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REWIEW : Role of the CXC12-CXCR4 Axis and CXCL16 in Inflammatory Bowel Disease
( Hiroshi Nakase ),( Minoru Matsuura ),( Sakae Mikami ),( Norimitsu Uza ),( Tsutomu Chiba ) 대한장연구학회 2012 Intestinal Research Vol.10 No.2
Numerous studies of colitis in IBD (inflammatory bowel diseases) patients and in animal models have demonstrated that both inflammatory cytokines and chemokines are up-regulated in settings of active inflammation. Blockade or absence of various cytokines and chemokines attenuates the disease in murine models of IBD. Therefore, identifying cytokines and chemokines involved in intestinal inflammation provide promising targets for the development of new drugs in the treatment of IBD. In general, chemokines have been implicated in many fundamental immune processes including lymphoid organogenesis, immune cell differentiation, development and positioning. Many chemokines are markedly increased in intestinal tissue from patients with IBD. In this study, we focused on the role of CXCL12-CXCR4 and CXCL16. CXCL12-CXCR4 axis plays a crucial role in the pathophysiology of IBD, especially UC, while SR-PSOX/CXCL16 plays a significant role in the pathophysiology of CD. Our present data suggest new insights into the etiology of IBD and we hope that the manipulation of these chemokines may have therapeutic value. (Intest Res 2012;10:125-133)
( Hiroshi Nakase ),( Yusuke Honzawa ),( Takahiko Toyonaga ),( Satoshi Yamada ),( Naoki Minami ),( Takuya Yoshino ),( Minoru Matsuura ) 대한장연구학회 2014 Intestinal Research Vol.12 No.1
Human cytomegalovirus (HCMV) is a member of the herpesvirus family. HCMV infection persists throughout the host lifespan in a latent state following primary infection. The ability of HCMV to escape control by the host immune system and its resulting reactivation suggests the importance of ongoing immune surveillance in the prevention of HCMV reactivation. HCMV is a common cause of opportunistic infection that causes severe and fatal disease in immune-compromised individuals. In inflammatory bowel disease patients, particularly those with ulcerative colitis (UC), HCMV is often reactivated because these patients are frequently treated with immunosuppressive agents. This reactivation exacerbates colitis. Additionally, HCMV infection can induce severe colitis, even in patients with UC who have never been treated with immunosuppressive agents. However, the role of HCMV in colonic inflammation in patients with UC remains unclear. Here, we present previous and current clinical data on the diagnosis and treatment of HCMV infection in UC. Additionally, our experimental data from a newly established mouse model mimicking UC with concomitant CMV infection clearly demonstrate that inflammation could result in the exacerbation of UC disease activity with induction of HCMV reactivation. In summary, optimal control of colonic inflammation should be achieved in UC patients who are refractory to conventional immunosuppressive therapies and are positive for HCMV. (Intest Res 2014;12:5-11)
( Hiroshi Nakase ),( Bora Keum ),( Byoung Duk Ye ),( Soo Jung Park ),( Hoon Sup Koo ),( Chang Soo Eun ) 대한장연구학회 2016 Intestinal Research Vol.14 No.3
Background/Aims: Inflammatory bowel disease (IBD) management guidelines have been released from Western countries, but no adequate data on the application of these guidelines in Asian countries and no surveys on the treatment of IBD in real practice exist. Since there is a growing need for a customized consensus for IBD treatment in Asian countries, Asian Organization of Crohn’s and Colitis performed a multinational survey of medical doctors who treat IBD patients in Asian countries. Methods: A questionnaire was developed between August 2013 and November 2013. It was composed of 4 domains: personal information, IBD diagnosis, IBD treatment, and quality of IBD care. Upon completion of the questionnaire, a web-based survey was conducted between 17 March 2014 and 12 May 2014. Results: In total, 353 medical doctors treating IBD from ten Asian countries responded to the survey. This survey data suggested a difference in available medical treatments (budesonide, tacrolimus) among Asian countries. Therapeutic strategies regarding refractory IBD (acute severe ulcerative colitis [UC] refractory to intravenous steroids and refractory Crohn’s disease [CD]) and active UC were coincident, however, induction therapies for mild to moderate inflammatory small bowel CD are different among Asian countries. Conclusions: This survey demonstrated that current therapeutic approaches and clinical management of IBD vary among Asian countries. Based on these results and discussions, we hope that optimal management guidelines for Asian IBD patients will be developed.
