Details of a Researcher - NAKASE Hiroshi

Papers - NAKASE Hiroshi

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大腸癌の内視鏡Up-to-date 大腸ESD後潰瘍および穿孔部の縫縮テクニック

吉井新二, 山野泰穂, 仲瀬裕志

大腸がんperspective ( (株)メディカルレビュー社 ) 4 ( 4 ) 332 - 334 2020.03

今だから聞きます、胆石をどうしていますか? 治療困難肝内結石に対するSpyGlass DSを用いた胆道鏡下治療

川上裕次郎, 本谷雅代, 大和田紗恵, 平野雄大, 我妻康平, 石上敬介, 柾木喜晴, 伊東文子, 阿久津典之, 佐々木茂, 仲瀬裕志

日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集 ( 日本消化器病学会-北海道支部 ) 126回・120回 32 - 32 2020.03

Timing of indocyanine green injection prior to laparoscopic colorectal surgery for tumor localization: a prospective case series.

Tetsuta Satoyoshi, Kenji Okita, Masayuki Ishii, Atsushi Hamabe, Akihiro Usui, Emi Akizuki, Koichi Okuya, Toshihiko Nishidate, Hiroo Yamano, Hiroshi Nakase, Ichiro Takemasa

Surgical endoscopy 35 ( 2 ) 763 - 769 2020.02 [Refereed] [International journal]

BACKGROUND: Accurate identification of tumor sites during laparoscopic colorectal surgery helps to optimize oncological clearance. We aimed to assess the timing of the local injection preoperatively and clarify the usefulness and limitation of tumor site marking using indocyanine green (ICG) fluorescence imaging. METHODS: Consecutive patients who underwent primary colorectal cancer surgery from September 2017 to January 2019 were included. Preoperatively, lower endoscopy was used to inject the ICG solution into the submucosal layer near the tumor. During laparoscopic surgery, ICG fluorescence marking as the tumor site marking was detected using a laparoscopic near-infrared camera system. The detection rate and factors associated with successful intraoperative ICG fluorescence visualization including the interval between local injection and surgery were evaluated. RESULTS: One hundred sixty-five patients were enrolled. Using the laparoscopic near-infrared system, the intraoperative detection rates of ICG marking were 100% for ICG injection within 6 days preoperatively, 60% for injection between 7 and 9 days preoperatively, and 0% for injection earlier than 10 days preoperatively. There were no complications associated with ICG marking. Additionally, this method did not disturb the progress of the surgical procedure because injected ICG in the submucosal layer did not cause any tissue inflammation, and if ICG spilled into the serosa, it was invisible by white light. CONCLUSION: Advantages of ICG fluorescence tumor site marking were high visibility of infrared imaging during laparoscopic colorectal surgery and minimal adverse events of surgery. One of the most important findings regarding practical use was a rapid decrease in fluorescence marking visibility if one week passed from the time of ICG local injection.

DOI PubMed

Development of anti-centromere antibody-positive autoimmune hepatitis after childbirth.

Mitsunobu Saito, Noriyuki Akutsu, Yasunao Numata, Keisuke Ishigami, Shigeru Sasaki, Hiroshi Nakase

Clinical journal of gastroenterology 13 ( 5 ) 855 - 859 2020.01 [Refereed] [Domestic journal]

This is the first case involving the development of anti-centromere antibody (ACA)-positive autoimmune hepatitis (AIH) after childbirth that triggered nailfold bleeding. A 32-year-old woman visited a dermatologist presenting with nailfold bleeding 6 months after the delivery of her second baby. Blood tests revealed liver dysfunction, and she was admitted to our hospital. Tests for hepatitis virus, antinuclear antibody, and anti-mitochondrial antibody were negative. She had no history of alcohol consumption or oral medication. Because of nailfold bleeding, we performed tests for ACA, anti-Scl-70 antibody, anti-RNA polymerase III antibody, and anti-U1 RNP antibodies; only ACA was positive. A liver biopsy was performed for the diagnosis of liver dysfunction. Histological examination of the liver biopsy specimen showed moderate infiltration of inflammatory cells, interface hepatitis, bridging fibrosis, and bile duct injury. The AIH international score was 17, and thus, we diagnosed AIH. Oral prednisolone (PSL) 0.6 mg/day/body weight was initiated. Two weeks post-treatment, the liver enzyme levels normalized and the nailfold bleeding disappeared. In case of nailfold bleeding complicated with liver dysfunction post-childbirth, ACA-positive AIH should be considered as a differential diagnosis.

