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Genomic medicine in clinical practice:national genomic medicine program in Japan

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Cancer Biology & Medicine 2024年第1期21卷 4-9页

作者： Teruhiko Yoshida Yasushi Yatabe Ken Kato Genichiro Ishii Akinobu Hamada Hiroyuki Mano Kuniko Sunami Noboru Yamamoto Takashi Kohno Department of Genetic Medicine and Services National Cancer Center HospitalTokyo 104-0045Japan Department of Diagnostic Pathology National Cancer Center HospitalTokyo 104-0045Japan Clinical Research Support Offce Clinical Research Coordinating SectionBiobank Translational Research Support SectionNational Cancer Center HospitalTokyo 104-0045Japan Department of Pathology and Clinical Laboratories National Cancer Center Hospital EastChiba 277-8577Japan Division of Molecular Pharmacology National Cancer Center Research InstituteTokyo 104-0045Japan National Cancer Center Research Institute Tokyo 104-0045Japan Department of Laboratory Medicine National Cancer Center HospitalTokyo 104-0045Japan Department of Experimental Therapeutics National Cancer Center HospitalTokyo 104-0045Japan Division of Genome Biology National Cancer Center Research InstituteTokyo 104-0045Japan

Cancer statistics in Japan Cancer is the most common cause of death in Japan based on Statistics 2021~1.Since statistics were first gathered,infectious diseases,such as tuberculosis,and cerebrovascular disease have been the main causes of death in Japan.Cancer surpassed cerebrovascular disease as the main cause of death in 1981,and the number of cancer deaths has increased.Approximately 38,000 people died of cancer in 2021.The National Cancer Center(NCC)reported that the 5-year survival rate for patients with cancer was improving(62%for males and 66.9%for females)in a population-based cancer registry.

关键词： Cancer cancer death

Non-robotic minimally invasive gastrectomy as an independent risk factor for postoperative intra-abdominal infectious complications: A single-center, retrospective and propensity score-matched analysis

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World Journal of Gastroenterology 2020年第11期26卷 1172-1184页

作者： Susumu Shibasaki Koichi Suda Masaya Nakauchi kenichi nakamura Kenji Kikuchi Kazuki Inaba Ichiro Uyama Department of Surgery Fujita Health UniversityToyoake 470-1192AichiJapan Collaborative Laboratory for Research and Development in Advanced Surgical Technology Fujita Health University School of MedicineToyoake 470-1192AichiJapan

BACKGROUND Minimally invasive surgery for gastric cancer(GC) has gained widespread use as a safe curative procedure especially for early GC.AIM To determine risk factors for postoperative complications after minimally invasive gastrectomy for GC.METHODS Between January 2009 and June 2019, 1716 consecutive patients were referred to our division for primary GC. Among them, 1401 patients who were diagnosed with both clinical and pathological Stage Ⅲ or lower GC and underwent robotic gastrectomy(RG) or laparoscopic gastrectomy(LG) were enrolled. Retrospective chart review and multivariate analysis were performed for identifying risk factors for postoperative morbidity.RESULTS Morbidity following minimally invasive gastrectomy was observed in 7.5% of the patients. Multivariate analyses demonstrated that non-robotic minimally invasive surgery, male gender, and an operative time of ≥ 360 min were significant independent risk factors for morbidity. Therefore, morbidity was compared between RG and LG. Accordingly, propensity-matched cohort analysis revealed that the RG group had significantly fewer intra-abdominal infectious complications than the LG group(2.5% vs 5.9%, respectively;P = 0.038), while no significant differences were noted for other local or systemic complications.Multivariate analyses of the propensity-matched cohort revealed that non-robotic minimally invasive surgery [odds ratio = 2.463(1.070–5.682);P = 0.034] was a significant independent risk factor for intra-abdominal infectious complications.CONCLUSION The findings showed that robotic surgery might improve short-term outcomes following minimally invasive radical gastrectomy by reducing intra-abdominal infectious complications.

关键词： Stomach neoplasms Gastrectomy Robotic surgical procedure Minimally invasive procedures Morbidity Pancreatic fistula

Prognostic factors of minimally invasive surgery for gastric cancer: Does robotic gastrectomy bring oncological benefit?

