Shirô Nakamura

Kansai Medical University

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Nobuyuki Hida

Suita Tokushukai Hospital

Nobuhide Oshitani

Obihiro Kyokai Hospital

Kenji Watanabe

National Institute for Materials Science

Yoko Yokoyama

Hyogo University

Koji Kamikozuru

Hyogo University

Kazuhide Higuchi

The Japanese Society of Gastroenterological Surgery

Takayuki Matsumoto

Kyushu University

Tetsuo Arakawa

Osaka Hospital

Takako Miyazaki

Osaka University of Pharmaceutical Sciences

Atsuo Kitano

Toho University Medical Center Sakura Hospital

Cooperative Institutions

Osaka City University

177

The University of Tokyo

167

Hyogo Medical University

Tohoku University

Kyoto University

Osaka University

The Japanese Society of Gastroenterological Surgery

116

Liechtenstein Institute

112

Kyushu University

108

Keio University

105

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Adalimumab for the Treatment of Japanese Patients With Intestinal Behçet’s Disease

Clinical Gastroenterology and Hepatology (2014)

Satoshi Tanida Nagamu Inoue Kiyonori Kobayashi Makoto Naganuma Fumihito Hirai

Background & AimsBehçet's disease is a chronic, relapsing inflammatory disease that can involve the mouth, skin, eyes, genitals, and intestines. Active intestinal Behçet's disease can be complicated by gastrointestinal (GI) bleeding and perforation. We performed a multicenter, open-label, uncontrolled study to evaluate the efficacy and safety of adalimumab, a fully human monoclonal antibody against tumor necrosis factor α, in patients with intestinal Behçet's disease who were refractory to corticosteroid and/or immunomodulator therapies.MethodsThe study was conducted at 12 sites in Japan, from November 2010 through October 2012. Twenty patients were given 160 mg adalimumab at the start of the study and 80 mg 2 weeks later, followed by 40 mg every other week for 52 weeks; for some patients, the dose was increased to 80 mg every other week. A composite efficacy index, combining GI symptom and endoscopic assessments, was used to evaluate efficacy. The primary efficacy end point was the percentage of patients with scores of 1 or lower for GI symptom and endoscopic assessments at week 24. Secondary end points included complete remission and resolution of non-GI Behçet's-related symptoms.ResultsNine patients (45%) had GI symptom and endoscopic assessment scores of 1 or lower at week 24 of treatment, and 12 patients (60%) had these scores by week 52. Four patients (20%) achieved complete remission at weeks 24 and 52. Individual global GI symptom and endoscopic scores improved for most patients at weeks 24 and 52. Two thirds of patients with oral aphthous ulcers, skin symptoms, and genital ulcers, and 88% of patients with erythema nodosum had complete resolution of these conditions at week 52. A total of 9 of 13 patients (69%) taking steroids at baseline were able to taper (n = 1) or completely discontinue steroids (n = 8) during the study. No new safety signals were observed.ConclusionsAdalimumab is a potentially effective treatment for intestinal Behçet's disease in Japanese patients who are refractory to conventional treatments. ClinicalTrials.gov number: NCT01243671.

Behcet disease

10.1016/j.cgh.2014.08.042

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Citations (94)

GC/MS-based profiling of amino acids and TCA cycle-related molecules in ulcerative colitis

Inflammation Research (2011)

Makoto Ooi Shin Nishiumi Tomoo Yoshie Yuuki Shiomi Michitaka Kohashi

Trichloroacetic acid

10.1007/s00011-011-0340-7

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Citations (145)

Classification and therapy of germ cell tumors in anterior mediastinum

Kokyuuki geka/Kokyūki geka (1987)

