Takeshi Azuma

Kobe University, Kōbe, Hyōgo, Japan

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Publications (399)2005.95 Total impact

  • Journal of Gastroenterology 06/2015; DOI:10.1007/s00535-015-1074-z · 4.02 Impact Factor
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    05/2015; DOI:10.1055/s-0034-1391665
  • Gastrointestinal Endoscopy 05/2015; 81(5):AB277. DOI:10.1016/j.gie.2015.03.1389 · 4.90 Impact Factor
  • Gastrointestinal Endoscopy 05/2015; 81(5):AB451. DOI:10.1016/j.gie.2015.03.851 · 4.90 Impact Factor
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    ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) is histologically characterized by the aberrant accumulation of lipid droplets in the liver, which is positively correlated with insulin resistance. Within the spectrum of this disease, patients can develop hepatitis and cirrhosis; i.e., non-alcoholic steatohepatitis (NASH). The mechanisms responsible for the progression of NAFLD are not fully understood. Triacylglycerol (TAG), which is mainly found in lipid droplets, is currently considered to act as a buffer against the accumulation of non-TAG toxic lipid species. In line with this, recent studies have revealed that insulin resistance is driven by the accumulation of phosphatidic acid and diacylglycerol in hepatocytes and that cholesterol-overloaded stellate cells are associated with fibrosis in the liver. Therefore, it is important to identify the toxic lipid species that contribute to NAFLD progression in order to clarify the pathogenesis of NASH and find novel targets for its treatment. In this review, we divided lipids into five classes; i.e., into fatty acyls, glycerophospholipids, glycerolipids, sphingolipids, and sterol lipids, and described their molecular structures, distributions, and metabolism under physiological conditions, as well as the contributions they make to the progression of NAFLD.
    Current drug targets 04/2015; · 3.60 Impact Factor
  • Gastroenterology 04/2015; 148(4):S-137. DOI:10.1016/S0016-5085(15)30471-6 · 13.93 Impact Factor
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    ABSTRACT: Hepatitis B virus (HBV) infection is major global issue, because chronic HBV infection is strongly associated with liver cancer. HBV spread worldwide with various mutations and variations. This variability, called quasispecies, is derived from no proof-reading capacity of viral reverse transcriptase. So far, thousands of studies reported that the variety of genome is closely related to the geographic distribution and clinical characteristics. Recent technological advances including capillary sequencer and next generation sequencer have made in easier to analyze mutations. The variety of HBV genome is related to not only antigenicity of HBs-antigen but also resistance to antiviral therapies. Understanding of these variations is important for the development of diagnostic tools and the appropriate therapy for chronic hepatitis B. In this review, recent publications in relation to HBV mutations and variations are updated and summarized.
    03/2015; 7(3):583-92. DOI:10.4254/wjh.v7.i3.583
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    ABSTRACT: Endoscopic submucosal dissection (ESD) is now widely accepted as a strategy to treat superficial esophageal neoplasms. The rate of adverse events, such as perforation, has been decreasing with the improvement of devices and techniques. In this paper, we report a case of esophageal cancer that had a diverticulum under cancerous epithelium. The diverticulum was not detected during preoperative examination, and led to perforation during the ESD procedure. Our case shows that, although rare, some diverticula can exist underneath the mucosal surface without obvious depression. If there is any sign of hidden diverticula during ESD, surgeons should proceed with caution or, depending on the case, the procedure should be discontinued to avoid adverse events.
