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Biomedical subjects

K Akazawa

Publications and source records attributed to K Akazawa.

At least 19 recordsLinked to original sources

Number of positive lymph nodes independently affects long-term survival after resection in patients with ampullary carcinoma.

AIM: The nodal status is an established prognostic factor in ampullary carcinoma. The aim of this study was to compare the prognostic power of the anatomic location of positive nodes with that of the number of positive nodes. METHODS: Of 73 consecutive patients treated for ampullary carcinoma, 62 underwent pancreaticoduodenectomy with regional lymphadenectomy. A survival analysis of these 62 patients by nodal status was conducted retrospectively. A total of 1942 lymph nodes taken from the patients were examined histologically for metastasis. The location of positive regional nodes was classified into 4 categories, according to the Japanese staging system. The number of positive regional nodes was recorded for each patient. The median follow-up period was 124 months. RESULTS: Nodal disease was found in 31 patients, of whom 23 had 1-3 positive regional nodes and 8 had >or=4 positive regional nodes. Univariate analysis revealed that both the location (p<0.0001) and the number (p<0.0001) of positive nodes were significant prognostic factors. Multivariate analysis revealed that the number of positive nodes was an independent prognostic factor (p=0.007), while the location failed to remain as an independent variable. The median survival time was 59 months with a 5-year survival rate of 48% in patients with 1-3 positive nodes, whereas all patients with >or=4 positive nodes died of the disease within 29 months of resection (p=0.0001). CONCLUSION: The number, not the location, of positive regional lymph nodes independently affects long-term survival after resection in patients with ampullary carcinoma.

Adult↗

MYCN gene amplification is a powerful prognostic factor even in infantile neuroblastoma detected by mass screening.

MYCN is the most powerful prognostic factor in cases of older children. However, how MYCN is related to the prognosis of infantile cases is not clear. A mass screening program was carried out by measuring urinary catecholamine metabolites (VMA and HVA) from 6-month-old infants. Of 2084 cases detected by the screening program, MYCN amplification (MNA) was examined by Southern blot analyses in 1533 cases from 1987 to 2000. Of the 1533 cases examined, 1500 (97.8%) showed no MNA, 20 cases (1.3%) showed MNA from three to nine copies, and 13 (0.8%) cases showed more than 10 copies. The 4-year overall survival rates of these three groups (99, 89 and 53%, respectively) were significantly different (P<0.001), indicating that MYCN copy number correlates with the prognosis. Cases with MNA more than 10 copies were more advanced than those without amplification (stage III, IV vs I, II, IVs; P<0.001). Patients with MNA more than 10 copies had significantly higher serum levels of neuron-specific-enolase (NSE) and ferritin than non-amplified patients (P=0.049, P=0.025, respectively). MYCN amplification was strongly correlated with a poor prognosis in infantile neuroblastoma cases. Therefore, for the selection of appropriate treatment, an accurate determination of MNA is indispensable.

Biomarkers, Tumor↗

Etiology and prognostic significance of severe uremic pruritus in chronic hemodialysis patients.

Although uremia is well known as the most common cause of pruritus, the mechanisms of pruritus in chronic hemodialysis patients remain unclear. The purpose was to characterize uremic pruritus in more detail and to investigate whether severe pruritus is a marker for poor prognosis. A total of 1773 adult hemodialysis patients were studied. A questionnaire was given to each patient to assess the intensity and frequency, as well as pruritus-related sleep disturbance. We analyzed the relationship between clinical and laboratory data and the severity of pruritus in hemodialysis patients and followed them for 24 months prospectively. In total, 453 patients had severe pruritus with a visual analogue scale (VAS) score more than or equal to 7.0. Among them, more than 70% complained of sleep disturbance, whereas the majority of patients with a VAS score of less than 7.0 had no sleep disturbance. Male gender, high levels of blood urea nitrogen, beta2-microglobulin (beta2MG), hypercalcemia, and hyperphosphatemia were identified as independent risk factors for the development of severe pruritus, whereas a low level of calcium and intact-parathyroid hormone were associated with reduced risk. During the follow-up, 171 (9.64%) patients died. The prognosis of patients with severe pruritus was significantly worse than the others. Moreover, severe pruritus was independently associated with death even after adjusting for other clinical factors including diabetes mellitus, age, beta2MG, and albumin. Severe uremic pruritus caused by multiple factors, not only affects the quality of life but may also be associated with poor outcome in chronic hemodialysis patients.

