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| 1 | Liquid biopsy in patients with hepatocellular carcinoma: Circulating tumor cells and cell-free nucleic acids显示文摘Hepatocellular carcinoma(HCC), with its high incidence and mortality rate, is one of the most common malignant tumors. Despite recent development of a diagnostic and treatment method, the prognosis of HCC remains poor. Therefore, to provide optimal treatment for each patient with HCC, more precise and effective biomarkers are urgently needed which could facilitate a more detailed individualized decision-making during HCC treatment, including the following; risk assessment, early cancer detection, prediction of treatment or prognostic outcome. In the blood of cancer patients, accumulating evidence about circulating tumor cells and cell-free nucleic acids has suggested their potent clinical utilities as novel biomarker. This concept, so-called 'liquid biopsy' is widely known as an alternative approach to cancer tissue biopsy. This method might facilitate a more sensitive diagnosis and better decision-making by obtaining genetic and epigenetic aberrations that are closely associated with cancer initiation and progression. In this article, we review recent developments based on the available literature on both circulating tumor cells and cell-free nucleic acids in cancer patients, especially focusing on Hepatocellular carcinoma. | wataru okajima shuhei komatsu daisuke ichikawa mahito miyamae takuma ohashi taisuke imamura jun kiuchi keiji nishibeppu tomohiro arita hirotaka konishi atsushi shiozaki ryo morimura hisashi ikoma kazuma okamoto eigo otsuji | 2017 | World Journal of Gastroenterology2017，23，31： | 22 |
| 2 | ACE and ACE2 in kidney disease显示文摘Renin angiotensin system(RAS) activation has a significant influence on renal disease progression. The classical angiotensin-converting enzyme(ACE)-angiotensin Ⅱ(Ang Ⅱ)-Ang Ⅱ type 1(AT1) axis is considered to control the effects of RAS activation on renal disease.However, since its discovery in 2000 ACE2 has also been demonstrated to have a significant impact on the RAS.The synthesis and catabolism of Ang Ⅱ are regulated via a complex series of interactions, which involve ACE and ACE2. In the kidneys, ACE2 is expressed in the proxima tubules and less strongly in the glomeruli. The synthesisof inactive Ang 1-9 from Ang Ⅰ and the catabolism of Ang Ⅱ to produce Ang 1-7 are the main functions of ACE2. Ang 1-7 reduces vasoconstriction, water retention, salt intake, cell proliferation, and reactive oxygen stress, and also has a renoprotective effect. Thus, in the nonclassical RAS the ACE2-Ang 1-7-Mas axis counteracts the ACE-Ang Ⅱ-AT1 axis. This review examines recent human and animal studies about renal ACE and ACE2. | Sonoo Mizuiri Yasushi Ohashi | 2015 | World Journal of Nephrology2015，4，1： | 15 |
| 3 | Alcoholic liver disease: A current molecular and clinical perspective显示文摘Heavy alcohol use is the cause of alcoholic liver disease(ALD).The ALD spectrum ranges from alcoholic steatosis to steatohepatitis,fibrosis,and cirrhosis.In Western countries,approximately 50%of cirrhosis-related deaths are due to alcohol use.While alcoholic cirrhosis is no longer considered a completely irreversible condition,no effective anti-fibrotic therapies are currently available.Another significant clinical aspect of ALD is alcoholic hepatitis(AH).AH is an acute inflammatory condition that is often comorbid with cirrhosis,and severe AH has a high mortality rate.Therapeutic options for ALD are limited.The established treatment for AH is corticosteroids,which improve short-term