Tooru Shimosegawa

Tohoku University, Miyagi, Japan

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Publications (856)4368.23 Total impact

  • No preview · Article · Jan 2016 · Pancreatology
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    ABSTRACT: Aims . Antitumor necrosis factor antibodies and calcineurin inhibitors have shown good therapeutic efficacy for steroid-refractory ulcerative colitis (UC). Although some studies have compared the efficacy of infliximab (IFX) and cyclosporin A, there are no published studies comparing IFX and tacrolimus (Tac). This study aimed to compare therapeutic efficacies between IFX- and Tac-based strategies for steroid-refractory UC. Methods . Between July 2009 and August 2013, 95 patients with steroid-refractory UC received either IFX ( n = 48 ) or Tac ( n = 47 ) in our hospital. In the IFX group, the patients continued to receive maintenance treatment with IFX. In the Tac group, patients discontinued Tac treatment up to 3 months and subsequently received thiopurine. We retrospectively compared the therapeutic outcomes between the groups. Results . There was no significant difference in the colectomy-free rate, clinical remission rate, and clinical response rate at 2 months between the groups. However, relapse-free survival was significantly higher in the IFX group than in the Tac group ( p < 0.001 ; log-rank test). The proportions of serious adverse events did not differ between the groups. Conclusion. The findings of our study showed that IFX and Tac have similar short-term therapeutic efficacy for steroid-refractory UC. Maintenance treatment with IFX, however, yields better long-term outcomes than Tac-thiopurine bridging treatment.
    Preview · Article · Jan 2016 · Gastroenterology Research and Practice
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    ABSTRACT: Chronic infection with the bacterial H. pylori is a major cause of gastric and duodenal ulcer disease, gastric mucosal atrophy and cancer. H. pylori-induced expression of the intestinal epithelial-specific transcription factor Cdx2 contributes to intestinal metaplasia (IM), a precursor event to gastric cancer. Given a role for the bacterial pattern recognition molecule NOD1 in the innate immune response to bacterial infection, we investigated mechanisms used by NOD1 to regulate H. pylori infection and its propensity towards the development of IM. We found that Cdx2 was induced by H. pylori infection in both normal and neoplastic gastric epithelial cells in a manner that was inversely related to NOD1 signaling. Mechanistic investigations revealed that Cdx2 induction relied upon activation of NF-κB but was suppressed by NOD1-mediated activation of TRAF3, a negative regulator of NF-κB. In vivo, prolonged infection of NOD1-deficient mice with H. pylori led to increased Cdx2 expression and intestinal metaplasia. Furthermore, gastric epithelial cells from these mice exhibited increased nuclear expression of the NF-κB p65 subunit and decreased expression of TRAF3. Overall, our findings illuminated a role for NOD1 signaling in attenuating H. pylori-induced Cdx2 expression in gastric epithelial cells, suggesting a rationale to augment NOD1 signaling in H. pylori-infected patients to limit their risks of accumulating precancerous gastric lesions.
    No preview · Article · Jan 2016 · Cancer Research
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    ABSTRACT: Background Pancreatic stellate cells (PSCs) play a pivotal role in pancreatic fibrosis, a characteristic feature of pancreatic cancer. Although it is still controversial, previous studies have suggested that PSCs promote the progression of pancreatic cancer by regulating the cell functions of cancer cells. PSCs produce large amounts of IL-6, which promotes the accumulation of myeloid-derived suppressor cells via a signal transducers and activator of transcription 3 (STAT3)-dependent mechanism. But the role of IL-6/STAT3 pathway in the interaction between PSCs and pancreatic cancer cells remains largely unknown. Aims To clarify the role of IL-6/STAT3 in the interaction between PSCs and cancer cells. Methods Human pancreatic cancer cells (Panc-1 and SUIT-2 cells) were treated with conditioned medium of immortalized human PSCs (PSC-CM). The effects of PSC-CM and IL-6 neutralization on the mRNA expression profiles were examined using Agilent’s microarray. Activation of STAT3 was assessed by Western blotting using an anti-phospho-specific antibody. Cellular migration was examined by a two-chamber assay. The expression of markers related to epithelial–mesenchymal transition (EMT) was assessed by real-time reverse transcription PCR. Results PSC-CM induced the activation of STAT3 in pancreatic cancer cells. Neutralization of IL-6 suppressed the PSC-CM-induced upregulation of genes including complement factor B, lipocalin, and chemokine (C–C motif) ligand 20. Inhibition of IL-6/STAT3 pathway by anti-IL-6 antibody or a STAT3 inhibitor (NSC74859) inhibited the PSC-CM-induced migration and the expression of EMT-related markers (Snail and cadherin-2) in pancreatic cancer cells. Conclusion IL-6/STAT3 pathway regulates the PSC-induced EMT and alterations in gene expression in pancreatic cancer cells.