Aged↗

A modified method of activity-based costing for objectively reducing cost drivers in hospitals.

OBJECTIVES: Activity-based costing (ABC) is widely used to precisely allocate indirect costs to medical services. In the ABC method, the indirect cost is divided among the medical services in proportion to the volume of "cost drivers", for example, labor hours and the number of hours of surgery. However, the workload of data collection of cost drivers can be time-consuming and a considerable burden if there are many cost drivers. The authors aim to develop a method for objectively reducing the cost drivers used in the ABC method. METHODS: In the ABC method, the cost driver is assigned for each activity. We assume that these activities and cost drivers are the best combination. Our method, that is cost driver reduction (CDR), can objectively select surrogates of the cost drivers for each activity in ABC from candidate cost drivers. Concretely, the total indirect cost of an activity is temporarily allocated to the medical services using each candidate of cost drivers. The difference between the costs calculated by each candidate and the proper cost driver used in ABC is calculated to evaluate the similarity by the evaluation function. RESULTS: We estimated the cost of laboratory tests using our method and revealed that the number of cost drivers could be reduced from seven in the ABC to four. Similarly, the results of cost estimation obtained by our method were as accurate as those calculated using the ABC. CONCLUSIONS: Our method provides two advantages compared to the ABC method: 1) it provides results that are as accurate as those of the ABC method, and 2) it is simpler to perform complicated estimation of hospital costs.

Accounting↗

Clinical significance of mucin phenotype, beta-catenin and matrix metalloproteinase 7 in early undifferentiated gastric carcinoma.

BACKGROUND: The aim of this study was to examine the clinical significance of mucin phenotypes of early undifferentiated gastric carcinoma, and to identify variables that might be used to select patients suitable for minimally invasive surgery. METHODS: A total of 129 patients with early undifferentiated gastric carcinoma were studied. The mucin phenotype was determined immunohistochemically using markers for M1, apomucin (MUC) 6 and MUC2. Tumours were classified into gastric (G), intestinal, gastrointestinal (GI) or unclassified type. Undifferentiated carcinomas were classified into signet-ring cell carcinoma (SIG) and non-SIG. The immunoreactivity of matrix metalloproteinase (MMP) 7 and beta-catenin was also investigated. RESULTS: GI-type tumours more commonly expressed non-SIG than SIG histology. The GI phenotype was associated with a higher incidence of submucosal invasion, lymphatic invasion, MMP-7 expression and nuclear accumulation of beta-catenin than the G type. Non-SIG histology, and the combination of GI type and nuclear accumulation of beta-catenin were independent predictors of submucosal invasion. The combination of GI type and MMP-7 expression independently predicted lymphatic invasion. MMP-7 expression correlated with lymph node metastasis. CONCLUSION: GI-type early undifferentiated carcinomas and those with non-SIG histology had increased potential for invasion and metastasis. GI type, MMP-7 expression and nuclear accumulation of beta-catenin might prove useful markers in the selection of patients for less invasive surgery.

Cytoskeletal Proteins↗

Interleukin-6 (IL-6)--373 A9T11 allele is associated with reduced susceptibility to chronic periodontitis in Japanese subjects and decreased serum IL-6 level.

We investigated whether interleukin-6 (IL-6) gene polymorphisms could be associated with chronic periodontitis (CP) and serum IL-6 level. One hundred and twelve CP and 77 non-CP Japanese subjects were analyzed for IL-6 -597 (G/A), -572 (C/G), -373 (A(n)T(m)), -190 (C/T), and -174 (G/C) polymorphisms. We could only detect -572 and -373 polymorphisms and found that the frequency and carriage rate of the -373 A9T11 allele were significantly higher in non-CP subjects. Enzyme-linked immunosorbent assay confirmed that the -572 and -373 G[A9T11] haplotypes were associated with lower serum IL-6 level. These findings suggest that IL-6 -373 A9T11 allele could be associated with reduced susceptibility to CP among Japanese subjects and decreased serum IL-6 level.

