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author:("Oka, miki")
1.  Histological comparison between preoperative and surgical specimens of non-small cell lung cancer for distinguishing between "squamous" and "non-squamous" cell carcinoma 
Diagnostic Pathology  2014;9:103.
Non-small cell lung cancers (NSCLCs) are frequently heterogeneous and in approximately 70% of cases, NSCLCs are diagnosed and staged by small biopsies or cytology rather than by examination of surgically resected specimens. Thus, in most patients, the diagnosis is established based on examination of preoperative specimens alone. Recently, classification of NSCLC into pathologic subtypes has been shown to be important for selecting the appropriate systemic therapy, from both the point of view of treatment efficacy and prevention of toxicity.
We retrospectively reviewed the data of 225 patients to compare the preoperative classification of the NSCLC subtype on biopsy specimens with the postoperative classification based on examination of the resected specimens, in order to compare the accuracy of the two for the diagnosis of various histological subtypes of NSCLC.
In 169 of the 225 (75.1%) patients, the preoperative diagnosis was definite malignancy. Histologically, the final pathologic diagnosis made from the surgical specimens was adenocarcinoma (ADC) in 169 patients, and in 75.5% of these cases, the diagnosis was concordant with the preoperative diagnosis. Among the patients who had squamous cell carcinoma (SQC) in the preoperative specimens, the diagnosis was concordant with the preoperative diagnosis in 65.7% of cases. Misclassified preoperative biopsies included an even number of SQCs and ADCs, with all the misclassified biopsies being ADCs morphologically mimicking SQC due to solid growth. Significantly higher specificity, negative predictive value and accuracy were observed for the diagnosis of SQC.
Our study suggested that the concordance rates for diagnosis of the NSCLC subtypes, especially the "squamous" or "non-squamous" histologies, between preoperative and surgical specimens were satisfactory, as compared with previous reports. Therefore, pretreatment diagnosis of lung cancer using small samples is reasonable for selecting the optimal treatment. However, in order not to lose the opportunity for selecting an effective treatment, we should be aware that the diagnosis in preoperative small samples might be different from that based on examination of the surgical specimens.
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PMCID: PMC4099154  PMID: 24885169
2.  Nutritional deficits in elderly smokers with respiratory symptoms that do not fulfill the criteria for COPD 
Background and objective
Whereas nutrition deficits are recognized as an expression of systemic inflammation in the elderly with diagnosed chronic obstructive pulmonary disease (COPD), if they occur in symptomatic elderly smokers, unfulfilled COPD criteria are not confirmed.
Respiratory function, anthropometry assessment, and diet intake evaluation of 13 COPD patients (COPD group), ten symptomatic elderly smokers (SYSM group), and 27 healthy volunteers (control group) were compared. All were 70 years old or older.
The SYSM group had lower body weight, body mass index, percentage ideal body weight, body fat percentage, arm muscle circumference, tricep skin fold thickness, serum albumin, prealbumin, and transferrin than the control group and were similar to the COPD group (P < 0.05 each and nonsignificant each). Resting energy expenditure was no different among the groups. Intake of energy, vitamins (A, B1, B2, and C), calcium, iron, fiber, and sodium was also lower in the SYSM group than in the control group (P < 0.05 all) and was similar to the COPD group.
Elderly smokers who are symptomatic but who do not fulfill the COPD diagnostic criteria have nutritional deficits related to insufficient energy intake that are similar to those seen in COPD patients.
PMCID: PMC3257953  PMID: 22259244
chronic obstructive pulmonary disease (COPD); nutritional status; body composition; resting energy expenditure (REE)
3.  Comparison of T-Cell Interferon-γ Release Assays for Mycobacterium tuberculosis-Specific Antigens in Patients with Active and Latent Tuberculosis 
Lung  2010;188(4):283-287.
