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Novel strategies for the treatment of inflammatory bowel disease: Selective inhibition of cytokines and adhesion molecules

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World Journal of Gastroenterology 2006年第29期12卷 4628-4635页

作者： Kazuhiko Nakamura Kuniomi Honda Takahiro Mizutani Hirotada Akiho naohiko harada Department of Medicine and Bioregulatory Science Graduate School of Medical Sciences Kyushu UniversityFukuoka 812-8582Japan Fukuoka-Higashi Medical Center Koga 811-3195 Japan

The etiology of inflammatory bowel disease （IBD） has not yet been clarified and immunosuppressive agents which non-specifically reduce inflammation and immunity have been used in the conventional therapies for IBD. Evidence indicates that a dysregulation of mucosal immunity in the gut of IBD causes an overproduction of inflammatory cytokines and trafficking of effector leukocytes into the bowel, thus leading to an uncontrolled intestinal inflammation. Such recent advances in the understanding of the pathogenesis of IBD created a recent trend of novel biological therapies which specifically inhibit the molecules involved in the inflammatory cascade. Major targets for such treatment are inflammatory cytokines and their receptors, and adhesion molecules. A chimeric anti-TNF-α monoclonal antibody, infiiximab, has become a standard therapy for CD and it is also likely to be beneficial for UC. Several anti-TNF reagents have been developed but most of them seem to not be as efficacious as infliximab. A humanized anti-TNF monoclonal antibody, adalimumab may be useful for the treatment of patients who lost responsiveness or developed intolerance to infliximab. Antibodies against IL-12 p40 and IL-6 receptor could be alternative new anti-cytokine therapies for IBD. Antiinterferon-γ and anti-CD25 therapies were developed, but the benefit of these agents has not yet been established. The selective blocking of migration of leukocytes into intestine seems to be a nice approach. Antibodies against α4 integrin and α4β7 integrin showed benefit for IBD. Antisense oligonucleotide of intercellular adhesion molecule 1 （ICAM-1） may be efficacious for IBD. Clinical trials of such compounds have been either recently reported or are currently underway. In this article, we review the efficacy and safety of such novel biological therapies for IBD.

关键词： Inflammatory bowel disease Cytokine Adhesion molecule Treatment

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Adult case of an omphalomesenteric cyst resected by laparoscopic-assisted surgery

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World Journal of Gastroenterology 2006年第5期12卷 825-827页

作者： Fumi Sawada Rie Yoshimura Kenichi Ito Kazuhiko Nakamura Hajime Nawata Kazuhiro Mizumoto Shuji Shimizu Takahiro Inoue Takashi Yao Masazumi Tsuneyoshi Atushi Kondo naohiko harada Department of Medicine and Bioregulatory Science Department of Surgery and Oncology Department of Anatomic Pathology Graduate School of Medical SciencesKyushu UniversityFukuoka 812-8582FukuokaJapan Department of Gastroenterology Aso Iizuka HospitalIizuka 820-8505FukuokaJapan Department of Gastroenterology Fukuoka Higashi Medical CenterKoga 811-3195FukuokaJapan

This report describes an extremely rare adult case of an omphalomesenteric cyst resected by laparoscopicassisted surgery. A 29-years-old Japanese man was referred and admitted to Kyushu University Hospital because of an abdominal mass and an elevated serum CEA （carcinoembryonic antigen） level （21.3 ng/mL） in August 2001. Abdominal CT and US demonstrated a cystic mass with septum and calcification. Laparoscopy showed a large mass to be attached to his abdominal wall, measuring 110 mm × 70 mm× 50 mm and filled with mucus. The mass was resected by laparoscopicassisted surgery. The histological findings of its wall showed fibromuscular tissue, adipose tissue, calcification, and an intestinal structure. It was finally diagnosed to be an omphalomesenteric cyst.

关键词： Omphalomesenteric cyst Laparoscopicassisted surgery

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Endoscopic mucosal resection vs endoscopic submucosal dissection for superficial non-ampullary duodenal tumors

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World Journal of Gastrointestinal Oncology 2020年第8期12卷 918-930页