    No preview · Article · Jan 2016 · Digestive Diseases and Sciences
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    ABSTRACT: Chronic pancreatitis is considered to be an irreversible progressive chronic inflammatory disease. The etiology and pathology of chronic pancreatitis are complex; therefore, it is important to correctly understand the stage and pathology and provide appropriate treatment accordingly. The newly revised Clinical Practice Guidelines of Chronic Pancreatitis 2015 consist of four chapters, i.e., diagnosis, staging, treatment, and prognosis, and includes a total of 65 clinical questions. These guidelines have aimed at providing certain directions and clinically practical contents for the management of chronic pancreatitis, preferentially adopting clinically useful articles. These revised guidelines also refer to early chronic pancreatitis based on the Criteria for the Diagnosis of Chronic Pancreatitis 2009. They include such items as health insurance coverage of high-titer lipase preparations and extracorporeal shock wave lithotripsy, new antidiabetic drugs, and the definition of and treatment approach to pancreatic pseudocyst. The accuracy of these guidelines has been improved by examining and adopting new evidence obtained after the publication of the first edition.
    No preview · Article · Jan 2016 · Journal of Gastroenterology
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    ABSTRACT: We report the case of a 68-year-old Japanese man diagnosed with lymphocytic esophagitis (LE), a rare disease associated with refractory dysphagia. He had severe dysphagia and heartburn since 2007. The findings of esophagogastroduodenoscopy (EGD) performed by a local physician in 2010 showed pale mucosa with white exudate and lateral furrows in the esophagus. He was referred to our clinic in 2012, because the symptoms did not improve, despite regular use of a proton pump inhibitor (PPI). At that time, EGD revealed the coexistence of a slight stricture in the upper esophagus, the histopathological findings of which included a predominantly peri-papillary distribution of abundant, infiltrating CD3(+) /CD4(+) /CD8(+) /CD20(-) lymphocytes without any granulocytes (CD4(+) : CD8(+) = 3.3:1). These were consistent with a diagnostic criteria of LE. Thereafter, severe dysphagia with food impaction occurred twice a month, despite the long-term use of a PPI, and EGD showed worsened strictures, where endoscopic ultrasonography findings showed marked circumferential thickness of the mucosal and submucosal layers. Then, one session of endoscopic balloon dilatation dramatically improved the dysphagia. Accordingly, LE should be considered an important differential diagnosis of refractory dysphagia based on the characteristic features of endoscopic and pathological findings.