DOI PubMed

Optimizing the Use of Current Treatments and Emerging Therapeutic Approaches to Achieve Therapeutic Success in Patients with Inflammatory Bowel Disease.

Hiroshi Nakase

Gut and liver 14 ( 1 ) 7 - 19 2020.01 [Refereed] [International journal]

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.

DOI PubMed

Automatic, computer-aided determination of endoscopic and histological inflammation in patients with mild to moderate ulcerative colitis based on red density.

Peter Bossuyt, Hiroshi Nakase, Séverine Vermeire, Gert de Hertogh, Tom Eelbode, Marc Ferrante, Tadashi Hasegawa, Hilde Willekens, Yousuke Ikemoto, Takao Makino, Raf Bisschops

Gut 2020.01 [Refereed] [International journal]

BACKGROUND: The objective evaluation of endoscopic disease activity is key in ulcerative colitis (UC). A composite of endoscopic and histological factors is the goal in UC treatment. We aimed to develop an operator-independent computer-based tool to determine UC activity based on endoscopic images. METHODS: First, we built a computer algorithm using data from 29 consecutive patients with UC and 6 healthy controls (construction cohort). The algorithm (red density: RD) was based on the red channel of the red-green-blue pixel values and pattern recognition from endoscopic images. The algorithm was refined in sequential steps to optimise correlation with endoscopic and histological disease activity. In a second phase, the operating properties were tested in patients with UC flares requiring treatment escalation. To validate the algorithm, we tested the correlation between RD score and clinical, endoscopic and histological features in a validation cohort. RESULTS: We constructed the algorithm based on the integration of pixel colour data from the redness colour map along with vascular pattern detection. These data were linked with Robarts histological index (RHI) in a multiple regression analysis. In the construction cohort, RD correlated with RHI (r=0.74, p<0.0001), Mayo endoscopic subscores (r=0.76, p<0.0001) and UC Endoscopic Index of Severity scores (r=0.74, p<0.0001). The RD sensitivity to change had a standardised effect size of 1.16. In the validation set, RD correlated with RHI (r=0.65, p=0.00002). CONCLUSIONS: RD provides an objective computer-based score that accurately assesses disease activity in UC. In a validation study, RD correlated with endoscopic and histological disease activity.

DOI PubMed

Frequent mutations that converge on the NFKBIZ pathway in ulcerative colitis.

Nobuyuki Kakiuchi, Kenichi Yoshida, Motoi Uchino, Takako Kihara, Kotaro Akaki, Yoshikage Inoue, Kenji Kawada, Satoshi Nagayama, Akira Yokoyama, Shuji Yamamoto, Minoru Matsuura, Takahiro Horimatsu, Tomonori Hirano, Norihiro Goto, Yasuhide Takeuchi, Yotaro Ochi, Yusuke Shiozawa, Yasunori Kogure, Yosaku Watatani, Yoichi Fujii, Soo Ki Kim, Ayana Kon, Keisuke Kataoka, Tetsuichi Yoshizato, Masahiro M Nakagawa, Akinori Yoda, Yasuhito Nanya, Hideki Makishima, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Masashi Sanada, Eiji Sugihara, Taka-Aki Sato, Takashi Maruyama, Hiroyuki Miyoshi, Makoto Mark Taketo, Jun Oishi, Ryosaku Inagaki, Yutaka Ueda, Shinya Okamoto, Hideaki Okajima, Yoshiharu Sakai, Takaki Sakurai, Hironori Haga, Seiichi Hirota, Hiroki Ikeuchi, Hiroshi Nakase, Hiroyuki Marusawa, Tsutomu Chiba, Osamu Takeuchi, Satoru Miyano, Hiroshi Seno, Seishi Ogawa