Alleles↗

Polymorphisms in the IL-6 receptor (IL-6R) gene: strong evidence that serum levels of soluble IL-6R are genetically influenced.

We have investigated the association of the recently identified IL6R polymorphisms with the serum levels of soluble IL-6 receptor (sIL-6R). sIL-6R is generated by shedding of the membrane-bound receptor (IL-6Ralpha) or alternative mRNA splicing. In total, 115 healthy volunteers were genotyped, with 70 of them analyzed for sIL-6R levels. Using the PCR/RFLP methods, two important polymorphic sites were selected for genotyping: the 48892A/C (D358A) in exon 9 and the -183G/A in the promoter region. In exon 9, C allele carriers had higher sIL-6R level (P<0.0001) showing that this sequence variation, which corresponds to the proteolytic cleavage site of IL-6Ralpha, strongly influences the serum sIL-6R levels. In the promoter region, G allele carriers had lower sIL-6R levels (P<0.0082) compared with the A allele carriers. This could be attributed to the linkage disequilibrium (D'=0.54, chi2=51.3, P<0.0001) between the -183G/A and the 48892A/C gene polymorphisms.

Adult↗

Association between RCAS1 expression and clinical outcome in uterine endometrial cancer.

RCAS1, which acts as a ligand for a putative receptor on immune cells such as peripheral lymphocytes and natural killer cells, is strongly expressed in human cancers. RCAS1 can induce these cells to undergo apoptotic cell death, which suggests that RCAS1 expression may prohibit the stromal reaction occurring in a tumour. To clarify the clinical significance of RCAS1 expression in uterine endometrial cancer, we analysed the association between RCAS1 expression and clinicopathologic variables by statistical methods. With the use of immunohistochemical techniques, we performed a retrospective study of RCAS1 expression in resected tumour tissue from 147 patients with uterine endometrial cancer. We evaluated the statistical correlation between RCAS1 expression and clinicopathologic variables. RCAS1 was expressed in 106 of 147 patients with uterine endometrial cancer; 30 of these 147 patients showed RCAS1 overexpression. Overexpression of RCAS1 was significantly correlated with age at surgery, stage, extent of myometrial invasion, and positive peritoneal cytologic results. Multivariate analysis revealed that RCAS1 expression and metastasis were clinically significant prognostic factors for the overall survival. These findings indicated that analysis for RCAS1 expression can provide crucial information about the clinical behaviour of uterine endometrial cancer, which may be valuable for the management of patients with this disease.

Adult↗

Loss of motility-related protein 1 (MRP1/CD9) and integrin alpha3 expression in endometrial cancers.

BACKGROUND: MRP1/CD9 and integrin alpha3 have played crucial roles in cell adhesion, motility, and signaling events. The loss of MRP1/CD9 and integrin alpha3 has been involved in tumor growth and metastasis of cancer cells. The aim of the current study was to clarify the clinical significance of MRP1/CD9 and integrin alpha3 in endometrial cancer. METHODS: The expression of MRP1/CD9 and integrin alpha3 from the same tissue sample were examined immunohistochemically in 15 patients with normal endometrium and in 56 patients with uterine endometrioid adenocarcinoma. Disease-free survival curves were estimated using the Kaplan-Meier method and analyzed by the log-rank test between the positive and reduced expression statuses of both MRP1/CD9 and integrin alpha3. These expressions and clinicopathologic variables were analyzed univariately and multivariately. RESULTS: In normal endometrium, MRP/CD9 was expressed at the cell membrane of cell contact sites, and the expression of integrin alpha3 was detected also at the cell membrane of cell contact sites and at borders of stromal tissues. In patients with endometrioid adenocarcinoma, 17 cases showed reduced expression of MRP1/CD9, and 20 cases had reduced expression of integrin alpha3. Fourteen cases indicated a reduced expression of both MRP1/CD9 and integrin alpha3. Each reduced expression of MRP1/CD9 or integrin alpha3 was significantly correlated with histologic grade and metastasis. Multivariate analysis using the Cox regression model disclosed that age at surgery, metastasis, and expression status of MRP1/CD9 were significant prognostic factors for disease-free survival. CONCLUSIONS: These findings suggested that the analysis for the expression statuses of MRP1/CD9 and integrin alpha3 may provide important information on the clinical behavior of endometrial cancer.

