Oral appliance therapy for obstructive sleep apnea in multiple system atrophy with floppy epiglottis: a case series of three patients.

PURPOSE: A recent study demonstrated that continuous positive airway pressure (CPAP) may exacerbate obstructive sleep apnea (OSA) in patients with multiple system atrophy (MSA) and a floppy epiglottis (FE) as the CPAP promotes downward displacement of the epiglottis into the laryngeal inlet. In this case series, we examined the effectiveness of an oral appliance (OA) for treating OSA in three patients with MSA and an FE. METHODS: Patients with MSA were demonstrated to have an FE on fiberoptic laryngoscopy under sedation using intravenous propofol. The therapeutic intervention was fitting an OA. Polysomnography (PSG) was performed subsequently with the OA in place. RESULTS: In three patients with MSA, some parameters used to assess the severity of OSA improved with an OA. Both apnea-hypopnea index (AHI) and arousal index (ArI) decreased while wearing the OA in two cases while in the third case, apnea index (AI) and cumulative time at peripheral oxygen saturation (SpO2) below 90% (CT90) decreased, but AHI and ArI increased. The only side effects were transient TMJ discomfort, masseter muscle pain, and tooth discomfort. CONCLUSION: OA therapy using a two-piece type mandibular advancement device (MAD) may be a useful treatment intervention for patients with OSA who have MSA and FE.

HEATR1, a novel interactor of Pontin/Reptin, stabilizes Pontin/Reptin and promotes cell proliferation of oral squamous cell carcinoma.

Pontin and Reptin are closely related proteins belonging to the AAA+ (ATPases Associated with various cellular Activities) family. They form a hetero-oligomeric complex, Pontin/Reptin, which is involved in protein stability and assembly of the protein complexes as a molecular chaperone. Overexpression of Pontin and Reptin in tumor cells has been reported and is implicated in the development of various cancers. However, the molecular mechanism of Pontin/Reptin function in oral squamous cell carcinoma (OSCC) development remains unclear. Here, we identify HEAT repeat-containing protein 1 (HEATR1) as a novel binding factor of Pontin/Reptin. Functionally, HEATR1 stabilizes Pontin/Reptin and positively regulates OSCC cell proliferation by activating mTOR and pre-rRNA synthesis. We also find that HEATR1 expression is markedly upregulated in tumor region of OSCC tissue. Hence, we propose that HEATR1 is involved in the regulation of mTOR and ribosome biogenesis as a potential protein stabilizer of Pontin/Reptin in OSCC.

Influence of XRCC4 expression by breast cancer cells on ipsilateral recurrence after breast-conserving therapy.

BACKGROUND: We examined the expression of nonhomologous end-joining (NHEJ) proteins by breast cancer cells in patients with or without ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy. We also investigated whether there was a difference of NHEJ-related protein expression by tumor cells between two types of IBTR, i.e., true recurrence (TR) with regrowth from the tumor bed or development of a new primary tumor (NP). PATIENTS AND METHODS: The original cohort comprised 560 breast cancer patients who received breast-conserving therapy between February 1995 and March 2006, including 520 patients without IBTR and 40 patients with IBTR. Propensity score matching was employed to select 40 trios (120 patients) consisting of 1 patient with IBTR and 2 patients without IBTR. Immunohistochemical examination of proteins related to NHEJ was performed in surgical specimens. RESULTS: The 40 patients with IBTR included 22 patients who developed TR and 18 who had NP. The 15-year overall survival rate was 85.9% for patients with NP and 95.5% for those with TR, while it was 96.5% for patients without IBTR. Patients with high XRCC4 expression in tumor cells had significantly higher IBTR rates than those with low XRCC4 expression (P < 0.001). The frequency of TR was significantly higher in patients with high expression of XRCC4 than in those with low XRCC4 expression (p < 0.001). XRCC4 expression by tumor cells was not significantly related to development of NP. CONCLUSION: IBTR due to TR may be related to low radiosensitivity of tumor cells, possibly related to high XRCC4 expression.

