1.Ulcerative colitis-associated neoplasms often harbor poor prognostic histologic components with low detection by biopsy
Ryoya SAKAKIBARA ; Shinya SUGIMOTO ; Kaoru TAKABAYASHI ; Hiroki KIYOHARA ; Yusuke WAKISAKA ; Yuta KAIEDA ; Miho KAWAIDA ; Yusuke YOSHIMATSU ; Tomohisa SUJINO ; Naoki HOSOE ; Motohiko KATO ; Masayuki SHIMODA ; Yohei MIKAMI ; Yasushi IWAO ; Takanori KANAI
Intestinal Research 2024;22(4):428-438
Background/Aims:
Poorly differentiated adenocarcinoma, signet-ring cell carcinoma, and mucinous adenocarcinoma (por/sig/muc), which are considered to be histologic subtypes with a poor prognosis, occur more frequently with colitis-associated cancer than with sporadic tumors. However, their invasiveness and manifestations are unclear. This study aimed to determine the prevalence of the por/sig/muc component in ulcerative colitis-associated neoplasms (UCANs) and its association with invasiveness and to clarify its clinicohistologic and endoscopic features.
Methods:
This retrospective observational study included patients diagnosed with ulcerative colitis-associated high-grade dysplasia or adenocarcinoma from 1997 to 2022 who were divided according to the presence or absence of a por/sig/muc component.
Results:
Thirty-five patients had UCAN with a por/sig/muc component and 66 had UCAN without this component. The 5-year survival rate was significantly lower in the por/sig/muc group than in the tub group (67% vs. 96%, P= 0.001), which was attributed to disease above stage III and depth to below the subserosa. Biopsy-based diagnosis before resection detected a por/sig/muc component in only 40% of lesions (14/35). Lesions with a por/sig/muc component were prevalent even in the early stages: stage 0 (4/36, 11%), I (8/20, 40%), II (7/12, 58%), III (10/14, 71%), and IV (6/8, 75%).
Conclusions
This is the first investigation that shows UCANs with a por/sig/muc component tended to be deeply invasive and were often not recognized preoperatively. Endoscopists should be aware that UCAN often has a por/sig/muc component that is not always recognized on biopsy, and the optimal treatment strategy needs to be carefully considered.
2.Risk of venous thromboembolism with a central venous catheter in hospitalized Japanese patients with inflammatory bowel disease: a propensity score-matched cohort study
Yasuhiro AOKI ; Hiroki KIYOHARA ; Yohei MIKAMI ; Kosaku NANKI ; Takaaki KAWAGUCHI ; Yusuke YOSHIMATSU ; Shinya SUGIMOTO ; Tomohisa SUJINO ; Kaoru TAKABAYASHI ; Naoki HOSOE ; Haruhiko OGATA ; Yasushi IWAO ; Takanori KANAI
Intestinal Research 2023;21(3):318-327
Background/Aims:
Thromboprophylaxis is recommended for hospitalized patients with inflammatory bowel disease (IBD) in Western countries, although it is selectively administered to high-risk patients in East Asia. A central venous catheter (CVC) is commonly placed in patients with IBD. Although CVC placement is considered a risk factor for venous thromboembolism (VTE), the degree of increased risk in patients with IBD is uncertain. This study aimed to identify the risk of VTE with CVC placement in hospitalized Japanese patients with IBD without thromboprophylaxis.
Methods:
This retrospective cohort study included patients with ulcerative colitis or Crohn’s disease who were admitted for disease flares at Keio University Hospital between January 2016 and December 2020. Patients who already had thrombosis or were administered any antithrombotic treatment on admission were excluded. VTE development during the hospitalization was surveyed, and VTE risk associated with CVC indwelling was estimated using propensity score matching and inverse probability of treatment weighting analyses.
Results:
Altogether, 497 hospitalized patients with IBD (ulcerative colitis, 327; Crohn’s disease, 170) were enrolled. VTE developed in 9.30% (12/129) of catheterized patients and in 0.82% (3/368) of non-catheterized patients. The propensity score matching yielded 127 matched pairs of patients. The catheterized group demonstrated higher odds for VTE than the non-catheterized group (odds ratio, 13.15; 95% confidence interval, 1.68–102.70). A similar result was obtained in the inverse probability of treatment weighting analysis (odds ratio, 11.02; 95% confidence interval, 2.64–46.10).
Conclusions
CVC placement is a major risk factor for VTE among hospitalized Japanese patients with IBD without thromboprophylaxis.