    No preview · Article · Nov 2015 · Digestive Endoscopy
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    ABSTRACT: Objectives: The evaluation of Barrett's glands buried underneath esophageal squamous epithelium becomes increasingly important to achieve curative treatments. However, clinically available endoscopies have critical limitations in depicting the subsurface structure, resulting in non-curative treatments. Optical coherence tomography (OCT) can acquire a high-resolution cross-sectional image, equivalent to an 'optical biopsy'. We aimed to assess the feasibility of the in vivo use of probe-type OCT imaging to evaluate Barrett's mucosa buried underneath esophageal squamous epithelium METHODS: We conducted a single-center prospective study with 14 consecutive patients with Barrett's adenocarcinoma from 2008 to 2014. The enrolled patients were examined by a probe-type OCT in vivo, followed by en bloc endoscopic submucosal dissection (ESD) with electric marking. Then, the one-to-one correlations between the OCT images of the buried mucosa and their histological assessment were examined. Results: The overall accuracy, sensitivity, specificity, positive predictive value and negative predictive value of the buried mucosa in the OCT imaging were 85.7% (12/14), 77.8% (7/9), 100% (5/5), 100% (7/7) and 71.4% (5/7), respectively. However, OCT could not easily distinguish non-dysplastic glands from dysplastic glands. Additionally, the linear distance from the histological squamo-columnar junction in correct cases tended to be longer than that in incorrect cases (mm, median [range]: 2.0 [0.7-7.5] vs. 0.5 [0.5-0.5]). Conclusions: We demonstrated, for the first time, that pre-operative OCT imaging might be feasible for detecting the oral side extension of buried Barrett's mucosa to remove the entire area with malignant potential by ESD. This article is protected by copyright. All rights reserved.
    No preview · Article · Nov 2015 · Digestive Endoscopy
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    ABSTRACT: Radiation therapy (RT) may be suitable for treating patients with hepatocellular carcinoma (HCC) who are difficult to treat with any other option. However, it remains unclear whether RT extends survival in these patients. Among the 957 HCC patients treated at Tohoku University Hospital from January 2007 to December 2013, only 49 patients received RT. We therefore retrospectively analyzed the outcomes of these patients; they were divided into three groups based on the reasons for choosing RT: 27 patients at Stage IV A (67.1 ± 1.6 years, 50.5 ± 2.1 Gy), 9 patients with alternative therapy (72.2 ± 2.4 years, 58.9 ± 1.1 Gy), and 13 patients who received RT after transarterial chemoembolization (TACE) (75.6 ± 2.1 years, 56.5 ± 1.5 Gy). RT was employed to ensure the local control of the lesion. The patients at Stage IV A were treated with radical RT (n = 16) or with palliative RT (n = 11). In radical RT group, the response rate was 37.5% and the complete response rate was 25%. The survival rate was 12.5 ± 2.6 months after radical RT. This is considered relatively good for Stage IV A. The disease-free survival rate was 13.0 ± 2.8 months after RT. This excellent disease-free survival indicates that RT is an alternative to other treatments. In the TACE group, patients who received the RT had the significantly long disease-free survival rate than only-TACE (18.0 ± 3.8 months vs. 11.2 ± 0.58 months). We propose that RT is effective and safe for HCC.
    Full-text · Article · Nov 2015 · The Tohoku Journal of Experimental Medicine
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    ABSTRACT: An international symposium entitled “Acute pancreatitis: progress and challenges” was held on November 5, 2014 at the Hapuna Beach Hotel, Big Island, Hawaii, as part of the 45th Anniversary Meeting of the American Pancreatic Association and the Japanese Pancreas Society. The course was organized and directed by Drs. Stephen Pandol, Tooru Shimosegawa, Robert Sutton, Bechien Wu, and Santhi Swaroop Vege. The symposium objectives were to: (1) highlight current issues in management of acute pancreatitis, (2) discuss promising treatments, (3) consider development of quality indicators and improved measures of disease activity, and (4) present a framework for international collaboration for development of new therapies. This article represents a compilation and adaptation of brief summaries prepared by speakers at the symposium with the purpose of broadly disseminating information and initiatives.
