A case of cytokeratin 20-positive large-cell neuroendocrine carcinoma of the breast

We report a rare case of large-cell neuroendocrine carcinoma of the breast. A 63-year-old woman was admitted to our hospital with a firm mass in the right breast. Mammography revealed a high-density mass with specula, and ultrasonography showed a heterogeneous hypoechoic mass with irregular margin and posterior acoustical shadowing. She underwent breast-conserving surgery with axillary lymph node dissection. Histopathologically, the tumor consisted of large cells with polygonal and prominent nuclei and a small amount of eosinophilic cytoplasm, and these cells showed palisading arrangement with fibrous stroma. The tumor cells were positive for neuroendocrine markers such as NSE, synaptophysin, CD56 (NCAM), but not for chromogranin A. Interestingly, the tumor cells showed reactivity for cytokeratin 20 but not for cytokeratin 7. The immunostaining pattern is different from the usual adenocarcinoma of the breast. The patient received postoperative radiotherapy and was given adjuvant chemotherapy. She has remained disease-free for 44?months.     

New fluorimetric assay of horseradish peroxidase using sesamol as substrate and its application to EIA

Horseradish peroxidase (HRP) is generally used as a label enzyme in enzyme immunoassay (EIA). The procedure used for HRP detection in EIA is critical for sensitivity and precision. This paper describes a novel fluorimetric assay for horseradish peroxidase (HRP) using sesamol as substrate. The principle of the assay is as follow: sesamol (3,4-methylenedioxy phenol) is reacted enzymatically in the presence of hydrogen peroxide to produce dimeric sesamol. The dimer is fluorescent and can be detected sensitively at ex. 347 nm, em. 427 nm.The measurable range of HRP was 1.0×10^?18 to 1.0×10^?15 mol/assay, with a detection limit of 1.0×10^?18 mol/assay. The coefficient of variation (CV, n=8) was examined at each point on the standard curve, with a mean CV percentage of 3.8%. This assay system was applied to thyroid stimulating hormone (TSH) EIA using HRP as the label enzyme.     

Increase of serum CA19-9 level without an evident lesion on conventional imaging is insufficient for justification of 18FDG-PET examination

BACKGROUND/AIMS: The serum tumor marker carbohydrate associated antigen 19-9 (CA19-9) has been used for screening for cancer, because its increase has been associated with many cancers. We aimed to evaluate the clinical value of positron emission tomography using F-18 fluorodeoxyglucose (18FDG-PET) that was prompted by increases of serum CA19-9 without findings on conventional imaging. METHODOLOGY: Twenty-two patients were retrospectively selected. Eleven were without a history of cancer and eleven had a history of cancer and were treated with curative intent. All 18FDG-PET findings were compared with the findings of histopathology by surgery or biopsy, or clinical follow-up for at least 1 year. RESULTS: We found only two true positive cases, and eleven cases without a cancer history included 10 true negatives and one false positive. CONCLUSIONS: Increases in serum CA19-9 are caused by many benign conditions. Increases of CA19-9 without findings on conventional imaging do not justify 18FDG-PET examination, particularly in patients without a cancer history.     

Asian variant of CD5+ intravascular large B-cell lymphoma with splenic infarction

A 57-year-old man was admitted with fever and epigastralgia, and presented with splenomegaly and pancytopenia. A CT scan revealed splenic infarctions. There were no lymphadenopathies, skin lesions, or neurological abnormalities. A splenectomy was performed. Bone marrow involvement with hemophagocytosis was noted. The diagnosis of Asian variant of intravascular diffuse large B-cell lymphoma was based on intravascular and sinusoidal distribution of large CD5+ B cells. The patient died of the disease 11 months after onset. To our knowledge, this is the first report of AIVL that presented with splenic infarction. This distinct lymphoma should be included in the differential diagnosis of splenic infarction.     

