Naoya Izumi

Changes in oropharyngeal airway and respiratory function during sleep after orthognathic surgery in patients with mandibular prognathism

The aim of this study was to examine the effects of mandibular setback surgery on pharyngeal airway space and respiratory function during sleep. The subjects were 22 patients in whom mandibular prognathism was corrected by bilateral sagittal split ramus osteotomy; either one jaw or two jaw surgery. Polysomnography was performed before surgery and 6 months after surgery, and the apnea hypopnea index (AHI) and arterial oxygen saturation during sleep were measured to assess respiratory function during sleep. Morphological changes were studied using cephalograms taken immediately before, a few days after and 6 months after surgery. As a control, 10 subjects without sleep-disordered breathing underwent the same examinations. AHI was not changed significantly after surgery, although two patients were diagnosed with mild obstructive sleep apnea (OSA) syndrome after surgery. They were not obese, but the amounts of mandibular setback at surgery were large. In conclusion, a large amount of mandibular setback might inhibit biological adaption and cause sleep-disordered breathing, and it might be better to consider maxillary advance or another technique that does not reduce the airway for patients with skeletal class III malocclusions who have large anteroposterior discrepancy and/or maxillary hypoplasia.

Osteoclast differentiation in ectopic bone formation induced by recombinant human bone morphogenetic protein 2 (rhBMP-2).

Osteoclast differentiation in the process of ectopic bone formation induced by recombinant human bone morphogenetic protein 2 (rhBMP-2) was examined to clarify the relationship between osteoclast development and rhBMP-2-induced bone formation. A combination of rhBMP-2 with a porous microsphere (PMS) and blood clot was implanted subcutaneously on the bilateral chest muscles of rats. Tartrate-resistant acid phosphatase (TRAPase) activity, cathepsin K (cath K), and calcitonin receptor (CTR), as markers of osteoclasts and their precursors, were examined using enzyme and immunohistochemical analysis up to 7 days after implantation. Mononuclear cells positive for TRAPase, cath K, and CTR first appeared on day 3 in connective tissue surrounding the PMS after implantation of rhBMP-2. Simultaneously, alkaline phosphatase activity became detectable in mesenchymal cells in the connective tissue. Electron microscopy demonstrated some mononuclear cells with abundant mitochondria and poorly developed rough endoplasmic reticulum in the proximity of mesenchymal cells. However, there was no evidence of cartilage or bone matrix formation on day 3. Osteoclasts in various stages of development, classified by the pattern of immunoreactivity for cath K, were observed by day 7. The polarized intracellular distribution of cath K was found only in osteoclasts attached to bone matrix. In conclusion, we have demonstrated for the first time the appearance of osteoclast precursors before bone matrix formation induced by rhBMP-2, suggesting that bone matrix is not a prerequisite for osteoclast precursor recruitment. Furthermore, we suggest that differentiation into polarized functional osteoclasts is accomplished when the osteoclasts attach to the bone matrix.

Tetraspanin gene expression levels as potential biomarkers for malignancy of gingival squamous cell carcinoma

Accurate assessment of malignancy in oral squamous cell carcinoma is essential to optimize treatment planning. To detect a biomarker related to malignant propensity in gingival squamous cell carcinoma (GSCC), quantitative gene expression analysis of tetraspanin family genes was conducted. In 73 cases of GSCC, total RNA was extracted from carcinoma tissues, and gene expression was analyzed by quantitative real time‐PCR. Six tetraspanin family genes (CD9, CD63, CD81, CD82, CD151, NAG‐2) were investigated. Housekeeping genes (ACTB and GAPDH), anchor protein genes (JUP and PXN) and an integrin gene (ITGA3) were used as reference genes. Forty‐five gene expression ratios were calculated from these 11 gene expression levels and were analyzed with clinical parameters using multivariate statistical methods. According to the results of the logistic regression analysis subjecting cervical lymph node metastasis as a target variable, CD9/ACTB (p = 0.013) or CD9/CD82 (p = 0.013) in addition to tumor size (p = 0.028) were detected as significant factors. In Cox proportional hazards regression analysis, delayed cervical lymph node metastasis (p = 0.039) and tumor cell positive surgical margin (p = 0.032) in addition to CD151/GAPDH (p = 0.024) were detected as significant factors for death outcome. A Kaplan‐Meier survival curve presented a significantly lower survival rate of the group with a CD151/GAPDH value of 10 or more (log rank and generalized Wilcoxon tests: p = 0.0003). Results of this study present the usefulness of CD9 and CD151 expression levels as biomarkers for assessment of malignancy in GSCC. They also indicate that detection of residual tumor cells at the surgical margin and the biological malignancy of a tumor interdependently affects prognosis.

Effects of orthognathic surgery on psychological status of patients with jaw deformities

The purpose of this study was to determine the effect of orthognathic surgery on psychological status. The subjects were 119 patients (38 males and 81 females, mean age 25.5±9.4 years) who underwent orthognathic surgery. They were divided into class III (84 patients), class II (20 patients), and class I (15 patients) groups according to the anteroposterior skeletal pattern, and they were also divided into an asymmetry group (51 patients) and a symmetry group (68 patients). We assessed psychological status using the Minnesota Multiphasic Personality Inventory (MMPI) before surgery and at more than 6 months after surgery. The MMPI scores for the depression, hysteria, psychasthenia, and social introversion scales were significantly higher than standard values before surgery, and the hypomania scale significantly lower. The cannot say scale, depression scale, and hysteria scale decreased significantly after surgery. A comparison of MMPI scores among the groups showed the depression scale in the class III group to be higher than those in the class I and II groups; there was no significant difference between the asymmetry and symmetry groups. In conclusion, orthognathic surgery has a positive influence on the psychological status of patients with jaw deformities, especially patients with skeletal class III malocclusion.