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PURPOSE: Medication-related osteonecrosis of the jaw (MRONJ) occasionally occurs following tooth extractions in cancer patients receiving denosumab (Dmab). However, there are currently no established guidelines for perioperative antibiotic administration during tooth extraction in these patients. The primary objective was to develop guidelines for the dose and frequency of antibiotics during tooth extraction by investigating the correlation between the current status of antibiotic administration and the development of MRONJ. METHODS: This study included 68 cancer patients receiving high-dose Dmab who had tooth extractions between 2012 and 2022 at 10 hospitals. The relationship between the way of perioperative antibiotic administration and the development of MRONJ was analyzed. A P-value < .05 was considered significant. RESULTS: There was considerable variability across hospitals and surgeons regarding the type, dosage, and duration of antibiotic administration. Amoxicillin (AMPC) was the most commonly used antibiotic. Focusing exclusively on teeth extracted under AMPC administration, MRONJ developed in 21 out of 123 teeth (17.0%). No significant relationship was found between the development of MRONJ and the dosage or duration of perioperative AMPC administration. CONCLUSION: Perioperative antibiotic administration alone may not be sufficient to prevent MRONJ. Therefore, a single preoperative dose is likely adequate for effective and appropriate AMPC administration. .

DOI： 10.7759/cureus.67237

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OBJECTIVES: Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse effect of antiresorptive and/or antiangiogenic agents. As the treatment application for MRONJ is controversial, we aimed to identify the risk factors for poor prognosis and to help determine appropriate management. METHODS: This study included 119 patients. Relevant clinical data were obtained for all the patients. In computed tomography images, osteosclerosis, osteolysis, cortical perforation (buccal or lingual), periosteal reaction, and sequestration were evaluated. RESULTS: Multivariate analyses showed statistically significant associations between poor prognosis in patients with MRONJ and conservative treatment alone (hazard ratio [HR] 1.89), osteolysis (HR 4.67), and the absence of sequestration (HR 5.33). CONCLUSIONS: Conservative treatment alone without clear objectives needs to be avoided, and osteolytic change could be the criteria for surgical intervention. As the boundary between the lesion and vital bone is indistinct, we recommend extensive surgery in cases with unpredictable sequestration.

DOI： 10.1002/hed.27574

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Currently, over 500 rare genetic bone disorders are identified. These diseases are often accompanied by dental abnormalities, which are sometimes the first clue for an early diagnosis. However, not many dentists are sufficiently familiar with phenotypic abnormalities and treatment approaches when they encounter patients with rare diseases. Such patients often need dental treatment but have difficulties in finding a dentist who can treat them appropriately. Herein we focus on major dental phenotypes and summarize their potential causes and mechanisms, if known. We discuss representative diseases, dental treatments, and their effect on the oral health of patients and on oral health-related quality of life. This review can serve as a starting point for dentists to contribute to early diagnosis and further investigate the best treatment options for patients with rare disorders, with the goal of optimizing treatment outcomes.

DOI： 10.1002/ca.24117

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DOI： 10.1007/s00774-023-01448-5

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DOI： 10.1038/s41598-023-38352-x

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INTRODUCTION: Necrotizing fasciitis as a complication of medication-related osteonecrosis of the jaw (MRONJ), which we named "ONJ-NF", has been sometimes reported. This study aimed to investigate the usefulness of the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score for predicting ONJ-NF. MATERIALS AND METHODS: We included patients with acute MRONJ who required hospitalization at a single institution from April 2013 to June 2022. They were divided into two groups: patients with ONJ-NF and those with severe cellulitis as a complication of MRONJ, which we named "ONJ-SC." LRINEC scores were compared between the groups and the cut-off value of the score was set by creating a receiver operating characteristic curve. RESULTS: Eight patients with ONJ-NF and 22 patients with ONJ-SC were included. The LRINEC score was significantly higher in patients with ONJ-NF (median: 8.0 points, range 6-10 points) than in those with ONJ-SC (median: 2.5 points, range 0-6 points). A LRINEC score of ≥ 6 points had a sensitivity of 100.0%, a specificity of 77.3%, and an area under the curve of 0.97. Among 6 parameters of LRINEC score, only C-reactive protein (CRP) and white blood cell count (WBC) had significant differences between two groups. Most of the patients with ONJ-NF were rescued by antibiotic therapy and surgical drainage including debridement of necrotic tissues, but unfortunately, one patient did not survive. CONCLUSION: Our results suggested that the LRINEC score may be a useful diagnostic tool to predict ONJ-NF but valuating only CRP and WBC may be sufficient particularly in patients with osteoporosis.

