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Helicobacter pylori and gastric mucosa-associated lymphoid tissue lymphoma:Recent progress in pathogenesis and management

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World Journal of Gastroenterology 2013年第45期19卷 8181-8187页

作者： Shotaro Nakamura takayuki matsumoto Department of R/D for Surgical Support System Center for Advanced Medical Innovation Kyushu University Fukuoka 812-8582 Japan Department of Medicine and Clinical Science Graduate School of Medical Sciences Kyushu UniversityFukuoka 812-8582 Japan Division of Gastroenterology Department of Internal Medicine Iwate Medical University Morioka 020-8505 Japan

Recent progress in the research regarding the molecular pathogenesis and management of gastric mucosa-associated lymphoid tissue (MALT) lymphoma is reviewed. In approximately 90% of cases, Helicobacter pylori (H. pylori) infection plays the causative role in the pathogenesis, and H. pylori eradication is nowadays the first-line treatment for this disease, which leads to complete disease remission in 50%-90% of cases. In H. pylori-dependent cases, microbe-generated immune responses, including interaction between B and T cells involving CD40 and CD40L co-stimulatory molecules, are considered to induce the development of MALT lymphoma. In H. pylori-independent cases, activation of the nuclear factor-κB pathway by oncogenic products of specific chromosomal translocations such as t(11;18)/API2-MALT1, or inactivation of tumor necrosis factor alpha-induced protein 3 (A20) are considered to contribute to the lymphomagenesis. Recently, a large-scale Japanese multicenter study confirmed that the long-term clinical outcome of gastric MALT lymphoma after H. pylori eradication is excellent. Treatment modalities for patients not responding to H. pylori eradication include a “watch and wait” strategy, radiotherapy, chemotherapy, rituximab immunotherapy, and a combination of these. Because of the indolent behavior of MALT lymphoma, second-line treatment should be tailored in consideration of the clinical stage and extent of the disease in each patient.

关键词： Gastric lymphoma, Mucosa-associated lymphoid tissue lymphoma, Helicobacter pylori, Nuclear factor κ B

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Genetic analysis is helpful for the diagnosis of small bowel ulceration

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World Journal of Gastroenterology 2018年第28期24卷 3198-3200页

作者： Junji Umeno takayuki matsumoto Atsushi Hirano Yuta Fuyuno Motohiro Esaki Department of Medicine and Clinical Science Graduate School of Medical SciencesKyushu UniversityFukuokaFukuoka 812-8582Japan Division of Gastroenterology Department of Internal MedicineFaculty of MedicineIwate Medical UniversityMoriokaIwate 020-8505Japan Department of Endoscopic Diagnostics and Therapeutics Saga University HospitalSaga 849-8501Japan

The widespread use of capsule endoscopy and balloonassisted endoscopy has provided easy access for detailed mucosal assessment of the small intestine. However, the diagnosis of rare small bowel diseases, such as cryptogenic multifocal ulcerous stenosing enteritis(CMUSE), remains difficult because clinical and morphological features of these diseases are obscure even for gastroenterologists. In an issue of this journal in 2017, Hwang et al reviewed and summarized clinical and radiographic features of 20 patients with an established diagnosis of CMUSE. Recently, recessive mutations in the PLA2G4A and SLCO2A1 genes have been shown to cause small intestinal diseases. The small bowel ulcers in each disease mimic those in the other and furthermore those found in nonsteroidal anti-inflammatory drug-induced enteropathy. These recent and novel findings suggest that a clinical diagnosis exclusively based on the characteristics of small bowel lesions is possibly imprecise. Genetic analyses seem to be inevitable for the diagnosis of rare small bowel disorders such as CMUSE.

关键词： cryptogenic multifocal ulcerous stenosing enteritis chronic nonspecific multiple ulcers of the small intestine chronic enteropathy associated with SLCO2A1 gene Crohn’s disease

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Long-term efficacy of infliximab maintenance therapy for perianal Crohn’s disease

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World Journal of Gastroenterology 2011年第9期17卷 1174-1179页

作者： Motoi Uchino Hiroki Ikeuchi Toshihiro Bando Hiroki Matsuoka Yoshio Takesue Yoshiko Takahashi takayuki matsumoto Naohiro Tomita Departments of Lower Gastroenterological Surgery Hyogo College of Medicine Infection Control and Prevention Hyogo College of Medicine Department of Internal Medicine Division of Lower GastroenterologyHyogo College of Medicine