survival but do not affect long-term survival.Liver transplantation is a curative treatment option for alcoholic cirrhosis and AH,but patients must abstain from alcohol use for 6 months to qualify.Additional effective therapies are needed.The molecular mechanisms underlying ALD are complex and have not been fully elucidated.Various molecules,signaling pathways,and crosstalk between multiple hepatic and extrahepatic cells contribute to ALD progression.This review highlights established and emerging concepts in ALD clin-icopathology,their underlying molecular mechanisms,and current and future ALD treatment options. | Koichiro Ohashi Michael Pimienta Ekihiro Seki | 2018 | Liver Research2018，2，4： | 15 |
| 4 | 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 |
| 5 | Comprehensive and innovative techniques for livertransplantation in rats: A surgical guide显示文摘AIM: To investigate our learning curves of orthotopic liver transplantation (OLT) in rats and the most important factor for successful surgery. METHODS: We describe the surgical procedures for our rat OLT model, and determined the operator learning curves. The various factors that contributed to successful surgery were determined. The most important surgical factors were evaluated between successful and unsuccessful surgeries.RESULTS: Learning curve data indicated that 50 cases were required for operator training to start a study. Operative time, blood loss, warm ischemic time, anhepatic phase, unstable systemic hemodynamic state, and body temperature after surgery significantly affected surgery success by univariate analysis, while the anhepatic phase was the most critical factor for success by multivariate analysis. CONCLUSION: OLT in rats is the only liver transplantation model that provides clinically relevant and reliable results. Shortened anhepatic phase is key to success in this model. | Tomohide Hori Justin H Nguyen Yasuhiro Ogura Toshiyuki Hata Shintaro Yagi Ann-Marie T Baine Norifumi Ohashi Christopher B Eckman Aimee R Herdt Hiroto Egawa Yasutsugu Takada Fumitaka Oike Seisuke Saka-moto Mureo Kasahara Kohei Ogawa Koichiro Hata Taku Iida Yukihide Yonekawa Lena Sibulesky Kagemasa Kuribayashi Takuma Kato Kanako Saito Mie Torii Naruhiko Sahara Naoko Kamo Tomoko Sahara Motohiko Yasutomi Shinji Uemoto | 2010 | World Journal of Gastroenterology2010，16，25： | 14 |
| 6 | 'Extended' radical cholecystectomy for gallbladder cancer:Long-term outcomes, indications and limitations显示文摘AIM:To delineate indications and limitations for 'ex tended' radical cholecystectomy for gallbladder cancer:a procedure which was instituted in our department in 1982. METHODS:Of 145 patients who underwent a radi cal resection for gallbladder cancer from 1982 through 2006, 52 (36%) had an extended radical cholecystec tomy, which involved en bloc resection of the gallblad der, gallbladder fossa, extrahepatic bile duct, and the regional lymph nodes (first-and second-echelon node groups). A retrospective analysis of the 52 patients was conducted including at least 5 years of follow up. Residual tumor status was judged as no residual tumor (R0) or microscopic/macroscopic residual tumor (R1 2). athological findings were documented according tothe American Joint Committee on Cancer Cancer Stag ing anual (7th edition). RESULTS:he primary t mor as classified as patho-logical T1 (pT1) in 3 patients, pT2 in 36, pT3 in 12, and pT4 in 1. Twenty three patients had lymph node metastases; 11 had a single positive node, 4 had two positive nodes, and 8 had three or more positive nodes. None of the three patients with pT1 tumors had nodal