研究者詳細 - 仲瀬　裕志

論文 - 仲瀬　裕志

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Gastrointestinal follicular lymphoma: review of the literature.

Shuji Yamamoto, Hiroshi Nakase, Kouhei Yamashita, Minoru Matsuura, Mariko Takada, Chiharu Kawanami, Tsutomu Chiba

Journal of gastroenterology ( SPRINGER TOKYO ) 45 ( 4 ) 370 - 88 2010年04月 [査読有り] [国内誌]

Gastrointestinal follicular lymphoma (GI-FL) is a relatively rare disease, accounting for only 1%-3.6% of gastrointestinal non-Hodgkin's lymphoma. Although the duodenum and terminal ileum are considered to be the most common sites of origin, the development of wireless capsule endoscopy and double-balloon enteroscopy has increased the detection of GI-FL in every part of the small intestine. Approximately 70% of patients with GI-FL are estimated to have multiple lesions throughout the entire gastrointestinal tract. FL is a low-grade lymphoma that usually develops very slowly. If the lymphoma causes no symptoms, immediate treatment may not be necessary. Standard therapy has not yet been established for GI-FL, but chemotherapy, radiotherapy, monoclonal antibody therapy, or a combination of these therapies, is sometimes performed based on the therapeutic regimens for nodal FL. Regimens including conventional chemotherapy with rituximab, which achieve high response rates in nodal FL, are commonly used for GI-FL. The long-term clinical outcome of GI-FL is unclear. The results of a few series on the long-term outcomes of patients with GI-FL treated with conventional therapy indicate a median relapse-free time ranging from 31 to 45 months. On the other hand, in patients with GI-FL who were followed without treatment, the median time to disease progression was 37.5 months. Thus, whether to initiate aggressive therapy or whether to continue watchful waiting in patients with GI-FL is a critically important decision. Ongoing research on biomarkers to guide individualized GI-FL therapy may provide invaluable information that will lead to the establishment of a standard therapeutic regimen.

DOI PubMed CiNii

TNF-alpha is an important pathogenic factor contributing to reactivation of cytomegalovirus in inflamed mucosa of colon in patients with ulcerative colitis: lesson from clinical experience.

Hiroshi Nakase, Tsutomu Chiba

Inflammatory bowel diseases ( JOHN WILEY & SONS INC ) 16 ( 4 ) 550 - 1 2010年04月 [査読有り] [国際誌]

Heat shock protein 47 is a new candidate molecule as anti-fibrotic treatment of Crohn's disease

H. Nakase, Y. Honzawa, T. Chiba

ALIMENTARY PHARMACOLOGY & THERAPEUTICS ( WILEY-BLACKWELL PUBLISHING, INC ) 31 ( 8 ) 927 - 927 2010年04月 [査読有り]

Oral tacrolimus (FK 506) in refractory paediatric ulcerative colitis: authors' reply

S. Yamamoto, H. Nakase, T. Chiba

ALIMENTARY PHARMACOLOGY & THERAPEUTICS ( WILEY-BLACKWELL PUBLISHING, INC ) 31 ( 6 ) 677 - 678 2010年03月 [査読有り]

Efficacy of oral tacrolimus on intestinal Behcet's disease.

Kayoko Matsumura, Hiroshi Nakase, Tsutomu Chiba

Inflammatory bowel diseases ( JOHN WILEY & SONS INC ) 16 ( 2 ) 188 - 9 2010年02月 [査読有り] [国際誌]

Development of oral drug delivery system with cyclosporine in experimental colitis.

Fukata n, Uchida K, Kusuda T, Koyabu M, Fukui T, Matsushita M, Nishio A, Nakase H, Chiba T, Tabata Y, Okazaki K

Digestive disease week 2010（2010.5.3 New Orleans） ( W B SAUNDERS CO-ELSEVIER INC ) 138 ( 5 ) S413 - S414 2010年 [査読有り]

An open-label prospective randomized multicenter study shows very rapid remission of ulcerative colitis by intensive granulocyte and monocyte adsorptive apheresis as compared with routine weekly treatment.

