Transcutaneous carbon dioxide suppresses skeletal muscle atrophy in a mouse model of oral squamous cell carcinoma.

Cancer cachexia causes skeletal muscle atrophy, impacting the treatment and prognosis of patients with advanced cancer, but no treatment has yet been established to control cancer cachexia. We demonstrated that transcutaneous application of carbon dioxide (CO2) could improve local blood flow and reduce skeletal muscle atrophy in a fracture model. However, the effects of transcutaneous application of CO2 in cancer-bearing conditions are not yet known. In this study, we calculated fat-free body mass (FFM), defined as the skeletal muscle mass, and evaluated the expression of muscle atrophy markers and uncoupling protein markers as well as the cross-sectional area (CSA) to investigate whether transcutaneous application of CO2 to skeletal muscle could suppress skeletal muscle atrophy in cancer-bearing mice. Human oral squamous cell carcinoma was transplanted subcutaneously into the upper dorsal region of nude mice, and 1 week later, CO2 gas was applied to the legs twice a week for 4 weeks and FFM was calculated by bioimpedance spectroscopy. After the experiment concluded, the quadriceps were extracted, and muscle atrophy markers (muscle atrophy F-box protein (MAFbx), muscle RING-finger protein 1 (MuRF-1)) and uncoupling protein markers (uncoupling protein 2 (UCP2) and uncoupling protein 3 (UCP3)) were evaluated by real-time polymerase chain reaction and immunohistochemical staining, and CSA by hematoxylin and eosin staining. The CO2-treated group exhibited significant mRNA and protein expression inhibition of the four markers. Furthermore, immunohistochemical staining showed decreased MAFbx, MuRF-1, UCP2, and UCP3 in the CO2-treated group. In fact, the CSA in hematoxylin and eosin staining and the FFM revealed significant suppression of skeletal muscle atrophy in the CO2-treated group. We suggest that transcutaneous application of CO2 to skeletal muscle suppresses skeletal muscle atrophy in a mouse model of oral squamous cell carcinoma.

Development of Cu application using dual-energy computed tomography for detecting medication-related osteonecrosis of the jaw.

INTRODUCTION: The present study developed an application using dual-energy computed tomography (DECT) focused on Cu for detecting medication-related osteonecrosis of the jaw (MRONJ). MATERIALS AND METHODS: First, we performed two types of phantom studies using a Cu wire syringe and pig mandible with Cu wire to detect Cu on DECT. Second, DECT examinations of 44 patients with MRONJ were performed to compare lesion and normal bone sites using single-energy CT, DECT-virtual non-calcium (VNCa), and DECT-Cu applications. Quantitative analyses of VNCa CT and CT values were performed, and a cut-off value was calculated using receiver operating characteristic analysis. Third, we compared the Cu content in the MRONJ and normal bone groups using inductively coupled plasma atomic emission spectroscopy (ICP-AES). RESULTS: The material-specific differences in attenuation between the two different energies enabled the accurate separation of Cu from Ca in phantom studies. The sensitivity and specificity for single-energy CT, DECT-VNCa, and DECT-Cu applications were 97.7% and 2.3%, 86.4% and 81.8%, and 88.6% and 97.7%, respectively. Thus, VNCa CT values obtained on DECT-Cu application images showed the highest area under the curve value and maximal diagnostic efficacy in differentiating lesion sites from normal bone sites. On ICP-AES analyses, the Cu content was significantly higher in the MRONJ group than in the normal bone group. CONCLUSION: DECT-Cu application demonstrated better diagnostic performance in detecting MRONJ compared with single-energy CT or DECT-VNCa.

Relationship of Mitochondrial-Related Protein Expression with the Differentiation, Metastasis, and Poor Prognosis of Oral Squamous Cell Carcinoma.