DOI： 10.1007/s00774-023-01441-y

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Osteoradionecrosis (ORN) often results in pathological fractures through progression. We aimed to identify the risk factors for pathological fracture in patients with mandibular ORN. Seventy-four patients with mandibular ORN were included in this retrospective study. We investigated various risk factors for pathological fracture in patients with mandibular ORN, including number of mandibular teeth with a poor prognosis each at initial evaluation before radiation therapy (RT) and when fracture occurred, and the proportion of antibiotic administration period in a follow-up duration after RT. The rate of occurrence of pathological fractures in patients with mandibular ORN was 25.7%. The median of duration between RT completion and fracture occurrence was 74.0 months. We found that pathological fracture was significantly associated with a larger number of mandibular teeth with a poor prognosis at initial evaluation before RT (P = 0.024) and when fracture occurred (P = 0.009). Especially, a larger number of mandibular teeth with P4 periodontitis, in other words severe periodontal status, was related to pathological fracture in both timings. The proportion of antibiotic administration period in a follow-up duration was also significant risk factor (P = 0.002). Multivariate analyses showed statistically significant associations between pathological fracture and a larger number of mandibular teeth with a poor prognosis when fracture occurred (hazard ratio 3.669). The patient with a larger number of mandibular teeth with P4 periodontitis may have a risk of not only occurrence of ORN but resulting in pathological fracture by accumulation of infection. Surgeons should consider extraction of those teeth regardless of before/after RT if necessary for infection control.

DOI： 10.1038/s41598-023-30735-4

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BACKGROUND: Empyema is a life-threatening infection often caused by oral microbiota. To the best of our knowledge, no reports have investigated the association between the objective assessment of oral health and prognosis in patients with empyema. MATERIALS AND METHODS: A total of 63 patients with empyema who required hospitalization at a single institution were included in this retrospective study. We compared non-survivors and survivors to assess risk factors for death at three months, including the Renal, age, pus, infection, diet (RAPID) score, and Oral Health Assessment Tool (OHAT) score. Furthermore, to minimize the background bias of the OHAT high-score and low-score groups determined based on the cut-off value, we also analyzed the association between the OHAT score and death at 3 months using the propensity score matching method. RESULTS: The 3-month mortality rate was 20.6% (13 patients). Multivariate analysis showed that a RAPID score ≥5 points (odds ratio (OR) 8.74) and an OHAT score ≥7 points (OR 13.91) were significantly associated with death at 3 months. In the propensity score analysis, a significant association was found between a high OHAT score (≥7 points) and death at 3 months (P = 0.019). CONCLUSION: Our results indicated that oral health assessed using the OHAT score may be a potential independent prognostic factor in patients with empyema. Similar to the RAPID score, the OHAT score may become an important indicator for the treatment of empyema.

DOI： 10.1371/journal.pone.0282191

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BACKGROUND: Severe odontogenic infections in the head and neck region, especially necrotizing soft tissue infection (NSTI) and deep neck abscess, are potentially fatal due to their delayed diagnosis and treatment. Clinically, it is often difficult to distinguish NSTI and deep neck abscess in its early stage from cellulitis, and the decision to perform contrast-enhanced computed tomography imaging for detection is often a challenge. This retrospective case-control study aimed to examine the utility of routine blood tests as an adjunctive diagnostic tool for NSTI in the head and neck region and deep neck abscesses. METHODS: Patients with severe odontogenic infections in the head and neck region that required hospitalization were classified into four groups. At admission, hematologic and inflammatory parameters were calculated according to the blood test results. In addition, a decision tree analysis was performed to detect NSTI and deep neck abscesses. RESULTS: There were 271 patients, 45.4% in Group I (cellulitis), 22.5% in Group II (cellulitis with shallow abscess formation), 27.3% in Group III (deep neck abscess), and 4.8% in Group IV (NSTI). All hematologic and inflammatory parameters were higher in Groups III and IV. The Laboratory Risk Indicator for Necrotizing Fasciitis score, with a cut-off value of 6 and C-reactive protein (CRP) + the neutrophil-to-lymphocyte ratio (NLR), with a cut-off of 27, were remarkably useful for the exclusion diagnosis for Group IV. The decision tree analysis showed that the systemic immune-inflammation index (SII) of ≥ 282 or < 282 but with a CRP + NLR of ≥ 25 suggests Group III + IV and the classification accuracy was 89.3%. CONCLUSIONS: Hematologic and inflammatory parameters calculated using routine blood tests can be helpful as an adjunctive diagnostic tool in the early diagnosis of potentially fatal odontogenic infections. An SII of ≥ 282 or < 282 but with a CRP + NLR of ≥ 25 can be useful in the decision-making for performing contrast-enhanced computed tomography imaging.