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    ABSTRACT: Recently, endoscopic submucosal dissection (ESD) has been applied for superficial colorectal neoplasms and the number of publications about it has been increasing, but little is known about the outcomes of colorectal ESD for the lesions >50 mm. In this study, we evaluated the feasibility and safety of colorectal ESD for the lesions >50 mm compared with the lesions <50 mm. A total of 674 superficial colorectal neoplasms in 629 patients treated by ESD at Kobe University Hospital from July 2008 to July 2013 were included in the analysis. The median operation time (range) in the large lesion group (≥5 cm) was 109 (37 to 596) minutes, and it was 55 (6 to 248) minutes in the small lesion group (<5 cm). Median procedure speed (range) in the large lesion group was 0.28 (0.06 to 0.83) cm/min, and it was 0.19 (0.04 to 0.83) cm/min in the small lesion group. The en bloc resection rate and the curative resection rate in the small lesion group was 98.7% and 96.0%, and those were 95.7% and 91.4% in the large lesion group, respectively. In terms of adverse events, perforation, muscle damage, and postoperative bleeding occurred at similar frequency in both groups. ESD on colorectal lesions >50 mm takes longer operation time; however, it is resected time effectively without increasing the risk of adverse events compared with smaller lesions by ESD.
    Surgical laparoscopy, endoscopy & percutaneous techniques 03/2015; 25(3). DOI:10.1097/SLE.0000000000000135 · 0.94 Impact Factor
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    ABSTRACT: Afferent loop obstruction caused by cancer recurrence after pancreaticoduodenectomy (PD) can be managed by either surgical or nonsurgical treatment. The general condition of patients with recurrent pancreaticobiliary cancer is often not good enough for them to undergo surgery, so less invasive nonsurgical treatment is desirable. We report a case of a 66-year-old male who had undergone PD for pancreatic head adenocarcinoma 10 months previously and who presented at our hospital with fever and jaundice due to afferent loop obstruction caused by pancreatic cancer recurrence. An endoscopic self-expandable metal stent (SEMS) was placed for afferent loop obstruction without any complications. He quickly recovered after SEMS placement. He retained a good quality of life by receiving chemotherapy until his death due to cancer progression. Our case indicates that this method could be an easy, effective, safe, and less invasive treatment, which may confer a better quality of life for patients with afferent loop obstruction due to cancer recurrence after PD.
    Clinical Journal of Gastroenterology 02/2015; DOI:10.1007/s12328-015-0556-0
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    ABSTRACT: Finding a noninvasive method to predict liver fibrosis using inexpensive and easy-to-use markers is important. We aimed to clarify whether NX-des-γ-carboxyprothrombin (NX-DCP) could become a new noninvasive model to predict liver fibrosis in hepatitis C virus (HCV) related liver disease. We performed a prospective cohort study on a consecutive group of 101 patients who underwent liver biopsy for HCV-related liver disease at Kobe University Hospital. Laboratory measurements were performed on the same day as the biopsy. Factors associated with significant fibrosis (F3-4) were assessed by multivariate analyses. A comparison of predictive ability between multivariate factors and abovementioned noninvasive models was also performed. Increase in serum NX-DCP was significantly related to increase in fibrosis stage (P = 0.006). Moreover, NX-DCP was a multivariate factor associated with the presence of significant fibrosis F 3-4 (median 21 of F0-2 group vs. median 22 of F3-4 group with P = 0.002). The AUC of NX-DCP showed no significant differences compared with those of the AST-to-platelet ratio index (APRI), modified-APRI, the Göteborg University Cirrhosis Index (GUCI), the Lok index, the Hui score, cirrhosis discriminating score (CDS) and the Pohl score (P > 0.05). NX-DCP correlated positively with fibrosis stage and could discriminate well between HCV-related patients with or without significant fibrosis. Moreover, NX-DCP had a similar predictive ability to the abovementioned models, and thereby could be a new noninvasive prediction tool for fibrosis.