Nature 577 ( 7789 ) 260 - 265 2020.01 [Refereed] [International journal]

Chronic inflammation is accompanied by recurring cycles of tissue destruction and repair and is associated with an increased risk of cancer1-3. However, how such cycles affect the clonal composition of tissues, particularly in terms of cancer development, remains unknown. Here we show that in patients with ulcerative colitis, the inflamed intestine undergoes widespread remodelling by pervasive clones, many of which are positively selected by acquiring mutations that commonly involve the NFKBIZ, TRAF3IP2, ZC3H12A, PIGR and HNRNPF genes and are implicated in the downregulation of IL-17 and other pro-inflammatory signals. Mutational profiles vary substantially between colitis-associated cancer and non-dysplastic tissues in ulcerative colitis, which indicates that there are distinct mechanisms of positive selection in both tissues. In particular, mutations in NFKBIZ are highly prevalent in the epithelium of patients with ulcerative colitis but rarely found in both sporadic and colitis-associated cancer, indicating that NFKBIZ-mutant cells are selected against during colorectal carcinogenesis. In further support of this negative selection, we found that tumour formation was significantly attenuated in Nfkbiz-mutant mice and cell competition was compromised by disruption of NFKBIZ in human colorectal cancer cells. Our results highlight common and discrete mechanisms of clonal selection in inflammatory tissues, which reveal unexpected cancer vulnerabilities that could potentially be exploited for therapeutics in colorectal cancer.

DOI PubMed

A novel endoscopic imaging system for quantitative evaluation of colonic mucosal inflammation in patients with quiescent ulcerative colitis.

Yusuke Honzawa, Minoru Matsuura, Hirokazu Higuchi, Takaki Sakurai, Hiroshi Seno, Hiroshi Nakase

Endoscopy international open 8 ( 1 ) E41-E49 2020.01 [Refereed] [International journal]

Background and study aims Mucosal healing (MH) is associated with clinical outcome in ulcerative colitis (UC) patients. In most clinical trials, a Mayo endoscopic subscore (MES) of 0 or 1 is defined as MH. However, several recent studies have reported that clinical outcome is different between UC patients with MES 0 and those with MES 1. In addition, the MES is subjective and may differ among endoscopists. Therefore, a repeatable and objective scoring system is required to distinguish MES 0 from MES 1, even in clinically quiescent UC. Here, we assessed the usefulness of new image-enhancing endoscopic technology, the i-scan TE-c, to quantitatively evaluate colonic inflammation in patients with quiescent UC. Methods We retrospectively reviewed the data from 52 UC patients in clinical remission who had undergone routine colonoscopy with standard white light. The white-light images were reassessed using the new system, and the degree of colonic mucosal inflammation was quantified according to the MAGIC (Mucosal Analysis of Inflammatory Gravity by i-scan TE-c Image) score. We used the i-scan TE-c system to investigate the association among the MAGIC score, MES, and histologic activity (Geboes score). Results The MAGIC score was significantly higher in the MES 1 group than in the MES 0 group ( P = 0.0034). The MAGIC score significantly correlated with the Geboes score ( P = 0.015). Conclusions Our novel image-enhancing endoscopic system was useful for objective and quantitative evaluation of MH in patients with quiescent UC. Further clinical studies using this imaging system are required to confirm its clinical benefit for the management of UC patients.

DOI PubMed

Multiloop as a novel traction method in accelerating colorectal endoscopic submucosal dissection.