Mitochondrial dysfunction and respiratory function changes have been consistently associated with the initiation and progression of cancer. The purpose of this study was to retrospectively investigate the expression of mitochondrial tumor-suppressor and DNA-repair proteins in patients with oral squamous cell carcinoma (OSCC) and to evaluate the relationship between their expression and prognosis. We enrolled 197 patients with OSCC who underwent surgical resection between August 2013 and October 2018. Clinical, pathological, and epidemiological data were retrospectively collected from hospital records. The expression of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), mitochondrial transcription factor A, mitochondrial tumor suppressor gene 1, silent information regulator 3, and 8-hydroxyguanine DNA glycosylase was investigated using immunochemistry. The 3-year disease-specific survival (DSS) rates of patients showing positive expression of all selected proteins were significantly higher than those of patients showing a lack of expression. Multivariate analysis revealed that the expression of PGC-1α (hazard ratio, 4.684) and vascular invasion (hazard ratio, 5.690) can predict the DSS rate (p < 0.001). Low PGC-1α expression and vascular invasion are potential clinically effective predictors of the prognosis of OSCC.

Transcutaneous carbon dioxide application suppresses the expression of cancer-associated fibroblasts markers in oral squamous cell carcinoma xenograft mouse model.

Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer. Cancer-associated fibroblasts (CAFs) are the main stromal cells in the tumor microenvironment (TME). As CAFs promote tumor progression and hypoxia in the TME, regulating the conversion of normal fibroblasts (NFs) into CAFs is essential for improving the prognosis of patients with OSCC. We have previously reported the antitumor effects of transcutaneous carbon dioxide (CO2) application in OSCC. However, the effects of reducing hypoxia in the TME remain unclear. In this study, we investigated whether CO2 administration improves the TME by evaluating CAFs marker expression. Human OSCC cells (HSC-3) and normal human dermal fibroblasts (NHDF) were coinjected subcutaneously into the dorsal region of mice. CO2 gas was applied twice a week for 3 weeks. The tumors were harvested six times after transcutaneous CO2 application. The expression of CAFs markers (α-SMA, FAP, PDPN, and TGF-ß) were evaluated by using real-time polymerase chain reaction and immunohistochemical staining. The expression of α-SMA, FAP, PDPN, and TGF-ß was significantly increased over time after co-injection. In the CO2-treated group, tumor growth was significantly suppressed after treatment initiation. In addition, the mRNA expression of these markers was significantly inhibited. Furthermore, immunohistochemical staining revealed a significant decrease in the protein expression of all CAFs markers in the CO2-treated group. We confirmed that transcutaneous CO2 application suppressed CAFs marker expression and tumor growth in OSCC xenograft mouse model.

Local application of a transcutaneous carbon dioxide paste prevents excessive scarring and promotes muscle regeneration in a bupivacaine-induced rat model of muscle injury.

In postoperative patients with head and neck cancer, scar tissue formation may interfere with the healing process, resulting in incomplete functional recovery and a reduced quality of life. Percutaneous application of carbon dioxide (CO2 ) has been reported to improve hypoxia, stimulate angiogenesis, and promote fracture repair and muscle damage. However, gaseous CO2 cannot be applied to the head and neck regions. Previously, we developed a paste that holds non-gaseous CO2 in a carrier and can be administered transdermally. Here, we investigated whether this paste could prevent excessive scarring and promote muscle regeneration using a bupivacaine-induced rat model of muscle injury. Forty-eight Sprague Dawley rats were randomly assigned to either a control group or a CO2 group. Both groups underwent surgery to induce muscle injury, but the control group received no treatment, whereas the CO2 group received the CO2 paste daily after surgery. Then, samples of the experimental sites were taken on days 3, 7, 14, and 21 post-surgery to examine the following: (1) inflammatory (interleukin [IL]-1ß, IL-6), and transforming growth factor (TGF)-ß and myogenic (MyoD and myogenin) gene expression by polymerase chain reaction, (2) muscle regeneration with haematoxylin and eosin staining, and (3) MyoD and myogenin protein expression using immunohistochemical staining. Rats in the CO2 group showed higher MyoD and myogenin expression and lower IL-1ß, IL-6, and TGF-ß expression than the control rats. In addition, treated rats showed evidence of accelerated muscle regeneration. Our study demonstrated that the CO2 paste prevents excessive scarring and accelerates muscle regeneration. This action may be exerted through the induction of an artificial Bohr effect, which leads to the upregulation of MyoD and myogenin, and the downregulation of IL-1ß, IL-6, and TGF-ß. The paste is inexpensive and non-invasive. Thus, it may be the treatment of choice for patients with muscle damage.

