Faculty Profiles - HIRAOKA Sakiko

Papers - HIRAOKA Sakiko

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A Calcium Enterolith in a Patient with Crohn's Disease and Its In Vitro Dissolubility in Citric Acid. Reviewed

Iwamuro M, Urata H, Hiraoka S, Ohmori M, Kondo Y, Kawahara Y, Okada H

Case reports in gastrointestinal medicine 2017 2951547 2017

Two Cases of Rectal Xanthoma Presenting as Yellowish to Whitish Lesions during Colonoscopy. Reviewed International journal

Iwamuro M, Tanaka T, Takei D, Sugihara Y, Harada K, Hiraoka S, Kawahara Y, Okada H

Case reports in gastrointestinal medicine 2017 5975107 - 5975107 2017

Language：English

Two cases of rectal xanthomas are described. One case is that of a 56-year-old Japanese man in whom multiple yellowish spots measuring approximately 3 to 5 mm were observed in the rectum during colonoscopy. The other case is that of a 78-year-old Japanese man in whom colonoscopy showed a whitish plaque of 4 mm in diameter in the rectum. Biopsy examinations performed on both patients revealed the deposition of xanthoma cells within the rectal mucosa. Within the gastrointestinal tract, xanthomas most frequently arise in the stomach, whereas the colorectum is rarely affected. Despite this infrequency, the two cases indicate that xanthomas should be recalled when yellowish to whitish lesions are observed in the colorectum.

DOI： 10.1155/2017/5975107

P2-10 慢性腸炎マウスモデルにおけるベルベリンの改善効果と作用機序の検討

高原政宏, 高木章乃夫, 平岡佐規子, 池田愛璃, 足立卓哉, 松下浩志, 小池和子, 岡田裕之

日本臨床免疫学会会誌 40 ( 4 ) 311b - 311b 2017

Language：Japanese Publisher：日本臨床免疫学会

<p>【背景】生薬であるベルベリン（BBR）は下痢止めとして臨床応用されているが，抗炎症など多彩な作用も有することが明らかになっている．BBRは細胞のエネルギーの調節因子であるAMPKを活性化させることが知られており，近年，このAMPKがT細胞を含む免疫細胞の応答に関わっていることが報告されている．【目的，方法】慢性腸炎マウスモデルを用いて，大腸炎粘膜のCD4⁺T細胞（LP CD4⁺T細胞）におけるBBRの抗炎症作用とその機序についての検証をin vitroおよびIn vivoで行う．1）CD4⁺CD45RB^highT細胞移入腸炎マウスのLPCD4⁺T細胞をPMA/Ionomysinで刺激し，IFN-γ産生細胞を誘導，BBRの効果について，AMPKの関与も含めて検討．2）上記腸炎マウスにBBRを含んだ餌を投与し，腸炎の抑制効果について検討．【結果】1）LP CD4⁺T細胞はBBRと共培養すると，IFN-γ産生細胞が優位に低下し，ウェスタンブロッティングでは，AMPKの活性化を認めた．次に，AMPKのagonistとantagonistを用いた培養系でIFN-γの産生を調べたところ，agonistで抑制，antagonistで増加を認めた．以上から，BBRにより活性化されたAMPKがIFN-γを制御していることが示唆された．2）上記腸炎マウスにBBRを経口投与した結果，腸炎は優位に抑制された．【結論】BBRは，慢性腸炎マウスモデルの腸炎を抑制し，その作用機序の一つとしてAMPKを介した機序が示唆された．</p>

DOI： 10.2177/jsci.40.311b

A Novel Role of Spred2 in the Colonic Epithelial Cell Homeostasis and Inflammation Reviewed

Sakuma Takahashi, Teizo Yoshimura, Takahiro Ohkura, Masayoshi Fujisawa, Soichiro Fushimi, Toshihiro Ito, Junya Itakura, Sakiko Hiraoka, Hiroyuki Okada, Kazuhide Yamamoto, Akihiro Matsukawa

