Michihide Kono

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.

Navigation surgery for Le Fort 1 osteotomy in a fibrous dysplasia patient

Orthognathic surgery is sometimes performed for fibrous dysplasia to correct malocclusion or facial asymmetry. However, Le Fort 1 osteotomy for this disease is difficult because of severe anatomical abnormality. Computerassisted surgery is a rapidly developing technique in oral and maxillofacial surgery that is helping to ensure the safety of the surgery. We report a case of polyostotic craniofacial fibrous dysplasia in which two-jaw orthognathic surgery was performed using a navigation system with the Le Fort 1 osteotomy procedure. A 29-year-old woman presented with swelling and asymmetry on the right side of her face. Craniofacial fibrous dysplasia on the right side had been previously diagnosed, and she had undergone conservative surgery several times before. The disease extended to the right mandible, maxilla, and zygomatic, temporal frontal, and orbital areas, including the skull base. We first performed conservative contouring around the frontal and orbital areas, and then Le Fort I osteotomy and sagittal split ramus osteotomy to correct the asymmetry and cant of the occlusal plane. A passive infrared navigation system (Vector Vision surgical navigation system) was used for the Le Fort I osteotomy. The postoperative course was stable, and the facial asymmetry and cant of the occlusal plane improved and remained suitable 2 years after surgery. Thus, Le Fort 1 osteotomy can be performed safely in fibrous dysplasia with the aid of a passive infrared navigation system.

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.

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.