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| 1 | Association of Fusobacterium nucleatum with immunity andmolecular alterations in colorectal cancer显示文摘The human intestinal microbiome plays a major role in human health and diseases, including colorectal cancer. Colorectal carcinogenesis represents a heterogeneous process with a differing set of somatic molecular alterations, influenced by diet, environmental and microbial exposures, and host immunity. Fusobacterium species are part of the human oral and intestinal microbiota. Metagenomic analyses have shown an enrichment of Fusobacterium nucleatum(F. nucleatum) in colorectal carcinoma tissue. Using 511 colorectal carcinomas from Japanese patients, we assessed the presence of F. nucleatum. Our results showed that the frequency of F. nucleatum positivity in the Japanese colorectal cancer was 8.6%(44/511), which was lower than that in United States cohort studies(13%). Similar to the United States studies, F. nucleatum positivityin Japanese colorectal cancers was significantly associated with microsatellite instability(MSI)-high status. Regarding the immune response in colorectal cancer, high levels of infiltrating T-cell subsets(i.e., CD3+, CD8+, CD45RO+, and FOXP3+ cells) have been associated with better patient prognosis. There is also evidence to indicate that molecular features of colorectal cancer, especially MSI, influence T-cell-mediated adaptive immunity. Concerning the association between the gut microbiome and immunity, F. nucleatum has been shown to expand myeloid-derived immune cells, which inhibit T-cell proliferation and induce T-cell apoptosis in colorectal cancer. This finding indicates that F. nucleatum possesses immunosuppressive activities by inhibiting human T-cell responses. Certain micro RNAs are induced during the macrophage inflammatory response and have the ability to regulate host-cell responses to pathogens. Micro RNA-21 increases the levels of IL-10 and prostaglandin E2, which suppress antitumor T-cell-mediated adaptive immunity through the inhibition of the antigen-presenting capacities of dendritic cells and T-cell proliferation in colorectal cancer cells. Thus, emerging evidence may provide insights for strategies to target microbiota, immune cells and tumor molecular alterations for colorectal cancer prevention and treatment. Further investigation is needed to clarify the association of Fusobacterium with T-cells and micro RNA expressions in colorectal cancer. | Katsuhiko Nosho Yasutaka Sukawa Yasushi Adachi Miki Ito Kei Mitsuhashi Hiroyoshi Kurihara Shinichi Kanno Itaru Yamamoto Keisuke Ishigami Hisayoshi Igarashi Reo Maruyama Kohzoh Imai Hiroyuki Yamamoto Yasuhisa Shinomura | 2016 | World Journal of Gastroenterology2016，22，2： | 44 |
| 2 | Review of the diagnosis and management of gastrointestinal bezoars显示文摘The formation of a bezoar is a relatively infrequentdisorder that affects the gastrointestinal system.Bezoars are mainly classified into four types dependingon the material constituting the indigestible mass of thebezoar phytobezoars, trichobezoars, pharmacobezoars,and lactobezoars. Gastric bezoars often cause ulcerativelesions in the stomach and subsequent bleeding,whereas small intestinal bezoars present with smallbowel obstruction and ileus. A number of articles haveemphasized the usefulness of Coca-Cola? administrationfor the dissolution of phytobezoars. However, persimmonphytobezoars may be resistant to such dissolutiontreatment because of their harder consistency comparedto other types of phytobezoars. Better understanding ofthe etiology and epidemiology of each type of bezoarwill facilitate prompt diagnosis and management.Here we provide an overview of the prevalence, classification,predisposing factors, and manifestations ofbezoars. Diagnosis and management strategies arealso discussed, reviewing mainly our own case series.Recent progress in basic research regarding persimmonphytobezoars is also briefly reviewed. | Masaya Iwamuro Hiroyuki Okada Kazuhiro Matsueda Tomoki Inaba Chiaki Kusumoto Atsushi Imagawa Kazuhide Yamamoto | 2015 | World Journal of Gastrointestinal Endoscopy2015，7，4： | 22 |
| 3 | Association of glypican-3 expression with growth signaling molecules in hepatocellular carcinoma显示文摘AIM:To clarify the association of glypican-3(GPC3)expression with Wnt and other growth signaling molecules in hepatocellular carcinoma(HCC). METHODS:Expression of GPC3,Wnt,matrix metalloproteinases(MMPs),sulfatase(SULF)1,SULF2,and other growth signaling molecules was analyzed in HCC cell lines and tissue samples by real-time reverse transcriptionpolymerase chain reaction,immunoblotting,and/or immunostaining.Expression of various genes in GPC3 siRNA-transfected HCC cells was analyzed. RESULTS:GPC3 was overexpressed in most HCCs at mRNA and protein levels and its serum levels weresignificantly higher in patients with HCC than in non- HCC subjects(P<0.05).Altered expressions of various MMPs and growth signaling molecules,some of which were correlated with GPC3 expression,were observed in HCCs.Down-regulation of GPC3 expression by siRNA in GPC3-overexpressing HCC cell lines resulted in a significant decrease in expressions of MMP2,MMP14,fibroblast growth factor receptor 1,insulin-like growth factor 1 receptor.GPC3 expression was significantly correlated with nuclear/cytoplasmic localization ofβ-catenin. CONCLUSION:These results suggest that GPC3,in conjunction with MMPs and growth signaling molecules, might play an important role in the progression of HCC. | Noriyuki Akutsu Hiroyuki Yamamoto Shigeru Sasaki Hiroaki Taniguchi Yoshiaki Arimura Kohzoh Imai Yasuhisa Shinomura | 2010 | World Journal of Gastroenterology2010，16，28： | 20 |