DOI： 10.1186/s12879-022-07934-x

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Lower third molar extraction is the most common surgical treatment among routine dental and oral surgical procedures. while the surgical procedures for lower third molar extraction are well established, the difficulty of tooth extraction and the frequency of postoperative complications differ depending on the patient's background. To establish a management protocol for the lower third molars, the prevalence of and risk factors for postoperative complications after lower third molar extraction were investigated in a large number of Japanese patients in a multicenter prospective study. During 6 consecutive months in 2020, 1826 lower third molar extractions were performed at the 20 participating institutions. The medical records of the patients were reviewed, and relevant data were extracted. The prevalence of and risk factors for postoperative complications were analyzed. The prevalence of postoperative complications after lower third molar extraction was 10.0%. Multivariate analysis indicated that age (≤32 vs >32, odds ratio [OR]: 1.428, 95% confidence interval [95% CI]: 1.040-1.962, P < .05), the radiographic anatomical relationship between the tooth roots and mandibular canal (overlapping of the roots and canal vs no close anatomical relationship between the roots and the superior border of the canal, OR: 2.078, 95% CI: 1.333-3.238, P < .01; overlapping of the roots and canal vs roots impinging on the superior border of the canal, OR: 1.599, 95% CI: 1.050-2.435, P < .05), and impaction depth according to the Pell and Gregory classification (position C vs position A, OR: 3.7622, 95% CI: 2.079-6.310, P < .001; position C vs position B, OR: 2.574, 95% CI: 1.574-4.210, P < .001) are significant independent risk factors for postoperative complications after lower third molar extraction. These results suggested that higher age and a deeply impacted tooth might be significant independent risk factors for postoperative complications after lower third molar extraction.

DOI： 10.1097/MD.0000000000029989

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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.

DOI： 10.1016/j.bjoms.2022.06.001

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PURPOSE: The purpose of this study was to investigate the risk factors associated with post-extraction persistent bleeding in patients on warfarin or direct-acting oral anticoagulants (DOACs) and the ability of risk scores to predict post-extraction bleeding. METHODS: Three hundred ninety-one patients taking warfarin or DOACs underwent tooth extractions. Various risk factors for post-extraction bleeding, including number of tooth extraction, with antiplatelet therapy, and risk scores, were investigated by univariate and multivariate analyses. A post-extraction bleeding was classified into grades 1-3. RESULTS: The incidence of post-extraction bleeding was 26.8% (77 out of 287 patients; grade 1: 63, grade 2:14) in patients taking warfarin, and 26.0% (27 out of 104 patients; grade 1: 20, grade 2:7) in patients taking warfarin DOACs. Multivariate analyses showed that multiple teeth extractions and HAS-BLED scores (above 3 points) in patients taking warfarin, and only multiple teeth extractions in patients taking DOAC, were significantly associated with post-extraction bleeding, respectively. CONCLUSION: Most of the post-extraction bleedings were grade 1, which can be stopped by eligibly pressing gauze by surgeons. If patients taking anticoagulants are scheduled to undergo multiple teeth extractions or their HAS-BLED score are above 3 points (if warfarin), we recommend informing patients risk of post-extraction bleeding before operation, taking carefully hemostasis, and instructing patients to bite down accurately on the gauze for longer than usual.

