研究者詳細 - 金井　隆典

論文 - 金井　隆典

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Impact of Antimicrobial Prophylaxis for Severe Acute Pancreatitis on the Development of Invasive Candidiasis: A Large Retrospective Multicenter Cohort Study

Horibe M., Sanui M., Sasaki M., Honda H., Ogura Y., Namiki S., Sawano H., Goto T., Ikeura T., Takeda T., Oda T., Yasuda H., Miyazaki D., Hirose K., Kitamura K., Chiba N., Ozaki T., Yamashita T., Koinuma T., Oshima T., Yamamoto T., Hirota M., Yamamoto S., Oe K., Ito T., Masuda Y., Saito N., Iwasaki E., Kanai T., Mayumi T.

Pancreas （Pancreas） 48 （ 4 ） 537 - 543 2019年04月

ISSN 08853177

© 2019 Wolters Kluwer Health, Inc. All rights reserved. Objective Antimicrobial prophylaxis is not generally recommended for patients with severe acute pancreatitis (SAP) owing to the limited clinical benefits. Nonetheless, it is frequently administered in actual practice given the patients' critical condition and the lack of solid evidence showing adverse effects of antimicrobial prophylaxis. We evaluated herein an association between antimicrobial prophylaxis and invasive pancreatic candidiasis as an adverse effect in patients with SAP. Methods This is a retrospective cohort study of all consecutive patients with SAP who were admitted to the study institutions (n = 44) between January 1, 2009, and December 31, 2013. We performed multivariable logistic regression analysis adjusting for the extent of pancreatic necrosis and surgical interventions for invasive pancreatic candidiasis. Results Of the 1097 patients with SAP, 850 (77.5%) received antimicrobial prophylaxis, and 21 (1.9%) had invasive pancreatic candidiasis. In multivariable logistic regression analysis, antimicrobial prophylaxis was significantly associated with the development of invasive pancreatic candidiasis (adjusted odds ratio, 4.23; 95% confidence interval, 1.14-27.6) (P = 0.029). Conclusions The results suggest that antimicrobial prophylaxis may contribute to the development of invasive pancreatic candidiasis, and therefore, the routine use of antimicrobial prophylaxis for SAP may be discouraged.

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Correction: Vedolizumab in Japanese patients with ulcerative colitis: A Phase 3, randomized, double-blind, placebo-controlled study (PLoS ONE (2019) 14:2 (e0212989) DOI: 10.1371/journal.pone.0212989)

Motoya S., Watanabe K., Ogata H., Kanai T., Matsui T., Suzuki Y., Shikamura M., Sugiura K., Oda K., Hori T., Araki T., Watanabe M., Hibi T.

PLoS ONE （PLoS ONE） 14 （ 4 ） 2019年04月

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Clinical and endoscopic findings to assist the early detection of duodenal adenoma and adenocarcinoma

Matsuzaki J., Suzuki H., Shimoda M., Mori H., Fukuhara S., Miyoshi S., Masaoka T., Iwao Y., Kanai Y., Kanai T.

United European Gastroenterology Journal （United European Gastroenterology Journal） 7 （ 2 ） 250 - 260 2019年03月

ISSN 20506406

© Author(s) 2018. Background: Sporadic nonampullary duodenal adenocarcinoma is a rare malignant neoplasm in which poor prognosis is often associated with delayed diagnosis. Objective: A case-control study was designed to evaluate the clinical and endoscopic characteristics of patients with nonampullary duodenal epithelial tumours (NADETs). Methods: Patients with NADETs were chronologically divided into a discovery and a validation sets. Two age- and sex-matched control individuals for each case in the discovery set were randomly selected from individuals without NADET. A prediction model for the presence of NADET, constructed in the discovery set, was evaluated in the validation set. Results: In total, 368 adenomas, 81 adenocarcinomas, and 314 controls were analysed. Current smoking, Barrett oesophagus, fundic gland polyps, history of malignant disease, and absence of dyslipidaemia were independently associated with the presence of NADET. The combination of these five factors enabled significant discrimination for NADET in the bulb with a sensitivity of 0.81 in the validation set. We also showed that duodenal adenocarcinomas in the bulb had greater invasive potential than adenocarcinomas in the second portion. Conclusion: The presence of a duodenal tumour in the bulb could be predicted by clinical and endoscopic findings, which helps improve the prognosis and quality of life of patients.