| 4 | Transcriptional silencing of Dickkopf gene family by CpG island hypermethylation in human gastrointestinal cancer显示文摘AIM: To clarify alterations of Dickkopfs (Dkks) and Kremen2 (Krm2) in gastrointestinal cancer. METHODS: We investigated the expression profiles and epigenetic alterations of Dkks and Krm2 genes in gastrointestinal cancer using RT-PCR, tissue microarray analysis, and methylation specific PCR (MSP). Cancer cells were treated with the demethylating agent and/or histone deacetylase inhibitor. WST-8 assays and in vitro invasion assays after treatment with specific siRNA for those genes were performed. RESULTS: Dkks and Krm2 expression levels were reduced in a certain subset of the gastrointestinal cancer cell lines and cancer tissues. This was correlated with promoter hypermethylation. There were significant correlations between Dkks over-expression levels and beta-catenin over-expression in colorectal cancer. In colorectal cancers with beta-catenin over-expression, Dkk-1 expression levels were significantly lower in those with lymph node metastases than in those without. Down-regulation of Dkks expression by siRNA resulted in a significant increase in cancer cell growth and invasiveness in vitro.CONCLUSION: Down-regulation of the Dkks associated to promoter hypermethylation appears to be frequently involved in gastrointestinal tumorigenesis. | Tadateru Maehata Hiroaki Taniguchi Hiroyuki Yamamoto Katsuhiko Nosho Yasushi Adachi Nobuki Miyamoto Chie Miyamoto Noriyuki Akutsu Satoshi Yamaoka Fumio Itoh | 2008 | World Journal of Gastroenterology2008，14，17： | 19 |
| 5 | Alterations in the human epidermal growth factor receptor 2-phosphatidylinositol 3-kinase-v-Akt pathway in gastric cancer显示文摘AIM:To investigate human epidermal growth factor receptor 2(HER2)-phosphatidylinositol 3-kinase(PI3K)-vAkt murine thymoma viral oncogene homolog signaling pathway.METHODS:We analyzed 231 formalin-fixed,paraffinembedded gastric cancer tissue specimens from Japanese patients who had undergone surgical treatment.The patients' age,sex,tumor location,depth of invasion,pathological type,lymph node metastasis,and pathological stage were determined by a review of the medical records.Expression of HER2 was analyzed by immunohistochemistry(IHC) using the HercepTest TM kit.Standard criteria for HER2 positivity(0,1+,2+,and 3+) were used.Tumors that scored 3+ were considered HER2-positive.Expression of phospho Akt(pAkt) was also analyzed by IHC.Tumors were considered pAkt-positive when the percentage of positive tumor cells was 10% or more.PI3K,catalytic,alpha polypeptide(PIK3CA) mutations in exons 1,9 and 20 were analyzed by pyrosequencing.Epstein-Barr virus(EBV) infection was analyzed by in situ hybridization targeting EBV-encoded small RNA(EBER) with an EBER-RNA probe.Microsatellite instability(MSI) was analyzed by polymerase chain reaction using the mononucleotide markers BAT25 and BAT26.RESULTS:HER2 expression levels of 0,1+,2+ and 3+ were found in 167(72%),32(14%),12(5%) and 20(8.7%) samples,respectively.HER2 overexpression(IHC 3+) significantly correlated with intestinal histological type(15/20 vs 98 /205,P = 0.05).PIK3CA mutations were present in 20 cases(8.7%) and significantly correlated with MSI(10/20 vs 9/211,P < 0.01).The mutation frequency was high(21%) in T4 cancers and very low(6%) in T2 cancers.Mutations in exons 1,9 and 20 were detected in 5(2%),9(4%) and 7(3%) cases,respectively.Two new types of PIK3CA mutation,R88Q and R108H,were found in exon1.All PIK3CA mutations were heterozygous missense singlebase substitutions,the most common being H1047R(6/20,30%) in exon20.Eighteen cancers(8%) were EBV-positive and this positivity significantly correlated with a diffuse histological type(13/18 vs 93/198,P = 0.04).There were 7 cases of lymphoepithelioma-like carcinomas(LELC) and 6 of those cases were EBV-positive(percent/EBV:6/18,33%;percent/all LELC:6/7,86%).pAkt expression was positive in 119(53%) cases but showed no correlation with clinicopathological characteristics.pAkt expression was significantly correlated with HER2 overexpression(16/20 vs 103/211,P < 0.01) but not with PIK3CA mutations(12/20 vs 107/211,P = 0.37) or EBV infection(8/18 vs 103/211,P = 0.69).The frequency of pAkt expression was higher in cancers with exon20 mutations(100%) than in those with exon1(40%) or exon9(56%) mutations.One case showed both HER2 overexpression and EBV infection and 3 cases showed both PIK3CA mutations and EBV infection.However,no cases showed both PIK3CA mutations and HER2 overexpression.One EBVpositive cancer with PIK3CA mutation(H1047R) was MSI-positive.Three of these 4 cases were positive for pAkt expression.In survival analysis,pAkt expression significantly correlated with a poor prognosis(hazard ratio 1.75;95%CI:1.12-2.80,P = 0.02).CONCLUSION:HER2 expression,PIK3CA mutations and EBV infection in gastric cancer were characterized.pAkt expression significantly correlates with HER2 expression and with a poor prognosis. | Yasutaka Sukawa Hiroyuki Yamamoto Katsuhiko Nosho Hiroaki Kunimoto Hiromu Suzuki Yasushi Adachi Mayumi Nakazawa Takayuki Nobuoka Mariko Kawayama Masashi Mikami Takashi Matsuno Tadashi Hasegawa Koichi Hirata Kohzoh Imai Yasuhisa Shinomura | 2012 | World Journal of Gastroenterology2012，18，45： | 19 |