Yuichiro Suzuki, Tokuma Tanuma, Masanori Nojima, Gota Sudo, Masakazu Akahonai, Hidetaka Hamamoto, Hironori Aoki, Taku Harada, Akio Katanuma, Hiroshi Nakase

Gastrointestinal endoscopy 91 ( 1 ) 185 - 190 2020.01 [Refereed] [International journal]

BACKGROUND AND AIMS: Traction methods have been reported to speed up endoscopic submucosal dissection (ESD). We used the multiloop (M-loop) method as a traction method for colorectal ESD and recorded the submucosal dissection time (SDT) and submucosal dissection speed (SDS). METHODS: From January to August 2018, we used the M-loop method for colorectal ESD procedures and timed the duration and recorded the outcomes. Two experts and eight nonexperts performed the procedures, which were carried out at a tertiary endoscopic center in Japan. RESULTS: A total of 50 patients were treated by colorectal ESD using the M-loop method. The mean SDT was 42.1 ± 4.16 minutes and the mean SDS was 28.0 ± 2.89 mm2/minutes. The mean SDS was 38.9 ± 6.9 mm2/minutes for experts and 25.3 ± 3.1 mm2/minutes for nonexperts. En bloc resection was achieved in 100% of cases. There were 3 adverse events and unfavorable outcomes. CONCLUSIONS: Traction by the M-loop method improved SDS in colorectal ESD. The method can be an effective tool to assist colorectal ESD. Further evaluation of the usefulness of the M-loop method is required in direct comparison with conventional ESD.

DOI PubMed

Down-regulation of RalGTPase-Activating Protein Promotes Colitis-Associated Cancer via NLRP3 Inflammasome Activation.

Tomoya Iida, Daisuke Hirayama, Naoki Minami, Minoru Matsuura, Kohei Wagatsuma, Kentaro Kawakami, Kanna Nagaishi, Masanori Nojima, Hiroki Ikeuchi, Seiichi Hirota, Ryutaro Shirakawa, Hisanori Horiuchi, Hiroshi Nakase

Cellular and molecular gastroenterology and hepatology ( Elsevier BV ) 9 ( 2 ) 277 - 293 2020 [Refereed] [International journal]

BACKGROUND & AIMS: Ral guanosine triphosphatase-activating protein α2 (RalGAPα2) is the major catalytic subunit of the negative regulators of the small guanosine triphosphatase Ral, a member of the Ras subfamily. Ral regulates tumorigenesis and invasion/metastasis of some cancers; however, the role of Ral in colitis-associated cancer (CAC) has not been investigated. We aimed to elucidate the role of Ral in the mechanism of CAC. METHODS: We used wild-type (WT) mice and RalGAPα2 knockout (KO) mice that showed Ral activation, and bone marrow chimeric mice were generated as follows: WT to WT, WT to RalGAPα2 KO, RalGAPα2 KO to WT, and RalGAPα2 KO to RalGAPα2 KO mice. CAC was induced in these mice by intraperitoneal injection of azoxymethane followed by dextran sulfate sodium intake. Intestinal epithelial cells were isolated from colon tissues, and we performed complementary DNA microarray analysis. Cytokine expression in normal colon tissues and CAC was analyzed by quantitative polymerase chain reaction. RESULTS: Bone marrow chimeric mice showed that immune cell function between WT mice and RalGAPα2 KO mice was not significantly different in the CAC mechanism. RalGAPα2 KO mice had a significantly larger tumor number and size and a significantly higher proportion of tumors invading the submucosa than WT mice. Higher expression levels of matrix metalloproteinase-9 and matrix metalloproteinase-13 were observed in RalGAPα2 KO mice than in WT mice. The expression levels of interleukin 1β, NLRP3, apoptosis associated speck-like protein containing a CARD, and caspase-1 were apparently increased in the tumors of RalGAPα2 KO mice compared with WT mice. NLRP3 inhibitor reduced the number of invasive tumors. CONCLUSIONS: Ral activation participates in the mechanism of CAC development via NLRP3 inflammasome activation.

DOI PubMed

Current clinical issue of skin lesions in patients with inflammatory bowel disease.

