Tooru Shimosegawa

Tohoku University, Miyagi, Japan

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Publications (807)3957.47 Total impact

  • [Show abstract] [Hide abstract]
    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.
    Digestive Endoscopy 11/2015; DOI:10.1111/den.12578 · 2.06 Impact Factor
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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.
    Digestive Endoscopy 11/2015; DOI:10.1111/den.12576 · 2.06 Impact Factor

  • Pancreas 11/2015; 44(8):1195-1210. DOI:10.1097/MPA.0000000000000500 · 2.96 Impact Factor
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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.
    The Tohoku Journal of Experimental Medicine 10/2015; 237(3):173-182. DOI:10.1620/tjem.237.173 · 1.35 Impact Factor
  • 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.
    Current pharmaceutical design 09/2015; 21(999). DOI:10.2174/1381612821666150915105330 · 3.45 Impact Factor
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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.
    Pancreas 09/2015; 44(7):1053-64. DOI:10.1097/MPA.0000000000000449 · 2.96 Impact Factor
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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.
    Pancreas 09/2015; 44(7). DOI:10.1097/MPA.0000000000000438 · 2.96 Impact Factor
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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.
    AJP Gastrointestinal and Liver Physiology 08/2015; DOI:10.1152/ajpgi.00241.2015 · 3.80 Impact Factor
  • Atsushi Masamune · Shin Hamada · Tooru Shimosegawa ·

    Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 08/2015; 112(8):1464-73. DOI:10.11405/nisshoshi.112.1464
  • Source
    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.
    08/2015; 7(9):872-80. DOI:10.4253/wjge.v7.i9.872
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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.
    International Journal of Colorectal Disease 08/2015; DOI:10.1007/s00384-015-2334-3 · 2.45 Impact Factor
  • 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.
    Gastroentérologie Clinique et Biologique 07/2015; 39. DOI:10.1016/j.clinre.2015.05.018 · 1.64 Impact Factor
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    Naoki Asano · Katsunori Iijima · Tomoyuki Koike · Akira Imatani · Tooru Shimosegawa ·
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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.
    07/2015; 21(26):8014-8020. DOI:10.3748/wjg.v21.i26.8014
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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.
    07/2015; 21(25):7709-17. DOI:10.3748/wjg.v21.i25.7709
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    ABSTRACT: Acid-related diseases (ARD) including gatroesophageal reflux disease (GERD) and peptic ulcer disease (PUD) are treated by acid suppression drugs, especially proton pump inhibitor (PPI). Use of PPI as a first line therapy for ARD is recommended in various guidelines. Recently, vonoprazan, a new class of acid secretion inhibitor called potassium-competitive acid blocker (P-CAB) developed in Japan for the treatment of ARD. The drug is covered by the Japanese medical insurance for the treatment of ARD, and it is reported that Helicobacter pylori (HP) eradication rate with it is more than 90%.
    Nippon rinsho. Japanese journal of clinical medicine 07/2015; 73(7):1136-46.
  • Katsunori Iijima · Tomoyuki Koike · Tooru Shimosegawa ·
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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. The overall gastric acid secretion level of Japanese men relatively increased during the last 20 years with a successive decline in the Helicobacter pylori (H. pylori) infection rate, and this trend will continue for several more decades in Japan. However, considering that gastric acid secretion remained unchanged in H. pylori-negative Japanese men over the 20-year period at a level much lower than that in Occidental subjects, upper gastrointestinal disease profiles in the Asian population including Japanese people will still differ from those in Western countries in the post-H. pylori era.
    Nippon rinsho. Japanese journal of clinical medicine 07/2015; 73(7):1093-7.
  • Takeshi Kanno · Katsunori Iijima · Tomoyuki Koike · Tooru Shimosegawa ·
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    ABSTRACT: There had been several reports about the increasing of peptic ulcers under a large-scale disaster or a war. But in human, it was still unclear that a severe psychological stress itself cause peptic ulcer independently of two major causes (Helicobacter pylori infection and nonsteroidal anti-inflammatory drugs). After Great East Japan earthquake in March 11th, 2011, one of the five most powerful earthquakes in the world since modern record keeping began in 1900, we also noticed remarkable increasing of patients with peptic ulcer in wide stricken area. Reports after this gigantic earthquake gave us two new important viewpoints. Disaster (psychological) stress possibly induce peptic ulcer independently of two major causes. And, people living in refugee shelter immediately after a disaster are strong risk group of peptic ulcer bleeding as well as an intake of anti-thrombotic agents.
    Nippon rinsho. Japanese journal of clinical medicine 07/2015; 73(7):1209-14.
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    Kazuhiro Kikuta · Atsushi Masamune · Tooru Shimosegawa ·
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    ABSTRACT: Acute pancreatitis (AP) is an acute inflammatory disease of the exocrine pancreas. In spite of the pivotal role of the endocrine pancreas in glucose metabolism, the impact of impaired glucose tolerance on AP has not been fully elucidated. A meta-analysis of seven observational studies showed that type 2 diabetes mellitus (DM) was associated with an increased risk of AP. The increased risk of AP shown in the meta-analysis was independent of hyperlipidemia, alcohol use and gallstones. Anti-diabetic drugs including incretins might increase the risk of AP, but no intervention trials have confirmed this. Although a controversial finding, DM seems to be associated with severe attacks and organ failure in AP. We analyzed the results of a nationwide epidemiological survey of AP in Japan. We studied the impact of pre-existing DM on the clinical course of AP in 1954 cases for which information on DM status was available at the onset of AP. The prevalence of DM in AP patients (12.8%) was higher than that in the general population in Japan (10.5%). AP patients with DM had higher morbidity of cardiovascular and renal failure than those without DM. About 35% of the idiopathic AP patients with DM had renal failure. The mortality of AP patients with DM (4.0%) was higher than that of AP patients without DM (1.7%). If stratified by etiology, idiopathic, but not alcoholic or biliary, AP patients with DM were predisposed to increased mortality (9.7%). In conclusion, impaired glucose tolerance might have an impact on the development and clinical outcome of AP. However, the impact might depend on the cause of hyperglycemia, the condition of DM including severity, duration and treatment, and the characteristics of the AP patients including age, etiology and comorbidity.
    06/2015; 21(24):7367-74. DOI:10.3748/wjg.v21.i24.7367
  • Kaname Uno · Katsunori Iijima · Tomoyuki Koike · Tooru Shimosegawa ·
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    ABSTRACT: The minimal invasiveness of endoscopic submucosal dissection (ESD) prompted us to apply this technique to large-size early esophageal squamous cell carcinoma and Barrett's adenocarcinoma, despite the limitations in the study population and surveillance duration. A post-ESD ulceration of greater than three-fourths of esophageal circumference was advocated as an important risk factor for refractory strictures that require several sessions of dilation therapy. Most of the preoperative conditions are asymptomatic, but dilatation treatment for dysphagia associated with the stricture has potential risks of severe complications and a worsening of quality of life. Possible mechanisms of dysphasia were demonstrated based on dysmotility and pathological abnormalities at the site: (1) delayed mucosal healing; (2) severe inflammation and disorganized fibrosis with abundant extracellular matrices in the submucosa; and (3) atrophy in the muscularis proper. However, reports on the administration of anti-scarring agents, preventive dilation therapies, and regenerative medicine demonstrated limited success in stricture prevention, and there were discrepancies in the study designs and protocols of these reports. The development and consequent long-term assessments of new prophylactic technologies on the promotion of wound healing and control of the inflammatory/tumor microenvironment will require collaboration among various research fields because of the limited accuracy of preoperative staging and high-risk of local recurrence.
    06/2015; 21(23):7120-33. DOI:10.3748/wjg.v21.i23.7120
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    ABSTRACT: It has been reported that acute hepatitis B (AHB) patients with genotype A HBV (HBV/A) have been increasing since the 1990s in metropolitan areas in Japan. However, little is known about the trends of HBV genotypes in AHB patients in northeast Japan where genotype B HBV (HBV/B) prevails more than in other areas. In this study we aimed to clarify the changes in the HBV genotypes and clinical characteristics of AHB patients in this area. HBV genotypes were determined by direct sequencing (n = 125) or enzyme immunoassay (n = 9) using serum samples from AHB patients including fulminant hepatitis in 1987-2014. Among 134 patients, 26 (19%), 33 (25%), and 75 (56%) patients were infected with HBV of genotypes A, B, and C, respectively. HBV/A emerged from 2001 and the percentage was increased gradually up to 48% in 2010-2014, whereas HBV/B was reduced from 40% in 1987-1994 to 10% in 2010-2014. Phylogenetic analysis showed that 3 major subgenotype A2 strains had come into this area serially. The levels of HBV DNA and prothrombin time were higher in HBV/A patients than other genotypes. This study could not show significant difference in the HBsAg-positive period among genotypes nor the effect of nucleoside analogues to shorten the HBsAg-positive period. A higher level of initial HBV DNA was associated with late disappearance of HBsAg. In conclusion, the percentage of HBV/A in AHB patients has been increasing in northeast Japan since 2001, which is later than metropolitan areas, whereas that of HBV/B is decreasing. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Journal of Medical Virology 06/2015; DOI:10.1002/jmv.24309 · 2.35 Impact Factor

Publication Stats

13k Citations
3,957.47 Total Impact Points


  • 1995-2015
    • Tohoku University
      • • Department of Gastroenterology
      • • Division of Internal Medicine
      Miyagi, Japan
  • 2012-2014
    • Tokyo Metropolitan Komagome Hospital
      Edo, Tōkyō, Japan
    • Miyagi Cancer Center
      Сендай, Miyagi, Japan
    • Kansai Medical University
      • Department of Gastroenterology and Hepatology
      Moriguchi, Osaka-fu, Japan
  • 2013
    • The University of Manchester
      Manchester, England, United Kingdom
    • The University of Tokyo
      • Department of Gastroenterology
      Tōkyō, Japan
    • University of Lodz
      Łódź, Łódź Voivodeship, Poland
  • 2010
    • Mayo Clinic - Rochester
      Рочестер, Minnesota, United States
  • 2009
    • Hokkaido University Hospital
      Sapporo, Hokkaidō, Japan
  • 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
    • Social Insurance Chukyo Hospital
      Nagoya, Aichi, Japan
    • Iwate Prefectural Central Hospital
      Aomori, Aomori, Japan
  • 2000
    • Sendai University
      Sendai, Kagoshima, Japan
  • 1992
    • Shizuoka University
      Sizuoka, Shizuoka, Japan