| 6 | Multicenter study of endoscopic preoperative biliary drainage for malignant distal biliary obstruction显示文摘AIM: To determine the optimal method of endoscopic preoperative biliary drainage for malignant distal biliary obstruction.METHODS: Multicenter retrospective study was conducted in patients who underwent plastic stent(PS) or nasobiliary catheter(NBC) placement for resectable malignant distal biliary obstruction followed by surgery between January 2010 and March 2012. Procedurerelated adverse events, stent/catheter dysfunction(occlusion or migration of PS/NBC, developmentof cholangitis, or other conditions that required repeat endoscopic biliary intervention), and jaundice resolution(bilirubin level < 3.0 mg/d L) were evaluated. Cumulative incidence of jaundice resolution and dysfunction of PS/NBC were estimated using competing risk analysis. Patient characteristics and preoperative biliary drainage were also evaluated for association with the time to jaundice resolution and PS/NBC dysfunction using competing risk regression analysis.RESULTS: In total, 419 patients were included in the study(PS, 253 and NBC, 166). Primary cancers included pancreatic cancer in 194 patients(46%), bile duct cancer in 172(41%), gallbladder cancer in three(1%), and ampullary cancer in 50(12%). The median serum total bilirubin was 7.8 mg/d L and 324 patients(77%) had ≥ 3.0 mg/d L. During the median time to surgery of 29 d [interquartile range(IQR), 30-39 d]. PS/NBC dysfunction rate was 35% for PS and 18% for NBC [Subdistribution hazard ratio(SHR) = 4.76; 95%CI: 2.44-10.0, P < 0.001]; the pig-tailed tip was a risk factor for PS dysfunction. Jaundice resolution was achieved in 85% of patients and did not depend on the drainage method(PS or NBC).CONCLUSION: PS has insufficient patency for preoperative biliary drainage. Given the drawbacks of external drainage via NBC, an alternative method of internal drainage should be explored. | Naoki Sasahira Tsuyoshi Hamada Osamu Togawa Ryuichi Yamamoto Tomohisa Iwai Kiichi Tamada Yoshiaki Kawaguchi Kenji Shimura Takero Koike Yu Yoshida Kazuya Sugimori Shomei Ryozawa Toshiharu Kakimoto Ko Nishikawa Katsuya Kitamura Tsunao Imamura Masafumi Mizuide Nobuo Toda Iruru Maetani Yuji Sakai Takao Itoi Masatsugu Nagahama Yousuke Nakai Hiroyuki Isayama | 2016 | World Journal of Gastroenterology2016，22，14： | 18 |
| 7 | A candidate targeting molecule of insulin-like growth factor-Ⅰ receptor for gastrointestinal cancers显示文摘Advances in molecular research in cancer have brought new therapeutic strategies into clinical usage.One new group of targets is tyrosine kinase receptors,which can be treated by several strategies,including small molecule tyrosine kinase inhibitors(TKIs) and monoclonal antibodies(mAbs).Aberrant activation of growth factors/receptors and their signal pathways are required for malignant transformation and progression in gastrointestinal(GI) carcinomas.The concept of targeting specif ic carcinogenic receptors has been validated by successful clinical application of many new drugs.Type I insulin-like growth factor(IGF) receptor(IGF-IR) signaling potently stimulates tumor progression and cellular differentiation,and is a promising new molecular target in human malignancies.In this review,we focus on this promising therapeutic target,IGF-IR.The IGF/IGF-IR axis is an important modifier of tumor cell proliferation,survival,growth,and treatment sensitivity in many malignant diseases,including human GI cancers.Preclinical studies demonstrated that downregulation of IGF-IR signals reversed the neoplastic phenotype and sensitized cells to anticancer treatments.These results were mainly obtained through our strategy of adenoviruses expressing dominant negative IGF-IR(IGF-IR/dn) against gastrointestinal cancers,including esophagus,stomach,colon,and pancreas.We also summarize a variety of strategies to interrupt the IGFs/IGF-IR axis and their preclinical experiences.Several mAbs and TKIs targeting IGF-IR have entered clinical trials,and early results have suggested that these agents have generally acceptable safety profiles as single agents.We summarize the advantages and disadvantages of each strategy and discuss the merits/demerits of dual targeting of IGF-IR and other growth factor receptors,including Her2 and the insulin receptor,as well as other alternatives and possible drug combinations.Thus,IGF-IR might be a candidate for a molecular therapeutic target in human GI carcinomas. | Yasushi Adachi Hiroyuki Yamamoto Hirokazu Ohashi Takao Endo David P Carbone Kohzoh Imai Yasuhisa Shinomura | 2010 | World Journal of Gastroenterology2010，16，46： | 14 |