Acute Severe Ulcerative Colitis: Optimal Strategies for Drug Therapy
Nakase Hiroshi 거트앤리버 소화기연관학회협의회 2023 Gut and Liver Vol.17 No.1
Acute severe ulcerative colitis (ASUC) is a life-threatening medical emergency with considerable morbidity (30% to 40%). Patients with ASUC require hospitalization for prompt medical treatment, and colectomy is considered if medical therapy fails. Corticosteroids remain the primary initial therapy, although one-third of patients do not respond to treatment. Clinical data have indicated that cyclosporine, tacrolimus, and infliximab can be used to treat patients with ASUC who do not respond to intravenous corticosteroids. The effectiveness and safety of sequential therapy have recently been reported; however, the data are not convincing. Importantly, timely decision-making with rescue therapy or surgical treatment is critical to manage ASUC without compromising the health or safety of the patients. In addition, risk stratification and the use of predictive clinical parameters have improved the clinical outcome.of ASUC. Multidisciplinary teams that include inflammatory bowel disease experts, colorectal surgeons, and other medical staff contribute to the better management of patients with ASUC. In this review, we introduce current evidence and present a clinical approach to manage ASUC.
Hiroshi Nakase 거트앤리버 소화기연관학회협의회 2020 Gut and Liver Vol.14 No.1
The current goal of inflammatory bowel disease (IBD) treatment is a symptom-free everyday life accompanied by mucosal healing with minimal use of corticosteroids. Recent therapeutic advances, particularly, the emergence of anti-tumor necrosis factor (anti-TNF) antibodies, have changed the natural history of IBD. Additionally, these advances also led to the emergence of the therapeutic concept of the “treat to target” strategy. With the development of new drugs and clinical trials, not only biologics but also small molecules have been applied to clinical practice to better individualize and optimize therapy. However, if newer drugs, including anti-TNF therapies, are recommended for all patients diagnosed with IBD, a significant number of patients will be overtreated. The basic goal of IBD treatment is still to make the best use of conventional treatments based on IBD pathophysiology. Thus, physicians should be familiar with the modes of action of the available drugs. In this review, the author discusses the existing data for many approved drugs and provide insights for optimizing current treatments for the management of patients with IBD in the era of biologics.
Ischemic enteritis with intestinal stenosis
( Yorimitsu Koshikawa ),( Hiroshi Nakase ),( Minoru Matsuura ),( Takuya Yoshino ),( Yusuke Honzawa ),( Naoki Minami ),( Satoshi Yamada ),( Yumiko Yasuhara ),( Shigehiko Fujii ),( Toshihiro Kusaka ),( 대한장연구학회 2016 Intestinal Research Vol.14 No.1
A 75-year-old man was admitted to our hospital with sudden onset of vomiting and abdominal distension. The patient was taking medication for arrhythmia. Computed tomography showed stenosis of the ileum and a small bowel dilatation on the oral side from the region of stenosis. A transnasal ileus tube was placed. Enteroclysis using contrast medium revealed an approximately 6-cm afferent tubular stenosis 10 cm from the terminal ileum and thumbprinting in the proximal bowel. Transanal double-balloon enteroscopy showed a circumferential shallow ulcer with a smooth margin and edema of the surrounding mucosa. The stenosis was so extensive that we could not perform endoscopic balloon dilation therapy. During hospitalization, the patient’s nutritional status deteriorated. In response, we surgically resected the region of stenosis. Histologic examination revealed disappearance of the mucosal layer and transmural ulceration with marked fibrosis, especially in the submucosal layer. Hemosiderin staining revealed sideroferous cells in the submucosal layers. Based on the pathologic findings, the patient was diagnosed with ischemic enteritis. The patient’s postoperative course was uneventful. (Intest Res 2016;14:89-95)
