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대한장연구학회> Intestinal research (Intest Res)> Quantitative histology-based classification system for assessment of the intestinal mucosal histological changes in patients with celiac disease

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Quantitative histology-based classification system for assessment of the intestinal mucosal histological changes in patients with celiac disease

Prasenjit Das , Gaurav Ps Gahlot , Alka Singh , Vandana Baloda , Ramakant Rawat , Anil K Verma , Gaurav Khanna , Maitrayee Roy , Archana George , Ashok Singh , Aasma Nalwa , Prashant Ramteke , Rajni Yadav , Vineet Ahuja , Vishnubhatla Sreenivas , Siddhartha Datta Gupta , Govind K Makharia
  • : 대한장연구학회
  • : Intestinal research (Intest Res) 17권3호
  • : 연속간행물
  • : 2019년 07월
  • : 387-397(11pages)

DOI


목차

INTRODUCTION
METHODS
RESULTS
DISCUSSION
FINANCIAL SUPPORT
CONFLICT OF INTEREST
AUTHOR CONTRIBUTION
ACKNOWLEDGEMENTS
REFERENCES

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Background/Aims: The existing histological classifications for the interpretation of small intestinal biopsies are based on qualitative parameters with high intraobserver and interobserver variations. We have developed and propose a quantitative histological classification system for the assessment of intestinal mucosal biopsies. Methods: We performed a computer-assisted quantitative histological assessment of digital images of duodenal biopsies from 137 controls and 124 patients with celiac disease (CeD) (derivation cohort). From the receiver-operating curve analysis, followed by multivariate and logistic regression analyses, we identified parameters for differentiating control biopsies from those of the patients with CeD. We repeated the quantitative histological analysis in a validation cohort (105 controls and 120 patients with CeD). On the basis of the results, we propose a quantitative histological classification system. The new classification was compared with the existing histological classifications for interobserver and intraobserver agreements by a group of qualified pathologists. Results: Among the histological parameters, intraepithelial lymphocyte count of ≥25/100 epithelial cells, adjusted villous height fold change of ≤0.7, and crypt depth-to-villous height ratio of ≥0.5 showed good discriminative power between the mucosal biopsies from the patients with CeD and those from the controls, with 90.3% sensitivity, 93.5% specificity, and 96.2% area under the curve. Among the existing histological classifications, our quantitative histological classification showed the highest intraobserver (69.7%-85.03%) and interobserver (24.6%-71.5%) agreements. Conclusions: Quantitative assessment increases the reliability of the histological assessment of mucosal biopsies in patients with CeD. Such a classification system may be used for clinical trials in patients with CeD. (Intest Res 2019;17:387-397)

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  • : 의약학분야  > 내과학
  • : KCI등재
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  • : 1598-9100
  • : 2288-1956
  • : 학술지
  • : 연속간행물
  • : 2003-2019
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1Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn's disease in Asia

저자 : Choon Jin Ooi , Ida Hilmi , Rupa Banerjee , Sai Wei Chuah , Siew Chien Ng , Shu Chen Wei , Govind K Makharia , Pises Pisespongsa , Min Hu Chen , Zhi Hua Ran , Byong Duk Ye , Dong Il Park , Khoon Lin Ling

발행기관 : 대한장연구학회 간행물 : Intestinal research (Intest Res) 17권 3호 발행 연도 : 2019 페이지 : pp. 285-310 (26 pages)

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The Asia-Pacific Working Group on inflammatory bowel disease (IBD) was established in Cebu, Philippines, under the auspices of the Asian Pacific Association of Gastroenterology with the goal of improving IBD care in Asia. This consensus is carried out in collaboration with Asian Organization for Crohn's and Colitis. With biologic agents and biosimilars becoming more established, it is necessary to conduct a review on existing literature and establish a consensus on when and how to introduce biologic agents and biosimilars in the conjunction with conventional treatments for ulcerative colitis (UC) and Crohn's disease (CD) in Asia. These statements also address how pharmacogenetics influence the treatments of UC and CD and provide guidance on response monitoring and strategies to restore loss of response. Finally, the review includes statements on how to manage treatment alongside possible hepatitis B and tuberculosis infections, both common in Asia. These statements have been prepared and voted upon by members of IBD workgroup employing the modified Delphi process. These statements do not intend to be all-encompassing and future revisions are likely as new data continue to emerge. (Intest Res 2019;17:285-310)