Antigens, CD↗

A simple computerized program for the calculation of the required sample size necessary to ensure statistical accuracy in medical experiments.

We developed a sample size estimation program (SSEP) with which medical researchers can easily estimate the appropriate sample size for a specific significance level and statistical power using their favorite WWW browsers. SSEP can estimate the sample sizes for six statistical methods by Monte-Carlo simulation: Student's t-test, Welch's t-test, Analysis of variance, Wilcoxon's rank sum test, Kruskal-Wallis test, and the Cochran-Armitage test for linear trends. The SSEP simulation programs were created using the SAS software macro language. Medical researchers can interactively use this program and determine reliable sample sizes when planning new prospective clinical studies and animal experiments.

Computer Simulation↗

Sarcomere lengths of thick skeletal muscle specimens measured under an epi-illumination-type polarization microscope.

The purpose of this study was to measure sarcomere lengths of thick muscle fiber bundles at resting and at isometric tetanic contractions. We developed a novel measurement system using an epi-illumination-type polarization microscope and an image processing algorithm using an ellipse-type Gabor filter. Images with striation patterns of frog skeletal muscle were obtained by the microscope and the image processing algorithm. Individual lengths of 10 consecutive sarcomeres of a single muscle fiber were measured by gauging each width of the striation pattern, which was proved to be derived from striation structures of the single fiber by performing experiments using different polarization lights and different focus depths. At the resting state, each sarcomere length was identical at the fixed muscle length and in proportion to the length ranging over 91-123% of the natural length. Each sarcomere length was unchanged at the steady state during isometric tetanic contractions. Individual sarcomere lengths in the central part of the skeletal muscle were identical at resting and at isometric tetanic contractions even in the thick muscle fiber specimen.

Algorithms↗

The impact of covariate imbalance on the size of the logrank test in randomized clinical trials.

This paper examines the baseline imbalance incidental to stratified random sampling in clinical trials. We assume that patients are randomly sampled from a stratum-specific population and assigned to either treatment or control groups. Prognostic factors not used for the stratification cause within-stratum patient heterogeneity. The patient heterogeneity is investigated with an analysis of the prognostic index, or the log-relative-hazard. An index V, used to measure the degree of baseline imbalance between the groups, is defined using the prognostic index. The degree of baseline imbalance resulting from the stratified random sampling of a population of heterogeneous patients is examined. A method to estimate the exact size of the stratified logrank test is developed and applied to data obtained from a cancer clinical trial.

Adult↗

Changes in biological characteristics during the cellular aging of ligament fibroblasts derived from patients with prolapsus uteri.

Prolapsus uteri in pelvic support disorders are common in elderly women. The etiology is unclear and more likely to be multifactorial. We examined changes in biological characteristics and responsiveness to growth factors during the in vitro cellular aging of cardinal ligamental fibroblasts derived from patients with prolapsus uteri (HPLiF), and compared them with those of cells from age-matched control subjects (HCLiF). HPLiF and HCLiF had almost the same in vitro life span and the age-related patterns of biological parameters were essentially the same. However, the saturation density was significantly higher in HPLiF than in HCLiF. Furthermore, the high proliferative activity of HPLiF to serum mitogens, especially to platelet-derived growth factor, was retained throughout the in vitro life span. p53 protein levels in HPLiF increased at late passages, but were significantly less than in aged HCLiF. These results indicate that the higher proliferative activity in prolapsus fibroblasts may result from the decreased expression of p53 protein and may lead to a decrease in the synthesis and deposition of extracellular matrix components. These results support the hypothesis that functional alterations in ligament fibroblasts are involved in the mechanism of the development of prolapsus uteri.

Aged↗

High dose chemotherapy as adjuvant treatment in operable breast cancer with 10 or more involved axillary lymph nodes.

