Tooru Shimosegawa

Tokyo Metropolitan Komagome Hospital, Edo, Tōkyō, Japan

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Publications (694)2953.02 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: General interest in functional gastrointestinal disorders is increasing among Japanese doctors as well as patients. This increase can be attributed to a number of factors, including recent increased interest in quality of life and advances in our understanding of the pathophysiology of gastrointestinal disease. Japan recently became the world's first country to list "functional dyspepsia" as a disease name for national insurance billing purposes. However, recognition and understanding of functional dyspepsia (FD) remain poor, and no standard treatment strategy has yet been established. Accordingly, the Japanese Society of Gastroenterology (JSGE) developed an evidence-based clinical practice guideline for FD, consisting of five sections: concept, definition, and epidemiology; pathophysiology; diagnosis; treatment; and prognosis and complications. This article summarizes the Japanese guideline, with particular focus on the treatment section. Once a patient is diagnosed with FD, the doctor should carefully explain the pathophysiology and benign nature of this condition, establish a good doctor-patient relationship, and then provide advice for daily living (diet and lifestyle modifications, explanations, and reassurance). The proposed pharmacological treatment is divided into two steps: initial treatment including an acid inhibitory drug (H2RA or PPI) or prokinetics, (strong recommendation); second-line treatment including anxiolytics, antidepressants, and Japanese traditional medicine (weak recommendation). H. pylori eradication, strongly recommended with a high evidence level, is positioned separately from other treatment flows. Conditions that do not respond to these treatment regimens are regarded as refractory FD. Patients will be further examined for other organic disorders or will be referred to specialists using other approaches such as psychosomatic treatment.
    Journal of gastroenterology. 01/2015;
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    ABSTRACT: Background Recently in Japan, the morbidity of colorectal polyp has been increasing. As a result, a large number of cases of colorectal polyps that are diagnosed and treated using colonoscopy has now increased, and clinical guidelines are needed for endoscopic management and surveillance after treatment. Methods Three committees [the professional committee for making clinical questions (CQs) and statements by Japanese specialists, the expert panelist committee for rating statements by the modified Delphi method, and the evaluating committee by moderators] were organized. Ten specialists for colorectal polyp management extracted the specific clinical statements from articles published between 1983 and September 2011 obtained from PubMed and a secondary database, and developed the CQs and statements. Basically, statements were made according to the GRADE system. The expert panel individually rated the clinical statements using a modified Delphi approach, in which a clinical statement receiving a median score greater than seven on a nine-point scale from the panel was regarded as valid. Results The professional committee created 91CQs and statements for the current concept and diagnosis/treatment of various colorectal polyps including epidemiology, screening, pathophysiology, definition and classification, diagnosis, treatment/management, practical treatment, complications and surveillance after treatment, and other colorectal lesions (submucosal tumors, nonneoplastic polyps, polyposis, hereditary tumors, ulcerative colitis-associated tumor/carcinoma). Conclusions After evaluation by the moderators, evidence-based clinical guidelines for management of colorectal polyps have been proposed for 2014.
    Journal of Gastroenterology 01/2015; · 4.02 Impact Factor
  • Yasuteru Kondo, Osamu Kimura, Tooru Shimosegawa
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    ABSTRACT: In addition to surgical procedures, radiofrequency ablation is commonly used for the treatment of hepatocellular carcinomas (HCCs) of limited size and number. Transcatheter arterial chemoembolization (TACE), using iodized poppy seed oil, Lipiodol and anticancer drugs, has been actively performed for the treatment of unresectable HCC, particularly in Asian countries. Recently, Sorafenib become available for advanced HCCs when the liver is still sufficiently functional. Sorafenib is an oral multikinase inhibitor with antiproliferative and antiangiogenic effects. However, the effect of sorafenib seems to be inadequate to control the progression of HCC. Radiation therapy (RT) for HCC has a potential role across all stages of HCC. However, RT is generally not considered an option in HCC consensus documents or national guidelines, primarily because of insufficient supporting evidence. However, the method of RT has much improved because of advances in technology. Moreover, combined treatment of RT plus other treatments (TACE, sorafenib and chemotherapy etc.) has become one of the alternative therapies for HCC. Therefore, we should understand the various kinds of RT available for HCC. In this review, we focus on various kinds of external beam radiation therapy.
    World journal of gastroenterology : WJG. 01/2015; 21(1):94-101.