Tomoya Iida, Tokimasa Hida, Minoru Matsuura, Hisashi Uhara, Hiroshi Nakase

Clinical journal of gastroenterology 12 ( 6 ) 501 - 510 2019.12 [Refereed] [Domestic journal]

Inflammatory bowel disease (IBD) is associated with a number of extraintestinal complications, including skin lesions. Most reports have shown that skin lesions are found in 10-15% of IBD cases, although this depends on the definition of skin lesions. The representative skin lesions in patients with IBD are erythema nodosum, pyoderma gangrenosum, Sweet's syndrome, and so on. These lesions are often associated with IBD progression, and intestinal lesions in particular require appropriate treatment. Recently, another clinical issue regarding skin lesions in patients with IBD, a so-called paradoxical reaction, during the treatment with anti-tumor necrosis factor (TNF)-α agents has emerged. These reactions are termed paradoxical reactions because the skin lesions sometimes resemble psoriasis, although the anti-TNF-α agents have been historically used to treat psoriasis. Paradoxical reactions are reportedly found in approximately 5-10% of patients using anti-TNF-α agents and are no longer rare. Now that the use of biologics is at its culmination, reports regarding paradoxical reactions are predicted to increase in number; thus, we must recognize skin lesions with IBD patients including this type of adverse events and manage them appropriately while consulting with dermatologists.

DOI PubMed

Brunner's Gland Hamartoma Arising From the Pyloric Ring.

Gota Sudo, Toshihisa Kobayashi, Hiroshi Nakase

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 17 ( 13 ) e155 2019.12 [Refereed] [International journal]

DOI PubMed

肝細胞癌におけるBRD4阻害の抗腫瘍効果メカニズムの解析(Analysis of the anti-tumor mechanism of BRD4 inhibition in hepatocellular carcinoma)

佐々木基, 北嶋洋志, 新沼猛, 若杉英樹, 石黒一也, 萬顕, 須藤豪太, 畠平知, 阿久津典之, 山本英一郎, 甲斐正広, 佐々木茂, 仲瀬裕志, 鈴木拓

札幌医学雑誌 ( 札幌医科大学 ) 88 ( 1-6 ) 21 - 35 2019.12

BRD4を含むBETファミリー蛋白質はアセチル化ヒストンのリーダー蛋白質であり、転写調節において重要な役割を担っている。BRD4阻害剤は様々な悪性腫瘍において抗腫瘍効果を示す事が報告されている。今回我々は、肝細胞癌におけるBRD4阻害の抗腫瘍効果メカニズムの解明を目的とした。まずBRD4阻害剤JQ1の抗腫瘍効果を9種類の肝癌細胞株を用いて検証した結果、増殖抑制、細胞周期停止、アポトーシスの誘導が認められた。次に我々は、JQ1が遺伝子発現に与える影響をマイクロアレイによって解析した。その結果、JQ1が細胞周期やアポトーシス関連遺伝子に強い影響を与えること、そしてBCAT1、DDR1、GDF15、FANCD2、SENP1、TYRO3など複数の肝細胞癌関連遺伝子の発現を抑制することを見いだした。これらの遺伝子のプロモーター領域へのBRD4結合が確認されたことから、これらは肝細胞癌におけるBRD4の標的遺伝子と考えられた。今回の結果から、BRD4阻害剤は複数の癌関連遺伝子を抑制することで、肝細胞癌に対する抗腫瘍効果を示すと考えられた。(著者抄録)

Sessile serrated adenoma/polyp showed rapid malignant transformation in the final 13 months.