Through the use of QuantiFERON-TB Gold, a commercial IFN-γ assay, we compared differences in quantitative T-cell responses to Mycobacterium tuberculosis (MTB)-specific antigens [QuantiFERON TB-2G (QFT-2G)] between patients with active tuberculosis (TB) disease and those with latent TB infection (LTBI). The patient group consisted of 180 patients with active TB disease (culture-positive for MTB) and 50 screening contacts with LTBI-positive response to the QFT-2G test. We prospectively performed a tuberculin skin test (TST) and a QFT-2G test for all subjects. The median IFN-γ levels upon the application of both antigens, ESAT-6 and CFP-10, were significantly higher in patients with active TB disease than in those with LTBI. A combined positive response to both antigens occurred at a higher rate in patients with active TB disease than in those with LTBI. There were no significant relationships between the quantitative responses of IFN-γ to both antigens and the maximum induration on TST in both patient groups. We demonstrated significant differences in the quantitative responses of IFN-γ to MTB between patients with active TB disease and those with LTBI in this study. However, there was an overlap in the IFN-γ levels between active TB disease and LTBI groups. Therefore, it would be difficult to use the QFT-2G test to completely discriminate active TB disease from LTBI.
PMCID: PMC2899021  PMID: 20422203
Active tuberculosis (TB) disease; Latent tuberculosis infection (LTBI); Tuberculin skin test (TST); QuantiFERON TB-2G (QFT-2G)
4.  Radiographic features of Mycoplasma pneumoniae pneumonia: differential diagnosis and performance timing 
The Japanese Respiratory Society guidelines propose a differential diagnosis for atypical pneumonia and bacterial pneumonia using a scoring system for the selection of appropriate antibiotic. In order to improve this scoring system, the guidelines are seeking new specific parameter. The purpose of this study was to clarify the pattern of abnormalities with Mycoplasma pneumoniae pneumonia on chest computed tomography (CT) and whether the radiographic findings could distinguish M. pneumoniae pneumonia from Streptococcus pneumoniae pneumonia.
A retrospective review was performed of the CT findings of 64 cases and 68 cases where M. pneumoniae and S. pneumoniae, respectively, were the only pathogen identified by the panel of diagnostic tests used.
Of the 64 patients with M. pneumoniae pneumonia, bronchial wall thickening was observed most frequently (81%), followed by centrilobular nodules (78%), ground-glass attenuation (78%), and consolidation (61%). Bronchial wall thickening and centrilobular nodules were observed more often in M. pneumoniae patients than in S. pneumoniae patients (p < 0.0001). The presence of bilateral bronchial wall thickening or centrilobular nodules was only seen in patients with M. pneumoniae pneumonia. Using the scoring system of the Japanese Respiratory Society guidelines and chest CT findings, 97% of M. pneumoniae patients were suspected to be M. pneumoniae pneumonia without serology. When comparing the CT findings between early stage and progressed stage in the same patients with severe pneumonia, the radiographic features of early stage M. pneumoniae pneumonia were not observed clearly in the progressed stage.
The present results indicate that the diagnosis of M. pneumoniae pneumonia would appear to be reliable when found with a combination of bronchial wall thickening and centrilobular nodules in the CT findings. However, these CT findings are not observed in progressed severe M. pneumoniae pneumonia patients.
PMCID: PMC2680832  PMID: 19400968
5.  Rapid and Simple Diagnosis of Chlamydophila pneumoniae Pneumonia by an Immunochromatographic Test for Detection of Immunoglobulin M Antibodies▿  
To evaluate a newly developed immunochromatographic test (the MySet test) for the detection of Chlamydophila pneumoniae-specific immunoglobulin M antibodies, the results obtained by the MySet test were compared with those obtained by two serological tests. The sensitivity and specificity of the MySet test were 100% and 92.9%, respectively. The MySet test is rapid and simple to use and is thought to be a useful tool for the selection of appropriate antibiotic therapy.
