Takayoshi Tobita

Development of an in vitro model for radiation-induced effects on oral keratinocytes.

Changes in epithelial cell activity and the production of pro-inflammatory cytokines were examined utilizing an organotypic culture system as an in vitro model to study the effects of radiation on oral keratinocytes to simulate what is thought to occur in radiation-induced oral mucositis. Monolayer cultures of oral keratinocyte were irradiated by varying the dose. Cell injury was assessed using a colony forming efficiency (CFE) assay. Third passage oral keratinocytes were seeded onto AlloDerm to form a 3D construct of an ex vivo produced oral mucosa equivalent (EVPOME) which was irradiated with 0, 1, 3 and 8Gy. Formalin-fixed sections of the EVPOME were used for histology and immunohistochemistry to examine proliferative capacity. Epithelial cell viability of EVPOME was measured by MTT assay. Spent culture medium was used to determine post-radiation pro-inflammatory cytokine production. Basal cells became more swollen and pyknotic as radiation increased, implying loss of cell viability also determined by MTT assay. The number of Ki-67 immunopositive cells and CFE showed negative correlation with radiation, indicating loss of cell proliferative capacity. The production of pro-inflammatory cytokines, IL-1alpha and IL-8, tended to increase in a radiation dose dependent manner. The EVPOME lacking submucosal cellular components was a useful model.

Constitutive Release of Cytokines by Human Oral Keratinocytes in an Organotypic Culture

PURPOSE The Food and Drug Administration requires an accurate determination of the dose and potency of tissue-engineered or combination products as is required for drugs. This needs to be done as a rapid, quantitative, and noninvasive measurement of biologic function/activity in a way so as not to perturb the tissue-engineered product being developed. The aim of this study was to correlate constitutive release of cytokine(s) from unstimulated cells, at different stages of development, within a 3-dimensional (3D) organotypic ex vivo produced oral mucosa equivalent (EVPOME) to be used for intraoral grafting, with oral keratinocyte cell viability of the EVPOME. MATERIALS AND METHODS Tissue culture medium was assayed with an enzyme-linked immunosorbent assay from monolayer culture of oral keratinocytes and a 3D EVPOME to determine the constitutive release of interleukin (IL) 1alpha, IL-6, IL-8, and vascular endothelial growth factor (VEGF). VEGF messenger ribonucleic acid expression by oral keratinocytes within the 3D EVPOME was detected by in situ hybridization at days 4, 7, and 11. The number of viable oral keratinocytes within the EVPOME was extrapolated from VEGF release by use of a modified MTT assay. RESULTS Both VEGF release level and the number of viable cells in the monolayer cultures and 3D EVPOME as measured by MTT assay significantly increased in a time-dependent manner (P < .001, r = 0.743). CONCLUSION These results suggest that the increasing detectable levels of VEGF associated with the increasing number of viable cells in the EVPOME may provide a useful noninvasive/nondestructive means of assessing both cellular viability (dose) and biologic function/activity (potency) of a combination cell-based device such as the EVPOME.

Assessment of skeletal stability of intraoral vertical ramus osteotomy with one-day maxillary-mandibular fixation followed by early jaw exercise.

PURPOSE Intraoral vertical ramus osteotomy (IVRO) is an effective surgical technique for cases of mandibular setback, is simpler and has a lower incidence of mental paraesthesia when compared to sagittal split ramus osteotomy (SSRO). However, IVRO has a disadvantage in the prolonged duration of postoperative maxillary-mandibular fixation (MMF) required due to the absence of rigid bone fixation. To avoid an extended MMF period, we developed a postoperative management protocol for our IVRO patients, using jaw exercises with elastic bands starting on the second day after surgery. METHODS We evaluated the cephalometric skeletal and dental stabilities of 16 IVRO patients as they followed our protocol. RESULTS The stabilities were confirmed and were similar to those of previous reports. CONCLUSION One-day MMF and early initiation of jaw exercise after IVRO did not affect the jaw position stability. Moreover, our findings suggest that starting jaw exercise earlier after IVRO surgery is beneficial, as it allows patients to avoid a long period of rigid MMF so that they can resume their normal daily activities sooner.

Treatment outcome of Photofrin-based photodynamic therapy for T1 and T2 oral squamous cell carcinoma and dysplasia

BACKGROUND Photodynamic therapy (PDT) is a minimally invasive treatment modality for early and superficial malignancy or premalignancy in the head and neck regions. However, few studies have examined the use of Photofrin-mediated PDT to manage early carcinoma and dysplasia in the oral cavity. METHODS Between January 2004 and November 2008, 25 T1 to T2 patients with N0 oral squamous cell carcinoma and mucosal dysplasia in the oral cavity were treated by Porfimer sodium (Photofrin(®))-mediated PDT at Nagasaki University Hospital. Clinical responses were evaluated according to the guidelines of the Response Evaluation Criteria in Solid Tumors (RECIST). After the PDT and a 2-year follow-up period, disease specific survival rates were then calculated. RESULTS A total of 30 regions in 25 patients (18 with squamous cell carcinoma and 7 with epithelial dysplasia with hyperkeratosis in the oral cavity) were treated by PDT. Complete response was achieved in 24 of the 25 patients (96%), with a partial response found in the remaining patient. For the three patients who exhibited recurrence at 4, 5, and 15 months after PDT, salvage surgery or a second PDT was performed. Of these three patients, one died due to another disease, while one died due to local lymphatic metastasis that occurred during the follow-up period. Overall, the disease specific survival rate was 95.8%. Treatment-related edema and pain emerged within 24h after irradiation. Pain control using non-steroid anti-inflammatory drugs and opiates was required for 3-4 weeks in all patients. Complete healing was attained at 4-6 weeks after the treatment. No persistent problems related to functional or esthetic outcomes were noted.