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World Journal of Gastroenterology 2021年第39期27卷 6659-6672页

作者： Masaya Nakauchi Koichi Suda Susumu Shibasaki kenichi nakamura Shinichi Kadoya Kenji Kikuchi Kazuki Inaba Ichiro Uyama Department of Gastroenterological Surgery Fujita Health UniversityToyoake 470-1192AichiJapan Department of Gastroenterological Surgery Ishikawa Prefectural Central HospitalKanazawa 920-8535IshikawaJapan

BACKGROUND Gastric cancer is the third leading cause of cancer-related death worldwide and surgical resection remains the sole curative treatment for gastric cancer.Minimally invasive gastrectomy including laparoscopic and robotic approaches has been increasingly used in a few decades.Thus far,only a few reports have investigated the oncological outcomes following minimally invasive gastrectomy.AIM To determine the 5-year survival following minimally invasive gastrectomy for gastric cancer and identify prognostic predictors.METHODS This retrospective cohort study identified 939 patients who underwent gastrectomy for gastric cancer during the study period.After excluding 125 patients with non-curative surgery(n=77),other synchronous cancer(n=2),remnant gastric cancer(n=25),insufficient physical function(n=13),and open gastrectomy(n=8),a total of 814 consecutive patients with primary gastric cancer who underwent minimally invasive R0 gastrectomy at our institution between 2009 and 2014 were retrospectively examined.Accordingly,5-year overall and recurrence-free survival were analyzed using the Kaplan–Meier method with the log-rank test and Cox regression analyses,while factors associated with survival were determined using multivariate analysis.RESULTS Our analysis showed that age>65 years,American Society of Anesthesiologists(ASA)physical status 3,total or proximal gastrectomy,and pathological T4 and N positive status were independent predictors of both 5-year overall and recurrencefree survival.Accordingly,the included patients had a 5-year overall and recurrence-free survival of 80.3%and 78.2%,respectively.Among the 814 patients,157(19.3%)underwent robotic gastrectomy,while 308(37.2%)were diagnosed with pathological stage II or III disease.Notably,our findings showed that robotic gastrectomy was an independent positive predictor for recurrence-free survival in patients with pathological stage II/III[hazard ratio:0.56(0.33-0.96),P=0.035].Comparison of recurrence-free survival between the robotic and laparoscopic

关键词： Laparoscopy Gastric cancer Minimally invasive surgery Prognostic factor Stomach neoplasms

Analysis for Effects of Temperature Rise of PV Modules upon Driving Distance of Vehicle Integrated Photovoltaic Electric Vehicles

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Energy and Power Engineering 2024年第4期16卷 131-150页

作者： Masafumi Yamaguchi Yasuyuki Ota Taizo Masuda Christian Thiel Anastasios Tsakalidis Arnulf Jaeger-Waldau Kenji Araki Kensuke Nishioka Tatsuya Takamoto Takashi Nakado Kazumi Yamada Tsutomu Tanimoto Yosuke Tomita Yusuke Zushi kenichi Okumura Takashi Mabuchi Akinori Satou Kyotaro nakamura Ryo Ozaki Nobuaki Kojima Yoshio Ohshita Toyota Technological Institute Nagoya Japan Faculty of Engineering Miyazaki University Miyazaki Japan Toyota Motor Corporation Susono Japan European Commission— Joint Research Centre Ispra Italy Sharp Corporation Nara Japan Toyota Motor Corporation Toyota Japan Nissan Motor Corporation Yokosuka Japan

