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The present study evaluated the efficacy and safety of pemetrexed, carboplatin and bevacizumab, followed by maintenance pemetrexed and bevacizumab, in chemotherapy-naive patients with stage IIIB/IV non-squamous non-small cell lung cancer (NSCLC). The patients were administered pemetrexed (500 mg/m 2 ), carboplatin (area under the concentration-time curve, 6.0 mg/ml x min) and bevacizumab (15 mg/kg) intravenously every three weeks for up to six cycles. Patients who did not experience tumor progression remained on maintenance pemetrexed and beva- cizumab until disease progression or unacceptable toxicity occurred. The primary endpoint was the overall response rate. Of the 26 patients enrolled between March 2010 and April 2011, three were excluded due to brain metastases, therefore the intention-to-treat (ITT) population consisted of 23 patients. The median age was 64 years (range, 40-74 years) and 15 patients were male. In total, six patients had a perfor- mance status of 0, and 20 had stage IV tumors. The response rate was 69.6% (95% confidence interval (CI), 47.1-86.8), the disease control rate was 100% and the time to response was 1.2 months (95% CI, 0.72-1.93). The median progression-free survival time was 8.6 months (95% CI, 5.9-10.9) and the median overall survival time was 18.6 months (95% CI, 12.9- 24.8). There were no grade 3 or worse hemorrhagic events and the feasibility was modest. Overall, pemetrexed and carboplatin plus bevacizumab, followed by maintenance pemetrexed and bevacizumab, was effective and tolerable in the patients with non-squamous NSCLC, and the time to response was relatively short.

Owing to the advance of supportive care and the development of molecular targeted therapies, the elderlies or patients who have comorbidities have been treated more than before. The assessment of the comorbidity is indispensable to select the appropriate treatment or the control of following therapy. Some indices to determine them have been developed in western countries but not in Japan. The index which is used most is the Charlson comorbidity index (CCI). This index has never been evaluated in Japan. So we investigated the utility of the index for Japanese population. We surveyed retrospectively 498 patients aged 65 or more patients with colon cancer, breast cancer, lung cancer that have been treated in our hospital during 2002-2007. According to CCI, patients are classified into three groups and verified 1-year and 3-year survival rate. 1-year survival rate was 76.9% in groups of 0 points, 83.5% in groups of1 -5 points, 75.0% in the group of six or more points respectively (p=0.19). 3-year survival rate were 59.0%, 63.1%, 75.0%, respectively (p=0.46). Multivariate analysis identified age (≥ 50), Sex (man), stage (III and IV) as significant predictors for worse OS at 3-year. However, there was no significant difference in CCI. There are some items which frequency is zero, so the items of CCI may not match to Japanese population. Presence of existing disease is an important factor for the cancer therapy, and it should be evaluated accurately. It is urgently necessary to develop an evaluation method and establish the scale.

Hepatitis B virus(HBV)reactivation has been reported as a fatal complication following systemic chemotherapy or other immunosuppressive therapies. The Japanese Guidelines for HBV reactivation were published in 2009. Despite the publication of these guidelines, there have been some reports of fulminant hepatitis B. Therefore, it was suggested that the guidelines were not yet been widely implemented. We investigated whether the guidelines had been implemented in our hospital. After the evaluation, it was determined that 89%of HBV cases were screened for the HBV surface antigen(HBs-Ag). Additionally, the screening for HBV surface antibody(HBs-Ab)and HBV core antibody(HBc-Ab)should be performed in cases negative for HBs-Ag, which was performed in only 17% of HBs-Ag-negative cases. It was concluded that the guidelines had not been implemented in our hospital. Therefore, we conducted educational activities to promote the implementation of the guidelines. Screening tests were performed in all 270 HBV cases between January and June 2013. Two antigen-positive carriers were identified. The rate of HBs-Ag-negative and/or HBc antibody -positive cases was 20.3%. Of these, 76.4%were tested using a DNA quantitative test, but DNA quantification did not increase in any case. HBV reactivation is expected to increase due to the development of new drugs and the use of diverse regimens. All physicians who perform immunotherapy and chemotherapy should immediately participate in educational activities.

