Cadmium (Cd), a highly toxic heavy metal, is distributed widely in the general environment of today. The characteristic clinical manifestations of chronic Cd intoxication include renal proximal tubular dysfunction, general osteomalacia with severe pains, and anemia. We have recently reported that the serum level of erythropoietin (EPO) remained low despite the severe anemia in patients with Itai-itai disease, the most severe form of chronic Cd intoxication. In order to prove that the anemia observed in chronic Cd intoxication arises from low production of EPO in the kidneys following the renal injury, we administered Cd to rats for a long period and performed the analysis of EPO mRNA inducibility in the kidneys. The rats administered Cd for 6 and 9 months showed anemia with low levels of plasma EPO as well as biochemical and histological renal tubular damage, and also hypoinduction of EPO mRNA in the kidneys. The results indicate that chronic Cd intoxication causes anemia by disturbing the EPO-production capacity of renal cells.

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Background and study aims The safety and efficacy of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) in very elderly patients remains unclear. The aim of this study was to evaluate the safety and efficacy of ESD for EGC in patients age 85 years and older. Patients and methods Patients who underwent ESD for EGC between September 2003 and April 2015 were divided into 3 groups: the very elderly (≥ 85 years; 43 patients), the elderly (65 – 84 years; 511 patients), and the non-elderly ( ≤ 64 years; 161 patients). Adverse events (AEs) were used as the primary endpoint to assess the safety of ESD, and the ESD treatment outcomes (i. e., en bloc resection rate, complete en bloc resection rate, and curative resection rate) and the overall survival rate after ESD were the secondary endpoints. These parameters were retrospectively evaluated in the 3 groups. Results There were no significant differences in AEs (non-elderly, elderly, and very elderly: 7.3, 9.5, and 12.5 %, respectively, P = 0.491) or in the en bloc resection and complete en bloc resection rates among the three groups. However, there was a significant difference in the curative resection rates (non-elderly, elderly, and very elderly: 91.5, 84.1, and 77.1 %, respectively, P = 0.014). Regarding overall survival, there was a significant difference among the three groups (1-, 5-, and 10-year overall survival rates: non-elderly: 98.6, 90.2, and 74.7 %; elderly: 97.2, 86.2, and 61.9 %; and very elderly: 92.7, 66.8, and 34.4 %, respectively, P = 0.001). Moreover, the overall survival rate in the very elderly patients with cardiovascular disease was significantly lower than that in the very elderly patients without cardiovascular disease (P < 0.001). Conclusions ESD is an acceptable treatment for EGC in patients 85 years of age or older in terms of safety. However, the overall survival after ESD in the very elderly patients with cardiovascular disease was short.

Abstract.As gemcitabine is a key anti-tumor agent for unresectable pancreatic ductal adenocarcinoma (PDAC), it is important to predict the outcomes of gemcitabine chemotherapy. The present study aimed to confirm whether the derived neutrophil-to-lymphocyte ratio (dNLR) is able to predict chemotherapy outcomes. To elucidate the role of dNLR in patients that underwent chemotherapy, the current study evaluated clinicopathological variables in 31 patients with unresectable PDAC treated with gemcitabine. The correlation between clinicopathological variables, and progression-free survival (PFS) and overall survival (OS) time were investigated. Univariate analysis revealed that there were no significant differences in PFS and OS as a function of age (<65 vs. ≥65 years), gender, tumor location (pancreas head vs. body/tail), tumor diameter (<23 vs. ≥23 mm) or serum carbohydrate antigen 19-9 concentration level (<3,800 vs. ≥3,800 U/ml). However, disease stage (locally advanced vs. metastatic) and the dNLR (<2.5 vs. ≥2.5) significantly affected PFS and OS. Multivariate analysis subsequently revealed that a dNLR of ≥2.5 was an independent prognostic factor for poor PFS (P=0.003) and OS (P=0.026). In conclusion, data from the present study suggests that the pre-treatment dNLR is an independent prognostic factor to predict PFS and OS in patients with unresectable PDAC treated with gemcitabine. This indicates that dNLR has a potential role in stratifying patients that may benefit from gemcitabine therapy.