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Gut pathobionts underlie intestinal barrier dysfunction and liver T helper 17 cell immune response in primary sclerosing cholangitis

Nakamoto N., Sasaki N., Aoki R., Miyamoto K., Suda W., Teratani T., Suzuki T., Koda Y., Chu P., Taniki N., Yamaguchi A., Kanamori M., Kamada N., Hattori M., Ashida H., Sakamoto M., Atarashi K., Narushima S., Yoshimura A., Honda K., Sato T., Kanai T.

Nature Microbiology （Nature Microbiology） 4 （ 3 ） 492 - 503 2019年03月

© 2019, The Author(s), under exclusive licence to Springer Nature Limited. Primary sclerosing cholangitis (PSC) is a chronic inflammatory liver disease and its frequent complication with ulcerative colitis highlights the pathogenic role of epithelial barrier dysfunction. Intestinal barrier dysfunction has been implicated in the pathogenesis of PSC, yet its underlying mechanism remains unknown. Here, we identify Klebsiella pneumonia in the microbiota of patients with PSC and demonstrate that K. pneumoniae disrupts the epithelial barrier to initiate bacterial translocation and liver inflammatory responses. Gnotobiotic mice inoculated with PSC-derived microbiota exhibited T helper 17 (T H 17) cell responses in the liver and increased susceptibility to hepatobiliary injuries. Bacterial culture of mesenteric lymph nodes in these mice isolated K. pneumoniae, Proteus mirabilis and Enterococcus gallinarum, which were prevalently detected in patients with PSC. A bacterial-organoid co-culture system visualized the epithelial-damaging effect of PSC-derived K. pneumoniae that was associated with bacterial translocation and susceptibility to T H 17-mediated hepatobiliary injuries. We also show that antibiotic treatment ameliorated the T H 17 immune response induced by PSC-derived microbiota. These results highlight the role of pathobionts in intestinal barrier dysfunction and liver inflammation, providing insights into therapeutic strategies for PSC.

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Novel mainstream capnometer system is safe and feasible even under CO <inf>2</inf> insufflation during ERCP-related procedure: A pilot study

Takimoto Y., Iwasaki E., Masaoka T., Fukuhara S., Kawasaki S., Seino T., Katayama T., Minami K., Tamagawa H., Machida Y., Ogata H., Kanai T.

BMJ Open Gastroenterology （BMJ Open Gastroenterology） 6 （ 1 ） 2019年02月

© Author(s) (or their employer(s)) 2019. Background and aims There is a need to safely achieve conscious sedation during endoscopic retrograde cholangiopancreatography (ERCP). We evaluated the safety and feasibility of a mainstream capnometer system to monitor apnoea during ERCP under CO 2 insufflation. Methods Non-intubated adult patients undergoing ERCP-related procedures with intravenous sedation were enrolled. End-tidal CO 2 (EtCO 2 ) was continuously monitored during the procedure under CO 2 insufflation using a mainstream capnometer system, comprising a capnometer and a specially designed bite block for upper gastrointestinal endoscopy and ERCP. Oxygen saturation (SpO 2) was also monitored continuously during the procedure. In this study, we evaluated the safety and feasibility of the capnometer system. Results Eleven patients were enrolled. Measurement of EtCO 2 concentration was possible from the beginning to the end of the procedure in all 11 cases. There was no measurement failure, dislocation of the bite block, or adverse event related to the bite block. Apnoea linked to hypoxaemia occurred five times (mean duration, 174.4 s). Conclusion This study confirmed that apnoea was detected earlier than when using a percutaneous oxygen monitor. Measurement of EtCO 2 concentration using the newly developed mainstream capnometer system was feasible and safe even under CO 2 insufflation.

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Vedolizumab in Japanese patients with ulcerative colitis: A Phase 3, randomized, double-blind, placebo-controlled study

Motoya S., Watanabe K., Ogata H., Kanai T., Matsui T., Suzuki Y., Shikamura M., Sugiura K., Oda K., Hori T., Araki T., Watanabe M., Hibi T.

