Tooru Shimosegawa

Tokyo Metropolitan Komagome Hospital, Edo, Tōkyō, Japan

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Publications (678)2822.91 Total impact

  • [Show abstract] [Hide abstract]
    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;
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    ABSTRACT: The cystic fibrosis transmembrane conductance regulator (CFTR) gene, responsible for the development of cystic fibrosis, is known as a pancreatitis susceptibility gene. Direct DNA sequencing of PCR-amplified CFTR gene segments is a first-line method to detect unknown mutations, but it is a tedious and labor-intensive endeavor given the large size of the gene (27 exons, 1,480 amino acids). Next-generation sequencing (NGS) is becoming standardized, reducing the cost of DNA sequencing, and enabling the generation of millions of reads per run. We here report a comprehensive analysis of CFTR variants in Japanese patients with chronic pancreatitis using NGS coupling with target capture. Exon sequences of the CFTR gene from 193 patients with chronic pancreatitis (121 idiopathic, 46 alcoholic, 17 hereditary, and nine familial) were captured by HaloPlex target enrichment technology, followed by NGS. The sequencing data covered 91.6 % of the coding regions of the CFTR gene by ≥20 reads with a mean read depth of 449. We could identify 12 non-synonymous variants including three novel ones [c.A1231G (p.K411E), c.1753G>T (p.E585X) and c.2869delC (p.L957fs)] and seven synonymous variants including three novel ones in the exonic regions. The frequencies of the c.4056G>C (p.Q1352H) and the c.3468G>T (p.L1156F) variants were higher in patients with chronic pancreatitis than those in controls. Target sequence capture combined with NGS is an effective method for the analysis of pancreatitis susceptibility genes.
    Digestive Diseases and Sciences 12/2014; · 2.26 Impact Factor
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    ABSTRACT: In Japan, after the revision of the gastrointestinal endoscopic guidelines for patients taking antithrombotics, endoscopic biopsies were permitted while continuing antithrombotics treatment. However, the risk of bleeding after the biopsy with or without cessation of antithrombotics has not been fully evaluated because bleeding events are very rare. So the aim of this prospective study was to evaluate the risk for bleeding after upper gastrointestinal biopsy without cessation of antithrombotics. Consecutive patients who underwent upper gastrointestinal endoscopic biopsy from December 2011 to March 2014 were enrolled in this study. The medication of antithrombotics and its cessation status was checked at the enrollment. To confirm bleeding events associated with biopsy, medical examination at the hospital or confirmation by telephone directly was done within one month after the biopsy. Among the 3758 patients who underwent endoscopic biopsies, 394 patients (10.5%) were medicated with antithrombotics, and 286 of them (72.6% of the total antithrombotics users) did not undergo cessation. Bleeding after the biopsy occurred in 6 cases (0.16%, 95%CI; 0.09%∼0.22%), but there was only 1 case who had continued taking antithrombotics. The incidence of bleeding after biopsy was not significantly higher in the patients who had continued taking antithrombotics, compared with the others (0.35% vs 0.14%, P=0.38). This prospective study showed that continuation of antithrombotics did not increase the bleeding risk after upper gastrointestinal endoscopic biopsy. (UMIN000014369). This article is protected by copyright. All rights reserved.
    Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society. 11/2014;
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    ABSTRACT: Two types of autoimmune pancreatitis (AIP) have been reported, lymphoplasmacytic sclerosing pancreatitis and idiopathic duct-centric chronic pancreatitis (IDCP), which are now recognized as type 1 and type 2 AIP, respectively. Since the clinical features of type 2 AIP have not been fully elucidated and this condition is frequently accompanied by inflammatory bowel disease (IBD), we performed a nationwide survey of patients with AIP complicated with IBD to precisely characterize this disease entity.
    Journal of gastroenterology. 11/2014;
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    ABSTRACT: Several recent studies have revealed that microRNAs (miRNAs) have a role in carcinogenesis and cancer development, and that it is stably detectable in plasma/serum. The aim of this study was to test whether miR‑483-3p as well as miR‑21 could be plasma biomarkers for PDAC. The plasma samples were obtained from three groups including 32 pancreatic ductal adenocarcinoma (PDAC) patients, 12 patients with intraductal papillary mucinous neoplasm (IPMN) patients and 30 healthy controls (HC). We evaluated the plasma miR‑483-3p and miR‑21 expression level by quantitative RT-PCR. We compared the differences in the plasma level of these miRNAs among the three groups, and investigated the relevance of their plasma expression level to the clinical factors in PDAC. The expressions of miR‑483-3p and miR‑21 were detected in all examined plasma samples. The plasma expression levels of these miRNAs were significantly higher in PDAC compared to HC (P<0.01). The plasma miR‑483-3p expression was significantly higher in PDAC patients than IPMN patients (P<0.05). The plasma miR‑21 level was associated with advanced stage (P<0.05), metastasis to lymph node and liver (P<0.01), and shorter survival (P<0.01) of the PDAC patients. Together, these findings suggest that measurement of the plasma miR‑483-3p level is useful for discriminating PDAC from IPMN, and that the plasma miR‑21 level predicts outcome of PDAC patients.