2Stem cell-based therapy for inflammatory bowel disease

저자 : Hiromichi Shimizu , Kohei Suzuki , Mamoru Watanabe , Ryuichi Okamoto

발행기관 : 대한장연구학회 간행물 : Intestinal research (Intest Res) 17권 3호 발행 연도 : 2019 페이지 : pp. 311-316 (6 pages)

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Inflammatory bowel disease (IBD) is an idiopathic, multi-etiological disease characterized by inflammation and mucosal destruction of the gastrointestinal tract. Despite the remarkable advance in immunomodulating therapies, there still remains a certain population of patients who are refractory to conventional as well as biologic therapies and fail to achieve mucosal healing. To improve the prognosis of those patients, at least 2 types of stem cells have been tested for their potential therapeutic use. Transplantation of hematopoietic stem cells or mesenchymal stem cells have been tested in several clinical studies, but their beneficial effect still remains controversial. In this review, we would like to overview the recent clinical challenges of stem cell-based therapies in IBD and also introduce our new therapeutic plan of intestinal stem cell transplantation for IBD, based on our ex vivo intestinal organoid culture technique. (Intest Res 2019;17:311-316)

3Prevalence and risk factors of colorectal cancer in Asia

저자 : Martin Cs Wong , Hanyue Ding , Jingxuan Wang , Paul Sf Chan , Junjie Huang

발행기관 : 대한장연구학회 간행물 : Intestinal research (Intest Res) 17권 3호 발행 연도 : 2019 페이지 : pp. 317-329 (13 pages)

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Globally, colorectal cancer (CRC) is a substantial public health burden, and it is increasingly affecting populations in Asian countries. The overall prevalence of CRC is reported to be low in Asia when compared with that in Western nations, yet it had the highest number of prevalent cases. This review described the prevalence of CRC in Asia according to the International Agency for Research on Cancer from World Health Organization (WHO) database and summarized its major risk factors. Non-modifiable factors include genetic factors, ethnicity, age, gender, family history and body height; smoking, alcohol drinking, weight, Westernized diet, physical inactivity, chronic diseases and microbiota were involved in environmental factors. These risk factors were separately discussed in this review according to published literature from Asian countries. CRC screening has been playing an important role in reducing its disease burden. Some recommendations on its screening practices have been formulated in guidelines for Asia Pacific countries. (Intest Res 2019;17:317-329)

4Iranian Registry of Crohn's and Colitis: study profile of first nation-wide inflammatory bowel disease registry in Middle East

저자 : Masoud M Malekzadeh , Alireza Sima , Sudabeh Alatab , Anahita Sadeghi , Nasser Ebrahimi Daryani , Payman Adibi , Iradj Maleki , Hassan Vossoughinia , Hafez Fakheri , Abbas Yazdanbod , Seyed Alireza Taghavi , Ra

발행기관 : 대한장연구학회 간행물 : Intestinal research (Intest Res) 17권 3호 발행 연도 : 2019 페이지 : pp. 330-339 (10 pages)

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Background/Aims: A recent study revealed increasing incidence and prevalence of inflammatory bowel disease (IBD) in Iran. The Iranian Registry of Crohn's and Colitis (IRCC) was designed recently to answer the needs. We reported the design, methods of data collection, and aims of IRCC in this paper. Methods: IRCC is a multicenter prospective registry, which is established with collaboration of more than 100 gastroenterologists from different provinces of Iran. Minimum data set for IRCC was defined according to an international consensus on standard set of outcomes for IBD. A pilot feasibility study was performed on 553 IBD patients with a web-based questionnaire. The reliability of questionnaire evaluated by Cronbach's α. Results: All sections of questionnaire had Cronbach's α of more than 0.6. In pilot study, 312 of participants (56.4%) were male and mean age was 38 years (standard deviation=12.8) and 378 patients (68.35%) had ulcerative colitis, 303 subjects (54,7%) had college education and 358 patients (64.74%) were of Fars ethnicity. We found that 68 (12.3%), 44 (7.9%), and 13 (2.3%) of participants were smokers, hookah and opium users, respectively. History of appendectomy was reported in 58 of patients (10.48%). The most common medication was 5-aminosalicylate (94.39%). Conclusions: To the best of our knowledge, IRCC is the first national IBD registry in the Middle East and could become a reliable infrastructure for national and international research on IBD. IRCC will improve the quality of care of IBD patients and provide national information for policy makers to better plan for controlling IBD in Iran. (Intest Res 2019;17:330-339)

