An imaging­based diagnostic approach to vascular anomalies of the oral and maxillofacial region.

The accurate diagnosis of vascular anomalies (VAs) is considered a challenging endeavor. Misdiagnosis of VAs can lead clinicians in the wrong direction, such as the performance of an unnecessary biopsy or inappropriate surgical procedures, which can potentially lead to unforeseen consequences and increase the risk of patient injury. The purpose of the present study was to develop an approach for the diagnosis of VAs of the oral and maxillofacial region based on computed tomography (CT), magnetic resonance imaging (MRI) and dynamic contrast-enhanced MRI (DCE-MRI). In the present study, the CT and MR images of 87 VAs were examined, and the following imaging features were evaluated: Detectability of the lesion, the periphery of the lesion, the inner nature of the lesion, the density of the lesion on CT, the signal intensity of the lesion on MRI, the detectability of phleboliths and the shape of the lesion. A total of 29 lesions were further evaluated using the contrast index (CI) curves created from the DCE-MRI images. A diagnostic diagram, which is based on the imaging features of VAs and CI curve patterns, was subsequently extrapolated. The results obtained demonstrated that the VAs were detected more readily by MRI compared with CT, whereas the detectability of phleboliths was superior when using CT compared with MRI. VAs showed a propensity for homogeneous isodensity on CT, whereas, by contrast, they exhibited a propensity for heterogeneous hyperdensity on CE-CT. VAs also showed a propensity for homogeneous intermediate signal intensity when performing T1-weighted imaging (T1WI), heterogeneous high signal intensity when performing short tau inversion recovery MRI, and heterogeneous high signal intensity when performing fat-saturated CE-T1WI. The CI curves of VAs were found to exhibit a specific pattern: Of the 29 CI curves, 23 (79.3%) showed early weak enhancement, followed by a plateau leading up to 400-600 sec. An imaging-based diagnostic diagram was ultimately formulated. This diagram can act as an aid for radiologists when they are expecting to find a VA, and hopefully serve the purpose of simplifying the diagnostic process. Taken together, the findings of the present study indicated that DCE-MRI may be considered a useful tool for the diagnosis of VAs.

Factors Influencing Parenting Stress in the Mothers of Infants and the Effects of Artwork Production.

Background: The importance of support for the mothers of infants to cope with parenting stress due to isolated parenting environments is being emphasized. In order to reduce the parenting stress in parenting mothers while improving the quality of parenting support for them, it is important to identify factors influencing such stress. We investigated the effects of artwork production in different styles, conducted self-evaluation of such production, and identified factors influencing parenting stress in mothers, involving those who participated in a handprint artwork production workshop. Methods: We included 140 mothers who participated in a handprint artwork production workshop, dividing them into 2 groups: A: 70 with children younger than 3 years of age who engaged in artwork production alone; and B: 70 who engaged in it through collaboration with their children aged 3 years or older. The instructor distributed an anonymous, self-administered questionnaire to all the mothers, and collected their responses. The questionnaire examined the following items: attributes, the number of participations in the workshop, artwork production self-evaluation, and parenting stress. Results: There were 140 (100%) responses, and the number of valid responses was 65 from Group A and 54 from Group B, a total of 119 (85%). The mean [parenting strain] score was significantly higher in Group B. Multiple regression analysis identified the child's age and presence/absence of his/her siblings overall and in Group A, and , an item for artwork production self-evaluation, in Group B as factors influencing the total [parenting strain] score. Conclusion: The present results suggest that the child's age and presence/absence of his/her siblings could influence parenting stress in the mothers. Additionally, there was a correlation between the level of parenting stress and score for among the mothers who engaged in artwork production through collaboration with their children.

Prognostic factors in patients in the terminal phase of haematological malignancies who are receiving home medical care.

