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| 1 | Importance of adequate immunosuppressive therapy for the recovery of patients with 'life-threatening' severe exacerbation of chronic hepatitis B显示文摘AIM: Hepatitis B virus (HBV) re-activation often occurs spontaneously or after withdrawal of immunosuppressive therapy in patients with chronic hepatitis B. Severe exacerbation, sometimes developing into fulminant hepatic failure, is at high risk of mortality. The efficacy of corticosteroid therapy in 'clinically severe' exacerbation of chronic hepatitis B has not been well demonstrated. In this study we evaluated the efficacy of early introduction of high-dose corticosteroid therapy in patients with lifethreatening severe exacerbation of chronic hepatitis B.METHODS: Twenty-two patients, 14 men and 8 women,were defined as 'severe' exacerbation of chronic hepatitis B using uniform criteria and enrolled in this study. Eleven patients were treated with corticosteroids at 60 mg or more daily with or without anti-viral drugs within 10 d after the diagnosis of severe disease ('early high-dose'group) and 11 patients were either treated more than 10 d or untreated with corticosteroids ('non-early high-dose'group).RESULTS: Mean age, male-to-female ratio, mean prothrombin time (PT) activity, alanine transaminase (ALT)level, total bilirubin level, positivity of HBeAg, mean IgMHBc titer, and mean HBV DNA polymerase activity did not differ between the two groups. Ten of 11 patients of the 'early high-dose' group survived, while only 2 of 11 patients of the 'non-early high-dose' group survived (P<0.001). During the first 2 wk after the introduction of corticosteroids, improvements in PT activities and total bilirubin levels were observed in the 'early high-dose'group. Both ALT levels and HBV DNA polymerase levels fell in both groups.CONCLUSION: The introduction of high-dose corticosteroid can reverse deterioration in patients with 'clinically lifethreatening' severe exacerbation of chronic hepatitis B,when used in the early stage of illness. | Keiichi Fujiwara Osamu Yokosuka Hiroshige Kojima Tatsuo Kanda Hiromitsu Saisho Hiroyuki Hirasawa Hiroshi Suzuki | 2005 | World Journal of Gastroenterology2005，11，8： | 20 |
| 2 | 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 |
| 3 | Xanthogranulomatous cholecystitis:Difficulty in differentiating from gallbladder cancer显示文摘AIM: To compare cases of xanthogranulomatous cholecystitis(XGC) and advanced gallbladder cancer and discuss the differential diagnoses and surgical options.METHODS: From April 2000 to December 2013, 6 XGC patients received extended surgical resections. During the same period, 16 patients were proven to have gallbladder(GB) cancer, according to extended surgical resection. Subjects chosen for analysis in this study were restricted to cases of XGC with indistinct borders with the liver as it is often difficult to distinguish these patients from those with advanced GB cancer. We compared the clinical features and computed tomography findings between XGC and advanced GB cancer. The following clinical features were retrospectively assessed: age, gender, symptoms, and tumor markers. As albumin and the neutrophil/lymphocyte ratio(NLR) are prognostic in several cancers, we compared serum albumin levels and the NLR between the two groups. The computerized tomography findings were used to compare the two diseases, determine the coexistence of gallstones, the pattern of GB thickening(focal or diffuse), the presence of a hypoattenuated intramural nodule, and continuity of the mucosal line.RESULTS: Based on the preoperative image findings, we suspected GB carcinoma in all cases includingXGC in this series. In addition, by pathological examination, we found that the group of patients with XGC developed inflammatory disease after surgery. Patients with XGC tended to have abdominal pain(4/6, 67%). However, there was no significant difference in clinical symptoms, including fever, between the two groups. Serum albumin and NLR were also similar in the two groups. Serum tumor markers, such as carcinoembryonic antigen(CEA) and carbohydrate antigen 19-9(CA19-9), tended to increase in patients with GB cancer. However, no