SCIENTIFIC REPORTS 6 37531 2016.11

Language：English Publishing type：Research paper (scientific journal) Publisher：NATURE PUBLISHING GROUP

Rapid and adequate mucosal healing is important for a remission of ulcerative colitis (UC) patients. Here, we examined whether Spred2, a member of the Sprouty-related EVH1-domain-containing proteins that inhibit the Ras/Raf/ERK pathway, plays a role in colonic mucosal homeostasis and inflammation by using Spred2 knockout (KO) mice. We first detected increased epithelial cell proliferation and cadherin 1 expression in the colon of naive Spred2 KO mice compared to wild-type mice. Interestingly, Spred2 KO mice were resistant to dextran sulfate sodium (DSS)-induced acute colitis as indicated by lower levels of body weight loss and disease activity index. Histologically, epithelial cell injury and inflammation were milder in the colonic mucosa of Spred2 KO mice on day 3 and almost undetectable by day 8. Experiments with bone chimeric mice indicated that Spred2 deficiency in non-hematopoietic cells was responsible for the reduced sensitivity to DSS. Finally, Spred2 KO mice developed significantly fewer tumors in response to azoxymethane plus DSS. Taken together, our results demonstrate, for the first time, that Spred2 plays an important role in the regulation of colonic epithelial cell proliferation and inflammation by potentially down-regulating the activation of ERK. Thus, Spred2 may be a new therapeutic target for the treatment of UC.

DOI： 10.1038/srep37531

Ulcerative colitis patients in clinical remission demonstrate correlations between fecal immunochemical test results, mucosal healing, and risk of relapse Reviewed

Asuka Nakarai, Jun Kato, Sakiko Hiraoka, Shiho Takashima, Daisuke Takei, Toshihiro Inokuchi, Yuusaku Sugihara, Masahiro Takahara, Keita Harada, Hiroyuki Okada

WORLD JOURNAL OF GASTROENTEROLOGY 22 ( 21 ) 5079 - 5087 2016.6

Language：English Publishing type：Research paper (scientific journal) Publisher：BAISHIDENG PUBLISHING GROUP INC

AIM: To assess the risk of relapse in ulcerative colitis (UC) patients in clinical remission using mucosal status and fecal immunochemical test (FIT) results.
METHODS: The clinical outcomes of 194 UC patients in clinical remission who underwent colonoscopy were based on evaluations of Mayo endoscopic subscores (MESs) and FIT results.
RESULTS: Patients with an MES of 0 (n = 94, 48%) showed a ten-fold lower risk of relapse than those with an MES of 1-3 (n = 100, 52%) (HR = 0.10, 95%CI: 0.05-0.19). A negative FIT result (fecal hemoglobin concentrations <= 100 ng/mL) was predictive of patients with an MES of 0, with a sensitivity of 0.94 and a specific of 0.76. Moreover, patients with a negative FIT score had a six-fold lower risk of clinical relapse than those with a positive score (HR = 0.17, 95%CI: 0.10-0.28). Inclusion of the distinguishing parameter, sustaining clinical remission > 12 mo, resulted in an even stronger correlation between negative FIT results and an MES of 0 with respect to the risk of clinical relapse (HR = 0.11, 95%CI: 0.04-0.23).
CONCLUSION: Negative FIT results one year or more after remission induction correlate with complete mucosal healing (MES 0) and better prognosis. Performing FIT one year after remission induction may be useful for evaluating relapse risk.