Atsushi Sakuraba, Satoshi Motoya, Kenji Watanabe, Masakazu Nishishita, Kazunari Kanke, Toshiyuki Matsui, Yasuo Suzuki, Tadayuki Oshima, Reiko Kunisaki, Takayuki Matsumoto, Hiroyuki Hanai, Ken Fukunaga, Naoki Yoshimura, Toshimi Chiba, Shinsuke Funakoshi, Nobuo Aoyama, Akira Andoh, Hiroshi Nakase, Yohei Mizuta, Ryoichi Suzuki, Taiji Akamatsu, Masahiro Iizuka, Toshifumi Ashida, Toshifumi Hibi

The American journal of gastroenterology ( NATURE PUBLISHING GROUP ) 104 ( 12 ) 2990 - 5 2009年12月 [査読有り] [国際誌]

OBJECTIVES: Granulocyte and monocyte adsorptive apheresis (GMA) has shown efficacy in patients with active ulcerative colitis (UC). However, with routine weekly treatment, it may take several weeks to achieve remission, and to date, the efficacy of a more frequent treatment schedule remains unknown. The aim of this study was to assess the clinical efficacy and safety of intensive GMA treatment in patients with active UC. METHODS: This was an open-label, prospective, randomized multicenter study to compare an intensive, two GMA sessions per week, with the routine, one GMA session per week. A total of 163 patients with mild-to-moderately active UC were randomly assigned to routine weekly treatment or intensive treatment. The maximum number of sessions of GMA permitted was 10. However, when patients achieved remission, GMA was discontinued. Remission rate at the end of the study, time to remission, and adverse events were assessed in both groups. RESULTS: Of the 163 patients, 149 were available for efficacy analysis as per protocol, 76 were in weekly GMA, and 73 were in intensive GMA. At the end of the study period, clinical remission was achieved in 41 of 76 patients (54.0%) in weekly GMA and in 52 of 73 patients (71.2%) in intensive GMA (P=0.029). The mean time to remission was 28.1+/-16.9 days in the weekly GMA treatment group and 14.9+/-9.5 days in the intensive GMA group (P<0.0001). Intensive GMA was well tolerated without GMA-related serious adverse side effects. CONCLUSIONS: Intensive GMA in patients with active UC seems to be more efficacious than weekly treatment, and significantly reduced the patients' morbidity time without increasing the incidence of side effects.

Acute Epstein-Barr virus infection presenting as severe gastroenteritis without infectious mononucleosis-like manifestations.

Mikio Fujiwara, Shin'ichi Miyamoto, Kouta Iguchi, Toshihiro Matsunaka, Hiromi Sakashita, Tatsuaki Tsuruyama, Hirokazu Kanegane, Hiroyuki Marusawa, Hiroshi Nakase, Tsutomu Chiba

Clinical journal of gastroenterology 2 ( 6 ) 398 - 403 2009年12月 [査読有り] [国内誌]

Primary Epstein-Barr virus (EBV) infection is usually a self-limiting disease. Although it is sometimes accompanied by severe complications such as thrombocytopenia, hemolytic anemia, and splenic rupture, predominantly gastrointestinal complications are rarely reported. We studied an unusual case of primary EBV infection associated with severe hemorrhagic gastroenteritis. EBV infection was confirmed in the biopsy specimen by demonstrating the presence of EBV DNA by polymerase chain reaction, and of EBV-encoded small RNA (EBER)-positive cells by in-situ hybridization. Our patient was suspected of having primary EBV infection from the serological findings-EBV-viral capsid antigen IgM (+) and EBV nuclear antigen (-)-but he did not show typical clinical features of infectious mononucleosis such as lymph node swelling, pharyngitis, liver dysfunction, and splenomegaly. A definite diagnosis of primary EBV infection was made using biopsy specimens by demonstrating the presence of EBV DNA and EBER-positive cells.

Upregulation of T-bet and tight junction molecules by Bifidobactrium longum improves colonic inflammation of ulcerative colitis.

Yasuhiro Takeda, Hiroshi Nakase, Kazuyoshi Namba, Satoko Inoue, Satoru Ueno, Norimitsu Uza, Tsutomu Chiba

Inflammatory bowel diseases ( JOHN WILEY & SONS INC ) 15 ( 11 ) 1617 - 8 2009年11月 [査読有り] [国際誌]

Role of double-balloon endoscopy in the diagnosis of small-bowel tumors: the first Japanese multicenter study.