significant differences in tumor markers were identified. On the other hand, gallstones were more frequently observed in patients with XGC(5/6, 83%) than in patients with GB cancer(4/16, 33%)(P = 0.0116). A hypoattenuated intramural nodule was found in 3 patients with XGC(3/6, 50%), but in only 1 patient with GB cancer(1/16, 6%)(P = 0.0024). The GB thickness, continuous mucosal line, and bile duct dilatation showed no significant differences between XGC and GB cancer.CONCLUSION: Although XGC is often difficult to differentiate from GB carcinoma, it is possible to obtain an accurate diagnosis by careful intraoperative gross observation, and several intraoperative frozen sections. | Hideki Suzuki Satoshi Wada Kenichiro Araki Norio Kubo Akira Watanabe Mariko Tsukagoshi Hiroyuki Kuwano | 2015 | World Journal of Gastroenterology2015，21，35： | 18 |
| 4 | High-density circulating fluidized bed gasifier for advanced IGCC/IGFC-Advantages and challenges显示文摘Coal-fired Integrated Gasification Combined Cycle(IGCC)and Integrated coal Gasification Fuel-cell Combined cycle(IGFC)are being developed as high-efficiency electric power generation technology.However,the highest theoretical gross thermal efficiency of the conventional IGCC/IGFC is still below 52%.In order to obtain higher power generation efficiency,an advanced IGCC(A-IGCC)or advanced IGFC(A-IGFC)system making use of the exergy recuperation concept by recycling waste heat from gas turbine or fuel cells for steam gasification of coal and biomass was proposed in our laboratory.Corresponding to this system,a novel high-density triple-bed combined circulating fluidized bed(TBCFB)gasifier,composed of a downer pyrolyzer,a bubbling fluidized bed char gasifier,and a riser combustor,was proposed to replace traditional gasifiers such as the entrained flow bed gasifier.The new system is expected to more effectively utilize the waste heat from gas turbines or fuel cells and the heat produced by the combustion of the unreacted char in the riser combustor for pyrolysis and gasification of coal and biomass.In this short review,the advantages and future challenges in the development of high-density TBCFB gasifier are presented and discussed. | Guoqing Guan Chihiro Fushimi Atsushi Tsutsumi Masanori Ishizuka Satoru Matsuda Hiroyuki Hatano Yoshizo Suzuki | 2010 | Particuology2010，8，6： | 17 |
| 5 | 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 |
| 6 | Pancreatic stents for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis should be inserted up to the pancreatic body or tail显示文摘AIM To investigate the location to which a pancreatic stent should be inserted to prevent post-endoscopic retrograde cholangiopancreatography(ERCP) pancreatitis(PEP).METHODS Over a ten-year period at our hospital, 296 patients underwent their first ERCP procedure and had a pancreatic stent inserted; this study included 147 patients who had ERCP performed primarily for biliary investigation and had a pancreatic stent inserted to prevent PEP. We dividedthese patients into two groups: 131 patients with a stent inserted into the pancreatic head(head group) and 16 patients with a stent inserted up to the pancreatic body or tail(body/tail group). Patient characteristics and ERCP factors were compared between the groups.RESULTS Pancreatic amylase isoenzyme(p-AMY) levels in the head group were significantly higher than those in the body/tail group [138.5(7.0-2086) vs 78.5(5.0-1266.5), P = 0.03] [median(range)]. No cases of PEP were detected in the body/tail group [head group, 12(9.2%)]. Of the risk factors for post-ERCP hyperamylasemia(≥ p-AMY median, 131 IU/L), procedure time ≥ 60 min [odds ratio(OR) 2.65, 95%CI: 1.17-6.02, P = 0.02) and stent insertion into the pancreatic head(OR 3.80, 95%CI: 1.12-12.9, P = 0.03) were identified as independent risk factors by multivariate analysis.CONCLUSION Stent insertion up to the pancreatic body or tail reduces the risk of post-ERCP hyperamylasemia and may reduce the risk of PEP. | Mitsuru Sugimoto Tadayuki Takagi Rei Suzuki Naoki Konno Hiroyuki Asama Yuki Sato Hiroki Irie Ko Watanabe Jun Nakamura Hitomi Kikuchi Yuichi Waragai Mika Takasumi Takuto Hikichi Hiromasa Ohira | 2018 | World Journal of Gastroenterology2018，24，22： | 13 |