DOI： 10.3748/wjg.v22.i21.5079

【IBD治療のcritical point-私ならこうする】潰瘍性大腸炎ステロイド依存性の見極めと治療方針チオプリン製剤による寛解維持療法

井口俊博, 平岡佐規子, 高嶋志保, 半井明日香, 高原政宏, 岡田裕之

臨床消化器内科 31 ( 6 ) 655 - 659 2016.5

Language：Japanese Publisher：(株)日本メディカルセンター

チオプリン製剤は潰瘍性大腸炎においてステロイド依存例に対するステロイド減量効果,および寛解維持効果を有する貴重な薬剤である.活性体である6-TGN(6-thioguanine nucleotide)に変換され安定して薬効を発揮するまでに時間が必要であり,しばしば副作用を伴うことから使用に当たり習熟が不可欠である.しかし投与開始後から慎重にモニタリングを行うことで対応可能であり,その有効性,利便性,医療経済の観点から抗TNFα抗体製剤に優先してチオプリン製剤を活用すべきである.(著者抄録)

Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2016&ichushi_jid=J01937&link_issn=&doc_id=20160530220007&doc_link_id=10.19020%2FJ01937.2016299263&url=https%3A%2F%2Fdoi.org%2F10.19020%2FJ01937.2016299263&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Lymphoid hyperplasia of the colon and its association with underlying allergic airway diseases Reviewed

Masaya Iwamuro, Sakiko Hiraoka, Hiroyuki Okada, Yoshinari Kawai, Yoshio Miyabe, Katsuyoshi Takata, Seiji Kawano, Kazuhide Yamamoto

INTERNATIONAL JOURNAL OF COLORECTAL DISEASE 31 ( 2 ) 313 - 317 2016.2

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER

The purpose of this study was to determine the prevalence of lymphoid hyperplasia in the lower gastrointestinal tract and its role in patients undergoing colonoscopic examinations, particularly focusing on any allergic predisposition.
A database search performed at the Department of Gastroenterology at Onomichi Municipal Hospital identified seven patients with lymphoid hyperplasia in the large intestine (i.e., cecum, colon, and/or rectum). Data regarding the endoscopic, biological, and pathological examinations performed and the allergic histories for each patient were retrospectively reviewed from the clinical records.
Median age of the patients (four males, three females) was 50 years. Lymphoid hyperplasia was seen in the cecum (n = 5), ascending colon (n = 2), and transverse colon (n = 1). Six patients (85.7 %) had one of the allergic airway diseases: allergic rhinoconjunctivitis for pollen (n = 3), bronchial asthma (n = 1), infantile asthma (n = 1), or allergic bronchitis (n = 1). Drug allergy (n = 3) and urticaria (n = 2) were also found. All seven patients had one or more allergic diseases; however, none had a history of food allergy. Blood tests for allergens revealed that six patients (85.7 %) had positive reactions to inherent allergens, whereas only one patient had a positive reaction to food allergens.
Our results indicate that lymphoid hyperplasia in the large intestine may be associated with allergic airway diseases rather than with food allergies; thus, its presence may be useful to detect patients with underlying airway hyperreactivity.

DOI： 10.1007/s00384-015-2392-6

Fecal immunochemical test as a biomarker for inflammatory bowel diseases: Can it rival fecal calprotectin? Reviewed

Jun Kato, Sakiko Hiraoka, Asuka Nakarai, Shiho Takashima, Toshihiro Inokuchi, Masao Ichinose

Intestinal Research 14 ( 1 ) 5 - 14 2016

Language：English Publisher：Korean Association for the Study of Intestinal Diseases

Accurate evaluation of disease activity is essential for choosing an appropriate treatment and follow-up plan for patients with inflammatory bowel disease (IBD). Endoscopy is required for accurately evaluating disease activity, but the procedures are sometimes invasive and burdensome to patients. Therefore, alternative non-invasive methods for evaluating or predicting disease activity including mucosal status are desirable. Fecal calprotectin (Fcal) is the most widely used fecal marker for IBD, and many articles have described the performance of the marker in predicting disease activity, mucosal healing (MH), treatment efficacy, and risk of relapse. Fecal immunochemical test (FIT) can quantify the concentration of hemoglobin in stool and was originally used for the screening of colorectal cancer. We recently reported that FIT is also a useful biomarker for IBD. A direct comparison between the use of Fcal and FIT showed that both methods predicted MH in ulcerative colitis equally well. However, in the case of Crohn's disease, FIT was less sensitive to lesions in the small intestine, compared to Fcal. FIT holds several advantages over Fcal in regards to user-friendliness, including a lower cost, easy and clean handling, and the ability to make rapid measurements by using an automated measurement system. However, there is insufficient data to support the application of FIT in IBD. Further studies into the use of FIT for evaluating the inflammatory status of IBD are warranted.