disease, whereas 23 of 49 (47%) with pT2 or more advanced tumors had nodal disease. One patient died during the hospital stay for definitive resection, giv ing an in hospital mortality rate of 2%. Overall survival (OS) after extended radical cholecystectomy was 65% at 5 years and 53% at 10 years in all 52 patients. OS differed according to the p classification ( < 0.001) and the nodal status ( = 0.010). All of 3 patients with pT1 tumors and most (29 of 36) patients with pT2 tu mors survived for more than 5 years. Of 12 patients with pT3 tumors, 8 who had an R1 2 resection, distant metastasis, or extensive extrahepatic organ involve ment died soon after resection. Of the remaining four pT3 patients who had localized hepatic spread through the gallbladder fossa and underwent an R0 resection, 2 survived for more than 5 years and another survived for 4 years and 2 mo. The only patient with pT4 tumor died of disease soon after resection. Among 23 node positive patients, 11 survived for more than 5 years, and of these, 10 had a modest degree of nodal disease (one or two positive nodes). CONCLUSION:Extended radical cholecystectomy is indicated for pT2 tumors and some pT3 tumors with localized hepatic invasion, provided that the regional nodal disease is limited to a modest degree (up to two positive nodes). Extensive pT3 disease, pT4 disease, or marked nodal disease appears to be beyond the scope of this radical procedure. | Yoshio Shirai Jun Sakata Toshifumi Wakai Taku Ohashi Katsuyoshi Hatakeyama | 2012 | World Journal of Gastroenterology2012，18，34： | 11 |
| 7 | Glucagon-like peptide-1 analogue prevents nonalcoholic steatohepatitis in non-obese mice显示文摘AIM: To investigate whether a glucagon-like peptide-1(GLP-1) analogue inhibits nonalcoholic steatohepatitis(NASH), which is being increasingly recognized in Asia, in non-obese mice. METHODS: A methionine-choline-deficient diet(MCD) along with exendin-4(20 μg/kg per day, ip), a GLP-1 analogue, or saline was administered to male db/db mice(non-obese NASH model). Four or eight weeks after commencement of the diet, the mice were sacrificed and their livers were excised. The excised livers were examined by histochemistry for evidence of hepatic steatosis and inflammation. Hepatic triglyceride(TG) and free fatty acid(FFA) content was measured, and the expression of hepatic fat metabolism- and inflammation-related genes was evaluated. Oxidative stress-related parameters and macrophage recruitment were also examined using immunohistochemistry.RESULTS: Four weeks of MCD feeding induced hepatic steatosis and inflammation and increased the hepatic TG and FFA content. The expression of fattyacid transport protein 4(FATP4), a hepatic FFA influxrelated gene; macrophage recruitment; and the level of malondialdehyde(MDA), an oxidative stress marker, were significantly augmented by a 4-wk MCD. The levels of hepatic sterol regulatory element-binding protein-1c(SREBP-1c) m RNA(lipogenesis-related gene) and acyl-coenzyme A oxidase 1(ACOX1) m RNA(β-oxidation-related gene) had decreased at 4 wk and further decreased at 8 wk. However, the level of microsomal triglyceride transfer protein m RNA(a lipid excretion-related gene) remained unchanged. The administration of exendin-4 significantly attenuated the MCD-induced increase in hepatic steatosis, hepatic TG and FFA content, and FATP4 expression as well as the MCD-induced augmentation of hepatic inflammation, macrophage recruitment, and MDA levels. Additionally, it further decreased the hepatic SREBP-1c level and alleviated the MCD-mediated inhibition of the ACOX1 m RNA level. CONCLUSION: These results suggest that GLP-1 inhibits hepatic steatosis and inflammation through the inhibition of hepatic FFA influx and oxidative stress in a non-obese NASH model. | Takaya Yamamoto Yukiomi Nakade Taeko Yamauchi Yuji Kobayashi Norimitsu Ishii Tomohiko Ohashi Kiyoaki Ito Ken Sato Yoshitaka Fukuzawa Masashi Yoneda | 2016 | World Journal of Gastroenterology2016，22，8： | 10 |
