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Suguru Tokiwa,1 Hiroaki Shimmura,1 Shuhei Nomura,2–4 Ryota Watanabe,1 Minoru Kurita,1 Naoto Yoshida,1 Kaori Yamashita,1 Yoshitaka Nishikawa,5 Alexander Kouzmenko,6 Shigeaki Kato4 1Department of Urology, Jyoban Hospital, Tokiwa Foundation, Iwaki, Fukushima, Japan; 2Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK; 3Department of Global Health Policy, Graduate School of Medicine, The University of Tokyo, Tokyo, 4Research Institute of Innovative Medicine, Tokiwa Foundation, Iwaki, 5Department of Health Informatics, School of Public Health, Kyoto University, Kyoto, Japan; 6Department of Life Sciences, Alfaisal University, Riyadh, Kingdom of Saudi Arabia Introduction: Therapeutically induced androgen deficiency (AD) is a standard treatment for patients with prostate cancer, but it is often associated with various adverse effects (AEs) that may lead to discontinuation. Some AEs may depend on the patient’s health condition, while others may be due to complications of the drug delivery method. Degarelix is a gonadotropin-releasing hormone (GnRH) antagonist widely used for the treatment of androgen-dependent prostate cancer. This study aimed to ascertain the following: 1) the compatibility of degarelix treatment with diabetes and 2) any specific causal associations of degarelix injections with increased blood clotting and antithrombotic therapy requirements.Patients and methods: The medical records of 162 patients with prostate cancer who had undergone degarelix treatment were retrospectively examined. The association of a medical history of diabetes and anticoagulant co-treatment with degarelix treatment discontinuation was analyzed statistically.Results: Rapid and significant decreases in prostate-specific antigen (PSA) levels during the course of degarelix treatment were detected for patients with prostate cancer regardless of clinical state. During the 27 months of treatment, 68 subjects (48%) ceased degarelix treatment, owing to several reasons, mainly financial issues. Among these subjects, 19 had diabetes, while 35 were treated with antithrombotics. Extensive statistical analysis indicated that there were no causal associations between degarelix treatment discontinuation and preexisting diabetes or antithrombotic therapy.Conclusion: Our study suggests that preexisting diabetes and antithrombotic therapy were not significant factors for the discontinuation of degarelix treatment in patients with prostate cancer. Keywords: GnRH antagonists, prostate cancer, degarelix, discontinuation, diabetes, antithrombotic treatment

Google Scholar Google Preview OpenURL Placeholder Text WorldCat COPAC 8 The 144th Radiation Council Conference Note on January 25th. The world is facing increasing numbers of natural and man-made disasters.[1] It is of paramount importance that an interdisciplinary, cohesive response is mobilized to best cope with all such emergencies, to minimize negative health impacts and protect human life. Google Scholar Google Preview OpenURL Placeholder Text WorldCat COPAC 9 Ristevski B, Chen M. Big data analytics in medicine and healthcare. [Extracted from the article]

Yasufumi Kuroda,1 Chie Hirayama,2 Hitoshi Hotoda,2 Yasuhiro Nishikawa,2 Akinori Nishiwaki21Daiichi Sankyo Pharma Development, Edison, NJ, USA; 2Daiichi Sankyo Company, Limited, Tokyo, JapanPurpose: Edoxaban is an oral, once-daily, selective, direct factor Xa inhibitor approved in Japan for the prevention of venous thromboembolism following major orthopedic surgery. Currently, edoxaban is in Phase III clinical development for the prevention of stroke and systemic embolic events in patients with atrial fibrillation, and for the treatment and prevention of recurrences of venous thromboembolism. This report describes the adverse drug reactions (ADRs) spontaneously reported during early postmarketing phase vigilance from the time of its commercial launch in Japan.Materials and methods: All spontaneously reported ADRs following edoxaban use received by Daiichi Sankyo during early postmarketing phase vigilance from July 19, 2011, to January 18, 2012, were entered into the safety database and included in this review. Approximately 20,000 patients were estimated to have been treated with edoxaban.Results: The mean age of patients was 74.2 years, their mean weight was 59.4 kg, and approximately 70% were female. A total of 67 ADRs were reported in 56 patients, of which the majority included bleeding events (51 ADRs in 42 patients). Of these, 15 ADRs (in 14 patients) were serious, including cerebral hemorrhage (n = 1), gastric hemorrhage (n = 2; gastric hemorrhage [n = 1] and gastric ulcer hemorrhage [n = 1]), and surgical-site hemorrhage (n = 12; hemorrhage [n = 6], subcutaneous hemorrhage [n = 3], wound hemorrhage [n = 2], and wound hematoma [n = 1]). Most ADRs occurred within the first week of treatment and there were no fatalities. Nonserious ADRs associated with bleeding that occurred in >1 patient included subcutaneous hemorrhage (n = 9), wound hemorrhage (n = 5), postprocedural hematoma (n = 4), anemia (n = 4), and hemarthrosis (n = 3). Other nonserious ADRs not associated with bleeding and occurring in >1 patient included abnormal hepatic function (n = 4) and diarrhea (n = 2). Conclusion: Safety data from the first 6 months of postmarketing experience with edoxaban did not identify any unforeseen safety signals, consistent with the known safety profile of edoxaban.Keywords: edoxaban, venous thromboembolism, factor Xa, early postmarketing phase vigilance, thromboprophylaxis, spontaneous reporting

Yoshikuni Inokawa,1 Shuji Nomoto,1 Mitsuhiro Hishida,1 Masamichi Hayashi,1 Mitsuro Kanda,1 Yoko Nishikawa,1 Shin Takeda,2 Michitaka Fujiwara,1 Masahiko Koike,1 Hiroyuki Sugimoto,1 Tsutomu Fujii,1 Goro Nakayama,1 Suguru Yamada,1 Chie Tanaka,1 Daisuke Kobayashi,1 Yasuhiro Kodera11Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya Japan; 2Department of Surgery, Nagoya Medical Center, Nagoya, JapanBackground: To identify genes associated with hepatocellular carcinoma (HCC) pathogenesis, we developed a triple combination array strategy comprising methylation, gene expression, and single nucleotide polymorphism (SNP) array analysis.Methods: Surgical specimens obtained from a 68-year-old female HCC patient were analyzed by triple combination array, and identified Dynamin 3 (DNM3) as a candidate tumor suppressor gene in HCC. Subsequently, samples from 48 HCC patients were evaluated for DNM3 methylation and expression status using methylation specific polymerase chain reaction (PCR; MSP) and semi-quantitative reverse transcriptase (RT)-PCR, respectively. The relationship between clinicopathological factors and DNM3 methylation status was also investigated.Results: DNM3 was shown to be hypermethylated (methylation value 0.879, range 0–1.0) in cancer tissue compared with adjacent normal tissue (0.213) by methylation array in the 68-year-old female patient. Expression arrays revealed decreased expression of DNM3 in cancerous tissue. SNP arrays revealed that the copy number of chromosome 1q24.3, in which DNM3 resides, was normal. MSP revealed hypermethylation of the DNM3 promoter region in 33 of 48 tumor samples. A trend toward decreased DNM3 expression was observed in patients with DNM3 promoter methylation (P = 0.189). Furthermore, patients with reduced expression of DNM3 in tumor tissues exhibited worse prognosis with decreased disease specific survival compared to patients without decreased expression (P = 0.014).Conclusion: The present study indicates that a triple combination array strategy is an effective method to detect novel genes related to HCC. We propose that DNM3 is a tumor suppressor gene in HCC.Keywords: DNM3, hepatocellular carcinoma, methylation, triple combination array