DOI： 10.5217/ir.2016.14.1.5

Clinical Features of Intestinal Behcet's Disease Associated with Myelodysplastic Syndrome and Trisomy 8 Reviewed

Seiji Kawano, Sakiko Hiraoka, Hiroyuki Okada, Mitsuhiro Akita, Masaya Iwamuro, Kazuhide Yamamoto

ACTA MEDICA OKAYAMA 69 ( 6 ) 365 - 369 2015.12

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

Several studies have identified a relationship between myelodysplastic syndrome and Beket's disease (BD), especially intestinal BD, and trisomy 8 appears to play an important role in these disorders. Despite this, only few case reports or series have been reported in gastroenterology, meaning that endoscopic findings and characteristics of intestinal 131) have not been clarified yet. In this report, we describe three cases of intestinal BD associated with myelodysplastic syndrome and trisomy 8, and discuss the clinical features and problems of these disorders from a gastroenterology perspective.

DOI： 10.18926/AMO/53912

An open-label prospective randomized multicenter study of intensive versus weekly granulocyte and monocyte apheresis in active crohn's disease Reviewed

Naoki Yoshimura, Yoko Yokoyama, Katsuyoshi Matsuoka, Hiroki Takahashi, Ryuichi Iwakiri, Takayuki Yamamoto, Tomoo Nakagawa, Takumi Fukuchi, Satoshi Motoya, Reiko Kunisaki, Shingo Kato, Fumihito Hirai, Yoh Ishiguro, Satoshi Tanida, Sakiko Hiraoka, Keiichi Mitsuyama, Shunji Ishihara, Shinji Tanaka, Michiro Otaka, Taro Osada, Takashi Kagaya, Yasuo Suzuki, Hiroshi Nakase, Hiroyuki Hanai, Kenji Watanabe, Nobuhito Kashiwagi, Toshifumi Hibi

BMC GASTROENTEROLOGY 15 163 2015.11

Language：English Publishing type：Research paper (scientific journal) Publisher：BIOMED CENTRAL LTD

Background: Granulocyte and monocyte adsorptive apheresis (GMA) has shown efficacy in patients with active Crohn's disease (CD). However, with routine weekly therapy, it may take several weeks to achieve remission. This study was performed to assess clinical efficacy and safety of intensive GMA in patients with active CD.
Methods: In an open-label, prospective, randomized multicentre setting, 104 patients with CD activity index (CDAI) of 200 to 450 received intensive GMA, at two sessions per week (n = 55) or one session per week (n = 49). Clinical remission was defined as a CDAI score <150. Patients in each arm could receive up to 10 GMA sessions. However, GMA treatment could be discontinued when CDAI decreased to <150 (clinical remission level).
Results: Of the 104 patients, 99 were available for efficacy evaluation as per protocol, 45 in the weekly GMA group, and 54 in the intensive GMA group. Remission was achieved in 16 of 45 patients (35.6 %) in the weekly GMA and in 19 of 54 (35.2 %) in the intensive GMA (NS). Further, the mean time to remission was 35.4 +/- 5.3 days in the weekly GMA and 21.7 +/- 2.7 days in the intensive GMA (P = 0.0373). Elevated leucocytes and erythrocyte sedimentation rate were significantly improved by intensive GMA, from 8005/mu L to 6950/mu L (P = 0.0461) and from 54.5 mm/hr to 30.0 mm/hr (P = 0.0059), respectively. In both arms, GMA was well tolerated and was without safety concern.
Conclusions: In this study, with respect to remission rate, intensive GMA was not superior to weekly GMA, but the time to remission was significantly shorter in the former without increasing the incidence of side effects. UMIN registration # 000003666.