| 8 | Liquid biopsy in patients with pancreatic cancer: Circulating tumor cells and cell-free nucleic acids显示文摘Despite recent advances in surgical techniques and perioperative management, the prognosis of pancreatic cancer(PCa) remains extremely poor. To provide optimal treatment for each patient with Pca, superior biomarkers are urgently needed in all phases of management from early detection to staging, treatment monitoring, and prognosis. In the blood of patients with cancer, circulating tumor cells(CTCs) and cell-free nucleic acids(cf NAs), such as DNA, m RNA, and noncoding RNA have been recognized. In the recent years, their presence in the blood has encouraged researchers to investigate their potential use as novel blood biomarkers, and numerous studies have demonstrated their potential clinical utility as a biomarker for certain types of cancer. This concept, called 'liquid biopsy' has been focused on as a less invasive, alternative approach to cancer tissue biopsy for obtaining genetic and epigenetic aberrations that contribute to oncogenesis and cancer progression. In this article, we review the available literature on CTCs and cfN As in patients with cancer, particularly focusing on PCa, and discuss future perspectives in this field. | Taisuke Imamura Shuhei Komatsu Daisuke Ichikawa Tsutomu Kawaguchi Mahito Miyamae Wataru Okajima Takuma Ohashi Tomohiro Arita Hirotaka Konishi Atsushi Shiozaki Ryo Morimura Hisashi Ikoma Kazuma Okamoto Eigo Otsuji | 2016 | World Journal of Gastroenterology2016，22，25： | 10 |
| 9 | 云南汉族HLA-DRB1多态性分析及与9个汉族群体的比较显示文摘应用聚合酶链反应—微孔板杂交 (PolymeraseChainReactionandMicrotitrePlateHybridization ,PCR MPH)的方法对云南 12 9个无亲缘关系的汉族样品进行了HLA DRB1的遗传多态性分析 ,对MPH初分出的DRB1 15组的样品进行了单链构象多态 (Single StrandConformationPolymorphism ,SSCP)检测。共发现 36种等位基因 ,其中等位基因频率大于 0 0 5的有DRB1 15 0 1(0 12 4 0 ) ,DRB1 0 90 12 (0 0 96 9) ,DRB1 0 80 32 (0 0 930 ) ,DRB1 12 0 2(0 0 891) ,DRB1 12 0 1(0 0 814 ) ,DRB1 14 0 1(0 0 775 ) ,DRB1 0 70 1(0 0 6 2 0 )。云南汉族HLA DRB1等位基因频率与中国其他 9个汉族群体进行 χ2 检验 ,结果显示与云南汉族比较 χ2 >10的有西安汉族 (DR8,χ2 =13 9712 )、上海汉族 (DR4 ,χ2 =10 16 32 )、广东汉族 (DR9,χ2 =12 6 12 1)和南京汉族 (DR4 ,χ2 =10 5 796 )。从遗传距离分析发现 ,在 9个国内汉族群体中云南汉族与辽宁汉族有最近的距离 (0 0 5 4 1) ,而与广东汉族最远 (0 185 1)。云南汉族在构成上可能与辽宁汉族更为接近 ,尽管地处南方 ,但已不属典型的南方汉族。这也可能因云南汉族与当地的少数民族存在基因交流 。 | 许绍斌 陶玉芬 黄小琴 初正韬 班贵宏 钱亚屏 OHASHI Jun TOKUNAGA Katsushi 褚嘉祐 | 2004 | 遗传2004，26，6： | 9 |
| 10 | Transnasal endoscopic retrograde chalangiopancreatography using an ultrathin endoscope: A prospective comparison with a routine oral procedure显示文摘AIM: To investigate if transnasal endoscopic retrograde cholangiopancreatography (n-ERCP) using an ultrathin forward-viewing scope may overcome the disadvantages of conventional oral ERCP (o-ERCP) related to the large- caliber side-viewing duodenoscope. METHODS: The study involved 50 patients in whom 25 cases each were assigned to the o-ERCP and n-ERCP groups. We compared the requirements of esophagogastroduodenoscopy (EGD) prior to ERCP, rates and times required for successful cannulation into the pancreatobiliary ducts, incidence of post-procedure hyperamylasemia, cardiovascular parameters during the procedure, the dose of a sedative drug, and successful rates of endoscopic naso-biliary drainage (ENBD). RESULTS: Screening gastrointestinal observations were easily performed by the forward-viewing scope and thus no prior EGD was required in the n-ERCP group. There was no significant difference in the rates or times for cannulation, or incidence of hyperamylasemia between the groups. However, the cannulation was relatively difficult in n-ERCP when the scope appeared U-shape under fluoroscopy. Increments of blood pressure and the amount of a sedative drug were significantly lower in the n-ERCP group. ENBD was successfully performed succeeding to the n-ERCP in which mouth-to-nose transfer of the drainage tube was not required. CONCLUSION: n-ERCP is likely a well-tolerable methodwith less cardiovascular stress and no need of prior EGD or mouth-to-nose transfer of the ENBD tube. However, a deliberate application is needed since its performance is difficult in some cases and is not feasible for some endoscopic treatments such as stenting. | Akihiro Mori Noritsugu Ohashi Takako Maruyama Hideharu Tatebe Katsuhisa Sakai Takashi Shibuya Hiroshi Inoue Shoudou Takegoshi Masataka Okuno | 2008 | World Journal of Gastroenterology2008，14，10： | 6 |
| 11 | Effects on coagulation factor production following primary hepatomitogen-induced direct hyperplasia显示文摘AIM:To investigate the molecular mechanisms involved in coagulation factor expression and/or function during direct hyperplasia(DH) -mediated liver regeneration.METHODS:Direct hyperplasia-mediated liver regeneration was induced in female C57BL/6 mice by administering 1,4-bis[2-(3,5-dichloropyridyloxy) ] benzene(TCPOBOP) ,a representative hepatomitogen.Mice were weighed and sacrificed at various time points [Day 0(D0:prior to injection) ,3 h,D1,D2,D3,and D10] after TCPOBOP administration to obtain liver and blood samples.Using the RNA samples extracted from the liver,a comprehensive analysis was performed on the hepatic gene expression profiling of coagulation-related factors by real-time RT-PCR(fibrinogen,prothrombin,factors Ⅴ,Ⅶ,Ⅷ,Ⅸ,Ⅹ,Ⅺ,Ⅻ,XⅢβ,plasminogen,antithrombin,protein C,protein S,ADAMTS13,and VWF) .The corresponding plasma levels of coagulation factors(fibrinogen,prothrombin,factors Ⅴ,Ⅶ,Ⅷ,Ⅸ,Ⅹ,Ⅺ,Ⅻ,XⅢ,and VWF) were also analyzed and compared with their mRNA levels.RESULTS:Gavage administration of TCPOBOP(3 mg/kg body weight) resulted in a marked and gradual increase in the weight of the mouse livers relative to the total body weight to 220% by D10 relative to the D0(control) ratios.At the peak of liver regeneration(D1 and D2) ,the gene expression levels for most of the coagulationrelated factors(fibrinogen,prothrombin,factors Ⅴ,Ⅶ,Ⅷ,Ⅸ,Ⅺ,Ⅻ,XⅢβ,plasminogen,antithrombin,protein C,ADAMTS13,VWF) were found to be downregulated in a time-dependent manner,and gradually recovered by D10 to the basal levels.Only mRNA levels of factor Ⅹ and protein S failed to show any decrease during the regenerative phase.As for the plasma levels,5 clotting factors(prothrombin,factors Ⅷ,Ⅸ,Ⅺ,and Ⅻ) demonstrated a significant decrease(P < 0.05) during the regeneration phase compared with D0.Among these 5 factors,factor Ⅸ and factor Ⅺ showed the most dramatic decline in their activities by about 50% at D2 compared to the basal levels,and these reductions in plasma activity for both factors were consistent with our RT-PCR findings.In contrast,the plasma activities of the other coagulation factors(fibrinogen,factors Ⅴ,Ⅶ,XⅢ,and VWF) were not significantly reduced,despite the reduction in the liver mRNA levels.Unlike the other factors,FX showed a temporal increase in its plasma activity,with significant increases(P < 0.05) detected at D1.CONCLUSION:Investigating the coagulation cascade protein profiles during liver regeneration by DH may help to better understand the basic biology of the liver under normal and pathological conditions. | Kohei Tatsumi Kazuo Ohashi Sanae Taminishi Soichi Takagi Rie Utoh Akira Yoshioka Midori Shima Teruo Okano | 2009 | World Journal of Gastroenterology2009，15，42： | 5 |