( Naoki Minami ),( Minoru Matsuura ),( Yorimitsu Koshikawa ),( Satoshi Yamada ),( Yusuke Honzawa ),( Shuji Yamamoto ),( Hiroshi Nakase ) 대한장연구학회 2017 Intestinal Research Vol.15 No.1
Background/Aims: Our physicians work to expand the possibilities to treat female patients with inflammatory bowel disease (IBD) who wish to become pregnant. Although many drugs, including 5-aminosalicylate (5-ASA), corticosteroids, immunomodulators, and biologics, are used safely during pregnancy, few reports have described the therapeutic regimen throughout pregnancy and the management of patients who relapse during pregnancy precisely. The aim of this study was to assess the management of patients with IBD during pregnancy. Methods: We identified 19 patients (five with Crohn`s disease and 14 with ulcerative colitis [UC]) who became pregnant with a total of 23 pregnancies between May 2005 and May 2015 by reviewing the medical records of Kyoto University Hospital. The following data were collected: the maternal variables, the IBD treatment type, the disease activity, the pregnancy outcome, and the mode of delivery. Results: Among the 19 patients, 18 had become pregnant after being diagnosed with IBD, while one had developed UC newly after pregnancy. Throughout the gestation, all patients were treated with probiotics, 5-ASA, prednisolone, cytapheresis, or infliximab. The relapse rate during pregnancy was 21.7% (5/23 cases). The five patients who experienced a relapse were able to pursue their pregnancy after intensification of their treatments. There were no adverse fetal or neonatal problems, except in one case that required an emergency Caesarean section because of placental dysfunction and in which a very low-birth-weight infant was born preterm. Conclusions: Our present data confirmed that even if the disease flares up during pregnancy, good pregnancy outcomes can be achieved with an optimal intensification of the patient`s treatment. (Intest Res 2017;15:90-96)
( Tomoya Iida ),( Suguru Nakagaki ),( Shuji Satoh ),( Haruo Shimizu ),( Hiroyuki Kaneto ),( Hiroshi Nakase ) 대한장연구학회 2017 Intestinal Research Vol.15 No.2
Background/Aims: Although multiple treatment options exist for the management of sigmoid colon volvulus, no study has examined the factors associated with successful endoscopic detorsion. This study aimed to examine the clinical course of patients with sigmoid colon volvulus and to identify factors related to successful endoscopic detorsion. Methods: This study included 30 cases (21 patients) of sigmoid volvulus from among 545 cases of intestinal obstruction at a single center. We retrospectively examined the clinical course and the factors associated with the possibility of endoscopic detorsion of sigmoid colon volvulus. Results: The rate of laxative use among the study participants was 76.2%; the rate of comorbid neuropsychiatric disorders was 61.9%; and 57.1% of patients had a history of open abdominal surgery. All patients were initially treated with endoscopic detorsion, and this procedure had a 61.9% success rate. The recurrence rate after detorsion was as high as 46.2%, but detorsion during revision endoscopy was possible in all cases. Statistical analysis revealed that the absence of abdominal tenderness (P =0.027), the use of laxatives (P =0.027), and a history of open abdominal surgery (P =0.032) were factors predictive of successful endoscopic detorsion. Conclusions: The results of our study are consistent with previous reports with respect to the success rate of endoscopic detorsion, the subsequent recurrence rate, and the proportion of patients requiring surgical treatment. In addition, we identified the absence of abdominal tenderness, the use of laxatives, and history of open abdominal surgery as factors predicting successful endoscopic detorsion of sigmoid colon volvulus. (Intest Res 2017;15:215-220)