DOI： 10.1186/s12876-015-0390-3

[A case of asymptomatic Sjögren's syndrome who developed interstitial pneumonia during monoclonal antibody therapy of Crohn's disease]. Reviewed

Kohno H, Okada H, Hiraoka S, Tanaka T

Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology 112 ( 7 ) 1326 - 1333 2015.7

Language：Japanese Publisher：The Japanese Society of Gastroenterology

A 67-year-old woman was diagnosed with ileocolic Crohns disease at 61 years of age. Remission had been induced by the monoclonal antibody adalimumab, and maintenance therapy had continued since her diagnosis. However, she developed respiratory symptoms, including a dry cough. A chest CT scan revealed interstitial shadows in the lower pulmonary lobes. Although no sicca symptoms were noted, she was serologically positive for both anti-Sjögrens syndrome-related antigen A and B antibodies, and salivary gland biopsy showed lymphocytic infiltration. Consequently, she was diagnosed as having asymptomatic Sjögrens syndrome. Infection or drug-induced pulmonary disease was considered unlikely, and the interstitial pneumonia was considered an extra-glandular presentation of Sjögrens syndrome. Thus, interstitial shadows, which appear during immunotherapy for Crohns disease, could indicate asymptomatic Sjögrens syndrome; clinicians should consider this rare clinical picture when assessing such a patient.

DOI： 10.11405/nisshoshi.112.1326

Other Link： http://search.jamas.or.jp/link/ui/2015305791

Endoscopic radial incision and cutting method for refractory stricture of a rectal anastomosis after surgery Reviewed

Keita Harada, Seiji Kawano, Sakiko Hiraoka, Yoshiro Kawahara, Yoshitaka Kondo, Hiroyuki Okada

ENDOSCOPY 47 E552 - E553 2015

An Effective and Safe Sedation Technique Combining Target-Controlled Infusion Pump with Propofol, Intravenous Pentazocine, and Bispectral Index Monitoring for Peroral Double-Balloon Endoscopy Reviewed

Seiji Kawano, Hiroyuki Okada, Masaya Iwamuro, Yoshiyasu Kouno, Kou Miura, Toshihiro Inokuchi, Hiromitsu Kanzaki, Keisuke Hori, Keita Harada, Sakiko Hiraoka, Yoshiro Kawahara, Kazuhide Yamamoto

DIGESTION 91 ( 2 ) 112 - 116 2015

Language：English Publishing type：Research paper (scientific journal) Publisher：KARGER

Background/Aims: Because peroral double-balloon endoscopy (DBE) is a time-consuming, painful procedure, sedation with analgesics, and/or anesthetics is generally required. The aim of this prospective study was to investigate the safety and efficacy of our sedation protocol for peroral DBE, which consisted of target-controlled infusion (TCI) anesthesia with propofol, an intravenous bolus of pentazocine, and bispectral index (BIS) monitoring. Methods: A total of 34 consecutive patients who underwent DBE by the oral approach were enrolled. Patients were primarily sedated with a continuous infusion of propofol and adjusted in accordance with the BIS levels. The bolus infusion of pentazocine was performed when the propofol infusion was insufficient. The primary outcome measure of this study was to ensure the safety and efficacy of this sedation technique. The secondary purpose was to identify the characteristics of the patient who required the bolus infusion of pentazocine. Results: Five patients (14.7%) required a reduction in the dose of propofol. However, no patient experienced any serious adverse events. All patients (100%) and 80.6% (25/31) of endoscopists answered that the sedation protocol was 'excellent' or 'enough' for peroral DBE. Eleven patients (32.3%) required a bolus injection of pentazocine. Age < 60 years and a total procedure time of > 70 min were significant risk-factors for pentazocine use. Conclusions: A combination of propofol via TCI pump, bolus injection of pentazocine as needed, and BIS monitoring was a safe and effective procedure for peroral DBE. Reasonable satisfaction indices were obtained from both patients and endoscopists. Pentazocine was required for young patients and in cases with longer procedure times. (c) 2015 S. Karger AG, Basel