The development of vehicle integrated photovoltaics-powered electric vehicles (VIPV-EV) significantly reduces CO2 emissions from the transport sector to realize a decarbonized society. Although long-distance driving of VIPV-EV without electricity charging is expected in sunny regions, driving distance of VIPV-EV is affected by climate conditions such as solar irradiation and temperature rise of PV modules. In this paper, detailed analytical results for effects of climate conditions such as solar irradiation and temperature rise of PV modules upon driving distance of the VIPV-EV were presented by using test data for Toyota Prius and Nissan Van demonstration cars installed with high-efficiency InGaP/GaAs/InGaAs 3-junction solar cell modules with a module efficiency of more than 30%. The temperature rise of some PV modules studied in this study was shown to be expressed by some coefficients related to solar irradiation, wind speed and radiative cooling. The potential of VIPV-EV to be deployed in 10 major cities was also analyzed. Although sunshine cities such as Phoenix show the high reduction ratio of driving range with 17% due to temperature rise of VIPV modules, populous cities such as Tokyo show low reduction ratio of 9%. It was also shown in this paper that the difference between the driving distance of VIPV-EV driving in the morning and the afternoon is due to PV modules’ radiative cooling. In addition, the importance of heat dissipation of PV modules and the development of high-efficiency PV modules with better temperature coefficients was suggested in order to expand driving range of VIPV-EV. The effects of air-conditioner usage and partial shading in addition to the effects of temperature rise of VIPV modules were suggested as the other power losses of VIPV-EV.

关键词： Vehicle Integrated Photovoltaics (VIPV) VIPV-Powered Electric Vehicles Driving Distance PV Modules Solar Irradiation Temperature Rise Radiative Cooling

Monocyte-derived fibrocytes elimination had little contribution on liver fibrosis

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Hepatobiliary & Pancreatic Diseases International 2019年第4期18卷 348-353页

作者： Yoshinori Ozono Kotaro Shide Fumiyo Toyoshima Yuuka Takaishi Mai Tsuchimochi Ayako Kamiunten Takuro Kameda kenichi nakamura Tadashi Miike Kazunori Kusumotoa Hisayoshi Iwakiri Satoru Hasuikea Kenji Nagata Akira Sawaguchi Kazuya Shimoda Department of Gastroenterology and Hematology Faculty of MedicineUniversity of Miyazaki5200 KiharaKiyotakeMiyazaki 889-1601Japan Department of Anatomy Ultrastructural Cell BiologyFaculty of MedicineUniversity of Miyazaki5200 KiharaKiyotakeMiyazaki 889-1601Japan Department of Liver disease University of Miyazaki HospitalMiyazakiJapan

Background:Monocyte-derived fibrocytes play an important role in the progression of fibrosis in the skin,lungs,heart and kidney.However,the contribution of fibrocytes to liver fibrosis is unclear.The aim of this study was to investigate whether fibrocytes contributed to fibrosis progression in the livers of carbon tetrachloride(CCl 4)-treated mice.Methods:C57BL/6J mice were divided into 4 groups:normal control group,CCl 4-treated group,CCl 4+control liposome-treated group,and CCl 4+clodronate liposome-treated group.For the elimination of systemic monocyte and monocyte-derived fibrocyte,one group was treated with clodronate liposome,and another group with control liposome as a control.After 4 weeks of treatment,hepatic mononuclear cells were subjected to immunofluorescent(IF)staining and fluorescence-activated cell sorter(FACS)analysis to detect fibrocytes.Measurement of collagen-positive Sirius red stained area and collagen-I mRNA expression in the liver were performed to evaluate the degree of liver fibrosis quantitatively.Results:In the liver of the CCl 4-treated and CCl 4+control liposome-treated groups,the number of fibrocytes,the area positive for Sirius red staining and collagen-I mRNA expression significantly increased compared with those in the normal control group.In the liver of the CCl 4+clodronate liposome-treated group,few fibrocytes was observed as in the normal control group,but Sirius red staining positive area and collagen-I mRNA expression were increased and equivalent to the CCl 4-treated and CCl 4+control liposome-treated groups.Conclusion:Monocyte-derived fibrocytes play a minimal role in CCl 4-induced liver fibrosis.Cells other than fibrocytes such as hepatic stellate cells play a central role in liver fibrosis.