| 12 | Pulmonary tumor thrombotic microangiopathy of hepatocellular carcinoma: A case report and review of literature显示文摘BACKGROUND Pulmonary tumor thrombotic microangiopathy(PTTM)is a rare condition in patients with hepatocellular carcinoma(HCC);to date,few cases have been reported.While hepatic dysfunction has been focused on the later stages of HCC,the management of symptoms in PTTM is important for supportive care of the cases.For the better understanding of PTTM in HCC,the information of our recent case and reported cases have been summarized.CASE SUMMARY A patient with HCC exhibited acute and severe respiratory failure.Radiography and computed tomography of the chest revealed the multiple metastatic tumors and a frosted glass–like shadow with no evidence of infectious pneumonia.We diagnosed his condition as acute respiratory distress syndrome caused by the lung metastases and involvement of the pulmonary vessels by tumor thrombus.Administration of prednisolone to alleviate the diffuse alveolar damages including edematous changes of alveolar wall caused by the tumor cell infiltration and ischemia showed mild improvement in his symptoms and imaging findings.An autopsy showed the typical pattern of PTTM in the lung with multiple metastases.CONCLUSION PTTM is caused by tumor thrombi in the arteries and thickening of the pulmonary arterial endothelium leading to the symptoms of dyspnea in terminal staged patients.Therefore,supportive management of symptoms is necessary in the cases with PTTM and hence we believe that the information presented here is of great significance for the diagnosis and management of symptoms of PTTM with HCC. | Shinichi Morita Kenya Kamimura Hiroyuki Abe Yukari Watanabe-Mori Chiyumi Oda Takamasa Kobayashi Yoshihisa Arao Yusuke Tani Riuko Ohashi Yoichi Ajioka Shuji Terai | 2019 | World Journal of Gastroenterology2019，25，48： | 4 |
| 13 | Overexpression of c-met in the early stage of pancreatic carcinogenesis; altered expression is not sufficient for progression from chronic pancreatitis to pancreatic cancer显示文摘瞄准:在早胰腺的致癌作用期间调查遇见 c 的表示。方法:我们使用了 46 体积纸巾和 36 件微把样品,包括正常的胰,慢性胰炎,和胰腺的癌症,为量的即时反向的抄写聚合酶链反应。结果:大批,组织分析,胰腺的癌症纸巾显著地表示了高水平比遇见 c 做了慢性胰炎和正常的胰纸巾。遇见 c 的层次没在慢性胰炎和正常的胰纸巾之间不同。在基于 microdissection 的分析,遇见 c 比在正常管的上皮细胞在微把的胰腺的癌症房间和影响胰腺炎的上皮细胞在高水平被表示(两, P <
0.01 ) 。有趣地,影响胰腺炎的上皮细胞表示了层次遇见 c 类似于那些胰腺的癌症房间。结论:Overexpression 遇见 c 在胰腺的致癌作用的早阶段期间发生,并且遇见 c 的表示的单个改变不为到胰腺的癌症房间的长期的影响胰腺炎的上皮细胞的前进是足够的。 | Kenoki Ohuchida Kazuhiro Mizumoto Nami Ishikawa Yasuhiro Ogura Daisuke Yamada Takuya Egami Hayato Fujita Seiji Ohashi Eishi Nagai Masao Tanaka | 2006 | World Journal of Gastroenterology2006，12，24： | 4 |
| 14 | Simple and reproducible hepatectomy in the mouse using the clip technique显示文摘AIM: To investigate the reliability of massive hepatectomy models by using clip techniques. METHODS: We analyzed anatomical findings in 100 mice following massive hepatectomy induced by liver reduction > 70%. The impact of various factors in the different models was also analyzed, including learning curves, operative time, survival curves, and histopathological findings.RESULTS: According to anatomical results, models with 75%, 80%, and 90% hepatectomy produced massive hepatectomy. Learning curves and operative times were most optimal with the clip technique. Each hepatectomy performed using the clip technique produced a reasonable survival curve, and there were no differences in histopathological findings between the suture and clip techniques. CONCLUSION: Massive hepatectomy by the clip technique is simple and can provide reliable and relevant data. | Tomohide Hori Norifumi Ohashi Feng Chen Ann-Marie T Baine Lindsay B Gardner Toshiyuki Hata Shinji Uemoto Justin H Nguyen | 2012 | World Journal of Gastroenterology2012，18，22： | 4 |