| 8 | Interrelationship between microsatellite instability and microRNA in gastrointestinal cancer显示文摘There is an increasing understanding of the roles that microsatellite instability (MSI) plays in Lynch syndrome (by mutations) and sporadic (by mainly epigenetic changes) gastrointestinal (GI) and other cancers. Deficient DNA mismatch repair (MMR) results in the strong mutator phenotype known as MSI, which is the hallmark of cancers arising within Lynch syndrome. MSI is characterized by length alterations within simple repeated sequences called microsatellites. Lynch syndrome occurs primarily because of germline mutations in one of the MMR genes, mainly MLH1 or MSH2 , less frequently MSH6 , and rarely PMS2 . MSI is also observed in about 15% of sporadic colorectal, gastric, and endometrial cancers and in lower frequencies in a minority of other cancers where it is often associated with the hypermethylation of the MLH1 gene. miRNAs are small noncoding RNAs that regulate gene expression at the posttranscriptional level and are critical in many biological processes and cellular pathways. There is accumulating evidence to support the notion that the interrelationship between MSI and miRNA plays a key role in the pathogenesis of GI cancer. As a possible new mechanism underlying MSI, overexpression of miR-155 has been shown to downregulate expression of MLH1, MSH2, and MSH6. Thus, a subset of MSI-positive (MSI+) cancers without known MMR defects may result from miR-155 overexpression. Target genes of frameshift mutation for MSI are involved in various cellular functions, such as DNA repair, cell signaling, and apoptosis. A novel class of target genes that included not only epigenetic modifier genes, such as HDAC2 , but also miRNA processing machinery genes, including TARBP2 and XPO5 , were found to be mutated in MSI+ GI cancers. Thus, a subset of MSI+ colorectal cancers (CRCs) has been proposed to exhibit a mutated miRNA machinery phenotype. Genetic, epigenetic, and transcriptomic differences exist between MSI+ and MSI cancers. Molecular signatures of miRNA expression apparently have the potential to distinguish between MSI+ and MSI CRCs. In this review, we summarize recent advances in the MSI pathogenesis of GI cancer, with the focus on its relationship with miRNA as well as on the potential to use MSI and related alterations as biomarkers and novel therapeutic targets. | Hiroyuki Yamamoto Yasushi Adachi Hiroaki Taniguchi Hiroaki Kunimoto Katsuhiko Nosho Hiromu Suzuki Yasuhisa Shinomura | 2012 | World Journal of Gastroenterology2012，18，22： | 14 |
| 9 | Treatment and prevention of gastrointestinal bleeding in patients receiving antiplatelet therapy显示文摘Antiplatelet therapy is the standard of care for the secondary prevention of acute coronary syndrome and ischemic stroke, especially after coronary intervention. However, this therapy is associated with bleeding complications such as gastrointestinal bleeding, which is one of the most common life-threatening complications. Early endoscopy is recommended for most patients with acute upper gastrointestinal bleeding. After successful endoscopic hemostasis, immediate resumption of antiplatelet therapy with proton-pump inhibitors(PPIs) is recommended to prevent further ischemic events. PPI prophylaxis during antiplatelet therapy reduces the risk of upper gastrointestinal bleeding. The potential negative metabolic interaction between PPIs and clopidogrel is still unclear. | Hiroshi Yasuda Yasumasa Matsuo Yoshinori Sato Sun-ichiro Ozawa Shinya Ishigooka Masaki Yamashita Hiroyuki Yamamoto Fumio Itoh | 2015 | World Journal of Critical Care Medicine2015，4，1： | 13 |
| 10 | An updated review of gastric cancer in the next-generation sequencing era:Insights from bench to bedside and vice versa显示文摘Gastric cancer(GC)is one of the most common malignancies and remains the second leading cause of cancer-related death worldwide.There is an increasing understanding of the roles that genetic and epigenetic alterations play in GCs.Recent studies using nextgeneration sequencing(NGS)have revealed a number of potential cancer-driving genes in GC.Whole-exome sequencing of GC has identified recurrent somatic mutations in the chromatin remodeling gene ARID1A and alterations in the cell adhesion gene FAT4,a member of the cadherin gene family.Mutations in chromatin remodeling genes(ARID1A,MLL3 and MLL)have been found in 47%of GCs.Whole-genome sequencing and whole-transcriptome sequencing analyses have also discovered novel alterations in GC.Recent studies of cancer epigenetics have revealed widespread alterations in genes involved in the epigenetic machinery,such as DNA methylation,histone modifications,nucleosome positioning,noncoding RNAs and microRNAs.Recent advances in molecular research on GC have resulted in the introduction of new diagnostic and therapeutic strategies into clinical settings.The antihuman epidermal growth receptor 2(HER2)antibody trastuzumab has led to an era of personalized therapy in GC.In addition,ramucirumab,a monoclonal antibody targeting vascular endothelial growth factor receptor(VEGFR)-2,is the first biological treatment that showed survival benefits as a single-agent therapy in patients with advanced GC who progressed after firstline chemotherapy.Using NGS to systematically identify gene alterations in GC is a promising approach with remarkable potential for investigating the pathogenesis of GC and identifying novel therapeutic targets,as well as useful biomarkers.In this review,we will summarize the recent advances in the understanding of the molecular pathogenesis of GC,focusing on the potential use of these genetic and epigenetic alterations as diagnostic biomarkers and novel therapeutic targets. | Hiroyuki Yamamoto Yoshiyuki Watanabe Tadateru Maehata Ryo Morita Yoshihito Yoshida Ritsuko Oikawa Shinya Ishigooka Shun-ichiro Ozawa Yasumasa Matsuo Kosuke Hosoya Masaki Yamashita Hiroaki Taniguchi Katsuhiko Nosho Hiromu Suzuki Hiroshi Yasuda Yasuhisa Shinomura Fumio Itoh | 2014 | World Journal of Gastroenterology2014，20，14： | 12 |