BACKGROUND: it is well known that breast cancer patients with more than 10 axillary lymph nodes involved have poor prognosis even with extensive adjuvant chemotherapy. To improve this poor outcome, high-dose adjuvant chemotherapy has been applied to the these patients. This study was intended to clarify the efficacy and usefulness of high dose adjuvant chemotherapy (HDC) for high-risk breast cancer patients and its efficacy was compared with conventional adjuvant chemotherapy (non-HDC group). PATIENTS AND METHODS: Twelve patients with breast cancer involving more than 10 axillary nodes received high-dose chemotherapy with peripheral progenitor-stem cell transplantation (PBSCT). This regimen consists of BCNU (carmustine) 130 mg/m(2) x 3, CBDCA (carboplantin) 500 mg/m(2) x 3 and CPA (chyclophosphamide) 50 mg/kgx 2 after induction chemotherapy with 3 cycles of CE (chyclophosphamide 600 mg/m(2), epirubicin 60 mg/m(2)). RESULTS: Twelve patients completed the high-dose chemotherapy regimen as planned, no patient died of chemotherapy related toxicity. After a median follow-up period of 44 months, disease-free and overall survival at 48 months after the operation for 12 patients determined by Kaplan-Meier methods was 63 % and 83 %, respectively. Disease-free survival was superior in the high-dose chemotherapy group compared with the control group but a statistical difference was not observed. CONCLUSION: High-dose chemotherapy seems to be an effective and feasible treatment for high-risk breast cancer patients. However, the usefulness of high-dose adjuvant chemotherapy for high-risk breast cancer patients should be confirmed by a large-scale randomized trial.

Adult↗

Serum vascular endothelial growth factor: a new predictive indicator for the occurrence of coronary artery lesions in Kawasaki disease.

UNLABELLED: We investigated serum vascular endothelial growth factor (SVEGF) levels in Kawasaki disease and determined whether these levels had any association with the development of coronary artery lesions. We measured SVEGF levels in 66 patients with Kawasaki disease, 18 patients with active infections and 18 afebrile controls. SVEGF levels of patients in the acute phase of Kawasaki disease (0.0-2003.6 pg/ml, median 59.87 pg/ml) were significantly higher than those of patients with active infections (0.0-45.2 pg/ml, median 8.10 pg/ml; P < 0.05) or afebrile controls (0.0-49.8 pg/ml, median 7.75 pg/ml; P < 0.05) and decreased to undetectable or low levels in the recovery phase (n = 31, acute phase: 0.0-2003.6 pg/ml, median 62.50 pg/ml versus recovery phase: 0.0-146.5 pg/ml, median 26.90 pg/ml; P = 0.0007) of the disease. There existed a positive correlation between SVEGF levels and serum C-reactive protein concentrations in the acute phase of Kawasaki disease (rs = 0.347, P = 0.0051). In addition, SVEGF level and duration of fever were found to be major risk factors for the occurrence of coronary artery lesions by univariate (P = 0.012 and P = 0.003, respectively) and multivariate (P = 0.037, OR 6.16 and P = 0.0059, OR 7.59, respectively) analyses. CONCLUSION: Serum vascular endothelial growth factor level, in combination with persistence of fever, could be a powerful predictor for the development of coronary aneurysms.

Biomarkers↗

Low cell binding ability of HCV is closely related to interferon treatment especially in patients with HCV genotype 2a/2b. A large series prospective study on Japanese patients with chronic hepatitis C.

BACKGROUND/AIMS: We have previously shown that the quantity of antibody-free virion in the pre-treatment sera of the patients with chronic hepatitis C is a good predictive factor for the efficacy of interferon treatment. However, the biological significance of the free virion should be verified by a prospective study. METHODS: We prospectively evaluated 152 consecutive patients with chronic hepatitis C who received a standardized interferon treatment, and analyzed the free virion and the binding titers, the ability of hepatitis C virus (HCV) to bind to the human lymphocytic cell line. RESULTS: Sixty-five patients achieved a long-term sustained remission, 76 patients did not respond to the interferon therapy, and 11 patients dropped out. The sera from the patients with genotype 2a/2b had significantly lower free virion and cell binding titers than those with genotype 1b. A multivariate analysis showed three independent variables associated with the interferon response; cell binding titer <10(0.5)/ml, viral load <10(4.5) copies/50 microl, and genotype 2a/2b with odds ratios of 14.6, 11.8, and 9.8, respectively. CONCLUSIONS: The low level of in vitro cell binding ability of HCV helped to clarify the good responsiveness to interferon observed in patients especially with a high viral load of genotype 2a/2b.

Adult↗