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Perimuscular connective tissue contains more and larger lymphatic vessels than the shallower layers in human gallbladders

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World Journal of Gastroenterology 2007年第33期13卷 4480-4483页

作者： masayuki nagahashi Yoshio Shirai Toshifumi Wakai Jun Sakata Yoichi Ajioka Katsuyoshi Hatakeyama Division of Digestive and General Surgery Niigata University Graduate School of Medicaland Dental Sciences Niigata Japan Division of Molecular and Diagnostic Pathology Niigata University Graduate School of Medical and Dental Sciences Asahimachi-dori Niigata City Japan

AIM： To clarify whether perimuscular connective tissue contains more lymphatic vessels than the shallower layers in human gallbladders. METHODS： Lymphatic vessels were stained immunohistochemically with monoclonal antibody D2-40, which is a specific marker of lymphatic endothelium, in representative sections of 12 normal human gallbladders obtained at the time of resection for colorectal carcinoma liver metastases. In individual gallbladder specimens, nine high-power （×200） fields with the highest lymphatic vessel density （LVD）, termed ＂hot spots＂; were identified for each layer （mucosa, muscle layer, and perimuscular connective tissue）. In individual hot spots, the LVD and relative lymphatic vessel area （LVA） were measured microscopically using a computer-aided image analysis system. The mean LVD and LVA values for the nine hot spots in each layer were used for statistical analyses. RESULTS： In the mucosa, muscle layer, and perimuscular connective tissue, the LVD was 16.1 ± 9.2, 35.4 ± 15.7, and 65.5 ± 12.2, respectively, and the LVA was 0.4 ± 0.4, 2.1 ± 1.1, and 9.4 ± 2.6, respectively. Thus, both the LVD and LVA differed significantly （P 〈 0.001 and P 〈 0.001, respectively; KruskaI-Wallis test） among the individual layers of the wall of the gallbladder, with the highest LVD and LVA values in the perimuscular connective tissue. Most （98 of 108） of the hot spots within the perimuscular connective tissue were located within 500 μm of the lower border of the muscle layer. CONCLUSION： The perimuscular connective tissue contains more and larger lymphatic vessels than the shallower layers in the human gallbladder. This observation partly explains why the incidence of lymph node metastasis is high in T2 （tumor invading the perimuscular connective tissue） or more advanced gallbladder carcinoma.

关键词： Gallbladder Lymphatic vessels Monoclonal antibody D2-40 Gallbladder neoplasms Lymphaticmetastasis

Inverted Meckel's diverticulum as a cause of occult lower gastrointestinal hemorrhage

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World Journal of Gastroenterology 2012年第42期18卷 6155-6159页

作者： Omar M Rashid Joseph K Ku masayuki nagahashi Akimitsu Yamada Kazuaki Takabe Department of Surgery Virginia Commonwealth UniversityRichmondVA 23220United States Precision Plastic Surgery RiversideCA 92506United States

Meckel's diverticulum is a common asymptomatic congenital gastrointestinal anomaly,but rarely it can present with *** the last few years inverted Meckel's diverticulum has been reported in the literature with increasing frequency as an occult source of lower gastrointestinal ***,we report a case of a 54-year-old male,who was referred for surgical evaluation with persistent anemia and occult blood per rectum after a work up which failed to localize the source over 12 mo,including upper and capsule endoscopy,colonoscopy,enteroclysis,Meckel scan,and tagged nuclear red blood cell *** abdominal computed tomography scan showed a possible mid-ileal intussusception and intraluminal *** the abdominal exploration,inverted Meckel's diverticulum was diagnosed and *** review the literature,discuss the forms in which the disease presents,the diagnostic modalities utilized,pathological findings,and *** less than 40 cases have been reported in the English literature from 1978 to 2005,19 cases have been reported in the last 6 years alone(2006-2012) due to improved diagnostic *** diagnosis and treatment of this disease requires a high index of clinical suspicion,which is becoming increasingly relevant to general gastroenterologists.