| 11 | Chromoendoscopy of gastric adenoma using an acetic acid indigocarmine mixture显示文摘AIM:To investigate the usefulness of chromoendoscopy,using an acetic acid indigocarmine mixture(AIM),for gastric adenoma diagnosed by forceps biopsy.METHODS:A total of 54 lesions in 45 patients diagnosed as gastric adenoma by forceps biopsy were prospectively enrolled in this study and treated by endoscopic submucosal dissection(ESD)between January 2011 and January 2012.AIM-chromoendoscopy(AIMCE)was performed followed by ESD.AIM solution was sprinkled and images were recorded every 30 s for 3min.Clinical characteristics such as tumor size(<2cm,≥2 cm),surface color in white light endoscopy(WLE)(whitish,normochromic or reddish),macroscopic appearance(flat or elevated,depressed),and reddish change in AIM-CE were selected as valuables.RESULTS:En bloc resection was achieved in all 54 cases,with curative resection of fifty two lesions(96.3%).Twenty three lesions(42.6%)were diagnosed as welldifferentiated adenocarcinoma and the remaining 31lesions(57.4%)were gastric adenoma.All adenocarcinoma lesions were well-differentiated tubular adenocarcinomas and were restricted within the mucosal layer.The sensitivity of reddish color change in AIM-CE is significantly higher than that in WLE(vs tumor size≥2 cm,P=0.016,vs normochromic or reddish surface color,P=0.046,vs depressed macroscopic type,P=0.0030).On the other hand,no significant differences were found in the specificity and accuracy.In univariate analysis,normochromic or reddish surface color in WLE(OR=3.7,95%CI:1.2-12,P=0.022)and reddish change in AIM-CE(OR=14,95%CI:3.8-70,P<0.001)were significantly related to diagnosis of early gastric cancer(EGC).In multivariate analysis,only reddish change in AIM-CE(OR=11,95%CI:2.3-66,P=0.0022)was a significant factor associated with diagnosis of EGC.CONCLUSION:AIM-CE may have potential for screening EGC in patients initially diagnosed as gastric adenoma by forceps biopsy. | Yoshiyasu Kono Ryuta Takenaka Yoshiro Kawahara Hiroyuki Okada Keisuke Hori Seiji Kawano Yasushi Yamasaki Koji Takemoto Takayoshi Miyake Shigeatsu Fujiki Kazuhide Yamamoto | 2014 | World Journal of Gastroenterology2014，20，17： | 12 |
| 12 | 早胃的癌症用的程度的诊断灵活光谱成像颜色改进显示文摘 The demarcation line between the cancerous lesion and the surrounding area could be easily recognized with flexible spectral imaging color enhancement (FICE) system compared with conventional white light images. The characteristic f inding of depressed-type early gastric cancer (EGC) in most cases was revealed as reddish lesions distinct from the surrounding yellowish non-cancerous area without magnification. Conventional endoscopic images provide little information regarding depressed lesions located in the tangential line, but FICE produces higher color contrast of such cancers. Histological f indings in depressed area with reddish col- or changes show a high density of glandular structure and an apparently irregular microvessel in intervening parts between crypts, resulting in the higher color con- trast of FICE image between cancer and surrounding area. Some depressed cancers are shown as whitish lesion by conventional endoscopy. FICE also can pro- duce higher color contrast between whitish cancerous lesions and surrounding atrophic mucosa. For nearly flat cancer, FICE can produce an irregular structuralpattern of cancer distinct from that of the surrounding mucosa, leading to a clear demarcation. Most elevated-type EGCs are detected easily as yellowish lesions with clearly contrasting demarcation. In some cases, a partially reddish change is accompanied on the tumor surface similar to depressed type cancer. In addition, the FICE system is quite useful for the detection of minute gastric cancer, even without magnif ication. These new contrasting images with the FICE system may have the potential to increase the rate of detection of gastric cancers and screen for them more effectively as well as to determine the extent of EGC. | Hiroyuki Osawa Hironori Yamamoto Yoshimasa Miura Mitsuyo Yoshizawa Keijiro Sunada Kiichi Satoh Kentaro Sugano | 2012 | World Journal of Gastrointestinal Endoscopy2012，4，8： | 11 |