DOI： 10.1007/s10006-022-01039-0

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Language：Japanese   Publisher：(公社)日本口腔外科学会  

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Pre-existing inflammation, corticosteroid therapy, periapical periodontitis, longer duration of denosumab therapy, and female sex were significantly associated with an increased risk of denosumab-related osteonecrosis of the jaw after tooth extraction in patients with cancer on oncologic doses of denosumab. A short drug holiday did not protect against this complication. INTRODUCTION: This study retrospectively investigated the relationship between various risk factors, including brief discontinuation of denosumab, and development of denosumab-related osteonecrosis of the jaw (DRONJ) after tooth extraction in patients with cancer who were receiving oncologic doses of this agent. METHODS: Data were collected on demographic characteristics, duration of denosumab therapy, whether or not denosumab was discontinued before tooth extraction (drug holiday), duration of discontinuation, presence of pre-existing inflammation, and whether or not additional surgical procedures were performed. Risk factors for DRONJ after tooth extraction were evaluated by univariate and multivariate analyses. RESULTS: A total of 136 dental extractions were performed in 72 patients (31 men, 41 women) with cancer who were receiving oncologic doses of denosumab. Post-extraction DRONJ was diagnosed in 39 teeth (28.7%) in 25 patients. Tooth extraction was significantly associated with development of DRONJ only in patients with pre-existing inflammation (odds ratio [OR] 243.77), those on corticosteroid therapy (OR 73.50), those with periapical periodontitis (OR 14.13), those who had been taking oncologic doses of denosumab for a longer period (OR 4.69), and in women (OR 1.04). There was no significant difference in the occurrence of DRONJ between patients who had a drug holiday before tooth extraction and those who did not. CONCLUSIONS: These findings suggest that inflamed teeth should be extracted immediately in patients with cancer who are receiving oncologic doses of denosumab. Drug holidays have no significant impact on the risk of DRONJ.

DOI： 10.1007/s00198-021-05995-3

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PURPOSE: In maxillary wisdom tooth extraction, the necessity of CT is unknown. The purpose of this study was to investigate whether CT adding to orthopantomography is useful for predicting oroantral perforation during maxillary third molar extraction. METHODS: Various risk factors for oroantral perforation during maxillary third molar extraction were investigated by univariate and multivariate analyses. We analyzed those of all patients and the patients who underwent CT, respectively. The proximity of the roots to the maxillary sinus floor (root-sinus [RS] classification) and Archer classification were assessed using panoramic radiography. The number of roots and vertical relationship were assessed using CT. RESULTS: A total of 604 out of 3299 patients underwent CT adding to orthopantomography. In all cases, multivariate analyses except for CT findings showed that the RS classification type III/IV and the Archer classification Type B/C/D in panoramic findings were significantly correlated with oroantral perforation as radiological findings. In cases for which CT was performed, multivariate analyses showed that one root (OR 12.87) and the vertical relationship Type D (OR 5.63) in CT findings, besides the RS classification type III/IV (OR 4.47) in panoramic findings, were significantly related to oroantral perforation. CONCLUSION: The RS classification and the Archer classification in panoramic findings can predict the risk of oroantral perforation. The usefulness of CT adding to orthopantomography is limited. However, when the relationship between the upper wisdom tooth and maxillary sinus floor (RS classification) is unclear, to check whether the number of roots is one and the apex of one root is projecting into the maxillary sinus in CT findings, is useful for the prediction.

DOI： 10.1007/s10006-020-00878-z

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BACKGROUND: Necrotizing fasciitis (NF) is an acute and life-threatening soft-tissue infection however rarely seen in oro-cervical region. Therefore, the details of oro-cervical NF (OCNF) are not well known. The purpose of this study was to investigate the characteristics of OCNF by comparing it with severe cellulitis of oro-cervical region (OCSC) or NF of other body regions (e.g., limb, perineum, and trunk) (BNF), respectively. MATERIALS AND METHODS: At first, various risk factors for OCNF in oro-cervical severe infection (OCSI; composed of OCNF and OCSC), including neutrophil-to-lymphocyte ratio (NLR) and Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score, were investigated by univariate and multivariate analyses. Next, the differences between OCNF and BNF, including inflammatory markers and mortality, were investigated. RESULTS: In the present study, 14 out of 231 OCSI patients had OCNF. Multivariate analyses of OCSI patients showed that NLR ≥15.3 and LRINEC score ≥6 points were significantly related to OCNF. During the same period, 17 patients had BNF. The OCNF group had significantly higher inflammatory markers than the BNF group when diagnosis, but significantly lower clinical stages at the time and mortality as outcomes. CONCLUSION: We found that compared to BNF, OCNF can be detected at lower clinical stage by using indexes, such as NLR and LRINEC score, besides clinical findings, which may help contributing to patient's relief.