Autotransplantation or replantation of cryopreserved teeth: a case series and literature review.

BACKGROUND: The aim of this report was to evaluate the outcome of autotransplantation or replantation of cryopreserved teeth clinically and radiographically. Donor teeth were slowly frozen in a controlled-rate freezer using 5% dimethylsulfoxide (DMSO) and 6% hydroxyethyl starch (HES) as protectants. Seven cryopreserved teeth, with duration of storage ranging from 4 to 36 months, were autotransplanted or replanted at Niigata University Medical and Dental Hospital. Endodontic treatment involving root canal debridement followed by interim root canal filling with calcium hydroxide was started 3 weeks after the operation and continued with replacement of the calcium hydroxide filling at 2-week to 3-month intervals. Three transplants showed periodontal regeneration clinically and radiographically, whereas replacement root resorption was observed in the remaining transplants. From the results, it can be concluded that cryopreserved tooth autotransplantation has potential for clinical use; however, the risk of replacement root resorption remains.

Evaluation of oral health-related quality of life in patients with temporomandibular disorders.

OBJECTIVE: To evaluate oral health-related quality of life (OHRQoL) in patients with temporomandibular disorders (TMDs). METHODS: Subjects included 56 patients diagnosed with TMD. Control subjects consisted of 30 individuals without temporomandibular joint symptoms. OHRQoL was evaluated using the Japanese version of the Oral Health Impact Profile (OHIP-J54) before and 4 months after treatment. RESULTS: Total score and all subscale scores of the OHIP-J54 in patients before treatment were significantly higher than those of the control subjects and were significantly improved after treatment, except for social disability. Gender and NRS pain scores had statistically significant effects on OHRQoL, which was low in females and patients with severe pain. CONCLUSION: OHIP-J54 appeared to be useful for understanding psychological and social problems as a screening tool and for assessing the extent of changes in the well-being of patients with TMD.

Positional advantages of supine MRI for diagnosis prior to breast­conserving surgery.

The present study aimed to evaluate the rate of positive surgical margins for magnetic resonance imaging (MRI) performed in the supine position prior to breast-conserving surgery (BCS). The rate of positive surgical margins and the clinicopathological factors were examined in consecutive patients with BCS who underwent preoperative MRI performed in the supine position at Sapporo Medical University Hospital (Sapporo, Japan) and related hospitals and clinics between January 2012 and December 2013. Of 1,175 eligible patients, 1,150 were included after excluding 25 patients with either bilateral breast cancer or stage IV disease. Positive margin was defined as no cancer seen on the resected margin. The primary endpoint was the rate of positive surgical margins when preoperative MRI was performed in the supine position and the secondary endpoint was identification of the factors that predict positive margins. Of the 1,150 female patients (median age, 55 years; range, 29-97 years) who underwent BCS for breast cancer following MRI performed in the supine position, 215 (18.8%) had positive margins, which is similar to the rate with MRI in the prone position, and 930 (81.2%) had negative margins. The rate of positive surgical margins in patients of the human epidermal growth factor receptor 2 (HER2) type was significantly higher than that in the non-HER2 type group (6.5 and 2.9%; χ2 P=0.0103). There was no increase in the rate of positive margins in breast cancers with a diameter of >T2. The rate of positive surgical margins following MRI performed in the supine position was 18.8%. Supine MRI appears to be suitable for informing on the extent of resection of breast cancer.

Prognostic value of preoperative systemic inflammatory response as a prognostic indicator in patients with early-stage oral squamous cell carcinoma.