| 13 | Overexpression of the receptor tyrosine kinase EphA4 in human gastric cancers显示文摘AIM: To clarify the expression and role of Ephrin receptor A4 (EphA4) in gastric cancer in relation to clinicopathological characteristics and the expression of fibroblast growth factor receptor 1 (FGFR1) and ephrin ligands. METHODS: Eleven gastric carcinoma cell lines, 24 paired surgical fresh specimens of gastric adenocarcinoma and adjacent nontumor tissue, 74 conventional formalin-fixed, paraffin-embedded tumor specimens, and 55 specimens spotted on tissue microarray (TMA) were analyzed. Reverse transcription-PCR (RT-PCR), real-time RT-PCR, immunohistochemistry, and cell growth assays were performed. RESULTS: Overexpression of EphA4 mRNA expres-sion was observed in 8 (73%) of 11 gastric cancer cell lines and 10 (42%) of 24 gastric cancer tissues. Over-expression of EphA4, analyzed by immunohistochemistry, was observed in 62 (48%) of 129 gastric cancer tissues. EphA4 overexpression, at the protein level, was significantly associated with depth of invasion and recurrence. EphA4 overexpression was also correlated with FGFR1 overexpression. Patients with EphA4-positive cancer had significantly shorter overall survival periods than did those with EphA4-negative cancer (P = 0.0008). The mRNAs for ephrin ligands were coexpressed in various combinations in gastric cancer cell lines and cancer tissues. Downregulation of EphA4 expression by siRNA in EphA4-overexpressing gastric cancer cell lines resulted in a significant decrease in cell growth. CONCLUSION: Our results suggest that overexpres-sion of EphA4 plays a role in gastric cancer. | Mariko Oki Hiroyuki Yamamoto Hiroaki Taniguchi Yasushi Adachi Kohzoh Imai Yasuhisa Shinomura | 2008 | World Journal of Gastroenterology2008，14，37： | 11 |
| 14 | Treating inflammatory bowel disease by adsorptive leucocytapheresis:A desire to treat without drugs显示文摘Ulcerative colitis and Crohn’s disease are the major phenotypes of the idiopathic inflammatory bowel disease(IBD),which afflicts millions of individuals throughout the world with debilitating symptoms,impairing function and quality of life.Current medications are aimed at reducing the symptoms or suppressing exacerbations.However,patients require life-long medications,and this can lead to drug dependency,loss of response together with adverse side effects.Indeed,drug side effects become additional morbidity factor in many patients on long-term medications.Nonetheless,the efficacy of anti-tumour necrosis factors(TNF)-αbiologics has validated the role of inflammatory cytokines notably TNF-αin the exacerbation of IBD.However,inflammatory cytokines are released by patients’own cellular elements including myeloid lineage leucocytes,which in patients with IBD are elevated with activation behaviour and prolonged survival.Accordingly,these leucocytes appear logical targets of therapy and can be depleted by adsorptive granulocyte/monocyte apheresis(GMA)with an Adacolumn.Based on this background,recently GMA has been applied to treat patients with IBD in Japan and in the European Union countries.Efficacy rates have been impressive as well as disappointing.In fact the clinical response to GMA seems to define the patients’disease course,response to medications,duration of active disease,and severity at entry.The best responders have been first episode cases(up to 100%)followed by steroid nave and patients with a short duration of active disease prior to GMA.Patients with deep ulcers together with extensive loss of the mucosal tissue and cases with a long duration of IBD refractory to existing medications are not likely to benefit from GMA.It is clinically interesting that patients who respond to GMA have a good long-term disease course by avoiding drugs including corticosteroids in the early stage of their IBD.Additionally,GMA is very much favoured by patients for its good safety profile.GMA in 21st century reminds us of phlebotomy as a major medical practice at the time of Hippocrates.However,in patients with IBD,there is a scope for removing from the body the sources of proinflammatory cytokines and achieve disease remission.The bottom line is that by introducing GMA at an early stage following the onset of IBD or before patients develop extensive mucosal damage and become refractory to medications,many patients should respond to GMA and avoid pharmacologics.This should fulfill the desire to treat without drugs. | Abbi R Saniabadi Tomotaka Tanaka Toshihide Ohmori Koji Sawada Takayuki Yamamoto Hiroyuki Hanai | 2014 | World Journal of Gastroenterology2014，20，29： | 11 |
| 15 | Prognosis of ulcerative colitis differs between patients with complete and partial mucosal healing, which can be predicted from the platelet count显示文摘AIM:To determine the difference in clinical outcome between ulcerative colitis(UC)patients with Mayo endoscopic subscore(MES)0 and those with MES 1.METHODS:UC patients with sustained clinical remission of 6 mo or more at the time of colonoscopy were examined for clinical outcomes and the hazard ratios of clinical relapse according to MES.Parameters,including blood tests,to identify predictive factors for MES 0and slight endoscopic recurrence in clinically stablepatients were assessed.Moreover,a receiver operating characteristic curve was generated,and the area under the curve was calculated to indicate the utility of the parameters for the division between complete and partial mucosal healing.All P values were two-sided and considered significant when less than 0.05.RESULTS:A total of 183 patients with clinical remission were examined.Patients with MES 0(complete mucosal healing:n=80,44%)were much less likely to relapse than those with MES 1(partial mucosal healing:n=89,48%)(P<0.0001,log-rank test),and the hazard ratio of risk of relapse in patients with MES 1 vs MES0 was 8.17(95%CI:4.19-17.96,P<0.0001).The platelet count(PLT)<26×104/μL was an independent predictive factor for complete mucosal healing(OR=4.1,95%CI:2.15-7.99).Among patients with MES 0 at the initial colonoscopy,patients of whom colonoscopy findings shifted to MES 1 showed significant increases in PLT compared to those who maintained MES 0(3.8×104/μL vs-0.6×104/μL,P<0.0001).CONCLUSION:The relapse rate differed greatly between patients with complete and partial mucosal healing.A shift from complete to partial healing in clinically stable UC patients can be predicted by monitoring PLT. | Asuka Nakarai Jun Kato Sakiko Hiraoka Toshihiro Inokuchi Daisuke Takei Yuki Moritou Mitsuhiro Akita Sakuma Takahashi Keisuke Hori Keita Harada Hiroyuki Okada Kazuhide Yamamoto | 2014 | World Journal of Gastroenterology2014，20，48： | 11 |