| 15 | Recurrence pattern of squamous cell carcinoma of the thoracic esophagus after extended radical esophagectomy with three-field lymphadenectomy显示文摘 | Satoru Nakagawa Tatsuo Kanda Shin-ichi Kosugi Manabu Ohashi Tsutomu Suzuki Katsuyoshi Hatakeyama | 2004 | Journal of the American College of Surgeons2004，，2： | 3 |
| 16 | Disease-Free Survival as a Surrogate for Overall Survival in Adjuvant Trials of Gastric Cancer: A Meta-Analysis显示文摘 | Koji Oba Xavier Paoletti Steven Alberts Yung-Jue Bang Jacqueline Benedetti Harry Bleiberg Paul Catalano Florian Lordick Stefan Michiels Satoshi Morita Yasuo Ohashi Jean-pierre Pignon Philippe Rougier Mitsuru Sasako Junichi Sakamoto Daniel Sargent Kohei Sh | 2013 | JNCI Journal of the National Cancer Institute2013，，21： | 3 |
| 17 | Prognostic Significance of Intraperitoneal Cancer Cells in Gastric Carcinoma: Analysis of Real Time Reverse Transcriptase-Polymerase Chain Reaction after 5 Years of Followup显示文摘 | Yasuhiro Kodera Hayao Nakanishi Seiji Ito Yoshinari Mochizuki Norifumi Ohashi Yoshitaka Yamamura Michitaka Fujiwara Masahiko Koike Masae Tatematsu Akimasa Nakao | 2006 | Journal of the American College of Surgeons2006，，： | 3 |
| 18 | Matrix metalloproteinase-9 contributes to parenchymal hemorrhage and necrosis in the remnant liver after extended hepatectomy in mice显示文摘AIM:To investigate the effect of matrix metalloproteinase-9(MMP-9) on the remnant liver after massive hepatectomy in the mouse.METHODS:Age-matched,C57BL/6 wild-type(WT),MMP-9(-/-),and tissue inhibitors of metalloproteinases(TIMP)-1(-/-) mice were used.The mice received 80%-partial hepatectomy(PH).Samples were obtained at 6 h after 80%-PH,and we used histology,immunohistochemical staining,western blotting analysis and zymography to investigate the effect of PH on MMP-9.The role of MMP-9 after PH was investigated using a monoclonal antibody and MMP inhibitor.RESULTS:We examined the remnant liver 6 h after 80%-PH and found that MMP-9 deficiency attenuated the formation of hemorrhage and necrosis.There were significantly fewer and smaller hemorrhagic and necrotic lesions in MMP-9(-/-) remnant livers compared with WT and TIMP-1(-/-) livers(P < 0.01),with no difference between WT and TIMP-1(-/-) mice.Serum alanine aminotransaminase levels were significantly lower in MMP-9(-/-) mice compared with those in TIMP-1(-/-) mice(WT:476 ± 83 IU/L,MMP-9(-/-):392 ± 30 IU/L,TIMP-1(-/-):673 ± 73 IU/L,P < 0.01).Western blotting and gelatin zymography demonstrated a lack of MMP-9 expression and activity in MMP-9(-/-) mice,which was in contrast to WT and TIMP-1(-/-) mice.No change in MMP-2 expression was observed in any of the study groups.Similar to MMP-9(-/-) mice,when WT mice were treated with MMP-9 monoclonal antibody or the synthetic inhibitor GM6001,hemorrhagic and necrotic lesions were significantly smaller and fewer than in control mice(P < 0.05).These results suggest that MMP-9 plays an important role in the development of parenchymal hemorrhage and necrosis in the small remnant liver.CONCLUSION:Successful MMP-9 inhibition attenuates the formation of hemorrhage and necrosis and might be a potential therapy to ameliorate liver injury after massive hepatectomy. | Norifumi Ohashi Tomohide Hori Florence Chen Sura Jermanus Christopher B Eckman Akimasa Nakao Shinji Uemoto Justin H Nguyen | 2012 | World Journal of Gastroenterology2012，18，19： | 3 |