Free-to-total leptin ratio in maternal plasma is constant throughout human pregnancy

To clarify the mechanism of leptin resistance during pregnancy, we measured plasma leptin concentrations, free to total leptin ratio (percent free leptin) and soluble leptin receptor concentrations in pregnant women, and compared the results with those in non-pregnant women. We collected plasma samples from 23 non-pregnant and 31 pregnant women in the third trimester. Plasma samples from 5 pregnant women were collected longitudinally in each trimester. Plasma leptin concentrations in pregnant women in the second trimester (17.4 +/- 3.2 ng/ml) were higher than those in the first trimester of pregnancy (11.0 +/- 2.8 ng/ml, n = 5), as previously reported. However, percent free leptin did not change significantly throughout pregnancy. Percent free leptin correlated with total leptin concentrations (ng/ml) in non-pregnant women (r = 0.727, P < 0.0001), but not in women in the third trimester of pregnancy (r = 0.006). Constant percent free leptin during pregnancy despite increased leptin concentrations indicates increased leptin binding capacity in pregnant women, that might partly contribute to the establishment of leptin resistance. On the other hand, soluble leptin receptor concentrations showed significant negative correlation with BMI and plasma leptin concentrations in pregnant women (r = -0.470, P < 0.01 and r = -0.493, P < 0.01, respectively) but not in non-pregnant women. These data suggest the possibility that soluble leptin receptor is a minor component of leptin binding capacity in the plasma of pregnant women.     

Survey to determine the efficacy and safety of guideline-based pharmacological therapy for chronic obstructive pulmonary disease patients not previously receiving maintenance treatment

Objective: To investigate the potential beneficial effects of guideline-based pharmacological therapy on pulmonary function and quality of life (QOL) in Japanese chronic obstructive pulmonary disease (COPD) patients without prior treatment.

Research design and methods: Multicenter survey, open-label study of 49 Japanese COPD patients aged ≥ 40 years; outpatients with >10 pack years of smoking history; ratio of forced expiratory volume in 1 s (FEV₁)/forced vital capacity (FVC) < 70%; predicted FEV₁ < 80%; treated with bronchodilators and/or inhaled corticosteroids as maintenance therapy until week 48.

Main outcome measures: The primary endpoint was change in pulmonary function (trough FEV₁, trough FVC); secondary endpoints were QOL and physical activity at 48 weeks after initiation of therapy.

Results: Airway reversibility was confirmed in untreated patients. Significant changes over time were not observed for FEV₁ and FVC, indicating lung function at initiation of treatment was maintained during the observation period. COPD assessment test scores showed statistical and clinical improvements. Cough, sputum, breathlessness, and shortness of breath were significantly improved.

Conclusions: Lung function and QOL of untreated Japanese COPD patients improved and improvements were maintained by performing a therapeutic intervention that conformed to published guidelines.     

Cigarette smoking augments sympathetic nerve activity in patients with coronary heart disease

It has been shown that cigarette smoking increases blood pressure (BP) and heart rate (HR), and decreases muscle sympathetic nerve activity (MSNA) in healthy young smokers. The decrease in MSNA might be secondary to baroreflex responses to the pressor effect. We tested the hypothesis that cigarette smoking increases MSNA in smokers with impaired baroreflex function. The effects of cigarette smoking on BP, HR, forearm blood flow (FBF), forearm vascular resistance (FVR), and MSNA were examined in 14 patients with stable effort angina (59+/-3 years, group CAD) and 10 healthy smokers (23+/-1 years, group C). In group CAD, the arterial baroreflex sensitivity (BRS) was significantly lower than in group C (4.7+/-0.8 versus 15.1+/-2.2 msec/mmHg, P<0.01). In both groups, cigarette smoking increased the plasma concentration of nicotine, systolic and diastolic BP, HR, and FVR significantly (P<0.01), but decreased FBF significantly (P<0.01). After smoking, MSNA was decreased significantly in group C (from 35.2+/-3.5 to 23.5+/-3.2 bursts/100 beats, P<0.01), but increased significantly in group CAD (from 48.8+/-5.4 to 57.3+/-5.5 bursts/100 beats, P<0.01). There was significant correlation between BRS and changes in MSNA (r= -0.62, P<0.01). Cigarette smoking increased MSNA in smokers with impaired baroreflex function. This demonstrates that cigarette smoking stimulates sympathetic nerve activity by both a direct peripheral effect and a centrally mediated effect.