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Pathological response measured using virtual microscopic slides for gastric cancer patients who underwent neoadjuvant chemotherapy

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World Journal of Gastroenterology 2019年第35期25卷 5334-5343页

作者： sadayuki kawai Tadakazu Shimoda Takashi Nakajima Masanori Terashima Katsuhiro Omae Nozomu Machida Hirofumi Yasui Division of Gastrointestinal Oncology Shizuoka Cancer Center Sunto-gun 411-8777 Shizuoka Japan Division of Pathology Shizuoka Cancer Center Suntogun 411-8777 Shizuoka Japan Division of Gastric Surgery Shizuoka Cancer Center Nagaizumi 411- 0932 Shizuoka Japan Clinical Research Center Shizuoka Cancer Center Sunto-gun 411-8777 Shizuoka Japan Department of Gastrointestinal Oncology Shizuoka Cancer Center Suntogun 411-8777 Shizuoka Japan

BACKGROUND Although pathological response is a common endpoint used to assess the efficacy of neoadjuvant chemotherapy (NAC) for gastric cancer, the problem of a low rate of concordance from evaluations among pathologists remains unresolved. Moreover, there is no globally accepted consensus regarding the optimal evaluation. A previous study based on a clinical trial suggested that pathological response measured using digitally captured virtual microscopic slides predicted patients’ survival well. However, the pathological concordance rate of this approach and its usefulness in clinical practice were unknown. AIM To investigate the prognostic utility of pathological response measured using digital microscopic slides in clinical practice. METHODS We retrospectively evaluated pathological specimens of gastric cancer patients who underwent NAC followed by surgery and achieved R0 resection between March 2009 and May 2015. Residual tumor area and primary tumor beds were measured in one captured image slide, which contained the largest diameter of the resected specimens. We classified patients with < 10% residual tumor relative to the primary tumorous area as responders, and the rest as non-responders;we then compared overall survival (OS) and relapse-free survival (RFS) between these two groups. Next, we compared the prognostic utility of this method using conventional Japanese criteria. RESULTS Fifty-four patients were evaluated. The concordance rate between two evaluators was 96.2%. Median RFS of 25 responders and 29 non-responders was not reached (NR) vs 18.2 mo [hazard ratio (HR)= 0.35, P = 0.023], and median OS was NR vs 40.7 mo (HR = 0.3, P = 0.016), respectively. This prognostic value was statistically significant even after adjustment for age, eastern cooperative oncology group performance status, macroscopic type, reason for NAC, and T- and Nclassification (HR = 0.23, P = 0.018). This result was also observed even in subgroup analyses for different macroscopic types (Borrmann type 4/non-type 4) and histologica

关键词： Stomach neoplasm Neoadjuvant therapy Drug therapy Pathology Prognostic factor

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Impact of sleep on gastrointestinal cancer

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World Journal of Clinical Oncology 2024年第6期15卷 677-683页

作者： Joshua Lo Pahnwat T Taweesedt Makoto kawai Department of Internal Medicine Santa Clara Valley Medical CenterSan JoseCA 95128United States Department of Psychiatry and Behavioral Sciences Stanford UniversityStanfordCA 94305United States Sierra Pacific Mental Illness Research Educationand Clinical Center(MIRECC)VA Palo Alto Health Care SystemPalo AltoCA 94304United States Department of Psychiatry and Behavioral Sciences School of MedicineStanford UniversityRedwood CityCA 94063United States

Sleep problems have become a significant public health concern,affecting a large portion of the global population and have been linked to increased morbidity and mortality.The incidence of gastrointestinal(GI)cancers continues to rise,posing a substantial burden on healthcare systems worldwide.This editorial aims to delve into the impact of sleep on GI cancers,including esophageal,gastric,colorectal,hepatobiliary,and pancreatic cancer.Recent literature investigating the potential connections between GI cancers and sleep was reviewed.We considered aspects such as sleep duration,sleep disorders,and circadian rhythmicity,in order to explore the underlying mechanisms that can contribute to the development of GI cancers and propose avenues for future research.