PLoS ONE （PLoS ONE） 14 （ 2 ） 2019年02月

© 2019 Motoya et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background Vedolizumab safety and efficacy have been established in many populations all over the world, but have never been studied in Japan. We report results from a Phase 3, randomized, double-blind, placebo-controlled study of vedolizumab in Japanese patients with active ulcerative colitis (UC). Methods Patients with moderate-to-severe UC were enrolled into Cohort 1 (double-blinded) or Cohort 2 (open-label) in the induction phase. Cohort 1 was randomized 2:1 to receive 300 mg vedolizumab or placebo, while Cohort 2 received vedolizumab 300 mg only, at Weeks 0, 2, and 6. Patients from Cohorts 1 and 2 showing a clinical response to vedolizumab at Week 10 were randomized 1:1 to receive vedolizumab or placebo (double-blinded) at Week 14 and then every 8 weeks up to Week 54 as the maintenance phase. The primary endpoint was clinical response at Week 10, for the induction phase, and clinical remission at Week 60, for the maintenance phase. Results A total of 292 patients were enrolled into the induction phase (246 in Cohort 1, 46 in Cohort 2); 83 patients achieved response to vedolizumab and were subsequently enrolled into the maintenance phase. Clinical response rates at Week 10 were 39.6% (65/164) and 32.9% (27/82) in the vedolizumab and placebo groups in Cohort 1, respectively (adjusted odds ratio [AOR] = 1.37, 95% CI 0.779–2.399; p = 0.2722). In the maintenance phase, clinical remission rate at Week 60 was significantly higher in the vedolizumab group, at 56.1% (23/ 41), versus 31.0% (13/42) for placebo (AOR = 2.88, 95% CI 1.168–7.108; p = 0.0210). Most adverse events were mild to moderate in intensity, and no deaths occurred during the study period. Conclusions Vedolizumab showed numerically greater efficacy compared with placebo as induction therapy, but the difference was not statistically significant. Vedolizumab was significantly superior to placebo as maintenance therapy in Japanese patients with UC. Vedolizumab has favourable safety and tolerability in these patients.

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Current new challenges in the management of ulcerative colitis

Fukuda T., Naganuma M., Kanai T.

Intestinal Research （Intestinal Research） 17 （ 1 ） 36 - 44 2019年01月

ISSN 15989100

© 2019, Korean Association for the Study of Intestinal Diseases. All rights reserved. Ulcerative colitis (UC) is a chronic inflammatory condition of the gastrointestinal tract. Although the cause of UC is postulated to be multifactorial in nature, including genetic predisposition, epithelial barrier defects, dysregulation of immune responses, and environmental factors, the specific pathogenesis of UC is still incompletely understood. In the treatment of UC so far, a method of suppressing immunity and treating it has been mainstream. Immunosuppressant drugs, including thiopurines (azathioprine or 6-mercaptopurine), anti-tumor necrosis factor-α (anti-TNF-α) antibody (infliximab and adalimumab), and calcineurin inhibitor, can be used in treat patients with corticosteroid-dependent and/or corticosteroid-refractory moderateto-severe UC. Recently, in addition to such a conventional therapeutic agent, golimumab, which is the first transgenic human monoclonal anti-TNF-α antibody to be fabricated, anti α-4/β-7 integrin antibody, and Janus kinase inhibitor have been reported to novel immunosuppressant therapy. Furthermore, other treatments with unique mechanisms different from immunosuppression, have also been suggested, including fecal microbiota transplantation and Indigo naturalis, which is a Chinese herbal medicine. We compared the features and efficacy of these new treatments. In this issue, the features and treatment options for these new treatments is reviewed.

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First report of hepatobiliary Mycobacterium avium infection developing obstructive jaundice in a patient with neutralizing anti–interferon-gamma autoantibodies

Namkoong H., Asakura T., Ishii M., Yoda S., Masaki K., Sakagami T., Iwasaki E., Yamagishi Y., Kanai T., Betsuyaku T., Hasegawa N.

New Microbes and New Infections （New Microbes and New Infections） 27 4 - 6 2019年01月

ISSN 20522975

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Negative effect of fatty liver on visualization of pancreatic cystic lesions at screening transabdominal ultrasonography

Kashiwagi K., Seino T., Makino K., Shimizu-Hirota R., Takayama M., Yoshida T., Iwasaki E., Sugino Y., Inoue N., Iwao Y., Kanai T.

Journal of Evaluation in Clinical Practice （Journal of Evaluation in Clinical Practice） 26 （ 1 ） 256 - 261 2019年