关键词： Inverted Meckel's diverticulum Gastrointestinal hemorrhage Lower gastrointestinal bleeding Intussusceptions

Resolvins and omega three polyunsaturated fatty acids: Clinical implications in inflammatory diseases and cancer

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World Journal of Clinical Cases 2016年第7期4卷 155-164页

作者： Kazuki Moro masayuki nagahashi Rajesh Ramanathan Kazuaki Takabe Toshifumi Wakai Division of Digestive and General Surgery Niigata University Graduate School of Medical and Dental Sciences Division of Surgical Oncology Department of Surgery Virginia Commonwealth University School of Medicine and the Massey Cancer Center

Inflammation is a central process in several disorders and contributes to cancer progression. Inflammation involves a complex cascade of pro-inflammatory and anti-inflammatory signaling events with protein and lipid mediators. Recent advances in lipid detection have revealed the importance of lipid mediators in inflammation. Omega three polyunsaturated fatty acids(ω-3 PUFA) are found naturally in fish oil and have been extensively studied in multiple inflammatory diseases with improved outcomes. Resolvins are thought to be the active metabolites of ω-3 PUFA, and are responsible for facilitating the resolving phase of acute inflammation. Clinically, resolvins have been associated with resolution of acute kidney injury and acute lung injury, micro and macro vascular response to injury, and inhibition of microglia-activated inflammation in neurodegenerative disorders. In addition to inflammatory diseases, ω-3 PUFA and resolvins appear to modulate cancer progression. ω-3 PUFA intake has been associated with reduced inflammation in colorectal cancer, and favorable phenotype in breast cancer. Resolvins offer promising therapeutic potential as they may modulate inflammation with minimal side-effects, in contrast to currently available anti-inflammatory medications. This review describes the roles of ω-3 PUFA and resolvins in the inflammatory cascade, various inflammatory diseases, and specific cancers. Additionally, it will discuss the clinical therapeutic potential of resolvins astargets in inflammatory diseases and cancers.

关键词： Anti-inflammatory lipid mediators Resolvin Omega three polyunsaturated fatty acids Inflammatory diseases Cancer

Bile acids as global regulators of hepatic nutrient metabolism

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Liver Research 2017年第1期1卷 10-16页

作者： Phillip B.Hylemon Kazuaki Takabe Mikhail Dozmorov masayuki nagahashi Huiping Zhou Department of Microbiology and Immunology Medical College of Virginia CampusVirginia Commonwealth UniversityRichmondVAUSA McGuire VA Medical Center RichmondVAUSA Department of Surgery Medical College of Virginia CampusVirginia Commonwealth UniversityRichmondVAUSA Department of Biostatistics Medical College of Virginia CampusVirginia Commonwealth UniversityRichmondVAUSA Department of Surgery Niigata UniversityJapan

Bile acids(BA)are synthesized from cholesterol in the *** are essential for promotion of the absorption of lipids,cholesterol,and lipid-soluble vitamins from the *** are hormones that regulate nutrient metabolism by activating nuclear receptors(farnesoid X receptor(FXR),pregnane X receptor,vitamin D)and G protein-coupled receptors(e.g.,TGR5,sphingosine-1-phosphate receptor 2(S1PR2))in the liver and *** the liver,S1PR2 activation by conjugated BAs activates the extracellular signal-regulated kinase 1/2 and AKT signaling pathways,and nuclear sphingosine kinase *** latter produces sphingosine-1-phosphate(S1P),an inhibitor of histone deacetylases 1/2,which allows for the differential up-regulation of expression of genes involved in the metabolism of sterols and *** discuss here the emerging concepts of the interactions of BAs,FXR,insulin,S1P signaling and nutrient metabolism.

关键词： Sphingosine-1-phosphate Sphingosine kinase 2 Sphingosine-1-phosphate receptor 2 Fatty liver Epigenetics

Genetic changes of p53,K-ras,and microsatellite instability in gallbladder carcinoma in high-incidence areas of Japan and Hungary

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World Journal of Gastroenterology 2008年第1期14卷 70-75页

作者： masayuki nagahashi Yoichi Ajioka Istvan Lang Zoltan Szentirmay Miklos Kasler Hiroto Nakadaira Naoyuki Yokoyama Gen Watanabe Ken Nishikura Toshifumi Wakai Yoshio Shirai Katsuyoshi Hatakeyama Masaharu Yamamoto Division of Molecular and Diagnostic Pathology Niigata University Graduate School of Medical and Dental Sciences Niigata 951-8510 Japan Department of Medical Oncology "B" National Institute of Oncology Budapest H-1122 Hungary Department of Molecular Pathology National Institute of Oncology Budapest H-1122 Hungary Department of Head and Neck Surgery National Institute of Oncology Budapest H-1122 Hungary Department of Nursing Faculty of Nursing Social Welfare and Psychology Niigata Seiryo University Niigata 951-8510 Japan Division of Digestive and General Surgery Niigata University Graduate School of Medical and Dental Sciences Niigata 951-8510 Japan Department of Community Preventive Medicine Niigata University Graduate School of Medical and Dental Sciences Niigata 951-8510 Japan