关键词： Fibrocytes Liver fibrosis Carbon tetrachloride Clodronate Collagen-I

Overview of genetic and epigenetic alterations in the pathogenesis of esophagogastric junctional adenocarcinoma and esophageal adenocarcinoma: recent fi ndings by next generation sequencing

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Journal of Cancer Metastasis and Treatment 2015年第1期1卷 123-129页

作者： Yu Imamura Ryuma Tokunaga kenichi nakamura Hideo Baba Masayuki Watanabe Department of Gastroenterological Surgery Cancer Institute Hospital of Japanese Foundation for Cancer ResearchTokyo 135-8550Japan Department of Gastroenterological Surgery Graduate School of Medical SciencesKumamoto UniversityKumamoto 860-8555Japan.

Esophagogastric junctional adenocarcinoma is commonly treated as esophageal adenocarcinoma(EAC)and has dramatically increased in Western countries for several decades.The similar trend has been observed in Asian countries(not in China).Barrett’s esophagus(BE)is a widely accepted precursor of EAC.Recent advances of next-generation sequencing could provide researchers with a better understanding of genetic and epigenetic alterations in the carcinogenesis of EAC.In this review,we have summarized the recently reported major genetic and epigenetic alterations in both BE and EAC.Sonic hedgehog/bone morphogenetic protein axis,which is a key signaling for esophageal development,plays an important role in BE intestinal metaplasia.Single nucleotide polymorphisms related to esophageal organogenesis,such as FOXF1 and FOXP3,are frequently detected in BE patients.During the progression of BE to adenocarcinoma,lacking of normal function of TP53 and CDKN2A by loss of heterozygosity(LOH),mutation,or promoter methylation has been frequently observed.LOH at 9p(coding CDKN2A)is an earlier event to EAC carcinogenesis compared to that at 17q(coding TP53)LOH.In order to further elucidate the pathogenesis of BE and EAC,it will be necessary to analyze these genetic/epigenetic alterations in combination with clinical data in a large-scale cohort.

关键词： Barrett’s esophagus carcinogenesis epigenetic esophageal adenocarcinoma esophagogastric junctional adenocarcinoma genetic intestinal metaplasia

Efficacy and safety of sofosbuvir and ledipasvir in Japanese patients aged 75 years or over with hepatitis C genotype 1

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World Journal of Hepatology 2017年第36期9卷 1340-1345页

作者： Yoshinori Ozono Kenji Nagata Satoru Hasuike Hisayoshi Iwakiri kenichi nakamura Mai Tsuchimochi Yuri Yamada Yuka Takaishi Mitsue Sueta Tadashi Miike Yoshihiro Tahara Shojiro Yamamoto Kotaro Shide Tomonori Hidaka Yoko Kubuki Kazunori Kusumoto Toshimasa Ochiai Junya Kato Naoto Komada Shuichi Hirono Kazuo Kuroki Masafumi Shigehira Kazuya Shimoda Department of Gastoroenterology and Hematology Faculty of Medicine University of Miyazaki Department of Liver Disease University of Miyazaki Hospital Department of Internal Medicine Koga General Hospital Department of Internal Medicine National Hospital Organization Miyakonojo Medical Center Department of Internal Medicine Hirono Naika Clinic Department of Internal Medicine Kushima Municipal Hospital Department of Internal Medicine Shigehira Clinic

AIM To evaluate the efficacy and safety of a regimen containing sofosbuvir(SOF) and ledipasvir(LDV) in Japanese patients aged ≥ 75 years with hepatitis C genotype 1.METHODS This multicenter, retrospective study consisted of 246 Japanese patients with HCV genotype 1 at nine centers in Miyazaki prefecture in Japan. Demographic, clinical, virological, and adverse effects(AE)-related data obtained during and after SOF/LDV therapy were collected from medical records. These patients were divided into two groups, younger(aged < 75 years) and elderly(aged ≥ 75 years). Virological data and AEs were analyzed by age group.RESULTS The sustained virological response(SVR) rates at 12 wk after treatment were 99.2%, 99.4%, and 98.7% in the overall population and in patients aged < 75 and ≥ 75 years, respectively. Common AEs during therapy were headache, pruritus, constipation, and insomnia. These occurred in fewer than 10% of patients, and their incidence was not significantly different between the younger and elderly groups. Two patients discontinued treatment, one due to a skin eruption and the other due to cerebral bleeding. CONCLUSION Compared with younger patients, elderly patients had a similar virological response and tolerance to SOF/LDV therapy.