| 7 | 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 |
| 8 | Hyperglycemia is a significant prognostic factor of hepatocellular carcinoma after curative therapy显示文摘AIM:To evaluate whether metabolic factors are related to distant recurrence of hepatocellular carcinoma(HCC) and survival after curative treatment.METHODS:This retrospective study included 344 patients whose HCC was treated curatively by radiofrequency ablation(RFA) therapy.The mean age was 67.6 years and the mean observation period was 4.04 years.The etiological background of liver disease was hepatitis B virus infection in 30,hepatitis C virus infection in 278,excessive alcohol drinking in 9,and other in 27 patients.The Child-Pugh classification grade was A(n = 307) or B(n = 37).The number of HCC nodules was one in 260,two in 61,and three in 23 patients.For surveillance of HCC recurrence after curative therapy with RFA,patients were radiologically evaluated every 3 mo.Factors associated with distant recurrence of HCC or survival were studied.RESULTS:Inadequate maintenance of blood glucose in diabetic patients was associated with higher incidence of distant recurrence.The 1-,2-,and 3-year recurrence rates were significantly higher in diabetic patients with inadequate maintenance of blood glucose compared with the others:50.6% vs 26.8%,83.5% vs 54.4%,and 93.8% vs 73.0%,respectively(P = 0.0001).Inadequate maintenance of blood glucose was an independent predictor of distant recurrence [adjusted relative risk 1.97(95%CI,1.33-2.91),(P = 0.0007)] after adjustment for other risk factors,such as number of HCC nodules [2.03(95%CI,1.51-2.73),P < 0.0001] and initial level of serum alpha fetoprotein(AFP) [1.43(95%CI,1.04-1.97),P = 0.028].Obesity was not an independent predictor of recurrence.The incidence of distant recurrence did not differ between diabetic patients with adequate maintenance of blood glucose and non-diabetic patients.Among 232 patients who had HCC recurrence,138 had a second recurrence.The 1-,2-,and 3-year rates of second recurrence were significantly higher in diabetic patients with inadequate maintenance of blood glucose than in the others:9.0% vs 5.9%,53.1% vs 24.3%,and 69.6% vs 42.3%,respectively(P = 0.0021).Inadequate maintenance of blood glucose in diabetic patients [1.99(95%CI,1.23-3.22),P = 0.0049] and presence of multiple HCC nodules [1.53(95%CI,1.06-2.22),P = 0.024] were again significantly associated with second HCC recurrence.Inadequate maintenance of blood glucose in diabetic patients was also a significant predictor of poor survival [2.77(95%CI,1.38-5.57),P = 0.0046] independent of excessive alcohol drinking [6.34(95%CI,1.35-29.7),P = 0.019],initial level of serum AFP [3.40(95%CI,1.88-6.18),P < 0.0001] and Child-Pugh classification grade B [2.24(95%CI,1.12-4.46),P = 0.022].Comparing diabetic patients with inadequate maintenance of blood glucose vs the others,the 1-,2-,and 3-year survival rates were significantly lower in diabetic patients with inadequate maintenance of blood glucose:92% vs 99%,85% vs 96%,and 70% vs 92%,respectively(P = 0.0003).CONCLUSION:Inadequate maintenance of blood glucose in diabetic patients is a significant risk factor for recurrence of HCC and for poor survival after curative RFA therapy. | Takanori Hosokawa Masayuki Kurosaki Kaoru Tsuchiya Shuya Matsuda Masaru Muraoka Yuichiro Suzuki Nobuharu Tamaki Yutaka Yasui Toru Nakata Takashi Nishimura Shoko Suzuki Ken Ueda Hiroyuki Nakanishi Jun Itakura Yuka Takahashi Namiki Izumi | 2013 | World Journal of Gastroenterology2013，19，2： | 12 |
| 9 | Vitamin D and calcium are required at the time of denosumab administration during osteoporosis treatment显示文摘To evaluate the differences in outcomes of treatment with denosumab alone or denosumab combined with vitamin D and calcium supplementation in patients with primary osteoporosis. Patients were split into a denosumab monotherapy group(18 cases) or a denosumab plus vitamin D supplementation group(combination group; 23 cases). We measured serum bone alkaline phosphatase(BAP), tartrate-resistant acid phosphatase(TRACP)-5 b and urinary N-terminal telopeptide of type-I collagen(NTX) at baseline, 1 week, as well as at 1 month and 2, 4, 8 and 12 months. We