Although there are many prognostic models for patients in the terminal phase of solid tumours, a reliable prognostic scoring system in patients in the terminal phase of haematological malignancies (HM) has not been established. We retrospectively evaluated 180 patients in the terminal phase of HM who were receiving home medical care (HMC). Multivariate analyses revealed that clinician's estimate, consciousness, loss of appetite, dyspnoea, neutrophil count, lymphocyte count, and lactate dehydrogenase were associated with overall survival (OS). Based on this result, we developed a novel prognostic scoring system, the Japan palliative haematological oncology prognostic estimates, in which four risk groups were shown to clearly differ in survival (p < 0.001): a low-risk group (n = 41, median OS of 434 days), an intermediate-low-risk group (n = 80, median OS of 112 days), an intermediate-high-risk group (n = 38, median OS of 31.5 days), and a high-risk group (n = 21, median OS of 10 days). This is the first investigation of prognostic factors that influence the OS of patients in the terminal phase of HM who are receiving HMC. Providing patients with reliable information about their prognosis is important for them to consider how to spend their remaining life.

Influence of mesiodens on adjacent teeth and the timing of its safe removal.

Purpose: To focus on the effects of the presence of mesiodens on adjacent teeth and to investigate the timing of its safe removal. Materials and Methods: Cone-beam computed tomography examinations, obtained at Okayama University Hospital over a three-year period, were inspected. Data were recorded including the number of mesiodens; associated abnormalities; and the relationship with neighboring structures. Depending on multiple factors, the risk of developing complications due to early extraction of a mesiodens was divided into three categories: high, medium, and low risk. Results: A total of 5,958 cone-beam computed tomography exams were obtained, 460 patients aged 3-85 years were diagnosed with a total of 568 mesiodens, 382 (67.3%) of which were discovered in young patients (age <10 years), and 333 (87.2%) of these were associated with abnormalities. Regarding the risk categories, 11 (1.9%) were considered to be in the high-risk, five (0.9%) in the medium-risk and 552 (97.2%) in the low-risk categories. Moreover, eight out of 11 high-risk mesiodens were extracted and no post-operative complications have been seen. Conclusion: As the results showed that no postoperative complications were seen in all the extracted cases of high-risk mesiodens, this indicates the possibility of safe extraction at an early age which could reduce related future complications.

FOXO1 cooperates with C/EBPδ and ATF4 to regulate skeletal muscle atrophy transcriptional program during fasting.

Catabolic conditions, such as starvation, inactivity, and cancer cachexia, induce Forkhead box O (FOXO) transcription factor(s) expression and severe muscle atrophy via the induction of ubiquitin-proteasome system-mediated muscle proteolysis, resulting in frailty and poor quality of life. Although FOXOs are clearly essential for the induction of muscle atrophy, it is unclear whether there are other factors involved in the FOXO-mediated transcriptional regulation. As such, we identified FOXO-CCAAT/enhancer-binding protein δ (C/EBPδ) signaling pathway as a novel proteolytic pathway. By comparing the gene expression profiles of FOXO1-transgenic (gain-of-function model) and FOXO1,3a,4-/- (loss-of-function model) mice, we identified several novel FOXO1-target genes in skeletal muscle including Redd1, Sestrin1, Castor2, Chac1, Depp1, Lat3, as well as C/EBPδ. During starvation, C/EBPδ abundance was increased in a FOXOs-dependent manner. Notably, knockdown of C/EBPδ prevented the induction of the ubiquitin-proteasome system and decrease of myofibers in FOXO1-activated myotubes. Conversely, C/EBPδ overexpression in primary myotubes induced myotube atrophy. Furthermore, we demonstrated that FOXO1 enhances the promoter activity of target genes in cooperation with C/EBPδ and ATF4. This research comprehensively identifies novel FOXO1 target genes in skeletal muscle and clarifies the pathophysiological role of FOXO1, a master regulator of skeletal muscle atrophy.

Dynamic contrast-enhanced MRI as a predictor of programmed death ligand-1 expression in patients with oral squamous cell carcinoma.