5Ustekinumab is effective in biological refractory Crohn's disease patients-regardless of approval study selection criteria

저자 : Sadik Saman , Martin Goetz , Judith Wendler , Nisar P. Malek , Jan Wehkamp , Thomas Klag

발행기관 : 대한장연구학회 간행물 : Intestinal research (Intest Res) 17권 3호 발행 연도 : 2019 페이지 : pp. 340-348 (9 pages)

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Background/Aims: Ustekinumab is effective in active Crohn's disease. In a retrospective study, we assessed the clinical outcome in nonresponders to anti-tumor necrosis factor therapy, and/or conventional therapy and/or the α4β7-integrin inhibitor vedolizumab. As approval study populations do not always reflect the average “real world” patient cohort, we assessed weather patients who would not have qualified for approval studies show similar outcomes. Methods: Forty-one patients with mild to severe active Crohn's disease were treated with ustekinumab (intravenous 6 mg per kg/body weight) followed by subcutaneous ustekinumab (90 mg) at week 8. Depending on the clinical response maintenance therapy was chosen every 8 or 12 weeks. Clinical response was defined by Crohn's Disease Activity Index (CDAI) decline, decline of stool frequency or clinical improvement. Inclusion criteria for approval studies were assessed. Results: The 58.5% (24/41) showed clinical response to ustekinumab. The 58.3% of this group (14/24) achieved clinical remission. Clinical response correlated significantly with drop of stool frequency and improvement of CDAI score. The 39 out of 41 patients had no side effects and we observed no serious infections. About a third of our patients would not have met ustekinumab approval study criteria. However, patients who did not meet study criteria showed clinical improvement numerically in the same range compared to patients who would have qualified for approval studies. Conclusions: Ustekinumab is effective, safe and well tolerated in a highly therapy refractory patient cohort. Even though a reasonable number of patients did not meet ustekinumab approval study criteria, approval study results seem to be representative to the overall patient cohort. (Intest Res 2019;17:340-348)

6Adherence to Asacol once daily versus divided regimen for maintenance therapy in ulcerative colitis: a prospective, multicenter, randomized study

저자 : Soo-kyung Park , Sang Hyun Park , Chang Soo Eun , Geom Seog Seo , Jong Pil Im , Tae Oh Kim , Dong-il Park

발행기관 : 대한장연구학회 간행물 : Intestinal research (Intest Res) 17권 3호 발행 연도 : 2019 페이지 : pp. 349-356 (8 pages)

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Background/Aims: A once-daily (OD) regimen of 5-aminosalicylic acid (5-ASA) was easier to comply with than a divided daily (DD) regimen, and that treatment efficacy for ulcerative colitis (UC) was not affected by the dosing regimen. This study evaluated treatment adherence of OD and DD dosing in the Korean UC patients. Methods: This study was a prospective, multicenter, randomized trial. UC patients were enrolled who have been in remission for more than 3 months. Patients were randomly assigned to the OD or DD group in a 1:1 ratio. The primary endpoint was adherence rate measured by tablet counts and self-reported adherence rate at 3, 6, 9, and 12 months. The relapse rate was measured at 1 year. Results: Data from the 180 patients who were randomized were analyzed. Both self-reported adherence rate and adherence rate measured by tablet counts were not different at every points, including 1 year. The patients' satisfaction of the OD group was higher than that of the DD group (P<0.001). At 1 year, 91.2% and 95.5% of patients in the OD group and DD group had maintained clinical remission, respectively (P=0.37). Conclusions: The adherence rates were not different between the OD group and DD group. The patients' satisfaction was higher in the OD group than in the DD group. 5-ASA OD dosing might have the same effect as DD for the maintenance of UC remission. (Intest Res 2019;17:349-356)