DOI： 10.1371/journal.pone.0260740

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BioMed Central Ltd  

DOI： 10.1186/s12903-020-01326-w

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PURPOSE: The present retrospective multicenter study intended to investigate the factors associated with severe oral mucositis and candidiasis in patients undergoing radiotherapy for oral and oropharyngeal carcinomas. METHODS: A total of 326 patients who underwent radiotherapy for oral and oropharyngeal cancers were enrolled in the study. The patients' age, sex, body mass index, primary site, diabetes, serum albumin, creatinine, hemoglobin, leukocyte and lymphocyte, concurrent cisplatin or cetuximab, method of radiation, total radiation dose, feeding route, use of spacers, pilocarpine hydrochloride, and corticosteroid ointment were examined, and the associations of each variable with oral mucositis and candidiasis were analyzed by multivariate Cox regression analysis. RESULTS: Grade 3 oral mucositis occurred in 136 (41.7%) patients. Male sex, oropharyngeal cancer, low hemoglobin levels, low leukocytes or lymphocytes, concurrent cisplatin or cetuximab, and oral feeding were found to be significantly associated with a higher incidence of severe oral mucositis. Oral candidiasis occurred in 101 (31.0%) patients. Oropharyngeal cancer, low leukocyte count, and oral mucositis of grade 2 or higher were found to be significantly associated with a higher incidence of oral candidiasis. The use of a topical steroid ointment was not found to be a risk factor for oral candidiasis. CONCLUSIONS: The present retrospective study demonstrated that certain factors may predispose patients with oral and oropharyngeal cancers receiving radiotherapy to develop severe oral mucositis and oral candidiasis. A preventive strategy for severe oral mucositis needs to be established in the future for high-risk cases.

DOI： 10.1007/s00520-019-04885-z

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Language：Japanese   Publisher：(一社)日本口腔腫瘍学会  

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BACKGROUND: Postoperative pneumonia can be a fatal complication that may occur after lung resection in cancer patients. Some reports have shown that the incidence of postoperative pneumonia is decreased after esophageal surgery by perioperative oral care; however, there exist no data to suggest that a lack of perioperative oral care can be a risk factor for postoperative pneumonia after lung resection. To investigate the association between the preventive effect of oral care and postoperative pneumonia, we conducted a multicenter, retrospective study of lung cancer patients who underwent lung resection. METHODS: Between January 2014 and December 2016, a total of 721 patients underwent lung resections at 1 of the 6 hospitals included in our study. Among 721 patients, 280 (38.8%) received perioperative oral care, and the remaining 441 (61.2%) did not receive any such care. Propensity score matching was performed to minimize selection biases associated with the comparison of retrospective data between the oral care and control groups. RESULTS: Of the 721 patients, 54 (7.5%) experienced postoperative pneumonia involving 13 of the 280 patients (4.6%) in the oral care group and 41 of the 441 patients (9.3%) in the control group (P = .02). On propensity score analysis, a significant difference was also found between oral care intervention and incidence of postoperative pneumonia (P = .002). CONCLUSION: Our results suggest that perioperative oral care is an effective method to decrease the occurrence of postoperative pneumonia in patients who have undergone lung resection.

DOI： 10.1016/j.surg.2018.11.020

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BACKGROUND/AIM: We recently investigated the contribution of the iPS-related genes SOX2, OCT4, and Nanog to de-differentiation by assaying for their mRNA levels. Given that mRNA expression does not always correlate with the protein levels, the aim of this study was to retrospectively determine the expression of these four iPS-related factors in human OSCC specimens by immunohistochemistry and examine their association with patient prognosis. MATERIALS AND METHODS: iPS cell-related gene expression in 89 OSCC patients by tissue microarray, and its correlation with clinicopathological factors, differentiation, metastasis, and poor prognoses were investigated. RESULTS: No evidence of statistically significant relationships was found between the expression of iPS cell-related genes and clinicopathological parameters. However, our data indicated that KLF4 expression was associated with survival, and poor tumor differentiation. In addition, high expression of KLF4 was an independent poor prognostic factor (p=0.004) for OSCC patients. CONCLUSION: In preoperative biopsies, higher KLF4 and poor differentiation may be clinically effective predictors for the prognosis of oral cancer.

DOI： 10.21873/anticanres.13231

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DOI： 10.1007/s00198-018-4746-8

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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.