ISSN 13561294

© 2019 John Wiley & Sons, Ltd. Rationale, aims, and objectives: The aim of this observational study is to identify factors by which some pancreatic cystic lesions (PCLs) were undetectable at transabdominal ultrasonography (TAUS), using magnetic resonance imaging (MRI) as reference standard. Methods: The database for 781 consecutive subjects who underwent a health checkup including fat computed tomography and upper abdominal MRI as option was searched. The presence of fatty liver and fatty pancreas was diagnosed by TAUS, and atrophic pancreas was determined by reevaluating the image of the pancreas in the chest computed tomography for screening. Subjects with PCL detected and those undetected at TAUS were statistically compared in clinical characteristics. Results: The prevalence of PCL detected at MRI was 17.8% in the general population. Multivariate logistic regression analysis showed that fatty liver, body mass index, and the size of PCL were significantly associated with the factors influencing the visualization of PCL at TAUS (odds ratio [OR]: 0.337, 95% confidence interval [CI]: 0.154-0.734, P = 0.006; OR: 0.852, 95% CI: 0.737-0.985, P = 0.030; OR:1.120, 95% CI: 1.045-1.200, P =.001). Thirty-six PCLs (64.3%) in a total of 56 PCLs were undermeasured by TAUS. Additionally, nine (56%) out of 16 PCLs (≥ 15 mm) were undermeasured by 5 mm or more by TAUS, although a significantly higher detection rate was observed for PCLs (≥ 15 mm) in comparison with that for PCLs (< 15 mm) (80% vs 33.6%, P =.000). Conclusions: It should be noted that coexisting fatty liver may lower the detection of PCL, and its size may be underestimated by TAUS.

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Long-term effect of NUDT15 R139C on hematologic indices in inflammatory bowel disease patients treated with thiopurine

Akiyama S., Matsuoka K., Fukuda K., Hamada S., Shimizu M., Nanki K., Mizuno S., Kiyohara H., Arai M., Sugimoto S., Iwao Y., Ogata H., Hisamatsu T., Naganuma M., Motobayashi M., Suzuki K., Takenaka K., Fujii T., Saito E., Nagahori M., Ohtsuka K., Mochizuki M., Watanabe M., Hashiguchi M., Kanai T.

Journal of Gastroenterology and Hepatology (Australia) （Journal of Gastroenterology and Hepatology (Australia)） 34 （ 10 ） 1751 - 1757 2019年

ISSN 08159319

© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd Background and Aim: A missense variant of the nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) gene (R139C) predisposes Asian patients with inflammatory bowel disease (IBD) to thiopurine-induced leukopenia. This study evaluates the long-term effect of NUDT15 R139C heterozygosity on hematological parameters during thiopurine administration. Methods: We enrolled 83 Japanese IBD patients who were on anti-tumor necrosis factor-α agents and had used thiopurine. NUDT15 R139C was genotyped by polymerase chain reaction. We retrospectively reviewed patient clinical charts to collect data on white blood cell (WBC) count, mean corpuscular volume (MCV), hemoglobin, and platelet count during the 24 months following thiopurine initiation. Results: The included patients had either Crohn's disease (54; 65.1%) or ulcerative colitis (29; 34.9%). Genotyping of NUDT15 R139C identified 62 patients (74.7%) of genotype C/C and 21 (25.3%) of genotype C/T. The median dose of thiopurine was lower in the C/T group than in the C/C group after starting thiopurine. At 6 months, the mean WBC count of the C/T group became significantly lower than that of the C/C group (P = 0.008) and remained lower through the 24 months. The C/T group developed grade 2–4 leukopenia by 6 months, which persisted through 12–24 months. The mean MCV in the C/T group became higher than that of the C/C group after 3 months. Conclusions: NUDT15 R139C heterozygosity affected the WBC count and MCV for 24 months after thiopurine administration. Our results indicate that careful monitoring of leukopenia and dose adjustment are necessary throughout treatment in IBD patients heterozygous for the NUDT15 R139C.

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Development of an Indigo Naturalis Suppository for Topical Induction Therapy in Patients with Ulcerative Colitis

Yoshimatsu Y., Naganuma M., Sugimoto S., Tanemoto S., Umeda S., Fukuda T., Nomura E., Yoshida K., Ono K., Mutaguchi M., Nanki K., Mizuno S., Mikami Y., Fukuhara K., Sujino T., Takabayashi K., Ogata H., Iwao Y., Kanai T.