7Risk of surgery in patients with stricturing type of Crohn's disease at the initial diagnosis: a single center experience

저자 : Yuji Maehata , Yutaka Nagata , Tomohiko Moriyama , Yuichi Matsuno , Atsushi Hirano , Junji Umeno , Takehiro Torisu , Tatsuya Manabe , Takanari Kitazono , Motohiro Esaki

발행기관 : 대한장연구학회 간행물 : Intestinal research (Intest Res) 17권 3호 발행 연도 : 2019 페이지 : pp. 357-364 (8 pages)

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Background/Aims: It remains uncertain which patients with stricturing-type Crohn's disease (CD) require early small bowel surgery after the initial diagnosis. We aimed to clarify clinical characteristics associated with the intervention in such condition of CD. Methods: We retrospectively evaluated the clinical course of 53 patients with CD and small bowel strictures who were initially treated with medications after the initial diagnosis. We investigated possible associations between small bowel surgery and the following: clinical factors and radiologic findings at initial diagnosis and the types of medications administered during follow-up. Results: Twenty-eight patients (53%) required small bowel resection during a median follow-up period of 5.0 years (range, 0.5-14.3 years). The cumulative incidence rates of small bowel surgery at 2, 5, and 10 years were 26.4%, 41.0%, and 63.2%, respectively. Univariate analysis indicated that obstructive symptoms (P=0.036), long-segment stricture (P<0.0001), and prestenotic dilation (P<0.0001) on radiography were associated with small bowel surgery, and immunomodulatory (P=0.037) and biological therapy (P=0.008) were significant factors during follow-up. Multivariate analysis revealed that long-segment stricture (hazard ratio [HR], 4.25; 95% confidence interval [CI], 1.78-10.53; P=0.001) and prestenotic dilation (HR, 3.41; 95% CI, 1.24-9.62; P=0.018) on radiography showed a positive correlation with small bowel surgery, and biological therapy (HR, 0.40; 95% CI, 0.15-0.99; P=0.048) showed a negative correlation. Conclusions: CD patients with long-segment stricture and prestenotic dilation on radiography seem to be at a higher risk of needing small bowel surgery. For such patients, early surgical intervention might be appropriate, even at initial diagnosis. (Intest Res 2019;17:357-364)

8Real-time data monitoring for ulcerative colitis: patient perception and qualitative analysis

저자 : Alissa Walsh , Lawrence Matini , Christopher Hinds , Vanashree Sexton , Oliver Brain , Satish Keshav , John Geddes , Guy Goodwin , Gary Collins , Simon Travis , Michele Peters

발행기관 : 대한장연구학회 간행물 : Intestinal research (Intest Res) 17권 3호 발행 연도 : 2019 페이지 : pp. 365-374 (10 pages)

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Background/Aims: TrueColours ulcerative colitis (TCUC) is a comprehensive web-based program that functions through email, providing direct links to questionnaires. Several similar programs are available, however patient perspectives are unexplored. Methods: A pilot study was conducted to determine feasibility, usability and patient perceptions of real-time data collection (daily symptoms, fortnightly quality of life, 3 monthly outcomes). TCUC was adapted from a web-based program for patients with relapsing-remitting bipolar disorder, using validated UC indices. A semi-structured interview was developed and audio-recorded face-to-face interviews were conducted after 6 months of interaction with TCUC. Transcripts were coded in NVivo11, a qualitative data analysis software package. An inductive approach and thematic analysis was conducted. Results: TCUC was piloted in 66 patients for 6 months. Qualitative analysis currently defies statistical appraisal beyond “data saturation,” even if it has more influence on clinical practice than quantitative data. A total of 28 face-to-face interviews were conducted. Six core themes emerged: awareness, control, decision-making, reassurance, communication and burden of treatment. There was a transcending overarching theme of patient empowerment, which cut across all aspects of the TCUC experience. Conclusions: Patient perception of the impact of real-time data collection was extremely positive. Patients felt empowered as a product of the self-monitoring format of TCUC, which may be a way of improving self-management of UC whilst also decreasing the burden on the individual and healthcare services. (Intest Res 2019;17:365-374)

9Efficacy and safety of abrilumab, an α4β7 integrin inhibitor, in Japanese patients with moderate-to-severe ulcerative colitis: a phase II study