Keigo Mitsui, Shu Tanaka, Hironori Yamamoto, Tsuyoshi Kobayashi, Akihito Ehara, Tomonori Yano, Hidemi Goto, Hiroshi Nakase, Shinji Tanaka, Toshiyuki Matsui, Mitsuo Iida, Kentaro Sugano, Choitsu Sakamoto

Gastrointestinal endoscopy ( MOSBY-ELSEVIER ) 70 ( 3 ) 498 - 504 2009年09月 [査読有り] [国際誌]

BACKGROUND: The early diagnosis of small-bowel tumors (SBT) was a difficult task until the advent of capsule endoscopy (CE) and double-balloon endoscopy (DBE) allowed access to the disease site. However, although CE and DBE have greatly simplified the task, DBE studies have yet to provide sufficient data on the diagnosis and outcome of patients with SBTs. OBJECTIVE: To determine the efficacy of DBE examination in the detection and diagnosis of SBT. DESIGN: A retrospective analysis of cross-sectional case series. SETTING: Seven major medical centers in Japan. PATIENTS: The first 1035 consecutive DBE cases at these major Japanese centers since the introduction of DBE. MAIN OUTCOME MEASUREMENTS: The percentage of subjects with SBT and a diagnosis of SBT, their indications for DBE, and diagnostic and therapeutic DBE procedures carried out for SBT. RESULTS: SBTs were identified in 144 of 1035 subjects (13.9%) who underwent DBE between September 2000 and December 2005. For subjects with SBT, the most common indication for DBE was the suspected presence of a SBT (61/144 [42.4%]). For subjects without SBT, the most common indication was obscure GI bleeding (OGIB) (419/891 [47.0%]). Malignant lymphoma and GI stromal tumor (GIST) were the most frequent (31/144 [21.5%]) and the second-most frequent SBTs (27/144 [18.8%]), respectively, in this database. We also performed 85 biopsies and 45 therapeutic procedures for the evaluation and treatment of SBTs in 144 patients. Although complications were encountered in 5.3% of cases (14/266 sessions), none of these were life threatening in the present study. CONCLUSION: DBE proved a valuable tool for the detection and diagnosis of SBTs, especially when tumors were suspected. Biopsies and therapeutic procedures were also possible in most of these patients, which directed our management of the disease.

Modulation of the Th1/Th2 balance by infliximab improves hyperthyroidism associated with a flare-up of ulcerative colitis.

Kayoko Matsumura, Hiroshi Nakase, Shuji Yamamoto, Takuya Yoshino, Yasuhiro Takeda, Katsuhiro Kasahara, Satoru Ueno, Norimitsu Uza, Tsutomu Chiba

Inflammatory bowel diseases ( JOHN WILEY & SONS INC ) 15 ( 7 ) 967 - 8 2009年07月 [査読有り] [国際誌]

Alteration of CXCR4 expression and Th1/Th2 balance of peripheral CD4-positive T cells can be a biomarker for leukocytapheresis therapy for patients with refractory ulcerative colitis.

Hiroshi Nakase, Sakae Mikami, Tsutomu Chiba

Inflammatory bowel diseases ( JOHN WILEY & SONS INC ) 15 ( 7 ) 963 - 4 2009年07月 [査読有り] [国際誌]

High prevalence of vitamin K and D deficiency and decreased BMD in inflammatory bowel disease

A. Kuwabara, K. Tanaka, N. Tsugawa, H. Nakase, H. Tsuji, K. Shide, M. Kamao, T. Chiba, N. Inagaki, T. Okano, S. Kido

OSTEOPOROSIS INTERNATIONAL ( SPRINGER LONDON LTD ) 20 ( 6 ) 935 - 942 2009年06月 [査読有り]

Vitamin K and D deficiency and decreased bone mineral density (BMD) were highly prevalent in patients with inflammatory bowel disease (IBD), especially Crohn's disease (CD). Dietary intakes of these vitamins, however, were above the Japanese adequate intakes in IBD patients, suggesting that malabsorption is the basis for hypovitaminosis K and D and decreased BMD. We have studied the possible involvement of vitamin K and D deficiency in the pathogenesis of decreased BMD in IBD. Seventy patients with IBD were evaluated for their BMD; plasma levels of vitamin K; phylloquinone (PK), menaquinone-7 (MK-7), and 25OH-D; serum PTH, protein induced by vitamin K absence (PIVKA-II), and undercarboxylated osteocalcin (ucOC) levels; and their food intake. Compared with ulcerative colitis (UC) patients, CD patients had significantly lower plasma vitamin K and 25OH-D concentrations; significantly higher serum levels of PTH, PIVKA-II, and ucOC; and significantly lower BMD scores at almost all measurement sites. More IBD patients were vitamin K deficient in bone than in liver. Multiple regression analyses revealed that low plasma concentrations of vitamin K and 25OH-D were independent risk factors for low BMD and that they were associated with the patients' fat intake, but not with their intake of these vitamins. IBD patients have high prevalence of decreased BMD and vitamin K and D deficiency probably caused by malabsorption of these vitamins.