    No preview · Article · Nov 2015 · Pancreas
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    ABSTRACT: Sorafenib, an oral multi-kinase inhibitor, is the final therapy prior to palliative care for advanced hepatocellular carcinoma (HCC). However, due to its adverse effects, 20% of patients must discontinue sorafenib within 1 month after first administration. To identify ways to predict the adverse effects and administer the drug for longer periods, we explored the relationship between the duration of sorafenib treatment and the pharmacokinetics of sorafenib and its major metabolite, sorafenib N-oxide. Twenty-five subjects enrolled in the study were divided into two groups: patients with dosage reduced or withdrawn due to adverse effects (n = 8), and patients with dosage maintained for 1 month after initial administration (n = 17). We evaluated early sorafenib accumulation as the area under the curve of sorafenib and sorafenib N-oxide concentrations during days 1-7 (AUCsorafenib and AUCN-oxide, respectively). Inter-group comparison revealed that AUCN-oxide and AUC ratio (AUCN-oxide /AUCsorafenib) were significantly higher in the dosage reduction/withdrawal group (P = 0.031 and P = 0.0022, respectively). Receiver operating characteristic analysis indicated that AUCN-oxide and AUC ratio were reliable predictors of adverse effects. When patients were classified by cut-off points (AUCN-oxide: 2.0 μ g∙day/mL, AUC ratio: 0.13), progression-free survival was significantly longer in patients with AUCN-oxide ≤ 2.0 μ g∙day/mL (P = 0.0048, log-rank test). In conclusion, we recommend to simultaneously monitor serum levels of sorafenib and its N-oxide during the early stage after the first administration, which enables us to provide safe and long-term therapy for each HCC patient with sorafenib.
    Preview · Article · Oct 2015 · The Tohoku Journal of Experimental Medicine
  • Katsunori Iijima · Tooru Shimosegawa
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    ABSTRACT: Nowadays, low-dose aspirin is widely administered at low dose as an antithrombotic drug for the prevention of cerebrovascular and cardiovascular diseases. However, aspirin, even at a low dose, can induce varying degrees of gastroduodenal mucosal injury (erosion, ulcer, ulcer bleeding). Hence, co-prescription of proton pump inhibitors with low-dose aspirin is recommended for those at high risk for adverse gastroduodenal events. At present, a history of peptic ulcer, especially that of complicated ulcer, is the most important risk factor for low-dose aspirin-associated gastroduodenal adverse events. Additionally, concomitant use of non-steroidal anti-inflammatory drugs including COX-2 selective inhibitors, anti-platelet agents, anti-coagulants, and oral corticosteroid is recognized to increase the risk for adverse gastroduodenal events in low-dose aspirin users. H. pylori infection could also be associated with the increased risk for adverse gastroduodenal events in low-dose aspirin users, especially in patients with histories of peptic ulcers. Therefore, eradication therapy for such patients can prevent ulcer recurrence. However, the efficacy of eradication therapy on low-dose aspirin-related gastroduodenal lesions in unselected H. pylori-positive low-dose aspirin users without histories of peptic ulcers remains to be clarified.
    No preview · Article · Sep 2015 · Current pharmaceutical design
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    ABSTRACT: Objectives: In addition to surgery, procedures for patients with pancreatolithiasis are developing; therefore, establishing practical guidelines for the management of pancreatolithiasis is required. Methods: Three committees (the professional committee for asking clinical questions (CQs) and statements by Japanese endoscopists, the expert panel committee for rating statements by the modified Delphi method, and the evaluating committee by moderators) were organized. Eight endoscopists and a surgeon for pancreatolithiasis made the CQs and statements from a total of 694 reports of published literature by PubMed search (from 1983 to 2012). The expert panelists individually rated these clinical statements using a modified Delphi approach, in which a clinical statement receiving a median score greater than 7 on a 9-point scale from the panel was regarded as valid. Results: The professional committee made 3, 7, and 10 CQs and statements for the concept and pathogenesis, diagnosis, and treatment, respectively. The expert panelists regarded them as valid after a 2-round modified Delphi approach. Conclusions: After evaluation by the moderators, the Japanese clinical guidelines for pancreatolithiasis were established. Further discussions and studies for international guidelines are needed.