| 16 | Endoscopic features and prognoses of mantle cell lymphoma with gastrointestinal involvement显示文摘AIM: To evaluate the endoscopic manifestations and prognoses of gastrointestinal (GI) mantle cell lymphoma (MCL). METHODS: A database search at the Department of Pathology of Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences revealed 57 MCL patients with GI involvement. Clinical records were available for 35 of the 57 patients from 21 institutions, and those 35 patients were enrolled in this study. We summarized the gross types of endoscopic features, event-free survival (EFS), and overall survival (OS) of those patients.RESULTS: Of the 35 patients, GI involvement in the esophagus, stomach, and duodenum was found in 2 (5.7%), 26 (74.3%), and 12 (34.3%) patients, respectively. Twenty-one of the 35 patients underwent colonoscopy; among them, GI involvement in the ileum, cecum, colon, and rectum was found in 10 (47.6%), 3 (14.3%), 12 (57.1%), and 10 (47.6%), respectively. Various lesions, such as superficial, protruded, fold thickening, or ulcerative, were found in the stomach, whereas multiple lymphomatous polyposis (MLP) was dominant from the duodenum to the rectum. Twelve patients were treated with a hyper-CVAD/MA regimen, and they had better OS (3-year rate, 88.3% vs 46.4%, P < 0.01) and better EFS (3-year rate, 66.7% vs 33.8%, P < 0.05) than the remaining 23 patients who were not treated with this regimen. CONCLUSION: MLP was a representative form of intestinal involvement, whereas a variety of lesions were found in the stomach. The hyper-CVAD/MA regimen may improve survival in these patients. | Masaya Iwamuro Hiroyuki Okada Yoshiro Kawahara Katsuji Shinagawa Toshiaki Morito Tadashi Yoshino Kazuhide Yamamoto | 2010 | World Journal of Gastroenterology2010，16，37： | 9 |
| 17 | Unsedated transnasal small-caliber esophagogastroduoden oscopy in elderly and bedridden patients显示文摘AIM:To evaluate the safety of unsedated transnasal small-caliber esophagogastroduodenoscopy(EGD)for elderly and critically ill bedridden patients. METHODS:One prospective randomized comparative study and one crossover comparative study between transnasal small-caliber EGD and transoral conventional EGD was done(Study 1).For the comparative study, we enrolled 240 elderly patients aged>65 years old. For the crossover analysis,we enrolled 30 bedridden patients with percutaneous endoscopic gastrostomy (PEG)(Study 2).We evaluated cardiopulmonary effects by measuring arterial oxygen saturation(SpO2)and calculating the rate-pressure product(RPP)(pulse rate×systolic blood pressure/100)at baseline,2 and 5 min after endoscopic intubation in Study 1.To assess the risk for endoscopy-related aspiration pneumoniaduring EGD,we also measured blood leukocyte counts and serum C-reactive protein(CRP)levels before and 3 d after EGD in Study 2. RESULTS:In Study 1,we observed significant decreases in SpO2 during conventional transoral EGD, but not during transnasal small-caliber EGD(0.24%vs -0.24%after 2 min,and 0.18%vs-0.29%after 5 min, P=0.034,P=0.044).Significant differences of the RPP were not found between conventional transoral and transnasal small-caliber EGD.In Study 2,crossover analysis showed statistically significant increases of the RPP at 2 min after intubation and the end of endoscopy (26.8 and 34.6 vs 3.1 and 15.2,P=0.044,P=0.046), and decreases of SpO2(-0.8%vs-0.1%,P=0.042) during EGD with transoral conventional in comparison with transnasal small-caliber endoscopy.Thus,for bedridden patients with PEG feeding,who were examined in the supine position,transoral conventional EGD more severely suppressed cardiopulmonary function than transnasal small-caliber EGD.There were also significant increases in the markers of inflammation, blood leukocyte counts and serum CRP values,in bedridden patients after transoral conventional EGD,but not after transnasal small-caliber EGD performed with the patient in the supine position.Leukocyte count increased from 6053±1975/L to 6900±3392/L(P=0.0008)and CRP values increased from 0.93±0.24 to 2.49±0.91 mg/dL(P=0.0005)at 3 d after transoral conventional EGD.Aspiration pneumonia,possibly caused by the endoscopic examination,was found subsequently in two of 30 patients after transoral conventional EGD. CONCLUSION:Transnasal small-caliber EGD is a safer method than transoral conventional EGD in critically ill, bedridden patients who are undergoing PEG feeding. | Mika Yuki Yuji Amano Yoshinori Komazawa Hiroyuki Fukuhara Toshihiro Shizuku Shun Yamamoto Yoshikazu Kinoshita | 2009 | World Journal of Gastroenterology2009，15，44： | 8 |