Detection of bone marrow edema in differential diagnoses of odontogenic cysts using dual-energy computed tomography.

PURPOSE: In this study, we prospectively investigated the relationship between bone marrow edema (BME) and odontogenic cysts and explored the possibility of using dual-energy computed tomography (DECT) as an auxiliary tool for the diagnosis of odontogenic cysts. METHODS: This cross-sectional study included 73 patients who underwent the DECT scan and surgery for odontogenic cysts or odontogenic tumors. The virtual noncalcium (VNCa) computed tomography (CT) values and CT values were measured at several sites. The predictor variable was diagnosis, and the other variables included age, sex, and sites. The primary outcome was VNCa CT value. Variables were tested using the chi-square test or the Kruskal-Wallis test. The VNCa CT and CT values were tested using the Scheffe test for multiple comparisons. All variables were analyzed as independent variables affecting the VNCa CT values around the lesion in the multiple regression analysis. RESULT: There were 35 men and 38 women. The mean patient age was 50.0 ± 19.5 years (range: 8-86). The VNCa CT values (- 6.2 ± 34.3) around the lesion in patients with RCs were significantly higher than those in patients with dentigerous cysts (- 44.4 ± 28.6) and odontogenic keratocysts (- 67.3 ± 19.5). In multiple regression analysis, the VNCa CT values around the lesion showed a significant positive correlation with histological results (regression coefficient: - 0.605, P < 0.001). CONCLUSION: The presence of BME is associated with radicular cysts, and DECT can be used as an auxiliary tool for radicular cyst diagnosis.

Effect of compression on mandibular fracture haematoma-derived cells.

Mechanical stress induces a variety of biochemical and morphological reactions in bone cell biology. This study aimed to investigate appropriate pressures of osteogenesis on the biological responses of 3-dimensional cultured human mandibular fracture haematoma-derived cells by compressive loading. Six patients with mandibular fractures who underwent open reduction and internal fixation were included in the study. During the operation, fracture haematomas that formed fibrin clots were manually removed before irrigation. First, pressures were applied to human mandibular fracture haematoma-derived cell-seeded collagen sponges. The sponges were subjected to mechanical compression using loading equipment applied at no compression, 0.5, or 1 mm. Compressive loading was applied to the samples prior to compression for 0, 6, 12, or 24 hours. Collagen sponge samples were collected for quantification of mRNA using several parameters including alkaline phosphatase (ALP), osteopontin (OPN), osterix (OSX), runt-related gene 2 (RUNX2), protein level, and immunocytochemistry (anti-sclerostin). Among these the 0.5 mm compression group compared with the control and 1.0 mm compression groups upregulated mRNA expression of OPN and OSX after 24 hours. Additionally, compared with the control group, a significantly higher OSX gene expression was observed in both the 0.5 mm and 1.0 mm groups after 6, 12, and 24 hours of compression (p < 0.05). However, no significant differences were observed regarding ALP and RUNX2 expression. These results indicated increased stimulation of osteogenesis of the mandibular fracture-line gap in the 0.5 mm compression group compared with the control and 1.0 mm compression groups.

Exploratory clinical trial to evaluate the efficacy and safety of carbon dioxide paste in healthy people.