关键词： Sleep Cancer Gastrointestinal cancer Esophagus Stomach Colon Liver

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Real-world efficacy and safety of tofacitinib treatment in Asian patients with ulcerative colitis

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World Journal of Gastroenterology 2024年第13期30卷 1871-1886页

作者： Kentaro Kojima Kenji Watanabe Mikio kawai Soichi Yagi Koji Kaku Maiko Ikenouchi Toshiyuki Sato Koji Kamikozuru Yoko Yokoyama Tetsuya Takagawa Masahito Shimizu Shinichiro Shinzaki Department of Gastroenterology Hyogo Medical UniversityNishinomiya 663-8501Japan Department of Gastroenterology Gifu University Graduate School of MedicineGifu 501-1194Japan Department of Internal Medicine for Inflammatory Bowel Disease The University of ToyamaToyama 930-0194Japan Center for Clinical Research and Education Hyogo Medical UniversityNishinomiya 663-8501Japan

BACKGROUND Real-world data on tofacitinib(TOF)covering a period of more than 1 year for a sufficient number of Asian patients with ulcerative colitis(UC)are scarce.AIM To investigate the long-term efficacy and safety of TOF treatment for UC,including clinical issues.METHODS We performed a retrospective single-center observational analysis of 111 UC patients administered TOF at Hyogo Medical University as a tertiary inflammatory bowel disease center.All consecutive UC patients who received TOF between May 2018 and February 2020 were enrolled.Patients were followed up until August 2020.The primary outcome was the clinical response rate at week 8.Secondary outcomes included clinical remission at week 8,cumulative persistence rate of TOF administration,colectomy-free survival,relapse after tapering of TOF and predictors of clinical response at week 8 and week 48.RESULTS The clinical response and remission rates were 66.3%and 50.5%at week 8,and 47.1%and 43.5%at week 48,respectively.The overall cumulative clinical remission rate was 61.7%at week 48 and history of anti-tumor necrosis factor-alpha(TNF-α)agents use had no influence(P=0.25).The cumulative TOF persistence rate at week 48 was significantly lower in patients without clinical remission than in those with remission at week 8(30.9%vs 88.1%;P<0.001).Baseline partial Mayo Score was significantly lower in responders vs non-responders at week 8(odds ratio:0.61,95%confidence interval:0.45-0.82,P=0.001).Relapse occurred in 45.7%of patients after TOF tapering,and 85.7%of patients responded within 4 wk after re-increase.All 6 patients with herpes zoster(HZ)developed the infection after achieving remission by TOF.CONCLUSION TOF was more effective in UC patients with mild activity at baseline and its efficacy was not affected by previous treatment with anti-TNF-αagents.Most relapsed patients responded again after re-increase of TOF and nearly half relapsed after tapering off TOF.Special attention is needed for tapering and HZ.

关键词： Ulcerative colitis Tofacitinib Janus kinase inhibitor Real-world Biologics

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Initial decrease in the lipoprotein(a)level is a novel prognostic biomarker in patients with acute coronary syndrome

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World Journal of Cardiology 2024年第6期16卷 329-338页

作者： Yasuhiko Saeki Jun Sawaguchi Satori Akita Taka-aki Takamura Kosuke Fujibayashi Minoru Wakasa Hironobu Akao Michihiko Kitayama Yasuyuki kawai Kouji Kajinami Department of Cardiology Kanazawa Medical UniversityUchinada 9200293Japan Trans-catheter Cardiovascular Therapeutics Kanazawa Medical UniversityUchinada 9200293Japan

BACKGROUND Lipoprotein(a)[Lp(a)]is a causal risk factor for atherosclerotic cardiovascular diseases;however,its role in acute coronary syndrome(ACS)remains unclear.AIM To investigate the hypothesis that the Lp(a)levels are altered by various conditions during the acute phase of ACS,resulting in subsequent cardiovascular events.METHODS From September 2009 to May 2016,377 patients with ACS who underwent emergent coronary angiography,and 249 who completed≥1000 d of follow-up were enrolled.Lp(a)levels were measured using an isoform-independent assay at each time point from before percutaneous coronary intervention(PCI)to 48 h after PCI.The primary endpoint was the occurrence of major adverse cardiac events(MACE;cardiac death,other vascular death,ACS,and non-cardiac vascular events).RESULTS The mean circulating Lp(a)level decreased significantly from pre-PCI(0 h)to 12 h after(19.0 mg/dL to 17.8 mg/dL,P<0.001),and then increased significantly up to 48 h after(19.3 mg/dL,P<0.001).The changes from 0 to 12 h[Lp(a)Δ0-12]significantly correlated with the basal levels of creatinine[Spearman’s rank correlation coefficient(SRCC):-0.181,P<0.01]and Lp(a)(SRCC:-0.306,P<0.05).Among the tertiles classified according to Lp(a)Δ0-12,MACE was significantly more frequent in the lowest Lp(a)Δ0-12 group than in the remaining two tertile groups(66.2%vs 53.6%,P=0.034).A multivariate analysis revealed that Lp(a)Δ0-12[hazard ratio(HR):0.96,95%confidence interval(95%CI):0.92-0.99]and basal creatinine(HR:1.13,95%CI:1.05-1.22)were independent determinants of subsequent MACE.CONCLUSION Circulating Lp(a)levels in patients with ACS decreased significantly after emergent PCI,and a greater decrease was independently associated with a worse prognosis.