also measured bone mineral density(BMD) of L1–4 lumbar vertebrae(L)-BMD and bilateral hips(H)-BMD at baseline and at 4, 8 and 12 months. There was no significant difference in patient background. TRACP-5 b and urinary NTX were significantly suppressed in both groups from 1 week to 12 months(except at 12 months for NTX). In the combination group, TRACP-5 b was significantly decreased compared with the denosumab monotherapy group at 2 and 4 months(P < 0.05).BAP was significantly suppressed in both groups at 2–12 months. L-BMD significantly increased at 8 and12 months(8.9%) in the combination group and at 4, 8 and 12 months(6.0%) in the denosumab monotherapy group, compared with those before treatment. H-BMD was significantly increased in the combination group(3.6%) compared with the denosumab group(1.2%) at 12 months(P < 0.05). Compared with denosumab monotherapy, combination therapy of denosumab with vitamin D and calcium stopped the decrease in calcium caused by denosumab, inhibited bone metabolism to a greater extent, and increased BMD(especially at the hips). | Yukio Nakamura Takako Suzuki Mikio Kamimura Kohei Murakami Shota Ikegami Shigeharu Uchiyama Hiroyuki Kato | 2017 | Bone Research2017，5，4： | 11 |
| 10 | Is hepatic arterial infusion chemotherapy effective treatment for advanced hepatocellular carcinoma resistant to transarterial chemoembolization?显示文摘AIM:To evaluate the effectiveness of hepatic arterial infusion chemotherapy(HAIC) for advanced hepatocellular carcinoma(HCC) resistant to transarterial chemoembolization(TACE).METHODS:This study was conducted on 42 patients who received HAIC for advanced HCC between 2001and 2010 at our hospital.5-fluorouracil(5-FU) was administered continuously for 24 h from day 1 to day 5 every 2-4 wk via an injection reservoir.Intra-arterial cisplatin or subcutaneous interferon was administered in combination with the 5-FU.The patients enrolled in this retrospective study were divided into two groups according to whether or not they fulfilled the criteria for resistance to TACE proposed by the Japan Society of Hepatology in 2010(written in Japanese);one group of patients who did not fulfill the criteria for TACE resistance(group A,n = 23),and another group who fulfilled the criteria for TACE resistance(group B,n = 19).We compared the outcomes in terms of the response and survival rates between the two groups.RESULTS:Both the response rate and tumor suppression rate following HAIC were significantly superior in group A than in group B(response rate:48% vs 16%,P = 0.028,tumor suppression rate:87% vs 53%,P = 0.014).Furthermore,both the progression-free survival rate and survival time were significantly superior in group A than in group B(3-,6-,12-,and 24-mo = 83%,70%,29% and 20% vs 63%,42%,16% and 0%,respectively,P = 0.040,and 9.8 mo vs 6.2 mo,P = 0.040).A multivariate analysis(Cox proportional hazards regression model) showed that resistance to TACE was an independent predictor of poor survival(P = 0.007).CONCLUSION:HAIC administrating 5-FU was not effective against advanced HCC resistant to TACE.Other tools for treatment,i.e.,molecular-targeting agents may be considered for these cases. | Hiroyuki Kirikoshi Masato Yoneda Hironori Mawatari Koji Fujita Kento Imajo Shingo Kato Kaori Suzuki Noritoshi Kobayashi Kensuke Kubota Shin Maeda Atsushi Nakajima Satoru Saito | 2012 | World Journal of Gastroenterology2012，18，16： | 9 |
| 11 | Usefulness of vonoprazan,a potassium ion-competitive acid blocker,for primary eradication of Helicobacter pylori显示文摘AIM To investigate usefulness of triple therapy with vonoprazan,a potassium ion-competitive acid blocker and antibiotics,for Helicobacter pylori(H.pylori) eradication.METHODS The H.pylori eradication rate was examined in 2507 patients(2055 undergoing primary eradication and 452 undergoing secondary eradication,excluding patients with subtotal gastrectomy) at the Japanese Red Cross Kyoto Daiichi Hospital from March 2013 to September 2015.For patients treated from March 2013 to February 2015,a proton pump inhibitor(PPI) was used to reduce acid secretion,while vonoprazan was used after March 2015.The success rates of the 2 regimens(PPI + amoxicillin + clarithromycin/metronidazole,or