Digestion （Digestion） 101 （ 4 ） 492 - 498 2019年

ISSN 00122823

© 2019 S. Karger AG, Basel. All rights reserved. Background: Indigo naturalis (IN) consists of ligands for the aryl hydrocarbon receptor and exhibits anti-inflammatory effects. Previously, we demonstrated that an 8-week treatment with oral IN is effective in inducing a clinical response in patients with ulcerative colitis (UC). Some UC patients with proctitis are refractory to topical mesalamine or corticosteroids and therefore require an alternative topical treatment. Objectives: We aimed to prospectively evaluate the safety and efficacy of IN suppositories in UC patients. Method: We performed an open-label, single-center, prospective pilot study from February 2018 to October 2018. A total of 10 patients with active UC, who had moderate to severe inflammation from the rectum to the sigmoid colon, were enrolled. The patients received a daily dose of 50 mg IN suppository for 4 weeks. The primary endpoint was safety at week 4. Results: Although 1 patient experienced anal pain, no serious adverse events were observed. At week 4, the rates of clinical remission and mucosal healing were 30 and 40%, respectively. Mayo rectal bleeding subscores significantly improved after treatment (1.80 ± 0.13 vs. 0.90 ± 0.28; p = 0.009). Approximately 80% of the patients with a baseline Mayo endoscopic subscore in the rectum (r-MES) of 2 achieved mucosal healing, but those with a baseline r-MES of 3 did not. Conclusions: We found that 4 weeks of IN suppository can be tolerated by UC patients, but its efficacy was limited by the severity of the disease. Further investigation will be needed in order to confirm the optimum dose of IN suppository for patients with UC.

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Colonic diverticular bleeding and predictors of the length of hospitalization: An observational study

Wada M., Nishizawa T., Kato M., Hirai Y., Kinoshita S., Mori H., Nakazato Y., Fujimoto A., Kikuchi M., Uraoka T., Kanai T.

Journal of Gastroenterology and Hepatology (Australia) （Journal of Gastroenterology and Hepatology (Australia)） 34 （ 8 ） 1351 - 1356 2019年

ISSN 08159319

© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd Background and Aim: A significant percentage of patients with colonic diverticular bleeding (CDB) experience bleeding that is severe enough to necessitate prolonged hospitalization. Prolonged hospitalization causes deterioration in patients' quality of life, as well as difficulties with cost-effective utilization of medical resources, and is a financial burden to the society. Therefore, we investigated the factors associated with the length of hospitalization for the optimal management of patients hospitalized with CDB. Methods: This study included patients who were hospitalized for the treatment of CDB and underwent colonoscopy between July 2008 and February 2016. Logistic regression analysis was performed to investigate the association between the length of hospitalization and the patients' baseline characteristics, in-hospital procedures performed, and the clinical outcomes. Results: The study included 223 patients. Diabetes mellitus (odds ratio [OR] 3.4, P = 0.014) and blood transfusion (OR 3.1, P = 0.0006) were identified as risk factors for prolonged hospitalization (≥ 8 days). Urgent colonoscopy (OR 0.41, P = 0.0072) predicted a shorter length of hospitalization (≤ 7 days). The study also indicated that endoscopic treatment showed a stronger association with urgent colonoscopy (OR 7.8, P < 0.0001) than with elective colonoscopy and that urgent colonoscopy was not associated with an increased rate of adverse events or re-bleeding. Conclusions: Compared with elective colonoscopy, urgent colonoscopy shortens the length of hospitalization in patients with CDB. Moreover, it is not associated with an increased rate of adverse events. Urgent colonoscopy may be impracticable in a few cases; however, if possible, aggressive urgent colonoscopy should be considered for the efficient management of the patient's hospital stay.

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Capsule endoscopy for small-intestinal disorders: Current status

Hosoe N., Takabayashi K., Ogata H., Kanai T.

Digestive Endoscopy （Digestive Endoscopy） 31 （ 5 ） 498 - 507 2019年

ISSN 09155635

© 2019 Japan Gastroenterological Endoscopy Society Small-bowel capsule endoscopy (SBCE) is used widely because of its non-invasive and patient-friendly nature. SBCE can visualize entire small-intestinal mucosa and facilitate detection of small-intestinal abnormalities. In this review article, we focus on the current status of SBCE. Several platforms for SBCE are available worldwide. Third-generation SBCE (PillCam ® SB3) has a high-resolution camera equipped with an adaptive frame rate system. Several software modes have been developed to reduce the reading time for capsule endoscopy and to minimize the possibility of missing lesions. The main complication of SBCE is capsule retention. Thus, the main contraindication for SBCE is known or suspected gastrointestinal obstruction unless intestinal patency is proven. Possible indications for SBCE are obscure gastrointestinal bleeding, Crohn's disease, small-intestinal polyps and tumors, and celiac disease. Colon capsule endoscopy (CCE) can observe inflamed colonic mucosa non-invasively, and allows for the continuous and non-invasive observation of the entire intestinal tract (pan-endoscopy). Recently, application of CCE as pan-enteric endoscopy for inflammatory bowel diseases (including Crohn's disease) has been reported. In the near future, reading for CE will be assisted by artificial intelligence, and reading CE videos for long periods will not be required.