Clinical challenges and images in GI. Image 4. Transplant-associated thrombotic microangiopathy of the colon accompanied by graft-versus-host disease.

Shuji Yamamoto, Hiroshi Nakase, Tsutomu Chiba, Kouhei Yamashita, Masafumi Ito

Gastroenterology 136 ( 7 ) 2067, 2418 2009年06月 [査読有り] [国際誌]

Massive jejunal bleeding due to Heyde syndrome successfully treated with double balloon endoscopy.

Sakiko Ohta, Tomohiro Watanabe, Shuko Morita, Satoru Ueno, Yoshihisa Tsuji, Hiroshi Nakase, Tsutomu Chiba

Clinical journal of gastroenterology 2 ( 3 ) 187 - 189 2009年06月 [査読有り] [国内誌]

There is a well-documented relationship between aortic valve stenosis and recurrent gastrointestinal bleeding from angiodysplasia in elderly patients, called Heyde syndrome. We report a case of Heyde syndrome with massive jejunal bleeding. Capsule endoscopy showed bleeding from jejunal angiodysplasia. Spurting bleeding from jejunal angiodysplasia was identified and treated by double balloon endoscopy. No gastrointestinal bleeding was seen after the endoscopic treatment and aortic valve replacement was performed. This case suggests that capsule endoscopy and double balloon endoscopy were very useful for the diagnosis and treatment of small intestinal bleeding due to Heyde syndrome.

Clinical challenges and images in GI. Image 1. Relapsing polychondritis.

Shuji Yamamoto, Hiroshi Nakase, Mariko Takada

Gastroenterology 136 ( 7 ) 2064, 2415 2009年06月 [査読有り] [国際誌]

Combination of Endoscopic Resection and Heat Ablation Is a Promising Endoscopic Therapy for Adenoma-Like Dysplastic Lesion in Chronic Ulcerative Colitis.

Kayoko Matsumura, Hiroshi Nakase, Tsutomu Chiba

Case reports in gastroenterology 3 ( 1 ) 121 - 124 2009年04月 [査読有り] [国際誌]

In January 2007, a 74-year-old male was admitted to our hospital for treatment of an adenoma-like dysplastic lesion (ALM). He had a four-year history of ulcerative colitis. Endoscopic findings revealed that a protruded lesion with an approximate size of 3 cm at the splenic flexure was surrounded by pseudopolyps. Lifting of the tumor was poor despite injection of normal saline around it. Therefore, the combination of endoscopic resection and heat ablation therapy with argon plasma coagulation was performed. Histopathological examination of the resected specimen showed tubular adenoma with high-grade atypia. Endoscopic examination 15 months after this treatment revealed no occurrence of ALM. Whether or not there is a possibility of local recurrence after ablation therapy in addition to endoscopic resection performed in this case remains unclear. However, this endoscopic therapy is a promising option for ALM in chronic ulcerative colitis.

The effect of proteasome inhibitor MG132 on experimental inflammatory bowel disease

S. Inoue, H. Nakase, M. Matsuura, S. Mikami, S. Ueno, N. Uza, T. Chiba

CLINICAL AND EXPERIMENTAL IMMUNOLOGY ( WILEY-BLACKWELL PUBLISHING, INC ) 156 ( 1 ) 172 - 182 2009年04月 [査読有り]