AIM:To assess the long-term efficacy of seton drainage with infliximab maintenance therapy in treatment of stricture for perianal Crohn’s disease(CD). METHODS:Sixty-two patients with perianal CD who required surgical treatment with or without infliximab between September 2000 and April 2010 were identified from our clinic’s *** activities of the perianal lesions were evaluated using the modified perianal CD activity index(mPDAI)*** primary endpoint was a clinical response at 12-15 wk after surgery as a shortterm *** endpoints were recurrence as reflected in the mPDAI score,defined as increased points in every major *** clinical responses were classified as completely healed(mPDAI=0),partially improved(mPDAI score decreased more than 4 points),and failure or recurrence(mPDAI score increased or decreased less than 3 points). RESULTS:There were 43 males and 19 females,of whom 26 were consecutively treated with infliximab after surgery as maintenance *** healing was not *** was seen in 10/36(27.8%) patients without infliximab and 4/26(15.4%)patients with infliximab(P=0.25).Partial improvement was seen in 26/36(72.2%)patients without infliximab and 22/26(88.5%)patients with infliximab(P=0.25). Short-term improvement was achieved in 48/62(77.4%) *** the mPDAI score improved significantly with surgery regardless of infliximab,it decreased more from baseline in patients with infliximab(50.0%) than in those without infliximab(28.6%),(P=0.003). In the long-term,recurrence rates were low regardless of infliximab in patients without anorectal *** patients with anorectal stricture,cumulative recurrence incidences increased gradually and exceeded 40%at 5 years regardless of *** efficacy of infliximab treatment was found(P=0.97).Although the cumulative rate of ostomy creation was also low in patients without stricture and high in patients with stricture,no protective efficacy was found wit

关键词： Crohn’s disease Perianal fistula Infliximab Anorectal stricture Long-term efficacy

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Appropriate leucine-richα-2 glycoprotein cut-off value for Japanese patients with ulcerative colitis

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World Journal of Clinical Cases 2023年第32期11卷 7753-7760页

作者： Masanao Yamazato Shunichi Yanai Tomofumi Oizumi Makoto Eizuka Shun Yamada Yosuke Toya Noriyuki Uesugi Tamotsu Sugai takayuki matsumoto Division of Gastroenterology and Hepatology Department of Internal MedicineIwate Medical UniversityYahaba 028-3695Japan Division of Molecular Diagnostic Pathology Iwate Medical UniversityYahaba 028-3695Japan

BACKGROUND It has been suggested that serum leucine-richα-2 glycoprotein(LRG)could be a novel monitoring biomarker for the assessment of disease activity in inflammatory bowel *** particular,the relationship between LRG levels and the endoscopically assessed activity of ulcerative colitis(UC)has become a matter of *** To clarify appropriate LRG cut-off values for the prediction of endoscopic and histologic remission in Japanese patients with *** This was a cross-sectional,single-center,observational study of Japanese patients with *** 213 patients with UC,in whom LRG was measured from September 2020 to February 2022,we recruited 30 patients for whom a total colonoscopy and measurements of LRG and C-reactive protein(CRP)were performed on the same *** retrospectively analyzed correlations between the LRG and CRP levels and endoscopic indices,including the Mayo endoscopic subscore and UC endoscopic index of *** Correlations between the LRG values and the Mayo endoscopic subscore or UC endoscopic index of severity were significant(r=0.754,P<0.0001;r=0.778,P<0.0001,respectively).There were also significant correlations between CRP levels and Mayo endoscopic subscore or UC endoscopic index of severity(r=0.599,P=0.0005;r=0.563,P=0.0012,respectively),although the correlation coefficients were higher for *** LRG cutoff value for predicting endoscopic remission was 13.4μg/mL for a Mayo endoscopic subscore of 0[area under the curve(AUC):0.871;95%confidence interval(CI):0.744-0.998],and 13.4μg/mL for an UC endoscopic index of severity of 0 or 1(AUC:0.904;95%CI:0.792-1.000).CONCLUSION LRG may be a surrogate marker for endoscopic activity in UC,with a cut-off value of around 13.4μg/mL for endoscopically inactive disease.

关键词： Ulcerative colitis Leucine-rich alpha-2 glycoprotein C-reactive protein Japanese patients

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Efficacy of low-dose thiopurine therapy for the induction of remission in steroid-dependent ulcerative colitis: Comparison with cytapheresis

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Open Journal of Gastroenterology 2012年第1期2卷 9-14页

作者： Shuji Kochi Shotaro Nakamura takayuki matsumoto Department of Medicine and Clinical Science Graduate School of Medical Sciences Kyushu University Fukuoka Japan.