DOI： 10.1016/j.bjps.2018.06.010

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Enhancing the antitumor effect of radiation, while reducing damage to organs, is a significant challenge in radiation therapy for head and neck malignancies. One promising radiosensitizer is gold. The present study aimed to determine whether gold nanoparticles (AuNPs) have the potential to enhance the effects of X-ray irradiation on head and neck cancer cells. The human head and neck carcinoma cell line HSC-3 was used. Total cell number and the levels of cell proliferation and apoptosis were compared between control cells and cells treated with 5-nm AuNPs alone at four concentrations (0.1, 0.4, 1.0 and 10.0 nM), X-ray irradiation alone at three doses (2, 4 and 8 Gy), or a combination of 4 Gy X-ray irradiation and 1.0 nM AuNPs. Analysis of variance and Tukey-Kramer testing were performed to compare the different groups. The total number of cells significantly decreased following 4 and 8 Gy X-ray irradiation, compared with in the control group (control vs. 4Gy, P=2.19×10-4; control vs. 8Gy, P=1.28×10-6). The combination of 4 Gy X-ray irradiation and 1.0 nM AuNPs significantly reduced the total number of cells compared with 4 Gy X-ray irradiation alone (P=2.95×10-4). Cell proliferation was not affected by AuNP treatment alone, 4 Gy X-ray irradiation alone or the combination of X-ray irradiation and AuNPs. The combination of 4 Gy irradiation and 1.0 nM AuNPs significantly increased the number of apoptotic cells compared with 4 Gy irradiation alone (P=0.0261). In conclusion, AuNPs combined with X-ray irradiation enhanced the cytotoxic effect on human head and neck cancer cells in vitro, through the induction of apoptosis, but not inhibition of cell proliferation.

DOI： 10.3892/br.2018.1142

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Radiotherapy (RT) is one of the main treatment modalities for oral squamous cell carcinoma (OSCC), however, radioresistance is a major impediment to its clinical success and poses as a concern that needs to be addressed. Tumor hypoxia is known to be significantly associated with radioresistance in various malignancies, hence, resolving the hypoxic state of a tumor may improve the antitumor effect of RT on OSCC. We have previously revealed that transcutaneous CO2 induced mitochondrial apoptosis and suppressed tumor growth in OSCC by resolving hypoxia. Considering the previous study, we hypothesized that transcutaneous CO2 may enhance the antitumor effect of RT on OSCC by improving intratumoral hypoxia, thereby overcoming radioresistance. In the present study, the combination of transcutaneous CO2 and RT significantly inhibited tumor growth compared with other treatments. This combination therapy also led to decreased expression of HIF-1α in parallel with increased expression of the cleaved forms of caspase-3-8-9 and PARP, which play essential roles in mitochondrial apoptosis. Additionally, the combination therapy increased the expression of ROS modulator 1 and subsequent mitochondrial ROS production, compared to RT alone. These results indicated that transcutaneous CO2 could potentially improve the antitumor effect of RT by decreasing the intratumoral hypoxia and increasing the mitochondrial apoptosis. Our findings indicated that CO2 therapy may be a novel adjuvant therapy in combination with RT for OSCC.

DOI： 10.3892/or.2018.6444

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PURPOSE: The appearance of osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ) is similar, but clinically important differences between ORN and MRONJ exist. The aim of this study was to compare the clinical data between ORN and MRONJ and to reveal the critical differences between these diseases. METHODS: We retrospectively reviewed the epidemiological data, clinical findings, and treatment in 27 ORN and 61 MRONJ patients. Radiographic signs before the initiation of treatment were also assessed. RESULTS: The median age (P = 0.0474) and the ratio of female to male patients (P < 0.0001) were significantly higher in MRONJ patients. There were significantly more MRONJ patients who reported a history of pain when compared with ORN patients (P = 0.0263). As an aetiological factor, tooth extraction was significantly more relevant to MRONJ than ORN (P = 0.0352). When assessing the radiographic signs on computed tomographic images, periosteal reaction was found only in MRONJ patients (P = 0.0158). Minimal debridement was performed significantly more frequently for MRONJ (P = 0.0093), and by contrast, surgical resection was performed more frequently for ORN (P = 0.0002). CONCLUSIONS: Understanding the clinical and underlying pathological differences between ORN and MRONJ probably contributes to the selection of appropriate treatment for each patient.