DOI： 10.1159/000369614

Prognosis of ulcerative colitis differs between patients with complete and partial mucosal healing, which can be predicted from the platelet count Reviewed

Asuka Nakarai, Jun Kato, Sakiko Hiraoka, Toshihiro Inokuchi, Daisuke Takei, Yuki Moritou, Mitsuhiro Akita, Sakuma Takahashi, Keisuke Hori, Keita Harada, Hiroyuki Okada, Kazuhide Yamamoto

WORLD JOURNAL OF GASTROENTEROLOGY 20 ( 48 ) 18367 - 18374 2014.12

Language：English Publishing type：Research paper (scientific journal) Publisher：BAISHIDENG PUBLISHING GROUP INC

AIM: To determine the difference in clinical outcome between ulcerative colitis (UC) patients with Mayo endoscopic subscore (MES) 0 and those with MES 1.
METHODS: UC patients with sustained clinical remission of 6 mo or more at the time of colonoscopy were examined for clinical outcomes and the hazard ratios of clinical relapse according to MES. Parameters, including blood tests, to identify predictive factors for MES 0 and slight endoscopic recurrence in clinically stable patients were assessed. Moreover, a receiver operating characteristic curve was generated, and the area under the curve was calculated to indicate the utility of the parameters for the division between complete and partial mucosal healing. All P values were two-sided and considered significant when less than 0.05.
RESULTS: A total of 183 patients with clinical remission were examined. Patients with MES 0 (complete mucosal healing: n = 80, 44%) were much less likely to relapse than those with MES 1 (partial mucosal healing: n = 89, 48%) (P < 0.0001, log-rank test), and the hazard ratio of risk of relapse in patients with MES 1 vs MES 0 was 8.17 (95% CI: 4.19-17.96, P < 0.0001). The platelet count (PLT) < 26 x 10(4)/mu L was an independent predictive factor for complete mucosal healing (OR = 4.1, 95% CI: 2.15-7.99). Among patients with MES 0 at the initial colonoscopy, patients of whom colonoscopy findings shifted to MES 1 showed significant increases in PLT compared to those who maintained MES 0 (3.8 x 10(4)/mu L vs -0.6 x 10(4)/mu L, P < 0.0001).
CONCLUSION: The relapse rate differed greatly between patients with complete and partial mucosal healing. A shift from complete to partial healing in clinically stable UC patients can be predicted by monitoring PLT. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

DOI： 10.3748/wjg.v20.i48.18367

Long-term follow-up of ulcerative colitis patients treated on the basis of their cytomegalovirus antigen status Reviewed

Toshihiro Inokuchi, Jun Kato, Sakiko Hiraoka, Hideyuki Suzuki, Asuka Nakarai, Tomoko Hirakawa, Mitsuhiro Akita, Sakuma Takahashi, Keita Harada, Hiroyuki Okada, Kazuhide Yamamoto

WORLD JOURNAL OF GASTROENTEROLOGY 20 ( 2 ) 509 - 517 2014.1

Language：English Publishing type：Research paper (scientific journal) Publisher：BAISHIDENG PUBL GRP CO LTD

AIM: To clarify the impact of cytomegalovirus (CMV) activation and antiviral therapy based on CMV antigen status on the long-term clinical course of ulcerative colitis (UC) patients.
METHODS: UC patients with flare-up were divided into CMV-positive and -negative groups according to the CMV antigenemia assay. The main treatment strategy provided for the patients in the CMV-positive group comprised a dose reduction of corticosteroids and administration of ganciclovir.
RESULTS: The median number of days to initial remission was significantly greater for the patients in the CMV-positive group (21 d vs 16 d, P = 0.009). However, the relapse rate after remission and colectomy rate during more than 30 mo of observation did not differ between the two groups. Multivariate analysis revealed that administration of ganciclovir was the only independent factor for avoiding colectomy in patients of the CMV-positive group.
CONCLUSION: CMV antigen status did not significantly affect the long-term prognosis in UC patients under treatment with appropriate antiviral therapy. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.