vonoprazan + amoxicillin + clarithromycin/metronidazole) were compared.RESULTS The success rate of primary H.pylori eradication was significantly higher in the vonoprazan group.When stratified by the underlying disease,a significant increase of the H.pylori eradication rate was observed in patients with chronic gastritis.A significantly lower H.pylori eradication rate was observed in younger patients compared to older patients in the PPI group,but there was no difference according to age in the vonoprazan group.On the otherhand,the success rate of secondary eradication was similar at approximately 90% in both groups.CONCLUSION Vonoprazan is very useful for primary eradication of H.pylori,and may become a first-line acid secretion inhibitor instead of PPIs. | Shinya Yamada Takumi Kawakami Yoshikazu Nakatsugawa Takahiro Suzuki Hideki Fujii Naoya Tomatsuri Hideki Nakamura Hideki Sato Yusuke Okuyama Hiroyuki Kimura Norimasa Yoshida | 2016 | World Journal of Gastrointestinal Pharmacology and Therapeutics2016，7，4： | 8 |
| 12 | Growth and low-energy electron microscopy characteri- zation of monolayer hexagonal boron nitride on epitaxial cobalt显示文摘低精力的电子显微镜学(LEEM ) 习惯于原子地薄的六角形的硼氮化物(h-BN ) 的层的结构,起始的生长取向,生长前进,和数字拍摄的学习。h-BN 电影在低压力用化学蒸汽免职(CVD ) 在 heteroepitaxial 公司上被种。我们从 LEEM 的调查结果学习包括有二的单层电影的生长,与公司格子同量的相对地面向的、三角形的 BN 领域。h-BN 的生长看起来在单层自我限制,与仅仅出现在补丁的更厚的领域,大概在领域边界之间开始了。更厚的 h-BN 电影的反射率大小显示出通过 h-BN 电影的使量子化的电子状态源于反响的电子传播的摆动,与与 h-BN 层的数字扩大规模的最小的数字。第一原则密度功能的理论(DFT ) 计算证明摆动的位置与 h-BN 的电子乐队结构有关。 | Carlo M. Orofeo Satoru Suzuki Hiroyuki Kageshima Hiroki Hibino | 2013 | Nano Research2013，6，5： | 7 |
| 13 | 胆道肿瘤临床实践指南(英文第三版)显示文摘日本肝胆胰外科学会(JSHBPS)于2007年出版第一版胆道肿瘤(胆管癌、胆囊癌及壶腹癌)临床实践指南,于2014年更新第二版,2021年英文第三版胆道肿瘤临床实践指南围绕6个主题提出若干临床问题,基于相关循证医学证据并组织专家讨论后,最终确定推荐意见、推荐强度以及推荐说明。根据证据推荐分级的评估、制订与评价(GRADE)系统,推荐强度被分为1级(强)或者2级(弱)。英文第三版胆道肿瘤临床实践指南中提出的31个临床问题涵盖:(1)预防性治疗;(2)诊断;(3)胆道引流;(4)外科治疗;(5)化疗;(6)放疗。31个临床问题中,14个问题给予推荐强度为强的推荐意见,14个问题给予推荐强度为弱的推荐意见,剩余的3个问题未给予推荐意见。每条推荐意见都进行推荐强度说明。最新版指南基于循证医学证据,为临床提供了重要建议。未来与癌症登记数据库协作将是评估指南和建立新证据的关键。 | Masato Nagino Satoshi Hirano Hideyuki Yoshitomi Taku Aoki Katsuhiko Uesaka Michiaki Unno Tomoki Ebata Masaru Konishi Keiji Sano Kazuaki Shimada Hiroaki Shimizu Ryota Higuchi Toshifumi Wakai Hiroyuki Isayama Takuji Okusaka Toshio Tsuyuguchi Yoshiki Hirooka Junji Furuse Hiroyuki Maguchi Kojiro Suzuki Hideya Yamazaki Hiroshi Kijima Akio Yanagisawa Masahiro Yoshida Yukihiro Yokoyama Takashi Mizuno Itaru Endo 杨翼飞(译) 仇毓东(译) 赵梦珂(译) 伏旭(译) 蔡正华(译) 毛凉(审校) | 2021 | 中华消化外科杂志2021，20，4： | 7 |
| 14 | Efficacy of endoscopic ultrasonography-guided fine needle aspiration for pancreatic neuroendocrine tumor grading显示文摘AIM: To evaluate the efficacy of endoscopic ultrasonography-guided fine needle aspiration(EUS-FNA) for grading pancreatic neuroendocrine tumors(PNETs).METHODS: A total of 22 patients were diagnosed with PNET by EUS-FNA between October 2001 and December 2013 at Fukushima Medical University Hospital.Among these cases,we targeted 10 PNET patients who were evaluated according to the World Health Organization(WHO) 2010 classification.Surgery was performed in eight patients,and chemotherapy was performed in two patients due to multiple liver metastases.Specimens obtained by EUS-FNA were first stained with hematoxylin and eosin and then stained with chromogranin,synaptophysin,CD56,and Ki-67.The specimens were graded by the Ki-67 index according to the WHO 2010 classification.Specimens obtained by surgery were graded by the Ki-67 indexand mitotic count(WHO 2010 classification).For the eight specimens obtained by EUS-FNA,the Ki-67 index results were compared with those obtained by surgery.In the two cases treated with chemotherapy,the effects and prognoses were evaluated.RESULTS: The sampling rate for histological diagnosis by EUS-FNA was 100%.No adverse effects were observed.The concordance rate between specimens obtained by EUS-FNA and surgery was 87.5%(7/8).Fo r t h e t w o c a s e s t re a t e d w i t h c h e m o t h e ra p y,case 1 received somatostatin analog therapy and transcatheter arterial infusion(TAI) targeting multiple liver metastases.Subsequent treatment consisted of everolimus.During chemotherapy,the primary tumor remained unconfirmed,although the multiple liver metastases