    International journal of oncology. 11/2014;
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    ABSTRACT: This study aimed to estimate the association of alcohol consumption and pancreatitis in Japan.
    Pancreas 11/2014; · 2.95 Impact Factor
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    ABSTRACT: Single preoperative biliary drainage for malignant perihilar biliary stricture occasionally fails to control jaundice and cholangitis. Multiple biliary drainage is required in such cases, but their clinical background is unclear. We determined the clinical characteristics associated with the requirement for multiple biliary drainage.
    Surgical endoscopy. 10/2014;
  • Morihisa Hirota, Toshihiko Mayumi, Tooru Shimosegawa
    Journal of Hepato-Biliary-Pancreatic Sciences. 10/2014;
  • Pancreas 10/2014; 43(7):1125-1126. · 2.95 Impact Factor
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    ABSTRACT: The poor clinical outcome in pancreatic ductal adenocarcinoma (PDA) is attributed to intrinsic chemoresistance and a growth-permissive tumor microenvironment. Conversion of quiescent to activated pancreatic stellate cells (PSCs) drives the severe stromal reaction that characterizes PDA. Here, we reveal that the vitamin D receptor (VDR) is expressed in stroma from human pancreatic tumors and that treatment with the VDR ligand calcipotriol markedly reduced markers of inflammation and fibrosis in pancreatitis and human tumor stroma. We show that VDR acts as a master transcriptional regulator of PSCs to reprise the quiescent state, resulting in induced stromal remodeling, increased intratumoral gemcitabine, reduced tumor volume, and a 57% increase in survival compared to chemotherapy alone. This work describes a molecular strategy through which transcriptional reprogramming of tumor stroma enables chemotherapeutic response and suggests vitamin D priming as an adjunct in PDA therapy. PAPERFLICK:
    Cell 09/2014; 159(1):80–93. · 31.96 Impact Factor
  • Kennichi Satoh, Shin Hamada, Tooru Shimosegawa
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    ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is an intractable disease as a result of its rapid dissemination and resistance to conventional chemotherapy and radiotherapy. Surgical resection is the only curative therapy, but most of the tumors are unresectable at the time of diagnosis. The molecular mechanisms underlying the biological aggressiveness of this tumor type remain to be clarified. Epithelial to mesenchymal transition (EMT) is a developmental process that leads the phenotype shift from an epithelial morphology to a motile, fibroblast-like morphology. Recent studies showed that EMT is involved in the invasion and metastasis of many types of carcinomas including PDAC. In addition, PDAC cells with the EMT phenotype also exhibit chemoresistance and the cancer stem cell property. Various factors such as cytokines, growth factors, or transcriptional factors were found to promote the EMT program in PDAC cells. In this review, we summarize the current knowledge about the EMT in PDAC cells, focusing on the involvement of this process and its regulatory molecules including microRNA during the development of PDAC cells.
    Journal of gastroenterology. 09/2014;
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    ABSTRACT: Received June 12, 2014; accepted July 31, 2014 Clinical practice guidelines for pancreatic cancer based on evidence-based medicine (2006) were published by the Japan Pancreas Society (Committee for revision of clinical guidelines for pancreatic cancer) in March 2009 in Japanese, revised to Clinical Practice Guidelines for Pancreatic Cancer based on evidence-based medicine (2009) in July 2009 in Japanese and further revised to Clinical Practice Guidelines for Pancreatic Cancer (2013) in October 2013 in Japanese. These guidelines were established according to evidence-based medicine. A total of 629 papers were collected from among 4612 reports concerning pancreatic cancer listed in PubMed and Igakuchuo Zasshi between May 2007 and January 2011. This new set of guidelines was written by members of the Committee for the Revision of Clinical Practice Guidelines for Pancreatic Cancer in the Japan Pancreas Society. The guidelines provide an algorithm for the diagnosis (Fig. 1) and treatment (Fig. 2) of pancreatic cancer and address six subjects (Diagnosis, Surgery, Adjuvant therapy, Radiation therapy, Chemotherapy and stent therapy), with 35 clinical questions and 57 recommendations.