关键词： Lipoprotein(a) Acute coronary syndrome Percutaneous coronary intervention Major adverse cardiac events Prognosis

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SPERA Hydrogen System^(TM)by LOHC-MCH Method for Massive Hydrogen Storage and Transportation

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Journal of Environmental Science and Engineering(A) 2024年第2期13卷 50-60页

作者： Yoshimi Okada Kaji Naohiro Osamu Ikeda Kenichi Imagawa Hironori kawai Masashi Nagai Yasuhiro Inoue Frontier Business Division Chiyoda Corporation4-6-2 Minatomirai Nishi-kuYokohama 2208765Japan Hydrogen Business Department Chiyoda Corporation4-6-2 Minatomirai Nishi-kuYokohama 2208765Japan R&D Center Chiyoda Corporation3-13 Moriya-cho Kanagawa-kuYokohama 2208765Japan Technology Development Department Chiyoda Corporation4-6-2 Minatomirai Nishi-kuYokohama 2208765Japan

Expanding the hydrogen energy utilization is essential for decarbonization,and the commercialization of hydrogen energy carrier systems that can“store”and“transport”hydrogen in a large scale is necessary.The organic chemical hydride method incorporates hydrogen atoms into the molecular structure of a LOHC(Liquid Organic Hydrogen Carrier)to store and transport hydrogen in a liquid state under normal temperature and pressure,and is a highly safe method with low business risk.Chiyoda has been developing the technology since 2002,completed a pilot demonstration in 2014 and named it the SPERA Hydrogen^(TM) System,and successfully completed an international supply chain demonstration that transports hydrogen from Brunei to Japan in a large scale in 2020,moving to the commercialization stage.Currently,Chiyoda is conducting feasibility studies with a number of domestic and foreign companies with the aim of commercializing the system as soon as possible.In this paper,outline,features,development status and our efforts in commercialization of SPERA HydrogenTM System are introduced.

关键词： Hydrogen carrier LOHC Methylcyclohexane MCH toluene

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Current perspectives of viral

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World Journal of Gastroenterology 2024年第18期30卷 2402-2417页

作者： Daisuke Usuda Yuki Kaneoka Rikuo Ono Masashi Kato Yuto Sugawara Runa Shimizu Tomotari Inami EriNakajima Shiho Tsuge Riki Sakurai Kenji kawai Shun Matsubara Risa Tanaka Makoto Suzuki ShintaroShimozawa Yuta Hotchi Ippei Osugi Risa Katou Sakurako Ito Kentaro Mishima Akihiko Kondo KeikoMizuno Hiroki Takami Takayuki Komatsu Tomohisa Nomura Manabu Sugita Department of Emergency and Critical Care Medicine Juntendo University Nerima HospitalNerima 177-8521TokyoJapan Department of Sports Medicine Faculty of MedicineJuntendo UniversityBunkyo 113-8421TokyoJapan

Viral hepatitis represents a major danger to public health,and is a globally leading cause of death.The five liver-specific viruses:Hepatitis A virus,hepatitis B virus,hepatitis C virus,hepatitis D virus,and hepatitis E virus,each have their own unique epidemiology,structural biology,transmission,endemic patterns,risk of liver complications,and response to antiviral therapies.There remain few options for treatment,in spite of the increasing prevalence of viral-hepatitiscaused liver disease.Furthermore,chronic viral hepatitis is a leading worldwide cause of both liver-related morbidity and mortality,even though effective treatments are available that could reduce or prevent most patients’complications.In 2016,the World Health Organization released its plan to eliminate viral hepatitis as a public health threat by the year 2030,along with a discussion of current gaps and prospects for both regional and global eradication of viral hepatitis.Today,treatment is sufficiently able to prevent the disease from reaching advanced phases.However,future therapies must be extremely safe,and should ideally limit the period of treatment necessary.A better understanding of pathogenesis will prove beneficial in the development of potential treatment strategies targeting infections by viral hepatitis.This review aims to summarize the current state of knowledge on each type of viral hepatitis,together with major innovations.