diminished dramatically.Case 2 was classified as neuroendocrine carcinoma(NEC) according to the Ki-67 index of a specimen obtained by EUS-FNA; therefore,cisplatin and irinotecan therapy was started.However,severe adverse effects,including renal failure and diarrhea,were observed,and the therapy regimen was changed to cisplatin and etoposide.TAI targeting multiple liver metastases was performed.Although the liver metastases diminished,the primary tumor remained unconfirmed.These chemotherapy regimens had immediate effects for both unresectable neuroendocrine tumor(NET) and NEC cases.These two subjects are still alive.CONCLUSION: EUS-FNA was effective for PNET diagnosis and Ki-67 index grading for WHO 2010 classification,enabling informed decisions on unresectable PNET treatment by identifying NET or NEC. | Mitsuru Sugimoto Tadayuki Takagi Takuto Hikichi Rei Suzuki Ko Watanabe Jun Nakamura Hitomi Kikuchi Naoki Konno Yuichi Waragai Hiroyuki Asama Mika Takasumi Hiroshi Watanabe Katsutoshi Obara Hiromasa Ohira | 2015 | World Journal of Gastroenterology2015，21，26： | 6 |
| 15 | Long-term follow-up of ulcerative colitis patients treated on the basis of their cytomegalovirus antigen status显示文摘AIM:To clarify the impact of cytomegalovirus(CMV)activation and antiviral therapy based on CMV antigen status on the long-term clinical course of ulcerative colitis(UC)patients.METHODS:UC patients with flare-up were divided into CMV-positive and-negative groups according to the CMV antigenemia assay.The main treatment strategy provided for the patients in the CMV-positive group comprised a dose reduction of corticosteroids and administration of ganciclovir.RESULTS:The median number of days to initial remission was significantly greater for the patients in the CMV-positive group(21 d vs 16 d,P=0.009).However,the relapse rate after remission and colectomy rate during more than 30 mo of observation did not differ between the two groups.Multivariate analysis revealed that administration of ganciclovir was the only independent factor for avoiding colectomy in patients of the CMV-positive group.CONCLUSION:CMV antigen status did not significantly affect the long-term prognosis in UC patients under treatment with appropriate antiviral therapy. | Toshihiro Inokuchi Jun Kato Sakiko Hiraoka Hideyuki Suzuki Asuka Nakarai Tomoko Hirakawa Mitsuhiro Akita Sakuma Takahashi Keita Harada Hiroyuki Okada Kazuhide Yamamoto | 2014 | World Journal of Gastroenterology2014，20，2： | 6 |
| 16 | The increase in surface CXCR4 expression on lung extravascular neutrophils and its effects on neutrophils during endotoxin-induced lung injury显示文摘Inflammatory stimuli,such as a microbes or lipopolysaccharides,induce a rapid release of neutrophils from the bone marrow and promote neutrophil migration into inflamed sites to promote host defense.However,an excess accumulation and retention of neutrophils in inflamed tissue can cause severe tissue injuries in the later stages of inflammation.Recent studies have reported that both CXCL12 levels in injured lungs and its receptor,CXCR4,on accumulated neutrophils in injured lungs,increased;furthermore,these studies showed that the CXCL12/CXCR4 signaling pathway participated in neutrophil accumulation in the later stages of lipopolysaccharide(LPS)-induced lung injury.However,the mechanisms underlying this increase in surface CXCR4 expression in neutrophils remain unclear.In this study,we found that surface CXCR4 expression increased in extravascular,but not intravascular,neutrophils in the lungs of LPS-induced lung injury model mice.Furthermore,ex vivo studies revealed that CXCL12 acted not only as a chemoattractant,but also as a suppressor of cell death for the lung neutrophils expressing CXCR4.Sulfatide,one of the native ligands for L-selectin,induced the increase of surface CXCR4 expression on isolated circulating neutrophils,suggesting that the activation of L-selectin may be involved in the increase in surface CXCR4.Our findings show that surface CXCR4 levels on neutrophils increase after extravasation into injured lungs,possibly through the activation of L-selectin.The CXCL12/CXCR4 signaling pathway plays an important role in the modulation of neutrophil activity during acute lung injury,not only by promoting chemotaxis but also by suppressing cell death. | Mitsuhiro Yamada Hiroshi Kubo Seiichi Kobayashi Kota Ishizawa Mei He Takaya Suzuki Naoya Fujino Hiroyuki Kunishima Masamitsu Hatta Katsushi Nishimaki Tetsuji Aoyagi Kouichi Tokuda Miho Kitagawa Hisakazu Yano Hirokazu Tamamura Nobutaka Fujii Mitsuo Kaku | 2011 | Cellular & Molecular Immunology2011，8，4： | 6 |