저자 : Toshifumi Hibi , Satoshi Motoya , Toshifumi Ashida , Souken Sai , Yukinori Sameshima , Shiro Nakamura , Atsuo Maemoto , Masahiro Nii , Barbara A Sullivan , Robert A. Gasser Jr , Yasuo Suzuki

발행기관 : 대한장연구학회 간행물 : Intestinal research (Intest Res) 17권 3호 발행 연도 : 2019 페이지 : pp. 375-386 (12 pages)

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Background/Aims: Inhibition of α4β7 integrin has been shown to be effective for induction and maintenance therapy in patients with ulcerative colitis (UC). We investigated the effects of varying doses of the α4β7 inhibitor abrilumab in Japanese patients with moderate-to-severe UC despite conventional treatments. Methods: In this randomized, double-blind, placebo-controlled study, 45 UC patients were randomized to abrilumab 21 mg (n=11), 70 mg (n=12), 210 mg (n=9), or placebo (n=13) via subcutaneous (SC) injection for 12 weeks. The double-blind period was followed by a 36-week open-label period, in which all patients received abrilumab 210 mg SC every 12 weeks, and a 28-week safety follow-up period. The primary efficacy variable was clinical remission at week 8 (total Mayo score ≤2 points with no individual subscore >1 point). Results: Clinical remission at week 8 was 4 out of 31 (12.9%) overall in the abrilumab groups versus 0 out of 13 in the placebo group (abrilumab 21 mg, 1/10 [10.0%]; 70 mg, 2/12 [16.7%]; 210 mg, 1/9 [11.1%]). In both the double-blind and open-label periods, fewer patients in the abrilumab groups experienced ≥1 adverse event compared with those in the placebo group. There were no cases of progressive multifocal leukoencephalopathy and no deaths. Conclusions: Abrilumab 70 mg and 210 mg yielded numerically better results in terms of clinical remission rate at Week 8 than placebo, with the 210 mg dose showing more consistent treatment effects. Abrilumab was well tolerated in Japanese patients with UC. (Intest Res 2019;17:375-386)

10Quantitative histology-based classification system for assessment of the intestinal mucosal histological changes in patients with celiac disease

저자 : Prasenjit Das , Gaurav Ps Gahlot , Alka Singh , Vandana Baloda , Ramakant Rawat , Anil K Verma , Gaurav Khanna , Maitrayee Roy , Archana George , Ashok Singh , Aasma Nalwa , Prashant Ramteke , Rajni Yadav

발행기관 : 대한장연구학회 간행물 : Intestinal research (Intest Res) 17권 3호 발행 연도 : 2019 페이지 : pp. 387-397 (11 pages)

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Background/Aims: The existing histological classifications for the interpretation of small intestinal biopsies are based on qualitative parameters with high intraobserver and interobserver variations. We have developed and propose a quantitative histological classification system for the assessment of intestinal mucosal biopsies. Methods: We performed a computer-assisted quantitative histological assessment of digital images of duodenal biopsies from 137 controls and 124 patients with celiac disease (CeD) (derivation cohort). From the receiver-operating curve analysis, followed by multivariate and logistic regression analyses, we identified parameters for differentiating control biopsies from those of the patients with CeD. We repeated the quantitative histological analysis in a validation cohort (105 controls and 120 patients with CeD). On the basis of the results, we propose a quantitative histological classification system. The new classification was compared with the existing histological classifications for interobserver and intraobserver agreements by a group of qualified pathologists. Results: Among the histological parameters, intraepithelial lymphocyte count of ≥25/100 epithelial cells, adjusted villous height fold change of ≤0.7, and crypt depth-to-villous height ratio of ≥0.5 showed good discriminative power between the mucosal biopsies from the patients with CeD and those from the controls, with 90.3% sensitivity, 93.5% specificity, and 96.2% area under the curve. Among the existing histological classifications, our quantitative histological classification showed the highest intraobserver (69.7%-85.03%) and interobserver (24.6%-71.5%) agreements. Conclusions: Quantitative assessment increases the reliability of the histological assessment of mucosal biopsies in patients with CeD. Such a classification system may be used for clinical trials in patients with CeD. (Intest Res 2019;17:387-397)

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