4.Efficacy of Slow Nutrient Drinking Test for Evaluating Postprandial Distress Symptom in Japanese Patients With Functional Dyspepsia
Takahiro WATANABE ; Tatsuhiro MASAOKA ; Hisako KAMEYAMA ; Takanori KANAI
Journal of Neurogastroenterology and Motility 2022;28(3):424-430
Background/Aims:
Functional dyspepsia (FD), one of the functional gastrointestinal disorders, is highly prevalent. Impaired gastric accommodation is proposed as a pathophysiology of FD. In order to assess gastric accommodation, a slow nutrient drinking test was developed. This study aims to evaluate the effectiveness of this slow nutrient drinking test among patients with FD in Japan.
Methods:
Asymptomatic/healthy participants (n = 26) and those with FD (n = 16), were enrolled. An infusion pump was used to deliver the liquid meal into cups. They were requested to score their meal-related and abdominal symptoms at 5-minute intervals, using a 100 mm visual analog scale. They were instructed to end the test when they felt unable to ingest more or until after 50 minutes.
Results:
The test ending time was significantly shorter in patients with FD than in healthy participants (22.3 ± 10.6 vs 45.0 ± 7.5 minutes, P < 0.001). The receiver operating characteristic curve indicated that the optimal cutoff time for detecting patients with FD was 30 minutes. The severity of meal-related and abdominal symptoms between healthy participants and those with FD was continuously different. Univariate and multivariate analyses revealed that the presence of symptoms of postprandial distress syndrome contributed to the short test ending time.
Conclusion
The 30-minute slow nutrient drinking test is a minimally invasive method of effectively evaluating symptoms of postprandial distress syndrome among patients with FD, in Japan.
5.Risk Factors for Prolonged Hospital Stay after Endoscopy
Toshihiro NISHIZAWA ; Shuntaro YOSHIDA ; Osamu TOYOSHIMA ; Tatsuya MATSUNO ; Masataka IROKAWA ; Toru ARANO ; Hirotoshi EBINUMA ; Hidekazu SUZUKI ; Takanori KANAI ; Kazuhiko KOIKE
Clinical Endoscopy 2021;54(6):851-856
Background/Aims:
The recovery room used after endoscopy has limited capacity, and an efficient flow of the endoscopy unit is desired. We investigated the duration of hospital stay after endoscopy and the risk factors for prolonged hospital stay among outpatients.
Methods:
We retrospectively studied consecutive patients who underwent esophagogastroduodenoscopy or colonoscopy at the Toyoshima Endoscopy Clinic. We collected data on age, sex, body weight, midazolam and pethidine dosage, respiratory depression during endoscopy, and duration of hospital stay after endoscopy (scope out to check out). Risk factors for prolonged hospital stay (>100 minutes) were identified using multiple logistic regression analysis.
Results:
We enrolled 3,898 patients, including 3,517 (90.2%) patients tested under sedation and 381 (9.8%) patients tested without sedation. Overall, 442 (11.3%) patients had prolonged stay (>100 min). The mean time difference between sedation group and non-sedation group was 44.2 minutes for esophagogastroduodenoscopy and 39.1 minutes for colonoscopy. Age (odds ratio [OR], 1.025; 95% confidence interval [CI], 1.014−1.036), female sex (OR, 1.657; 95% CI, 1.220−2.249), and midazolam dose (OR, 1.019; 95% CI, 1.013−1.026) were independently associated with prolonged hospital stay after esophagogastroduodenoscopy, with similar results for colonoscopy.
Conclusions
Old age, female sex, and midazolam dose were independent risk factors for prolonged hospital stay after endoscopy.
6.Efficacy of Novel Ultrathin Single-Balloon Enteroscopy for Crohn’s Disease:A Propensity Score-Matched Study
Kaoru TAKABAYASHI ; Naoki HOSOE ; Motohiko KATO ; Yukie HAYASH ; Ryoichi MIYANAGA ; Kosaku NANKI ; Kayoko FUKUHARA ; Yohei Mikami SHINTA MIZUNO ; Tomohisa SUJINO ; Makoto MUTAGUCHI ; Makoto NAGANUMA ; Naohisa YAHAGI ; Haruhiko OGATA ; Takanori KANAI ; Shinta MIZUNO
Gut and Liver 2020;14(5):619-625
Background/Aims:
The evaluation of small bowel lesions of Crohn’s disease (CD) using balloon-assisted enteroscopy (BAE) is crucial because mucosal healing is associated with a good prognosis. However, BAE procedures are invasive, requiring sedation or analgesia to reduce the patient’s pain.This study evaluated the clinical usefulness of a novel ul-trathin single-balloon enteroscopy (SBE) procedure for CD.