    Hepatitis Monthly 02/2015; 15(2):e22978. DOI:10.5812/hepatmon.22978 · 1.80 Impact Factor
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    ABSTRACT: Our understanding of the mechanism of cancer dormancy is emerging, but the underlying mechanisms are not fully understood. Here we analyzed mouse xenograft tumors derived from human breast cancer tissue and the human breast cancer cell line MDA-MB-231 to identify the molecules associated with cancer dormancy. In immunohistological examination using the proliferation marker Ki-67, the tumors included both proliferating and dormant cancer cells, but the number of dormant cells was remarkably increased when they metastasized to the lung. In the gene expression analysis of the orthotopic cancer cells by a single-cell multiplex real-time quantitative reverse transcription PCR followed by flow cytometric analysis, restrained cellular proliferation was associated with downregulation of the chemokine receptor CXCR4. In the immunohistological and flow cytometric analyses, the expression level of CXCR4 in the metastasized cancer cells was decreased compared with that in the cancer cells in orthotopic tumors, although the expression level of the CXCR4 ligand CXCL12 was not reduced in the lung. In addition, the proliferation of the metastasized cancer cells was further decreased by the CXCR4 antagonist administration. In the ex vivo culture of the metastasized cancer cells, the expression level of CXCR4 was increased, and in the xenotransplantation of ex vivo cultured cancer cells, the expression level of CXCR4 was again decreased in the metastasized cancer cells in the lung. These findings indicate that CXCR4 is downregulated in metastasized breast cancer cells and implicated in their dormancy.
    PLoS ONE 01/2015; 10(6):e0130032. DOI:10.1371/journal.pone.0130032 · 3.53 Impact Factor
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    ABSTRACT: New strategies for the care of irritable bowel syndrome (IBS) are developing and several novel treatments have been globally produced. New methods of care should be customized geographically because each country has a specific medical system, life style, eating habit, gut microbiota, genes and so on. Several clinical guidelines for IBS have been proposed and the Japanese Society of Gastroenterology (JSGE) subsequently developed evidence-based clinical practice guidelines for IBS. Sixty-two clinical questions (CQs) comprising 1 definition, 6 epidemiology, 6 pathophysiology, 10 diagnosis, 30 treatment, 4 prognosis, and 5 complications were proposed and statements were made to answer to CQs. A diagnosis algorithm and a three-step treatment was provided for patients with chronic abdominal pain or abdominal discomfort and/or abnormal bowel movement. If more than one alarm symptom/sign, risk factor and/or routine examination is positive, colonoscopy is indicated. If all of them, or the subsequent colonoscopy, are/is negative, Rome III or compatible criteria is applied. After IBS diagnosis, step 1 therapy consisting of diet therapy, behavioral modification and gut-targeted pharmacotherapy is indicated for four weeks. Non-responders to step 1 therapy proceed to the second step that includes psychopharmacological agents and simple psychotherapy for four weeks. In the third step, for patients non-responsive to step 2 therapy, a combination of gut-targeted pharmacotherapy, psychopharmacological treatments and/or specific psychotherapy is/are indicated. Clinical guidelines and consensus for IBS treatment in Japan are well suited for Japanese IBS patients; as such, they may provide useful insight for IBS treatment in other countries around the world.
    Journal of Gastroenterology 12/2014; 50(1). DOI:10.1007/s00535-014-1017-0 · 4.02 Impact Factor
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    ABSTRACT: Proton-pump inhibitors are known to be effective in the treatment and prevention of ulcers related to low-dose aspirin (LDA), but few reports address H2 -receptor antagonists (H2RAs) and gastroprotective agents (GPs). This study was intended to compare the therapeutic effects of an H2RA and a GP against gastroduodenal mucosal injuries in patients taking LDA. The subjects consisted of patients requiring continuous LDA treatment, in whom no peptic ulcer was found on endoscopy at enrollment. The patients were randomized to either famotidine 20 mg/day (group F) or teprenone 150 mg/day (group T). The study medication was administered for 12 weeks. The patients underwent endoscopy after administration of the study medication in order to obtain a Lanza score. A total of 66 patients (38 in group F, 28 in group T) were included in the efficacy analysis population. The Lanza score changed as follows: in group F, it improved significantly, from 0.89 ± 1.03 (mean ± standard deviation) before medication to 0.39 ± 0.75 after medication (P = 0.006); in group T, no significant difference was observed: 0.75 ± 0.93 before medication and 0.68 ± 0.82 after medication. Famotidine is better than teprenone in terms of reducing the number of the erosions under use of LDA. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.
