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( 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)
( Takuya Yoshino ),( Minoru Matsuura ),( Naoki Minami ),( Satoshi Yamada ),( Yusuke Honzawa ),( Masamichi Kimura ),( Yorimitsu Koshikawa ),( Ali Madian ),( Takahiko Toyonaga ),( Hiroshi Nakase ) 대한장연구학회 2015 Intestinal Research Vol.13 No.3
Background/Aims: Early use of biologics in patients with Crohn`s disease (CD) improves quality of life. However, the effects of the early use of immunomodulators on long-term outcomes remain unclear. This study aimed to evaluate the effects of immunomodulatorsin patients with CD. Methods: Between January 2004 and December 2011, 47 biologic-naive CD patients treated with thiopurines alone for remission maintenance were analyzed. The patients were classified into 2 groups depending on the presence or absence of digestive complications. We evaluated the efficacy of and predictive factors for thiopurine use for remission maintenance. Results: The cumulative relapse rates at 24 and 60 months were 13.7% and 35.4%, respectively. Regarding patient characteristics, there was a significant difference in patient history of surgery between the non-relapse and relapse groups (P =0.021). The cumulative relapse rate was lower in patients without a history of surgery than in those with such a history (27.2% and 52.9% at 60.0 months, respectively). Multivariate analysis suggested that the prevalence of stricturing and penetrating complications is an independent factor for relapse. The cumulative relapse rate in patients without a history ofsurgery was significantly lower in the non-stricturing and non-penetrating group than in the stricturing and penetrating group (11.8% at 85.0 months vs. 58.5% at 69.0 months; P =0.036). Conclusions: Thiopurine use might be beneficial for the long-term maintenance of remission in biologic-naive Crohn`s disease patients without digestive complications and a history of surgery. (Intest Res 2015;13:266-273)
Sako, Keisuke,Fukuhara, Shigetomo,Minami, Takashi,Hamakubo, Takao,Song, Haihua,Kodama, Tatsuhiko,Fukamizu, Akiyoshi,Gutkind, J. Silvio,Koh, Gou Young,Mochizuki, Naoki American Society for Biochemistry and Molecular Bi 2009 The Journal of biological chemistry Vol.284 No.9
<P>Angiopoietin-1 (Ang1) regulates both vascular quiescence and angiogenesis through the receptor tyrosine kinase Tie2. We and another group have recently shown that Ang1 and Tie2 form distinct signaling complexes at cell-cell and cell-matrix contacts and further demonstrated that the former selectively induces expression of Krüppel-like factor 2 (KLF2), a transcription factor involved in vascular quiescence. Here, we investigated the mechanism of how Ang1/Tie2 signal induces KLF2 expression to clarify the role of KLF2 in Ang1/Tie2 signal-mediated vascular quiescence. Ang1 stimulated KLF2 promoter-driven reporter gene expression in endothelial cells, whereas it failed when a myocyte enhancer factor 2 (MEF2)-binding site of KLF2 promoter was mutated. Depletion of MEF2 by siRNAs abolished Ang1-induced KLF2 expression, indicating the requirement of MEF2 in KLF2 induction by Ang1. Constitutive active phosphoinositide 3-kinase (PI3K) and AKT increased the MEF2-dependent reporter gene expression by enhancing its transcriptional activity and stimulated the KLF2 promoter activity cooperatively with MEF2. Consistently, inhibition of either PI3K or AKT and depletion of AKT abrogated Ang1-induced KLF2 expression. In addition, we confirmed the dispensability of extracellular signal-regulated kinase 5 (ERK5) for Ang1-induced KLF2 expression. Furthermore, depletion of KLF2 resulted in the loss of the inhibitory effect of Ang1 on vascular endothelial growth factor (VEGF)-mediated expression of vascular cell adhesion molecule-1 in endothelial cells and VEGF-mediated monocyte adhesion to endothelial cells. Collectively, these findings indicate that Ang1/Tie2 signal stimulates transcriptional activity of MEF2 through a PI3K/AKT pathway to induce KLF2 expression, which may counteract VEGF-mediated inflammatory responses.</P>