AIM： To disclose geographic differences in genetic changes involved in gallbladder carcinogenesis between two distinct high-incidence areas of Japan and Hungary. METHODS： We examined 42 cases of gallbladder carcinoma： 22 Japanese and 20 Hungarian cases, p53 mutations at exons 5 to 8 and K-ras mutations at codon 12 were tested by direct sequencing. Microsatellite instability was determined from fluorescent dye-labeled PCR amplifications of flve-microsatellite markers （BAT-25, BAT-26, D2S123, DSS346, and D17S250）. RESULTS： Mutations of p53 were detected in 11 of 22 Japanese cases and 6 of 18 Hungarian cases （11/22 vs 6/18, P = 0.348）. Transition at CpG sites was found in none of 11 Japanese cases and 2 of 6 Hungarian cases; the difference was marginally significant （0/11 vs 2/6,P = 0.110）. K-ras mutations were detected in only one of the Hungarian cases. Eight of 19 （42.1%） ]apanese cases were MSI-high （presence of novel peaks in more than one of the five loci analyzed）, whereas only 1 of 15 （6.7%） Hungarian cases was MSI-high （P = 0.047）. CONCLUSION： It appears that the p53 mutations and MSI differ in patients with gallbladder carcinoma between two distinct high-incidence areas. Geographic variation might exist in the process of gallbladder carcinogenesis.

关键词： Gallbladder Gallbladder Neoplasms K-ras Microsatellite instability p53

Cost-Effectiveness Analysis of Neoadjuvant Chemotherapy with Zoledronic Acid for HER2-Negative Breast Cancer in Japan: The JONIE1 Study

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Health 2019年第8期11卷 1017-1027页

作者： Kyoko Nakazawa Shota Saito masayuki nagahashi Akimitsu Yamada Akira Toyama Kouhei Akazawa Department of Medical Informatics and Statistics Niigata University Graduate School of Medical and Dental Sciences Niigata Japan Department of Pharmacy Niigata University Medical and Dental Hospital Niigata Japan Department of Health Informatics Niigata University of Health and Welfare Niigata Japan Division of Digestive and General Surgery Niigata University Graduate School of Medical and Dental Sciences Niigata Japan Department of Gastroenterological Surgery Yokohama City University School of Medicine Kanagawa Japan Department of Medical Informatics Niigata University Medical and Dental Hospital Niigata Japan

Objective: Zoledronic acid (ZOL) is a nitrogen-containing bisphosphonate that induces osteoclast apoptosis and inhibits bone resorption. Adding ZOL to neoadjuvant chemotherapy has been shown to have potential anticancer benefits in women with HER2-negative breast cancer. The objective of the present study was to investigate ZOL’s cost-effectiveness from the perspective of health care payers in Japan. Methods: A Markov model was developed to evaluate the costs and effectiveness associated with ZOL + chemotherapy (CTZ) and chemotherapy (CT) alone over a 10-year time horizon. Monthly transition probabilities were estimated according to JONIE1 (Japan Organization of Neoadjuvant Innovative Expert) Study data and an extrapolated Weibull model. Health outcomes were measured in quality-adjusted life years (QALYs). Costs were calculated using year-2018 Japanese yen (JPY) (1.00 US dollars (USD) = 110.4 JPY). Model robustness was addressed through one-way and probabilistic sensitivity analysis. The costs and QALYs were discounted at a rate of 2% per year. Results: In the base case, the use of CTZ was associated with a gain of 3.94 QALYs. The incremental cost per QALY of the CTZ gain was 681,056.1 JPY (6168.99 USD) per QALY. Conclusion: It is convincing that neoadjuvant CTZ for patients with breast cancer would be expected to have statistically significant clinical efficacy. Addition of ZOL to CT might be a cost-effective option compared with CT alone.

关键词： Cost-Effectiveness Incremental Cost-Effectiveness Ratio (ICER) Quality-Adjusted Life Year (QALY) Chemotherapy HER2-Negative Breast Cancer

Prophylactic lateral pelvic lymph node dissection in stage Ⅳ low rectal cancer

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World Journal of Clinical Oncology 2017年第5期8卷 412-419页

作者： Hiroshi Tamura Yoshifumi Shimada Hitoshi Kameyama Ryoma Yagi Yosuke Tajima Takuma Okamura Mae Nakano Masato Nakano masayuki nagahashi Jun Sakata Takashi Kobayashi Shin-ichi Kosugi Hitoshi Nogami Satoshi Maruyama Yasumasa Takii Toshifumi Wakai Division of Digestive and General Surgery Niigata University Graduate School of Medical and Dental Sciences Department of Digestive and General Surgery Uonuma Institute of Community MedicineNiigata University Medical and Dental Hospital Department of Surgery Niigata Cancer Center Hospital