DOI： 10.3748/wjg.v20.i2.509

【大腸側方発育型腫瘍(LST)-新たな時代へ】LSTの遺伝子学的特徴大腸癌の発癌機序からみたLSTの位置づけ

平岡佐規子, 原田馨太, 加藤順

Intestine 18 ( 1 ) 53 - 60 2014.1

Language：Japanese Publisher：(株)日本メディカルセンター

側方に発育する大腸腫瘍であるLST-G,LST-NG,sessile serrated adenoma/polyp(SSA/P)は,分子生物学的にも違いがあり,それぞれ異なった発癌過程を反映する形態変化と考えられる.形態により違いのみられるおもな遺伝子変化は,RAS/RAF/MAPK系シグナルの遺伝子変異(K-ras,BRAF変異)とDNAメチル化の頻度(CIMP)であり,LST-GはK-ras変異,CIMP-low,LST-NGはCIMP-negative,SSA/PはBRAF変異,CIMP-highがそれぞれ特徴的である.(著者抄録)

Slight Increases in the Disease Activity Index and Platelet Count Imply the Presence of Active Intestinal Lesions in C-reactive Protein-negative Crohn's Disease Patients Reviewed

Asuka Nakarai, Jun Kato, Sakiko Hiraoka, Toshihiro Inokuchi, Daisuke Takei, Yuki Morito, Mitsuhiro Akita, Sakuma Takahashi, Keisuke Hori, Keita Harada, Hiroyuki Okada, Kazuhide Yamamoto

INTERNAL MEDICINE 53 ( 17 ) 1905 - 1911 2014

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPAN SOC INTERNAL MEDICINE

Objective Although the serum C-reactive protein (CRP) level may, to some extent, predict the disease activity in patients with Crohn's disease (CD), it is not always elevated during periods of disease activity. This study aimed to identify factors predicting the presence of active intestinal lesions in CD patients without an elevated CRP level.
Methods CD patients in whom the presence or absence of active intestinal lesions was evaluated using endoscopic and/or radiologic modalities were divided into two groups based on a negative (< 3 mg/L) or positive (>= 3 mg/L) CRP level. The correlations between the presence of active intestinal lesions and various clinical variables, including the Crohn's Disease Activity Index (CDAI), leukocyte and platelet counts and hemoglobin, serum albumin and CRP levels, were determined in the CRP-negative patients.
Results Of the 128 patients examined, 70 had a negative CRP status, approximately half of whom had active intestinal lesions. The multivariate analysis revealed a CDAI of > 100 and platelet count of > 33x10(4)/mu L to be significant predictive factors for the presence of active lesions in the CRP-negative patients [CDAI > 100, odds ratio (OR) = 5.55; 95% confidence interval (CI), 1.80-18.74, platelet count > 33x10(4)/mu L, OR = 5.94; 95% CI, 1.34-28.87]. The sensitivity of fulfillment of either criterion for the presence of active intestinal lesions was 83%, while the specificity of fulfillment of both criteria was 94%.
Conclusion A relatively low CDAI and platelet count were identified as predictive markers of the presence of active intestinal lesions in CRP-negative CD patients. These results suggest that symptoms and laboratory data should be evaluated very carefully in such patients.