To determine the usefulness of lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and inflammatory response biomarker (IRB) score for predicting disease-specific survival and delayed cervical lymph node metastasis in early-stage oral squamous cell carcinoma (OSCC). We retrospectively analyzed 72 patients with early-stage OSCC. Receiver operating characteristic curve analysis was used to determine the cutoff values for LMR, NLR, and PLR. IRB score was determined as follows: high LMR, high NLR, and low PLR, which were each rated as 1. These scores were added to obtain IRB score (range: 0-3). From univariate analysis, gender, poor mode of invasion, and high IRB score were identified as significant risk factors for disease-specific survival. However, there were no independent factors for poor prognosis in multivariate analysis. On the other hand, for delayed cervical lymph node metastasis, poor mode of invasion, low LMR, high NLR, high PLR, and high IRB score were identified as significant risk factors from univariate analysis, and in multivariate analysis, poor mode of invasion and high IRB score were confirmed as independent risk factors. IRB score and mode of invasion are potentially independent risk factors for delayed cervical lymph node metastasis in early-stage OSCC.

Crosstalk between oral squamous cell carcinoma cells and cancer-associated fibroblasts via the TGF-ß/SOX9 axis in cancer progression.

Cancer-associated fibroblasts (CAFs) have important roles in promoting cancer development and progression. We previously reported that high expression of sex-determining region Y (SRY)-box9 (SOX9) in oral squamous cell carcinoma (OSCC) cells was positively correlated with poor prognosis. This study developed three-dimensional (3D) in vitro models co-cultured with OSCC cells and CAFs to examine CAF-mediated cancer migration and invasion in vitro and in vivo. Moreover, we performed an immunohistochemical analysis of alpha-smooth muscle actin and SOX9 expression in surgical specimens from 65 OSCC patients. The results indicated that CAFs promote cancer migration and invasion in migration assays and 3D in vitro models. The invading OSCC cells exhibited significant SOX9 expression and changes in the expression of epithelial-mesenchymal transition (EMT) markers, suggesting that SOX9 promotes EMT. TGF-ß1 signalling inhibition reduced SOX9 expression and cancer invasion in vitro and in vivo, indicating that TGF-ß1-mediated invasion is dependent on SOX9. In surgical specimens, the presence of CAFs was correlated with SOX9 expression in the invasive cancer nests and had a significant impact on regional recurrence. These findings demonstrate that CAFs promote cancer migration and invasion via the TGF-ß/SOX9 axis.

A simple technique for repositioning of the mandible by a surgical guide prepared using a three-dimensional model after segmental mandibulectomy.

BACKGROUND: Mandibular reconstruction is performed after segmental mandibulectomy, and precise repositioning of the condylar head in the temporomandibular fossa is essential for maintaining preoperative occlusion. METHODS: In cases without involvement of soft tissue around the mandibular bone, the autopolymer resin in a soft state is pressed against the lower border of the mandible and buccal and lingual sides of the 3D model on the excised side. After hardening, it is shaved with a carbide bar to make the proximal and distal parts parallel to the resected surface in order to determine the direction of mandibular resection. On the other hand, in cases that require resection of soft tissue around the mandible such as cases of a malignant tumor, right and left mandibular rami of the 3D model are connected with the autopolymer resin to keep the preoperative position between proximal and distal segments before surgical simulation. The device is made to fit the lower border of the anterior mandible and the posterior border of the mandibular ramus. The device has a U-shaped handle so that adaptation of the device will not interfere with the soft tissue to be removed and has holes to be fixed on the mandible with screws. RESULTS: We successfully performed the planned accurate segmental mandibulectomy and the precise repositioning of the condylar head by the device. CONCLUSIONS: The present technique and device that we developed proved to be simple and useful for restoring the preoperative condylar head positioning in the temporomandibular fossa and the precise resection of the mandible.

Keratin 17 is co-expressed with 14-3-3 sigma in oral carcinoma in situ and squamous cell carcinoma and modulates cell proliferation and size but not cell migration.