M Irako Masaaki Ohata Mamoru Iida Kazumitsu Ohmori Yasushi Nakaoka

A total of 12 cases of anterior mediastinal germ cell tumors observed in our laboratory for 30 years from 1957 to 1986 were classified into 6 types according to the additionally modified Dixon and Moore's classification and the therapies and prognoses of each type were investigated and the following results were obtained.1. There are various nomenclatures used to describe germ cell tumors in anterior mediastinum and their classification has not yet been established, therefore our classification seemed practically useful in the surgical clinical field.2. In the cases of Type II (embryonal carcinoma pure, or with seminoma) and VI (yolk sac tumor) prognoses were extremely resistant to treatment whereas that of Type III was satisfactory.3. AFP and hCG used as a tumor marker were very useful as an indicator for chemotherapeutic effectiveness and the recurrence of postectomy, and the immunohistochemical study of ectomized tumors was inevitable which was useful for postoperative classification and therapy.4. Prolonged survival can be expected by combining radiotherapy with operation in the treatment of Type III. Furthermore, it is desirable to additionally perform chemotherapy after operations when a positive picture was found immunohistochemically.5. For the patients with germ cell tumors producing AFP, adjuvant surgery was applied after chemotherapy using cisplatin as a main agent, then the prognostic convalescence of the difficult anterior mediastinal germ cell tumors could be predicted.

Embryonal carcinoma

10.2995/jacsurg1987.1.64

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Location of superoxide anion generation in human colonic mucosa obtained by biopsy.

Gut (1993)

Nobuhide Oshitani Atsuo Kitano Hirohisa Okabe Shirô Nakamura Takayuki Matsumoto

To identify which cells generate superoxide, inflamed human mucosa was tested with nitro-blue tetrazolium as a probe, because it is reduced by strong reducing agents to form insoluble blue formazan, which then precipitates in tissues. Biopsy specimens from control subjects and patients with ulcerative colitis were studied. The specimens were organ cultured with bubbling air or nitrogen, and inhibition of the reduction by catalase (a hydrogen peroxide scavenger), para-benzoquinone (a tissue permeable superoxide scavenger), or superoxide dismutase (a superoxide scavenger) was assayed. The dye was reduced by epithelial cells, vascular endothelium, and infiltrating mononuclear cells of the mucosa. Its reduction by vascular endothelium and infiltrating mononuclear cells was greater in inflamed mucosa. The reduction by vascular endothelium and infiltrating mononuclear cells was inhibited in cultures with nitrogen saturation or with 1 mM para-benzoquinone. The vascular endothelium seems to produce superoxide in the inflamed mucosa, which would exacerbate tissue injury in ulcerative colitis.

Intestinal mucosa

10.1136/gut.34.7.936

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Citations (63)

USEFULNESS OF THE COLON WALL THICKNESS / UCEIS SCORE FOR DIFFERENTIATING 5ASA INTOLERANCE IN PATIENTS WITH ULCERATIVE COLITIS

Gastrointestinal Endoscopy (2022)

Ryoji Koshiba kazuki kakimoto Keijiro Numa Yuka Kawasaki Naohiko Kinoshita

Corporation

10.1016/j.gie.2022.04.497

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Supplementary Material for: Isoliquiritigenin Ameliorates Indomethacin-Induced Small Intestinal Damage by Inhibiting NOD-Like Receptor Family, Pyrin Domain-Containing 3 Inflammasome Activation

Figshare (2018)

Shirô Nakamura Toshio Watanabe Tetsuya Tanigawa Sunao Shimada Yuji Nadatani

Activation of the NOD-Like Receptor Family, Pyrin Domain-Containing 3 (NLRP3) inflammasome, which consists of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and pro-caspase-1, triggers pro-caspase-1 cleavage promoting the processing of pro-interleukin (IL)-1β into mature IL-1β, which is critical for the development of non-steroidal anti-inflammatory drug (NSAID)-induced enteropathy. We investigated the effects of isoliquiritigenin, a flavonoid derived from the roots of Glycyrrhiza species, on NSAID-induced small intestinal damage and the inflammasome activation. To induce enteropathy, mice were administered indomethacin by gavage with or without isoliquiritigenin pretreatment. Some mice received an intraperitoneal injection of recombinant murine IL-1β in addition to isoliquiritigenin and indomethacin. Indomethacin induced small intestinal damage and increased protein levels of cleaved caspase-1 and mature IL-1β in the small intestine. Treatment with 7.5 and 75 mg/kg isoliquiritigenin inhibited indomethacin-induced small intestinal damage by 40 and 56%, respectively. Isoliquiritigenin also inhibited the indomethacin-induced increase in cleaved caspase-1 and mature IL-1β protein levels, whereas it did not affect the mRNA expression of NLRP3, ASC, caspase-1, and IL-1β. Protection against intestinal damage in isoliquiritigenin-treated mice was completely abolished with exogenous IL-1β. NLRP3^–/– and caspase-1^–/– mice exhibited resistance to intestinal damage, and isoliquiritigenin treatment failed to inhibit the damage in NLRP3^–/– and caspase-1^–/– mice. Isoliquiritigenin prevents NSAID-induced small intestinal damage by inhibiting NLRP3 inflammasome activation.