| 17 | MicroRNA-31 expression in colorectal serrated pathway progression显示文摘MicroRNAs have been increasingly recognized as useful biomarkers for colorectal cancers(CRC).We have recently observed that microRNA-31(miR-31)expression is associated with BRAF mutation and prognosis in CRC.Moreover,high miR-31 expression is frequently detected in sessile serrated adenomas compared with hyperplastic polyps(HPs).These results suggest that miR-31 may contribute to the progression of serrated lesions.At a follow-up colonoscopy,we observed the case of a 75-year-old man with a 7-mm flat-elevated lesion in the cecum and diagnosed the lesion as an early invasive carcinoma with serrated features.Tissue specimens were obtained from the representative areas to compare the molecular alterations in the carcinoma component with those in the HP component.Higher miR-31 expression was observed in the carcinoma component(57-fold increase)and the HP component(8-fold increase)compared with the paired normal mucosa,suggesting that miR-31 may be one of the key molecules in serrated pathway progression. | Hironori Aoki Katsuhiko Nosho Hisayoshi Igarashi Miki Ito Kei Mitsuhashi Takafumi Naito Eiichiro Yamamoto Tokuma Tanuma Masafumi Nomura Hiroyuki Maguchi Toshiya Shinohara Hiromu Suzuki Hiroyuki Yamamoto Yasuhisa Shinomura | 2014 | World Journal of Gastroenterology2014，20，34： | 5 |
| 18 | Familial pancreatic cancer: Concept, management and issues显示文摘Familial pancreatic cancer (FPC) is broadly defined as two first-degree-relatives with pancreatic cancer (PC) and accounts for 4%-10% of PC. Several genetic syndromes, including Peutz-Jeghers syndrome, hereditary pancreatitis, hereditary breast-ovarian cancer syndrome(HBOC), Lynch syndrome, and familial adenomatous polyposis (FAP), also have increased risks of PC, but the narrowest definition of FPC excludes these known syndromes. When compared with other familial tumors, proven genetic alterations are limited to a small proportion (<20%) and the familial aggregation is usually modest. However, an ethnic deviation (Ashkenazi Jewish>Caucasian) and a younger onset are common also in FPC. In European countries, 'anticipation' is reported in FPC families, as with other hereditary syndromes; a trend toward younger age and worse prognosis is recognized in the late years. The resected pancreases of FPC kindred often show multiple pancreatic intraepithelial neoplasia (Pan IN) foci, with various K-ras mutations, similar to colorectal polyposis seen in the FAP patients. As with HBOC patients, a patient who is a BRCA mutation carrier with unresectable pancreatic cancer (accounting for 0%-19% of FPC patients) demonstrated better outcome following platinum and Poly (ADP-ribose) polymerase inhibitor treatment. Western countries have established FPC registries since the 1990 s and several surveillance projects for highrisk individuals are now ongoing to detect early PCs. Improvement in lifestyle habits, including non-smoking, is recommended for individuals at risk. In Japan, the FPC study group was initiated in 2013 and the Japanese FPC registry was established in 2014 by the Japan Pancreas Society. | Hiroyuki Matsubayashi Kyoichi Takaori Chigusa Morizane Hiroyuki Maguchi Masamichi Mizuma Hideaki Takahashi Keita Wada Hiroko Hosoi Shinichi Yachida Masami Suzuki Risa Usui Toru Furukawa Junji Furuse Takamitsu Sato Makoto Ueno Yoshimi Kiyozumi Susumu Hijioka Nobumasa Mizuno Takeshi Terashima Masaki Mizumoto Yuzo Kodama Masako Torishima Takahisa Kawaguchi Reiko Ashida Masayuki Kitano Keiji Hanada Masayuki Furukawa Ken Kawabe Yoshiyuki Majima Toru Shimosegawa | 2017 | World Journal of Gastroenterology2017，23，6： | 5 |