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Adverse events in patients with ulcerative colitis treated with indigo naturalis: a Japanese nationwide survey

Naganuma M., Sugimoto S., Suzuki H., Matsuno Y., Araki T., Shimizu H., Hayashi R., Fukuda T., Nakamoto N., Iijima H., Nakamura S., Kataoka M., Tamura Y., Tatsumi K., Hibi T., Suzuki Y., Kanai T., Yoshimatsu Y., Chu P., Uchino M., Watanabe K., Hirano A., Esaki M., Ueno Y., Yamamoto T., Sawada K., Kawashima K., Ishihara S., Hashimoto S., Yokoyama J., Ashizuka S., Toyokawa T., Sakuraba H., Matsueda K., Yoshimura N., Ohmiya N., Kayashima Y., Yanai S., Matsumoto T., Kobayashi H., Nakajima S., Nishida T., Takeuchi Y., Ina K., Kawamura T.

Journal of Gastroenterology （Journal of Gastroenterology） 54 （ 10 ） 891 - 896 2019年

ISSN 09441174

© 2019, Japanese Society of Gastroenterology. Background: Although indigo naturalis (IN) is effective for patients with active ulcerative colitis (UC), IN was associated with adverse events (AEs), including pulmonary arterial hypertension (PAH). Our aim was to evaluate the occurrence of IN-associated AEs and to evaluate any IN dose–effect on AEs. Methods: A nationwide survey, using questionnaires, was conducted by conducted by the research group funded by the Ministry of Health, Labour and Welfare of Japan, between June 2017 and September 2018. A first questionnaire determined the occurrence of AEs associated with the therapeutic use of IN or herbal medicines containing IN in patients with UC. A second survey identified the clinical characteristics of patients who developed IN-associated critical AEs, namely, liver dysfunction, PAH, and intussusception. Results: Across 337 participating institutions, 49,320 patients with UC were identified, with IN used in 877 (1.8%). AEs were reported in 91 patients (107 events), including liver dysfunction (n = 40), gastrointestinal symptoms (n = 21), headache (n = 13), and PAH (n = 11). No dose–effect relationship between IN and AEs was identified. Liver dysfunction tended to be mild and reversible. Ten cases of intussusception were reported, with 40% of these patients requiring surgical resection. IN-induced PAH was recovered in patients who discontinued to use IN. No IN-associated deaths were reported. Conclusions: IN-associated AEs were identified among patients with UC, with liver dysfunction often being reversible, while surgical resection was required in a high proportion of patients who developed intussusception. Both healthcare workers and patients should adequately recognize the potential for AEs with the use of IN.

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Withdrawal of thiopurines in Crohn’s disease treated with scheduled adalimumab maintenance: a prospective randomised clinical trial (DIAMOND2)

Hisamatsu T., Kato S., Kunisaki R., Matsuura M., Nagahori M., Motoya S., Esaki M., Fukata N., Inoue S., Sugaya T., Sakuraba H., Hirai F., Watanabe K., Kanai T., Naganuma M., Nakase H., Suzuki Y., Watanabe M., Hibi T., Nojima M., Matsumoto T., Endo K., Hanai H., Kobayashi T., Hiraoka S., Hisamatsu T., Honda Y., Inoue T., Inoue S., Ishida T., Ito H., Iwakiri R., Izumi M., Kagaya T., Kamata N., Naganawa Y., Kaneto H., Kani K., Kinjyo F., Yasaka H., Kurahara K., Kyouwon L., Yano Y., Matsui T., Tanaka H., Munemoto Y., Naito Y., Nakagawa T., Yokoyama Y., Nakamura S., Okazaki K., Ouchi S., Saruta M., Sasaki M., Takeshima F., Tamaki H., Tanaka S., Tanida S., Mizoshita T., Tominaga K., Yamashita M., Yoshida A., Yoshimura N.

