Currently, the low-energy diet is the only recognized nutrition therapy for type 2 diabetes in Japan. However, in recent decades, many foreign scientific organizations have accepted various nutritional approaches to manage diabetes, such as the low-carbohydrate diet, the Mediterranean diet, diet approaches to stop hypertension (DASH), and the vegetarian diet. Moreover, growing evidence has called into question classical nutritional approaches such as the low-fat diet for the prevention of cardiovascular disease and the low-protein diet for the prevention of diabetic kidney disease. Similarly, the recommended nutrition therapy for diabetes may change in near future. Such changes in nutrition therapy must be dynamic and based on not only scientific evidence but also each patient’s narrative.

Anemia in chronic kidney disease (CKD) is a risk factor for cardiovascular diseases and is treated by long-acting erythropoiesis-stimulating agents (ESAs). Although the results of previous studies have shown that hemoglobin levels could not be maintained at the initiation of dialysis in CKD patients treated with recombinant human erythropoietin, it remains undetermined whether long-acting ESAs are effective in preventing the progression of anemia at the initiation of dialysis. In the present study, hemoglobin levels in 40 CKD patients treated with darbepoetin alfa (DA) and 15 CKD patients treated with a continuous erythropoietin receptor activator (CERA) were retrospectively compared during the 6 months period before the initiation of dialysis. Results showed that DA and CERA both maintained hemoglobin levels at around 10 g/dL from 6 months to 1 month before dialysis. However, hemoglobin levels at the initiation of dialysis significantly decreased to 9.1 ± 1.2 g/dL in the DA group and to 9.0 ± 1.0 g/dL in the CERA group. Although the total doses of ESAs used during the 6-month period were similar between the two groups, DA-treated CKD patients received subcutaneous injections more frequently than did patients treated with CERA. These results suggest that CKD patients require more intense ESA therapy to prevent a decline in hemoglobin levels at the initiation of dialysis, including those treated with long-acting ESAs. The results also raise the possibility that CERA is more useful than DA for reducing the number of injections during the pre-dialysis period.

Precision Cancer Medicine: Tumors are classified into several molecular subtypes by Genomic Sequencing. Comprehensive targeted-gene panel provides more therapeutic options. CANCERPLEX-JP version 4.0 includes 435 actionable genes, which clinical approaches are available. Utilizing the gene panel platform, we assessed the genes and pathways most frequently altered in Japanese and US cases (Genome Med 2016;8:136). We demonstrate concordance of CANCERPLEX-JP with whole-exome sequencing from the TCGA in identifying hypermutated samples and microsatellite instability in multiple cancer types, such as colorectal and gastric cancer. We introduced our activity for precision medicine at 4th US-Japan Clinical Trials in Oncology Workshop sponsored by Embassy of Japan, at Washington DC, held in June 9, 2016. We highlight the clinical utility of CANCERPLEX-JP (435 genes) in guiding treatment strategies with targeted therapy in solid tumors, thus providing rationale for Comprehensive Genomic Sequencing in actualizing precision medicine. The goal of Precision Medicine is cost effectiveness and realization of genome drug discovery.

Super-computing System: This introduction plan is based on the massive medical big data (cancer gene mutation information, genomic data, image data, etc.) possessed by Niigata Prefecture and Niigata University, to construct an integrated analysis system incorporating deep learning, and introduces a high-performance computer system for the development and activation of related industries. Therefore, it is necessary to have an operation system that can connect to the hospital electronic medical record without interference.

(Presented at the 1943rd Meeting, July 5, 2017)

Surgeons in the US are trained to be leaders during their surgical residencies as part of their postgraduate education. Leadership is considered to be essential, since the surgeon directs the medical team. Every surgeon is expected to gain leadership skills. I would like to introduce the leadership training that I received as an ASCO Leadership Development Program graduate and as a Scholarship recipient of Geisel Leadership Course at Dartmouth in addition to General Surgery Residency at University of California San Diego. I will also present our research on Precision Medicine.

(Presented at the 1943rd Meeting, July 5, 2017)

The first clinical trials of cell therapy in stroke were first published in the 2000s and consisted of neural stems cells transplanted via the intracerebral pathway. Since mesenchymal stem cells showed similar capacities to differentiate into neural cells and allowed autologous cell transplantation, they were then preferentially studied, including diabetes and hypertension. More recently, bone marrow derived mononuclear cells were successfully transplanted in stroke with no need of culture processing, and simple collection by density gradient centrifugation rendering them immediately ready for use. They improve post-stroke neurological deficit in rodents and clinical trials have shown the feasibility of intra-arterial or intravenous administration. The underlying mechanisms are not yet understood. We investigated the therapeutic potential of peripheral blood derived mononuclear cells (PB-MNC) harvested from diabetic patients and stimulated by ephrin-B2 (PB-MNC+). We showed that intravenously injected PB-MNC+ after cerebral ischemia reduced infarct volume at day 3, increased cell proliferation in the peri-infarct area and the subventricular zone, decreased microglial cell density, and upregulated TGF-β expression. At D14, microvessel density was increased and functional recovery enhanced, whereas plasma levels of BDNF were increased in treated mice. Ephrin-B2 induced phenotype switching of PB-MNC by upregulating genes controlling cell proliferation, inflammation and angiogenesis, as confirmed by adhesion and Matrigel assays. PB-MNC+ transplantation in stroke is a promising approach and should be investigated for the development of rapid, non-invasive bedside cell therapy strategies in stroke.

(Presented at the 1944th Meeting, July 19, 2017)