| 19 | Nuclear heat shock protein 110 expression is associated with poor prognosis and hyperthermo-chemotherapy resistance in gastric cancer patients with peritoneal metastasis显示文摘AIM To investigate the significance of heat shock protein 110(HSP110) in gastric cancer(GC) patients with peritoneal metastasis undergoing hyperthermochemotherapy.METHODS Primary GC patients(n = 14) with peritoneal metastasis or positive peritoneal lavage cytology who underwent distal or total gastrectomy between April 2000 and December 2011 were enrolled in this study. The patients underwent postoperative intraperitoneal hyperthermo-chemotherapy using a Thermotron RF-8 heating device two weeks after surgery. We analyzed nuclear HSP110 expression in surgically resected tumors using immunohistochemistry. Additionally, the effect of HSP110 suppression on hyptherthermochemosensitivity was assessed in vitro in the MKN45 GC cell line using the HSP inhibitor KNK437. RESULTS HSP110 immnohistochemical staining in 14 GC patients showed that five(35.7%) samples belonged to the low expression group, and nine(64.3%) samples belonged to the high expression group. Progression-free survival was significantly shorter in the HSP110 high-expression group than in the low-expression group(P = 0.0313). However, no significant relationships were identified between HSP110 expression and the clinicopathological characteristics of patients. Furthermore, high HSP110 expression was not an independent prognostic factor in GC patients with peritoneal metastasis(P = 0.0625). HSP110 expression in MKN45 cells was suppressed by KNK437 at the hyperthermic temperature of 43 ℃ in vitro. Comparison of MKN45 cell proliferation in the presence and absence of KNK437 at 43 ℃, revealed that proliferation was significantly decreased when HSP110 was inhibited by KNK437. Additionally, HSP110 suppression via HSP inhibitor treatment increased cellular sensitivity to hyperthermo-chemotherapy in vitro.CONCLUSION The expression of nuclear HSP110 in GC patients might be a new marker of chemosensitivity and a therapeutic target for patients who are tolerant to existing hyperthermo-chemotherapies. | Akiharu Kimura Kyoichi Ogata Bolag Altan Takehiko Yokobori Erito Mochiki Mitsuhiro Yanai Norimichi Kogure Toru Yanoma Masaki Suzuki Tuya Bai Hiroyuki Kuwano | 2017 | World Journal of Gastroenterology2017，23，42： | 5 |
| 20 | Endoscopic naso-pancreatic drainage for the treatment of pancreatic fistula occurring after LDLT显示文摘Pancreatic fistula is a quite rare complication in patients who undergo living donor liver transplantation(LDLT).However,in the cases that show pancreatic fistula,the limited volume of the graft and the resultant inadequate liver function may complicate the management of the fistula.As a result,the pancreatic fistula may result in the death of the patient.We present 2 cases in whichendoscopic treatment was effective against pancreatic fistulas that developed after LDLT.In case 1,a 61-yearold woman underwent LDLT for primary biliary cirrhosis.Because of a portal venous thrombus caused by a splenorenal shunt,the patient underwent portal vein reconstruction,and a splenorenal shunt was ligated on postoperative day(POD)7.The main pancreatic duct was injured during the manipulation to achieve hemostasis,thereby necessitating open drainage.However,discharge of pancreatic fluid continued even after POD 300.Endoscopic naso-pancreatic drainage(ENPD)was performed,and this procedure resulted in a remarkable decrease in drain output.The refractory pancreatic fistula healed on day 40 after ENPD.In case 2,a 58-year-old man underwent LDLT for cirrhosis caused by the hepatitis C virus.When the portal vein was exposed during thrombectomy,the pancreatic head was injured,which led to the formation of a pancreatic fistula.Conservative therapy was ineffective;therefore,ENPD was performed.The pancreatic fistula healed on day 38 after ENPD.The findings in these 2 cases show that endoscopic drainage of the main pancreatic duct is a less invasive and effective treatment for pancreatic fistulas that develop after LDLT. | Akihisa Nagatsu Toshiya Kamiyama Satoru Todo Masahiko Taniguchi Tomomi Suzuki Hiroyuki Furukawa Tsuyoshi Shimamura Kenichiro Yamashita Hiroshi Kawakami Daisuke Abo | 2011 | World Journal of Gastroenterology2011，17，30： | 5 |
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