INTRODUCTION: Scarring and pain are postoperative complications in patients after head and neck cancer treatment; however, there is no effective treatment. These complications are affected by local blood flow disorders, and it is well known that the transcutaneous application of carbon dioxide (CO2) improves local blood flow. Previously, we have shown that the transcutaneous application of carbon dioxide causes absorption of CO2 and increase the oxygen (O2) pressure in the treated tissue; it is expected that the application of CO2 may reduce scarring and pain caused by cancer treatment. We newly introduced the CO2 paste as a new CO2 application method, which does not need to use CO2 gas directly. In this study, we aimed to apply of CO2 paste to healthy people and to investigate its usefulness, safety and feasibility by analysing the increase in blood flow and frequency of adverse events. METHODS: We applied carbon dioxide paste to skin over the sternocleidomastoid and gastrocnemius muscles of eight healthy volunteers. The changes in blood flow before and after the CO2 paste application using dynamic MRI, and changes in the vital signs were evaluated. RESULTS: In the neck area and middle layer of the lower leg, the signal intensity (SI) significantly increased 60 seconds after application. In the surface layer of the lower leg, the SI was significantly increased 60 and 300 seconds after paste application. Although mild heat was noted after the paste application, no obvious adverse events occurred. CONCLUSION: We demonstrated the increase in SI by dynamic MRI at the site of the carbon dioxide paste application, which indicates the paste application is effective in improving the blood flow.

Success of dental implants in patients with large bone defect and analysis of risk factors for implant failure: a non-randomized retrospective cohort study.

OBJECTIVES: This study aimed to retrospectively investigate the success and survival rates of dental implants used for dentomaxillary prostheses at our hospital and the risk factors associated with large bone defects. MATERIALS AND METHODS: A total of 138 external joint system implants used for dentomaxillary prostheses in 40 patients with large bone defects were included in this study. The alveolar bone at the site of implant insertion was evaluated using panoramic radiography and computed tomography. Various risk factors (demographic characteristics, dental status, and operative factors such as the employment of alveolar bone augmentation, the site, the length, and diameter of implants) for implant failure and complete implant loss were investigated using univariate and multivariate analyses. The associations between the variables and the success and survival rates of dental implants were analyzed using the multivariate Cox proportional hazard models. RESULTS: The 10-year overall success and survival rates were 81.3% and 88.4% in this study. Multivariable analysis showed that the male sex (HR 6.22), shorter implants (≤ 8.5 mm) (HR 5.21), and bone augmentation (HR 2.58) were independent predictors of success rate. Bone augmentation (HR 5.14) and narrow implants (≤ 3.3 mm) (HR 3.86) were independent predictors of the survival rate. CONCLUSION: Male sex, shorter or narrow implants, and bone augmentation were independent risk factors for dental implants used in dentomaxillary prostheses in patients with large bone defects. CLINICAL RELEVANCE: Clinicians should consider these risk factors and pay close attention to the management of these patients.

Local Application of Transcutaneous Carbon Dioxide Paste Decreases Inflammation and Accelerates Wound Healing.

INTRODUCTION:  Delayed wound healing after surgery lowers the long-term quality of a patient's life and leads to discomfort and pain. However, treatments for wound healing are often difficult and have not yet been fully established. In this study, we investigated the effect of a special paste that can be administered transdermally and holds a non-gaseous carbon dioxide (CO2) source in its carrier, which can be applied to the head and neck region for wound healing in a rat skin defect model. METHODS: Forty-eight Sprague Dawley rats were randomized into control and CO2 groups. We punched a 6.2-mm wound on the back of each rat. The control rats were left untreated, whereas rats in the CO2 group were treated with the CO2 paste every day after surgery. We evaluated wound healing 3, 7, 14, and 21 days after wounding by analyzing the diameter of the wound, gene expression of inflammatory markers vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-ß, hypoxia-inducible factor (HIF)-1α, interleukin (IL)-1ß, and IL-6 using quantitative real-time polymerase chain reaction, hematoxylin and eosin, and immunohistochemical staining patterns. RESULTS: Rats in the CO2 group showed accelerated wound healing compared to those in the control group. Furthermore, VEGF and TGF-ß were overexpressed, whereas HIF-1α, IL-1ß, and IL-6 were downregulated in the rats treated with CO2. Immunohistochemical analysis also revealed similar patterns of expression. CONCLUSION: Taken together, the CO2 paste promoted wound healing by regulating the hypoxic environment, reducing inflammation, and accelerating angiogenesis.