Expression of keratin (K) 13 is replaced with that of K17 when squamous cells of the oral mucosa transform from normal and dysplastic epithelia to carcinoma in situ (CIS) and squamous cell carcinoma (SCC). Since 14-3-3 sigma is functionally associated with K17, we examined possible relationships between expression of K17 and 14-3-3 sigma in oral CIS and SCC tissues by immunohistochemistry. We furthermore examined whether or not K17 expression or knockdown by small interfering RNA (siRNA) modulates the behavior of SCC cells in culture in terms of cell proliferation and migration. In tissue specimens of oral SCC and CIS, the pattern of cytoplasmic expression of 14-3-3 sigma and K17 was similar but neither was expressed in normal or dysplastic epithelia. Both proteins were demonstrated in the cytoplasm of control oral SCC ZK-1 cells, but expression of 14-3-3 sigma changed from cytoplasmic to nuclear upon knockdown of K17. In carcinoma cells, therefore, cytoplasmic localization of 14-3-3 sigma seems to accompany expression of K17. In K17-knockdown cells, proliferation was significantly suppressed at 4 days after seeding. In addition, the cell size of K17-knockdown cells was significantly smaller than that of control cells; as a result of which in the migration experiments, we found delayed closure of scratch wounds but migration as such was not affected. We conclude that K17 expression promotes SCC cell growth and cell size but does not affect cell migration. K17 expression is accompanied by cytoplasmic expression of 14-3-3 sigma, indicative of their functional relationship.

Intramuscular keratocyst as a soft tissue counterpart of keratocystic odontogenic tumor: differential diagnosis by immunohistochemistry.

Keratocystic odontogenic tumor (KCOT), a developmental jaw cyst previously referred to as odontogenic keratocyst (OKC), typically arises in the jawbone. In this article, however, we report a case of KCOT located within the temporalis muscle. We compared its immunohistochemical profiles with those of authentic jaw KCOT, orthokeratinized odontogenic cyst, and epidermoid cyst in order to consider whether a soft tissue counterpart of KCOT could be a separate disease entity. The patient was a 46-year-old man with a well-defined cystic lesion within the left temporalis muscle. On computed tomographic images, the lesion was recognized as a cystic lesion, although KCOT was not included in the clinical differential diagnoses. The location of the lesion was not within bone but, rather, within the temporalis muscle that was attached to the jawbones. Our review of the literature has disclosed more than 20 peripheral KCOT cases of the oral mucosa and more than 10 cases of the skin, but only 1 case arising in muscle. Immunohistochemical investigation of the present intramuscular case reveals KCOT-characteristic profiles distinct from the other 3 types of cysts investigated. The results indicate that KCOT-like lesions can arise within soft tissues, although use of the term odontogenic might seem inappropriate in those cases.

Emergence of keratin 17 vs. loss of keratin 13: their reciprocal immunohistochemical profiles in oral carcinoma in situ.

To evaluate differential expressions for keratin (K) subtypes 13 and 17 in oral borderline malignancies, we examined 67 surgical specimens of the oral mucosa for their immunohistochemical profiles. From those specimens, 173 foci of epithelial dysplasia, 152 foci of carcinoma in situ (CIS), and 82 foci of squamous cell carcinoma (SCC) were selected according to our diagnostic criteria, along with 20 areas of normal epithelia. In normal epithelia, there was no K17 positivity (0%), whereas definite K13 positivity (100%) was observed. The same tendencies were obtained in mild (undefined) and moderate (true) epithelial dysplasias (K17: 0%; K13: 100%). In contrast, all CIS (100%) had K17 positivities, while K13 positivities were lost in many of them (7%). Similar tendencies were confirmed in invasive SCC (K17: 100%, K13: 4%). Simultaneous immunopositivities for K17 and K13 were found only in SCC (7%) and CIS (4%) foci with distinct keratinization. These foci also showed K10 positivities, though K10 positive areas were not identical to K13 positive areas. The results indicate that expressions of K17 and K13 are reciprocal in oral epithelial lesions and that the K17 emergence is related to malignancies.