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)
( Satoshi Yamada ),( Takuya Yoshino ),( Minoru Matsuura ),( Masamichi Kimura ),( Yorimitsu Koshikawa ),( Naoki Minami ),( Takahiko Toyonaga ),( Yusuke Honzawa ),( Hiroshi Nakase ) 대한장연구학회 2015 Intestinal Research Vol.13 No.3
Background/Aims: The long-term clinical outcomes of patients with bio-naive ulcerative colitis (UC) who maintain remission with thiopurine are unclear. The aim of this study was to assess the long-term efficacy and safety of maintenance treatment with thiopurine in UC patients. Methods: This was a retrospective observational cohort analysis conducted at a single center. Between December 1998 and August 2013, 59 of 87 patients with bio-naive UC who achieved remission after induction with treatments other than biologics were enrolled. Remission maintenance with thiopurine was defined as no concomitant treatment needed other than 5-aminosalicylate without relapse. We assessed the remissionmaintenance rate, mucosal healing rate, colectomy-free rate, and treatment safety in UC patients who received thiopurineas maintenance treatment. Results: The 84-month cumulative remission-maintenance and colectomy-free survival rates in the UC patients who were receiving maintenance treatment with thiopurine and 5-aminosalicylate were 43.9% and 88.0%, respectively. Of the 38 patients who underwent colonoscopy during thiopurine maintenance treatment, 23 (60.5%) achieved mucosal healing. Of the 59 patients who achieved clinical remission with thiopurine, 6 patients (10.2%) discontinued the thiopurine therapy because of adverse events. Conclusions: Our study demonstrates the long-term efficacy and safety of thiopurine treatment in patients with bio-naive UC. (Intest Res 2015;13:250-258)
Tadayuki Takagi,Mitsuru Sugimoto,Hidemichi Imamura,Yosuke Takahata,Yuki Nakajima,Rei Suzuki,Naoki Konno,Hiroyuki Asama,Yuki Sato,Hiroki Irie,Jun Nakamura,Mika Takasumi,Minami Hashimoto,Tsunetaka Kato 대한소화기내시경학회 2023 Clinical Endoscopy Vol.56 No.1
high tumors. Therefore, sufficient sampling of histological specimens is necessary in cases of unresectable pancreatic cancer (UR-PC). This multicenter study investigated the efficacy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) using a Franseen needlefor MSI evaluation in patients with UR-PC. Methods: A total of 89 patients with UR-PC who underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) orEUS-FNB using 22-G needles at three hospitals in Japan (2018–2021) were enrolled. Fifty-six of these patients (FNB 23 and FNA 33)were followed up or evaluated for MSI. Patient characteristics, UR-PC data, and procedural outcomes were compared between patientswho underwent EUS-FNB and those who underwent EUS-FNA. Results: No significant difference in terms of sufficient tissue acquisition for histology was observed between patients who underwentEUS-FNB and those who underwent EUS-FNA. MSI evaluation was possible significantly more with tissue samples obtained usingEUS-FNB than with tissue samples obtained using EUS-FNA (82.6% [19/23] vs. 45.5% [15/33], respectively; p<0.01). In the multivariateanalysis, EUS-FNB was the only significant factor influencing the possibility of MSI evaluation. Conclusions: EUS-FNB using a Franseen needle is desirable for ensuring sufficient tissue acquisition for MSI evaluation.