关键词： Chronic hepatitis C Sofosbuvir Ledipasvir Sustained virological response Direct acting antivirals

Circulating tumor cells in gastric cancer

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Journal of Cancer Metastasis and Treatment 2018年第1期4卷 380-390页

作者： kenichi nakamura Masaaki Iwatsuki Junji Kurashige Takatsugu Ishimoto Yoshifumi Baba Yuji Miyamoto Naoya Yoshida Masayuki Watanabe Hideo Baba Division of Gastric Surgery Shizuoka Cancer CenterShizuoka 411-8777Japan Department of Gastroenterological Surgery Graduate School of Medical SciencesKumamoto UniversityKumamoto 860-8556Japan Esophageal Cancer Division Gastroenterological SurgeryCancer Institute Hospital of Japanese Foundation for Cancer ResearchTokyo 135-8550Japan

Circulating tumor cells(CTCs)have received a lot of attention as a novel biomarker for cancer research in past decades.CTCs infiltrate the bloodstream derived from the primary tumor,and are significantly involved in cancer metastasis and recurrence.Although clinical applications have been challenging owing to the difficulties of CTC identification,recent development of technology for specific enrichment and detection of CTCs contributes to diagnosis and treatment.Furthermore,CTC analyses will shed new light on the biological mechanisms of cancer progression and metastasis.A number of clinical studies have already been carried out on the basis of CTC technology.Nevertheless,the clinical utility of CTCs is still unknown in gastric cancer.In this review,we elaborate on the latest advances of CTC research in gastric cancer.

关键词： Circulating tumor cells gastric cancer cancer progression and metastasis tumor heterogeneity epithelial mesenchymal transition cancer stem cells immune check point blockade

Corticospinal excitability during motor imagery is diminished by continuous repetition-induced fatigue

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Neural Regeneration Research 2021年第6期16卷 1031-1036页

作者： Akira Nakashima Takefumi Moriuchi Daiki Matsuda Takashi Hasegawa Jirou nakamura Kimika Anan Katsuya Satoh Tomotaka Suzuki Toshio Higashi kenichi Sugawara Department of Rehabilitation Juzenkai HospitalNagasakiJapan Graduate School of Biomedical Sciences Nagasaki UniversityNagasakiJapan School of Rehabilitation Kanagawa University of Human ServicesYokosukaJapan

Application of continuous repetition of motor imagery can improve the performance of exercise tasks.However,there is a lack of more detailed neurophysiological evidence to support the formulation of clear standards for interventions using motor imagery.Moreover,identification of motor imagery intervention time is necessary because it exhibits possible central fatigue.Therefore,the purpose of this study was to elucidate the development of fatigue during continuous repetition of motor imagery through objective and subjective evaluation.The study involved two experiments.In experiment 1,14 healthy young volunteers were required to imagine grasping and lifting a 1.5-L plastic bottle using the whole hand.Each participant performed the motor imagery task 100 times under each condition with 48 hours interval between two conditions:500 mL or 1500 mL of water in the bottle during the demonstration phase.Mental fatigue and a decrease in pinch power appeared under the 1500-mL condition.There were changes in concentration ability or corticospinal excitability,as assessed by motor evoked potentials,between each set with continuous repetition of motor imagery also under the 1500-mL condition.Therefore,in experiment 2,12 healthy volunteers were required to perform the motor imagery task 200 times under the 1500-mL condition.Both concentration ability and corticospinal excitability decreased.This is the first study to show that continuous repetition of motor imagery can decrease corticospinal excitability in addition to producing mental fatigue.This study was approved by the Institutional Ethics Committee at the Nagasaki University Graduate School of Biomedical and Health Sciences(approval No.18121302)on January 30,2019.

关键词： central nervous system concentration continuous repetition of motor imagery corticospinal excitability mental fatigue motor evoked potential motor imagery muscle fatigue neurophysiology transcranial magnetic stimulation