Background: The role of azathioprine (AZA) and 6-mercaptopurine (6-MP) in the induction of remission in patients with ulcerative colitis (UC) remains unclear. Aims: To compare the efficacy and safety of low-dose thiopurine (AZA/6-MP) and cytapheresis (CAP) for the induction of remission in patients with steroid- dependent UC. Patients and Methods: We reviewed the clinical course of 65 patients with steroid-dependent UC with moderate activity, who were treated with either low-dose AZA/6-MP (T-group, n = 38) or with CAP (C-group, n = 27). The efficacy and safety for the first 10 weeks after the start of the therapies were compared between the two groups. The cumulative probability curves of treatment failure were estimated by the Kaplan-Meier method. Clinical remission was defined as an ulcerative colitis activity index value of less than 150 without any other treatments. Results: Neither clinical characteristics, concomitant therapies, nor laboratory data (except for serum albumin levels) were different between the two groups. The remission rate at 10 weeks was not different between the two groups (55.3% in the T-group and 70.4% in the C-group, p = 0.22 in the intention-to-treat analysis). The frequencies of adverse events did not differ be- tween the two groups (p = 0.12). The cumulative pro- bability of treatment failure at 10 weeks was 44.7% for the T-group and 29.6% for the C-group (p = 0.23). Conclusions: Low-dose thiopurine therapy is an alter- native candidate for the induction of remission in pa- tients with steroid-dependent, moderate UC.

关键词： Ulcerative Colitis Azathioprine 6-Mercaptopurine Cytapheresis Induction of Remission

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Practical fecal calprotectin cut-off value for Japanese patients with ulcerative colitis

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World Journal of Gastroenterology 2018年第38期24卷 4384-4392页

作者： Jun Urushikubo Shunichi Yanai Shotaro Nakamura Keisuke Kawasaki Risaburo Akasaka Kunihiko Sato Yosuke Toya Kensuke Asakura Takahiro Gonai Tamotsu Sugai takayuki matsumoto Division of Gastroenterology Department of Internal Medicine School of Medicine Iwate Medical University Division of Molecular Diagnostic Pathology Department of Pathology School of Medicine Iwate Medical University

AIM To determine appropriate fecal calprotectin cut-off values for the prediction of endoscopic and histologic remission in Japanese patients with ulcerative colitis(UC). METHODS We performed a cross-sectional observational study of 131 Japanese patients with UC and measured fecal calprotectin levels by fluorescence enzyme immunoassay. The clinical activity of UC was assessed with the partial Mayo score(PMS). Relapse was defined as increase of PMS by 2 points or more in stool frequency or rectal bleeding subscore. The endoscopic and histologic activities of UC were evaluated in 50 patients within a 2-mo period from fecal sampling. Endoscopic activity was determined by Mayo endoscopic subscore, Rachmilewitz endoscopic index, and ulcerative colitis endoscopic index of severity. The histologic grade of inflammation was evaluated with biopsy specimens obtained from the endoscopically most severely inflamed site, according to the scheme by Matts grade and Riley's *** Fecal calprotectin levels varied from 1-20783 μg/g. There was a significant correlation between the partial Mayo score and fecal calprotectin levels(r = 0.548, P < 0.001). In 50 patients who underwent colonoscopy with biopsy, levels were significantly correlated with the Mayo endoscopic subscore(r = 0.574, P < 0.001), Rachmilewitz endoscopic index(r = 0.628, P < 0.001), ulcerative colitis endoscopic index of severity(r = 0.613, P < 0.001), Riley's histologic score(r = 0.400, P = 0.006), and Matts grade(r = 0.586, P < 0.001). Receiver-operating characteristic analyses identified the best cut-off value for the prediction of endoscopic remission as 288 μg/g, with an area under the curve of 0.777 or 0.823, while that for histologic remission was 123 or 125 μg/g, with an AUC of 0.881 or 0918, respectively. Of the 131 study patients, 88 patients in clinical remission were followed up 6 mo. During the follow-up period, 19 patients relapsed. The best fecal calprotectin cut-off value for predicting relapse

关键词： Ulcerative colitis Remission Mucosal healing Colonoscopy Histology Biomarker Feces Calprotectin

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Effect of tumor necrosis factor-α antagonists on oxidative stress in patients with Crohn's disease

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World Journal of Gastroenterology 2015年第35期21卷 10208-10214页