Pyrin domain

Isoliquiritigenin

10.6084/m9.figshare.5827380

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Topical Tacrolimus Therapy for Antibiotic-Refractory Pouchitis

Diseases of the Colon & Rectum (2013)

Motoi Uchino Hiroki Ikeuchi Hiroki Matsuoka Toshihiro Bando Nobuyuki Hida

BACKGROUND: Pouchitis is the most common complication after restorative proctocolectomy for ulcerative colitis, and it leads to pouch failure. The administration of oral antibiotics is the main treatment for pouchitis; however, in some cases, antibiotic-refractory pouchitis may develop, which requires further medical therapy. OBJECTIVE: We investigated the applicability of topical tacrolimus for refractory pouchitis. DESIGN: We performed a prospective pilot study. The study protocols were registered with the University Hospital Medical Information Network Clinical Trials Registry, 000006658. SETTING: This study was conducted in the Surgical Department of Hyogo College of Medicine. PATIENTS: Patients with antibiotic-refractory pouchitis were treated for 8 weeks with a tacrolimus enema. MAIN OUTCOME MEASURES: The efficacy was assessed by comparing Pouchitis Disease Activity Index scores. Safety was assessed by measuring whole blood tacrolimus trough levels. RESULTS: Ten patients with refractory pouchitis were enrolled. No severe adverse events occurred. The mean scores decreased from 15.9 ± 0.8 to 7.8 ± 0.8 during 8 weeks of treatment (p < 0.01). Specifically, the clinical symptom, endoscopic finding, and histological finding subscores decreased to 0.8 ± 0.6, 3.9 ± 0.2, and 2.9 ± 0.4. Nine patients recovered from their clinical symptoms, and 3 patients recovered from pouchitis. LIMITATIONS: This small study was neither blinded nor randomized. CONCLUSIONS: This study demonstrates that the use of topical tacrolimus for the treatment of refractory pouchitis is safe and effective in the short term for clinical symptoms. Although complete endoscopic healing was not achieved, this treatment may have early rescue efficacy in the treatment of antibiotic-refractory pouchitis.

Pouchitis

Refractory (planetary science)

Proctocolectomy

10.1097/dcr.0b013e31829ebd83

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Citations (37)

Prognostic Impact of Ectopic Fat Deposition within Psoas Muscle in Stage IV Gastric Cancer Patients Undergoing Systemic Chemotherapy

Journal of Cancer (2022)

Takako Ikegami Hiroki Nishikawa Masahiro Goto Fukutaro Shimamoto Tetsuji Terazawa

Aims:In this study, we focused on the fat ratio within psoas muscle (FRPM) and sought to clarify the impact of FRPM on overall survival (OS) in stage IV gastric cancer (GC) patients undergoing systemic chemotherapy (n = 79, median age = 69 years, 59 males).Methods: The median FRPM was 1.67 %.Forty patients with FRPM ≥1.67 % were defined as the FRPM-high group, and the remaining 39 patients was defined as the FRPM-low group.The median PMI in male and female patients was 4.35 cm 2 /m 2 and 2.88 cm 2 /m 2 .Thirty male patients with PMI ≥4.35 cm 2 /m 2 and 10 female patients with PMI ≥2.88 cm 2 /m 2 was defined as the PMI-high group, and the remaining 39 patients was defined as the PMI-low group.Results: The 1-, 2-and 3-year cumulative OS rate for all cases was 70.8%, 24.3% and 14.6%.The proportion of ECOG-PS 2 or 3 in patients with FRPM-high and FRPM-low was 17.5% (7/40) and 2.6% (1/39).The 1-, 2-and 3-year cumulative OS rate in patients with FRPM-high and FRPM-low was 67.3%, 14.3% and 7.6% in the FRPM-high group and 74.8%, 40.5% and 32.4% in the FRPM-low group (P = 0.0341).The 1-, 2-and 3-year cumulative OS rate in patients with PMI-high and PMI-low was 86.7%, 40.4% and 30.0% in the PMI-high group and 55.8%, 12.8% and 6.4% in the PMI-low group (P < 0.0001).In the multivariate analysis of factors associated with OS, PMI (P = 0.0047) and FRPM (P = 0.0019) were independent predictors for the OS.Conclusion: Higher FRPM can be associated with decreased physical activity, and not only skeletal muscle mass but also skeletal muscle function can be an essential prognostic factor in stage IV GC patients undergoing systemic chemotherapy.