Immune checkpoint inhibitors (ICIs) targeting programmed death ligand-1 (PD-L1) are highly promising therapies for oral squamous cell carcinoma (OSCC). The assessment of PD-L1 expression may help predicting the therapeutic effect of ICIs and, thus, benefit patient selection. Contrast index (CI) parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) have been proven as efficient to assess microvessel density (MVD) in OSCC. The present study aimed to determine the correlation between DCE-MRI parameters and MVD and between DCE-MRI parameters and PD-L1 expression to determine whether DCE-MRI could be used non-invasively to evaluate PD-L1 expression in patients with OSCC. A total of 21 patients with primary OSCC who had undergone a 3T MRI scan, including DCE-MRI, were included in the present study, and CI curve-derived parameters were examined. The MVD and PD-L1 expression in the surgically resected specimens were analyzed using immunohistochemistry (IHC) staining for CD31 and IHC staining for PD-L1, respectively. The results demonstrated that the expression levels of these markers were correlated with DCE-MRI parameters. PD-L1 expression levels were found to be significantly correlated with the maximum CI (CI-max; P=0.007), peak CI (CI-peak; P=0.007), maximum CI gain (CI-gain; P=0.006) and MVD (P=0.001) values. The mean CI-max, CI-peak, CI-gain and MVD values were significantly higher in tumors with high PD-L1 expression (P<0.05). MVD levels were also significantly correlated with the time of CI-max (T-max; P=0.003) and CI-gain (P=0.037). The mean CI-gain was significantly increased, and the mean T-max was significantly shorter in high MVD tumors (P<0.05 and P<0.01, respectively). In summary, the findings from the present study confirmed the correlation between CI parameters, derived from DCE-MRI, and MVD, and suggested that these parameters may be correlated with PD-L1 expression in OSCC tumor cells.

Incidental findings in the thyroid gland on computed tomography images of the oral and maxillofacial region.

The numbers of abnormal findings incidentally detected in adjacent regions are increasing with advances in imaging modalities. The present study aimed to examine the prevalence and characteristics of incidental findings in the thyroid gland on computed tomography (CT) images of the oral and maxillofacial region. CT scans of the oral and maxillofacial region in patients obtained between January 2012 and December 2016 were retrospectively reviewed. Images that revealed incidental findings in the thyroid gland, including nodules, were recorded, together with the sizes and characteristics of the findings. The Japan Association of Breast and Thyroid Sonology (JABTS) guidelines were used for classification. The rate of descriptions of these findings in the radiographic interpretation reports were also examined. Of the 1,135 patients examined, 326 (28.7%) had several types of incidental findings. In particular, 169 (14.9%) of the 1,135 patients had nodules >5 mm in diameter, for which further careful examination is recommended in the JABTS guideline. The description rate for nodules >5 mm in diameter in the radiographic interpretation reports was 30.8% (52/169 patients), of whom 17.3% (9/52 patients) were referred to the endocrinology department for further careful examination. Incidental findings in the thyroid gland were relatively common on CT images of the oral and maxillofacial region. Oral radiologists tend to focus specifically on the oral and maxillofacial region during diagnosis on oral and maxillofacial CT images, but should pay the same careful attention to observe adjacent regions, such as the thyroid gland.

Health Promotion Effects of Soy Isoflavones.

Soybeans contain several physiologically active ingredients, such as soy phytosterol, soyasaponin, soy protein, and lecithin, and are therefore expected to express the functionalities of said ingredients. Among them, soy isoflavones have been studied in recent years for their various functions, including their obesity-preventing effect, blood glucose level reducing effect, osteoporosis and breast cancer risk reduction, and anti-oxidative effect, and several health promoting effects and disease preventing effects are expected. For example, it has been determined that soy isoflavones reduce body and fat weight in experiments in which mice were fed a diet containing soy isoflavones in studies on anti-obesity. Epidemiologic studies with humans have also shown that women who consume more soybeans have lower BMI than those who consume less. We previously found that soy isoflavones may have anti-obesity effects in myoblasts through the activation of transcriptional coactivator PGC-1ß, which increases energy expenditure. In recent studies, a decrease in blood glucose level due to soy isoflavone was seen in an experiment in which diabetic model mice were fed a diet containing soy isoflavone. It has also been suggested that soy isoflavone intake may increase bone mineral density in postmenopausal women and reduce the risk of breast cancer. This review focuses on the actions of soy isoflavones known to date, including their anti-obesity and anti-diabetic effects, bone loss preventing effects, and cancer risk reduction effects, and introduces reports on the health promotion and disease prevention effects of soy isoflavones.

