aimed to estimate the frequency of resolution of slow-flow vascular malformations and to identify risk and prognostic factors associated with resolution in potassium titanyl phosphate (KTP) laser treatment. METHODS This study was designed as a prospective cohort study. Patients who had diagnosed slow-flow vascular malformations were continuously assigned to receive KTP laser therapy. All patients had intralesional laser photocoagulation performed under local anesthesia. Administered power of the KTP laser was fixed at 2 watts throughout the procedure in all patients. The primary endpoint was to understand the frequency of resolution of slow-flow vascular malformations in KTP laser treatment. Secondary endpoints were: treatment outcomes based on lesion size; treatment outcomes based on location; treatment outcomes based on total energy in joules; types of complications. Treatment outcomes were judged by a clinical assessment as well as reduction in lesion size on magnetic resonance imaging. RESULTS Data were obtained from 26 patients (9 men, 17 women) with 38 lesions. The average lesion size was 13.5 ± 7.7 mm. Treatment outcomes based on lesion size showed that cure and regression were obtained in lesions less than 30 mm in size. However, lesions larger than 30 mm showed no response. Lesions in the tongue and lips showed higher cure rates than in other areas. Treatment outcomes based on administered total energy in joules showed that 68% of lesions were treated and responded well at less than 400 joules. Complication rate was relatively high in the buccal mucosal lesions. Immediate postoperative complications such as necrosis were more common in high-energy administration than in low-energy administration. CONCLUSION Our results indicated that KTP laser therapy was effective for slow-flow vascular malformations less than 30 mm in size without significant side effects.

Ultrasound-guided intralesional photocoagulation of intramuscular vascular malformation in the masseter muscle.

Intramuscular vascular malformations are rare anomalies accounting for less than 1% of all vascular lesions. Because of their anatomic location, surgical intervention usually is the choice of treatment. However, a vascular malformation of the masseter muscle requires a large extraoral incision to access the lesion. The major drawbacks of this procedure include the development of postoperative facial scars and the risk of injury to the facial nerve. Treatment of vascular malformations by intralesional laser photocoagulation (ILP) was first reported by Apfelberg in 1995. Subsequently, Achauer et al developed ILP using an 18-gauge angiocatheter to deliver a bare fiber into the vascular malformation that minimizes cutaneous damage. Although their report showed that ILP was effective, the accuracy of intralesional puncture remains uncertain if the lesion is not superficially visible. In the present case, a bare fiber was delivered into an intramuscular vascular malformation of the masseter muscle using an ultrasound-guided method.

Correlation between the malignancy and prognosis of oral squamous cell carcinoma in the maximum standardized uptake value

Positron emission tomography/computed tomography (PET/CT) examinations are indispensable in determining the stage, evaluating the treatment response, and diagnosing recurrence and metastasis during oral cancer treatment. In this study, we examined the correlation between the maximum standardized uptake value (SUVmax) for 18F-FDG PET/CT and the progressive factors, biological characteristics, and prognosis of oral cancer. We included 52 cases of oral squamous cell carcinoma with surgery as the initial treatment. Inclusion criteria included tumor diameter of ≥ 1 cm excluding superficial cancer. We performed 18F-FDG PET/CT examinations before surgery and determined the correlation between SUVmax and clinicopathological factors, such as histological grade, Ki-67 expression, as well as progress factors. SUVmax was significantly correlated with clinical T stage, vascular invasion, lymphatic invasion, Ki-67 expression, and postoperative event (recurrence or metastasis) in Student’s t test. Using a cut-off SUVmax of 8.0, clinical T stage, lymph node metastasis, vascular invasion, infiltrative pattern, and Ki-67 expression significantly correlated in chi-squared test. Although observed and expected 3-year overall survival rates were not significantly different, observed and expected 3-year disease-free survival rates were significantly different. Analyzing each clinicopathological factor using various data obtained from 18F-FDG PET/CT scans may be useful to determine prognosis during oral cancer treatment.

Toll-like receptor 2 activation implicated in oral squamous cell carcinoma development

Recent studies have revealed that Toll-like receptors (TLRs) are highly expressed and activated in many types of cancer. Physiologically, TLR2 recognizes bacteria and other microorganisms in the oral cavity; however, the role of TLR2 in oral squamous cell carcinoma (OSCC) is unclear. In this study, we demonstrated that TLR2 is highly expressed in OSCC in comparison with adjacent non-malignant tissue. TLR2 was also expressed in OSCC-derived cell lines, and its expression was activated by ligands derived from bacteria and mycoplasma. Furthermore, to elucidate the mechanism of OSCC progression via TLR2 signal transduction, we focused on microRNAs (miRNAs) that are induced by TLR2 activation. Interestingly, ligand activation of TLR2 induced the expression of miR-146a and we found that downregulation of caspase recruitment domain-containing protein 10 (CARD10) mRNA in OSCC-derived cell lines. Moreover, knockdown of CARD10 induced resistance to cisplatin-induced apoptosis in OSCC cells. These findings suggest that the activation of TLR2 by bacterial components can enhance the progression of OSCC and may be implicated in acquired resistance to cisplatin-induced apoptosis through regulation of the miR-146a pathway.