AIM To assess the clinical significance of prophylactic lateral pelvic lymph node dissection (LPLND) in stage Ⅳ low rectal *** We selected 71 consecutive stage Ⅳ low rectal cancer patients who underwent primary tumor resection,and enrolled 50 of these 71 patients without clinical LPLN *** patients had distant metastasis such as liver,lung,peritoneum,and paraaortic *** LPLN metastasis was defined as LN with a maximum diameter of 10 mm or more on preoperative pelvic computed tomography *** patients underwent primary tumor resection,27 patients underwent total mesorectal excision(TME) with LPLND(LPLND group),and 23 patients underwent only TME(TME group).Bilateral LPLND was performed simultaneously with primary tumor resection in LPLND group.R0 resection of both primary and metastatic sites was achieved in 20 of 50 *** evaluated possible prognostic factors for 5-year overall survival (OS),and compared 5-year cumulative local recurrence between the LPLND and TME *** For OS,univariate analyses revealed no significant benefit in the LPLND compared with the TME group (28.7% vs 17.0%,P = 0.523); multivariate analysis revealed that R0 resection was an independent prognostic *** cumulative local recurrence,the LPLND group showed no significant benefit compared with TME group (21.4% vs 14.8%,P = 0.833).CONCLUSION Prophylactic LPLND shows no oncological benefits in patients with Stage Ⅳ low rectal cancer without clinical LPLN metastasis.

关键词： Prophylactic lateral pelvic lymph node dissection StageⅣ Low rectal cancer

Dynamic Force Reduction and Heat Transfer Improvement for Horizontal Tubes in Large-Particle Gas-Fluidized Beds

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Journal of Thermal Science 2008年第1期17卷 77-83页

作者： Yusumi nagahashi John R.Grace Kok-Seng Lim Yutaka Asako Dept.Mech.Eng. Kochi National College of Technol.KochiJAPAN Professor Dept.Chem.Biological Eng. The University of British ColumbiaVancouverCANADA CSIRO Minerals VictoriaAUSTRALIA Dept.Mech.Eng. Tokyo Metropolitan UniversityTokyoJAPAN

The effects of tube bank configuration on forces and heat transfer were investigated for both two-dimensional and three-dimensional gas fluidized beds. Effective dynamic forces and heat transfer coefficients were measured for several tube bank configurations, and it was found that the average forces are smaller than for a single tube. The heat transfer coefficient can be increased by providing sufficient space for particles to descend around both sides of the tube bank. The results provide useful guidelines for optimizing the configuration of tube banks to achieve high heat transfer coefficients while reducing tube erosion due to dynamic forces.

关键词： fluidized beds forces heat transfer tube arrangement sofid circulation

Adult stem cells in neural repair: Current options, limitations and perspectives

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World Journal of Stem Cells 2015年第2期7卷 477-482页

作者： Eric Domingos Mariano Manoel Jacobsen Teixeira Suely Kazue nagahashi Marie Guilherme Lepski Department of Neurology Medicine SchoolUniversity of Sao Paulo Sao Paulo SP 01246-903 Brazil Center for Cellular and Molecular Studies and Therapy-NAP-NETCEM University of Sao Paulo Sao Paulo SP 01246-903 Brazil Department of Neurosurgery Medicine SchoolUniversity of Sao Paulo Sao Paulo SP 01246-903 Brazil Department of Neurosurgery Eberhard-Karls University 72074 Tuebingen Germany

Stem cells represent a promising step for the future of regenerative medicine. As they are able to differentiate into any cell type, tissue or organ, these cells are great candidates for treatments against the worst diseasesthat defy doctors and researchers around the world. Stem cells can be divided into three main groups:(1) embryonic stem cells;(2) fetal stem cells; and(3) adult stem cells. In terms of their capacity for proliferation, stem cells are also classified as totipotent, pluripotent or multipotent. Adult stem cells, also known as somatic cells, are found in various regions of the adult organism, such as bone marrow, skin, eyes, viscera and brain. They can differentiate into unipotent cells of the residing tissue, generally for the purpose of repair. These cells represent an excellent choice in regenerative medicine, every patient can be a donor of adult stem cells to provide a more customized and efficient therapy against various diseases, in other words, they allow the opportunity of autologous transplantation. But in order to start clinical trials and achieve great results, we need to understand how these cells interact with the host tissue, how they can manipulate or be manipulated by the microenvironment where they will be transplanted and for how long they can maintain their multipotent state to provide a full regeneration.

关键词： Stem cells Stem cell therapy Adult stem cells Neural stem cells Bone marrow stem cells Mesenchymal stem cells Olfactory ensheathing cells