Bacterial Colonization of the Condyle in Patients with Advanced Mandibular Osteoradionecrosis: Analysis of Hemimandibulectomy Specimens.

Advanced mandibular osteoradionecrosis (ORN) sometimes requires extended resection (e.g., hemimandibulectomy). Bacterial infection contributes to ORN pathogenesis. To control infection and determine the extent of debridement required, an understanding of bacterial spread within sites of mandibular ORN is important. The current study used a histopathological approach to assess bacterial colonization in the mandibular condyle and elucidate possible paths of bacterial spread towards the mandibular condyle. Four hemimandibulectomy specimens were selected. Areas of bone destruction were macroscopically assessed and confirmed using hematoxylin and eosin staining. Bacterial presence within mandibular condyle was confirmed with Gram staining. Bone exposure was observed in the molar area in all specimens. Macroscopic bone destruction was apparent especially near the medial side of the cortical wall. Gram staining revealed bacterial colonization of the mandibular condyle in three of the four specimens. In conclusion, bacteria tended to spread posteriorly and through the medial side of the mandibular cortical wall. In patients with advanced ORN, the potential for bacterial colonization of the mandibular condyle should be considered during treatment.

Tongue Osseous Choristoma in an 11-Year-Old Female: A Case Report and Literature Review Focusing on Pediatric Cases.

Osseous choristoma is an uncommon benign lesion characterized by the presence of ectopic mature bone within soft tissue. In most cases, these lesions occur on the dorsum of the tongue in patients in their third and fourth decades of life. This article describes a case of lingual osseous choristoma in a pediatric patient. An eleven-year-old girl with a lingual mass was referred to our hospital from a dental clinic. Total excisional biopsy and histological examination were performed, and osseous choristoma was diagnosed. The postoperative course was uneventful with no signs of recurrence during the 12 months after surgery. Moreover, a literature review focusing on pediatric cases with lingual osseous choristoma was performed to know the etiology, clinicopathological characteristics, and course of treatment of the lesion.

Transcutaneous Carbon Dioxide Decreases Immunosuppressive Factors in Squamous Cell Carcinoma In Vivo.

INTRODUCTION: In recent years, the tumour immunosuppressive mechanism has attracted attention as a cause of tumour chemoresistance. Although chemoresistance and immunosuppression of tumours have been reported to be associated with a hypoxic environment, effective treatments to improve hypoxia in tumours have not yet been established. We have previously applied carbon dioxide (CO2) to squamous cell carcinoma and have shown that improvement in local oxygenation has an antitumour effect. However, the effects of local CO2 administration on tumour immunosuppression, chemoresistance, and combination with chemotherapy are unknown. In this study, we investigated the effects of local CO2 administration on squamous cell carcinoma and the effects of combined use with chemotherapy, focusing on the effects on tumour immunosuppressive factors. METHODS: Human oral squamous cell carcinoma (HSC-3) was transplanted subcutaneously into the back of a nude mouse, and CO2 and cisplatin were administered. After administration twice a week for a total of 4 times, tumours were collected and the expression of tumour immunosuppressive factors (PD-L1, PD-L2, and galectin-9) was evaluated using real-time polymerase chain reaction and immunostaining. RESULTS: Compared with the control group, a significant decrease in the mRNA expression of PD-L1 was observed in both, CO2-treated and combination groups. Similarly, the expression of PD-L2 and galectin-9 decreased in the CO2-treated and combination groups. Furthermore, immunostaining also showed a significant decrease in the protein expression of tumour immunosuppressive factors in the CO2-treated and combination groups. CONCLUSION: It was confirmed that the tumour immunosuppressive factors decreased due to local CO2 administration to the mouse model. CO2 administration has the potential to improve the hypoxic environment in tumours, and combined use with chemotherapy may also improve tumour immunosuppression.

JCAD expression and localization in human blood endothelial cells.