DOI： 10.1007/s10006-017-0667-5

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Language：Japanese   Publisher：(公社)日本口腔外科学会  

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J01073&link_issn=&doc_id=20180227400009&doc_link_id=10.5794%2Fjjoms.64.83&url=https%3A%2F%2Fdoi.org%2F10.5794%2Fjjoms.64.83&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：(公社)日本顎顔面インプラント学会  

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Language：Japanese   Publisher：(一社)日本口腔感染症学会  

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Language：Japanese   Publisher：(一社)日本口腔感染症学会  

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Language：Japanese   Publisher：(一社)日本口腔感染症学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Ltd  

DOI： 10.1016/j.ajoms.2016.12.010

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND/AIM: Cancer stem cells are suspected to contribute to malignancy in tumors. Hypoxia affects cell differentiation and induces stem-cell-like characteristics in malignancies. Induced pluripotency was demonstrated in mouse fibroblasts by reprogramming with four transcriptional factors: Oct3/4, Sox2, c-Myc, and Klf4. Conversely, oncogenic transformations frequently express transcriptional factors and Nanog. Therefore, cancer cells present some similarities with induced pluripotent stem (iPS) cells. MATERIALS AND METHODS: We investigated the expression of iPS-related genes in vitro and in clinical samples to identify their relationships with hypoxia and tumorigenesis. RESULTS: Oral squamous cell carcinoma (SCC) cells were used to show that expression levels of Oct3/4, Sox2, and Nanog were significantly increased in hypoxic condition in vitro and in moderately- and poorly-differentiated samples. CONCLUSION: We propose that Oct3/4, Sox2 and Nanog are associated with tumor hypoxia characterized in oral SCC and that these factors may also contribute to the undifferentiated potency observed in oral SCC clinically.

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Mandibular cortical bone measurement with x-ray imaging is known to be a potentially useful tool in the detection of dimensional changes caused by bisphosphonate. The primary purpose of this study was to assess the meaning and limitation of cortical bone measurement with computed tomography (CT) in patients with medication-related osteonecrosis of the jaw (MRONJ). The investigators obtained DentaScan images of the mandible from 15 patients with MRONJ, 15 patients with a history of antiresorptive agent administration without symptoms of MRONJ (non-MRONJ), and 15 control subjects. The cortical bone width measured on DentaScan images was compared between the three groups (ANOVA and Tukey's test). Interobserver reliability between two observers was also assessed. The values of interclass correlation coefficient were 0.48 in the MRONJ group, 0.29 in the Non-MRONJ group, and 0.34 in control group. The cortical bone widths calculated both by observer 1 and observer 2 were thicker in patients with MRONJ than in the non-MRONJ group and controls. There were significant differences in cortical bone width among the MRONJ, non-MRONJ, and control groups in observer 1 (P < 0.001) and observer 2 (P < 0.001), specifically comparing the MRONJ group with the non-MRONJ group and the control group. Cortical bone width measurement is useful for the distinction between medication-related osteonecrosis of the jaw and normal bone, in spite of the low interobserver reliability.

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Language：English   Publishing type：Research paper (scientific journal)  

The purpose of this study was to retrospectively investigate the outcomes of Brånemark System Mk III TiUnite/Groovy implants placed in patients at Kobe University Hospital. Various risk factors for implant failure, including mechanical coupling, were investigated by univariate and multivariate analysis. The predictive variables investigated included age, sex, smoking habit, general health, history of radiation therapy, application of a dentomaxillary prosthesis, type of prosthesis, use of alveolar bone augmentation, site of implant insertion, mechanical coupling between implants, and the length and diameter of the implants. Of the 907 implants investigated, only 23 were unsuccessful; the overall survival rate was 96.7%. Increased age, radiation therapy, application of a removable prosthesis or dentomaxillary prosthesis, lack of mechanical coupling between implants, and shorter implants (≤8.5mm) were significant risk factors for implant failure according to univariate analysis (P<0.05). Multivariate analysis identified a significant association (P<0.05) between dental implant failure and a lack of mechanical coupling between implants (odds ratio 6.88) and shorter implants (≤8.5mm) (odds ratio 3.43). The findings of this study demonstrated multivariate relationships between various risk factors and dental implant failure.