    Journal of Gastroenterology and Hepatology 12/2014; 29 Suppl S4:11-15. DOI:10.1111/jgh.12768 · 3.63 Impact Factor
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    ABSTRACT: Cancer cachexia is a multifactorial syndrome characterized by progressive loss of weight and muscle atrophy. Using metabolomics, we investigated serum markers and their intra-day variation in advanced pancreatic cancer patients with cachexia. Patients were enrolled in two groups: those with or without cachexia. Blood samples collected at 6:30 AM, 11:30 AM, 4:30 PM, and 9:30 PM were analyzed using metabolomics, and serum levels of IL-6, TNF-α, and leptin were measured and compared between the two groups. Intra-day variation was then evaluated. Twenty-one patients were enrolled in total. In the cachexia group (n = 9), median body weight loss rate over 6 months was greater, performance status was poorer, and anorexia was more severe than in the non-cachexia group (n = 12). Each metabolites level showed substantial intra-day variation, and some of them displayed significant differences between the two groups. Levels of paraxanthine remained markedly lower in the cohort with cachexia at all measurement points. Besides, median IL-6 and TNF-α levels appeared higher and leptin concentration appeared lower in the cachexia group, albeit without statistical significance. Some metabolites and some serological marker levels were affected by cancer cachexia. Although paraxanthine levels were consistently lower in patients with cachexia, we identified that many metabolites indicated large intra- and inter-day variation and that it might be necessary to pay attention to intra-day variation in metabolomics research.
    PLoS ONE 11/2014; 9(11):e113259. DOI:10.1371/journal.pone.0113259 · 3.53 Impact Factor
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    ABSTRACT: A case in which a self-expandable biodegradable (BD) esophageal stent was used for a refractory esophageal anastomotic stricture (EAS) in a 5-year-old female is presented. The patient underwent closure of a tracheoesophageal fistula and gastrostomy in the neonatal period. Esophagoesophagostomy was performed at 18 months of age after a multistaged extrathoracic esophageal elongation procedure. The patient developed refractory EAS and required repeated esophageal balloon dilation. Four sessions of esophageal BD stenting were performed from the age of 5-8 years. Each BD stenting allowed her to eat chopped food, but the anastomotic stricture recurred 4-7 months after the procedure. No major complications were observed, though transient chest pain and dysphagia were observed after each stenting. Finally, at 8 years of age, EAS resection and esophagoesophageal anastomosis were performed. The resected specimens showed thickened scar formation at the EAS lesion, while the degree of esophageal wall damage, both at the proximal and distal ends of the stricture, was slight. To the best of our knowledge, this is the first case report of this kind of treatment and assessment of damage to the esophageal wall microscopically. The advantages and problems of the use of BD stents in children are discussed.
    Clinical Journal of Gastroenterology 11/2014; DOI:10.1007/s12328-014-0537-8
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    ABSTRACT: Objective Superficial colorectal tumors can be treated effectively by endoscopic submucosal dissection (ESD). Few data are available concerning ESD for residual or recurrent tumors after first endoscopic resection. This study was aimed to evaluate the efficacy of ESD for these lesions.Methods Twenty-eight patients with residual or recurrent colorectal superficial tumors were referred at the Kobe University Hospital for ESD. The therapeutic outcomes and the possible factors predictive of procedure difficulties for ESD were analyzed.ResultsIn total, 27/28 lesions (96%) were successfully treated. There was no related immediate complication. One patient had a delayed perforation treated surgically. En bloc R0 resection was possible in all the patients and curative resection in 26/28 patients (92.8%). One invasive cancer was treated surgically. More than one previous endoscopic resection was the only significant predictive factor for the ESD difficulty. None of the patients experienced recurrence after 22 months (range 3-41) follow-up.Conclusions This study showed that ESD allowed a high rate of en bloc resection for residual or locally recurrent colorectal tumors. Furthermore, these lesions should be treated by ESD as the first-line treatment.