作者： Mitsuru Esaki Kazuhiro Haraguchi Kazuya Akahoshi Naru Tomoeda Akira Aso Soichi Itaba Haruei Ogino Yusuke Kitagawa Hiroyuki Fujii Kazuhiko Nakamura Masaru Kubokawa naohiko harada Yosuke Minoda Sho Suzuki Eikichi Ihara Yoshihiro Ogawa Department of Medicine and Bioregulatory Science Graduate School of Medical SciencesKyushu UniversityFukuoka 8128582Japan Division of Gastroenterology and Hepatology Department of MedicineNihon University School of MedicineTokyo 1738610Japan Department of Gastroenterology Hara-Sanshin HospitalFukuoka 8120033Japan Department of Gastroenterology Aso Iizuka HospitalIizuka 8208502Japan Department of Gastroenterology Clinical Research InstituteNational Hospital Organization Kyushu Medical CenterFukuoka 8108564Japan Department of Gastroenterology Kitakyushu Municipal Medical CenterKitakyushu 8020077Japan Department of Gastroenterology Kyushu Rosai HospitalKitakyushu 8000296Japan Department of Internal Medicine Saiseikai Fukuoka General HospitalFukuoka 8100001Japan Department of Gastroenterology and Hepatology National Hospital Organization Fukuokahigashi Medical CenterKoga 81103195Japan Department of Gastroenterology and Metabolism Graduate School of Medicine SciencesKyushu UniversityFukuoka 8128582Japan

BACKGROUND The selection of endoscopic treatments for superficial non-ampullary duodenal epithelial tumors(SNADETs)is *** To compare the efficacy and safety of endoscopic mucosal resection(EMR)and endoscopic submucosal dissection(ESD)for *** We retrospectively analyzed the data of patients with SNADETs from a database of endoscopic treatment for SNADETs,which included eight hospitals in Fukuoka,Japan,between April 2001 and October 2017.A total of 142 patients with SNADETs treated with EMR or ESD were *** score matching was performed to adjust for the differences in the patient characteristics between the two *** analyzed the treatment outcomes,including the rates of en bloc/complete resection,procedure time,adverse event rate,hospital stay,and local or metastatic *** Twenty-eight pairs of patients were *** characteristics of patients between the two groups were similar after *** EMR group had a significantly shorter procedure time and hospital stay than those of the ESD group[median procedure time(interquartile range):6(3-10.75)min vs 87.5(68.5-136.5)min,P<0.001,hospital stay:8(6-10.75)d vs 11(8.25-14.75)d,P=0.006].Other outcomes were not significantly different between the two groups(en bloc resection rate:82.1%vs 92.9%,P=0.42;complete resection rate:71.4%vs 89.3%,P=0.18;and adverse event rate:3.6%vs 17.9%,P=0.19,local recurrence rate:3.6%vs 0%,P=1;metastatic recurrence rate:0%in both).Only one patient in the ESD group underwent emergency surgery owing to intraoperative *** EMR has significantly shorter procedure time and hospital stay than ESD,and provides acceptable curability and safety compared to ***,EMR for SNADETs is associated with lower medical costs.

关键词： Endoscopic mucosal resection Endoscopic submucosal dissection Superficial non-ampullary duodenal epithelial tumor Short-term Outcome Propensity score matching

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Dual therapy for third-line Helicobacter pylori eradication and urea breath test prediction

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World Journal of Gastroenterology 2012年第21期18卷 2735-2738页

作者： Toshihiro Nishizawa Hidekazu Suzuki Takama Maekawa naohiko harada Tatsuya Toyokawa Toshio Kuwai Masanori Ohara Takahiro Suzuki Masahiro Kawanishi Kenji Noguchi Toshiyuki Yoshio Shinji Katsushima Hideo Tsuruta Eiji Masuda Munehiro Tanaka Shunsuke Katayama Norio Kawamura Yuko Nishizawa Toshifumi Hibi Masahiko Takahashi Division of Gastroenterology National Hospital Organization Tokyo Medical CenterTokyo 1528902 Japan Division of Gastroenterology and Hepatology Department of Internal Medicine Keio University School of MedicineTokyo 1608582 Japan Division of Gastroenterology National Hospital Organization Kyoto Medical CenterKyoto 6128555 Japan Division of Gastroenterology National Kyushu Medical CenterFukuoka 8108563 Japan Division of Gastroenterology National Hospital Organization Fukuyama Medical CenterFukuyama 7208520 Japan Division of Gastroenterology National Hospital Organization Kure Medical CenterKure 7370023 Japan Division of Gastroenterology National Hospital Organization Hakodate Medical CenterHakodate 0418512 Japan Division of Gastroenterology National Hospital Organization Maizuru Medical CenterMaizuru 6258502 Japan Division of Gastroenterology National Hospital Organization Higashihiroshima Medical CenterHigashihiroshima 7390041 Japan Division of Gastroenterology National Hospital Organization Sendai Medical CenterSendai 9838520 Japan Division of Gastroenterology National Hospital Organization Osaka Medical CenterOsaka 5400006 Japan Division of Gastroenterology National Hospital Organization Ureshino Medical CenterUreshino 8430393 Japan Division of Gastroenterology National Hospital Organization Osaka Minami Medical CenterKawachinagano 5868521 Japan Division of Gastroenterology National Hospital Organization Fukuoka Higashi Medical CenterKoga 8113195 Japan Division of Gastroenterology National Hospital Organization Yonago Medical CenterYonago 6838518 Japan Division of Gastroenterology National Hospital Organization Disaster Medical CenterTachikawa 1900014 Japan Pharmaceutical Department National Center for Global Health and MedicineTokyo 1658655 Japan