    No preview · Article · Sep 2015 · Pancreas
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    ABSTRACT: The aim of the study was to clarify clinicopathological features of type 2 autoimmune pancreatitis (AIP) in Japan; a multicenter survey was carried out. The first screening collected patients with pancreatitis whose pancreatic tissue samples were available and who fulfilled at least 1 of the following 3 criteria as possible type 2 AIP: (1) histological presence of granulocytic epithelial lesion, (2) age of 50 years or younger, and (3) association of ulcerative colitis, Sjogren syndrome, and/or primary biliary cirrhosis. Patients with histologically confirmed type 1 AIP were also collected as a control. Clinical information was gathered by questionnaire. A histological re-evaluation identified 8 patients with type 2 AIP and 20 with type 1 AIP. Three of the latter had intralobular neutrophilic infiltration. Factors more frequent in type 2 included age younger than 40 years, abdominal pain, and elevation of serum amylase and lipase, whereas patients with type 1 more frequently showed jaundice, elevated serum IgG and IgG4, presence of autoantibodies, association of IgG4-related disease, sclerosing cholangitis and diabetes mellitus, and imaging findings of intrapancreatic biliary stenosis and extrapancreatic biliary dilatation. The clinical features of type 2 AIP in Japan were similar to those of western countries. Intralobular neutrophilic infiltration in type 1 is a potential pitfall, especially in the biopsy-based diagnosis.
    No preview · Article · Sep 2015 · Pancreas
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    ABSTRACT: Genetic alterations in the carboxypeptidase A1 gene (CPA1) are associated with early-onset chronic pancreatitis (CP). Besides CPA1, there are two other human pancreatic carboxypeptidases: CPA2 and CPB1. Here we examined whether CPA2 and CPB1 alterations are associated with CP in Japan and Germany. All exons and flanking introns of CPA2 and CPB1 were sequenced in 477 Japanese patients with CP (234 alcoholic, 243 non-alcoholic) and in 497 German patients with non-alcoholic CP by targeted next generation sequencing and/or Sanger sequencing. Secretion and enzymatic activity of CPA2 and CPB1 variants were determined after transfection into HEK 293T cells. We identified six non-synonymous CPA2 variants (p.V67I, p.G166R, p.D168E, p.D173H, p.R237W and p.G388S); eight non-synonymous CPB1 alterations (p.S65G, p.N120S, p.D172E, p.R195H, p.D208N, p.F232L, p.A317V and p.D364Y) and one splice-site variant (c.687+1G>T) in CPB1. Functional analysis revealed essentially complete loss of function in CPA2 variants p.R237W and p.G388S and CPB1 variants p.R110H and p.D364Y. None of the CPA2 or CPB1 variants, including those resulting in a marked loss of function, were overrepresented in patients with CP. In conclusion, CPA2 and CPB1 variants are not associated with CP. Copyright © 2015, American Journal of Physiology- Gastrointestinal and Liver Physiology.
    No preview · Article · Aug 2015 · AJP Gastrointestinal and Liver Physiology
  • Atsushi Masamune · Shin Hamada · Tooru Shimosegawa

    No preview · Article · Aug 2015 · Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology
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    Kaname Uno · Tomoyuki Koike · Tooru Shimosegawa
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    ABSTRACT: Endoscopic diagnosis with histological evidence is necessary to decide the best strategy for treating esophageal squamous cell carcinoma and Barrett's-associated neoplasia, and the recent development of endoscopic technologies have made possible real-time information of malignant hallmarks. We focused on the development of optical coherence tomography (OCT), the only technology that can depict real-time cross-sectional images with high resolution. With the improvements in image resolution, acquisition rate and demonstrable area of three-dimensional devices with Doppler capability, OCT imaging was shown to enable visualization of structural/functional alterations in the mucosal/submucosal tissue of the esophagus, resulting in more accurate preoperative diagnosis of such malignancies. Moreover, it approved to be useful for targeting malignant areas for biopsy and treatment as well as for predicting the treatment effects. Therefore, further development of this technology is expected to overcome the current clinical issues in management strategies of esophageal malignancies.