    Japanese Journal of Clinical Oncology 09/2014; · 1.90 Impact Factor
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    ABSTRACT: Abstract Background. We assessed the controversial topic of using 22-gauge needles in endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for the diagnosis and evaluation of Ki67 labeling indices (Ki67LI) of pancreatic neuroendocrine tumors (pNET). Methods. Thirty-eight patients with pNET who underwent EUS-FNA between January 1, 2008 and December 31, 2012 were enrolled in this study. When available, the Ki67LI and WHO classifications obtained by EUS-FNA and surgical resection were compared. Results. EUS-FNA with a 22-gauge needle acquired sufficient histological sample to correctly diagnose pNET in 35 cases (92.1%). Both EUS-FNA and surgical histological specimens were available for 19 cases, and grading classes of the 2 procedures were consistent in 17 cases (89.5%) according to the WHO classification based on the Ki67LI. Tumor size was associated with a difference in the Ki67LI between the 2 procedures, although the Ki67LI was almost completely consistent for tumors less than 18 mm in size. Conclusions. EUS-FNA with a 22-gauge needle is a safe and highly accurate technique for the diagnosis of pNET. There was a clear correlation between the Ki67LI of histological specimens acquired by EUS-FNA and surgery. EUS-FNA with a 22-gauge needle is useful to predict the WHO classification of pNET.
    Scandinavian journal of gastroenterology. 09/2014;
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    ABSTRACT: Objectives A nationwide survey was conducted to clarify the epidemiological features of patients with chronic pancreatitis (CP) in Japan. Methods In the first survey, both the prevalence and the incidence of CP in 2011 were estimated. In the second survey, the clinicoepidemiological features of the patients were clarified by mailed questionnaires. Patients were diagnosed by the Japanese diagnostic criteria for chronic pancreatitis 2009. Results The estimated annual prevalence and incidence of CP in 2011 were 52.4/100,000 and 14.0/100,000, respectively. The sex ratio (male/female) of patients was 4.6, with a mean age of 62.3 years. Alcoholic (67.5%) was the most common and idiopathic (20.0%) was the second most common cause of CP. Comorbidity with diabetes mellitus (DM) and pancreatic calcifications (PC) occurred more frequent in ever smokers independently of their drinking status. Among patients without drinking habit, the incidences of DM and PC were significantly higher in ever smokers than in never smokers. The multiple logistic regression analysis revealed smoking was an independent factor of DM and PC in CP patients: DM, Odds ratio (OR) 1.644, 95% confidence interval (CI) 1.202 to 2.247 (P=0.002): PC, OR 2.010, 95% CI 1.458 to 2.773 (P<0.001). On the other hand, smoking was not identified as an independent factor for the appearance of abdominal pain by this analysis. Conclusion The prevalence of Japanese patients with CP has been increasing. Smoking was identified as an independent factor related to DM and PC in Japanese CP patients.
    Pancreatology 09/2014; · 2.04 Impact Factor
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    ABSTRACT: Dysphagia caused by pharyngo-upper esophageal stricture is a complication of treatment for head and neck cancer. Endoscopic balloon dilation (EBD) is in widespread use as an effective and safe treatment for stricture in many areas of the gastrointestinal tract. In this study, we investigated the efficacy and safety of EBD for pharyngo-upper esophageal strictures that developed after treatment for head and neck cancer.
    Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society. 08/2014;
  • Atsushi Kanno, Atsushi Masamune, Tooru Shimosegawa
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    ABSTRACT: Autoimmune pancreatitis (AIP) is characterized by diffuse pancreatic enlargement and irregular narrowing of the main pancreatic duct (MPD). IgG4-related sclerosing cholangitis (IgG4-SC) associated with AIP frequently appears as a bile duct stricture. Therefore, it is important to differentiate AIP and IgG4-SC from pancreatic cancer and cholangiocarcinoma or primary sclerosing cholangitis, respectively. Endoscopy plays a central role in the diagnosis of AIP and IgG4-SC, because it provides imaging of the MPD and bile duct strictures as well as the ability to obtain tissue samples for histological evaluations. Diffuse irregular narrowing of MPD on endoscopic retrograde cholangiopancreatography (ERCP) is rather specific to AIP, but localized narrowing of the MPD is often difficult to differentiate from MPD stenosis caused by pancreatic cancer. A long stricture (>1/3 the length of the MPD) and lack of upstream dilatation from the stricture (<5mm) might be key features of AIP on ERCP. Some cholangiographic features, such as segmental strictures, strictures of the lower bile duct, and long strictures with prestenotic dilatation, are more common in IgG4-SC than in cholangiocarcinoma. Intraductal ultrasonography with ERCP provides high resolution images of the bile duct wall that can be used to discriminate IgG4-SC from cholangiocarcinoma. Endoscopic ultrasonography (EUS) reveals diffuse hypoechoic pancreatic enlargement, sometimes with hypoechoic inclusions, in patients with AIP. In addition, EUS-elastography and contrast-enhanced harmonic EUS have been developed with promising results. The usefulness of EUS-guided fine needle aspiration has been increasingly recognized for obtaining adequate tissue samples for the histological diagnosis of AIP. Further improvement of endoscopic procedures and devices will contribute to more accurate diagnosis of AIP and IgG4-SC.