Immunoproteasome up-regulation enhances the processing of nuclear factor-kappa B (NF-kappa B) and degradation of I kappa B alpha, which correlates with increased amounts of NF-kappa B in the various cells. Aberrant activation of NF-kappa B is involved in the pathogenesis of inflammatory bowel disease (IBD). The aim of this study was to elucidate the effect of proteasome inhibitor MG132 on experimental IBD. We investigated the effects of MG132 on intestinal inflammation and epithelial regeneration in both interleukin-10-deficient (IL-10(-/-)) mice and mice with dextran sulphate sodium (DSS)-induced colitis. Body weight, histological findings and tumour necrosis factor (TNF)-alpha mRNA expression, epithelial cell proliferation and NF-kappa B p65 activity in colonic tissues were examined. The effects of MG132 on cell proliferation, migration and multiple drug resistance 1 (MDR1) gene expression were determined in vitro. MG132 ameliorated intestinal inflammation of IL-10(-/-) mice by decreasing TNF-alpha mRNA expression in the colonic tissues, which was associated with suppression of NF-kappa B activation, and reduced significantly the number of Ki-67-positive intestinal epithelial cells. On the other hand, MG132 did not reduce intestinal inflammation in mice with DSS-induced colitis, and delayed significantly the recovery of body weight and epithelial regeneration. MG132 also suppressed significantly epithelial cell proliferation, cell migration and MDR1 gene expression in vitro. Proteasome inhibition reduces T cell-mediated intestinal inflammation, but may interrupt both epithelial regeneration and barrier function of colonic mucosa. Optimal use of proteasome inhibitor should be kept in mind when we consider its clinical application for patients with IBD.

Involvement of lupus enteritis in a patient with lupus cystitis and nephritis.

Reiko Akitake, Hiroshi Nakase, Satoru Ueno, Shinichi Miyamoto, Noriyuki Iehara, Tsutomu Chiba

Digestion ( KARGER ) 80 ( 3 ) 160 - 4 2009年 [査読有り] [国際誌]

We present the case of a patient with lupus enteritis accompanied by both lupus cystitis and lupus nephritis without a history of systemic lupus erythematosus. The patient had a 2-month history of diarrhea and pollakiuria and was admitted to our hospital. Physical examination showed abdominal tenderness. Laboratory data revealed reductions in both total protein and albumin, elevated serum creatinine levels, and elevated antinuclear and anti-Smith antibodies. Urinalysis revealed proteinuria. Stool and urine cultures were negative. Abdominal computed tomography revealed diffuse edematous wall thickening, dilatation of the small intestine suggesting paralytic ileus, and irregular wall thickening of the urinary bladder. Histological results of the cystic and renal biopsies revealed interstitial cystitis and membranous nephropathy which were suggestive of lupus cystitis and lupus nephritis, respectively. The patient's gastrointestinal symptoms were finally diagnosed as resulting from lupus enteritis. After initiating 30 mg oral prednisolone daily, the diarrhea and pollakiuria subsided, and renal function became normal. Lupus enteritis should always be considered in the differential diagnosis when patients complaining of chronic diarrhea of unknown etiology are encountered.

Simultaneous occurrence of inflammatory bowel disease and myelodysplastic syndrome due to chromosomal abnormalities in bone marrow cells.

Fumiyasu Nakamura, Tomohiro Watanabe, Kimiko Hori, Yoshiaki Ohara, Kouhei Yamashita, Yoshihisa Tsuji, Yoshihide Ueda, Sakae Mikami, Hiroshi Nakase, Tsutomu Chiba

Digestion ( KARGER ) 79 ( 4 ) 215 - 9 2009年 [査読有り] [国際誌]

BACKGROUND/AIMS: Although chromosomal abnormalities in bone marrow (BM) cells, such as trisomy 8, are risk factors for the development of inflammatory bowel diseases (IBD) as well as myelodysplastic syndrome (MDS), the mechanisms of how these cytogenetic abnormalities cause intestinal inflammation are poorly understood. METHODS AND RESULTS: A 55-year-old man with a 3-month history of watery diarrhea, fever and abdominal pain was admitted. Blood examinations revealed pancytopenia. Pathological analysis and endoscopic images of the entire colon led to the diagnosis of IBD of unclassified type. BM examination showed that the pancytopenia was due to MDS and that his BM cells had dual chromosomal abnormalities: 47, XY, +1, der(1;7)(q10;p10), +8. Immunological studies using peripheral blood monocytes from this patient revealed that the dual chromosomal abnormalities of BM cells led to the development of colitogenic monocytes producing a large amount of pro-inflammatory cytokines and showing resistance to apoptosis upon stimulation with microbial antigens. CONCLUSION: An abnormal karyotype of BM cells is not only responsible for the development of MDS, but also for IBD in this case.

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