Journal of Gastroenterology （Journal of Gastroenterology） 54 （ 10 ） 860 - 870 2019年

ISSN 09441174

© 2019, Japanese Society of Gastroenterology. Background: The risk:benefit ratio of concomitant use of thiopurines with scheduled adalimumab (ADA) maintenance therapy for Crohn’s disease is controversial. The aim of this study is to identify the influence of withdrawal of thiopurines in patients in remission with combination therapy in an open-label, randomised, controlled trial (DIAMOND2; UMIN000009596). Methods: Patients in corticosteroid-free clinical remission (CFCR) for ≥ 6 months with ADA (40 mg, s.c., every other week) scheduled maintenance combined with thiopurines were randomised into two groups, “continue” (Con) or “discontinue” (Dis) group of thiopurines, whereas all other patients kept receiving scheduled ADA maintenance therapy for 52 weeks. The primary endpoint was the proportion of patients in CFCR at week 52. Secondary endpoints were endoscopic remission (ER), trough levels of ADA in serum, and safety. Results: Fifty patients were randomised to Con or Dis groups. Characteristics of patients were not significantly different between the groups. CFCR and ER prevalence at week 52 were not significantly different between groups (log rank, P = 0.704, P = 1.000, respectively). Trough levels of ADA were not significantly different between groups (P = 0.515). The proportion of patients with AAA positivity at week 52 was not significantly different (P = 0.437). ER at week 0 was involved in ER and triple remission at week 52. No serious adverse effects were observed in either group. Conclusion: Continuation of thiopurines > 6 months offers no clear benefit over scheduled ADA monotherapy. CFCR, ER, and ADA trough level at week 52 were not significantly different between groups. ER at week 0 may be involved in better long-term clinical outcomes.

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Toll-Like Receptor 7 Agonist–Induced Dermatitis Causes Severe Dextran Sulfate Sodium Colitis by Altering the Gut Microbiome and Immune Cells

Kiyohara H., Sujino T., Teratani T., Miyamoto K., Arai M., Nomura E., Harada Y., Aoki R., Koda Y., Mikami Y., Mizuno S., Naganuma M., Hisamatsu T., Kanai T.

Cellular and Molecular Gastroenterology and Hepatology （Cellular and Molecular Gastroenterology and Hepatology） 7 （ 1 ） 135 - 156 2019年

© 2018 The Authors Background & Aims: Psoriasis and inflammatory bowel disease (IBD) are both chronic inflammatory diseases occurring in the skin and gut, respectively. It is well established that psoriasis and IBD have high concordance rates, and similar changes in immune cells and microbiome composition have been reported in both conditions. To study this connection, we used a combination murine model of psoriatic dermatitis and colitis in which mice were treated topically with the Toll-like receptor 7 agonist imiquimod (IMQ) and fed dextran sulfate sodium (DSS). Methods: We applied IMQ topically to B6 mice (IMQ mice) and subsequently fed them 2% DSS in their drinking water. Disease activity and immune cell phenotypes were analyzed, and the microbial composition of fecal samples was investigated using 16S ribosomal RNA sequencing. We transplanted feces from IMQ mice to germ-free IQI/Jic (IQI) mice and fed them DSS to assess the effect of the gut microbiome on disease. Results: We first confirmed that IMQ mice showed accelerated DSS colitis. IMQ mice had decreased numbers of IgD + and IgM + B cells and increased numbers of non–cytokine-producing macrophages in the gut. Moreover, the gut microbiomes of IMQ mice were perturbed, with significant reductions of Lactobacillus johnsonii and Lactobacillus reuteri populations. Germ-free mice transplanted with feces from IMQ mice, but not with feces from untreated mice, also developed exacerbated DSS colitis. Conclusions: These results suggest that skin inflammation may contribute to pathogenic conditions in the gut via immunologic and microbiological changes. Our finding of a novel potential skin–gut interaction provides new insights into the coincidence of psoriasis and IBD.

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Transient hypotension during endoscopic resection of gangliocytic paraganglioma with ampullary involvement

Katayama T., Iwasaki E., Minami K., Fukuhara S., Kanai T.

VideoGIE （VideoGIE） 5 （ 1 ） 26 - 28 2019年

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The Effect of an Invasive Strategy for Treating Pancreatic Necrosis on Mortality: a Retrospective Multicenter Cohort Study

Minami K., Horibe M., Sanui M., Sasaki M., Iwasaki E., Sawano H., Goto T., Ikeura T., Takeda T., Oda T., Yasuda H., Ogura Y., Miyazaki D., Kitamura K., Chiba N., Ozaki T., Yamashita T., Koinuma T., Oshima T., Yamamoto T., Hirota M., Tokuhira N., Azumi Y., Nagata K., Takeda K., Furuya T., Lefor A., Mayumi T., Kanai T.