Metabolomic Analysis of Skeletal Muscle in Aged Mice.

Sarcopenia is the age-induced, progressive loss of skeletal muscle mass and function. To better understand changes in skeletal muscle during sarcopenia, we performed a metabolomic analysis of skeletal muscle in young (8-week-old) and aged (28-month-old) mice by using capillary electrophoresis with electrospray ionization time-of-flight mass spectrometry. Principal component analysis showed clear changes in metabolites between young and aged mice. Glucose metabolism products were decreased in aged mice, specifically fructose 1,6-diphosphate (0.4-fold) and dihydroxyacetone phosphate (0.6-fold), possibly from decreased glycolytic muscle fibers. Multiple metabolic products associated with phospholipid metabolism were significantly changed in aged mice, which may reflect changes in cell membrane phospholipids of skeletal muscle. Products of polyamine metabolism, which are known to increase nucleic acid and protein synthesis, decreased in spermine (0.5-fold) and spermidine (0.6-fold) levels. By contrast, neurotransmitter levels were increased in skeletal muscle of aged mice, including acetylcholine (1.8-fold), histamine (2.6-fold), and serotonin (1.7-fold). The increase in acetylcholine might compensate for age-associated dropout of neuromuscular junctions, whereas the increases in histamine and serotonin might be due to muscle injury associated with aging. Further analysis focusing on the altered metabolites observed in this study will provide essential data for understanding aging muscles.

Oropharyngeal adenoid cystic carcinoma invading the mandibular bone through the mandibular foramen.

Adenoid cystic carcinoma (ACC) is a rare epithelial tumor of the head and neck region, and one of the most common malignant tumors of the salivary glands. ACC is a slow-growing tumor characterized by perineural invasion and often has a high-recurrence rate. We describe a case of oropharyngeal ACC invading the mandibular bone through the mandibular foramen that showed a rare pattern of origin and invasion. A 70-year-old woman complained of noise and pain around the right temporomandibular joint. Osteomyelitis was suspected on the initial imaging examinations, although the findings were slightly atypical. However, a mass was observed in the right oropharyngeal wall on subsequent imaging examinations, and mandibular bone invasion, rather than osteomyelitis, was additionally suspected. The mass in the right oropharyngeal wall and right mandible was surgically excised. On postoperative histopathological examination, the mass was finally diagnosed as ACC. As tumor cells were also observed around the inferior alveolar nerve, mandibular bone invasion through the mandibular foramen was suspected. An oropharyngeal ACC invading the mandibular bone through the mandibular foramen is extremely rare. The present case suggests that bone invasion should be considered carefully with several imaging examinations when a malignant tumor such as ACC is observed around the jaw bone.

A case of sublingual adenoid cystic carcinoma involving the mandible presenting as a "skip lesion".