DOI： 10.2169/internalmedicine.53.2627

Serum Glycan Markers for Evaluation of Disease Activity and Prediction of Clinical Course in Patients with Ulcerative Colitis Reviewed

Koji Miyahara, Kazuhiro Nouso, Shunsuke Saito, Sakiko Hiraoka, Keita Harada, Sakuma Takahashi, Yuki Morimoto, Sayo Kobayashi, Fusao Ikeda, Yasuhiro Miyake, Hidenori Shiraha, Akinobu Takaki, Hiroyuki Okada, Maho Amano, Kazuko Hirose, Shin-Ichiro Nishimura, Kazuhide Yamamoto

PLoS ONE 8 ( 10 ) e74861 2013.10

Language：English Publishing type：Research paper (scientific journal)

Background:The aims of this study were to determine the change of whole-serum N-glycan profile in ulcerative colitis (UC) patients and to investigate its clinical utility.Methods:We collected serum from 75 UC patients at the time of admission and the same number of age/sex-matched healthy volunteers. Serum glycan profile was measured by comprehensive quantitative high-throughput glycome analysis and was compared with disease activity and prognosis.Results:Out of 61 glycans detected, 24 were differentially expressed in UC patients. Pathway analysis demonstrated that highly sialylated multi-branched glycans and agalactosyl bi-antennary glycans were elevated in UC patients
in addition, the glycan ratio m/z 2378/1914, which also increased in UC, showed the highest Area under Receiver Operating Characteristic curve (0.923) for the diagnosis of UC. Highly sialylated multi-branched glycans and the glycan ratio m/z 2378/1914 were higher in the patients with total colitis, Clinical Activity Index &gt
10, Mayo endoscopic score 3, or a steroid-refractory status. In particular, the glycan ratio m/z 2378/1914 (above median) was an independent prognostic factor for the need for an operation (hazard ratio, 2.67
95% confidence interval, 1.04-7.84).Conclusions:Whole-serum glycan profiles revealed that the glycan ratio m/z 2378/1914 and highly sialylated multi-branched glycans increase in UC patients, and are correlated with disease activity. The glycan ratio m/z 2378/1914 was an independent predictive factor of the prognosis of UC. © 2013 Miyahara et al.

DOI： 10.1371/journal.pone.0074861

潰瘍性大腸炎の活動性・予後予測における血清糖鎖マーカーの有用性

宮原孝治, 能祖一裕, 平岡佐規子, 森元裕貴, 高橋索真, 小林沙代, 斎藤俊介, 原田馨太, 山本和秀, 天野麻穂, 西村紳一郎

日本臨床分子医学会学術総会プログラム・抄録集 50回 76 - 76 2013.4

Noninvasive evaluation of mucosal healing in inflammatory bowel diseases Reviewed

Jun Kato, Sakiko Hiraoka, Asuka Nakarai, Masao Ichinose

Clinical Journal of Gastroenterology 6 ( 1 ) 1 - 7 2013.2

Language：English

Current opinions increasingly cite the need to achieve not only clinical response but also endoscopic mucosal healing in the treatment of both types of inflammatory bowel disease: ulcerative colitis (UC) and Crohn's disease (CD). Although endoscopic procedures are necessary for confirmation of mucosal healing, undergoing colonoscopy is invasive and burdensome to patients. Therefore, alternative noninvasive methods of evaluating or predicting mucosal status have been eagerly desired. For this purpose, blood, fecal, and radiologic modalities have been suggested and examined. C-reactive protein and fecal markers such as fecal calprotectin can evaluate active inflammation to some extent in both UC and CD. However, their predictive values for mucosal healing have not yet been fully evaluated and current knowledge indicates that the values were rather insufficient. Radiologic modalities such as computed tomography, magnetic resonance, and ultrasound can also evaluate mucosal inflammation but are currently not suitable for detection of healing. Capsule endoscopy may be optimal for evaluating mucosal status of the small bowel in CD patients, but sufficient data are not yet available, particularly for mucosal healing. Thus, these candidates for the surrogate modality are currently imperfect for evaluation of mucosal healing, but the changes in values/findings of these modalities after initiation of therapy appear to be rather promising as a marker of efficacy of the therapy. Finally, our recent data showed that a fecal immunochemical test for evaluation of mucosal healing in UC was very promising and this method should be further evaluated in CD also. © 2012 Springer Japan.

DOI： 10.1007/s12328-012-0346-x

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