    Journal of Digestive Diseases 11/2014; 16(1). DOI:10.1111/1751-2980.12207 · 1.92 Impact Factor
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    ABSTRACT: Objective: The long-term administration of a nucleos(t)ide analogue (NA) for the treatment of chronic hepatitis B may encourage the emergence of viral mutations associated with drug resistance. Minor populations of viruses may exist before treatment, but are difficult to detect because of technological limitations. Identifying minor viral quasispecies should be useful in the clinical management of hepatitis B virus (HBV) infection. Methods: Six treatment-naïve Indonesian patients with chronic HBV infection participated in this study. The polymerase region of the HBV genome, including regions with known drug-resistant mutations, was subjected to capillary sequencing and MiSeq sequencing (Illumina). Mutations were analyzed with Genomics Workbench software version 6.0.1 (CLC bio). Results: The mean mapping reads for the six samples was 745,654, and the mean number of amplified fragments ranged from 17,926 to 25,336 DNA reads. Several known drug-resistant mutations in the reverse transcriptase region were identified in all patients, although the frequencies were low (0.12-1.06%). The proportions of the total number of reads containing mutations I169L/M, S202R, M204I/L or N236S were >1.0%. Conclusion: Several known NA-resistant mutations were detected in treatment-naïve patients in Indonesia using deep sequencing. Careful management of such patients is essential to prevent drug-resistant mutations from spreading to other patients. © 2014 S. Karger AG, Basel.
    Intervirology 10/2014; 57(6):384-392. DOI:10.1159/000366420 · 1.77 Impact Factor
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    ABSTRACT: The potential of supercritical fluid extraction (SFE) as a preparation method for mass spectrometry of dried blood spots (DBS) was examined. SFE is generally used for the extraction of hydrophobic compounds, but hydrophilic metabolites such as amino acids, amines, and nucleic-acid-related metabolites could be extracted by adding a low level of methanol as a modifier. Under the optimized conditions, over 200 metabolites were detected from a dried serum spot, of which over 160 metabolites could be analyzed stably (RSD <20%). These results show that SFE is an effective extraction method of metabolites with a wide range of polarity in DBS.
    Journal of Chromatography B 10/2014; 969:199–204. DOI:10.1016/j.jchromb.2014.08.013 · 2.69 Impact Factor

Publication Stats

8k Citations
2,005.95 Total Impact Points


  • 2007–2015
    • Kobe University
      • • Division of Gastroenterology
      • • Department of Internal Medicine
      Kōbe, Hyōgo, Japan
  • 2013
    • Chiang Mai University
      Amphoe Muang Chiang Mai, Chiang Mai, Thailand
  • 2010
    • Kobe Gakuin University
      Kōbe, Hyōgo, Japan
  • 2008
    • Tohoku University
      • Institute of Development, Aging and Cancer
      Sendai, Kagoshima, Japan
  • 2001–2008
    • University of Fukui
      Hukui, Fukui, Japan
    • Shiga University of Medical Science
      Ōtu, Shiga Prefecture, Japan
  • 1984–2008
    • Kyoto Prefectural University of Medicine
      • Division of Preventive Medicine
      Kioto, Kyōto, Japan
  • 2005–2007
    • Hokkaido University
      • • Graduate School of Science
      • • Institute for Genetic Medicine
      Sapporo-shi, Hokkaido, Japan
  • 1998–2007
    • Fukui University
      Hukui, Fukui, Japan
    • University Hospitals Of Leicester NHS Trust
      Leiscester, England, United Kingdom
  • 1998–2005
    • Okinawa Chubu Hospital
      Okinawa, Okinawa, Japan
  • 2002–2004
    • Fukui General Hospital
      Hukui, Fukui, Japan
    • Tokyo Medical University
      Edo, Tōkyō, Japan
  • 2000
    • Nagoya Second Red Cross Hospital
      Nagoya, Aichi, Japan
    • Fukui Prefectural University
      Hukui, Fukui, Japan
  • 1988–1995
    • Wayne State University
      • School of Medicine
      Detroit, Michigan, United States
  • 1992
    • University of Texas Southwestern Medical Center
      • Department of Pediatrics
      Dallas, TX, United States
  • 1990–1992
    • Kyoto Prefectural University
      Kioto, Kyōto, Japan