Journal of Gastrointestinal Surgery （Journal of Gastrointestinal Surgery） 24 （ 9 ） 2037 - 2045 2019年

ISSN 1091255X

© 2019, The Society for Surgery of the Alimentary Tract. Background: Infected acute necrotic collections (ANC) and walled-off necrosis (WON) of the pancreas are associated with high mortality. The difference in mortality between open necrosectomy and minimally invasive therapies in these patients remains unclear. Methods: This retrospective multicenter cohort study was conducted among 44 institutions in Japan from 2009 to 2013. Patients who had undergone invasive treatment for suspected infected ANC/WON were enrolled and classified into open necrosectomy and minimally invasive treatment (laparoscopic, percutaneous, and endoscopic) groups. The association of each treatment with mortality was evaluated and compared. Results: Of 1159 patients with severe acute pancreatitis, 122 with suspected infected ANC or WON underwent the following treatments: open necrosectomy (33) and minimally invasive treatment (89), (laparoscopic three, percutaneous 49, endoscopic 37). Although the open necrosectomy group had a significantly higher mortality on univariate analysis (p = 0.047), multivariate analysis showed no significant associations between open necrosectomy or Charlson index and mortality (p = 0.29, p = 0.19, respectively). However, age (for each additional 10 years, p = 0.012, odds ratio [OR] 1.50, 95% confidence interval [CI] 1.09–2.06) and revised Atlanta criteria-severe (p = 0.001, OR 7.84, 95% CI 2.40–25.6) were significantly associated with mortality. Conclusions: In patients with acute pancreatitis and infected ANC/WON, age and revised Atlanta criteria-severe classification are significantly associated with mortality whereas open necrosectomy is not. The mortality risk for patients undergoing open necrosectomy and minimally invasive treatment does not differ significantly. Although minimally invasive surgery is generally preferred for patients with infected ANC/WON, open necrosectomy may be considered if clinically indicated.

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Neutrophil-activating Protein Polymorphism of Helicobacter pylori Determines the Host Risk of Dyspepsia

Matsuzaki J., Tsugawa H., Kashiwazaki Y., Mori H., Yamamoto Y., Kameyama H., Masaoka T., Kanai T., Suzuki H.

Cellular and Molecular Gastroenterology and Hepatology （Cellular and Molecular Gastroenterology and Hepatology） 8 （ 2 ） 295 - 297.e6 2019年

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Middle-term prognosis in patients with ulcerative colitis who achieved clinical and endoscopic remission by budesonide rectal foam

Naganuma M., Hirai F., Kobayashi K., Watanabe K., Takeuchi K., Aoyama N., Nozawa H., Motoya S., Ohmori T., Harada A., Nagai Y., Abe T., Yamada Y., Inagaki K., Shimizu N., Kanai T., Watanabe M., Tanaka S., Arai T., Kishi M., Watanabe C., Sakata Y., Ashida T., Maemoto A., Sai S., Kitano A., Sameshima Y., Yokoyama K., Kobayashi T., Suekane T., Matsuda K., Obata H., Fujiya M., Shirai T., Tominaga K., Takedatsu H., Suzuki R.

PLoS ONE （PLoS ONE） 14 （ 8 ） 2019年

© 2019 Naganuma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background Budesonide foam is effective in inducing clinical remission in ulcerative colitis (UC) patients with active proctosigmoiditis. The aim of this study was to evaluate the duration of remission and predictors of relapse in UC patients who achieved clinical remission and mucosal healing by 6-week treatment with topical budesonide. Methods This is a retrospective, observational, multicenter study with a 2-year follow-up period. UC patients who were treated with budesonide foam in phase 2 or phase 3 clinical trials and achieved both clinical remission and mucosal healing were enrolled. Results Among 84 patients who met the eligibility criteria, 60 participated in the study. Eighteen of the 60 patients (30.0%; 95% confidence interval [CI]: 18.9–43.2) experienced no relapse (i.e., maintenance of remission) during the 2-year follow-up period. The median relapse-free survival time was 0.82 years (95% CI: 0.51–1.52). Of 37 patients with a Mayo endoscopic subscore of 0 after inducing remission with budesonide foam, 25 (67.6%) relapsed within 2 years. Patients with a disease duration of <1 year experienced a worse clinical outcome than patients with a disease duration of >5 years, and the hazard ratio was 2.38 (95% CI: 1.04–5.45). Conclusion This is the first study to evaluate the short- to middle-term prognosis in UC patients who achieved mucosal healing with topical preparations. After inducing remission by budesonide foam, treatment for maintaining remissions and strict follow-up may be needed for patients with shorter disease duration.

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金井　隆典

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