    Preview · Article · Aug 2015
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    ABSTRACT: Since colorectal endoscopic submucosal dissection (ESD) requires higher-level skills than endoscopic mucosal resection (EMR), it is recommended to acquire sufficient experience in gastric ESD prior to attempting colorectal ESD. We evaluated the ability of experienced endoscopists with limited experience in gastric ESD to perform colorectal ESD. We retrospectively reviewed 120 colorectal ESDs performed by two endoscopists who had expertise in colonoscopy and colorectal EMR but experience of fewer than five gastric ESDs. Main outcomes were the en bloc resection rate with tumor-free margins (R0 resection rate) and adverse events rate. Using only clinical characteristics prior to ESD, we also identified factors affecting outcomes. A total of 113 patients (94.2 %) received en bloc resection, and the R0 resection rate was 80.0 % (96/120). Perforation and postoperative hemorrhage occurred in eight (6.7 %) and two (1.7 %) patients, respectively. Dividing the 120 cases into three learning phases, R0 resection and perforation rates improved from 77.5 % (31/40) and 12.5 % (5/40) in phase 1 to 85.0 % (34/40) and 2.5 % (1/40) in phase 3, respectively. Multivariate analysis revealed that lesions at junctions (dentate line, sigmoid-descending junction, splenic flexure, hepatic flexure, ileocecal valve) and lesions with factors reflecting fibrosis in the submucosal layer (based on endoscopic findings before ESD) were significantly correlated with R0 resection failure, with adjusted odds ratios of 10.5 (95 % CI 2.1-67.6) and 10.4 (2.7-48.6), respectively. Colorectal ESD is feasible for experienced endoscopists with limited experience in gastric ESD. Novices should avoid lesions at junctions or those with factors reflecting fibrosis.
    No preview · Article · Aug 2015 · International Journal of Colorectal Disease
  • Atsushi Masamune · Tooru Shimosegawa
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    ABSTRACT: There is accumulating evidence that activated pancreatic stellate cells (PSCs) play a pivotal role in the development of pancreatic fibrosis within the pancreatic cancer tissue. Not only do they produce extracellular matrix components, PSCs dynamically interact with other cell types to constitute the cancer-conditioned microenvironment. There exist bidirectional interactions between PSCs and pancreatic cancer cells. Pancreatic cancer cells promote the proliferation, migration, extracellular matrix production and degradation, and angiogenetic responses in PSCs. In turn, PSCs promote the proliferation and migration, and inhibit the apoptosis of pancreatic cancer cells. PSCs also induce epithelial-mesenchymal transition and stem cell like phenotypes in pancreatic cancer cells, resulting in resistance to conventional therapies, distant metastasis, and recurrence. PSCs interact with endothelial cells, neural cells and β-cells, leading to angiogenesis, neurogenesis and β-cell dysfunction and apoptosis. PSCs cause impaired immune responses and help pancreatic cancer cells escape from host immune-surveillance. PSCs induce the differentiation of myeloid-derived suppressor cells, induce the apoptosis of T cells, inhibit the infiltration of T cells, and induce the activation of mast cells. Overall, these interactions appear to promote the progression of pancreatic cancer, and anti-stroma therapies targeting PSCs are under intense investigation. Further elucidation of these interactions could lead to the identification of novel therapeutic targets in pancreatic cancer. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    No preview · Article · Jul 2015 · Gastroentérologie Clinique et Biologique
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    ABSTRACT: Since Isaacson and Wright first reported on the extra-nodal marginal zone B-cell lymphoma of the stomach in 1983, following studies have clarified many aspects of this disease. We now know that the stomach is the most affected organ by this disease, and approximately 90% of gastric mucosa-associated lymphoid tissue (MALT) lymphomas are related to Helicobacter pylori (H. pylori) infection. This implies that approximately 10% of gastric MALT lymphomas occur independent of H. pylori infection. The pathogenesis of these H. pylori-negative gastric MALT lymphomas remains unclear. To date, there have been several speculations. One possibility is that genetic alterations result in nuclear factor-kappa B (NF-κB) activation. Among these alterations, t(11;18)(q21;q21) is more frequently observed in H. pylori-negative gastric MALT lymphomas, and such translocation results in the synthesis of fusion protein API2-MALT1, which causes canonical and noncanonical NF-κB activation. Another possibility is infection with bacteria other than H. pylori. This could explain why H. pylori eradication therapy can cure some proportions of H. pylori-negative gastric MALT lymphoma patients, although the bacteria responsible for MALT lymphomagenesis are yet to be defined. Recent advances in endoscopy suggest magnifying endoscopy with narrow band imaging as a useful tool for both detecting gastric MALT lymphoma lesions and judging the response to treatment. A certain proportion of H. pylori-negative gastric MALT lymphoma patients respond to eradication therapy; hence, H. pylori eradication therapy could be considered as a first-line treatment for gastric MALT lymphomas regardless of their H. pylori infection status.