| 19 | Cancer detection by ubiquitin carboxyl-terminal esterase L1 methylation in pancreatobiliary fluids显示文摘AIM:To evaluate the utility of measuring epigenetic alterations in pancreatic and biliary fluids in determining molecular markers for pancreatobiliary cancers.METHODS:DNA was extracted from undiluted pancreatic and biliary fluids.As a surrogate for a genomewide hypomethylation assay,levels of long interspersed nuclear element-1(LINE-1) methylation were analyzed using bisulfite pyrosequencing.CpG island hypermethylation of 10 tumor-associated genes,aryl-hydrocarbon receptor repressor,adenomatous polyposis coli,calcium channel,voltage dependent,T type α1G subunit,insulin-like growth factor 2,O-6-methyl-guanine-DNA methyltransferase,neurogenin 1,CDKN2A,runt-related transcription factor 3(RUNX3),secreted frizzled-related protein 1,and ubiquitin carboxyl-terminal esterase L1(UCHL1),was analyzed using MethyLight.To examine the role of CpG methylation and histone deacetylation in the silencing of UCHL1,human gallbladder carcinoma cell lines and pancreatic carcinoma cell lines were treated with 2 or 5 μmol/L 5-AZA-dC for 72 h or 100 nmol/L Trichostatin A for 24 h.After the treatment,UCHL1 expression was analyzed by real-time reverse transcription-polymerase chain reaction.RESULTS:Pancreatobiliary cancers exhibited significantly lower LINE-1 methylation levels in pancreatic and biliary fluids than did noncancerous pancreatobiliary disease(58.7% ± 4.3% vs 61.7% ± 2.2%,P = 0.027;53.8% ± 6.6% vs 57.5% ± 1.7%,P = 0.007);however,LINE-1 hypomethylation was more evident in pancreatic cancer tissues than in pancreatic fluids(45.4% ± 5.5% vs 58.7% ± 4.3%,P < 0.001).CpG island hypermethylation of tumor-associated genes was detected at various frequencies,but it was not correlated with LINE-1 hypomethylation.Hypermethylation of the UCHL1 gene was cancer-specific and most frequently detected in pancreatic(67%) or biliary(70%) fluids from patients with pancreatobiliary cancer.As a single marker,hypermethylation of the UCHL1 gene in pancreatic and biliary fluids was most useful for the detection of pancreatic and pancreatobiliary cancers,respectively(100% specificity).Hypermethylation of the UCHL1 and RUNX3 genes in pancreatic and biliary fluids was the most useful combined marker for pancreatic(87% sensitivity and 100% specificity) and pancreatobiliary(97% sensitivity and 100% specificity) cancers.Treatment with a demethylating agent,5-AZA-2'-deoxycytidine,restored UCHL1 expression in pancreatobiliary cancer cell lines.CONCLUSION:Our results suggest that hypermethylation of UCHL1 and RUNX3 in pancreatobiliary fluid might be useful for the diagnosis of pancreatobiliary cancers. | Norihiro Kato Hiroyuki Yamamoto Yasushi Adachi Hirokazu Ohashi Hiroaki Taniguchi Hiromu Suzuki Mayumi Nakazawa Hiroyuki Kaneto Shigeru Sasaki Kohzoh Imai Yasuhisa Shinomura | 2013 | World Journal of Gastroenterology2013，19，11： | 3 |
| 20 | Associations between circulating microRNAs (miR-21, miR-34a, miR-122 and miR-451) and non-alcoholic fatty liver显示文摘 | Hiroya Yamada Koji Suzuki Naohiro Ichino Yoshitaka Ando Akira Sawada Keisuke Osakabe Keiko Sugimoto Koji Ohashi Ryouji Teradaira Takashi Inoue Nobuyuki Hamajima Shuji Hashimoto | 2013 | Clinica Chimica Acta2013，，： | 3 |
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