10.7150/jca.78407

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Looking for predictive factors of clinical response to adsorptive granulocyte and monocyte apheresis in patients with ulcerative colitis: markers of response to GMA

BMC Gastroenterology (2013)

Yoko Yokoyama Mikio Kawai Ken Fukunaga Koji Kamikozuru Kazuko Nagase

Adsorptive granulocyte and monocyte apheresis (GMA) with an Adacolumn in patients with ulcerative colitis (UC) has been applied as a non-pharmacological treatment strategy, but the efficacy has been encouraging as well as discouraging, depending on patients' demography at entry. In this study, we looked for predictive factors for clinical response to GMA in patients with UC. In a retrospective setting, 43 outpatients who had been treated with GMA for active UC were evaluated. Patients were divided into remission group and non-remission group based on Lichtiger's clinical activity index (CAI) before and after 10, once a week GMA sessions. The efficacy was analysed in relation to patients' demographic variables. To determine predictive factors that closely related to the response to GMA, receiver operating characteristic (ROC) curve, and multiple logistic regression analyses were applied. After 10 GMA sessions, the overall clinical remission rate (CAI < 4) was 53.5%. Multiple logistic regression and ROC analyses showed that the interval between relapse and the first GMA session was a significant and independent predictive factor for clinical response to GMA (P = 0.016); the clinical response was better in patients who received GMA immediately after a relapse and vice versa. Likewise, univariate analyses showed that, the duration of UC (P = 0.036) and the cumulative prednisolone (PSL) dose (P = 0.006) before the first GMA session were significantly greater in the GMA non-responder group as compared with the responder group. Additionally, a lower white blood cell (WBC) count at first GMA session was related to clinical response to GMA (P = 0.032). In this study, patients with a short duration of UC and low cumulative PSL dose seemed to respond well to GMA. However, we found that the best responders were patients who received GMA immediately after a clinical relapse. Additionally, GMA was effective in patients with low WBC count at the first GMA session. The findings of this study should spare medical cost and reduce morbidity time for many patients, relevant for decision making in clinical settings.

White blood cell

Prednisolone

10.1186/1471-230x-13-27

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Citations (32)

P125. Developments of novel diagnostic findings on capsule endoscopy in the small bowel of patients with Crohn's disease

Journal of Crohn s and Colitis (2015)

Kenji Watanabe Atsushi Noguchi Tatsuya Miyazaki Kenichi Morimoto Shuhei Hosomi

without anemia and 41 with normal iron status.The median age was 37 years [31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47], and 55% were women.Median hemoglobin was 12.9g/dL in the iron deficient group and 14 in the normal iron group (p=0.02).There were no differences in age, type of IBD, treatment or illness behavior between groups.The prevalence of female patients was higher in the group with iron deficiency (RR: 1.87 95% CI 1.33-2.62,p<0.01).The median global value of the IBDQ-36 was 227 in the iron deficient group and 231 in the normal iron status group (p=ns), but restoration of health was significantly less frequent in iron deficient patients than in patients with normal iron status (RR: 2.5 IC 95% 1.15-5.51,p=0.018).Conclusions: Iron deficiency in absence of anemia negatively impacts the normal perception of health-related quality of life in IBD patients in remission.Correction of iron deficiency may be a new target in the treatment of these patients.

Crohn disease

10.1093/ecco-jcc/jju027.242

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