    Full-text · Article · Jul 2015
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    Katsunori Iijima · Tooru Shimosegawa
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    ABSTRACT: Aspirin, even at low doses, has been known to cause upper gastro-intestinal complications, such as gastroduodenal ulcers, despite the definite benefits from its antithrombotic effects. Helicobacter pylori (H. pylori) is major pathogen responsible for gastroduodenal ulcer formation. There have been conflicting results about the potential interaction between these two ulcerogenic factors and the geographic areas involved. In Western countries, the prevalence of gastroduodenal ulcers is consistently higher in H. pylori-positive low-dose aspirin (LDA) users than in H. pylori-negative ones, suggesting that H. pylori infection exacerbates LDA-induced gastroduodenal mucosal injury in these geographic areas. Meanwhile, previous studies from Japan have generally reported a similar prevalence of LDA-induced gastroduodenal mucosal injury regardless of the presence of H. pylori infection, indicating that the infection is not an overall exacerbating factor for drug-induced injury. H. pylori infection could have a synergistic or antagonistic interaction with LDA use in adverse gastroduodenal events depending on gastric acid secretion. It is well-recognized that the net effect of H. pylori infection on gastric acid secretion shows considerable geographic variation at the population level. While gastric acid secretion levels were not decreased and were well-preserved in most patients with H. pylori infection from Western countries, the majority of Japanese patients with H. pylori infection exhibited decreased gastric acid secretion. Such large geographic differences in the net effect of H. pylori infection on gastric acid secretion could be at least partly responsible for the geographically distinct interaction between LDA use and H. pylori infection on adverse gastroduodenal lesions.
    Preview · Article · Jul 2015

Publication Stats

14k Citations
4,368.23 Total Impact Points


  • 1995-2015
    • Tohoku University
      • • Department of Gastroenterology
      • • Division of Internal Medicine
      Miyagi, Japan
  • 2014
    • Tokyo Medical and Dental University
      • Department of Gastroenterology and Hepatology
      Edo, Tokyo, Japan
  • 2012-2014
    • Tokyo Metropolitan Komagome Hospital
      Edo, Tōkyō, Japan
    • Miyagi Cancer Center
      Сендай, Miyagi, Japan
  • 2013
    • The University of Manchester
      Manchester, England, United Kingdom
    • University of Lodz
      Łódź, Łódź Voivodeship, Poland
    • The University of Tokyo
      • Department of Gastroenterology
      Tōkyō, Japan
  • 2010
    • Mayo Clinic - Rochester
      Рочестер, Minnesota, United States
  • 2008
    • Tokyo Women's Medical University
      Edo, Tōkyō, Japan
    • Numazu City Hospital
      Sizuoka, Shizuoka, Japan
  • 2004
    • University of Tsukuba
      • Institute of Clinical Medicine
      Tsukuba, Ibaraki, Japan
  • 2002-2003
    • Hokkaido University
      • • Central Research Institute
      • • Department of Internal Medicine
      Sapporo, Hokkaidō, Japan
    • Keio University
      • Department of Internal Medicine
      Edo, Tōkyō, Japan
  • 2001
    • Iwate Prefectural Central Hospital
      Aomori, Aomori, Japan
  • 2000
    • Sendai University
      Sendai, Kagoshima, Japan
  • 1992
    • Shizuoka University
      Sizuoka, Shizuoka, Japan