BACKGROUND: Junctional Cadherin 5 Associated (JCAD) is an endothelial, cell-cell junction protein, and its expression is associated with cardiovascular diseases including atherosclerosis and hypertension. However, to date, there are few studies confirming JCAD expression and precise localization in human tissues by immunohistochemical staining. METHODS: JCAD expression and localization was assessed in four human submandibular gland (SMG) specimens by immunohistochemical staining. One specimen of SMG with sialoadenitis was accompanied by severe inflammation and fibrosis, while the other was largely normal. Other two SMGs were accompanied by severe fibrosis because of irradiation. RESULTS: Immunohistochemical analysis of human SMGs revealed JCAD localization at the blood endothelial cell-cell junctions. JCAD expression was more evident in microvessels and arteries in areas affected by inflammation. CONCLUSIONS: The localization of JCAD at endothelial cell-cell junctions was confirmed in human tissues. JCAD expression may be affected by pathological conditions.

Effect of low-intensity pulsed ultrasound after intraoral vertical ramus osteotomy.

OBJECTIVE: The present study investigated the effect of low-intensity pulsed ultrasound (LIPUS) on long-term osseous healing of the cleavage space between bone fragments after intraoral vertical ramus osteotomy (IVRO). STUDY DESIGN: Patients undergoing IVRO were randomly assigned to the LIPUS group (n = 12) or the control group (n = 9) after surgery. LIPUS treatments were applied daily to the cleavage space between bone fragments for 3 weeks. We observed 3-dimensional quantitative color mapping of the whole mandible created by computed tomography (CT) data at 1 month, 6 months, and 1 year postoperatively. On the basis of CT values, the color grades were classified as D1 to D5 by using the Misch criteria. We then calculated mean CT values and rated each color grade in different selection ranges. RESULTS: The mean CT values of the LIPUS group were significantly higher than those of the control group at 1 month, 6 months and 1 year postoperatively (P < .01). The color grades of the cleavage between bone fragments increased from D5 to D1 over time. CONCLUSIONS: Our results indicated that LIPUS promoted osseous healing after IVRO, thus improving bone density and offering clinical benefits.

A radiologic evaluation of the incidence and morphology of maxillary sinus septa in Japanese dentate maxillae.

PURPOSE: Evaluation of the inner aspect of the maxillary sinus is important for the success of a sinus lift procedure. The most common surgical complication is perforation of the Schneiderian membrane, which is thought to occur because of the presence of maxillary sinus septa. Therefore, we retrospectively investigated the incidence and morphology of maxillary sinus septa using multiplanar reformatted computed tomographic (CT) images from dentate Japanese patients. METHODS: A total of 276 patients and 552 maxillary sinus segments were evaluated. The maxillary sinus septa were divided into four locations: forefront, anterior, middle, and posterior. The heights of the septa were measured at three sites from the deepest point of the sinus floor: lateral, mid-point, and medial. RESULTS: Sinus septa were identified in 191 of 552 (34.6%) maxillary sinus segments obtained from 111 of 276 (40.2%) patients. One unilateral septum was most commonly detected, and the sinus septa were most often located in the middle of the maxillary sinus. The average height of the identified septa was 8.69 ± 4.68 mm (mean ± standard deviation). CONCLUSION: Multiplanar reformatted CT images can identify maxillary sinus septa in any plane. The height of maxillary sinus septa in the dentate maxillae was higher than detected in previous studies. Appropriate treatment planning using CT images should be considered to prevent surgical complications.

Lymphangiogenesis and Lymph Node Metastasis in Oral Squamous Cell Carcinoma.

BACKGROUND/AIM: Tumor lymphangiogenesis plays a key role in lymph node (LN) metastasis in oral squamous cell carcinoma (OSCC). The purpose of this study was to investigate podoplanin and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) and their relationship to nodal metastasis and other clinicopathological variables. PATIENTS AND METHODS: Podoplanin and LYVE-1 expression of the primary tumor and normal tissue were investigated by means of a quantitative real-time PCR assay and immunohistochemistry in samples from 33 cases of OSCC. RESULTS: The mRNA high expression levels of both genes had a statistically significantly higher rate of LN metastasis (p<0.01) and histological grade (p<0.01 for podoplanin, p<0.05 for LYVE-1). High expression of each gene, as shown by immunohistochemistry, had a statistically significant higher rate of LN metastasis (p<0.01 for podoplanin, p<0.05 for LYVE-1). CONCLUSION: Podoplanin and LYVE-1 were strongly associated with LN metastasis.