Antitumor effects on primary tumor and metastatic lymph nodes by superselective intra-arterial concurrent chemoradiotherapy for oral cancer

OBJECTIVE Superselective intra-arterial infusion of anticancer agents with concurrent delivery of external beam radiotherapy was applied to 13 previously untreated cases of oral cancer for the purpose of avoiding surgical resection of the primary tumor. STUDY DESIGN The catheter tips were placed in the tumor feeder arteries via the superficial temporal artery and/or occipital artery. The catheters were retained for 6 weeks to infuse anticancer agents daily with concurrent radiotherapy for 6 weeks. The total radiation doses to the primary tumor and neck were 60.0 Gy and 40.0 Gy, respectively. RESULTS Complete response of the primary tumor was achieved in all 13 patients; complete response of neck node metastasis was achieved in 5 out of 6 patients. CONCLUSION This strategy is quite effective for oral cancer at both the primary site and metastatic lymph nodes, and it has the potential to be curative in advanced cases that are inoperable.

Ancient Schwannoma in the Buccal Region

Abstract Ancient Schwannoma is a rare benign tumour, and the number of ancient schwannomas occurring in the oral cavity is very small. This report describes a patient with an ancient Schwannoma in the buccal region, which was surgically removed twice over 23 years. The patient is being followed up on an outpatient basis and no further recurrence has been observed thus far.

Correction of an asymmetric maxillary dental arch by alveolar bone distraction osteogenesis

This case report describes a new surgical orthodontic approach involving alveolar bone distraction osteogenesis for correction of an asymmetric maxillary dental arch. The treatment was combined with conventional orthognathic surgery to improve the mandibular lateral deviation. This new treatment strategy produced an ideal dental arch and a symmetric facial appearance efficiently and effectively.

Sinus augmentation surgery after endoscopic sinus surgery for the treatment of chronic maxillary sinusitis: a case report.

Chronic sinusitis develops when the ostiomeatal complex becomes stenosed by the swelling of the sinus mucosa. Previously, the Caldwell-Luc method was performed for the treatment of chronic sinusitis. But postoperative complications, such as discomfort of the buccal skin and recurrence of sinusitis, frequently occurred after the operation. Today, endoscopic sinus surgery (ESS) has become widely used for the treatment of chronic sinusitis. The features of ESS allow for the restoration of the physical function of the sinus membrane and preservation of the physiological environment of the sinus. Therefore, sinus augmentation surgery can be safely performed at an insufficient alveolar bone height below the maxillary sinus when sinusitis is eliminated by the ESS. This article documents a patient history involving chronic sinusitis that was treated by the ESS therapy before sinus augmentation surgery as a pretreatment for insertion of dental implants.

Oral Rehabilitation With Orthognathic Surgery After Dental Implant Placement for Class Iii Malocclusion With Skeletal Asymmetry and Posterior Bite Collapse.

Increasing numbers of older patients are seeking orthognathic surgery to treat jaw deformity. However, orthodontic and orthognathic surgical treatment is difficult in cases without occlusal vertical stop. A 55-year-old man presented with Class III malocclusion and mandibular protrusion including esthetic problems and posterior bite collapse. He underwent dental implant treatment to reconstruct an occlusal vertical stop before orthognathic surgery. His occlusal function and esthetic problems improved after surgery, and his skeletal and occlusal stability has been maintained for 6 years. Dental implant placement at appropriate positions could help to determine the position of the proximal segment at orthognathic surgery and could shorten the time required to restore esthetic and occlusal function. This case demonstrates how skeletal and dental stability can be maintained long after surgery in a patient with jaw deformity and posterior bite collapse.

The three-dimensional assessment of dynamic changes of the proximal segments after intraoral vertical ramus osteotomy

Objectives: The aim of this study was to assess the positional changes of the proximal segments after intraoral vertical ramus osteotomy (IVRO). Method: Fifteen patients underwent IVRO and were followed according to the authors’ unique postoperative management regimen. The analyses of the positions and angles of the proximal segments were performed on frontal and lateral cephalograms, which were taken before surgery (T1) and within 3 days (T2), at 4 weeks (T3), and later than 6 months after surgery (T4). The three-dimensional positions of the condylar heads were also assessed by CT images, which were taken before and 1 year after surgery. Results: The proximal segments temporarily swung posteriorly and laterally with a center on the condylar head as a fulcrum point at T2 and T3, compared with T1, and they repositioned at T4. The condylar heads moved inferior approximately 2 mm with lateral rotation one year after surgery, as seen in the CT. Discussion: The condylar heads changed their positions physiologically for newly established jaw movement after IVRO with the authors’ post-operative management regimen because the post-operative skeletal stability and the jaw function were good and stable using this method.