( 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)
Takai, Tomoaki,Inamoto, Teruo,Komura, Kazumasa,Yoshikawa, Yuki,Uchimoto, Taizo,Saito, Kenkichi,Tanda, Naoki,Kouno, Junko,Minami, Koichiro,Uehara, Hirofumi,Takahara, Kiyoshi,Hirano, Hajime,Nomi, Hayahi Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.6
Background: Despite widely adopted standard methods for follow-up including cystoscopy plus cytology, recurrence rates of non muscle-invasive bladder cancer (NMIBC) have not improved over the past decades, still ranging from 60% through 70%. Hence, widely acceptable surveillance strategies with excellent sensitivity are needed. Early recurrence has led to the development of a novel cystoscopy technique utilizing photodynamic diagnosis (PDD). Although, no studies have evaluated the efficacy of PDD for patients of MIBC, BCG failure or 2nd-transurethelial resection (TUR). Materials and Methods: The present study was performed from October 2012 through May 2013. IRB approved 25 patients initially underwent a cystoscopy examination of white light and blue light followed by the resection of tumors identified. Resections were performed from bladder mucosa areas considered suspicious at PDD, along with PDD negative normal bladder mucosa area resected by random biopsy. Specimens were divided into two groups, PDD positive and negative. Primary endpoints were sensitivity and specificity. Results: A total of 147 specimens extracted from 25 patients were included in the analysis. Some 45 out of 92 PDD-positive specimens were confirmed to have bladder cancer, and 51 out of PDD-negative 55 specimens were confirmed to be cancer negative. The sensitivity of PDD was 91.8% (45/49) and specificity was 52.0% (51/98). The sensitivity:specificity was 89.5% (17/19) : 47.6% (30/63) in 12 2nd-TUR patients, 90.5% (19/21) : 61.1% (11/18) in seven MIBC patients, and 95.0% (19/20) : 48.5% (16/33) in eight failed BCG cases. Conclusions: PDD-TURBT has high sensitivity to diagnose BC even for 2nd-TUR, MIBC or BCG failure cases.
Takai, Tomoaki,Inamoto, Teruo,Komura, Kazumasa,Tsujino, Takuya,Matsunaga, Tomohisa,Yoshikawa, Yuki,Uchimoto, Taizo,Saito, Kenkichi,Tanda, Naoki,Minami, Koichiro,Uehara, Hirofumi,Ibuki, Naokazu,Takahar Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.3
Background: We vigorously reviewed patients' operation record who had adhesion of the Denonvilliers' fascia and found out most of these patients had prostatic bleeding after prostatic gland biopsies. We examined the magnitude of prostatic bleeding and frequency after biopsies and the relationship with oncological outcomes. Materials and Methods: A total of 285 patients were selected for the final analyses. Inclusion criteria were as follows: receiving MRI three weeks after biopsiesand laparoscopic radical prostatectomy within 300 days after biopsy. We divided the patients into two groups with (group A) or without (group B) prostatic bleeding. We examined the magnitude of prostatic bleeding after biopsies and the relationship with operation time (OT), positive surgical margin (PSM), biochemical recurrence (BCR) and other factors. Furthermore, we created a logistic-regression model to derive a propensity score for prostatic bleeding after biopsies, which included all patient and hospital characteristics as well as selected interaction terms, and we examined the relationship with PSM and BCR. Results: In all patients, the OT in the group B was shorter than the group A (p < 0.001). Prostatic bleeding was associated with PSM (p=0.000) and BCR (p=0.036). In this propensity-matched cohort, 11 of 116 patients in the group B had PSM as compared with 36 of 116 patients from group A (match-adjusted odds ratio, 4.30; 95%CI confidence interval, 2.06 to 8.96; P=0.000). In addition, eight of 116 patients in group B encountered BCR, as compared with 18 of 116 patients in group A (match-adjusted odds ratio, 2.48; 95%CI, 1.03 to 5.96; P=0.042). Kaplan-Meier analysis in the propensity matching cohort showed a significant biochemical recurrence-free survival advantage for being free of prostate bleeding after biopsies. Conclusions: Our findings in the present cohort should help equip surgeons to pay attention to careful excision especially for those who experienced deferred prostatic bleeding.