Methods:
This single-center retrospective study included 102 CD patients who underwent trans-anal SBE between Janu-ary 2012 and May 2018. Of these patients, 82 underwent enteroscopy using conventional SBE, while 20 underwent ultrathin SBE. Patients were analyzed using propensity score matching, with 20 patients per group. The median duration of the examination, terminal ileum intubation rate, median cecum intubation time, median insertion depth, adverse events, and sedated dose in each group were compared.
Results:
Before propensity score matching, the conventional SBE group had a larger number of surgical history patients than the ultrathin SBE group (p=0.05). After matching, the two groups did not significantly differ clinically. There were no significant differences in the mean duration of the examina-tion, cecum intubation time, or terminal ileal intubation rate between ultrathin SBE and conventional SBE. The mean in-sertion depth of ultrathin SBE tended to be deeper than that of conventional SBE (p=0.09). The use of ultrathin SBE also reduced the sedative dose during needed for enteroscopy compared with conventional SBE (p=0.005).
Conclusions
Novel ultrathin SBE may be less painful for CD patients than conventional SBE.
7.5-Aminosalicylic acid intolerance is associated with a risk of adverse clinical outcomes and dysbiosis in patients with ulcerative colitis
Shinta MIZUNO ; Keiko ONO ; Yohei MIKAMI ; Makoto NAGANUMA ; Tomohiro FUKUDA ; Kazuhiro MINAMI ; Tatsuhiro MASAOKA ; Soichiro TERADA ; Takeshi YOSHIDA ; Keiichiro SAIGUSA ; Norimichi HIRAHARA ; Hiroaki MIYATA ; Wataru SUDA ; Masahira HATTORI ; Takanori KANAI
Intestinal Research 2020;18(1):69-78
Background/Aims:
5-Aminosalicylic acid (ASA) causes intolerance reactions in some patients. This study was performed to examine the prognosis of patients with ulcerative colitis (UC) and 5-ASA intolerance, and to evaluate the potential interaction between 5-ASA intolerance and the intestinal microbiota.
Methods:
We performed a retrospective cohort study of patients with UC who visited participating hospitals. The primary endpoint was to compare the incidence of hospitalization within 12 months between the 5-ASA intolerance group and the 5-ASA tolerance group. The secondary endpoint was to compare the risk of adverse clinical outcomes after the start of biologics between the 2 groups. We also assessed the correlation between 5-ASA intolerance and microbial change in an independently recruited cohort of patients with UC.
Results:
Of 793 patients, 59 (7.4%) were assigned to the 5-ASA intolerance group and 734 (92.5%) were assigned to the 5-ASA tolerance group. The admission rate and incidence of corticosteroid use were significantly higher in the intolerance than tolerance group (P< 0.001). In 108 patients undergoing treatment with anti-tumor necrosis factor biologics, 5-ASA intolerance increased the incidence of additional induction therapy after starting biologics (P< 0.001). The 5-ASA intolerance group had a greater abundance of bacteria in the genera Faecalibacterium, Streptococcus, and Clostridium than the 5-ASA tolerance group (P< 0.05).
Conclusions
In patients with UC, 5-ASA intolerance is associated with a risk of adverse clinical outcomes and dysbiosis. Bacterial therapeutic optimization of 5-ASA administration may be important for improving the prognosis of patients with UC.
8.Anti-MAdCAM-1 antibody (PF-00547659) for active refractory Crohn’s disease in Japanese and Korean patients: the OPERA study
Masayuki SARUTA ; Dong Il PARK ; Young-Ho KIM ; Suk-Kyun YANG ; Byung-Ik JANG ; Jae Hee CHEON ; Jong Pil IM ; Takanori KANAI ; Tatsuro KATSUNO ; Yoh ISHIGURO ; Makoto NAGAOKA ; Naoki ISOGAWA ; Yinhua LI ; Anindita BANERJEE ; Alaa AHMAD ; Mina HASSAN-ZAHRAEE ; Robert CLARE ; Kenneth J. GORELICK ; Fabio CATALDI ; Mamoru WATANABE ; Toshifumi HIBI
Intestinal Research 2020;18(1):45-55
Background/Aims:
PF-00547659 is a monoclonal antibody against human mucosal addressin cell adhesion molecule-1 (MAdCAM-1) that prevents the binding of α4β7+ lymphocytes to MAdCAM-expressing sites in the gastrointestinal tract with high affinity and selectivity, and is being developed for the treatment of Crohn’s disease (CD).
