Aim Hepatocellular carcinoma (HCC) is the second leading cause of cancer mortality worldwide. An excess of iron in liver tissue causes oxidative stress, leading to hepatocellular carcinogenesis. Iron metabolism, which is regulated by a complex mechanism, is important for cancer cell survival. The aim of this study is to clarify the role of iron regulatory protein in the progression of HCC and in patient outcome. Methods and results We first investigated the mRNA level of iron metabolism‐related genes, including hepcidin, ferroportin 1 (FPN‐1) and transferrin receptor (TFR)‐1/2. TFR‐1/2 protein expression was then evaluated in surgical specimens from 210 cases using immunohistochemistry, and we compared clinicopathological factors with TFR‐1/2 expression. The mRNA expression levels of TFR‐1 were significantly increased in HCC tissues compared with adjacent non‐cancerous tissues (P = 0.0013), but there were no differences in other genes. High expression of TFR‐1 in HCC was associated with the absence of alcohol abuse (P = 0.0467), liver cirrhosis (P < 0.0001), higher alpha‐fetoprotein (AFP; P < 0.0001), smaller tumour size (P = 0.0022), poor histological differentiation (P < 0.0001) and morphological features (P < 0.0001). In contrast, high expression of TFR‐2 in HCC was associated with lower AFP (P < 0.0001), well‐differentiated histological grade (P < 0.0001) and morphological features (P = 0.0010). Multivariate analysis for both overall survival and recurrence‐free survival indicated that high TFR‐1 expression was a significant prognostic factor for poor outcome. Conclusions We found an inverse correlation of TFR‐1 and TFR‐2 expression in AFP and tumour differentiation. TFR‐1 overexpression suggests a higher risk of recurrence and death in HCC patients following liver resection.
Pharmaceutical interventions are sometimes ineffective in patients who take dietary supplements (DS) because the medical staff providing the treatment are not aware that the patient is taking DS.This study was performed to analyze pharmaceutical interventions administered to inpatients taking DS. The pharmaceutical interventions were chosen by the pharmacists in charge of each ward with the support of a nutritional representative・supplement adviser. Then, we tried to develop a systematic pharmaceutical management strategy for patients who were taking DS based on this analysis. This study examined 32 interventions (involving 28 patients including 3 patients who were treated multiple times), and 20 patients (63%) who stopped taking DS during the study period. The most serious issues that arose during the interventions included DS-drug interactions (6, 19%), issues associated with perioperative management (6, 19%), direct DS-induced damage (including suspected cases) (5, 16%), and conditions that required immediate attention (5, 16%). We found that by examining the patients' characteristics including their disease status and any medications that they were taking we were able to avoid drug treatment failure. This indicates that it is necessary for pharmacists to be aware of patients' use of DS. We developed a systematic "pharmaceutical management algorithm" based on our analysis of the above-mentioned pharmaceutical interventions. We consider that this algorithm will aid the selection of pharmaceutical management strategies by pharmacists.In future, we will improve the practicality and efficacy of the algorithm based on feedback from clinical pharmacists.
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