ObjectiveProgrammed cell death-1 (PD-1) and its ligands (PD-L1 and PD-L2) inhibit T-cell proliferation and activation. This inhibition down-regulates the immune responses. The association of a PD-L1 polymorphism with Graves' disease (GD) was studied.DesignThe association of an A/C polymorphism at position 8923 in PD-L1 intron 4 with GD was studied.PatientsThe study included 327 GD patients and 192 controls, of which 252 GD patients were followed over 5–10 years.MeasurementsPD-L1 intron 4 position 8923 A/C polymorphism was typed using the PCR-restriction fragment length polymorphism method.ResultsThe A/C genotype frequencies were significantly different between GD patients and controls. The A/C and C/C frequencies were higher in GD patients than in controls. The A/A frequencies were lower in GD patients than in controls. C-allele frequency was higher in GD patients than in controls. A total of 252 GD patients were followed over 5–10 years; 200 had discontinued antithyroid drugs (ATD) while 52 continued to take ATD. Of these 200, 176 continued to be in remission and 24 had relapsed into hyperthyroidism. Significant differences in the duration of positive TBII, positive thyroid-stimulating antibodies, and ATD treatment were noted between the patients in remission and those that had relapsed. Significant differences in the A- and C-allele frequencies were noted between the two. The C-allele frequency was higher in GD patients who did not achieve remission than in those who achieved remission.ConclusionAn A/C polymorphism at position 8923 in PD-L1 is associated with GD. The PD-L1 polymorphism plays a role in GD development. GD patients with the C allele at position 8923 in PD-L1 gene had difficulty in achieving remission.

123I-Metaiodobenzylguanidine (123I-MIBG)-accumulation in angiomyolipoma (AML) is demonstrated. A 24-year-old Japanese woman presented with tumors in the right retroperitoneal space. The tumors, which accumulated 123I-MIBG, had been thought to be adrenal pheochromocytoma before surgery. They were removed, and were found to be AML. 123I-MIBG was accumulated in AML. 123I-MIBG-accumulation in AML led to a false-positive diagnosis of adrenal pheochromocytoma. Catecholamine levels had been normal. No chromaffin cells were found in the histological examination of the tumors. MIBG accumulation does not necessarily indicate the presence of pheochromocytoma.

Catecholamines strongly promote lipolysis and thermogenesis, and play a central role in the regulation of body fat content. The beta1 adrenergic receptor (BAR-1) is a major mediator of catecholamine-induced lipolysis and thermogenesis. To explore whether mutations in the BAR-1 gene contribute to morbid obesity in Japanese, we scanned for mutations in the coding sequence of the gene in 50 morbid obese [body mass index (BMI)>==35.0kg/m(2); 99.7th percentile] Japanese subjects. Direct DNA sequencing was performed following polymerase chain reaction (PCR) amplification. Two common polymorphisms, Gly49Arg and Arg389Ser, were detected in these subjects. The frequencies of these polymorphisms, as determined by PCR-restriction fragment length polymorphism (RFLP) analysis, showed no significant difference between 180 severely obese subjects (BMI>==30.0kg/m(2); 97th percentile) and 132 control (BMI

Summary Activated interleukin (IL)-4Rα stimulates production of IgE through signal transducer and activator of transcription-6 (Stat6) activation in lymphocytes. Genetic studies have shown an association between polymorphisms in the genes encoding IL-4Rα and Stat6 and elevated serum IgE in patients with atopic disease. Some authors, including us, have reported an association of Graves' disease and elevated serum IgE. To analyse the relationship between IL-4Rα and Stat6 polymorphisms and elevated serum IgE in patients with Graves' disease, 169 patients with Graves' disease were studied. We investigated whether these polymorphisms affect IL-4Rα–Stat6 signalling in cultured human lymphocytes. A high frequency of both the Ile50 polymorphism in IL-4Rα and 13GT repeat variants of the Stat6 gene was observed in patients with Graves' disease and elevated serum IgE (Ile50 allele; P

e18081 Background: Until recently non–small-cell lung cancer was treated as a single disease with “platinum-based doublet chemotherapy” comprising first-line treatment for advanced disease. However, survival outcome of advanced non-squamous non–small-cell lung cancer are improving since the appearance of pemetrexed and bevacizumab. These drugs show a high effect especially to Adenocarcinoma, but there are few reports of the regimen which combined these both agents. Then, we designed this study to evaluate the efficacy and safety of pemetrexed, carboplatin, and bevacizumab followed by maintenance pemetrexed and bevacizumab in patients with chemotherapy-naïve Japanese stage IIIB or stage IV non-squamous non–small-cell lung cancer. Methods: Patients received pemetrexed 500 mg/m2, carboplatin area under the concentration-time curve of 6, and bevacizumab 15 mg/kg every 3 weeks for up to six cycles. For patients who is not progressed after pemetrexed, carboplatin and bevacizumab therapy, pemetrexed and bevacizumab were continued until disease progression or unacceptable toxicity. Primarity endpoint is response rate. Results: 23 patients were enrolled between March 2010 and April 2011 and treated. Median age was 64 (40-74), 15 patients were male, 6 patients were PS 0, 20 patients were Stage IV. Response rate was 69.5% and disease control rate was 100%. Median PFS was 8.5 months and median OS was not reached. Median time to response was 1.2 months. There were no grade 3 or worse hemorrhagic events. The feasibility was modest. Conclusions: Pemetrexed and carboplatin plus bevacizumab with maintenance pemetrexed and bevacizumab was efficacy and tolerable regimen in Japanese patients with non-squamous non-small-cell lung cancer. This regimen also has a trend of shorter period for response. It may contribute to the better QoL.