| 18 | Improvement of prognosis for unresectable biliary tract cancer显示文摘AIM:To evaluate the chemotherapeutic outcomes and confirm the recent improvement of prognosis for unresectable biliary tract cancer.METHODS:A total of 186 consecutive patients with unresectable biliary tract cancer,who had been treated with chemotherapy between 2000 and 2009 at five institutions in Japan,were retrospectively analyzed.These patients were divided into three groups based on the year beginning chemotherapy:Group A(2000-2003),Group B(2004-2006),and Group C(2007-2009).The data were fixed at the end of December 2011.Overall survival and time-to-progression were analyzed and compared chronologically.RESULTS:No patient characteristics were significantly different among the three groups.The gallbladder was involved in about half of the patients in each group,and metastatic biliary tract cancer was present in three quarters of the enrollees.In Group A,5-fluorouracilbased chemotherapies were primarily selected as firstline chemotherapy,and only 24% were treated with second-line chemotherapy.In Group B,gemcitabine or S-1 monotherapy was mainly introduced as firstline chemotherapy,and 51% of the patients who were refractory to first-line chemotherapy were treated with second-line chemotherapy mainly with monotherapy.In Group C,the combination therapy with gemcitabine and S-1 was mainly chosen as first-line chemotherapy,and 53% of the patients refractory to first-line chemotherapy were treated with second-line chemotherapy mainly with combination therapy.The median timeto-progressions were 4.4 mo,3.5 mo and 5.9 mo in Groups A,B and C,respectively(4.4 mo vs 3.5 mo vs 5.9 mo,P < 0.01).The median overall survivals were 7.1,7.3,and 11.7 mo in Groups A,B and C(7.1 mo vs 7.3 mo vs 11.7 mo,P = 0.03).Induction rates of all three drugs(gemcitabine,platinum analogs,and fluoropyrimidine) in Groups A,B and C were 4%,2% and 27%(4% vs 2% vs 27%,P < 0.01).CONCLUSION:The prognosis of unresectable biliary tract cancer has improved recently.Using three effective drugs(gemcitabine,platinum analogs,and fluoropyrimidine) may improve the prognosis of this cancer. | Takashi Sasaki Hiroyuki Isayama Yousuke Nakai Naminatsu Takahara Naoki Sasahira Hirofumi Kogure Suguru Mizuno Hiroshi Yagioka Yukiko Ito Natsuyo Yamamoto Kenji Hirano Nobuo Toda Minoru Tada Masao Omata Kazuhiko Koike | 2013 | World Journal of Gastroenterology2013，19，1： | 8 |
| 19 | Clinical outcomes of enteroscopy using the double-balloon method for strictures of the small intestine显示文摘AIM: To evaluate the clinical outcome of enteroscopy, using the double-balloon method, focusing on the involvement of neoplasms in strictures of the small intestine.METHODS: Enteroscopy, using the double-balloon method, was performed between December 1999 and December 2002 at Jichi Medical School Hospital, Japan and strictures of the small intestine were found in 17 out of 62 patients. These 17 consecutive patients were subjected to analysis.RESULTS: The double-balloon enteroscopy contributed to the diagnosis of small intestinal neoplasms found in 3out of 17 patients by direct observation of the strictures as well as biopsy sampling. Surgical procedures were chosen for these three patients, while balloon dilation was chosen for the strictures in four patients diagnosed with inflammation without involvement of neoplasm.CONCLUSION: Double-balloon enteroscopy is a useful method for the diagnosis and treatment of strictures in the small bowel. | Keijiro Sunada Hironori Yamamoto Hiroto Kita Tomonori Yano Hiroyuki Sato Yoshikazu Hayashi Tomohiko Miyata Yutaka Sekine Akiko Kuno Michiko Iwamoto Hirohide Ohnishi Kenichi Ido Kentaro Sugano | 2005 | World Journal of Gastroenterology2005，11，7： | 6 |
| 20 | Non-steroidal anti-inflammatory drug-induced small bowel injuries identified by double-balloon endoscopy显示文摘AIM: To clarify clinical features of the NSAID-induced small bowel lesions using a new method of endoscopy.METHODS: This is a retrospective study and we analyzed seven patients with small bowel lesions while taking NSAIDs among 61 patients who had undergone doubleballoon endoscopy because of gastro-intestinal bleeding or anemia between September 2000 and March 2004, at Jichi Medical School Hospital in Japan. Neither conventional EGD nor colonoscopy revealed any lesions of potential bleeding sources including ulcerations. Double-balloon endoscopy was carried out from oral approach in three patients, from anal approach in three patients, and from both approaches in one patient.RESULTS: Ulcers or erosions were observed in the ileum in six patients and in the jejunum in one patient, respectively.The ulcers were multiple in all the patients with different features from tiny punched out ulcers to deep ulcerations with oozing hemorrhage or scar. All the patients recovered uneventfully and had full resolution of symptoms after suspension of the drug.CONCLUSION: NSAIDs can induce injuries in the small bowel even in patients without any lesions in both the stomach and colon. | Yoshikazu Hayashi Hironori Yamamoto Hiroto Kita Keijiro Sunada Hiroyuki Sato Tomonori Yano Michiko Iwamoto Yutaka Sekine Tomohiko Miyata Akiko Kuno Takaaki Iwaki Yoshiyuki Kawamura Hironari Ajibe Kenichi Ido Kentaro Sugano | 2005 | World Journal of Gastroenterology2005，11，31： | 6 |
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