    Digestive Endoscopy 08/2014; · 1.61 Impact Factor
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    ABSTRACT: Background: We investigated the association between long-segment Barrett's esophagus and obesity in the Japanese population in a multicenter case-control trial. Methods: One hundred thirteen patients with endoscopically detected Barrett's esophagus with a length of more than 2 cm and the same number of sex- and age-matched controls were prospectively enrolled. Barrett's esophagus was diagnosed based on the Prague C and M criteria. The body mass index (BMI) of the subjects was categorized into the following groups: normal, BMI <22.9; overweight, BMI 23.0-24.9, and obese, BMI >25.0. To determine the association between BMI and the risk of Barrett's esophagus, multivariate logistic regression analyses were performed. Results: The basically adjusted regression model adjusted for smoking and alcohol consumption revealed that overweight and obesity were significantly associated with an elevated risk of Barrett's esophagus (OR 2.4, 95% CI 1.2-4.7, and OR 2.5, 95% CI 1.3-4.6, respectively). The intensity of the association was not attenuated even after adjustment for gastroesophageal reflux disease-related parameters. Conclusions: An increased BMI was associated with an increased risk for Barrett's esophagus through a gastroesophageal reflux-independent mechanism in the Japanese population. Further, unlike in Caucasian populations, being even slightly overweight with a BMI of 23.0-24.9 was an independent risk factor in the Japanese population. © 2014 S. Karger AG, Basel.
    Digestion 07/2014; 90(1):1-9. · 1.94 Impact Factor
  • Kaname Uno, Katsuaki Kato, Tooru Shimosegawa
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    ABSTRACT: Helicobacter pylori (H. pylori) infects the human stomach during infancy and develops into chronic active inflammation. The majority of H. pylori tend to colonize within the mucous gel layer of the stomach. The stomach lacks its own immune function, thus innate immunity as the first line of defense is vital for specific immunity against H. pylori. We review recent discoveries in the pathophysiologic roles of toll-like receptors (TLRs), mainly TLR2 and TLR4, in H. pylori-induced inflammation. In addition, the TLR pathways activated by H. pylori-induced inflammation have been shown to be closely associated not only with gastric carcinogenesis, but also with formation of the tumor microenvironment through the production of pro-inflammatory cytokines, chemokines, and reactive oxygen species. Although the correlation between single nucleotide polymorphisms of TLRs and gastric cancer risk remains unclear, a recent study demonstrated that STAT3-driven up-regulation of TLR2 might promote gastric tumorigenesis independent of inflammation. Further research on the regulation of TLRs in H. pylori-associated gastric carcinogenesis will uncover diagnostic/predictive biomarkers and therapeutic targets for gastric cancer.
    World Journal of Gastroenterology 05/2014; 20(18):5244-5251. · 2.55 Impact Factor
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    Katsunori Iijima, Tooru Shimosegawa
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    ABSTRACT: Over the last 3 decades, the incidence of esophageal adenocarcinoma has dramatically increased in Western countries; a similar increase may be observed in Asian countries in the near future. Esophageal adenocarcinoma arises from a sequential gastroesophageal reflux disease (GERD) spectrum from reflux erosive esophagitis, to Barrett's esophagus, and finally to esophageal adenocarcinoma. At present, gastric acid and bile are assumed to be primarily involved in the etiology of the GERD spectrum. We reported in 2002 that, at the gastroesophageal junction in humans, abundant amounts of nitric oxide (NO) are generated luminally through the entero-salivary re-circulation of dietary nitrate. Since then, we have carried out a series of experiments to demonstrate that NO diffuses into the adjacent epithelium at cytotoxic levels. This diffusion results in disruption of the epithelial barrier function, exacerbation of inflammation, acceleration of columnar transformation in the esophagus (Barrett's esophagus) via the induction of caudal-type homeobox 2, and the shifting of carcinogenic N-nitroso compound formation from the luminal to epithelial compartment. These results suggest that, in addition to conventionally recognized causative factors, luminal NO could also be involved in the pathogenesis of the GERD spectrum. In addition, we recently showed that there is a prominent gender-related difference in NO-related cytotoxicity in the esophagus and that estrogen attenuated the esophageal tissue damage via the estrogen receptor in female rats. The role of estrogen in attenuating the esophageal tissue damage in NO-related esophageal damage could explain the well-recognized male predominance in the GERD spectrum in humans.