作者： Kazunari Yamamoto Toshimi Chiba takayuki matsumoto Division of Gastroenterology Department of Internal MedicineSchool of MedicineIwate Medical University

AIM: To investigate changes in oxidative stress in Crohn's disease(CD) before and after anti-tumor necrosis factor(TNF)-α ***: A total of 42 patients with active CD, who were scheduled to be treated by anti-TNF-α antibodies, were enrolled. Serum levels of diacron-reactive oxygen metabolites(d-ROM), biological antioxidant potential(BAP), and modified ratio of oxidative stress and antioxidant capacity(m-OA) were measured using the Free Radical Analytical System before and 8 wk after induction of therapy with infliximab or adalimumab. The values for oxidative stress were correlated with disease activity and clinical response as determined by the CD activity index(CDAI) at 8 and 54 wk after the ***: Prior to treatment, d-ROM showed significant correlations with CDAI(r = 0.42, P < 0.01). There was a significant negative correlation between m-OA and CDAI before and after treatment(r =-0.48 vs r =-0.42, P < 0.01). CDAI and d-ROM had decreased significantly by 8 wk after treatment(CDAI; 223.3 ± 113.2 vs 158.3 ± 73.4, P < 0.01, d-ROM; 373 ± 133 vs 312 ± 101, P < 0.05). However, neither BAP nor m-OA had changed significantly. In patients who had responded to the treatment at 8 wk, d-ROM, BAP, and m-OA levels before treatment did not differ significantly between patients with and without loss of ***: Anti-TNF-α therapy decreases oxi-dative stress in patients with CD, but does not alter the production of antioxidants. Dysregulation of antioxidants may be associated with the disease.

关键词： Crohn’s disease Severity Oxidative stress Anti-tum

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Association between white opaque substance under magnifying colonoscopy and lipid droplets in colorectal epithelial neoplasms

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World Journal of Gastroenterology 2017年第47期23卷 8367-8375页

作者： Keisuke Kawasaki Makoto Eizuka Shotaro Nakamura Masaki Endo Shunichi Yanai Risaburo Akasaka Yosuke Toya Yasuko Fujita Noriyuki Uesugi Kazuyuki Ishida Tamotsu Sugai takayuki matsumoto Division of Gastroenterology Department of Internal MedicineIwate Medical University Department of Diagnostic Pathology Iwate Medical University Kaiunbashi Endoscopy Clinic

AIM To examine the association between white opaque substance(WOS) and histologically verified lipiddroplets in colorectal epithelial *** We reviewed colonoscopy records at our institution from 2014 to 2016 and identified cases of endoscopically or surgically resected colorectal epithelial neoplasms observed by magnifying narrow-band imaging(M-NBI) colonoscopy. Immunohistochemistry was used to stain tumors with a monoclonal antibody specific to adipophilin as a marker of lipids. The expression and distribution of adipophilin were compared between WOS-positive and WOS-negative lesions and among tumors classified by histologic type and depth of *** Under M-NBI colonoscopy, 81 lesions were positive for WOS and 48 lesions were negative for WOS. The rate of adipophilin expression was significantly higher in WOS-positive lesions(95.1%) than in WOS-negative lesions(68.7%)(P = 0.0001). The incidence of deep adipophilin expression was higher in WOS-positive lesions(24.7%) than in WOS-negative lesions(4.2%)(P = 0.001). The incidence of deep expression was predominant among cancers with massive submucosal invasion(62.5%) compared to adenoma(7.2%) and high-grade dysplasia or cancers with slight submucosal invasion(12.7%)(P = 0.0001).CONCLUSION The distribution of lipid droplets may be closely associated with the visibility of WOS under M-NBI colonoscopy, and with histologic grade and depth of tumor invasion.

关键词： White opaque substance Adipophilin Magnifying narrow-band imaging Colorectal neoplasm Magnifying endoscopy

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Case of gastric neuroendocrine carcinoma showing an interesting tumorigenic pathway

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World Journal of Clinical Cases 2017年第11期5卷 397-402页

作者： Noriyuki Uesugi Ryo Sugimoto Makoto Eizuka Yasuko Fujita Mitsumasa Osakabe Keisuke Koeda Takashi Kosaka Shunichi Yanai Kazuyuki Ishida Akira Sasaki takayuki matsumoto Tamotsu Sugai Department of Diagnostic Molecular Pathology School of MedicineIwate Medical University Department of Surgery School of MedicineIwate Medical University Division of Gastroenterology Department of Internal MedicineSchool of MedicineIwate Medical University