We evaluated the efficacy and tolerability of a dual therapy with rabeprazole and amoxicillin (AMX) as an empiric third-line rescue therapy. In patients with failure of first-line treatment with a proton pump inhibitor (PPI)- AMX-clarithromycin regimen and second-line treatment with the PPI-AMX-metronidazole regimen, a third-line eradication regimen with rabeprazole (10 mg q.i.d.) and AMX (500 mg q.i.d.) was prescribed for 2 wk. Eradication was confirmed by the results of the 13C-urea breath test (UBT) at 12 wk after the therapy. A total of 46 patients were included; however, two were lost to followup. The eradication rates as determined by per-protocol and intention-to-treat analyses were 65.9% and 63.0%,respectively. The pretreatment UBT results in the subjects showing eradication failure; those patients showing successful eradication comprised 32.9 ± 28.8 permil and 14.8 ± 12.8 permil, respectively. The pretreatment UBT results in the subjects with eradication failure were significantly higher than those in the patients with successful eradication (P = 0.019). A low pretreatment UBT result (≤ 28.5 permil) predicted the success of the eradication therapy with a positive predictive value of 81.3% and a sensitivity of 89.7%. Adverse effects were reported in 18.2% of the patients, mainly diarrhea and stomatitis. Dual therapy with rabeprazole and AMX appears to serve as a potential empirical third-line strategy for patients with low values on pretreatment UBT.

关键词： Helicobacter pylori Amoxicillin Dual therapy Eradication Urea breath test

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Hepcidin/ferroportin expression levels involve efficacy of pegylated-interferon plus ribavirin in hepatitis C virusinfected liver

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World Journal of Gastroenterology 2015年第11期21卷 3291-3299页

作者： Motoyuki Kohjima Tsuyoshi Yoshimoto Munechika Enjoji Nobuyoshi Fukushima Kunitaka Fukuizumi Tsukasa Nakamura Miho Kurokawa Nao Fujimori Yusuke Sasaki Yasushi Shimonaka Yusuke Murata Susumu Koyama Ken Kawabe Kazuhiro Haraguchi Yorinobu Sumida naohiko harada Masaki Kato Kazuhiro Kotoh Makoto Nakamuta Department of Gastroenterology and Clinical Research Center National Hospital Organization Kyushu Medical Center Health Care Center Fukuoka University Product Research Department Chugai Pharmaceutical Co.Ltd. Department of Medicine and Bioregulatory Science Kyushu University

AIM:To investigate the relationship between the ironmetabolism-related gene expression profiles and efficacy of antiviral therapy in chronic hepatitis C ***:The hepatic expression profile of ironmetabolism-related genes was analyzed and its association with virological response to pegylated-interferon plus ribavirin combination therapy was evaluated.A hundred patients with chronic hepatitis C(genotype1b,n = 50; genotype 2,n = 50) were enrolled and retrospectively *** biopsy samples were subjected to quantitative polymerase chain reaction for iron-metabolismrelated genes and protein expression(Western blotting analysis) for *** a control,normal liver tissue was obtained from 18 living donors of liver *** hepcidin level was measured by sensitive liquid chromatography/electrospray ionization tandem mass ***:Iron overload is associated with liver damage by increasing oxidative stress and hepatitis C virus(HCV)is reported to induce iron accumulation in hepatocytes in ***,iron administration suppresses HCV replication in ***,the association between HCV infection and iron metabolism remains *** with controls,patients had significantly higher gene expression for transferrin,iron-regulatoryproteins 1 and 2,divalent metal transporter 1,and ferroportin,but similar for transferrin receptors 1 and2,and *** the expression profiles were compared between sustained virological response(SVR)and non-SVR patients,the former showed significantly lower transcription and protein expression of hepcidin and *** of hepcidin-regulating genes,BMPR1,BMPR2,and hemojuvelin,was significantly increased,whereas BMP2 was decreased in HCV-infected ***2 and hemojuvelin expression was significantly lower in the SVR than non-SVR *** infection affects the expression of iron-metabolism-related genes,leading to iron accumulation in ***:Decrea

关键词： Chronic hepatitis C Iron-metabolism Hepcidin Ferro

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