Adenoid cystic carcinoma (ACC) is a slowly growing malignant neoplasm with a propensity for perineural invasion. Microscopic invasion of ACC often prevents its detection on computed tomography (CT) or magnetic resonance imaging (MRI). We herein report a rare case of sublingual ACC presenting as a "skip lesion" that rapidly infiltrated the mandible after tumor resection. A 64-year-old man presented to Okayama University Hospital with an 18-month history of swelling in the right floor of the mouth. Clinical examination displayed an ulcerated swollen mass in that region. An enhanced mass was detected in the right sublingual space on CT and MRI. Bone surface erosion was observed at the inferior border of the mandible, but continuity with the sublingual mass or mass around that lesion was not detected by imaging. Sublingual tumor resection and selective neck dissection were performed by the pull-through method. Histopathologically, the surgical margins were free of cancer cells, and the tumor was diagnosed as ACC. Continuity with the sublingual mass and mandibular bone was not detected intraoperatively. However, marked bone resorption was detected in the anterior mandible 3 months after the operation. Biopsy was performed, and the findings indicated the same histological type of sublingual ACC. This case suggests that a malignant tumor close to the jaw bone requires the clinician to consider the possibility of bone invasion and to observe a wide region surrounding the tumor using imaging examination.

Assessment of MRI findings and clinical symptoms in patients with temporomandibular joint disorders.

OBJECTIVES: To investigate the correlations among various temporomandibular joint (TMJ) findings on MRI and the relationships between MRI findings and symptoms. METHODS: 425 patients (850 TMJs) with temporomandibular joint disorders (TMDs) who underwent MRI were enrolled. Oblique sagittal proton density-weighted and T2 weighted images in open- and closed-mouth positions were evaluated. MRI findings included disc configuration, disc position, condylar morphology, bone marrow pattern, and joint effusion. Symptoms included TMJ pain, TMJ noise, and limitation of mouth opening. For statistical analyses, Spearman's rank correlation coefficient and logistic regression analysis were applied. RESULTS: Folded disc, disc displacement without reduction (DDWOR), and osteophytes had significant negative correlations with other normal MRI findings (p < 0.01). DDWOR and marrow edema were associated with TMJ pain. Conversely, osteophytes [odds ratio (OR): 0.52; 95% CI (0.30-0.90)] and combination-type condylar degeneration [OR: 0.45; 95% CI (0.24-0.83)] were associated with decreased risk of TMJ pain. Condylar flattening was positively associated with TMJ noise [OR: 5.25; 95% CI (1.44-19.07)] and negatively associated with limitation of mouth opening [OR: 0.34; 95% CI (0.11-0.99)]. High-grade joint effusion was significantly associated with TMJ pain and noise. CONCLUSIONS: DDWOR and high-grade joint effusion (an indicator of inflammation in the articular cavity) were associated with TMD symptoms. This finding suggests that treatment strategy for DDWOR and decreasing inflammation might lessen clinical TMD symptoms. Condylar degeneration was not associated with indicators of inflammation or TMJ symptoms. These results suggest that patients with TMD symptoms should undergo initial MRI to allow rapid selection of appropriate therapies.

Chronic high-fat feeding impairs adaptive induction of mitochondrial fatty acid combustion-associated proteins in brown adipose tissue of mice.

Since brown adipose tissue (BAT) is involved in thermogenesis using fatty acids as a fuel, BAT activation is a potential strategy for treating obesity and diabetes. However, whether BAT fatty acid combusting capacity is preserved in these conditions has remained unclear. We therefore evaluated expression levels of fatty acid oxidation-associated enzymes and uncoupling protein 1 (Ucp1) in BAT by western blot using a diet-induced obesity C57BL/6J mouse model. In C57BL/6J mice fed a high-fat diet (HFD) over 2-4 weeks, carnitine palmitoyltransferase 2 (Cpt2), acyl-CoA thioesterase (Acot) 2, Acot11 and Ucp1 levels were significantly increased compared with baseline and control low-fat diet (LFD)-fed mice. Similar results were obtained in other mouse strains, including ddY, ICR and KK-Ay, but the magnitudes of the increase in Ucp1 level were much smaller than in C57BL/6J mice, with decreased Acot11 levels after HFD-feeding. In C57BL/6J mice, increased levels of these mitochondrial proteins declined to near baseline levels after a longer-term HFD-feeding (20 weeks), concurrent with the accumulation of unilocular, large lipid droplets in brown adipocytes. Extramitochondrial Acot11 and acyl-CoA oxidase remained elevated. Treatment of mice with Wy-14,643 also increased these proteins, but was less effective than 4 week-HFD, suggesting that mechanisms other than peroxisome proliferator-activated receptor α were also involved in the upregulation. These results suggest that BAT enhances its fatty acid combusting capacity in response to fat overload, however profound obesity deprives BAT of the responsiveness to fat, possibly via mitochondrial alteration.

Should incidental findings in diagnostic imaging be reported?

BACKGROUND: Recent improvements in image quality have contributed to an increasing number of incidental findings (IF). Also called as "incidentalomas", this generic term refers to an entity discovered unexpectedly on an imaging examination performed for other reason. Commonly, normal variants, minor developmental anomalies and imaging artifacts are described as potential pathology. Some IF were reported in magnetic resonance imaging (MRI) exam of temporomandibular joint (TMJ), including IF in the brain, maxillary sinus, ethmoidal cells, mastoid cells, salivary glands, muscles. The aim of this study is to evaluate the prevalence of IF on MRI of TMJ from Japanese patients. METHODS: An image archive from 872 patients referred to MRI evaluation due to TMJ symptomatology was assessed. Three experienced radiologists evaluated all images, and the final diagnosis was achieved by consensus. The data regarding IF was recorded, considering only tumor and tumor-like lesions. RESULTS: A total of 12 (1.38%) of tumor and tumor-like lesions were observed from all 872 MRI exams evaluated. The most frequent lesion was arachnoid cyst (0.45%), followed by neoplastic lesions (0.22%). CONCLUSIONS: The question "should every IF be reported?" is still difficult to answer. Relevant IF are rare, and radiologists are expected to be reasonable: think about the adverse effects of reporting an IF, and, based on their own judgment, choose for a positive or a negative answer.

Possible role of thymidine phosphorylase in gynecological tumors as an individualized treatment strategy.

Thymidine phosphorylase (TP) is structurally similar to platelet-derived endothelial cell growth factor, and it activates 5-fluorouracil (5-FU) prodrugs and also promotes angiogenesis. In the present study, the possibility of using TP expression as a biomarker for 5-FU prodrugs, and the significance of TP as an angiogenic factor, were investigated in patients with gynecological tumors. The subjects enrolled in the study were 188 patients with gynecological tumors who provided informed consent and underwent tumor resection at the Department of Obstetrics and Gynecology of Tokai University Hospital between February 2002 and January 2010. Measurement of the enzymatic activity of TP and dihydropyrimidine dehydrogenase (DPD) was performed by enzyme-linked immunosorbent assay. In addition, immunohistochemistry (IHC) analysis of microvessels by monochrome imaging, western blotting and reverse transcription-polymerase chain reaction were performed. The mean TP activity and the TP/DPD ratio were increased in squamous cell carcinoma of the cervix (306.9 and 2.2 U/mg protein, respectively) and adenosquamous carcinoma (317.6 and 1.4 U/mg protein, respectively) compared with benign tumors and other malignancies, including endometrial (uterine) carcinoma, ovarian serous adenocarcinoma and ovarian mucinous adenocarcinoma. However, these parameters were also elevated in other histological types of cancer such as clear cell adenocarcinoma of the ovary (115.2 and 2.1 U/mg protein, respectively), in which the microvessel area was the largest of all the histological types analyzed. Since high TP expression and a high TP/DPD ratio were identified in other tumors besides cervical cancer, it is possible that patients for whom 5-FU prodrugs are indicated could be selected appropriately if their TP activity is determined and their TP expression is analyzed by IHC prior to initiation of the treatment.

Successful treatment of an elderly frail patient with acquired idiopathic thrombotic thrombocytopenic purpura under close monitoring of ADAMTS13 activity and anti-ADAMTS13 antibody titers.

A 68-year-old woman was admitted to the regional hospital because of hemolytic anemia, thrombocytopenia, and neurological abnormalities including unconsciousness. One week before admission, she suffered from diarrhea and subsequently passed out and hit her face on the ground. She was suspected of having TTP and was transferred to our hospital. We performed the assays of ADAMTS13 activity and anti-ADAMTS13 antibody titers, and confirmed the diagnosis of acquired idiopathic TTP with total deficiency of ADAMTS13 activity with its inhibitor. She was initially treated with plasma exchange combined with corticosteroids, however, we were forced to substitute plasma exchange with fresh frozen plasma infusion due to procedure-associated complications. The infusion of fresh frozen plasma was known as less effective and more likely to boost inhibitor titers compared to plasma exchange. In this circumstance, we could successfully switch the plasma therapy under close monitoring of ADAMTS13 activity and anti-ADAMTS13 antibody titers which precisely revealed the disease status of TTP in our patient, and eventually she achieved complete remission with normal level of ADAMTS13 activity and no inhibitor. Our experience suggested that the measurement of ADAMTS13 activity and inhibitor titer might be valuable not only for making the diagnosis but also for guiding treatment decisions by precise evaluating of disease status in patients with the acquired form of TTP.

Alterations of hypoxia-induced factor signaling pathway due to mammalian target of rapamycin (mTOR) suppression in ovarian clear cell adenocarcinoma: in vivo and in vitro explorations for clinical trial.

OBJECTIVES: Before setting into the clinical trial using a combination of mammalian target of rapamycin (mTOR) inhibitors (rapamycin and everolimus) and other anticancer drugs, this study was conducted to confirm the efficacy of the new therapeutic strategy for ovarian clear cell adenocarcinoma (CCA), which targeted mTOR-hypoxia-induced factor (HIF) signal transduction system. MATERIALS AND METHODS: Using the cultured cells of CCA and animal models, alteration of mTOR-HIF cofactors and cell proliferation under the mTOR inhibitor-treated condition were analyzed. RESULTS: Mammalian target of rapamycin-HIF cofactors were inhibited dependent on concentration by mTOR inhibitor, resulting in suppression of the cultured CCA proliferation. However, von Hippel-Lindau was up-regulated at the messenger RNA level. In the nude mice with subcutaneously implanted CCA cells, apoptosis and necrosis were detected especially around the center of the tumors in the mTOR inhibitor-treated group more conspicuously than in the nontreated group. In the assessment of combination therapy with other antitumor agents, a combined treatment with mTOR inhibitor and chemotherapeutic agents caused a significant decrease in tumor size compared to the chemotherapeutic agents-only group. CONCLUSIONS: Treatment by mTOR inhibitor is expected to down-regulate the cell proliferation of the CCA as a new therapeutic strategy.

Case series: conditions inhibiting eruption of permanent first molars.

PURPOSE: The purpose of this study was to evaluate the radiological and histopathological findings of 11 patients with unerupted first molars to verify the factors obstructing spontaneous eruption. METHODS: The patients' clinical, radiological, and histopathological data were evaluated retrospectively to determine histopathological diagnosis, radiographic findings, methods of surgical management, and postoperative course. RESULTS: This study involved 4 male and 7 female patients (mean age=9.5 years old). Nine cases involved the mandible. The patients' histopathological diagnoses included 3 odontogenic tumors, 2 odontogenic cysts, and 6 hyperplastic dental follicles. Radiographically, 10 cases showed characterless enlargement of the follicular space, while only 1 displayed radiopaque bodies. One patient with a tumor underwent enucleation, and 1 with a cyst underwent cystectomy and tooth extraction. The others underwent wide excision or partial excision of the surrounding tissue at the top of the impacted tooth. Tumor relapse was observed in 3 cases. CONCLUSION: Surgeons should perform aggressive treatment for patients with unerupted teeth because spontaneous eruption is rare in cases involving non-neoplastic lesions such as hyperplastic dental follicles.