    Journal of Gastroenterology and Hepatology 05/2014; 29(5):898-905. · 3.33 Impact Factor
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    ABSTRACT: Most patients with chronic pancreatitis develop intractable abdominal pain and malnutrition. A low-fat diet is one of the options used to manage intractable abdominal pain and malnutrition. However, few reports have examined the pain-suppression effect. To investigate the effects of oral ingestion of a low-fat elemental diet composed of purified amino acids on pain and nutritional status in patients with chronic pancreatitis, a multicenter prospective study was conducted. Patients with chronic pancreatitis with symptoms of abdominal pain were enrolled. In addition to meals, patients ingested a low-fat elemental diet composed of purified amino acids for 12 weeks. Before and after treatment, patients were asked to indicate their pain grade using a 100-mm horizontal visual analog scale, and nutritional indices, including body mass index and blood levels of pancreatic enzymes, were measured. A total of 596 patients were eligible for analysis. Marked pain reduction was observed with a significant decrease of the mean visual analog scale score by 32.9 mm from 52.9 mm after 12 weeks (P < 0.001). There were also significant improvements in nutritional indices. An oral low-fat elemental diet composed of purified amino acids, which requires no special treatment procedures, may improve patients' quality of life.
    Pancreas 04/2014; 43(3):451-7. · 2.95 Impact Factor

Publication Stats

9k Citations
2,822.91 Total Impact Points


  • 2012–2014
    • Tokyo Metropolitan Komagome Hospital
      Edo, Tōkyō, Japan
  • 2013
    • Cardarelli Hospital
      Napoli, Campania, Italy
    • Israelitisches Krankenhaus Hamburg
      Hamburg, Hamburg, Germany
  • 2012–2013
    • Miyagi Cancer Center
      Сендай, Miyagi, Japan
  • 2009–2013
    • Teikyo University Hospital
      Edo, Tōkyō, Japan
    • National Hospital Organization Sendai Medical Center
      Сендай, Miyagi, Japan
    • Nagoya University
      • Division of Emergency and Critical Care Medicine
      Nagoya-shi, Aichi-ken, Japan
  • 1985–2013
    • Tohoku University
      • • Department of Gastroenterology
      • • Division of Internal Medicine
      • • Graduate School of Medicine
      Sendai, Kagoshima-ken, Japan
  • 2010–2012
    • Kyushu University
      • • Department of Surgery and Oncology
      • • Graduate School of Medical Sciences
      Fukuoka-shi, Fukuoka-ken, Japan
  • 2011
    • Mayo Clinic - Rochester
      Rochester, Minnesota, United States
  • 2008
    • Tokyo Women's Medical University
      Edo, Tōkyō, Japan
    • Jichi Medical University
      • Division of Virology
      Totigi, Tochigi, Japan
  • 2007–2008
    • Numazu City Hospital
      Sizuoka, Shizuoka, Japan
    • University of California, Davis
      • Division of Rheumatology/Allergy/Clinical Immunology
      Davis, CA, United States
  • 2006
    • Kansai Medical University
      • Third Department of Internal Medicine
      Moriguchi, Ōsaka, Japan
  • 2004–2006
    • VA Greater Los Angeles Healthcare System
      Los Angeles, California, United States
    • University of Tsukuba
      • Institute of Clinical Medicine
      Tsukuba, Ibaraki, Japan
  • 2002
    • Sendai City Hospital
      Sendai, Kagoshima, Japan
  • 2001
    • Social Insurance Chukyo Hospital
      Nagoya, Aichi, Japan
  • 2000
    • Akita University
      • First Department of Internal Medicine
      Akita-shi, Akita-ken, Japan
    • Iwaki Kyoritsu General Hospital
      Ивакуни, Yamaguchi, Japan