DOI： 10.1016/j.ijom.2016.10.014

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PURPOSE: The objectives of this study were to retrospectively describe the characteristics and outcomes of patients with oral squamous cell carcinoma (OSCC) with level IV/V metastases, and to evaluate the multivariate relationships among potential risk factors for metastasis and prognosis. MATERIALS AND METHODS: We evaluated 291 patients (178 men and 113 women; mean age, 65.9 ± 13.5 years). Clinicopathological data, time of development of level IV/V metastases, and clinical course were investigated. RESULTS: Twenty-three patients (7.9%) developed level IV/V metastases. The 3-year overall survival rates when level IV/V metastasis first developed were 27.3% upon initial treatment, 57.1% when metachronous neck metastasis developed, and 40.0% when the tumor recurred. Oral tongue tumor subsite, high N staging, neck dissection when metachronous neck metastasis developed, as well as recurrence were independent risk factors for level IV/V metastasis. CONCLUSION: We demonstrate here the multivariate relationships among the risk factors indicated above for level IV/V metastasis and their prognostic significance for patients with OSCC. Oral tongue tumors, high N staging, and neck dissection upon the occurrence of metachronous neck metastasis or recurrence were risk factors for level IV/V metastasis and positive extracapsular spread, presence of multiple lymph metastases, and moderate or poor differentiation were poor prognostic factors.

DOI： 10.1016/j.jcms.2016.10.011

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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.

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Oral squamous cell carcinoma (OSCC) is the most common form of oral cancers. Recent studies have shown that the malignant transformation of various carcinomas, including OSCC, is associated with epithelial-mesenchymal transition (EMT), and that expression of the EMT factors are significantly associated with tumor invasion, tumor metastasis, and survival rates in OSCC patients. Hence, there is a possibility that EMT suppression may improve the prognosis of OSCC patients. Hypoxia inducible factor-1α (HIF-1α) is a crucial microenvironmental factor in tumor progression, which induces the expression of EMT factors. We previously reported that transcutaneous CO2 suppresses both human OSCC tumor growth and metastasis to the regional lymph nodes by improving hypoxia in treated tissue. According to this background, we hypothesized that increased EMT with HIF-1α expression may increase the progression and the metastatic potential of OSCC, and that decreased hypoxia by transcutaneous CO2 could suppress EMT. In the present study, in vitro studies showed that hypoxic conditions increased the expression of HIF-1α and EMT factors in OSCC cells. In addition, in vivo studies revealed that transcutaneous CO2 increased E-cadherin expression with the decreased expression of HIF-1α, Snail, Slug, N-cadherin, and Vimentin in tumor treatment. These results suggest that transcutaneous CO2 could suppress EMT by improving hypoxia, resulting in the reduction of metastatic potential of OSCC. The findings indicate that transcutaneous CO2 may be able to improve the prognosis of OSCC patients through the suppression of EMT.

DOI： 10.3892/ijo.2016.3380

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Language：Japanese   Publisher：(一社)日本口腔診断学会  

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2015&ichushi_jid=J02383&link_issn=&doc_id=20151102230010&doc_link_id=10.15214%2Fjsodom.28.208&url=https%3A%2F%2Fdoi.org%2F10.15214%2Fjsodom.28.208&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: The purpose of this study was to retrospectively investigate the multivariate relationships among the various risk factors for postoperative delirium in patients undergoing oral cancer surgery. MATERIAL AND METHODS: The medical records of all patients with oral cancer who underwent curative head and neck surgery between April 2011 and March 2013 at our institution were retrospectively reviewed. There was a total of 188 patients, including 110 males and 78 females. RESULTS: We found that older age, extensive surgical procedure, longer operation, excessive hemorrhage, blood transfusion, longer postoperative management in the intensive care unit, longer postoperative hospital stay, lower albumin level in the preoperative blood test, and lower total protein, albumi, n and hemoglobin levels and a higher C-reactive protein (CRP) level in the postoperative blood tests were significant variables in the univariate analysis (p < 0.05). We also determined that an older age (odds ratio [OR] = 6.83), intraoperative lower hemoglobin levels (OR = 6.82), and excessive hemorrhage (OR = 3.62) during surgery were significant variables in the multivariate analysis. CONCLUSION: Clinicians should pay special attention to preventing delirium during the postoperative management of older patients with these risk factors. Furthermore, increasing the hemoglobin levels during surgery may be able to prevent postoperative delirium.

DOI： 10.1016/j.jcms.2015.06.011

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Language：Japanese   Publisher：(一社)日本口腔感染症学会  

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Language：Japanese   Publisher：(一社)日本口腔診断学会  

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J02383&link_issn=&doc_id=20141029210010&doc_link_id=10.15214%2Fjsodom.27.253&url=https%3A%2F%2Fdoi.org%2F10.15214%2Fjsodom.27.253&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif