Kanchu Tei

Assessment of cervical lymph node metastases using FDG-PET in patients with head and neck cancer

ObjectiveTo evaluate the diagnostic accuracy of fluorodeoxyglucose positron emission tomography (FDG-PET) relative to computed tomography (CT) for detecting metastatic cervical lymph nodes in patients with squamous cell carcinoma of the head and neck (HNSCC), and to ascertain the factors that affect this accuracy.MethodsA total of 1076 lymph nodes obtained from 35 neck dissections in 26 HNSCC patients who preoperatively underwent both FDG-PET and CT were retrospectively analyzed. For pathological metastatic lymph nodes, the lymph node size (short-axis diameter), the ratio of intranodal tumor deposits, and the size of intranodal tumor deposits (maximum diameter of metastatic foci in each lymph node) were histologically recorded.ResultsForty-six lymph nodes from 23 neck sides were pathologically diagnosed metastases. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of FDG-PET evaluated individually per neck side were 74%, 92%, 80%, 94%, and 65%, respectively, whereas those of CT were 78%, 58%, 71%, 78%, and 58%, respectively. FDG-PET detected 100% of metastatic lymph nodes ≥10 mm, intranodal tumor deposits ≥9 mm, and intranodal tumor deposits with a ratio >75%, whereas no nodes or tumor deposits smaller than 5 mm were detected. The spatial resolution limitations of FDG-PET were responsible for 16 of 20 (80%) false-negative PET results in lymph nodes.ConclusionsFDG-PET is a useful tool for preoperative evaluation of the neck because it accurately detects metastatic lymph nodes ≥10 mm and has fewer false-positive cases than CT. The high specificity of FDG-PET for lymph node metastases may play an important role in avoiding unnecessary neck dissection.

Role of radiotherapy for mucoepidermoid carcinoma of salivary gland.

This report analyzes 61 patients with mucoepidermoid carcinomas of the salivary gland treated by surgery alone or by surgery plus radiotherapy. Local control for all 61 patients at 5 and 10 years was achieved for 88.8 and 79.7% of the cases. Although the rate of positive surgical margin was higher in patients treated with surgery and radiotherapy (radiotherapy group) than in patients treated by surgery alone (surgery group), the local control rates of the two groups showed no statistically significant differences. There was no local recurrence in seven patients receiving post-operative radiotherapy above 55 Gy while there were three local relapses among 17 patients receiving 55 Gy or lower doses (P < 0.05). The 5- and 10-year actual survival rates were 73.4 and 63.3% respectively. Histopathologic subtype of mucoepidermoid carcinomas correlated with regional lymph node involvement and survival. There were no differences in the local control and survival rates of patients with major salivary gland tumors and patients with minor salivary gland tumors. Radiotherapy using 55 Gy or more combined with operation achieved local control and survival rates comparable with complete resection of tumors even if a positive surgical margin was more frequent in the radiotherapy groups.

Specific p53 mutations predict poor prognosis in oral squamous cell carcinoma

In this study, we focused on p53 mutations in specific regions, including DNA-binding surface regions, to clarify the correlation between mutations within the specific regions of p53 and clinical outcomes of patients with oral cancers. We analyzed p53 mutations in 121 fresh primary oral squamous cell carcinomas (SCCs) by polymerase chain reaction-single-strand conformation polymorphism or a yeast functional assay. p53 mutations were detected in 51/121 (42%) cases. Mutation of p53 was not associated with any clinicopathological parameters; however, tumors containing specific p53 mutations, e.g. DNA-binding surface regions (L2, L3 and the LSH motif) and conserved regions (II-V), had significantly poorer prognoses than tumors with mutations outside of those regions. Moreover, locoregional failure, lymph node metastasis and the occurrence of subsequent distant metastasis were also significantly associated with mutations within DNA-binding surface regions. These data indicate that specific mutations of p53 could be important prognostic factors in oral SCCs.

Effects of bisphosphonates on osteoclastogenesis in RAW264.7 cells.

Bisphosphonates are used as therapeutic agents for the management of osteoporosis and other bone diseases. However, the precise effects and mechanisms of bisphosphonates on osteoclastogenesis are unclear, as previous studies have reported contradictory findings and no studies have circumstantially assessed the effects of bisphosphonates on osteoclastogenesis. Therefore, the aim of this study was to determine the effects of bisphosphonates on osteoclastogenesis in RAW264.7 (RAW) cells. To examine the direct effects of bisphosphonates on osteoclast differentiation via receptor activator of nuclear factor-κB (RANK) ligand (RANKL), RAW cells were cultured with bisphosphonates. Addition of bisphosphonates to RAW cells led to a significant decrease in the number of osteoclasts and large osteoclasts (≥ 8 nuclei) in a bisphosphonate concentration-dependent and time-dependent manner. The cytotoxicity of non-nitrogen-containing bisphosphonates was specific to osteoclasts, while nitrogen-containing bisphosphonates were cytotoxic and induced cell death in both osteoclasts and RAW cells. Resorption activity was significantly diminished by treatment with bisphosphonates, thus confirming that bisphosphonates impair the absorptive activity of osteoclasts. We also investigated the effects of bisphosphonates on the mRNA expression of genes associated with osteoclastogenesis, osteoclast-specific markers and apoptosis-related genes using quantitative real-time PCR. The results suggest that bisphosphonates suppress osteoclast differentiation and infusion, and induce osteoclast apoptosis. With regard to osteoclast apoptosis induced by bisphosphonates, we further investigated the detection of DNA fragmentation and Caspase-Glo 3/7 assay. DNA fragmentation was confirmed after treatment with bisphosphonates, while caspase-3/7 activity increased significantly when compared with controls. In conclusion, bisphosphonates directly inhibited RANKL-stimulated osteoclast differentiation and fusion in RAW cells. It was confirmed that bisphosphonates impair osteoclast resorption activity and induce apoptosis. The effects of non-nitrogen-containing bisphosphonates were also specific to osteoclasts, while nitrogen-containing bisphosphonates were cytotoxic and induced cell death in both osteoclasts and RAW cells.

Radioresistance in Oral Squamous Cell Carcinoma With p 53 DNA Contact Mutation

Reliable variables to predict the radiosensitivity of each tumor have not been identified. Recent studies have demonstrated that specific regions of mutations within the core domain of p53 protein correlate with responses to chemotherapy and radiotherapy in some tumor types. In this study, we evaluated the relationship between specific p 53 mutations and radiosensitivity in 49 patients with oral squamous cell carcinomas (SCCs) who underwent preoperative radiotherapy. Exons 5 through 8 of the p 53 gene were examined by polymerase chain reaction-single-strand conformation polymorphism and direct sequencing. We detected p 53 mutations in 27 (55.1%) cases. DNA contact mutations were detected in 11 (40.7%) of these 27 cases in L3 loop, loop-sheet-helix motif, and zinc-binding residues. Tumors containing p 53 DNA contact mutations had significantly poorer responses to radiation than the other tumors, although no statistically significant difference between tumors with and without p 53 mutations was found. These data indicate that DNA contact mutation of p 53 could be a useful marker to predict the radioresistance of oral SCCs.

Relationships between perceived chewing ability and muscle strength of the body among the elderly

The aim of the present study was to elucidate whether self-assessed masticatory ability (masticatory ability) is significantly related to muscle strength of the body evaluated as handgrip strength and skeletal muscle mass of the whole body (kg) (SMM) after adjusting for confounding variables, including, age, gender, height, weight, employment status, type of household, educational background, social interaction, chronic medical conditions, smoking habit, drinking habits and dentition status among the elderly. A total of 381 persons aged 67-74 years were enrolled. Masticatory ability was classified into one of three categories: ability to chew all kinds of food, ability to chew only slightly hard food or ability to chew only soft or pureed food. Handgrip strength was measured, and bioimpedance analysis was used to estimate SMM. One-way analysis of variance and Bonferroni methods were used to examine differences in handgrip strength and SMM among the three groups of masticatory ability. An ordinal regression model was conducted with masticatory ability as the dependent variable and handgrip strength as the principal independent variable. Handgrip strength was significantly lower in those individuals who could chew only soft or pureed food than in those individuals who could chew all kinds of food. No significant difference in SMM was found among the three groups of masticatory ability. Masticatory ability was significantly related to handgrip strength after adjusting for SMM, dentition status and background factors. Chewing ability may be related to muscle strength of the body evaluated as handgrip strength, but not evaluated as SMM.

Gene expression profile changes correlated with lymph node metastasis in oral squamous cell carcinoma

The purpose of this research was to identify biomarkers for predicting cervical lymph node metastasis in oral squamous cell carcinoma (OSCC). We surveyed the expressions of 1289 cancer-related genes in 41 cases of OSCC by cDNA array analysis. We extracted genes upregulated or downregulated in their expression in association with lymph node metastasis. Of 1289 cancer-related genes, we identified 39 genes differentially expressed in OSCC with or without lymph node metastasis. Expression levels of 9 genes were lower, and those of 30 genes were higher, in node-positive cases. The genes expressed at higher levels in node-positive cases included angiogenesis-related molecules, cell adhesion molecules, and proteolytic enzymes. We suggest that these characteristic genes could provide, if verifiable, useful information for predicting the risk of lymph node metastasis in OSCC.

Associations between self-assessed masticatory ability and higher brain function among the elderly.

Among the elderly, the quality of higher brain function is a contributing factor in performing activities of daily living. The aim of the study is to elucidate, epidemiologically, associations between mastication and higher brain function. A total of 208 community-dwelling elderly persons, aged 70-74 years, were enrolled. Self-assessed masticatory ability (masticatory ability) was classified into one of three categories: ability to chew all kinds of food, ability to chew only slightly hard food, or ability to chew only soft or pureed food. Brain function was assessed by four neuropsychological tests: Ravens Colored Progressive Matrices (RCPM) test, the Verbal Paired Associates 1 (VerPA) task and the Visual Paired Associates 1 task (from the Wechsler Memory Scale Revised Edition), and the Block Design subtest (from the Wechsler Adult Intelligence Scales-Third Edition). Correlations between masticatory ability and each test were examined using Spearman rank correlation coefficients. Multinominal logistic regression models were conducted with the neuropsychological tests as the dependent variables and masticatory ability as the principal independent variable to adjust for age, gender, educational background, social activity, drinking/smoking habits, chronic medical conditions and dental status. Significant correlations were found between the RCPM test, the VerPA task, the Block Design test and masticatory ability. In multinominal logistic regression models, poor masticatory ability was significantly and independently related to the categories under the mean-s.d. points compared with those of the mean ± s.d. ranges for RCPM test and the VerPA task. Significant associations may exist between mastication and higher brain function among the elderly.

Self-assessed masticatory ability and hospitalisation costs among the elderly living independently.

The escalating medical costs are a social problem in many countries. Masticatory ability is thought to be related to the general health conditions. The purpose of this study was to show relationships between self-assessed masticatory ability and medical costs among the elderly living independently in community. Data on background factors and self-assessed masticatory ability were collected from 702 Japanese elderly persons by questionnaires. An intra-oral examination was performed to examine the number of remaining teeth. Self-assessed masticatory ability was classified into one of three categories: ability to chew all kinds of food (Good), ability to chew only slightly hard food (Fair) or ability to chew only soft or pureed food (Poor). Data on the annual medical excluding dental costs were obtained from the Japanese National Health Insurance system. The Kruskal-Wallis test was used to examine differences in outpatient costs and hospitalisation costs among the three groups of self-assessed masticatory ability. Univariate unconditional logistic regression models and multivariate logistic regression models were used with medical costs as the dependent variable and self-assessed masticatory ability as the principal independent variable. A significant difference (P=0·039) in hospitalisation costs but not outpatient costs was found among the three groups of self-assessed masticatory ability. The multivariate logistic regression analysis showed that severely impaired masticatory ability (Poor) was significantly related to higher costs of hospitalisation. Self-assessed impairment of masticatory ability may be a significant and independent indicator of higher costs of hospitalisation among community-dwelling elderly persons.

SELF-ASSESSED IMPAIRMENT OF MASTICATORY ABILITY AND LOWER SERUM ALBUMIN LEVELS AMONG COMMUNITY-DWELLING ELDERLY PERSONS

SUMMARY Background: Serum albumin is considered a key nutrient that is significantly related to general health among elderly persons. The aim of the present study was to determine the relationship between masticatory ability and serum albumin levels in the elderly. Methods: A total of 768 persons were enrolled in the study. Data on background factors and the self-assessed masticatory ability were collected by means of questionnaires. An intraoral examination was performed to examine the pattern of occluding pairs of natural teeth, and blood samples were collected from the cutaneous vein to measure serum albumin levels. A forward stepwise multivariate logistic model was constructed with serum albumin levels as the dependent variable and the self-assessed masticatory ability as the principal independent variable, to adjust for potential confounding variables. Results: Sex, current employment status, social interaction, and self-assessed masticatory ability were retained in the final model, and they were significantly associated with serum albumin levels. The odds ratios for lower levels of serum albumin (≤ 40 g/L) were 1.88 for males, 1.70 for non-working status, 1.55 for low social activity status, and 1.43 for the self-assessed impairment of masticatory ability. Conclusion: A weak, statistically significant relationship may exist between self-assessed impairment of masticatory ability and lower levels of serum albumin in the elderly living independently. [International Journal of Gerontology 2010; 4(2): 89–95]