Sadahiro Amemori, Hiro-O Yamano, Yoshihito Tanaka, Kenjiro Yoshikawa, Hiro-O Matsushita, Ryo Takagi, Eiji Harada, Yuko Yoshida, Kazunori Tsuda, Bunichiro Kato, Eri Tamura, Makoto Eizuka, Tamotsu Sugai, Yasushi Adachi, Eiichiro Yamamoto, Hiromu Suzuki, Hiroshi Nakase

Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 32 ( 6 ) 979 - 983 2019.11 [Refereed] [International journal]

Based on the concept of the adenoma-carcinoma sequence, most colorectal cancers are considered to arise from conventional adenomas. However, recent studies suggested that a subset of colorectal cancers develop through the serrated neoplastic pathway. It has also been documented that serrated polyps can rapidly transform into invasive cancers even when they are small in size. We now describe a case of a sessile serrated adenoma/polyp which had been followed up for 4 years but eventually showed rapid transformation into an advanced cancer accompanied by a remarkable morphological change within only 13 months. Retrospective genetic and epigenetic analyses showed microsatellite instability, CpG island methylator phenotype-positive, and BRAF mutation in the lesion, suggesting the tumor had developed through the serrated neoplastic pathway. This case may provide valuable information about the natural history of sessile serrated adenoma/polyps which eventually progress to advanced cancers.

DOI PubMed

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

Tadakazu Hisamatsu, Shingo Kato, Reiko Kunisaki, Minoru Matsuura, Masakazu Nagahori, Satoshi Motoya, Motohiro Esaki, Norimasa Fukata, Satoko Inoue, Takeshi Sugaya, Hirotake Sakuraba, Fumihito Hirai, Kenji Watanabe, Takanori Kanai, Makoto Naganuma, Hiroshi Nakase, Yasuo Suzuki, Mamoru Watanabe, Toshifumi Hibi, Masanori Nojima, Takayuki Matsumoto

Journal of gastroenterology 54 ( 10 ) 860 - 870 2019.10 [Refereed] [Domestic journal]

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.

DOI PubMed

Therapeutic Efficacy and Adverse Events of Tacrolimus in Patients with Crohn's Disease: Systematic Review and Meta-Analysis.

Tomoya Iida, Masanori Nojima, Hiroshi Nakase

Digestive diseases and sciences 64 ( 10 ) 2945 - 2954 2019.10 [Refereed] [International journal]

BACKGROUND: Only a few randomized controlled trials (RCTs) and some uncontrolled trials have reported the efficacy and adverse events (AEs) of tacrolimus (Tac) in patients with refractory Crohn's disease (CD). The aim of this study was to undertake a systematic review and meta-analysis of the therapeutic efficacy and AEs of Tac in patients with CD. METHODS: We investigated studies reporting the therapeutic efficacy of Tac in patients with CD from 1950 until December 2017. Study subjects were categorized into three groups: systemic administration of Tac for patients with luminal CD (Group 1); systemic administration of Tac for patients with perianal CD (Group 2); and topical administration of Tac for patients with localized CD (Group 3). The primary endpoint of this study was the remission rate. Secondary endpoints were partial response rate, factors related to remission, and the incidence of AEs. RESULTS: The remission rate of Group 1, 2, and 3 was 37.1, 32.0, and 22.7%, respectively. The partial response rate of those was 42.3, 42.9, and 44.3%, respectively. In addition, the incidence of AEs of those was 50.9, 65.5, and 40.0%, respectively. No life-threatening AEs were observed in any study. CONCLUSION: This systematic review and meta-analysis demonstrated that Tac therapy was effective for subpopulation of CD patients and that the incidence of AEs was tolerable. Therefore, Tac therapy should be considered an option for patients with CD. However, there have been few well-designed RCTs on this subject and further studies are required.