关键词： Hepatitis A virus Hepatitis B virus Hepatitis C virus Hepatitis D virus Hepatitis E virus Current perspectives

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Assessment of delayed bleeding after endoscopic submucosal dissection of early-stage gastrointestinal tumors in patients receiving direct oral anticoagulants

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World Journal of Gastroenterology 2023年第19期29卷 2916-2931页

作者： Mitsushige Sugimoto Masaki Murata Takashi kawai Department of Gastroenterological Endoscopy Tokyo Medical University HospitalTokyo 160-0023Japan Department of Gastroenterology National Hospital Organization Kyoto Medical CenterKyoto 612-8555Japan

Delayed bleeding is a major and serious adverse event of endoscopic submucosal dissection(ESD)for early-stage gastrointestinal tumors.The rate of post-ESD bleeding for gastric cancer is higher(around 5%-8%)than that for esophagus,duodenum and colon cancer(around 2%-4%).Although investigations into the risk factors for post-ESD bleeding have identified several procedure-,lesion-,physician-and patient-related factors,use of antithrombotic drugs,especially anticoagulants[direct oral anticoagulants(DOACs)and warfarin],is thought to be the biggest risk factor for post-ESD bleeding.In fact,the post-ESD bleeding rate in patients receiving DOACs is 8.7%-20.8%,which is higher than that in patients not receiving anticoagulants.However,because clinical guidelines for management of ESD in patients receiving DOACs differ among countries,it is necessary for endoscopists to identify ways to prevent post-ESD delayed bleeding in clinical practice.Given that the pharmacokinetics(e.g.,plasma DOAC level at both trough and T_(max))and pharmacodynamics(e.g.,anti-factor Xa activity)of DOACs are related to risk of major bleeding,plasma DOAC level and anti-FXa activity may be useful parameters for monitoring the anti-coagulate effect and identifying DOAC patients at higher risk of post-ESD bleeding.

关键词： Direct oral anticoagulants Gastrointestinal tumors Endoscopic submucosal dissection Delayed bleeding Adverse events Anticoagulants

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Square-Scheme Electrochemistry in Battery Electrodes

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Accounts of Materials Research 2022年第1期3卷 33-41页

作者： Masashi Okubo Kosuke kawai Zihan Ma Atsuo Yamad Department of Electrical Engineering and Bioscience School of Advanced Science and EngineeringWaseda UniversityTokyo 169-8555Japan Department of Chemical System Engineering School of EngineeringThe University of TokyoTokyo 113-8656Japan

CONSPECTUS:Sustainable development cannot be achieved without substantial technological advancements.For instance,flexible electricity management requires smart power sourcing with advanced energy storage/conversion technologies.Remedies for abrupt power spikes/drops observed in renewable energy sources such as solar and wind require rapid load-leveling using high-power energy storage systems when they are integrated into a microgrid.Electrochemical energy storage devices efficiently convert electrical and chemical energy,which can potentially function as distributed power sources.Among these,lithium-ion batteries are a present de facto standard with their relatively high energy density and energy efficiencies that are based on topochemical intercalation chemistry,whereby guest lithium ions are(de)intercalated reversibly with simultaneous redox reactions and minimal structural changes.However,their energy density,power density,life-cycle cost,calendar life,and safety remain unsatisfactory for widespread use.When the storage capacity is maximized,as a result of which a labile deep charge/discharge state is generated,to develop batteries with high energy density,subsequent irreversible phase transformations or chemical reactions occur in many cases.The combination of the reversible electrode reactions and the subsequent irreversible phase transformations sometimes causes a charge/discharge curve characterized by a large voltage hysteresis with 100%Coulombic efficiency.Because a large voltage hysteresis significantly degrades the energy efficiency,unveiling the reaction mechanism is of primary importance in mitigating energy loss.