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    ABSTRACT: The prevalence of Helicobacter pylori-negative and non-steroidal anti-inflammatory drug (NSAID)-negative peptic ulcers, commonly known as idiopathic peptic ulcers (IPUs), has been reported to be very low (0.9-2.6%) in Japan based on data from the 1990s. However, recent trends have yet to be been reported. Herein, we present a multicenter prospective analysis between 2012 and 2013 investigating current trends in the prevalence and characteristics of IPUs in Japan. Clinical data of all peptic ulcer subjects detected via endoscopy at four participating hospitals were prospectively collected between April 2012 and March 2013. Enrolled subjects were classified according to H. pylori infection status and intake of NSAIDs. Multiple logistic regression analyses were used to determine the risk factors for IPUs. Of 382 enrolled patients with peptic ulcers, 46 (12%) were judged to have IPUs. Compared to those with simple H. pylori-positive ulcers, patients with IPUs were significantly older (p < 0.02), and more often had underlying comorbidities such as hypertension (p < 0.02) and hyperlipidemia (p < 0.05). Multivariate regression analysis indicated that the presence of multiple underlying diseases was the only significant risk factor for IPUs, with an odds ratio of 3.8 (95% confidence interval, 1.3-11.1). This study revealed that the prevalence of IPUs in patients with peptic ulcers in Japan is 12%, much higher than previously reported. Presence of multiple underlying comorbid diseases, rather than aging itself, is an important risk factor for IPUs. This article is protected by copyright. All rights reserved.
    Journal of Gastroenterology and Hepatology 12/2014; · 3.33 Impact Factor
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    ABSTRACT: The gastric acid secretion level is an important determinant for the manifestation of the gastroesophageal reflux disease spectrum, finally leading to the development of esophageal adenocarcinoma (EAC). Although the incidence of EAC has remained low in Asia, understanding the recent trend in gastric acid secretion should be helpful in estimating future incidences of EAC in that area. We investigated the latest chronological change (1995-2014) in gastric acid secretion in normal Japanese patients. A total of 307 asymptomatic Japanese men who attended the clinic for annual endoscopic checkups from 1995 to 2014 were enrolled in this analysis. Gastrin-stimulated gastric acid secretion was estimated with the endoscopic gastrin test. The association between gastric acid secretion and chronological period was assessed with a multivariate linear regression analysis. Overall gastric acid secretion gradually increased over the 20-year period in the entire cohort in the unadjusted analysis (p < 0.05). However, the apparent increase was largely related to the relative decreasing rate of H. pylori infection, which profoundly inhibited gastric acid secretion. Gastric acid secretion did not change over the 20-year period in H. pylori-negative subjects, and it showed only a mild increase during this period in H. pylori-positive subjects. Considering that gastric acid secretion remained unchanged in H. pylori-negative Japanese men over a 20-year period at a level much lower than that in Occidental subjects, upper gastrointestinal disease profiles in the Japanese population will differ from those in Western countries in the post-H. pylori era.
    Journal of Gastroenterology 12/2014; · 4.02 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; · 4.02 Impact Factor
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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; · 4.02 Impact Factor
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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; · 2.77 Impact Factor
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    ABSTRACT: This study aimed to estimate the association of alcohol consumption and pancreatitis in Japan.
    Pancreas 11/2014; · 3.01 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; · 3.31 Impact Factor
  • Morihisa Hirota, Toshihiko Mayumi, Tooru Shimosegawa
    Journal of Hepato-Biliary-Pancreatic Sciences. 10/2014;
  • Pancreas 10/2014; 43(7):1125-1126. · 3.01 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. · 33.12 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; · 4.02 Impact Factor
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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; · 1.75 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; · 2.33 Impact Factor
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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; · 2.50 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;

Publication Stats

9k Citations
2,953.02 Total Impact Points


  • 2012–2014
    • Tokyo Metropolitan Komagome Hospital
      Edo, Tōkyō, Japan
    • Kyushu University
      • Department of Surgery and Oncology
      Fukuoka-shi, Fukuoka-ken, Japan
    • Tokai University
      Hiratuka, Kanagawa, Japan
  • 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
      • • Department of Pathology
      Sendai, Kagoshima-ken, Japan
  • 2006–2012
    • Kansai Medical University
      • • Department of Gastroenterology and Hepatology
      • • Third Department of Internal Medicine
      Moriguchi, Osaka-fu, Japan
  • 2008
    • Tokyo Women's Medical University
      Edo, Tōkyō, Japan
  • 2007–2008
    • Numazu City Hospital
      Sizuoka, Shizuoka, Japan
  • 2004–2006
    • VA Greater Los Angeles Healthcare System
      Los Angeles, California, United States
    • University of Tsukuba
      • Institute of Clinical Medicine
      Tsukuba, Ibaraki, Japan
  • 2001
    • Social Insurance Chukyo Hospital
      Nagoya, Aichi, Japan