Effect of local application of transcutaneous carbon dioxide on survival of random-pattern skin flaps.

INTRODUCTION: Skin flap procedures are widely used to reconstruct skin and soft tissue defects. Skin flap necrosis is a serious postoperative complication. Many researchers have introduced pharmacological agents to improve flap ischemia in experimental studies. However, outcomes of these studies remain controversial. We previously demonstrated that transcutaneous CO2 application improves hypoxia in fracture repair. In this study, we hypothesized that improving hypoxia by transcutaneous CO2 application can improve the blood flow in skin flaps and increase angiogenesis. We investigated whether transcutaneous CO2 application can increase the survival of random-pattern skin flaps. MATERIALS AND METHODS: Six-week-old male Sprague-Dawley rats were divided into two equal groups: the control group (n = 6) and CO2 group (n = 6). A random-pattern skin flap was constructed in these rats. Topical CO2 was applied using a hydrogel every day for 5 days in the CO2 group. The flap survival area was measured on postoperative days 1, 3, and 5. The vessel density and expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and hypoxia-inducible factor-1α (HIF-1α) were evaluated on postoperative day 5. RESULTS: A statistically significant difference was found in the percentage of the flap survival area between the two groups on postoperative days 3 and 5 (p < 0.05). Furthermore, the expression of VEGF and bFGF was significantly higher and that of HIF-1α was significantly lower in the CO2 than in the control group (p < 0.05). CONCLUSIONS: Transcutaneous CO2 application can improve the blood flow in skin flaps and increase angiogenesis, thus increasing the survival of random-pattern skin flaps.

Risk factors associated with oroantral perforation during surgical removal of maxillary third molar teeth.

PURPOSE: The relationship between radiographic findings and the occurrence of oroantral perforation is controversial. Few studies have quantitatively analyzed the risk factors contributing to oroantral perforation, and no study has reported multivariate analysis of the relationship(s) between these various factors. This retrospective study aims to fill this void. METHODS: Various risk factors for oroantral perforation during maxillary third molar extraction were investigated by univariate and multivariate analysis. The proximity of the roots to the maxillary sinus floor (root-sinus [RS] classification) was assessed using panoramic radiography and classified as types 1-5. The relationship between the maxillary second and third molars was classified according to a modified version of the Archer classification. The relative depth of the maxillary third molar in the bone was classified as class A-C, and its angulation relative to the long axis of the second molar was also recorded. RESULTS: Performance of an incision (OR 5.16), mesioangular tooth angulation (OR 6.05), and type 3 RS classification (i.e., significant superimposition of the roots of all posterior maxillary teeth with the sinus floor; OR 10.18) were all identified as risk factors with significant association to an outcome of oroantral perforation. CONCLUSION: To our knowledge, this is the first multivariate analysis of the risk factors for oroantral perforation during surgical extraction of the maxillary third molar. This RS classification may offer a new predictive parameter for estimating the risk of oroantral perforation.

Observation of osseous healing after intraoral vertical ramus osteotomy: focus on computed tomography values.

PURPOSE: The purpose of this study was to observe long-term osseous healing of the cleavage space between bone fragments after intraoral vertical ramus osteotomy using computed tomographic (CT) values. PATIENTS AND METHODS: CT examinations were performed to observe long-term osseous healing immediately after intraoral vertical ramus osteotomy and at 6 months, 1 year, and 2 years postoperatively. Bone fragments were observed on the interior and lateral sides. CT values between bone fragments were used to measure the range of each point within a 1.7- × 1.7-mm square, and the mean of the measurements was calculated. RESULTS: CT values between bone fragments increased significantly over time at 1 month, 6 months, 1 year, and 2 years after surgery. CONCLUSIONS: Osseous healing in the cleavage between bone fragments after intraoral vertical ramus osteotomy was successful according to CT values.