DOI PubMed

ペプシノゲンIIと低分化混在早期胃癌の関連

三橋慧, 上野あかり, 斎藤潤信, 守谷洋, 柴田泰洋, 風間友江, 須藤豪太, 五十嵐央祥, 久保俊之, 山本英一郎, 能正勝彦, 山下健太郎, 山野泰穂, 仲瀬裕志

Gastroenterological Endoscopy ( (一社)日本消化器内視鏡学会 ) 61 ( Suppl.2 ) 2151 - 2151 2019.10

新規治療薬時代におけるクローン病患者のビタミンK栄養状態

辻秀美, 幣憲一郎, 青未空, 桑原晶子, 長嶋一昭, 山田聡, 松浦稔, 仲瀬裕志, 田中清, 稲垣暢也

日本病態栄養学会誌 ( (一社)日本病態栄養学会 ) 22 ( 4 ) 253 - 257 2019.10

我々は以前、クローン病(CD)患者において血中ビタミンK(VK)濃度が顕著に低下し、原因として脂質摂取制限による吸収障害が疑われることを報告した。近年薬物治療の進歩を承けて、脂質摂取制限が緩和されたため、血中VK関連指標を再調査した。VK摂取中央値は目安量を上回っていたが、肝臓および骨におけるVK不足の指標である血清PIVKA-II及びucOC異常高値者の割合は高く、VK不足が示唆された。VK摂取量は血清PIVKA-II・ucOCと相関せず、脂質摂取量がPIVKA-IIと有意な負の相関を示した。血清PIVKA-II濃度は、小腸切除群で有意に高値を示し、血清ucOC濃度に有意差は見られなかった。VK必要量は肝臓より骨で多く、CD患者ではVK不足者の割合は依然として高く、特に小腸切除群では吸収面積減少に加え腸肝循環の障害により、肝臓に必要な量すらVKが供給されていない可能性が示唆された。(著者抄録)

自己免疫性膵炎(AIP)におけるEUS-FNAの病理学的診断能の検討

本谷雅代, 柾木喜春, 石上敬介, 伊東文子, 阿久津典之, 仲地耕平, 佐々木茂, 仲瀬裕志

Gastroenterological Endoscopy ( (一社)日本消化器内視鏡学会 ) 61 ( Suppl.2 ) 2184 - 2184 2019.10

Concerns and Side Effects of Azathioprine During Adalimumab Induction and Maintenance Therapy for Japanese Patients With Crohn's Disease: A Subanalysis of a Prospective Randomised Clinical Trial [DIAMOND Study].

Tadakazu Hisamatsu, Takayuki Matsumoto, Kenji Watanabe, Hiroshi Nakase, Satoshi Motoya, Naoki Yoshimura, Tetsuya Ishida, Shingo Kato, Tomoo Nakagawa, Motohiro Esaki, Masakazu Nagahori, Toshiyuki Matsui, Yuji Naito, Takanori Kanai, Yasuo Suzuki, Masanori Nojima, Mamoru Watanabe, Toshifumi Hibi

Journal of Crohn's & colitis 13 ( 9 ) 1097 - 1104 2019.09 [Refereed] [International journal]

BACKGROUND: Combining a thiopurine with the human anti-tumour necrosis factor-α monoclonal antibody adalimumab for Crohn's disease [CD] treatment is controversial with regard to efficacy and safety. By conducting a subanalysis of a multicentre, randomised, prospective, open-label trial [the DIAMOND study, UMIN registration number 000005146], we studied the risk of discontinuation of thiopurine in combination with adalimumab. METHODS: In the preceding DIAMOND study, we analysed the: [i] timing and reasons for dropout in the monotherapy group and combination group; [ii] risk factors for dropout in the combination group. RESULTS: There was no significant difference in the dropout rate up to Week 52 between the monotherapy group and combination group [p = 0.325]. The main reason for study dropout was active CD in the monotherapy group, whereas it was adverse effects in the combination group [Fisher's exact test, p <0.001]. Kaplan-Meier analyses revealed significantly earlier dropout in the combination group [log-rank test, p = 0.001]. Multivariable analysis revealed low body weight to be a risk for dropout due to adverse effects in the combination group. CONCLUSIONS: Combination of azathioprine with adalimumab resulted in dropout in the early stage of the study due to side effects of azathioprine, in comparison with late dropout due to active CD in the adalimumab monotherapy group.

DOI PubMed

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Papers - NAKASE Hiroshi