PMCID: PMC2446634  PMID: 18480232
6.  Effects of Renal Function on Pharmacokinetics of Recombinant Human Granulocyte Colony-Stimulating Factor in Lung Cancer Patients 
Animal studies suggest that the kidney is involved in the elimination of recombinant human granulocyte colony-stimulating factor (rhG-CSF), which is used for patients with neutropenia during cancer chemotherapy. Since anticancer drugs induce nephrotoxicity, it is important to clarify the role of the kidney in the pharmacokinetics of rhG-CSF in cancer patients. Our study was designed to evaluate the relationship between the pharmacokinetics of rhG-CSF and renal function in lung cancer patients compared to the absolute neutrophil count (ANC). The pharmacokinetic studies were conducted with 25 lung cancer patients. Following chemotherapy using platinum-based compounds, a bolus 5 μg of rhG-CSF/kg of body weight was intravenously injected from the first day of leukopenia or neutropenia. Pharmacokinetic parameters were estimated by fitting the concentration in serum-time data to a two-compartment model according to the population pharmacokinetics and the Bayesian method. Creatinine clearance (CLCR) was predicted by the Cockcroft-Gault formula. rhG-CSF clearance (CLG-CSF) correlated significantly with the ANC (r = 0.613; P < 0.001) and CLCR (r = 0.632; P < 0.001). Multiple linear regression analysis showed that the combination of the ANC and CLCR accounted for 57.4% of the variation of CLG-CSF. In patients with an ANC of <1,000/μl, CLCR accounted for 72.9% of the variation of CLG-CSF (P < 0.001). Our findings suggest that renal function and neutrophil counts correlate with CLG-CSF and that the role of renal function in eliminating rhG-CSF is important in lung cancer patients with neutropenia.
PMCID: PMC90583  PMID: 11408206
7.  Interactions of Ofloxacin and Erythromycin with the Multidrug Resistance Protein (MRP) in MRP-Overexpressing Human Leukemia Cells 
To investigate interactions between the multidrug resistance protein (MRP) and antimicrobial agents, we examined the effects of 12 agents on vincristine sensitivity and efflux of the calcein acetoxy-methyl ester (calcein-AM) of a MRP substrate in MRP-overexpressing cells. Only ofloxacin and erythromycin enhanced sensitivity with increased intracellular vincristine accumulation and inhibited the calcein-AM efflux. Our findings suggest that the two agents are possible MRP substrates and may competitively inhibit MRP function as a drug efflux pump.
PMCID: PMC89936  PMID: 10817732
8.  Close Association between Clearance of Recombinant Human Granulocyte Colony-Stimulating Factor (G-CSF) and G-CSF Receptor on Neutrophils in Cancer Patients 
Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is used to counter chemotherapy-induced neutropenia. Our previous study showed an inverse correlation between serum rhG-CSF levels and the number of circulating neutrophils in cancer patients (H. Takatani, H. Soda, M. Fukuda, M. Watanabe, A. Kinoshita, T. Nakamura, and M. Oka, Antimicrob. Agents Chemother. 40:988–991, 1996). The aim of this study was to clarify the relationship between rhG-CSF clearance and G-CSF receptors on circulating neutrophils. In five cancer patients receiving chemotherapy, a bolus dose of rhG-CSF (5 μg/kg) was injected intravenously during defined phases of posttreatment neutropenia and neutrophilia. Serum rhG-CSF levels were measured by a chemiluminescence enzyme immunoassay and analyzed by moment analysis. G-CSF receptors on neutrophils were detected by flow cytometry with biotinylated rhG-CSF. rhG-CSF clearance was significantly higher at neutrophilia than at neutropenia (1,497 ± 132 versus 995 ± 266 ml/h; P < 0.01). The percentage of G-CSF receptor-positive neutrophils, reflecting the number of G-CSF receptors per cell, was low at neutropenia without rhG-CSF therapy (44.5% ± 22.1%) and high at neutrophilia with rhG-CSF therapy (73.0% ± 11.4%; P < 0.01). rhG-CSF clearance closely correlated with the percentage of G-CSF receptor-positive neutrophils (r2 = 0.91; P < 0.0001) and neutrophil count (r2 = 0.72; P < 0.005). Our results indicate that, in cancer patients receiving chemotherapy, rhG-CSF increases the number of G-CSF receptors per cell as well as circulating neutrophil counts, resulting in modulation of its own clearance.
PMCID: PMC89014  PMID: 9869559

Results 1-8 (8)