Methods:
OPERA is a randomized, multicenter, double-blind, placebo-controlled study to investigate the efficacy, safety, and pharmacokinetics of PF-00547659 following subcutaneous administration in subjects with active CD, a history of failure or intolerance to anti-tumor necrosis factor and/or immunosuppressants, high-sensitivity C-reactive protein > 3.0 mg/L, and ulcers on colonoscopy. The primary endpoint was Crohn’s Disease Activity Index-70 response at week 8 or 12. Subpopulation analyses for Asian subjects were performed as some differences are observed in genetics and clinical phenotypes in Asian CD patients compared with Western patients.
Results:
In this study, 265 CD subjects were randomized, with a subpopulation of 21 subjects (8 Japanese and 13 Korean) defined as the Asian population. In the overall and Asian populations; PF-00547659 was pharmacologically active as evidenced by soluble MAdCAM and circulating β7+ central memory CD4+ T-lymphocytes, although no clear evidence of efficacy was observed in any clinical endpoints; pharmacokinetics of PF-00547659 in the Asian subpopulation was generally comparable to the overall population; and the safety profile of PF-00547659 appeared acceptable up to 12 weeks of treatment.
Conclusions
In the overall and Asian populations, efficacy of PF-00547659 could not be demonstrated using any clinical endpoints compared with placebo. Pharmacokinetics and safety of PF-00547659 were generally comparable. Further studies with larger numbers of patients are required to confirm our results. (Trial Registration Number: NCT01276509)
9.5-Aminosalicylic acid aggravates colitis mimicking exacerbation of ulcerative colitis.
Jun MIYOSHI ; Katsuyoshi MATSUOKA ; Atsushi YOSHIDA ; Makoto NAGANUMA ; Tadakazu HISAMATSU ; Tomoharu YAJIMA ; Nagamu INOUE ; Susumu OKAMOTO ; Yasushi IWAO ; Haruhiko OGATA ; Fumiaki UENO ; Toshifumi HIBI ; Takanori KANAI
Intestinal Research 2018;16(4):635-640
Ulcerative colitis (UC) is one of the major clinical phenotypes of inflammatory bowel diseases. Although 5-aminosalicylic acid (5-ASA) is widely used for UC and its efficacy and safety have been demonstrated, a few patients paradoxically develop a severe exacerbation of colitis by 5-ASA administration. It is crucial to know clinical features including endoscopic findings in this condition for making a correct diagnosis and a prompt decision to withdraw the medication. Here, we report case series with UC exacerbated by 5-ASA. Medical records of 8 UC patients experiencing an exacerbation of colitis after induction of 5-ASA that was improved by the withdrawal of 5-ASA but also re-aggravated by dose increase or re-administration of 5-ASA were reviewed. The patients were newly diagnosed with UC, started 5-ASA and developed an exacerbation in approximately 2 to 3 weeks. They did not appear to have systemic allergic reactions. Seven of the 8 patients had a high fever. Three of 5 patients who undertook total colonoscopy showed right-side-dominant colitis. These findings suggest clinical characteristics in this condition. Further assessment of clinical and endoscopic features in more cases is necessary for establishing diagnostic criteria and understanding underlying mechanisms in those cases where 5-ASA aggravates the colitis.
Colitis*
;
Colitis, Ulcerative*
;
Colonoscopy
;
Diagnosis
;
Fever
;
Humans
;
Hypersensitivity
;
Inflammatory Bowel Diseases
;
Medical Records
;
Mesalamine*
;
Phenotype
;
Ulcer*
10.Effect of elemental diet combined with infliximab dose escalation in patients with Crohn's disease with loss of response to infliximab: CERISIER trial.
Tadakazu HISAMATSU ; Reiko KUNISAKI ; Shiro NAKAMURA ; Tomoyuki TSUJIKAWA ; Fumihito HIRAI ; Hiroshi NAKASE ; Kenji WATANABE ; Kaoru YOKOYAMA ; Masakazu NAGAHORI ; Takanori KANAI ; Makoto NAGANUMA ; Hirofumi MICHIMAE ; Akira ANDOH ; Akihiro YAMADA ; Tadashi YOKOYAMA ; Noriko KAMATA ; Shinji TANAKA ; Yasuo SUZUKI ; Toshifumi HIBI ; Mamoru WATANABE
Intestinal Research 2018;16(3):494-498
No abstract available.
Crohn Disease*
;
Food, Formulated*
;
Humans
;
Infliximab*

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