关键词： Battery lithium irreversible

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Extracellular matrix gene expression in human trabecular meshwork cells following mechanical fluid flow stimulation

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International Journal of Ophthalmology(English edition) 2022年第3期15卷 388-393页

作者： Koichi Yoshida Motofumi kawai Tsugiaki Utsunomiya Akihiro Ishibazawa Young-Seok Song Mariana Sayuri BUdo Yoshikazu Tasaki Akitoshi Yoshida Department of Ophthalmology Asahikawa Medical UniversityAsahikawaHokkaido 078-8510Japan Department of Hospital Pharmacy&Pharmacology Asahikawa Medical UniversityAsahikawaHokkaido 078-8510Japan

AIM: To investigate changes in extracellular matrix(ECM) gene expression in human trabecular meshwork(HTM) cells in response to mechanical fluid flow stimulation.METHODS: HTM cells were grown on a glass plate coated with 0.02% type Ⅰ collagen(COL) and exposed to shear stress(0, 0.2, 1.0 dyne/cm;) for 12 h.Changes in genes related to the ECM were evaluated by real-time reverse transcriptase-polymerase chain reaction.Phosphorylation of Smad2 protein was investigated by Western blotting.RESULTS: After mechanical stimulation, COL type 4 alpha 2, COL type 6 alpha 1, and fibronectin-1 mRNA were significantly higher than the static control(P<0.05, <0.05, and <0.01, respectively).The metalloproteinase-2 and plasminogen activator inhibitor-1 mRNA were significantly higher than the static control(P<0.05 and <0.01, respectively), while the differences in the tissue inhibitors of metalloproteinases-2 mRNA were not significant.The phosphorylation of Smad2 levels was significantly higher compared to the static control cells.CONCLUSION: Changes in the expressions of genes associated ECM metabolism result in HTM cells after mechanical stimulation.The mechanical stimulation of the aqueous humor to the trabecular meshwork may promote ECM turnover and contribute to intraocular pressure homeostasis.

关键词： trabecular meshwork shear stress aqueous humor extracellular matrix glaucoma intraocular pressure

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Effects of General Anesthesia on the Results of Cardiac Catheterization in Pediatric Patients with Ventricular Septal Defect

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Congenital Heart Disease 2023年第2期18卷 235-243页

作者： Kiyotaka Go Taichi Kato Machiko Kito Yoshihito Morimoto Satoru kawai Hidenori Yamamoto Yoshie Fukasawa Kazushi Yasuda Department of Pediatric Cardiology Aichi Children’s Health and Medical CenterObu474-8710Japan Department of Pediatrics Nagoya University Graduate School of MedicineNagoya466-8560Japan

Background:There is no gold standard sedation method for pediatric cardiac catheterization.In congenital heart diseases with intracardiac shunts,hemodynamic parameters are prone to change depending on the ventilation conditions and anesthetics,although few studies have examined these effects.The purpose of this study was to investigate the effects of two different sedation methods on the hemodynamic parameters.Methods:This study retrospectively evaluated consecutive patients with ventricular septal defect(VSD)below 1 year of age who underwent cardiac catheterization at Aichi Children’s Health and Medical Center,who were divided into age-and VSD diameter-matched general anesthesia(GA)and monitored anesthesia care(MAC)under the natural airway groups(n=40 each),for comparison of hemodynamic parameters.Results:In the GA group,arterial blood pH and arterial partial pressure of oxygen were significantly higher(p<0.01),whereas arterial partial pressure of carbon dioxide was significantly lower than in the MAC group(p<0.01).Mean pulmonary artery pressure(p<0.05)and systemic blood pressure(p<0.01)were lower in the GA group.Pulmonary vascular resistance index(p<0.01)and systemic vascular resistance index(p<0.01)were also significantly lower in the GA group than the MAC group.There were no significant differences in pulmonary blood flow index,systemic blood flow index,and pulmonary/systemic blood flow ratio between the two groups.Conclusions:Cardiac catheterization under GA in VSD patients results in different hemodynamic parameters compared to that under MAC.In particular,when using pulmonary artery pressure and pulmonary vascular resistance measured under GA for judgment regarding the surgical indications or perioperative management,consideration should be given to the fact that these parameters might be lower compared to those measured under MAC.

关键词： Ventricular septal defect cardiac catheterization general anesthesia monitored anesthesia care

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