Here, we report a case of gastric neuroendocrine carcinoma showing an interesting tumorigenic pathway. A 57-year-old Japanese woman presented with epigastric tenderness, and distal gastrectomy was performed. In the surgical specimen, histologically, the tumor tissue was composed of three subtypes of tumor components showing different histological architecture and cellular atypia, diagnosed as neuroendocrine tumor(NET) G2, NET G3, and neuroendocrine carcinoma(NEC) components. Immunohistochemically, the Ki-67-positive rates of NET G2, NET G3, and NEC components were 6.5%, 99.5% and 88.1%, respectively. Although allelic imbalance(AI) on chromosomes 1p, 3p, 8q, TP53, 18q and 22 q was commonly found in all components, AI of 4p was found in NET G3 and NEC components(but not in the NET G2 component). In contrast, AIs of 5q and 9p were found in only the NEC component. Thus, we showed the progression from NET G2 to NEC, via NET G3, within the same tumor.

关键词： stomach neuroendocrine tumor G2 neuroendocrine tumor G3 neuroendocrine carcinoma

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Measurement of prostaglandin metabolites is useful in diagnosis of small bowel ulcerations

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World Journal of Gastroenterology 2019年第14期25卷 1753-1763页

作者： Yuichi Matsuno Junji Umeno Motohiro Esaki Yoichiro Hirakawa Yuta Fuyuno Yasuharu Okamoto Atsushi Hirano Shigeyoshi Yasukawa Fumihito Hirai Toshiyuki Matsui Shuhei Hosomi Kenji Watanabe Naoki Hosoe Haruhiko Ogata Tadakazu Hisamatsu Shunichi Yanai Shuji Kochi Koichi Kurahara Tsuneyoshi Yao Takehiro Torisu Takanari Kitazono takayuki matsumoto Department of Medicine and Clinical Science Graduate School of Medical Sciences Kyushu University Department of Endoscopic Diagnostics and Therapeutic Saga University Hospital Department of Epidemiology and Public Health Graduate School of Medical Sciences Kyushu University Department of Gastroenterology Fukuoka University Chikushi Hospital Department of Gastroenterology Osaka City University Graduate School of Medicine Department of Intestinal Inflammation Research Hyogo College of Medicine Center for Diagnostic and Therapeutic Endoscopy School of Medicine Keio University the Third Department of Internal Medicine Kyorin University School of Medicine Division of Gastroenterology Department of Internal Medicine Iwate Medical University Division of Gastroenterology Matsuyama Red Cross Hospital Department of Gastroenterology Sada Hospital

BACKGROUND We recently reported on a hereditary enteropathy associated with a gene encoding a prostaglandin transporter and referred to as chronic enteropathy associated with SLCO2 A1 gene(CEAS). Crohn's disease(CD) is a major differential diagnosis of CEAS, because these diseases share some clinical features. Therefore, there is a need to develop a convenient screening test to distinguish CEAS from *** To examine whether prostaglandin E major urinary metabolites(PGE-MUM) can serve as a biomarker to distinguish CEAS from *** This was a transactional study of 20 patients with CEAS and 98 patients with *** was diagnosed by the confirmation of homozygous or compound heterozygous mutation of SLCO2 A1. We measured the concentration of PGEMUM in spot urine by radioimmunoassay, and the concentration was compared between the two groups of patients. We also determined the optimal cut-off value of PGE-MUM to distinguish CEAS from CD by receiver operating characteristic(ROC) curve *** Twenty Japanese patients with CEAS and 98 patients with CD were ***-MUM concentration in patients with CEAS was significantly higher than that in patients with CD(median 102.7 vs 27.9 μg/g × Cre, P < 0.0001). One log unit increase in PGE-MUM contributed to 7.3 increase in the likelihood for the diagnosis of CEAS [95% confidence interval(CI) 3.2-16.7]. A logistic regression analysis revealed that the association was significant even after adjusting confounding factors(adjusted odds ratio 29.6, 95%CI 4.7-185.7). ROC curve analysis revealed the optimal PGE-MUM cut-off value for the distinction of CEAS from CD to be 48.9 μg/g × Cre with 95.0% sensitivity and 79.6% *** PGE-MUM measurement is a convenient, non-invasive and useful test for the distinction of CEAS from CD.

关键词： Chronic enteropathy associated with SLCO2A1 gene Prostaglandin E major urinary metabolites Chronic nonspecific multiple ulcers of the small intestine Crohn's disease Small intestine

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